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  • 1. Balog, Piroska
    et al.
    Janszky, Imre
    Chen, Hua
    Rafael, Beatrix
    Hemmingsson, Tomas
    Stockholm University, Faculty of Social Sciences, Department of Public Health Sciences. Karolinska Institute, Sweden.
    László, Krisztina D.
    Social relations in late adolescence and incident coronary heart disease: a 38-year follow-up of the Swedish 1969-1970 Conscription Cohort2019In: BMJ Open, E-ISSN 2044-6055, Vol. 9, no 12, article id e030880Article in journal (Refereed)
    Abstract [en]

    Objectives Increasing evidence suggests that low social support is associated with an elevated risk of coronary heart disease (CHD). Earlier studies in this field were conducted in predominantly middle-aged or older samples; thus, the associations reported previously may have been confounded by subclinical manifestations of the disease. We investigated whether social relationships in late adolescence, that is, well before symptoms of subclinical disease manifest, are associated with CHD during a 38-year follow-up.

    Setting Sweden.

    Participants Men born 1949-1951 and conscripted for military service in Sweden during 1969-1970 (n=49321). At conscription, participants completed questionnaires about social relationships, lifestyle and health-related factors and underwent a medical examination.

    Primary and secondary outcome measures CHD, acute myocardial infarction (AMI).

    Results We found no relationship between having no confidant and frequency of confidential discussions with friends and the risk of CHD or AMI in the first 30 years of follow-up. However, after 30 years, men with no confidant at baseline had increased CHD and AMI risks relative to those having a confidant; the childhood socioeconomic status-adjusted HR and 95% Cls (CI) were 1.25 (1.10 to 1.41) and 1.27 (1.08 to 1.49), respectively. The frequency of confidential discussions with friends had an inverse Ushaped relationship with the outcomes after 30 years; the HR (95% CI) for 'sometimes' versus 'quite often' was 1.16 (1.04 to 1.29) for CHD and 1.16 (1.01 to 1.33) for AMI. These associations persisted after adjusting for mental ill-health, lifestyle factors and systolic blood pressure. A low number of friends in late adolescence was not related to an increased CHD or AMI risk.

    Conclusions Not having a confidant in late adolescence was associated positively, while the frequency of confidential discussions with friends had an inverse U-shaped relationship with CHD and AMI after 30 years of follow-up, suggesting that these associations are not due to subclinical disease manifestations.

  • 2. Baniol, Marion
    et al.
    Murganti, Francesca
    Smialowska, Agata
    Stockholm University, Faculty of Science, Department of Biochemistry and Biophysics. Stockholm University, Science for Life Laboratory (SciLifeLab).
    Panula, Joni
    Lázár, Enikő
    Brockman, Viveka
    Giatrellis, Sarantis
    Derks, Wouter
    Bergmann, Olaf
    Identification and characterization of distinct cell cycle stages in cardiomyocytes using the FUCCI transgenic system2021In: Experimental Cell Research, ISSN 0014-4827, E-ISSN 1090-2422, Vol. 408, no 2, article id 112880Article in journal (Refereed)
    Abstract [en]

    Understanding the regulatory mechanism by which cardiomyocyte proliferation transitions to endoreplication and cell cycle arrest during the neonatal period is crucial for identifying proproliferative factors and developing regenerative therapies. We used a transgenic mouse model based on the fluorescent ubiquitination-based cell cycle indicator (FUCCI) system to isolate and characterize cycling cardiomyocytes at different cell cycle stages at a single-cell resolution. Single-cell transcriptome analysis of cycling and noncycling cardiomyocytes was performed at postnatal days 0 (P0) and 7 (P7). The FUCCI system proved to be efficient for the identification of cycling cardiomyocytes with the highest mitotic activity at birth, followed by a gradual decline in the number of cycling and mitotic cardiomyocytes during the neonatal period. Cardiomyocytes showed premature cell cycle exit at G1/S shortly after birth and delayed G1/S progression during endoreplication at P7. Single-cell RNA-seq confirmed previously described signaling pathways involved in cardiomyocyte proliferation (Erbb2 and Hippo/YAP), and maturation-related transcriptional changes during postnatal development, including the metabolic switch from glycolysis to fatty acid oxidation in cardiomyocytes. Importantly, we generated transcriptional profiles specific to cell division and endoreplication in cardiomyocytes at different developmental stages that may facilitate the identification of genes important for adult cardiomyocyte proliferation and heart regeneration. In conclusion, the FUCCI mouse provides a valuable system to study cardiomyocyte cell cycle activity at single cell resolution that can help to decipher the switch from cardiomyocyte proliferation to endoreplication, and to revert this process to facilitate endogenous repair.

  • 3.
    Carballo-Casla, Adrián
    et al.
    Stockholm University, Faculty of Social Sciences, Aging Research Center (ARC), (together with KI). Universidad Autónoma de Madrid, Spain; Center for Networked Biomedical Research in Epidemiology and Public Health (CIBERESP), Spain; University College London, UK.
    Stefler, Denes
    Ortolá, Rosario
    Chen, Yuntao
    Knuppel, Anika
    Kubinova, Ruzena
    Pajak, Andrzej
    Rodríguez-Artalejo, Fernando
    Brunner, Eric J.
    Bobak, Martin
    The Southern European Atlantic diet and all-cause and cause-specific mortality: a European multicohort study2023In: European Journal of Preventive Cardiology, ISSN 2047-4873, E-ISSN 2047-4881, Vol. 31, no 3, p. 358-367Article in journal (Refereed)
    Abstract [en]

    Aims: The Southern European Atlantic diet (SEAD) is the traditional dietary pattern of northwestern Spain and northern Portugal, but it may resemble that of central, eastern, and western European countries. The SEAD has been found associated with lower risk of myocardial infarction and mortality in older adults, but it is uncertain whether this association also exists in other European populations and if it is similar as that found in its countries of origin.

    Methods and results: We conducted a prospective analysis of four cohorts with 35 917 subjects aged 18–96 years: ENRICA (Spain), HAPIEE (Czechia and Poland), and Whitehall II (United Kingdom). The SEAD comprised fresh fish, cod, red meat and pork products, dairy, legumes and vegetables, vegetable soup, potatoes, whole-grain bread, and moderate wine consumption. Associations were adjusted for sociodemographic variables, energy intake, lifestyle, and morbidity. After a median follow-up of 13.6 years (range = 0–15), we recorded 4 973 all-cause, 1 581 cardiovascular, and 1 814 cancer deaths. Higher adherence to the SEAD was associated with lower mortality in the pooled sample. Fully adjusted hazard ratios and 95% confidence interval per 1-standard deviation increment in the SEAD were 0.92 (0.89, 0.95), 0.91 (0.86, 0.96), and 0.94 (0.89, 0.99) for all-cause, cardiovascular, and cancer mortality, respectively. The association of the SEAD with all-cause mortality was not significantly different between countries [Spain = 0.93 (0.88, 0.99), Czechia = 0.94 (0.89,0.99), Poland = 0.89 (0.85, 0.93), United Kingdom = 0.98 (0.89, 1.07); P for interaction = 0.16].

    Conclusion: The SEAD was associated with lower all-cause, cardiovascular, and cancer mortality in southern, central, eastern, and western European populations. Associations were of similar magnitude as those found for existing healthy dietary patterns.

  • 4. Chen, Hua
    et al.
    Hemmingsson, Tomas
    Stockholm University, Faculty of Social Sciences, Department of Public Health Sciences. Karolinska Institutet, Sweden.
    Forsell, Yvonne
    Rostila, Mikael
    Stockholm University, Faculty of Social Sciences, Department of Public Health Sciences, Centre for Health Equity Studies (CHESS).
    Janszky, Imre
    László, Krisztina D.
    Death of a Parent During Childhood and the Risk of Ischemic Heart Disease and Stroke in Adult Men2020In: Psychosomatic Medicine, ISSN 0033-3174, E-ISSN 1534-7796, Vol. 82, no 9, p. 810-816Article in journal (Refereed)
    Abstract [en]

    Objective

    The death of a parent during childhood is a severe life event with potentially long-term consequences. Earlier studies have shown an increased risk of cardiovascular diseases (CVD) after the death of a spouse, child, or sibling. Whether parental death during childhood is associated with an increased risk of incident CVD is unknown and was investigated in this study.

    Methods

    We studied 48,992 men born 1949 to 1951 and enlisted for military conscription in 1969 to 1970. We obtained information on death of a parent during childhood, CVD up to 2008, and covariates by linking the questionnaire and the clinical examination data from conscription with nationwide socioeconomic and health registers.

    Results

    Men who lost a parent during childhood had an increased risk of ischemic heart disease (IHD; adjusted hazard ratio (HR) and 95% confidence interval [CI] = 1.30 [1.13-1.49]) but not of stroke during the 39-year follow-up (adjusted HR [95% CI] = 0.87 [0.66-1.15]). Maternal death was associated with IHD both when the loss was due to cardiovascular (adjusted HR [95% CI] = 2.04 [1.02-4.08]) and unnatural causes (adjusted HR [95% CI] = 2.50 [1.42-4.42]); in case of paternal death, an increased IHD risk was observed only when the loss was due to cardiovascular causes (adjusted HR [95% CI] = 1.82 [1.37-2.42]). There were no substantial differences in CVD according to the child's age at the loss.

    Conclusions

    Parental death during childhood was associated with an increased risk of IHD in men. If these associations are confirmed in future studies, the long-term effects of childhood bereavement may warrant attention.

  • 5. Chen, Hua
    et al.
    Li, Jiong
    Wei, Dang
    Rostila, Mikael
    Stockholm University, Faculty of Social Sciences, Department of Public Health Sciences, Centre for Health Equity Studies (CHESS).
    Janszky, Imre
    Forsell, Yvonne
    Hemmingsson, Tomas
    Stockholm University, Faculty of Social Sciences, Department of Public Health Sciences. Institute of Environmental Medicine, Karolinska Institutet, Sweden.
    László, Krisztina D.
    Death of a Parent and the Risk of Ischemic Heart Disease and Stroke in Denmark and Sweden2022In: JAMA Network Open, E-ISSN 2574-3805, Vol. 5, no 6, article id e2218178Article in journal (Refereed)
    Abstract [en]

    IMPORTANCE Increasing evidence suggests that parental death is associated with unhealthy behaviors and mental ill-health. Knowledge regarding the link between parental death and the risk of ischemic heart disease (IHD) and stroke remains limited.

    OBJECTIVES To investigate whether parental death is associated with an increased risk of IHD and stroke and whether these associations differ by the characteristics of the loss.

    DESIGN, SETTING, AND PARTICIPANTS This population-based cohort study, involving linkages between several nationwide registers, included 3 766 918 individuals born between 1973 and 1998 in Denmark and between 1973 and 1996 in Sweden. Participants were followed up until 2016 in Denmark and 2014 in Sweden. Data were analyzed from December 2019 to May 2021.

    EXPOSURES Death of a parent.

    MAIN OUTCOMES AND MEASURES Diagnosis with or death due to IHD or stroke. Poisson regression was used to analyze the associations between parental death and IHD and stroke risk.

    RESULTS Altogether, 48.8% of the participants were women, and 42.7% were from Denmark. A total of 523 496 individuals lost a parent during the study period (median age at loss, 25 years; IQR, 17-32 years). Parental death was associated with a 41% increased risk of IHD (incidence rate ratio [IRR], 1.41; 95% CI, 1.33-1.51) and a 30% increased risk of stroke [IRR, 1.30; 95% CI, 1.21-1.38). The associations were observed not only if the parent died because of cardiovascular or other natural causes but also in cases of unnatural deaths. The associations were stronger when both parents had died (IHD: IRR, 1.87; 95% CI, 1.59-2.21; stroke: IRR, 1.64; 95% CI, 1.35-1.98) than when 1 parent had died (IHD: IRR, 1.37; 95% CI, 1.28-1.47; stroke: IRR, 1.27; 95% CI, 1.19-1.36) but did not differ substantially by the offspring's age at loss or the deceased parents' sex. The risk of acute myocardial infarction was highest in the first 3 months after loss.

    CONCLUSIONS AND RELEVANCE In this cohort study, parental death in the first decades of life was associated with an increased risk of IHD and stroke. The associations were observed not only in cases of parental cardiovascular and other natural deaths but also in cases of unnatural deaths. Family members and health professionals may need to pay attention to the cardiovascular disease risk among parentally bereaved individuals.

  • 6. Chen, Hua
    et al.
    Wei, Dang
    Janszky, Imre
    Dahlström, Ulf
    Rostila, Mikael
    Stockholm University, Faculty of Social Sciences, Department of Public Health Sciences, Centre for Health Equity Studies (CHESS).
    László, Krisztina D.
    Bereavement and Prognosis in Heart Failure: A Swedish Cohort Study2022In: JACC. Heart failure, ISSN 2213-1779, E-ISSN 2213-1787, Vol. 10, no 10, p. 753-764Article in journal (Refereed)
    Abstract [en]

    Background: The role of stress in the prognosis of heart failure (HF) is unclear. This study investigated whether the death of a close family member, a severe source of stress, is associated with mortality in HF.

    Objectives: This study assessed whether the death of a close family member is associated with mortality in HF.

    Methods: Patients from the Swedish Heart Failure Registry during 2000-2018 and/or in the Swedish Patient Register with a primary diagnosis of HF during 1987-2018 (N = 490,527) were included in this study. Information was obtained on death of family members (children, partner, grandchildren, siblings, and parents), mortality, sociodemographic variables, and health-related factors from several population-based registers. The association between bereavement and mortality was analyzed by using Poisson regression.

    Results: Loss of a family member was associated with an increased risk of dying (adjusted relative risk: 1.29; 95% CI: 1.27-1.30). The association was present not only in case of the family member's cardiovascular deaths and other natural deaths but also in case of unnatural deaths. The risk was higher for 2 losses than for 1 loss and highest in the first week after the loss. The association between bereavement and an increased mortality risk was observed for the death of a child, spouse/partner, grandchild, and sibling but not of a parent.

    Conclusions: Death of a family member was associated with an increased risk of mortality among patients with HF. Further studies are needed to investigate whether less severe sources of stress can also contribute to poor prognosis in HF and to explore the mechanisms underlying this association.

