Eating behaviors and their relationship with cardiovascular disease. A case/case-control study.

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.

Endothelial dysfunction, but not structural atherosclerosis, is evident early in children with heterozygous familial hypercholesterolemia.

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.

Atherosclerosis, biomarkers of atherosclerosis and Alzheimer's disease.

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 ß-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.

Statin therapy and outcome after ischemic stroke: systematic review and meta-analysis of observational studies and randomized trials.

BACKGROUND AND PURPOSE: Although experimental data suggest that statin therapy may improve neurological outcome after acute cerebral ischemia, the results from clinical studies are conflicting. We performed a systematic review and meta-analysis investigating the relationship between statin therapy and outcome after ischemic stroke. METHODS: The primary analysis investigated statin therapy at stroke onset (prestroke statin use) and good functional outcome (modified Rankin score 0 to 2) and death. Secondary analyses included the following: (1) acute poststroke statin therapy (≤ 72 hours after stroke), and (2) thrombolysis-treated patients. RESULTS: The primary analysis included 113 148 subjects (27 studies). Among observational studies, statin treatment at stroke onset was associated with good functional outcome at 90 days (pooled odds ratio [OR], 1.41; 95% confidence interval [CI], 1.29-1.56; P<0.001), but not 1 year (OR, 1.12; 95% CI, 0.9-1.4; P=0.31), and with reduced fatality at 90 days (pooled OR, 0.71; 95% CI, 0.62-0.82; P<0.001) and 1 year (OR, 0.80; 95% CI, 0.67-0.95; P=0.01). In the single randomized controlled trial reporting 90-day functional outcome, statin treatment was associated with good outcome (OR, 1.5; 95% CI, 1.0-2.24; P=0.05). No reduction in fatality was observed on meta-analysis of data from 3 randomized controlled trials (P=0.9). In studies restricted to of thrombolysis-treated patients, an association between statins and increased fatality at 90 days was observed (pooled OR, 1.25; 95% CI, 1.02-1.52; P=0.03, 3 studies, 4339 patients). However, this association was no longer present after adjusting for age and stroke severity in the largest study (adjusted OR, 1.14; 95% CI, 0.90-1.44; 4012 patients). CONCLUSIONS: In the largest meta-analysis to date, statin therapy at stroke onset was associated with improved outcome, a finding not observed in studies restricted to thrombolysis-treated patients. Randomized trials of statin therapy in acute ischemic stroke are needed.

Adherence to the Mediterranean diet in relation to acute coronary syndrome or stroke nonfatal events: a comparative analysis of a case/case-control study.

BACKGROUND: Although the role of Mediterranean diet on cardiovascular disease prevention has long been evaluated and understood, its association with the development of stroke has been rarely examined. The aim of the present work was to comparatively evaluate the association between adherence to the Mediterranean diet and the development of an acute coronary syndrome (ACS) or ischemic stroke. METHODS: During the period from 2009 to 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 population-based, control subjects, 1-for-1 matched to the patients by age and sex. Sociodemographic, clinical, psychological, dietary, and other lifestyle characteristics were measured. Adherence to the Mediterranean diet was assessed by the validated MedDietScore (theoretical range 0-55). RESULTS: After various adjustments were made, it was observed that for each 1-of-55-unit increase of the MedDietScore, the corresponding odds ratio for having an ACS was 0.91 (95% CI 0.87-0.96), whereas regarding stroke, it was 0.88 (95% CI 0.82-0.94). CONCLUSIONS: The present work extended the current knowledge about the cardioprotective benefits from the adoption of the Mediterranean diet by showing an additional protective effect on ischemic stroke development.

Snakebites of fingers or toes by viperidae family members: an orthopaedic approach.

The purpose of this study was to review current principles of therapy for affected patients and determine whether an emergent surgical approach or expectant management should be selected in cases of snakebites of fingers or toes by Viperidae family members. Over the past five years (January 2004 to December 2009), 12 patients bitten by Vipera ammodytes were admitted in our department. We retrospectively reviewed their demographic and epidemiological characteristics as well as their symptoms, laboratory findings, and complications. All snake bites occurred at the extremities (fingers and toes). The main complications were oedema, disseminated intravascular coagulation, and decrease in haematocrit. None of the patients developed compartment syndrome or required surgical debridement. The majority of the patients with snakebites of fingers or toes by Vipera ammodytes can be treated conservatively. Surgery is indicated only in case of compartment syndrome, where fasciotomies should be performed without delay after diagnosis.

Rosuvastatin-associated adverse effects and drug-drug interactions in the clinical setting of dyslipidemia.

