Specific Aims: The metabolic syndrome is a common problem which is associated with cardiovascular disease. This proposal tests the null hypothesis that the degree of arterial calcification in adults with the metabolic syndrome is not related to race or to bone mineral density (BMD). Specific Aim 1. To determine if the metabolic syndrome is associated with coronary artery calcification, we will examine the relations between coronary artery calcification score and the presence or absence of the metabolic syndrome. We will also look for the effects of association between the metabolic syndrome and race, age, gender, lipids, history of smoking as well as levels of C-reactive protein and arterial calcification. Specific Aim 2. To determine if coronary artery calcification is associated with lower bone mineral density (BMD) in African American (AA) and Caucasian (Cau) participants, we will examine the relationship between arterial calcification and bone mineral density in AA and Cau subjects. Taking into account the possibility of subclinical bone loss, we will also examine the relationship between markers of bone turnover and arterial calcification in the two groups.

Background and Significance: The metabolic syndrome is a disorder characterized by decreased tissue responsiveness to insulin; clinical features include dyslipidemia, hypertension and impaired glucose intolerance. It is a major cause or morbidity and mortality due to its association with cardiovascular disease, type 2 diabetes mellitus, polycystic ovarian syndrome and non alcoholic fatty liver disease. The metabolic syndrome is a common problem in the United States. It is estimated that one in three to four adults are affected, and this number is expected to increase given the current trends in obesity, type 2 diabetes mellitus, sedentary lifestyle and longevity. Nine out of ten of the 16 million type 2 diabetics are estimated to have the metabolic syndrome. Subjects with the metabolic syndrome usually have one or more traditional cardiovascular risk factors, but their risk of cardiovascular disease tends to exceed what is based on their risk factor profile, and is associated with a poorer prognosis. For example, a recent study reported that the relative risk for developing cardiovascular disease is increased by 1.7 and 2.2 respectively, among subjects with normal glucose tolerance and type 2 diabetes mellitus when they have the metabolic syndrome. These subjects had a higher cardiovascular mortality than those without the metabolic syndrome. Indeed the presence of the metabolic syndrome often renders it impossible to predict cardiovascular risk based on traditional cardiovascular risk factors. Cardiovascular abnormalities that have been described in the metabolic syndrome include the presence of a highly atherogenic lipid profile (high triglyceride levels and low HDL concentrations, with small dense LDL particles), high levels of plasminogen activator inhibitor-1 (with defective fibrinolysis), disorders of inflammation, and endothelial dysfunction. All these disorders favor the development and progression of atherosclerotic cardiovascular disease. An area that has not been properly studied is the association between the metabolic syndrome and arterial calcification, a well known marker of subclinical atherosclerotic disease and an independent predictor of cardiovascular morbidity and mortality. Interestingly, the phenomenon of arterial calcification tends to co-exist with osteoporosis in autoimmune diseases, old age and estrogen deficient females. These subjects tend to have a heightened risk for cardiovascular disease, and some researchers have suggested that these two processes might be linked. A properly designed and well conducted study should clarify the association between the metabolic syndrome and arterial calcification, race and arterial calcification, the processes involved in arterial calcification itself, and whether or not arterial calcification is associated with bone loss.