Kones Richard
The Cardiometabolic Research Institute, Houston, TX 77054, USA.
Drug Des Devel Ther. 2011;5:325-80. doi: 10.2147/DDDT.S14934. Epub 2011 Jun 13.
A recent explosion in the amount of cardiovascular risk and incipient, undetected subclinical cardiovascular pathology has swept across the globe. Nearly 70% of adult Americans are overweight or obese; the prevalence of visceral obesity stands at 53% and continues to rise. At any one time, 55% of the population is on a weight-loss diet, and almost all fail. Fewer than 15% of adults or children exercise sufficiently, and over 60% engage in no vigorous activity. Among adults, 11%-13% have diabetes, 34% have hypertension, 36% have prehypertension, 36% have prediabetes, 12% have both prediabetes and prehypertension, and 15% of the population with either diabetes, hypertension, or dyslipidemia are undiagnosed. About one-third of the adult population, and 80% of the obese, have fatty livers. With 34% of children overweight or obese, prevalence having doubled in just a few years, type 2 diabetes, hypertension, dyslipidemia, and fatty livers in children are at their highest levels ever. Half of adults have at least one cardiovascular risk factor. Not even 1% of the population attains ideal cardiovascular health. Despite falling coronary death rates for decades, coronary heart disease (CHD) death rates in US women 35 to 54 years of age may now be increasing because of the obesity epidemic. Up to 65% of patients do not have their conventional risk biomarkers under control. Only 30% of high risk patients with CHD achieve aggressive low density lipoprotein (LDL) targets. Of those patients with multiple risk factors, fewer than 10% have all of them adequately controlled. Even when patients are titrated to evidence-based targets, about 70% of cardiac events remain unaddressed. Undertreatment is also common. About two-thirds of high risk primary care patients are not taking needed medications for dyslipidemia. Poor patient adherence, typically below 50%, adds further difficulty. Hence, after all such fractional reductions are multiplied, only a modest portion of total cardiovascular risk burden is actually being eliminated, and the full potential of risk reduction remains unrealized. Worldwide the situation is similar, with the prevalence of metabolic syndrome approaching 50%. Primordial prevention, resulting from healthful lifestyle habits that do not permit the appearance of risk factors, is the preferred method to lower cardiovascular risk. Lowering the prevalence of obesity is the most urgent matter, and is pleiotropic since it affects blood pressure, lipid profiles, glucose metabolism, inflammation, and atherothrombotic disease progression. Physical activity also improves several risk factors, with the additional potential to lower heart rate. Given the current obstacles, success of primordial prevention remains uncertain. At the same time, the consequences of delay and inaction will inevitably be disastrous, and the sense of urgency mounts. Since most CHD events arise in a large subpopulation of low- to moderate-risk individuals, identifying a high proportion of those who will go on to develop events with accuracy remains unlikely. Without a refinement in risk prediction, the current model of targeting high-risk individuals for aggressive therapy may not succeed alone, especially given the rising burden of risk. Estimating cardiovascular risk over a period of 10 years, using scoring systems such as Framingham or SCORE, continues to enjoy widespread use and is recommended for all adults. Limitations in the former have been of concern, including the under- or over-estimation of risk in specific populations, a relatively short 10-year risk horizon, focus on myocardial infarction and CHD death, and exclusion of family history. Classification errors may occur in up to 37% of individuals, particularly women and the young. Several different scoring systems are discussed in this review. The use of lifetime risk is an important conceptual advance, since ≥90% of young adults with a low 10-year risk have a lifetime risk of ≥39%; over half of all American adults have a low 10-year risk but a high lifetime risk. At age 50 the absence of traditional risk factors is associated with extremely low lifetime risk and significantly greater longevity. Pathological and epidemiological data confirm that atherosclerosis begins in early childhood, and advances seamlessly and inexorably throughout life. Risk factors in childhood are similar to those in adults, and track between stages of life. When indicated, aggressive treatment should begin at the earliest indication, and be continued for years. For those patients at intermediate risk according to global risk scores, C-reactive protein (CRP), coronary artery calcium (CAC), and carotid intima-media thickness (CIMT) are available for further stratification. Using statins for primary prevention is recommended by guidelines, is prevalent, but remains underprescribed. Statin drugs are unrivaled, evidence-based, major weapons to lower cardiovascular risk. Even when low density lipoprotein cholesterol (LDL-C) targets are attained, over half of patients continue to have disease progression and clinical events. This residual risk is of great concern, and multiple sources of remaining risk exist. Though clinical evidence is incomplete, altering or raising the blood high density lipoprotein cholesterol (HDL-C) level continues to be pursued. Of all agents available, rosuvastatin produces the greatest reduction in LDL-C, LDL-P, and improvement in apoA-I/apoB, together with a favorable safety profile. Several recent proposals and methods to lower cardiovascular risk are reviewed. A combination of approaches, such as the addition of lifetime risk, refinement of risk prediction, guideline compliance, novel treatments, improvement in adherence, and primordial prevention, including environmental and social intervention, will be necessary to lower the present high risk burden.