  • 7.
    Ding, Mozhu
    et al.
    Stockholm University, Faculty of Social Sciences, Aging Research Center (ARC), (together with KI).
    Fratiglioni, Laura
    Stockholm University, Faculty of Social Sciences, Aging Research Center (ARC), (together with KI). Stockholm Gerontology Research Center, Sweden.
    Johnell, Kristina
    Stockholm University, Faculty of Social Sciences, Aging Research Center (ARC), (together with KI).
    Fastbom, Johan
    Stockholm University, Faculty of Social Sciences, Aging Research Center (ARC), (together with KI).
    Ljungdahl, Maria
    Qiu, Chengxuan
    Stockholm University, Faculty of Social Sciences, Aging Research Center (ARC), (together with KI).
    Atrial fibrillation and use of antithrombotic medications in older people: A population-based study2017In: International Journal of Cardiology, ISSN 0167-5273, E-ISSN 1874-1754, Vol. 249, p. 173-178Article in journal (Refereed)
    Abstract [en]

    Background: Trends in the use of antithrombotic drugs in elderly patients with atrial fibrillation (AF) are largely unknown. We estimated the prevalence of AF in an older population, and examined whether use of anticoagulant and antiplatelet drugs in older AF patients has changed over time. Methods: Data from the population-based Swedish National study on Aging and Care in Kungsholmen (n = 3363, age = 60 years, 64.9% women) were used (2001-2004 and 2007-2010). AF cases were identified through 12-lead electrocardiogram, physician examinations, and patient register records (ICD-10 code I48). We used the CHADS(2) and CHA(2)DS(2)-VASc scores to estimate stroke risk, and an incomplete HAS-BLED score to estimate bleeding risk. Results: At baseline (2001-2004), 328 persons (9.8%) were ascertained to have AF. The prevalence of AF increased significantly with age from 2.8% in people aged 60-66 years to 21.2% in those = 90 years, and was more common in men than in women (11.2% vs. 9.0%). Among AF patients with CHADS2 score = 2 at baseline, 25% were taking anticoagulant drugs and 54% were taking antiplatelet drugs. High bleeding risk was significantly associated with not using anticoagulant drugs in AF patients (multi-adjusted OR = 2.50, p = 0.015). Between 2001-2004 and 2007-2010, use of anticoagulant drugs increased significantly, especially in AF patients with CHA2DS2-VASc score >= 2 (23% vs. 33%, p = 0.008) and in those with HAS-BLED score <3 (32% vs. 53%, p = 0.004). Conclusion: AF is common among old people. The use of anticoagulant drugs increased over time in AF patients, yet still two-thirds of those with high stroke risk remained untreated.

  • 8. Dludla, Phiwayinkosi V.
    et al.
    Nkambule, Bongani B.
    Tiano, Luca
    Louw, Johan
    Jastroch, Martin
    Stockholm University, Faculty of Science, Department of Molecular Biosciences, The Wenner-Gren Institute. Helmholtz-Zentrum München, German Research Center for Environmental Health (GmbH), Germany; German Center for Diabetes Research (DZD), Germany.
    Mazibuko-Mbeje, Sithandiwe E.
    Uncoupling proteins as a therapeutic target to protect the diabetic heart2018In: Pharmacological Research, ISSN 1043-6618, E-ISSN 1096-1186, Vol. 137, p. 11-24Article, review/survey (Refereed)
    Abstract [en]

    Myocardial remodeling and dysfunction caused by accelerated oxidative damage is a widely reported phenomenon within a diabetic state. Altered myocardial substrate preference appears to be the major cause of enhanced oxidative stress-mediated cell injury within a diabetic heart. During this process, exacerbated free fatty acid flux causes an abnormal increase in mitochondrial membrane potential leading to the overproduction of free radical species and subsequent cell damage. Uncoupling proteins (UCPs) are expressed within the myocardium and can protect against free radical damage by modulating mitochondrial respiration, leading to reduced production of reactive oxygen species. Moreover, transgenic animals lacking UCPs have been shown to be more susceptible to oxidative damage and display reduced cardiac function when compared to wild type animals. This suggests that tight regulation of UCPs is necessary for normal cardiac function and in the prevention of diabetes-induced oxidative damage. This review aims to enhance our understanding of the pathophysiological mechanisms relating to the role of UCPs in a diabetic heart, and further discuss known pharmacological compounds and hormones that can protect a diabetic heart through the modulation of UCPs.

  • 9. Eisenberg, Tobias
    et al.
    Abdellatif, Mahmoud
    Schroeder, Sabrina
    Primessnig, Uwe
    Stekovic, Slaven
    Pendl, Tobias
    Harger, Alexandra
    Schipke, Julia
    Zimmermann, Andreas
    Schmidt, Albrecht
    Tong, Mingming
    Ruckenstuhl, Christoph
    Dammbrueck, Christopher
    Gross, Angelina S.
    Herbst, Viktoria
    Magnes, Christoph
    Trausinger, Gert
    Narath, Sophie
    Meinitzer, Andreas
    Hu, Zehan
    Kirsch, Alexander
    Eller, Kathrin
    Carmona-Gutierrez, Didac
    Büttner, Sabrina
    Stockholm University, Faculty of Science, Department of Molecular Biosciences, The Wenner-Gren Institute. University of Graz, Austria.
    Pietrocola, Federico
    Knittelfelder, Oskar
    Schrepfer, Emilie
    Rockenfeller, Patrick
    Simonini, Corinna
    Rahn, Alexandros
    Horsch, Marion
    Moreth, Kristin
    Beckers, Johannes
    Fuchs, Helmut
    Gailus-Durner, Valerie
    Neff, Frauke
    Janik, Dirk
    Rathkolb, Birgit
    Rozman, Jan
    de Angelis, Martin Hrabe
    Moustafa, Tarek
    Haemmerle, Guenter
    Mayr, Manuel
    Willeit, Peter
    von Frieling-Salewsky, Marion
    Pieske, Burkert
    Scorrano, Luca
    Pieber, Thomas
    Pechlaner, Raimund
    Willeit, Johann
    Sigrist, Stephan J.
    Linke, Wolfgang A.
    Muehlfeld, Christian
    Sadoshima, Junichi
    Dengjel, Joern
    Kiechl, Stefan
    Kroemer, Guido
    Sedej, Simon
    Madeo, Frank
    Cardioprotection and lifespan extension by the natural polyamine spermidine2016In: Nature Medicine, ISSN 1078-8956, E-ISSN 1546-170X, Vol. 22, no 12, p. 1428-1438Article in journal (Refereed)
    Abstract [en]

    Aging is associated with an increased risk of cardiovascular disease and death. Here we show that oral supplementation of the natural polyamine spermidine extends the lifespan of mice and exerts cardioprotective effects, reducing cardiac hypertrophy and preserving diastolic function in old mice. Spermidine feeding enhanced cardiac autophagy, mitophagy and mitochondrial respiration, and it also improved the mechano-elastical properties of cardiomyocytes in vivo, coinciding with increased titin phosphorylation and suppressed subclinical inflammation. Spermidine feeding failed to provide cardioprotection in mice that lack the autophagy-related protein Atg5 in cardiomyocytes. In Dahl salt-sensitive rats that were fed a high-salt diet, a model for hypertension-induced congestive heart failure, spermidine feeding reduced systemic blood pressure, increased titin phosphorylation and prevented cardiac hypertrophy and a decline in diastolic function, thus delaying the progression to heart failure. In humans, high levels of dietary spermidine, as assessed from food questionnaires, correlated with reduced blood pressure and a lower incidence of cardiovascular disease. Our results suggest a new and feasible strategy for protection against cardiovascular disease.

  • 10. Ekelund, Ulf
    et al.
    Tarp, Jakob
    Steene-Johannessen, Jostein
    Hansen, Bjørge H.
    Jefferis, Barbara
    Fagerland, Morten W.
    Whincup, Peter
    Diaz, Keith M.
    Hooker, Steven P.
    Chernofsky, Ariel
    Larson, Martin G.
    Spartano, Nicole
    Vasan, Ramachandran S.
    Dohrn, Ing-Mari
    Stockholm University, Faculty of Social Sciences, Aging Research Center (ARC), (together with KI).
    Hagströmer, Maria
    Stockholm University, Faculty of Social Sciences, Aging Research Center (ARC), (together with KI). Karolinska University Hospital, Sweden.
    Edwardson, Charlotte
    Yates, Thomas
    Shiroma, Eric
    Anderssen, Sigmund A.
    Lee, I-Min
    Dose-response associations between accelerometry measured physical activity and sedentary time and all cause mortality: systematic review and harmonised meta-analysis2019In: The BMJ, E-ISSN 1756-1833, Vol. 366, article id l4570Article, review/survey (Refereed)
    Abstract [en]

    OBJECTIVE

    To examine the dose-response associations between accelerometer assessed total physical activity, different intensities of physical activity, and sedentary time and all cause mortality.

    DESIGN

    Systematic review and harmonised meta-analysis.

    DATA SOURCES

    PubMed, PsycINFO, Embase, Web of Science, Sport Discus from inception to 31 July 2018.

    ELIGIBILITY CRITERIA

    Prospective cohort studies assessing physical activity and sedentary time by accelerometry and associations with all cause mortality and reported effect estimates as hazard ratios, odds ratios, or relative risks with 95% confidence intervals.

    DATA EXTRACTION AND ANALYSIS

    Guidelines for meta-analyses and systematic reviews for observational studies and PRISMA guidelines were followed. Two authors independently screened the titles and abstracts. One author performed a full text review and another extracted the data. Two authors independently assessed the risk of bias. Individual level participant data were harmonised and analysed at study level. Data on physical activity were categorised by quarters at study level, and study specific associations with all cause mortality were analysed using Cox proportional hazards regression analyses. Study specific results were summarised using random effects meta-analysis.

    MAIN OUTCOME MEASURE

    All cause mortality.

    RESULTS

    39 studies were retrieved for full text review; 10 were eligible for inclusion, three were excluded owing to harmonisation challenges (eg, wrist placement of the accelerometer), and one study did not participate. Two additional studies with unpublished mortality data were also included. Thus, individual level data from eight studies (n=36 383; mean age 62.6 years; 72.8% women), with median follow-up of 5.8 years (range 3.0-14.5 years) and 2149 (5.9%) deaths were analysed. Any physical activity, regardless of intensity, was associated with lower risk of mortality, with a non-linear dose-response. Hazards ratios for mortality were 1.00 (referent) in the first quarter (least active), 0.48 (95% confidence interval 0.43 to 0.54) in the second quarter, 0.34 (0.26 to 0.45) in the third quarter, and 0.27 (0.23 to 0.32) in the fourth quarter (most active). Corresponding hazards ratios for light physical activity were 1.00, 0.60 (0.54 to 0.68), 0.44 (0.38 to 0.51), and 0.38 (0.28 to 0.51), and for moderate-to-vigorous physical activity were 1.00, 0.64 (0.55 to 0.74), 0.55 (0.40 to 0.74), and 0.52 (0.43 to 0.61). For sedentary time, hazards ratios were 1.00 (referent; least sedentary), 1.28 (1.09 to 1.51), 1.71 (1.36 to 2.15), and 2.63 (1.94 to 3.56).

    CONCLUSION

    Higher levels of total physical activity, at any intensity, and less time spent sedentary, are associated with substantially reduced risk for premature mortality, with evidence of a non-linear dose-response pattern in middle aged and older adults.

  • 11. Farioli, Andrea
    et al.
    Hemmingsson, Tomas
    Stockholm University, Faculty of Social Sciences, Centre for Social Research on Alcohol and Drugs (SoRAD). Karolinska Institutet, Sweden.
    Kriebel, David
    Vascular risk factors and rhegmatogenous retinal detachment: a follow-up of a national cohort of Swedish men2016In: British Journal of Ophthalmology, ISSN 0007-1161, E-ISSN 1468-2079, Vol. 100, no 7, p. 907-913Article in journal (Refereed)
    Abstract [en]

    Background We aimed to investigate the role of vascular risk factors in the genesis of rhegmatogenous retinal detachment (RRD) using data from a large cohort of Swedish conscripts. Methods We used data from a nationwide cohort of 49 321 Swedish men born during 1949-1951, conscripted for compulsory military service in 19691970 with nearly complete follow-up to 2009. Information on surgically treated RRD between 1973 and 2009 was collected from the National Patient Register. We fitted Cox regression models stratified on myopia degree and including blood pressure levels, body mass index and cigarette smoking. Population attributable fractions of RRD were estimated through maximum likelihood methods. Results We observed 262 cases of RRD in 1 725 770 person-years. At multivariate analysis, the number of cigarettes per day showed a reverse association with the risk of RRD (p for trend 0.01). Conscripts with obesity presented a higher risk compared with normal subjects (adjusted HR 2.51, 95% CI 1.02 to 6.13). We found weak evidence of an association between blood pressure and RRD (HR for men with hypertension compared with normotension 1.41, 95% CI 0.93 to 2.13). All the observed associations were stronger when the analysis was restricted to non-myopic conscripts. In particular, the HR for hypertension was 2.33 (95% CI 1.30 to 4.19) compared with normotension. If this association is causal, we estimated that 42.0% of RRD cases (95% CI 11.5% to 62.0%) occurring among non-myopics are attributable to elevated blood pressure. Conclusions Vascular risk factors may be important determinants of RRD, particularly among non-myopics. Further investigations on the role of hypertension and obesity are needed.

  • 12. Fattahi, Nina
    et al.
    Rosenblad, Andreas
    Stockholm University, Faculty of Social Sciences, Department of Statistics. Uppsala University, Sweden.
    Kragsterman, Björn
    Hultgren, Rebecka
    Risk factors in 50-year-old men predicting development of abdominal aortic aneurysm2020In: Journal of Vascular Surgery, ISSN 0741-5214, E-ISSN 1097-6809, Vol. 72, no 4, p. 1337-1346Article in journal (Refereed)
    Abstract [en]

    Background: Abdominal aortic aneurysm (AAA) is a potentially lethal condition associated with several well-known risk factors including age, smoking, and male sex. The aim of this study was to identify risk factors predicting future development of AAA, which could influence future prevention strategies.

    Methods: This study collected the data sets of the Westmannia Cardiovascular Risk Factors Study (WICTORY) from 1990 to 1999 and combined them with cases of individuals who have undergone ultrasound examination of the infrarenal aortic diameter as part of the Vastmanland County's ongoing AAA screening program that commenced in 2007 or for other purposes. The study analyzed 5817 men aged 50 years at the time they participated in WICTORY and who underwent an ultrasound examination of the infrarenal aorta on average 15 years later.

