Procedural Results and Clinical Outcomes of Transcatheter Aortic Valve Implantation in Switzerland: An Observational Cohort Study of Sapien 3 Versus Sapien XT Transcatheter Heart Valves.

BACKGROUND: New generation transcatheter heart valves (THV) may improve clinical outcomes of transcatheter aortic valve implantation. METHODS AND RESULTS: In a nationwide, prospective, multicenter cohort study (Swiss Transcatheter Aortic Valve Implantation Registry, NCT01368250), outcomes of consecutive transfemoral transcatheter aortic valve implantation patients treated with the Sapien 3 THV (S3) versus the Sapien XT THV (XT) were investigated. An overall of 153 consecutive S3 patients were compared with 445 consecutive XT patients. Postprocedural mean transprosthetic gradient (6.5±3.0 versus 7.8±6.3 mm Hg, P=0.17) did not differ between S3 and XT patients, respectively. The rate of more than mild paravalvular regurgitation (1.3% versus 5.3%, P=0.04) and of vascular (5.3% versus 16.9%, P<0.01) complications were significantly lower in S3 patients. A higher rate of new permanent pacemaker implantations was observed in patients receiving the S3 valve (17.0% versus 11.0%, P=0.01). There were no significant differences for disabling stroke (S3 1.3% versus XT 3.1%, P=0.29) and all-cause mortality (S3 3.3% versus XT 4.5%, P=0.27). CONCLUSIONS: The use of the new generation S3 balloon-expandable THV reduced the risk of more than mild paravalvular regurgitation and vascular complications but was associated with an increased permanent pacemaker rate compared with the XT. Transcatheter aortic valve implantation using the newest generation balloon-expandable THV is associated with a low risk of stroke and favorable clinical outcomes. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT01368250.

Genetic associations at 53 loci highlight cell types and biological pathways relevant for kidney function.

Reduced glomerular filtration rate defines chronic kidney disease and is associated with cardiovascular and all-cause mortality. We conducted a meta-analysis of genome-wide association studies for estimated glomerular filtration rate (eGFR), combining data across 133,413 individuals with replication in up to 42,166 individuals. We identify 24 new and confirm 29 previously identified loci. Of these 53 loci, 19 associate with eGFR among individuals with diabetes. Using bioinformatics, we show that identified genes at eGFR loci are enriched for expression in kidney tissues and in pathways relevant for kidney development and transmembrane transporter activity, kidney structure, and regulation of glucose metabolism. Chromatin state mapping and DNase I hypersensitivity analyses across adult tissues demonstrate preferential mapping of associated variants to regulatory regions in kidney but not extra-renal tissues. These findings suggest that genetic determinants of eGFR are mediated largely through direct effects within the kidney and highlight important cell types and biological pathways.

Identification of Low-Risk Patients with Acute Symptomatic Pulmonary Embolism for Outpatient Therapy.

RATIONALE: Patients with acute symptomatic pulmonary embolism (PE) deemed to be at low risk for early complications might be candidates for partial or complete outpatient treatment. OBJECTIVES: To develop and validate a clinical prediction rule that accurately identifies patients with PE and low risk of short-term complications and to compare its prognostic ability with two previously validated models (i.e., the Pulmonary Embolism Severity Index [PESI] and the Simplified PESI [sPESI]) METHODS: Multivariable logistic regression of a large international cohort of patients with PE prospectively enrolled in the RIETE (Registro Informatizado de la Enfermedad TromboEmbólica) registry. MEASUREMENTS AND MAIN RESULTS: All-cause mortality, recurrent PE, and major bleeding up to 10 days after PE diagnosis were determined. Of 18,707 eligible patients with acute symptomatic PE, 46 (0.25%) developed recurrent PE, 203 (1.09%) bled, and 471 (2.51%) died. Predictors included in the final model were chronic heart failure, recent immobilization, recent major bleeding, cancer, hypotension, tachycardia, hypoxemia, renal insufficiency, and abnormal platelet count. The area under receiver-operating characteristic curve was 0.77 (95% confidence interval [CI], 0.75-0.78) for the RIETE score, 0.72 (95% CI, 0.70-0.73) for PESI (P < 0.05), and 0.71 (95% CI, 0.69-0.73) for sPESI (P < 0.05). Our RIETE score outperformed the prognostic value of PESI in terms of net reclassification improvement (P < 0.001), integrated discrimination improvement (P < 0.001), and sPESI (net reclassification improvement, P < 0.001; integrated discrimination improvement, P < 0.001). CONCLUSIONS: We built a new score, based on widely available variables, that can be used to identify patients with PE at low risk of short-term complications, assisting in triage and potentially shortening duration of hospital stay.

