Background: Patients with primary elevations of low-density lipoprotein cholesterol (LDL-C) ≥190 mg/dL are at a higher risk of atherosclerotic cardiovascular disease as a result of long-term exposure to markedly elevated LDL-C levels. Therefore, initiation of statin therapy is recommended for these individuals. However, there is a lack of randomized trial evidence supporting these recommendations in primary prevention. In the present analysis, we provide hitherto unpublished data on the cardiovascular effects of LDL-C lowering among a primary prevention population with LDL-C ≥190 mg/dL.

Methods: We aimed to assess the benefits of LDL-C lowering on cardiovascular outcomes among individuals with primary elevations of LDL-C ≥190 mg/dL without preexisting vascular disease at baseline. We performed post hoc analyses from the WOSCOPS (West of Scotland Coronary Prevention Study) randomized, placebo-controlled trial, and observational posttrial long-term follow-up, after excluding individuals with evidence of vascular disease at baseline. WOSCOPS enrolled 6595 men aged 45 to 64 years, who were randomly assigned to pravastatin 40 mg/d or placebo. In the present analyses, 5529 participants without evidence of vascular disease were included, stratified by LDL-C levels into those with LDL-C <190 mg/dL (n=2969; mean LDL-C 178±6 mg/dL) and those with LDL-C ≥190 mg/dL (n=2560; mean LDL-C 206±12 mg/dL). The effect of pravastatin versus placebo on coronary heart disease and major adverse cardiovascular events were assessed over the 4.9-year randomized controlled trial phase and on mortality outcomes over a total of 20 years of follow-up.

Results: Among 5529 individuals without vascular disease, pravastatin reduced the risk of coronary heart disease by 27% (P=0.002) and major adverse cardiovascular events by 25% (P=0.004) consistently among those with and without LDL-C ≥190 mg/dL (P-interaction >0.9). Among individuals with LDL-C ≥190 mg/dL, pravastatin reduced the risk of coronary heart disease by 27% (P=0.033) and major adverse cardiovascular events by 25% (P=0.037) during the initial trial phase and the risk of coronary heart disease death, cardiovascular death, and all-cause mortality by 28% (P=0.020), 25% (P=0.009), and 18% (P=0.004), respectively, over a total of 20 years of follow-up.

Conclusions: The present analyses provide robust novel evidence for the short- and long-term benefits of lowering LDL-C for the primary prevention of cardiovascular disease among individuals with primary elevations of LDL-C ≥190 mg/dL.

背景：长期接触低密度脂蛋白胆固醇（LDL-C）水平显着升高的患者，原发性低密度脂蛋白胆固醇（LDL-C）≥190mg / dL升高的人群罹患动脉粥样硬化性心血管疾病的风险较高。因此，建议这些人开始他汀类药物治疗。但是，缺乏在初级预防中支持这些建议的随机试验证据。在当前的分析中，我们提供了迄今为止尚未发表的有关LDL-C≥190mg / dL的一级预防人群中LDL-C降低对心血管的影响的数据。

方法：我们旨在评估在基线时原发性血管疾病未曾存在血管疾病的情况下，LDL-C降低对原发性LDL-C≥190 mg / dL的个体心血管结果的益处。在排除基线有血管疾病证据的个体后，我们进行了WOSCOPS（苏格兰西部冠状动脉预防研究）的随机，安慰剂对照试验和观察性的试验后长期随访的事后分析。WOSCOPS招募了6595名年龄在45至64岁之间的男性，他们被随机分配给普伐他汀40 mg / d或安慰剂。在本次分析中，纳入了5529名无血管疾病证据的参与者，按LDL-C水平分为LDL-C <190 mg / dL（n = 2969；平均LDL-C 178±6 mg / dL）和那些。 LDL-C≥190mg / dL（n = 2560；平均LDL-C 206±12 mg / dL）。

结果：在5529名无血管疾病的个体中，普伐他汀将LDL-C≥190 mg的患者的冠心病风险降低了27％（P = 0.002），重大心血管不良事件的发生率降低了25％（P = 0.004）。 / dL（P-相互作用> 0.9）。在初始试验阶段，在LDL-C≥190mg / dL的个体中，普伐他汀将冠心病的风险降低了27％（P = 0.033），并将主要的不良心血管事件降低了25％（P = 0.037）。冠心病死亡，心血管死亡和全因死亡率分别降低了28％（P = 0.020），25％（P = 0.009）和18％（P= 0.004），总共进行了20年的随访。

结论：目前的分析为降低LDL-C对初次升高LDL-C≥190mg / dL的个体的心血管疾病的短期和长期获益提供了有力的新证据。