    Results: The prevalence of AAA in our study was 2.6%. Age, smoking status, angina pectoris treatment, prior myocardial infarction, blood pressure treatment, body mass index, waist circumference, systolic blood pressure, heart rate, and total cholesterol level were found to be associated with the development of AAA later in life in the univariate analysis. In the multivariate analysis, current smokers at age 50 years had 11 times higher risk for later development of AAA (hazard ratio [HR], 11.178; confidence interval [CI], 6.277-19.908; P < .001). Former smokers did not suffer a similar risk of AAA development. Elevated total cholesterol concentration at baseline was associated with later AAA development (HR, 1.275; CI, 1.119-1.451; P < .001), as were increasing age (HR, 1.702; CI, 1.153-2.512; P = .007) and waist circumference (HR, 1.019; CI, 1.002-1.037; P = .031).

    Conclusions: Both the well-known and the somewhat less established possible predictors for future development of AAA identified in this study can support improvement of strategic preventive measures toward specific risk groups and thereby possibly reduce the risk for development of AAA later in life or at least increase the possibility of an early diagnosis in patients with intact AAA.

  • 13. Felix Garrido, Ananda Lais
    et al.
    Duarte, Adriana de Sousa
    Santana, Patricia Teixeira
    Rodrigues, Gabriella Habib
    Pellegrino, Pollyanna
    Ramos Nogueira, Luciana Fidalgo
    Cipolla-Neto, Jose
    de Castro Moreno, Claudia Roberta
    Stockholm University, Faculty of Social Sciences, Department of Psychology, Stress Research Institute. University of São Paulo, Brazil.
    Marqueze, Elaine Cristina
    Eating habits, sleep, and a proxy for circadian disruption are correlated with dyslipidemia in overweight night workers2021In: Nutrition (Burbank, Los Angeles County, Calif.), ISSN 0899-9007, E-ISSN 1873-1244, Vol. 83, article id 111084Article in journal (Refereed)
    Abstract [en]

    Objective: The aim of this study was to evaluate the relationship between proxy for circadian disruption, eating habits, sleep characteristics, and dyslipidemic parameters.

    Methods: This was a randomized, double-blind, crossover controlled clinical trial, and for this study, only baseline data were used. The sample was composed of 36 overweight female nurses who worked on a fixed night shift (12 × 36 h). Linear regression models were used to assess the relationship between the mentioned variables.

    Results: The participants’ average age was 39.4 y (Standard error (SE) 1 y) and the average nighttime sleep duration was 5.76 h (SE 0.16 h). The average chronotype indicated a moderate early type (03:03 h; SE 20 min) and the average social jetlag was 03:42 h (SE 10 min). It was found that 1 h less of nighttime sleep increased very-low-density lipoprotein cholesterol levels by 2.75 mg/dL and triacylglyceride levels by 3.62 mg/dL. Additionally, higher social jetlag was associated with higher low-density lipoprotein cholesterol levels. On the other hand, each additional hour in the chronotype increased high-density lipoprotein cholesterol levels by 3.06 mg/dL and a time interval >2 h between the last meal and sleep onset was associated with higher high-density lipoprotein cholesterol levels.

    Conclusion: Short duration of nighttime sleep and high social jetlag are risk factors for dyslipidemia, whereas the late type and the longer time interval between the last meal and sleep onset appear to be protective factors for dyslipidemia.

  • 14.
    Fransson, Eleonor I.
    et al.
    Stockholm University, Faculty of Social Sciences, Stress Research Institute. Karolinska Institutet, Sweden; Jönköping University, Sweden.
    Nyberg, Solja T.
    Heikkilä, Katriina
    Alfredsson, Lars
    Bjorner, Jakob B.
    Borritz, Marianne
    Burr, Hermann
    Dragano, Nico
    Geuskens, Goedele A.
    Goldberg, Marcel
    Hamer, Mark
    Hooftman, Wendela E.
    Houtman, Irene L
    Joensuu, Matti
    Jokela, Markus
    Knutsson, Anders
    Koskenvuo, Markku
    Koskinen, Aki
    Kumari, Meena
    Leineweber, Constanze
    Stockholm University, Faculty of Social Sciences, Stress Research Institute.
    Lunau, Thorsten
    Madsen, Ida E. H.
    Magnusson Hanson, Linda
    Stockholm University, Faculty of Social Sciences, Stress Research Institute.
    Nielsen, Martin L.
    Nordin, Maria
    Oksanen, Tuula
    Pentti, Jaana
    Pejtersen, Jan H.
    Rugulies, Reiner
    Salo, Paula
    Shipley, Martin J.
    Steptoe, Andrew
    Suominen, Sakari B.
    Theorell, Töres
    Stockholm University, Faculty of Social Sciences, Stress Research Institute.
    Toppinen-Tanner, Salla
    Vahtera, Jussi
    Virtanen, Marianna
    Väänänen, Ari
    Westerholm, Peter J. M.
    Westerlund, Hugo
    Stockholm University, Faculty of Social Sciences, Stress Research Institute.
    Zins, Marie
    Britton, Annie
    Brunner, Eric J.
    Singh-Manoux, Archana
    Batty, G. David
    Kivimäki, Mika
    Job strain and the risk of stroke: an individual-participant data meta-analysis2015In: Stroke, ISSN 0039-2499, E-ISSN 1524-4628, Vol. 46, no 2, p. 557-559Article in journal (Refereed)
    Abstract [en]

    BACKGROUND AND PURPOSE: Psychosocial stress at work has been proposed to be a risk factor for cardiovascular disease. However, its role as a risk factor for stroke is uncertain.

    METHODS: We conducted an individual-participant-data meta-analysis of 196 380 males and females from 14 European cohort studies to investigate the association between job strain, a measure of work-related stress, and incident stroke.

    RESULTS: In 1.8 million person-years at risk (mean follow-up 9.2 years), 2023 first-time stroke events were recorded. The age- and sex-adjusted hazard ratio for job strain relative to no job strain was 1.24 (95% confidence interval, 1.05;1.47) for ischemic stroke, 1.01 (95% confidence interval, 0.75;1.36) for hemorrhagic stroke, and 1.09 (95% confidence interval, 0.94;1.26) for overall stroke. The association with ischemic stroke was robust to further adjustment for socioeconomic status.

    CONCLUSION: Job strain may be associated with an increased risk of ischemic stroke, but further research is needed to determine whether interventions targeting job strain would reduce stroke risk beyond existing preventive strategies.

  • 15. Fuks, Kateryna B.
    et al.
    Weinmayr, Gudrun
    Basagana, Xavier
    Gruzieva, Olena
    Hampel, Regina
    Oftedal, Bente
    Sorensen, Mette
    Wolf, Kathrin
    Aamodt, Geir
    Aasvang, Gunn Marit
    Aguilera, Inmaculada
    Becker, Thomas
    Beelen, Rob
    Brunekreef, Bert
    Caracciolo, Barbara
    Stockholm University, Faculty of Social Sciences, Aging Research Center (ARC), (together with KI).
    Cyrys, Josef
    Elosua, Roberto
    Eriksen, Kirsten Thorup
    Foraster, Maria
    Fratiglioni, Laura
    Stockholm University, Faculty of Social Sciences, Aging Research Center (ARC), (together with KI). Stockholm Gerontology Research Center, Sweden.
    Hilding, Agneta
    Houthuijs, Danny
    Korek, Michal
    Kunzli, Nino
    Marrugat, Jaume
    Nieuwenhuijsen, Mark
    Östenson, Claes-Göran
    Penell, Johanna
    Pershagen, Göran
    Raaschou-Nielsen, Ole
    Swart, Wim J. R.
    Peters, Annette
    Hoffmann, Barbara
    Long-term exposure to ambient air pollution and traffic noise and incident hypertension in seven cohorts of the European study of cohorts for air pollution effects (ESCAPE)2017In: European Heart Journal, ISSN 0195-668X, E-ISSN 1522-9645, Vol. 38, no 13, p. 983-990Article in journal (Refereed)
    Abstract [en]

    Aims We investigated whether traffic-related air pollution and noise are associated with incident hypertension in European cohorts. Methods and results We included seven cohorts of the European study of cohorts for air pollution effects (ESCAPE). We modelled concentrations of particulate matter with aerodynamic diameter <= 2.5 mu m (PM2.5), <= 10 mu m (PM10), >2.5, and <= 10 mu m (PMcoarse), soot (PM2.5 absorbance), and nitrogen oxides at the addresses of participants with land use regression. Residential exposure to traffic noise was modelled at the facade according to the EU Directive 2002/49/EC. We assessed hypertension as (i) self-reported and (ii) measured (systolic BP >= 140mmHg or diastolic BP >= 90mmHg or intake of BP lowering medication (BPLM). We used Poisson regression with robust variance estimation to analyse associations of traffic-related exposures with incidence of hypertension, controlling for relevant confounders, and combined the results from individual studies with random-effects meta-analysis. Among 41 072 participants free of self-reported hypertension at baseline, 6207 (15.1%) incident cases occurred within 5-9 years of follow-up. Incidence of self-reported hypertension was positively associated with PM2.5 (relative risk (RR) 1.22 [95%-confidence interval (CI): 1.08; 1.37] per 5 mu g/m(3)) and PM2.5 absorbance (RR 1.13 [95% CI: 1.02; 1.24] per 10(-5) m(-1)). These estimates decreased slightly upon adjustment for road traffic noise. Road traffic noise was weakly positively associated with the incidence of self-reported hypertension. Among 10 896 participants at risk, 3549 new cases of measured hypertension occurred. We found no clear associations with measured hypertension. Conclusion Long-term residential exposures to air pollution and noise are associated with increased incidence of self-reported hypertension.

  • 16. Gimeno-Miguel, Antonio
    et al.
    Gracia Gutiérrez, Anyuli
    Poblador-Plou, Beatriz
    Coscollar-Santaliestra, Carlos
    Ignacio Pérez-Calvo, J.
    Divo, Miguel J.
    Calderón-Larrañaga, Amaia
    Stockholm University, Faculty of Social Sciences, Aging Research Center (ARC), (together with KI).
    Prados-Torres, Alexandra
    Ruiz-Laiglesia, Fernando J.
    Multimorbidity patterns in patients with heart failure: an observational Spanish study based on electronic health records2019In: BMJ Open, E-ISSN 2044-6055, Vol. 9, no 12, article id e033174Article in journal (Refereed)
    Abstract [en]

    Objectives To characterise the comorbidities of heart failure (HF) in men and women, to explore their clustering into multimorbidity patterns, and to measure the impact of such patterns on the risk of hospitalisation and mortality.

    Design Observational retrospective population study based on electronic health records.

    Setting EpiChron Cohort (Aragon, Spain).

    Participants All the primary and hospital care patients of the EpiChron Cohort with a diagnosis of HF on 1 January 2011 (ie, 8488 women and 6182 men). We analysed all the chronic diseases registered in patients electronic health records until 31 December 2011.

    Primary outcome We performed an exploratory factor analysis to identify the multimorbidity patterns in men and women, and logistic and Cox proportional-hazards regressions to investigate the association between the patterns and the risk of hospitalisation in 2012, and of 3-year mortality.

    Results Almost all HF patients (98%) had multimorbidity, with an average of 7.8 chronic diseases per patient. We identified six different multimorbidity patterns, named cardiovascular, neurovascular, coronary, metabolic, degenerative and respiratory. The most prevalent were the degenerative (64.0%) and cardiovascular (29.9%) patterns in women, and the metabolic (49.3%) and cardiovascular (43.2%) patterns in men. Every pattern was associated with higher hospitalisation risks; and the cardiovascular, neurovascular and respiratory patterns significantly increased the likelihood of 3-year mortality.

    Conclusions Multimorbidity is the norm rather than the exception in patients with heart failure, whose comorbidities tend to cluster together beyond simple chance in the form of multimorbidity patterns that have different impact on health outcomes. This knowledge could be useful to better understand common pathophysiological pathways underlying this condition and its comorbidities, and the factors influencing the prognosis of men and women with HF. Further large scale longitudinal studies are encouraged to confirm the existence of these patterns as well as their differential impact on health outcomes.

  • 17.
    Goodman, Anna
    et al.
    Stockholm University, Faculty of Social Sciences, Centre for Health Equity Studies (CHESS). London School of Hygiene and Tropical Medicine, UK.
    Kajantie, Eero
    Osmond, Clive
    Eriksson, Johan
    Koupil, Ilona
    Stockholm University, Faculty of Social Sciences, Centre for Health Equity Studies (CHESS).
    Thornburg, Kent
    Phillips, David IW
    The relationship between umbilical cord length and chronic rheumatic heart disease: a prospective cohort study2015In: European Journal of Preventive Cardiology, ISSN 2047-4873, E-ISSN 2047-4881, Vol. 22, no 9, p. 1154-1160Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: One previous, preliminary study reported that the length of the umbilical cord at birth is related to the risk of developing chronic rheumatic heart disease in later life. We sought to replicate this finding.

    DESIGN: Prospective, population-based birth cohort.

    METHODS: We traced 11,580 individuals born between 1915 and 1929 in Uppsala, Sweden. We identified cases with a main or secondary diagnosis of chronic rheumatic heart disease in the Swedish national inpatient, outpatient or death registers. Archived obstetric records provided data on umbilical cord length, gestational age, birthweight and placental weight.

    RESULTS: There were 136 patients with chronic rheumatic heart disease (72 men and 64 women) with a mean age at first hospital admission of 68 years (range 36-92). There was evidence of a positive association between umbilical cord length and risk of subsequent chronic rheumatic heart disease. The overall hazard ratio in the Swedish study (1.13, 95% confidence interval 1.01 to 1.27) was similar to that of the previous study, with some suggestion of larger effect in men than in women. No other birth characteristics were predictive except for weak evidence of a protective effect of higher birthweight in men.

    CONCLUSIONS: People with longer umbilical cords at birth are more likely to develop chronic rheumatic heart disease in later life. As longer umbilical cords have more spiral arteries and a higher vascular resistance, we hypothesize that the increased pressure load on the heart leads to changes in endothelial biology and increased vulnerability to the autoimmune process initiated by infection with β-haemolytic streptococci.

