ABSTRACT
BACKGROUND: Arterial elastance to left ventricular elastance ratio assessed by echocardiography is widely used as a marker of ventricular-arterial coupling. MATERIALS AND METHODS: We investigated whether the ratio of carotid-femoral pulse wave velocity, as a marker of arterial stiffness, to global longitudinal strain, as a marker of left ventricular performance, could be better associated with vascular and cardiac damage than the established arterial elastance/left ventricular elastance index. In 299 newly-diagnosed untreated hypertensives we measured, carotid-femoral pulse wave velocity, and carotid intima-media thickness, coronary-flow reserve, arterial elastance/left ventricular elastance, global longitudinal strain, and markers of left ventricular diastolic function (E/A and E') by echocardiography. RESULTS: Pulse wave velocity-to-global longitudinal strain ratio (PWV/GLS) was lower in hypertensives than controls (-0.61 ± 0.21 vs -0.45 ± 0.11 m/sec%, P < 0.001). Low PWV/GLS values were associated with carotid-intima media thickness > 0.9 mm (P = 0.003), E/A ≤ 0.8 (P = 0.019) and E' ≤ 9 cm/sec (P = 0.002) and coronary-flow reserve < 2.5 (P = 0.017), after adjustment for age, sex and mean arterial pressure. Low PWV/GLS was also associated with increased left ventricular mass and left atrial volume in the univariate (P = 0.003 and 0.038) but not in the multivariate model. In hypertensives, there was no significant association of arterial elastance-to-left ventricular elastance index with carotid intima media thickness, coronary flow reserve, E/A, E', or left atrial volume with the exception of an inverse association with left ventricular mass (P = 0.027). CONCLUSIONS: Pulse wave velocity-to-global longitudinal strain ratio but not the echocardiography-derived arterial elastance-to left ventricular elastance index is related to impaired carotid-intima media thickness, coronary-flow reserve and diastolic function in hypertensives.
Subject(s)
Hypertension/physiopathology , Blood Flow Velocity/physiology , Carotid Artery, Common/physiology , Carotid Artery, Internal/physiology , Carotid Intima-Media Thickness , Case-Control Studies , Elasticity/physiology , Female , Femoral Artery/physiology , Fractional Flow Reserve, Myocardial/physiology , Humans , Male , Middle Aged , Pulse Wave Analysis , Stress, Mechanical , Vascular Stiffness/physiology , Ventricular Function, Left/physiologyABSTRACT
OBJECTIVE: The aim of this report is to describe a case of atrial fibrillation and shock precipitated by deliberate self-poisoning with theophylline. CLINICAL PRESENTATION AND INTERVENTION: An 85-year-old male with severe theophylline intoxication in a suicide attempt was admitted with severe cardiac arrhythmia and shock; despite poor prognosis, he fully recovered gradually after proper diagnosis and treatment. Theophylline is a rather forgotten medication; thus, intoxication is not usually considered among the etiologies of potentially treatable cardiologic emergencies, especially when its use is intentionally concealed. CONCLUSION: This case highlights the importance of identifying a comprehensive medication history using all available sources of information as early as possible in an emergency department presentation.
