The contribution of risk factors to blood pressure heritability estimates in young adults: the East flanders prospective twin study.

The heritability of blood pressure estimated in previous studies may be confounded by the influence of potential blood pressure risk factors. We applied the classical twin design to estimate the contribution of these covariates to blood pressure heritability. The study consisted of 173 dizygotic and 251 monozygotic twin pairs aged 18-34 years, randomly selected from the East Flanders Prospective Twin Survey. In a standardized examination, blood pressure and anthropometry was measured, a questionnaire was completed, and a fasting blood sample was taken. In univariate and bivariate modeling, diastolic and systolic heritability were estimated both unadjusted and adjusted for potential risk factors. Also, covariate interaction was modeled. Bivariate analysis gave heritability estimates of 0.63 (95%CI 0.55-0.59), 0.74 (95%CI: 0.68-0.79), and 0.78 (95%CI: 0.70-0.84) for diastolic, systolic, and cross-trait heritability, respectively. The remaining variances could be attributed to unique environmental influences. These heritability estimates did not change substantially in univariate analyses or after adjustment for risk factors. A sex-limitation model showed that the heritability estimates for women were significantly higher than for men, but the same genetic factors were operating across sexes. Sex and cigarette smoking appeared to be statistically significant interaction terms. The heritability of blood pressure is relatively high in young adults. Potential risk factors of blood pressure do not appear to confound the heritability estimates. However, gene by sex by smoking interaction is indicated.     

Genetic Influences on Changes in Body Mass Index: A Longitudinal Analysis of Women Twins

AUSTIN, MELISSA A, YECHIEL FRIEDLANDER, BETH NEWMAN, KAREN EDWARDS, ELIZABETH J MAYER-DAVIS, MARY-CLAIRE KING. Genetic influences on changes in body mass index: a longitudinal analysis of women twins. Numerous studies have demonstrated genetic influences on body fat, but there also may be genetic effects on its intraindividual variation over time. This study examined changes in body mass index (BMI) using longitudinal data from two examinations of the Kaiser Permanente Women Twins Study, performed a decade apart. The analysis included 630 women, 185 monozygotic and 130 dizygotic twin pairs, with average ages of 41 years and 51 years at the two examinations, respectively. Age adjusted heritability estimates for the change in BMI over the decade ranged from 0.57 to 0.86 (all ρ≤0.001) using three different statistical analysis approaches, indicating that at least half, and possibly as much as 85%, of the variance in the change in BMI is attributable to genetic influences under a polygenic model. These estimates remained statistically significant after adjusting for environmental factors (ranging from 0.57 to 0.78) and with additional adjustment for BMI at baseline (ranging from 0.41 to 0.79), although dizygotic intraclass correlations were low after these adjustments. Thus, in addition to known environmental and behavioral influences, these results provide evidence for genetic influences on changes in BMI over a decade in women.     

Sib-pair linkage analysis of longitudinal changes in lipoprotein risk factors and lipase genes in women twins

Based on longitudinal twin data in women, we have previously demonstrated a genetic influence on changes in lipoprotein risk factors, blood pressure measurements, and body mass index over a decade. The present study examined the linkage between changes in lipoprotein variables and candidate genes encoding the hormone-sensitive lipase (HSL), hepatic lipase (HL), and lipoprotein lipase (LPL). The sample consisted of 126 dizygotic (DZ) pairs of women twins who participated in the two examinations of the Kaiser Permanente Women Twins Study, performed a decade apart. Using quantitative sib-pair linkage analysis, a linkage was demonstrated between the locus for hormone-sensitive lipase and age-adjusted changes in plasma triglyceride (P = 0.015), which became more significant after adjustment for environmental factors and the exam-1 level (P = 0.005). There was also evidence suggesting linkage between the locus for hepatic lipase and changes in triglyceride (P = 0.023), but no linkage was detected for lipoprotein lipase and changes of lipid levels with time. These findings suggest that variation at these candidate gene loci may underlie a portion of the intraindividual variations in these coronary heart disease (CHD) risk factors, and that studies to identify the functional variants could provide new insights into genetic susceptibility to cardiovascular disease.     

The genetics of coronary heart disease: the contribution of twin studies.

