Lp(a) above 175 nmol/L explains 3% of population cardiovascular disease burden, and lowering it 80% could cut CHD risk by 24%, an analysis of 413,734 UK Biobank participants (Eur J Prev Cardiol 2022)

Original title: Lipoprotein(a) and cardiovascular disease: prediction, attributable risk fraction, and estimating benefits from novel interventions

Eur J Prev Cardiol · 9 February 2022 · 8

Welsh P, Welsh C, Celis-Morales CA, Brown R, Ho FK, Ferguson LD, Mark PB, Lewsey J, Gray SR, Lyall DM, Gill JMR, Pell JP et al.

In 413,734 UK Biobank participants (median Lp(a) 19.7 nmol/L, IQR 7.6-75.3), 20.8% had Lp(a) above 100 nmol/L and 9.2% above 175 nmol/L. After adjustment for classical risk factors, each 1-SD increment in log Lp(a) was associated with a hazard ratio of 1.12 (95% CI 1.10-1.15) for fatal or non-fatal cardiovascular disease, with similar associations for coronary heart disease, peripheral vascular disease and aortic stenosis. Adding Lp(a) to a traditional risk factor model modestly improved discrimination in primary prevention (C-index +0.0017, 95% CI 0.0008-0.0026). Population attributable fraction was 5.8% (95% CI 4.9-6.7%) for Lp(a) above 100 nmol/L and 3.0% (95% CI 2.4-3.6%) for Lp(a) above 175 nmol/L; assuming causality and an achievable 80% Lp(a) reduction, an ongoing trial targeting patients with cardiovascular disease and Lp(a) above 175 nmol/L was modelled to reduce cardiovascular risk by 20.0% and coronary heart disease risk by 24.4%. The findings support population Lp(a) screening to identify those who could benefit most from future Lp(a)-lowering therapy.

Original abstract

Aims: To investigate the population attributable fraction due to elevated lipoprotein (a) (Lp(a)) and the utility of measuring Lp(a) in cardiovascular disease (CVD) risk prediction.

Methods And Results: In 413 734 participants from UK Biobank, associations of serum Lp(a) with composite fatal/non-fatal CVD (n = 10 066 events), fatal CVD (n = 3247), coronary heart disease (CHD; n = 18 292), peripheral vascular disease (PVD; n = 2716), and aortic stenosis (n = 901) were compared using Cox models. Median Lp(a) was 19.7 nmol/L (interquartile interval 7.6-75.3 nmol/L). About 20.8% had Lp(a) values >100 nmol/L; 9.2% had values >175 nmol/L. After adjustment for classical risk factors, 1 SD increment in log Lp(a) was associated with a hazard ratio for fatal/non-fatal CVD of 1.12 [95% confidence interval (CI) 1.10-1.15]. Similar associations were observed with fatal CVD, CHD, PVD, and aortic stenosis. Adding Lp(a) to a prediction model containing traditional CVD risk factors in a primary prevention group improved the C-index by +0.0017 (95% CI 0.0008-0.0026). In the whole cohort, Lp(a) above 100 nmol/L was associated with a population attributable fraction (PAF) of 5.8% (95% CI 4.9-6.7%), and for Lp(a) above 175 nmol/L the PAF was 3.0% (2.4-3.6%). Assuming causality and an achieved Lp(a) reduction of 80%, an ongoing trial to lower Lp(a) in patients with CVD and Lp(a) above 175 nmol/L may reduce CVD risk by 20.0% and CHD by 24.4%. Similar benefits were also modelled in the whole cohort, regardless of baseline CVD.

Conclusion: Population screening for elevated Lp(a) may help to predict CVD and target Lp(a) lowering drugs, if such drugs prove efficacious, to those with markedly elevated levels.

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