The Inheritance of Atherosclerosis and Left Ventricular Structure: A Scottish Twin Study

Cardiovascular disease is a major cause of morbidity and mortality in Scotland. Coronary atherosclerosis alone accounts for 450 premature deaths per 100,000 males and 180 per 100,000 in females each year. The pathological processes underlying these clinical manifestations of cardiovascular disease are multifactorial in causation. However, it is unclear to what extent the Scottish population has a genetic predisposition to these disorders. Twin studies are a highly informative method of delineating the varying genetic and environmental contributions to non-Mendelian parameters. Utilising a population of monozygotic and dizygotic twins allows the contribution of genetic factors to be quantified by comparing intra-class correlations between the monozygotic and dizygotic groups. Previous twin studies have primarily evaluated the genetic influences over known cardiovascular risk factors but little is known about the interplay of these factors in a population from the West of Scotland with its high prevalence of cardiovascular pathology. Few studies have focused on the inheritance of the actual extent of arterial disease. The determination of degree of heritability over a given phenotype is an important first step before embarking on the investigation of potential candidate genes. The cohort investigated in this study consisted of 151 pairs of monozygotic and dizygotic twins aged 30-85 years old (82 monozygotic pairs and 68 dizygotic pairs). All pairs were; recruited from the general population and were of Caucasian origin. Using a classic twin methodology the heritability of a wide range of cardiovascular phenotypes were assessed. Resting and 24-hour assessments of blood pressure were performed. 24-hour measures of diastolic and mean blood pressure were under a significant degree of genetic control. This was particularly true for night-time measurements (night-time mean and diastolic pressures - heritability of 0.53 (p=0.03) and 0.58 (p=0.02) respectively). The degree of heritability was stronger for these parameters than resting or 24-hour measures of systolic blood pressure. Genes were important in the aetiology of left ventricular (LV) mass in this cohort. Heritability for LV mass was 0. 69 (p=0.008). This genetic influence was not explained by similarities In age, sex, size or blood pressure and persisted following correction for these potential confounders (h2 = 0.53; p=0.006). Impaired lung function, as measured by spirometry, is a risk factor for cardiovascular events. Intra-class correlation coefficients were measured for FEV1 and FVC in the monozygotic and dizygotic groups. The baseline data and the data corrected for height both showed a significant percentage of the variability in these measurements were under genetic control. The heritability estimates for the height corrected spirometry variables were 0.61 (p=0.02) for FEV1 and 0.71 (p=0.007) for FVC. When these variables were expressed as a percentage of their predicted value only the FEV1 result remained significant (h2=0.61, p=0.002). The genetic contribution towards the extent of atheroma formation was assessed using B-mode ultrasound of the carotid arteries. This technique measures carotid intima media thickness a marker of atherogenesis in the cerebral and coronary beds. None of the carotid measurements revealed any degree of genetic control. Environmental and familial influences appeared to be more important than narrow-sense heritability in the determination of carotid intima media thickness. Numerous biochemical and haematological parameters were assessed in the twin cohort. A genetic basis was established for many of them including Lipoprotein A, HDL-Cholesterol, urate, haematocrit and platelet level. In summary this population-based adult twin study, which recruited subjects from a high-risk catchment area (the West of Scotland) demonstrated that many important risk factors are genetically determined. Candidate gene investigations should be directed towards the study of phenotypes with the strongest heritability estimates. A clearer understanding of the aetiology of, and relationships between, the risk factors investigated in this study is necessary to enable effective targeting of preventative and therapeutic strategies