HMG-CoA reductase inhibitors (statins) are the mainstay in the pharmacologic management of dyslipidemia. Since they are widely prescribed, their safety remains an issue of concern. Rosuvastatin has been proven to be efficacious in improving serum lipid profiles. Recently published data from the JUPITER study confirmed the efficacy of this statin in primary prevention for older patients with multiple risk factors and evidence of inflammation. Rosuvastatin exhibits high hydrophilicity and hepatoselectivity, as well as low systemic bioavailability, while undergoing minimal metabolism via the cytochrome P450 system. Therefore, rosuvastatin has an interesting pharmacokinetic profile that is different from that of other statins. However, it remains to be established whether this may translate into a better safety profile and fewer drug-drug interactions for this statin compared with others. Herein, we review evidence with regard to the safety of this statin as well as its interactions with agents commonly prescribed in the clinical setting. As with other statins, rosuvastatin treatment is associated with relatively low rates of severe myopathy, rhabdomyolysis, and renal failure. Asymptomatic liver enzyme elevations occur with rosuvastatin at a similarly low incidence as with other statins. Rosuvastatin treatment has also been associated with adverse effects related to the gastrointestinal tract and central nervous system, which are also commonly observed with many other drugs. Proteinuria induced by rosuvastatin is likely to be associated with a statin-provoked inhibition of low-molecular-weight protein reabsorption by the renal tubules. Higher doses of rosuvastatin have been associated with cases of renal failure. Also, the co-administration of rosuvastatin with drugs that increase rosuvastatin blood levels may be deleterious for the kidney. Furthermore, rhabdomyolysis, considered a class effect of statins, is known to involve renal damage. Concerns have been raised by findings from the JUPITER study suggesting that rosuvastatin may slightly increase the incidence of physician-reported diabetes mellitus, as well as the levels of glycated hemoglobin in older patients with multiple risk factors and low-grade inflammation. Clinical trials proposed no increase in the incidence of neoplasias with rosuvastatin treatment compared with placebo. Drugs that antagonize organic anion transporter protein 1B1-mediated hepatic uptake of rosuvastatin are more likely to interact with this statin. Clinicians should be cautious when rosuvastatin is co-administered with vitamin K antagonists, cyclosporine (ciclosporin), gemfibrozil, and antiretroviral agents since a potential pharmacokinetic interaction with those drugs may increase the risk of toxicity. On the other hand, rosuvastatin combination treatment with fenofibrate, ezetimibe, omega-3-fatty acids, antifungal azoles, rifampin (rifampicin), or clopidogrel seems to be safe, as there is no evidence to support any pharmacokinetic or pharmacodynamic interaction of rosuvastatin with any of these drugs. Rosuvastatin therefore appears to be relatively safe and well tolerated, sharing the adverse effects that are considered class effects of statins. Practitioners of all medical practices should be alert when rosuvastatin is prescribed concomitantly with agents that may increase the risk of rosuvastatin-associated toxicity.

Pharmaceutical modulation of the Renin Angiotensin aldosterone system for stroke prevention: a review of experimental and clinical evidence.

The renin angiotensin aldosterone system (RAAS) has been implicated in the pathogenesis of cerebrovascular diseases. During the past decades, AU: INCLUDE A NUMBER? RAAS has gained attention as an important therapeutic target in cardiovascular medicine. Modulation of the RAAS for primary and secondary stroke prevention seems an appealing strategy. Several experimental studies have showed that pre-treatment with RAAS inhibitors prior to the initiation of ischemia exerts favorable effects on infarct volume, brain edema, and cerebral blood flow in the marginal zone. Furthermore, the activation of angiotensin receptor type 2 has been associated with neuroprotective effects. Accumulating evidence based on recent clinical trials indicate that blockade of RAAS has a potential role in stroke prevention. This review summarizes the pathophysiological aspects of brain RAAS and its constituents, presents experimental data on the neuroprotective actions of RAAS inhibitors and available evidence regarding their effects on stroke risk, and discuss future directions for research.

Apolipoprotein B-to-A1 ratio as a predictor of acute ischemic nonembolic stroke in elderly subjects.

