Systemic lupus erythematosus (SLE) is a relatively common rheumatologic condition affecting 1 in 700 females. Besides SLE, another autoimmune disorder is idiopathic membranous nephropathy which is the most common primary cause of nephrotic syndrome in adults in Western societies. Both SLE and membranous nephropathy are associated with an increased risk of coronary artery disease (CAD) and thrombotic events. Hypercholesterolemia, common to these autoimmune diseases, is a risk factor for CAD. Additionally, elevated levels of lipoprotein a [Lp(a)], an independent risk factor for CAD in the general population, are also frequently seen in these patient populations. Lp(a) is a low-density plasma lipoprotein composed of lipids and two major protein components, apolipoprotein (apo) B-100 and apo (a). Apo(a) has structural similarities to plasminogen, but is not a protease zymogen. Several studies have shown that Lp(a) competes with plasminogen for the cell surface binding sites that are necessary for tissue-type plasminogen activator (t-PA) to cleave plasminogen to plasmin. Additionally, elevated levels of Lp(a) may be a risk factor for thrombotic events, as increased levels have been associated with cerebrovascular disease. This study will evaluate the effects of niacin-induced changes in cholesterol and Lp(a) on fibrinolytic parameters (FP). This open-label, paralled-design pilot trial involves a total of 30 patients who have SLE and/or membranous nephropathy with hyperlipidemia and normolipidemia (15 with and IS without elevated Lp(a) greater than or equal to 25 mg/dL). Patients will receive niacin 3 g/day for a 6-week period following an initial 4-week titration period. FP will be assessed at baseline, at Weeks 2 and 4 of the titration period, and at Weeks 7 and 10 of full-dose niacin therapy. Niacin therapy will then be discontinued, and FP will be reassessed in 6 weeks.
