High-density lipoprotein cholesterol in the cardiovascular equation: does the "good" still count?

This article will discuss our current understanding of the role of HDL-C in the statin era, focusing on the question as to whether HDL-C still “counts” when determining cardiovascular risk. Epidemiologic evidence consistently demonstrates that low HDL-C is a strong and independent risk factor for CHD. The epidemiologic evidence is complimented by clinical data showing that interventions that raise HDL-C are associated with reductions in CHD risk, as well as by a growing body of experimental data demonstrating biologically plausible mechanisms that may underlie the observed clinical findings. Analyses of large statin trials also indicate that the significant and independent relationship between HDL-C and CHD risk persists despite the therapeutic effects of statins, and that HDL-C levels in statin-treated patients, both at baseline and in response to statin therapy, are relevant. Early studies on novel HDL targeting therapies are promising, but their long term safety profile and impact on clinical outcomes is yet to be determined in larger studies. Recent guidelines emphasize low HDL-C as an independent risk factor for cardiovascular disease, specifically identify HDL-C as a target for intervention, and encourage the use of HDL-C raising interventions in high-risk patients with low HDL-C levels.     

General practitioners' satisfaction with and attitudes to out-of-hours services

Background  

In recent years, Dutch general practitioner (GP) out-of-hours service has been reorganised into large-scale GP cooperatives. Until now little is known about GPs' experiences with working at these cooperatives for out-of-hours care. The purpose of this study is to gain insight into GPs' satisfaction with working at GP cooperatives for out-of-hours care in separated and integrated cooperatives.     

Extent to which accepted serum lipid goals are achieved in a contemporary general medical population with coronary heart disease risk equivalents

This study examined lipid levels and the use of lipid-altering drugs in a contemporary general medical population without documented coronary heart disease (CHD) but with CHD risk equivalents. On the basis of present national guidelines, the following lipid values (in milligrams per deciliter) were considered optimal for this population: low-density lipoprotein cholesterol <100, high-density lipoprotein (HDL) cholesterol >or=40 in men and >or=50 in women, and non-HDL cholesterol <130 if triglycerides are >or=200. Of 44,052 active patients screened, 877 with CHD risk equivalents as defined by the Adult Treatment Panel III guidelines were identified. Most patients did not meet optimal lipid targets for low-density lipoprotein cholesterol (59%), HDL cholesterol (66%), and non-HDL cholesterol (72%). Indeed, 88% of patients did not meet >or=1 lipid goal. Statins were used in 57% of patients. In patients with low HDL cholesterol, only 4.7% were taking niacin and 4.9% fibrates. In the subgroup of patients with triglycerides >or=200 mg/dl, only 9.5% were taking fibrates and 8.2% niacin. In conclusion, the present analysis highlights the dramatic need to further improve preventive measures in a substantial proportion of high-risk patients with CHD risk equivalents.     

Endothelial function and soluble endoglin in smokers with heart failure

Background:

Although cigarette smoking is a risk factor for heart failure (HF), smokers with HF have lower mortality rates during/following hospitalization compared to nonsmokers. We examined vascular endothelial function in chronic smokers and nonsmokers with HF as it relates to this smoker's paradox.

Hypothesis:

Smokers with HF will have attenuated endothelial dysfunction compared to non‐smokers with HF.

Methods:

Brachial artery flow‐mediated dilation (FMD), a measure of conduit vessel endothelial function, was measured in 33 smoking and nonsmoking patients with HF vs controls. In addition, soluble endoglin (sEng), a circulating mediator of endothelial function, was measured in a separate group of 36 smoking and nonsmoking patients with HF vs controls.

Results:

FMD was significantly lower in smokers without HF compared to the nonsmokers without HF (P < 0.05). FMD was significantly higher in smokers with HF vs nonsmokers with HF (P < 0.05) and did not differ from values seen in nonsmokers without HF (P > 0.05). There were no differences in sEng between smokers and nonsmokers without HF (P > 0.05). sEng was lower in smokers with HF vs nonsmokers with HF (P < 0.05) and did not differ from values seen in nonsmokers without HF (P > 0.05).

