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Background: Insulin response to diet might predict the risk of mortality; however, the evidence is limited. We prospectively evaluated the link between the dietary hyperinsulinemia index (DHI) and dietary insulin resistance index (DIRI) with all-cause and cause-specific (cardiovascular disease [CVD] and cancer) mortality.Methods: The National Health and Nutrition Examination Survey (1999-2010) database was used. Vital status through December 31, 2011, was ascertained. Stepwise linear regression models consisted of 39 macro/micronutrients applied, and fasting plasma C-peptide for the DHI and triglyceride/high-density lipoprotein cholesterol ratio (TG/HDL-C) for the DIRI were used. Adjusted Cox regression (followed by propensity score matching) was performed to determine the hazard ratios (HRs) and 95% confidence interval (95% CIs).Results: Overall, 22,246 participants were included (mean age = 47.8 years; 48.9% men). There was a significant increasing risk of mortality across the quartiles of DHI, i.e., participants with a highest score of DHI (Q4) had a greater risk of all-cause (HR: 1.21, 95% CI: 1.17-1.26), CVD (HR: 1.17, 95% CI: 1.07-1.29), and cancer (HR: 1.15, 95% CI: 1.08-1.23) mortality compared with the first quartile (Q1; p < 0.001 for all comparisons). Similarly, participants in the highest DIRI quartile (Q4) had 23% and 31% higher risk of all-cause and CVD mortality, respectively, compared with Q1, while the association between cancer mortality and DIRI was non-significant (HR: 0.88, 95% CI: 0.35-2.61).Conclusions: These findings highlight, for the first time, the detrimental role (association) of insulinemia and insulin resistance potential of diet on all-cause and cause-specific mortality. Our findings support the role of C-peptide and TG/HDL-C ratio as cost-effective and practical biomarkers in clinical settings. These results need to be confirmed to establish their implications. [ABSTRACT FROM AUTHOR]

Objective: Familial hypercholesterolaemia (FH) is a common autosomal dominant inherited disease, affecting 1 in 200-500 individuals worldwide. FH is characterized by elevated circulating low-density lipoprotein cholesterol (LDL-C) concentrations. Its association with increased risk of coronary heart disease (CHD) (>10-fold, compared with patients without FH) is well documented. However, the association between FH and non-CHD atherosclerotic cardiovascular disease (ASCVD) risk has been poorly documented.Methods: PubMed was searched for English language publications regarding the association between FH and carotid artery stenosis, stroke, peripheral artery disease (PAD; lower limbs and other arterial beds), aortic valve calcification (AoVC), aortic and renal artery disease, chronic kidney disease, atrial fibrillation and heart failure, from conception until 22 December 2019.Results: Despite the small number of available studies, as well as their characteristics (sample size, diagnostic criteria used, retrospective or cross-sectional design), there is evidence for a positive association between FH and stroke, PAD or AoVC. More data are needed for definitive conclusions regarding aortic and renal artery disease, chronic kidney disease, atrial fibrillation and heart failure. There is paucity of data with respect to homozygous FH. Increased lipoprotein (a) concentrations, often seen in FH patients, may also contribute to this non-CHD atherosclerotic process. A key question is whether statins or other LDL-C-lowering therapies, provide an additional reduction in the risk of these less-recognized vascular and non-vascular complications in FH patients.Conclusions: Heterozygous FH is associated with increased risk for stroke, PAD and AoVC. Clinicians should take these non-CHD ASCVD aspects into consideration for optimal management of FH patients. [ABSTRACT FROM AUTHOR]

Stroke is a leading cause of death and disability worldwide. Approximately 15% of all first-ever strokes occur due to atheroembolism from a previously undetected/untreated asymptomatic carotid stenosis (ACS). Despite that, international guidelines do not recommend screening for ACS. The rationale for not recommending screening include: (a) the harm associated with screening, (b) the questionable clinical benefit associated with surgery, (c) the lack of proven reduction in the risk of stroke, (d) the large number of false positive/false negative tests, and (e) the cost-effectiveness of such screening programs. A critical analysis of each of these arguments is presented. Patients with ACS have a very high risk of all-cause and cardiac mortality. Detection of ACS should not be viewed as an indication for surgery, but rather as an opportunity to implement best medical treatment (BMT) and lifestyle changes to prevent not only strokes, but also cardiac events. The implementation of screening programs for abdominal aortic aneurysms (AAAs) has led to a considerable reduction in the number of ruptured AAAs and AAA-related deaths. Similarly, screening high-risk individuals for ACS would enable timely identification of patients with ACS and implementation of BMT and lifestyle measures to prevent future strokes and cardiac events. [ABSTRACT FROM AUTHOR]

Background: In animal models, histological and biochemical changes are observed in response to choline deficiency. It is unclear whether dietary choline is linked to non-alcoholic fatty liver disease (NAFLD). Objective: We examined the link among liver tests, fatty liver index (FLI), and choline consumption. Furthermore, we evaluated the impact of adiposity on this association. Method: The National Health and Nutrition Examination Survey (NHANES) was used to obtain data on choline intake and liver function biomarkers. Masked variance and weighting methodology were performed to account for the complex NHANES data. Results: Of the 20,643 participants, 46.8% were men and 45.6% had NAFLD (defined as United States FLI ≥30). In a fully adjusted model (for demographic, dietary, and clinical factors), a significant negative association was found between FLI and choline consumption (β = -0.206, p < 0.001). Participants in the highest quartile (Q4) of choline intake had a 14% lower risk of NAFLD compared with those in the first quartile (Q1). This link was stronger for postmenopausal women; women in Q4 had a 26% lower risk of NAFLD compared with those in Q1. Body mass index (BMI) strongly moderated the link between FLI and choline intake. For example, when choline consumption increased from low (272 mg/d) to high (356 mg/d), FLI decreased from 79.3 to 74.1 in the low BMI category (mean BMI = 22.1 kg/m2) and from 32.1 to 20.6 in the high BMI category (mean BMI =35.9 kg/m2). Conclusions: Our results suggest the presence of a reverse significant association between choline intake and risk of NAFLD. Furthermore, BMI was shown to mediate this relationship since changes in FLI, in relation to choline consumption, were more pronounced in participants with a higher BMI. [ABSTRACT FROM AUTHOR]

