Claudio Borghi

Red yeast rice improves lipid pattern, high-sensitivity C-reactive protein, and vascular remodeling parameters in moderately hypercholesterolemic Italian subjects

Despite a recent health claim by the European Agency on Food Safety, the effect of high doses of dietary monacolin supplements from red yeast rice on cholesterolemia has not been tested in Italian subjects. Our aim via a crossover, double-blind, placebo-controlled randomized clinical trial was to test if a short-term treatment with 10 mg monacolins could improve lipid pattern, high-sensitivity C-reactive protein (hs-CRP), and vascular remodeling biomarkers in a small cohort of Mediterranean subjects. Thus, 25 healthy, mildly hypercholesterolemic subjects were enrolled, and after 4 weeks of a stabilization diet, subjects were randomized to the sequence placebo-washout-monacolins or monacolins-washout-placebo, with each period being 4 weeks long. At each study step, a complete lipid pattern, safety parameters, hs-CRP, and matrix metalloproteinases 2 and 9 levels were measured. When compared to the placebo group, monacolins-treated patients experienced a more favorable percent change in total cholesterol (-12.45%, 95% CI -16.19 to -8.71), low-density lipoprotein cholesterol (-21.99%, 95% CI -26.63 to -17.36), non-high-density lipoprotein cholesterol (-14.67%, 95% CI -19.22 to -10.11), matrix metalloproteinase 2 (-28.05%, 95% CI -35.18 to -20.93), matrix metalloproteinase 9 (-27.19%, 95% CI -36.21 to -18.15), and hs-CRP (-23.77%, 95% CI -30.54 to -17.01). No significant differences were observed in regards to triglycerides, high-density lipoprotein cholesterol, and safety parameters. On the basis of our data, we demonstrate that a 10-mg monacolin nutraceutical appears to safely reduce cholesterolemia, hs-CRP, and markers of vascular remodeling in Italian subjects. These results have to be confirmed in larger patient samples and longer studies.

Omega 3 Polyunsaturated Fatty Acids Supplementation and Blood Pressure Levels in Hypertriglyceridemic Patients with Untreated Normal-High Blood Pressure and With or Without Metabolic Syndrome: A Retrospective Study

Recent evidence suggests that at least a part of the polyunsaturated fatty acids (PUFAs) heart protective effect is mediated by a relatively small but significant decrease in blood pressure level. We retrospectively evaluated the long-term effect of a PUFA supplementation on the blood pressure level of 111 hypertriglyceridemic subjects with untreated normal-high blood pressure that were prescribed a 2 grams PUFA supplementation in order to improve their plasma lipid pattern. After 12 months of treatment, systolic blood pressure (SBP) meanly decreased by 2.7 ± 2.5 mmHg (p =u2009 0.001) and diastolic blood pressure (DBP) by 1.3 ± 3.3 mmHg (p < 0.001), while basal heart rate decreased by 4.0 ± 4.4 bpm (p < 0.001). Both SBP and DBP reduction were significantly related to the baseline SBP (p < 0.001) and DBP (p < 0.001), respectively. Diastolic blood pressure change was also inversely related to the patients age (p = 0.004). No significant difference was perceived in the metabolic syndrome subgroup. In our retrospective study, highly purified omega-3 PUFA long-term supplementation is associated with a significant reduction in SBP, DBP, Pulse pressure (PP), and basal heart rate in hypertriglyceridemic patients with normal-high blood pressure. No significant difference was perceived in the metabolic syndrome subgroup. The main determinants of the PUFA anti-hypertensive effect appear to be the basal blood pressure level and age.

Inner ear dysfunction of uncertain origin: A multidisciplinary approach could give something more

In order to find out any possible cause of an alteration of the vasomotor reactivity which can be responsible for a more or less severe sufferance of the inner ear, announced by the onset or the enhancement of sensorineural hearing loss, tinnitus, and some kind of dizziness and vertigo, a multidisciplinary approach should be considered. The possibility of an influence of hemodynamic imbalance due to hypotensive changes followed by vasomotor changes affecting the microcirculation of the inner ear has already been widely discussed; moreover, an increase in prevalence of tinnitus (which in many cases can be considered as a symptom of sufferance of the inner ear) has been found in subjects submitted to an aggressive antihypertensive therapy as well as in patients with severe heart failure, thus demonstrating a relationship between hemodynamic changes and inner ear dysfunction. For the same reason, the research for this mechanism of imbalance could concern other conditions possibly activating an abnormal response of the autonomic nervous system, which could in turn lead to a circulatory impairment of the labyrinth: among these, affections concerning central nervous system, endocrine system, metabolism, renal apparatus and even gastroenteric diseases with a functional component and any other factor which could interfere with vasomotor regulation should be considered. Thus, the absence of reliable causes for a sufferance of the inner ear should not lead to catalogue it as a disorder of idiopathic nature, but should represent a reason for a multidisciplinary investigation on all the possible causes of hemodynamic imbalance and/or autonomic dysregulation.

