Primary prevention of coronary heart disease: role of cholesterol control in the United States

The benefit of cholesterol-lowering drug therapy in patients with existing coronary heart disease (CHD) is well established through clinical trials. Prevention of recurrent coronary morbidity and mortality in CHD patients is called secondary prevention. In contrast, primary prevention is delaying or preventing altogether new-onset CHD. There are three categories of primary prevention: high-risk, moderate-risk, and long-term (life-time). A recent clinical trial has documented benefit of cholesterol-lowering drugs for prevention of coronary morbidity and mortality and total mortality in hypercholesterolemic, middle-aged men. This trial lends support for including aggressive cholesterol reduction in high-risk primary prevention. However, for such therapy to be cost effective at present-day prices of cholesterol-lowering drugs, only those patients in the higher ranges of risk can be selected for treatment. This leaves a large number of people at moderately high risk for premature CHD because of high cholesterol levels. These persons deserve increased professional attention to risk reduction. In general the nondrug approach is indicated. The latter approach includes eliminating other risk factors, e.g. cigarette smoking and hypertension, and reducing serum cholesterol levels by decreased intakes of saturated fatty acids, cholesterol, and excess total calories. Some moderate-risk patients may require low doses of cholesterol-lowering drugs to achieve the goals for cholesterol reduction. Finally, public health strategies need to be developed for applying the same nondrug approach for the general population for reducing the overall incidence of CHD.     

The role of coronary artery calcium in allocating pharmacotherapy for primary prevention of cardiovascular disease: The ABCs of CAC

Determining optimal candidates for the numerous potential pharmacotherapies for primary prevention of atherosclerotic cardiovascular disease remains challenging. Selective use of coronary artery calcium (CAC) scoring is recommended by the 2018 and 2019 American Heart Association/American College of Cardiology Cholesterol and Primary Prevention Guidelines as a tool for refining cardiovascular disease risk assessment. A growing body of research shows that CAC has potential value in allocation of primary prevention aspirin, determining blood pressure targets and treatment intensity, the intensity of cholesterol management, and use of the more expensive medications for type 2 diabetes. We also review the literature regarding very elevated CAC scores greater than 400 or 1000 and how these scores appear to confer a risk for cardiovascular disease on par with secondary prevention cohorts.     

从指南到临床:谈阿司匹林在心脑血管疾病一级预防中的应用

心脑血管疾病是全球性的健康问题,位居全球死亡原因之首。因其高发病率、高患病率、高病死率、高致残率以及高复发率,给社会和家庭带来沉重的负担。一级预防是减少心脑血管疾病发病和减轻其疾病负担的关键。阿司匹林是目前循证医学证据     

Aspirin therapy and primary prevention of cardiovascular disease in diabetes mellitus

The benefits of aspirin therapy in reducing the subsequent risk of myocardial infarction, stroke and death is well documented in individuals with cardiovascular disease including those with diabetes mellitus (DM). The evidence for aspirin use in primary prevention of cardiovascular events in DM is debatable and meta-analyses do not suggest a proven benefit. Despite the lack of evidence, low-dose aspirin therapy has been recommended by many current diabetes guidelines. This article reviews the results of two recently published large randomized clinical trials that have looked at primary prevention of cardiovascular events using aspirin in patients with DM.     

Glycaemic status and cardiovascular disease in type 2 diabetes mellitus: re-visiting glycated haemoglobin targets for cardiovascular disease prevention

Cardiovascular disease (CVD) is the leading cause of death among people with type 2 diabetes. Recent attention has focused on chronic hyperglycaemia as an additional risk factor in people with diabetes since their excess CVD risk is not entirely explained by traditional cardiovascular risk factors. Clinical trials of intensive glucose control to reduce CVD events have been equivocal, but recent epidemiological studies have shown that HbAlc, a measure of chronic hyperglycaemia, predicts incident cardiovascular events. This review, which focuses on type 2 diabetes, summarizes (i) the epidemiological literature examining the relation between glycaemic status, as assessed by glycated haemoglobin (HbAlc) and CVD, (ii) the controversy regarding treatment goals for HbAlc in terms of preventing microvascular disease vs. macrovascular disease and (iii) on-going clinical trials of intensive glycaemic control for CVD prevention.     