The associations of egg consumption with total, coronary heart disease (CHD), and stroke mortality are poorly understood. We prospectively evaluated the link between total, CHD, and stroke mortality with egg consumption using a randomly selected sample of U.S. adults. Next we validated these results within a meta-analysis and systematic review of all available prospective results. We assessed the mean of cardiometabolic risk factors across the intake of eggs. We made the analysis based on data from the National Health and Nutrition Examination Surveys (NHANES; 1999-2010). In NHANES, vital status through December 31, 2011, was ascertained. Cox proportional hazard regression models were used to relate baseline egg consumption with all-cause and cause-specific mortality. PubMed, Scopus, Web of Science, and Google Scholar databases were also searched (up to December 2017). The DerSimonian-Laird method and generic inverse variance methods were used for quantitative data synthesis. Overall, 23,524 participants from NHANES were included (mean age of 47.7 years; 48.7% were men). Across increasing the intake of eggs, adjusted mean levels of cardiometabolic risk factors worsened. Adjusted logistic regression showed that participants in the highest category of egg intake had a greater risk of diabetes (T2DM; 30%) and hypertension (HTN; 48%). With regard to total and CHD mortality, multivariable Cox regression in a fully adjusted model showed no link in males and females. In males, egg intake had a reverse (66%) association with stroke mortality, while this link was not significant among females. The results of pooling data from published prospective studies also showed no link between CHD and total mortality with egg consumption, whereas we observed a reverse (28%) association between egg intake and stroke mortality. These findings were robust after sensitivity analysis. According to our findings, egg intake had no association with CHD and total mortality, whereas was associated with lower risk of mortality from stroke. Egg consumption was associated with T2DM, HTN, C-reactive protein, and markers of glucose/insulin homeostasis. If confirmed in clinical trials (causation), this information may have applications for population-wide health measures. Key teaching points No link between total and CHD mortality with eggs intake in males and females. In males, egg intake had a reverse association with stroke mortality, while this link was not significant among females. The results of pooling data from published prospective studies also showed no link between CHD and total mortality with egg consumption, whereas we observed a reverse association between egg intake and stroke mortality. [ABSTRACT FROM AUTHOR]

Background: Apolipoprotein C-III (apo C-III) is a key regulator of triglycerides metabolism. The aim of this meta-analysis was to assess the effect of fish omega-3 polyunsaturated fatty acids (PUFAs) on apo C-III levels. Methods: Randomized placebo-controlled trials investigating the impact of omega-3 on apo C-III levels were searched in PubMed-Medline, SCOPUS, Web of Science and Google Scholar. A random-effects model and generic inverse variance method were used for quantitative data synthesis. Sensitivity analysis was conducted using the leave-one-out method. A weighted random-effects meta-regression was performed to evaluate the impact of potential confounders on glycemic parameters. Results: This meta-analysis comprising 2062 subjects showed a significant reduction of apo C-III concentrations following treatment with omega-3 (WMD: −22.18 mg/L, 95% confidence interval: −31.61, −12.75, p < .001; I2: 88.24%). Subgroup analysis showed a significant reduction of plasma apo C-III concentrations by eicosapentaenoic acid (EPA) ethyl esters but not omega-3 carboxylic acids or omega-3 ethyl esters. There was a greater apo C-III reduction with only EPA as compared with supplements containing EPA and docosahexaenoic acid (DHA) or only DHA. A positive association between the apo C-III-lowering effect of omega-3 with baseline apo C-III concentrations and treatment duration was found. Conclusions: This meta-analysis has shown that omega-3 PUFAs might significantly decrease apo C-III. Key messages: Omega-3 PUFA supplements significantly reduce apo C-III plasma levels, particularly in hypertriglyceridemic patients when applied in appropriate dose (more than 2 g/day) Triglyceride (TG)-lowering effect is achieved via peroxisome proliferator-activated receptors α Further studies should address the effect of omega-3 PUFAs alone or with other lipid-lowering drugs in order to provide a final answer whether apo C-III could be an important target for prevention of cardiovascular disease New apo C-III antisense oligonucleotide drug (Volanesorsen) showed to be promising in decreasing elevated TGs by reducing levels of apo C-III mRNA [ABSTRACT FROM AUTHOR]

Artichoke is a component of the Mediterranean diet. Therefore, the aim of this meta-analysis was to determine if artichoke extract supplementation affected human lipid parameters. The search included PubMed-Medline, Scopus, Web of Science and Google Scholar databases up to March 28, 2017, to identify RCTs investigating the impact of artichoke extracts on plasma lipid levels. Quantitative data synthesis was performed using a random-effects model, with weighed mean difference (WMD) and 95% confidence interval (CI) as summary statistics. Meta-analysis of data from 9 trials including 702 subjects suggested a significant decrease in plasma concentrations of total cholesterol (WMD: -17.6 mg/dL, 95%CI: -22.0, -13.3, p < 0.001), Low Density Lipoprotein-Cholesterol (LDL-C; WMD: -14.9 mg/dL, 95%CI: -20.4, -9.5, p = 0.011) and triglycerides (WMD: -9.2 mg/dL, 95%CI: -16.2, -2.1, p = 0.011). No significant alteration in plasma High Density Lipoprotein-Cholesterol (HDL-C) concentrations was observed (WMD: 1.0 mg/dL, 95%CI: -1.1, 3.1, p = 0.333). A significant association between the LDL-lowering effect of artichoke and baseline LDL-C concentrations (slope: -0.170; 95%CI: -0.288, 0.051; p = 0.005) was observed. Thus, supplementation with artichoke extract was associated with a significant reduction in both total and LDL-C, and triglycerides, suggesting that supplementation may be synergistic with lipid-lowering therapy in patients with hyperlipidemia. [ABSTRACT FROM AUTHOR]

Introduction: The elderly population (i.e. aged ≥ 65 years) is increasing worldwide. Ageing is associated with a higher incidence and prevalence of cardiovascular disease (CVD). Areas covered: The prevalence of CVD risk factors including type 2 diabetes mellitus, hypertension and dyslipidaemia also increases with advancing age, contributing to the higher absolute CVD risk observed in the elderly. The present narrative review comments on the associations of dyslipidaemia with CVD as well as the effects of lifestyle measures and lipid-lowering drugs on lipids and CVD risk with a special focus on the elderly population. Individual treatment goals and therapeutic options according to current guidelines are also reviewed. Finally, we discuss special characteristics of the elderly that may influence the efficacy and safety of drug therapy and should be considered before selection of hypolipidaemic pharmacotherapy. Expert commentary: There may be a greater CVD benefit in older patients following drug therapy compared with younger ones. Treatment goals and therapeutic options should be individualized according to current guidelines. Specific characteristics that may influence the efficacy and safety of drug therapy in the elderly should be considered in relation to dyslipidaemia treatment. [ABSTRACT FROM PUBLISHER]

