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Aim: To assess the impact of cholesterol lowering on positive exercise stress tests in hypercholesterolaemic patients with normal coronary angiograms.Methods: 43 non-diabetic patients aged 43-61 years, with total serum cholesterol concentrations of more than 7.75 mmol/l, positive exercise tests, and normal coronary angiograms, were started on the American Heart Association step 1 diet. After 12 weeks these patients were randomly assigned to treatment for another 16 weeks with the diet alone (diet group, n = 20) or with the diet plus lovastatin or simvastatin (statin group, n = 23). After this 28 week run in period, statins were withdrawn and lipid profile tests and exercise tests were done and repeated 20 weeks later.Results: At week 28, the statin group but not the diet group had significant reductions from baseline (week 12) in plasma total cholesterol (p < 0.0001), low density lipoprotein (p < 0.0001), and triglyceride (p < 0.0001). The number of patients with positive exercise tests decreased from 23 to three in the statin group and from 20 to 15 in the diet group (p = 0.01). After the final 20 weeks without statins, lipid profiles returned to baseline levels in all 17 patients remaining in the statin group, and exercise tests were again positive in 15 of these patients.Conclusions: In hypercholesterolaemic patients with normal coronary arteries, cholesterol lowering treatment reduces myocardial ischaemia, as shown by the beneficial effects on exercise testing. [ABSTRACT FROM AUTHOR] more...

Blood pressure (BP) reduction was compared between patients receiving angiotensin-converting enzyme inhibitors alone and patients receiving these medications plus statins after 3 months of dietary intervention. Although BP was similarly reduced at week 4, the statin-treated group had a greater reduction in BP and total cholesterol levels at week 16, suggesting a synergistic effect between cholesterol lowering with statins and angiotensin-converting enzyme inhibitor treatment for hypertensive patients. [ABSTRACT FROM AUTHOR] more...

Coronary flow reserve is mainly influenced by the combination of luminal stenosis and vascular dilation capacity. Thus, after statin treatment, the reduction of ischemic threshold in patients submitted to exercise testing could be intensely influenced by angiographic severity. In this study, we verify the effect of statin treatment on exercise-induced myocardial ischemia in hypercholesterolemic patients with a broad range of coronary angiographic severities. Patients with 2 consecutive positive exercise tests, coronary stenosis > or =70%, total cholesterol > or =300 mg/dl, and triglycerides < or =200 mg/dl were randomly assigned to a 16-week treatment period with either diet alone (n = 39) or diet plus statins (simavastatin, n = 31 and pravastatin, n = 10). Statin-treated patients had a significant variation in total cholesterol (-46% vs -2.7%; p <0.01), low-density lipoprotein cholesterol (-58% vs 0.8%; p <0.01), and high-density cholesterol (+28% vs -6%; p <0.05) in comparison with the diet-only group. After 16 weeks of treatment, 36 patients (92%) in the diet group still had positive exercise tests, whereas only 7 patients (15%) of the statin group had a positive test (p <0.01). The proportion of positive tests was significantly reduced in subgroups of patients with 1-, 2-, or 3-vessel disease. Regarding the severity of coronary stenosis, the proportion of positive tests was significantly reduced in patients with stenosis between 70% and 90% and in patients with stenosis > or =90%. Moreover, the proportion of positive tests tended to decrease to a greater extent in patients with mild coronary disease. In conclusion, cholesterol-lowering treatment with statins reduces exercise-induced myocardial ischemia in hypercholesterolemic patients with mild or severe epicardial coronary stenosis. [ABSTRACT FROM AUTHOR] more...

Resveratrol (RSV) improves metabolic functions, but its tissue-specific effects on diabetes remain unclear. This study investigated RSV's impact on molecular pathways in an experimental model of diabetes in cardiac and skeletal muscles and adipose tissue. Wistar rats were assigned to control (C), control treated with RSV (RC), diabetic (D), and diabetic treated with RSV (RD). Diabetes was induced using streptozotocin and nicotinamide, and RSV was administered for six weeks. In diabetic rats, RSV treatment significantly reduced collagen accumulation in cardiac and skeletal muscle tissues compared to untreated diabetic controls, although it did not restore muscle mass. Adipose tissue in diabetic rats exhibited a significant reduction of 3.4 times in collagen levels following RSV treatment. However, this reduction was not associated with any measurable improvement in tissue function. In cardiac tissue, RSV downregulated phosphorylated protein kinase B (AKT)/AKT and phosphorylated ribosomal protein S6 (rpS6)/rpS6 while mammalian target of rapamycin (mTOR) activity remained unchanged. In skeletal muscle, RSV suppressed rpS6 phosphorylation without affecting (mTOR) signaling. RSV enhanced mTOR and Beclin-1 expression in adipose tissue, though metabolic dysfunction persisted. RSV reduced receptors for advanced glycation end-product expression in all tissues, indicating the modulation of hyperglycemia-driven pathways. RSV improved fibrosis and signaling pathways but failed to reverse abnormal tissue growth patterns, including cardiac hypertrophy, skeletal muscle atrophy, and adipose tissue atrophy. more...

Background: Limited research has explored sex-specific differences in death predictors of HF patients with ischemic (iCMP) and nonischemic (niCMP) cardiomyopathy. This study assessed sex differences in niCMP and iCMP prognosis., Methods: We studied 7487 patients with HF between February 2017 and September 2020. Clinical features and echocardiographic findings were collected. We used Kaplan-Meier, Cox proportional hazard models, and chi-square scores of Cox regression to determine death predictors in women and men., Results: The mean age was 64.3 ± 14.2 years, with 4417 (59%) males. Women with iCMP and niCMP exhibited a significantly higher mean age, higher mean left ventricular ejection fraction, and smaller left ventricular diastolic diameter than men. Over 2.26 years of follow-up, 325 (14.7%) women and 420 (15.7%) men, and 211 women (24.5%) and 519 men (29.8%) with niCMP ( p = NS) and iCMP ( p = 0.004), respectively, died. The cumulative incidence of death was higher in men with iCMP (log-rank p < 0.0001) but similar with niCMP. Cox regression showed chronic kidney disease, diabetes, stroke, atrial fibrillation, age, and myocardial infarction as the main predictors of death for iCMP in women and men., Conclusions: Women exhibited a better prognosis than men with iCMP, but similar for niCMP. Nevertheless, sex was not an independent predictor of death for both CMP. more...