  • 18. Hantikainen, Essi
    et al.
    Löf, Marie
    Grotta, Alessandra
    Stockholm University, Faculty of Social Sciences, Department of Public Health Sciences. Karolinska Institutet, Sweden.
    Lagerros, Ylva Trolle
    Serafini, Mauro
    Bellocco, Rino
    Weiderpass, Elisabete
    Dietary non-enzymatic antioxidant capacity and risk of stroke: The Swedish Women's Lifestyle and Health Cohort2020In: Nutrition (Burbank, Los Angeles County, Calif.), ISSN 0899-9007, E-ISSN 1873-1244, Vol. 73, article id UNSP 110723Article in journal (Refereed)
    Abstract [en]

    Objective: Consumption of antioxidant-rich foods has been associated with a reduced risk for stroke. However, antioxidant supplementation is not recommended owing to controversial findings reported in clinical trials. The aim of this study was to better understand the effect of dietary antioxidants by investigating the effect of dietary non-enzymatic antioxidant capacity (NEAC), reflecting the antioxidant potential of the whole diet, on the risk for stroke. Methods: In the Women's Lifestyle and Health Cohort, 45 882 women 30 to 49 y of age and free from cardiovascular diseases were followed through record linkages from 1991 to 2012. Dietary NEAC was assessed by a validated food frequency questionnaire collected at baseline and categorized into quintiles. Multivariable Cox proportional hazard regression models were fitted to estimate hazard ratios with 95% confidence intervals for overall stroke and ischemic and hemorrhagic stroke separately. Results: During a mean follow-up time of 20.2 y, we detected 871 incidence cases of stroke (516 ischemic, 296 hemorrhagic, and 59 unspecified strokes). After adjusting for potential confounders, we did not find any association between dietary NEAC and stroke, either overall, or ischemic or hemorrhagic stroke (P-trend > 0.05). Conclusion: Higher dietary NEAC was not associated with any type of stroke in young and middle-aged Swedish women.

  • 19. Hantikainen, Essi
    et al.
    Löf, Marie
    Grotta, Alessandra
    Stockholm University, Faculty of Social Sciences, Centre for Health Equity Studies (CHESS). Karolinska Institutet, Sweden.
    Trolle Lagerros, Ylva
    Serafini, Mauro
    Bellocco, Rino
    Weiderpass, Elisabete
    Dietary non enzymatic antioxidant capacity and the risk of myocardial infarction in the Swedish women's lifestyle and health cohort2018In: European Journal of Epidemiology, ISSN 0393-2990, E-ISSN 1573-7284, Vol. 33, no 2, p. 213-221Article in journal (Refereed)
    Abstract [en]

    Foods rich in antioxidants have been associated with a reduced risk of myocardial infarction. However, findings from randomized clinical trials on the role of antioxidant supplementation remain controversial. It has been suggested that antioxidants interact with each other to promote cardiovascular health. We therefore investigated the association between dietary Non Enzymatic Antioxidant Capacity (NEAC), measuring the total antioxidant potential of the whole diet, and the risk of myocardial infarction. We followed 45,882 women aged 30-49 years and free from cardiovascular diseases through record linkages from 1991 until 2012. Dietary NEAC was assessed by a validated food frequency questionnaire collected at baseline. Total dietary NEAC was categorized into quintiles and multivariable Cox proportional hazard regression models were fitted to estimate hazard ratios (HR) with 95% confidence intervals (CI). During a mean follow-up time of 20.3 years we detected 657 incident cases of myocardial infarction. After adjusting for potential confounders, we found a significant 28% lower risk of myocardial infarction among women in the fourth (HR: 0.72; 95% CI 0.55-0.95) and a 40% lower risk among women in the fifth quintile (HR: 0.60, 95% CI 0.45-0.81) of dietary NEAC compared to women in the first quintile, with a significant trend (p-value < 0.001). Higher dietary NEAC is associated with a lower risk of myocardial infarction in young to middle-aged women. These findings support the hypothesis that dietary antioxidants protect from myocardial infarction and that this effect might be exerted through interactions between antioxidants.

  • 20. Heikkila, Katriina
    et al.
    Pentti, Jaana
    Madsen, Ida E. H.
    Lallukka, Tea
    Virtanen, Marianna
    Stockholm University, Faculty of Social Sciences, Department of Psychology, Stress Research Institute. Finnish Institute of Occupational Health, Finland; University of Uppsala, Sweden.
    Alfredsson, Lars
    Bjorner, Jakob
    Borritz, Marianne
    Brunner, Eric
    Burr, Hermann
    Ferrie, Jane E.
    Knutsson, Anders
    Koskinen, Aki
    Leineweber, Constanze
    Stockholm University, Faculty of Social Sciences, Department of Psychology, Stress Research Institute.
    Hanson, Linda L. Magnusson
    Stockholm University, Faculty of Social Sciences, Department of Psychology, Stress Research Institute.
    Nielsen, Martin L.
    Nyberg, Solja T.
    Oksanen, Tuula
    Pejtersen, Jan H.
    Pietilainen, Olli
    Rahkonen, Ossi
    Rugulies, Reiner
    Singh-Manoux, Archana
    Steptoe, Andrew
    Suominen, Sakari
    Theorell, Tores
    Stockholm University, Faculty of Social Sciences, Department of Psychology, Stress Research Institute.
    Vahtera, Jussi
    Vaananen, Ari
    Westerlund, Hugo
    Stockholm University, Faculty of Social Sciences, Department of Psychology, Stress Research Institute.
    Kivimaki, Mika
    Job Strain as a Risk Factor for Peripheral Artery Disease: A Multi-Cohort Study2020In: Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease, ISSN 2047-9980, E-ISSN 2047-9980, Vol. 9, no 9, article id e013538Article in journal (Refereed)
    Abstract [en]

    Background: Job strain is implicated in many atherosclerotic diseases, but its role in peripheral artery disease (PAD) is unclear. We investigated the association of job strain with hospital records of PAD, using individual-level data from 11 prospective cohort studies from Finland, Sweden, Denmark, and the United Kingdom.

    Methods and Results: Job strain (high demands and low control at work) was self-reported at baseline (1985-2008). PAD records were ascertained from national hospitalization data. We used Cox regression to examine the associations of job strain with PAD in each study, and combined the study-specific estimates in random effects meta-analyses. We used tau(2), I-2, and subgroup analyses to examine heterogeneity. Of the 139 132 participants with no previous hospitalization with PAD, 32 489 (23.4%) reported job strain at baseline. During 1 718 132 person-years at risk (mean follow-up 12.8 years), 667 individuals had a hospital record of PAD (3.88 per 10 000 person-years). Job strain was associated with a 1.41-fold (95% CI, 1.11-1.80) increased average risk of hospitalization with PAD. The study-specific estimates were moderately heterogeneous (tau(2)=0.0427, I-2: 26.9%). Despite variation in their magnitude, the estimates were consistent in both sexes, across the socioeconomic hierarchy and by baseline smoking status. Additional adjustment for baseline diabetes mellitus did not change the direction or magnitude of the observed associations.

    Conclusions: Job strain was associated with small but consistent increase in the risk of hospitalization with PAD, with the relative risks on par with those for coronary heart disease and ischemic stroke.

  • 21. Hunter, Amanda L.
    et al.
    Unosson, Jon
    Bosson, Jenny A.
    Langrish, Jeremy P.
    Pourazar, Jamshid
    Raftis, Jennifer B.
    Miller, Mark R.
    Lucking, Andrew J.
    Boman, Christoffer
    Nyström, Robin
    Donaldson, Kenneth
    Flapan, Andrew D.
    Shah, Anoop SV
    Pung, Louis
    Sadiktsis, Ioannis
    Stockholm University, Faculty of Science, Department of Analytical Chemistry.
    Masala, Silvia
    Stockholm University, Faculty of Science, Department of Analytical Chemistry.
    Westerholm, Roger
    Stockholm University, Faculty of Science, Department of Analytical Chemistry.
    Sandström, Thomas
    Blomberg, Anders
    Newby, David E.
    Mills, Nicholas L.
    Effect of wood smoke exposure on vascular function and thrombus formation in healthy fire fighters2014In: Particle and Fibre Toxicology, E-ISSN 1743-8977, Vol. 11, article id 62Article in journal (Refereed)
    Abstract [en]

    Background

    Myocardial infarction is the leading cause of death in fire fighters and has been linked with exposure to air pollution and fire suppression duties. We therefore investigated the effects of wood smoke exposure on vascular vasomotor and fibrinolytic function, and thrombus formation in healthy fire fighters.

    Methods

    In a double-blind randomized cross-over study, 16 healthy male fire fighters were exposed to wood smoke (~1 mg/m3 particulate matter concentration) or filtered air for one hour during intermittent exercise. Arterial pressure and stiffness were measured before and immediately after exposure, and forearm blood flow was measured during intra-brachial infusion of endothelium-dependent and -independent vasodilators 4–6 hours after exposure. Thrombus formation was assessed using the ex vivo Badimon chamber at 2 hours, and platelet activation was measured using flow cytometry for up to 24 hours after the exposure.

    Results

    Compared to filtered air, exposure to wood smoke increased blood carboxyhaemoglobin concentrations (1.3% versus 0.8%; P < 0.001), but had no effect on arterial pressure,augmentation index or pulse wave velocity (P > 0.05 for all). Whilst there was a dose-dependent increase in forearm blood flow with each vasodilator (P < 0.01 for all), there were no differences in blood flow responses to acetylcholine, sodium nitroprusside or verapamil between exposures (P > 0.05 for all). Following exposure to wood smoke, vasodilatation tobradykinin increased (P = 0.003), but there was no effect on bradykinin-induced tissue-plasminogen activator release, thrombus area or markers of platelet activation (P > 0.05 for all).

    Conclusions

    Wood smoke exposure does not impair vascular vasomotor or fibrinolytic function, or increase thrombus formation in fire fighters. Acute cardiovascular events following firesuppression may be precipitated by exposure to other air pollutants or through other mechanisms, such as strenuous physical exertion and dehydration.

  • 22.
    Imahori, Yume
    et al.
    Stockholm University, Faculty of Social Sciences, Aging Research Center (ARC), (together with KI).
    Vetrano, Davide L.
    Stockholm University, Faculty of Social Sciences, Aging Research Center (ARC), (together with KI). Stockholm Gerontology Research Center, Sweden.
    Ljungman, Petter
    Laukka, Erika J.
    Stockholm University, Faculty of Social Sciences, Aging Research Center (ARC), (together with KI). Stockholm Gerontology Research Center, Sweden.
    Wu, Jing
    Stockholm University, Faculty of Social Sciences, Aging Research Center (ARC), (together with KI).
    Grande, Giulia
    Stockholm University, Faculty of Social Sciences, Aging Research Center (ARC), (together with KI).
    Rizzuto, Debora
    Stockholm University, Faculty of Social Sciences, Aging Research Center (ARC), (together with KI). Stockholm Gerontology Research Center, Sweden.
    Fratiglioni, Laura
    Stockholm University, Faculty of Social Sciences, Aging Research Center (ARC), (together with KI). Stockholm Gerontology Research Center, Sweden.
    Qiu, Chengxuan
    Stockholm University, Faculty of Social Sciences, Aging Research Center (ARC), (together with KI).
    Association of ischemic heart disease with long-term risk of cognitive decline and dementia: A cohort study2023In: Alzheimer's & Dementia: Journal of the Alzheimer's Association, ISSN 1552-5260, E-ISSN 1552-5279, Vol. 19, no 12, p. 5541-5549Article in journal (Refereed)
    Abstract [en]

    INTRODUCTION: The independent and joint effect of ischemic heart disease (IHD) and coexisting atrial fibrillation (AF) and heart failure (HF) on dementia risk is largely unknown.

    METHODS: This population-based cohort study included 2568 dementia-free participants (age ≥60 years) in SNAC-K, who were regularly examined from 2001–2004 through 2013–2016. Dementia was diagnosed following the Diagnostic and Statistical Manual of Mental Disorders, 4th edition (DSM-IV) criteria. Global cognitive function was assessed using a global cognitive composite z-score derived from five cognitive domains. Data were analyzed using Cox, Fine-Gray, and linear mixed-effects models.

    RESULTS: Overall, IHD at baseline was associated with multivariable-adjusted hazard ratio (HR) of 1.39 (95% confidence interval = 1.06−1.82) for dementia and multivariable-adjusted β-coefficient of −0.02 (−0.03 to −0.01) for annual changes in global cognitive z-score, independent of AF, HF, and cerebrovascular disease. Coexisting AF or HF did not add further risk to dementia and cognitive decline.

    DISCUSSION: IHD is independently associated with dementia and cognitive decline in older adults, whereas coexisting AF/HF is not associated with an increased risk.

  • 23.
    Imahori, Yume
    et al.
    Stockholm University, Faculty of Social Sciences, Aging Research Center (ARC), (together with KI).
    Vetrano, Davide L.
    Stockholm University, Faculty of Social Sciences, Aging Research Center (ARC), (together with KI). Fondazione Policlinico “A-Gemelli” IRCCS, Italy; Catholic University of Rome, Italy.
    Ljungman, Petter
    Qiu, Chengxuan
    Stockholm University, Faculty of Social Sciences, Aging Research Center (ARC), (together with KI).
    Electrocardiographic Predictors of Cognitive Decline and Dementia: A Systematic Review2021In: Journal of Alzheimer's Disease, ISSN 1387-2877, E-ISSN 1875-8908, Vol. 84, no 3, p. 1303-1322Article, review/survey (Refereed)
    Abstract [en]

    Background: Markers of altered cardiac function might predict cognitive decline and dementia. Objective: This systematic review aims to review the literature that examines the associations of various electrocardiogram (ECG) markers with cognitive decline and dementia in middle-aged and elderly populations. Methods: We searched PubMed, Embase, and Web of Science through 1 July 2020 for literature and conducted a systematic literature review. We included studies examining the associations of ECG markers (e.g., left ventricular hypertrophy [LVH], spatial QRS-T angle, and QT prolongation) with cognitive function and dementia in adult populations regardless of study setting and design, but excluded studies examining atrial fibrillation and heart rate variability. Results: Fourteen community-based cross-sectional and longitudinal studies were identified. ECG markers were investigated in association with dementia in four prospective studies, and with cognitive decline in ten prospective studies. ECG-assessed LVH was associated with dementia in one study while five heterogeneous prospective studies yielded inconsistent associations with cognitive decline. Regarding ventricular repolarization markers, spatial QRS-T angle was associated with cognitive decline in one study while another study found no association between QT prolongation and cognitive decline. High resting heart rate was associated with both dementia and cognitive decline in one study but not associated with dementia in another study. P-wave abnormality was significantly associated with incident dementia and cognitive decline in one prospective study. Conclusion: Some ECG markers were associated with incident dementia and cognitive decline. However, limited number of heterogeneous studies did not allow us to make firm conclusions. Further studies are needed.