Background and aim: Growing evidence suggests that some of the effects of diet on cardiovascular disease (CVD) occur through mechanisms involving subclinical inflammation. We assessed the relationship between selected dietary constituents and serum high-sensitivity C-reactive protein (hsCRP) concentration in a population-based sample of United States adults. Methods: In this cross-sectional analysis, participants were selected from the US National Health and Nutrition Examination Survey (NHANES) and restricted to those with available data on dietary intake, biochemical and anthropometric measurements from 2001 to 2010. All statistical analyses accounted for the survey design and sample weights by using SPSS Complex Samples v22.0 (IBM Corp, Armonk, NY). Results: Of the 17,689 participants analysed, 8607 (48.3%) were men. The mean age was 45.8 years in the overall sample, 44.9 in men and 46.5 in women (p = .047). The age-, race-, sex-, energy intake- and body mass index-adjusted mean dietary intakes of total dietary fibre, polyunsaturated fatty-acids, vitamin E, vitamin A, vitamin B6, total folate, vitamin B family, vitamin C, vitamin K, magnesium, iron, copper and potassium monotonically decreased across increasing hsCRP quarters (p < .001 for all), whereas sugar intake increased (p < .001). In analysis of covariance adjusted for potential confounders (age-, race-, sex-, energy intake- and body weight-) hsCRP levels increased across increasing quarters of sugar intake (p < .001). Conclusions: This study provides further evidence of an association between dietary sugar, polyunsaturated fatty-acids, fibre and antioxidant intake and hsCRP levels, a subclinical inflammation marker. hsCRP concentrations are likely modulated by dietary intake. [ABSTRACT FROM AUTHOR]

In this article, the authors focus on studies which reveal that fasting or non-fasting triglycerides (TG) do not lead to risk of cardiovascular diseases (CVD). It mentions that null mutation was observed in apolipoprotein C3 gene which is associated with cardioprotective lipid profile and association of lower triglyceride levels with lower risk of cardiovascular disease. It highlights that apart from statin treatment targeting TG levels can reduce risk factors of CVD.

Objective:There is a paucity of data regarding the attainment of lipid-lowering treatment goals according to the recent American College of Cardiology/American Heart Association (ACC/AHA) guidelines. The aim of the present study was to assess how applicable these 2013 recommendations are in the setting of an Outpatient University Hospital Lipid Clinic. Methods:This was a retrospective (from 1999 to 2013) observational study including 1000 consecutive adults treated for hyperlipidemia and followed up for ≥3 years. Comparisons for the applicability of current European Society of Cardiology/European Atherosclerosis Society (ESC/EAS) and recent ACC/AHA guidelines were performed. Results:Achievement rates of low density lipoprotein cholesterol (LDL-C) targets set by ESC/EAS were 21%, 44% and 62% among patients at very high, high and moderate cardiovascular risk, respectively, receiving statin monotherapy. Among individuals on high-intensity statins only 47% achieved the anticipated ≥50% LDL-C reduction, i.e. the ACC/AHA target. The corresponding rate was significantly greater among those on statin + ezetimibe (76%, p < 0.05). Likewise, higher rates of LDL-C target attainment according to ESC/EAS guidelines were observed in patients on statin + ezetimibe compared with statin monotherapy (37, 50 and 71% for the three risk groups, p < 0.05 for the very high risk group). Conclusion:The application of the ACC/AHA guidelines may be associated with undertreatment of high risk patients due to suboptimal LDL-C response to high-intensity statins in clinical practice. Adding ezetimibe substantially increases the rate of the ESC/EAS LDL-C target achievement together with the rate of LDL-C lowering response suggested by the ACC/AHA. [ABSTRACT FROM PUBLISHER]

Administration of high intensity statins prior to percutaneous coronary intervention (PCI) for acute coronary syndrome (ACS) or stable coronary artery disease has been shown to reduce short-, mid-, and long-term cardiovascular disease (CVD) morbidity and mortality as well as overall mortality compared with lower intensity statins or no statin treatment. The mechanisms involved are probably related to the pleiotropic effects of statins. Improved endothelial function, reduced low grade inflammation and decreased thrombotic diathesis might reduce cardiac injury, diffuse cardiac necrosis, myocardial infarction and no-reflow phenomenon. A decreased risk of contrast-induced nephropathy (CIN) post-PCI might be an extracardiac mechanism that contributes to the reduction in all cause and CVD mortality. These results support the need for the administration of statins before PCI. [ABSTRACT FROM PUBLISHER]

The ACC/AHA lipid guidelines need to be reconsidered before full implementation. A new cardiovascular disease (CVD) risk estimation, preferably based in interventional multiethnic studies, will be ideal. Specific LDL-C targets may also be necessary because there are data pointing out that they are useful and pragmatic. The risk/benefit ratio should be a key issue because medicine is all about this concept (Hippocrates 460 - c. 370 BC: 'first do not harm'; and then in the Hippocratic Oath: 'I will follow that system of regimen which, according to my ability and judgment, I consider for the benefit of my patients, and abstain from whatever is deleterious and mischievous'). [ABSTRACT FROM AUTHOR]

The article discusses a study which compared the risk of disease, hospitalization and death between blood donors (BDs) and non blood donors (nBDs) in Italy. Topics discussed include higher age of death, lower mortality rates and shorter length-of-stay in hospitals among BDs, no link observed between blood donation and the increased risk of malignancies, and comparison of Charlson comorbidity index score between BDs and nBDs.

