Flow-mediated-paradoxical vasoconstriction is independently associated with asymptomatic myocardial ischemia and coronary artery disease in type 2 diabetic patients

BACKGROUND: To investigate whether flow-mediated dilation (FMD) impairment, which precedes overt atherosclerosis, is associated with silent myocardial ischemia (SMI) and asymptomatic coronary artery disease (CAD) in type 2 diabetes. METHODS: Forearm FMD was measured by ultrasonography in 25 healthy control, 30 non-diabetic overweight or obese patients and 118 asymptomatic type 2 diabetic patients with a high cardiovascular risk profile. SMI (abnormal stress myocardial scintiscan and/or stress dobutamine echocardiogram) and CAD (coronary angiography in the patients with SMI) were assessed in the diabetic cohort. RESULTS: FMD was lower in diabetic patients (median 0.61% (upper limits of first and third quartiles -1.22;3.2)) than in healthy controls (3.95% (1.43;5.25), p < 0.01) and overweight/obese patients (4.25% (1.74;5.56), p < 0.01). SMI was present in 60 diabetic patients, including 21 subjects with CAD. FMD was lower in patients with SMI than in those without (0.12% (-2.3;1.58) vs 1.64% (0;3.69), p < 0.01), with a higher prevalence of paradoxical vasoconstriction (50.0% vs 29.3%, p < 0.05). FMD was also lower in patients with than without CAD (-1.22% (-2.5;1) vs 1.13% (-0.4;3.28), p < 0.01; paradoxical vasoconstriction 61.9% vs 34.4%, p < 0.05). Logistic regression analyses considering the parameters predicting SMI or CAD in univariate analyses with a p value <0.10 showed that paradoxical vasoconstriction (odds ratio 2.7 [95% confidence interval 1.2-5.9], p < 0.05) and nephropathy (OR 2.6 [1.2-5.7], p < 0.05) were independently associated with SMI; and only paradoxical vasoconstriction (OR 3.1 [1.2-8.2], p < 0.05) with CAD. The negative predictive value of paradoxical vasoconstriction to detect CAD was 88.7%. CONCLUSIONS: In diabetic patients, FMD was independently associated with SMI and asymptomatic CAD. TRIAL REGISTRATION: Trial registration number NCT00685984.