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Despite the publication of several national/international guidelines, the optimal management of patients with asymptomatic carotid stenosis (AsxCS) remains controversial. This article compares 3 recently released guidelines (the 2020 German–Austrian, the 2021 European Stroke Organization [ESO], and the 2021 Society for Vascular Surgery [SVS] guidelines) vs the 2017 European Society for Vascular Surgery (ESVS) guidelines regarding the optimal management of AsxCS patients. The 2017 ESVS guidelines defined specific imaging/clinical parameters that may identify patient subgroups at high future stroke risk and recommended that carotid endarterectomy (CEA) should or carotid artery stenting (CAS) may be considered for these individuals. The 2020 German–Austrian guidelines provided similar recommendations with the 2017 ESVS Guidelines. The 2021 ESO Guidelines also recommended CEA for AsxCS patients at high risk for stroke on best medical treatment (BMT), but recommended against routine use of CAS in these patients. Finally, the SVS guidelines provided a strong recommendation for CEA+BMT vs BMT alone for low-surgical risk patients with >70% AsxCS. Thus, the ESVS, German–Austrian, and ESO guidelines concurred that all AsxCS patients should receive risk factor modification and BMT, but CEA should or CAS may also be considered for certain AsxCS patient subgroups at high risk for future ipsilateral ischemic stroke. [ABSTRACT FROM AUTHOR]

Introduction: The reported relationship between coffee intake and renal function is poorly understood. By applying two-sample Mendelian randomization (MR) and systematic review and meta-analysis we investigated the association of caffeine and coffee intake with prevalent CKD and markers of renal function.Material and methods: For the individual data analysis we analyzed the National Health and Nutrition Examination Surveys (NHANES) data on renal function markers and caffeine intake. MR was implemented by using summary-level data from the largest ever genome-wide association studies (GWAS) conducted on coffee intake (N = 91,462) and kidney function (N = 133,413). The inverse variance weighted method (IVW), weighted median-based method, MR-Egger, MR-RAPS, and MR-PRESSO were applied. Random effects models and generic inverse variance methods were used to synthesize quantitative and pooled data for the meta-analysis, followed by a leave-one-out method for sensitivity analysis.Results: Finally, we included the data of 18,436 participants; 6.9% had prevalent CKD (based on eGFR). Caffeine intake for the general population was 131.1 ±1.1 mg. The percentage of participants with CKD, by caffeine quartile, was 16.6% in the first (lowest) quartile, 13.9% in the second, 12.2% in the third and 11.0% in the top quartile (p < 0.001). After adjustment, for increasing quartiles for caffeine consumption, mean urine albumin, albumin-creatinine ratio and estimated glomerular filtration rate (GFR) did not change significantly (p > 0.234). In fully adjusted logistic regression models, there was no significant difference in chances of CKD prevalence (p-trend = 0.745). In the same line, the results of MR showed no impact of coffee intake on CKD (IVW: β = -0.0191, SE = 0.069, p = 0.781) or on eGFR (overall = IVW: β = -0.0005, SE = 0.005, p = 0.926) either in diabetic (IVW: β = -0.006, SE = 0.009, p = 0.478) or non-diabetic patients (IVW: β = -6.772, SE = 0.006, p = 0.991). Results from the meta-analysis indicated that coffee consumption was not significantly associated with CKD (OR = 0.85, 95% CI: 0.71-1.02, p = 0.090, n = 6 studies, I2 = 0.32). These findings were robust in sensitivity analyses.Conclusions: Implementing different strategies, we detected no significant association between coffee consumption and renal function or risk of CKD. [ABSTRACT FROM AUTHOR]

Current guidelines state that systemic inflammation, together with endothelial dysfunction, calcification, and hypercoagulability, predispose to premature atherosclerosis in patients with inflammatory bowel disease (IBD). We assessed whether IBD can affect aortic stiffness, a well-recognized vascular biomarker and an independent risk factor for cardiovascular (CV) disease (CVD) in several populations. Recent studies reported that aortic stiffness is increased in adults with IBD compared with matched controls. This association is dependent on inflammatory burden and disease duration, and is reduced by antitumor necrosis factor therapy. Considered together, current findings suggest that increased aortic stiffness is an extraintestinal manifestation of IBD. This is clinically relevant since measuring aortic stiffness in patients with IBD could improve risk assessment, especially in those without established CVD. Moreover, effective control of inflammation could lower CV risk in patients with IBD by reducing aortic stiffness. Further longitudinal studies are needed to better clarify (i) the relationship between disease duration and irreversible changes of the arterial wall, (ii) the clinical characteristics of patients with IBD that have an increased arterial stiffness at least in part reversible, and (iii) whether arterial stiffness is useful to evaluate the efficacy of immunosuppressive therapy. [ABSTRACT FROM AUTHOR]

