| Title: | Life's Essential 8, genetic susceptibility and risk of degenerative valvular heart disease |
| Journal: | - |
| Published: | 9 Mar 2026 |
| DOI: | https://doi.org/10.1097/re9.0000000000000012 |
Publication 17441
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Abstract
Background: Adherence to high cardiovascular health (CVH) is effective for preventing atherosclerotic cardiovascular disease, whereas its impact on degenerative valvular heart disease (VHD) remains poorly understood. We aimed to investigate the associations of CVH status, reflected by Life's Essential 8 (LE8), with incident VHD, and the potential modification of genetic susceptibility. Methods: A total of 262,864 participants without VHD at baseline were included from the UK Biobank. CVH status was categorized into three groups according to LE8 scores: low (0-49), moderate (50-79), and high (80-100). Genetic susceptibility to aortic valve stenosis (AS) was assessed using a polygenic risk score (PRS) and categorized into tertiles. Fine-Gray competing risk models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs), and multiplicative and additive interactions between CVH and PRS were evaluated. Results: The mean (SD) age was 56.0 (8.1) years, and 51.1% of participants were female. During a mean follow-up of 13.4 years, 6,371 incident VHD cases were recorded, including 2,754 AS, 1,013 aortic valve regurgitation (AR), and 3,089 mitral valve regurgitation (MR). Compared with individuals with low LE8 scores, the multivariable-adjusted HRs of incident VHD risk for those with moderate and high LE8 scores were 0.82 (95% confidence interval [CI]: 0.74-0.90) and 0.79 (95% CI: 0.70-0.90), respectively. Notably, optimal CVH status was significantly associated with a reduced risk of incident AS, but not with MR or AR. Compared with low CVH status, AS risk was decreased by 33% and 50% in the moderate (HR 0.67, 95% CI: 0.59-0.77) and high CVH groups (HR 0.50, 95% CI: 0.41-0.61), respectively. The polygenic risk score of AS did not modify these associations. Nonetheless, adults with both low CVH status and high genetic susceptibility had the highest risk of AS, with a nearly 4-fold increase compared with those with high CVH condition and low genetic predisposition. Both lifestyle behaviors and biological features of CVH were significantly associated with AS incidence. Among the individual LE8 components, body mass index, sleep duration, and nicotine exposure had the strongest effects on valvular outcomes. Conclusion: Higher LE8 scores were significantly associated with a lower incidence of AS, irrespective of genetic susceptibility. These findings indicate that optimal cardiovascular health is associated with a lower risk of AS across genetic backgrounds. </p>
11 Authors
- Di Wu
- Yiding Gong
- Shuang Bing
- Jiaqi Wang
- Huangke Xiang
- Zhanchao Chen
- Bo Yu
- Yang Ping
- Jiacheng Li
- Yiying Zhang
- Shanjie Wang
1 Application
| Application ID | Title |
|---|---|
| 429905 | Mitochondrial genetic variants, unhealthy lifestyle, and susceptibility of cardiometabolicc disorders |
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