Determinants of coronary endothelial dysfunction in hypertensive patients

Abstract

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Objectives: Coronary endothelial function is impaired at early stage of atherosclerosis in hypertensive patients. However, the magnitude of endothelial dysfunction is different among patients. Thus, we examined the determinants of coronary endothelial dysfunction in the relationship between atherogenic factors and hypertension.

Methods: This study included 22 untreated essential hypertensive patients without left ventricular hypertrophy (mean age 51±12 years old) and 12 age-matched healthy controls. Patients with a history or clinical evidence of coronary artery disease, diabetes mellitus with HbA1c > 5.8%, hyperlipidemia with total cholesterol > 260 mg/dl, or of age more than 70 years old were excluded. Myocardial blood flow (MBF) was measured at rest and during sympathetic stimulation induced by cold pressor test (CPT) by using ¹⁵O-water PET. Coronary vascular resistance (CVR) was calculated by dividing the mean blood pressure by MBF for correcting the effect of blood pressure. CVR during CPT (CPT-CVR) was used as a marker of coronary endothelial function.

Results: Body mass index (BMI), left ventricular mass index (LVMI), LDL cholesterol, blood sugar (BS), and resting CVR were similar in the two groups. Blood pressure (BP) and CPT-CVR in hypertensive patients was significantly higher than those in healthy controls (144±14/82±10 vs. 116±12/65±11 mmHg, 122±33 vs. 93±20 mmHg/ (ml/g/min); respectively, p<0.01). In univariate analysis, CPT-CVR in hypertension patients was correlated with LDL cholesterol (r=0.57, p<0.01), malondialdehyde (r=0.41, p=0.07), and interleukin-6 (IL-6) (r=0.43, p<0.05), but not with age, resting BP, BMI, BS, HDL cholesterol, high-sensitivity CRP, TNF-alpha, NOX, or LVMI. In multivariate analysis, BP, LDL cholesterol and IL-6 were independent determinants of CPT-CVR.

Conclusions: ¹⁵O-water PET and CPT is valuable for early detection of subclinical coronary atherosclerosis. Moreover, our data suggest that BP, LDL cholesterol and IL-6 are the major determinants of coronary endothelial dysfunction in hypertensive patients.