Abstract Background The health outcomes associated with extremely low or high plasma concentrations of high-density lipoprotein cholesterol (HDL-C) are not well documented mainly because of the small numbers of participants with such values included in the clinical trials. Objective We prospectively investigated the association between extremely low and high HDL-C with: 1) the risk of overall, coronary heart disease (CHD), cerebrovascular and cancer mortality, and, 2) their link with inflammatory factors. Methods Analysis was based on subjects ≥18 years old from the National Health and Nutrition Examination Surveys (NHANES). We categorized HDL-C levels as follows: [low HDL-C group ≤30 (extremely low), 30–40 (low), and ≥40 (reference)] [high HDL-C group = 40–80 (reference), 80–100 (high) and ≥100 mg/dl (extremely high). Cox proportional hazard regression models and analysis of covariance accounted for survey design, masked variance and sample weights. Results After adjustment for age, race and sex, we found that the very low HDL-C category (<30 mg/dl) had a greater risk of total mortality (risk ratio [RR]: 3.00, 95%CI: 2.20–4.09). RR for CHD and stroke mortality was 2.00 and 2.53, respectively; there was no link between cancer and level of HDL-C (p = 0.235). The association between total mortality, CHD and stroke with the level of HDL-C attenuated but remained significant even after adjustment for demographics, dietary, cardiovascular risk factors and treatment for dyslipidemia (all p < 0.001). After adjustments, subjects with extremely high HDL-C levels had a higher risk of mortalities (all p < 0.001). Mexican-American ethnicity, subjects in the low level of HDL-C (30–40 mg/dl) category had higher risk of mortalities than those with a very low level (all p < 0.001). Concentration of C-reactive protein, fibrinogen and white blood count significantly decreased as the level of the HDL-C increased; these findings were robust after adjustment for demographics, dietary, cardiovascular risk factors and treatment for dyslipidemia (all p < 0.001); further subjects with extremely high HDL-C levels have a greater levels of inflammatory factors (all p < 0.001). Conclusions Both extremely low and high HDL-C levels were associated with greater risk of mortalities (total, CHD and stroke) and higher level of inflammatory factors, while there was no link between level of HDL-C and risk of cancer. Moreover, we found evidence of an HDL-C paradox in Mexican-American ethnicity participants. Highlights • After adjustment we found that the very low HDL-C category (<30 30 mg/dl) had three times greater risk of total mortality. • RR for CHD and stroke mortality was 2.00 and 2.53, respectively; there was no link between cancer and level of HDL-C. • After adjustments, subjects with extremely high HDL-C levels had a higher risk of mortalities (all p < 0.001). • Concentration of CRP, fibrinogen and white blood count significantly decreased as the level of the HDL-C increased. [ABSTRACT FROM AUTHOR]

Lipid-lowering therapies, particularly non-statin regimens, are underutilized as ~2/3 of patients with atherosclerotic cardiovascular (CV) disease (CVD) are not optimally managed, and do not attain target low-density lipoprotein cholesterol (LDL-C) concentrations, despite statin treatment. Statins have been the mainstay of hypolipidemic therapies; however, they are plagued by adverse effects, which have partly hindered their more widespread use. Ezetimibe is often the first added mode of treatment to attain LDL-C goals as it is efficacious and also allows the use of a smaller dose of statin, while the need for more expensive therapies is obviated. We herein provide a comprehensive review of the effects of ezetimibe in lipid lowering and reducing CV events and improving outcomes. Of the hypolipidemic therapies, oral ezetimibe, in contrast to newer agents, is the most convenient and/or affordable regimen to be utilized as mono- or combined therapy supported by data from CV outcomes studies attesting to its efficacy in reducing CVD risk and events. When combined with a statin, the statin dose could be lower, thus curtailing side-effects, while the hypolipidemic effect is enhanced (by ~20%) as the percentage of patients with target level LDL-C (<70 mg/dL) is higher with combined treatment versus a high-intensity statin. Ezetimibe could also serve as an alternative treatment in cases of statin intolerance. In conclusion, ezetimibe has an excellent safety/tolerability profile; it is the first added treatment to a statin that can attain LDL-C targets. In the combined therapy, the hypolipidemic effect is enhanced while the dose of statin could be lower, thus limiting the occurrence of side-effects. Ezetimibe could also serve as an alternative mode of treatment in cases of statin intolerance. [ABSTRACT FROM AUTHOR]

The article offers perspectives on pericoronary adipose tissue (PCAT) in atherosclerosis. It provides an overview of two research studies on the expression of mircoRNAs within PCAT close to coronary atherosclerotic lesions and plaque-free segments and the expression of microRNAs in PCAT of coronary artery disease (CAD) patients undergoing coronary artery bypass surgery (CABG). It suggests the potential use of PCAT attenuation to reclassify cardiovascular risk and diagnose atherosclerosis.

