Twenty-year trends in major cardiovascular risk factors in hospitalized patients with acute myocardial infarction in Beijing / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Hypertension, diabetes mellitus, hypercholesterolaemia and current smoking are the strongest modifiable cardiovascular risk factors for acute myocardial infarction (AMI). We examined their changing trends over the last 20 years.</p><p><b>METHODS</b>The clinical data of 3498 patients hospitalized in Peking University People's Hospital with AMI from 1991 to 2010 were used. Information was collected regarding to patients' demographic data, cardiovascular risk factors (hypertension, diabetes mellitus, hypercholesterolemia and current smoking). To assess trends over time in the prevalence of risk factors, we categorized patients into four groups (1991 to 1995, 1996 to 2000, 2001 to 2005 and 2006 to 2010).</p><p><b>RESULTS</b>Highly significant increases were observed in the prevalence of hypertension from 40.8% to 55.6% for males and from 58.0% to 69.0% for females; and diabetes mellitus from 12.9% to 30.8% for males and from 23.0% to 42.3% for females. Similarly, the prevalence of hypercholesterolaemia decreased from 53.1% to 30.7% for males and from 57.0% to 44.0% for females. The prevalence of current smoking decreased in females from 29.0% to 11.1%, but remained unchanged in males. In addition, the proportion of patients with more than three modifiable risk factors increased from 19.0% to 27.1% and the age at onset of AMI extended to younger as well as older individuals.</p><p><b>CONCLUSIONS</b>The prevalence of hypertension and diabetes mellitus are still increasing in patients with AMI in Beijing and although the prevalence of hypercholesterolaemia and current smoking decreased, high clustering of risk factors were commonly present. These adverse trends show a compelling need for more effective management of cardiovascular risk factors.</p>

A meta-analysis on the safety of combination therapy with fenofibrate and statins / 中华心血管病杂志

<p><b>OBJECTIVE</b>The aim of this study was to assess the safety of fenofibrate-statin combination therapy.</p><p><b>METHODS</b>Medline, Cochrane Library, Web of Knowledge and CNKI were searched for 2184 randomized controlled trials. Finally, twenty-six studies with a total of 9494 participants were included in this analysis.</p><p><b>RESULTS</b>Compared with statins group, the fenofibrate-statin group had significantly higher incidence of aminotransferase elevations (OR 1.67, 95%CI 1.22-2.30, P < 0.05) . The two groups had identical incidence of creatin kinase elevations (OR 0.86, 95%CI 0.62-1.20, P > 0.05) , muscle-associated adverse events (OR 0.98, 95%CI 0.88-1.09, P > 0.05) and withdrawals due to hepatotoxicity or muscle toxicity. The safety of fenofibrate + standard-dose statin regimens were similar to those in fenofibrate-statin group.</p><p><b>CONCLUSION</b>Combined fenofibrate-statin treatment is generally safe and well tolerated, liver function should be monitored before and during and after therapy.</p>

High density lipoprotein suppresses lipoprotein associated phospholipase A2 in human monocytes-derived macrophages through peroxisome proliferator-activated receptor-γ pathway / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Lipoprotein-associated phospholipase A2 (Lp-PLA2) is mainly secreted by macrophages, serving as a specific marker of atherosclerotic plaque and exerting pro-atherogenic effects. It is known that high-density lipoprotein (HDL) plays an important role against atherosclerosis by inhibiting pro-inflammatory factors, however, the relationship between HDL and Lp-PLA2 remains elusive.</p><p><b>METHODS</b>In this study, reverse transcription-polymerase chain reaction (RT-PCR), Western blotting, and a platelet-activating factor (PAF) acetylhydrolase assay were performed to determine the Lp-PLA2 mRNA level, protein expression and activity in human monocyte-derived macrophages upon HDL treatment of different concentrations and durations. To investigate the underlying mechanism of HDL-induced Lp-PLA2 action, pioglitazone, a peroxisome proliferator-activated receptor-γ (PPARγ) ligand, was introduced to human monocyte-derived macrophages and mRNA and protein levels of Lp-PLA2, as well as its activity, were determined.</p><p><b>RESULTS</b>Lp-PLA2 mRNA levels, protein expression and activity were significantly inhibited in response to HDL treatment in a dose and time dependent manner in human monocyte-derived macrophages. Pioglitazone treatment (1 - 10 ng/ml) upregulated the Lp-PLA2 mRNA level, protein expression and activity in human monocyte-derived macrophages, while the effects were markedly reversed by HDL. In addition, pioglitazone resulted in a significant increase in PPARγ phosphorylation in human monocyte-derived macrophages, which could be inhibited by HDL.</p><p><b>CONCLUSION</b>These findings indicate that HDL suppresses the expression and activity of Lp-PLA2 in human monocyte-derived macrophages, and the underlying mechanisms may be mediated through the PPARγ pathway.</p>

