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Metabolic acidosis may occasionally develop in the course of treatment with drugs used in everyday clinical practice, as well as with the exposure to certain chemicals. Drug-induced metabolic acidosis, although usually mild, may well be life-threatening, as in cases of lactic acidosis complicating antiretroviral therapy or treatment with biguanides. Therefore, a detailed medical history, with special attention to the recent use of culprit medications, is essential in patients with acid-base derangements. Effective clinical management can be handled through awareness of the adverse effect of certain pharmaceutical compounds on the acid-base status. In this review, we evaluate relevant literature with regard to metabolic acidosis associated with specific drug treatment, and discuss the clinical setting and underlying pathophysiological mechanisms. These mechanisms involve renal inability to excrete the dietary H+ load (including types I and IV renal tubular acidoses), metabolic acidosis owing to increased H+ load (including lactic acidosis, ketoacidosis, ingestion of various substances, administration of hyperalimentation solutions and massive rhabdomyolysis) and metabolic acidosis due to HCO3- loss (including gastrointestinal loss and type II renal tubular acidosis). Determinations of arterial blood gases, the serum anion gap and, in some circumstances, the serum osmolar gap are helpful in delineating the pathogenesis of the acid-base disorder. In all cases of drug-related metabolic acidosis, discontinuation of the culprit medications and avoidance of readministration is advised. [ABSTRACT FROM AUTHOR]

The renoprotective effect of statins has been recently disputed because of observations of proteinuria associated with rosuvastatin treatment, the newest drug of the class. Statin-induced proteinuria findings were mainly based on crudely quantitative dipstick assays. The authors quantitatively evaluated the effect of rosuvastatin at the recommended starting dose of 10 mg/d, on urine protein excretion in patients with primary dyslipidemia. Serum lipid and nonlipid parameters as well as urinary electrolyte, creatinine, and protein (total, albumin, immunoglobulin G, and alpha-1 microglobulin) levels were measured in 40 patients treated with rosuvastatin and 30 controls at baseline and after 12 weeks. The protein-to-creatinine ratios were used to assess urinary protein excretion. Rosuvastatin improved the lipid profile, produced no deterioration of kidney function, but induced a small but significant increase in the excretion of alpha-1 microglobulin (by 16%, P < .05) indicating that statin-related proteinuria involves low-molecular-weight proteins and is of proximal tubular origin. [ABSTRACT FROM AUTHOR]

Hyperhomocysteinemia is regarded as an independent risk factor for cardiovascular disease. Lipid-lowering agents, such as fibrates, can modify homocysteine levels. However, less is known about the effect of statin therapy on homocysteine. The authors compared the effects of atorvastatin (40 mg/day), simvastatin (40 mg/day), and micronized fenofibrate (200 mg/day) on the serum concentrations of total homocysteine, vitamin B12, and folic acid in patients with primary hyperlipidemia. A total of 128 patients with primary hyperlipidemia (total cholesterol > 240 mg/dL and triglycerides < 350 mg/dL) were assigned to atorvastatin, simvastatin, or fenofibrate. Serum lipid and metabolic parameters were measured at baseline and at 6 and 12 weeks of treatment. Homocysteine correlated positively with serum creatinine and uric acid levels and inversely with serum folic acid levels. All treatment modalities reduced total, low-density lipoprotein (LDL) cholesterol, and triglyceride concentrations. High-density lipoprotein (HDL) cholesterol levels significantly increased only in the fenofibrate-treated patients (47.9 +/- 12.5 vs. 50.7 +/- 12.6 vs. 51.2 +/- 12.8 mg/dL, p < 0.01). Atorvastatin and fenofibrate treatment resulted in a significant reduction of serum uric acid levels (5.3 +/- 1.6 vs. 4.9 +/- 1.4 vs. 4.8 +/- 1.4 mg/dL, p < 0.0001 for atorvastatin; 5.6 +/- 1.6 vs. 4.3 +/- 1.4 vs. 4.4 +/- 1.4 mg/dL, p < 0.0001 for fenofibrate). Homocysteine levels were significantly increased only by fenofibrate (10.3 +/- 3.3 vs. 14.1 +/- 3.8 vs. 14.2 +/- 3.6 microU/L, p < 0.001) but did not change from baseline following statin treatment. Neither statins nor fenofibrate had any effect on serum vitamin B12 and folic acid levels. In contrast to fenofibrate, therapeutic dosages of atorvastatin and simvastatin have a neutral effect on serum homocysteine levels, which is in favor of their 'cardioprotective' properties. [ABSTRACT FROM AUTHOR]

