Associations between plasma osteopontin, sex, and 2-year global and cardiorenal outcomes in older outpatients screened for CKD: A secondary analysis of the SCOPE study

Background: Plasma osteopontin (pOPN) is a promising aging-related biomarker among individuals with and without kidney disease. The interaction between sex, pOPN levels, and global and cardiorenal outcomes among older individuals was not previously evaluated. Methods: In this study we investigated the association of pOPN with 24-month global mortality, major cardiovascular events (MACEs), MACEs + cardiovascular (CV) mortality, and renal decline among older individuals; we also evaluated whether sex modified observed associations. pOPN levels were measured in a cohort of 2013 outpatients (908 men and 1105 women) aged 75 years or more enrolled in the context of a multicenter prospective cohort study in Europe. Multivariable linear regression, Cox and Fine Gray models, and linear mixed regression models were fitted to evaluate whether sex modified the associations between biomarkers and study outcomes. Results: In total, 2013 older participants with a median age of 79 years, 54.9% of whom women, were included in the study; increased pOPN levels were associated with all-cause mortality specifically among women [reduced fully adjusted model resulting from backward selection, hazard ratio, 95% confidence interval (CI): 1.84, 1.20-2.89]. Addition of pOPN to models containing age, eGFR, and albumin-to-creatinine ratio (ACR) improved the time-dependent area under the curve (AUC) at 6, 12, and 24 months, among women only. No significant association was found between the biomarker levels, MACE, and MACE + CV mortality. Conversely, increased baseline pOPN was associated with eGFR decline in all patients (-0.45, 95%CI: -0.68 to -0.22 ml/min/1.73 m2 year) but with slightly steeper declines in women compared to men (-0.57, -0.99 to -0.15 vs -0.47, -0.88 to -0.07). Conclusions: pOPN levels were significantly lower in women than in men but associated with all-cause mortality in women only; increase in serum pOPN was associated with eGFR decline over time in all patients, but with stronger associations among women. Assessment of pOPN may help identifying older female participants at risk of poor outcomes.