Objective: To explore the association between dietary acid load, potential renal acid load (PRAL) and net endogenous acid production (NEAP), and peripheral arterial disease (PAD) in a national representative sample of American adults.Methods: The National Health and Nutrition Examination Survey (NHANES) database (for 1999-2002) was used. PAD was diagnosed by ankle brachial index assessment. Analysis of covariance was used to examine adjusted mean of different dietary acid load by PAD status; multivariable logistic regression was used to relate dietary acid load with prevalent PAD. Sample weighting was accounted for in all analyses.Results: Of the 4864 eligible participants aged 40-85, 2482 (51.0%) were men, and 269 (5.5%) had PAD. After adjustment for age-, sex-, race-, estimated glomerular filtration rate (eGFR), smoking, dietary fat, carbohydrates, protein, saturated fat, and dietary fiber, and energy intake, body mass index, hypertension, cholesterol, triglyceride and diabetes, estimated glomerular filtration rate, participants with PAD had higher mean of (PRAL: 16.2 vs 9.1mEq/d, NEAP: 56.2 vs 50.1mEq/d, both p<0.001) than PAD-free participants. In logistic regression with same cofounders, the top quarter of PRAL (more acidic) was associated with 31% higher odds of the PAD compared with the bottom quarter (more alkaline) [odds ratio: 1.31, 95% confidence interval: 1.11-1.57].Conclusion: Our findings, for the first time, suggest that dietary acids load, an index of acid-base balance, is associated with the likelihood of PAD after adjustment for main clinical and anthropometrical confounding factors. These results support the hypothesis that diet plays an important role in chronic disease occurrence. [ABSTRACT FROM AUTHOR]

Carotid artery stenting (CAS) is increasingly offered to patients with carotid artery stenosis. Although CAS is a less invasive (and thus more attractive) alternative compared with carotid endarterectomy, it requires the use of contrast material. A possible side effect from the use of contrast material during CAS is the development of contrast-induced acute kidney injury (CI-AKI). This review discusses the incidence/prevalence and clinical significance of CI-AKI developing after CAS. We also discuss possible measures to reduce the incidence of CI-AKI after CAS. [ABSTRACT FROM AUTHOR]

The importance of metabolic syndrome (MetS) lies in its associated risk of cardiovascular disease and type 2 diabetes, as well as other harmful conditions such as nonalcoholic fatty liver disease. In this report, the available scientific evidence on the associations between lifestyle changes and MetS and its components is reviewed to derive recommendations for MetS prevention and management. Weight loss through an energy-restricted diet together with increased energy expenditure through physical activity contribute to the prevention and treatment of MetS. A Mediterranean-type diet, with or without energy restriction, is an effective treatment component. This dietary pattern should be built upon an increased intake of unsaturated fat, primarily from olive oil, and emphasize the consumption of legumes, cereals (whole grains), fruits, vegetables, nuts, fish, and low-fat dairy products, as well as moderate consumption of alcohol. Other dietary patterns (Dietary Approaches to Stop Hypertension, new Nordic, and vegetarian diets) have also been proposed as alternatives for preventing MetS. Quitting smoking and reducing intake of sugar-sweetened beverages and meat and meat products are mandatory. Nevertheless, there are inconsistencies and gaps in the evidence, and additional research is needed to define the most appropriate therapies for MetS. In conclusion, a healthy lifestyle is critical to prevent or delay the onset of MetS in susceptible individuals and to prevent cardiovascular disease and type 2 diabetes in those with existing MetS. The recommendations provided in this article should help patients and clinicians understand and implement the most effective approaches for lifestyle change to prevent MetS and improve cardiometabolic health. [ABSTRACT FROM AUTHOR]

Higher C-reactive protein (CRP) and lower albumin levels are indicators of inflammation and are associated with inflammatory disease (Balta et al., 2014; Sheikh et al., 2015). An independent indicator of erectile dysfunction is C-reactive protein/albumin ratio. The CRP-albumin ratio (CAR) may be a widely accessible, easily obtained and reproducible biomarker of inflammation for vascular diseases and related diseases such as ED. [Extracted from the article]

Implementation of best medical treatment (BMT) is the cornerstone of the management of patients with either asymptomatic or symptomatic carotid artery stenosis. We review the literature to define the components of BMT. Smoking cessation, maintaining a healthy body weight, moderate exercise, and a Mediterranean diet are essential lifestyle measures. Moderate alcohol consumption may also be beneficial but recommending it to patients may be hazardous if they consume too much. The importance of lifestyle measures is largely underestimated by both physicians and patients. Blood pressure and diabetes control, antiplatelet agents, and lipid-lowering treatment with statins/ezetimibe comprise the pharmacological components of BMT. Initiation of an intensive regimen of BMT is a sine qua non for patients with carotid artery stenosis whether or not they are offered or undergo an invasive revascularization procedure. [ABSTRACT FROM AUTHOR]

After 25 years of evaluating bilirubin as a possible protective agent in neonatal and cardiovascular disease, interest has moved on to a exploring a possible protective role in diabetes mellitus (DM). This review finds conflicting prospective data for a protective relationship though there are retrospective, case-controlled data, that can only show association, which is not causality. Only prospective studies can show causality. Also, it would appear that the underlying biochemical assumptions do not readily translate from the animal to the human setting. Given that many factors impact on circulating bilirubin levels, it is not surprising that a clear-cut answer is not available; the jury is still out. Any relationship between DM and bilirubin might relate to intermediates in bilirubin metabolism, including relationships involving the genes for the enzymes participating in those steps. Nevertheless, the pursuit of bilirubin in disease causation is opening new avenues for research and if it is established that serum bilirubin can predict risks, much will have been achieved. The answer may have to come from molecular genetic analyses. [ABSTRACT FROM AUTHOR]

Statins might exert diabetogenic effects, potentially increasing insulin resistance and worsening glucose control. However, patients with diabetes mellitus are at high or very high cardiovascular risk and, thus, statin use is strongly recommended. Adding ezetimibe to statins might be helpful in achieving lipid targets and reducing cardiovascular risk without adversely affecting glucose metabolism. [ABSTRACT FROM AUTHOR]

The authors discusses perivascular adipose tissue and its pathophysiological links with atherosclerosis, thrombosis and inflammation. Topics include a study which assessed the gene expression of inflammatory markers and adipokines in the neck adipose tissue (NAT) of patients with carotid stenosis (CS) undergoing endarterectomy and the evaluation of pericarotid adipose tissue (PCAT) and subcutaneous adipose tissue (SAT).

