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The optimal management of patients with asymptomatic carotid stenosis (AsxCS) is enduringly controversial. We updated our 2021 Expert Review and Position Statement, focusing on recent advances in the diagnosis and management of patients with AsxCS. A systematic review of the literature was performed up to August 1, 2023, using PubMed/PubMed Central, EMBASE and Scopus. The following keywords were used in various combinations: "asymptomatic carotid stenosis," "carotid endarterectomy" (CEA), "carotid artery stenting" (CAS), and "transcarotid artery revascularization" (TCAR). Areas covered included (i) improvements in best medical treatment (BMT) for patients with AsxCS and declining stroke risk, (ii) technological advances in surgical/endovascular skills/techniques and outcomes, (iii) risk factors, clinical/imaging characteristics and risk prediction models for the identification of high-risk AsxCS patient subgroups, and (iv) the association between cognitive dysfunction and AsxCS. BMT is essential for all patients with AsxCS, regardless of whether they will eventually be offered CEA, CAS, or TCAR. Specific patient subgroups at high risk for stroke despite BMT should be considered for a carotid revascularization procedure. These patients include those with severe (≥80%) AsxCS, transcranial Doppler-detected microemboli, plaque echolucency on Duplex ultrasound examination, silent infarcts on brain computed tomography or magnetic resonance angiography scans, decreased cerebrovascular reserve, increased size of juxtaluminal hypoechoic area, AsxCS progression, carotid plaque ulceration, and intraplaque hemorrhage. Treatment of patients with AsxCS should be individualized, taking into consideration individual patient preferences and needs, clinical and imaging characteristics, and cultural, ethnic, and social factors. Solid evidence supporting or refuting an association between AsxCS and cognitive dysfunction is lacking. The optimal management of patients with AsxCS should include BMT for all individuals and a prophylactic carotid revascularization procedure (CEA, CAS, or TCAR) for some asymptomatic patient subgroups, additionally taking into consideration individual patient needs and preference, clinical and imaging characteristics, social and cultural factors, and the available stroke risk prediction models. Future studies should investigate the association between AsxCS with cognitive function and the role of carotid revascularization procedures in the progression or reversal of cognitive dysfunction. [ABSTRACT FROM AUTHOR]

Background: The optimal antithrombotic (antiplatelet or anticoagulant) treatment of patients undergoing extracranial carotid artery interventions is a subject of debate. The aim of this multidisciplinary document was to critically review the recommendations of current guidelines, taking into consideration the results of recendy published studies. Methods:The various antithrombotic strategies reported were evaluated for asymptomatic and symptomatic patients undergoing extracranial carotid artery interventions (endarterectomy, transfemoral carotid artery stenting [CAS] or transcarotid artery revascularization [TCAR]). Based on a critical review, a series of recommendations were formulated by an international expert panel. Results: For asymptomatic patients, we recommend low-dose aspirin (75-100 ing/day) or dopidogrel (75 mg/day) with the primary goal to reduce the risk of myocardial infarction and cardiovascular event rates rather than to reduce the risk of stroke. For symptomatic patients, we recommend dual antiplatelet treatment (DAFT) initiated within 24 h of the index event to reduce the risk of recurrent events. We suggest that following transfemoral CAS or TCAR, patients continue DAFT for 1 month after which a single antiplatelet agent is used. High level of evidence to support anticoagulant treatment for patients with carotid artery disease is lacking. Condusions: The antithrombotic treatment offered to carotid patients should be individualized, taking into account the presence of symptoms, the type of intervention and the goal of the treatment. The duration and type of DAFr (ticagrelor instead of dopidogrel) should be evaluated in future trials. [ABSTRACT FROM AUTHOR]

