Inverse association of total testosterone with central haemodynamics and left ventricular mass in hypertensive men.

BACKGROUND: There is evidence for inverse association between endogenous testosterone and blood pressure. Furthermore, low plasma testosterone is associated with increased risk of major cardiovascular events in middle-aged hypertensive men. Central (aortic) blood pressures determine left ventricular hypertrophy and predict cardiovascular mortality. The aim of the present study was to assess the relationship of total testosterone (TT) with central haemodynamics and left ventricular mass in hypertensive men. METHODS: We investigated 134 non-diabetic, middle-aged, hypertensive men and 60 age-matched normotensive males. All participants were subject to measurement of aortic systolic (aoSBP) and pulse pressure (aoPP) by pulse wave analysis using the SphygmoCor device. Wave reflections were assessed by the measurement of heart rate corrected augmentation index (AIx75). Echocardiography was performed in all individuals and left ventricular mass (LVM) was calculated using the Devereux's formula. Plasma TT was measured by enzyme immunoassay. RESULTS: In hypertensive men, univariate analysis showed an inverse, significant correlation between TT and aoSBP (r = -20, p = 0.02), aoPP (r = -0.21, p = 0.01), AIx75 (r = -0.22, p = 0.01) and LVM (r = -0.19, p = 0.008). Multivariate regression analysis demonstrated an independent inverse association of TT with aoPP (b = -0.21, p = 0.02), AIx75 (b = -0.19, p = 0.03) and LVM (b = -0.28, p = 0.005) after adjustment for age, BMI, smoking, total cholesterol, triglycerides, fasting glucose, mean arterial pressure, antihypertensive treatment and statin use. Independent associations were retained even after inclusion of normotensive subjects in the analysis. CONCLUSIONS: In hypertensive men, TT is independently and inversely associated with central pulse pressure, wave reflections and left ventricular mass. Considering the adverse prognostic role of central blood pressures and LV hypertrophy on cardiovascular outcomes in hypertensive patients, the present findings might explain part of the increased cardiovascular risk associated with low testosterone. Whether measurement of central haemodynamics may improve risk stratification in hypertensive men with low testosterone warrants further investigation.

Prediction of cardiovascular events with aortic stiffness in patients with erectile dysfunction.

Erectile dysfunction confers an independent risk for cardiovascular events and total mortality. Aortic pulse wave velocity (PWV) is an important predictor of cardiovascular events and all-cause mortality. We investigated whether PWV predicts major adverse cardiovascular events (MACEs) in patients with erectile dysfunction beyond traditional risk factors. MACEs in relation to PWV were analyzed with proportional hazards models in 344 patients (mean age, 56 years) without established cardiovascular disease. During a mean follow-up of 4.7 years (range, 1-8.5 years), 24 of 344 participants (7.0%) experienced a MACE. Subjects in the highest PWV tertile (>8.8 m/s) had a 4-fold higher risk of MACEs compared with those in the lowest PWV tertile (<7.6 m/s; adjusted hazard ratio, 3.97; P=0.035). A PWV value of 7.81 m/s was associated with a negative predictive value (ability to rule out MACE) of 98.1%. Addition of PWV to standard risk factor model yielded correct patient reclassification to higher or lower risk category by 27.6% (P=0.0332) in the whole cohort. Our results show that higher aortic stiffness is associated with increased risk for a MACE in patients with erectile dysfunction without known cardiovascular disease. Aortic PWV improves risk prediction when added to standard risk factors and may represent a valuable biomarker of prediction of cardiovascular disease risk in these patients.

Beneficial effect of vardenafil on aortic stiffness and wave reflections.

Although vardenafil is widely prescribed for erectile dysfunction (ED), its effect on arterial function is not defined. Aortic stiffness, aortic pressures, and wave reflections are predictors of cardiovascular risk. The investigators assessed the hypothesis that vardenafil acutely improves aortic stiffness, aortic pressures, and wave reflections in ED patients. Twelve ED patients (mean age 58 ± 9 years) received vardenafil 20 mg in a randomized, placebo-controlled, double-blind, 2-way crossover design. Aortic stiffness was evaluated with carotid-femoral pulse wave velocity (PWV); wave reflections and aortic pressures were evaluated with augmentation index (AIx) and systolic, diastolic, and pulse pressure of the aortic pressure waveform, respectively. PWV, aortic pressures, and AIx were measured at baseline and for 3 hours after vardenafil intake or placebo. PWV decreased significantly (by 0.7 m/s, P = .001), denoting a decrease in aortic stiffness. AIx decreased significantly (by 7%, P = .008), denoting a decreased effect of wave reflections from the periphery. Aortic pressures decreased significantly (all P < .05). Statin use at baseline significantly interacted with the effects of treatment on both PWV and AIx (P = .003 and P < .001, respectively). This study shows, for the first time, that vardenafil has a favorable acute effect on aortic stiffness and wave reflection in ED patients.

Relationships of osteoprotegerin with albuminuria and asymmetric dimethylarginine in essential hypertension: integrating vascular dysfunction.

