Elevated alpha-1 antitrypsin and C-reactive protein: association on all-cause and cause-specific mortality in older...

Alpha-1 antitrypsin (AAT) deficiency in younger people is well characterized, but the effects of elevated AAT levels in older age are unclear. We examined the effect of elevated AAT levels and mortality in a longitudinal cohort of older adults, alongside high-sensitivity C-reactive protein (hs-CRP) levels. This post hoc analysis of the ASPirin in Reducing Events in the Elderly (ASPREE) trial included 11,879 adults aged ≥ 70 years without prior cardiovascular disease, dementia or life-limiting illness at enrolment. Cox proportional hazard models estimated adjusted hazard ratios (aHRs) for all-cause and cause-specific mortality (cancer, cardiovascular and other) over a median follow-up of 10.9 years. AAT and hs-CRP were analyzed in deciles, comparing the highest decile to the middle 80% as reference. Median (IQR) levels of AAT and hs-CRP in the top decile were 1.69 (1.65-1.78) g/L and 10.40 (7.97-15.53) mg/L, respectively. Individuals in highest AAT decile had a 53% higher likelihood of mortality during follow-up (aHR 1.53, 95% CI 1.28-1.65). Risk of cancer, cardiovascular and 'other' deaths were all elevated. The associations remained significant after excluding participants with elevated hs-CRP. Participants in the highest hs-CRP decile had a 32% higher likelihood of mortality (aHR 1.32, 95% CI 1.18-1.48). Elevated hs-CRP was associated with cancer and 'other' mortality but not cardiovascular mortality. Elevated AAT is a robust predictor of mortality in older adults, independent of hs-CRP, and may reflect subtle, age-related changes in systemic inflammation. These findings support the potential utility of AAT as a biomarker of biological ageing and mortality risk.