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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]

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.

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]

Background: The anti-DFS70 autoantibodies are one of the most commonly and widely described agent of unknown clinical significance, frequently detected in healthy individuals. It is not known whether the DFS70 autoantibodies are protective or pathogenic. One of the factors suspected of inducing the formation of anti-DFS70 antibodies is increased oxidative stress. We evaluated the coexistence of anti-DFS70 antibodies with selected markers of oxidative stress and investigated whether these antibodies could be considered as indirect markers of oxidative stress. Methods: The intensity of oxidative stress was measured in all samples via indices of free-radical damage to lipids and proteins such as total oxidant status (TOS), concentrations of lipid hydroperoxides (LPH), lipofuscin (LPS), and malondialdehyde (MDA). The parameters of the non-enzymatic antioxidant system, such as total antioxidant status (TAS) and uric acid concentration (UA), were also measured, as well as the activity of superoxide dismutase (SOD). Based on TOS and TAS values, the oxidative stress index (OSI) was calculated. All samples were also tested with indirect immunofluorescence assay (IFA) and 357 samples were selected for direct monospecific anti DFS70 enzyme-linked immunosorbent assay (ELISA) testing. Results: The anti-DFS70 antibodies were confirmed by ELISA test in 21.29% of samples. Compared with anti-DFS70 negative samples we observed 23% lower concentration of LPH (P =.038) and 11% lower concentration of UA (P =.005). TOS was 20% lower (P =.014). The activity of SOD was up to 5% higher (P =.037). The Pearson correlation showed weak negative correlation for LPH, UA, and TOS and a weak positive correlation for SOD activity. Conclusion: In samples positive for the anti-DFS70 antibody a decreased level of oxidative stress was observed, especially in the case of samples with a high antibody titer. Anti-DFS70 antibodies can be considered as an indirect marker of reduced oxidative stress or a marker indicating the recent intensification of antioxidant processes. [ABSTRACT FROM AUTHOR]

The obesity pandemic is accompanied by increased risk of developing metabolic syndrome (MetS) and related conditions: non-alcoholic fatty liver disease (NAFLD)/non-alcoholic steatohepatitis (NASH), type 2 diabetes mellitus (T2DM) and cardiovascular (CV) disease (CVD). Lifestyle, as well as an imbalance of energy intake/expenditure, genetic predisposition, and epigenetics could lead to a dysmetabolic milieu, which is the cornerstone for the development of cardiometabolic complications. Glucagon-like peptide-1 (GLP-1) receptor agonists (RAs) and dual glucose-dependent insulinotropic polypeptide (GIP)/GLP-1 RAs promote positive effects on most components of the " cardiometabolic continuum " and consequently help reduce the need for polypharmacy. In this review, we highlight the main pathophysiological mechanisms and risk factors (RFs), that could be controlled by GLP-1 and dual GIP/GLP-1 RAs independently or through synergism or differences in their mode of action. We also address the evidence on the use of GLP-1 and dual GIP/GLP-1 RAs in the treatment of obesity, MetS and its related conditions (prediabetes, T2DM and NAFLD/NASH). In conclusion, GLP-1 RAs have already been established for the treatment of T2DM, obesity and cardioprotection in T2DM patients, while dual GIP/GLP-1 RAs appear to have the potential to possibly surpass them for the same indications. However, their use in the prevention of T2DM and the treatment of complex cardiometabolic metabolic diseases, such as NAFLD/NASH or other metabolic disorders, would benefit from more evidence and a thorough clinical patient-centered approach. There is a need to identify those patients in whom the metabolic component predominates, and whether the benefits outweigh any potential harm. [ABSTRACT FROM AUTHOR]

Diabetes mellitus (DM) is a chronic and complex metabolic disorder and also an important cause of cardiovascular (CV) disease (CVD). Patients with type 2 DM (T2DM) and obesity show a greater propensity for visceral fat deposition (and excessive fat deposits elsewhere) and the link between adiposity and CVD risk is greater for visceral than for subcutaneous (SC) adipose tissue (AT). There is growing evidence that epicardial AT (EAT) and pericardial AT (PAT) play a role in the development of DM-related atherosclerosis, atrial fibrillation (AF), myocardial dysfunction, and heart failure (HF). In this review, we will highlight the importance of PAT and EAT in patients with DM. We also consider therapeutic interventions that could have a beneficial effect in terms of reducing the amount of AT and thus CV risk. EAT is biologically active and a likely determinant of CV morbidity and mortality in patients with DM, given its anatomical characteristics and proinflammatory secretory pattern. Consequently, modification of EAT/PAT may become a therapeutic target to reduce the CV burden. In patients with DM, a low calorie diet, exercise, antidiabetics and statins may change the quantity of EAT, PAT or both, alter the secretory pattern of EAT, improve the metabolic profile, and reduce inflammation. However, well-designed studies are needed to clearly define CV benefits and a therapeutic approach to EAT/PAT in patients with DM. [ABSTRACT FROM AUTHOR]

