Relationship of Glycated Hemoglobin A1c with All-Cause and Cardiovascular Mortality among Patients with Hypertension

Both low and high glycated hemoglobin A1c (HbA1c) levels are well-established causal risk factors for all-cause and cardiovascular mortality in the general population and diabetic patients. However, the relationship between HbA1c with all-cause and cardiovascular mortality among patients with hypertension is unclear. We used NHANES data from 1999 to 2014 as the basis for this population-based cohort study. Based on HbA1c levels (HbA1c > 5, HbA1c > 5.5, HbA1c > 6, HbA1c > 6.5, HbA1c > 7%), hypertensive patients were divided into five groups. An analysis of multivariable Cox proportional hazards was conducted based on hazard ratios (HRs) and respective 95% confidence intervals (CIs). The relationship between HbA1c and mortality was further explored using Kaplan-Meier survival curves, restricted cubic spline curves, and subgroup analyses. In addition, 13,508 patients with hypertension (average age 58.55 +/- 15.56 years) were included in the present analysis, with 3760 (27.84%) all-cause deaths during a follow-up of 127.69 +/- 57.9 months. A U-shaped relationship was found between HbA1c and all-cause and cardiovascular mortality (all p for likelihood ratio tests were 0.0001). The threshold value of HbA1c related to the lowest risk for all-cause and cardiovascular mortality was 5.3% and 5.7%, respectively. Below the threshold value, increased HbA1c levels reduced the risk of all-cause mortality (HR 0.68, 95% CI 0.51-0.90, p = 0.0078) and cardiovascular mortality (HR 0.77, 95% CI 0.57-1.05, p = 0.0969). Inversely, above the threshold value, increased HbA1c levels accelerated the risk of all-cause mortality (HR 1.14, 95% CI 1.11-1.18, p < 0.0001) and cardiovascular mortality (HR 1.22, 95% CI 1.16-1.29, p < 0.0001). In conclusion, A U-shape relationship was observed between HbA1c and all-cause and cardiovascular mortality among hypertensive patients.