Apostolos I. Hatzitolios

The syndrome of rhabdomyolysis: Complications and treatment

Rhabdomyolysis is a syndrome of skeletal muscle cell damage that leads to the release of toxic intracellular material into the systemic circulation. The pathogenesis of rhabdomyolysis is based on an increase in free ionized calcium in the cytoplasm. Its main complications include (a) acute renal failure, which is triggered by renal vasoconstriction and ischemia, (b) myoglobin cast formation in the distal convoluted tubules, and (c) direct renal toxic effect of myoglobin on the epithelial cells of proximal convoluted tubules. Other major complications include electrolyte disorders, such as hyperkalemia, which may cause cardiac arrhythmias, metabolic acidosis, hyperphosphatemia, early hypocalcemia, and late hypercalcemia. Compartmental syndrome and disseminated intravascular coagulopathy may also emerge. The management of myoglobinuric acute renal failure includes aggressive fluid administration to restore the hypovolemia and urine alkalization. The concomitant electrolyte and metabolic disorders should also be treated appropriately; hemodialysis should be considered when life-threatening hyperkalemia and metabolic acidosis exist. In the case of compartmental syndrome, it is important to monitor the intra-compartmental pressure and to perform fasciotomy, if required. When diagnosed early and if the appropriate treatment is initiated promptly, the complications of rhabdomyolysis are preventable and the syndrome has a good prognosis.

Risk factors and drug interactions predisposing to statin-induced myopathy: implications for risk assessment, prevention and treatment

HMG-CoA reductase inhibitors (‘statins’) represent the most effective and widely prescribed drugs currently available for the reduction of low-density lipoprotein cholesterol, a critical therapeutic target for primary and secondary prevention of cardiovascular atherosclerotic disease. In the face of the established lipid lowering and the emerging pleiotropic properties of statins, the patient population suitable for long-term statin treatment is expected to further expand. An overall positive safety and tolerability profile of statins has been established, although adverse events have been reported. Skeletal muscle-related events are the most common adverse events of statin treatment. Statin-induced myopathy can (rarely) manifest with severe and potentially fatal cases of rhabdomyolysis, thus rendering the identification of the underlying predisposing factors critical.The purpose of this review is to summarize the factors that increase the risk of statin-related myopathy. Data from published clinical trials, meta-analyses, postmarketing studies, spontaneous report systems and case reports for rare effects were reviewed. Briefly, the epidemiology, clinical spectrum and molecular mechanisms of statin-associated myopathy are discussed. We further analyse in detail the risk factors that precipitate or increase the likelihood of statin-related myopathy. Individual demographic features, genetic factors and co-morbidities that may account for the significant inter-individual variability in the myopathic risk are presented. Physicochemical properties of statins have been implicated in the differential risk of currently marketed statins. Pharmacokinetic interactions with concomitant medications that interfere with statin metabolism and alter their systemic bioavailability are reviewed. Of particular clinical interest in cases of resistant dyslipidaemia is the interaction of statins with other classes of lipid-lowering agents; current data on the relative safety of available combinations are summarized. Finally, we provide an update of current guidelines for the prevention and management of statin myopathy.The identification of patients with an increased proclivity to statin-induced myopathy could allow more cost-effective approaches of monitoring and screening, facilitate targeted prevention of potential complications, and further improve the already overwhelmingly positive benefit-risk ratio of statins.

Target Organ Damage in “White Coat Hypertension” and “Masked Hypertension”

BACKGROUND In this study we investigated (i) the prevalence of white coat hypertension (WCH) and masked hypertension (MH) in patients who had never been treated earlier with antihypertensive medication, and (ii) the association of these conditions with target organ damage. METHODS A total of 1,535 consecutive patients underwent office blood pressure (BP) measurements, 24-h ambulatory BP monitoring (ABPM), echocardiography, and ultrasonography of the carotid arteries. Subjects who showed normotension or hypertension on the basis of both office and ambulatory BP (ABP) measurement were characterized as having confirmed normotension or confirmed hypertension, respectively. WCH was defined as office hypertension with ambulatory normotension, and MH as office normotension with ambulatory hypertension. RESULTS WCH was found in 17.9% and MH in 14.5% of the subjects. The prevalence of WCH was significantly higher in subjects with obesity, while the prevalence of MH was significantly higher in normal-weight subjects. The confirmed hypertensive subjects as well as the masked hypertensive subjects had significantly higher left ventricular mass (LVM) (corrected for body surface area) and carotid intima media thickness (cIMT) than the confirmed normotensive subjects did (108.9 +/- 30.6, 107.1 +/- 29.1 vs. 101.4 +/- 29.9 g/m(2) and 0.68 +/- 0.16, 0.68 +/- 0.21 vs. 0.63 +/- 0.15 mm, respectively, P < 0.005). White coat hypertensive subjects did not have a significantly higher LVM index than confirmed normotensive subjects (101.5 +/- 25.9 vs. 101.4 +/- 29.9 g/m(2)); they tended to have higher cIMT than the confirmed normotensive subjects, but the difference was not statistically significant (0.67 +/- 0.15 vs. 0.63 +/- 0.15 mm). CONCLUSIONS WCH and MH are common conditions in patients who visit hypertension outpatient clinics. Confirmed hypertension and MH are accompanied by increased LVM index and cIMT, even after adjusting for other risk factors.