BACKGROUND: Several antioxidants have been found to have conflicting results in attenuating myocardial reperfusion injury. These studies were done primarily in experimental protocols that did not approximate clinical situations.OBJECTIVE: The aim of this study was to test the efficacy of 3 different antioxidants (ascorbic acid [AA], desferrioxamine, and N-acetylcysteine [NAC]) administered IV alone and in combination in a closed-chest pig model.METHODS: Farm-raised domestic male pigs (aged 3-5 months, weight of 30-35 kg) were assigned to 1 of 5 groups to receive treatment as follows: group A, AA 100 mg/kg; group B, desferrioxamine 60 mg/kg; group C, a loading dose of NAC 100 mg/kg for 20 minutes and a 20-mg/kg maintenance dose; group D, all 3 drugs in combination; and group E, normal saline (control group). The infusion of all drugs was started 15 minutes before and completed 5 minutes after reperfusion, except for the administration of NAC, which was terminated 60 minutes postreperfusion. Myocardial ischemia (45 minutes) and reperfusion (210 minutes) were achieved percutaneously by circumflex artery balloon occlusion. Ejection fraction, left ventricular end-diastolic pressure (LVEDP), flow in the infarcted artery, and all ventricular arrhythmias were recorded. Oxidative stress was estimated by serial measurements of thiobarbituric acid reactive substance (TBARS) concentration in coronary sinus blood. Infarct size was assessed as a percentage of the area at risk (I/R ratio) using the tetrazolium red staining method.RESULTS: The 25 pigs were divided into 5 groups of 5 pigs each. No significant between-group differences were found in I/R ratio or in oxidative stress (as measured by TBARS concentration). Group C developed significantly more ventricular arrhythmias than the control group (80% vs 0%, P = 0.02). No other differences among groups were found. LVEDP was significantly elevated in all treatment groups (mean LVEDP difference [SD] for group A, 6.0 [1.6} mm Hg; group B, 17.6 [1.9} mm Hg; group C, 3.6 [1.7] mm Hg; group D, 6.8 [3.2] and group E, 5.4 [3.4] mm Hg). LVEDP elevation was found to be significantly higher in group B compared with all the other groups (all, P < 0.001). No significant between-group differences were found in the other parameters measured.CONCLUSION: In this experimental pig model, the antioxidants AA, desferrioxamine, and NAC administered alone or in combination did not reduce the deleterious effects of reperfusion injury and specifically the extent of myocardial necrosis. [ABSTRACT FROM AUTHOR]

Introduction: Perivascular epithelioid cell tumor (PECOMA) is a rare mesenchymal neoplasm which expresses both myogenic and melanocytic markers showing a benign course,although malignant tumors have also been reported. To date there are approximately 33 cases of published hepatic pecomas., Presentation of Case: We describe a 47-year-old man with a 27-year past medical history of systemic lupus erythematosus (SLE) who underwent left liver lobectomy due to a liver pecoma. His postoperative course complicated with infection, thrombosis of hepatic artery and liver ischemia as well as drug fever., Discussion: Treatment protocol especially for hepatic PECOMA has not reached a consensus although surgical resection is the preferred therapy., Conclusion: This is the first case of coexistence of liver pecoma and SLE., (Copyright © 2018 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Patients with gastrointestinal bleeding often require large volume blood transfusion. Among the various side effects of blood transfusion, the increase of potassium levels is a serious one which is often overlooked. We report a case of severe hyperkalemia in a patient with gastric bleeding after large volume transfusion of packed red blood cells. The patient had hyperkalemia at baseline associated with his receiving medication as well as acute renal failure following hypovolemia. The baseline hyperkalemia was further aggravated after massive transfusions of packed red blood cells in a short period of time. The associated pathogenetic mechanisms resulting in the increase of potassium levels are presented. A number of risk factors which increase the risk of hyperkalemia after blood transfusion are discussed. Moreover, appropriate management strategies for the prevention of blood transfusion associated hyperkalemia are also presented. Physicians should always keep in mind the possibility of hyperkalemia in cases of blood transfusion., Competing Interests: Conflict-of-interest statement: All the authors have no conflicts of interests to declare.

