Stavros Tzortzis

Incremental Value of Pulse Wave Velocity in the Determination of Coronary Microcirculatory Dysfunction in Never-treated Patients With Essential Hypertension

BACKGROUND Coronary microcirculation is disturbed in essential hypertension. We investigated whether arterial stiffness determines coronary flow reserve (CFR) in hypertensive patients. METHODS We examined 100 never-treated hypertensives and 20 healthy controls. We measured (i) carotid-to-femoral pulse wave velocity (PWV); (ii) Systolic (V (s)) and diastolic (V (d)) coronary flow velocity, time integral (V (TI)-V (d)) of diastolic velocity and CFR after adenosine by transthoracic echocardiography; (iii) ratio of E wave from mitral inflow to Em of mitral annulus, as an index of left ventricular (LV) diastolic pressures using tissue Doppler; (iv) carotid intima-media thickness (IMT), as an index of vascular damage; and (v) 24-h blood pressure parameters using ambulatory blood pressure monitoring. RESULTS Patients had abnormal PWV, IMT, E/Em, resting V (d)/V (s), 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). PWV and E/Em were independent determinants of CFR and V (d)/V (s) (P < 0.05) in hypertensives. When added to a model including age, sex, smoking, LV mass (LVM), heart rate, 24-h systolic blood pressure (SBP), and E/Em, PWV had an incremental value in the determination of CFR (r (2) change from 0.25 to 0.46, P < 0.01). PWV >10.7 m/s predicted a CFR <2 with 79 and 75% and a CFR <2.6 with 83 and 82% sensitivity and specificity, respectively, using adjusted-receiver operating characteristic curve (ROC) analysis. CONCLUSIONS Elevated LV diastolic compressive forces on coronary microcirculation and the presence of generalized 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.

Cognitive Impairment Is Related to Increased Arterial Stiffness and Microvascular Damage in Patients With Never-Treated Essential Hypertension

BACKGROUND It is known that essential hypertension may be implicated in the development of cognitive impairment that is associated to microvascular disease of the brain. It has been hypothesized that increased arterial stiffness of the large arteries may lead to microvascular changes due to increased pulsatile flow. Our study tests the hypothesis that large artery stiffness and microvascular damage are related to brain microcirculation changes as reflected by impaired cognitive function. METHODS We studied 110 nondiabetic patients aged 40-80 years (mean age 53.8 +/- 11.2 years, 57 men) with recently diagnosed stage I-II essential hypertension. Mini-Mental State Examination (MMSE) was used as a screening test for global cognitive impairment. We performed both 2-D echocardiography and carotid-femoral pulse wave velocity (PWV) in order to evaluate arterial stiffness. Twenty-four hour urine microalbumin excretion was measured as a marker of microvascular damage. RESULTS In the entire population, MMSE was negatively correlated with age (r = -0.42, P < 0.001), 24-h pulse pressure (PP) (r = -0.18, P < 0.05), and PWV (r = -0.3, P = 0.003). Additionally, MMSE was not independently correlated with microalbuminuria in patients aged over 65 years (r = -0.58, P = 0.003). CONCLUSIONS Impaired cognitive function is associated with increased large artery stiffness and microalbumin excretion in newly diagnosed, untreated hypertensive patients. These findings support the hypothesis that cognitive impairment induced by impaired microcirculation is linked to large artery stiffness and microvascular damage.

Increased benefit of interleukin-1 inhibition on vascular function, myocardial deformation, and twisting in patients with coronary artery disease and coexisting rheumatoid arthritis.

Background—We investigated the effects of anakinra, an interleukin-1 receptor antagonist, on coronary and left ventricular function in coronary artery disease (CAD) patients with rheumatoid arthritis. Methods and Results—In a double-blind crossover trial, 80 patients with rheumatoid arthritis (60 with CAD and 20 without) were randomized to a single injection of anakinra or placebo and after 48 hours to the alternative treatment. At baseline and 3 hours after treatment, we assessed (1) flow-mediated dilation of brachial artery; (2) coronary flow reserve, ejection fraction, systemic arterial compliance, and resistance by echocardiography; (3) left ventricular global longitudinal and circumferential strain, peak twisting, untwisting velocity by speckle tracking; and (4) interleukin-1&bgr;, nitrotyrosine, malondialdehyde, protein carbonyl, and Fas/Fas ligand levels. At baseline, patients with CAD had 3-fold higher interleukin-1&bgr;, protein carbonyl, higher nitrotyrosine, malondialdehyde, and Fas/Fas ligand than non-CAD (P<0.05). After anakinra, there was a greater improvement of flow-mediated dilation (57±4% versus 47±5%), coronary flow reserve (37±4% versus 29±2%), arterial compliance (20±18% versus 2±17%), resistance (−11±19% versus 9±21%), longitudinal strain (33±5% versus 18±2%), circumferential strain (22±5% versus 13±5%), peak twisting (30±5% versus 12±5%), untwisting velocity (23±5% versus 13±5%), ejection fraction (12±5% versus 0.5±5%), apoptotic and oxidative markers, and, in particular, of protein carbonyl (35±20% versus 14±9%) in CAD than in non-CAD patients (P<0.01). No changes in the examined markers were observed after placebo. Conclusions—Interleukin-1 inhibition causes a greater improvement in endothelial, coronary aortic function in addition to left ventricular myocardial deformation and twisting in rheumatoid arthritis patients with CAD than in those without. Clinical Trial Registration—URL: http://www.clinicaltrials.gov. Unique identifier: NCT01566201.

