Rosalba Massaro

Effect of Long-Acting Testosterone Treatment on Functional Exercise Capacity, Skeletal Muscle Performance, Insulin Resistance, and Baroreflex Sensitivity in Elderly Patients With Chronic Heart Failure. A Double-Blind, Placebo-Controlled, Randomized Study

OBJECTIVES This study investigated the effect of a 12-week long-acting testosterone administration on maximal exercise capacity, ventilatory efficiency, muscle strength, insulin resistance, and baroreflex sensitivity (BRS) in elderly patients with chronic heart failure (CHF). BACKGROUND CHF is characterized by a metabolic shift favoring catabolism and impairment in skeletal muscle bulk and function that could be involved in the pathophysiology of heart failure. METHODS Seventy elderly patients with stable CHF-median age 70 years, ejection fraction 31.8 +/- 7%-were randomly assigned to receive testosterone (n = 35, intramuscular injection every 6 weeks) or placebo (n = 35), both on top of optimal medical therapy. At baseline and at the end of the study, all patients underwent echocardiogram, cardiopulmonary exercise test, 6-min walk test (6MWT), quadriceps maximal voluntary contraction (MVC), and isokinetic strength (peak torque) and BRS assessment (sequences technique). RESULTS Baseline peak oxygen consumption (VO(2)) and quadriceps isometric strength showed a direct relation with serum testosterone concentration. Peak VO(2) significantly improved in testosterone but was unchanged in placebo. Insulin sensitivity was significantly improved in testosterone. The MVC and peak torque significantly increased in testosterone but not in placebo. The BRS significantly improved in testosterone but not in placebo. Increase in testosterone levels was significantly related to improvement in peak VO(2) and MVC. There were no significant changes in left ventricular function either in testosterone or placebo. CONCLUSIONS These results suggest that long-acting testosterone therapy improves exercise capacity, muscle strength, glucose metabolism, and BRS in men with moderately severe CHF. Testosterone benefits seem to be mediated by metabolic and peripheral effects.

Testosterone therapy in women with chronic heart failure: A pilot double-blind, randomized, placebo-controlled study

OBJECTIVES The primary objective of this study was to assess the effect of a 6-month testosterone supplementation therapy on functional capacity and insulin resistance in female patients with chronic heart failure (CHF). BACKGROUND Patients with CHF show decreased exercise capacity and insulin sensitivity. Testosterone supplementation improves these variables in men with CHF. No study has evaluated the effects of testosterone supplementation on female patients with CHF. METHODS Thirty-six elderly female patients with stable CHF, (ejection fraction 32.9 ± 6) were randomly assigned (2:1 ratio) to receive testosterone transdermal patch (T group, n = 24) or placebo (P group, n = 12), both on top of optimal medical therapy. At baseline and after 6 months, patients underwent 6-min walking test (6MWT), cardiopulmonary exercise test, echocardiogram, quadriceps maximal isometric voluntary contraction, dynamic quadriceps isokinetic strength (peak torque), and insulin resistance assessment by homeostasis model. RESULTS Distance walked at 6MWT as well as peak oxygen consumption significantly improved in the T group, whereas they were unchanged in the P group (p < 0.05 for all comparisons). The homeostasis model was significantly reduced in the T group in comparison with the P group (-16.5% vs. +5%, respectively; p < 0.05). Maximal voluntary contraction and peak torque increased significantly in the T group but did not change in the P group. Increase in distance walked at 6MWT was related to the increase in free testosterone levels (r = 0.593, p = 0.01). No significant changes in echocardiographic parameters were observed in either group. No side effects requiring discontinuation of T were detected. CONCLUSIONS Testosterone supplementation improves functional capacity, insulin resistance, and muscle strength in women with advanced CHF. Testosterone seems to be an effective and safe therapy for elderly women with CHF.