Subject(s)
Atrial Fibrillation/chemically induced , Shock/chemically induced , Theophylline/adverse effects , Vasodilator Agents/adverse effects , Aged, 80 and over , Diagnosis, Differential , Humans , Male , Suicide, Attempted , Treatment OutcomeABSTRACT
BACKGROUND: Cardiopulmonary fitness is associated with reduced cardiovascular risk. Abnormal systolic blood pressure (SBP) response during recovery has been found to have diagnostic role for detecting cardiovascular risk. Aim of the study was to determine whether increased arterial stiffness associates with reduced aerobic exercise capacity after maximal cardiopulmonary exercise test (CPET) in a cohort of recently diagnosed hypertensive patients with a delayed decline in SBP during recovery. METHODS: Eighty-four hypertensive patients with recently diagnosed I-II essential hypertension and under treatment with RAAS antagonists ± HCTZ, underwent pulse wave velocity (PWV) estimation and a maximal CPET. Fifty-four healthy normotensive subjects served as a control group. Blood pressure recovery ratio (BPRR) was defined as the SBP after 3 min recovery divided by SBP at peak exercise. RESULTS: PWV was significantly increased in hypertensives vs normotensives (p < 0.001). A non-independent, reverse association between PWV and VO2PEAK was revealed in hypertensives with delayed BPRR (r = - 0.49, p < 0.05). Age and sex independently predicted VO2PEAK in hypertensives with delayed BPRR. CONCLUSIONS: Delayed blood pressure response detected during recovery in treated hypertensives implies a reverse relationship between any given impaired aerobic exercise capacity and expected persistent peripheral vascular resistance during exercise.
Subject(s)
Blood Pressure/physiology , Exercise Tolerance/physiology , Exercise/physiology , Hypertension/physiopathology , Vascular Stiffness/physiology , Exercise Test , Humans , Hypertension/pathology , Male , Middle Aged , Risk FactorsABSTRACT
BACKGROUND: The impact of wild-type transthyretin-related cardiac amyloidosis (ATTRwt) on functional and structural peripheral vascular measures is unknown. In the present study, we explored patterns of vascular dysfunction in patients with ATTRwt in comparison to diseases with similar cardiac phenotype. METHODS: Treatment-naïve patients with ATTRwt (n = 32) were compared to: 1. Age-and sex-matched reference population without amyloidosis (n = 32), 2. Age-and sex-matched patients with systemic AL amyloidosis (n = 32), and 3. patients with cardiac AL amyloidosis (AL-HF, n = 23) or elderly patients with heart failure with preserved ejection fraction (HFpEF) (n = 16). All subjects underwent peripheral vascular assessment using carotid artery ultrasonography, brachial artery flow-mediated dilation (FMD), measurement of arterial stiffness and aortic hemodynamics including heart rate-adjusted time of return of reflected waves (Tr/HR). RESULTS: After adjustment for traditional cardiovascular risk factors and coronary artery disease (core model), peripheral and aortic blood pressures (BP) were lower in patients with ATTRwt (p < 0.05) whereas other vascular markers were preserved compared to the reference non-amyloidosis group. ATTRwt was independently associated with lower BP and longer Tr/HR compared to AL. Compared to AL-HF, FMD was lower in ATTRwt (p = 0.033). ATTRwt patients had lower BP and higher Tr/HR than HFpEF (p < 0.05). By ROC analysis, Tr/HR discriminated ATTRwt vs. AL-HF (sensitivity 93%, specificity 75%) and HFpEF (sensitivity 100%, specificity 94%) and lower FMD increased the likelihood for ATTRwt at low Tr/HR values. CONCLUSION: ATTRwt patients present a distinct peripheral vascular fingerprint which is different from AL-HF or HFpEF, consisting of lower peripheral and aortic BP, prolonged Tr/HR and FMD at reference-population range.
Subject(s)
Amyloid Neuropathies, Familial , Amyloidosis , Heart Failure , Immunoglobulin Light-chain Amyloidosis , Amyloid Neuropathies, Familial/diagnostic imaging , Amyloidosis/complications , Amyloidosis/diagnostic imaging , Heart Failure/complications , Heart Failure/diagnostic imaging , Humans , Prealbumin , Stroke Volume/physiologyABSTRACT
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.
