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

Lookup NU author(s): Dr Claire WelshORCiD, Dr Carlos Celis Morales



This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).


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.

Publication metadata

Author(s): Welsh P, Welsh CE, Celis-Morales CA, Brown R, Ho FK, Ferguson LD, Mark PB, Lewsey J, Gray SR, Lyall DM, Gill JMR, Pell JP, de Lemos JA, Willeit P, Sattar N

Publication type: Article

Publication status: Published

Journal: European Journal of Preventive Cardiology

Year: 2021

Volume: 28

Issue: 18

Pages: 1991-2000

Print publication date: 01/12/2021

Online publication date: 07/10/2020

Acceptance date: 26/08/2020

Date deposited: 04/06/2021

ISSN (print): 2047-4873

ISSN (electronic): 2047-4881

Publisher: Oxford University Press


DOI: 10.1093/eurjpc/zwaa063


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