Aim: We evaluated the lipid-lowering (LL) effect of proprotein convertase subtilisin/kexin type 9 inhibitors (PCSK9i) in patients with heterozygous familial hypercholesterolemia (HeFH) treated with LL-drugs and lipoprotein apheresis (LA). Patients and Methods: The PCSK9i treatment (evolocumab 420 mg/4 weeks, alirocumab 150 mg/2 weeks, or alirocumab 75 mg/2 weeks: 9, 6, and 2 patients, respectively) was initiated in patients with HeFH (n = 17; aged 35-69 years, 10 men, previously treated with statins + ezetimibe ± colesevelam and LA sessions for 2-12 years). A lipid profile was obtained before and immediately after the LA session and before, 1 and 2 months after switching to PCSK9i treatment. The duration of PCSK9i therapy ranged from 3 to 18 months. Results: Median total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), highdensity lipoprotein cholesterol (HDL-C), and triglycerides (TG) levels before LA were 268, 198, 46, and 126 mg/dL, respectively, and decreased (at the end of the LA session) to 117, 50, 40, and 51 mg/dL, respectively (P < .001 for TC and P = .001 for all other comparisons). The median time-averaged LDL-C levels following LA were 155 (121, 176; median [25th, 75th percentile]) mg/dL. Median TC, LDL-C, and TG levels before PCSK9i therapy were 269, 190, and 127 mg/dL and decreased to 152, 100, and 95 mg/dL, respectively (P = .002, P < .002, and P < .03, respectively). Steady LDL-C levels with PCSK9i treatment were significantly lower compared with time-averaged LDL-C levels following LA (median value: 100 vs 155 mg/dL; P = .008). With PCSK9i, from 13 patients with CHD, 6 (46.1%) patients achieved LDL-C <70 mg/dL, and 2 patients (15.4%) achieved LDL-C <100 mg/dL. Lipoprotein apheresis was discontinued in all patients except for 2 who continued once monthly. Conclusions: PCSK9i can reduce LDL-C more consistently over time compared with a transient decrease following LA in HeFH patients. PCSK9i therapy may reduce the frequency of LA. Larger trials are required to establish the clinical implications of PCSK9i in patients previously on LA. [ABSTRACT FROM AUTHOR]

Diabetes mellitus (DM) is also a cause of cardiovascular (CV) disease (CVD). Addressing the atherosclerotic CVD (ASCVD) burden in DM should reduce premature death and improve quality of life. Diabetes mellitus--associated ASCVD can lead to complications in all vascular beds (carotids as well as coronary, lower extremity, and renal arteries). This narrative review considers the diagnosis and pharmacological treatment of noncardiac atherosclerotic vascular disease (mainly in patients with DM). Based on current knowledge and the fact that modern DM treatment guidelines are based on CV outcome trials, it should be noted that patients with noncardiac CVD may not have the same benefits from certain drugs compared with patients who predominantly have cardiac complications. This leads to the conclusion that in the future, consideration should be given to conducting well-designed trials that will answer which pharmacological treatment modalities will be of greatest benefit to patients with noncardiac ASCVD. [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]

Cardiovascular disease (CVD) remains the major cause of death and disability worldwide, and residual risk after implementing all current therapies is still high. In this context, the latest (2016) European Cardiology Society/European Atherosclerosis Society guidelines recommend that triglyceride (TG)-lowering drugs should be used in high-risk patients with TGs levels >2.3 mmol/L (200 mg/dL), after lifestyle measures fail to lower them. After several neutral CVD outcome trials with n-3 fatty acids, the Reduction of Cardiovascular Events with EPA–Intervention Trial met its primary end point, that is, among patients with elevated TGs levels despite the use of statins, the risk of ischemic events, including cardiovascular death, was significantly lower in those who received 4 g of icosapent ethyl daily. In this review, we comment on the findings of previous and recently published randomized controlled CVD outcome trials assessing n-3 fatty acids supplementation. Both efficacy and safety, as well as future perspectives, are discussed. [ABSTRACT FROM AUTHOR]

An introduction is presented in which the editor discusses various reports within the issue on topics including abdominal aortic aneurysm, cardiovascular diseases, and mortality.

