Association of the Pan-Immune-Inflammation Value-to-Albumin Ratio as a Novel Cardiovascular Disease Predictor in Type 2 Diabetes: A Prospective Cohort Study
Objectives: Individuals with type 2 diabetes (T2D) remain at high cardiovascular disease (CVD) risk. The pan-immune-inflammation value (PIV) integrates circulating neutrophils, monocytes, platelets, and lymphocytes but does not capture albumin-related nutritional and inflammatory reserve. We investigated associations between the PIV-to-albumin ratio (PIVA) and incident CVD, cardiovascular mortality, and disease progression in individuals with T2D. Methods: This prospective study included 15,355 UK Biobank participants with T2D and no baseline CVD. PIVA was calculated from peripheral blood cell counts and serum albumin and was natural log-transformed. Fine–Gray competing-risk and cause-specific Cox models were used to evaluate incident CVD and cardiovascular mortality. Multi-state models characterized transitions from T2D to CVD and death. We also examined nonlinear associations, renal biomarker mediation, joint associations with the CVD polygenic risk score and triglyceride–glucose index, sensitivity analyses, and external validation of cardiovascular mortality in the National Health and Nutrition Examination Survey. Results: During median follow-ups of 12.94 years for incident CVD and 14.49 years for cardiovascular mortality, 4829 incident CVD events and 514 cardiovascular deaths occurred. Each 1-unit increase in lnPIVA was associated with higher risks of incident CVD (subdistribution hazard ratio [sHR], 1.140; 95% confidence interval [CI], 1.088–1.194) and cardiovascular mortality (sHR, 1.449; 95% CI, 1.247–1.684). Associations were nonlinear. Higher lnPIVA was also associated with transitions from T2D to CVD, from T2D directly to cardiovascular death, and from incident CVD to cardiovascular death. Cystatin C explained a larger proportion of these associations than creatinine. Elevated lnPIVA identified excess cardiovascular risk across strata of genetic susceptibility and insulin resistance, and the findings were generally supported by sensitivity and external validation analyses. Conclusions: lnPIVA was associated with incident CVD, cardiovascular mortality, and adverse cardiovascular transitions in individuals with T2D. As an immune-inflammatory and albumin-based index, PIVA may help identify high-risk individuals beyond conventional cardiometabolic and genetic risk profiles.