Endothelial dysfunction is considered as an early change in atherogenesis. Raised levels of systemic inflammatory markers are associated with cardiovascular disease (CVD). Endocan (previously known as endothelial cell specific molecule-1, ESM-1), is a potential immunoinflammatory marker that may be linked to CVD. Endocan is released by vascular endothelial cells in several organs. Endocan may play an important role in regulating cell adhesion and raised plasma levels may reflect endothelial dysfunction. Endocan levels are elevated in conditions such as chronic kidney disease, renal transplant rejection, tumor progression and hypertension. Endocan is a potential inflammatory and CVD marker. Further studies are needed to assess the relevance of endocan in clinical practice. [ABSTRACT FROM AUTHOR]

An editorial is presented the multispecialty consensus statement from the European Society of Cardiology on the diagnosis and management of carotid artery stenosis, addressing key issues such as individualized management for asymptomatic patients, tailored approaches for symptomatic patients with carotid-related strokes, and variations in procedural outcomes and patient adherence across different clinical settings.

ETC-1002 is a new investigational low density lipoprotein cholesterol (LDL-C)-lowering agent (Esperion Therapeutics, Inc.). ETC-1002 is a dicarboxylic acid derivative with a novel mechanism of action targeting two hepatic enzymes – adenosine triphosphate-citrate lyase (ACL) and adenosine monophosphate-activated protein kinase (AMPK), inhibiting sterol and fatty acid synthesis and promoting mitochondrial long-chain fatty acid oxidation. This agent is currently in phase II clinical research. Available data report that ETC-1002 significantly decreased LDL-C levels (up to 32%) in both patients with normal and elevated baseline levels of triglycerides. Such beneficial effect is superior to currently approved non-statin lipid lowering agents. The levels of apolipoprotein B (apoB) and non-high density lipoprotein cholesterol (non-HDL-C) were also reduced with beneficial effect on other cardiometabolic factors such as inflammatory markers, blood pressure and body weight. Although, the safety and tolerability of ETC-1002 needs to be confirmed in ongoing and future, larger studies, this agent has, so far, been generally safe and well tolerated. This novel, oral, once-daily, small molecule may lead to effective LDL-C lowering treatment in hypercholesterolaemic subjects who are statin intolerant or as add-on therapy in those who are unable to reach the LDL-C goals despite being on statin therapy. This agent might not only exert lipid-lowering related benefits, but also favourable cardiometabolic effects. [ABSTRACT FROM AUTHOR]

Endothelial dysfunction is regarded as the initial lesion in the development of atherosclerosis. Endocan, previously called endothelial cell–specific molecule 1 (ESM-1), is a new candidate immunoinflammatory marker that may be associated with cardiometabolic risk factors. Therefore, we assessed serum levels of endocan in newly diagnosed patients with untreated essential hypertension (HT). A total of 18 patients with HT and 23 normotensive control participants were included in the study. Serum endocan levels, carotid intima–media thickness (cIMT), and high-sensitivity C-reactive protein (hsCRP) were measured. Serum endocan levels were significantly higher in the HT group (P < .001). In patients with HT, serum endocan levels correlated positively with cIMT and hsCRP (r = .551, P < .001 and r = .644, P < .001, respectively). Our findings suggest that circulating endocan levels represent a new marker in patients with essential HT. Endocan may be a surrogate endothelial dysfunction marker and may have a functional role in endothelium-dependent pathological disorders. [ABSTRACT FROM PUBLISHER]

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]