Proteins play a crucial role in metabolism, in maintaining fluid and acid-base balance and antibody synthesis. Dietary proteins are important nutrients and are classified into: 1) animal proteins (meat, fish, poultry, eggs and dairy), and, 2) plant proteins (legumes, nuts and soy). Dietary modification is one of the most important lifestyle changes that has been shown to significantly decrease the risk of cardiovascular (CV) disease (CVD) by attenuating related risk factors. The CVD burden is reduced by optimum diet through replacement of unprocessed meat with low saturated fat, animal proteins and plant proteins. In view of the available evidence, it has become acceptable to emphasize the role of optimum nutrition to maintain arterial and CV health. Such healthy diets are thought to increase satiety, facilitate weight loss, and improve CV risk. Different studies have compared the benefits of omnivorous and vegetarian diets. Animal protein related risk has been suggested to be greater with red or processed meat over and above poultry, fish and nuts, which carry a lower risk for CVD. In contrast, others have shown no association of red meat intake with CVD. The aim of this expert opinion recommendation was to elucidate the different impact of animal vs vegetable protein on modifying cardiometabolic risk factors. Many observational and interventional studies confirmed that increasing protein intake, especially plant-based proteins and certain animal-based proteins (poultry, fish, unprocessed red meat low in saturated fats and low-fat dairy products) have a positive effect in modifying cardiometabolic risk factors. Red meat intake correlates with increased CVD risk, mainly because of its non-protein ingredients (saturated fats). However, the way red meat is cooked and preserved matters. Thus, it is recommended to substitute red meat with poultry or fish in order to lower CVD risk. Specific amino acids have favourable results in modifying major risk factors for CVD, such as hypertension. Apart from meat, other animal-source proteins, like those found in dairy products (especially whey protein) are inversely correlated to hypertension, obesity and insulin resistance. [ABSTRACT FROM AUTHOR]

We evaluated the association of egg consumption with liver tests (LTs) and non-alcoholic fatty liver disease (NAFLD). This relationship is poorly documented. The National Health and Nutrition Examination Survey (NHANES, 2005–2010) database was used. Analysis of covariance, adjusted linear and logistic regression models were used. Of the 14,369 participants, 46.8% were men and 45.2% had NAFLD. After correction for several variables including: age, gender, race, education, poverty to income ratio, alcohol intake, energy intake, smoking, and physical activity - fatty liver index (FLI), serum aspartate aminotransferase (AST) alanine aminotransferase (ALT) were 36.9, 25.8 (U/L) and 23.9 (U/L), respectively, in the first tertile (T1) reaching 68.7, 34.9 and 36.5, respectively, in the third tertile (T3) (p < 0.001 for all comparisons). In the model with same covariates, there was significant positive linear relationship between FLI (standard β coefficient (β): 0.196), AST (β: 0.099) and ALT (β: 0.112) with egg consumption and participants in the highest tertile (T3) of egg consumption had 11% higher chance of NAFLD compared with T1 (odds ratio: 1.11 and 95% confidence interval: 1.07–1.17). Of note, after more correction for triglycerides, hypertension and diabetes, the significant link between egg consumption and LTs and/or NAFLD attenuated and disappeared. Our findings highlight the adverse role of egg consumption on LTs and likelihood of NAFLD. These associations seem to be attributable to cardio-metabolic risk factors. These findings require confirmation to improve our understanding of the role of egg consumption in the pathogenesis of NAFLD. • The association of egg consumption with non-alcoholic fatty liver disease (NAFLD) was evaluated. • After adjustment, participants in the third tertile (T3) of egg consumption had 11% higher chance of NAFLD compared with T1. • After further correction, the significant link between egg consumption and NAFLD attenuated and disappeared. [ABSTRACT FROM AUTHOR]

Associations between dietary fats and mortality are unclear. We evaluated the relationship between quartiles of total fat, mono-unsaturated (MUFA), polyunsaturated (PUFA) and saturated fatty acid (SFA) consumption, and all-cause, coronary heart disease (CHD), stroke, and type 2 diabetes (T2D)-associated mortality in 24,144 participants from the National Health and Nutrition Examination Surveys (NHANES) 1999–2010. We added our results to a meta-analysis based on searches until November 2018. In fully adjusted Cox-proportional hazard models in our prospective study, there was an inverse association between total fat (HR: 0.90, 95% confidence interval 0.82, 0.99, Q4 vs Q1) and PUFA (0.81, 0.78–0.84) consumption and all-cause mortality, whereas SFA were associated with the increased mortality (1.08, 1.04–1.11). In the meta-analysis of 29 prospective cohorts (n = 1,164,029) we found a significant inverse association between total fat (0.89, 0.82–0.97), MUFA (0.94, 0.89–0.99) and PUFA (0.89, 0.84–0.94) consumption and all-cause mortality. No association was observed between total fat and CVD (0.93, 0.80–1.08) or CHD mortality (1.03 0.99–1.09). A significant association between SFA intake and CHD mortality (1.10, 1.01–1.21) was observed. Neither MUFA nor PUFA were associated with CVD or CHD mortality. Inverse associations were observed between MUFA (0.80, 0.67–0.96) and PUFA (0.84, 0.80–0.90) intakes and stroke mortality. We showed differential associations of total fat, MUFA and PUFA with all-cause mortality, but not CVD or CHD mortalities. SFA was associated with higher all-cause mortality in NHANES and with CHD mortality in our meta-analysis. The type of fat intake appears to be associated with important health outcomes. [ABSTRACT FROM AUTHOR]