Background: Low socioeconomic status is associated with poorer cardiovascular health., Objectives: The aim of the present work was to evaluate how social and economic factors influence modifiable cardiovascular disease risk factors and thus, acute coronary syndrome or ischemic stroke presence., Methods: One thousand participants were enrolled; 250 consecutive patients with a first acute coronary syndrome (83% were male, 60 ± 12 years old) and 250 control subjects, as well as 250 consecutive patients with a first ischemic stroke (56% were male, 77 ± 9 years old) and 250 control subjects. The control subjects were population-based and age-sex matched with the patients. Detailed information regarding their medical records, lifestyle characteristics, education level, financial status satisfaction, and type of occupation were recorded., Results: After controlling for potential confounding factors, significant inverse associations were observed regarding financial status satisfaction and sedentary/mental type occupation with acute coronary syndrome or stroke presence, but not with the educational level. Nevertheless, further evaluation using path analysis, revealed quite different results, indicating that the education level influenced the type of occupation and financial satisfaction, hence affecting indirectly the likelihood of developing a cardiovascular disease event., Conclusions: Social and economic parameters interact with modifiable cardiovascular disease risk factors through multiple pathways., (Copyright © 2015 World Heart Federation (Geneva). Published by Elsevier B.V. All rights reserved.)

We compared the effects of lipid lowering with rosuvastatin (RSV) monotherapy versus intensified treatment by combining RSV with ezetimibe (EZT) on kidney function in patients undergoing vascular surgery. Patients were randomly assigned to either 10 mg/d RSV (n = 136) or RSV 10 mg/d plus EZT 10 mg/d (RSV/EZT, n = 126). At 12 months, a similar decrease in estimated glomerular filtration rate (eGFR) was noted. Patients who achieved a low-density lipoprotein cholesterol (LDL-C) of <100 mg/dL had less eGFR decrease than those patients having an LDL-C limit of more than 100 mg/dL. There were no significant changes in the urinary total protein to creatinine ratio in either group. Significant microalbuminuria was evident in both the groups. Patients undergoing vascular surgery show deterioration in their renal function during the first year, despite statin therapy. Intensified lipid-lowering therapy by adding EZT does not appear to have any renoprotective effect., (© The Author(s) 2014.)

The aim of the present work was to evaluate the combined role of eating behaviors and to investigate their effect on the likelihood of developing an acute coronary syndrome (ACS) or an ischemic stroke. During 2009-2010, 1000 participants were enrolled; 250 consecutive patients with a first ACS (83% males, 60 ± 12 years) and 250 control subjects, as well as 250 consecutive patients with a first ischemic stroke (56% males, 77 ± 9 years) and 250 controls. The controls were population-based and age-sex matched with the patients. Detailed information regarding their anthropometric data, medical records and lifestyle characteristics (dietary and smoking habits, physical activity, psychological state and eating practices -using a special questionnaire-) were recorded. Five eating behaviors were selected to compose an eating behavior score for the purposes of this work: adherence to the Mediterranean diet (using the MedDietScore), frequency of breakfast consumption, eating while being stressed, eating while working and skipping meals. Eating behaviors with beneficial health effects were scored with 0, while those with negative effects were assigned score 1. The total range of the score was between 0 and 5. Higher scores reveal "unhealthier" eating practices. After controlling for potential confounding factors, each unit increase of the eating behavior score was associated with 70% (95% CI: 1.29-2.22) higher likelihood of developing an ACS. Insignificant associations were observed regarding ischemic stroke. The overall adoption of specific "unhealthy" eating practices seems to have a detrimental effect on cardiovascular health, and especially coronary heart disease., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

Ischemic heart disease and cerebrovascular disease remain major health problems with associated mortality and quality-of-life consequences. Antiplatelet agents, including thienopyridines and the new P2Y12 inhibitors, have been shown to improve survival in the secondary prevention setting. We review the available evidence on the effectiveness and safety of previous established as well as novel antithrombotic agents in the secondary prevention of cardiovascular disease with a special focus on cerebrovascular disease., (© The Author(s) 2013.)

