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

Welsh, P. et al. (2021) Lipoprotein(a) and cardiovascular disease: prediction, attributable risk fraction and estimating benefits from novel interventions. European Journal of Preventive Cardiology, 28(18), pp. 1991-2000. (doi: 10.1093/eurjpc/zwaa063) (PMID:33624048)

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.

• Item Type: Articles
• Additional Information: This work was supported by a grant from Chest, Heart, and Stroke Association Scotland [Res16/A165], and by the British Heart Foundation Research Excellence Award 20 [RE/18/6/34217].
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Gill, Professor Jason and Ho, Dr Frederick and Welsh, Dr Claire and Ferguson, Dr Lyn and Brown, Miss Rosemary and Mark, Professor Patrick and Welsh, Professor Paul and Lewsey, Professor Jim and Celis, Dr Carlos and Gray, Professor Stuart and Pell, Professor Jill and Sattar, Professor Naveed and Lyall, Dr Donald
• Authors: Welsh, P., Welsh, C., Celis-Morales, C. A., Brown, R., Ho, F. K., Ferguson, L. D., Mark, P. B., Lewsey, J., Gray, S. R., Lyall, D. M., Gill, J. M.R., Pell, J. P., de Lemos, J. A., Willeit, P., and Sattar, N.
• College/School: College of Medical Veterinary and Life Sciences > School of Cardiovascular & Metabolic Health; College of Medical Veterinary and Life Sciences > School of Health & Wellbeing > Health Economics and Health Technology Assessment; College of Medical Veterinary and Life Sciences > School of Health & Wellbeing > Mental Health and Wellbeing; College of Medical Veterinary and Life Sciences > School of Health & Wellbeing > Public Health
• Journal Name: European Journal of Preventive Cardiology
• Publisher: Oxford University Press
• ISSN: 2047-4873
• ISSN (Online): 2047-4881
• Published Online: 07 October 2020
• Copyright Holders: Copyright © 2020 The Authors
• First Published: First published in European Journal of Preventive Cardiology 28(18): 1991-2000
• Publisher Policy: Reproduced under a Creative Commons Licence

Project Code	Award No	Project Name	Principal Investigator	Funder's Name	Funder Ref	Lead Dept
303944		BHF Centre of Excellence	Rhian Touyz	British Heart Foundation (BHF)	RE/18/6/34217	CAMS - Cardiovascular Science