Conventional observational studies have suggested that 25-hydroxyvitamin D (25(OH)D) is inversely associated with telomere shortening. We aimed to apply two-sample Mendelian randomization (MR) to assess the causal association between serum 25(OH) D and telomere length (TL). MR was implemented by using summary-level data from the largest genome-wide association studies (GWAS) on vitamin D (n = 73 699) and TL (n = 37 684). Inverse variance weighted method (IVW) was used to estimate the causal estimates. Weighted median (WM)-based method, and MR-Egger, leave-one-out were applied as sensitivity analysis. The results of MR demonstrated no effect of 25(OH)D on TL (IVW = β:-0.104, p = 0.219, WM = β:-0.109, p = 0.188; MR Egger = β:-0.127, p = 0.506). None of the 25(OH)D-related single nucleotide polymorphisms (SNPs) were significantly associated with TL. Heterogeneity tests did not detect heterogeneity. Furthermore, MR pleiotropy residual sum and outlier (MR-PRESSO) did not highlight any outliers (p = 0.424). Results of leave-one-out method demonstrated that the links are not driven because of the single SNPs. Our study does not support any causal effect of 25(OH) D on TL. [ABSTRACT FROM AUTHOR]

Despite the publication of various national/international guidelines, several questions concerning the management of patients with asymptomatic (AsxCS) and symptomatic (SxCS) carotid stenosis remain unanswered. The aim of this international, multi-specialty, expert-based Delphi Consensus document was to address these issues to help clinicians make decisions when guidelines are unclear. Fourteen controversial topics were identified. A three-round Delphi Consensus process was performed including 61 experts. The aim of Round 1 was to investigate the differing views and opinions regarding these unresolved topics. In Round 2, clarifications were asked from each participant. In Round 3, the questionnaire was resent to all participants for their final vote. Consensus was reached when ≥75% of experts agreed on a specific response. Most experts agreed that: (1) the current periprocedural/in-hospital stroke/death thresholds for performing a carotid intervention should be lowered from 6% to 4% in patients with SxCS and from 3% to 2% in patients with AsxCS; (2) the time threshold for a patient being considered "recently symptomatic" should be reduced from the current definition of "6 months" to 3 months or less; (3) 80% to 99% AsxCS carries a higher risk of stroke compared with 60% to 79% AsxCS; (4) factors beyond the grade of stenosis and symptoms should be added to the indications for revascularization in AsxCS patients (eg, plaque features of vulnerability and silent infarctions on brain computed tomography scans); and (5) shunting should be used selectively, rather than always or never. Consensus could not be reached on the remaining topics due to conflicting, inadequate, or controversial evidence. The present international, multi-specialty expert-based Delphi Consensus document attempted to provide responses to several unanswered/unresolved issues. However, consensus could not be achieved on some topics, highlighting areas requiring future research. [ABSTRACT FROM AUTHOR]