Among traditional cardiovascular risk factors, apolipoprotein (apo)B/apoA1 ratio is considered to have the strongest predictive value for ischemic stroke. Nevertheless, there are imsufficient data to support this ratio as an independent risk predictor of ischemic stroke in elderly individuals. In this case-control study, we evaluated apoB/apoA1 ratio as a predictor of ischemic stroke in a cohort of elderly subjects. A total of 163 patients aged>70 years (88 men) admitted due to a first-ever acute ischemic/nonembolic stroke and 166 volunteers (87 men) with no history of cardiovascular disease were included. The association between apoB/apoA1 ratio and stroke was determined by multivariate logistic regression modeling after adjusting for potential confounding factors, including lipid parameters. Stroke patients exhibited a higher apoB/apoA1 ratio than controls (1.04±0.33 vs 0.86±0.22; P<.001). In univariate analysis, crude odds ratio (OR) for apoB/apoA1 ratio was 1.27 per 0.1 increase (95% confidence interval [CI]=1.15-1.39; P<.001). Compared with subjects with an apoB/apoA1 ratio in the lowest quartile, those within the highest quartile had a 6.3-fold increase in the odds of suffering an ischemic stroke (95% CI=3.17-12.48; P<.001). This association remained significant after controlling for potential confounders, including sex, age, smoking status, body mass index, waist circumference, glucose and insulin levels, the presence of hypertension and diabetes mellitus, and lipid profile parameters (adjusted OR=3.02; 95% CI=1.16-7.83; P=.02). Our findings support elevated apoB/apoA1 ratio as an independent predictor of ischemic stroke in individuals over age 70.

A review of drug-induced hypocalcemia.

Hypocalcemia (defined as total serum calcium lower than 8.5 mg/dl or as ionized serum calcium lower than 4.7 mg/dl) is a relatively common metabolic abnormality observed in hospitalized patients. Although it is associated with certain pharmacological agents such as bisphosphonates and cisplatin, hypocalcemia may occasionally develop in the course of treatment with drugs used in everyday clinical practice, including antiepileptics, aminoglycosides, and proton pump inhibitors. Hypocalcemia associated with drug treatment can be easily missed as a consequence of coexistence of multiple factors contributing to low serum calcium levels. Drug-related hypocalcemia is usually mild and asymptomatic but may be severe as well. Effective clinical management can be handled through awareness of this adverse effect induced by certain pharmaceutical compounds on serum calcium concentrations. Herein, we review pertinent clinical information on the incidence of hypocalcemia associated with specific drug treatment and discuss the underlying pathophysiological mechanisms.

Dose-dependent effect of rosuvastatin treatment on HDL-subfraction phenotype in patients with primary hyperlipidemia.

Although the raising effect of rosuvastatin on high-density lipoprotein cholesterol is well-established, there is a paucity of data regarding the effect of this statin on the high-density lipoprotein subfraction phenotype. A total of 150 participants without evidence of cardiovascular disease were randomized to therapeutic lifestyle modification (nonstatin-treated group) or to therapeutic lifestyle modification plus rosuvastatin at 10 mg/d (RSV10 group) or 20 mg/d (RSV20 group). We assessed the effect of rosuvastatin on the cholesterol mass of high-density lipoprotein subfractions at baseline as well as after 12 weeks post-treatment. Rosuvastatin treatment dose-dependently increased the high-density lipoprotein cholesterol (3.4% vs 5.3% in the RSV10 and RSV20 groups, respectively, P = .02). A dose-related rosuvastatin-induced increase in the cholesterol concentration of large high-density lipoprotein particles was also noted (by 11.4% in RSV10 group vs 22.0% in the RSV20 group, P = .01). Rosuvastatin treatment increases the high-density lipoprotein cholesterol by increasing the cholesterol mass only of the larger high-density lipoprotein particles in a dose-dependent manner.

Metabolic syndrome and its components as predictors of ischemic stroke in type 2 diabetic patients.

BACKGROUND AND PURPOSE: The available data regarding the association between metabolic syndrome (MS) or MS components and ischemic stroke in type 2 diabetics are limited and inconsistent. This study aimed to investigate these associations. METHODS: Five hundred ninety-nine consecutive type 2 diabetic patients (mean age 60.4+/-9.6 years, 54% men) were followed-up for 10.1 years (median period). Baseline clinical and laboratory characteristics and the occurrence of a first-ever ischemic stroke during follow-up were recorded. RESULTS: Seventy-eight patients developed a first-ever ischemic stroke. According to Cox proportional hazard model, waist circumference (hazard ratio, HR:1.006, 95% CI:1.002 to 1.010, P=0.003) and age (HR:1.061, 95% CI:1.002 to 1.125, P=0.04) were significant predictors. After incorporating various combinations of MS components in multivariate models, only age and waist circumference remained significant. CONCLUSIONS: MS per se at baseline or combinations of its components do not predict the development of ischemic stroke in type 2 diabetic patients. Waist circumference represents an independent prognostic factor and could be used as a clinical tool for stroke prevention in this population.

The relative value of metabolic syndrome and cardiovascular risk score estimates in premature acute coronary syndromes.