Prognostic value of PCSK9 levels in patients with acute coronary syndromes.

AIMS: Proprotein convertase subtilisin kexin 9 (PCSK9) is an emerging target for the treatment of hypercholesterolaemia, but the clinical utility of PCSK9 levels to guide treatment is unknown. We aimed to prospectively assess the prognostic value of plasma PCSK9 levels in patients with acute coronary syndromes (ACS). METHODS AND RESULTS: Plasma PCSK9 levels were measured in 2030 ACS patients undergoing coronary angiography in a Swiss prospective cohort. At 1 year, the association between PCSK9 tertiles and all-cause death was assessed adjusting for the Global Registry of Acute Coronary Events (GRACE) variables, as well as the achievement of LDL cholesterol targets of <1.8 mmol/L. Patients with higher PCSK9 levels at angiography were more likely to have clinical familial hypercholesterolaemia (rate ratio, RR 1.21, 95% confidence interval, CI 1.09-1.53), be treated with lipid-lowering therapy (RR 1.46, 95% CI 1.30-1.63), present with longer time interval of chest pain (RR 1.29, 95% CI 1.09-1.53) and higher C-reactive protein levels (RR 1.22, 95% CI 1.16-1.30). PCSK9 increased 12-24 h after ACS (374 ± 149 vs. 323 ± 134 ng/mL, P < 0.001). At 1 year follow-up, HRs for upper vs. lower PCSK9-level tertiles were 1.13 (95% CI 0.69-1.85) for all-cause death and remained similar after adjustment for the GRACE score. Patients with higher PCSK9 levels were less likely to reach the recommended LDL cholesterol targets (RR 0.81, 95% CI 0.66-0.99). CONCLUSION: In ACS patients, high initial PCSK9 plasma levels were associated with inflammation in the acute phase and hypercholesterolaemia, but did not predict mortality at 1 year.

Impact of Aldosterone Antagonists on Sudden Cardiac Death Prevention in Heart Failure and Post-Myocardial Infarction Patients: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

BACKGROUND AND OBJECTIVES: Sudden cardiac death (SCD) is a severe burden of modern medicine. Aldosterone antagonist is publicized as effective in reducing mortality in patients with heart failure (HF) or post myocardial infarction (MI). Our study aimed to assess the efficacy of AAs on mortality including SCD, hospitalization admission and several common adverse effects. METHODS: We searched Embase, PubMed, Web of Science, Cochrane library and clinicaltrial.gov for randomized controlled trials (RCTs) assigning AAs in patients with HF or post MI through May 2015. The comparator included standard medication or placebo, or both. Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines were followed. Event rates were compared using a random effects model. Prospective RCTs of AAs with durations of at least 8 weeks were selected if they included at least one of the following outcomes: SCD, all-cause/cardiovascular mortality, all-cause/cardiovascular hospitalization and common side effects (hyperkalemia, renal function degradation and gynecomastia). RESULTS: Data from 19,333 patients enrolled in 25 trials were included. In patients with HF, this treatment significantly reduced the risk of SCD by 19% (RR 0.81; 95% CI, 0.67-0.98; p = 0.03); all-cause mortality by 19% (RR 0.81; 95% CI, 0.74-0.88, p<0.00001) and cardiovascular death by 21% (RR 0.79; 95% CI, 0.70-0.89, p<0.00001). In patients with post-MI, the matching reduced risks were 20% (RR 0.80; 95% CI, 0.66-0.98; p = 0.03), 15% (RR 0.85; 95% CI, 0.76-0.95, p = 0.003) and 17% (RR 0.83; 95% CI, 0.74-0.94, p = 0.003), respectively. Concerning both subgroups, the relative risks respectively decreased by 19% (RR 0.81; 95% CI, 0.71-0.92; p = 0.002) for SCD, 18% (RR 0.82; 95% CI, 0.77-0.88, p < 0.0001) for all-cause mortality and 20% (RR 0.80; 95% CI, 0.74-0.87, p < 0.0001) for cardiovascular mortality in patients treated with AAs. As well, hospitalizations were significantly reduced, while common adverse effects were significantly increased. CONCLUSION: Aldosterone antagonists appear to be effective in reducing SCD and other mortality events, compared with placebo or standard medication in patients with HF and/or after a MI.