Association of total cholesterol and atherosclerotic cardiovascular disease in patients with follicular thyroid cancer: A real-world study from Chinese populations

The association between serum total cholesterol (TC) level and incident atherosclerotic cardiovascular disease (ASCVD) in patients with follicular thyroid cancer postthyroidectomy is unknown.This was a retrospective study and patients (n = 384) were divided into low and high TC groups according to the median TC level. Incidence of composite ASCVD (myocardial infarction, ischemic stroke, and cardiovascular death) was compared between these 2 groups and factors contributing to the association of TC and ASCVD were evaluated.Patients in the high TC group were older and more likely to have diabetes and have higher C-reactive protein level. After thyroidectomy, serum levels of free triiodothyronine and free thyroxine were lower while thyroid-stimulating hormone level was higher in the high TC group. 31.6% and 39.7% of patients developed hypothyroidism in the low and high TC groups (P < .05) postthyroidectomy. The incidence rate of composite ASCVD was higher in the high TC versus low TC groups, with incidence rate ratio of 1.69 (95% confidence interval [CI]: 1.07–2.69), which was mainly driven by a higher incidence rate of myocardial infarction in the high TC group (incidence rate ratio: 2.11 and 95% CI: 1.10–4.20). In unadjusted model, higher TC was associated with 73% higher risk of composite ASCVD. After adjustment for hypothyroidism, the association of higher TC and composite ASCVD was attenuated into insignificance, with hazard ratio of 0.92 and 95% CI: 0.81 to 1.34.Increased TC level was associated with composite ASCVD, which might be attributed to hypothyroidism postthyroidectomy. The use of levothyroxine might help to prevent hypercholestemia and reduce the incidence of ASCVD.     

阿司匹林心血管病一级预防新证据

本文详细介绍了阿司匹林在心血管疾病一级预防的新证据：高血压最佳治疗研究（HOT）的肾功能异常亚组分析和澳大利亚Fremantle糖尿病研究,并对美国3个学会的声明进行评述,认为这些最新的证据进一步证实了阿司匹林的一级预防效益。     

Cholesterol confusion in primary prevention of coronary artery disease

Summary Despite the impressive relation between an increased blood cholesterol and increased mortality from coronary artery disease and despite the persuasive results of cholesterol-lowering trials in secondary prevention, there are increasing reservations about the wisdom of lowering moderately raised blood cholesterol levels in patients who have no symptoms of coronary artery disease. In particular, there are important differences between total mortality and cardiovascular mortality, and between relative and absolute risks. A policy that may be practiced by clinical cardiologists is proposed. In essence, each patient should be assessed for all the chief cardiovascular risk factors in that particular individual. Primary prevention by cholesterol reduction in the absence of symptoms of coronary artery disease requires very careful judgement and should only be undertaken when there is good evidence that the risk of coronary artery disease can be reduced in absolute terms. For primary prevention to be effective requires that the whole gamut of coronary risk factors should be addressed.     

残余胆固醇与心血管疾病风险的研究现状

残余胆固醇(remnant cholesterol,RC)所趋使的残余风险近来被欧美等国家高度重视。相比于传统血脂四项(低密度脂蛋白胆固醇、总胆固醇、甘油三酯、高密度脂蛋白胆固醇),RC在动脉粥样硬化性心脏病、支架内再狭窄、主动脉瓣狭窄等多种心血管疾病中有着非常重要的预测价值,并且这种预测价值是独立于传统血脂四项的。重视及调控残余胆固醇水平对于改善这些心血管疾病患者的预后具有重要意义。     

Comparison of current guidelines for primary prevention of coronary heart disease