Lowering interleukin-1 activity with anakinra improves myocardial deformation in rheumatoid arthritis.

Objective: Inhibition of interleukin-1 activity improves nitro-oxidative stress, endothelial and coronary function. The authors investigated (a) the association of nitro-oxidative stress and endothelial function with myocardial deformation, (b) the effects of anakinra, an interleukin-1a receptor antagonist on myocardial deformation in patients with rheumatoid arthritis (RA). Methods: The authors compared 46 RA patients to 23 normal controls. 23 patients received anakinra (150 mg subcutaneously once daily) and 23 patients a 5-mg increase of prednisolone dose for 30 days. At baseline and post-treatment this study assessed (a) the left ventricular (LV) longitudinal, circumferential and radial strain and strain rate, using speckle tracking echocardiography, (b) the coronary flow reserve (CFR), (c) the flow-mediated endothelial-dependent dilation of the brachial artery (FMD) and (d) nitrotyrosine (NT) and malondialdehyde blood levels. Results: Patients had impaired baseline myocardial deformation indices compared to controls (p<0.05). CFR and NT levels were related to longitudinal strain, systolic and diastolic strain rate, circumferential strain and systolic strain rate (p<0.05). FMD was related to longitudinal and circumferential diastolic strain rate (p<0.01). Compared to baseline, anakinra-treated patients increased the longitudinal strain (−17.8% (3.7%) vs −22.1% (3.5%)), systolic (−1.02 (0.23) l/s vs −1.25 (0.23) l/s) and diastolic (0.96 (0.37) l/s vs 1.20 (0.39) l/s) longitudinal strain rate, circumferential strain and strain rate (p<0.05 for all comparisons). No significant changes were observed among prednisolone-treated patients Conclusions: Myocardial deformation is impaired in RA patients and is related to nitro-oxidative stress and endothelial dysfunction. Chronic inhibition of IL-1 improves LV deformation in parallel with endothelial function and nitro-oxidative stress.

Association of Target Organ Damage With Three Arterial Stiffness Indexes According to Blood Pressure Dipping Status in Untreated Hypertensive Patients

BACKGROUND Subclinical organ damage represents an intermediate stage in the continuum of vascular disease and a determinant of overall cardiovascular risk. We investigated the associations of pulse wave velocity (PWV), ambulatory arterial stiffness index (AASI), and office pulse pressure (PP) with several target organ damages (TODs) in newly diagnosed and never-treated patients with essential hypertension with respect to their dipping profile. METHODS One hundred sixty-eight hypertensive patients with recently diagnosed and never-treated stage I-II essential hypertension were evaluated with respect to the relationship of PWV, AASI, and office PP with TOD including microalbumin (MAU) levels, cognitive function, intima-media thickness (IMT), coronary flow reserve (CFR), left ventricular mass (LVM), left ventricular filling pressures, diastolic dysfunction, and left atrium (LA) enlargement. RESULTS Simultaneous estimation of AASI, PWV, and office PP independently associated with the following: (i) CFR (P < 0.01), 24-h urine albumin excretion rates (P < 0.05), left ventricular diastolic dysfunction (P < 0.01), and LA enlargement (P < 0.01) in never-treated hypertensive patients; (ii) CFR (P < 0.05), IMT (P < 0.01), left ventricular diastolic dysfunction (P < 0.05), and LA enlargement (P < 0.05) in dippers; and (iii) CFR (P < 0.05) and LA enlargement (P < 0.01) in nondippers. Nonindependent relationships revealed between (i) AASI and left ventricular filling pressures and (ii) PWV and cognitive dysfunction in never-treated hypertensive patients. CONCLUSIONS The simultaneous estimation of three noninvasive indexes of arterial stiffness leads to valuable information regarding their association with TOD including CFR, MAU levels, IMT, left ventricular diastolic dysfunction, and LA enlargement in never-treated hypertensive patients regarding their dipping status.

Association of impaired left ventricular twisting-untwisting with vascular dysfunction, neurohumoral activation and impaired exercise capacity in hypertensive heart disease.