Elevated plasma lipoprotein-associated phospholipase A₂ activity is associated with plaque rupture in patients with coronary artery disease / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Lipoprotein-associated phospholipase A(2) (Lp-PLA(2)) has recently been shown to be positively related to coronary events in patients with coronary artery disease (CAD). However, direct evidence about the relationship between circulation Lp-PLA(2) activity and vulnerable plaque in patients with CAD remains lacking.</p><p><b>METHODS</b>Plasma Lp-PLA(2) activity was determined in 146 consecutive patients with CAD who underwent clinically-indicated coronary angiography and preinterventional intravascular ultrasound (IVUS).</p><p><b>RESULTS</b>Eighty-three patients were included in the final analysis after the initial screening. Sixty (72.3%) were acute coronary syndrome (ACS) patients and 23 (27.7%) were stable angina pectoris (SAP) patients. Plaque rupture occurred in 39 (47.0%) patients, and 34 (87.2%) were from ACS patients and 5 (12.8%) from SAP patients. There were no significant differences in clinical and angiographic characteristics between patients with plaque rupture and those without plaque rupture, except for smoking, high-sensitive C-reactive protein (hs-CRP) level and Lp-PLA(2) activity (all P < 0.05). IVUS measurement uncovered that patients with plaque rupture had more frequent positive remodeling (74.4% vs. 43.2%, P = 0.004), soft plaques (64.1% vs. 36.4%, P = 0.012) and higher remodeling index (1.13 ± 0.16 vs. 0.99 ± 0.11, P = 0.041) as compared with those without plaque rupture. Multivariate Logistic regression analysis showed that plasma Lp-PLA(2) activity was independently associated with plaque rupture after adjusting for smoking, positive remodeling and soft plaque (Model 1: odds ratio (OR) 1.13, 95% confidence interval (CI): 1.06 - 1.20) or adjusting for smoking, hs-CRP level, positive remodeling and soft plaque (Model 2: OR 1.11, 95%CI: 1.04 - 1.19).</p><p><b>CONCLUSIONS</b>Plasma Lp-PLA(2) activity is associated with plaque rupture in patients with CAD, independently of traditional CAD risk factors, hs-CRP level and IVUS parameters. Lp-PLA(2) may be a risk marker for vulnerable plaques.</p>

Simvastatin suppress lipopolysaccharides induced upregulation of lipoprotein associated phospholipase A(2) expression in macrophages via inactivation of p38MAPK pathway / 中华心血管病杂志

<p><b>OBJECTIVE</b>To investigate the effects of simvastatin on lipopolysaccharides (LPS) induced upregulation of Lp-PLA(2) in human peripheral blood monocytes-macrophages and the related mechanisms.</p><p><b>METHODS</b>Peripheral blood monocytes of healthy volunteer were isolated and incubated for 2-3 days. Monocytes were incubated with various concentrations of LPS for 6 h or with 1 µg/ml of LPS for different times in LPS group. In simvastatin group and MAPK inhibitors groups, cells were pre-treated with simvastatin (10(-2) - 10(-7) mmol/L) or various MAPK inhibitors (10 µmol/L SB203580, 20 µmol/L U0126, and 20 µmol/L SP600125) before LPS co-incubation. Lp-PLA(2) activity was measured by chronometry, Lp-PLA(2) mRNA expression was detected by RT-PCR. Protein expressions of Lp-PLA(2) and p38MAPK and phosphorylated p38MAPK were examined by Western blot.</p><p><b>RESULTS</b>(1) LPS significantly upregulated Lp-PLA(2) mRNA and protein expression, as well as the enzyme activity in a time and concentration dependent manner, which could be significantly attenuated by simvastatin in a time and concentration dependent manner. (2) Simvastatin significantly reduced LPS-induced p38MAPK phosphorylation. The p38 MAPK inhibitor SB203580, but not MEK1/2 inhibitor U0126 and JNK inhibitor SP600125, completely prevented LPS-mediated up-regulation of Lp-PLA(2) at protein level.</p><p><b>CONCLUSION</b>This study demonstrated that LPS significantly upregulated Lp-PLA(2) mRNA and protein expression, as well as the enzyme activity in a time and concentration dependent manner via Rho-p38MAPK pathway, which could be significantly suppressed by simvastatin.</p>

Tongxinluo improves vascular endothelial function in patients with type 2 diabetes / 中华心血管病杂志

<p><b>OBJECTIVE</b>To investigate the effects of Tongxinluo on vascular endothelial function in patients with type 2 diabetes.</p><p><b>METHODS</b>A total of 80 patients with type 2 diabetes were recruited and divided into two groups: Tongxinluo therapy group (n = 40) and conventional therapy group (n = 40). Plasma levels of NO, ET, 6-keto-PGF1alpha and TXB2 and diastolic functions of humeral arteries (measured by high-resolution ultrasound) were measured at baseline and 4 weeks later.</p><p><b>RESULTS</b>The flow-mediated dilation was significantly increased from (8.19 +/- 0.71)% to (12.47 +/- 0.98)% (P < 0.05) in Tongxinluo therapy group after 4 weeks therapy compare to baseline level. Their plasma NO was significantly increased [(47.65 +/- 4.38) pg/ml to (52.91 +/- 4.83) pg/ml, P < 0.001] and plasma ET significantly reduced [(31.23 +/- 2.46) pg/ml to (24.34 +/- 2.46) pg/ml, P < 0.001] post 4 week Tongxinluo therapy. Parameters remained unchanged in the placebo group (P > 0.05) at baseline and 4 weeks later. Non-flow-mediated dilation was unaffected by Tongxinluo therapy.</p><p><b>CONCLUSIONS</b>Tongxinluo improved the vascular endothelial dependent diastolic function in patients with type 2 diabetes by regulating the balance of plasma NO/ET.</p>

