Association of HbA1c With Cardiovascular Outcomes: The Role of Diabetes Duration and Cardiometabolic Factors

Abstract

Background Glycated hemoglobin (HbA1c) is widely used as a marker of glycemic control and has been associated with cardiovascular disease (CVD); however, whether HbA1c is independently associated with prevalent CVD after accounting for traditional cardiometabolic risk factors remains uncertain. Methodology We conducted a cross-sectional analysis of 30,804 U.S. adults aged ≥18 years from the National Health and Nutrition Examination Survey (NHANES). Cardiovascular outcomes (coronary artery disease (CAD), myocardial infarction, and stroke) were defined using self-reported physician diagnoses. Associations between HbA1c and cardiovascular outcomes were evaluated using sequential logistic regression models with adjustment for demographic, metabolic, socioeconomic, and diabetes-related variables. Results Higher HbA1c levels were associated with increased odds of cardiovascular outcomes in unadjusted analyses. These associations were attenuated after adjustment for age and sex and were no longer statistically significant in fully adjusted models. Diabetes duration demonstrated a strong age-dependent gradient and contributed to attenuation of HbA1c effects. In stratified analyses, HbA1c was not significantly associated with outcomes in either individuals with diabetes or those without diabetes. Interaction analyses showed no consistent effect modification, except for a potential interaction between HbA1c and diabetes status for CAD. Conclusions The observed associations between HbA1c and prevalent cardiovascular outcomes were attenuated after adjustment for demographic, metabolic, socioeconomic, and diabetes-related variables. Because some adjustment variables may lie on the causal pathway, these findings should be interpreted cautiously and as observational associations rather than evidence of causality.