Lipoprotein(a) and Coronary Artery Disease Polygenic Risk Scores Do Not Improve Secondary Manifestations of Arterial Disease Score Prediction of Coronary Events After Ischemic Stroke
- 1Monash University Victorian Heart Institute
- 2University of Adelaide
- 3Monash University
Abstract
Background Survivors of ischemic stroke are at high risk for coronary artery disease (CAD), but individual risk varies. Lipoprotein(a) [Lp(a)] and CAD polygenic risk scores (CAD‐PRS) improve risk prediction in primary prevention; however, their prognostic value after stroke remains uncertain. We assessed whether Lp(a) and CAD‐PRS add predictive value to the Secondary Manifestations of Arterial Disease (SMART) secondary prevention score. Methods We analyzed 1202 UK Biobank participants of European ancestry with prior ischemic stroke and no CAD at baseline (2006–2022). Baseline clinical characteristics, Lp(a), and CAD‐PRS were recorded. The primary outcome was incident CAD, identified from hospital, primary care, and death records. Competing‐risk models compared SMART alone with SMART plus Lp(a), CAD‐PRS, or both. Ten‐year model performance was assessed using the area under the receiver operating characteristic curve and Brier score. Prespecified subgroup analyses examined age, sex, diabetes, and low‐density lipoprotein cholesterol. Results During a median follow‐up of 13.4 years, 155 participants (12.9%) developed CAD. SMART alone provided moderate discrimination (area under the receiver operating characteristic curve, 0.69 [95% CI, 0.64–0.75]) and a Brier score of 0.08. Adding Lp(a), CAD‐PRS, or both did not improve prediction (change in area under the receiver operating characteristic curve, ≤0.002; all P >0.6; continuous net reclassification improvement, ≤0.03; all P >0.20). Results were consistent across subgroups, with no significant interactions after correction for multiple comparisons. Conclusions Among survivors of ischemic stroke without CAD, neither Lp(a) nor CAD‐PRS improved prediction of incident CAD beyond the SMART score. These findings do not support their incremental use for coronary risk stratification in this population.
Related
- Polygenic Risk Profiles and the Manifestations of Alcohol Use Disorder and Related Outcomes
- Coronary artery disease polygenic risk score and recurrent cardiovascular events after coronary artery revascularization: A UK Biobank analysis
- From Measurement to Management ― Lipoprotein(a) After Acute Coronary Syndrome ―
- Temporal changes in lipoprotein(a) after acute coronary syndrome
- Utility of a coronary artery disease polygenic risk score in a low-risk primary prevention cohort
BibTeX
@article{muthalaly2026lipoproteina,
title = {{Lipoprotein(a) and Coronary Artery Disease Polygenic Risk Scores Do Not Improve Secondary Manifestations of Arterial Disease Score Prediction of Coronary Events After Ischemic Stroke}},
author = {Rahul G. Muthalaly and Sean Tan and Julian Giovannucci and Nitesh Nerlekar and Andrew Lin and Adam J Nelson and Thanh Phan and Henry Ma and Stephen J Nicholls},
journal = {Journal of the American Heart Association},
year = {2026},
month = oct,
doi = {10.1161/jaha.125.048213},
url = {https://www.ahajournals.org/doi/10.1161/JAHA.125.048213},
note = {CC BY-NC-ND},
}
RIS
TY - JOUR
TI - Lipoprotein(a) and Coronary Artery Disease Polygenic Risk Scores Do Not Improve Secondary Manifestations of Arterial Disease Score Prediction of Coronary Events After Ischemic Stroke
AU - Rahul G. Muthalaly
AU - Sean Tan
AU - Julian Giovannucci
AU - Nitesh Nerlekar
AU - Andrew Lin
AU - Adam J Nelson
AU - Thanh Phan
AU - Henry Ma
AU - Stephen J Nicholls
PY - 2026
DA - 2026/10/20
JO - Journal of the American Heart Association
DO - 10.1161/jaha.125.048213
UR - https://www.ahajournals.org/doi/10.1161/JAHA.125.048213
AB - Background Survivors of ischemic stroke are at high risk for coronary artery disease (CAD), but individual risk varies. Lipoprotein(a) [Lp(a)] and CAD polygenic risk scores (CAD‐PRS) improve risk prediction in primary prevention; however, their prognostic value after stroke remains uncertain. We assessed whether Lp(a) and CAD‐PRS add predictive value to the Secondary Manifestations of Arterial Disease (SMART) secondary prevention score. Methods We analyzed 1202 UK Biobank participants of European ancestry with prior ischemic stroke and no CAD at baseline (2006–2022). Baseline clinical characteristics, Lp(a), and CAD‐PRS were recorded. The primary outcome was incident CAD, identified from hospital, primary care, and death records. Competing‐risk models compared SMART alone with SMART plus Lp(a), CAD‐PRS, or both. Ten‐year model performance was assessed using the area under the receiver operating characteristic curve and Brier score. Prespecified subgroup analyses examined age, sex, diabetes, and low‐density lipoprotein cholesterol. Results During a median follow‐up of 13.4 years, 155 participants (12.9%) developed CAD. SMART alone provided moderate discrimination (area under the receiver operating characteristic curve, 0.69 [95% CI, 0.64–0.75]) and a Brier score of 0.08. Adding Lp(a), CAD‐PRS, or both did not improve prediction (change in area under the receiver operating characteristic curve, ≤0.002; all P >0.6; continuous net reclassification improvement, ≤0.03; all P >0.20). Results were consistent across subgroups, with no significant interactions after correction for multiple comparisons. Conclusions Among survivors of ischemic stroke without CAD, neither Lp(a) nor CAD‐PRS improved prediction of incident CAD beyond the SMART score. These findings do not support their incremental use for coronary risk stratification in this population.
SN - 2047-9980
ER -