The role of sex and systemic inflammation in the development of cardiovascular disease in osteoarthritis: A population-based cohort study using the CLSA

Cardiovascular disease (CVD) is increased in osteoarthritis (OA), particularly in females. This longitudinal, population-based study investigated CVD development in OA vs. no-OA. We hypothesized a) having OA confers an additional risk beyond the Framingham Risk Score (FRS), and b) systemic inflammation contributes to the OA-CVD link, and to a greater extent in females. Data: Canadian Longitudinal Study on Aging cycles 1-3 (6 years of follow-up). Respondents completed questionnaires and provided blood samples. Individuals with OA were age-sex-matched to individuals without OA. Baseline FRS-risk (largely reflecting metabolic factors) and a systemic inflammation variable (comprising four factors) were derived. Cox regressions examined time-to-CVD for OA vs. non-OA, exploring the roles of FRS and systemic inflammation, adjusting for sociodemographics, comorbidities, physical activity, and BMI. Sample: 2123 individuals with, 2123 without OA. CVD incidence/10,000 person-years: 123.0 and 65.0 in females (p = 0.008), 187.6 and 166.4 in males (p = 0.670), with and without OA. Model results: Among females only, OA was associated with increased CVD risk (HR=1.78 (1.22, 2.58)). FRS-risk distribution was similar for OA and non-OA, and 'high-risk' FRS was similarly associated with CVD development for both sexes. In females only, OA was associated with higher systemic inflammation, and higher systemic inflammation with increased CVD risk (HR=1.77 (1.02, 3.05)). CVD risk in females with OA is underestimated by the FRS, an algorithm often used in clinical settings. While increased systemic inflammation, a potential intervention target, contributes to the OA-CVD link in females, there remains still unexplained increased CVD risk in OA.