Sodium-glucose co-transporter-2 inhibitors (SGLT2i) are oral antidiabetic agents that exert their glucose-lowering effect by increasing renal excretion of glucose. These drugs have been reported to beneficially affect cardiovascular (CV) and renal outcomes. However, concerns have recently been raised in relation to increased risk of lower-extremities amputation with canagliflozin and it remains unclear whether and to what extent this side effect could also occur with other SGLT2i. The present expert panel overview focuses on the three SGLT2i available and widely used in the US and Europe, i.e. empagliflozin, canagliflozin and dapagliflozin and only refers briefly to other SGLT2i for which less data are available. The results of large CV outcome trials with these SGLT2i are presented, focusing specifically on the data in relation to amputation risk. The potential pathophysiological mechanisms involved in this side effect are discussed. Furthermore, available data reporting amputation cases in SGLT2i users are critically reviewed. The expert panel concludes that, based on current data, increased amputation risk seems to be related only to canagliflozin, thus representing a drug-effect rather than a SGLT2i class-effect. The exact pathways underlying this drug-induced adverse event, possibly related to off-target drug effects rather than SGLT2 inhibition per se, should be elucidated in future studies. Continuous monitoring and pharmacovigilance is necessary and head to head trials would also be essential to provide definitive conclusions. [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]

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]

Background Statins are well-established low-density lipoprotein cholesterol–lowering drugs. Elevated apolipoprotein CIII (Apo CIII) levels are associated with elevated triglyceride-rich particles, which are also considered to be a possible risk factor for cardiovascular disease. Objective The aim of this meta-analysis of randomized placebo-controlled clinical trials was to assess the effect of statins on Apo CIII concentrations. Methods Randomized placebo-controlled trials investigating the impact of statin treatment on cholesterol lowering that include lipoprotein measurement were searched in PubMed, MEDLINE, Scopus, Web of Science, and Google Scholar databases (up to July 31, 2017). 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 Apo CIII concentrations. Results This meta-analysis of data from 6 randomized placebo-controlled clinical trials (10 statin arms) involving 802 subjects showed that statin therapy significantly decreased circulating Apo CIII concentrations (weighted mean difference [WMD]: −2.71, 95% confidence interval [CI]: −3.74 to –1.68, P < .001; I 2 : 73.83%). The effect size was robust in the leave-one-out sensitivity analysis and not driven by any single study. Subgroup analysis showed a reduction of Apo CIII concentrations by atorvastatin (WMD: –4.74, 95% CI: –3.74 to –1.68, P = .002; I 2 : 84.02%), rosuvastatin (WMD: –2.68, 95% CI: –4.52 to –0.84, P = .004; I 2 : 0%), and lovastatin (WMD: –1.64, 95% CI: –2.22 to –1.07, P < .001; I 2 : 0%). Conclusion This meta-analysis suggests that statin treatment significantly reduces plasma Apo CIII levels. [ABSTRACT FROM AUTHOR]

Background: Statins are the most common used lipid lowering drugs but they may cause adverse effects and despite their well-established therapeutic benefits residual cardiovascular (CV) risk remains. The use of other lipid lowering drugs and nutraceuticals alone or as add-on lipid-modifying therapy can be an option in such cases. Several studies have reported health-related properties of the Citrus fruits, among which bergamot (Citrus bergamia Risso) differs from others by particularly high content of certain compounds.Purpose: This narrative review summarizes the current evidence on the effects of bergamot on lipid parameters based on studies involving animals and humans.Main Evidence: This natural supplement may lead to effective lipid-lowering treatment. Its lipid-lowering activity is attributed to different flavonoids. However, the exact mechanisms involved remain unclear.Conclusion: It is expected that ongoing and future studies will confirm the benefit of bergamot in dyslipidemic and other cardiometabolic disorders, potentially leading to reduced overall CV risk. [ABSTRACT FROM AUTHOR]