Background : Sirtuin 1 (SIRT1) has been associated with longevity and protection against cardiometabolic diseases, but little is known about how it influences human vascular function. Therefore, this study evaluated the effects of SIRT1 activation by resveratrol and energy restriction on vascular reactivity in adults. Methods : A randomized trial allocated 48 healthy adults (24 women and 24 men), aged 55 to 65 years, to resveratrol supplementation or energy restriction for 30 days. Blood lipids, glucose, insulin, C-reactive protein, noradrenaline, SIRT1 (circulating and gene expression), and flow-mediated vasodilation (FMD) and nitrate-mediated vasodilation (NMD) were measured. Results : Both interventions increased circulating SIRT1 ( p < 0.001). Pre- and post-tests changes of plasma noradrenaline were significant for both groups (resveratrol: p = 0.037; energy restriction: p = 0.008). Baseline circulating SIRT1 was inversely correlated with noradrenaline (r = -0.508; p < 0.01), and post-treatment circulating SIRT1 was correlated with NMD (r = 0.433; p < 0.01). Circulating SIRT1 was a predictor of FMD in men ( p = 0.045), but not in women. SIRT1 was an independent predictor of NMD ( p = 0.026) only in the energy restriction group. Conclusions : Energy restriction and resveratrol increased circulating SIRT1 and reduced sympathetic activity similarly in healthy adults. SIRT1 was independently associated with NMD only in the energy restriction group. more...

The Kansas City Cardiomyopathy Questionnaire-12 (KCCQ-12) is a simple, feasible, and sensitive questionnaire developed in English for assessing the health status (symptoms, function, and quality of life) of patients with heart failure (HF). We aimed to assess the internal consistency and construct validity of the Portuguese version of KCCQ-12. We administered the KCCQ-12, the Minnesota Living Heart Failure (MLHFQ), and the New York Heart Association (NYHA) classification by telephone. Internal consistency was assessed with Cronbach's Alpha (α-Cronbach) and construct validity with correlations to the MLHFQ and NYHA. Internal consistency was high (α-Cronbach = 0.92 for the Overall Summary score and 0.77-0.85 for the subdomains). Construct validity was supported by finding high correlations between the KCCQ-12 Physical Limitation and the Symptom Frequency domains with the physical domain of the MLHFQ (r = -0.70 and r = -0.76, p < 0.001 for both) and the Overall Summary scale with NYHA classifications (r = -0.72, p < 0.001). The Portuguese version of KCCQ-12 has high internal consistency and shows a convergent construct validity with other measures quantifying the health status of patients with chronic HF and can be used confidently in Brazil for research and clinical care. more...

The myocardial infarction (MI) types 4a and 5 guidelines recommend cardiac troponin (cTn) diagnostic decision limits of 5 and 10 times the 99th percentile, respectively. Different cTn kits elicit different responses, so the MI diagnosis is still challenging. The study aimed to establish the cutoff values and the accuracy of three different cTnI kits in the diagnosis of post-procedural MI. We analyzed 115 patients with multivessel stable chronic coronary artery disease; 26 underwent percutaneous coronary intervention, and 89 underwent coronary artery bypass graft. Delayed-enhancement magnetic resonance imaging was performed before and after each intervention for definitive MI diagnoses. Two contemporary and one high-sensitivity cTnI immunoassays were used. ROC curves determined the accuracy of each assay. Low accuracy was observed after applying the current guidelines recommendations. The three cTnI assays accuracies improved when adjusted by the new ROC cutoffs, reaching 82% for MI type 5 for all assays, and 78%, 88%, and 87% for MI type 4 for Siemens, Beckman, and Abbott, respectively. The ultrasensitive and contemporary tests' accuracy for MI types 4a and 5 diagnoses are equivalent when adjusted for these new cutoffs. The hs-cTnI assays had lower accuracy than contemporary tests for MI types 4a and 5 diagnoses. more...

Background: Heart failure (HF) is one of the leading causes of death worldwide. Studies show that women have better survival rates than men despite higher hospitalizations. However, little is known about differences in mortality and predictors of death in women and men with HF with preserved (HFpEF), mildly reduced (HFmrEF), and reduced ejection fraction (HFrEF)., Methods: From February 2017 to September 2020, mortality and predictors of death were analyzed in women and men with HF. Baseline data included clinical characteristics and echocardiographic findings., Results: A total of 11,282 patients, 63.9 ± 14.4 years, including 6256 (55.4%) males, were studied. Females were older, had a higher baseline mean left ventricular ejection fraction (LVEF) and lower left ventricular diastolic diameter. During follow-ups, 1375 (22%) men and 925 (18.4%) women died. Cumulative incidence of death was higher in men with HFrEF but similar for HFmrEF and HFpEF. Cox regression for death showed renal dysfunction, stroke, diabetes, atrial fibrillation, age, LVEF, valve disease, MI, and hypertensive CMP as independent death predictors for all HF patients., Conclusions: Women had a better prognosis than men in HFrEF and similar mortality for HFmrEF and HFpEF, but sex was not an independent predictor of death for all HF subtypes. more...

Introduction: HDL function has gained prominence in the literature as there is a greater predictive capacity for risk in early coronary artery disease when compared to the traditional parameters. However, it is unclear how dietary energy restriction and atorvastatin influence HDL function., Methods: A randomized controlled trial with 39 women with early CAD divided into three groups (n = 13): energy restriction (30% of VET), atorvastatin (80 mg), and control. Analyses of traditional biochemical markers (lipid and glucose profile), circulating Sirt-1, and HDL function (lipid composition, lipid transfer, and antioxidant capacity)., Results: Participants' mean age was 50.5 ± 3.8 years. Energy restriction increased Sirt-1 by 63.6 pg/mL (95%CI: 1.5-125.7; p = 0.045) and reduced BMI by 0.8 kg/m 2 (95%CI: -1.349--0.273; p = 0.004) in a manner independent of other cardiometabolic factors. Atorvastatin reduced LDL-c by 40.0 mg/dL (95%CI: -69.910--10.1; p = 0.010). Increased Sirt-1 and reduced BMI were independently associated with reduced phospholipid composition of HDL (respectively, β = -0.071; CI95%:-0.136--0.006; p = 0.033; β = 7.486; CI95%:0.350-14.622; p = 0.040). Reduction in BMI was associated with lower HDL-free cholesterol (β = 0.818; CI95%:0.044-1.593; p = 0.039). LDL-c reduction by statins was associated with reduced maximal lipid peroxide production rate of HDL (β = 0.002; CI95%:0.000-0.003; p = 0.022) and total conjugated diene generation (β = 0.001; CI95%:0.000-0.001; p = 0.029)., Conclusion: This study showed that energy restriction and atorvastatin administration were associated with changes in lipid profile, serum Sirt-1 concentrations, and HDL function. more...

