Nonalcoholic Fatty Pancreas Disease: Role in Metabolic Syndrome, "Prediabetes," Diabetes and Atherosclerosis.

Fat accumulation in the pancreas associated with obesity and the metabolic syndrome (MetS) has been defined as "non-alcoholic fatty pancreas disease" (NAFPD). The aim of this review is to describe the association of NAFPD with obesity, MetS, type 2 diabetes mellitus (T2DM) and atherosclerosis and also increase awareness regarding NAFPD. Various methods are used for the detection and quantification of pancreatic fat accumulation that may play a significant role in the differences that have been observed in the prevalence of NAFPD. Endoscopic ultrasound provides detailed images of the pancreas and its use is expected to increase in the future. Obesity and MetS have been recognized as NAFPD risk factors. NAFPD is strongly associated with non-alcoholic fatty liver disease (NAFLD) and it seems that the presence of both may be related with aggravation of NAFLD. A role of NAFPD in the development of "prediabetes" and T2DM has also been suggested by most human studies. Accumulation of fat in pancreatic tissue possibly initiates a vicious cycle of beta-cell deterioration and further pancreatic fat accumulation. Additionally, some evidence indicates a correlation between NAFPD and atherosclerotic markers (e.g., carotid intima-media thickness). Weight loss and bariatric surgery decreases pancreatic triglyceride content but pharmacologic treatments for NAFPD have not been evaluated in specifically designed studies. Hence, NAFPD is a marker of local fat accumulation possibly associated with beta-cell function impairment, carbohydrate metabolism disorders and atherosclerosis.

Mean Platelet Volume as a Surrogate Marker for Platelet Activation in Patients With Idiopathic Pulmonary Fibrosis.

BACKGROUND: Idiopathic pulmonary fibrosis (IPF) is associated with a prothrombotic state. AIM: To study mean platelet volume (MPV) and Platelet Distribution Width (PDW) as markers of platelet activation and their potential association with lung function in patients with recently diagnosed IPF. MATERIALS AND METHODS: This study included 56 patients with IPF (age 64.9±7.4 years) and 79 controls (age 64.2 ± 5.9 years). RESULTS: An inverse relation was demonstrated between platelet count and MPV in the control group but not among patients with IPF. Platelet count was significantly lower in patients with IPF compared with controls (230 ± 60 vs 256 ± 75 × 10(3)/µL, P = .038). Conversely, MPV was higher in patients versus controls (10.3 ± 1.2 vs 9.8 ± 1.2 fl, P = .024), while there was no difference between the groups in PDW. Respiratory function was, as expected, significantly impaired in patients with IPF versus controls in terms of forced expiratory volume in first second (FEV1; 67.2 ± 23.1 vs 102.6 ± 15.9% of predicted value, P < .001), forced vital capacity (FVC; 65.3 ± 21 vs 95.2 ± 16.1% of predicted value, P < .001), FEV1/FVC (83.1 ± 15 vs 87.5 ± 6.4%, P = .041) and partial pressure of oxygen in arterial blood (PaO2; 67.1 ± 10.3 vs 81.5 ± 15.2 mm Hg, P < .001). No significant correlation was seen between MPV and FVC (r = -.1497, P = .275), MPV and lung diffusion capacity for carbon monoxide (r = .035, P = .798) and total lung capacity (r = .032, P = .820). CONCLUSIONS: Patients with IPF exhibit higher MPV values and lower platelet count. Further studies are needed to assess the clinical implications of these findings.

Emerging Vascular Risk Factors in Women: Any Differences from Men?

Gender differences have been reported for traditional vascular risk factors such as smoking, obesity, diabetes, hypertension, dyslipidemia, age and family history of premature coronary heart disease. The prevalence, severity, associations and response to treatment of several emerging cardiovascular disease (CVD) risk factors may also differ between men and women. Such CVD risk factors include certain inflammatory and hemostatic markers, endothelial dysfunction, homocysteine, lipid disorders, microalbuminuria/proteinuria, coronary artery calcium score, arterial stiffness, periodontitis, inflammatory bowel syndrome, obstructive sleep apnea, impaired glucose metabolism, metabolic syndrome and non-alcoholic fatty liver disease. Further larger prospective studies are needed to establish these relationships. Hormone replacement therapy may also affect vascular risk. These data should be taken into consideration when assessing and treating CVD risk in women.

Long-term Mortality in Patients with Asymptomatic Carotid Stenosis: Implications for Statin Therapy.