Background Previous studies have suggested that for clinical purposes, subjects with fasting triglycerides (TGs) between 89–180 mg/dl (1–2 mmol/l) would benefit from postprandial TGs testing. Objective To determine the postprandial TG response in 2 independent studies and validate who should benefit diagnostically from an oral-fat tolerance test (OFTT) in clinical practice. Methods A population of 1002 patients with coronary heart disease (CHD) from the CORDIOPREV clinical trial and 1115 white US subjects from the GOLDN study underwent OFTTs. Subjects were classified into 3 groups according to fasting cut points of TGs to predict the usefulness of OFTT: (1) TG < 89 mg/dl (<1 mmol/l); (2) TG, 89–180 mg/dl (1–2 mmol/l); and (3) TG > 180 mg/dl (>2 mmol/l). Postprandial TG concentration at any point > 220 mg/dl (>2.5 mmol/l) has been pre-established as an undesirable postprandial response. Results Of the total, 49% patients with CHD and 42% from the general population showed an undesirable response after the OFTT. The prevalence of undesirable postprandial TG in the CORDIOPREV clinical trial was 12.8, 50.3, and 89.7%, in group 1, 2, and 3, respectively ( P < .001) and 11.2, 58.1, and 97.5% in group 1, 2, and 3, respectively ( P < .001) in the GOLDN study. Conclusions These two studies validate the predictive values reported in a previous consensus. Moreover, the findings of the CORDIOPREV and GOLDN studies show that an OFTT is useful to identify postprandial hyperlipidemia in subjects with fasting TG between 1–2 mmol/l (89–180 mg/dL), because approximately half of them have hidden postprandial hyperlipidemia, which may influence treatment. An OFTT does not provide additional information regarding postprandial hyperlipidemia in subjects with low TG (<1 mmol/l, <89 mg/dL) or increased TG (>2 mmol/l, >180 mg/dl). [ABSTRACT FROM AUTHOR]

Non-alcoholic fatty liver (NAFLD) is the most common liver disease worldwide, progressing from simple steatosis to necroinflammation and fibrosis (leading to non-alcoholic steatohepatitis, NASH), and in some cases to cirrhosis and hepatocellular carcinoma. Inflammation, oxidative stress and insulin resistance are involved in NAFLD development and progression. NAFLD has been associated with several cardiovascular (CV) risk factors including obesity, dyslipidemia, hyperglycemia, hypertension and smoking. NAFLD is also characterized by atherogenic dyslipidemia, postprandial lipemia and high-density lipoprotein (HDL) dysfunction. Most importantly, NAFLD patients have an increased risk for both liver and CV disease (CVD) morbidity and mortality. In this narrative review, the associations between NAFLD, dyslipidemia and vascular disease in NAFLD patients are discussed. NAFLD treatment is also reviewed with a focus on lipid-lowering drugs. Finally, future perspectives in terms of both NAFLD diagnostic biomarkers and therapeutic targets are considered. [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]

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]

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]

Statins are a class of cholesterol-lowering drugs that inhibit 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase. Anti-inflammatory and antioxidant properties, as well as improvement of endothelial function and plaque stabilization have also been proposed as parts of the pleiotropic effects of statins. Specialized pro-resolving mediators (SPMs) are endogenous lipid-derived molecules originating from ω-6 and ω-3 polyunsaturated fatty acids, such as arachidonic, docosahexaenoic and eicosapentaenoic acid that trigger and modulate the resolution of inflammation. Impaired SPM biosynthesis can lead to excessive or chronic inflammation and is implicated in the pathogenesis of several diseases. Exogenous administration of SPMs, including lipoxin, maresin, protectin, have been shown to improve both bacterial and viral infections, mainly in preclinical models, thus minimizing inflammation. Statin-triggered-SPM production in several in vitro and in vivo models may represent another anti-inflammatory pathway involving these drugs. This commentary discusses scientific publications on the effects of statins on SPMs and the resolution of inflammation process. Statins can promote SPMs generation and thus subsequently enhance the resolution of inflammation in certain diseases, such as cardiovascular disease, sepsis, rheumatoid arthritis, bacterial and viral infections [Display omitted] [ABSTRACT FROM AUTHOR]

Purpose Epilepsy is associated with increased cardiovascular disease (CVD) morbidity and mortality. The exact causes of this link are not clearly defined. The role of antiepileptic drugs (AEDs) in influencing CVD risk in patients with epilepsy remains controversial. A link between epilepsy, AEDs and cardiac arrhythmias has been proposed and may be responsible for sudden unexpected death in epilepsy (SUDEP). Methods We searched MEDLINE up to December 1, 2013 for relevant publications using combinations of keywords. We also examined the reference list of articles identified by this search and selected those we judged relevant. These were included in this narrative review. Results AEDs may exert both beneficial and adverse cardiovascular effects. This narrative review considers the influence of AEDs on some predictors of vascular risk [i.e. weight, insulin resistance, metabolic syndrome, lipids, lipoprotein (a), C-reactive protein, homocysteine, vitamins, coagulation factors, uric acid, carotid intima media thickness, markers of oxidative status and matrix metalloproteinase-9]. Certain AEDs can also have pro-arrhythmic properties. Conclusions AEDs may exert different effects on various established and emerging predictors of vascular risk. Furthermore, pharmacokinetic interactions between AEDs and drugs used to reduce vascular risk (e.g. statins) need to be better documented. Whether this knowledge, in terms of individualizing antiepileptic and CVD prevention treatment, will prove to be relevant in clinical practice remains to be established. [ABSTRACT FROM AUTHOR]