Evaluation of: Janczyk W, Socha P, Lebensztejn D et al. Omega-3 fatty acids for treatment of non-alcoholic fatty liver disease: design and rationale of randomized controlled trial. BMC Pediatrics 13(23), 85-94 (2013). This article discusses the design and rationale of a randomized, multicenter, double-blind, placebo-controlled trial of omega-3 fatty acids (450-1300 mg of docosahexaenoic acid + eicosapentaenoic acid daily) for the treatment of nonalcoholic fatty liver disease (NAFLD) in children, adolescents and young adults (5-19 years of age) in comparison with placebo. The primary end point of the trial is the number of patients who experience a decrease in alanine aminotransferase activity >30% of the upper limit of normal. The main secondary end points are improvement in the biochemical liver tests, liver steatosis on ultrasound, markers of insulin resistance and difference in fat/lean body mass composition after 24 weeks of intervention. There is evidence that long-chain omega-3 fatty acids improve the lipid profile by lowering triglycerides, as well as decreasing insulin resistance and cytokine synthesis, thus tackling the mechanisms involved in the pathogenesis of NAFLD. There is evidence that long-chain omega-3 fatty acids are effective at normalizing metabolic syndrome-related aberrations, even in adolescents. Hence, long-chain omega-3 fatty acids may be a promising option for the treatment of NAFLD, even in children and adolescents. However, other aspects and measures should be considered. [ABSTRACT FROM AUTHOR]

Cigarette smoking, active or passive, kills about 6 million people each year worldwide. Cardiovascular disease (CVD) is responsible for 40% of all smoking-related deaths, lung cancer accounts for 20% of all smoking-related deaths, and chronic obstructive pulmonary disease is related to another 20% of deaths. In this narrative review we consider the relationship between cigarette smoking and CVD. We discuss disease states and/or CVD risk factors related to smoking, such as dyslipidaemia, vascular inflammation, endothelial dysfunction, arterial stiffness, insulin resistance, type 2 diabetes mellitus (T2DM), chronic kidney disease (CKD), and non-alcoholic fatty liver disease (NAFLD) as well as their complex interrelations. Smoking cessation can correct abnormalities related to smoking; however, success rates are relatively low. In cases of inability to quit, measures to minimize the adverse effects of smoking specifically related to CVD should be taken. Smokers should receive best practice treatment, according to guidelines, as for non-smokers. [ABSTRACT FROM AUTHOR]

Abstract Objective: The available data on statin effects in chronic kidney disease (CKD) patients are still conflicting. We investigated the impact of short- and long-term statin therapy on lipid profiles in CKD patients requiring or not requiring dialysis. Research design and methods: Data from Scopus, PubMed, Web of Science, and the Cochrane Library from 1966 to May 2012 were searched for studies that investigated this effect. We included all randomized controlled clinical trials that investigated the impact of statin therapy on lipids and lipoproteins. Results: The final analysis included 16 trials with 3594 subjects. In CKD patients, statin therapy significantly reduced total cholesterol (TC), triglycerides (TG) and low-density lipoprotein cholesterol (LDL-C) (p < 0.003 for all comparisons), and the effect insignificantly intensified with duration of statin therapy (56.3 vs 66.8, 22.5 vs 24.1, and 53 vs 56.1 mg/dl, respectively). Comparing statin therapy for <=3 and >3 months in CKD patients on dialysis, the magnitude of TC and LDL-C decreased (26.3 vs 25.9, and 42.2 vs 29.8 mg/dl, respectively, p > 0.05 for both), while TG increased modestly (4.5 vs 13.4 mg/dl). Short-term statin therapy increased high density lipoprotein cholesterol by a mean 0.7 mg/dl (p = 0.04), and long-term therapy was associated with a mean reduction of 2.4 mg/dL. Conclusions: Statin therapy significantly modifies the lipid profile in CKD patients not on dialysis therapy (with the trend to be more effective with longer therapy), and have less beneficial effect in patients on dialysis with the trend to be less effective with longer duration of therapy. [ABSTRACT FROM AUTHOR]

The article discusses the type 2 diabetes mellitus (T2DM) with primary focus on statin therapy and new-onset diabetes. It mentions T2DM as a complex metabolic disorder characterized by peripheral insulin resistance and impaired pancreatic-cell function. It also focuses on the use of statin treatment in increasing fasting plasma glucose levels in the body.

Atrial fibrillation (AF) is the most common arrhythmia encountered in clinical practice. Until recently, a rhythm control strategy for AF has been limited by drug toxicity and side-effects, and landmark AF trials have shown that such a strategy is not superior to a rate control one. New antiarrhythmic drugs, free of undesired effects, would enhance the rhythm control strategy, with the possibility of sinus rhythm restoration and maintenance. One of the promising drugs recently approved for clinical use is dronedarone. This drug has amiodarone-like antiarrhythmic and electrophysiological properties, despite it having a modified structure and lacking an iodine moiety. Thus, dronedarone lacks amiodarone's organ toxicity (including adverse thyroid and pulmonary effects). The efficacy of dronedarone has been investigated in several clinical trials, proving its effect in the prevention of AF recurrence, rate control in paroxysmal/persistent and permanent AF, reduction of cardiovascular hospitalization or death from any cause, and others. Indirect comparisons with amiodarone, as well as one head-to-head study of the two drugs, indicate that the relative safety of dronedarone may be at a cost of its lower antiarrhythmic efficacy compared with amiodarone. [ABSTRACT FROM AUTHOR]

Abstract In January 2011 the American Diabetes Association (ADA) published the latest guidelines for the diagnosis and treatment of diabetes mellitus (DM)(1,2). Despite some controversies, glycated hemoglobin A(1c) (HbA(1c)), an established marker of long-term glycemia traditionally used to assess the quality of DM management, remained an independent criterion for the diagnosis of DM, and indeed now appears to be well established in the USA. This has far-reaching implications for clinical practice worldwide. [ABSTRACT FROM AUTHOR]

The prevalence of obesity is growing rapidly worldwide, and therefore there is a need for effective treatment strategies. The rationale of combination therapy in treating chronic diseases, such as obesity, is the potential additive or synergistic effects. This review considers the results of phase III clinical trials with naltrexone sustained-release (SR) ++ bupropion SR combination therapy in obese patients with or without type 2 diabetes mellitus. We also discuss the potential therapeutic applications of this weight-reducing treatment option. Recent clinical trials have shown that the administration of naltrexone SR ++ bupropion SR resulted in effective weight loss. Furthermore, this treatment was associated with improvement in cardiometabolic variables. Depression and suicidal ideation were more frequently reported in the placebo compared with the combination groups. However, significantly more patients on naltrexone SR ++ bupropion SR experienced adverse events, mainly nausea, and discontinued treatment compared with placebo. Increases in blood pressure and pulse rate were observed only in the combination groups. Further investigation is needed to clarify the clinical significance of this weight-reducing therapeutic option. [ABSTRACT FROM AUTHOR]