OBJECTIVE: Recent studies with asymptomatic carotid patients on best medical management have shown that the annual risk of stroke has decreased to approximately 1%. There is no evidence that a similar decrease in mortality has occurred. In addition, the intensity of statin therapy for these patients has not yet been determined. The aims of this review were to determine (a) the reported long-term all-cause and cardiac-related mortality in patients with asymptomatic carotid stenosis (ACS) > 50%, (b) whether there has been a decrease in mortality in recent years, (c) the available methods of mortality risk stratification, and (d) whether the latest ACC/AHA guidelines on the treatment of serum lipids can be applied to this group of patients. METHODS: Systematic review of PubMed, EuroPubMed, and Cochrane Library and meta-analysis using random effects for pooled proportions were performed regarding long-term all-cause and cardiac-related mortality and the associated risk factors in ACS patients. The last day for literature search was October 30, 2014. RESULTS: Seventeen studies were retrieved reporting 5-year all-cause mortality in 11,391 patients with ACS >50%. The 5-year cumulative all-cause mortality across all 17 studies was 23.6% (95% CI 20.50-26.80). Twelve additional studies, reporting both all-cause and cardiac mortality with a minimum of 2 year follow-up and involving 4,072 patients were identified. Of the 930 deaths reported, 589 (62.9%; 95% CI 58.81-66.89) were cardiac-related. This translates into an average cardiac-related mortality of 2.9% per year. CONCLUSIONS: All-cause and cardiac mortality in ACS patients are very high. Although risk stratification is possible, most patients are classified as high risk. In view of this high risk, aggressive statin therapy is indicated if the new ACC/AHA guidelines on serum lipids are to be adhered to.

Impact of metabolic syndrome in surgical patients: should we bother?

Clinicians inevitably encounter patients who meet the diagnostic criteria for the metabolic syndrome (MetS); these criteria include central obesity, hypertension, atherogenic dyslipidaemia, and hyperglycaemia. Regardless of the variations in its definition, MetS may be associated with adverse outcomes in patients undergoing both cardiac and non-cardiac surgery. There is a paucity of data concerning the anaesthetic management of patients with MetS, and only a few observational (mainly retrospective) studies have investigated the association of MetS with perioperative outcomes. In this narrative review, we consider the impact of MetS on the occurrence of perioperative adverse events after cardiac and non-cardiac surgery. Metabolic syndrome has been associated with higher rates of cardiovascular, pulmonary, and renal perioperative events and wound infections compared with patients with a non-MetS profile. Metabolic syndrome has also been related to increased health service costs, prolonged hospital stay, and a greater need for posthospitalization care. Therefore, physicians should be able to recognize the MetS in the perioperative period in order to formulate management strategies that may modify any perianaesthetic and surgical risk. However, further research is needed in this field.

High-density lipoprotein, vascular risk, cancer and infection: a case of quantity and quality?

Low levels of high-density lipoprotein cholesterol (HDL-C) have been associated with increased cardiovascular (CV) risk. These beneficial effects of HDL can be, at least partly, attributed to its anti-inflammatory, antithrombotic, antioxidant and endothelial-protective properties. However, the results of some clinical trials aiming at raising HDL-C levels are conflicting in terms of CV protection suggesting that alterations in HDL quality (and not only quantity) are involved in the atherosclerotic process. In this context, inflammation, oxidation, infection, hyperglycemia and activated platelets may modify HDL components, thus transforming HDL to a dysfunctional molecule with pro-atherogenic properties. Furthermore, some recent trials with HDL-raising drugs, such as niacin and torcetrapib, reported a lack of benefit in terms of vascular risk as well as adverse events including cancer and infections. In this narrative review, the findings of recent HDL clinical studies in relation to CV events as well as the associations of HDL with cancer and infections are discussed. The possible pathogenic mechanisms of these associations are also considered. The clinical implications of HDL function in treating patients at high CV risk remains to be established in future trials.

Elevated serum levels of endocan in patients with psoriasis vulgaris: correlations with cardiovascular risk and activity of disease.