Conclusions:

Smokers with HF had higher brachial FMD and lower sEng than nonsmokers with HF, and values were comparable to nonsmokers without HF. These findings offer novel insight into the smoker's paradox and suggest that improved short‐term outcome in patients hospitalized with HF may in part be mediated by preservation of vascular endothelial function in this setting. © 2011 Wiley Periodicals, Inc. The authors have no funding, financial relationships, or conflicts of interest to disclose.     

2010年欧洲神经病学联盟阿尔茨海默病诊疗指南

一、概述 (一)目的 2008年成立工作组的目的是修改前一版欧洲神经病学联盟(EFNS)的阿尔茨海默病(AD)诊疗指南.前一版指南采用了第4版诊断和统计手册(DSM Ⅳ)及美国国立神经病学、语言障碍和脑卒中研究所-阿尔茨海默病及相关疾病学会(NINCDS-ADRDA)对痴呆综合征和AD的诊断标准.     

Systematic Review for the 2018 AHA/ACC/AACVPR/AAPA/ABC/ACPM/ADA/AGS/APhA/ASPC/NLA/PCNA Guideline on the Management of Blood Cholesterol: A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines

BackgroundThe 2013 American College of Cardiology/American Heart Association guidelines for the treatment of blood cholesterol found little evidence to support the use of nonstatin lipid-modifying medications to reduce atherosclerotic cardiovascular disease (ASCVD) events. Since publication of these guidelines, multiple randomized controlled trials evaluating nonstatin lipid-modifying medications have been published.MethodsWe performed a systematic review to assess the magnitude of benefit and/or harm from additional lipid-modifying therapies compared with statins alone in individuals with known ASCVD or at high risk of ASCVD. We included data from randomized controlled trials with a sample size of >1,000 patients and designed for follow-up >1 year. We performed a comprehensive literature search and identified 10 randomized controlled trials for intensive review, including trials evaluating ezetimibe, niacin, cholesterol-ester transfer protein inhibitors, and PCSK9 inhibitors. The prespecified primary outcome for this review was a composite of fatal cardiovascular events, nonfatal myocardial infarction, and nonfatal stroke.ResultsThe cardiovascular benefit of nonstatin lipid-modifying therapies varied significantly according to the class of medication. There was evidence for reduced ASCVD morbidity with ezetimibe and 2 PSCK9 inhibitors. Reduced ASCVD mortality rate was reported for 1 PCSK9 inhibitor. The use of ezetimibe/simvastatin versus simvastatin in IMPROVE-IT (Improved Reduction of Outcomes: Vytorin Efficacy International Trial) reduced the primary outcome by 1.8% over 7 years (hazard ratio: 0.90; 95% CI: 0.84–0.96], 7-year number needed to treat: 56). The PSCK9 inhibitor evolocumab in the FOURIER study (Further Cardiovascular Outcomes Research with PCSK9 Inhibition in Subjects with Elevated Risk) decreased the primary outcome by 1.5% over 2.2 years (hazard ratio: 0.80; 95% CI: 0.73–0.88; 2.2=year number needed to treat: 67). In ODYSSEY OUTCOMES (Evaluation of Cardiovascular Outcomes After an Acute Coronary Syndrome During Treatment With Alirocumab), alirocumab reduced the primary outcome by 1.6% over 2.8 years (hazard ratio: 0.86; 95% CI: 0.79–0.93; 2.8-year number needed to treat: 63). For ezetimibe and the PSCK9 inhibitors, rates of musculoskeletal, neurocognitive, gastrointestinal, or other adverse event risks did not differ between the treatment and control groups. For patients at high risk of ASCVD already on background statin therapy, there was minimal evidence for improved ASCVD risk or adverse events with cholesterol-ester transfer protein inhibitors. There was no evidence of benefit for the addition of niacin to statin therapy. Direct comparisons of the results of the 10 randomized controlled trials were limited by significant differences in sample size, duration of follow-up, and reported primary outcomes.ConclusionsIn a systematic review of the evidence for adding nonstatin lipid-modifying therapies to statins to reduce ASCVD risk, we found evidence of benefit for ezetimibe and PCSK9 inhibitors but not for niacin or cholesterol-ester transfer protein inhibitors.