Background: We assessed the influence of atorvastatin on selected indicators of an inflammatory condition, left ventricular function, hospitalizations and mortality in patients with dilated cardiomyopathy (DCM). Methods: We included 68 DCM patients with left ventricular ejection fraction (LVEF) ⩽40% treated optimally in a prospective, randomized study. They were observed for 5 years. Patients were divided into two groups: patients who were commenced on atorvastatin 40 mg daily for two months followed by an individually matched dose of 10 or 20 mg/day (group A), and patients who were treated according to current recommendations without statin therapy (group B). Results: After 5-year follow-up we assessed 45 patients of mean age 59 ± 11 years - 22 patients in group A (77% male) and 23 patients in group B (82% male). Interleukin-6, tumor necrosis factor alpha, and uric acid concentrations were significantly lower in the statin group than in group B (14.96 ± 4.76 vs. 19.02 ± 3.94 pg/ml, p = 0.012; 19.10 ± 6.39 vs. 27.53 ± 7.39 pg/ml, p = 0.001, and 5.28 ± 0.48 vs. 6.53 ± 0.46 mg/dl, p = 0.001, respectively). In patients on statin therapy a reduction of N-terminal pro-brain natriuretic peptide concentration (from 1425.28 ± 1264.48 to 1098.01 ± 1483.86 pg/ml, p = 0.045), decrease in left ventricular diastolic (from 7.15 ± 0.90 to 6.67 ± 0.88 cm, p = 0.001) and systolic diameters (from 5.87 ± 0.92 to 5.17 ± 0.97, p = 0.001) in comparison to initial values were observed. We also showed the significant increase of LVEF in patients after statin therapy (from 32.0 ± 6.4 to 38.8 ± 8.8%, p = 0.016). Based on a comparison of curves using the log-rank test, the probability of survival to 5 years was significantly higher in patients receiving statins (p = 0.005). Conclusions: Atorvastatin in a small dose significantly reduce levels of inflammatory cytokines and uric acid, improve hemodynamic parameters and improve 5-year survival in patients with DCM. [ABSTRACT FROM AUTHOR]

Abstract: The metabolic syndrome (MetS) is a cluster of risk factors including insulin resistance, dyslipidemia and hypertension which are also relevant for the development of chronic kidney disease (CKD). It has proven difficult to elucidate whether the renal dysfunction in MetS is due to the MetS itself or the individual risk factors. For example, obesity – which is also part of the MetS – may enhance the risk of renal dysfunction development probably through mechanisms associated with renal hyperfiltration, hyperperfusion and focal glomerulosclerosis. Insulin resistance also promotes kidney disease by worsening renal hemodynamics. In patients with MetS, tubular atrophy, interstitial fibrosis, and arteriolar sclerosis indicating the presence of vascular damage, have also been described. As yet, there has been little evidence that preventing or treating symptoms of the MetS protects patients from renal impairment. [Copyright &y& Elsevier]

Like the earlier multicenter General Anesthesia (GA) versus Local Anaesthesia (LA) for carotid surgery (GALA) trial, a recent independent study showed no difference in transient ischemic attack, stroke, myocardial infarction, and death rates between carotid endarterectomy (CEA) performed under LA compared with GA. Besides these outcomes, however, several additional issues may be of interest when comparing the 2 modalities. Examples include the occurrence of post-CEA patient delirium, cognitive dysfunction, and health-related quality of life, as well as the cost-effectiveness, length of hospitalization, and resource utilization. This commentary discusses and compares these outcomes of CEA performed under LA versus GA. [ABSTRACT FROM AUTHOR]

Abstract: High density lipoprotein (HDL) has many properties, which contribute to its atheroprotective role. However, some recent clinical trials have identified subjects with the progression of atherosclerosis despite normal levels of HDL cholesterol. This raises the question if all subfractions of HDL have the same properties. Moreover, recent investigations have shown that both acute and chronic inflammation may lead to structural and functional changes of HDL, which render the particles proinflammatory. Although therapeutic agents that increase HDL levels are now quite well established it is not clear whether they influence HDL quality. We review the current state of knowledge on the properties of HDL and factors/therapeutic agents which may restrain the transformation of normal HDL into dysfunctional HDL. [Copyright &y& Elsevier]

Abstract: Maintenance of normal potassium (K+) homeostasis has become an increasingly important limiting factor in the therapy of heart failure (HF). With the application of loop diuretics and digoxin, hypokalemia has become a frequent and feared side effect of treatment. Low serum K+ in HF may be also a marker of increased neurohormonal activity and disease progression. To gain the maximum benefit from treatment, we need to individualize drug use and carefully monitor electrolytes. Symptomatic HF patients (New York Heart Association class III–IV) should be prescribed the lowest dose of diuretic necessary to maintain euvolemia. Mild hypokalemia may be corrected by the use of aldosterone receptor antagonists such as spironolactone or eplerenone. However, a more severe hypokalemia should preferably be corrected using K+ supplement. Serum K levels should be frequently checked and maintained between 4.0 and 5.5mEq/l (mmol/l). [Copyright &y& Elsevier]

The article discusses the role of antiplatelet agents, statins, anticoagulants, and other agents in maintaining vascular access patency rates (arteriovenous [AV] fistula or AV graft) in vascular access dysfunction patients. Several studies including the Dialysis Outcomes and Practice Patterns Study (DOPPS) are mentioned. It is concluded that while agents, statins, and other drugs improved vascular access patency rates, the role of combined or newer antiplatelet therapies need to be evaluated.

A letter to the editor is presented in response to the article "Endovascular Versus Open Repair of Abdominal Aortic Aneurysm," by the United Kingdom Endovascular Aneurysm Repair (EVAR) Trial investigators in the May 2010 issue.