Malnutrition in end stage liver disease: Recommendations and nutritional support

Malnutrition has increasingly been acknowledged as an important prognostic factor which can influence the clinical outcome of patients suffering from end‐stage liver disease (ESLD). Despite the fact that malnutrition is not included in the Child–Pugh classification, its presence should alert clinicians to the same extent as do other complications, such as ascites and hepatic encephalopathy. The pathophysiological mechanisms and the clinical conditions that drive cirrhotic patients to an ill‐balanced metabolic state are multiple and they intertwine. Inadequate offer of nutrients, the hypermetabolic state in cirrhosis, the diminished synthetic capacity of the liver and the impaired absorption of nutrients are the main reasons that disrupt the metabolic balance in ESLD. Identifying patients that are approaching the state of malnutrition by simple and easily applied methods is necessary in order to provide nutritional support to those that need it most. According to the European Society for Clinical Nutrition and Metabolism, simple bedside methods such as Subjective Global Assessment and anthropometric parameters are reliable in assessing the nutritional state of cirrhotic patients. Correcting the nutrient deficit of the affected patients is mandatory. Avoidance of alcohol and excess fat and ingestion of 4–6 meals/day containing carbohydrates and protein are the most common recommendations. In severe malnutrition, initiation of enteral feeding and/or use of special formulae such as branched‐chain amino acid‐enriched nutrient mixtures are often recommended. Enteral nutrition improves nutritional status and liver function, reduces complications, prolongs survival and is therefore indicated.

Increased values of mean platelet volume and platelet size deviation width may provide a safe positive diagnosis of idiopathic thrombocytopenic purpura.

Introduction: It has been shown recently that platelet indices like mean platelet volume (MPV), platelet size deviation width (PDW) and platelet-to-large-cell ratio (P-LCR) are helpful in the discrimination between hyperdestructive thrombocytopenia like idiopathic thrombocytopenic purpura (ITP) and hypoproductive thrombocytopenia (HT). The aim of the study is to assess the reliability of these indices in the differentiation of ITP from other thrombocytopenias. Methods: We recruited 134 thrombocytopenic patients (69 men, 65 women) who were divided into two groups according to the underlying disease: group I (n = 63) included ITP patients, whereas group II (n = 71) included patients with HT due to myelosuppression secondary to chemotherapy for hematological malignancies. Platelet indices were derived from a Sysmex automated cell counter. Sensitivity, specificity, positive prognostic value, negative prognostic value, efficiency and Youden index were calculated. Results: Concerning MPV and PDW indices, sensitivity, specificity, positive prognostic value, negative prognostic value, efficiency and Youden index were 100% for the diagnosis of ITP. On the contrary, the values for P-LCR were significantly lower. Conclusions: MPV and PDW can be safely relied on for a positive diagnosis of ITP. MPV and PDW were superior to P-LCR.

N-Terminal Pro-Brain Natriuretic Peptide Levels Are Elevated in Patients with Acute Ischemic Stroke

Brain natriuretic peptide (BNP) is a counterregulatory hormone released by the ventricles of the heart. Its main actions are natriuresis and vasodilation. The authors studied N-terminal pro-brain natriuretic peptide (NT-proBNP) levels soon after an acute ischemic stroke. They compared plasma NT-proBNP concentrations in 30 patients with an acute ischemic stroke with those of 30 controls. The 2 groups were adjusted for age and gender, and there were no significant differences in vascular risk factors and left ventricular systolic and diastolic function. Venous samples were collected within the first 11.8 ±1.2 hours after the onset of symptoms and again on day 6. Brain computed tomography/magnetic resonance imaging (CT/MRI) was performed on the same days (day 0 and day 6) in order to assess the site (carotid or vertebrobasilar), cause (atherothrombotic, cardioembolic, or lacunar), and size (large, medium, or small) of the brain infarct. NT-proBNP levels were elevated in patients with acute stroke (129.9 ±9.9 fmol/mL) compared with the controls (90.8 ±6.3 fmol/mL, p<0.05). These levels remained elevated at day 6 (113.5 ±13.0 fmol/mL). NT-proBNP at admission was significantly higher in cardioembolic compared with atherothrombotic infarctions. There was no correlation between circulating NT-proBNP and stroke topography, infarct size, or severity as assessed by the National Institutes of Health Stroke Scale (NIHSS) at any of the 2 time points (admission and day 6). NT-proBNP levels were raised in patients with acute ischemic stroke; this effect persisted until day 6. The authors suggest that neurohumoral activation occurs in patients with acute ischemic stroke, either reflecting a counterbalancing vasodilating response to the cerebral ischemia or direct myocardial dysfunction.