Introduction: The aim of this study was to investigate the effect of the Mediterranean diet on the likelihood of having a non-fatal cardiovascular outcome, taking into account anxiety and depression status., Methods: This was a case-control study with individual matching by age and sex. During 2009-2010, 1000 participants were enrolled; 250 were consecutive patients with a first acute coronary syndrome (ACS), 250 were consecutive patients with a first ischemic stroke, and 500 were population-based control subjects, one-for-one matched to the patients by age and sex. Among other characteristics, adherence to the Mediterranean diet was assessed by the MedDietScore, anxiety was assessed with the Spielberger State-Trait Anxiety Inventory form Y-2, while depressive symptomatology was evaluated by the Zung Depression Rating Scale., Results: Higher adherence to the Mediterranean diet was associated with a lower likelihood of ACS and ischemic stroke, even after adjusting for anxiety or depression (ACS: OR=0.92, 95%CI 0.87-0.98 and 0.93, 0.88-0.98, respectively; ischemic stroke: 0.91, 0.84-0.98 and 0.90, 0.83-0.97, respectively). For both ACS and stroke patients, anxiety and depression were associated with a higher likelihood of ACS and stroke. When stratifying for depression or anxiety status, the Mediterranean diet remained a significantly protective factor only for people with low levels of depression and anxiety for ACS, and only for people with low levels of anxiety, as far as stroke was concerned., Conclusion: Anxiety and depression seem to play a mediating role in the protective relationship between adherence to the Mediterranean diet and the likelihood of developing cardiovascular events.

The role of vitamin D (VitD) has recently been expanded beyond bone homeostasis and regulation of calcium levels. VitD deficiency has been proposed as a new risk factor for cardiovascular disease, including stroke. Low 25(OH)VitD levels are very common among post-stroke patients, probably due to their limited mobility and decreased sunlight exposure along with a higher prevalence of malnutrition, and they have been associated with previous and incident cerebrovascular events. Contributing mechanisms have been linked to the association of VitD deficiency with the presence of hypertension, diabetes mellitus and atherosclerosis. Moreover, there is experimental evidence demonstrating that VitD exerts neuroprotective effects, such as stimulation of neurotrophic factors, quenching of oxidative hyperactivity and regulation of neuronal death, as well as antithrombotic properties. It is plausible that VitD supplementation could be a beneficial intervention for the prevention and/or treatment of cerebrovascular disease possibly by decreasing the aforementioned cerebrovascular risk factors and simultaneously by improving neurologic and cognitive functions, thereby reducing falls and fractures in post-stroke patients. However, study results are still conflicting and data from large, randomized clinical trials are needed to clarify these speculations.

Alzheimer's disease (AD) is the most prevalent type of dementia, involving progressive deterioration of neuronal networks. Although the pathophysiological mechanism of AD is not fully elucidated, apart from β-amyloid and tau protein, a diverse number of factors such as cardiovascular risk factors, inflammation, and lipids metabolism may play a significant role. Numerous epidemiological and laboratory studies support vascular injury and inflammation, as key pathological processes. The present review is focused on cardiovascular risk factors, lipids, and circulating biomarkers of inflammation, discussing them as independent mechanisms converging to the same final pathogenetic cascade of AD.

Children with heterozygous familial hypercholesterolemia (heFH) are prone to premature atherosclerosis. Vascular endothelial dysfunction may predict increased cardiovascular risk in children with heFH. The aim of this study was to assess for early functional and structural vascular changes in children with heFH. This cross-sectional study included 30 children with heFH (mean age 12 years) and 30 age- and sex-matched controls. Brachial artery flow-mediated dilation (FMD), carotid intima-media thickness (cIMT), carotid-femoral pulse wave velocity, and large- and small vessel compliance were measured noninvasively. HeFH children exhibited significantly greater total and LDL cholesterol, apolipoprotein B, and lipoprotein (a) levels (p < 0.05 for all) and lower FMD (6.23 ± 3.88 vs. 9.46 ± 4.54 %, p < 0.004) compared with controls. When children were divided in age subgroups, FMD was found to be significantly decreased in heFH compared with control subjects only in ages >10 years (p < 0.05). However, FMD was found to be similarly impaired in heFH children in all age subgroups (two-way analysis of variance, p = 0.39). No differences in other vascular function indices were found. In heFH patients, but not in controls, FMD was inversely correlated with cIMT (r = -0.378, p = 0.036). In conclusion, endothelial dysfunction occurs early in heFH children indicating an increased risk for premature cardiovascular disease and reflecting probably the need for early initiation of anticholesterolemic treatment. Decreased FMD is detected before structural atherosclerotic changes occur.