Whilst CPR training is widely recommended, quality of performance is infrequently explored. We evaluated whether a checklist can be an adequate tool for chest compression quality assessment in schoolchildren, compared with a real-time software. This observational study (March 2019-2020) included 104 schoolchildren with no previous CPR training (11-17 years old, 66 girls, 84 primary schoolchildren, 20 high schoolchildren). Simultaneous evaluations of CPR quality were performed using an observational checklist and real-time software. High-quality CPR was determined as a combination of 70% correct maneuvers in compression rate (100-120/min), depth (5-6 cm), and complete release, using a real-time software and three positive performance in skills using a checklist. We adjusted a multivariate logistic regression model for age, sex, and BMI. We found moderate to high agreement percentages in quality of CPR performance (rate: 68.3%, depth: 79.8%, and complete release: 91.3%) between a checklist and real-time software. Only 38.5% of schoolchildren (~14 years-old, ~54.4 kg, and ~22.1 kg/m 2 ) showed high-quality CPR. High-quality CPR was more often performed by older schoolchildren (OR = 1.43, 95%IC:1.09-1.86), and sex was not an independent factor (OR = 1.26, 95%IC:0.52-3.07). For high-quality CPR in schoolchildren, a checklist showed moderate to high agreement with real-time software. Better performance was associated with age regardless of sex and BMI. more...

Background: cardiovascular diseases (CVD) are Brazil's leading causes of death in women and men. This study analyzed age-adjusted death rate (DRaj) trends from all causes of death (ACD), CVD, ischemic heart disease (IHD), and stroke in women and men aged 35 to 74 years from 1996 to 2019., Methods: We analyzed DRaj trends for all causes of death (ACD), CVD, IHD, and stroke. Data were from the Ministry of Health mortality database. Joinpoint Regression Program™ performed trend analysis and adjustments in death rates. Average annual percentage change (AAPC) determined the intensity of changes., Results: In women, DRaj reduced for ACD (AAPC = -1.6%); CVD (AAPC = -2.6%); IHD (AAPC = -1.9%); and stroke (AAPC = -4.6%) ( p < 0.001 for all). In men, ACD reduced from 1996 to 2004 (AAPC = -0.9%; p < 0.001), from 2012 to 2019 (AAPC = -1.9%; p < 0.001), and unchanged from 2004 to 2012; CVD (AAPC = -2.1%); IHD (AAPC = -1.5%); stroke (AAPC = -4.9%) ( p < 0.001 for all) reduced from 1996 to 2019. From 1996 to 2019, the male/female ratio for ACD remained unchanged. CVD increased from 1.58 to 1.83, IHD from 1.99 to 2.30, and stroke from 1.52 to 1.83., Conclusion: ACD, CVD, IHD, and stroke were reduced more significantly in women, and the ratio of CVD, IHD, and CVD in men and women increased more in men. Future studies will be needed to determine the main factors responsible for a better outcome in women. more...

Background: The COVID-19 epidemic overloaded the São Paulo metropolitan area (SPMA) health system in 2020. The leading hospitals directed their attention to patients with COVID-19. At the same time, the SPMA Health Secretary decreed social isolation (SI), which compromised the care for cardiovascular diseases (CVD), even though higher cardiovascular events were expected., Methods: This study analyzed mortality from CVD, ischemic heart disease (IHD), and stroke, along with hospital admissions for CVD, IHD, stroke, and SI in the SPMA in 2020. Data regarding hospitalization and mortality from CVD were obtained from the SPMA Health Department, and data regarding SI was obtained from the São Paulo Intelligent Monitoring System. Time-series trends were analyzed by linear regression, as well as comparisons between these trends., Results: there was an inverse correlation between SI and hospitalizations for CVD (R 2 = 0.70; p < 0.001), IHD (R 2 = 0.70; p < 0.001), and stroke (R 2 = 0.39; p < 0.001). The most significant hospitalization reduction was from March to May, when the SI increased from 43.07% to 50.71%. The increase in SI was also associated with a reduction in CVD deaths (R 2 = 0.49; p < 0.001), IHD (R 2 = 0.50; p < 0.001), and stroke (R 2 = 0.26; p < 0.001)., Conclusions: Increased social isolation was associated with reduced hospitalizations and deaths from CVD, IHD, and stroke. more...

Objective: Stroke is an important cause of disability and death in adults worldwide. However, it is preventable in most cases and treatable as long as patients recognize it and reach capable medical facilities in time. This community-based study investigated students' stroke knowledge, Emergency Medical Services (EMS) activation, associated risk factors, warning signs and symptoms, and prior experience from different educational levels in the KIDS SAVE LIVES BRAZIL project., Methods: The authors conducted the survey with a structured questionnaire in 2019‒2020., Results: Students from the elementary-school (n = 1187, ∼13 y.o., prior experience: 14%, 51% women), high-school (n = 806, ∼17 y.o., prior experience: 13%, 47% women) and University (n = 1961, ∼22 y.o., prior experience: 9%, 66% women) completed the survey. Among the students, the awareness of stroke general knowledge, associated risk factors, and warning signs and symptoms varied between 42%‒66%. When stimulated, less than 52% of the students associated stroke with hypercholesterolemia, smoking, diabetes, and hypertension. When stimulated, 62%‒65% of students recognized arm weakness, facial drooping, and speech difficulty; only fewer identified acute headache (43%). Interestingly, 67% knew the EMS number; 81% wanted to have stroke education at school, and ∼75% wanted it mandatory. Women, higher education, and prior experience were associated with higher scores of knowing risk factors (OR = 1.28, 95% CI: 1.10‒1.48; OR = 2.12, 95% CI: 1.87‒2.40; OR = 1.46, 95% CI: 1.16‒1.83; respectively), and warning signs- symptoms (OR = 2.22, 95% CI: 1.89‒2.60; OR = 3.30, 95% CI: 2.81‒3.87; OR = 2.04, 95% CI: 1.58‒2.63; respectively)., Conclusion: Having higher education, prior experience, and being a woman increases stroke-associated risk factors, and warning signs and symptoms identification. Schoolchildren and adolescents should be the main target population for stroke awareness., Competing Interests: Conflicts of interest The authors declare no conflicts of interest., (Copyright © 2022 HCFMUSP. Published by Elsevier España, S.L.U. All rights reserved.) more...

Background: Coffee is one of the most popular beverages globally and contains several bioactive compounds that are relevant to human health. Many nutritional strategies modulate sirtuin-1, thereby impacting aging and cardiometabolic health. This study investigated the influence of different blended coffees on serum sirtuin-1, blood lipids, and plasma homocysteine. Methods: An eight-week randomized clinical trial that included 53 healthy adults of both sexes analyzed the effects of daily intake of 450 to 600 mL of pure Arabica or blended (Arabica + Robusta) coffee intake of filtered coffee on blood sirtuin-1, lipids, and homocysteine. Results: Both Arabica and blended coffees similarly increased serum sirtuin-1 concentration, from 0.51 to 0.58 ng/mL (p = 0.004) and from 0.40 to 0.49 ng/mL (p = 0.003), respectively, without changing plasma homocysteine, folic acid, glucose, and CRP. However, the blended coffee intake increased total cholesterol from 4.70 to 5.17 mmol/L (p < 0.001) and LDL-cholesterol from 2.98 to 3.32 mmol/L (p < 0.001), as well as HDL-c from 1.26 to 1.36 mmol/L (p < 0.001). Conclusion: Both coffee powders increased sirtuin-1 expression, but our results suggest that blended coffee had hypercholesterolemic effects which could increase cardiovascular risk. Therefore, preference should be given to Arabica coffee for the best cardiometabolic benefits of coffee. more...