Despite the decline in coronary heart disease in many European countries, the disease remains an enormous public health problem. Although we know a great deal about environmental risk factors for coronary heart disease, a heritable component was recognized a long time ago. The earliest and best known examples of how our genetic constitution may determine cardiovascular risk relate to lipoprotein(a), familial hypercholesterolaemia and apolipoprotein E. In the past 20 years a fair number of polymorphisms assessed singly have shown strong associations with the disease but most are subject to poor repeatability. Twins constitute a compelling natural experiment to establish the genetic contribution to coronary heart disease and its risk factors. GenomEUtwin, a recently funded Framework 5 Programme of the European Community, affords the opportunity of comparing the heritability of risk factors in different European Twin Registries. As an illustration we present the heritabilities of systolic and diastolic blood pressure, based on data from over 4000 twin pairs from six different European countries and Australia. Heritabilities for systolic blood pressure are between 52 and 66% and for diastolic blood pressure between 44 and 66%. There is no evidence of sex differences in heritability estimates and very little to no evidence for a significant contribution of shared family environment. A non-twin based prospective case/cohort study of coronary heart disease and stroke (MORGAM) will allow hypotheses relating to cardiovascular disease, generated in the twin cohorts, to be tested prospectively in adult populations. Twin studies have also contributed to our understanding of the life course hypothesis, and GenomEUtwin has the potential to add to this.     

Comparison of year-of-exam- and age-matched estimates of heritability in the Framingham Heart Study data

Several different approaches can be used to examine generational and temporal trends in family studies. The measurement of offspring and parents can be made over a short period of time with parents and offspring having quite different ages, or measurements can be made at the same ages but with decades between parent and offspring measures. A third approach, used in the Framingham Heart Study, has repeated examinations across a broad range of age and time, and provides a unique opportunity to compare these approaches. Parents and offspring were matched both on (year of exam) and on age. Heritability estimates for systolic blood pressure, body mass index, height, weight, cholesterol, and glucose were obtained by regressing offspring on midparent values with and without adjustment for age. Higher estimates of heritability were obtained for age-matched than for year-of-exam-matched data for all traits considered. For most traits, estimates of the heritability of the change over time (slope) of the trait were near zero. These results suggest that the optimal design to identify genetic effects in traits with large age-related effects may be to measure parents and offspring at similar ages and not to rely on age-adjustment or longitudinal measures to account for these temporal effects.     

Heritability of eleven metabolic phenotypes in Danish and Chinese twins: A cross‐population comparison

Objectives : A twin‐based comparative study on the genetic influences in metabolic endophenotypes in two populations of substantial ethnic, environmental, and cultural differences was performed. Design and Methods : Data on 11 metabolic phenotypes including anthropometric measures, blood glucose, and lipids levels as well as blood pressure were available from 756 pairs of Danish twins (309 monozygotic and 447 dizygotic twin pairs) with a mean age of 38 years (range: 18‐67) and from 325 pairs of Chinese twins (183 monozygotic and 142 dizygotic twin pairs) with a mean age of 40.5 years (range: 18‐69). Twin modeling was performed on full and nested models with the best fitting models selected. Results : Heritability estimates were compared between Danish and Chinese samples to identify differential genetic influences on each of the phenotypes. Except for hip circumference, all other body measures exhibited similar heritability patterns in the two samples with body weight showing only a slight difference. Higher genetic influences were estimated for fasting blood glucose level in Chinese twins, whereas the Danish twins showed more genetic regulation over most lipids phenotypes. Systolic blood pressure was more genetically controlled in Danish than in Chinese twins. Conclusions : Metabolic endophenotypes show disparity in their genetic determinants in populations under distinct environmental conditions.     

Leptin,Insulin, and Obesity‐related Phenotypes: Genetic Influences on Levels and Longitudinal Changes

This study estimated the genetic and environmental determinants of plasma leptin and insulin levels and of obesity‐related phenotypes. Included in this analysis were family members from 80 families living in kibbutz settlements, who participated in two examinations 8–10 years apart. We estimated that polygenes explained 30–50% of the adjusted leptin and insulin levels and 30–70% of the anthropometric phenotypes. This study demonstrated a significant genetic influence on longitudinal changes in leptin and BMI (h² = 0.45) and small‐to‐moderate heritability estimates for changes in insulin and other obesity‐related phenotypes. In bivariate genetic analyses, we observed positive genetic correlations between leptin and anthropometric phenotypes, suggesting that shared effects of the same sets of loci account for 20–30% of the additive genetic variance in these pairs of variables. Shared genetic factors also account for 20–25% of the additive genetic variance in insulin—anthropometric pairs of variables.     