OBJECTIVE: In primary prevention of atherosclerotic disease, it is difficult to decide when medical treatment should be initiated. The main goal of the study was to compare different guidelines for coronary heart disease (CHD) risk assessment and initiation of lipid-lowering therapy. DESIGN: Cross-sectional evaluation. SETTING: An outpatient lipid and diabetes clinic in a university hospital. PARTICIPANTS/METHODS: Risk factor data obtained on 100 consecutive patients (58 men and 42 women) without clinical evidence of cardiovascular disease were used to compare the Framingham risk equation, the U.S. National Cholesterol Education Program (Adult Treatment Panel III) (NCEP ATP III) guidelines, the joint European Societies guidelines, the joint British guidelines, the revised Sheffield table, and the Munster Heart Study calculator (PROCAM) CHD risk assessment and lipid-lowering therapy. RESULTS: Guidelines could be applied to different subsets of the cohort, ranging from 22% (PROCAM) to 95% of the cohort (revised Sheffield table). All guidelines (except PROCAM) could be applied to a total of 62 patients. Guidelines predicted > or =20% risk for developing CHD over 10 years in 53% (NCEP ATP III), 26% (European) and 32% (British), while Framingham predicted this risk level in 34%. CHD risk was estimated to be > or =3%/year in 5% according to Sheffield, while Framingham predicted this risk in 13%. Lipid-lowering drug therapy is recommended in 52% by NCEP ATP III, while European, British, and Sheffield guidelines recommend this in 26%, 35%, and 5%, respectively. CONCLUSIONS: Guidelines for assessing CHD risk and lipid-lowering therapy differ greatly. Therefore, these algorithms must be used with caution.     

老年人群心血管疾病的健康管理及预防

我国心血管疾病(CVD)患病人数持续上升,国民CVD危险因素个体暴露显著增加。老年人群作为特殊群体,其CVD患病率及死亡率均高,并带来了沉重的社会及经济负担。通过有效的CVD健康管理及预防能够有效降低老年人CVD患病率及死亡率,不仅可以延长老年人寿命,而且可以改善老年人生活质量。合理的方式包括:生活方式的干预;血压、血脂、血糖的控制及监测;小剂量阿司匹林的应用。老年人群CVD的健康管理模式需个体化,同时要注意评估衰弱、老年共病、多重用药及个人意愿。     

The role of lipid-lowering therapy in preventing coronary heart disease in patients with type 2 diabetes

Coronary heart disease is the most common cause of death among diabetic patients. The increased risk of coronary heart disease in type 2 diabetes is due, in part, to lipid abnormalities often present in the diabetic patient. Diabetic dyslipidemia is characterized by elevated triglycerides, low high-density lipoprotein cholesterol (HDL-C) and an increased preponderance of small, dense low-density lipoprotein cholesterol (LDL-C) particles. Current guidelines for the prevention of coronary heart disease in diabetic patients identify elevated LDL-C as the primary target of lipid-lowering therapy, and recommend statins as the first-line treatment for diabetic dyslipidemia. This review evaluates the large statin trials that have included diabetic patients, and discusses the role of combination therapy in managing dyslipidemia in diabetic patients.     

Small dense low‐density lipoprotein cholesterol is a promising biomarker for secondary prevention in older men with stable coronary artery disease

Aim

The study objective was to investigate whether small dense low‐density lipoprotein cholesterol (sdLDL‐C) is superior to low‐density lipoprotein cholesterol (LDL‐C) and other biomarkers to predict future cardiovascular events (CE) in secondary prevention.

Methods

sdLDL‐C measured by a homogeneous assay, remnant lipoprotein cholesterol, LDL particle diameter and other biomarkers were compared in 345 men aged ≥65 years with stable coronary artery disease. Baseline LDL‐C was 100.5 ± 30.1 mg/dL. CE including cardiovascular death, onset of acute coronary syndrome, need for arterial revascularization, hospitalization for heart failure, surgery procedure for cardiovascular disease and hospitalization for stroke were monitored for 5 years.

