Differential Effects of Atorvastatin and Pitavastatin on Inflammation, Insulin Resistance, and the Carotid Intima-Media Thickness in Patients with Dyslipidemia.

AIMS: 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors (statins) have multiple pleiotropic effects, such as anti-inflammatory and vascular endothelium protection, that are independent of their low-density-lipoprotein (LDL) cholesterol lowering effects. However, whether different statins exert diverse effects on inflammation, insulin resistance, and the progression of carotid atherosclerosis [as indicated by the intima-media thickness (CIMT)] in patients with dyslipidemia remains unclear. METHODS: A total of 146 patients with hypercholesterolemia without known cardiovascular disease were randomly assigned to receive 5 mg/day of atorvastatin (n=73) or 1 mg/day of pitavastatin (n=73). RESULTS: At baseline, age, gender, blood pressure, lipid profiles, and the serum monocyte chemoattractant protein (MCP)-1, homeostasis model assessment of insulin resistance (HOMA-IR) and CIMT values were comparable between the groups. After 12 months of treatment, atorvastatin and pitavastatin equally reduced the LDL cholesterol levels; however, atorvastatin increased the HOMA-IR by ＋26% and pitavastatin decreased this parameter by －13% (p＜0.001). The MCP-1 values were reduced by －28% in the patients treated with pitavastatin and only －11% in those treated with atorvastatin (p=0.016). A greater percent decrease in the mean CIMT from baseline was observed in the patients treated with pitavastatin than in those treated with atorvastatin (－4.9% vs. －0.5%, p=0.020). CONCLUSIONS: These data indicate that, while these agents significantly and equally reduce the LDL cholesterol levels, atorvastatin and pitavastatin have different effects on inflammation, insulin resistance, and the progression of carotid atherosclerosis in patients with dyslipidemia.

Effect of long-term nitrate treatment on cardiac events in patients with vasospastic angina.

BACKGROUND: Nitrates have been widely used as anti-ischemic drugs in patients with vasospastic angina (VSA). However, the effect of long-term nitrate treatment on cardiac events in VSA patients remains unclear. METHODS AND RESULTS: Two-hundred and thirty-one patients with VSA who had not been receiving any antiischemic drugs, including calcium channel blockers (CCBs), nitrates, nicorandil, or any combination of these medications were prospectively enrolled in the present study. All patients had a positive acetylcholine provocation test with normal coronary angiograms, and they received CCBs after enrollment. They were divided into 2 groups based on whether nitrates were included in the treatment: a nitrate group (n=86) and a without nitrate group (n=145). The baseline clinical characteristics and frequency of anginal attacks within 48h before enrollment were similar between the 2 groups. With a median follow-up period of 70.5 months, 29 patients developed cardiac events, including 7 sudden cardiac deaths and 22 re-admissions for acute coronary syndrome. Cardiac events occurred in 19.8% of the nitrate group and in only 8.3% of the patients who were not taking nitrates (P=0.015). In a multivariate analysis, long-term nitrate treatment (hazard ratio 5.18, 95% confidence interval: 1.69-15.89, P=0.004) was an independent predictor of cardiac events. CONCLUSIONS: These data indicate that long-term nitrate treatment in addition to CCBs might not reduce cardiac events in VSA patients.

Upregulation of monocyte tissue factor activity is significantly associated with carotid intima-media thickness in patients with metabolic syndrome.