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.

Evidence suggests that there is platelet activation in obstructive sleep apnea syndrome (OSAS) and chronic obstructive pulmonary disease (COPD). Our objective is to evaluate mean platelet volume (MPV) and platelet distribution width (PDW) in patients with overlap syndrome (OS), that is, concurrent COPD with OSAS. Mean platelet volume and PDW were assessed in consecutive patients who had undergone polysomnography and pulmonary function testing. They were divided into the following groups: controls (apnea–hypopnea index [AHI] <5/hour, and forced expiratory volume in 1st second [FEV1]/forced vital capacity [FVC] >70%), OSAS group (AHI ≥5/hour and FEV1/FVC >70%), and OS group (AHI ≥5/hour and FEV1/FVC <70%). A total of 485 patients (360 males and 125 females) were included. Mean platelet volume in controls was lower compared with the other groups: 10 ± 0.9 fL for controls versus 10.3 ± 1.2 fL for OSAS (P = .006), versus 10.7 ± 1 fL for OS (P < .001). Additionally, MPV was higher in OS group than OSAS: 10.7 ± 1 fL versus 10.3 ± 1.2 fL, respectively (P = .002). Platelet distribution width was lower in controls compared with the other groups: 12.9 ± 2 fL for controls versus 13.6 ± 1.9 fL for OSAS (P = .007), versus 13.8 ± 2.3 fL for OS (P = .008), while there was no difference between OS and OSAS groups. Mean platelet volume and PDW are increased in patients with OS compared with healthy controls, with respiratory function being the major contributor in platelet activation in this series. [ABSTRACT FROM AUTHOR]

The identification/selection of appropriate patient subgroups with asymptomatic carotid artery stenosis and the performance of prophylactic carotid endarterectomy (CEA)/carotid artery stenting (CAS) exclusively on these asymptomatic patient subgroups is currently one of the "hottest" topics in vascular surgery. It is now clear that offering CEA/CAS to asymptomatic carotid patients based only on the degree of carotid stenosis is unjustified and scientifically flawed. On the other hand, offering only best medical therapy to every asymptomatic patient, irrespective of certain high-risk criteria (such as the detection of microemboli by transcranial Doppler, intraplaque hemorrhage, silent embolic infarcts on brain computed tomography/magnetic resonance imaging, elevated biomarkers, family history), is equally wrong. The validation of specific measures to identify those asymptomatic patients at high risk for developing symptoms is crucial to achieve optimal use of carotid interventions and avoid wasting stroke prevention resources. [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 no-reflow (NR) phenomenon represents an acute reduction in coronary blood flow without coronary vessel obstruction, coronary vessel dissection, spasm, or thrombosis. No reflow is an important complication among patients with acute ST-segment elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention (pPCI). The complete blood count (CBC) is one of the most frequently ordered laboratory tests in clinical practice. Various studies have evaluated the performance of CBC parameters to predict disease severity and mortality risk. Automated cell counters are routinely available in many clinical laboratories and can be used to determine red blood cell distrubiton width (RDW), platetecrit, platelet count, and and some ratios like the neutrophil-lymphocyte ratio and RDW-platelet ratio. These hematological markers have been reported to be independent predictors of impaired angiographic reperfusion and long-term mortality among patients with STEMI undergoing pPCI. In this context, we reviewed the role of admission CBC parameters for the prediction of NR in patients with STEMI undergoing pPCI. [ABSTRACT FROM AUTHOR]

Circulating markers relevant to the development of abdominal aortic aneurysm (AAA) are currently required. Lipoprotein(a), Lp(a), is considered a candidate marker associated with the presence of AAA. The present meta-analysis aimed to evaluate the association between circulating Lp(a) levels and the presence of AAA. The PubMed-based search was conducted up to April 30, 2015, to identify the studies focusing on Lp(a) levels in patients with AAA and controls. Quantitative data synthesis was performed using a random effects model, with standardized mean difference (SMD) and 95% confidence interval (CI) as summary statistics. Overall, 9 studies were identified. After a combined analysis, patients with AAA were found to have a significantly higher level of Lp(a) compared to the controls (SMD: 0.87, 95% CI: 0.41-1.33, P < .001). This result remained robust in the sensitivity analysis, and its significance was not influenced after omitting each of the included studies from the meta-analysis. The present meta-analysis confirmed a higher level of circulating Lp(a) in patients with AAA compared to controls. High Lp(a) levels can be associated with the presence of AAA, and Lp(a) may be a marker in screening for AAA. Further studies are needed to establish the clinical utility of measuring Lp(a) in the prevention and management of AAA. [ABSTRACT FROM AUTHOR]

An introduction is presented in which the author discuss issue on topics including role of perirenal fat as an emerging cardiovascular risk factor, the risk of coronary heart disease, and absence of alcohol abuse or other chronic liver diseases.