Polyphenol intake and mortality risk: a re-analysis of the PREDIMED trial

Background: Polyphenols may lower the risk of cardiovascular disease (CVD) and other chronic diseases due to their antioxidant and anti-inflammatory properties, as well as their beneficial effects on blood pressure, lipids and insulin resistance. However, no previous epidemiological studies have evaluated the relationship between the intake of total polyphenols intake and polyphenol subclasses with overall mortality. Our aim was to evaluate whether polyphenol intake is associated with all-cause mortality in subjects at high cardiovascular risk. Methods: We used data from the PREDIMED study, a 7,447-participant, parallel-group, randomized, multicenter, controlled five-year feeding trial aimed at assessing the effects of the Mediterranean Diet in primary prevention of cardiovascular disease. Polyphenol intake was calculated by matching food consumption data from repeated food frequency questionnaires (FFQ) with the Phenol-Explorer database on the polyphenol content of each reported food. Hazard ratios (HR) and 95% confidence intervals (CI) between polyphenol intake and mortality were estimated using time-dependent Cox proportional hazard models. Results: Over an average of 4.8 years of follow-up, we observed 327 deaths. After multivariate adjustment, we found a 37% relative reduction in all-cause mortality comparing the highest versus the lowest quintiles of total polyphenol intake (hazard ratio (HR) = 0.63; 95% CI 0.41 to 0.97; P for trend = 0.12). Among the polyphenol subclasses, stilbenes and lignans were significantly associated with reduced all-cause mortality (HR =0.48; 95% CI 0.25 to 0.91; P for trend = 0.04 and HR = 0.60; 95% CI 0.37 to 0.97; P for trend = 0.03, respectively), with no significant associations apparent in the rest (flavonoids or phenolic acids). Conclusions: Among high-risk subjects, those who reported a high polyphenol intake, especially of stilbenes and lignans, showed a reduced risk of overall mortality compared to those with lower intakes. These results may be useful to determine optimal polyphenol intake or specific food sources of polyphenols that may reduce the risk of all-cause mortality.

Effects of cobalt-chromium everolimus eluting stents or bare metal stent on fatal and non-fatal cardiovascular events: patient level meta-analysis

Objectives: To examine the safety and effectiveness of cobalt-chromium everolimus eluting stents compared with bare metal stents. Design: Individual patient data meta-analysis of randomised controlled trials. Cox proportional regression models stratified by trial, containing random effects, were used to assess the impact of stent type on outcomes. Hazard ratios with 95% confidence interval for outcomes were reported. Data sources and study selection: Medline, Embase, the Cochrane Central Register of Controlled Trials. Randomised controlled trials that compared cobalt-chromium everolimus eluting stents with bare metal stents were selected. The principal investigators whose trials met the inclusion criteria provided data for individual patients. Primary outcomes: The primary outcome was cardiac mortality. Secondary endpoints were myocardial infarction, definite stent thrombosis, definite or probable stent thrombosis, target vessel revascularisation, and all cause death. Results: The search yielded five randomised controlled trials, comprising 4896 participants. Compared with patients receiving bare metal stents, participants receiving cobalt-chromium everolimus eluting stents had a significant reduction of cardiac mortality (hazard ratio 0.67, 95% confidence interval 0.49 to 0.91; P=0.01), myocardial infarction (0.71, 0.55 to 0.92; P=0.01), definite stent thrombosis (0.41, 0.22 to 0.76; P=0.005), definite or probable stent thrombosis (0.48, 0.31 to 0.73; P<0.001), and target vessel revascularisation (0.29, 0.20 to 0.41; P<0.001) at a median follow-up of 720 days. There was no significant difference in all cause death between groups (0.83, 0.65 to 1.06; P=0.14). Findings remained unchanged at multivariable regression after adjustment for the acuity of clinical syndrome (for instance, acute coronary syndrome v stable coronary artery disease), diabetes mellitus, female sex, use of glycoprotein IIb/IIIa inhibitors, and up to one year v longer duration treatment with dual antiplatelets. Conclusions: This meta-analysis offers evidence that compared with bare metal stents the use of cobalt-chromium everolimus eluting stents improves global cardiovascular outcomes including cardiac survival, myocardial infarction, and overall stent thrombosis.