Subject(s)
Cardiomyopathy, Hypertrophic/diagnosis , Coronary Artery Disease/diagnosis , Heart Diseases/diagnosis , Vascular Fistula/diagnosis , Aged, 80 and over , Cardiomyopathy, Hypertrophic/complications , Coronary Artery Disease/complications , Female , Heart Diseases/complications , Heart Ventricles , Humans , Vascular Fistula/complicationsABSTRACT
We investigated the effects of optimizing blood pressure control on cardiac deformation and vascular function. For this purpose, in 200 untreated patients with essential hypertension, we assessed at baseline as well as after 3 years of optimal blood pressure control: arterial stiffness and coronary microcirculatory function as well as longitudinal and torsional deformation parameters. Compared to baseline, after 3 years of optimal blood pressure control, there was an improvement of longitudinal strain, twisting as well as untwisting parameters of the left ventricle. In parallel, there was an improvement in coronary microcirculatory function, arterial stiffness, left ventricular mass, and ventricular-arterial interaction. The reduction of arterial stiffness was independently associated with the respective improvement of cardiac deformation markers and coronary flow reserve after adjusting for blood pressure improvement. Blood pressure optimization improves LV longitudinal and torsional mechanics in hypertensives in parallel with arterial stiffness, resulting in improved ventricular-arterial interaction and coronary flow reserve. Trial registration: ClinicalTrials.gov Identifier: NCT02346695.
Subject(s)
Antihypertensive Agents/therapeutic use , Blood Pressure/drug effects , Coronary Circulation/drug effects , Hypertension/drug therapy , Microcirculation/drug effects , Torsion Abnormality/drug therapy , Vascular Stiffness/drug effects , Ventricular Dysfunction, Left/drug therapy , Ventricular Function, Left/drug effects , Adult , Aged , Female , Follow-Up Studies , Humans , Hypertension/diagnostic imaging , Hypertension/physiopathology , Male , Middle Aged , Time Factors , Torsion Abnormality/diagnostic imaging , Torsion Abnormality/physiopathology , Treatment Outcome , Ventricular Dysfunction, Left/diagnostic imaging , Ventricular Dysfunction, Left/physiopathologyABSTRACT
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.
Subject(s)
Blood Pressure , Carotid Arteries/physiopathology , Coronary Artery Disease/etiology , Coronary Circulation , Femoral Artery/physiopathology , Hypertension/physiopathology , Adenosine , Adult , Aged , Blood Flow Velocity , Carotid Arteries/diagnostic imaging , Case-Control Studies , Coronary Artery Disease/physiopathology , Echocardiography, Doppler, Color , Elasticity , Female , Femoral Artery/diagnostic imaging , Fractional Flow Reserve, Myocardial , Humans , Hypertension/complications , Hypertension/diagnostic imaging , Male , Microcirculation/physiopathology , Middle Aged , Models, Cardiovascular , Myocardial Contraction , Prospective Studies , ROC Curve , Time Factors , Ventricular Function, Left , Ventricular PressureABSTRACT
Angiotensin converting enzyme (ACE) promotes cardiac fibrosis. LV myocardial deformation and torsion are markers of subclinical myocardial dysfunction. We investigated the association of serum ACE levels with LV deformation markers in untreated hypertensives. In 120 untreated patients (age: 53.5 ± 11.2 years) with essential hypertension and 60 healthy controls, we measured (a) LV longitudinal, circumferential and radial strain (S), peak torsion and the percentage changes between peak twisting and untwisting at the end of early diastolic filling (%dpTw-UtwEDF) using speckle tracking echocardiography and (b) serum levels of ACE and NTproBNP. Compared to controls, patients had decreased longitudinal strain (-19.1 ± 2.9 vs. -21.7 ± 1.8%), increased peak twisting (19.1 ± 4.6 vs.14.0 ± 3.7 deg) but decreased %dpTw-UtwEDF (78 ± 8 vs. 86 ± 8%) and higher serum ACE levels (27.6 ± 8.0 vs 20.9 ± 7.1 U/ml) (p < 0.05 for all comparisons). Increasing serum ACE levels were related to impaired radial strain and longitudinal systolic SR (b = -0.41 and b = 0.31 respectively, p < 0.01), as well as to reduced %dpTw-UtwEDF (b = -0.37, p < 0.05). Furthermore, increasing serum ACE levels were related to increasing NTproBNP levels (b = 0.41, p < 0.01). In multivariate analysis, the above relations of serum ACE levels and LV function parameters remained significant after adjustment for other confounding factors (p < 0.01). The close link between serum ACE levels and impaired LV deformation suggests that activation of renin-angiotensin system is involved in the impairment of LV function resulting in elevated LV filling pressures causing the concomitant elevation of BNP levels in untreated hypertensive patients.
