The association between body height and coronary heart disease among Finnish twins and singletons

Karri Silventoinen1,2, Jaakko Kaprio2,3, Markku Koskenvuo4 and Eero Lahelma2

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 55454–1015, USA. E-mail: silventoinen{at}epi.umn.edu


    Abstract
 Top
 Abstract
 Data and Methods
 Results
 Discussion
 References
 
Objectives An inverse association between body height and the incidence of coronary heart disease (CHD) has been observed. However, the mechanisms behind this association are still largely unknown. We will examine the role of genetic and familial factors behind the association in a large twin data set.

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 25–69 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: 1.14–1.57). 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: 0.95–1.48) 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.


Keywords Body height, genetic factors, coronary heart disease, follow-up studies, risk factors

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.1–8 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 results13–15 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.


    Data and Methods
 Top
 Abstract
 Data and Methods
 Results
 Discussion
 References
 
The data derive from the Finnish Twin Cohort Study.19 The baseline sample consists of all same sex twin pairs born before 1958 with both co-twins alive in 1974 to whom a questionnaire was mailed in 1975. The original cohort also included other subjects who had the same family name, the same home parish, and were born on the same day, but were not twins. These people are included in this study as singletons. The response rate for twins was 85.5%. Twin zygosity was determined by a validated questionnaire method of high accuracy.20 Zygosity could not be determined for 1071 twin individuals who were excluded from the analysis. Body height is self-reported, but self-reported and measured body height correlated highly in a subsample of the twins.21

  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 410–414). 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 25–69 years at baseline. Table 1Go displays the distribution of all participants as well as CHD cases by birth cohort, sex, and zygosity.


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Table 1 The proportion of participants (coronary heart disease (CHD) events and total number) by sex, zygosity, and age on 1 January 1976
 
  Relative hazard ratios (HR) were computed by Cox regression model for all subjects considered as individuals while the risk within CHD discordant twin pairs was assessed by a conditional logistic regression model with the STATA statistical package.23 Due to possible non-linearity in the relation between body height and the risk of CHD, body height was classified to four classes, each including roughly 25% of men and women. Due to the unsmooth distribution of self-reported body height we were unable to form exact quartiles. We also calculated trend estimates by using scores (1,2,3,4) for body height quartiles and entering the score as a continuous variable in the model. Education, physical activity, alcohol consumption per day, smoking status, diabetes, and hypertension were adjusted for as they might confound the association between body height and CHD. The data structure of the twin sample was considered when standard errors were estimated by taking into account the within-pair correlations in CHD using the cluster-option in the Cox regression procedure.


    Results
 Top
 Abstract
 Data and Methods
 Results
 Discussion
 References
 
Among men a linear trend between stature and CHD events was seen in all subjects (HR = 1.17, 95% CI: 1.09–1.25) as well as among singletons (HR = 1.19, 95% CI: 1.00–1.41), MZ twins (HR = 1.14, 95% CI: 1.00–1.32), and DZ twins (HR = 1.18, 95% CI: 1.08–1.28) adjusted for age only (Table 2Go). When all confounding factors were adjusted for, the association remained statistically significant for DZ twins (HR = 1.15, 95% CI: 1.05–1.26) and for all subjects (HR = 1.13, 95% CI: 1.06–1.21). Among women the association was borderline statistically significant among MZ twins only (HR = 1.18, 95% CI: 1.00–1.39). The differences between the zygosity categories in the risk of CHD were not statistically significant. The general risk for CHD was similar among MZ twins, DZ twins, and singletons among men and women. Further, we did not find statistically significant differences between twins and singletons as well as MZ and DZ twins in the association between body height and CHD among men and women. (data not shown)


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Table 2 Relative risk (hazard ratio HR) for coronary heart disease (CHD) events in singletons, and monozygotic and dizygotic twins by stature. Men and women
 
  Sex and zygosity interactions in the association between body height and CHD were not statistically significant, and therefore data on men and women were combined. We also tested the sex interaction by studying sex and age-standardized body height but this interaction was not statistically significant either. In the pooled data, the association between body height and CHD was statistically significant among MZ and DZ twins in all models, and among singletons when only age was adjusted for. When all zygosity groups were analysed together an increased risk of CHD was seen only in the shortest quartile (HR = 1.34, 95% CI: 1.14–1.57).

  Table 3Go 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 (twin’s stature taller, shorter or same than the co-twin). In this analysis the OR among men was 0.74 (95% CI: 0.43–1.27) for MZ and 1.23 (95% CI: 0.93–1.64) for DZ pairs. Among women the OR were 1.12 (95% CI: 0.57– 2.21) for MZ and 1.12 (95% CI: 0.81–1.56) 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: 0.95–1.48). 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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Table 3 The distribution of twins with (case) and without coronary heart disease (CHD) (control) among discordant pairs by body height quartiles by sex and zygosity.
 

    Discussion
 Top
 Abstract
 Data and Methods
 Results
 Discussion
 References
 
An inverse association between body height and CHD was found, and this was largely similar between sexes and zygosity groups in population-level analyses. This result is in accordance with other studies where an inverse association between CHD and body height has been found.1–8 When studying all zygosity groups, and men and women together, we found that only those in the shortest quartile had an increased risk of CHD. This suggests that the factors behind the association between body height and CHD are associated with short stature but not with normal variation of body height. This may indicate the role of social deprivation in the background of this association. It is also possible that other factors that specifically cause short stature, rather than variability in height in general, may be responsible.

  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

  • The inverse association between body height and coronary heart disease (CHD) is well described but poorly understood.
  • We found that in Finland there was an inverse association between body height and CHD and this association was very similar among singletons, monzygotic (MZ) twins, and dizygotic (DZ) twins as well as men and women.
  • When men and women as well as all zygosity groups were pooled a higher risk was found only in the shortest quartile of height, which may indicate the role of social deprivation.
  • When we studied the difference in body height among twin pairs discordant by CHD we found a suggestive increased risk among DZ twins but not among MZ twins, which may suggest a role for genetic liability underlying the association between CHD and body height.

 


    Acknowledgments
 
This study is funded by Academy of Finland, Research Council for Health (grant #37800) and Yrjö Jahnsson Foundation (grant #4744). We thank Professor Seppo Sarna from the Department of Public Health, University of Helsinki, for statistical consultation.


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 Data and Methods
 Results
 Discussion
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