Cardiovascular disease (CVD) and non-alcoholic fatty liver disease (NAFLD) share common risk factors and may have a parallel course. Statin treatment alone or in combination with other drugs has a substantially beneficial effect on CVD morbidity and mortality. The question was if these regimens were harmful for the liver. Mounting data suggest that statin monotherapy or statin-based treatments are safe in patients with NAFLD and can improve liver tests and liver ultrasonographic evidence of NAFLD. Recent data suggest that statin-based therapies are beneficial to the liver and at the same time reduce CVD morbidity and mortality in patients with NAFLD more than in subjects without it. These findings suggest that with statins we are able to get two birds with one stone. [ABSTRACT FROM AUTHOR]

Objective: The effect of seasonal variation on the occurrence of stroke remains controversial. The objective of this study was to determine whether there is a seasonal variation in the occurrence of stroke in Northern Greece. Methods: We recorded the seasonal stroke rates over a 10 year period (from January 1997 to December 2006) in 8204 patients in Northern Greece. The findings were analysed separately for ischemic stroke (IS), intracerebral hemorrhage (ICH), subarachnoid hemorrhage (SAH) and transient ischemic attack (TIA). Results: In patients with IS, there was a significant seasonal variation (p<0·001), with the peak incidence in spring (8·4% above average) and the lowest rate in summer (10·4% below average). There was no significant seasonal variation in the occurrence of the other stroke subtypes (ICH, SAH and TIA) when they were considered individually. Discussion: The seasonal effect on stroke incidence needs to be defined so as to improve the provision of preventive measures. [ABSTRACT FROM AUTHOR]

Endogenous carbon monoxide (CO) production was first described 60 years ago. CO is a by-product of the metabolism of haeme to biliverdin. This, in turn, becomes bilirubin. During the past 15 years epidemiological studies and animal experiments have identified bilirubin as a molecule at the crossroads of the protection of the body against reactive oxygen species (ROS). The studies have focused on bilirubin as a biomarker of arterial disease. Recently the potential of CO as a therapeutic agent has been explored. This review assesses the current state of evidence and sets the data in the context of whether CO is an endogenous signalling molecule, a marker of vascular disease and, whether, together with bilirubin, CO could be a potential therapeutic agent. [ABSTRACT FROM AUTHOR]

This Editorial comments on the recently published JUPITER trial (Justification for the Use of Statins in Prevention: an Intervention Trial Evaluating Rosuvastatin), the further evidence it provides for supporting the role of statins in primary prevention and the major implications this may hold for vascular risk assessment and clinical practice guidelines. [ABSTRACT FROM AUTHOR]

Endothelial dysfunction plays an important role in the pathogenesis of hypertension. Other risk factors of atherosclerosis also affect its development. The aim of the study was to assess nitric oxide metabolites concentration (nitrites and nitrates Nox) and endothelin (ET-1) in plasma and cyclic 3,5-guanosine monophosphate (cGMP) in 24 h-urine collection in patients with noncomplicated hypertension without risk factors of atherosclerosis and in hypertensive patients with coronary artery disease (CAD). Sixty-eight subjects were included in the study (44 men, 24 women), aged 47 ± 76 years, allotted into four groups: I - controls (18 clinically healthy subjects); II - 12 subjects with hypertension without risk factors of atherosclerosis; III - 16 subjects with hypertension and risk factors of atherosclerosis; and IV - 22 subjects with hypertension and CAD. Plasma NOx concentration was determined using the Greiss method, plasma ET-1 by ELISA, and urine cGMP using the immunoenzymatic method. Plasma NOx concentration was 14.00 ± 6.88 μmol/L in group I, in group II - 18.62 ± 5.84 μmol, in group III - 9.96 ± 4.72 μmol/L, and in group IV - 8.78 ± 3.72 μmol/L. Statistically significant differences were between groups I and III (p < 0.05) and I and IV (p < 0.04) and groups II and III (p < 0.01) and II and IV (p < 0.01). The concentration of cGMP in 24 h urine collection was in group I - 40 ± 24 pmol/L; in group II - 54 ± 41 pmol/L; in group III - 38 ± 32 pmol/L; and in group IV - 42 ± 36 pmol/L. There were no significant differences between the groups. Plasma ET-1 concentration was 3.86 ± 0.52 pg/mL in group I, in group II - 4.05 ± 0.71 pg/mL, in group III - 4.22 ± 0.79 pg/mL and in group IV - 4.38 ± 0.75 pg/mL. Statistically significant differences were between group I and III (p < 0.05), I and IV (p < 0.03), and between group II and IV (p < 0.04). Endothelial dysfunction was not found in hypertensive patients without a family history of cardiovascular diseases and without other risk factors of atherosclerosis. Deterioration of endothelial function was observed in patients with hypertension with risk factors of atherosclerosis. It was most pronounced in those with CAD. [ABSTRACT FROM AUTHOR]

Statin treatment is essential for the prevention of vascular disease. Despite the established benefits of statins, discontinuation of these agents is frequent. Whether statin discontinuation leads to adverse outcomes is still debated and the most convincing evidence is mainly restricted to patients who experienced an acute vascular event. It is important to establish if this phenomenon extends to other populations, like those without vascular disease but with a high calculated risk. Overall, it appears that even a brief discontinuation of statins might be harmful. Therefore, statin treatment should not be interrupted except if there is a very good reason. Moreover, patients should be instructed as to why they must adhere to their medication. Adherence should be monitored regularly. [ABSTRACT FROM AUTHOR]

Objective: To elucidate the clinical relevance of carotid bruits. Methods: A search using PubMed was performed using the terms: 'carotid bruit', 'stroke', 'cerebrovascular symptoms', 'carotid artery stenosis' and 'carotid artery disease' in various combinations. The reference lists of the gathered reports were also considered. Results: Current evidence shows that a carotid bruit is a useful clinical sign with a high specificity (>90%) for the detection of carotid artery stenosis. The negative predictive value (>90%), as well as the accuracy (>90%), of this inexpensive method, are additional advantages. The low sensitivity (<30%) and low positive predictive values (<30%) of carotid auscultation are its main disadvantages. A carotid bruit is also a useful indicator of systemic atherosclerosis. Carotid bruits are also associated with a higher prevalence of vascular risk factors. Discussion: Carotid auscultation is a useful and inexpensive diagnostic tool that should be included as part of a general physical examination. Its clinical relevance in terms of carotid disease, however, needs to be verified by further investigation (e.g. ultrasonography). Since carotid bruits are predictors of systemic atherosclerosis, their detection provides an opportunity to initiate further investigations and preventive measures. [ABSTRACT FROM AUTHOR]

