Antonio Ruvolo

Effects of a nutraceutical combination (berberine, red yeast rice and policosanols) on lipid levels and endothelial function randomized, double-blind, placebo-controlled study

BACKGROUND AND AIMS Some nutraceuticals are prescribed as lipid-lowering substances. However, doubts remain about their efficacy. We evaluated the effects of a nutraceutical combination (NC), consisting of 500 mg berberine, 200mg red yeast rice and 10mg policosanols, on cholesterol levels and endothelial function in patients with hypercholesterolemia. METHODS AND RESULTS In this single centre, randomized, double-blind, placebo-controlled study, 50 hypercholesterolemic patients (26 males and 24 females, mean age 55±7 years, total cholesterol 6.55±0.75 mmol/l, BMI 28±3.5) were randomized to 6 weeks of treatment with a daily oral dose of NC (25 patients) or placebo (25 patients). In a subsequent open-label extension of 4 weeks, the whole sample received NC. The main outcome measure was decrease total cholesterol (C) levels in the NC arm. Secondary outcome measures were decreased low-density lipoprotein cholesterol (LDL-C) and triglyceride levels, and improved endothelial-dependent flow-mediated dilation (FMD) and insulin sensitivity in relation to NC. Evaluation of absolute changes from baseline showed significant reductions in NC versus placebo for C and LDL-C (C: -1.14±0.88 and -0.03±0.78 mmol/l, p<0.001; LDL-C: -1.06±0.75 and -00.4±0.54 mmol/l, p<0.001), and a significant improvement of FMD (3±4% and 0±3% respectively, p<0.05). After the extension phase, triglyceride levels decreased significantly from 1.57±0.77 to 1.26±0.63 mmol/l, p<0.05 and insulin sensitivity improved in a patient subgroup with insulin resistance at baseline (HOMA: from 3.3±0.4 to 2.5±1.3, p<0.05). No adverse effect was reported. CONCLUSIONS This NC reduces cholesterol levels. The reduction is associated with improved endothelial function and insulin sensitivity.

Cardiovascular abnormalities in Klinefelter Syndrome

BACKGROUND Several epidemiological studies have demonstrated an increased mortality from cardiovascular causes in patients with Klinefelter Syndrome (KS). Little information is available about the nature of the underlying cardiovascular abnormalities. Aim of the study was to investigate exercise performance, left ventricular architecture and function, vascular reactivity, and carotid intima-media thickness in a group of patients with KS. MATERIALS AND METHODS Sixty-nine patients with KS and 48 age-matched controls participated in our population-controlled study. Forty-eight Klinefelter subjects were on testosterone treatment at the time of the investigation while 21 were naive and underwent a complete Doppler echocardiographic examination, a cardiopulmonary exercise test as well as a vascular study including measures of carotid intima-media thickness and endothelial function with flow-mediated dilation of the brachial artery. Patients with KS on testosterone therapy (n=48) were also matched against a population of men with treated secondary hypogonadism (n=21). RESULTS Patients with KS exhibited a wide array of cardiovascular abnormalities including left ventricular diastolic dysfunction, reduced maximal oxygen consumption (p<0.01), increased intima-media thickness (p<0.05) (-34% and +42% vs. controls, respectively) and a high prevalence of chronotropic incompetence (55% of patients, p<0.01). No significant difference was found between treated and untreated KS in variance with men treated for secondary hypogonadism. CONCLUSION Left ventricular diastolic dysfunction, impaired cardiopulmonary performance, chronotropic incompetence, and increased intima-media thickness suggest that cardiovascular abnormalities are a common finding in KS that is not reversed by testosterone replacement therapy and may represent the pathophysiological underpinnings of the increased risk of dying from heart disease.

A nutraceutical combination improves insulin sensitivity in patients with metabolic syndrome

AIM To test the efficacy of a proprietary nutraceutical combination in reducing insulin resistance associated with the metabolic syndrome (MetS). METHODS Sixty-four patients with MetS followed at a tertiary outpatient clinic were randomly assigned to receive either placebo or a proprietary nutraceutical combination (AP) consisting of berberine, policosanol and red yeast rice, in a prospective, double-blind, placebo-controlled study. Evaluations were performed at baseline and after 18 wk of treatment. The homeostasis model assessment of insulin resistance (HOMA-IR) index was the primary outcome measure. Secondary endpoints included lipid panel, blood glucose and insulin fasting, after a standard mixed meal and after an oral glucose tolerance test (OGTT), flow-mediated dilation (FMD), and waist circumference. RESULTS Fifty nine patients completed the study, 2 withdrew because of adverse effects. After 18 wk there was a significant reduction in the HOMA-IR index in the AP group compared with placebo (ΔHOMA respectively -0.6 ± 1.2 vs 0.4 ± 1.9; P < 0.05). Total and low density lipoprotein cholesterol also significantly decreased in the treatment arm compared with placebo (Δlow density lipoprotein cholesterol -0.82 ± 0.68 vs -0.13 ± 0.55 mmol/L; P < 0.001), while triglycerides, high density lipoprotein cholesterol, and the OGTT were not affected. In addition, there were significant reductions in blood glucose and insulin after the standard mixed meal, as well as an increase in FMD (ΔFMD 1.9 ± 4.2 vs 0 ± 1.9 %; P < 0.05) and a significant reduction in arterial systolic blood pressure in the AP arm. CONCLUSION This short-term study shows that AP has relevant beneficial effects on insulin resistance and many other components of MetS.