Subject(s)
Echocardiography, Doppler/methods , Hypertension/diagnostic imaging , Myocardial Contraction , Peptidyl-Dipeptidase A/blood , Renin-Angiotensin System , Ventricular Dysfunction, Left/diagnostic imaging , Ventricular Function, Left , Adult , Aged , Biomarkers/blood , Biomechanical Phenomena , Chi-Square Distribution , Female , Fibrosis , Humans , Hypertension/complications , Hypertension/physiopathology , Linear Models , Male , Middle Aged , Multivariate Analysis , Natriuretic Peptide, Brain/blood , Peptide Fragments/blood , Predictive Value of Tests , Prognosis , Risk Factors , Stress, Mechanical , Torsion, Mechanical , Up-Regulation , Ventricular Dysfunction, Left/etiology , Ventricular Dysfunction, Left/physiopathology , Ventricular PressureABSTRACT
AIM: To investigate the association of arterial wave reflection with coronary flow reserve (CFR) in coronary artery disease (CAD) patients after successful revascularization. METHODS: We assessed 70 patients with angiographically documented CAD who had undergone recent successful revascularization. We measured (1) reactive hyperemia index (RHI) using fingertip peripheral arterial tonometry (RH-PAT Endo-PAT); (2) carotid to femoral pulse wave velocity (PWVc-Complior); (3) augmentation index (AIx), the diastolic area (DAI%) and diastolic reflection area (DRA) of the central aortic pulse wave (Arteriograph); (4) CFR using Doppler echocardiography; and (5) blood levels of lipoprotein-phospholipase A2 (Lp-PLA2). RESULTS: After adjustment for age, sex, blood pressure parameter, lipidemic, diabetic and smoking status, we found that coronary flow reserve was independently related to AIx (b = -0.38, r = 0.009), DAI (b = 0.36, P = 0.014), DRA (b = 0.39, P = 0.005) and RT (b = -0.29, P = 0.026). Additionally, patients with CFR < 2.5 had higher PWVc (11.6 ± 2.3 vs 10.2 ± 1.4 m/s, P = 0.019), SBPc (139.1 ± 17.8 vs 125.2 ± 19.1 mmHg, P = 0.026), AIx (38.2% ± 14.8% vs 29.4% ± 15.1%, P = 0.011) and lower RHI (1.26 ± 0.28 vs 1.50 ± 0.46, P = 0.012), DAI (44.3% ± 7.9% vs 53.9% ± 6.7%, P = 0.008), DRA (42.2 ± 9.6 vs 51.6 ± 11.4, P = 0.012) and LpPLA2 (268.1 ± 91.9 vs 199.5 ± 78.4 ng/mL, P = 0.002) compared with those with CFR ≥ 2.5. Elevated LpPLA2 was related with reduced CFR (r = -0.33, P = 0.001), RHI (r = -0.37, P < 0.001) and DRA (r = -0.35, P = 0.001) as well as increased PWVc (r = 0.34, P = 0.012) and AIx (r = 0.34, P = 0.001). CONCLUSION: Abnormal arterial wave reflections are related with impaired coronary flow reserve despite successful revascularization in CAD patients. There is a common inflammatory link between impaired aortic wall properties, endothelial dysfunction and coronary flow impairment in CAD.