This editorial discusses whether measuring C-reactive protein (CRP) levels can be used as a predictor of vascular risk. The agents that reduce CRP levels and the evidence for a possible causative role of CRP in the pathogenesis of coronary events and atherosclerosis are also considered. There is a need to further elucidate the role of CRP, as well as the clinical relevance, if any, of CRP-lowering agents. [ABSTRACT FROM AUTHOR]

Background: Recent studies suggest that the distribution of lipoprotein subfractions is an independent predictor of vascular events. Therefore, we evaluated the effect of ezetimibe (a selective cholesterol transport inhibitor) on the concentrations of lipoprotein subfractions in patients with primary dyslipidaemia.Materials and Methods: Patients (n = 50) with primary dyslipidaemias were recruited. The concentrations of the individual lipoprotein subfractions were measured using the Lipoprint system at baseline and after 16 weeks of treatment.Results: Ezetimibe reduced total, low-density lipoprotein cholesterol (LDL-C) and non-high-density lipoprotein cholesterol (HDL-C) values as well as apolipoprotein B concentrations. Subfractionation of apolipoprotein B-containing lipoproteins showed that the reduction in LDL-C values was due to a fall in the concentrations of all LDL subfractions. However, a more pronounced trend towards a decrease in the concentrations of dense LDL subfractions was observed. Patients with triglyceride values >1.7 mmol/L had significantly greater reductions in the concentrations of small, dense LDL particles compared with those with normal triglyceride levels (49 vs. 19%, respectively; p < 0.05). Ezetimibe decreased the concentrations of HDL-C mainly due to a fall in the concentration of dense HDL subfractions.Conclusion: Ezetimibe can favourably affect the distribution of LDL subfractions, especially in patients with elevated triglyceride values. Further studies are needed to clarify the significance of the ezetimibe-induced reduction in the concentrations of dense HDL particles. [ABSTRACT FROM AUTHOR]

Objective: Metallothioneins (MTs) are antioxidant proteins expressed in response to injury. We evaluated MT immunoreactivity in carotid plaques obtained from asymptomatic and symptomatic patients. We also assessed the relationship between ultrasonic plaque echodensity, histological grading, computed tomography findings and MT expression. Methods and Results: In this ongoing prospective study, patients (n = 123, mean age (+/-SD) 68.4 +/- 7.7 years, 97 men) with high-grade carotid stenosis underwent carotid endarterectomy. Specimens were assessed histologically and immunohistochemically. Echolucent plaques (types 1+2) were more common in symptomatic patients (p < 0.0001) and had more advanced histological lesions (p < 0.0001). Echolucent plaques expressed MTs (in macrophages, fibroblasts and T-lymphocytes) significantly more than echogenic plaques (types 3+4) (all p < 0.0001). MT expression was mainly related to carotid plaque echolucency rather than the presence of symptoms. MT expression was significantly more common in advanced histological lesions. Plaques from asymptomatic or symptomatic patients with abnormal computed tomography findings also showed increased MT expression. There was a time-dependent fall in MT expression after cerebrovascular events (p < or = 0.011). Conclusions: MT overexpression may be triggered in unstable plaques as a local protective factor. There is a need to identify both causative and protective predictors of the 'vulnerable plaque' in the 'vulnerable patient'. Further studies are needed to resolve these issues. [ABSTRACT FROM AUTHOR]

The article assesses the efficacy and safety of the pharmacological treatment of non-alcoholic steatohepatitis (NASH). It refers to studies using liver biopsies for the diagnosis of NASH as well as for the evaluation of treatment effects. Consistent evidence from clinical trials showing that glitazones may be safe and effective in the treatment of NASH is discussed. It also describes studies that did not use biopsy for the diagnosis and/or evaluation of treatment effect.

A large number of patients require antiplatelet therapy (mainly aspirin and/or clopidogrel). Recent studies suggest that the combination of these agents is useful in patients with acute coronary syndrome and after percutaneous coronary intervention with stent placement. On the other hand, bleeding complications, most of which arise from the upper gastrointestinal (UGI) tract, can limit the use of antiplatelet drugs. Clopidogrel appears to be associated with fewer UGI side effects and bleeding compared with aspirin. However, a history of previous UGI bleeding is a major risk factor for clopidogrel-associated bleeding. The use of proton-pump inhibitors (PPIs) decreases the rate of UGI bleeding in patients receiving aspirin or clopidogrel. Furthermore, a recent study suggested that the administration of low-dose aspirin plus high-dose esomeprazole (a potent PPI) was associated with fewer episodes of UGI bleeding than clopidogrel alone in patients with a history of recent UGI haemorrhage. However, this study had several limitations and its results should be cautiously extrapolated into clinical practice. The combination of aspirin plus clopidogrel increases the risk of UGI bleeding. Unfortunately, there are no data on the effect of PPI prophylaxis in this setting. Available evidence suggests that where aspirin and/or clopidogrel are to be started or continued in patients with a recent history of UGI ulceration or bleeding (after ulcer healing and eradication of H. pylori infection), treatment with a PPI is a useful precaution. The patients should also be carefully monitored for recurrence of UGI bleeding. [ABSTRACT FROM AUTHOR]

