Arnold Natalie, Goßling Alina, Bay Benjamin, Weimann Jessica, Blaum Christopher, Brunner Fabian J, Ferrario Marco M, Brambilla Paolo, Cesana Giancarlo, Leoni Valerio, Palmieri Luigi, Donfrancesco Chiara, Padró Teresa, Andersson Jonas, Jousilahti Pekka, Ojeda Francisco, Zeller Tanja, Linneberg Allan, Söderberg Stefan, Iacoviello Licia, Gianfagna Francesco, Sans Susana, Veronesi Giovanni, Thorand Barbara, Peters Annette, Tunstall-Pedoe Hugh, Kee Frank, Salomaa Veikko, Schnabel Renate B, Kuulasmaa Kari, Blankenberg Stefan, Waldeyer Christoph, Koenig Wolfgang
Department of Cardiology, University Heart & Vascular Center Hamburg, University Medical Center Hamburg-Eppendorf, Hamburg; Hamburg, Germany.
German Center for Cardiovascular Research (DZHK), partner site Hamburg/Kiel/Luebeck, Germany.
Eur J Prev Cardiol. 2025 Jun 12. doi: 10.1093/eurjpc/zwaf340.
AIMS: Deleterious effects Lipoprotein (a) (Lp(a)) might be mitigated by overall cardiovascular (CV) risk reduction. However, data on the relationship between increased Lp(a) and incident coronary heart disease (CHD) according to the distribution of modifiable CV risk factors (CVRF) at baseline are still scarce. We investigated the association between high Lp(a) and incident CHD in the general population, depending on the presence/absence of four major CVRFs (hypertension, diabetes, hypercholesterolemia, smoking) at baseline. METHODS: Overall 66,495 CHD-free individuals from eight European prospective population-based cohorts were included. The cohort was stratified according to CVRF burden at baseline in "0/1 CVRF" (low risk; n= 41,770) and"≥2 CVRFs" (increased risk; n=24,725). Fine and Gray competing risk-adjusted models were calculated for the association between Lp(a) mass (<90th versus ≥90th percentile (pctl.); cut-off 43.2 mg/dL) and future CHD events. RESULTS: During a median follow-up of 9.7 years, 3,467 incident CHD events occurred. Despite being at very low absolute risk based on traditional CVRF, individuals with 0/1CVRF demonstrated a strong association between increased Lp(a) mass (≥90th pctl.) and future CHD events, which was comparable to the association observed among individuals with ≥2 CVRFs. The fully-adjusted sub-distribution Hazard Ratios [sHRs] for elevated Lp(a) were 1.38 (95% CI, 1.12-1.71) versus 1.27 (95% CI, 1.10-1.46) in those having 0/1 versus ≥2 CVRFs at baseline (Pinteraction0.50). CONCLUSION: Among CHD-free subjects, high Lp(a) was related to adverse outcome even in individuals with no or only one CVRF at baseline, thereby generating substantial challenges in mitigating Lp(a)-associated CHD risk in very low risk populations.
目的：降低总体心血管（CV）风险可能会减轻脂蛋白（a）[Lp（a）]的有害影响。然而，根据基线时可改变的CV风险因素（CVRF）分布情况，关于Lp（a）升高与冠心病（CHD）发病之间关系的数据仍然很少。我们根据基线时四种主要CVRF（高血压、糖尿病、高胆固醇血症、吸烟）的有无，研究了普通人群中高Lp（a）与CHD发病之间的关联。 方法：纳入了来自八个欧洲前瞻性人群队列的66495名无CHD个体。根据基线时的CVRF负担，将队列分为“0/1个CVRF”（低风险；n = 41770）和“≥2个CVRF”（风险增加；n = 24725）。计算了Lp（a）质量（<第90百分位数与≥第90百分位数（pctl.）；临界值43.2mg/dL）与未来CHD事件之间关联的Fine和Gray竞争风险调整模型。 结果：在中位随访9.7年期间，发生了3467例CHD发病事件。尽管基于传统CVRF的绝对风险非常低，但0/1个CVRF的个体显示Lp（a）质量增加（≥第90百分位数）与未来CHD事件之间存在很强的关联，这与≥2个CVRF的个体中观察到的关联相当。基线时0/1个与≥2个CVRF的个体中，Lp（a）升高的完全调整后的亚分布风险比[sHRs]分别为1.38（95%CI，1.12 - 1.71）和1.27（95%CI，1.10 - 1.46）（P相互作用 = 0.50）。 结论：在无CHD的受试者中，即使是基线时无或只有一个CVRF的个体，高Lp（a）也与不良结局相关，从而在降低极低风险人群中与Lp（a）相关的CHD风险方面带来了重大挑战。
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