OBJECTIVES: To investigate the inter-relationships of osteoprotegerin (OPG) with albumin to creatinine ratio (ACR) and asymmetric dimethylargine (ADMA) in hypertensive patients. METHODS: In 198 untreated non-diabetic hypertensive patients [130 males, mean age=51.5 years, office blood pressure (BP)=152/98 mmHg] ACR values and OPG and ADMA levels were determined. RESULTS: Based on the median value of OPG distribution (5.03 pmol/l) patients with high (n=101) compared with those with low OPG values (n=97) had greater 24-h systolic BP (152±5 versus 137±7 mmHg, p<0.0001), ACR [25.3 (5-190) versus 17.3 (5-92) mg/g, p=0.003) and ADMA [0.62 (0.58-0.68) versus 0.57 (0.48-0.62) µmol/l, p=0.001), independently of confounding factors. Multiple regression analyses revealed that ADMA (b=0.388, p<0.0001), 24-h systolic BP (b=0.228, p=0.01) and ACR (b=0.470, p<0.0001) were independent predictors of OPG (R2=0.398, p<0.0001). CONCLUSIONS: In hypertensive patients, high OPG levels are accompanied by pronounced albuminuria and endothelial dysfunction, as reflected by raised ADMA levels. Furthermore, the independent associations of OPG with ACR and ADMA, suggests a link between OPG and the progression of diffuse hypertensive vascular damage.

Quantitative analysis of left atrial function in asymptomatic patients with b-thalassemia major using real-time three-dimensional echocardiography.

BACKGROUND: There is strong evidence that left atrial (LA) size is a prognostic marker in a variety of heart diseases. Recently, real-time three-dimensional echocardiography (RT3DE) has been reported as a useful tool for studying the phasic changes of the left atrial volumes. The aim of this study was to investigate the performance of the left atrium in beta-thalassemic patients with preserved left ventricular ejection fraction (EF) and no iron overload, using RT3DE. METHODS: Twenty-eight asymptomatic b-thalassemic patients (32.2 ± 4.3 years old, 17 men) who were on iron chelating therapy, as well as 20 age- and sex-matched healthy controls underwent transthoracic RT3DE. The patient group had normal echocardiographic systolic and diastolic indices, while there was no myocardial iron disposition according to MRI. Apical full volume data sets were obtained and LA volumes were measured at 3 time points of the cardiac cycle: (1) maximum volume (LAmax) at end-systole, just before mitral valve opening; (2) minimum volume (LAmin) at end-diastole, just before mitral valve closure; and (3) volume before atrial active contraction (LApreA) obtained from the last frame before mitral valve reopening or at time of the P wave on the surface electrocardiogram. From the derived values, left atrial active and passive emptying volumes, as well as the respective emptying fractions were calculated. RESULTS: Left ventricular EF (59.2 ± 2.5% patients vs. 60.1 ± 2.1% controls), E/A, E/E' were similar between the two groups. Differences in the LAmax, LAmin and LApreA between b-thalassemic patients and controls were non-significant, LAmax:(35.5 ± 13.4 vs 31.8 ± 9.8)cm3, LAmin:(16.0 ± 6.0 vs. 13.5 ± 4.2)cm3, and LApreA:(25.4 ± 9.8 vs. 24.3 ± 7.2)cm3. However, left atrial active emptying fraction was reduced in the patient group as compared to the healthy population (34.3 ± 16.4% vs. 43.2 ± 11.4%, p < 0.05). CONCLUSION: RT3DE may be a novel technique for the evaluation of LA function in asymptomatic patients with b-Thalassemia Major. Among three-dimensional volumes and indices, left atrial active emptying fraction may be an early index of LA dysfunction in the specific patient population.

Role of right ventricular systolic function on long-term outcome in patients with newly diagnosed systolic heart failure.

BACKGROUND: Right ventricular (RV) systolic function has been recognized as a prognostic factor in endstage heart failure (HF) patients and in the present study we evaluated the effect of this dysfunction on prognosis in patients with newly-diagnosed systolic HF. METHODS AND RESULTS: We enrolled 180 consecutive patients with newly diagnosed systolic HF (ischemic or dilated cardiomyopathy). Echocardiographic evaluation was performed to assess biventricular function. Pulse-wave tissue Doppler imaging (TDI) readings were obtained from the lateral tricuspid annulus and the peak systolic annular velocity (Stv) was recorded. Patients were followed for a 2-year period and events (death or HF hospitalization) were recorded. During the follow-up, 79 patients (44%) had an adverse event. An inverse relationship was observed between the height of Stv and the probability of an event (odds ratio (OR) 0.716, 95% confidence interval (CI) 0.583-0.880, P=0.001), after controlling for potential confounders. Furthermore, creatinine clearance (CrCl) was inversely associated with the outcome: a 1-unit increase in CrCl was associated with a 0.98-times lower likelihood of having an event. When the analysis was stratified by CrCl < 60 ml/min or ≥ 60 ml/min, Stv predicted adverse events in both groups (CrCl < 60 ml/min: OR 0.62, 95%CI 0.39-0.98, P = 0.04; CrCl ≥ 60 ml/min: OR 0.78, 95%CI 0.61-1.01, P=0.06). CONCLUSIONS: Pulse-wave TDI readings of peak systolic velocity at the lateral tricuspid annulus, reflecting RV systolic function, has prognostic significance in newly-diagnosed systolic HF patients.