Peripheral arterial disease (PAD) is associated with platelet hyperaggregability as well as an increase in morbidity and mortality from myocardial infarction (MI) and stroke. Purinergic signaling has been shown, both experimentally and clinically, to play an important role in the activation of platelets. Platelets express three different purinergic receptors: P2Y1, P2Y12 and P2X1. We assessed the hypothesis that the hyperaggregability associated with PAD is partly due to an increased P2 receptor expression at the transcriptional and/or translational level. Patients with PAD ( n ?=?8) and controls ( n ?=?8) were studied. Using a high-resolution channelyzer, platelet shape change (PSC) was assessed by measuring the median platelet volume (MPV). The fall in free platelet count following the addition of ADP was also assessed. Real-time PCR was used to quantify the mRNA expression and Western blots to quantify the protein expression of P2 receptors in platelets. The median (and range) fall in free platelet count after adding ADP was significantly ( P ?=?0.02) greater for patients [11% (5–24); n ?=?8] than for controls [0.5% (0–10); n ?=?8] despite using a lower concentration of ADP for the patient samples. The MPV did not differ significantly. The mRNA levels for the three P2 receptors were similar in PAD patients and controls. Western blot detected no significant differences in protein expression between these groups. Thus, platelets from PAD patients show an increased activation after stimulation with ADP (even though all patients were on aspirin). This hyperactivity was neither due to an obvious up-regulation of the mRNA levels nor to altered protein levels of P2 receptors in the platelets. It is suggested that the increased sensitivity to ADP in PAD is caused by post-receptor mechanisms. [ABSTRACT FROM AUTHOR]

Declaration of interest: The GREACE study was conducted independently; no Company or Institution has supported it financially. Some of the authors have attended conferences and participated in other trials sponsored by various pharmaceutical companies.We assessed the possible ‘synergy’ of statins and aspirin (ASA) in reducing vascular events in patients with coronary heart disease, in a post hoc analysis of the GREek Atorvastatin and Coronary-heart-disease Evaluation (GREACE) study. All patients (n?=?1600) were divided into four groups according to long-term treatment: Group A (n?=?787; statin?+?ASA), B (n?=?93; statin?-?no ASA), C (n?=?599; no statin?-?on ASA) and D (n?=?121; no statin?-?no ASA). From all patients 692 were either on a statin or ASA monotherapy (Groups B?+?C). Relative risk reductions (RRRs) in ‘all events’ (primary endpoint) between groups were assessed. During the 3-year follow-up there were 292 cardiovascular events; 92 (12% of patients) in Group A, 14 (15%) in group B, 144 in Group C (24%) and 42 events in Group D (35%). The total number of events in Group B?+?C was 158 (23%). The RRRs in the primary endpoint were: Group A versus B 24% (P?=?0.1912), A versus C 51% (P<0.0001), A versus B?+?C 49% (P<0.0001) and A versus D 71% (P<0.0001). The RRRs in Group B versus C was 36% (P?=?0.0431) and B versus D 57% (P?=?0.0012), while in C versus D 33% (P?=?0.0084). Our findings show that statins and ASA have an additive effect in reducing cardiovascular events. Aggressive statin use in the absence of ASA also substantially reduced cardiovascular events. Treatment with ASA in the absence of statin use reduced clinical events in comparison to patients not treated with either drug. [ABSTRACT FROM AUTHOR]

Peripheral arterial disease (PAD) is associated with platelet hyperactivity. Aspirin and clopidogrel, two platelet inhibitors, act by different mechanisms. Aspirin inhibits thromboxane A 2 synthesis and clopidogrel acts on the P2Y 12 platelet ADP receptor. We evaluated the effect of clopidogrel (75 mg/day), aspirin (75 mg/day) and then both drugs on several platelet function indices in patients with PAD ( n = 20). There was a significant ( P = 0.0001) decrease in ADP-induced aggregation, after clopidogrel but not after taking aspirin. Clopidogrel plus aspirin significantly decreased spontaneous platelet aggregation (SPA) ( P = 0.01 to P = 0.002) but SPA was not significantly altered by either aspirin or clopidogrel monotherapy. Similarly, monotherapy did not inhibit serotonin (5HT)-induced aggregation but there was a significant inhibition ( P = 0.03 to P <0.02) after combination therapy. ADP (0.8 μM)-induced platelet shape change (PSC) was significantly inhibited by clopidogrel ( P = 0.004) or aspirin ( P = 0.01). This was also true for 5HT-induced PSC (clopidogrel, P = 0.01; aspirin, P = 0.03). Soluble P-selectin decreased significantly (from 32 ± 24 to 25 ± 17 ng/ml, P = 0.04) with combination therapy. Plasma platelet-derived growth factor and intraplatelet 5HT levels were not altered by combination therapy. In PAD, clopidogrel is a more potent inhibitor of ADP-induced platelet activation than aspirin; combination therapy is more effective than clopidogrel or aspirin monotherapy. These potentially clinically relevant findings should be evaluated in appropriately designed trials. [ABSTRACT FROM AUTHOR]

It has been suggested that thromboelastography (TEG) can help in limiting or directing the appropriate use of blood products during surgery. However, the contribution of platelets to the TEG profile has not been studied in detail. Blood was taken from eight healthy subjects and eight patients with peripheral arterial disease (PAD). Immunomagnetic separation was achieved by the addition of Dynabeads® labeled with a CD41 murine antibody (to the GPIIb/IIIa receptor) to achieve 90-100% depletion of platelets from blood. This was then titrated with whole blood to achieve platelet counts of approximately 0, 25 and 50% of the original count to compare with whole blood using TEG. Platelet function was also assessed by spontaneous platelet aggregometry (SPA) at baseline and at the 50% dilution. SPA, maximum amplitude (MA) and K time were significantly different in PAD patients compared to controls (P < 0.05). In both controls and PAD patients there was a strong linear correlation between Log[SUB10] [platelet count] and MA (r = 0.97 for controls, r = 0.89 for PAD) and K time (r = 30.86 for controls, r = 30.68 for PAD). Correlation between Log[SUB10] [platelet count] and R time was poor in both groups. The MA and K TEG parameters may be most useful for assessing platelet transfusion requirements. [ABSTRACT FROM AUTHOR]

