Familial Aggregation of Coronary Artery Calcium in Families with Type 2 Diabetes
Type 2 diabetes is recognized as a major risk factor for atherosclerotic cardiovascular disease including subclinical atherosclerosis as measured by non-invasive procedures. However, the role of genetic factors that contribute to various measures of subclinical atherosclerosis is largely unknown. We hypothesize that subclinical atherosclerosis, measured as coronary artery calcification (CAC), will be extensive in persons with type 2 diabetes, and that its presence depends on both genetic and environmental factors. The genetic factors will result in the familial aggregation of CAC. To determine the extent of familial aggregation of CAC in the presence of type 2 diabetes, we studied 122 persons with type 2 diabetes (mean age 60 years) and 13 persons without diabetes in 56 families. CAC was measured by fast gated helical computed tomography. Other measured factors included blood pressure, body size, lipids, HbA1c, and self-reported medical history. To test for an association between CAC and these factors while accounting for the potential familial correlation of CAC, generalized estimating equations were used. CAC was detectable in 80% of persons with diabetes (median score = 84, range 0 - 5776). Extent of CAC, adjusted for age, was associated with male gender (p=0.0003), reduced HDL (p=0.02), albumin-creatinine ratio (p=0.008), and cigarette pack-years (p=0.03). CAC was also associated with a history of angina, myocardial infarction, stroke and vascular procedure (all p<0.01). HbA1c and fasting glucose were positively, but non-significantly associated with extent of CAC (p=0.14 and 0.08, respectively). CAC, adjusted for age, sex, race and diabetes status was heritable (h 2 = 0.50, p=0.009). In multivariate analysis adjusting for HDL, BMI, hypertension, and smoking, h 2 = 0.40 (p=0.038). These results suggest that strong (independent) genetic factors as well as environmental factors contribute to the variance of CAC in persons with type 2 diabetes. In these data, CAC appears heritable and may serve as an important feature in designing studies to map genes contributing to both atherosclerosis and type 2 diabetes.