Paul Welsh1, Claire Welsh2, Carlos A Celis-Morales1,3, Rosemary Brown1, Frederick K Ho3, Lyn D Ferguson1, Patrick B Mark1, James Lewsey3, Stuart R Gray1, Donald M Lyall3, Jason M R Gill1, Jill P Pell3, James A de Lemos4, Peter Willeit5,6, Naveed Sattar1. 1. Institute of Cardiovascular and Medical Sciences, University of Glasgow, BHF Glasgow Cardiovascular Research Centre, 126 University Place, Glasgow G12 8TA, UK. 2. Population Health Sciences Institute, Faculty of Medical Sciences, Newcastle University, Newcastle, UK. 3. Institute of Health and Wellbeing, University of Glasgow, 1 Lilybank Gardens, Glasgow G12 8RZ, UK. 4. Division of Cardiology, Department of Medicine, University of Texas Southwestern Medical Center, 5323 Harry Hines Blvd, Dallas, TX 75390, USA. 5. Department of Neurology, Medical University of Innsbruck, Anichstraße 35, Innsbruck 6020, Austria. 6. Department of Public Health and Primary Care, University of Cambridge, Strangeways Research Laboratory, Worts Causeway, Cambridge CB1 8RN, UK.
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.
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.
Authors: Lisandro D Colantonio; Vera Bittner; Monika M Safford; Santica Marcovina; Todd M Brown; Elizabeth A Jackson; Mei Li; J Antonio G López; Keri L Monda; Timothy B Plante; Shia T Kent; Paul Muntner; Robert S Rosenson Journal: J Am Heart Assoc Date: 2022-05-27 Impact factor: 6.106
Authors: Jun-Xu Gu; Juan Huang; Shan-Shan Li; Li-Hua Zhou; Ming Yang; Yang Li; Ai-Min Zhang; Yue Yin; Na Zhang; Mei Jia; Ming Su Journal: Sci Rep Date: 2022-03-04 Impact factor: 4.379