BACKGROUND: To compare the relative value of metabolic syndrome (MetS) and cardiovascular risk score estimates in patients with acute coronary syndromes (ACS) aged <45 years. PATIENTS AND METHODS: Two hundred consecutive patients (183 men, mean age 40.8 +/- 3.5 years) presented with a first-ever ACS, and 200 age-and sex-matched controls were evaluated. Metabolic syndrome diagnostic criteria, European Risk SCORE estimation function, and the Framingham Risk Score (FRS) were assessed in all participants. RESULTS: The prevalence of the MetS was significantly higher in the patients' group compared with the control group (51.5% vs 26.0%, P < .001). No subjects with a SCORE >1.0% were identified. The mean 10-year FRS for patients and controls was 13.03% +/- 7.96% and 10.02 +/- 8.10%, respectively (P < .001), whereas only 22.5% of ACS patients had a 10-year risk >20.0% compared with 14.5% of controls (P = .04). After controlling for potential confounders, MetS was associated with 1.93 (95% CI 1.13-3.28, P = .01) higher odds of having an ACS. Moreover, the odds had a positive association with the increasing cumulative number of MetS components. Crude and adjusted ORs for the FRS were 1.05 (95% CI 1.029-1.08, P = .001) and 0.98 (95% CI 0.92-1.05, P = NS), respectively. CONCLUSION: Metabolic syndrome is highly associated with ACS in subjects <45 years of age and seems to be more valuable than established cardiovascular risk calculators.

The role of C-reactive protein in atherosclerotic cardiovascular disease: an overview.

C-reactive protein (CRP) is an acute-phase protein, which has been used in clinical practice as a non specific marker of inflammation. Many studies have shown that CRP is associated with atherosclerotic cardiovascular disease. It is currently unknown if CRP plays an active role as an etiologic factor in cardiovascular disease. The mechanisms by which CRP may contribute to the pathogenesis of cardiovascular disease are poorly understood. The effect of CRP on atherogenesis may include interactions with other factors of immunity and inflammation, such as the complement system, as well as a direct effect of CRP on the cells involved in atherosclerotic lesions. We review the literature concerning the mechanisms by which CRP may influence the development of cardiovascular disease and discuss the findings of clinical studies assessing the association between CRP and cardiovascular disease.

Effects of atorvastatin on red-blood cell Na(+)/Li(+) countertransport in hyperlipidemic patients with and without hypertension.

BACKGROUND: To explore the effect of short-term cholesterol-lowering treatment with atorvastatin on erythrocyte sodium-lithium countertransport (Na(+)/Li(+) CT) activity. METHODS: Group A consisted of 30 patients (14 men) with mild essential hypertension (systolic blood pressure (SBP), 140-159 mm Hg and/or diastolic BP, 90-99 mm Hg) and primary hypercholesterolemia low-density lipoprotein (LDL) cholesterol >4.1 mmol/l and triglycerides (TG) <2.8 mmol/l), group B of 30 normotensive patients (16 men) with primary hypercholesterolemia, while 37 (18 men) healthy volunteers comprised the control group. After a 6-week dietary lead-in, all eligible patients were prescribed 20 mg/day of atorvastatin. Anthropometric data, blood-pressure (BP) measurements and determinations of lipid, non-lipid metabolic parameters (including homeostasis model assessment index, (HOMA-IR)) and erythrocyte Na(+)/Li(+) CT activity were collected at baseline and after 12 weeks of treatment. RESULTS: At baseline Na(+)/Li(+) CT activity was significantly higher in group A and B compared with the control group and correlated directly with obesity indices, systolic and diastolic BP, total cholesterol, LDL-cholesterol, TG, apolipoprotein B (apoB), HOMA-IR, uric acid and inversely with high-density lipoprotein (HDL)-cholesterol and apoA1. Systolic and diastolic BP levels, HOMA-IR and Na(+)/Li(+) CT activity were significantly decreased after atorvastatin treatment in both patient groups. The reduction in Na(+)/Li(+) CT activity correlated with baseline Na(+)/Li(+) CT activity and the changes in HOMA-IR values. CONCLUSIONS: Short-term treatment with atorvastatin for patients with hypercholesterolemia, and with or without essential hypertension, is associated with a significant reduction in the erythrocyte Na(+)/Li(+) CT activity, BP levels and insulin resistance independent of concomitant changes in lipid parameters.

Baseline triglyceride levels and insulin sensitivity are major determinants of the increase of LDL particle size and buoyancy induced by rosuvastatin treatment in patients with primary hyperlipidemia.