Low testosterone levels are associated with coronary artery disease in male patients with angina

Historically, high androgen levels have been linked with an increased risk for coronary artery disease (CAD). However, more recent data suggest that low androgen levels are associated with adverse cardiovascular risk factors, including an atherogenic lipid profile, obesity and insulin resistance. The aim of the present study was to evaluate the relationship between plasma sex hormone levels and presence and degree of CAD in patients undergoing coronary angiography and in matched controls. We evaluated 129 consecutive male patients (mean age 58±4 years, range 43–72 years) referred for diagnostic coronary angiography because of symptoms suggestive of CAD, but without acute coronary syndromes or prior diagnosis of hypogonadism. Patients were matched with healthy volunteers. Out of 129 patients, 119 had proven CAD; in particular, 32 of them had one, 63 had two and 24 had three vessel disease, respectively. Patients had significantly lower levels of testosterone than controls (9.8±6.5 and 13.5±5.4 nmol/l, P<0.01) and higher levels of gonadotrophin (12.0±1.5 vs 6.6±1.9 IU/l and 7.9±2.1 vs 4.4±1.4, P<0.01 for follicle-stimulating hormone and luteinizing hormone, respectively). Also, both bioavailable testosterone and plasma oestradiol levels were lower in patients as compared to controls (0.84±0.45 vs 1.19±0.74 nmol/l, P<0.01 and 10.7±1.4 vs 13.3±3.5 pg/ml, P<0.05). Hormone levels were compared in cases with one, two or three vessel disease showing significant differences associated with increasing severity of coronary disease. An inverse relationship between the degree of CAD and plasma testosterone levels was found (r=−0.52, P<0.01). In conclusion, patients with CAD have lower testosterone and oestradiol levels than healthy controls. These changes are inversely correlated to the degree of CAD, suggesting that low plasma testosterone may be involved with the increased risk of CAD in men.

Long-term effects of nutraceuticals (berberine, red yeast rice, policosanol) in elderly hypercholesterolemic patients

IntroductionStatins are at the forefront of strategies to manage dyslipidemia, although they are not always well tolerated. At 6–7 months after the drug was supplied, discontinuation rates averaged 30%. Alternate agents to statins have been studied. Some nutraceuticals demonstrated an efficacy in reducing cholesterol concentrations. However, there are no data regarding the use of nutraceuticals in elderly dyslipidemic patients. The purpose of this study was to examine the efficacy, safety, and tolerability of a nutraceutical-based protocol in elderly hypercholesterolemic patients previously intolerant to statins.MethodsThis study was performed as a randomized, prospective, parallel group, single-blind study. Patients were included in the study if they had high total cholesterolemia, high low-density lipoprotein cholesterol (LDL-C), >75 years of age, statin-intolerant, and were refusing other pharmaceutical treatments for hypercholesterolemia. At the baseline visit, eligible patients were randomized to either nutraceutical-combined pill (containing berberine 500 mg, policosanol 10 mg, red yeast rice 200 mg, folic acid 0.2 mg, coenzyme Q10 2.0 mg, and astaxanthin 0.5 mg) or placebo, and the first dose was dispensed. The efficacy, safety, and tolerability of the proposed treatment were fully assessed after 3, 6, and 12 months of treatment.ResultsOut of 106 consecutive patients screened, 80 eligible patients were randomized to receive either nutraceutical-combined pill (40 patients) or placebo (40 patients). No patients were lost and no deaths occurred during the follow-up. There was a statistically significant reduction in total cholesterolemia (−20%), LDL-C (−31%), and insulin resistance (−10%) with nutraceutical treatment. No significant changes were detected for plasma high-density lipoprotein cholesterol (HDL-C). Furthermore, no statistical differences were found between baseline and end-study safety parameters. Medication compliance and tolerability were high.ConclusionIn this study the authors have demonstrated that combined nutraceuticals significantly reduce cholesterolemia and achieved acceptable plasma LDL-C levels in elderly hypercholesterolemic patients who were previously statin-intolerant. Combined nutraceuticals is also safe and well tolerated in these patients.

Tai Chi Enhances the Effects of Endurance Training in the Rehabilitation of Elderly Patients with Chronic Heart Failure

Purpose. To assess if Tai Chi added to endurance training (ET) is more effective than ET alone in improving exercise tolerance and quality of life (QOL) of elderly patients with chronic heart failure (CHF). Design. Sixty CHF patients, age 73.8 ± 6 years, M/F 51/9, were enlisted. Thirty pts were randomized to combined training (CT) performing Tai Chi +ET and 30 patients to ET (ET only). Methods. At baseline and after 12 weeks all patients underwent 6-minute walking test (6MWT), assessment of amino terminal probrain natriuretic peptide (NT-pro BNP), quadriceps maximal voluntary contraction (MVC) and peak torque (PT), QOL questionnaire (MacNewQLMI), blood pressure (BP), and heart rate (HR). All patients performed 4 sessions of exercise/week. Results. Distance at 6mwt improved in both groups with significant between-groups differences (P = .031). Systolic BP and NT-proBNP decreased significant in the CT group compared to ET (P = .025) and P = .015), resp.). CT group had a greater significant improvement in physical perception (P = .026) and a significant increase of PT compared to ET group. Conclusions. The association of Tai Chi and ET improves exercise tolerance and QOL of patients with CHF more efficiently than ET.