Objective: To compare the accuracy of a-priori and a-posteriori dietary patterns in the prediction of acute coronary syndrome (ACS) and ischemic stroke. This is actually the first study to employ state-of-the-art classification methods for this purpose., Methods and Materials: During 2009-2010, 1000 participants were enrolled; 250 consecutive patients with a first ACS and 250 controls (60±12 years, 83% males), as well as 250 consecutive patients with a first stroke and 250 controls (75±9 years, 56% males). The controls were population-based and age-sex matched to the patients. The a-priori dietary patterns were derived from the validated MedDietScore, whereas the a-posteriori ones were extracted from principal components analysis. Both approaches were modeled using six classification algorithms: multiple logistic regression (MLR), naïve Bayes, decision trees, repeated incremental pruning to produce error reduction (RIPPER), artificial neural networks and support vector machines. The classification accuracy of the resulting models was evaluated using the C-statistic., Results: For the ACS prediction, the C-statistic varied from 0.587 (RIPPER) to 0.807 (MLR) for the a-priori analysis, while for the a-posteriori one, it fluctuated between 0.583 (RIPPER) and 0.827 (MLR). For the stroke prediction, the C-statistic varied from 0.637 (RIPPER) to 0.767 (MLR) for the a-priori analysis, and from 0.617 (decision tree) to 0.780 (MLR) for the a-posteriori., Conclusion: Both dietary pattern approaches achieved equivalent classification accuracy over most classification algorithms. The choice, therefore, depends on the application at hand., (Copyright © 2013 Elsevier B.V. All rights reserved.)

Objectives: Statins may exhibit anti-inflammatory and antioxidant effects. Whether different statins at equivalent doses or the combination of low-dose statin with ezetimibe have comparable anti-inflammatory and antioxidant effects is unknown. The aim of this study was to compare the effects of simvastatin, simvastatin/ezetimibe or rosuvastatin at equivalent low-density lipoprotein cholesterol lowering doses on inflammation and oxidative stress indices in subjects with hypercholesterolemia., Methods: This was a pre-specified analysis of a prospective, randomized, open-label, blinded endpoint (PROBE) study. We enrolled one hundred and fifty three (n = 153) hypercholesterolemic subjects who were randomized to receive simvastatin 40 mg or simvastatin/ezetimibe 10/10 mg or rosuvastatin 10 mg daily. Plasma 8-Epi prostaglandin F2 alpha (8-epiPGF2a), oxidized LDL (oxLDL) and lipoprotein-associated phospholipase A2 (Lp-PLA2) activity and mass were measured at baseline and following 12 weeks of treatment., Results: A significant reduction in plasma 8-isoprostane and oxLDL levels was observed in all treatment groups [by 10%, 8% and 6% (p < 0.05 compared with baseline) and 41%, 40% and 39% (p < 0.001 compared with baseline) in simvastatin, simvastatin/ezetimibe and rosuvastatin groups, respectively]. In all treatment groups a significant reduction in total plasma Lp-PLA2 activity and mass was observed (by 36%, 31% and 38% and 36%, 32% and 32% for simvastatin, simvastatin/ezetimibe and rosuvastatin, respectively, p < 0.001 compared with baseline). No intergroup differences were observed., Conclusions: Simvastatin 40 mg, simvastatin/ezetimibe 10/10 mg and rosuvastatin 10 mg significantly reduced 8-epiPGF2a, oxLDL and Lp-PLA2 activity and mass to a similar extent., (Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.)

The aim of the present work was to compare the influence of classic cardiovascular disease (CVD) risk factors on the development of acute coronary syndrome (ACS) and ischemic stroke. During 2009-2010, 1,000 participants were enrolled: 250 were consecutive patients with a first ACS, 250 were consecutive patients with a first ischemic stroke, and 500 were population-based, control subjects, 1-for-1 matched to the patients by age and gender. The following CVD risk factors were evaluated: smoking/passive smoking, family history of CVD, physical inactivity, hypertension, hypercholesterolemia, diabetes mellitus, presence of overweight and obesity, trait anxiety (assessed with the Spielberger State-Trait Anxiety Inventory form Y-2), and adherence to the Mediterranean diet (assessed by the MedDietScore). Furthermore, participants graded the perceived significance of the aforementioned factors, using a scale from 1 (not important) to 9 (very important). The risk factors with the highest effect size for ACS, as determined by the Wald criterion, were smoking and hypercholesterolemia; regarding stroke, they were anxiety and family history of CVD (all p <0.01). When the odds ratios of each factor for ACS and stroke were compared, insignificant differences were observed, except for smoking. On the basis of the participants' health beliefs, smoking and stress emerged as the most important risk factors, whereas all subjects graded passive smoking as a least important factor. In conclusion, similarities of the risk factors regarding ACS and ischemic stroke facilitate simultaneous primary prevention measures., (Copyright © 2013 Elsevier Inc. All rights reserved.)