Objectives: To determine whether the time for peak exercise heart rate to return to resting heart rate after the 6-minute walk test (6MWT) can predict cardiac events in patients with heart failure (HF) within 2 years., Design: Prospective cohort study., Setting: HF outpatient facility at a tertiary teaching hospital., Participants: Seventy-six patients with HF, New York Heart Association functional classification II and III, and left ventricular ejection fraction <50%., Main Outcome Measures: Patients used a heart rate monitor to measure the time for peak exercise heart rate to return to resting heart rate after the 6MWT. Data were analysed using Polar Pro-Trainer 5 software (Kempele, Finland). Patients were followed for >2 years for cardiac events (hospitalisations and death)., Results: Thirty-four patients had cardiac events during the 2-year follow-up period. However, there was a significant difference in the time to return to resting heart rate between the groups with and without cardiac events {with 3.6 (SD 1.1) vs without 2.8 (SD 1.1) minutes; mean difference of 0.79 (95% confidence interval (CI) of the difference 0.28 to 1.28; P=0.003}. No significant differences between patients with and without cardiac events were found for mean walking distance, mean heart rate recovery at 1minute and mean heart rate recovery at 2minutes. The receiver operating curve discriminated between patients with and without cardiac events (área under the curve 0.71, 95% CI 0.61 to 0.81; P<0.001). Using logistic regression analysis, prolonged time to return to resting heart rate (≥3minutes) independently increased the risk for cardiac events 6.9-fold (95% CI 2.34 to 20.12; P<0.001). The Kaplan-Meier curve showed more cardiac events in patients with prolonged time to return to resting heart rate (P=0.028)., Conclusions: Prolonged time to return to resting heart rate (≥3minutes) after the 6MWT was an independent predictor of cardiac events in patients with HF., (Copyright © 2021 Chartered Society of Physiotherapy. Published by Elsevier Ltd. All rights reserved.) more...

Background: According to the World Health Organization, emerging countries will have an enormous growth in the number of heart attacks and related deaths. The main medical issue in Brazil is mortality caused by acute ST elevation myocardial infarction (STEMI). The Society of Cardiology in the State of São Paulo has never trained non-cardiologists as emergency personnel. Patients usually seek help from emergency departments instead of calling for an ambulance., Objectives: We aimed at reducing in-hospital death rates from acute myocardial infarction by training emergency personnel in the city of Sao Paulo., Methods: We used a training program for the personnel of five hospitals with >100 patients admitted with STEMI per year, and at least 15% in-hospital STEMI-associated mortality rate. We performed internet training, biannual-quarterly symposia for up to 400 participants, informative folders and handouts. Statistical analysis used the two proportion comparison test with p <0.05., Results: Nearly 200 physicians and 350 nurses attended at least one training from May 2010 to December 2013. Initially, many emergency physicians could not recognize an acute myocardial infarction on the electrocardiogram, but tele-electrocardiography is used in some emergency departments to determine the diagnosis. The death rate in the five hospitals decreased from 25.6%, in 2009, to 18.2%, in 2010 (p=0.005). After the entire period of training, the STEMI-associated death rate in all public hospitals of São Paulo decreased from 14.31%, in 2009, to 11.25%, in 2014 (p<0.0001)., Conclusion: Even simple training programs for emergency personnel can greatly reduce acute myocardial infarction death rates in undeveloped countries. more...

Background: Cardiovascular diseases (CVD) and cancer are the main causes of death worldwide. These diseases share many risk factors. Control of traditional risk factors for CVD was associated with lower incidence of cancers., Objective: To analyze CVD and cancer mortality rate trends in Brazilian population aged 35-74 years from 1996 to 2017., Methods: Crude and age-adjusted death rate trends were analyzed for all causes of death, CVD, and cancer. Data were obtained from mortality database of the Ministry of Health. Joinpoint Regression Program performed analysis of trends and adjustments in death rates. The degree of changes was determined by the average annual percent change (AAPC). Level of statistical significance was set at p <0.05., Results: Mortality from all causes of death (AAPC=-1.6%; p<0.001), CVD (AAPC=-2.3; p<0.001), ischemic heart disease (IHD) (AAPC=-1.6; p<0.001) and stroke (AAPC=-3.7; p<0.001) declined. Same trends were observed for CVD (p<0.001) in men and women. Death rates from all causes of cancer (AAPC=-0.1; p=0.201), in men (AAPC=-0.1; p=0.193) and in women (AAPC=-0.1; p=0,871) remained unchanged. In 2002, mortality from cancer exceeded the sum of deaths from IHD and stroke. If trends continue, cancer mortality will also exceed mortality from CVD by 2024. In women, death rates from breast, lung and colon cancer increased, and from cervical and gastric cancers decreased. In men, mortality from lung, stomach and esophagus cancer decreased, and from prostate cancer remained unchanged., Conclusion: CVD are currently the leading cause of death in Brazil, but death rates from cancer will exceed those from CVD in a few years. more...

Background: Chronic sympathetic nervous system activation is associated with endothelial dysfunction and cardiometabolic disease, which may be modulated by resveratrol (RSV) and energy restriction (ER). This study aimed to examine the effects of RSV and ER on plasma noradrenaline (NA), flow-mediated vasodilation (ed-FMD), and endothelium-independent nitrate-mediated vasodilation (ei-NMD). Methods : The study included 48 healthy adults randomized to 30-days intervention of RSV or ER. Results: Waist circumference, total cholesterol, HDL-c, LDL-c, apoA-I, and plasma NA decreased in the ER group, whilst RSV increased apoB and total cholesterol, without changing plasma NA. No effects on vascular reactivity were observed in both groups. Plasma NA change was positively correlated with total cholesterol ( r = 0.443; p = 0.002), triglycerides ( r = 0.438; p = 0.002), apoA-I ( r = 0.467; p = 0.001), apoB ( r = 0.318; p = 0.032) changes, and ei-NMD (OR = 1.294; 95%CI: 1.021-1.640). Conclusions : RSV does not improve cardiometabolic risk factors, sympathetic activity, and endothelial function. ER decreases plasma NA and waist circumference as well as improves blood lipids, but does not modify endothelial function. Finally, plasma NA was associated with ei-NMD, which could be attributed to a higher response to nitrate in patients with greater resting sympathetic vasoconstriction. more...