  • 24.
    Imahori, Yume
    et al.
    Stockholm University, Faculty of Social Sciences, Aging Research Center (ARC), (together with KI).
    Vetrano, Davide L.
    Stockholm University, Faculty of Social Sciences, Aging Research Center (ARC), (together with KI). Catholic University of Rome, Italy; Centro Medicina dell’Invecchiamento, Fondazione Policlinico “A- Gemelli” IRCCS, Italy.
    Xia, Xin
    Stockholm University, Faculty of Social Sciences, Aging Research Center (ARC), (together with KI).
    Grande, Giulia
    Stockholm University, Faculty of Social Sciences, Aging Research Center (ARC), (together with KI).
    Ljungman, Petter
    Fratiglioni, Laura
    Stockholm University, Faculty of Social Sciences, Aging Research Center (ARC), (together with KI). Stockholm Gerontology Research Center, Sweden.
    Qiu, Chengxuan
    Stockholm University, Faculty of Social Sciences, Aging Research Center (ARC), (together with KI).
    Association of resting heart rate with cognitive decline and dementia in older adults: A population-based cohort study2022In: Alzheimer's & Dementia: Journal of the Alzheimer's Association, ISSN 1552-5260, E-ISSN 1552-5279, Vol. 18, no 10, p. 1779-1787Article in journal (Refereed)
    Abstract [en]

    Introduction: Resting heart rate (RHR) predicts future risk for cardiovascular disease (CVD). However, longitudinal studies investigating the relationship of RHR with cognitive decline are scarce.

    Methods: This population-based cohort study included 2147 participants (age≥60) in SNAC-K who were free of dementia and regularly followed from 2001–2004 to 2013–2016. RHR was assessed with electrocardiogram. Dementia was diagnosed following the Diagnostic and Statistical Manual of Mental Disorders 4th Revision criteria. Global cognitive function was assessed using Mini-Mental State Examination (MMSE). Data were analyzed using Cox and linear mixed-effects models.

    Results: RHR≥80 (vs. 60–69) bpm was associated with a multi-adjusted hazard ratio of 1.55 (95% confidence interval 1.06−2.27) for dementia. The association remained significant after excluding participants with prevalent and incident CVDs. Similarly, RHR≥80 bpm was associated with a multi-adjusted β-coefficient of –0.13 (–0.21 to –0.04) for MMSE score.

    Discussion: Higher RHR is associated with increased risk for dementia and faster cognitive decline independent of CVDs in a general population of elderly people.

  • 25. Jonsson, Martin
    et al.
    Ljungman, Petter
    Härkönen, Juho
    Stockholm University, Faculty of Social Sciences, Department of Sociology. European University Institute, Italy.
    Van Nieuwenhuizen, Ben
    Møller, Sidsel
    Ringh, Mattias
    Nordberg, Per
    Relationship between socioeconomic status and incidence of out-of-hospital cardiac arrest is dependent on age2020In: Journal of Epidemiology and Community Health, ISSN 0143-005X, E-ISSN 1470-2738, Vol. 74, no 9, p. 726-731Article in journal (Refereed)
    Abstract [en]

    Background The association between socioeconomic  status (SES) and incidence of out-of-hospital cardiac arrest  (OHCA) is not fully understood. The aim of this study was  to see if area-level socioeconomic differences, measured  in terms of area-level income and education, are  associated with the incidence of OHCA, and if this  relationship is dependent on age. 

    Methods We included OHCAs that occurred in  Stockholm County between the 1st of January 2006 and  the 31st of December 2017, the victims being confirmed  residents (n=10 574). We linked the home address to  a matching neighbourhood (base unit) via available  socioeconomic and demographic information.  Socioeconomic variables and incidence rates were  assessed by using cross-sectional values at the end of  each year. We used zero-inflated negative binomial  regression to calculate incidence rate ratios (IRRs). 

    Results Among 1349 areas with complete SES  information, 10 503 OHCAs occurred between 2006 and  2017. The IRR in the highest versus the lowest SES area  was 0.61 (0.50–0.75) among persons in the 0–44 age  group. Among patients in the 45–64 age group, the  corresponding IRR was 0.55 (0.47–0.65). The highest SES  areas versus the lowest showed an IRR of 0.59  (0.50–0.70) in the 65–74 age group. In the two highest  age groups, no significant association was seen (75–84  age group: 0.93 (0.80–1.08); 85+ age group: 1.05  (0.84–1.23)). Similar crude patterns were seen among  both men and women. 

    Conclusions Areas characterised by high SES showed  a significantly lower incidence of OHCA. This relationship  was seen up to the age of 75, after which the relationship  disappeared, suggesting a levelling effect. 

  • 26. Journath, Gunilla
    et al.
    Hammar, Niklas
    Elofsson, Stig
    Stockholm University, Faculty of Social Sciences, Department of Social Work.
    Linnersjö, Anette
    Vikström, Max
    Walldius, Göran
    Krakau, Ingvar
    Lindgren, Peter
    de Faire, Ulf
    Hellenius, Mai-Lis
    Time Trends in Incidence and Mortality of Acute Myocardial Infarction, and All-Cause Mortality following a Cardiovascular Prevention Program in Sweden2015In: PLOS ONE, E-ISSN 1932-6203, Vol. 10, no 11, article id e0140201Article in journal (Refereed)
    Abstract [en]

    Background In 1988, a cardiovascular prevention program which combined an individual and a population-based strategy was launched within primary health-care in Sollentuna, a municipality in Stockholm County. The aim of this study was to investigate time trends in the incidence of and mortality from acute myocardial infarction and all-cause mortality in Sollentuna compared with the rest of Stockholm County during a period of two decades following the implementation of a cardiovascular prevention program. Materials and Methods The average population in Sollentuna was 56,589 (49% men) and in Stockholm County (Sollentuna included) 1,795,504 (49% men) during the study period of 1987-2010. Cases of hospitalized acute myocardial infarction and death were obtained for the population of Sollentuna and the rest of Stockholm County using national registries of hospital discharges and deaths. Acute myocardial infarction incidence and mortality were estimated using the average population of Sollentuna and Stockholm in 1987-2010. Results During the observation period, the incidence of acute myocardial infarction decreased more in Sollentuna compared with the rest of Stockholm County in women (-22% vs. -7%; for difference in slope <0.05). There was a trend towards a greater decline in Sollentuna compared to the rest of Stockholm County in the incidence of acute myocardial infarction (in men), acute myocardial mortality, and all-cause mortality but the differences were not significant. Conclusion During a period of steep decline in acute myocardial infarction incidence and mortality in Stockholm County the municipality of Sollentuna showed a stronger trend in women possibly compatible with favorable influence of a cardiovascular prevention program.

  • 27. Kerry, Miriam
    et al.
    Bell, J. Simon
    Keen, Claire
    Sluggett, Janet K.
    Ilomäki, Jenni
    Jokanovic, Natali
    Cooper, Tina
    Robson, Leonie
    Tan, Edwin C. K.
    Stockholm University, Faculty of Social Sciences, Aging Research Center (ARC), (together with KI). Monash University, Australia; The University of Sydney, Australia.
    Multiple antihypertensive use and risk of mortality in residents of aged care services: a prospective cohort study2020In: Aging Clinical and Experimental Research, ISSN 1594-0667, E-ISSN 1720-8319, Vol. 32, no 8, p. 1541-1549Article in journal (Refereed)
    Abstract [en]

    Aims The objective of this study is to investigate the association between multiple antihypertensive use and mortality in residents with diagnosed hypertension, and whether dementia and frailty modify this association.

    Methods This is a two-year prospective cohort study of 239 residents with diagnosed hypertension receiving antihypertensive therapy across six residential aged care services in South Australia. Data were obtained from electronic medical records, medication charts and validated assessments. The primary outcome was all-cause mortality and the secondary outcome was cardiovascular-related hospitalizations. Inverse probability weighted Cox models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for all-cause mortality. Covariates included age, sex, dementia severity, frailty status, Charlson's comorbidity index and cardiovascular comorbidities.

    Results The study sample (mean age of 88.1 +/- 6.3 years; 79% female) included 70 (29.3%) residents using one antihypertensive and 169 (70.7%) residents using multiple antihypertensives. The crude incidence rates for death were higher in residents using multiple antihypertensives compared with residents using monotherapy (251 and 173/1000 person-years, respectively). After weighting, residents who used multiple antihypertensives had a greater risk of mortality compared with monotherapy (HR 1.40, 95%CI 1.03-1.92). After stratifying by dementia diagnosis and frailty status, the risk only remained significant in residents with diagnosed dementia (HR 1.91, 95%CI 1.20-3.04) and who were most frail (HR 2.52, 95%CI 1.13-5.64). Rate of cardiovascular-related hospitalizations did not differ among residents using multiple compared to monotherapy (rate ratio 0.73, 95%CI 0.32-1.67).

    Conclusions Multiple antihypertensive use is associated with an increased risk of mortality in residents with diagnosed hypertension, particularly in residents with dementia and among those who are most frail.

  • 28.
    Kjellqvist, Sanela
    et al.
    Stockholm University, Faculty of Science, Department of Biochemistry and Biophysics. Stockholm University, Science for Life Laboratory (SciLifeLab).
    Klose, Christian
    Surma, Michal A.
    Hindy, George
    Mollet, Ines G.
    Johansson, Anna
    Stockholm University, Faculty of Science, Department of Biochemistry and Biophysics. Stockholm University, Science for Life Laboratory (SciLifeLab).
    Chavaux, Patrick
    Gottfries, Johan
    Simons, Kai
    Melander, Olle
    Fernandez, Celine
    Identification of Shared and Unique Serum Lipid Profiles in Diabetes Mellitus and Myocardial Infarction2016In: Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease, ISSN 2047-9980, E-ISSN 2047-9980, Vol. 5, no 12, article id e004503Article in journal (Refereed)
    Abstract [en]

    Background-Diabetes mellitus (DM) and cardiovascular disease are associated with dyslipidemia, but the detailed lipid molecular pattern in both diseases remains unknown. Methods and Results-We used shotgun mass spectrometry to determine serum levels of 255 molecular lipids in 316 controls, 171 DM, and 99 myocardial infarction (MI) events from a cohort derived from the Malmo Diet and Cancer study. Orthogonal projections to latent structures analyses were conducted between the lipids and clinical parameters describing DM or MI. Fatty acid desaturases (FADS) and elongation of very long chain fatty acid protein 5 (ELOVL5) activities were estimated by calculating product to precursor ratios of polyunsaturated fatty acids in complex lipids. FADS genotypes encoding these desaturases were then tested for association with lipid levels and ratios. Differences in the levels of lipids belonging to the phosphatidylcholine and triacylglyceride (TAG) classes contributed the most to separating DM from controls. TAGs also played a dominating role in discriminating MI from controls. Levels of C18:2 fatty acids in complex lipids were lower both in DM and MI versus controls (DM, P=0.004; MI, P=6.0E-06) at least due to an acceleration in the metabolic flux from C18: 2 to C20:4 (eg, increased estimated ELOVL5: DM, P=0.02; MI, P=0.04, and combined elongase-desaturase activities: DM, P=3.0E-06; MI, P=2.0E-06). Minor allele carriers of FADS genotypes were associated with increased levels of C18: 2 (P <= 0.007) and lower desaturase activity (P <= 0.002). Conclusions-We demonstrate a possible relationship between decreased levels of C18: 2 in complex lipids and DM or MI. We thereby highlight the importance of molecular lipids in the pathogenesis of both diseases.

  • 29. Lagerros, Ylva Trolle
    et al.
    Grotta, Alessandra
    Stockholm University, Faculty of Social Sciences, Department of Public Health Sciences, Centre for Health Equity Studies (CHESS).
    Freyland, Sara
    Grannas, David
    Andersson, Daniel Peter
    Risk of Death in Patients With Coronary Artery Disease Taking Nitrates and Phosphodiesterase-5 Inhibitors2024In: Journal of the American College of Cardiology, ISSN 0735-1097, E-ISSN 1558-3597, Vol. 83, no 3, p. 417-426Article in journal (Refereed)
    Abstract [en]

    BACKGROUND Phosphodiesterase-5 inhibitor (PDE5i) treatment for erectile dysfunction is associated with lower mortality compared with no treatment for erectile dysfunction after myocardial infarction (MI). There are conflicting results regarding the impact of PDE5i treatment on mortality in conjunction with nitrate medication. OBJECTIVES The purpose of this study was to investigate the association between PDE5i treatment and cardiovascular outcomes in men with stable coronary artery disease treated with nitrate medication. METHODS Using the Swedish Patient Register and the Prescribed Drug Register we included men with previous MI or revascularization in 2006-2013 who had 2 dispensed nitrate prescriptions within 6 months. Exposure was defined as at least 2 filled prescriptions of any PDE5i. We performed multivariable Cox proportional hazard regression to estimate HRs with 95% CIs for all -cause, cardiovascular, and noncardiovascular mortality, MI, heart failure, cardiac revascularization, and major cardiovascular events (MACE). RESULTS In total, 55,777 men were treated with nitrates and 5,710 men with nitrates and a PDE5i. The combined use of PDE5i treatment with nitrates was associated with higher mortality (HR: 1.39; 95% CI: 1.28-1.51), cardiovascular mortality (HR: 1.34; 95% CI: 1.11-1.62), noncardiovascular mortality (HR: 1.40; 95% CI: 1.27-1.54), MI (HR: 1.72; 95% CI: 1.55-1.90), heart failure (HR: 1.67; 95% CI: 1.48-1.90), cardiac revascularization (HR: 1.95; 95% CI: 1.78-2.13), and MACE (HR: 1.70; 95% CI: 1.58-1.83). CONCLUSIONS The use of a PDE5i in combination with nitrate medication in men with stable coronary artery disease may pose an increased hazard for cardiovascular morbidity and mortality. Careful patient -centered consideration before prescribing PDE5is to patients with cardiovascular disease using nitrate medication is warranted. (J Am Coll Cardiol 2024;83:417-426) (c) 2024 The Authors. Published by Elsevier on behalf of the American College of Cardiology Foundation. This is an open access article under the CC BY -NC -ND license (http://creativecommons.org/licenses/by-nc-nd/ 4.0/).