Abstract: Takotsubo cardiomyopathy is defined as acute chest pain during stressful incidents which is associated with ST-segment abnormalities and/or increased serum troponin levels. There is also regressive systolic dysfunction which is usually localized in the apical and medial left ventricles but there are no significant coronary artery lesions. The ventricular asynergy is also described in the right ventricle but is less common. Almost all the patients are women. The onset of this disease is typically triggered by an acute emotional or stress event or by an accumulation of trivial and repetitive stresses. The etiology of this syndrome remains unclear. Myocardial ischemia and reperfusion due to microvascular spasm, aborted myocardial infarction and related no-reflow phenomenon have been proposed as inducers of Takotsubo cardiomyopathy. The temporal relationship between the stressful event and the triggering of the clinical syndrome as well as the report of elevated catecholamine plasma levels during the acute phase suggest a possible involvement of the sympathetic nervous system. A smaller left ventricular size and hormonal disturbances in women may also play a role. [Copyright &y& Elsevier]

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]

The article discusses issues to be addressed to improve outcomes for patients with carotid stenosis. It informs that multi-disciplinary approach required to improve outcomes for patients with carotid stenosis included some removal of overreliance on biased randomized trial data, improved standards of research reporting and building quality assurance into practice and use of the savings to fund vital research.

The General Anesthesia vs. Local Anesthesia for Carotid Surgery (GALA) trial did not show a difference in 30-day postoperative stroke, myocardial infarction and death rates between patients undergoing carotid endarterectomy (CEA) under local vs. general anesthesia. The present article discusses some limitations of the GALA trial. Firstly, the expected stroke and death rates following CEA is so low, that it was unlikely that the GALA trial would show any significant difference between local and general anesthesia. Secondly, preoperative statin use was not recorded. Thirdly, intraoperative shunt usage rates (a possible parameter for the development of stroke) varied considerably between the 2 groups (43% vs. 14%, for general vs. local anesthesia, respectively; P < .0001), as well as between UK and non-UK surgeons who always (73.6% vs. 20.8%, respectively; P < .0001), never (4.2% vs. 26%, respectively; P < .0002), or selectively (22.2% vs. 53.2%, respectively; P < .0001) used a shunt. Furthermore, no information was provided regarding the type of shunts used; for example, a traumatic shunts may be associated with lower perioperative stroke rates. These limitations could influence the interpretation of the results of the GALA trial. Due to lack of differences between the 2 groups and the presence of the above limitations, it seems likely that this trial will have little effect on clinical practice. [ABSTRACT FROM AUTHOR]

Fifty-eight healthy progeny (mean age ± SD 13.9 ± 7.9 years) of 39 families with a positive history for Cardiovascular Diseases ([CVD] n = 44) or hyperlipidemia (n = 14) were included in the study and were compared with 30 age-matched control participants, with a negative family history, to evaluate lipid profile, ceruloplasmin (Cp), and lipid peroxidation product (malondialdehyde [MDA]) levels, as well as in vitro copper-induced Low-density lipoprotein (LDL) oxidizability. Mean serum levels of total cholesterol, LDL cholesterol (LDL-C), apolipoprotein B-100, and MDA of the participants were significantly higher than those of the controls. Lag time, an LDL resistance oxidation marker, was lower in the study group and negatively correlated with LDL-C (r = -.437, P < .05) and Cp (r = -.272, P < .05) serum levels. In conclusion, progeny with a positive family history for CVD or hyperlipidemia have an atherogenic lipid profile and increased LDL susceptibility to oxidation. High Cp levels seem to be related to lower resistance of LDL to oxidation. [ABSTRACT FROM AUTHOR]

Abstract: We investigated the possible role of reactive oxygen species (ROS) on renal function in experimental diabetes. Materials and Methods: Seven groups of male rats were studied. Group I consisted of control animals. Diabetes was induced (by streptozotocin) in the animals in the other groups and they received either insulin or vitamin E (300 or 600 mg/kg), both insulin and vitamin E, or no treatment for 4 weeks. At the end of the study, blood pressure was measured and parameters of kidney function and oxidative stress were evaluated in serum and kidney tissue samples. Results: Diabetic animals had higher blood pressures; increased serum glucose, urea, creatinine, cyclic guanosine monophosphate (cGMP); increased kidney tissue levels of malondialdehyde and inducible nitric oxide synthetase (iNOS); and reduced serum glutathione peroxidase when compared with control animals. Blood glucose levels in diabetic animals were controlled by insulin and not by any dose of vitamin E alone. However, all other measured parameters improved towards control levels with either insulin or vitamin E in either dose. An additive beneficial effect was observed on the levels of iNOS and cGMP when both forms of treatment were used in diabetic animals. Conclusions: We conclude that ROS may play an important role in diabetes-induced nephropathy in this rat model. Vitamin E supplementation in addition to insulin can have additive protective effects against deterioration of renal function in this model. [Copyright &y& Elsevier]

