BACKGROUND Low-density lipoprotein cholesterol (LDL-C) is an important causal risk factor for atherosclerotic cardiovascular disease (ASCVD). However, a sizable proportion of middle-aged individuals with elevated LDL-C level have not developed coronary atherosclerosis as assessed by coronary artery calcification (CAC). Whether presence of CAC modifies the association of LDL-C with ASCVD risk is unknown. We evaluated the association of LDL-C with future ASCVD events in patients with and without CAC. METHODS The study included 23 132 consecutive symptomatic patients evaluated for coronary artery disease using coronary computed tomography angiography (CTA) from the Western Denmark Heart Registry, a seminational, multicenter-based registry with longitudinal registration of patient and procedure data. We assessed the association of LDL-C level obtained before CTA with ASCVD (myocardial infarction and ischemic stroke) events occurring during follow-up stratified by CAC>0 versus CAC=0 using Cox regression models adjusted for baseline characteristics. Outcomes were identified through linkage among national registries covering all hospitals in Denmark. We replicated our results in the National Heart, Lung, and Blood Institute-funded Multi-Ethnic Study of Atherosclerosis. RESULTS During a median follow-up of 4.3 years, 552 patients experienced a first ASCVD event. In the overall population, LDL-C (per 38.7 mg/dL increase) was associated with ASCVD events occurring during follow-up (adjusted hazard ratio [aHR], 1.14 [95% CI, 1.04-1.24]). When stratified by the presence or absence of baseline CAC, LDL-C was only associated with ASCVD in the 10 792/23 132 patients (47%) with CAC>0 (aHR, 1.18 [95% CI, 1.06-1.31]); no association was observed among the 12 340/23 132 patients (53%) with CAC=0 (aHR, 1.02 [95% CI, 0.87-1.18]). Similarly, a very high LDL-C level (>193 mg/dL) versus LDL-C <116 mg/dL was associated with ASCVD in patients with CAC>0 (aHR, 2.42 [95% CI, 1.59-3.67]) but not in those without CAC (aHR, 0.92 [0.48-1.79]). In patients with CAC=0, diabetes, current smoking, and low high-density lipoprotein cholesterol levels were associated with future ASCVD events. The principal findings were replicated in the Multi-Ethnic Study of Atherosclerosis. CONCLUSIONS LDL-C appears to be almost exclusively associated with ASCVD events over ≈5 years of follow-up in middle-aged individuals with versus without evidence of coronary atherosclerosis. This information is valuable for individualized risk assessment among middle-aged people with or without coronary atherosclerosis.

中文翻译：

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低密度脂蛋白胆固醇主要与有冠状动脉粥样硬化证据的患者的动脉粥样硬化心血管疾病事件相关：丹麦西部心脏登记处。

背景 低密度脂蛋白胆固醇 (LDL-C) 是动脉粥样硬化性心血管疾病 (ASCVD) 的重要因果危险因素。然而，根据冠状动脉钙化 (CAC) 评估，相当大比例的 LDL-C 水平升高的中年人并未发展为冠状动脉粥样硬化。CAC 的存在是否会改变 LDL-C 与 ASCVD 风险的关联尚不清楚。我们评估了 LDL-C 与患有和未患有 CAC 的患者未来 ASCVD 事件的关联。方法 该研究纳入了 23 132 名连续有症状的患者，这些患者使用来自西丹麦心脏登记处的冠状动脉计算机断层扫描血管造影 (CTA) 评估冠状动脉疾病，该登记处是一个开创性的、基于多中心的登记处，对患者和手术数据进行纵向登记。我们评估了 CTA 前获得的 LDL-C 水平与随访期间发生的 ASCVD（心肌梗死和缺血性中风）事件的关联，使用针对基线特征调整的 Cox 回归模型按 CAC>0 与 CAC=0 分层。结果是通过覆盖丹麦所有医院的国家登记处之间的联系来确定的。我们在国家心脏、肺和血液研究所资助的动脉粥样硬化多种族研究中复制了我们的结果。结果 在 4.3 年的中位随访期间，552 名患者经历了首次 ASCVD 事件。在总体人群中，LDL-C（每增加 38.7 mg/dL）与随访期间发生的 ASCVD 事件相关（调整后的风险比 [aHR]，1.14 [95% CI，1.04-1.24]）。当按是否存在基线 CAC 进行分层时，LDL-C 仅与 10 792/23 132 名 CAC>0 患者 (47%) 的 ASCVD 相关（aHR，1.18 [95% CI，1.06-1.31]）；在 CAC=0 的 12 340/23 132 名患者 (53%) 中未观察到相关性 (aHR, 1.02 [95% CI, 0.87-1.18])。同样，非常高的 LDL-C 水平（>193 mg/dL）与 LDL-C <116 mg/dL 相比，在 CAC>0 的患者中与 ASCVD 相关（aHR，2.42 [95% CI，1.59-3.67]），但在那些没有 CAC 的人中没有（aHR，0.92 [0.48-1.79]）。在 CAC=0 的患者中，糖尿病、当前吸烟和低高密度脂蛋白胆固醇水平与未来的 ASCVD 事件相关。主要发现在动脉粥样硬化的多种族研究中得到重复。结论 LDL-C 似乎几乎完全与有冠状动脉粥样硬化证据的中年个体超过 5 年的随访期间的 ASCVD 事件相关。该信息对于患有或不患有冠状动脉粥样硬化的中年人进行个体化风险评估很有价值。