Genetic and Environmental Contributions to Phenotypic Components of Metabolic Syndrome: A Population‐based Twin Study

The increasing prevalence of metabolic syndrome (MS) poses a serious public‐health problem worldwide. Effective prevention and intervention require improved understanding of the factors that contribute to MS. We analyzed data on a large twin cohort to estimate genetic and environmental contributions to MS and to major MS components and their intercorrelations: waist circumference (WC), systolic (SBP) and diastolic blood pressure (DBP), fasting plasma glucose (FPG), triglycerides (TGs), and high‐density lipoprotein–cholesterol (HDL‐C). We applied structural equation modeling to determine genetic and environmental structure of MS and its major components, using 1,617 adult female twin pairs recruited from rural China. The heritability estimate for MS was 0.42 (95% confidence interval (CI): 0.00–0.83) in this sample with low MS prevalence (4.4%). For MS components, heritability estimates were statistically significant and ranged from 0.13 to 0.64 highest for WC, followed by TG, SBP, DBP, HDL‐C, and FPG. HDL‐C was mainly influenced by common environmental factors (0.62, 95% CI: 0.58–0.62), whereas the other five MS components were largely influenced by unique environmental factors (0.32–0.44). Bivariate Cholesky decomposition analysis indicated that the clinical clustering of MS components may be explained by shared genetic and/or environmental factors. Our study underscores the importance of examining MS components as intercorrelated traits, and to carefully consider environmental and genetic factors in studying MS etiology.     

Path analysis of familial resemblance in blood pressure in Middle Dalmatia,Croatia

The familial resemblance in blood pressure in Middle Dalmatia, Croatia, has been analyzed using the Path-analytic approach. The sample consisted of 1,126 examinees (526 males and 600 females, aged 17 to 87), inhabitants of the Middle Dalmatia's islands of Brac, Hvar, Korcula and the Peljesac peninsula. The Path analysis was performed with the assumption that each family member (father, mother, offspring 1 and 2) has a latent variable (C) that influences both the blood pressure values (P) and the morphological dimensions significantly correlated with blood pressure (Q). According to the estimates revealed from the most parsimonious models, the diastolic blood pressure has a more pronounced genetic component (h2 = 30-32%) than the systolic blood pressure (h2 = 15%). In contrast to the low intergenerational influences, the members of the same generation showed pronounced effects of shared environment. Common (non-transmitted) offsprings' environment (B) explains 44% of variance of the individual offspring's environment (C) in systolic and 33-35% in diastolic blood pressure. The correlation of father's and mother's environment (u2) was high in the case of diastolic blood pressure (33-44%) but for the systolic blood pressure it was not significantly different from zero. According to the presented results in insular/peninsular population of Middle Dalmatia, family resemblance of systolic and diastolic blood pressure differs. The resemblance is higher in diastolic blood pressure with stronger additive genetic component and stronger environmental and/or genetic component related with morphology. The sources of high heritability of diastolic blood pressure in Middle Dalmatia as well as the sources of high prevalence of hypertension in the same population are the phenomena that might be connected and thus deserve to be further explored in incoming analyses.     

Genetic and environmental influences on alcohol use: DF analysis of NLSY kinship data

Research designs to study alcohol use and abuse have included twin, adoption and family history/high risk studies. Results have consistently implied a genetic factor in the aetiology of alcohol abuse. However, less research has been conducted in search of environmental factors. This study uses kinship structure in a large national dataset (the National Longitudinal Survey of Youth) to estimate (using DeFries-Fulker analysis) the extent of the shared genetic, non-shared genetic, shared environmental and non-shared environmental influences on alcohol use. The NLSY kinship sample contained 3890 pairs of cousins, half-siblings, full-siblings and twins between the ages of 14 and 21 in the initial year of the survey (1979). Estimates of heritability (h2) and shared environment (c2) were small to moderate for the entire dataset for both light drinking and heavy drinking behaviour, with h2 estimates slightly higher in each case. Non-shared genetic measures of self-esteem and locus of control accounted for a significant portion of the remaining variance in heavy drinking behaviour. Race and gender patterns showed c2 and h2 estimates that were also small to moderate for both light and heavy drinking behaviour. Significant non-shared effects were found for the White group for heavy drinking behaviour, and for male pairs for both heavy and light drinking behaviour. Additionally, implications and future directions are discussed.     