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).

Systemic lupus erythematosus (SLE) is a chronic autoimmune disease of unknown etiology. A major cause of morbidity and mortality in SLE is accelerated atherosclerosis. Endothelial-specific molecule 1 (endocan) is a potential predictor of vascular events and is expressed in response to inflammatory cytokines in endothelial cells. We investigated the relationship between endocan and carotid intima–media thickness (cIMT) as a marker of early atherosclerosis. We included 44 women with SLE and 44 healthy women as controls. Disease severity of SLE was evaluated using the SLE Disease Activity Index. Endocan, C-reactive protein, erythrocyte sedimentation rate (ESR), and lipid panel were measured. The cIMT was 0.70 (range: 0.45-1.20) mm in patients with SLE and 0.40 (0.25-0.60) mm in controls (P < .001). Endocan value was 1.6 ± 0.9 ng/mL in controls and 2.2 ± 1.0 ng/mL in patients with SLE (P = .014). Endocan levels were positively correlated with cIMT (r = .469, P < .001), body mass index (r = .373, P = .013), and ESR (r = .393, P = .008). Endocan level may be associated with subclinical atherosclerosis in SLE. Consequently, endocan levels may be a promising clinical tool for patients with SLE as a guide for preventive strategy. [ABSTRACT FROM AUTHOR]

Inflammation plays an important role in the pathophysiology of vascular disease. In this review, we consider the associations between the neutrophil–lymphocyte ratio (NLR; an indicator of inflammation) and vascular disease and its associated risk factors. The NLR has received attention due to its role as an independent prognostic factor for coronary artery disease. The NLR can also be affected by atherosclerotic risk factors, such as hypercholesterolemia, metabolic syndrome, diabetes, and hypertension. Importantly, it can predict mortality in cardiovascular diseases. There are also reports of a positive correlation between the NLR and commonly used inflammatory markers. Inflammation is important not only in pathophysiology but also clinical outcomes of many diseases. The NLR is a widely available, easily derived, and reproducible marker of inflammation. Unlike many other inflammatory markers, the NLR is inexpensive and readily available and it provides additional risk stratification beyond conventional risk scores. [ABSTRACT FROM AUTHOR]

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]

Contrast-induced nephropathy (CIN) represents an important adverse effect of contrast media (CM) administration. Contrast-induced nephropathy is associated with prolonged hospitalization as well as increased cardiovascular morbidity, renal morbidity, and all-cause mortality. Several risk factors may predict CIN incidence, and various scores and ratios have been proposed to identify high-risk patients. Novel biomarkers may provide an earlier diagnosis of CIN. A multifactorial approach is required for CIN prevention including hydration, administration of low- or iso-osmolar CM, minimizing CM volume, and statin administration. Renal function may deteriorate after CM administration, even in the absence of CIN. Therefore, this deterioration may not be an “all or none” phenomenon; it may well occur in many patients receiving CM, with/without CIN, and may prove to be an underestimated risk factor. Patients should be followed up for longer periods as outpatients after CM exposure to assess kidney function and predict subsequent increased morbidity and mortality. [ABSTRACT FROM PUBLISHER]

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]

The relationship between echocardiographically measured epicardial fat thickness (EFT) and plasma concentrations of leptin, ghrelin, and adiponectin has not been evaluated in patients with noncachectic heart failure (HF). Patients with noncachectic HF and age- and sex-matched controls did not differ significantly in EFT, whereas EFT values showed significant positive correlation with body mass index (BMI) in both groups and were negatively related with brain natriuretic peptide and positively with log leptin values in the HF group. In the control group, a positive correlation with high-sensitivity C-reactive protein (hsCRP) and a negative correlation with log ghrelin were found. In multivariable analysis, log leptin was a significant predictor of EFT in patients with HF, but this effect was not retained after adjusting for BMI. In contrast, log ghrelin and hsCRP were significant predictors of EFT in controls even after adjusting for BMI. [ABSTRACT FROM AUTHOR]

The authors discuss the relationship of obstructive sleep apnea syndrome (OSAS) with metabolic syndrome (MetS) in association with increased risk of cardiovascular (CV) events. They highlight similar components between the two, including hypertension, insulin resistance, and low high-density lipoprotein cholestrerol (HDL-C), together with high levels of triglycerides (TG). They conclude that since they share common predisposing factors, both are associated with increased CV risk.