ABSTRACT
High-density lipoprotein cholesterol (HDL-C), a negative risk factor, is positively associated with a decreased risk of coronary heart disease. We investigated the association between high HDL-C levels and target organ damage (TOD) in never treated women with hypertension. We measured HDL-C levels in 117 women followed by estimation of TODs, that is, pulse wave velocity, microalbuminuria, left ventricular mass index, coronary flow reserve, and carotid intima-media thickness (cIMT). Women were divided into 2 groups (HDLH and HDLL), regarding HDL-C quartiles (upper quartile vs the first 3 lower quartiles). In HDLH group : HDL ≥70 mg/dL), cIMT was nonindependently, negatively related to HDL-C (ρ = -.42, P < .05). Using receiver -operating characteristic curve (ROC) analysis in the HDLH group, we concluded that the cutoff value of HDL ≥76.5 mg/dL moderately predicted the absence of carotid atherosclerosis (area under the curve: 0.77, P = .02; confidence interval: 0.57-0.97; sensitivity 73% and specificity 67%). Increased HDL-C may predict the absence of carotid atherosclerosis in middle-age women with untreated essential hypertension and consequently contribute to total cardiovascular risk estimation and treatment planning.
Subject(s)
Carotid Artery Diseases/blood , Cholesterol, HDL/blood , Hypertension/complications , Adult , Aged , Area Under Curve , Biomarkers/blood , Blood Pressure , Carotid Artery Diseases/complications , Carotid Artery Diseases/diagnosis , Carotid Intima-Media Thickness , Cross-Sectional Studies , Female , Humans , Hypertension/diagnosis , Hypertension/physiopathology , Linear Models , Middle Aged , Multivariate Analysis , Predictive Value of Tests , Prognosis , Protective Factors , ROC Curve , Risk Assessment , Risk Factors , Up-RegulationABSTRACT
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.
Subject(s)
Antihypertensive Agents/therapeutic use , Aorta/drug effects , Arterial Pressure/drug effects , Hypertension/drug therapy , Vascular Stiffness/drug effects , Adult , Aged , Aorta/physiopathology , Blood Pressure Monitoring, Ambulatory , Female , Follow-Up Studies , Humans , Hypertension/diagnosis , Hypertension/physiopathology , Longitudinal Studies , Male , Middle Aged , Predictive Value of Tests , Pulse Wave Analysis , Risk Factors , Severity of Illness Index , Time Factors , Treatment OutcomeABSTRACT
AIMS: 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 METHODS AND RESULTS: In 320 newly-diagnosed untreated hypertensive patients and 160 controls, we measured: pulse wave velocity (PWV); coronary flow reserve (CFR) by Doppler echocardiography; global longitudinal strain and strain rate, peak twisting, the percentage changes between peak twisting, and untwisting at mitral valve opening (%dpTw - UtwMVO ), at peak (%dpTw - UtwPEF ), and the end of early LV diastolic filling (%dpTw - UtwEDF ) by speckle tracking imaging; transforming growth factor (TGFb-1), metalloproteinase-9 (MMP-9), tissue inhibitor of matrix metalloptoteinase-1(TIMP-1), markers of collagen synthesis, and N-terminal pro-brain natriuretic peptide (NT-proBNP). Oxygen consumption (VO2 ), measured by means of cardiopulmonary exercise test, was assessed in a subset of 80 patients. The PWV, CFR, longitudinal strain and strain rate, %dpTw-UtwMVO , %dpTw-UtwPEF , and %dpTw-UtwEDF were impaired in hypertensive patients compared with controls. In multivariable analysis, CFR, PWV, LV mass, and systolic blood pressure were independent determinants of longitudinal strain, strain rate, and untwisting markers (P < 0.05). Increased TGFb-1 was related with increased collagen synthesis markers, TIMP-1 and MMP-9 and these biomarkers were associated with impaired longitudinal systolic strain rate, untwisting markers, CFR and PWV (P < 0.05). Delayed untwisting as assessed by reduced %dpTw - UtwEDF was related with increased NT-proBNP and reduced VO2 (P < 0.05). CONCLUSIONS: Impaired LV untwisting is associated with increased arterial stiffness and coronary microcirculatory dysfunction, and is linked to reduced exercise capacity and neurohumoral activation in hypertensive heart disease. A fibrotic process may be the common link between vascular dysfunction and abnormal myocardial deformation.