Abstract: Antihypertensive agents may, even within the same class, exert variable effects on arterial stiffness variables. Nebivolol could have a better impact than atenolol on arterial stiffness, by increasing the bioavailability of endothelium-derived nitric oxide. Angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs) increase plasma renin activity (enhancing the production of angiotensin II via non-ACE-related pathways) whereas aliskiren does not, potentially affecting central hemodynamics differently. We compared the effects of two renin-angiotensin-aldosterone system (RAAS) inhibitors (quinapril and aliskiren) and 2 beta-blockers (atenolol and nebivolol) on arterial stiffness variables. Treatment-naïve patients (n = 72; 68.1% males; age, 47.6 ± 10.6 years) with uncomplicated stage I-II essential hypertension were randomly assigned to quinapril, aliskiren, atenolol, or nebivolol for 10 weeks. Central systolic and diastolic blood pressure (BP), central pulse pressure (PP), augmentation index (AIx), and pulse wave velocity (PWV) were measured at baseline, 2, and 10 weeks. The same measurements were performed in 20 normotensive subjects (65.0% males; age, 40.0 ± 8.9 years). Peripheral and central systolic and diastolic BP, peripheral PP, and PWV were significantly and similarly reduced by all agents. However, PWV continued to decline between the second and last visit in patients on quinapril and aliskiren but did not change in those on nebivolol or atenolol. Central PP and AIx decreased in patients on quinapril, aliskiren, and nebivolol but did not change in those taking atenolol. The decrease in central PP and AIx did not differ between patients on quinapril, aliskiren, and nebivolol. Despite similar reductions in peripheral BP, atenolol is less effective than nebivolol and RAAS inhibitors in improving central pulsatile hemodynamics. Aliskiren exerts similar effects on markers of arterial stiffness as quinapril. The clinical relevance of these differences remains to be established. [Copyright &y& Elsevier]

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]

Abstract: Objective: Metabolic syndrome (MetS) and Cushing''s syndrome share common features. It has been proposed that increased glucocorticoid activity at peripheral tissues may play a role in the pathogenesis of MetS and obesity-related disorders. It is well-known that intracellular cortisol concentrations are determined not only by plasma levels but also by the activity of 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) which catalyzes the conversion of inactive cortisone to active cortisol, especially in the liver and adipose tissue. Another isoenzyme exists, the 11β-hydroxysteroid dehydrogenase type 2, which acts in the opposite direction inactivating cortisol to cortisone in the kidney. This review considers the significance of the 11β-HSD1 inhibition in the treatment of several features of MetS and provides current data about the development of 11β-HSD1 inhibitors, as new agents for this purpose. Materials/Methods: Using PubMed, we searched for publications during the last 20years regarding the development of 11β-HSD1 inhibitors. Results: Emerging data from animal and human studies indicate an association of 11β-HSD1 over-expression with obesity and disorders in glucose and lipid metabolism. This has led to the hypothesis that selective inhibition of 11β-HSD1 could be used to treat MetS and diabetes. Indeed, natural products and older agents such as thiazolidinediones and fibrates seem to exert an inhibitory effect on 11β-HSD1, ameliorating the cardiometabolic profile. In view of this concept, novel compounds, such as adamantyltriazoles, arylsulfonamidothiazoles, anilinothiazolones, BVT2733, INCB-13739, MK-0916 and MK-0736, are currently under investigation and the preliminary findings from both experimental and human studies show a favourable effect on glucose and lipid metabolism, weight reduction and adipokine levels. Conclusions: Many compounds inhibiting 11β-ΗSD1 are under development and preliminary data about their impact on glucose metabolism and obesity-related disorders are encouraging. [Copyright &y& Elsevier]