The aim of the study is to analyze the association between risk factors for the health of truck drivers and previous use of illicit drugs. A cross-sectional study examined the data from 2071 truck drivers between 2010 and 2016. Demographic variables, risk factors for cardiovascular disease (CVD) and the use of illicit drugs were analyzed. The stepwise logistic regression model was used for the adjusted analysis. The dependent variable was the previous use of illicit drugs, and independent variables were those with p < 0.1 at a bivariate analysis. The average age of the truck drivers was 42.27 ± 11.07 years, and the previous use of illicit drugs was reported or detected in 388 (18.7%) drivers. Compared to non-users, drug users were younger (37.25 ± 9.45 vs. 43.43 ± 11.1 years; p < 0.001) and single (43.3% vs. 28.4%; p < 0.001). The independent variables for illicit drugs were age (OR = 0.93 (95% CI: 0.91-0.95; p < 0.001)), smoking (OR = 2.18 (95% CI: 1.39-3.44; p = 0.001)), alcohol consumption (OR = 1.626 (95% CI: 1.06-2.49; p = 0.026)) and driving hours per day (OR = 1.08 (95% CI: 1.01-1.15; p = 0.012)). Users of illicit drugs had multiple risk factors for CVD and traffic accidents. more...

Background: Increased levels of periodontal pathogens disrupt the homeostasis between the host and its microbiota and increase susceptibility to periodontal diseases. Periodontitis increases the serum concentration of mannose-binding lectin (MBL), which exacerbates local inflammatory processes. In animal studies, sirtuin 1 (SIRT1) was associated with protection against inflammation. This study analyzed the influence of non-surgical periodontal treatment on serum levels of MBL and SIRT1., Methods: Forty patients with periodontitis and 38 periodontally healthy individuals (aged 45 to 79 years) were included. Periodontitis patients received scaling and root planing using machine driven and hand instruments. Clinical parameters, inflammatory biomarkers, MBL, and SIRT1 levels were measured at baseline and at post-treatment., Results: For all patients, an inverse correlation was observed between serum concentrations of MBL and SIRT1 (r = -0.30; P = 0.006). Periodontal treatment reduced serum concentrations of MBL (1,099.35 ± 916.59 to 861.42 ± 724.82 ng/mL; P < 0.001) and C-reactive protein (6.05 ± 8.99 to 2.49 ± 2.89 mg/L; P = 0.009). By contrast, SIRT1 serum levels increased (1.06 ± 1.03 to 1.66 ± 1.64 ng/mL; P < 0.001) following periodontal treatment., Conclusions: Periodontal treatment was associated with decreased serum concentrations of MBL and CRP and increased serum levels of SIRT1. Prospective studies are needed to assess the impact of these biomarkers on pathophysiology of periodontitis., (© 2019 American Academy of Periodontology.) more...

Background: Atherosclerosis and periodontal disease (PD) are inflammatory diseases that have been shown in studies to have a direct association. Mannose-binding lectin (MBL) is an immune system protein that binds to periodontal pathogens favoring phagocytosis. Conversely, increased serum sirtuin-1 (SIRT1) concentration reduces the inflammatory process., Methods: This was a prospective, case-controlled study that analyzed serum concentration of biomarkers in patients with or without coronary artery disease (CAD) and PD. A total of 78 patients were evaluated: 20 healthy individuals, 18 patients with CAD, 20 patients with PD, and 20 patients with both PD and CAD. Clinical and laboratory characteristics were analyzed before and after nonsurgical treatment of PD and also at two equivalent times in patients without PD. Serum MBL and SIRT1 concentration were analyzed by enzyme-linked immunosorbent assay., Results: A negative correlation was observed between changes in serum concentration of MBL and SIRT1 ( r  = -0.30; p  = 0.006). Comparison between pre- and post-treatment of PD showed a reduction in MBL levels (886.27 ± 906.72 versus 689.94 ± 808.36; p  = 0.002) and an increase in SIRT1 values (0.80 ± 1.01 versus 1.49 ± 1.55; p  = 0.005) in patients with PD and without CAD. The same result was observed in patients with PD and CAD for MBL and SIRT1, respectively, of 1312.43 ± 898.21 versus 1032.90 ± 602.52 ( p  = 0.010) and 1.32 ± 1.0 versus 1.82 ± 1.75 ( p  = 0.044)., Conclusion: PD treatment reduced MBL serum concentration and increased SIRT1 serum concentration in patients with and without CAD., Competing Interests: Conflict of interest statement: The authors declare that there is no conflict of interest., (© The Author(s), 2020.) more...

Background: Chronic heart failure is commonly associated with inspiratory muscle weakness. However, few studies have investigated the risk factors for inspiratory muscle weakness in individuals with chronic heart failure and systolic dysfunction (left-ventricular ejection fraction [LVEF] <40%)., Methods: Seventy subjects were recruited in a cardiac center. We assessed clinical parameters, smoking history, peripheral muscle strength, pulmonary function, echocardiographic variables, and brain natriuretic peptide. The subjects were classified with inspiratory muscle weakness when the maximum inspiratory pressure was <70% of predicted values., Results: Thirty-six subjects (51%) had inspiratory muscle weakness. The subjects with inspiratory muscle weakness and the subjects with no inspiratory muscle weakness were similar in age, sex, body mass index, medication use, and physical activity. However, the subjects with inspiratory muscle weakness had lower LVEF ( P = .003), systolic blood pressure ( P = .01), diastolic blood pressure ( P = .042), quadriceps muscle strength ( P = .02), lung function ( P = .035), increased brain natriuretic peptide ( P = .02), smoking history ( P = .01), and pulmonary hypertension incidence ( P = .03). Multivariate logistic regression analysis found a lower LVEF, increased smoking history, and lower systolic blood pressure as significant independent predictors for inspiratory muscle weakness., Conclusions: The combination of lower LVEF, lower systolic blood pressure, and smoking history predicted inspiratory muscle weakness. Patients with suspected inspiratory muscle weakness should be examined and, if inspiratory muscle weakness exists, then inspiratory muscle training should be provided. Reducing inspiratory muscle weakness has the potential to improve many of the deleterious effects of chronic heart failure., Competing Interests: The authors have disclosed no conflicts of interest., (Copyright © 2020 by Daedalus Enterprises.) more...

Aim: Some patients experience statin-associated muscle symptoms (SAMS) and elevated serum concentrations of CK. The relationship between SAMS and biomarkers of muscle damage was examined. Methods: We analyzed 359 consecutive patients taking statins with high CK values. Muscle-related symptoms and biochemical variables, including CK, MB isoenzyme of creatine kinase (CK-MB), troponin and carbonic anhydrase type III were evaluated. Results: SAMS was reported by 181 (50.4%) patients and they had greater BMI (p = 0.021) and a trend toward higher CK-MB values (p = 0.064). The use of simvastatin (OR: 2.24; 95% CI: 1.47-3.42), CK-MB (OR: 1.59; 95% CI: 1.02-2.49) and BMI (OR: 1.06; 95% CI: 1.01-1.10) were independent variables for SAMS. Conclusion: Simvastatin use, BMI and CK-MB were independent markers of SAMS. more...

