Multi-National Evaluation of Low-Density Lipoprotein Cholesterol Equations in Young Adulthood for Long-Term Risk of Atherosclerotic Cardiovascular Disease

Yaxing Meng; Feitong Wu; Markus Juonala; David R Jacobs Jr; Lydia A Bazzano; Stephen R Daniels; Terence Dwyer; Mika Kähönen; Alan R Sinaiko; Julia Steinberger; Elaine M Urbina; Alison J Venn; Jorma S A Viikari; Kara M Whitaker; Jessica G Woo; Olli T Raitakari; Costan G Magnussen

doi:10.1161/CIRCOUTCOMES.125.013678

Journal article

Multi-National Evaluation of Low-Density Lipoprotein Cholesterol Equations in Young Adulthood for Long-Term Risk of Atherosclerotic Cardiovascular Disease

Yaxing Meng, Feitong Wu, Markus Juonala, David R Jacobs Jr, Lydia A Bazzano, Stephen R Daniels, Terence Dwyer, Mika Kähönen, Alan R Sinaiko, Julia Steinberger, …

Circulation. Population health and outcomes, e013678

09/30/2026

DOI: 10.1161/CIRCOUTCOMES.125.013678

PMID: 42813263

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Abstract

Accurate low-density lipoprotein cholesterol (LDL-C) assessment in young adulthood is critical for atherosclerotic cardiovascular disease (ASCVD) prevention, yet the optimal estimation equation remains uncertain. We compared the Friedewald, Martin-Hopkins, and Sampson equations for evaluating long-term ASCVD risks. We included participants from 7 population-based cohorts within the International Childhood Cardiovascular Cohort Consortium who had LDL-C measurements in young adulthood (aged 20-39 years) and follow-up data for incident ASCVD. LDL-C levels were estimated using the Friedewald, Martin-Hopkins, and Sampson equations. For each pair of equations, participants were categorized into concordant (normal/normal, elevated/elevated) and discordant (normal/elevated, elevated/normal) groups based on LDL-C classifications (normal <130 mg/dL versus elevated ≥130 mg/dL). ASCVD events (myocardial infarction, stroke, transient ischemic attack, ischemic heart failure, angina, peripheral artery disease, carotid intervention, abdominal aortic aneurysm, coronary revascularization) were adjudicated from medical records. Associations between discordance and incident ASCVD were estimated using Fine-Gray regressions. Among 10 550 participants (56.8% females; mean baseline age [SD], 29.8 [4.3] years), 376 ASCVD events occurred over a mean follow-up of 22.7 years. Elevated LDL-C by all equations was associated with ASCVD events (subdistribution hazards ratio [95% CI]: Martin-Hopkins, 1.69 [1.35-2.12]; Sampson, 1.52 [1.22-1.90]; Friedewald, 1.47 [1.17-1.84]). Total discordance ranged from 2.3% to 2.9%. Compared with the concordant normal LDL-C group, normal LDL-C by Friedewald but elevated by Martin-Hopkins had higher ASCVD risks (3.32 [1.94-5.66]), with no excess risk in the reverse discordance (1.19 [0.47-3.05]). Normal Friedewald but elevated Sampson LDL-C had higher ASCVD risks (1.69 [0.93-3.05]); no participants had the reverse discordance. Normal Sampson LDL-C but elevated Martin-Hopkins LDL-C had higher ASCVD risks (3.94 [1.80-8.64]), whereas the reverse discordance showed no increased risk (0.86 [0.39-1.91]). The Martin-Hopkins equation provides more accurate LDL-C-based risk classification, identifying high-risk young adults missed by other equations and minimizing misclassification of those at normal risk.

Cholesterol

Heart Failure

atherosclerosis

cardiovascular diseases

myocardial infarction

Details

Title: Subtitle: Multi-National Evaluation of Low-Density Lipoprotein Cholesterol Equations in Young Adulthood for Long-Term Risk of Atherosclerotic Cardiovascular Disease
Creators: Yaxing Meng - Turku University Hospital
Feitong Wu - University of Science and Technology of China
Markus Juonala - Turku University Hospital
David R Jacobs Jr - University of Minnesota
Lydia A Bazzano - Tulane University
Stephen R Daniels - University of Colorado Anschutz
Terence Dwyer - Murdoch Children's Research Institute
Mika Kähönen - Tampere University Hospital
Alan R Sinaiko - University of Minnesota
Julia Steinberger - University of Minnesota
Elaine M Urbina - Cincinnati Children's Hospital Medical Center
Alison J Venn - University of Tasmania
Jorma S A Viikari - University of Turku
Kara M Whitaker - Department of Health and Human Physiology and Department of Epidemiology, University of Iowa (K.M.W.)
Jessica G Woo - Cincinnati Children's Hospital Medical Center
Olli T Raitakari - University of Turku
Costan G Magnussen - Turku University Hospital
Resource Type: Journal article
Publication Details: Circulation. Population health and outcomes, e013678
DOI: 10.1161/CIRCOUTCOMES.125.013678
PMID: 42813263
NLM abbreviation: Circ Popul Health Outcomes
ISSN: 3068-563X
eISSN: 3068-563X
Publisher: American Heart Association
Grant note: R01 HL002942 / NHLBI NIH HHS R01 HL066430 / NHLBI NIH HHS N01 HC055025 / NHLBI NIH HHS R01 HL061857 / NHLBI NIH HHS R03 AG060619 / NIA NIH HHS R01 HL062394 / NHLBI NIH HHS R01 HL034659 / NHLBI NIH HHS R01 ES021724 / NIEHS NIH HHS R01 GM028719 / NIGMS NIH HHS R33 AG057983 / NIA NIH HHS
Language: English
Electronic publication date: 09/30/2026
Academic Unit: Epidemiology; Health, Sport, and Human Physiology
Record Identifier: 9985240905502771

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