Lipoprotein(a) and Risk Stratification for Atherosclerotic Cardiovascular Disease Across the Cardiovascular‐Kidney‐Metabolic Continuum
- 1Fuwai Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College/National Center for Cardiovascular Diseases
Abstract
BACKGROUND: Lp(a) (lipoprotein(a)) is an established risk factor for atherosclerotic cardiovascular disease (ASCVD), but its prognostic relevance across the cardiovascular-kidney-metabolic (CKM) continuum remains uncertain. We examined whether Lp(a) was associated with incident ASCVD across CKM stages and whether it provided complementary risk stratification beyond CKM staging. METHODS: We included 333 321 UK Biobank participants free of clinical cardiovascular disease at baseline and classified them into CKM stages 0 to 3. Elevated Lp(a) was defined as ≥125 nmol/L. The primary outcome was incident ASCVD, defined as coronary artery disease or ischemic stroke. Cox proportional hazards models were used to estimate hazard ratios (HRs), and 10-year absolute risks were estimated using Kaplan-Meier methods. RESULTS: During a median follow-up of 15.3 years, 17 581 incident ASCVD events occurred. After adjustment for demographic characteristics, socioeconomic factors, lifestyle factors, low-density lipoprotein cholesterol, medications, and CKM stage, elevated Lp(a) was associated with higher ASCVD risk (HR, 1.31 [95% CI, 1.25-1.36]). In joint analyses, risk increased progressively across combined CKM-Lp(a) categories, with the highest risk observed in participants with CKM stage 3 and elevated Lp(a) versus CKM stage 0 and lower Lp(a) (HR, 3.43 [95% CI, 2.74-4.31]). Ten-year ASCVD risk ranged from 0.64% to 16.30%, and the absolute risk difference associated with elevated Lp(a) increased from 0.23% in stage 0 to 2.20% in stage 3. CONCLUSIONS: Elevated Lp(a) was associated with higher incident ASCVD risk across the CKM continuum. Although relative associations were broadly consistent across CKM stages, absolute risk increments associated with elevated Lp(a) were greater at more advanced CKM stages, supporting the integration of Lp(a) into CKM-based risk stratification for primary prevention.
Related
- A Literature Review on the Waist Circumference Criteria for Metabolic Syndrome in Japan: Evidence and Implications for Cardiovascular Risk Stratification
- NMR metabolomics for cardiovascular-kidney-metabolic risk stratification in an integrated healthcare system
- The cholesterol, high-density lipoprotein, and glucose index and its derivatives related to obesity and inflammation as novel metabolic markers for predicting new-onset cardiovascular-liver-metabolic multimorbidity: A prospective cohort study.
- A Literature Review on the Waist Circumference Criteria for Metabolic Syndrome in Japan: Evidence and Implications for Cardiovascular Risk Stratification
- A machine learning-derived aging index for risk stratification and mortality prediction in cardiovascular-kidney-metabolic syndrome: A retrospective cohort study
BibTeX
@article{fang2026lipoproteina,
title = {{Lipoprotein(a) and Risk Stratification for Atherosclerotic Cardiovascular Disease Across the Cardiovascular‐Kidney‐Metabolic Continuum}},
author = {Yanwen Fang and Xuyan Pei and Sizhuang Huang and Hao Zhang and Mingyang Li and Haihua Zhang and Weixian Yang and Mengyue Yu},
journal = {Journal of the American Heart Association},
year = {2026},
month = oct,
doi = {10.1161/jaha.126.051179},
url = {https://www.ahajournals.org/doi/10.1161/JAHA.126.051179},
note = {CC BY-NC-ND},
}
RIS
TY - JOUR
TI - Lipoprotein(a) and Risk Stratification for Atherosclerotic Cardiovascular Disease Across the Cardiovascular‐Kidney‐Metabolic Continuum
AU - Yanwen Fang
AU - Xuyan Pei
AU - Sizhuang Huang
AU - Hao Zhang
AU - Mingyang Li
AU - Haihua Zhang
AU - Weixian Yang
AU - Mengyue Yu
PY - 2026
DA - 2026/10/23
JO - Journal of the American Heart Association
DO - 10.1161/jaha.126.051179
UR - https://www.ahajournals.org/doi/10.1161/JAHA.126.051179
AB - BACKGROUND: Lp(a) (lipoprotein(a)) is an established risk factor for atherosclerotic cardiovascular disease (ASCVD), but its prognostic relevance across the cardiovascular-kidney-metabolic (CKM) continuum remains uncertain. We examined whether Lp(a) was associated with incident ASCVD across CKM stages and whether it provided complementary risk stratification beyond CKM staging. METHODS: We included 333 321 UK Biobank participants free of clinical cardiovascular disease at baseline and classified them into CKM stages 0 to 3. Elevated Lp(a) was defined as ≥125 nmol/L. The primary outcome was incident ASCVD, defined as coronary artery disease or ischemic stroke. Cox proportional hazards models were used to estimate hazard ratios (HRs), and 10-year absolute risks were estimated using Kaplan-Meier methods. RESULTS: During a median follow-up of 15.3 years, 17 581 incident ASCVD events occurred. After adjustment for demographic characteristics, socioeconomic factors, lifestyle factors, low-density lipoprotein cholesterol, medications, and CKM stage, elevated Lp(a) was associated with higher ASCVD risk (HR, 1.31 [95% CI, 1.25-1.36]). In joint analyses, risk increased progressively across combined CKM-Lp(a) categories, with the highest risk observed in participants with CKM stage 3 and elevated Lp(a) versus CKM stage 0 and lower Lp(a) (HR, 3.43 [95% CI, 2.74-4.31]). Ten-year ASCVD risk ranged from 0.64% to 16.30%, and the absolute risk difference associated with elevated Lp(a) increased from 0.23% in stage 0 to 2.20% in stage 3. CONCLUSIONS: Elevated Lp(a) was associated with higher incident ASCVD risk across the CKM continuum. Although relative associations were broadly consistent across CKM stages, absolute risk increments associated with elevated Lp(a) were greater at more advanced CKM stages, supporting the integration of Lp(a) into CKM-based risk stratification for primary prevention.
SN - 2047-9980
ER -