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Early and later life mechanisms in the aetiology of cardiovascular disease
Institutionen för folkhälsovetenskap, Karolinska institutet.
2010 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Evidence over the recent decades indicates that susceptibility to cardiovascular disease (CVD) may be established already prenatally and in early childhood, and that the aetiological processes of the disease involve biological and social influences occurring throughout a person’s life span. Numerous studies have shown that small size at birth is associated with increased risk of CVD later in life. This finding is suggested to reflect the influence of poor foetal nutrition on the body’s organ structure, physiology and metabolism. Surprisingly, there is little empirical evidence available to support the proposed causal mechanisms. The aim of this thesis is to study the mechanisms under­lying the inverse association of size at birth with CVD.

Three studies in the thesis are based on Uppsala Birth Cohort Study (UBCoS), a prospective cohort study which includes men and women, who were born at the Uppsala Academic Hospital between 1915 and 1929. Information from birth records, school catalogues, Hospital Discharge Register, Cause of Death Register and Censuses is used. One study is based on Stockholm Heart Epidemiology Program (SHEEP), a population based case-control study of risk factors for acute myocardial infarction (AMI) with study base including all Swedish citizens aged 45-70 years with no prior clinically diagnosed AMI, who lived in Stockholm County during 1992-1994. Data from birth records, questionnaire, health examination and blood sampling is used.

In both data materials small size at birth was associated with increased risk of disease. Further analyses showed that birth weight for gestational age in men was associated with ischemic heart disease (IHD) mortality within the non-manual class but not among the manual workers, even if the overall mortality rate was higher in the latter. There was no difference in the association by the men’s family’s social class at birth. For women, social class neither at birth nor in adulthood modified the association between birth weight for gestational age and IHD mortality.

We found that there was a synergistic interaction between low weight for gestational age and overweight in adulthood on risk of AMI.

The simultaneous analysis of foetal growth, cognitive ability and IHD mortality suggested that there is an indirect association between foetal growth and cognitive ability through childhood cognitive ability.

Finally, men with very low and very high birth weight for gestational age had a higher risk of dying after an AMI than men with intermediate birth size. Case fatality in women was not associated with their size at birth.

The results suggest that the effect of poor foetal nutrition on CVD may be modified by social exposures later in life. The synergistic interaction between small size at birth and high adult body mass index with respect to AMI risk supports the thrifty phenotype hypothesis according to which a mismatch between foetal and adult nutrition is causing the disease. The existence of an indirect association between foetal growth and IHD mortality through childhood cognitive ability implies that mechanisms related to brain development are contributing to the association between poor foetal nutrition and IHD, in addition to the effects on physiology and metabolism. As the association of size at birth with case fatality was different from the associations with incidence and mortality, the mechanisms that operate after the AMI event and determine the prognosis might partly be different from the mechanisms that drive the development of the disease.

Place, publisher, year, edition, pages
Stockholm: Institutionen för folkhälsovetenskap, Karolinska institutet , 2010. , 43 p.
Series
Health Equity Studies, ISSN 1651-5390 ; 15
National Category
Public Health, Global Health, Social Medicine and Epidemiology Public Health, Global Health, Social Medicine and Epidemiology
Research subject
Epidemiology
Identifiers
URN: urn:nbn:se:su:diva-48338ISBN: 978-91-7457-073-1 (print)OAI: oai:DiVA.org:su-48338DiVA: diva2:375281
Public defence
2010-11-12, Aula, plan 2, Norrbacka, Stockholm, 09:30 (English)
Opponent
Supervisors
Note
At the time of the doctoral defense, the following papers were unpublished and had a status as follows: Paper 2: Accepted. Paper 3: Manuscript. Available from: 2010-12-08 Created: 2010-12-07 Last updated: 2011-01-12Bibliographically approved
List of papers
1. Does the strength of the association between foetal growth rate and ischaemic heart disease mortality differ by social circumstances in early or later life?
Open this publication in new window or tab >>Does the strength of the association between foetal growth rate and ischaemic heart disease mortality differ by social circumstances in early or later life?
2008 (English)In: Journal of Epidemiology and Community Health, ISSN 0143-005X, E-ISSN 1470-2738, Vol. 62, no 5, e6- p.Article in journal (Refereed) Published
Abstract [en]

Objective: To study whether the effect of size at birth on the risk of ischaemic heart disease (IHD) death is modified by social circumstances in childhood or in adulthood.

Design: A cohort study. Data on circumstances at birth were retrieved from archived obstetric records, social characteristics in adulthood and mortality follow-up through routine registers.

