Background-Osteoprotegerin (OPG) is a secretory glycoprotein that belongs to the tumor necrosis factor receptor family.OPG-deficient mice develop severe osteoporosis and medial arterial calcification of the aorta and renal arteries. OPG immunoreactivity was demonstrated in the normal blood vessels and in early atherosclerotic lesions. A recent clinical study suggests that there is a significant correlation between elevated serum OPG levels and cardiovascular mortality. We examined whether serum OPG levels are associated with the progression of coronary artery disease (CAD). Methods and Results-Serum OPG levels were examined in 201 patients who underwent coronary angiography because of stable chest pain. The number of diseased vessels was used to represent the severity of CAD. Serum OPG levels were measured by ELISA and were significantly greater in patients with significant stenosis of the coronary arteries than in those without stenosis. As the severity of CAD increased, there was a significant increase in serum OPG levels. Serum OPG levels were 0.94Ϯ0. 1 Recently, it has been demonstrated that OPG is produced by a variety of tissues, including the cardiovascular system (heart, arteries, veins), lung, kidney, and immune tissues, as well as bone, 1,2 and that the expression and production of OPG are regulated by various cytokines and hormones. 3 It has been shown that OPGdeficient mice develop severe osteoporosis and medial arterial calcification of the aorta and renal arteries, 4 and that the development of osteoporosis and arterial calcification was completely prevented by restoration of the gene. 5 OPG is also expressed in vascular cells such as coronary smooth muscle cells and endothelial cells in vitro. 6 In endothelial cells, OPG has been demonstrated to act as an anti-apoptotic factor. 7 Moreover, OPG immunoreactivity was demonstrated not only in the nondiseased vessel wall, but also in early atherosclerotic lesions in human tissues. 8 These findings suggest that OPG may play an important role in the development of vascular disease. A recent clinical study reported that there is a significant correlation between elevated serum OPG levels and cardiovascular mortality, 9 suggesting that OPG may contribute to the progression of coronary artery disease (CAD). In this study, we assessed the severity of CAD by coronary angiography and examined whether serum OPG levels are associated with the progression of CAD. Methods PatientsThe present study involved 201 patients who underwent coronary angiography. All patients fulfilled the criteria of stable chest pain and/or signs of myocardial ischemia on exercise electrocardiography for clinical indication for cardiac catheterization. Patients with an acute coronary syndrome were excluded. At the time of a physical examination, blood pressure, body mass index (BMI), and a hematological and biochemical profile were determined. Age and history of cigarette use were assessed through an interview preceding the physical examination. Ninety-six subjects were receiving antian...

These results indicate that use of oral alfacalcidol was associated with reduced risk for cardiovascular death in this cohort of ESRD patients. The result of this observational study warrants further randomized controlled trials with 1alpha-hydroxy vitamin D3 to confirm the possibility that such medication improves survival of ESRD patients.

Abstract. Insulin resistance is closely associated with atherosclerosis and cardiovascular mortality in the general population. Patients with end-stage renal disease (ESRD) are known to have insulin resistance, advanced atherosclerosis, and a high cardiovascular mortality rate. We evaluated whether insulin resistance is a predictor of cardiovascular death in a cohort of ESRD. A prospective observational cohort study was performed in 183 nondiabetic patients with ESRD treated with maintenance hemodialysis. Insulin resistance was evaluated by the homeostasis model assessment method (HOMA-IR) using fasting glucose and insulin levels at baseline, and the cohort was followed for a mean period of 67 mo. Forty-nine deaths were recorded, including 22 cardiovascular deaths. Cumulative incidence of cardiovascular death by Kaplan-Meier estimation was significantly different between subjects in the top tertile of HOMA-IR (1.40 to 4.59) and those in the lower tertiles of HOMA-IR (0.28 to 1.39), and the hazard ratio (HR) was 2.60 (95% confidence interval [CI], 1.12 to 6.01; P ϭ 0.026) in the univariate Cox proportional hazards model. In multivariate Cox models, the positive association between HOMA-IR and cardiovascular mortality remained significant (HR, 4.60; 95% CI, 1.83 to 11.55; P ϭ 0.001) and independent of age, C-reactive protein, and presence of preexisting vascular complications. Further analyses showed that the effect of HOMA-IR on cardiovascular mortality was independent of body mass index, hypertension, and dyslipidemia. In contrast, HOMA-IR did not show such a significant association with noncardiovascular mortality. These results indicate that insulin resistance is an independent predictor of cardiovascular mortality in ESRD.

Objective. To determine whether arterial wall thickening is advanced in rheumatoid arthritis (RA) patients compared with healthy controls by measuring the intima-media thickness (IMT) of the common carotid and femoral arteries, and to evaluate the factors associated with arterial IMT in patients with RA.Methods. We studied 138 RA patients and 94 healthy controls (matched for age, sex, and other major risk factors for atherosclerosis). Conclusion. RA patients exhibited greater thickness of the common carotid and femoral arteries than healthy controls. The duration and severity of RA and decreased activities of daily living, but not corticosteroid treatment, were independently associated with the increased arterial wall thickness.