  • 30. L'Angiocola, Paolo Diego
    et al.
    Vetrano, Davide Liborio
    Stockholm University, Faculty of Social Sciences, Aging Research Center (ARC), (together with KI).
    Lardieri, Gerardina
    From bicuspid to quadricuspid aortic valve: The clinical case of a 38-year-old woman with chest pain2019In: Journal of Cardiovascular Echography, ISSN 2211-4122, Vol. 29, no 3, p. 119-122Article in journal (Refereed)
    Abstract [en]

    We report a case of a 38-year-old woman with an alleged diagnosis of bicuspid aortic valve disease that was correctly identified as quadricuspid aortic valve (QAV) disease in our cardiology unit. In this case report, we focus on echocardiographic features of this rare congenital valve disease aiming to provide useful tips to achieve correct differential diagnosis according to the updated echocardiographic international guidelines and recommendations, briefly reviewing other QAV cases reported in the current literature as well. In conclusion, we strongly recommend adhering to practical echocardiographic guidelines to reduce interobserver variability, not to miss the diagnosis of rare congenital defects like the one we reported.

  • 31.
    Liang, Yajun
    et al.
    Stockholm University, Faculty of Social Sciences, Aging Research Center (ARC), (together with KI).
    Vetrano, Davide Liborio
    Stockholm University, Faculty of Social Sciences, Aging Research Center (ARC), (together with KI).
    Qiu, Chengxuan
    Stockholm University, Faculty of Social Sciences, Aging Research Center (ARC), (together with KI).
    The role of biological age in the management of hypertension in old age: Does SPRINT tell the whole story?2016In: International Journal of Cardiology, ISSN 0167-5273, E-ISSN 1874-1754, Vol. 222, p. 699-700Article in journal (Other academic)
  • 32. Liperoti, Rosa
    et al.
    Vetrano, Davide L.
    Stockholm University, Faculty of Social Sciences, Aging Research Center (ARC), (together with KI). Università Cattolica del Sacro Cuore, Italy.
    Bernabei, Roberto
    Onder, Graziano
    Herbal Medications in Cardiovascular Medicine2017In: Journal of the American College of Cardiology, ISSN 0735-1097, E-ISSN 1558-3597, Vol. 69, no 9, p. 1188-1199Article in journal (Refereed)
    Abstract [en]

    Herbal medications are commonly used for clinical purposes, including the treatment of cardiovascular conditions. Compared with conventional medications, herbal medications do not require clinical studies before their marketing or formal approval from regulatory agencies, and for this reason their efficacy and safety are rarely proven. In this review, we summarize available evidence on herbal medications mostly used in cardiovascular medicine. We show that the use of these medications for the treatment of cardiovascular diseases is often not supported by scientific evidence. Despite most of these herbs showing an effect on biological mechanisms related to the cardiovascular system, data on their clinical effects are lacking. Potential relevant side effects, including increased risk of drug interactions, are described, and the possibility of contamination or substitution with other medications represents a concern. Physicians should always assess the use of herbal medications with patients and discuss the possible benefits and side effects with them.

  • 33. Liperoti, Rosa
    et al.
    Vetrano, Davide L.
    Stockholm University, Faculty of Social Sciences, Aging Research Center (ARC), (together with KI).
    Palmer, Katie
    Targowski, Tomasz
    Cipriani, Maria C.
    Lo Monaco, Maria R.
    Giovannini, Silvia
    Acampora, Nicola
    Villani, Emanuele Rocco
    Bernabei, Roberto
    Onder, Graziano
    Association between frailty and ischemic heart disease: a systematic review and meta-analysis2021In: BMC Geriatrics, ISSN 1471-2318, E-ISSN 1471-2318, Vol. 21, no 1, article id 357Article, review/survey (Refereed)
    Abstract [en]

    Background: Frailty is increasingly reported among older adults with cardiovascular diseases and it has been demonstrated to increase negative health outcomes and mortality. To date, no systematic review of the evidence is available regarding the association between frailty and ischemic heart disease (IHD). We performed a systematic review of literature and a meta-analysis to assess the association between frailty and IHD.

    Methods: We selected all the studies that provided information on the association between frailty and IHD, regardless of the study setting, study design, or definition of IHD and frailty. PubMed, Web of Science and Embase were searched for relevant papers. Studies that adopted the Fried definition for frailty were included in the meta-analyses. For each measure of interest (proportions and estimates of associations), a meta-analysis was performed if at least three studies used the same definition of frailty. Pooled estimates were obtained through random effect models and Mantel-Haenszel weighting.

    Results: Thirty-seven studies were included. Of these, 22 adopted the Fried criteria to define frailty and provided estimates of prevalence and therefore they were included in meta-analyses. The pooled prevalence of IHD in frail individuals was 17% (95% Confidence Interval [95%CI] 11-23%) and the pooled prevalence of frailty in individuals with IHD was 19% (95% CI 15-24%). The prevalence of frailty among IHD patients ranged from 4 to 61%. Insufficient data were found to assess longitudinal association between frailty and IHD.

    Conclusions: Frailty is quite common in older persons with IHD. The identification of frailty among older adults with IHD should be considered relevant to provide individualized strategies of cardiovascular prevention and care. Further research should specifically explore the association between frailty and IHD and investigate the potential common biological ground.

  • 34. Ljung Faxen, Ulrika
    et al.
    Hage, Camilla
    Andreasson, Anna
    Stockholm University, Faculty of Social Sciences, Stress Research Institute. Karolinska Institutet, Sweden.
    Donal, Erwan
    Daubert, Jean-Claude
    Linde, Cecilia
    Brismar, Kerstin
    Lund, Lars H.
    HFpEF and HFrEF exhibit different phenotypes as assessed by leptin and adiponectin2017In: International Journal of Cardiology, ISSN 0167-5273, E-ISSN 1874-1754, Vol. 228, p. 709-716Article in journal (Refereed)
    Abstract [en]

    Background: Heart failure with reduced ejection fraction (HFrEF) exhibits a reverse metabolic profile. Whether this profile exists in HF with preserved ejection fraction (HFpEF) is unknown. We tested the hypothesis that HFpEF and HFrEF are similar regarding concentrations of and prognostic impact of leptin and adiponectin.

    Methods: In patients with HFpEF(n = 79), HFrEF(n = 84), and controls(n = 71), we analyzed serum leptin and adiponectin concentrations, their correlations, and associations with outcome.

    Results: Leptin levels in HFpEF and HFrEF were increased (p < 0.05) compared to controls; with the highest levels in HFpEF, median (IQR), 23.1 (10.2-51.0), vs. HFrEF 15.0 (6.2-33.2), and vs. controls 10.8 (5.4-18.9) ng/mL. There was no difference between HFpEF and HFrEF p=0.125 (adjusted for gender, BMI and age). Leptin was inversely associated with NT-proBNP (r = -0.364 p = 0.001) and associated with better outcome in HFrEF (HR per ln increase of leptin 0.76, 95% CI 0.58-0.99, p = 0.044) but not in HFpEF.

    Crude levels of adiponectin were similar in HFpEF: 11.8 (7.9-20.1), HFrEF: 13.7 (7.0-21.1), and controls: 10.5 (7.4-15.1) mu g/L. In men, adjusted similarly as leptin, there was no difference between HFpEF and HFrEF, p = 0.310 but, compared to controls, higher levels in HFpEF (p - 0.044) and HFrEF (p - 0.001). Adiponectin correlated positively with NT-proBNP; r = 0.396 p < 0.001 and higher levels were associated with adverse outcome only in HFrEF (HR per ln increase 2.88 (95% CI 1.02-8.14, p = 0.045).

    Conclusion: HFpEF and HFrEF share elevated levels of leptin and adiponectin. However, the concept of reverse metabolic profile could not be confirmed in HFpEF, suggesting that HFpEF might have a conventional metabolic profile, rather than a distinct HF syndrome.

  • 35. Ljung Faxén, Ulrika
    et al.
    Hage, Camilla
    Benson, Lina
    Zabarovskaja, Stanislava
    Andreasson, Anna
    Stockholm University, Faculty of Social Sciences, Stress Research Institute. Karolinska institutet, Sweden.
    Donal, Erwan
    Daubert, Jean-Claude
    Linde, Cecilia
    Brismar, Kerstin
    Lund, Lars H.
    HFpEF and HFrEF Display Different Phenotypes as Assessed by IGF-1 and IGFBP-12017In: Journal of Cardiac Failure, ISSN 1071-9164, E-ISSN 1532-8414, Vol. 23, no 4, p. 293-303Article in journal (Refereed)
    Abstract [en]

    Background

    Anabolic drive is impaired in heart failure with reduced ejection fraction (HFrEF) but insufficiently studied in heart failure with preserved ejection fraction (HFpEF). Insulin-like growth factor 1 (IGF-1) mediates growth hormone effects and IGF binding protein 1 (IGFBP-1) regulates IGF-1 activity. We tested the hypothesis that HFpEF and HFrEF are similar with regard to IGF-1 and IGFBP-1.

    Methods and Results

    In patients with HFpEF (n = 79), HFrEF (n = 85), and controls (n = 136), we analyzed serum IGF-1 and IGFBP-1 concentrations, correlations, and associations with outcome. Age-standardized scores of IGF-1 were higher in HFpEF, median arbitrary units (interquartile range); 1.21 (0.57–1.96) vs HFrEF, 0.09 (-1.40–1.62), and controls, 0.22 (-0.47-0.96), P overall <.001. IGFBP-1 was increased in HFpEF, 48 (28–79), and HFrEF, 65 (29–101), vs controls, 27(14–35) µg/L, P overall <.001. These patterns persisted after adjusting for metabolic and HF severity confounders. IGF-1 was associated with outcomes in HFrEF, hazard ratio per natural logarithmic increase in IGF-1 SD score 0.51 (95% confidence interval 0.32–0.82, P = .005), but not significantly in HFpEF. IGFBP-1 was not associated with outcomes in either HFpEF nor HFrEF.

    Conclusion

    HFpEF and HFrEF phenotypes were similar with regard to increased IGFBP-1 concentrations but differed regarding IGF-1 levels and prognostic role. HFrEF and HFpEF may display different impairment in anabolic drive.

  • 36. Lv, Yaodong
    et al.
    Ma, Xiaotong
    Zhao, Weihua
    Ju, Jiachen
    Yan, Peng
    Li, Shan
    Xue, Yuan
    Sui, Yanling
    Shao, Sai
    Sun, Qinjian
    Qiu, Chengxuan
    Stockholm University, Faculty of Social Sciences, Aging Research Center (ARC), (together with KI). Shandong University, Jinan, Shandong, China.
    Association of plaque characteristics with long-term stroke recurrence in patients with intracranial atherosclerotic disease: a 3D high-resolution MRI-based cohort study2023In: European Radiology, ISSN 0938-7994, E-ISSN 1432-1084Article in journal (Refereed)
    Abstract [en]

    Objectives To evaluate the predictive ability of plaque characteristics for long-term stroke recurrence among patients with symptomatic intracranial atherosclerotic disease (ICAD).Methods This cohort study included 132 patients with acute ischemic stroke (AIS) attributed to ICAD who were recruited between July 2017 and December 2020 and followed until stroke recurrence or December 2021. Plaque surface irregularity, degree of stenosis, plaque burden, remodeling ratio, enhancement ratio, and intraplaque hemorrhage were assessed with 3-dimensional high-resolution magnetic resonance vessel wall imaging (3D HR-MRI). Data were analyzed using Cox models, receiver operating characteristic (ROC) curves, and Kaplan-Meier survival analysis.Results Of the 132 patients, during a median follow-up of 2.8 years, stroke recurrence occurred in 35 patients. The multivariable-adjusted hazard ratio (95% confidence interval) of stroke recurrence was 3.15 (1.34-7.42) per 10% increase in plaque burden and 2.17 (1.27-3.70) for enhancement ratio. The area under the curve (AUC) to predict stroke recurrence was 0.725 (95% CI 0.629-0.822) for plaque burden, 0.692 (95% CI 0.593-0.792) for enhancement ratio, and only 0.595 (95% CI 0.492-0.699) for the Essen stroke risk score. The Kaplan-Meier survival analysis further demonstrated significant differences in survival of free recurrent stroke between patients with plaque burden or enhancement ratio below and above the optimum cut-offs (both p < 0.001).Conclusion Higher plaque burden and enhancement ratio are independent risk factors for long-term stroke recurrence among patients with symptomatic ICAD, and valuable imaging markers for predicting and stratifying risk of stroke recurrence.

  • 37. Ma, Xiaotong
    et al.
    Wang, Qiuting
    Hu, Xinyan
    Wang, Xiang
    Zhao, Yuanyuan
    Liu, Xiaohui
    Li, Jifeng
    Du, Yifeng
    Wang, Mo
    Qiu, Chengxuan
    Stockholm University, Faculty of Social Sciences, Aging Research Center (ARC), (together with KI). Shandong University, People’s Republic of China.
    Sun, Qinjian
    Association of sdLDL-C With Incident Carotid Plaques With Stable and Vulnerable Morphology: A Prospective Cohort Study2024In: Stroke, ISSN 0039-2499, E-ISSN 1524-4628, Vol. 55, no 3, p. 576-585Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Small dense low-density lipoprotein cholesterol (sdLDL-C) particles are more atherogenic than large and intermediate low-density lipoprotein cholesterol (LDL-C) subfractions. We sought to investigate the association of sdLDL-C and the sdLDL-C/LDL-C ratio with incident carotid plaques with stable and vulnerable morphology in rural China.

    METHODS: This community-based cohort study used data from the RICAS study (Rose Asymptomatic Intracranial Artery Stenosis), which enrolled 887 participants (aged ≥40 years) who were living in Kongcun Town, Pingyin County, Shandong, and free of carotid plaques and had no history of clinical stroke or transient ischemic attack at baseline (2017). Incident carotid plaques and their vulnerability were detected by carotid ultrasound at follow-up (2021). Multivariable logistic regression models were used to explore the association of sdLDL-C or sdLDL-C/LDL-C ratio with incident carotid plaques while adjusting for demographic factors, vascular risk factors, and follow-up time.

    RESULTS: Of the 887 participants (mean age [SD], 53.89 [8.67%] years; 54.34% women), 179 (20.18%) were detected with incident carotid plaques during an average follow-up of 3.94 years (SD=0.14). Higher sdLDL-C or sdLDL-C/LDL-C ratio, but not LDL-C, was significantly associated with an increased risk of incident carotid plaques. The upper tertile of sdLDL-C (versus lower tertile) was associated with the multivariate-adjusted odds ratio of 2.48 (95% CI, 1.00–6.15; P=0.049; P for linear trend=0.046) for carotid plaques with vulnerable morphology (n=41), and the association remained significant in participants with normal LDL-C (<130 mg/dL; n=693; upper versus lower tertile: odds ratio, 3.38 [95% CI, 1.15–9.90]; P=0.027; P for linear trend=0.025). Moreover, the sdLDL-C/LDL-C ratio was associated with a higher odds ratio of incident carotid plaques in participants without diabetes (P for interaction=0.014).