Subject(s)
Heart Diseases/physiopathology , Hypertension/physiopathology , Biomarkers/blood , Blood Pressure , Echocardiography , Female , Heart Ventricles/physiopathology , Humans , Male , Matrix Metalloproteinase 9/blood , Middle Aged , Mitral Valve/physiopathology , Natriuretic Peptide, Brain/blood , Peptide Fragments/blood , Tissue Inhibitor of Metalloproteinase-1/blood , Transforming Growth Factor beta/bloodABSTRACT
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-1ß, nitrotyrosine, malondialdehyde, protein carbonyl, and Fas/Fas ligand levels. At baseline, patients with CAD had 3-fold higher interleukin-1ß, 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.
Subject(s)
Arthritis, Rheumatoid/drug therapy , Coronary Artery Disease/drug therapy , Coronary Circulation/drug effects , Coronary Vessels/physiopathology , Interleukin 1 Receptor Antagonist Protein/administration & dosage , Interleukin-1/antagonists & inhibitors , Vasodilation/drug effects , Antirheumatic Agents/administration & dosage , Arthritis, Rheumatoid/blood , Arthritis, Rheumatoid/complications , Blood Flow Velocity/drug effects , Brachial Artery/drug effects , Brachial Artery/physiopathology , Coronary Artery Disease/complications , Coronary Artery Disease/physiopathology , Coronary Vessels/drug effects , Cross-Over Studies , Double-Blind Method , Echocardiography , Female , Humans , Injections , Interleukin-1/metabolism , Male , Middle Aged , Treatment Outcome , Vascular Resistance/drug effects , Vasodilation/physiology , Ventricular Function, Left/drug effectsABSTRACT
BACKGROUND: Lipoprotein-associated Phospholipase A2 (Lp-PLA2), has a powerful inflammatory and atherogenic action in the vascular wall and is an independent marker of poor prognosis in coronary artery disease (CAD). We investigate the association of Lp-PLA2 with markers of vascular dysfunction and atherosclerosis with proven prognostic value in CAD. METHODS: In 111 patients with angiographically documented chronic CAD, we measured 1) carotid intima-media thickness (CIMT), 2) reactive hyperemia using fingertip peripheral arterial tonometry (RH-PAT), 3) coronary flow reserve (CFR), by Doppler echocardiography 4) pulse wave velocity (PWV) and 5) blood levels of Lp-PLA2. RESULTS: Patients with Lp-PLA2 concentration >234.5 ng/ml (50th percentile) had higher CIMT (1.44 ± 0.07 vs. 1.06 ± 0.06 mm), PWV (11.0 ± 2.36 vs. 9.7 ± 2.38 m/s) and lower RH-PAT(1.24 ± 0.25 vs. 1.51 ± 0.53) and CFR (2.39 ± 0.75 vs. 2.9 ± 0.86) compared to those with lower Lp-PLA (p < 0.05 for all comparisons). Lp-PLA2 was positively associated with CIMT (regression coefficient b: 0.30 per unit of Lp-PLA2, p = 0.02), PWV (b:0.201, p = 0.04) and inversely with RHI-PAT (b: -0.371, p < 0.001) and CFR (b:-0.32, p = 0.002). In multivariate analysis, Lp-PLA2 was an independent determinant of RHI-PAT, CFR, CIMT and PWV in a model including age, sex, smoking, diabetes, dyslipidemia and hypertension (p < 0.05 for all vascular markers). Lp-PLA2, RHI-PAT and CFR were independent predictors of cardiac events during a 3-year follow-up. CONCLUSIONS: Elevated Lp-PLA2 concentration is related with endothelial dysfunction, carotid atherosclerosis, impaired coronary flow reserve and increased arterial stiffness and adverse outcome in CAD patients. These findings suggest that the prognostic role of Lp-PLA2 in chronic CAD may be explained by a generalized detrimental effect of this lipase on endothelial function and arterial wall properties.
