Insulin resistance and elevated levels of tissue plasminogen activator in first-degree relatives of South Asian patients with ischemic cerebrovascular disease.

Abstract

South Asians in the United Kingdom suffer from an increased mortality from cerebrovascular disease compared with whites. Evidence suggests that the relatives of white stroke patients are at increased risk of vascular disease. The aim of this study was to investigate atherothrombotic risk factors in the first-degree relatives of South Asian patients suffering from ischemic cerebrovascular disease and to compare them with South Asian subjects free from clinically detectable cerebrovascular disease. We compared 143 relatives of South Asians with ischemic stroke (South Asian relatives group) with 146 South Asian control subjects from West Yorkshire, UK. The ages and ethnic and sex distributions of South Asian relatives and South Asian controls were similar. There were no significant differences in body mass index, waist-hip ratio, number of current smokers, and past medical history of hypertension, diabetes mellitus, or myocardial infarction between the 2 groups. Fasting blood glucose, glycosylated hemoglobin (HbA(1c)), total cholesterol, triglycerides, and HDL cholesterol were similar in the 2 groups. Fasting insulin (South Asian relatives, 12.0; South Asian controls, 8.5 mU/L; P<0.0001) (independent of tissue plasminogen activator) and insulin resistance (derived by Homeostasis Model Assessment) (South Asian relatives, 2.7; South Asian controls, 1.9; P=0.001) were significantly raised in stroke relatives. Stroke relatives showed elevated levels of tissue plasminogen activator (South Asian relatives, 11.6; South Asian controls, 8.4 ng/mL; P<0.0001), which was independent of plasma insulin. There were no differences in plasminogen activator inhibitor antigen or activity between the groups. South Asians stroke relatives exhibit hyperinsulinemia, increased insulin resistance, and increased tissue plasminogen activator levels. These observations might account for increased susceptibility to atherothrombotic disease in this ethnic group.