    CONCLUSIONS: Higher sdLDL-C was associated with an increased risk of incident carotid plaques, especially carotid plaques with vulnerable morphology, even in participants with normal LDL-C. This suggests the potential of sdLDL-C as a therapeutic target for stroke prevention.

  • 38. Maleki, Shohreh
    et al.
    Kjellqvist, Sanela
    Stockholm University, Faculty of Science, Department of Biochemistry and Biophysics. Stockholm University, Science for Life Laboratory (SciLifeLab).
    Paloschi, Valentina
    Magné, Joelle
    Branca, Rui Miguel Mamede
    Du, Lei
    Hultenby, Kjell
    Petrini, Johan
    Fuxe, Jonas
    Lehtiö, Janne
    Franco-Cereceda, Anders
    Eriksson, Per
    Björck, Hanna M.
    Mesenchymal state of intimal cells may explain higher propensity to ascending aortic aneurysm in bicuspid aortic valves2016In: Scientific Reports, E-ISSN 2045-2322, Vol. 6, article id 35712Article in journal (Refereed)
    Abstract [en]

    Individuals with a bicuspid aortic valve (BAV) are at significantly higher risk of developing aortic complications than individuals with tricuspid aortic valves (TAV) and defective signaling during the embryonic development and/or life time exposure to abnormal hemodynamic have been proposed as underlying factors. However, an explanation for the molecular mechanisms of aortopathy in BAV has not yet been provided. We combined proteomics, RNA analyses, immunohistochemistry, and electron microscopy to identify molecular differences in samples of non-dilated ascending aortas from BAV (N = 62) and TAV (N = 54) patients. Proteomic analysis was also performed for dilated aortas (N = 6 BAV and N = 5 TAV) to gain further insight into the aortopathy of BAV. Our results collectively showed the molecular signature of an endothelial/epithelial-mesenchymal (EndMT/EMT) transition-like process, associated with instability of intimal cell junctions and activation of RHOA pathway in the intima and media layers of ascending aorta in BAV patients. We propose that an improper regulation of EndMT/EMT during the spatiotemporally related embryogenesis of semilunar valves and ascending aorta in BAV individuals may result in aortic immaturity and instability prior to dilation. Exasperation of EndMT/EMT state in post embryonic life and/or exposure to non-physiological hemodynamic could lead to the aneurysm of ascending aorta in BAV individuals.

  • 39. Malki, Ninoa
    et al.
    Hägg, Sara
    Tiikkaja, Sanna
    Koupil, Ilona
    Stockholm University, Faculty of Social Sciences, Centre for Health Equity Studies (CHESS).
    Sparén, Pär
    Ploner, Alexander
    Short-term and long-term case-fatality rates for myocardial infarction and ischaemic stroke by socioeconomic position and sex: a population-based cohort study in Sweden, 1990-1994 and 2005-20092019In: BMJ Open, E-ISSN 2044-6055, Vol. 9, no 7, article id e026192Article in journal (Refereed)
    Abstract [en]

    Objective Case-fatality rates (CFRs) for myocardial infarction (MI) and ischaemic stroke (IS) have decreased over time due to better prevention, medication and hospital care. It is unclear whether these improvements have been equally distributed according to socioeconomic position (SEP) and sex. The aim of this study is to analyse differences in short-term and long-term CFR for MI and IS by SEP and sex between the periods 1990-1994 to 2005-2009 for the entire Swedish population.

    Design Population-based cohort study based on Swedish national registers.

    Methods We used logistic regression and flexible parametric models to estimate short-term CFR (death before reaching the hospital or on the disease event day) and long-term CFR (1 year case-fatality conditional on surviving short-term) across five distinct SEP groups, as well as CFR differences (CFRDs) between SEP groups for both MI and IS from 1990-1994 to 2005-2009.

    Results Overall short-term CFR for both MI and IS decreased between study periods. For MI, differences in short-term and long-term CFR between the least and most favourable SEP group were generally stable, except in long-term CFR among women; intermediate SEP groups mostly managed to catch up with the most favourable SEP group. For IS, short-term CFRD generally decreased compared with the most favourable group; but long-term CFRD were mostly stable, except for an increase for older subjects.

    Conclusion Despite a general decline in CFR for MI and IS across all SEP groups and both sexes as well as some reductions in CFRD, we found persistent and even increasing CFRD among the least advantaged SEP groups, older patients and women. We speculate that targeted prevention rather than treatment strategies have the potential to reduce these inequalities.

  • 40. Manousek, Jan
    et al.
    Andrsova, Irena
    Stejskal, Vera
    Stockholm University, Faculty of Science, Department of Molecular Biosciences, The Wenner-Gren Institute. Masaryk Universit, Czech Republic.
    Vlasinova, Jitka
    Sepsi, Milan
    Kuta, Jan
    Klanova, Jana
    Mazik, Michal
    Jarkovsky, Jiri
    Snajdrova, Lenka
    Benesova, Klara
    Novotny, Tomas
    Zadakova, Andrea
    Spinar, Jindrich
    Hypersensitivity to material and environmental burden as a possible cause of late complications of cardiac implantable electronic devices2018In: Europace, ISSN 1099-5129, E-ISSN 1532-2092, Vol. 20, no 9, p. e140-e147Article in journal (Refereed)
    Abstract [en]

    Aims

    To evaluate whether patients with late complications of pacemakers or implantable cardioverter-defibrillators have hypersensitivity reactions to some of the materials used in generators or in electrodes, or to environmental metal burden.

    Methods and results

    The cohort consisted of 20 men and 4 women (mean age: 62.3 +/- 17.2 years) who had a history of late complications of implanted devices. The control group involved 25 men and 8 women (mean age: 64.6 +/- 14.0 years) who had comparable devices, but no history of late complications. Lymphocyte transformation test was used to evaluate hypersensitivity to eight metal pollutants (antimony, manganese, mercury, molybdenum, nickel, platinum, tin, and titanium) selected by results of questionnaires on environmental burden, and by material analysis of generators and electrode surfaces. Exposures to metal pollutants were approximately the same in patients and in controls. Titanium alloy used in generators contained at least 99.32% of titanium and trace levels of other metals; higher levels of tin and platinum were detected in electrode surfaces. Hypersensitivity reactions to mercury and tin were significantly more frequent in patients than in controls (patients and controls: mercury: 68.2 and 31.1%, respectively; P = 0.022; tin: 25.0 and 3.2%, respectively; P = 0.035). In contrast, hypersensitivity to manganese was significantly more frequent in controls than in patients (patients and controls: 13.6 and 50.0%, respectively; P = 0.008).

    Conclusion

    Our findings suggest a possible relation between hypersensitivity to metals used in implantable devices or to environmental metal burden and the occurrence of their late complications.

  • 41. Manousek, Jan
    et al.
    Stejskal, Vera
    Stockholm University, Faculty of Science, Department of Molecular Biosciences, The Wenner-Gren Institute. Masaryk University, Czech Republic .
    Kubena, Petr
    Jarkovsky, Jiri
    Nemec, Petr
    Lokaj, Petr
    Dostalova, Ludmila
    Zadakova, Andrea
    Pavlusova, Marie
    Benesova, Klara
    Kala, Petr
    Miklik, Roman
    Spinar, Jindrich
    Parenica, Jiri
    Delayed-Type Hypersensitivity to Metals of Environmental Burden in Patients with Takotsubo Syndrome - Is There a Clinical Relevance?2016In: PLOS ONE, E-ISSN 1932-6203, Vol. 11, no 11, article id e0164786Article in journal (Refereed)
    Abstract [en]

    Objective Takotsubo syndrome (TS) is a heart condition characterised by a sudden transient left ventricular dysfunction; its pathophysiology is probably associated with elevated levels of catecholamines but the exact mechanism is not known as yet. Literature and clinical experience suggest that TS affects persons with various comorbidities. This pilot work aims to evaluate the frequency of comorbidities with potential pathological immune reactivity, and to evaluate the potential association between TS and hypersensitivity to metals assessed by LTT-MELISA (R). Methodology, Results A total of 24 patients (23 women, 1 man) with a history of TS attack and 27 healthy controls were evaluated. Hypersensitivity was evaluated by a lymphocyte transformation test (LTT-MELISA (R)); a questionnaire of environmental burden was used to select evaluated metals. A total of 19 patients (79%) had at least one condition that might potentially be associated with pathological immune reactivity (autoimmune thyroid disease, drug allergy, bronchial asthma, cancer, contact dermatitis, rheumatoid arthritis). Hypersensitivity to metals was identified significantly more frequently in TS patients than in healthy controls (positive reaction to at least one metal was identified in 95.8% of TS patients and in 59.3% of controls; p = 0.003); the difference was statistically significant for mercury (45.8% and 14.8%, respectively; p = 0.029). Conclusion Our work shows that conditions with pathological immune reactivity occur frequently in TS patients, and our data suggest a possible association between TS and hypersensitivity tometals (mercury in particular) evaluated by LTT-MELISA (R). We also suggest that apart from the triggering stress factor, potential existence of other serious conditions should be considered when taking medical history of TS patients.

  • 42. Mao, Ming
    et al.
    Liu, Rui
    Dong, Yi
    Wang, Chaoqun
    Ren, Yifei
    Tian, Na
    Tang, Shi
    Hou, Tingting
    Cong, Lin
    Wang, Yongxiang
    Stockholm University, Faculty of Social Sciences, Aging Research Center (ARC), (together with KI).
    Du, Yifeng
    Qiu, Chengxuan
    Stockholm University, Faculty of Social Sciences, Aging Research Center (ARC), (together with KI).
    Resting heart rate, cognitive function, and inflammation in older adults: a population-based study2023In: Aging Clinical and Experimental Research, ISSN 1594-0667, E-ISSN 1720-8319, Vol. 35, p. 2821-2829Article in journal (Refereed)
    Abstract [en]

    Background Emerging evidence has linked elevated resting heart rate (RHR) with poor cognitive function in older adults, but the mechanisms underlying their association are poorly understood.Methods This population-based cross-sectional study included 4510 dementia-free participants (age >= 65 years; 56.9% females; 38.3% no formal education) in the baseline examination of the Multidomain Interventions to Delay Dementia and Disability in Rural China study. Of these, 1,386 had data on serum proinflammatory cytokines and adhesion molecules. RHR was measured using 12-lead electrocardiograph. We used the Mini-Mental State Examination (MMSE) and a neuropsychological test battery to assess cognitive function. Data were analyzed using the general linear and restricted cubic splines models.Results People with high RHR were more likely to have cardiometabolic diseases and worse cognitive function (p < 0.05). There was an inverted J-shaped association of RHR with MMSE and attention scores. Having RHR >= 80 bpm (vs. 60-69 bpm) was significantly associated with the multivariable-adjusted beta coefficients of - 0.58 [95% confidence interval (CI), - 1.00, - 0.16] for MMSE score and - 0.08 (- 0.15, - 0.01) for attention score. In the serum biomarker subsample, RHR was linearly associated with serum interleukin-6 (IL-6) (beta coefficient = 0.19; 95%CI 0.14, 0.24), IL-8 (0.08; 0.02, 0.13), IL-10 (0.09; 0.04, 0.15), tumor necrosis factor-alpha (0.06; 0.01, 0.11), monocyte chemotactic protein-1 (0.09; 0.04, 0.15), intercellular adhesion molecule-1 (0.16; 0.11, 0.22), and vascular cell adhesion molecule-1 (0.11; 0.06, 0.16).Conclusions There is an inverted J-shaped association of RHR with attention and global cognition. Poor cognitive function and high RHR may be linked through systemic low-grade inflammation and endothelial injury.

  • 43. Marengoni, Alessandra
    et al.
    Zucchelli, Alberto
    Vetrano, Davide L.
    Stockholm University, Faculty of Social Sciences, Aging Research Center (ARC), (together with KI). Università Cattolica del Sacro Cuore, Italy.
    Aloisi, Gaetano
    Brandi, Vincenzo
    Ciutan, Marius
    Panait, Carmen Lavinia
    Bernabei, Roberto
    Onder, Graziano
    Palmer, Katie
    Heart failure, frailty, and pre-frailty: A systematic review and meta-analysis of observational studies2020In: International Journal of Cardiology, ISSN 0167-5273, E-ISSN 1874-1754, Vol. 316, p. 161-171Article, review/survey (Refereed)
    Abstract [en]

    Frailty is a syndrome characterized by reduced physiological reserves, increased vulnerability to stressors and adverse health outcomes. Frailty can change the prognosis and treatment approach of several chronic diseases, including heart failure (HF). The aim of this study was to conduct a systematic review and meta-analysis assessing the association of HF with frailty and pre-frailty. We employed PRISMA guidelines for reporting the results. We searched PubMed, Web of Science, and Embase from 01/01/2002 to 29/11/2019.The quality of the studies was evaluated with the Newcastle Ottawa Scale. Pooled estimates were obtained through random-effect models and Mantel-Haenszel weighting. Homogeneity (I2) and publication bias were assessed. We selected 54 studies (52 cross-sectional, one longitudinal, and one with both designs). The pooled prevalence of pre-frailty in individuals with HF was 46% (95% CI = 38–53; I2 = 93.1%) and 40% (95% CI = 31–48; I2 = 97%) for frailty. The proportion of pre-frail individuals with HF was 20% (95%CI = 15–25; I2 = 99.2%) and the proportion of frail individuals with HF was 31% (95% CI = 17–45; I2 = 98.7%). Two studies using the same frailty definition reported estimates for the association between frailty and HF (pooled OR = 3.44; 95% CI = 0.75–15.73; I2 = 95.8%). In conclusion, frailty and pre-frailty are frequent in people with HF. Persons with HF have 3.4-fold increased odds of frailty. Longitudinal studies examining bidirectional pathophysiological pathways between HF and frailty are needed to further clarify this relationship and to assess if specific treatment for HF may prevent or delay the onset of frailty and vice versa.