BACKGROUND: Psoriasis vulgaris is an inflammatory disease characterized by epidermal hyperproliferation, leucocyte adhesion molecule expression and leucocyte infiltration. Psoriasis is associated with an increased risk of cardiovascular disease. Endothelial dysfunction is widely regarded as being the initial process in the development of atherosclerosis. Human endothelial cell-specific molecule-1 (endocan) is a novel human endothelial cell-specific molecule. Previous studies suggested that endocan may be a novel endothelial dysfunction marker. OBJECTIVES: To investigate the relationship between serum levels of endocan and both cardiovascular risk and disease activity in patients with psoriasis vulgaris. METHODS: A total of 29 patients with psoriasis vulgaris and 35 control subjects were included in the study. Endocan, high-sensitivity C-reactive protein (hsCRP) and carotid artery intima-media thickness (cIMT) were measured in all subjects. RESULTS: Serum endocan levels were significantly different between the two groups (P < 0.001). In patients with psoriasis, serum endocan levels correlated with Psoriasis Area and Severity Index, hsCRP and cIMT (r = 0.477, P = 0.009; r = 0.484, P = 0.008; r = 0.408, P = 0.02, respectively). CONCLUSIONS: Circulating endocan may represent a new marker that correlates with cardiovascular risk as well as the severity of disease in patients with psoriasis vulgaris. Endocan may be a surrogate endothelial dysfunction marker and may have a functional role in endothelium-dependent pathological disorders. Whether endocan levels could become a treatment target merits further investigation.

Critique of the Carotid Revascularization Endarterectomy versus Stenting Trial (CREST): flaws in CREST and its interpretation.

The Carotid Revascularization Endarterectomy versus Stenting Trial (CREST) has been used to support the equivalence of carotid artery stenting (CAS) and carotid endarterectomy (CEA) in the treatment of carotid stenosis in both symptomatic and asymptomatic patients. This inclusion of two different forms of the disease decreased the power and significance of the CREST results and weakened the trial. Other flaws in CREST were the equal weighting of mostly minor myocardial infarctions (MIs) with strokes and death in the peri-procedural, composite 'end' point, but not in the 4-year, long-term 'end' point. Although CAS was associated with 50% fewer peri-procedural MIs compared with CEA, there were >2.5-fold more MIs after CAS than CEA at 4 years. The 4-year MI rate, however, was not a component of the primary 'end' point. Additionally, although the initial CREST report indicated that there was no difference in the outcomes of CAS and CEA according to symptomatic status or sex, subsequent subgroup analyses showed that CAS was associated with significantly higher stroke and death rates than CEA in symptomatic patients, in females and in individuals ≥ 65 years of age. The present article will examine these and other flaws and the details of CREST's results derived from the trial's preplanned subanalyses to show why the claims that CREST demonstrates equivalence of the two therapeutic procedures are unjustified.

Smoking and vascular risk: are all forms of smoking harmful to all types of vascular disease?

Smoking, both active and passive, is an established vascular risk factor. The present narrative review considers the effects of different forms of smoking (i.e. cannabis, cigar, pipe, smokeless tobacco and cigarette) on cardiovascular risk. Furthermore, the impact of smoking on several vascular risk factors [e.g. hypertension, diabetes mellitus (DM), dyslipidaemia and haemostasis] and on vascular diseases such as coronary heart disease (CHD), peripheral arterial disease (PAD), abdominal aortic aneurysms (AAA) and carotid arterial disease, is discussed. The adverse effects of all forms of smoking and the interactions between smoking and established vascular risk factors highlight the importance of smoking cessation in high-risk patients in terms of both primary and secondary vascular disease prevention. Healthcare providers should discourage people (especially the young) from becoming smokers, strongly encourage all vascular patients to stop smoking and support those who decide to quit by pharmaceutical and psychological interventions. In high-risk populations such as patients with CHD, DM and/or PAD, smoking cessation should always be a part of a multifactorial treatment to reduce vascular risk.

Cardiovascular benefits of bariatric surgery in morbidly obese patients.

Morbid obesity is associated with increased morbidity and represents a major healthcare problem with increasing incidence worldwide. Bariatric surgery is considered an effective option for the management of morbid obesity. We searched MEDLINE, Current Contents and the Cochrane Library for papers published on bariatric surgery in English from 1 January 1990 to 20 July 2010. We also manually checked the references of retrieved articles for any pertinent material. Bariatric surgery results in resolution of major comorbidities including type 2 diabetes mellitus, hypertension, dyslipidemia, metabolic syndrome, non-alcoholic fatty liver disease, nephropathy, left ventricular hypertrophy and obstructive sleep apnea in the majority of morbidly obese patients. Through these effects and possibly other independent mechanisms bariatric surgery appears to reduce cardiovascular morbidity and mortality. Laparoscopic Roux-en-Y gastric bypass (LRYGB) appears to be more effective than laparoscopic adjustable gastric banding (LAGB) in terms of weight loss and resolution of comorbidities. Operation-associated mortality rates after bariatric surgery are low and LAGB is safer than LRYGB. In morbidly obese patients bariatric surgery is safe and appears to reduce cardiovascular morbidity and mortality.

