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

Abstract

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.