Estimation of the heritability of latent variables which are included in a structural model for metabolic syndrome

In a study looking for risk factors of atherosclerosis in families with combined hyperlipidemia and hypertension, clinical and biochemical data of 1,149 persons were analyzed to develop two hypothetical multivariate scores concerning the degree to which a patient is affected by the metabolic syndrome. The scores are based on a structural model for low-density cholesterol (LDL) and high-density cholesterol (HDL), triglycerides, uric acid, creatinine, glucose, insulin, systolic blood pressure and waist-to-hip ratio. Age, gender and body mass index were used for adjusting all variables. In segregation analyses of 42 pedigrees without using genotype information, estimations of the heritabilities and environmentally caused variance and covariance components were computed for the individual score values of the two latent factors. The first score shows a heritability of 42%; the environment component disappeared. The score mainly reflects the HDL, LDL and triglyceride levels. The second score shows a heritability of 16% with an environment component of 7%. It includes mainly insulin, uric acid and creatinine. In the search for genetic causes, both scores could be a basis for further phenotypic classification of the metabolic syndrome.     

Randomised controlled trial evaluating cardiovascular screening and intervention in general practice: principal results of British family heart study. Family Heart Study Group.

OBJECTIVE--To measure the change in cardiovascular risk factors achievable in families over one year by a cardiovascular screening and lifestyle intervention in general practice. DESIGN--Randomised controlled trial in 26 general practices in 13 towns in Britain. SUBJECTS--12,472 men aged 40-59 and their partners (7460 men and 5012 women) identified by household. INTERVENTION--Nurse led programme using a family centred approach with follow up according to degree of risk. MAIN OUTCOME MEASURES--After one year the pairs of practices were compared for differences in (a) total coronary (Dundee) risk score and (b) cigarette smoking, weight, blood pressure, and random blood cholesterol and glucose concentrations. RESULTS--In men the overall reduction in coronary risk score was 16% (95% confidence interval 11% to 21%) in the intervention practices at one year. This was partitioned between systolic pressure (7%), smoking (5%), and cholesterol concentration (4%). The reduction for women was similar. For both sexes reported cigarette smoking at one year was lower by about 4%, systolic pressure by 7 mm Hg, diastolic pressure by 3 mm Hg, weight by 1 kg, and cholesterol concentration by 0.1 mmol/l, but there was no shift in glucose concentration. Weight, blood pressure, and cholesterol concentration showed the greatest difference at the top of the distribution. If maintained long term the differences in risk factors achieved would mean only a 12% reduction in risk of coronary events. CONCLUSIONS--As most general practices are not using such an intensive programme the changes in coronary risk factors achieved by the voluntary health promotion package for primary care are likely to be even smaller. The government''s screening policy cannot be justified by these results.     

The heritability of mortality due to heart diseases: a correlated frailty model applied to Danish twins.

Data of the Danish Twin Registry on monozygotic and dizygotic twins are used to analyse genetic and environmental influences on susceptibility to heart diseases for males and females, respectively. The sample includes 7955 like-sexed twin pairs born between 1870 and 1930. Follow-up was from 1 January 1943 to 31 December 1993 which results in truncation (twin pairs were included in the study if both individuals were still alive at the beginning of the follow-up) and censoring (nearly 40% of the study population was still alive at the end of the follow-up). We use the correlated gamma-frailty model for the genetic analysis of frailty to account for this censoring and truncation. During the follow-up 9370 deaths occurred, 3393 deaths were due to heart diseases in general, including 2476 deaths due to coronary heart disease (CHD). Proportions of variance of frailty attributable to genetic and environmental factors were analyzed using the structural equation model approach. Different standard biometric models are fitted to the data to evaluate the magnitude and nature of genetic and environmental factors on mortality. Using the best fitting model heritability of frailty (liability to death) was found to be 0.55 (0.07) and 0.53 (0.11) with respect to heart diseases and CHD, respectively, for males and 0.52 (0.10) and 0.58 (0.14) for females in a parametric analysis. A semi-parametric analysis shows very similar results. These analyses may indicate the existence of a strong genetic influence on individual frailty associated with mortality caused by heart diseases and CHD in both, males and females. The nature of genetic influences on frailty with respect to heart diseases and CHD is probably additive. No evidence for dominance and shared environment was found.     

Chorion type as a possible influence on the results and interpretation of twin study data.