Results

CE occurred in 96 patients during the study period. LDL‐C, sdLDL‐C non‐high‐density lipoprotein cholesterol, apolipoprotein B, remnant lipoprotein cholesterol, glucose, glycated hemoglobin and brain natriuretic peptide were significantly higher; LDL particle diameter and apolipoprotein A‐1 were significantly lower in patients with than in those without CE. Age‐adjusted Cox regression analysis showed that sdLDL‐C per 10 mg/dL, but not LDL‐C, was significantly associated with CE (HR 1.206, 95% CI 1.006–1.446). A significant association of sdLDL‐C and incident CE was observed in statin users (HR 1.252, 95% CI 1.017–1.540), diabetes patients (HR 1.219, 95% CI 1.018–1.460), patients without diabetes (HR 1.257, 95% CI 1.019–1.551) and patients with hypertriglyceridemia (HR 1. 376, 95% CI 1.070–1.770).

Conclusions

sdLDL‐C was the most effective predictor of residual risk of future CE in stable coronary artery disease patients using statins and in high‐risk coronary artery disease patients with diabetes or hypertriglyceridemia. Geriatr Gerontol Int 2018; 18: 965–972 .     

Antiplatelet strategy in primary and secondary prevention of cardiovascular disease in patients with type 2 diabetes mellitus: A perspective from the guideline appraisal

Aims/IntroductionTo appraise guidelines on the antiplatelet strategy of prevention of cardiovascular disease (CVD) in patients with type 2 diabetes mellitus, and highlight the consensuses and controversies to aid clinician decision‐making.Materials and MethodsA systematic search was carried out for guidelines regarding CVD prevention or focusing on type 2 diabetes patients. Appraisal of Guidelines for Research and Evaluation II instrument was utilized to appraise the quality of included guidelines.ResultsOf the 15 guidelines with discrepant Appraisal of Guidelines for Research and Evaluation II scores (66%; interquartile range 51–71%), 10 were defined as “strongly recommended” guidelines. For secondary prevention, >60% of guidelines advocated that the dual antiplatelet therapy was used within 12 months when the type 2 diabetes patients experienced acute coronary syndrome and/or post‐percutaneous coronary intervention or coronary artery bypass grafting, with subsequent long‐term aspirin use. For primary prevention, 80% of guidelines supported that aspirin should not be routinely used by patients with type 2 diabetes. No consensus on whether to prolong dual antiplatelet therapy in secondary prevention, and whether to use aspirin in type 2 diabetes patients with high CVD risk exists in current guidelines.ConclusionsPhysicians should use the recommendations from “strongly recommended” guidelines to make informed decisions and know the consensuses of current guidelines. Dual antiplatelet therapy should be used within 12 months when type 2 diabetes patients experience acute coronary syndrome and/or percutaneous coronary intervention/coronary artery bypass grafting, with subsequent long‐term aspirin use. In primary prevention, aspirin should not be routinely used by individuals with type 2 diabetes, but might be considered for those with high CVD risk.     

The impact of site and extent of clinically evident cardiovascular disease and atherosclerotic burden on new cardiovascular events in patients with Type 2 diabetes. The SMART study.

AIMS: Patients with Type 2 diabetes and coronary heart disease (CHD) have an excess cardiovascular risk. The relationship of both other sites [cerebrovascular disease, peripheral arterial disease (PAD)] and the extent of clinically evident cardiovascular disease (CVD) with the occurrence of new cardiovascular events have not been investigated previously in patients with diabetes. We aimed to quantify this relationship and to assess the additional influence of atherosclerotic burden. METHODS: From 1996 to 2005, 776 patients with Type 2 diabetes with (n = 458) and without (n = 318) clinically evident CVD were followed prospectively for cardiovascular events (cardiovascular death, non-fatal ischaemic stroke or myocardial infarction). CVD was classified according to the site (cerebrovascular disease, CHD, PAD); the extent of atherosclerosis was expressed as the number of affected sites. Carotid intima-media thickness and albuminuria were used as markers of atherosclerotic burden. RESULTS: Compared with patients with diabetes without CVD, the hazard ratio (HR) for a cardiovascular event was 3.8 (95% confidence interval 1.7, 8.5), adjusted for age, gender and potential confounders, in those with cerebrovascular disease, 4.3 (1.9, 9.5) in those with CHD, and 4.6 (2.1, 10.2) in those with PAD. Findings were similar after additional adjustment for atherosclerotic burden. Adjusted HR was 3.4 (1.6, 6.9) for patients with diabetes with one affected site and 6.6 (3.0, 14.3) for those with two or more sites. CONCLUSIONS: Patients with Type 2 diabetes and cerebrovascular disease, CHD or PAD have strongly increased risks for future cardiovascular events which are comparable. This risk increases markedly with the number of different cardiovascular sites affected and is irrespective of atherosclerotic burden.     