Hydrotherapy added to endurance training versus endurance training alone in elderly patients with chronic heart failure: A randomized pilot study

PURPOSE To assess if Hydrotherapy (HT) added to endurance training (ET) is more effective than ET alone in order to improve exercise tolerance of elderly male patients with chronic heart failure (CHF). METHODS Twenty-one male CHF patients, age 68+/-7 (mean+/-DS) years; ejection fraction 32+/-9. NYHA II-III were enrolled. Eleven pts were randomized to combined training (CT) group performing HT+ET and 10 patients to ET group (ET only). At baseline and after 24 weeks all patients underwent: 6-minute walking test (6MWT), assessment of quadriceps maximal voluntary contraction (MVC) and peak torque (PT), blood pressure and heart rate (HR), echocardiography and non-invasive hemodynamic evaluation. HT was performed 3 times/week in upright position at up to the xyphoid process at a temperature of 31°C. ET was performed 3 times/week. RESULTS Exercise was well tolerated. No patients had adverse events. Distance at 6MWT improved in both groups (CT group: 150+/-32 m; ET group:105+/-28 m) with significant intergroup differences (p 0.001). On land diastolic BP and HR significantly decreased in the CT group while remained unchanged in the ET group (-11 mmHg+/-2, p 0.04; e - 12 bpm, p 0.03; respectively) CO and SV had a relative despite no significant increase in CT group TPR on land significantly decreased in CT group (-23+/-3 mmHg/l/m; p 0.01) while remained unchanged in ET group. Patients of CT group had no significant higher increase of both MVC and PT than ET group. CONCLUSIONS CT training, significantly improves exercise tolerance and hemodynamic profile of patients with CHF.

Effectiveness of nebivolol and hydrochlorothiazide association on blood pressure, glucose, and lipid metabolism in hypertensive patients

IntroductionOnly 50% of hypertensive patients receive an appropriate treatment to normalize blood pressure (BP). Although monotherapy is often adequate in normalizing BP, it is sometimes necessary to start with combination therapy. The aim of the study was to evaluate the efficacy of nebivolol alone and in association with hydrochlorothiazide (HCT) in reducing BP in hypertensive patients with new-onset, mild-to-moderate hypertension, and to assess the effect of combination therapy on glucose and lipid metabolism.MethodsAt enrollment, patients underwent a full cardiovascular and metabolic evaluation. Patients were then prescribed nebivolol (5 mg/day). After 1 month, in those patients whose BP was not normalized, HCT 12.5 mg was added and increased further to 25 mg after 1 month in those whose BP still was not normalized. All patients were assessed at monthly intervals for a further 5 months.ResultsWe enrolled 233 treatment-naive patients. After the first month of treatment with nebivolol, 70% of patients had normalized BP. The addition of HCT increased responder rates to 94%. An improvement in glucose metabolism was noted with nebivolol alone (at 1 month, the reduction in Homeostasis Model Assessment of Insulin Resistance [HOMA-IR] was 26% and remained stable at 6 months); the adjunct of HCT blunted the reduction in HOMA-IR. No significant changes on lipid profile were noted with nebivolol, either alone or in combination therapy.ConclusionNebivolol is effective in mild-to-moderate hypertension and associated with favorable metabolic effects. The addition of HCT optimizes BP control in a high number of patients resistant to monotherapy without a negative impact on patients’ glucose and lipid profile.

Comparison of effectiveness of carvedilol versus bisoprolol for prevention of postdischarge atrial fibrillation after coronary artery bypass grafting in patients with heart failure.

