Department of Clinical Biochemistry, Copenhagen University Hospital-Herlev and Gentofte, Denmark; The Copenhagen General Population Study, Copenhagen University Hospital-Herlev and Gentofte, Denmark; Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
Department of Clinical Biochemistry, Copenhagen University Hospital-Herlev and Gentofte, Denmark; The Copenhagen General Population Study, Copenhagen University Hospital-Herlev and Gentofte, Denmark.
J Am Coll Cardiol. 2023 Dec 12;82(24):2265-2276. doi: 10.1016/j.jacc.2023.10.009.
BACKGROUND: Lp(a) (lipoprotein[a])-lowering therapy to reduce cardiovascular disease is under investigation in phase 3 clinical trials. High Lp(a) may be implicated in peripheral artery disease (PAD), abdominal aortic aneurysms (AAAs), and major adverse limb events (MALE). OBJECTIVES: The authors investigated the association of high Lp(a) levels and corresponding LPA genotypes with risk of PAD, AAA, and MALE. METHODS: The authors included 108,146 individuals from the Copenhagen General Population Study. During follow-up, 2,450 developed PAD, and 1,251 AAAs. Risk of MALE was assessed in individuals with PAD at baseline and replicated in the Copenhagen City Heart Study. RESULTS: Higher Lp(a) was associated with a stepwise increase in risk of PAD and AAA (P for trend <0.001). For individuals with Lp(a) levels ≥99th (≥143 mg/dL, ≥307 nmol/L) vs <50th percentile (≤9 mg/dL, ≤17 nmol/L), multivariable-adjusted HRs were 2.99 (95% CI: 2.09-4.30) for PAD and 2.22 (95% CI: 1.21-4.07) for AAA. For individuals with PAD, the corresponding incidence rate ratio for MALE was 3.04 (95% CI: 1.55-5.98). Per 50 mg/dL (105 nmol/L) genetically higher Lp(a) risk ratios were 1.39 (95% CI: 1.24-1.56) for PAD and 1.21 (95% CI: 1.01-1.44) for AAA, consistent with observational risk ratios of 1.33 (95% CI: 1.24-1.43) and 1.27 (95% CI: 1.15-1.41), respectively. In women smokers aged 70 to 79 years with Lp(a) <50th and ≥99th percentile, absolute 10-year risks of PAD were 8% and 21%, and equivalent risks in men 11% and 29%, respectively. For AAA, corresponding risks were 2% and 4% in women, and 5% and 12% in men. CONCLUSIONS: High Lp(a) levels increased risk of PAD, AAA, and MALE by 2- to 3-fold in the general population, opening opportunities for prevention given future Lp(a)-lowering therapies.
背景：脂蛋白(a)[Lp(a)]降低疗法可降低心血管疾病风险，目前正在进行 3 期临床试验。高水平的 Lp(a)可能与外周动脉疾病（PAD）、腹主动脉瘤（AAA）和主要不良肢体事件（MALE）有关。
目的：作者研究了高 Lp(a)水平及其相应的 LPA 基因型与 PAD、AAA 和 MALE 风险的相关性。
方法：作者纳入了来自哥本哈根普通人群研究的 108146 名个体。在随访期间，有 2450 人发生 PAD，1251 人发生 AAA。在基线时患有 PAD 的个体中评估了 MALE 的风险，并在哥本哈根城市心脏研究中进行了复制。
结果：Lp(a)水平越高，PAD 和 AAA 的风险呈逐步增加（趋势 P<0.001）。对于 Lp(a)水平≥99 百分位（≥143mg/dL，≥307nmol/L）与<50 百分位（≤9mg/dL，≤17nmol/L）的个体，多变量调整后的 HR 分别为 PAD 的 2.99（95%CI：2.09-4.30）和 AAA 的 2.22（95%CI：1.21-4.07）。对于患有 PAD 的个体，MALE 的相应发病率比为 3.04（95%CI：1.55-5.98）。每增加 50mg/dL（105nmol/L），Lp(a)的遗传风险比为 1.39（95%CI：1.24-1.56）用于 PAD 和 1.21（95%CI：1.01-1.44）用于 AAA，与观察性风险比 1.33（95%CI：1.24-1.43）和 1.27（95%CI：1.15-1.41）一致。在年龄在 70 至 79 岁的女性吸烟者中，Lp(a)处于<50 百分位和≥99 百分位时，PAD 的 10 年绝对风险分别为 8%和 21%，男性分别为 11%和 29%。对于 AAA，女性的相应风险分别为 2%和 4%，男性分别为 5%和 12%。
结论：在普通人群中，高水平的 Lp(a)使 PAD、AAA 和 MALE 的风险增加了 2 至 3 倍，为未来的 Lp(a)降低疗法提供了预防机会。
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