Kaur Gurleen, Berman Adam N, Biery David W, Besser Stephanie A, Wu Wanda Y, Weber Brittany, Honigberg Michael C, Nasir Khurram, Gulati Martha, Di Carli Marcelo F, Shaw Leslee J, Bhatt Deepak L, Blankstein Ron
Department of Medicine, Brigham and Women's Hospital Harvard Medical School Boston MA.
Division of Cardiovascular Medicine, Brigham and Women's Hospital Harvard Medical School Boston MA.
J Am Heart Assoc. 2025 May 6;14(9):e035353. doi: 10.1161/JAHA.124.035353. Epub 2025 Apr 16.
BACKGROUND: Sex-based differences in the association of lipoprotein(a) with cardiovascular outcomes have not been well established for those without prior atherosclerotic cardiovascular disease. METHODS AND RESULTS: Patients with no baseline atherosclerotic cardiovascular disease were identified in the MGB (Mass General Brigham) Lp(a) Registry, a retrospective cohort of patients who had lipoprotein(a) measured from 2000 to 2019. Lipoprotein(a) percentile groups were categorized as 1st to 50th (reference), 51st to 70th, 71st to 90th, and 91st to 100th. The primary outcome was a composite of fatal or nonfatal myocardial infarction, or fatal or nonfatal ischemic stroke. Cox proportional hazard modeling was used to assess the association of lipoprotein(a) with the primary outcome. Among 6238 patients with no baseline atherosclerotic cardiovascular disease, 45% were women. Women had higher total cholesterol, low-density lipoprotein cholesterol, and median lipoprotein(a) (33.2 versus 28.9 nmol/L; <0.001), whereas men had higher rates of diabetes and atrial fibrillation. Higher lipoprotein(a) was associated with an increased incidence of the primary composite outcome, with patients in the 91st to 100th percentile group (≥216 nmol/L) having an adjusted hazard ratio (HR) of 2.07 (95% CI, 1.31-3.25; <0.01) in women and 2.39 (95% CI, 1.57-3.65; <0.01) in men, with no interaction based on sex. When examining individual outcomes, the strongest association was present between lipoprotein(a) and fatal or nonfatal myocardial infarction (women: adjusted HR, 2.61 [95% CI, 1.48-4.61]; men: adjusted HR, 3.36 [95% CI, 2.01-5.60]). When stratifying by age, female sex was associated with a lower risk of fatal or nonfatal myocardial infarction in those aged <60 years; however, among older individuals, the risk conferred by elevated lipoprotein(a) was similar between men and women. CONCLUSIONS: Among individuals with no prior atherosclerotic cardiovascular disease, elevated lipoprotein(a) is associated with higher rates of cardiovascular outcomes, particularly myocardial infarction, in both women and men.
背景：对于那些无既往动脉粥样硬化性心血管疾病的患者，脂蛋白(a)与心血管结局之间基于性别的差异尚未完全明确。 方法与结果：在MGB（麻省总医院布莱根分院）脂蛋白(a)登记处中识别出无基线动脉粥样硬化性心血管疾病的患者，该登记处是一个对2000年至2019年期间进行脂蛋白(a)检测的患者的回顾性队列。脂蛋白(a)百分位数分组被分为第1至50百分位数（参考组）、第51至70百分位数、第71至90百分位数和第91至100百分位数。主要结局是致命或非致命性心肌梗死，或致命或非致命性缺血性卒中的复合结局。采用Cox比例风险模型评估脂蛋白(a)与主要结局之间的关联。在6238例无基线动脉粥样硬化性心血管疾病的患者中，45%为女性。女性的总胆固醇、低密度脂蛋白胆固醇水平较高，脂蛋白(a)中位数也较高（33.2对28.9 nmol/L；P<0.001），而男性的糖尿病和心房颤动发生率较高。较高的脂蛋白(a)与主要复合结局的发生率增加相关，第91至100百分位数组（≥216 nmol/L）的女性调整后风险比（HR）为2.07（95%CI，1.31 - 3.25；P<0.01），男性为2.39（95%CI，1.57 - 3.65；P<0.01），不存在基于性别的交互作用。在检查个体结局时，脂蛋白(a)与致命或非致命性心肌梗死之间的关联最强（女性：调整后HR，2.61[95%CI，1.48 - 4.61]；男性：调整后HR，3.36[95%CI，2.01 - 5.60]）。按年龄分层时，<60岁的女性中，女性性别与致命或非致命性心肌梗死风险较低相关；然而，在老年个体中，脂蛋白(a)升高所带来的风险在男性和女性中相似。 结论：在无既往动脉粥样硬化性心血管疾病的个体中，脂蛋白(a)升高与心血管结局发生率较高相关，尤其是心肌梗死，在女性和男性中均如此。
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