Role of phytosterols in lipid-lowering: current perspectives

The cholesterol-lowering effect of plant sterols was first discovered in the early 1950s. However, it is only recently that plant sterols have become clinically important, when advances in food-technology have made it possible to combine sterols with a variety of food products including margarines, yogurts, fruit juices and cereal bars. We review the clinical trial evidence of lipid-lowering efficacy of plant sterols and discuss their implications in routine clinical practice. To generate the evidence we searched the Pubmed database for English language literature, using relevant keywords and medical subject heading (MeSH) terms, and extracted the findings from recently published studies and meta-analyses on this topic. Our findings suggest that the short-term use of food supplements rich in plant sterols is a safe and effective strategy; to maximize the benefits of dietary and lifestyle therapy, either with or without statin therapy, among majority of dyslipidemic patients with need for additional lipid-lowering.

Circadian rhythm in sudden cardiac death : A retrospective study of 2,665 cases

Several studies have reported a circadian variation in sudden cardiac death. The aim of this study was to determine whether in northern Greece sudden cardiac death shows a circadian rhythm and/or a weekly and seasonal distribution. We studied 2,665 sudden deaths due to coronary heart disease from 13,832 sudden deaths that merited autopsy; 1,429 (53.6%) of them were due to acute myocardial infarction (AMI) and 1,236 (46.4%) to chronic ischemic heart disease (IHD). The time of death was determined on the basis of autopsy results and witness interviews. There was a circadian rhythm of sudden cardiac death (p<0.010), with a low incidence during the hours 04.00-08.00 (13.1%) and an increased incidence during 20.00-24.00 (19.8%) (p<0.05). Women did not show the same significant circadian variation. Time of occurrence of sudden cardiac death attributed either to AMI or to IHD showed a similar 24-hour distribution (lowest incidence during 04.00-08.00 hours, 12.8% and 13.5%, respectively, and higher during 20.00-24.00, 19.5% and 20.3%, respectively). Weekday distribution of sudden cardiac death showed a significant statistical variation (p<0.005) with the highest frequency on Monday (21.1%) and the lowest on Sunday (7.5%). The same distribution was observed in men, whereas in women the lower frequency was also on Sunday but the higher was on Tuesday. Sudden cardiac death was evenly distributed over the months of the year, with the highest incidence in summer (27.3%) and the lowest in autumn (22%). Sudden cardiac death shows a circadian rhythm and a significant variation during the week.

The Role of Insulin-Sensitizing Agents in the Treatment of Polycystic Ovary Syndrome

Polycystic ovary syndrome (PCOS) represents a heterogeneous spectrum of disorders, mainly characterized by chronic oligoanovulation and hyperandrogenism. Although not included in the diagnostic criteria, insulin resistance is recognized as a fundamental pathogenetic factor of the syndrome. Thus, the use of insulin-sensitizing drugs, such as metformin and thiazolidinediones, has been proposed for PCOS treatment. These agents are unique because they exert both metabolic and endocrine/ovarian beneficial effects.In this review the results of up-to-date clinical studies and meta-analyses on the possible gynaecological actions of insulin sensitizers are discussed. It has been shown that, as well as favourable metabolic influences, such as improvement in glucose, lipid and proinflammatory profiles, these agents also exert beneficial endocrine and ovarian effects, including amelioration of reproductive abnormalities, restoration of ovulation and menstrual cycles, increase in pregnancy rates and reduction of androgen production. Therefore, current data support the use of insulin sensitizers, along with lifestyle measures and/or other agents, in women with PCOS, especially in the presence of insulin- or clomifene-resistance.

Neuropeptide Y and alpha-melanocyte-stimulating hormone: interaction in obesity and possible role in the development of hypertension

Aim:  Obesity and hypertension frequently coexist and both represent important risk factors for cardiovascular disease. The mechanisms implicated in the regulation of food intake have not been completely elucidated. Recent data suggests that peripheral and central neuropeptides play an important role in the maintenance of energy balance. More specifically, leptin, neuropeptide Y (NPY) and alpha‐melanocyte‐stimulating hormone (a‐MSH) appear to be implicated in the pathogenesis of obesity and also contribute to the development of hypertension in obesity.