Association of cardiovascular-kidney-metabolic syndrome with risk of hip/knee osteoarthritis: A prospective cohort study.

BACKGROUND

Cardiovascular-kidney-metabolic syndrome reflects the interplay of metabolic, renal, and cardiovascular dysfunction and is linked to adverse health outcomes. Its association with osteoarthritis remains unclear.

METHODS

This prospective cohort study included 256,364 UK Biobank participants free of osteoarthritis at baseline. Cardiovascular-kidney-metabolic syndrome was classified into five stages (0-4) based on modified American Heart Association criteria. Genetic risk scores for hip/knee osteoarthritis were derived from established single nucleotide polymorphisms. Cox proportional hazards models were used to estimate hazard ratios and 95% confidence intervals for incident hip/knee osteoarthritis.

RESULTS

Over a median follow-up of 11.0 years, 8209 hip osteoarthritis and 12,729 knee osteoarthritis cases were identified. Higher cardiovascular-kidney-metabolic syndrome stages were associated with progressively increased risks of both outcomes. Compared with Stage 0, participants with Stage 4 had higher risks of hip osteoarthritis (hazard ratio 1.76, 95% confidence interval 1.58-1.95) and knee osteoarthritis (hazard ratio 2.67, 95% confidence interval 2.44-2.93). Associations were stronger in individuals <60 years and differed by sex: hip osteoarthritis risk was greater in men, while knee osteoarthritis risk was greater in women. Individuals with both high genetic susceptibility and Stage 4 cardiovascular-kidney-metabolic syndrome had the highest risks of hip osteoarthritis (hazard ratio 3.10, 95% confidence interval 2.60-3.70) and knee osteoarthritis (hazard ratio 4.00, 95% confidence interval 3.42-4.68). A positive additive interaction was observed between genetic susceptibility and cardiovascular-kidney-metabolic syndrome stage.

CONCLUSION

Our findings indicate that higher cardiovascular-kidney-metabolic syndrome stages are associated with increased hip/knee osteoarthritis risk, particularly in younger individuals.