Background and Aims: Although significant evidence exists regarding the role of specific foods and dietary patterns on the development of cardiovascular disease, the influence of eating practices has not been thoroughly examined and understood. The aim of the present work was to evaluate the independent role of eating practices on the likelihood of developing an acute coronary syndrome (ACS) or ischemic stroke., Methods and Results: During 2009-2010, 1000 participants were enrolled; 250 were consecutive patients with a first ACS, 250 were consecutive patients with a first ischemic stroke and 500 were population-based control subjects (250 age-sex matched one-for-one with ACS patients, and 250 age-sex matched one-for-one with stroke patients). Eating practices were evaluated using a special questionnaire. Socio-demographic, clinical, psychological, dietary and other lifestyle characteristics were also measured. After controlling for potential confounding factors, each 20 min prolongation of dinner-to-sleep time was associated with 10% lower likelihood of ischemic stroke (95%CI: 0.83-0.98). Furthermore, eating practices related to stress (i.e., eating while being stressed, eating while working at the same time, skipping a meal due to work obligations) were associated with higher likelihood of having an ACS. Finally, eating while watching television was associated with lower likelihood of having an ACS (OR: 0.46, 95%CI: 0.27-0.78) or stroke event (OR: 0.42, 95%CI: 0.23-0.77)., Conclusion: Results of this work, present novel information, indicating the significance of eating practices, in addition to dietary patterns, regarding the development of coronary heart disease and stroke, and could be used in the primary prevention of CVD., (Copyright © 2011 Elsevier B.V. All rights reserved.)

The effect of antihypertensive drugs on lipoprotein subfraction profile is still under investigation. In this study the effects of fixed combination of valsartan with either amlodipine (V-A) or hydrochlorothiazide (V-H) on low-density-lipoprotein (LDL) and high-density-lipoprotein (HDL) subfraction profile of patients with stage 2 or 3 hypertension were assessed. A total of 60 drug-naive patients were randomized to either V-A (160/5 mg, n=30) or V-H (160/12.5 mg, n=30). At baseline as well as 16 weeks post-treatment analysis of the LDL and HDL subfraction profile was conducted by using LDL Lipoprint System. Both V-A and V-H effectively reduced blood pressure (BP) to similar levels. An increase in the cholesterol concentration of small-dense LDL subfractions (by 18.2%, P<0.05) was observed in the V-H group, whereas this parameter remained unchanged in the V-A group. Therefore, mean LDL particle size was decreased in the V-H group (from 267 ± 5 to 266 ± 5Å, P<0.05). HDL-Cholesterol (HDL-C) levels were reduced by 4.7% (P<0.05) in the V-H group, mirrored by a reduction in the cholesterol mass of small and intermediate HDL particles. In conclusion, despite similar reductions in BP, V-H combination may adversely affect serum lipids as well as LDL and HDL subfraction profile as compared with V-A.

