BACKGROUND Absence of cardiovascular risk factors (CVRFs) is traditionally considered low risk for atherosclerosis; however, individuals without CVRFs, as currently defined, still have events. OBJECTIVES This study sought to identify predictors of subclinical atherosclerosis in CVRF-free individuals. METHODS Participants from the PESA (Progression of Early Subclinical Atherosclerosis) study (n = 4,184) without conventional CVRFs were evaluated (n = 1,779; 45.0 ± 4.1 years, 50.3% women). CVRF freedom was defined as no current smoking and untreated blood pressure <140/90 mm Hg, fasting glucose <126 mg/dl, total cholesterol <240 mg/dl, low-density lipoprotein cholesterol (LDL-C) <160 mg/dl, and high-density lipoprotein cholesterol ≥40 mg/dl. A subgroup with optimal CVRFs (n = 740) was also defined as having blood pressure <120/80 mm Hg, fasting glucose <100 mg/dl, glycosylated hemoglobin <5.7%, and total cholesterol <200 mg/dl. We evaluated ultrasound-detected carotid, iliofemoral, and abdominal aortic plaques; coronary artery calcification; serum biomarkers; and lifestyle. Adjusted odds ratios (with 95% confidence interval) and ordinal logistic regression models were used. RESULTS Subclinical atherosclerosis (plaque or coronary artery calcification) was present in 49.7% of CVRF-free participants. Together with male sex and age, LDL-C was independently associated with atherosclerosis presence and extent, in both the CVRF-free and CVRF-optimal groups (odds ratio [×10 mg/dl]: 1.14 to 1.18; p < 0.01 for all). Atherosclerosis presence and extent was also associated in the CVRF-free group with glycosylated hemoglobin levels. CONCLUSIONS Many CVRF-free middle-aged individuals have atherosclerosis. LDL-C, even at levels currently considered normal, is independently associated with the presence and extent of early systemic atherosclerosis in the absence of major CVRFs. These findings support more effective LDL-C lowering for primordial prevention, even in individuals conventionally considered at optimal risk. (Progression of Early Subclinical Atherosclerosis [PESA] Study; NCT01410318).

中文翻译：

---

在没有危险因素的情况下，正常的低密度脂蛋白胆固醇水平与亚临床动脉粥样硬化有关

背景 缺乏心血管危险因素 (CVRF) 传统上被认为是动脉粥样硬化的低风险。然而，目前定义的没有 CVRF 的个人仍然有事件。目的 本研究旨在确定无 CVRF 个体中亚临床动脉粥样硬化的预测因素。方法 评估了来自 PESA（早期亚临床动脉粥样硬化进展）研究（n = 4,184）的参与者（n = 1,779；45.0 ± 4.1 岁，50.3% 女性）。CVRF 自由定义为目前不吸烟且未经治疗的血压 <140/90 mmHg，空腹血糖 <126 mg/dl，总胆固醇 <240 mg/dl，低密度脂蛋白胆固醇 (LDL-C) <160 mg/dl和高密度脂蛋白胆固醇≥40 mg/dl。具有最佳 CVRF 的亚组 (n = 740) 也被定义为血压 <120/80 mm Hg，空腹血糖 <100 mg/dl，糖化血红蛋白 <5.7%，和总胆固醇 <200 mg/dl。我们评估了超声检测到的颈动脉、髂股和腹主动脉斑块；冠状动脉钙化；血清生物标志物；和生活方式。使用调整后的优势比（95% 置信区间）和有序逻辑回归模型。结果 49.7% 的无 CVRF 参与者存在亚临床动脉粥样硬化（斑块或冠状动脉钙化）。连同男性性别和年龄，在无 CVRF 组和 CVRF 最佳组中，LDL-C 与动脉粥样硬化的存在和程度独立相关（比值比 [×10 mg/dl]：1.14 至 1.18；所有 p < 0.01 ）。在无 CVRF 组中，动脉粥样硬化的存在和程度也与糖化血红蛋白水平相关。结论 许多无 CVRF 的中年人患有动脉粥样硬化。LDL-C，即使在目前被认为是正常的水平，在没有主要 CVRF 的情况下，与早期系统性动脉粥样硬化的存在和程度独立相关。这些发现支持更有效地降低 LDL-C 以进行原始预防，即使在传统上认为处于最佳风险的个体中也是如此。（早期亚临床动脉粥样硬化 [PESA] 研究的进展；NCT01410318）。