INTRODUCTION: Coronary microcirculation is disturbed in patients with arterial hypertension. Carotid intima-media thickness and arterial stiffness are markers of subclinical atherosclerosis with prognostic significance. We investigated whether arterial stiffness determines coronary flow reserve (CFR) in hypertensive patients as well as whether the combination of increased carotid intima-media thickness and arterial stiffness, has a greater predictive value for the presence of impaired of coronary flow reserve than each index alone in never-treated hypertensives. METHODS: We studied 110 untreated patients (age: 54.5±12 years) with newly diagnosed arterial hypertension and 20 healthy controls. We measured a) carotid-to-femoral pulse wave velocity (PWV) b) systolic (Vs) and diastolic (Vd) coronary flow velocity, decceleration time (DT-Vd) and time integral (VTI-Vd) of the diastolic component of coronary flow, as well as coronary flow reserve (CFR) after adenosine by means of colour-guided transthoracic Doppler echocardiography c) ratio of E wave from mitral inflow to Em of mitral annulus, as an index of LV diastolic pressures using tissue Doppler d) carotid intima-media thickness (IMT), as an index of vascular damage e) 24-hour blood pressure parameters using ambulatory blood pressure monitoring. RESULTS: Patients had abnormal PWV, IMT, E/Em, resting Vd/Vs, DT-Vd and CFR than controls (p<0.05). In hypertensives, PWV was related to abnormal IMT and E/Em which in turn were related to reduced CFR (p<0.05). Among other confounders, PWV and E/Em were independent determinants of CFR,Vd/Vs and DT-Vd (p<0.05) in hypertensives. ROC analysis showed that pulse wave velocity >10.2 m/s and intima-media thickness >1mm were the optimal cut-off values to predict a coronary flow reserve <2.5. When added to a model including age, sex, smoking, LV mass, heart rate, 24h-systolic blood pressure, and E/Em, PWV had an incremental value for the determination of CFR: 152 PWV>10.2 m/sec predicted a CFR <2 with 79% and 75% and a CFR< 2.5 with 83% and 82% sensitivity and specificity respectively using adjusted-ROC analysis. Arterial stiffness and intima-media thickness had an incremental value for the determination of coronary flow reserve when added to a model including other confounders (ρ2 change=4.423, p for change =0.038 after addition of intima-media thickness and ρ2 change=5.369, p for change =0.020 after addition of pulse wave velocity). Patients with ΗΜΣ >1 mm, PWV>10.2 m/s or their combination had an odds ratio of 3.5, 5.0 and 11.2, p<0.05, for a coronary flow reserve <2.5, respectively. CONCLUSIONS: Elevated LV diastolic compressive forces on coronary microcirculation and the presence of generalised vascular damage may explain the association between PWV and CFR. PWV has an incremental value in the determination of impaired coronary microcirculation in hypertensive patients. The combination of increased carotid intima-media thickness and arterial stiffness has a greater predictive value for impaired of coronary flow reserve than each index alone in never-treated hypertensives.