Meta-analysis of 100,540 participants finds elevated Lp(a) more than doubles premature ASCVD risk, strongest in South Asians (Eur Heart J Open 2024)

Original title: Association between lipoprotein(a) and premature atherosclerotic cardiovascular disease: a systematic review and meta-analysis

Eur Heart J Open · 26 April 2024 · 7

Tian X, Zhang N, Tse G, Li G, Sun Y, Liu T

This systematic review and meta-analysis searched PubMed and Embase through November 2023 for studies on Lp(a) and premature atherosclerotic cardiovascular disease (ASCVD), pooling 51 studies covering 100,540 participants (mean age 35.3-62.3 years). Higher Lp(a) was significantly associated with composite premature ASCVD (odds ratio 2.15, 95% CI 1.53-3.02), coronary artery disease specifically (odds ratio 2.44, 95% CI 2.06-2.90), and peripheral arterial disease (odds ratio 2.56, 95% CI 1.56-4.21), all P < 0.001. The association remained significant in patients with familial hypercholesterolaemia (odds ratio 3.11, 95% CI 1.63-5.96) and type 2 diabetes (odds ratio 2.23, 95% CI 1.54-3.23). Effects were particularly strong in South Asians (odds ratio 3.71, 95% CI 2.31-5.96) and Caucasians (odds ratio 3.17, 95% CI 2.22-4.52), and in patients with LDL cholesterol at or above 2.6 mmol/L. Elevated Lp(a) consistently predicts premature ASCVD across study designs, populations, and Lp(a) definitions, with the strongest signal in South Asian and Caucasian populations and in patients with familial hypercholesterolaemia or diabetes.

Original abstract

Aims: High lipoprotein(a) [Lp(a)] level has been demonstrated as an important risk factor for atherosclerotic cardiovascular diseases (ASCVD) amongst the older populations, whereas its effects in the younger population remain unclear. This study evaluated the associations between Lp(a) and the risk of premature ASCVD.

Method And Results: PubMed and Embase were searched for related studies until 12 November 2023. Fifty-one studies including 100 540 participants were included. Mean age of patients ranged from 35.3 to 62.3 years. The proportion of male participants ranged from 0% to 100%. The mean follow-up was provided in five studies ranging from 1 year to 40 years. The definition of elevated Lp(a) varied among studies, such as >30 mg/dL, >50 mg/dL, the top tertiles, the top quartiles, the top quintiles, and so on. Higher Lp(a) was significantly associated with the composite ASCVD [odds ratio (OR): 2.15, 95% confidence interval (95% CI): 1.53-3.02, P < 0.001], especially for coronary artery disease (OR: 2.44, 95% CI: 2.06-2.90, P < 0.001) and peripheral arterial disease (OR: 2.56, 95% CI: 1.56-4.21, P < 0.001). This association remained significant in familial hypercholesterolaemia (FH) (OR: 3.11, 95% CI: 1.63-5.96, P < 0.001) and type 2 diabetes mellitus (T2DM) patients (OR: 2.23; 95% CI: 1.54-3.23, P < 0.001).Significant results were observed in South Asians (OR: 3.71, 95% CI: 2.31-5.96, P < 0.001), Caucasians (OR: 3.17, 95% CI: 2.22-4.52, P < 0.001), and patients with baseline low-density lipoprotein cholesterol (LDL-c) level ≥ 2.6 mmol/L.

Conclusion: Elevated Lp(a) predicts the risk of the composite or individual ASCVD in young, regardless of study design, gender, population characteristics (community or hospitalized), different premature definitions, and various Lp(a) measurement approaches. This association was important in South Asians, Caucasians, FH patients, T2DM patients, and patients with baseline LDL-c level ≥ 2.6 mmol/L.

Summary written by lp-a.org from the published abstract; figures as published. Page updated 18 August 2026. Methods.