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]

This post hoc analysis of the Assessing The Treatment Effect in Metabolic Syndrome Without Perceptible diabeTes (ATTEMPT) study assesses the 3½ year incidence of new-onset diabetes (NOD) and related cardiovascular disease (CVD) events in patients with metabolic syndrome (MetS), after multifactorial (lifestyle and drug, including atorvastatin) intervention. Patients were randomized to group A (low-density lipoprotein cholesterol [LDL-C] target <100 mg/dL) and group B (<130 mg/dL). The incidence of NOD during the 42-month follow-up was very low, 0.83 to 1.00/100 patient-years in patients with MetS and MetS with impaired fasting glucose, respectively. Older age, increased waist circumference, and persistent MetS were determinants of NOD. One CVD nonfatal event occurred in the 28 patients with NOD. Our findings suggest that treating the characteristics of MetS is achievable and beneficial. New-onset diabetes incidence and CVD events were negligible and not different from what is expected in the general population. [ABSTRACT FROM AUTHOR]

Selected near-infrared spectroscopy (NIRS) parameters were assessed in healthy untrained participants and in peripheral arterial disease (PAD) trained patients to evaluate their usefulness in rehabilitative outcome. Forty-five PAD and 15 healthy participants were studied at entry and at 34 ± 2 weeks. Healthy participants performed their usual activities. Patients with PAD performed 2 home-based programs: structured at prescribed pace (S-pre, n = 31) and unstructured at free pace (U-free, n = 14). We measured ankle–brachial index (ABI), NIRS calf oxygen consumption at rest, NIRS dynamic muscle perfusion during an incremental test, and walking capacity. In all patients with PAD the NIRS parameters significantly increased approaching the stable values of untrained healthy participants. Among PAD, only S-pre group showed significant improvements in hemodynamic, functional, and NIRS parameters with selective adaptations in the worse legs. The assessment of NIRS parameters, that were found stable without training in healthy and modified in PAD only following structured training, might outline the local exercise-induced adaptations. [ABSTRACT FROM PUBLISHER]

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.

Aims: The metabolic syndrome (MetS) is associated with increased risk of cardiovascular disease (CVD) and diabetes mellitus (DM). Several definitions of MetS have been proposed. The aim of the present study was to estimate and compare the prevalence of MetS according to the National Cholesterol Education Program Adult Treatment Panel III (NCEP ATP III), American Heart Association-National Heart Lung and Blood Institute (AHA-NHLBI), International Diabetes Federation (IDF) and the more recent Joint Interim Statement (JIS) definitions in patients attending a hypertension clinic. Methods: The records of patients referred to the hypertension clinic at the University Hospital (Heraklion, Crete) from January 2001 to June 2009 were screened retrospectively. A total 384 patients (146 men) were included in the study. Results: The prevalence of MetS according to the IDF and JIS definitions was significantly higher compared with that of the NCEP ATP III in both genders (IDF: P = .009 and P = .002, JIS: P = .002 and P = 0.001 for men and women, respectively); this was the case for the AHA-NHLBI definition only among women (P = .03). All MetS components differed significantly (P from < .0001 to .02) between patients with and without MetS for all definitions. Conclusions: The prevalence of MetS varies considerably depending on the definition used in a hypertensive population in a Mediterranean country. These differences will influence risk assessment. [ABSTRACT FROM PUBLISHER]

Introduction: Platelet cholesterol (PC) could be used to assess “tissue” cholesterol of patients with vascular disease. However, the methods available so far to measure PC involve a complex extraction process. We developed a rapid method to measure PC and assessed its correlation with serum total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), LDL-C/HDL-C ratio, triglycerides (TG), and non-HDL-C. Methods: We assessed repeatability (20 times, 3 participants) and reproducibility (8 times, 2 participants). A group of 47 healthy participants was studied. Blood was collected to analyze serum TC, LDL-C, HDL-C, and TG. Citrated blood was used to prepare a platelet pellet. A “clear soup” was produced (by disrupting this pellet using freeze–thaw and sonication cycles) and used to measure PC. Results: Repeatability of PC showed a coefficient of variation (CV) of 4.8%. The reproducibility of PC over a period of 2 months was CV 7.5% and 8.1% (8 measurements for 2 participants). The PC of participants with serum LDL-C >2.6 mmol/L (treatment goal recommended by the National Cholesterol Education Program Adult Treatment Panel III) was 377 ± 120 μmol/1012 platelets (n = 25). There was a significant correlation (Spearman, correlation coefficient) of PC (n = 25) with serum LDL-C (rs = 0.45, P = .02), LDL-C/HDL-C (rs = 0.45, P = .02), TG (rs = 0.43, P = .03), and non-HDL-C (rs = 0.53, P = .007). Conclusion: This technique of measuring PC has the advantage of being reproducible, fast, and simpler than previous methods. Thus, it may be useful for multiple sampling when investigating changes in PC in hypercholesterolemic patients. More extensive evaluation is necessary. [ABSTRACT FROM PUBLISHER]

