BACKGROUND Studies have failed to establish a clear link between high-density lipoprotein (HDL) cholesterol and cardiovascular disease, leading to the hypothesis that the atheroprotective role of HDL lies in its biological activity rather than in its cholesterol content. However, to date, the association between HDL functional characteristics and acute coronary syndrome has not been investigated comprehensively. METHODS We conducted a case-control study nested within the PREDIMED (Prevención con Dieta Mediterránea) cohort, originally a randomized trial in which participants followed a Mediterranean or low-fat diet. Incident acute coronary syndrome cases (N=167) were individually matched (1:2) to control patients by sex, age, intervention group, body mass index, and follow-up time. We investigated 2 individual manifestations (myocardial infarction, unstable angina) as secondary outcomes. We measured the following functional characteristics: HDL cholesterol concentration (in plasma); cholesterol efflux capacity; antioxidant ability, measured by the HDL oxidative-inflammatory index; phospholipase A2 activity; and sphingosine-1-phosphate, apolipoproteins A-I and A-IV, serum amyloid A, and complement 3 protein (in apolipoprotein B-depleted plasma). We used conditional logistic regression models adjusted for HDL cholesterol levels and cardiovascular risk factors to estimate odds ratios (ORs) between 1-SD increments in HDL functional characteristics and clinical outcomes. RESULTS Low values of cholesterol efflux capacity (OR1SD, 0.58; 95% CI, 0.40-0.83) and low levels of sphingosine-1-phosphate (OR1SD, 0.70; 95% CI, 0.52-0.92) and apolipoprotein A-I (OR1SD, 0.58; 95% CI, 0.42-0.79) were associated with higher odds of acute coronary syndrome. Higher HDL oxidative inflammatory index values were marginally linked to acute coronary syndrome risk (OR1SD, 1.27; 95% CI, 0.99-1.63). Low values of cholesterol efflux capacity (OR1SD, 0.33; 95% CI, 0.18-0.61), sphingosine-1-phosphate (OR1SD: 0.60; 95% CI: 0.40-0.89), and apolipoprotein A-I (OR1SD, 0.59; 95% CI, 0.37-0.93) were particularly linked to myocardial infarction, whereas high HDL oxidative-inflammatory index values (OR1SD, 1.53; 95% CI, 1.01-2.33) and low apolipoprotein A-I levels (OR1SD, 0.52; 95% CI, 0.31-0.88) were associated with unstable angina. CONCLUSIONS Low cholesterol efflux capacity values, pro-oxidant/proinflammatory HDL particles, and low HDL levels of sphingosine-1-phosphate and apolipoprotein A-I were associated with increased odds of acute coronary syndrome and its manifestations in individuals at high cardiovascular risk. CLINICAL TRIAL REGISTRATION URL: https://www.controlled-trials.com/ISRCTN35739639. Unique identifier: ISRCTN35739639.

中文翻译：

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功能异常的高密度脂蛋白与心血管疾病高风险人群中急性冠脉综合征的发生率更高：一项嵌套的病例对照研究。

背景技术研究未能在高密度脂蛋白（HDL）胆固醇和心血管疾病之间建立明确的联系，从而导致以下假设：HDL的抗动脉粥样硬化作用在于其生物活性而不是胆固醇含量。然而，迄今为止，尚未对HDL功能特征与急性冠状动脉综合征之间的关联进行全面研究。方法我们进行了一项病例对照研究，该研究嵌套在PREDIMED（Prevencióncon DietaMediterránea）队列中，该队列最初是一项随机试验，参与者采用地中海或低脂饮食。根据性别，年龄，干预组，体重指数和随访时间，分别对急性冠脉综合征病例（N = 167）（1：2）进行匹配，以控制患者。我们调查了2种个体表现（心肌梗塞，不稳定型心绞痛）作为次要结局。我们测量了以下功能特征：HDL胆固醇浓度（血浆中）；胆固醇外流能力；抗氧化能力，通过HDL氧化-炎症指数测量；磷脂酶A2活性；以及鞘氨醇-1-磷酸，载脂蛋白AI和A-IV，血清淀粉样蛋白A和补体3蛋白（在载脂蛋白B耗尽的血浆中）。我们使用针对HDL胆固醇水平和心血管危险因素进行调整的条件逻辑回归模型来估计HDL功能特征和临床结局的1-SD增量之间的比值比（OR）。结果胆固醇外排能力低值（OR1SD，0.58; 95％CI，0.40-0.83）和低水平的鞘氨醇-1-磷酸（OR1SD，0.70; 95％CI，0.52-0.92）和载脂蛋白AI（OR1SD，0.58; 95％CI，0.42-0。79）与急性冠状动脉综合征的几率更高。较高的HDL氧化炎症指数值与急性冠状动脉综合征风险之间存在轻微关联（OR1SD，1.27； 95％CI，0.99-1.63）。胆固醇外排能力（OR1SD，0.33; 95％CI，0.18-0.61），鞘氨醇-1-磷酸（OR1SD：0.60; 95％CI：0.40-0.89）和载脂蛋白AI（OR1SD，0.59; 95％CI）低（0.37-0.93）与心肌梗死特别相关，而高HDL氧化-炎症指数值（OR1SD，1.53; 95％CI，1.01-2.33）和低载脂蛋白AI水平（OR1SD，0.52; 95％CI，0.31-0.88） ）与不稳定型心绞痛有关。结论：胆固醇外排能力值低，促氧化剂/促炎性HDL颗粒，HDL水平低的鞘氨醇-1-磷酸和载脂蛋白AI与急性冠脉综合征及其在心血管高危人群中的表现增加相关。临床试验注册网址：https：//www.control-trials.com/ISRCTN35739639。唯一标识符：ISRCTN35739639。