Subject(s)
1-Alkyl-2-acetylglycerophosphocholine Esterase/blood , Carotid Artery Diseases/blood , Carotid Artery Diseases/physiopathology , Coronary Artery Disease/blood , Coronary Artery Disease/physiopathology , Coronary Circulation , Hyperemia/blood , Hyperemia/physiopathology , Vascular Stiffness , Biomarkers/blood , Carotid Artery Diseases/complications , Carotid Intima-Media Thickness , Coronary Artery Disease/complications , Cross-Sectional Studies , Female , Fingers , Humans , Hyperemia/complications , Male , Middle Aged , Pulse Wave AnalysisABSTRACT
AIMS: Coronary microcirculation is disturbed in hypertensive patients. We investigated the association of coronary flow reserve (CFR) with the response of left ventricular (LV) function as assessed by tissue Doppler imaging (TDI) during adenosine stress echocardiography in never-treated hypertensive patients. METHODS AND RESULTS: We studied 90 hypertensive patients and 30 control subjects, matched for age and sex, by adenosine stress echocardiography. We measured: (i) CFR, E and A Doppler, S', E', A' mitral annulus velocities with TDI, as well as the E'/A' ratio and the E/E' ratio before and during adenosine infusion (ii) the %changes of the measured indices between baseline and adenosine infusion. After adenosine infusion, there was an increase in S', E', and A' in all patients and controls (P < 0.05). Compared with controls and patients with CFR ≥ 2.5, patients with CFR <2.5 showed a smaller increase in S' (28.6 vs. 30.0 vs. 11.1%, F for interaction = 14.592) and E' (33.3 vs. 33.3 vs.1.5%, F = 28.927) as well as a decrease in E'/A' (9.2 vs. 6.4% vs. -20.0%, F = 5.128) and an increase in E/E' (-6.1 vs. -1.6 vs. 30.5%. F = 12.780) after adenosine infusion (P < 0.05 for all comparisons). CFR was independently related to %changes of TDI parameters (regression coefficient b = 0.576 for S'; b = 0.517 for E'; b = 0.473 for E'/A'; b = -0.520 for E/E', respectively, P < 0.001). By the receiver operating curve, a CFR <2.5 predicted the median changes of all measured TDI markers, with a sensitivity and specificity over 70% (AUC >75%, P < 0.05). CONCLUSION: An abnormal response of the LV longitudinal function during adenosine stress echocardiography is related to impaired CFR in untreated hypertensive patients.
Subject(s)
Coronary Circulation , Echocardiography, Stress/methods , Hypertension/diagnostic imaging , Hypertension/physiopathology , Ventricular Dysfunction, Left/diagnostic imaging , Ventricular Dysfunction, Left/physiopathology , Adenosine , Analysis of Variance , Blood Flow Velocity , Case-Control Studies , Female , Humans , Hypertension/complications , Linear Models , Male , Microcirculation , Middle Aged , Prospective Studies , ROC Curve , Risk Factors , Sensitivity and Specificity , Ventricular Dysfunction, Left/complicationsABSTRACT
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 (ß) and flow (A × ß) 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, ß and A × ß (F = 20.6, p < 0.001 for A, F = 3.5, p = 0.03 for ß and F = 11.3, p < 0.001 for A × ß 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.