We investigated the association between left ventricular (LV) torsional deformation and vascular dysfunction, fibrosis, neurohumoral activation, and exercise capacity in patients with normal ejection fraction

Apical hypertrophic cardiomyopathy associated with multiple coronary artery–left ventricular fistulae: a report of a case and review of the literature

We present a rare case of multiple coronary artery-left ventricular (LV) fistulae, associated with apical hypertrophic cardiomyopathy in an 83-year-old woman with electrocardiographic abnormalities and a history of arterial hypertension and paroxysmal atrial fibrillation. In order to evaluate the clinical significance and obtain further insights into this unusual disease, the patient has undergone coronary angiography, left ventriculography, and magnetic resonance imaging which better substantiated the structural abnormalities of the LV and the coronary network.

Incremental predictive value of carotid intima–media thickness to arterial stiffness for impaired coronary flow reserve in untreated hypertensives

Coronary microcirculation is disturbed in patients with arterial hypertension. Carotid intima–media thickness (IMT) and arterial stiffness are markers of subclinical atherosclerosis with prognostic significance. We investigated whether the combination of increased carotid IMT and arterial stiffness has a greater predictive value for the presence of impaired coronary flow reserve (CFR) than each index alone in never-treated hypertensives. We studied 110 untreated patients (age: 54.5±12 years) with newly diagnosed arterial hypertension. We measured (1) carotid-to-femoral artery pulse wave velocity (PWV), (2) carotid IMT and (3) CFR by means of color-guided Doppler echocardiography after adenosine infusion. Among other confounders, arterial stiffness and IMT were independent determinants of CFR (coefficient B=−0.146 and B=−0.006, P<0.05). Arterial stiffness and IMT had an incremental value for the determination of CFR when added to a model including other confounders (χ2 change=4.423, P for change=0.038 after addition of IMT; and χ2 change=5.369, P for change=0.020 after addition of PWV). Receiver operating curve analysis showed that PWV>10.2 m s−1 and IMT>1 mm were the optimal cutoff values to predict a CFR<2.5. Patients with IMT>1 mm, PWV>10.2 m s−1 or their combination had an odds ratio of 3.5, 5.0 and 11.2, P<0.05, for a CFR<2.5, respectively. The combination of increased carotid IMT and arterial stiffness has a greater predictive value for impaired CFR than each index alone in never-treated hypertensives.

The effect of acute administration of statins on coronary microcirculation during the pre-revascularization period in patients with myocardial infraction

UNLABELLED The beneficial effects of statin pretreatment as well as of staccato reperfusion (SR) on myocardium have been demonstrated in patients undergoing cardiac interventions. In this study, we compared the effects of the acute statin administration prior to percutaneous coronary intervention (PCI) with the effects of staccato or abrupt reperfusion on coronary microcirculation in patients with myocardial infarction (MI). METHODS We randomly assigned 47 patients who had ST-elevation or non-ST-elevation MI 48 h prior to PCI, into three groups: staccato reperfusion (consisting of 6 periods of 10-s balloon inflation/deflation) plus statin therapy (SRSG), statin therapy plus abrupt reperfusion (SG), and abrupt reperfusion alone (ARG). Myocardial contrast echocardiography (MCE) was performed to assess the blood volume (A), velocity (β) and flow (A × β) of the segments associated with the PCI-treated artery the day following intervention and 30 days after. LV end-diastolic (EDV) and systolic volumes (ESVs), wall motion score index (WMSI) were evaluated. RESULTS Compared to ARG, SRSG and SG resulted in a greater improvement in A, β and A × β (F = 20.6, p < 0.001 for A, F = 3.5, p = 0.03 for β and F = 11.3, p < 0.001 for A × β for the overall effect of intervention) as well as a greater decrease of WMSI, EDV and ESV (p < 0.01) one month post-PCI. The changes of all echocardiography markers were greater in SRSG than SG (p < 0.01). The % changes in ESV correlated with the corresponding % changes in MCE indices in SRSG and SG (p < 0.05). CONCLUSION The acute statin administration prior to reperfusion either alone or in synergy with staccato reperfusion ameliorates coronary microcirculatory dysfunction in patients with myocardial infarction.

Is Arterial Hypertension Control Enough to Improve Aortic Stiffness in Untreated Patients With Hypertension? A 3-Year Follow-Up Study:

Aortic stiffness is an important determinant of cardiovascular risk. We studied the long-term influence of successful antihypertensive treatment after a 3-year follow-up, regarding aortic stiffness improvement from baseline evaluation in never treated middle-aged patients with mild to moderate essential hypertension. In 132 patients with hypertension, aortic stiffness was evaluated by carotid–femoral artery pulse wave velocity (PWV). Patients with 24-hour mean systolic and diastolic blood pressure ≤130/80 mm Hg after treatment at reevaluation were considered as well controlled. The PWV after treatment was significantly increased in all patients with hypertension (P < .01) and uncontrolled patients with hypertension (P < .001), remained unchanged in controlled patients with hypertension, and decreased in controlled patients with hypertension with baseline PWV ≥12.4 m/s (P = .004), independent of the corresponding blood pressure (BP) decrease. Our study provides evidence that successful antihypertensive treatment leads to PWV improvement when baseline aortic stiffness level is at least moderately increased. The magnitude of observed PWV decrease is independent of the corresponding BP decrease.