Atrial fibrillation (AF) occurs frequently soon after coronary artery bypass grafting (CABG) and often results in increased mortality and morbidity, particularly in patients with heart failure. New-onset AF is also a common event in the early period after discharge from a cardiac surgery clinic. Current guidelines recommend β blockers as first-line medication for the prevention of AF after CABG. In this prospective study, we investigated the effectiveness of the highly selective β1 receptor antagonist bisoprolol compared to the less selective β blocker carvedilol in preventing postdischarge AF after CABG in patients with decreased left ventricular function. Three hundred twenty patients (231 men, 89 women, mean age 66 ± 10 years) with ejection fraction <40% who underwent CABG and were then referred to an in-hospital cardiac rehabilitation program were randomized to receive bisoprolol (n = 160) or carvedilol (n = 160) starting 4 to 5 days after surgery. Bisoprolol was started at 1.25 mg 1 time/day and carvedilol was started 3.125 mg 2 times/day. All patients underwent continuous telemetric electrocardiographic monitoring for 5 days after entry in the study and thereafter 2 times/day routinely up to hospital discharge. During follow-up, 23 patients (14.6%) in the bisoprolol group and 37 patients (23%) in the carvedilol group developed AF (relative risk 0.6, confidence interval 0.4 to 0.9, p = 0.032). Twenty-six percent of all AF episodes were asymptomatic. At the 4-week outpatient visit, those in the bisoprolol group showed a significantly greater decrease in heart rate, being in sinus rhythm or AF (-15.6 ± 3 vs -9.4 ± 3 beats/min, p = 0.021), whereas changes in systolic and diastolic blood pressures did not differ significantly. In conclusion, bisoprolol is more effective than carvedilol in decreasing the incidence of postdischarge AF after CABG in patients with decreased left ventricular function.

Metabolic syndrome predicts lower functional recovery in female but not in male patients after an acute cardiac event

AIMS To evaluate whether metabolic syndrome MS has a gender dependent effect on the recovery of functional capacity in patients (pts) with coronary heart disease (CHD) undergoing a cardiac rehabilitation program. METHODS AND RESULTS We studied 286 CHD patients, age 66.2+/-10.6 (median+/-SD); M/F 187/99. Patients were divided into two groups according to the presence (MS, 48%) or not (nMS, 52%) of MS. MS was present in 48% of patients. Functional capacity was assessed by the distance walked at six minute walking test (6MWT), and by a maximal exercise test. Compared to patients without MS, those with MS walked a lower distance at 6MWT (438+/-110 vs 408+/-123 m; p<0.05), had a lower maximal exercise capacity (7.6+/-1.8 vs 9.3+/-1.2 MET; p<0.05) and a lower heart rate recovery (HRR) (16+/-9 vs 22+/-8; p<0.05). Male patients with or without MS had a similar degree of functional recovery (51%) while women with MS had a significantly lower recovery than nMS (20% vs 40%). In a multivariate logistic regression model, including body mass index, age, gender hypertension, ejection fraction and diabetes, MS predicted a reduced performance at 6MWT in the overall population (OR 1.4, 95% CI 1.7 to 2.4) and in women (OR 1.31; 95% CI 1.20-1.62), while it was not predictive in males. CONCLUSIONS CAD patients with MS have lower functional recovery and HRR than nMS. However MS is an independent predictor of lower exercise capacity only in female gender.

Comparison of Low-Dose Statin Versus Low-Dose Statin + Armolipid Plus in High-Intensity Statin-Intolerant Patients With a Previous Coronary Event and Percutaneous Coronary Intervention (ADHERENCE Trial)

Low-density lipoprotein cholesterol (LDL-C) reduction is associated with a significant decrease in mortality, and statins represent the most effective drugs to achieve this. However, side effects of statins are very common and may lead to treatment discontinuation. Nutraceuticals are a combination of natural components that have shown efficacy in lowering LDL-C concentration when used alone or in association with other agents in patients who are intolerant to high-dose statins. Our aim was to compare the efficacy and tolerability of low-dose statin (LDS) therapy versus combined therapy of LDS plus a nutraceutical combination containing red yeast rice, policosanol, berberine, folic acid, coenzyme Q10 and astaxanthin (Armolipid Plus) in high-risk patients. We performed a randomized (1:1), prospective, parallel group, single-blind trial in which participants had coronary artery disease (n = 100), had undergone percutaneous coronary intervention in the preceding 12 months, were high-dose statin intolerant, and did not achieve ≥50% reduction in LDL-C with LDS treatment alone. After 3 months, patients in the LDS + Armolipid Plus (n = 50) group presented with a significantly greater reduction of LDL-C and total cholesterol (p <0.0001), and 70% of patients in this group achieved the therapeutic target (LDL-C <70 mg/dl), whereas patients in the LDS group did not. Six patients (3 from each group) dropped out due to myalgia. In conclusion, in patients with coronary artery disease and high-dose statin intolerance, the combination of LDS and nutraceuticals represents a valuable therapeutic option.