Subject(s)
Angioplasty, Balloon, Coronary , Coronary Circulation/drug effects , Hydroxymethylglutaryl-CoA Reductase Inhibitors/administration & dosage , Microcirculation/drug effects , Myocardial Infarction/therapy , Aged , Angioplasty, Balloon, Coronary/instrumentation , Blood Flow Velocity/drug effects , Chi-Square Distribution , Combined Modality Therapy , Contrast Media , Echocardiography , Female , Greece , Humans , Linear Models , Male , Middle Aged , Myocardial Contraction/drug effects , Myocardial Infarction/diagnostic imaging , Myocardial Infarction/drug therapy , Myocardial Infarction/physiopathology , Phospholipids , Predictive Value of Tests , Regional Blood Flow/drug effects , Stents , Stroke Volume/drug effects , Sulfur Hexafluoride , Time Factors , Treatment Outcome , Ventricular Function, Left/drug effectsABSTRACT
OBJECTIVE: To investigate the effects of staccato reperfusion (SR) during percutaneous coronary intervention (PCI) on myocardial microcirculatory function as assessed by myocardial contrast echocardiography. SETTING: Tertiary centre. METHODS: Thirty-nine patients were randomised to SR (n=20) or abrupt reperfusion (AR, n=19) within 48 h of an acute coronary syndrome. Contrast intensity replenishment curves were constructed to assess the blood volume (An), velocity (ß) and flow (A×ß) of the segments associated with the PCI-treated artery before, 48 h, 1 and 12 months after PCI. Left ventricular (LV) end-diastolic (EDVs) and systolic volumes (ESVs) were evaluated. Plasma malondialdehyde (MDA) was determined immediately before and 18 min after PCI to assess oxidative stress. RESULTS: SR was related to a greater improvement in A(n), ß and A×ß at 48 h, 1 and 12 months after intervention compared with AR (mean A×ß: 0.91, 5.5, 7.14, 6.9 for SR vs 1.02, 3.34, 4.28, 3.71 for AR, p<0.01). After PCI, the mean MDA change was -27% in SR patients and +55% in the AR patients (p<0.05). The percentage change in MDA correlated with the percentage change in A(n) at all time points (r=0.468, r=0.682, r=0.674, p<0.01). Compared with AR, SR was related to a greater percentage decrease in EDV (-11.61% vs -4.13%) and ESV (-34.68% vs -14.83%) at 12 months after PCI (p<0.05). The percentage change in ESV at 12 months correlated with the corresponding percentage changes in A(n), ß and A×ß (r=-0.410, r=-0.509, r=-0.577, respectively, p<0.05). CONCLUSIONS: SR improves myocardial microcirculatory function after PCI, leading to a concomitant improvement in LV geometry, probably through reduction of oxidative stress.
Subject(s)
Acute Coronary Syndrome/therapy , Myocardial Infarction/therapy , Myocardial Reperfusion Injury/prevention & control , Myocardial Reperfusion/methods , Ventricular Remodeling/physiology , Acute Coronary Syndrome/diagnostic imaging , Anticoagulants/therapeutic use , Echocardiography , Female , Humans , Male , Microcirculation/physiology , Middle Aged , Myocardial Infarction/diagnostic imaging , Myocardial Reperfusion Injury/diagnostic imaging , Myocardial Reperfusion Injury/physiopathology , Ventricular Dysfunction, Left/diagnostic imaging , Ventricular Dysfunction, Left/etiologyABSTRACT
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.
Subject(s)
Blood Pressure , Hypertension/physiopathology , Vascular Resistance , Adult , Aged , Arteries/physiopathology , Blood Flow Velocity , Blood Pressure Monitoring, Ambulatory , Cardiovascular Diseases/etiology , Circadian Rhythm , Cross-Sectional Studies , Female , Humans , Male , Middle Aged , Pulsatile Flow , Pulse , RiskABSTRACT
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 (chi(2) change=4.423, P for change=0.038 after addition of IMT; and chi(2) 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.