Benefits of Better Cardiovascular Health for Calcific Aortic Valve Stenosis Stratified by Polygenic Risk Score

Q: What are the key findings of this study?

Higher Life's Essential 8 cardiovascular health scores were independently associated with a 28% lower risk of incident calcific aortic valve stenosis per standard deviation increase (HR 0.72, 95% CI 0.68-0.76, P < 2E-16) across all genetic risk strata.

Q: What is the clinical evidence from this study?

Study design: Cohort. Population: Calcific aortic valve stenosis (CAVS) (n=153312). Intervention: Life's Essential 8 (LE8) cardiovascular health score and polygenic risk score (PRS) vs. Lower LE8 score / Poor CVH (LE8 score 0-49) or Low genetic risk (bottom 20% PRS). Primary outcome: Incident calcific aortic valve stenosis (CAVS) (HR 0.72 per SD increase in LE8 score, 95% CI 0.68-0.76, p=< 2E-16).

Q: What does this research mean for the field?

Higher Life's Essential 8 cardiovascular health scores are independently associated with a 28% lower risk of incident calcific aortic valve stenosis across all genetic risk strata, with poor cardiovascular health and high genetic risk exhibiting a significant additive interaction. Novelty: ClaimNovelty.INCREMENTAL. Consensus alignment: ConsensusAlignment.NEUTRAL.

Q: What question did this study set out to answer?

To evaluate the independent and joint associations of cardiovascular health, measured by the Life's Essential 8 score, and polygenic risk with incident calcific aortic valve stenosis.

Yuexin Zhu; Bokang Qiao; Lü Jia; Haichu Wen; Wei Dong Pan; Yifan Wang; Shuangli Mi; Minxian Wang; Jie Du

doi:10.1093/gpbjnl/qzaf099

October 1, 2025Genomics Proteomics & BioinformaticsOpen Access

Benefits of Better Cardiovascular Health for Calcific Aortic Valve Stenosis Stratified by Polygenic Risk Score

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Key result

Higher Life's Essential 8 score is linked to ~28% lower aortic stenosis risk per SD.

HR 0.72 per SD increase in LE8 score
95% CI 0.68-0.76
P<2E-16
n=153,312

Figures

Graphical abstract published by Genomics Proteomics & Bioinformatics — Graphical abstract · Published by Genomics Proteomics & Bioinformatics · CC BY

Why the study?

With global aging, the prevalence of calcific aortic valve stenosis (CAVS) has increased and even mild CAVS elevates mortality risk, highlighting an urgent need for preventive strategies.

Does maintaining higher cardiovascular health as measured by Life's Essential 8 reduce the risk of incident calcific aortic valve stenosis across different polygenic risk strata in middle-aged and older adults?

Key Points

To evaluate the independent and joint associations of cardiovascular health, measured by the Life's Essential 8 score, and polygenic risk with incident calcific aortic valve stenosis.
Analyzed prospective cohort data from 153,312 UK Biobank participants followed for a median duration of 13.27 years.
Cardiovascular health was assessed using the American Heart Association Life's Essential 8 (LE8) metrics (poor: 0–49, moderate: 50–79, ideal: 80–100).
Genetic predisposition was quantified using polygenic risk scores (PRS) stratified into low (bottom 20%), intermediate (middle 60%), and high (top 20%) risk groups.
Higher LE8 score was independently associated with lower CAVS risk (HR per SD: 0.72, 95% CI: 0.68–0.76, P < 2E-16), while higher genetic risk increased risk (HR per SD: 1.63, 95% CI: 1.54–1.71, P < 2E-16).
A significant additive interaction between poor cardiovascular health and high genetic risk was observed (relative excess risk due to interaction: 3.77, 95% CI: 1.30–8.50).
Among individuals with high genetic risk, 10-year cumulative CAVS incidence was substantially lower with ideal versus poor cardiovascular health (0.33% vs. 1.80%, P < 0.001).

Study Design

Type

Cohort (n=153,312)

Multicenter

Yes

Structured PICO

Does maintaining higher cardiovascular health as measured by Life's Essential 8 reduce the risk of incident calcific aortic valve stenosis across different polygenic risk strata in middle-aged and older adults?

P

Population

153,312 UK Biobank adults (mean age 55.97 years, 53.53% female) free of baseline aortic valve stenosis or congenital/rheumatic valve disease, followed for a median of 13.27 years.

E

Exposure

Higher cardiovascular health (CVH) assessed by the American Heart Association Life's Essential 8 (LE8) score (0-100 scale, categorized as ideal [80-100], moderate [50-79], or poor [0-49]) stratified by polygenic risk score (PRS) for calcific aortic valve stenosis (low [bottom 20%], intermediate [middle 60%], and high [top 20%] genetic risk).

