ORIGINAL RESEARCH article
Front. Endocrinol.
Sec. Clinical Diabetes
Hemoglobin A1c-Systolic Blood Pressure Index as a Novel Predictor of Cardiovascular Disease: Evidence from Three Prospective Cohorts
Provisionally accepted
- 1Kunshan First People's Hospital affiliated to jiangsu University, Kunshan, China
- 2The Second Affiliated Hospital of Nanjing Medical University, Nanjing, China
Select one of your emails
You have multiple emails registered with Frontiers:
Notify me on publication
Please enter your email address:
If you already have an account, please login
You don't have a Frontiers account ? You can register here
Background: Hypertension and diabetes are major drivers of cardiovascular disease (CVD), and their coexistence confers excess risk. This study aimed to develop a hemoglobin A1c (HbA1c)-systolic blood pressure (SBP) index (HSI) to simultaneously capture glucose and blood pressure status and investigate the associations of baseline and cumulative HSI with incident CVD. Methods: Data were drawn from three population-based cohorts: the China Health and Retirement Longitudinal Study (CHARLS), the English Longitudinal Study of Ageing (ELSA), and the US Health and Retirement Study (HRS). Baseline HSI was calculated as HbA1c (%) × SBP (mmHg)/100. Cumulative HSI was derived from repeated measurements weighted by time intervals. Cause-specific Cox proportional hazards models were used to investigate linear associations of baseline and cumulative HSI with incident CVD. Additionally, restricted cubic splines were used to assess nonlinear relationships. Results: A total of 6,822 participants from CHARLS, 3,640 from ELSA, and 5,709 from HRS were included, with median follow-up of 9.0, 10.0, and 12.3 years, respectively. Across all three cohorts, the combination of elevated HbA1c and SBP was associated with the highest CVD risk. Higher baseline HSI were significantly associated with increased risks of CVD in the CHARLS (hazard ratio [HR] per 1 standard deviation [SD] increase =1.16, 95% confidence interval [CI] 1.11–1.22), ELSA (1.13, 95% CI 1.06–1.21), and HRS (1.14, 95% CI 1.10–1.19). Cumulative HSI levels were also significantly associated with elevated CVD risk (CHARLS: HR per 1 SD increase = 1.19, 95% CI 1.12–1.26; ELSA: 1.14, 95% CI 1.04–1.26; HRS, 1.15, 95% CI 1.08–1.22). No evidence of nonlinearity between baseline HSI and CVD was detected. The associations were almost consistent across demographic and clinical subgroups. The predictive performance of HSI was superior to HbA1c or SBP alone. Conclusions: HSI, a simple composite of HbA1c and SBP, was consistently associated with incident CVD across three international cohorts. Its predictive ability exceeded that of HbA1c or SBP alone, highlighting it as a pragmatic tool for integrated cardiometabolic risk assessment. The findings warrant further clinical validation.
Keywords: cardiovascular disease, Diabetes Mellitus, hemoglobin A1c, Hypertension, prediction, systolic blood pressure
Received: 05 Oct 2025; Accepted: 29 Jan 2026.
Copyright: © 2026 Zhang, Chen, Zhou, Xiang and Zhu. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence:
Boyang Xiang
Shushu Zhu
Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.