The interactions of Lipoprotein(a) with common cardiovascular risk factors in cardiovascular disease risk: evidence based on the UK Biobank

Background: : Although Lipoprotein(a) (Lp(a)) is associated with cardiovascular disease, it is unclear whether the associated risk is similar in the presence of other concomitant risk factors. Here, we aimed to investigate the interactions between Lp(a) and common cardiovascular risk factors on coro...

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Main Authors: Linjun Ao, Raymond Noordam, J Wouter Jukema, Diana van Heemst, Ko Willems van Dijk
Format: Article
Language:English
Published: Elsevier 2025-06-01
Series:American Journal of Preventive Cardiology
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Online Access:http://www.sciencedirect.com/science/article/pii/S2666667725000832
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author Linjun Ao
Raymond Noordam
J Wouter Jukema
Diana van Heemst
Ko Willems van Dijk
author_facet Linjun Ao
Raymond Noordam
J Wouter Jukema
Diana van Heemst
Ko Willems van Dijk
author_sort Linjun Ao
collection DOAJ
description Background: : Although Lipoprotein(a) (Lp(a)) is associated with cardiovascular disease, it is unclear whether the associated risk is similar in the presence of other concomitant risk factors. Here, we aimed to investigate the interactions between Lp(a) and common cardiovascular risk factors on coronary artery disease (CAD), calcific aortic valve stenosis (CAVS) and ischemic stroke (IS). Methods: : We included 127,958 unrelated European-ancestry participants from UK Biobank (54.7 % women) with data available on Lp(a) and without a baseline history of CAD, CAVS and IS. Multivariable-adjusted Cox proportional hazards interaction models were used to study whether the associations of Lp(a) with outcomes varied based on the level of total cholesterol (Total-C), low-density lipoprotein-cholesterol (LDL-C), triglycerides (TG) and other cardiovascular risk factors. Results: : Higher Lp(a) levels were associated with higher risks of CAD, CAVS and IS. Per 10 mg/dL increase in Lp(a), hazard ratios [95 % confidence interval] were 1.05 [1.04, 1.06], 1.06 [1.04, 1.09], and 1.01 [0.99, 1.03] for CAD, CAVS and IS, respectively. For CAD, interactions were observed between Lp(a) and Total-C (Pinteraction=0.001), LDL-C (Pinteraction=4e-4) and TG (Pinteraction=0.026). In more detail, participants with Lp(a) ≥ 50 mg/dL in the highest quartile of Total-C, LDL-C and TG showed evidence of additive interaction in CAD, with relative excess risk due to interaction (RERI) of 0.42 (0.17, 0.67), 0.44 (0.18, 0.71), and 0.39 (0.12, 0.67), respectively. No such interactions were observed in CAVS and IS. Conclusions: Lp(a)-associated CAD risk seems to particularly affect those having levels of Total-C, LDL-C and TG above the thresholds from clinical guidelines.
