Cardiovascular health and osteoarthritis risk: a prospective cohort study with proteomic insights from UK Biobank

Background Cardiovascular disease and osteoarthritis (OA) share risk factors, but the link between comprehensive cardiovascular health and OA incidence is unclear. We investigated the association of Life’s Essential 8 (LE8), a multidimensional health metric, with OA risk and explored proteomic mechanisms. Methods In 102 794 UK Biobank participants without OA at baseline, LE8 scores (0–100) were derived from eight components. Incident OA was ascertained from medical records. Cox models estimated HRs. Plasma proteomics in a subset identified proteins linked to LE8 and OA, used to construct a protein risk score. Results Over 13.1 median years, 15 984 OA cases occurred. The highest versus lowest LE8 quartile had a 32% lower OA risk (HR 0.68, 95% CI 0.64 to 0.71), consistent across knee (HR 0.56), hip (HR 0.72) and hand OA (HR 0.57). Each SD increase in LE8 reduced risk by 14% (HR 0.86, 95% CI 0.84 to 0.87). Protective associations were stronger in individuals with younger phenotypic age (HR 0.86, 95% CI 0.84 to 0.88). Proteomics identified nine associated proteins (eg, fibroblast growth factor 21, insulin-like growth factor-binding protein 1); a protein risk score showed graded positive associations with OA. Conclusions Higher cardiovascular health is associated with substantially lower OA risk, modified by biological ageing. Proteomic pathways involving metabolism, inflammation and tissue remodelling may underlie this relationship, supporting cardiovascular health optimisation for OA prevention.