Atrial fibrillation (AF) is a complex condition with several possible contributing factors. The rapid and irregular heartbeat produced by AF increases the risk of blood clot formation inside the heart. These clots may eventually become dislodged, causing embolism, stroke and other disorders. AF occurs in up to 15% of patients with hyperthyroidism compared to 4% of people in the general population and is more common in men and in patients with triiodothyronine (T3) toxicosis. The incidence of AF increases with advancing age. Also, subclinical hyperthyroidism is a risk factor associated with a 3-fold increase in development of AF. Thyrotoxicosis exerts marked influences on electrical impulse generation (chronotropic effect) and conduction (dromotropic effect). Several potential mechanisms could be invoked for the effect of thyroid hormones on AF risk, including elevation of left atrial pressure secondary to increased left ventricular mass and impaired ventricular relaxation, ischemia resulting from increased resting heart rate, and increased atrial eopic activity. Reentry has been postulated as one of the main mechanisms leading to AF. AF is more likely if effective refractory periods are short and conduction is slow. Hyperthyroidism is associated with shortening of action potential duration which may also contribute to AF. [ABSTRACT FROM AUTHOR]

Retrospective studies show that statin use prevents congestive heart failure and decreases mortality in patients with congestive heart failure; however, only one prospective study is available. In the Controlled Rosuvastatin Multinational Trial in Heart Failure study, rosuvastatin (10 mg/d) was compared with placebo in patients with advanced coronary heart disease-related congestive heart failure. There was no significant difference between rosuvastatin and placebo except for hospitalization rates. Statins must be given to all patients with coronary heart disease as early as possible because they may not work in patients with advanced congestive heart failure. [ABSTRACT FROM AUTHOR]

We assessed lipid goal achievement in patients at high risk for vascular events from a general practice (London, United Kingdom). Patients were identified as those with a prescription for hypolipidaemic medication, a significant (>20%) Framingham risk, and from the myocardial infarction register. Two hundred forty- five patients were currently taking a statin (average dose, 23.1 mg/day). Cholesterol, high-density lipoprotein-cholesterol, low-density lipoprotein-cholesterol, and triglycerides changed significantly following statin treatment. Of 285 patients who had taken statins at some time point, 11(3.9%) were intolerant, 5 of which subsequently tolerated another statin. Approximately 10.1% of patients discontinued statin treatment for unclear reasons. Only 64 patients (29.1% of 220) reached the Joint British Societies’ Guidelines on Prevention of Cardiovascular Disease target of a total cholesterol of <4.0 mmol/L; 50 patients (38.8% of 129) reached the low-density lipoprotein-cholesterol target of <2.0 mmol/L. This value of low-density lipoprotein-cholesterol is similar to that recommended by the American Heart Association/American College of Cardiology. With regard to the General Medical Services guidelines target for total cholesterol, 162 (73.6% of 220) patients reached ⩽5.0 mmol/L. The group that best achieved target cholesterol (Joint British Societies' Guidelines and General Medical Services) were those with comorbidities. In conclusion, while reaching General Medical Services targets was satisfactory, the percentage of patients reaching Joint British Societies' Guidelines targets was not. This discrepancy may reflect the presence of multiple guidelines. The current stricter lipid targets are difficult to achieve; possible methods that may be used to improve lipids further could involve using combination therapy, statin dose titration, and better education. [ABSTRACT FROM AUTHOR]

Platelet activation contributes to graft occlusion after bypass surgery. This study investigated platelet activation status before, during, and after bypass. Blood was taken preoperatively from patients undergoing femoro-popliteal bypass and at incision, after dissection, after ischemia, after reperfusion, 24 hours after surgery, and almost 2 years after bypass (and given aspirin or warfarin). Platelet aggregation was measured using a turbidimetric method and platelet activation with flow cytometry. Statistical analysis was performed using Mann-Whitney U and Wilcoxon's tests. Resting platelet activation was similar between controls and patients undergoing bypass. Platelet activation decreased at incision but remained highly reactive. Platelet aggregation increased after dissection and the ischemic phase but significantly decreased after reperfusion. Platelet aggregation and activation were increased at 24 hours and subsequently after bypass. Platelets in critical limb ischemia exist in the primed state and become activated by minimum stimuli. Increased platelet activation occurs after bypass grafting for critical limb ischemia despite adjunctive therapy. [ABSTRACT FROM AUTHOR]

The aim of this article is to investigate the association between internal carotid artery occlusion (ICAO) and the presence of atherosclerotic disease and vascular risk factors. The clinical characteristics and risk factors of 120 patients presenting with ICAO were retrospectively reviewed. All patients (n = 120) had at least 1 of the 4 vascular risk factor (diabetes, smoking, hypercholesterolemia, and hypertension); 2, 3, or all 4 risk factors were present in 14 to 82 of the patients (11.7% to 68.3%), 10 to 39 of the patients (8.3% to 325%), and 9 of the patients (7.5%), respectively. A total of 84 patients (70%) with ICAO had disease in at least 1 additional vascular bed (aorta, coronary or lower limb arteries). In addition to ICAO, vascular disease was present in 2 and all 3 of these arterial beds in 42 (35%) and 9 (7.5%) patients, respectively. Furthermore, stenosis or occlusion of the ipsilateral or contralateral vertebral arteries was recorded in 19 of 120 patients (15.8%). Regarding the contralateral carotid artery, 1 patient had bilateral ICAO. One patient had contralateral common carotid artery occlusion, and 1 patient was excluded from the analysis because of surgery to the contralateral carotid artery, Of the remaining 117 patients, 34 (29.0%) had less than 50% contralateral carotid artery stenosis. Thirty-two patients (27.4%) had 50% to 69%, and 51(43.6%) had 70% to 99% stenosis. Ultrasonographic imaging of the carotid plaque of the contralateral carotid artery revealed that 52 of the 120 arteries (43.3%) were uniformly or predominantly echolucent (types I and II, respectively), Fifty-nine (49.2%) were predominantly or uniformly echogenic (types III and IV), and 9 (7.5%) could not be classified. A similar distribution of echomorphology was observed on the occluded side. ICAO is associated with widespread atherosclerotic disease and a high prevalence of vascular risk factors, Detection of ICAO should prompt the investigation of other arterial beds and treatment of risk factors. [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]