Terlipressin infusion induces Tako-Tsubo syndrome in a cirrhotic man with hepato-renal syndrome

Dr. Di Micoli, Dr. Buccione, Prof. Trevisani: TakoTsubo cardiomyopathy (TTC), also known as transient left ventricular apical ballooning syndrome, is a clinical entity characterized by (1) reversible left ventricular apical wall motion abnormalities, (2) typical electrocardiographic changes and (3) relatively minor elevation of troponine, creatinine-kinase (CK) and CK-MB that mimics an acute myocardial infarction (AMI) without any acute obstructive coronary disease [1]. Typically, the left ventricular imbalance almost always recovers in a period of days to weeks, so that the management and prognosis of this condition are clearly different from those of AMI [2]. TTC is generally observed in post-menopausal women without prior history of heart disease or clear risk factors for coronary artery disease, who have often experienced recent emotional or physical stress, non-cardiac surgery or extracardiac diseases [1]. Recently, TTC has also been described in critically ill patients without prior heart disease admitted to a medical intensive care unit for severe non-cardiac diseases, such as sepsis, acute respiratory failure, systemic inflammatory response syndrome, anaphylaxis and trauma injuries [3, 4]. Herein, we report a case of TTC occurring in a cirrhotic man, waiting for liver transplantation (LT), probably favored by the intravenous infusion of terlipressin, a synthetic analog of vasopressin (AVP), for the treatment of hepato-renal syndrome (HRS). A 67-year-old Caucasian man with hepatitis B virusrelated cirrhosis and ascites, waiting for LT, was admitted to our unit because of the onset of hepatic encephalopathy, and the worsening of renal sodium retention. As a candidate for LT, he had undergone clinical, laboratory and instrumental tests aimed at excluding extrahepatic diseases precluding surgery. Myocardial single photon emission computed tomography had excluded ischemic damage, and trans-thoracic echocardiography had ruled out dyskinesia of ventricular segments and documented a normal (65%) left ventricular ejection fraction (LVEF). On admission, the patient presented with peripheral edema, ascites and grade III hepatic encephalopathy. Daily diuresis was around 200 mL. The ongoing therapy included oral diuretics (furosemide 25 mg b.i.d. and spironolactone 100 mg b.i.d.), lamivudine and tenofovir for HBV infection control, norfloxacine (400 mg/day) for secondary prophylaxis of the spontaneous peritoneal peritonitis, lactulose, and periodic albumin infusion. The serum creatinine was 2.2 mg/dL and blood urea nitrogen 0.9 g/dL, while serum electrolyte concentrations were normal (sodium 138 mEq/L, potassium 3.5 mEq/L, calcium 8.9 mg/dL and magnesium 2.6 mEq/L). The hemoglobin level was 10.4 g/dL, platelet count 134.000/lL, leukocytes 8.0 9 10/mmc, serum bilirubin 18.8 mg/dL, albumin 3.4 g/dL, INR 2.11. A. Di Micoli D. Buccione V. Santi L. Bastagli M. Bernardi F. Trevisani Dipartimento di Medicina Clinica, Alma Mater Studiorum-Universita degli Studi di Bologna, Bologna, Italy

Possible influence on heart rate on tinnitus

Assuming the possibility of the inner ear damage due to a hemodynamic imbalance essentially due to an abnormal vasomotor regulatory response, the possibility that heart rate (HR) has a correlation with the onset and/or the enhancement of tinnitus is hypothesized. In fact, recent studies have drawn the influence of other factors than blood pressure, in normotensive subjects, in taking part to the regulation of peripheral resistance, outlining the importance of both cardiac output (CO) - which is a function of heart rate (HR) and stroke volume (SV) and SV itself as a dynamic component to baroreflex control of muscle sympathetic nerve activity (MSNA). From this point of view, it could be possible that a condition of bradycardia can enhance tinnitus regardless of its cause, and conversely that a more elevated HR can be related to a relief of this symptom.

About plasma arginin vasopressin levels and Meniere ' s disease

International Journal of Audiology suggested elevated levels of plasma arginin vasopressin (AVP) during acute phases of Meniere ’ s disease are associated with the disease prognosis. Evidence of a possible causal relationship between enhanced AVP levels and Meniere ’ s disease has also been reported by Takeda et al (2000) and Naganuma et al (2006). Additional studies using a systematic approach are needed to examine factors inducing hemodynamic changes due to the involvement of a very complex, peripheral sensory organ that requires large amounts of energy from a small volume of blood perfusion. On the other hand, an ischemic and hypoxic, more or less transient, condition may be the origin of hydrops as well as other non-Menieric inner ear disorders. This idea has been advanced (Pirodda et al, 2010), possibly in relation with an abrupt lowering of blood pressure values followed by an abnormal sympathetic reaction (Pirodda et al, 1997, 2001, 2004). Actually, this orientation is in agreement with the experimental models proposed by Hultcrantz et al (1977) and Maass (1981), suggesting an effect of decreased blood pressure and changes in sympathetic tone on the cochlear circulation; however, the effect of the sympathetic system, the renin-angiotensin-aldosterone system, and vasopressin is generally considered as critical in maintaining blood pressure through a substantially synergic action. Considering an analogy between the kidney and the inner ear pathophysiology, the possibility that the inner ear proton pumps maintain their function under ischemia causing hydrops (Pirodda et al, 2010) suggests elevated plasma levels of vasopressin may be an effect rather than a cause of Meniere ’ s disease: An abrupt decrease in blood pressure followed by a sharp vasoconstriction and subsequent insuffi ciency of peripheral blood perfusion could transmit ‘ misleading ’ information to the local receptors, thus inducing an abnormal release of vasopressin. As thoroughly analysed by Aoki et al (2010), a sum of complex interactions between local and general effects of vasopressin on the labyrinth must be considered and further investigation is needed. However, the terminal type of the blood supply to this organ, the complexity of the mechanisms regulating systemic hemodynamic homeostasis, and the presence of labyrinthine volume receptors that can affect the entire body (Bartoli et al, 1989) could, in our opinion, make it more probable that Menieric attacks infl uence vasopressin release than result from elevated levels of vasopressin.

