Background:
Previous studies have suggested an association between severe hypoglycemic events (i.e. requiring external assistance) and coronary artery disease (CAD). However, whether this association varies across patients with different vascular risk remains unclear. We tested the hypothesis that prior severe hypoglycemia was independently associated with incident CAD in diabetes patients cared for in primary care, and that this association was increased for those with elevated vascular risk.
Methods:
We identified a diabetes cohort within a primary care practice network using electronic health records (EHR, N=9,173). Patients with severe hypoglycemic events at baseline (before 1/1/2006) were identified via ICD-9 codes, including 251.0-251.2, from emergency department, inpatient and outpatient visits. Incident CAD, including myocardial infarction, acute coronary syndrome, percutaneous transluminal coronary angiography and coronary artery bypass grafting, occurring after the hypoglycemic event, were determined through problem and procedure lists. Patients were followed until incident CAD, death, their last visit within the network, or 6/30/2012. We used Cox regression with time interaction to determine the association between hypoglycemia and CAD, with significance set at P <0.05. We also tested this association among high vascular risk patients (age ≥55 years, Hemoglobin A1c [HbA1c] ≥7.5% and ≥2 risk factors [dyslipidemia, hypertension or obesity]), and a subset aged ≥65 years.
Results:
A total of 285 (3%) patients had a history of severe hypoglycemia at baseline and 1,098 (12%) developed CAD during follow-up. Severe hypoglycemia was associated with a twofold increase in CAD risk [HR 1.90 (95%CI 1.09-3.31)], adjusting for time interaction, vascular risk factors, diabetes duration and HbA1c; the hypoglycemia-CAD association weakened over time (time interaction P=0.06). Further adjustment for microvascular complications and medication exposures attenuated the association [HR 1.67 (0.96-2.92)]. Among 1,823 (20% of the cohort) high vascular risk patients aged ≥55 years, CAD risk was elevated threefold [HR 3.01 (1.15-7.91)], and in those aged ≥65 years (N=996, 11%), fourfold [HR 4.62 (1.65-12.90)]. The association was not significant among lower vascular risk patients [HR 1.61 (0.97-3.75), N=7,350].
Conclusions:
Prior severe hypoglycemic episodes were strongly associated with incident CAD, especially among high vascular risk patients who were similar to those studied in the ACCORD trial. Whereas severe hypoglycemia was not as strongly associated with CAD in patients with fewer vascular risk factors. Results of studies like ACCORD only apply to a fifth of diabetes patients in this primary care cohort. Careful evaluation of diabetes treatment and close monitoring for CAD are especially needed in older high vascular risk patients with severe hypoglycemia.