The peroxisome proliferator-activated receptors (PPARs) represent the family of 3 nuclear receptor isoforms-PPARα, -γ, and -δ/β, which are encoded by different genes. As lipid sensors, they are primarily involved in regulation of lipid metabolism and subsequently in inflammation and atherosclerosis. Atherosclerosis considers accumulation of the cells and extracellular matrix in the vessel wall leading to the formation of atherosclerotic plaque, atherothrombosis, and other vascular complications. Besides existence of natural ligands for PPARs, their more potent synthetic ligands are fibrates and thiazolidindiones. Future investigations should now focus on the mechanisms of PPARs activation, which might present new approaches involved in the antiatherosclerotic effects revealed in this review. In addition, in this review we are presenting latest data from recent performed clinical studies which have focus on novel approach to PPARs agonists as potential therapeutic agents in the treatment of complex disease such as atherosclerosis. [ABSTRACT FROM PUBLISHER]

This commentary addresses the issue of optimal contemporary management of symptomatic and asymptomatic carotid artery stenosis. Based on current data, carotid endarterectomy (CEA) should be performed in the majority of patients with symptomatic carotid artery stenosis. Carotid artery stenting (CAS) should be reserved for a minority of these symptomatic patients, in whom CEA is contraindicated. In asymptomatic patients, all should be placed on best medical treatment (BMT). With the use of one or more of the proposed stroke risk stratification models or some as yet undetermined method, the identification of those asymptomatic individuals may be possible in whom stroke risk is higher than usual with BMT. This asymptomatic subgroup, which may be small and is yet to be determined with certainty, could be offered an invasive carotid procedure (either CAS or CEA). [ABSTRACT FROM AUTHOR]

Many theories aim at explaining the mechanisms of aging and death in humans. Decreased levels of androgens, growth hormone, and insulin-like growth factor accompany natural aging in men. Androgens influence the growth and maturation of men in various stages of their life. The action of androgens is performed by binding or not binding to androgen receptors. However, various actions of androgens were clarified after the discovery and genotyping of the androgen receptor. The influence of androgens on the lipid profile was reported by several researchers. This negative influence of androgens in men and the positive influence of estrogens in women are responsible for the higher impact of atherogenesis in men compared with women. In aging men, this negative influence of androgens on the lipid profile is more pronounced. This review considers the influence of age on lipid metabolism in men. [ABSTRACT FROM PUBLISHER]

Polycystic ovary syndrome (PCOS) is a common disorder in women of reproductive age, affecting around 10% of them. Polycystic ovary syndrome is considered to be related to increased risk for type 2 diabetes mellitus (T2DM) and cardiovascular disease (CVD). There are 2 definitions for PCOS: one adopted in 1990 (classical PCOS with phenotypes A and B) and the otherin 2003 (Rotterdam criteria with 4 phenotypes A to D). The latter is a wider definition including the 1990 phenotypes. There is mounting data suggesting that phenotypes C and D are not actually related to increased CVD risk, and thus screening for CVD risk factors of intervening for primary CVD prevention in young women is not cost-effective. There is an increasing number of suggestions to return to the 1990 criteria plus some metabolic parameters to identify real CVD risk in this population. However, such a strategy needs verification by large, prospective studies. [ABSTRACT FROM PUBLISHER]