  • 44.
    Martikainen, Pekka
    et al.
    Stockholm University, Faculty of Social Sciences, Centre for Health Equity Studies (CHESS). University of Helsinki, Finland; Max-Planck-Institute for Demographic Research, Germany.
    Korhonen, Kaarina
    Jelenkovic, Aline
    Lahtinen, Hannu
    Havulinna, Aki
    Ripatti, Samuli
    Borodulin, Katja
    Salomaa, Veikko
    Davey Smith, George
    Silventoinen, Karri
    Joint association between education and polygenic risk score for incident coronary heart disease events: a longitudinal population-based study of 26 203 men and women2021In: Journal of Epidemiology and Community Health, ISSN 0143-005X, E-ISSN 1470-2738, Vol. 75, no 7, p. 651-657Article in journal (Refereed)
    Abstract [en]

    Background Genetic vulnerability to coronary heart disease (CHD) is well established, but little is known whether these effects are mediated or modified by equally well-established social determinants of CHD. We estimate the joint associations of the polygenetic risk score (PRS) for CHD and education on CHD events.

    Methods The data are from the 1992, 1997, 2002, 2007 and 2012 surveys of the population-based FINRISK Study including measures of social, behavioural and metabolic factors and genome-wide genotypes (N=26 203). Follow-up of fatal and non-fatal incident CHD events (N=2063) was based on nationwide registers.

    Results Allowing for age, sex, study year, region of residence, study batch and principal components, those in the highest quartile of PRS for CHD had strongly increased risk of CHD events compared with the lowest quartile (HR=2.26; 95% CI: 1.97 to 2.59); associations were also observed for low education (HR=1.58; 95% CI: 1.32 to 1.89). These effects were largely independent of each other. Adjustment for baseline smoking, alcohol use, body mass index, igh-density lipoprotein (HDL) and total cholesterol, blood pressure and diabetes attenuated the PRS associations by 10% and the education associations by 50%. We do not find strong evidence of interactions between PRS and education.

    Conclusions PRS and education predict CHD events, and these associations are independent of each other. Both can improve CHD prediction beyond behavioural risks. The results imply that observational studies that do not have information on genetic risk factors for CHD do not provide confounded estimates for the association between education and CHD.

  • 45. Mazzarone, Tessa
    et al.
    Morelli, Virginia
    Giusti, Andrea
    Bianco, Maria Giovanna
    Maccioni, Lorenzo
    Cargiolli, Cristina
    Guarino, Daniela
    Virdis, Agostino
    Okoye, Chukwuma
    Stockholm University, Faculty of Social Sciences, Aging Research Center (ARC), (together with KI). University of Pisa, Italy; University of Milano-Bicocca, Italy.
    Predicting In-Hospital Acute Heart Failure Worsening in the Oldest Old: Insights from Point-of-Care Ultrasound2023In: Journal of Clinical Medicine, E-ISSN 2077-0383, Vol. 12, no 23, article id 7423Article in journal (Refereed)
    Abstract [en]

    The decompensation trajectory check is a basic step to assess the clinical course and to plan future therapy in hospitalized patients with acute decompensated heart failure (ADHF). Due to the atypical presentation and clinical complexity, trajectory checks can be challenging in older patients with acute HF. Point-of-care ultrasound (POCUS) has proved to be helpful in the clinical decision-making of patients with dyspnea; however, to date, no study has attempted to verify its role in predicting determinants of ADHF in-hospital worsening. In this single-center, cross-sectional study, we consecutively enrolled patients aged 75 or older hospitalized with ADHF in a tertiary care hospital. All of the patients underwent a complete clinical examination, blood tests, and POCUS, including Lung Ultrasound and Focused Cardiac Ultrasound. Out of 184 patients hospitalized with ADHF, 60 experienced ADHF in-hospital worsening. By multivariable logistic analysis, total Pleural Effusion Score (PEFs) [aO.R.: 1.15 (CI95% 1.02-1.33), p = 0.043] and IVC collapsibility [aO.R.: 0.90 (CI95% 0.83-0.95), p = 0.039] emerged as independent predictors of acute HF worsening after extensive adjustment for potential confounders. In conclusion, POCUS holds promise for enhancing risk assessment, tailoring diuretic treatment, and optimizing discharge timing for older patients with ADHF.

  • 46. Meng, Linghui
    et al.
    Hou, Dongqing
    Zhao, Xiaoyuan
    Hu, Yuehua
    Liang, Yajun
    Stockholm University, Faculty of Social Sciences, Aging Research Center (ARC), (together with KI). Jining Medical University, China.
    Liu, Junting
    Yan, Yinkun
    Mi, Jie
    Cardiovascular target organ damage could have been detected in sustained pediatric hypertension2015In: Blood Pressure, ISSN 0803-7051, E-ISSN 1651-1999, Vol. 24, no 5, p. 284-292Article in journal (Refereed)
    Abstract [en]

    The aim of this study was to assess sustained hypertension in children and its impact on cardiovascular target organ damage (TOD). Blood pressure (BP) was measured in children in Beijing in 2009. Primary hypertension was diagnosed based on three separate visits. Hypertensive children and normotensive children were followed up in 2011. According to these evaluations, three groups were defined: sustained hypertension, non-sustained hypertension and normotensive. Cardiovascular TOD and metabolic disorders were evaluated using pulse-wave velocity (PWV), carotid intima-media thickness (cIMT), and assessments of left ventricular structure and kidney function. A total of 3032 children aged 9-15 years participated in this survey, of whom 128 were diagnosed with hypertension after three separate BP measurements. Eighty out of 128 (62.5%) hypertensive and 158 normotensive children were available for follow-up in 2011. Forty-eight children were defined as having sustained hypertension, 38 as non-sustained hypertension and 152 as normotensive. Mean levels of brachial-ankle PWV (baPWV), left ventricular mass, left ventricular mass index (LVMI) and cIMT were significantly different between the three groups (p < 0.01). Compared to normotensives, the odds ratios and 95% confidence intervals for elevated LVM and cIMT were 5.27 (1.57-17.66) and 2.88 (1.03-8.09) in the non-sustained hypertensive group, and 3.28 (1.00-10.74) and 7.25 (2.69-19.58) in the sustained hypertensive group. The children with sustained hypertension have the highest risk of developing arterial stiffness, left ventricular hypertrophy and early blood vessel endothelium damage. The indices of cIMT, LVMI and PWV were useful to identify children at high risk of cardiovascular TOD.

  • 47. Minh, Tuan
    et al.
    Kåreholt, Ingemar
    Stockholm University, Faculty of Social Sciences, Aging Research Center (ARC), (together with KI). Jönköping University, Sweden.
    von Euler, Mia
    von Koch, Lena
    Eriksdotter, Maria
    Garcia-Ptacek, Sara
    Satisfaction with Stroke Care Among Patients with Alzheimer's and Other Dementias: A Swedish Register-Based Study2021In: Journal of Alzheimer's Disease, ISSN 1387-2877, E-ISSN 1875-8908, Vol. 79, no 2, p. 905-916Article in journal (Refereed)
    Abstract [en]

    Background: Patient dissatisfaction with stroke care is associated with poor self-rated health and unmet care needs. Dementia patients' satisfaction with stroke care is understudied.

    Objective: To compare satisfaction with stroke care in patients with and without dementia.

    Methods: This longitudinal cohort study included 5,932 dementia patients (2007-2017) who suffered a first stroke after dementia diagnosis and 39,457 non-dementia stroke patients (2007-2017). Data were retrieved by linking the Swedish Stroke Register, the Swedish Dementia Register, the Swedish National Patient Register, and the Swedish Prescribed Drug Register. The association between dementia and satisfaction was analyzed with ordinal logistic regression.

    Results: When dementia patients answered themselves, they reported significantly lower odds of satisfaction with acute stroke care (OR: 0.71; 95% CI: 0.60-0.85), healthcare staff's attitude (OR: 0.79; 95% CI: 0.66-0.96), communication with doctors (OR: 0.78; 95% CI: 0.66-0.92), stroke information (OR: 0.62; 95% CI: 0.52-0.74); but not regarding inpatient rehabilitation (OR: 0.93; 95% CI: 0.75-1.16), or outpatient rehabilitation (OR: 0.93; 95% CI: 0.73-1.18). When patients answered with caregivers' help, the association between dementia status and satisfaction remained significant in all items. Subgroup analyses showed that patients with Alzheimer's disease and mixed dementia reported lower odds of satisfaction with acute care and healthcare staff's attitude when they answered themselves.

    Conclusion: Patients with dementia reported lower satisfaction with stroke care, revealing unfulfilled care needs among dementia patients, which are possibly due to different (or less) care, or because dementia patients require adaptations to standard care.

  • 48.
    Okoye, Chukwuma
    et al.
    Stockholm University, Faculty of Social Sciences, Aging Research Center (ARC), (together with KI). University Hospital of Pisa, Italy.
    Mazzarone, Tessa
    Cargiolli, Cristina
    Guarino, Daniela
    Discontinuation of Loop Diuretics in Older Patients with Chronic Stable Heart Failure: A Narrative Review2023In: Drugs & Aging, ISSN 1170-229X, E-ISSN 1179-1969, Vol. 40, p. 981-990Article, review/survey (Refereed)
    Abstract [en]

    Loop diuretics (LDs) represent the cornerstone treatment for relieving pulmonary congestion in patients with heart failure (HF). Their benefit is well-recognized in the short term because of their ability to eliminate fluid retention. However, long term, they could adversely influence prognosis due to activation of the neurohumoral mechanism, particularly in older, frail patients. Moreover, the advent of new drugs capable of improving outcomes and reducing pulmonary and systemic congestion signs in HF emphasizes the possibility of a progressive reduction and discontinuation of LD treatment. Nevertheless, few studies were aimed at investigating the safety of LDs withdrawal in older patients with chronic stable HF. This current review aims to approach current evidence regarding the safety and effectiveness of LDs discontinuation in patients with chronic stable HF, and is based on the material obtained via the PubMed and Scopus databases from January 2000 to November 2022. Our search yielded five relevant studies, including two randomized controlled trials. All participants presented stable HF at the time of study enrolment. Apart from one study, all the investigations were conducted in patients with HF with reduced ejection fraction. The most common outcomes examined were the need for diuretic resumption or the event of death and rehospitalization after diuretic withdrawal. As a whole, although based on a few investigations with a low grade of evidence, diuretic therapy discontinuation might be a safe strategy that deserves consideration for patients with stable HF. However, extensive investigations in older adults, accounting for frailty status, are warranted to confirm these data in this peculiar class of patients.

  • 49.
    Okoye, Chukwuma
    et al.
    Stockholm University, Faculty of Social Sciences, Aging Research Center (ARC), (together with KI). University of Pisa, Italy.
    Mazzarone, Tessa
    Niccolai, Filippo
    Bencivenga, Leonardo
    Pescatore, Giulia
    Bianco, Maria Giovanna
    Guerrini, Cinzia
    Giusti, Andrea
    Guarino, Daniela
    Virdis, Agostino
    Predicting mortality and re-hospitalization for heart failure: a machine-learning and cluster analysis on frailty and comorbidity2023In: Aging Clinical and Experimental Research, ISSN 1594-0667, E-ISSN 1720-8319, Vol. 35, p. 2919-2928Article in journal (Refereed)
    Abstract [en]

    BackgroundMachine-learning techniques have been recently utilized to predict the probability of unfavorable outcomes among elderly patients suffering from heart failure (HF); yet none has integrated an assessment for frailty and comorbidity. This research seeks to determine which machine-learning-based phenogroups that incorporate frailty and comorbidity are most strongly correlated with death or readmission at hospital for HF within six months following discharge from hospital.MethodsIn this single-center, prospective study of a tertiary care center, we included all patients aged 65 and older discharged for acute decompensated heart failure. Random forest analysis and a Cox multivariable regression were performed to determine the predictors of the composite endpoint. By k-means and hierarchical clustering, those predictors were utilized to phenomapping the cohort in four different clusters.ResultsA total of 571 patients were included in the study. Cluster analysis identified four different clusters according to frailty, burden of comorbidities and BNP. As compared with Cluster 4, we found an increased 6-month risk of poor outcomes patients in Cluster 1 (very frail and comorbid; HR 3.53 [95% CI 2.30-5.39]), Cluster 2 (pre-frail with low levels of BNP; HR 2.59 [95% CI 1.66-4.07], and in Cluster 3 (pre-frail and comorbid with high levels of BNP; HR 3.75 [95% CI 2.25-6.27])).ConclusionsIn older patients discharged for ADHF, the cluster analysis identified four distinct phenotypes according to frailty degree, comorbidity, and BNP levels. Further studies are warranted to validate these phenogroups and to guide an appropriate selection of personalized, model of care.

  • 50. Ottosson, Filip
    et al.
    Emami Khoonsari, Payam
    Stockholm University, Faculty of Science, Department of Biochemistry and Biophysics. Stockholm University, Science for Life Laboratory (SciLifeLab). Lund University, Sweden.
    Gerl, Mathias J.
    Simons, Kai
    Melander, Olle
    Fernandez, Céline
    A plasma lipid signature predicts incident coronary artery disease2021In: International Journal of Cardiology, ISSN 0167-5273, E-ISSN 1874-1754, Vol. 331, p. 249-254Article in journal (Refereed)
    Abstract [en]

    Background: Dyslipidemia is a hallmark of cardiovascular disease but is characterized by crude measurements of triglycerides, HDL- and LDL cholesterol. Lipidomics enables more detailed measurements of plasma lipids, which may help improve risk stratification and understand the pathophysiology of cardiovascular disease.

    Methods: Lipidomics was used to measure 184 lipids in plasma samples from the Malmö Diet and Cancer – Cardiovascular Cohort (N = 3865), taken at baseline examination. During an average follow-up time of 20.3 years, 536 participants developed coronary artery disease (CAD). Least absolute shrinkage and selection operator (LASSO) were applied to Cox proportional hazards models in order to identify plasma lipids that predict CAD.

    Results: Eight plasma lipids improved prediction of future CAD on top of traditional cardiovascular risk factors. Principal component analysis of CAD-associated lipids revealed one principal component (PC2) that was associated with risk of future CAD (HR per SD increment =1.46, C·I = 1.35–1.48, P < 0.001). The risk increase for being in the highest quartile of PC2 (HR = 2.33, P < 0.001) was higher than being in the top quartile of systolic blood pressure. Addition of PC2 to traditional risk factors achieved an improvement (2%) in the area under the ROC-curve for CAD events occurring within 10 (P = 0.03), 15 (P = 0.003) and 20 (P = 0.001) years of follow-up respectively.

    Conclusions: A lipid pattern improve CAD prediction above traditional risk factors, highlighting that conventional lipid-measures insufficiently describe dyslipidemia that is present years before CAD. Identifying this hidden dyslipidemia may help motivate lifestyle and pharmacological interventions early enough to reach a substantial reduction in absolute risk.

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