Abstract
Background: We sought to evaluate whether there was a difference in the incidence rate of cardiovascular event (CVD) among different hemoglobin (Hb) A1c levels in diabetic patients without a history of atherosclerotic events. Methods: The Japanese primary prevention of atherosclerosis with aspirin for diabetes (JPAD) trial was a multicenter, prospective, randomized, open label, blinded, end-point study done from 2002 to 2008. After completion of the JPAD trial, we followed up with the patients until 2019. We defined the cardiovascular events as the following: acute myocardial infarction; stable angina; unstable angina; sudden cardiac death; stroke; transient ischemic attack; aortic disease; and peripheral artery disease. Among 2,535 JPAD patients, HbA1c levels of the JPAD patients were recorded on average 8 times. Based on the mean value of HbA1c, we divided the patients into three groups: a High HbA1c Group (n=899, HbA1c ≥7.5%); a Moderate HbA1c Group (n=581, 7.5% >HbA1c ≥7.0 %); or, a Low HbA1c Group (n=1055, 7.0% >HbA1c). We compared the incidence of CVD among the three groups. Results: The mean HbA1c (%) was 8.6 in the High HbA1c Group, 7.4 in the Moderate HbA1c Group, and 6.6 in the Low HbA1c Group on registration. During an 11.56-year follow-up, the incidence of CVD was significantly higher in the High HbA1c Group (P<0.0001, Figure) but was not significantly different between the Moderate HbA1c and the Low HbA1c Groups. Cox proportional hazards model analysis revealed that a High HbA1c level (HR, 1.61: 1.26-2.05, P=0.0001) was an independent factor after adjustment for proteinuria ≥±, age ≥65 years, male, body mass index ≥24 kg/m 2 , duration of diabetes ≥7.0% years, medications, eGFR ≥60 ml/min/1.73m 2 , and systolic blood pressure ≥140 mm Hg (Figure). Conclusions: Our study demonstrated that HbA1c ≥7.5% was independently associated with the incidence of CVD in diabetic patients without a history of atherosclerotic events while 7.5% >HbA1c ≥7.0 % was not.
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