Impact of genetic risk and lifestyles on cardiovascular disease-free and total life expectancy: a cohort study

TL;DR

This study shows that both genetic risk and lifestyle choices significantly affect how long people live without cardiovascular disease and overall life expectancy.

Contribution

The study introduces a polygenic risk score for CVD and evaluates its interaction with lifestyle on life expectancy in a large Chinese cohort.

Findings

Low genetic risk increases CVD-free life expectancy more than total life expectancy compared to high genetic risk.

Favorable lifestyles significantly extend both total and CVD-free life expectancy, especially for those with high genetic risk.

Lifestyle improvements benefit individuals with high genetic risk more than those with lower genetic risk.

Abstract

Understanding the role of genetic risk and lifestyles on life expectancy (LE) without cardiovascular disease (CVD) and total LE may help optimize healthy aging strategies after taking genetic background into account.

The China Kadoorie Biobank recruited participants from five urban and five rural areas across China during 2004–2008 and followed them up till December 31, 2018. A polygenic risk score (PRS) comprising 3.5 million genetic variants for overall CVD was constructed by combining multiple PRSs for CVD and CVD-related risk factors in 96,400 participants. Genetic risk was categorized into low, intermediate, and high according to the PRS, and lifestyles were categorized as favorable, intermediate, and unfavorable according to the number of unfavorable lifestyles. Using multistate life tables, we estimated CVD-free and total LE at age 40 for different genetic and lifestyle risk groups.

Genetic risk was more strongly associated with CVD onset than post-CVD mortality. As a result, the increase in LE without CVD associated with low genetic risk (4.9 years (95% CI 4.3–5.5) for women and 4.4 years (3.6–5.1) for men) was greater than the increase in total LE (2.9 years (1.8–3.8) for women and 2.6 years (1.5–3.5) for men) when compared to high genetic risk. In contrast, the association strengths of lifestyles with CVD onset and mortality after CVD were similar. Correspondingly, compared to those with unfavorable lifestyles, participants with favorable lifestyles had longer total LE and LE without CVD of 3.0 (1.5–4.3) and 4.0 (3.0–4.9) years in women and 5.7 (4.1–7.1) and 5.8 (4.7–6.9) years in men, respectively. Participants with high genetic risk benefited more from favorable lifestyles than those with low and intermediate genetic risk, gaining 5.9 (2.3–9.3) and 5.3 (3.0–7.6) years in women and 6.1 (0.8–10.6) and 6.2 (2.3–9.8) years in men for total and CVD-free LE, respectively.

Improving lifestyles is critical for reducing CVD-related healthcare burden and promoting healthy aging, especially for individuals with high genetic risk.

The online version contains supplementary material available at 10.1186/s13073-025-01487-9.

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