Background: The Department of Health launched a cardiovascular disease risk assessment initiative with particular reference to reducing health inequalities in ethnic minorities. Collaboration between HEART UK, Royal Free Hampstead NHS Trust and Hindu Temples resulted in vascular screening in North London. Methods: Subjects of South Asian origin were screened. A full lipid profile and glucose were measured using a point of care testing (POCT) Cholestech LDX analyser (LDX). Venous samples were analysed in our hospital laboratory. Results: The results (215 men; 191 women) were divided into tertiles and Bland-Altman plots were used to assess agreement. At high-density lipoprotein cholesterol (HDL-C) concentrations <1.0 mmol/L the LDX underestimated values by 20.2 mmol/L (P<0.0001). At HDL-C concentrations .1.3 mmol/L this bias disappeared. For total cholesterol the concentration-dependent negative bias was evident at concentrations of <4.1 mmol/L (P< 0.0001). This bias was less evident at higher concentrations. A similar pattern was seen for low-density lipoprotein cholesterol. There were also small variations in glucose and triglyceride values. However, there was excellent agreement in calculated cardiovascular disease risk using kappa analysis for JBS2, QRISK2, ETHRISK and Framingham (κ = 0.86, 0.92, 0.94 and 0.88, respectively). This was a high-risk population since 9.7- 19.4% had a ⩾20% 10-y probability of a vascular event depending on the risk engine and assay method used. The corresponding values for intermediate risk (11-19%) were 18.6-25.7%. Conclusions: There was a minimum mismatch irrespective of the type of risk calculator used. POCT measurements are adequate for the National Health Service Health Check. [ABSTRACT FROM AUTHOR]

Background and Aim: The treatment-of-choice for the optimal management of the dyslipidemia of the metabolic syndrome (MetS) is not clearly defined. We compared the efficacy of 4 drug regimes for the management of this dyslipidemia in a mouse model. Materials and Methods: A total of 60 C57Bl6 mice comprised the study group. The first 10 received standard mouse food for the whole experiment (control group). The remaining 50 mice received atherogenic diet for 14 weeks until the development of the MetS. The mice were then divided into 5 groups: the 1st group continued receiving atherogenic diet, while the other 4 groups received atherogenic diet plus ezetimibe (10 mg/kg per day), fenofibrate (100 mg/kg per day), low-dose atorvastatin (10 mg/kg per day), or high-dose (40 mg/kg per day) atorvastatin, respectively, for another 8 weeks. Results: High-dose atorvastatin treatment achieved the best lipid profile compared with low-dose atorvastatin, ezetimibe, and fibrate therapy. The lipid profile of mice receiving atherogenic diet plus high-dose atorvastatin treatment was similar with mice on regular chow. Conclusions: High-dose atorvastatin treatment resulted in optimization of the lipid profile in the presence of a high-fat atherogenic diet in a mouse model. Our results suggest that high-dose atorvastatin treatment may be the optimal treatment option for the dyslipidemia associated with MetS. Nevertheless, verification of these results in humans is required before any definite conclusions can be drawn. [ABSTRACT FROM PUBLISHER]

Antiplatelet drugs are important components in the management of atherothrombotic vascular disease. However, several limitations restrict the safety and efficacy of current antiplatelet therapy in clinical practice. Interpatient variability and resistance to aspirin and/or clopidogrel has spurred efforts for the development of novel agents. Indeed, several antiplatelet drugs are at various stages of evaluation; those at advanced stage of development are the focus of this review. [ABSTRACT FROM PUBLISHER]

Rosiglitazone may increase cardiovascular risk in patients with type 2 diabetes. Yet, its effects on atherogenic dyslipidemia are still not fully elucidated. In a prospective open-label study rosiglitazone (4 mg/day for 12 weeks) was added to a maximum of 2 oral antidiabetic drugs in 18 diabetic patients. We evaluated the effects on plasma lipids before and after an oral fat load. The size and subclasses of low-density lipoprotein (LDL) and high-density lipoprotein (HDL) were also determined (by gradient gel electrophoresis). Rosiglitazone improved glycosylated hemoglobin ([HbA1c] P = .0023), without significant effects on fasting and postprandial plasma lipids. Fasting LDL size increased (+1.4%, P = .034), with less small, dense LDL-IIIA (25.1%, P =.018). Post-prandially, larger HDL-2b reduced (-8.7%, P = .006) and smaller HDL-3b increased (+12.2%, P = .05), without any effects on HDL size. Rosiglitazone led to antiatherogenic changes in LDL size and subclasses, with proatherogenic changes in HDL subclasses, despite no effects on plasma lipids. Their clinical relevance remains to be established. [ABSTRACT FROM AUTHOR]

Most symptomatic patients should not be candidates for carotid artery stenting (CAS); at least not at present. In these patients, CAS is associated with higher stroke, as well as recurrent stenosis rates compared with carotid endarterectomy (CEA). Furthermore, CAS is considerably more expensive than CEA. These facts raise the question, why perform CAS in symptomatic patients when you have CEA, which is associated with lower stroke and recurrent stenosis rates, and is also a more cost-effective option. This article supports the theory that currently most symptomatic patients are not appropriate candidates for CAS. [ABSTRACT FROM AUTHOR]