Objective Heart failure (HF) is associated with intermittent hypoxia, and the effects of this hypoxia on the cardiovascular system are not well understood. This study was performed to compare the effects of acute hypoxia (10% oxygen) between patients with and without HF. Methods Fourteen patients with chronic HF and 17 matched control subjects were enrolled. Carotid artery changes were examined during the first period of hypoxia, and brachial artery changes were examined during the second period of hypoxia. Data were collected at baseline and after 2 and 4 minutes of hypoxia. Norepinephrine, epinephrine, dopamine, and renin were measured at baseline and after 4 minutes hypoxia. Results The carotid blood flow, carotid systolic diameter, and carotid diastolic diameter increased and the carotid resistance decreased in patients with HF. Hypoxia did not change the carotid compliance, distensibility, brachial artery blood flow and diameter, or concentrations of sympathomimetic amines in patients with HF, but hypoxia increased the norepinephrine level in the control group. Hypoxia increased minute ventilation and decreased the oxygen saturation and end-tidal carbon dioxide concentration in both groups. Conclusion Hypoxia-induced changes in the carotid artery suggest an intensification of compensatory mechanisms for preservation of cerebral blood flow in patients with HF. more...

Sirtuin-1 (Sirt-1) and an endogenous secretory receptor for an advanced glycation end product (esRAGE) are associated with vascular protection. The purpose of this study was to examine the effects of resveratrol (RSV) and caloric restriction (CR) on gene expression of Sirt-1 and esRAGE on serum levels of Sirt1 and esRAGE in healthy and slightly overweight subjects. The study included 48 healthy subjects randomized to 30 days of RSV (500 mg/day) or CR (1000 cal/day). Waist circumference ( p = 0.011), TC ( p = 0.007), HDL ( p = 0.031), non-HDL ( p = 0.025), ApoA1 ( p = 0.011), and ApoB ( p = 0.037) decreased in the CR group. However, TC ( p = 0.030), non-HDL ( p = 0.010), ApoB ( p = 0.034), and HOMA-IR ( p = 0.038) increased in the RSV group. RSV and CR increased serum levels of Sirt-1, respectively, from 1.06 ± 0.71 ng/mL to 5.75 ± 2.98 ng/mL ( p < 0.0001) and from 1.65 ± 1.81 ng/mL to 5.80 ± 2.23 ng/mL ( p < 0.0001). esRAGE serum levels were similar in RSV ( p = NS) and CR ( p = NS) groups. Significant positive correlation was observed between gene expression changes of Sirt-1 and esRAGE in RSV ( r = 0.86; p < 0.0001) and in CR ( r = 0.71; p < 0.0001) groups, but not for the changes in serum concentrations. CR promoted increases in the gene expression of esRAGE (post/pre). Future long-term studies are needed to evaluate the impact of these outcomes on vascular health. more...

Background: Inspiratory and peripheral muscle training improves muscle strength, exercise tolerance, and quality of life in patients with chronic heart failure (HF). However, studies investigating different workloads for these exercise modalities are still lacking., Objective: To examine the effects of low and moderate intensities on muscle strength, functional capacity, and quality of life., Design: A randomized controlled trial., Methods: Thirty-five patients with stable HF (aged >18 years, NYHA II/III, LVEF <40%) were randomized to: non-exercise control group (n = 9), low-intensity training group (LIPRT, n = 13, 15% maximal inspiratory workload, and 0.5 kg of peripheral muscle workload) or moderate-intensity training group (MIPRT, n = 13, 30% maximal inspiratory workload and 50% of one maximum repetition of peripheral muscle workload). The outcomes were: respiratory and peripheral muscle strength, pulmonary function, exercise tolerance by the 6-minute walk test, symptoms based on the NYHA functional class, and quality of life using the Minnesota Living with Heart Failure Questionnaire., Results: All groups showed similar quality-of-life improvements. Low and moderate intensities training programs improved inspiratory muscle strength, peripheral muscle strength, and walking distance. However, only moderate intensity improved expiratory muscle strength and NYHA functional class in HF patients., Conclusions: The low-intensity inspiratory and peripheral resistance muscle training improved inspiratory and peripheral muscle strength and walking distance, demonstrating that LIPRT is an efficient rehabilitation method for debilitated HF patients. In addition, the moderate-intensity resistance training also improved expiratory muscle strength and NYHA functional class in HF patients. more...

Background: The knowledge of the variables predicting mortality is important in clinical practice and for therapeutic monitoring in mitral valve disease., Objectives: To determine whether a quality of life score evaluated with the Functional Evaluation of Cardiac Health questionnaire would predict mortality in dogs with degenerative mitral valve disease (DMVD)., Methods: Thirty-six client-owned dogs with mitral valve disease underwent clinical, laboratory, and echocardiographic evaluations at baseline and were monitored for 6 months. Cardiovascular death was the primary outcome., Results: The 36 dogs were classified as survivors or nonsurvivors. Higher values of the following variables were obtained at baseline in the nonsurviving group (12 dogs): amino-terminal pro-B-type natriuretic peptide (NT-proBNP) levels, plasma norepinephrine, heart rate, quality of life score, diastolic left ventricular internal dimension to aortic root ratio, systolic left ventricular internal dimension to aortic root ratio, and left atrium to aortic root ratio. NT-proBNP levels and quality life score were independently associated with death in the multivariable analysis., Conclusion: The quality life score was an independent variable for cardiac death in dogs with DMVD. This result is encouraging, as this score is easy to apply and does not require any technology, only a veterinarian and an observant owner. more...

Cardiac remodeling in diabetes involves cardiac hypertrophy and fibrosis, and fibroblast growth factor 2 (FGF2) is an important mediator of this process. Resveratrol, a polyphenolic antioxidant, reportedly promotes the improvement of cardiac dysfunction in diabetic rats. However, little information exists linking the amelioration of the cardiac function promoted by resveratrol and the expression of FGF2 and its co-receptors, heparan sulfate proteoglycans (HSPGs: Glypican-1 and Syndecan-4), in cardiac muscle of Type 2 diabetic rats. Diabetes was induced experimentally by the injection of streptozotocin and nicotinamide, and the rats were treated with resveratrol for 6 weeks. According to our results, there is an up-regulation of the expression of genes and/or proteins of Glypican-1, Syndecan-4, FGF2, peroxisome proliferator-activated receptor gamma and AMP-activated protein kinase in diabetic rats. On the other hand, resveratrol treatment promoted the attenuation of left ventricular diastolic dysfunction and the down-regulation of the expression of all proteins under study. The trigger for the changes in gene expression and protein synthesis promoted by resveratrol was the presence of diabetes. The negative modulation conducted by resveratrol on FGF2 and HSPGs expression, which are involved in cardiac remodeling, underlies the amelioration of cardiac function., (Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.) more...