Effect of atorvastatin on endothelial function and inflammation in long-duration type 1 diabetic patients without coronary heart disease and arterial hypertension

Aim:  We evaluated the ability of atorvastatin, an HMG-CoA reductase inhibitor, to affect endothelial function and inflammation in long-duration (>10 years) type 1 diabetes mellitus (T1DM) patients without coronary heart disease (CHD) and arterial hypertension (AH).
Methods and Results:  We randomized 204 Caucasians with long-duration T1DM into either the atorvastatin 40 mg/day plus hypolipaemic diet group (n = 154) or the placebo plus hypolipaemic diet group (n = 50) for 6 months. Endothelium-dependent flow-mediated (FMD) and endothelium-independent flow-mediated vasodilatation, serum levels of plasminogen activator inhibitor-1 (PAI-1), von Willebrand factor (vWF) and high sensitivity C-reactive protein (hs-CRP) were estimated before and after treatment. After 6 months of therapy, FMD was increased by 44% in the atorvastatin plus diet group compared with the placebo plus diet group. Treatment with atorvastatin led to a significant reduction in levels of PAI-1 and hs-CRP; however, the elevation of vWF level was observed. In the placebo plus diet group, we observed a significant reduction in levels of hs-CRP but not of vWF and PAI-1.
Conclusions:  Atorvastatin improves endothelial function and reduces some proinflammatory and prothrombotic markers of atherosclerosis in T1DM patients without CHD and AH. The surprising effect of atorvastatin on serum vWF levels in T1DM requires further study.     

The impact of Type 2 diabetes and microalbuminuria on future cardiovascular events in patients with clinically manifest vascular disease from the Second Manifestations of ARTerial disease (SMART) study

Aims Type 2 diabetes mellitus and microalbuminuria are important risk factors for cardiovascular disease (CVD). Whether these two complications are important and independent risk factors for future CVD events in a high‐risk population with clinically manifest vascular disease is unknown. The objectives of this study were to examine the impact of Type 2 diabetes and microalbuminuria on future CVD events. Methods Patients with clinically manifest vascular disease (coronary, cerebral and peripheral vascular disease) from the Second Manifestation of Arterial disease study were followed up for 4 years. Data obtained from 1996–2006 were analysed. At baseline, there were 804 patients with Type 2 diabetes mellitus (mean age 60 years) and 2983 patients without. Incident CVD (n = 458) was defined as hospital‐verified myocardial infarction, stroke, vascular death and the composite of these vascular events. Results Both Type 2 diabetes [hazard ratio (HR) 1.42, 95% confidence interval (CI) 1.16, 1.75] and microalbuminuria (HR 1.86, 95% CI 1.49, 2.33) increased the risk of new cardiovascular events in univariate analyses. From multivariable models, presence of diabetes remained significantly and independently related to incident CVD (HR 1.42, 95% CI 1.11, 1.80). Presence of microalbuminuria also remained significantly independently related to incident CVD (HR 1.38, 95% CI 1.07, 1.77). In diabetes‐stratified analyses, the effect of microalbuminuria on CVD risk was observed only in patients with diabetes. In microalbuminuria‐stratified analyses, the significant and independent effect of diabetes on CVD risk was shown only in the non‐microalbuminuric group. Conclusions In this high‐risk population, both microalbuminuria and Type 2 diabetes are important and independent risk factors for future CVD.     

阿司匹林与心脑血管疾病一级预防:2011新进展

充分的循证医学证据证实阿司匹林在心脑血管疾病的一级预防、二级预防及急性期治疗中有明确的疗效,从而使得阿司匹林成为心脑血管疾病防治的基础用药。因证据充分,阿司匹林是目前惟一被指南推荐用于一级预防的抗血小板药物。在过去的