Familial aggregation of coronary artery calcium in families with type 2 diabetes

Type 2 diabetes is widely recognized as a major risk factor for atheroscler otic cardiovascular disease, including subclinical atherosclerosis as measu red by noninvasive procedures. However, the role of genetic factors that co ntribute to various measures of subclinical atherosclerosis is largely unkn own. We hypothesize that subclinical atherosclerosis, measured as coronary artery calcification (CAC), mill, be extensive in individuals with type 2 d iabetes and that its presence depends on both genetic and environmental fac tors. The genetic factors should result in the familial aggregation of CAC. To determine the extent of familial aggregation of CAC in the presence of type 2 diabetes, rye studied 122 individuals with type 2 diabetes (mean age 60 years) and 13 individuals without diabetes in 56 families. CAC was meas ured by fast-gated helical computed tomography. Other measured factors incl uded blood pressure, body size, lipids, HbA(1c), and self-reported medical history. To test for an association between CAC and these factors while acc ounting for the potential familial correlation of CAC, generalized estimati ng equations were used. CAC was detectable in 80% of individuals with diabe tes (median score 84, range 0-5,776). Extent of CAC, adjusted for age, was positively associated with male sex (P = 0.0003), reduced HDL (P = 0.02), a lbumin-to-creatinine ratio (P = 0.008), and cigarette pack-years (P = 0.03) . CAC was also positively associated with a history of angina, myocardial i nfarction, stroke, and vascular procedures (all P < 0.01). HbA(1c) and fast ing glucose were positively, but nonsignificantly, associated with the exte nt of CAC (P = 0.14 and 0.08, respectively). CAC, adjusted for age, sex, ra ce, and diabetes status, was heritable (h(2) = 0.50; P = 0.009). In multiva riate analysis with additional adjustment for HDL, BMI, hypertension, and s moking, h(2) = 0.40 (P = 0.038). These results suggest that strong (indepen dent) genetic factors as well as environmental factors contribute to the va riance of CAC in individuals with type 2 diabetes. In these data, CAC seems heritable and may serve as an important feature in designing studies to ma p genes contributing to both atherosclerosis and type 2 diabetes.