Background: Sirtuin 1 (Sirt1) plays an important role in vascular biology, and influences aspects of age-dependent atherosclerosis. In animals, the sirtuin system is strongly influenced by resveratrol and caloric restriction, but its expression in humans is controversial. This study investigated the effects of resveratrol and caloric restriction on Sirt1 serum concentrations and vascular biomarkers in a healthy human population., Methods and Results: Forty-eight healthy participants (24 women) aged 55-65years were randomized to either 30days of resveratrol administration (500mg/day) or caloric restriction (1000cal/day). Blood was collected at baseline and day 30. Laboratory data analyzed were triglycerides, total cholesterol, HDL, VLDL, LDL, apolipoprotein A1, apolipoprotein B, lipoprotein (a), non-esterified fatty acids (NEFA), glucose, insulin, oxidative stress, C-reactive protein, and Sirt1. Expression of the Sirt1 gene was analyzed using real-time PCR. Caloric restriction diminished the abdominal circumference and improved the lipid profile, but not resveratrol intervention. Resveratrol and caloric restriction increased serum concentrations of Sirt1, from 1.06±0.71 to 5.75±2.98ng/mL; p<0.0001, and from 1.65±1.81 to 5.80±2.23ng/mL; p<0.0001, respectively. Sirt1 increased in women and men in both interventions. On the other hand expression of Sirt1 mRNA was not different after caloric restriction and resveratrol treatment., Conclusions: Caloric restriction and resveratrol significantly increased plasma concentrations of Sirt1. The long-term impact of these interventions on atherosclerosis should be assessed., (Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.) more...

Marfan syndrome is an autosomal dominant genetic disorder that affects connective tissue and is caused by mutations in the fibrillin 1 gene present at chromosome 15. Aortic aneurysm is its main complication, and along the dilation of the aorta root and its descending portion (60-100%), with secondary aortic insufficiency, it increases risk of acute aortic dissection and death. Coronary artery anomalies affect between 0.3% and 1.6% of the general population and are the second leading cause of sudden death in young adults, especially if the anomalous coronary passes through aorta and pulmonary artery. The anomalous origin of the left main coronary artery in the right Valsalva sinus has a prevalence of 0.02%-0.05% and is commonly related to other congenital cardiac anomalies, such as transposition of great vessels, coronary fistulas, bicuspid aortic valve, and tetralogy of Fallot. Its association with Marfan syndrome is not known, and there is no previous report in the literature. We describe here a case of a female with Marfan syndrome diagnosed with symptomatic anomalous origin of the left coronary artery in the right Valsalva sinus. more...

This study aimed to evaluate the effects of carvedilol treatment and a regimen of supervised aerobic exercise training on quality of life and other clinical, echocardiographic, and biochemical variables in a group of client-owned dogs with chronic mitral valve disease (CMVD). Ten healthy dogs (control) and 36 CMVD dogs were studied, with the latter group divided into 3 subgroups. In addition to conventional treatment (benazepril, 0.3-0.5 mg/kg once a day, and digoxin, 0.0055 mg/kg twice daily), 13 dogs received exercise training (subgroup I; 10.3 ± 2.1 years), 10 dogs received carvedilol (0.3 mg/kg twice daily) and exercise training (subgroup II; 10.8 ± 1.7 years), and 13 dogs received only carvedilol (subgroup III; 10.9 ± 2.1 years). All drugs were administered orally. Clinical, laboratory, and Doppler echocardiographic variables were evaluated at baseline and after 3 and 6 months. Exercise training was conducted from months 3-6. The mean speed rate during training increased for both subgroups I and II (ANOVA, P>0.001), indicating improvement in physical conditioning at the end of the exercise period. Quality of life and functional class was improved for all subgroups at the end of the study. The N-terminal pro-brain natriuretic peptide (NT-proBNP) level increased in subgroup I from baseline to 3 months, but remained stable after training introduction (from 3 to 6 months). For subgroups II and III, NT-proBNP levels remained stable during the entire study. No difference was observed for the other variables between the three evaluation periods. The combination of carvedilol or exercise training with conventional treatment in CMVD dogs led to improvements in quality of life and functional class. Therefore, light walking in CMVD dogs must be encouraged. more...

Background: Multi-detector computed tomography angiography (MDCTA) is a promising method for risk assessment of patients with acute chest pain. However, its diagnostic performance in higher-risk patients has not been investigated in a large international multicenter trial. Therefore, in the present study we sought to estimate the diagnostic accuracy of MDCTA to detect significant coronary stenosis in patients with acute coronary syndrome (ACS)., Methods: Patients included in the CORE64 study were categorized as suspected-ACS or non-ACS based on clinical data. A 64-row coronary MDCTA was performed before invasive coronary angiography (ICA) and both exams were evaluated by blinded, independent core laboratories., Results: From 371 patients included, 94 were categorized as suspected ACS and 277 as non-ACS. Patient-based analysis showed an area under the receiver-operating-characteristic curve (AUC) for detecting ≥ 50% coronary stenosis of 0.95 (95% CI: 0.88-0.98) in ACS and 0.92 (95% CI: 0.88-0.95) in non-ACS group (P=0.29). The sensitivity, specificity, positive and negative predictive values of MDCTA were 0.90(0.80-0.96), 0.88(0.70-0.98), 0.95(0.87-0.99) and 0.77(0.58-0.90) in suspected ACS patients and 0.87(0.81-0.92), 0.86(0.79-0.92), 0.91(0.85-0.95) and 0.82(0.74-0.89) in non-ACS patients (P NS for all comparisons). The mean calcium scores (CS) were 282 ± 449 in suspected ACS and 435 ± 668 in non-ACS group. The accuracy of CS to detect significant coronary stenosis was only moderate and the absence or minimal coronary artery calcification could not exclude the presence of significant coronary stenosis, particularly in ACS patients., Conclusions: The diagnostic accuracy of MDCTA to detect significant coronary stenosis is high and comparable for both ACS and non-ACS patients., (Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.) more...

The tunable nature of weak polyelectrolyte multilayers makes them ideal candidates for drug loading and delivery, water filtration, and separations, yet the lateral transport of charged molecules in these systems remains largely unexplored at the single molecule level. We report the direct measurement of the charge-dependent, pH-tunable, multimodal interaction of single charged molecules with a weak polyelectrolyte multilayer thin film, a 10 bilayer film of poly(acrylic acid) and poly(allylamine hydrochloride) PAA/PAH. Using fluorescence microscopy and single-molecule tracking, two modes of interaction were detected: (1) adsorption, characterized by the molecule remaining immobilized in a subresolution region and (2) diffusion trajectories characteristic of hopping (D ∼ 10(-9) cm(2)/s). Radius of gyration evolution analysis and comparison with simulated trajectories confirmed the coexistence of the two transport modes in the same single molecule trajectories. A mechanistic explanation for the probe and condition mediated dynamics is proposed based on a combination of electrostatics and a reversible, pH-induced alteration of the nanoscopic structure of the film. Our results are in good agreement with ensemble studies conducted on similar films, confirm a previously-unobserved hopping mechanism for charged molecules in polyelectrolyte multilayers, and demonstrate that single molecule spectroscopy can offer mechanistic insight into the role of electrostatics and nanoscale tunability of transport in weak polyelectrolyte multilayers. more...