Effects of cobalt-chromium everolimus eluting stents or bare metal stent on fatal and non-fatal cardiovascular events: patient level meta-analysis

Objectives: To examine the safety and effectiveness of cobalt-chromium everolimus eluting stents compared with bare metal stents. Design: Individual patient data meta-analysis of randomised controlled trials. Cox proportional regression models stratified by trial, containing random effects, were used to assess the impact of stent type on outcomes. Hazard ratios with 95% confidence interval for outcomes were reported. Data sources and study selection: Medline, Embase, the Cochrane Central Register of Controlled Trials. Randomised controlled trials that compared cobalt-chromium everolimus eluting stents with bare metal stents were selected. The principal investigators whose trials met the inclusion criteria provided data for individual patients. Primary outcomes: The primary outcome was cardiac mortality. Secondary endpoints were myocardial infarction, definite stent thrombosis, definite or probable stent thrombosis, target vessel revascularisation, and all cause death. Results: The search yielded five randomised controlled trials, comprising 4896 participants. Compared with patients receiving bare metal stents, participants receiving cobalt-chromium everolimus eluting stents had a significant reduction of cardiac mortality (hazard ratio 0.67, 95% confidence interval 0.49 to 0.91; P=0.01), myocardial infarction (0.71, 0.55 to 0.92; P=0.01), definite stent thrombosis (0.41, 0.22 to 0.76; P=0.005), definite or probable stent thrombosis (0.48, 0.31 to 0.73; P<0.001), and target vessel revascularisation (0.29, 0.20 to 0.41; P<0.001) at a median follow-up of 720 days. There was no significant difference in all cause death between groups (0.83, 0.65 to 1.06; P=0.14). Findings remained unchanged at multivariable regression after adjustment for the acuity of clinical syndrome (for instance, acute coronary syndrome v stable coronary artery disease), diabetes mellitus, female sex, use of glycoprotein IIb/IIIa inhibitors, and up to one year v longer duration treatment with dual antiplatelets. Conclusions: This meta-analysis offers evidence that compared with bare metal stents the use of cobalt-chromium everolimus eluting stents improves global cardiovascular outcomes including cardiac survival, myocardial infarction, and overall stent thrombosis.

Factors predicting mortality in type 2 diabetes. With special reference to physical exercise, blood pressure, proteinuria, inflammation and P wave duration