The effects after withdrawal of simvastatin on brachial artery endothelial function in patient with coronary heart disease or risk factors / 中华心血管病杂志

<p><b>OBJECTIVE</b>Landmark trials have demonstrated that statins can reduce the risk of coronary events. Despite the widespread use of statins in the settings of primary and secondary prevention of CHD, withdrawal of statins is a frequent problem in clinical practice. Several recent clinical studies have suggested that withdrawal of statin therapy might be associated with an increase in thrombotic vascular events and the onset of acute coronary syndromes. However, the effects of discontinuing of statins treatment on endothelial function and underlying mechanism are unknown. Objectives We investigated the effects after withdrawal of simvastatin on brachial artery endothelial function in patients unreached cholesterol target with coronary heart disease (CHD) or CHD risk factors.</p><p><b>METHODS</b>We included 33 patients with established CHD or CHD risk factors, whose serum cholesterol did not achieve NCEP target level. They were administered simvastatin (20 mg) for 4 weeks. Endothelial dependent flow-mediated vasodilation (FMD) was assessed in the brachial artery using high-resolution ultrasound at baseline, after 4 weeks of simvastatin and after termination of therapy 1 week. We evaluated fasting serum lipid profiles and vasoactive substances simultaneously, included nitric oxide (NO), endothelin (ET), 6-keto-PGF1(alpha) and thromboxane B(2) (TXB(2)), which were measured as plasma prostacyclin and TXA(2) respectively.</p><p><b>RESULTS</b>Simvastatin treatment reduced low density lipoprotein cholesterol (LDL-C) and total cholesterol (TC) levels and improved endothelial-dependent vasodilation in patients after 4 weeks. Withdrawal of simvastatin, however, FMD showed a significant reduction [(4.82 +/- 0.71)% vs (11.51 +/- 0.87)%, P < 0.01], that remained in low level after 1 week, and the FMD were even lower than the baseline values [(4.82 +/- 0.71)% vs (5.89 +/- 0.65)%, P < 0.01]. After terminating simvastatin treatment, serum NO and plasma 6-keto-PGF1(alpha) levels decreased, as well as plasma ET and serum LDL-C levels increased. But there was no significant difference between plasma TXB(2) levels before and after withdrawal of simvastatin (P > 0.05). Overall, there were significant positive correlations between withdrawal-induced changes in FMD and serum NO level (r = 0.674, P = 0.004), whereas no correlations were shown between the changes in FMD and serum LDL-C level (r = -0.414, P = 0.083).</p><p><b>CONCLUSIONS</b>Abrupt withdrawal of simvastatin therapy resulted in the significant adverse impact on brachial artery endothelial function in patients unreached cholesterol target with CHD or CHD risk factors. Termination of therapy may suppress endothelial NO production and impair endothelial function that is independent of lipid-lowering effect.</p>

Efficacy and safety of combination therapy with simvastatin and fenofibrate for combined hyperlipidemia / 中华心血管病杂志

<p><b>OBJECTIVE</b>The aim of this study was to evaluate the efficacy and safety of combination therapy with simvastatin and fenofibrate in patients with combined hyperlipidemia.</p><p><b>METHODS</b>A total of 221 patients with combined hyperlipidemia were randomly assigned to receive 10 mg simvastatin (n = 72) or 200 mg fenofibrate (n = 68), or a combination of 10 mg simvastatin + 200 mg fenofibrate (n = 81) for 6 months. Lipid profiles, physical and laboratory investigations for adverse effects were assessed.</p><p><b>RESULTS</b>(1) Combination treatment were more effective in normalizing lipid profile than any monotherapy. Serum TC, LDL-C, and TG were reduced by 30%, 37% and 56% respectively, whilst HDL-C significantly increased by 24% (all P < 0.01). The improvement in TG and HDL-C achieved by combination treatment was superior to fenofibrate or simvastatin alone. (2) The success rate of TC, LDL-C and TG control in the combination therapy group were 51%, 55% and 61% respectively, with an overall success rate (all three together) of 45%, which was superior to either drug given as monotherapy. (3) All treatments were well tolerated with no increase in adverse events for combination therapy versus monotherapy.</p><p><b>CONCLUSION</b>The results of this study demonstrated that combination therapy with fenofibrate (200 mg/day) and low-dose simvastatin (10 mg/day) is more effective than monotherapy in patients with combined hyperlipidemia, and is generally safe and well tolerated.</p>