Prioritizing Modifiable Risk Factors for Cardiovascular Diseases in Adults With Hypertension: A Prospective Cohort Study
Med Research, 2026
Wei S., Zheng D., Chen L., Zhuang Z., Lin Z., Zhang J., Hu P., Yang Z., Huang Z., Zhang B., Lin H.
| Disease area | Application area | Sample type | Products |
|---|---|---|---|
CVD | Pathophysiology | Plasma |  Olink Explore 3072/384 |
Abstract
The relative importance and biological mechanisms of modifiable risk factors for cardiovascular diseases remain unclear among adults with hypertension. In a large prospective cohort of 134,417 adults with hypertension, we evaluated the individual and joint effects of modifiable risk factors on the incidence of eight cardiovascular diseases using Cox proportional hazards models, with joint effects quantified using a composite cardiovascular health score. Population attributable fractions were estimated to quantify and prioritize each risk factor’s contribution to cardiovascular disease burden. Mediation analyses quantified the extent to which proteins and metabolites accounted for the associations, and functional enrichment analysis identified underlying biological pathways. During a median follow‐up of 13.26 years, 29,099 participants (21.6%) developed cardiovascular diseases. More favorable risk factor profiles were consistently associated with lower risks across all outcomes, with hazard ratios per 10‐point increase in the cardiovascular health score ranging from 0.92 (95% CI: 0.87–0.97) for transient ischemic attack to 0.76 (95% CI: 0.72–0.79) for aneurysm. Among individual factors, nicotine exposure showed the largest population attributable fractions across multiple diseases (7.9%–36.4%), followed by body mass index. Mediation analyses identified 212 proteins and 111 metabolites that statistically accounted for part of these associations, whereas enrichment analyses suggested involvement of pathways related to cytokine–cytokine receptor interaction. Overall, modifiable risk factors differ in their relative contributions to cardiovascular disease burden among adults with hypertension. Beyond blood pressure, nicotine exposure showed relatively larger attributable fractions across several outcomes. Multi‐omics analyses point to inflammation‐related pathways as potential biological correlates.