Cardiometabolic disease–associated markers begin to increase at an A1C >5%

Introduction Risk of atherosclerosis and cardiovascular events increases as a function of increasing hemoglobin A1C (A1C), even in patients with normal A1C (<5.7%). Our objective was to determine whether increasing A1C correlates to increasing atherogenic particles (measured as apoB LDL-C discordance), vascular inflammation, and/or worsening metabolic disease. Method We queried the national laboratory information system of the Quest Center for Excellence for Cardiometabolic Testing at Cleveland HeartLab for all persons who had an A1C and apoB simultaneously measured in 2021-22. Results We identified 127,141 outpatients who had both tests simultaneously performed during the study period: average age of 61.6±14.4 years, 52% female, and 63.4% with an A1C <5.7%. LDL-C and apoB levels did not correlate with A1C, peaking at an A1C of 5.2% (108.9±36.4 mg/dL [LDL-C] and 91.5±25.2 mg/dL [apoB]). In contrast, the increased prevalence of apoB-LDL-C discordance correlated strongly with increasing A1C (r 2 =0.95), as did prevalence of vascular inflammation (r 2 =0.97), hypertriglyceridemia (r 2 =0.96), and insulin resistance (r 2 =0.95). Using these 4 markers, each 0.1% increase in A1C (between 5% and 5.7%) correlated with a 4% increase in the number of patients with early evidence of cardiometabolic disease. Discussion We identified a high-risk population, approaching 50% of people with 5%≤A1C<5.7%, who otherwise may be told their biomarker levels are within a "normal" range. Identifying these individuals at an early stage of cardiometabolic dysfunction could motivate aggressive lifestyle or pharmacological measures that reverse their condition and prevent disease.