心血管风险以及早期未被发现的亚临床心血管病变数量最近在全球范围内激增。近70%的美国成年人超重或肥胖;内脏肥胖的患病率为53%,且仍在上升。在任何时候,55%的人口在进行减肥饮食,但几乎所有人都失败了。不足15%的成年人或儿童进行了足够的锻炼,超过60%的人没有进行剧烈运动。在成年人中,11%-13%患有糖尿病,34%患有高血压,36%患有前期高血压,36%患有糖尿病前期,12%同时患有糖尿病前期和前期高血压,15%患有糖尿病、高血压或血脂异常的人群未被诊断出来。大约三分之一的成年人口以及80%的肥胖者患有脂肪肝。儿童超重或肥胖的患病率在短短几年内翻了一番,达到34%,儿童2型糖尿病、高血压、血脂异常和脂肪肝的患病率处于历史最高水平。一半的成年人至少有一个心血管危险因素。甚至不到1%的人口达到理想的心血管健康状态。尽管几十年来冠心病死亡率一直在下降,但由于肥胖流行,美国35至54岁女性的冠心病死亡率现在可能正在上升。高达65%的患者其传统风险生物标志物未得到控制。只有30%的冠心病高危患者实现了积极的低密度脂蛋白(LDL)目标。在那些有多种危险因素的患者中,不到10%的人所有危险因素都得到了充分控制。即使患者被滴定至基于证据的目标,仍有约70%的心脏事件未得到解决。治疗不足也很常见。大约三分之二的高危初级保健患者没有服用治疗血脂异常所需的药物。患者依从性差,通常低于50%,这进一步增加了困难。因此,在所有这些微小的降低幅度相乘之后,实际上只有一小部分心血管风险负担被消除,降低风险的全部潜力仍未实现。在全球范围内,情况类似,代谢综合征的患病率接近50%。通过健康的生活方式习惯预防危险因素出现的原始预防是降低心血管风险的首选方法。降低肥胖患病率是最紧迫的事情,而且具有多效性,因为它会影响血压、血脂谱、葡萄糖代谢、炎症和动脉粥样硬化血栓形成疾病的进展。体育活动也能改善多种危险因素,还有降低心率的额外潜力。鉴于目前的障碍,原始预防的成功仍不确定。与此同时,拖延和不作为的后果将不可避免地是灾难性的,紧迫感日益增强。由于大多数冠心病事件发生在大量低至中度风险个体的亚群体中,准确识别出高比例的将继续发生事件的个体仍然不太可能。如果不改进风险预测,当前针对高危个体进行积极治疗的模式可能无法单独取得成功,尤其是考虑到不断增加的风险负担。使用弗明汉或SCORE等评分系统来估计十年期心血管风险仍然被广泛使用,并被推荐用于所有成年人。前者的局限性一直受到关注,包括在特定人群中对风险的低估或高估、相对较短的十年风险期限、对心肌梗死和冠心病死亡的关注以及对家族史的排除。高达37%的个体可能会出现分类错误,尤其是女性和年轻人。本综述讨论了几种不同的评分系统。使用终生风险是一个重要的概念进步,因为≥90%十年期风险低的年轻人终生风险≥39%;超过一半的美国成年人十年期风险低但终生风险高。在50岁时不存在传统危险因素与极低的终生风险和显著更长的寿命相关。病理和流行病学数据证实动脉粥样硬化始于儿童早期,并在一生中持续无缝且不可阻挡地发展。儿童期的危险因素与成年人相似,并且在生命各阶段之间具有连续性。如有指征,应在最早出现指征时就开始积极治疗,并持续数年。对于根据全球风险评分处于中等风险的患者,C反应蛋白(CRP)、冠状动脉钙化(CAC)和颈动脉内膜中层厚度(CIMT)可用于进一步分层。指南推荐使用他汀类药物进行一级预防,这种情况很普遍,但处方量仍然不足。他汀类药物是降低心血管风险的无与伦比的、基于证据的主要武器。即使达到了低密度脂蛋白胆固醇(LDL-C)目标,仍有超过一半的患者疾病继续进展并发生临床事件。这种残余风险备受关注,并且存在多种剩余风险来源。尽管临床证据不完整,但人们仍在继续寻求改变或提高血液高密度脂蛋白胆固醇(HDL-C)水平。在所有可用药物中,瑞舒伐他汀在降低LDL-C、LDL-P以及改善载脂蛋白A-I/载脂蛋白B方面效果最佳,并且具有良好的安全性。本文综述了最近几种降低心血管风险的提议和方法。需要综合多种方法,如增加终生风险评估、改进风险预测、遵循指南、采用新疗法、提高依从性以及进行原始预防,包括环境和社会干预,以降低当前的高风险负担。