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]

Renal disease is often associated with an increased risk of vascular events. Moreover, an accelerated form of atherosclerosis commonly occurs in these patients. The reasons for these associations are not clearly defined but include the widespread presence of several established risk factors (eg, dyslipidemia, hypertension, and diabetes). Other predictors of atherosclerotic disease may also be abnormally elevated (eg, homocysteine, fibrinogen, and lipoprotein a). In addition, there is evidence that impaired renal function per se predicts vascular risk. Despite this high-risk background, the potential benefit of treatment with statins has not been widely investigated in these patients. The present review considers the evidence (experimental and clinical) that statins exert beneficial effects in patients with different types of renal disease. This includes improved renal function, decreased microalbuminuria, and a fall in blood pressure. Statins may also improve renal allograft survival. The potential mechanisms mediating these effects are considered. The interactions between statins and several risk factors that may be present in patients with impaired renal function are also considered. There is an urgent need to define the role of statins in these high-risk patients. Which is the statin of choice? This question is relevant because impaired renal function can interfere with statin pharmacokinetics. Furthermore, other drugs administered to these patients may cause serious interactions with statins. [ABSTRACT FROM AUTHOR]

Epidemiological evidence and clinical trials with fibrate therapy show a clear relationship between low levels of high-density lipoprotein cholesterol (HDL-C) and cardiovascular risk. In addition to lowering plasma levels of low-density lipoprotein cholesterol (LDL-C) and triglycerides (TG), the hydroxy-methylglutaryl-coenzyme A reductase inhibitors (statins), also raise the levels of HDL-C. This review summarizes the results of five randomized, multicenter studies in hypercholesterolaemic patients in which multiple doses of atorvastatin and simvastatin were compared for their effects on lipids and lipoproteins including HDL-C. Both statins reduced LDL cholesterol and achieved parallel decreases in TG, with atorvastatin showing a slight overall superiority in these studies. Both HDL-C and apolipoprotein (Apo) A-I, its associated apoprotein, were significantly and consistently increased by all doses of simvastatin. However, atorvastatin had a different dose–response effect from simvastatin on both lipid parameters. Whereas HDL-C and Apo A-I were elevated by low doses of atorvastatin, the effect diminished markedly with increasing dose suggesting a possible negative dose–response effect. At higher doses, simvastatin increased HDL-C and Apo A-I significantly more than atorvastatin. These data indicate that statins may not be identical in all their clinical properties relevant to reducing the risks of atherosclerosis. [Copyright &y& Elsevier]

Peripheral vascular disease (PVD) is a common condition often associated with cardiovascular risk factors and events. With the aid of B-mode ultrasound scanning, evidence is emerging that these risk factors and events are significantly related to an increased carotid and femoral intima-media thickness (IMT). More importantly, treatment of these risk factors is associated with a decrease or a diminished progression of the IMT, paralleled by a reduction in cardiovascular events and an improvement in the symptoms associated with PVD. This evidence is particularly strong for lipid lowering therapy. Additional predictors of cardiovascular risk like the IMT, could now influence the decision to intervene with medication. [Copyright &y& Elsevier]

Current guidelines do not recommend screening for asymptomatic carotid artery stenosis (AsxCS). The rationale behind this recommendation is that detection of AsxCS may lead to an unnecessary carotid intervention. In contrast, screening for abdominal aortic aneurysms is strongly recommended. A critical analysis of the literature was performed to evaluate the implications of detecting AsxCS. Patients with AsxCS are at high risk for future stroke, myocardial infarction and vascular death. Population-wide screening for AsxCS should not be recommended. Additionally, screening of high-risk individuals for AsxCS with the purpose of identifying candidates for a carotid intervention is inappropriate. Instead, selective screening for AsxCS should be considered and should be viewed as an opportunity to identify individuals at high risk for atherosclerotic cardiovascular disease and future cardiovascular events for the timely initiation of intensive medical therapy and risk factor modification. Although mass screening should not be recommended, there are several arguments suggesting that selective screening for AsxCS should be considered. The rationale supporting such selective screening is to optimize risk factor control and to initiate intensive medical therapy for prevention of future cardiovascular events, rather than to identify candidates for an intervention. • Patients with asymptomatic carotid stenosis are at high risk of future stroke, myocardial infarction and vascular death. • Selective screening for asymptomatic carotid stenosis should be considered to reduce cardiovascular events. • Early identification of patients with asymptomatic carotid stenosis would enable timely initiation of preventive measures. [ABSTRACT FROM AUTHOR]