Diagnosis of coronary artery disease (CAD) before symptoms appear can reduce mortality in diabetes (1). ST depression at exercise stress test (EST) independent of angina is a hallmark of CAD (2); however, if a positive EST is characterized by the lack of angina, a second test to better stratify the risk of ischemia is recommended (3). Heart rate response at EST with ST depression can improve risk stratification in the general population (4), but no such data are available in diabetic patients.
We studied the relationship between heart rate response and CAD in 33 consecutive patients with type 2 diabetes and silent ischemia at EST (i.e., horizontal or downsloping ST depression ≥1 mm at 0.08 s after J point, without angina). Patients (22 men and 11 women, age 59 ± 7 years, BMI 30 ± 4 kg/m2, duration of type 2 diabetes 11 + 6 years, and HbA1c 8.3 ± 1%) with no symptoms or resting electrocardiogram signs of ischemia were considered at “high risk” for CAD due to peripheral vascular disease and/or two additional atherogenic factors according to guidelines criteria (1). Cardiovascular drugs were stopped 48 h before the EST. Coronary angiography was considered positive if stenosis ≥70% was observed in a major epicardial artery or its main branches.
Maximal heart rate at the moment of ST depression was lower in 13 patients with three-vessel disease (7 of whom did not reach the 85% of predicted maximal heart rate) than in 20 patients with less than or equal to two- or no-vessel disease (4 of whom did not reach the 85% of predicted maximal heart rate) (127 ± 12 vs. 140 ± 13 bpm, P = 0.009).
Maximal heart rate <136 bpm (mean and median value) predicted three-vessel disease with an odds ratio (OR) of 7.7 (95% CI 1.5–38, P < 0.05) independent of both age and sex, or of each of the following potential confounders: BMI, diabetes duration, hypertension, smoking, and diabetes complications, including peripheral vascular disease (stenosis ≥40% at ultrasound doppler), nephropathy (urinary albumin excretion rate >20 μg/min), retinopathy (at fundoscopy), and neuropathy (at electromiography).
Heart rate reserve (i.e., maximal heart rate at the moment of ST depression minus resting heart rate) was lower in 13 patients with three-vessel disease than in 20 patients with less than or equal to two- or no-vessel disease (48.6 ± 12 vs. 61 ± 16 bpm, P = 0.01).
Heart rate reserve <56 bpm (mean and median value) predicted three-vessel disease with an OR of 5.0 (95% CI 1.1–24, P < 0.05) independent of both age and sex or each previously mentioned confounder.
Maximal heart rate and heart rate reserve were lower in 17 patients with ejection fraction <60% (mean value) than in 16 patients with ejection fraction >60% (126 ± 12 vs. 143 ± 13 bpm, P = 0.001 for maximal heart rate and 49 ± 12 vs. 63 ± 17 bpm, P = 0.01 for heart rate reserve).
Maximal heart rate <136 bpm (OR 10.9, 95% CI 1.8–66) and heart rate reserve <56 bpm (6.7, 1.3–33) predicted ejection fraction <60%, independent (P < 0.05) of both age and sex or each previously mentioned confounders but not of three-vessel disease.
In conclusion, maximal heart rate and heart rate reserve predict CAD severity and ejection fraction in “high risk” diabetic patients with silent ischemia at EST. The Coronary Artery Surgery Study (CASS) (5) showed that coronary artery bypass surgery improves the prognosis in silent diabetic patients with three-vessel disease and impaired ventricular function. Our present data suggest that maximal heart rate and heart rate reserve might serve the function of identifying these patients who could, therefore, undergo coronary angiography with no need of a second test, thus reducing time and cost of diagnosis.