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spelling doaj-art-e8cb3639876b4fbaa57d2b996ad3aa922025-08-20T03:21:47ZengElsevierAmerican Journal of Preventive Cardiology2666-66772025-06-012210100810.1016/j.ajpc.2025.101008The interactions of Lipoprotein(a) with common cardiovascular risk factors in cardiovascular disease risk: evidence based on the UK BiobankLinjun Ao0Raymond Noordam1J Wouter Jukema2Diana van Heemst3Ko Willems van Dijk4Department of Human Genetics, Leiden University Medical Center, Leiden, the Netherlands; Corresponding author. Linjun Ao MMed, Department of Human Genetics, Leiden University Medical Center, Leiden, the Netherlands.Department of Clinical Epidemiology, Leiden University Medical Center, Leiden, the Netherlands; Health Campus The Hague/Department of Public Health and Primary Care, Leiden University Medical Center, The Hague, The NetherlandsDepartment of Cardiology, Leiden University Medical Center, Leiden, the Netherlands; Netherlands Heart Institute, Utrecht, the NetherlandsDepartment of Internal Medicine, Section of Gerontology and Geriatrics, Leiden University Medical Center, Leiden, the NetherlandsDepartment of Human Genetics, Leiden University Medical Center, Leiden, the Netherlands; Department of Internal Medicine, Division of Endocrinology, Leiden University Medical Center, Leiden, the Netherlands; Einthoven Laboratory for Experimental Vascular Medicine, Leiden University Medical Center, Leiden, the NetherlandsBackground: : Although Lipoprotein(a) (Lp(a)) is associated with cardiovascular disease, it is unclear whether the associated risk is similar in the presence of other concomitant risk factors. Here, we aimed to investigate the interactions between Lp(a) and common cardiovascular risk factors on coronary artery disease (CAD), calcific aortic valve stenosis (CAVS) and ischemic stroke (IS). Methods: : We included 127,958 unrelated European-ancestry participants from UK Biobank (54.7 % women) with data available on Lp(a) and without a baseline history of CAD, CAVS and IS. Multivariable-adjusted Cox proportional hazards interaction models were used to study whether the associations of Lp(a) with outcomes varied based on the level of total cholesterol (Total-C), low-density lipoprotein-cholesterol (LDL-C), triglycerides (TG) and other cardiovascular risk factors. Results: : Higher Lp(a) levels were associated with higher risks of CAD, CAVS and IS. Per 10 mg/dL increase in Lp(a), hazard ratios [95 % confidence interval] were 1.05 [1.04, 1.06], 1.06 [1.04, 1.09], and 1.01 [0.99, 1.03] for CAD, CAVS and IS, respectively. For CAD, interactions were observed between Lp(a) and Total-C (Pinteraction=0.001), LDL-C (Pinteraction=4e-4) and TG (Pinteraction=0.026). In more detail, participants with Lp(a) ≥ 50 mg/dL in the highest quartile of Total-C, LDL-C and TG showed evidence of additive interaction in CAD, with relative excess risk due to interaction (RERI) of 0.42 (0.17, 0.67), 0.44 (0.18, 0.71), and 0.39 (0.12, 0.67), respectively. No such interactions were observed in CAVS and IS. Conclusions: Lp(a)-associated CAD risk seems to particularly affect those having levels of Total-C, LDL-C and TG above the thresholds from clinical guidelines.http://www.sciencedirect.com/science/article/pii/S2666667725000832Lipoprotein(a) riskInteraction effectsCommon cardiovascular risk factorsCoronary artery diseaseCalcific aortic valve stenosis
spellingShingle Linjun Ao
Raymond Noordam
J Wouter Jukema
Diana van Heemst
Ko Willems van Dijk
The interactions of Lipoprotein(a) with common cardiovascular risk factors in cardiovascular disease risk: evidence based on the UK Biobank
American Journal of Preventive Cardiology
Lipoprotein(a) risk
Interaction effects
Common cardiovascular risk factors
Coronary artery disease
Calcific aortic valve stenosis
title The interactions of Lipoprotein(a) with common cardiovascular risk factors in cardiovascular disease risk: evidence based on the UK Biobank
title_full The interactions of Lipoprotein(a) with common cardiovascular risk factors in cardiovascular disease risk: evidence based on the UK Biobank
title_fullStr The interactions of Lipoprotein(a) with common cardiovascular risk factors in cardiovascular disease risk: evidence based on the UK Biobank
title_full_unstemmed The interactions of Lipoprotein(a) with common cardiovascular risk factors in cardiovascular disease risk: evidence based on the UK Biobank
title_short The interactions of Lipoprotein(a) with common cardiovascular risk factors in cardiovascular disease risk: evidence based on the UK Biobank
title_sort interactions of lipoprotein a with common cardiovascular risk factors in cardiovascular disease risk evidence based on the uk biobank
topic Lipoprotein(a) risk
Interaction effects
Common cardiovascular risk factors
Coronary artery disease
Calcific aortic valve stenosis
url http://www.sciencedirect.com/science/article/pii/S2666667725000832
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