C

Comparator

Poor CVH (LE8 score 0-49) or ideal CVH reference group (LE8 score 80-100), and low genetic risk (bottom 20% PRS) or high genetic risk with poor CVH.

O

Outcome

Incident calcific aortic valve stenosis (CAVS) over a median follow-up of 13.27 years, ascertained via primary care data, linked hospital admission records, and death registry data.hard clinical

Main Result

Hazard Ratio: 0.72 (95% CI 0.68–0.76)

p-value: p=< 2E-16

Maintaining ideal cardiovascular health (Life's Essential 8 score >=80) is linearly associated with lower calcific aortic valve stenosis risk and substantially mitigates the excess risk conferred by high polygenic susceptibility.

Limitations

Observational design precludes causal inference
Limited generalizability to non-European populations as the majority of participants were of European ancestry
Potential 'healthy volunteer' selection bias in the UK Biobank cohort
Polygenic risk score may miss undetected genetic susceptibilities such as structural variants
Self-reported lifestyle metrics (dietary intake and physical activity) are subject to recall bias and potential changes over follow-up
Observational nature precludes causal inference.
Majority of participants were of European ancestry, limiting generalizability to non-European populations.
Healthy volunteer selection bias in the UK Biobank.
Some genetic susceptibilities such as structural variants may remain undetected by the PRS.
Self-reported LE8 metrics (physical activity and dietary intake) are subject to recall bias and temporal changes during follow-up.

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Implication

Higher LE8 scores may aid CAVS risk assessment across genetic strata; leaves open whether optimizing CVH prevents disease.

Abstract

With global aging, the prevalence of calcific aortic valve stenosis (CAVS) has significantly increased, and even mild CAVS elevates mortality risk, highlighting an urgent need for preventive strategies. In this study, we analyzed 153,312 participants from the UK Biobank. We found that a higher Life's Essential 8 (LE8) score was independently associated with a decreased CAVS risk [hazard ratio (HR)/standard deviation (SD): 0.72, 95% confidence interval (CI): 0.68-0.76, P < 2E-16], whereas a higher genetic risk score was independently associated with an increased CAVS risk (HR/SD: 1.63, 95% CI: 1.54-1.71, P < 2E-16). Restricted cubic spline analysis revealed approximately linear inverse associations between LE8 score and CAVS risk across all genetic risk groups. Although no multiplicative interaction was found between cardiovascular health (CVH) and genetic risk for CAVS, a significant additive interaction was identified (relative excess risk due to interaction: 3.77, 95% CI: 1.30-8.50). Among participants with high genetic risk, those with ideal CVH had a lower 10-year cumulative CAVS incidence rate than those with poor CVH (0.33% vs. 1.80%, P < 0.001). Besides, a significant multiplicative interaction was observed between LE8 score and age (P = 0.007). Similar trends were also observed for early-onset and late-onset CAVS. In conclusion, regardless of genetic risk groups, a higher LE8 score was associated with a lower CAVS risk in an approximately linear pattern. In particular, high genetic risk and poor CVH had a synergistic effect on CAVS risk, meaning that participants with high genetic risk and poor CVH would amplify their CAVS risk. Therefore, early and sustained optimization of CVH, particularly among those with high genetic risk, is essential to mitigate the risk of CAVS and its subtypes.

Discussion

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Cite This Study

Zhu et al. (2025) conducted a cohort in Calcific aortic valve stenosis (CAVS) (n=153,312). Life's Essential 8 (LE8) cardiovascular health score and polygenic risk score (PRS) vs. Lower LE8 score / Poor CVH (LE8 score 0-49) or Low genetic risk (bottom 20% PRS) was evaluated on Incident calcific aortic valve stenosis (CAVS) (HR 0.72 per SD increase in LE8 score, 95% CI 0.68-0.76, p=< 2E-16). Higher Life's Essential 8 cardiovascular health scores were independently associated with a 28% lower risk of incident calcific aortic valve stenosis per standard deviation increase (HR 0.72, 95% CI 0.68-0.76, P < 2E-16) across all genetic risk strata.

synapsesocial.com/papers/6ab360a7b8ac748de1debdce https://doi.org/10.1093/gpbjnl/qzaf099

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Benefits of Better Cardiovascular Health for Calcific Aortic Valve Stenosis Stratified by Polygenic Risk Score

Figures

Key Points

Study Design

Structured PICO

Main Result

Limitations

Ask about this paper

Implication

Abstract

Discussion

Cite This Study

Benefits of Better Cardiovascular Health for Calcific Aortic Valve Stenosis Stratified by Polygenic Risk Score

Figures

Key Points

Study Design

Structured PICO

Main Result

Limitations

Ask about this paper

Implication

Abstract

Discussion

Cite This Study

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