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. 2025 Jul 22;17(1):81.
doi: 10.1186/s13073-025-01487-9.

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

Dong Sun  1 , Qiufen Sun  1 , Yinqi Ding  1 , Canqing Yu  1   2   3 , Dianjianyi Sun  1   2   3 , Yuanjie Pang  1   3 , Pei Pei  2 , Ling Yang  4 , Iona Y Millwood  4 , Robin G Walters  4 , Huaidong Du  4 , Jun Zhang  5 , Dan Schmidt  4 , Junshi Chen  6 , Zhengming Chen  4 , Liming Li  7   8   9 , Jun Lv  10   11   12   13 ; China Kadoorie Biobank Collaborative Group
Collaborators, Affiliations

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

Dong Sun et al. Genome Med. .

Abstract

Background: 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.

Methods: 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.

Results: 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.

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

Keywords: Cardiovascular disease-free life expectancy; Cohort study; Lifestyles; Polygenic risk score.

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Conflict of interest statement

Declarations. Ethics approval and consent to participate: The study was conducted in accordance with Declaration of Helsinki and approved by the Ethics Committee of the Chinese Centre for Disease Control and Prevention (005/2004, Beijing, China), the Peking University Health Science Center (IRB00001052-20040, Beijing, China), and the Oxford Tropical Research Ethics Committee of the University of Oxford (025–04, Oxford, UK). All participants provided written informed consent. Consent for publication: Not applicable. Competing interests: The authors declare no competing interests.

Figures

Fig. 1
Fig. 1
Flow chart of the MetaPRS construction. AF, atrial fibrillation; AIC, Akaike information criterion; CAD, coronary artery disease; CVD, cardiovascular disease; C + T, clumping and thresholding; DBP, diastolic blood pressure; GL, glucose level; GWAS, genome-wide association study; HDL-C, high-density lipoprotein cholesterol; HF, heart failure; ICH, intracerebral hemorrhage; IS, ischemic stroke; LDL-C, low-density lipoprotein cholesterol; PAD, peripheral arterial disease; PRS, polygenic risk score; SBP, systolic blood pressure; TC, total cholesterol; TG, triglycerides; T2D, type 2 diabetes
Fig. 2
Fig. 2
Life expectancy at age 40 with and without cardiovascular disease according to genetic risk and lifestyles in the testing set. CI, confidence interval; CVD, cardiovascular disease; LE, life expectancy. The genetic risk and lifestyles were categorized in the same way as in Table 2
Fig. 3
Fig. 3
Life expectancy at age 40 with and without cardiovascular disease according to joint categories of genetic risk and lifestyles in the testing set. CI, confidence interval; CVD, cardiovascular disease; LE, life expectancy. The genetic risk and lifestyles were categorized in the same way as in Table 2
See this image and copyright information in PMC

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