1 Division of Epidemiology, School of Public Health, University of Minnesota, USA.
2 Department of Public Health, University of Helsinki, Finland.
3 National Public Health Institute, Finland
4 Department of Public Health, University of Turku, Finland.
Correspondence: Second Street, Minneapolis, MN 554541015, USA. E-mail: silventoinen{at}epi.umn.edu
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Abstract |
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Design and setting The data were derived from the Finnish Twin cohort including 2438 singletons, 4073 monozygotic (MZ) twins, and 9202 dizygotic (DZ) twins aged 2569 years at baseline in 1976. Incident CHD cases were derived from hospital discharge data and cause of death data between 1977 and 1995. Cox regression analysis and conditional logistic regression analysis were used.
Results In population-level analyses no differences in the general risk of CHD between zygosity groups were found. The association between body height and CHD was similar between sexes and zygosity groups. When men and women in all zygosity groups were studied together an increased risk of CHD was found only among the shortest quartile (hazard ratio [HR] = 1.34, 95% CI: 1.141.57). Among the twin pairs discordant for CHD a suggestive increased risk for the shorter twin was seen among DZ twins (odds ratio [OR] = 1.19, 95% CI: 0.951.48) when men and women were studied together.
Conclusion An inverse association between body height and CHD was broadly similar between sexes and twin zygosity groups and was associated with short stature. Among discordant twin pairs we found a weak association among DZ twins but not MZ twins. This may suggest the role of genetic liability behind the association between body height and CHD.
Accepted 23 October 2002
An inverse association between body height and coronary heart disease (CHD) is well described, but the background is still poorly understood.18 As short stature is associated with poor childhood environment the association may partly reflect the contribution of early nutrition to risk of cardiovascular diseases.9 Intrauterine conditions may be also important as body height is associated with birthweight.10 It is further possible that short stature correlates with narrow coronary arteries, which may predispose to CHD.11,12 There are also negative results1315 which raises the question whether the observed association is due to the inadequate adjustment for other socioeconomic factors or other study design issues.
The aim of this study is to examine this association among Finnish twins and singletons. Twin data give a good opportunity to analyse the association with a novel approach between body height and morbidity since twins share a common family background. Comparisons between monozygotic (MZ) and dizygotic (DZ) twins give also information about the background factors of the possible association. Monozygotic twins are genetically identical and if the association is due to common genetic factors behind short stature and higher risk of CHD the association should be seen within DZ but not within MZ twins. If the effect exists within both MZ and DZ pairs, it suggests the role of environmental factors not related to the family background. The stronger association within MZ pairs may indicate the role of intrauterine environment as there is more variation in an intrauterine environment within MZ than DZ twins due to differences in placentation and twin transfusion syndrome.16 However, previous studies17,18 have not shown higher risk of CHD among MZ twins and thus the factors affecting greater variation in birthweight among MZ twins need not be the same behind the increased risk of CHD.
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Data and Methods |
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The first occurrence or death from CHD was used as the outcome measure. These data derive from the Hospital Discharge Register and Causes of Death Bureau files at Statistics Finland. Follow-up was done from 1 January 1977 to 31 December 1995. The coverage of these registers is 100%. We used the International Classification of Diseases (ICD) codes (ICD-8 until 1985 and ICD-9 from 1986 onwards) to form the diagnostic category of CHD (ICD 410414). Participants who had died from causes of death other than CHD during the follow-up period, as well as those not reached due to migration, were treated as censored events. Those with cardiovascular diseases other than hypertension or venous disease at baseline were excluded as described in detail elsewhere.22 The final number of people in this study was 2438 singletons, 4073 MZ, and 9202 DZ twins aged 2569 years at baseline. Table 1 displays the distribution of all participants as well as CHD cases by birth cohort, sex, and zygosity.
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Results |
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Table 3 presents the distribution of discordant twin pairs by body height quartiles. The distribution was quite symmetrical between cases and controls, and significant differences were not observed. We also tested the odds ratio (OR) when pairs were classified to three categories (twins stature taller, shorter or same than the co-twin). In this analysis the OR among men was 0.74 (95% CI: 0.431.27) for MZ and 1.23 (95% CI: 0.931.64) for DZ pairs. Among women the OR were 1.12 (95% CI: 0.57 2.21) for MZ and 1.12 (95% CI: 0.811.56) for DZ pairs. When calculating the statistical significance of the differences in the OR between MZ and DZ twins by fitting an interaction term to the model we found that the difference was statistically significant (two-sided test) at the 10% level among men (P = 0.097). As we found among DZ pairs a slightly increased risk of CHD for the shorter twin, we combined male and female DZ pairs. The OR was 1.19 (95% CI: 0.951.48). We also calculated OR by using body height as a continuous variable but the statistical significance was weaker than in the above analyses. This was because there was some non-linearity between body height and CHD in the within pair analyses.
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Discussion |
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There was no increase in the general risk of CHD among twins compared with singletons. This is consistent with previous Swedish17 and Danish18 twin studies. Twins have a lower birthweight than singletons and they show a rapid catch-up growth in infancy, which has been found to be a risk factor of CHD at the population level.24 However, the causes of low birthweight in twins, mainly due to shorter pregnancy and slowing of growth in the last weeks of pregnancy as the uterus becomes crowded, are mostly different from singletons.16 The findings of this study confirm that the population-level risk factors do not predispose twins for CHD.
The main purpose of this study was to seek new information about the factors behind the association between body height and CHD. Some evidence was generated about a possible genetic factor as there was no association between body height and CHD among MZ twins but a borderline significant association among DZ twins. We calculated the power to find an OR of 1.2 in a matched case-control design based on the number of male and female DZ twins in our sample by using the nQuery Advisor statistical package.25 It was found that the power to reach a significance level of 0.05 was only 35%. It was also found that the difference between male MZ and DZ twins was borderline statistically significant (P < 0.1) but this was not the case among women. We are aware only of one previous study where body height has been compared within twin pairs discordant for CHD. A Swedish twin study including 15 MZ and 15 DZ discordant male twin pairs identified from the Swedish Twin Registry found that the mean body height was very similar within MZ twins (170.9 cm in affected twins and 170.7 cm in healthy twins).26 Among DZ twins there was a slight, but non-significant difference in mean body height (172.7 cm and 175.6 cm). Thus, we cannot, in the light of the current results, exclude the possible genetic effect of liability. However, the evidence is still weak and more research is needed to explore the possible genetic mechanisms between stature and CHD. Pooling results from other population cohorts of twins with measures of height and follow-up for CHD incidence are needed.
KEY MESSAGES
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Acknowledgments |
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References |
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