Participants: 6159 men and 5663 women who were born in Uppsala University Hospital, Sweden (the Uppsala Birth Cohort) during 1915–1929, were singleton births with more than 30 weeks of gestational age and were alive in 1961. Follow-up time 1961–2002 (from age 31–46 to 73–88 years).

Main outcome measure: Death from IHD. Multivariate Cox regression with age as the time scale, controlling for year of birth and stratified by gender.

Results: The risk of IHD death was lower among men and women with higher weight for gestational age. Lower social class in adulthood was associated with a higher risk of IHD death. The effect of size at birth on IHD mortality did not appear to be modified by social class at birth but was only present in men of higher social class in adulthood (hazard ratio per 1 SD weight for gestational age 0.84, 95% CI 0.75 to 0.93).

Conclusions: Weight for gestational age was inversely associated with the risk of IHD death in men and women; this effect was present in men of non-manual adult social class only but did not appear to be modified by adult social class in women or by social class at birth in either men or women.

National Category
Public Health, Global Health, Social Medicine and Epidemiology Public Health, Global Health, Social Medicine and Epidemiology
Identifiers
urn:nbn:se:su:diva-10191 (URN)10.1136/jech.2006.059147 (DOI)000254959700019 ()
Available from: 2008-06-11 Created: 2008-06-11 Last updated: 2017-12-13Bibliographically approved
2. Synergistic interaction between small size for gestational age and overweight in adulthood on acute myocardial infarction risk – the SHEEP study
Open this publication in new window or tab >>Synergistic interaction between small size for gestational age and overweight in adulthood on acute myocardial infarction risk – the SHEEP study
2010 (English)In: Epidemiology, ISSN 1044-3983, E-ISSN 1531-5487Article in journal (Refereed) Accepted
National Category
Public Health, Global Health, Social Medicine and Epidemiology Public Health, Global Health, Social Medicine and Epidemiology
Identifiers
urn:nbn:se:su:diva-48335 (URN)
Available from: 2010-12-07 Created: 2010-12-07 Last updated: 2017-12-11Bibliographically approved
3. The role of cognitive ability in the association between size at birth and ischemic heart disease mortality
Open this publication in new window or tab >>The role of cognitive ability in the association between size at birth and ischemic heart disease mortality
2010 (English)Manuscript (preprint) (Other academic)
National Category
Public Health, Global Health, Social Medicine and Epidemiology Public Health, Global Health, Social Medicine and Epidemiology
Identifiers
urn:nbn:se:su:diva-48337 (URN)
Available from: 2010-12-07 Created: 2010-12-07 Last updated: 2010-12-09Bibliographically approved
4. The effect of early life factors on 28 day case fatality after acute myocardial infarction
Open this publication in new window or tab >>The effect of early life factors on 28 day case fatality after acute myocardial infarction
2009 (English)In: Scandinavian Journal of Public Health, ISSN 1403-4948, E-ISSN 1651-1905, Vol. 37, no 7, 720-727 p.Article in journal (Refereed) Published
Abstract [en]

Aims: To study the association of size at birth and social circumstances at birth with 28 day case fatality of acute myocardial infarction (AMI). Methods: Based on 1,776 first cases of AMI occurring in Uppsala Birth Cohort (men and women born 1915—1929) between 1964 and 2002. Data on circumstances at birth retrieved from archived obstetric records; data on social characteristics in adulthood, hospitalizations, and date of death obtained through linkage to Censuses, Hospital Discharge Register, and Cause of Death Register. Results: We found a U-shaped association between standardized birth weight and case fatality of AMI in men (p = 0.045 for age and period adjusted quadratic trend over quintiles of standardized birth weight) that was driven by cases of AMI occurring during the early years of follow-up. We found no association between standardized birth weight and case fatality of AMI in women. There was a statistically non-significant inverse association of AMI case fatality with social class at birth as well as with social class and household income in adulthood in the cohort. Marital status was a strong determinant of case fatality in men. Conclusions: Standardized birth weight for gestational age was associated with case fatality of AMI in men. Social class at birth was weakly inversely associated with case fatality of AMI in the cohort.

National Category
Public Health, Global Health, Social Medicine and Epidemiology Public Health, Global Health, Social Medicine and Epidemiology
Identifiers
urn:nbn:se:su:diva-31300 (URN)10.1177/1403494809344445 (DOI)000269439900008 ()
Available from: 2009-11-10 Created: 2009-11-10 Last updated: 2017-12-12Bibliographically approved

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