Objective: Cardiovascular complications represent a major cause of morbidity and mortality in patients undergoing vascular surgery. This was a prospective randomized, open-label study to investigate the effect of lipid-lowering treatment by statin monotherapy or intensified by combining statin with ezetimibe on a  12-month  prognosis after vascular surgery., Methods: Patients were randomly assigned to receive rosuvastatin (RSV) 10 mg/d or rosuvastatin 10 mg/d plus ezetemibe (RSV/EZT) 10 mg/d, starting prior to scheduled surgical procedure. The primary end point was the first major cardiovascular event, including death from cardiac causes, nonfatal myocardial infarction, ischemic stroke, and unstable angina., Results: A total of 136 patients assigned to RSV and 126 to RSV/EZT completed the study protocol. As many as 6.6% of patients in the RSV group experience a major cardiovascular event within 30 days after surgery versus 5.6% in the RSV/EZT group (P = .72). From month 1 to 12 of the follow-up period, primary end point was observed (9 taking RSV vs 2 in the RSV/EZT group [P = .04]). Intensified lipid-lowering therapy with RSV/EZT was associated with a greater decrease in low-density lipoprotein cholesterol levels compared with RSV (75.87 ± 31.64 vs 87.19 ± 31.7, P = .004), while no differential effect on triglyceride, high-density lipoprotein cholesterol or high-sensitivity C-reactive protein levels was noted between groups., Conclusion: Our findings indicate that statin therapy intensified by ezetimibe may reduce the incidence of cardiovascular events within the first 12 months after vascular surgery. Nonetheless, whether the use of ezetimibe as an add-on therapy to reduce cardiovascular risk in these patients needs to be tested in larger future studies.

Objectives: Toll-like receptors (TLRs) are key players in the innate immune system. Recently, a pivotal role of TLR2 and TLR4 has been recognized in atherogenesis. We investigated the effect of simvastatin monotherapy or its combination with ezetimibe on TLR2 and TLR4 membrane expression and on lipopolysaccharide (LPS)-induced interleukin-1β (IL-1β) and interleukin-6 (IL-6) production in peripheral blood monocytes of patients with primary hypercholesterolemia., Methods: This was a prospective, randomized, open-label, blinded endpoint study. After a 3-month period of lifestyle changes patients (n = 60) (mean age 55 ± 13) with LDL-cholesterol levels above those recommended by the NCEP ATP III, were randomly allocated to open-label simvastatin 40 mg (n = 30) or simvastatin/ezetimibe 10/10 mg (n = 30) daily. Both groups were similar with regard to demographics, risk factors, medications and baseline lipid values. TLR2 and TLR4 membrane expression in monocytes, LPS-induced intracellular production of IL-1β and IL-6 were assessed by flow cytometry at baseline and 3 months post-treatment in both patient groups, as well as in 30 age- and sex-matched normolipidemic controls., Results: Hypercholesterolemic patients exhibited higher TLR2 and TLR4 membrane expression compared with controls (p < 0.02). LPS induced a significant increase in the intracellular levels of IL-1β and IL-6 in all groups however both patient groups exhibited significantly lower levels compared with controls. Three months of treatment with either simvastatin or its combination with ezetimibe resulted in a significant reduction of TLR2 and TLR4 expression (p < 0.01 compared with baseline values) with no intergroup differences. Furthermore, in both groups the post-treatment values of LPS-induced IL-1β and IL-6 production were significantly lower compared with baseline (p < 0.05 for all comparisons)., Conclusions: A high simvastatin dose or the combination of a low-dose simvastatin with ezetimibe reduce to a similar extent TLR2, TLR4 membrane expression and LPS-induced IL-6 and IL-1β production in monocytes of hypercholesterolemic patients. The pathophysiological significance of these effects regarding atherosclerosis, reserves further investigation., (Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.)

Objectives: The aim of the present work was to evaluate the association between salt and salty food consumption on the development of an acute coronary syndrome (ACS) or ischemic stroke, under the context of adherence to the Mediterranean diet., Methods: During 2009-2010, 1000 participants were enrolled; 250 were consecutive patients with a first ACS, 250 were consecutive patients with a first ischemic stroke and 500 population-based, control subjects, one-for-one matched to the patients by age and sex. Socio-demographic, clinical, psychological, dietary and other lifestyle characteristics were measured. Consumption of foods with high salt concentration was evaluated with a special score (range 0-10). Adherence to the Mediterranean diet was assessed by the validated MedDietScore (theoretical range: 0-55)., Results: After adjustment for potential confounding factors, use of salt added in table was associated with 81% higher likelihood of stroke (95% Confidence Interval: 1.03-3.20), whereas no association was observed regarding the development of ACS. Salt use during cooking was not associated with the development of ACS or stroke. Each unit increase of the score evaluating total salty food consumption was associated with 33% higher likelihood of stroke development (95% Confidence Interval: 1.08-1.64), but not with ACS. The effect of salt and salty food consumption regarding stroke presence was more evident for participants with lower adherence to the Mediterranean diet., Conclusion: Simple dietary changes, with emphasis on reducing salt and salty food consumption, along with better adherence to the Mediterranean diet, should be incorporated in public health strategies for the primary prevention of stroke., (Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.)