Two types of ADP receptors, P2Y[SUB1] and P2Y[SUB12] are involved in platelet aggregation. The P2X[SUB1] receptor is also present but its role, in terms of platelet function, is not yet defined. The aim of this study was to establish if the ADP receptors, P2Y[SUB1], P2Y[SUB12] and P2X[SUB1] play a role in controlling platelet shape change (PSC) in human platelets. PSC is an early phase of platelet activation that precedes aggregation. Using a high-resolution channelyzer, PSC was assessed by measuring the median platelet volume (MPV). The P2Y[SUB1] receptor antagonist MRS 2179 (1.06 - 10.25μmol/l) blocked ADP-induced PSC (by 100%). The median IC[SUB50] was 3.16 μmol/l. MRS 2179 also significantly (P = 0.01) inhibited PSC induced by the combination of ADP + serotonin (5HT). The P2Y[SUB12] receptor antagonist AR-C69931MX significantly inhibited (at 10s,P = 0.009; 15 s, P = 0.001 and 30 s, P = 0.015) ADP-induced PSC. The P2X[SUB1] receptor antagonist TNP-ATP had no significant effect on ADP- or ADP + 5HT-induced PSC. We conclude that the IC[SUB50] of a P2Y[SUB1] -blocker can be derived because of the high-resolution and reproducibility of the channelyzer technique. In addition to the P2Y[SUB1] purinoceptor, the P2Y[SUB12] receptor appears to be involved in ADP-induced PSC since this process was significantly inhibited by AR-C69931MX. The channelyzer technique may be more reliable than optical aggregometry to assess PSC. [ABSTRACT FROM AUTHOR]

Objectives: Urinary bladder hypertrophy and hyperplasia are common features of bladder outlet obstruction (BOO). The urinary bladder is known to synthesize endothelin-1 (ET-1), which is a potent vasoconstrictor peptide with mitogenic properties. Using an animal model of partial BOO, we investigated the potential role of ET-1 and its receptor subtypes (ET[sub A] and ET[sub B]) in bladder smooth muscle cell (SMC) proliferation. Materials and methods: Partial BOO was produced in adult male New Zealand White rabbits. After 3 weeks, the bladder was removed and SMCs from the dome and bladder neck were grown using standard explant methodology. At passage 2, the cells were made quiescent and then further incubated in foetal calf serum (FCS), control age-matched rabbit serum (CRS) or partial BOO serum (BRS) in the presence or absence of ET[sub A]-antagonist (BQ123) or ET[sub B]-antagonist (BQ788). SMC proliferation was then measured 24 h later with 5-bromo-2'deoxy-uracil and by cell counting using a haemocytometer at 48 h. Immunostaining for alpha-actin was performed on detrusor and bladder neck cells to confirm the presence of smooth muscle cells. Results: BQ123 and BQ788 did not influence detrusor or bladder neck SMC proliferation in FCS or CRS. However, in the presence of BRS, BQ123 and BQ788 (100 nmol/L) significantly (p = 0.008) inhibited detrusor and bladder neck SMC proliferation. Cell counts were significantly reduced from the detrusor (p = 0.03, p = 0.01 with BQ123 and BQ788, respectively) and bladder neck (p = 0.01 for both BQ123 and BQ78). Conclusions: These results suggest that ET antagonists may have a role in preventing SMC hyperplasia associated with partial BOO. [ABSTRACT FROM AUTHOR]

The relationship between lipids and the haemostatic mechanisms participating in the evolution of the atherosclerotic plaque have been undergoing extensive investigation for over a century. Circulating lipoproteins can enhance platelet activity. Among these lipid fractions, lipoprotein (a) (Lp(a)), a predictor of atherosclerotic disease, has been proposed as a link between lipids and haemostasis. In this review, we briefly consider lipid-platelet, and particularly Lp(a)-platelet, interactions which may be relevant to the pathogenesis of atherosclerotic disease and its complications. [ABSTRACT FROM AUTHOR]

Platelets play an important role in the process of atherothrombosis, and antiplatelet therapy is of proven efficacy in the prevention of vascular events in high-risk patients. In this review, we briefly consider the studies reporting that circulating atherogenic lipoproteins enhance platelet activity. We also evaluate the evidence showing that lipid-lowering interventions (including the use of statins) are associated with the normalisation of platelet activity. This beneficial effect should enhance the anti-atherogenic and anti-thrombotic potential of lipid-lowering interventions. [ABSTRACT FROM AUTHOR]

The article discusses a study on the achievement of fasting triglyceride (TG) target values in patients attending lipid clinic of the healthcare organization Spanish Arteriosclerosis Society. It states that an increase in the proportion of small dense low density lipoprotein (SDLDL) is another variable associated with hypertriglyceridemia. It also mentions the findings on the Spanish population who are involved in the Mediterranean diet, modern nutritional recommendation in Spain.

Non-alcoholic fatty liver disease (NAFLD) is the most common chronic liver disease and cause of elevated serum liver enzyme activities in the developed world1. Obesity, diabetes mellitus (DM), and dyslipidaemia, common components of the metabolic syndrome (MetS), are frequently associated with NAFLD; 75-100% of patients with MetS or DM have NAFLD2. NAFLD is characterized by hepatic triglyceride (TG) infiltration in the absence of alcohol abuse or chronic liver disease1. NAFLD includes a spectrum of conditions varying from steatosis to steatosis with inflammation [steatohepatitis (NASH)], necrosis, fibrosis or cirrhosis that rarely progresses to hepatocellular carcinoma3. NAFLD and NASH are the hepatic manifestations of MetS and are associated with increased cardiovascular disease (CVD) risk4. Most NAFLD/NASH patients die from CVD rather than from liver disease4,5. There is no universally accepted treatment for NAFLD1-5. [ABSTRACT FROM AUTHOR]

There is evidence that small dense low density lipoprotein (sdLDL) subfractions are more atherogenic than buoyant LDL. Therefore, it is relevant to assess the effect of lipid lowering drugs on LDL subfractions. In this editorial we discuss the effect of ezetimibe (EZE; a cholesterol transport inhibitor) alone or in combination with a statin, on sdLDL levels. We conclude that, based on currently available evidence, more studies are needed before a definitive answer can be provided regarding the effect of EZE on sdLDL levels. [ABSTRACT FROM AUTHOR]

Our main objective was to consider the substantial evidence showing that patients with familial hypercholesterolaemia (FH) have a high risk of developing non-coronary vascular disease[2]. Thus, FH patients can present to vascular specialists at a younger age, with more extensive non-coronary vascular disease and also have a worse prognosis after vascular interventions than patients without FH. [Extracted from the article]

The author reflects on the options for lowering plasma low density lipoprotein cholesterol (LDL-C) levels in patients with intolerance to statins due to myalgia but take ezetimibe. He relates the study by A. F. G. Cicero and colleagues in the October 1, 2016 issue. He discusses issues related to statin treatment adherence including the extent of the problem in statin adherence, the decision of patients to discontinue statins, and how to address them.