Lipoprotein(a) and cardiovascular disease: prediction, attributable risk fraction, and estimating benefits from novel interventions. (7th October 2020)

• Record Type: Journal Article
• Authors: Welsh, Paul; Welsh, Claire; Celis-Morales, Carlos A; Brown, Rosemary; Ho, Frederick K; Ferguson, Lyn D; Mark, Patrick B; Lewsey, James; Gray, Stuart R; Lyall, Donald M; Gill, Jason M R; Pell, Jill P; de Lemos, James A; Willeit, Peter; Sattar, Naveed
• Is Part Of: European journal of preventive cardiology. Volume 28:Number 18(2021)
• Page Start: 1991
• Page End: 2000
• Publication Date: 2020-10-07
• Subjects: Lipoprotein(a) -- Cardiovascular disease -- Epidemiology -- Risk prediction; Cardiovascular system -- Diseases -- Prevention -- Periodicals; Cardiac patients -- Rehabilitation -- Periodicals; 616.12
• DOI: 10.1093/eurjpc/zwaa063
• Languages: English
• ISSNs: 2047-4873

Abstract

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.