Background: Type 2 diabetes patients have a 2-4 fold risk of cardiovascular disease (CVD) compared to the general population. In type 2 diabetes, several CVD risk factors have been identified, including obesity, hypertension, hyperglycemia, proteinuria, sedentary lifestyle and dyslipidemia. Although much of the excess CVD risk can be attributed to these risk factors, a significant proportion is still unknown. Aims: To assess in middle-aged type 2 diabetic subjects the joint relations of several conventional and non-conventional CVD risk factors with respect to cardiovascular and total mortality. Subjects and methods: This thesis is part of a large prospective, population based East-West type 2 diabetes study that was launched in 1982-1984. It includes 1,059 middle-aged (45-64 years old) participants. At baseline, a thorough clinical examination and laboratory measurements were performed and an ECG was recorded. The latest follow-up study was performed 18 years later in January 2001 (when the subjects were 63-81 years old). The study endpoints were total mortality and mortality due to CVD, coronary heart disease (CHD) and stroke. Results: Physically more active patients had significantly reduced total, CVD and CHD mortality independent of high-sensitivity C-reactive protein (hs-CRP) levels unless proteinuria was present. Among physically active patients with a hs-CRP level >3 mg/L, the prognosis of CVD mortality was similar to patients with hs-CRP levels ≤3 mg/L. The worst prognosis was among physically inactive patients with hs-CRP levels >3 mg/L. Physically active patients with proteinuria had significantly increased total and CVD mortality by multivariate analyses. After adjustment for confounding factors, patients with proteinuria and a systolic BP <130 mmHg had a significant increase in total and CVD mortality compared to those with a systolic BP between 130 and 160 mmHg. The prognosis was similar in patients with a systolic BP <130 mmHg and ≥160 mmHg. Among patients without proteinuria, a systolic BP <130 mmHg was associated with a non-significant reduction in mortality. A P wave duration ≥114 ms was associated with a 2.5-fold increase in stroke mortality among patients with prevalent CHD or claudication. This finding persisted in multivariable analyses. Among patients with no comorbidities, there was no relationship between P wave duration and stroke mortality. Conclusions: Physical activity reduces total and CVD mortality in patients with type 2 diabetes without proteinuria or with elevated levels of hs-CRP, suggesting that the anti-inflammatory effect of physical activity can counteract increased CVD morbidity and mortality associated with a high CRP level. In patients with proteinuria the protective effect was not, however, present. Among patients with proteinuria, systolic BP <130 mmHg may increase mortality due to CVD. These results demonstrate the importance of early intervention to prevent CVD and to control all-cause mortality among patients with type 2 diabetes. The presence of proteinuria should be taken into account when defining the target systolic BP level for prevention of CVD deaths. A prolongation of the duration of the P wave was associated with increased stroke mortality among high-risk patients with type 2 diabetes. P wave duration is easy to measure and merits further examination to evaluate its importance for estimation of the risk of stroke among patients with type 2 diabetes.

Quantification and Clinical Relevance of Cystatin C

An aging population and increasing rates of diabetes mellitus contribute to a high prevalence of kidney dysfunction – approximately 10 percent of adults in developed countries have chronic kidney disease (CKD). CKD is a progressive loss of kidney function and this remains permanent. Early recognition of this condition is important for prevention or impeding severe adverse cardiac and renal outcomes. Cystatin C is a low molecular weight cysteine protease inhibitor that has emerged as a biomarker of kidney function. The special potential of plasma cystatin C in this setting is related to its independency of muscle mass, which is a remarkable limitation of the traditional marker creatinine. Cystatin C is a sensitive marker in diagnosing mild and moderate CKD, especially in small children, in the elderly and in conditions where muscle mass is affected. Cystatin C is quantified with immunoassays, mainly based on particle-enhanced nephelometry (PENIA) or turbidimetry (PETIA). The aim of this study was to develop a rapid and reliable assay for quantification of human cystatin C in plasma or serum by utilizing time-resolved fluorescence-based immunoassay methods. This was accomplished by utilizing different antibodies, including polyclonal and 7 monoclonal antibodies against cystatin C. Different assay designs were tested and the best assay was further modified to a dry-reagent double monoclonal assay run on an automated immunonalyzer. This assay was evaluated for clinical performance in estimating reduced kidney function and in predicting risk of adverse outcomes in patients with non-ST elevation acute coronary syndrome. Of the tested assay designs, heterogeneous non-competitive assay had the best performace and was chosen to be developed further. As an automated double monoclonal assay, this assay enabled a reliable measurement of clinically relevant cystatin C concentrations. It also showed a stronger concordance with the reference clearance method than the conventional PETIA method in patients with reduced kidney function. Risk of all-cause mortality and combined events, defined by death and myocardial infarction, increased with higher cystatin C and cystatin C remained an independent predictor of death and combined events after adjustment to nonbiochemical baseline factors. In conclusion, the developed dry-reagent double monoclonal assay allows rapid and reliable quantitative measurement of cystatin C. As measured with the developed assay, cystatin C is a potential predictor of adverse outcomes in cardiac patients.