Levosimendan - a calcium sensitising agent with potential anti-arrhythmic properties.

Levosimendan is a 'Ca(2+)sensitiser', which exerts its inotropic effect by increasing the affinity of troponin C for Ca(2+), directly stabilising the Ca(2+)-induced conformation of troponin C. It leads to a positive inotropic effect without impairing diastolic relaxation and causing cytosolic Ca(2+) ion overload, which might result in cardiac myocyte dysfunction, arrhythmias and cell death. Levosimendan may also have significant anti-inflammatory properties. Data from various studies suggest that levosimendan might have anti-arrhythmic effects, although the outcome of clinical trials on the effect of this agent in (for example) atrial fibrillation (AF) remains controversial. Currently, on the basis of available data, it is especially worth emphasising the potential role of this drug in the termination of AF after cardiac surgery, which significantly influences early- and long-term morbidity and mortality. This review considers the putative anti-arrhythmic properties of levosimendan and discusses the potential clinical application of such a drug.

Endothelial dysfunction in metabolic syndrome: prevalence, pathogenesis and management.

The metabolic syndrome (MetS) is characterized by the presence of central obesity, impaired glucose metabolism, dyslipidemia and hypertension. Several studies showed that MetS is associated with increased risk for type 2 diabetes mellitus (T2DM) and vascular events. All components of MetS have adverse effects on the endothelium. Endothelial dysfunction plays a role in the pathogenesis of atherosclerosis and might also increase the risk for insulin resistance and T2DM. We review the prevalence and pathogenesis of endothelial dysfunction in MetS. We also discuss the potential effects of lifestyle measures and pharmacological interventions on endothelial function in these patients. It remains to be established whether improving endothelial function in MetS will reduce the risk for T2DM and vascular events.

Clinical experience with ezetimibe/simvastatin in a Mediterranean population.

OBJECTIVES: This study aimed to describe the clinical experience of the ezetimibe (EZE)/simvastatin (SIMVA) combination in a hypercholesterolaemic Greek population who did not attain the cholesterol goals on statin treatment alone. METHODS: Patients already treated with a statin, at any dose, for at least 8 weeks, with LDL-C levels above the goal, (>100, >130 or >160 mg/dl according to their risk category), where the physician chose EZE/SIMVA as appropriate treatment, entered the study. Medical history, demographics and laboratory values were recorded at baseline and 2 months later. RESULTS: The study included 1514 patients (male 53.4%) of mean age 60.1 + or - 10.5 years. Diabetes mellitus was reported in 29.9% of the patients, 61.2% had hypertension, 39% were obese, 10.5% had a history of myocardial infarction and 6.8% had a history of stroke or peripheral arterial disease. Current and ex-smoking was reported in 46.8%. Atorvastatin (33%) and SIMVA (27.2%) were the most frequently used statins prior to using the EZE/SIMVA regimen. After 2 months of EZE/SIMVA therapy mean LDL-C was reduced by 33%, mean total cholesterol by 26%, mean triglycerides by 15%, while HDL-C was increased by 10%. The percentage of patients who achieved the LDL-C goal with EZE/SIMVA was 73.8%. One serious adverse event, not related to study treatment and 23 adverse events in total were recorded. There was a significant decrease in serum creatinine levels in patients with baseline values greater than 1.0 mg/dl (88 micromol/L). CONCLUSIONS: Treatment with the EZE/SIMVA combination appears an effective and safe therapeutic option for patients who do not achieve the LDL-C goals on statin therapy alone.

High prevalence of metabolic syndrome and cardiovascular risk factors in men with ankylosing spondylitis on anti-TNFalpha treatment: correlation with disease activity.