Long-term effect of epoetin alfa on clinical and biochemical markers in friedreich ataxia

Friedreich ataxia is an autosomal recessive disease with no available therapy. Clinical trials with erythropoietin in Friedreich ataxia patients have yielded conflicting results, and the long‐term effect of the drug remains unknown.

Endocrine Alterations Are the Main Determinants of Cardiac Remodelling in Restrictive Anorexia Nervosa

Objective. Anorexia nervosa is a condition of reduced hemodynamic load, characterized by varying degrees of cardiac remodelling, only in part related to reduced body mass; the mechanism for such variability, as well as its clinical significance, remains unknown. Aim of the study was to assess the possible influence of a great number of clinical, biochemical, and endocrine factors on cardiovascular parameters in restrictive anorexia nervosa. Method. Twenty-five female patients hospitalized for restrictive anorexia nervosa underwent extensive cardiovascular, clinical, and biochemical evaluation. Results. Height-adjusted and cardiac workload-matched left ventricular mass was significantly related to several endocrine parameters, blood pressure, and vasoreactivity. On multivariate analysis, IGF/GH ratio and systolic blood pressure were the only independent predictors of height-adjusted ventricular mass (adj-R 2 = 0.585; P = 0.001); when matching for cardiac workload, left ventricular mass was independently predicted only by GH and FT3 levels. All effects were independent of patients weight and BMI. Conclusions. Indices of endocrine impairment seem to be the most relevant determinants of left ventricular hypotrophy in anorectic patients, apparently independent of reduced hemodynamic load and BMI. In particular, IGF/GH ratio and FT3 seem to particularly affect left ventricular mass in this population.

Long term combination treatment for severe idiopathic pulmonary arterial hypertension

We report the long-term follow-up of 3 cases of severe idiopathic pulmonary arterial hypertension, in whom tadalafil plus sitaxentan combination therapy improved the clinical condition and exercise performance without any relevant adverse event.

Migraine attack restores the response of vascular smooth muscle cells to nitric oxide but not to norepinephrine

AIM To clarify whether the vasoconstrictory response is impaired and to study vascular function in patients with migraine during the headache attack. METHODS We studied vascular reactivity in the resistance arteries by using the forearm perfusion technique associated with plethysmography. We measured forearm blood flow by strain-gauge plethysmography during intra-brachial infusion of acetylcholine, sodium nitroprusside or norepinephrine in 11 controls and 13 patients with migraine, 11 of them (M) in the interval between the migraine attacks and 4 during a headache attack (MH). Written informed consent was obtained from patients and healthy controls, and the study was approved by the Ethics Committee of the University Federico II. RESULTS Compared to healthy control subjects, in patients with migraine studied during the interictal period, the vasodilating effect of acetylcholine, that acts through the stimulation of endothelial cells and the release of nitric oxide, was markedly reduced, but became normal during the headache attack (P < 0.05 by analysis of variance). The response to nitroprusside, which directly relaxes vascular smooth muscle cells (VSMCs), was depressed in patients with migraine studied during the interictal period, but normal during the headache attack (P < 0.005). During norepinephrine infusion, forearm blood flow decreased in control subjects (-40% ± 5%, P < 0.001). In contrast, in patients with migraine, either when studied during or free of the headache attack forearm blood flow did not change compared to the baseline value (-3% ± 13% and -10.4% ± 15%, P > 0.05). CONCLUSION In migrainers, the impaired relaxation of VSMCs is restored during the headache attack. The vasoconstrictory response is impaired and remains unchanged during the migraine attack.

Efficacy and safety of valsartan plus hydroclorothiazide for high blood pressure

AIM To evaluate efficacy and tolerability of the combination valsartan plus hydrochlorothiazide (160 mg and 25 mg daily, respectively) in young-middle aged males with high-normal blood pressure (BP) or first-degree arterial hypertension with evidence of target organ damage. METHODS Twenty males with high-normal BP or first-degree hypertension associated with left ventricular concentric remodeling and/or increased aortic stiffness were enrolled. BP at rest and during exercise, and echocardiographic parameters of the left ventricle (LV), were evaluated at baseline and after 3 mo of treatment. The effects of treatment on aortic stiffness, metabolic parameters, renal and erectile function were also assessed. RESULTS BP was significantly reduced by treatment both at rest (P < 0.001) and during exercise (P < 0.001), and 85% of patients achieved BP normalization (< 130/85 mmHg). Doppler echocardiography showed a significant reduction of LV mass (P < 0.005). LV hypertrophy was identified in 70% of subjects at baseline and in 5% after 3 mo of treatment. The ratio of early (E) to late (A) trans-mitral diastolic flow velocity increased, (P < 0.05), the relative wall thickness decreased (P < 0.05) and the left ventricular relaxation time shortened (P < 0.005). The left atrial diameter (P < 0.05) and the aortic diameter (P < 0.05) and stiffness (P < 0.005) also decreased. CONCLUSION The full-dose combination of valsartan plus hydrochlorothiazide produced optimal BP control with regression of target organ damage, already after 3 mo, without relevant side effects.

A Giant Pseudoaneurysm of the Forearm as Unusual Complication of Bacterial Endocarditis

A 59-year-old man with fever was diagnosed with endocarditis due to Streptococcus bovis. Two weeks after antibiotic therapy was started, he presented with red and painful swelling of the forearm without any sign of systemic inflammation. A giant hematoma connected to the radial artery was detected with ultrasound. Surgical intervention with the removal of multiple, sterile clots from the hematoma was performed, and the multiple lacerations of the artery detected were corrected. This is the first case reporting rupture of the radial artery as a complication of infective endocarditis.