The estimation of genetic effects from twin studies usually relies upon the equal environment assumption--that monozygous (MZ) and dizygous (DZ) twin pairs experience equal similarity of their environments from prenatal experiences through adulthood. However, the sharing of a chorion may make a subset of identical twins more similar, or in some cases, more different, than twins that do not share a chorion. Recent studies suggest monochorionic MZ twins resemble one another more than dichorionic MZ twins in cognitive abilities, personality, and risk for psychiatric disorder. To the extent that prenatal environment affects these characteristics, the traditional twin method will yield biased estimates of genetic and environmental influences. We develop models for quantifying this bias and estimating the influence of chorion type on estimates of heritability.     

Heritability and genetic correlations of metabolic disease-related phenotypes in Mexico: preliminary report from the GEMM Family Study

Cardiovascular disease (CVD) is a major cause of mortality in the Republic of Mexico, and metabolic syndrome, a complex of CVD risk factors, is increasingly prevalent. To date, however, there have been few studies of the genetic epidemiology of metabolic syndrome in Mexico. As a first step in implementing the GEMM Family Study, a large, multicenter collaborative study, we recruited 375 individuals in 21 extended families, without ascertainment on disease, at 9 medical institutions across Mexico. Participants were measured for anthropometric (stature, weight, waist circumference) and hemodynamic (blood pressure, heart rate) phenotypes; glucose, cholesterol, and triglyceride levels were measured in fasting blood. Variance components-based quantitative genetic analyses were performed using SOLAR. All phenotypes except diastolic blood pressure were significantly heritable. Consistent with the definition of metabolic syndrome, many phenotypes exhibited significant environmental correlation, and significant genetic correlations were found between measures of adiposity and fasting glucose and fasting triglyceride levels. These preliminary data represent the first heritability estimates for many of these phenotypes in the Republic of Mexico and indicate that this study design offers excellent power for future gene discovery relative to metabolic disease.     

Broad and narrow heritabilities of quantitative traits in a founder population

Estimation of the components of variance for a quantitative trait allows one to evaluate both the degree to which genetics influences the trait and the trait's underlying genetic architecture. For particular traits, the estimates also may have implications for discriminating between potential models of selection and for choosing an appropriate model for linkage analysis. Using a recently developed method, we estimate the additive and dominance components of variance--or, equivalently, the narrow and broad sense heritabilities--of several traits in the Hutterites, a founder population with extensive genealogical records. As a result of inbreeding and because Hutterite individuals are typically related through multiple lines of descent, we expect that power to detect dominance variance will be increased relative to that in outbred studies. Furthermore, the communal lifestyle of the Hutterites allows us to evaluate the genetic influences in a relatively homogeneous environment. Four phenotypes had a significant dominance variance, resulting in a relatively high broad heritability. We estimated the narrow and broad heritabilities as being, respectively,.36 and.96 for LDL,.51 and 1.0 for serotonin levels, and.45 and.76 for fat free mass (FFM). There was no significant additive component for systolic blood pressure (SBP), resulting in a narrow heritability of 0 and a broad heritability of.45. There were several traits for which we found no significant dominance component, resulting in equal broad and narrow heritability estimates. These traits and their heritabilities are as follows: HDL,.63; triglycerides,.37; diastolic blood pressure,.21; immunoglobulin E,.63; lipoprotein(a),.77; and body-mass index,.54. The large difference between broad and narrow heritabilities for LDL, serotonin, FFM, and SBP are indicative of strong dominance effects in these phenotypes. To our knowledge, this is the first study to report an estimate of heritability for serotonin and to detect a dominance variance for LDL, FFM, and SBP.     

Genetic analysis of indicators of cholesterol synthesis and absorption: lathosterol and phytosterols in Dutch twins and their parents.

Significant familial aggregation was observed for plasma levels of lathosterol (an indicator of whole-body cholesterol synthesis) and plant sterols campesterol and beta-sitosterol (indicators of cholesterol absorption) in 160 Dutch families consisting of adolescent mono- and dizygotic twin pairs and their parents. For lathosterol a moderate genetic heritability in parents and offspring (29%) was found. In addition, shared environment also contributed significantly (37%) to variation in plasma lathosterol concentrations in twin siblings. However, a model with different genetic heritabilities in the two generations (10% in parents and 68% in offspring) fitted the data almost as well. For plasma plant sterol concentrations high heritabilities were found. For campesterol heritability was 80% and for beta-sitosterol it was 73%, without evidence for differences in heritability between sexes or generations. No influence of common environmental influences shared by family members was seen for either campesterol or beta-sitosterol. Taken together, these results confirm and expand the hypothesis that individual differences in plasma levels of noncholesterol sterols are moderately (lathosterol) to highly (plant sterols) heritable.     