Mediterranean diet mediates the adverse effect of depressive symptomatology on short-term outcome in elderly survivors from an acute coronary event.

Aims. We evaluated the interaction effect between depressive symptoms and dietary habits on 30-day development of cardiovascular disease (CVD) (death or rehospitalization) in elderly, acute coronary syndrome (ACS) survivors. Methods. During 2006-2008, we recorded 277 nonfatal, consecutive ACS admissions (75 ± 6 years, 70% males, 70% had diagnosis of myocardial infarction) with complete 30-day follow-up. Assessment of recent depressive symptoms was based on the CES-D scale. Among sociodemographic, bioclinical, lifestyle characteristics, the MedDietScore that assesses the inherent characteristics of the Mediterranean diet was applied. Results. 22% of the ACS pts developed a CVD event during the first 30 days (14.8% rehospitalization and 9.4% death). Patients in the upper tertile of the CES-D scale (i.e., >18) had higher incidence of CVD events as compared with those in the lowest tertile (21% versus 8%, P = .01). Multiple logistic regression analysis revealed that 1-unit increase in CES-D was associated with 4% higher odds (95% CI 1.008-1.076, P = .01) of CVD events; however, when MedDietScore was entered in the model, CES-D lost its significance (P = .20). Conclusion. Short-term depressive symptoms are related to a worsen 30-day prognosis of ACS patients; however, this relationship was mediated by Mediterranean diet adherence.

Relationship of asymmetric dimethylarginine with penile Doppler ultrasound parameters in men with vasculogenic erectile dysfunction.

BACKGROUND: Asymmetric dimethylarginine (ADMA), a selective endogenous nitric oxide synthase inhibitor, is elevated in many conditions associated with erectile dysfunction (ED), such as hypertension, diabetes, hyperlipidemia, and renal failure; it is also increased in men with coronary artery disease and ED. The dynamic penile colour Doppler ultrasound is considered the gold standard for the evaluation of penile vascular damage. OBJECTIVE: We investigated whether the extent of ultrasonographically documented penile vascular disease is associated with higher ADMA levels. DESIGN, SETTING, AND PARTICIPANTS: One hundred four consecutive ED patients (mean age: 56 ± 9 yr) without manifest cardiovascular/atherosclerotic disease and 31 subjects with normal erectile function matched for age and traditional risk factors were studied. MEASUREMENTS: We evaluated penile dynamic colour Doppler parameters of arterial insufficiency (peak systolic velocity) and veno-occlusive dysfunction (end diastolic velocity) and measured systemic inflammatory markers/mediators. RESULTS AND LIMITATIONS: Compared to men without ED, ED patients had significantly higher ADMA levels (p<0.001). ADMA was significantly increased in patients with severe arterial insufficiency (PSV<25 cm/s) compared to subjects with borderline insufficiency and men with normal penile arterial function (p<0.001, by analysis of variance). Multivariable analysis adjusting for age, mean pressure, other risk factors, high-sensitivity C-reactive protein, testosterone, and treatment showed independent inverse association between ADMA level and peak systolic velocity (p<0.01). The combination of higher ADMA level with arterial insufficiency showed greater impact on 10-yr risk of a cardiovascular event compared to either parameter alone. CONCLUSIONS: ADMA level is independently associated with ultrasonographically documented poor penile arterial inflow. This finding underlines the important role of ADMA as a marker of penile arterial damage and implies a contribution of this compound to the pathophysiology of generalised vascular disease associated with ED.

Novel methodology for the detection of exercise-induced myocardial wall motion abnormalities by surface electrocardiogram during exercise test.

BACKGROUND: We investigated whether ischemia-induced wall motion abnormalities during exercise test modify electrical vector variation. METHODS: We performed treadmill exercise test and thallium 201 scintigraphy in 150 normotensives. Beat-to-beat change of direction of S wave in V(1) (reference lead) was compared with that of R wave in V(5) and aVF, representative of anterior and inferior walls, respectively. The percentage of neighboring QRS couples where S wave in V(1) and R wave in V(5) or aVF change toward the same direction (increase or decrease) constitutes V1-V5 and V1-aVF indexes. RESULTS: V1-V5 and V1-aVF indexes were significantly decreased in subjects with reversible anterior or inferior ischemia, respectively. A decrease in V1-V5 index ≥0.14 defines those with anterior wall ischemia (sensitivity, 100%; specificity, 75.5%), whereas a decrease in V1-aVF index ≥0.05 defines those with inferior wall ischemia (sensitivity, 92.3%; specificity, 61.5%). CONCLUSIONS: These novel electrocardiographic exercise test indexes improved significantly their sensitivities.