| Title: | Cardiorespiratory Fitness, Genetic Risk, and Incident Atherosclerotic Cardiovascular Events: A Prospective Cohort Study |
| Journal: | Mayo Clinic Proceedings |
| Published: | 21 Jan 2026 |
| Pubmed: | https://pubmed.ncbi.nlm.nih.gov/41563160/ |
| DOI: | https://doi.org/10.1016/j.mayocp.2025.07.036 |
Publication 18596
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Abstract
OBJECTIVE: To examine the prospective relationship of cardiorespiratory fitness (CRF) with incident atherosclerotic cardiovascular disease (ASCVD) across genetic susceptibility strata.</p>
PARTICIPANTS AND METHODS: We conducted a prospective study of 69,447 UK Biobank participants (mean age, 57.6 years; 37,554 [54.1%] female) who performed a fitness test between December 7, 2009, and June 7, 2013. Maximal oxygen consumption was estimated using a validated bike ergometry procedure, standardized within sex and age strata. Genetic susceptibility to ischemic heart disease was quantified with weighted polygenic risk scores. Participants were assigned to low (20th percentile), intermediate (20th to 80th percentile), and high (80th percentile) fitness and genetic risk groups, respectively. Cox regression models were used to estimate the hazard of development of ASCVD.</p>
RESULTS: During a median follow-up of 12 years, there were 5448 incident ASCVD events. Each 1-SD difference in sex- and age-standardized CRF (equivalent to 5.6 mLO2/kg per minute) was associated with an 8% (hazard ratio [HR], 0.92; 95% CI, 0.89 to 0.95) lower hazard of ASCVD, independent of demographic, lifestyle, and health-related factors and genetic risk. There was weak evidence of multiplicative interaction (P=.06), suggesting that the associations might be slightly stronger in the low genetic risk group (HR, 0.87; 95% CI, 0.80 to 0.94) compared with intermediate (HR, 0.94; 95% CI, 0.90 to 0.98] and high genetic risk groups (HR, 0.91; 95% CI, 0.86 to 0.97). There was no evidence of additive interaction (P=.79). The 10-year absolute risk differences between low and high CRF groups were 1.2% and 1.6% within high and low genetic risk categories, respectively.</p>
CONCLUSION: Across all strata of genetic risk for cardiovascular disease, higher CRF was strongly associated with lower risk of ASCVD. Adults should be encouraged to increase or maintain CRF levels, irrespective of genetic susceptibility.</p>
10 Authors
- Paul J Collings
- Mengyao Wang
- Ziyuan Chen
- Qiaoxin Shi
- Shan Luo
- Shiu Lun Au Yeung
- Tomas I Gonzales
- Stephen J Sharp
- Søren Brage
- Youngwon Kim
1 Application
| Application ID | Title |
|---|---|
| 43528 | Exploring the relationships of movement behaviours with adverse health outcomes. |
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