Percutaneous Coronary Intervention in Patients with Atrial Fibrillation: A Study of Factors Affecting Outcome, with a Special Emphasis on Periprocedural Antithrombotic Treatment

Antithrombotic treatment of patients with atrial fibrillation (AF) undergoing percutaneous coronary intervention (PCI) is a delicate balancing between the risk of thromboembolism and the risk of bleeding. The purpose of this dissertation was to analyze current antithrombotic treatment strategies at the periprocedural stage and report outcomes in-hospital and at 1-month follow-up, and to evaluate the effect of renal impairment and predictive values of various bleeding scores on 1-year outcome after PCI in patients with AF. The first article was based on retrospective data from 7 Finnish hospitals between 2002–2006 (n=377), while the others were based on a prospective 17-center European register (AFCAS) gathered between 2008–2010 (n=963). The main findings in patients with AF undergoing PCI were: The use of glycoprotein IIb/IIIa inhibitors during PCI was associated with a four- to five-fold increase in the risk of major bleeding (I). Uninterrupted warfarin treatment did not increase perioperative complications and seemed to decrease bleeding complications compared to heparin bridging (II). Already mild renal impairment (eGFR 60–90mL/min) was associated with a 2.3-fold risk of all-cause mortality during the 12 months following PCI (III). Major adverse cardiac events occurred in 4.5% and bleeding complications in 7.1% of patients in the AFCAS register by 1-month follow-up (IV). In a study of patients in AFCAS register, all currently used bleeding risk scores were poor predictors of bleeding complications by 1-year follow-up (V). The findings will help improve treatment strategies for this fragile patient population with a high risk of bleeding and thrombotic complications.

Oxidized LDL lipids as a risk factor for atherosclerosis

University of Turku, Faculty of Medicine, Department of Clinical Medicine, Department of Physical Activity and Health, Paavo Nurmi Centre, Doctoral Programme of Clinical Investigation, University of Turku, Turku, Finland. Annales Universitatis Turkuensis. Medica – Odontologica, Turku, Finland, 2014. Background: Atherosclerosis progression spans an entire lifetime and has a wide pool of risk factors. Oxidized LDL (oxLDL) is a crucial element in the progression of atherosclerosis. As a rather new member in the atherosclerosis risk factor family, its interaction with the traditional pro-atherogenic contributors that occur at different ages is poorly known. Aims: The aim of this study was to investigate oxLDL and its relation to major contributing risk factors in estimating atherosclerosis risk in data consisting mostly of adult men. The study subjects of this study consisted of four different sets of data, one of which contained also women. The age range of participants was 18-100 years and totaled 2337 participants (of whom 69% were men). Data on anthropometric and hormonal parameters, laboratory measures and medical records were assessed during 1998-2009. Results: Obesity was paralleled with high concentrations of oxLDL, which consequentially was reduced by weight reduction. Importantly, successful weight maintenance preserveed this benefit. A shift from insulin sensitivity to insulin resistance increased oxLDL. Smokers had more oxLDL than non-smokers. A combination of obesity and smoking, or smoking and low serum total testosterone,resulted in even higher levels of oxLDL than any of the three conditions alone. Proportioning oxLDL to HDL-c or apoA1 stood out as a risk factor of all-cause mortality in the elderly. Conclusions: OxLDL was associated with aging, androgens, smoking, obesity, insulin metabolism, weight balance and other circulating lipid classes. Through this variety of metabolic environments containing both constant conditions (aging and gender) as well as lifestyle issues, these findings supported an essential and multidimensional role that oxLDL plays in atherosclerosis pathogenesis.

