The hyperlipidemia associated with the nephrotic syndrome is well characterized. There is, however, a paucity of data in humans on the risk factors for atherosclerotic heart disease and the role of hyperlipidemia on the risk of progression of renal disease in this population. In our study, we retrospectively evaluated a large uniform population of patients (mean creatinine, 1.78 mg/dL; mean 24-hour proteinuria, 7.1 g) with idiopathic nephrotic syndrome for the presence of risk factors for coronary artery disease. One hundred patients with either focal segmental glomerulosclerosis (n = 56) or membranous nephropathy (n = 44) were assessed for the following cardiovascular risk factors: male sex or postmenopausal female, hyperlipidemia, hypertension, smoking history, and left ventricular hypertrophy. Sixty-six percent of the patients were either male or postmenopausal females; 35% were smokers. Hypertension and left ventricular hypertrophy were present in 53% and 13% of patients, respectively. Eighty-seven percent, 53%, and 25% of patients had a total cholesterol of more than 200 mg/dL, more than 300 mg/dL, and more than 400 mg/dL, respectively. Low-density lipoprotein cholesterol was greater than 130 mg/dL and greater than 160 mg/dL in 77.2% and 64.9% of patients, respectively. Virtually all patients (99%) had at least one risk factor for cardiovascular disease; over two thirds (68%) had two risk factors and over one quarter (26%) had three risk factors. In comparing the group that progressed to renal failure with the groups that did not, the initial mean serum cholesterol was lower in the group that progressed (292 mg/dL v 388 mg/dL, P < 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)