Non-high-density lipoprotein cholesterol is a practical predictor of long-term cardiac death after coronary artery bypass grafting.

BACKGROUND: Recent studies have demonstrated that non-high-density lipoprotein cholesterol (non-HDL-C) can predict the risk of cardiovascular events among general population without coronary heart disease (CHD). However, few studies have investigated the predictive value of non-HDL-C for long-term prognosis in patients with CHD. The purpose of this study was to investigate whether non-HDL-C can predict long-term cardiovascular events in patients with CHD who underwent coronary artery bypass grafting (CABG). METHODS: We enrolled 1074 consecutive patients who underwent CABG at Juntendo University Hospital between 1984 and 1994, and obtained mortality data through 2000. We divided the patients into 2 groups by the median non-HDL-C level at baseline (180 mg/dL) and used Kaplan-Meier method with log-rank test for survival analyses. Cox proportional-hazard regression model was used to calculate the relative risk (RR) of cardiac death. RESULTS: The mean follow-up period was 10.6±3.5 years. The survival rate of cardiac death was significantly lower in the high non-HDL-C group than that in the low non-HDL-C group (log-rank test; p=0.006). Furthermore, in proportional regression analysis adjusted for conventional coronary risk factors, metabolic syndrome, statin treatment, and use of artery bypass graft, the increased levels of non-HDL-C were significant and independent predictor of cardiac death beyond other lipid parameters (RR1.22; by 10 mg/dL non-HDL-C increasing, 95% confidence interval 1.03-1.44; p<0.05). CONCLUSIONS: The increased levels of non-HDL-C were significantly associated with an increased risk of cardiac death. Baseline non-HDL-C levels may be a practical predictor of long-term cardiac death in patients with CHD after CABG.

Involvement of cholesterol-enriched microdomains in class A scavenger receptor-mediated responses in human macrophages.

OBJECTIVE: Lipid rafts are cholesterol-enriched microdomains on cell membranes. We hypothesized that these microdomains could involve modified low-density lipoprotein (LDL) uptake. METHODS AND RESULTS: Co-localizations of cholesterol-enriched microdomains and CD204 during the uptake of acetyl LDL (AcLDL) and oxidized LDL were observed using Alexa488-labeled polyethylene glycol cholesteryl ester, which is a sensitive probe used to analyze the dynamics of cholesterol-rich lipid microdomains in living cells. The lipid raft disruptors, methyl-ß cyclodextrin and filipin, inhibited the uptake of AcLDL. CD204 siRNA treatments significantly reduced AcLDL uptake by 80%. We also demonstrated the presence of CD204 in the detergent-resistant membrane fraction (DRM) by immunoblotting analysis. The ratio of CD204/flotillin-1 in DRM was increased 11.5-fold by modified LDL administration. The PI3 kinase inhibitor LY294002, but not the Src kinase inhibitor PP1 or the Gαi/o inhibitor pertussis toxin, inhibited modified LDL uptake. The production of interleukin (IL)-8, but not CCL2, CXCL2, CXCL3, IL-6 or tumor necrosis factor-α was increased by AcLDL administration. The AcLDL-induced IL-8 production was inhibited by LY294002 and filipin. CONCLUSIONS: These data firstly demonstrated that PI3 kinase-associated cholesterol-enriched microdomains are involved in CD204-mediated modified LDL uptake in human macrophages. Cholesterol-enriched microdomains may play a critical role in inflammatory processes.

[Prevention and treatment for development and progression of diabetic macroangiopathy with pioglitazone and metformin].

Prevention and treatment for diabetic macroangiopathy, causing the main etiology for mortality in patients with diabetes mellitus, is crucial target point, but is still controversial. Many clinical studies improving glycemic control by insulin and oral drugs were not demonstrating enough prevention for diabetic macroangiopathy to improve life prognosis. Insulin resistance is now considered to be major pathogenesis for diabetic macroangiopathy. The agents that improve insulin resistance, such as metformin and pioglitazone, have multiple effects to improve glucose and lipid metabolism by increasing sensitivity for insulin without increasing insulin secretion and exert anti-atherogenic properties resulting in preventing development of atherosclerosis. Some clinical studies such as UKPDS 34 and PROactive demonstrated preventive effects of these agents for diabetic macroangiopathy.

Concentrations of interleukins, interferon, and C-reactive protein in stable and unstable angina pectoris.

We analyzed the concentrations of interleukins (IL)-6, IL-10, IL-12, and IL-18, interferon (IFN)-gamma, and high-sensitivity C-reactive protein (hsCRP) in 40 patients with unstable angina (UAP), 39 patients with stable angina (SAP), and 52 age- and gender-matched controls. Compared with the control group, IL-12 concentrations were significantly higher in both the SAP and UAP groups, especially in the UAP group, and the IL-18 concentrations tended to be higher in the UAP group. Conversely, IL-10 concentrations were significantly lower in the SAP and UAP groups. Both IL-6 and hsCRP concentrations were significantly higher in the UAP group. The levels of hsCRP were positively correlated with inflammatory or proinflammatory cytokines (IL-6, IL-12, and IL-18), and negatively correlated with anti-inflammatory cytokine (IL-10). Moreover, the levels of IL-12 were positively correlated with IL-18, and negatively correlated with IL-10, and the results revealed the T-helper 1 dominant state. These results suggested that the inflammatory response was strongly associated with coronary atherosclerosis and angina pectoris, and that the T-helper 1 dominance may play an important role in these diseases.