The influence of various statins on low-density-lipoprotein (LDL)-particle phenotype has been reportedly trivial or moderate. We assessed the effect of rosuvastatin (the newest statin available) on the LDL subfraction profile in patients with primary hyperlipidemia. One hundred and twenty patients with primary hyperlipidemia without evidence of cardiovascular disease were randomized to therapeutic lifestyle modification ('control' group, N=60) or therapeutic lifestyle modification plus rosuvastatin 20 mg/day (N=60). Laboratory evaluation was performed at baseline and 12 weeks post-treatment. LDL subfraction analysis was carried out electrophoretically using of high-resolution 3% polyacrylamide gel tubes and the Lipoprint LDL System. Rosuvastatin induced a redistribution of LDL-cholesterol from small-dense LDL particles to large-buoyant ones and increased the mean LDL particle size. This beneficial effect was observed only in patients with baseline triglyceride levels >or=150 mg/dl (mean LDL particle size 255+/-7 A vs 260+/-5 A, P<0.01), whereas the LDL subfraction profile was not altered in those with triglyceride levels <150 mg/dl. Stepwise multivariate linear regression analysis revealed that baseline triglyceride levels (R(2)=0.29, P=0.001) followed by baseline insulin resistance as assessed by the HOmeostasis Model Assessment (HOMA) (R(2)=0.25, P=0.001) were independently associated with the rosuvastatin-induced increase in the mean LDL particle size. In conclusion, rosuvastatin at 20 mg/day favorably modified the relative distribution of LDL-cholesterol distribution on LDL subfractions as well as on the mean LDL particle size in patients treated for primary dyslipidemia. Baseline triglyceride levels as well as baseline HOMA-index were found to be the major predictors of this beneficial action of rosuvastatin.

Effect of rosuvastatin treatment on plasma visfatin levels in patients with primary hyperlipidemia.

Visfatin is a novel adipokine involved in the process of atherosclerosis. We assessed the effect of rosuvastatin on plasma visfatin levels in patients with primary hyperlipidemia. Eighty hyperlipidemic patients without evidence of cardiovascular disease were randomized to receive either rosuvastatin 10 mg/day or therapeutic lifestyle changes intervention. Plasma visfatin levels were determined at baseline and after 12-weeks post-randomization. Rosuvastatin induced a significant decrease in plasma visfatin levels (17.1+/-2.1 versus 15.5+/-2.0 ng/ml, P=0.03). This effect correlated with baseline visfatin levels (r=0.51, P<0.01) and was independent of any lipid-lowering actions of rosuvastatin.

Metabolic syndrome and Alzheimer's disease: a link to a vascular hypothesis?

Current evidence from epidemiological, neuroimaging, pathological, pharmacotherapeutic, and clinical studies indicate an association of Alzheimer's disease with risk factors of vascular atherosclerotic disease either in isolation or in aggregate. "Metabolic syndrome" (MetS) is the name for a clustering of risk factors for cardiovascular disease and type 2 diabetes that are of metabolic origin. These include central obesity, elevated plasma glucose, high blood pressure, atherogenic dyslipidemia, a prothrombotic state, and a proinflammatory state. In this article, we provide an overview of the relevant literature with regard to the relationship of Alzheimer's disease with MetS. Accumulating evidence suggests a "vascular hypothesis" to be related to the pathology of Alzheimer's disease. In the light of this evidence, clinician may consider lifestyle interventions toward an early and effective cardiovascular risk-factor management to reduce the cardiometabolic and the cognitive decline risk, while further research of other preventive strategies may be warranted.

An overview of the extra-lipid effects of rosuvastatin.

Statins, in addition to their beneficial lipid modulation effects, exert a variety of several so-called "pleiotropic" actions that may result in clinical benefits. Rosuvastatin, the last agent of the class to be introduced, has proved remarkably potent in reducing low-density lipoprotein cholesterol levels. At present, no large-scale primary or secondary prevention clinical trials document either its long-term safety or its effectiveness in preventing cardiovascular events. A substantial number of experimental and clinical studies have indicate favorable effects of rosuvastatin on endothelial function, oxidized low-density lipoprotein, inflammation, plaque stability, vascular remodeling, hemostasis, cardiac muscle, and components of the nervous system. Available data regarding the effects of rosuvastatin on renal function and urine protein excretion do not seem to raise any safety concerns. Whether the established "pleiotropy" and/or lipid-lowering efficacy of rosuvastatin may translate into reduced morbidity and mortality remains to be shown in ongoing clinical outcome trials.

Effect of intravenous administration of antioxidants alone and in combination on myocardial reperfusion injury in an experimental pig model.

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 atrhythmias 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.