AIMS: Metabolic syndrome (MS) represents a cluster of cardiovascular risk factors and an increased risk of cardiovascular events. The carotid intima-media thickness (CIMT) is correlated with coronary and carotid atherosclerosis, and is a significant predictor of cardiovascular events. Tissue factor (TF) is an initiator of the extrinsic coagulation cascade and is expressed on peripheral blood monocytes and macrophages in atherosclerotic plaques. TF plays important roles in both thrombosis and atherosclerosis. No study has investigated the relationship between monocyte TF activity and CIMT in MS patients. METHODS: Peripheral blood mononuclear cells (PBMCs) were collected from 39 normal subjects and 110 patients with MS. The procoagulant activity (PCA) in monocytes was measured using a one-stage clotting assay and is expressed as the mean±SD (mU TF/10(6) PBMCs). RESULTS: The PCA in monocytes in MS patients was significantly higher than in normal subjects (86.2 ±69.5 vs. 52.4±9.9 mU TF/10(6) PBMCs, p < 0.001). In multivariate analysis, patient age (ß coefficient= 0.373, p < 0.001), high-density lipoprotein cholesterol (ß coefficient=-0.307, p = 0.001) and PCA (ß coefficient= 0.422, p =0.002) were each significantly and independently associated with CIMT. CONCLUSIONS: These data indicate that the upregulation of monocyte TF activity is significantly associated with CIMT in MS patients.

Impact of statin therapy on renal function and long-term prognosis in acute coronary syndrome patients with chronic kidney disease.

A recent study showed that statins reduce cardiovascular events in stable coronary artery disease patients with chronic kidney disease (CKD). However, it remains unclear whether acute coronary syndrome (ACS) patients with CKD benefit from statins. A total of 501 patients with ACS who underwent successful percutaneous coronary intervention were investigated and CKD was defined as an estimated glomerular filtration rate (eGFR) < 60 mL/minute/1.73 m(2) at discharge. Three hundred and twenty-four of 501 patients (64.7%) had CKD and 173 patients (34.5%) received statins. The patients with CKD were older and had higher blood pressure than those without CKD. With a mean follow-up of 5.2 years, irrespective of treatment assignment, 74 patients with CKD experienced cardiac events (22.8%) in comparison to 25 without CKD (14.1%, HR 1.81; 95% CI 1.15-2.84, P = 0.0095). Cardiac events occurred in only 18 of the patients with CKD treated with statins (16.2%) and in 56 of those treated with CKD without statins (26.3%, HR 0.58; 95% CI 0.34-0.98, P = 0.039), whereas, no significant reduction of the events was observed in the patients without CKD treated with statins versus without having statins (P = 0.130). These data indicate that statin therapy reduces cardiac events in ACS patients with CKD.

Upregulation of monocyte tissue factor activity is significantly associated with low-grade chronic inflammation and insulin resistance in patients with metabolic syndrome.

BACKGROUND: The metabolic syndrome (MetS) is a cluster of cardiovascular risk factors closely linked to inflammation and insulin resistance (IR). Tissue factor (TF) is an initiator of the extrinsic coagulation cascade and is expressed on peripheral blood monocytes and macrophages in atherosclerotic plaques. Monocytes are the principle cells capable of TF synthesis. Therefore, TF plays an important role in both thrombosis and atherosclerosis. Elevated levels of lipopolysaccharide (LPS), a strong stimulator of TF, have been observed in patients with MetS. No study has investigated the relationship between monocyte TF activity and inflammation, and IR in MetS. METHODS AND RESULTS: Peripheral blood mononuclear cells (PBMCs) were collected from 40 normal subjects and 77 patients with MetS. Mononuclear cell TF procoagulant activity (MPCA) was measured with and without 100 pg/ml LPS stimulation using a 1-stage clotting assay and expressed as the mean +/- SD (mU TF/10(6) PBMCs). MPCA in MetS was significantly greater than in normal subjects (without LPS: 88.0+/-74.8 vs 52.6+/-9.8 mU TF/10(6) PBMCs, P<0.001; with LPS: 269.6+/-165.6 vs 158.6+/-42.8 mU TF/10(6) PBMCs, P<0.001). The LPS-stimulated log MPCA in MetS patients was significantly associated with homeostasis model assessment of IR (r=0.256, P=0.024) and log high-sensitivity C-reactive protein (r=0.332, P=0.003). CONCLUSIONS: Upregulation of monocyte TF is significantly associated with low-grade inflammation and IR in MetS.