Serum Calcification Propensity and CPP2 Size - Deranged Mineral Buffering and The Risk of Mortality in Older Adults

Ageing is associated with increased vascular calcification. However, the parallels with chronic kidney disease are unclear, where secondary calciprotein particles (CPP2) are increasingly formed due to insufficient mineral buffering. CPP2 induce vascular dysfunction as well as calcification and thereby could increase mortality risk. This study aimed to assess whether indicators of deranged mineral buffering are associated with mortality in older adults. Serum calcification propensity (T₅₀) and hydrodynamic radius of CPP2 were assessed in 1,566 participants of the population-based Berlin Initiative (cohort) Study (BIS) of older adults with a mean age of 81.8 years. The associations with all-cause and cardiovascular mortality were assessed using multivariable Cox regression models, adjusted for cardiovascular risk factors. During a median follow-up of 9.1 years, 814 participants died, of whom 350 died from a cardiovascular cause. An increase of CPP2 size was associated with increased Hazard Ratios (HR) for all-cause mortality (age and sex adjusted HR [95% CI], 1.19 [1.10-1.28]; fully adjusted for other confounders HR [95% CI], 1.15 [1.06-1.24]) and cardiovascular mortality when age and sex adjusted (HR [95% CI], 1.17 [1.05-1.31]) but not when fully adjusted (HR [95% CI], 1.11 [0.98-1.25]). Furthermore, each 60 min decrease of T₅₀ was associated with increased HR for all-cause mortality when age and sex adjusted (HR [95% CI], 1.10 [1.03-1.17]) but not when fully adjusted (HR [95% CI], 1.06 [1.00-1.14]), and without clear association with cardiovascular mortality (fully adjusted, HR [95% CI], 0.98 [0.89-1.08]). Disturbed mineral buffering, as inferred from increased CPP2 size, may be a novel and independent risk factor for mortality in older adults.