Meniere's disease and the use of proton pump inhibitors.

PRINCIPLESnOn the basis of previous observations we examined the possibility of a favourable effect of proton pump inhibitors (PPI) on Menieres disease (MD). A preliminary step was made by retrospectively analysing the number of menieric crisis in group of patients suffering from MD and using PPI for other reasons as compared to a group of menieric subjects who had never used PPI.nnnMETHODSnBetween January 2001 and December 2006, 42 patients affected by MD were examined in the tertiary referral centre at the University Hospital of Bologna, Italy and in the private office of an ENT specialist in Cassino, Italy. Within the study group, 18 patients had used PPI for various reasons for at least 12 consecutive months, whilst 24 patients had never been prescribed them. We recorded the number of menieric crises reported in the observation period. The mean follow-up period was 21.9 months. Statistical analysis was performed by means of the x2 test and significance was defined when p<0.05.nnnRESULTSnMost of MD patients (72%) using PPI suffered less than one episode of menieric crisis/year. On the other hand patients who had never used a PPI, experienced considerably more episodes only 16.7% having less than one crisis per year. This difference was statistically significant (p<0, 001).nnnCONCLUSIONSnEven taking the limitations of this retrospective study into account the reported data nevertheless strongly suggest a possible role for proton pumps in the pathogenesis of MD. This could lead to interesting developments and contribute to a better definition of MD and the therapeutic possibilities.

How to avoid the depression of the adherence to antihypertensive treatment

A dherence is ‘the extent to which a person’s behaviour – taking medication, following a diet, and/or executing lifestyle changes – corresponds with agreed recommendations from a healthcare provider’. Adherence to antihypertensive treatment is a major problem for the correct management of cardiovascular diseases in general and for arterial hypertension in particular. In detail, it has been estimated that the proportion of hypertensive patients who are persistent in their medications after 3 years from the first prescription is about one-third of the treated population [2,3]. This can fairly explain the results of the EURIKA survey in which, despite the availability of very effective antihypertensive medications, the proportion of hypertensive patients who achieve an adequate blood pressure control does not exceed the value of 40% [1]. The negative consequences of this unsatisfactory situation are twofold ranging from a reduced preventive impact of drug strategies aimed at decreasing the burden of cardiovascular risk to a significant waste of economic resources because of the shortage of the expected benefit of the prescribed medications. On the contrary, a good adherence to prescribed antihypertensive medications has been associated with a significant reduction in the odds ratio of major cardiovascular events [4] supporting a primary role for adherence as a key factor for any successful strategy aimed at reducing the cardiovascular risk by improving blood pressure control. Despite its very high prevalence, poor adherence to treatment in the hypertensive population is a modifiable condition. The probability of an adequate use of medications is increased by the preliminary identification of the possible causes of nonadherence. Several factors can be responsible for a poor adherence to antihypertensive therapy [5] and among them the most common are: the patient’s perception of the efficacy of treatment, the

Could statins exert a protective effect on epistaxis of systemic origin

Epistaxis, that is a relatively frequent occurrence of hemorrhage from the nose, is reported in up to 60% of the population with peak incidences in subjects under the age of ten (essential epistaxis, usually linked to an altered vasomotor regulation) and, with even greater entity, over the age of 60. The cause of nosebleeds can generally be divided into two categories, local and systemic factors, although it should be remembered that a significant number of nosebleeds occur with no obvious cause. Actually, according to the common observation the epistaxis prone subject is an elderly with hypertension associated to some degree of vascular alteration. The statins essentially exert a competitive inhibition of 3-hydroxy-3 methyl glutaryl coenzyme A (HMG-CoA) reductase that results in cholesterol synthesis inhibition. In the last years, however, there has been a growing evidence that these drugs exert a number of vascular actions that are independent of lipid lowering and result in a vasoprotective effect. Due to their favourable influence on the vascular wall, and the consequent possible modulatory effect on blood pressure, a possible utility of statins in preventing many cases of nosebleed is hypothesized, to our knowledge for the first time.