The aim of the present work was to evaluate the association between adherence to the Mediterranean diet and the development of ischemic stroke according to cholesterol levels. During 2009-2010, 500 participants were enrolled; 250 were consecutive patients (77 ± 9 years, 55.6% men) with a first ischemic stroke and 250 population-based, control participants, matched to the patients by age and sex. Sociodemographic, clinical, dietary, and other lifestyle characteristics were measured. Adherence to the Mediterranean diet was assessed by the validated MedDietScore (theoretical range: 0-55). After various adjustments, each 1/55 unit increase in the MedDietScore was associated with 17% lower likelihood of having an ischemic stroke in nonhypercholesterolemic participants (95%CI: 0.72-0.96) and 10% lower likelihood in participants with hypercholesterolemia (95%CI: 0.81-0.99). The present work highlights the cardioprotective benefits from the adoption of the Mediterranean diet, by showing its beneficial effect regarding ischemic stroke development, regardless of the presence of hypercholesterolemia.

Hyponatremia is a common electrolyte disturbance associated with considerable morbidity and mortality. Hyponatremia may not infrequently be present during the course of an infection, does not cause specific symptoms and may be overlooked by clinicians. Nonetheless, it may reflect the severity of the underlying process. This review focuses on the clinical and pathophysiological aspects of hyponatremia associated with infectious diseases. In the majority of cases, the fall in serum sodium concentration is of multifactorial origin owing to increased secretion of the anti-diuretic hormone either appropriately or inappropriately. Inadvertent administration of fluids may worsen hyponatremia and prolong morbidity., (Copyright © 2011 The British Infection Association. Published by Elsevier Ltd. All rights reserved.)

Background and Aims: We undertook this study to compare the impact of aspirin vs. clopidogrel treatment on 5-year survival of patients experiencing a first-ever acute ischemic noncardioembolic stroke., Methods: This was a retrospective study involving patients with an acute ischemic stroke who had an indication for antiplatelet therapy (atherothrombotic, lacunar and cryptogenic stroke subtype). A total of 1228 (383 women) hospitalized due to an acute first-ever stroke and receiving aspirin (n = 880) or clopidogrel (n = 348) were finally involved. To determine the factors that independently predict 5-year survival statistical analysis including the Kaplan-Meier survival curve and multifactorial analysis (Cox regression) was performed., Results: Subjects treated with clopidogrel had improved 5-year survival compared with those receiving aspirin (log rank test: 16.4, p <0.0001). The difference in survival was evident as early as 6 months from index stroke: cumulative survival 93.8% for aspirin vs. 97% for clopidogrel (log rank test: 4.01, p = 0.045). The composite cardiovascular event (including stroke recurrence, myocardial infarction, unstable angina, coronary revascularization, aortic aneurysm rupture, peripheral atherosclerotic artery diseases, and sudden death) rates were lower in the clopidogrel group (n = 60, 17.2%) compared with the aspirin (n = 249, 28.3%) group (log rank test: 12.4, p <0.0001). This preferential effect of clopidogrel over aspirin was independent of age, gender, presence of cardiovascular disease other than stroke or cardiovascular risk factors as well as irrespective of the severity of stroke and days of hospitalization., Conclusions: This study supports that clopidogrel is superior to aspirin in preventing death and cardiovascular events after an acute noncardioembolic ischemic stroke., (Copyright © 2011 IMSS. Published by Elsevier Inc. All rights reserved.)

Hyponatremia is a common electrolyte abnormality with the potential for significant morbidity and mortality. Endocrine disorders, including adrenal deficiency and hypothyroidism, are uncommon causes of hyponatremia. Primary adrenal insufficiency (i.e. Addison's disease) may well be recognized by clear hall-marks of the disease, such as pigmentation, salt craving, hypotension, and concomitant hyperkalemia. Addison's disease is an important diagnosis not to be missed since the consequences can be grave. On the other hand, hypothyroidism and secondary adrenocortical insufficiency originating from diseases of the hypothalamus and/or pituitary (hypopituitarism) require a high index of suspicion, because the clinical signs can be quite subtle. This review focuses on clinical and pathophysiological aspects of hyponatremia due to endocrine disorders.