Structural analysis of the correlations of genetic markers with physiological indices

The structure of phenotypic and genetic correlations between ABO blood groups, MN, Rh(D), haptoglobins and concentration indications of the total cholesterol, of sugar curve, the levels of systolic and diastolic arterial pressure was studied in twins by the method for cluster analysis (121 monozygotic twin pairs, 120 dizygotic like sex twin pairs and 107 pairs of unlike sex twins). No correlation between the systems analysed and their indications on the phenotypic level was observed. By analysis of genetic correlations, the existence of correlations between the Rh system and arterial pressure, and the total cholesterol concentration, as well as between the ABO system and sugar concentration indexes, was established. Possible genetic causes for correlations obtained are being discussed.     

Lifetime Overweight Status in Relation to Serial Changes in Body Composition and Risk Factors for Cardiovascular Disease: The Fels Longitudinal Study

Objective: The aims were to determine if 1) individuals who became and maintained overweight during their entire lifetime differ from those who were never‐overweight in terms of annual changes in adiposity and concurrent changes in cardiovascular disease (CVD) risk factors; 2) the changes and their relationships to each other varied between these groups or by sex within the groups; and 3) alcohol usage, smoking habits, and level of physical activity differed between groups. Research Methods and Procedures: Data from 16,315 examinations of 414 individuals were utilized to assess lifetime overweight (body mass index [BMI] > 25 kg/m²) status. A regressive analytic approach was used to determine the average annual changes for each individual over an adult serial interval ranging from 4 to 20 years. Results: Men and women who have become and maintained overweight have higher blood pressure and a poorer lipid/lipoprotein risk profile than those who have never been overweight. There is an accelerated deterioration in the atherogenic profile of overweight men and women as indicated by annual changes in CVD risk factors about double that of their never‐overweight counterparts. In women, increased risk is derived from increasing systolic and diastolic blood pressure, whereas in men the increased risk comes not only from increasing diastolic blood pressure but also cholesterol, triglycerides, and low‐density lipoprotein cholesterol levels and, to a lesser extent, decreasing high‐density lipoprotein cholesterol. Discussion: The reduced physical activity observed in the overweight adults may be related to their accumulation of adipose tissue at a rate about double their never‐overweight counterparts, and this may be driving the higher rate of increase of CVD risk factors in the overweight groups.     

Obesity in 70‐Year‐Old Subjects as a Risk Factor for 15‐Year Coronary Heart Disease Incidence

Objective: To investigate the role of obesity in general and waist circumference (WC) and BMI in particular as risk factors for 15‐year incidence of coronary heart disease (CHD) in the elderly. Research Methods and Procedures: This prospective study was based on 1597 (737 males and 860 females) 70‐year‐olds free from CHD and participants of three birth cohorts examined in 1971 to 1972 (Cohort I), 1976 to 1977 (Cohort II), and 1981 to 1982 (Cohort III) at Göteborg, Sweden. Fifteen‐year incidence of CHD (fatal and nonfatal) was ascertained from follow‐up examinations and registers. Relative risk (RR) for first ever CHD in reference to the lowest quartiles of WC and BMI was calculated from Cox regression. Results: In males, RRs for CHD in the highest WC and BMI quartiles were 1.36 [95% confidence interval (CI) 1.00 to 1.85] and 1.42 (95% CI 1.04 to 1.92), respectively, after adjustment for cohorts, smoking habits, diabetes, systolic blood pressure, and total cholesterol. In men, the risk associated with WC was independent of BMI. Neither WC nor BMI was related to CHD risk in females. After exclusion of first 5‐year all‐cause deaths, the adjusted RRs in the highest WC and BMI quartiles in males were 1.47 (95% CI 1.06 to 2.04) and 1.42 (1.04 to 1.92), respectively. In females, a significantly higher RR of 1.41 (95% CI 1.02 to 1.94) was observed in the second BMI quartile only after such exclusions. Discussion: WC, an indicator of both central and general obesity, appears to be a stronger predictor of CHD than BMI in elderly males, but in females, obesity was not a risk factor for CHD.