OBJECTIVE: Ankylosing spondylitis (AS) may be associated with an increased risk for cardiovascular diseases (CVD). We investigated the prevalence of cardiovascular risk factors and metabolic syndrome (MetS) in men with AS and assessed any correlation with AS-related factors. METHODS: This was a cross-sectional study of 63 men with AS, median age 40 (19-69) years, and 126 age-matched controls. Patients were on anti-TNFalpha treatment because of considerable disease activity at some time during the course of the disease. MetS was assessed according to the modified National Cholesterol Education Program Adult Treatment Panel III criteria. The risk for CVD event within the next 10 years was estimated using the Framingham equation. RESULTS: Patients had lower high-density lipoprotein cholesterol (HDL-C) (p<0.001), higher systolic (p=0.001) and diastolic (p<0.01) blood pressure compared with controls. The prevalence of the MetS was higher in patients compared to controls (34.9% vs. 19.0%; p<0.05). AS patients with MetS were older (p<0.01), with higher Framingham risk score (p=0.001), had longer disease duration (p<0.05) and higher BASDAI (5.1 vs. 3.7; p<0.05) than those without MetS, while both BASFI and CRP had an inverse correlation with HDL-C levels. CONCLUSIONS: Men with AS have a higher prevalence of cardiovascular risk factors and MetS compared with controls. The presence of MetS was associated with increased 10 year CVD risk in these patients. The association of AS disease activity with MetS suggests that CVD in AS patients may, at least in part, be attributed to the inflammatory burden of the disease.

How safe is the use of thiazolidinediones in clinical practice?

BACKGROUND: Thiazolidinediones (TZDs) are widely used antidiabetic drugs with proven efficacy regarding mainly surrogate markers of diabetes management. However, efficacy on surrogate markers may not always translate into benefits in clinical outcomes. Thiazolidinediones are usually well tolerated; however, their use may be associated with several adverse effects. The first TZD, troglitazone, was withdrawn from the market owing to serious hepatotoxicity. However, this does not seem to be the case with newer TZDs. OBJECTIVE: The aim of the present review is to discuss the safety profile of this drug class. METHODS: We searched PubMed up to July 2008 using relevant keywords. CONCLUSIONS: Common side effects associated with TZDs include edema, weight gain, macular edema and heart failure. Moreover, they may cause hypoglycemia when combined with other antidiabetic drugs as well as decrease hematocrit and hemoglobin levels. Increased bone fracture risk is another TZD-related side effect. Thiazolidinediones tend to increase serum low density lipoprotein cholesterol levels, with rosiglitazone having a more pronounced effect compared with pioglitazone. Moreover, rosiglitazone increases low density lipoprotein particle concentration in contrast to pioglitazone where a decrease is observed. Rosiglitazone has been associated with an increase in myocardial infarction incidence. On the other hand, pioglitazone may reduce cardiovascular events. Overall, TZDs are valuable drugs for diabetes management but physicians should keep in mind that they are associated with several adverse events, the most prominent of which is heart failure.

Purinergic modulation of human corpus cavernosum relaxation.

The activation of P2Y(6) receptors has been previously reported to cause vascular smooth muscle constriction and relaxation. The aim of our study was to determine the effect of P2Y(6) receptor subtype activation on human cavernosal function. Cavernosal tissue was obtained from 23 patients undergoing gender reassignment surgery. Immunohistochemistry (IHC) and Western blotting were used to determine the presence of P2Y(6) receptors in corpus cavernosal tissue. The effects of UDP (a selective P2Y(6) receptor agonist) before and after the addition of distilled water (control), cibacron blue 3GA (CB, a P2Y(6) receptor antagonist; 10(-4) m) or N-nitro-L-arginine methyl esther (L-NAME, a NO synthase inhibitor; 10(-4) m) were assessed on phenylephrine (PE; 10(-4) m) pre-contracted cavernosal strips using organ baths. Electrical field stimulation (EFS; 0.5-32 Hz) was performed in the absence and presence of CB to determine neuronal-mediated P2Y(6) receptor responses. IHC and Western blotting revealed the presence of P2Y(6) receptors on cavernosal sections. UDP at 10(-4) m and 10(-3) m induced a 5% and 16% relaxation of the PE-mediated response (both p < 0.0001), respectively, which was significantly blocked by CB (48% reduction of the UDP 10(-3) m response, p < 0.002) but not affected by L-NAME. EFS-induced relaxations of pre-contraction strips were not significantly altered by CB. We have found the presence of P2Y(6) receptors in human cavernosal tissues, that when activated induce cavernosal smooth muscle cell relaxation via non-neuronal and non-nitric oxide dependent mechanism. Further investigation is needed to establish whether P2Y(6) receptors play a physiological role in penile erection.