In vitro studies attribute antiatherogenic and insulin-like properties to zinc (Zn). However, only a few conflicting clinical data exist concerning the relationship between Zn and coronary artery disease (CAD) as well as glycemic indices. We studied 72 patients without prior history of myocardial infarction or revascularization procedures, who underwent coronary angiography for evaluation of chest pain. Coronary artery disease severity was estimated using 3 angiographic scores. Zn in serum and 24-hour urine, as well as serum Zn/24-hour urine Zn ratio were determined. Serum Zn was not associated with CAD prevalence and severity. However, urinary Zn loss was significantly higher among patients with CAD and showed a positive association with CAD severity. Serum Zn/24-hour urine Zn ratio was inversely associated with CAD, as well as with diabetes mellitus prevalence, fasting glucose, and glycated hemoglobin levels. Low serum Zn/24-hour urine Zn ratio is associated with angiographically severe atherosclerosis and impaired glucose homeostasis. [ABSTRACT FROM AUTHOR]

The article presents a study on the effects of plant sterols and stanols beyond low-density lipoprotein in cholesterol lowering. It is inferred that consumption of foods and supplements enriched with plant sterols and stanols may aid in lowering low-density lipoprotein cholesterol (LDL-C) levels. The study suggests that consumption of plant sterols and stanols results in approximately nine percent reduction in LDL-C concentration, as well as their having beneficial effects on other lipid variables.

It is well recognized that the proliferation of vascular smooth muscle cells (VSMCs) is a key event in the pathogenesis of various vascular diseases, including atherosclerosis and hypertension. We have previously shown that among extracellular signal-regulated protein kinases (ERKs), the 42- and 44-kDa isoforms (ERK½) participate in the cellular mitogenic machinery triggered by several VSMCs activators, including insulin (INS) and thrombin (Thr). However, understanding of the intracellular signal transduction pathways involved is incomplete. This review considers the recent findings in INS and Thr signaling mechanisms that modulate the proliferation of VSMCs with particular emphasis on the ERK½ signaling pathway, an important mediator of VSMCs hypertrophy and vascular disease. Moreover, because the ERK½ pathway have been acknowledged as an important mediator of VSMCs hypertrophy, ERK ½ is identified as a key target for novel therapeutic interventions to minimize irreversible tissue damage associated with hypertension and atherosclerosis. [ABSTRACT FROM AUTHOR]

The role of vascular endothelial growth factor (VEGF) and erythropoietin (EPO) in mediating hypoxic preconditioning under the acute intermittent hypoxic condition (AIH) was investigated in this study. Male Wistar rats were randomly assigned and kept in normoxic conditions, (Nx) or in AIH conditions and subjected to brief cycles hypoxia/reoxygenation. Hearts were isolated, perfused, and subjected to in vitro global ischemia followed by reperfusion. During and at the end of reperfusion, left ventricular developed pressure (LVDP); LV end diastolic pressure (LVEDP); rate pressure product (RPP); peak left ventricular pressure rise (ΔP/Δtmax) and heart rate (HR) were measured. Hearts subjected to AIH displayed a significant higher LVDP (P < .001), RPP (P < .001), and ΔP/Δtmaxc (P < .001) Expression of VEGF and EPO were significantly increased at 3, 8, and 24 hours after AIH. Hypoxic training could provide a new approach to enhance endogenous cardioprotective mechanisms. [ABSTRACT FROM AUTHOR]

We investigated cardiovascular disease (CVD) risk factors in 1501 Greeks (613 men and 888 women, aged 40-65 years) referred to outpatients with metabolic syndrome (MetS) and without diabetes mellitus or CVD. The 10-year risk of fatal CVD events was calculated using European Society of Cardiology Systematic Coronary Risk Estimation (ESC SCORE), Hellenic- SCORE, and Framingham equations. Raised blood pressure (BP) and hypertriglyceridemia were more common in men (89.6% vs 84.2% and 86.8% vs 74.2%, respectively; P < .001). Low high-density lipoprotein cholesterol (HDL-C) and abdominal obesity were more common in women (58.2% vs 66.2% and 85.8% vs 97.1%, respectively; P < .001). The 10-year risk of fatal CVD events using HellenicSCORE was higher in men (6.3% ± 4.3% vs 2.7% ± 2.1%; P < .001). European Society of Cardiology Systematic Coronary Risk Estimation and Framingham yielded similar results. The risk equations gave similar assessments in a European Mediterranean population except for HellenicSCORE that calculated more MetS women requiring risk modification. This might justify local risk engine evaluation in event-based studies. (Clinical- Trials.gov ID: NCT00416741). [ABSTRACT FROM AUTHOR]