Gross proteinuria is a strong risk predictor for cardiovascular mortality in Brazilian type 2 diabetic patients

Increased proteinuria is recognized as a risk predictor for all-cause and cardiovascular mortality in diabetic patients; however, no study has evaluated these relationships in Brazilian patients. The aim of this study was to investigate the prognostic value of gross proteinuria for all-cause and cardiovascular mortalities and for cardiovascular morbidity in a cohort study of 471 type 2 diabetic individuals followed for up to 7 years. Several clinical, laboratory and electrocardiographic variables were obtained at baseline. The relative risks for all-cause, cardiovascular and cardiac mortalities and for cardiovascular and cardiac events associated with the presence of overt proteinuria (>0.5 g/24 h) were assessed by Kaplan-Meier survival curves and by multivariate Cox regression model. During a median follow-up of 57 months (range 2-84 months), 121 patients (25.7%) died, 44 from cardiovascular and 30 from cardiac causes, and 106 fatal or non-fatal cardiovascular events occurred. Gross proteinuria was an independent risk predictor of all-cause, cardiovascular and cardiac mortalities and of cardiovascular morbidity with adjusted relative risks ranging from 1.96 to 4.38 for the different endpoints. This increased risk remained significant after exclusion of patients with prior cardiovascular disease at baseline from the multivariate analysis. In conclusion, gross proteinuria was a strong predictor of all-cause, cardiovascular and cardiac mortalities and also of cardiovascular morbidity in a Brazilian cohort of type 2 diabetic patients. Intervention studies are necessary to determine whether the reduction of proteinuria can decrease morbidity and mortality of type 2 diabetes in Brazil.

Impact of β-2 Thr164Ile and combined β-adrenergic receptor polymorphisms on prognosis in a cohort of heart failure outpatients

Genetic polymorphisms of adrenergic receptors (ARs) have been associated with the development, progression, and prognosis of patients with heart failure (HF), with few data for the Brazilian population. We evaluated the role of the β2-AR Thr164Ile polymorphism at codon 164 on prognosis in a prospective study on 315 adult Brazilian HF patients, predominantly middle-aged Caucasian men in functional class I-II, with severe left ventricular systolic dysfunction. Genomic DNA was extracted from peripheral blood and β2-AR164 genotypes were detected by PCR followed by restriction fragment length analysis. During a median follow-up of 3 years, 95 deaths occurred and 57 (60%) were HF-related. Unexpectedly, Ile164 carriers (N = 12) had no HF-related events (log-rank P value = 0.13). Analysis using genotype combination with β1-AR polymorphisms at codons 49 and 389 identified patients with favorable genotypes (Thr164Ile of β2-AR, Gly49Gly of β1-AR and/or Gly389Gly of β1-AR), who had lower HF-related mortality (P = 0.01). In a Cox proportional hazard model adjusted for other clinical characteristics, having any of the favorable genotypes remained as independent predictor of all-cause (hazard ratio (HR): 0.41, 95%CI: 0.17-0.95) and HF-related mortality (HR: 0.12, 95%CI: 0.02-0.90). These data show that the β2-AR Thr164Ile polymorphism had an impact on prognosis in a Brazilian cohort of HF patients. When combined with common β1-AR polymorphisms, a group of patients with a combination of favorable genotypes could be identified.

Effects of propofol on damage of rat intestinal epithelial cells induced by heat stress and lipopolysaccharides

Gut-derived endotoxin and pathogenic bacteria have been proposed as important causative factors of morbidity and death during heat stroke. However, it is still unclear what kind of damage is induced by heat stress. In this study, the rat intestinal epithelial cell line (IEC-6) was treated with heat stress or a combination of heat stress and lipopolysaccharide (LPS). In addition, propofol, which plays an important role in anti-inflammation and organ protection, was applied to study its effects on cellular viability and apoptosis. Heat stress, LPS, or heat stress combined with LPS stimulation can all cause intestinal epithelial cell damage, including early apoptosis and subsequent necrosis. However, propofol can alleviate injuries caused by heat stress, LPS, or the combination of heat stress and LPS. Interestingly, propofol can only mitigate LPS-induced intestinal epithelial cell apoptosis, and has no protective role in heat-stress-induced apoptosis. This study developed a model that can mimic the intestinal heat stress environment. It demonstrates the effects on intestinal epithelial cell damage, and indicated that propofol could be used as a therapeutic drug for the treatment of heat-stress-induced intestinal injuries.