Terminal trajectory of HbA for 10 years supports the HbA paradox: a longitudinal study using Health and Retirement Study data.

Objectives: We aimed to assess the potential time-varying associations between HbA and mortality, as well as the terminal trajectory of HbA in the elderly to reveal the underlying mechanisms.

Design: The design is a longitudinal study using data from the Health and Retirement Study.

Setting And Participants: Data were from the Health and Retirement Study. A total of 10,408 participants aged ≥50 years with available HbA measurements at baseline (2006/2008) were included.

Methods: Longitudinal HbA measured at 2010/2012 and 2014/2016 were collected. HbA values measured three times for their associations with all-cause mortality were assessed using Cox regression and restricted cubic splines. HbA terminal trajectories over 10 years before death were analyzed using linear mixed-effect models with a backward time scale.

Results: Women constitute 59.6% of the participants with a mean age of 69 years, with 3,070 decedents during the follow-up (8.9 years). The mortality rate during follow-up was 29.5%. Increased mortality risk became insignificant for the highest quartile of HbA compared to the third quartile (aHR 1.148, 1.302, and 1.069 for a follow-up of 8.9, 6.5, and 3.2 years, respectively) with a shorter follow-up, while it became higher for the lowest quartile of HbA (aHR 0.986, 1.068, and 1.439 for a follow-up of 8.9, 6.5, and 3.2 years, respectively). Accordingly, for both decedents with and without diabetes, an initial increase in HbA was followed by an accelerating terminal decline starting 5-6 years before death.

Conclusions And Implications: The time-varying association between HbA and mortality mapped to the terminal trajectory in HbA. High and low HbA may have different clinical relationships with mortality. The HbA paradox may be partially explained by reverse causation, namely, early manifestation of death.