The retention and elution of proteins in ion-exchange chromatography is routinely controlled by adjusting the mobile phase salt concentration. It has repeatedly been observed, as judged from adsorption isotherms, that the apparent heterogeneity of adsorption is lower at more-eluting, higher ionic strength. Here, we present an investigation into the mechanism of this phenomenon using a single-molecule, super-resolution imaging technique called motion-blur Points Accumulation for Imaging in Nanoscale Topography (mbPAINT). We observed that the number of functional adsorption sites was smaller at high ionic strength and that these sites had reduced desorption kinetic heterogeneity, and thus narrower predicted elution profiles, for the anion-exchange adsorption of α-lactalbumin on an agarose-supported, clustered-charge ligand stationary phase. Explanations for the narrowing of the functional population such as inter-protein interactions and protein or support structural changes were investigated through kinetic analysis, circular dichroism spectroscopy, and microscopy of agarose microbeads, respectively. The results suggest the reduction of heterogeneity is due to both electrostatic screening between the protein and ligand and tuning the steric availability within the agarose support. Overall, we have shown that single molecule spectroscopy can aid in understanding the influence of ionic strength on the population of functional adsorbent sites participating in the ion-exchange chromatographic separation of proteins., (Copyright © 2014 Elsevier B.V. All rights reserved.) more...

Chromatographic protein separations, immunoassays, and biosensing all typically involve the adsorption of proteins to surfaces decorated with charged, hydrophobic, or affinity ligands. Despite increasingly widespread use throughout the pharmaceutical industry, mechanistic detail about the interactions of proteins with individual chromatographic adsorbent sites is available only via inference from ensemble measurements such as binding isotherms, calorimetry, and chromatography. In this work, we present the direct superresolution mapping and kinetic characterization of functional sites on ion-exchange ligands based on agarose, a support matrix routinely used in protein chromatography. By quantifying the interactions of single proteins with individual charged ligands, we demonstrate that clusters of charges are necessary to create detectable adsorption sites and that even chemically identical ligands create adsorption sites of varying kinetic properties that depend on steric availability at the interface. Additionally, we relate experimental results to the stochastic theory of chromatography. Simulated elution profiles calculated from the molecular-scale data suggest that, if it were possible to engineer uniform optimal interactions into ion-exchange systems, separation efficiencies could be improved by as much as a factor of five by deliberately exploiting clustered interactions that currently dominate the ion-exchange process only accidentally. more...

Objective: To examine the association of atherogenic and thrombogenic markers and lymphotoxin-alfa gene mutations with the risk of premature coronary disease., Methods: This cross-sectional, case-control, age-adjusted study was conducted in 336 patients with premature coronary disease (<50 years old) and 189 healthy controls. The control subjects had normal clinical, resting, and exercise stress electrocardiographic assessments. The coronary disease group patients had either angiographically documented disease (>50% luminal reduction) or a previous myocardial infarction. The laboratory data evaluated included thrombogenic factors (fibrinogen, protein C, protein S, and antithrombin III), atherogenic factors (glucose and lipid profiles, lipoprotein(a), and apolipoproteins AI and B), and lymphotoxin-alfa mutations. Genetic variability of lymphotoxin-alfa was determined by polymerase chain reaction analysis., Results: Coronary disease patients exhibited lower concentrations of HDL-cholesterol and higher levels of glucose, lipoprotein(a), and protein S. The frequencies of AA, AG, and GG lymphotoxin-alfa mutation genotypes were 55.0%, 37.6%, and 7.4% for controls and 42.7%, 46.0%, and 11.3% for coronary disease patients (p = 0.02), respectively. Smoking, dyslipidemia, family history, and lipoprotein(a) and lymphotoxin-alfa mutations in men were independent variables associated with coronary disease. The area under the curve (C-statistic) increased from 0.779 to 0.802 (p<0.05) with the inclusion of lipoprotein(a) and lymphotoxin-alfa mutations in the set of conventional risk factors., Conclusions: The inclusion of lipoprotein(a) and lymphotoxin-alfa mutations in the set of conventional risk factors showed an additive but small increase in the risk prediction of premature coronary disease. more...

We present a hardware-based method that can improve single molecule fluorophore observation time by up to 1500% and super-localization by 47% for the experimental conditions used. The excitation was modulated using an acousto-optic modulator (AOM) synchronized to the data acquisition and inherent data conversion time of the detector. The observation time and precision in super-localization of four commonly used fluorophores were compared under modulated and traditional continuous excitation, including direct total internal reflectance excitation of Alexa 555 and Cy3, non-radiative Förster resonance energy transfer (FRET) excited Cy5, and direct epi-fluorescence wide field excitation of Rhodamine 6G. The proposed amplitude-modulated excitation does not perturb the chemical makeup of the system or sacrifice signal and is compatible with multiple types of fluorophores. Amplitude-modulated excitation has practical applications for any fluorescent study utilizing an instrumental setup with time-delayed detectors. more...

Background: High-density-lipoprotein (HDL) has several antiatherogenic properties and, although the concentration of HDL-cholesterol negatively correlates with incidence of coronary artery disease (CAD), this is not sufficient to evaluate the overall HDL protective role. The aim was to investigate whether precocious CAD patients show abnormalities in lipid transfers to HDL, a fundamental step in HDL metabolism and function., Methods: Thirty normocholesterolemic CAD patients aged <50 y and 30 controls paired for sex, age and B.M.I. were studied. Fasting blood samples were collected for the in vitro lipid transfer assay and plasma lipid determination. A donor nanoemulsion labeled with radioactive free-cholesterol, cholesteryl esters, phospholipids and triglycerides was incubated with whole plasma and after chemical precipitation of non-HDL fractions, supernatant was counted for radioactivity in HDL., Results: LDL and HDL-cholesterol and triglycerides were equal in both groups. Transfers of free-cholesterol (3.8±1.2%vs 7.0±3.3%,p<0.0001) and triglycerides (3.7±1.7%vs 4.9±1.9%, p=0.0125) were diminished in CAD patients whereas cholesteryl ester transfer increased (6.5±1.9%vs 4.8±1.8%, p=0.0008); phospholipid transfer was equal (17.8±3.5% vs 19.5±3.9%)., Conclusion: Alterations in the transfer of lipids to HDL may constitute a new marker for precocious CAD and relation of this metabolic alteration with HDL antiatherogenic function should be investigated in future studies., (Copyright © 2011. Published by Elsevier B.V.) more...

Background: Changes in the proteoglycans glypican and syndecan-4 have been reported in several pathological conditions, but little is known about their expression in the heart during diabetes. The aim of this study was to investigate in vivo heart function changes and alterations in mRNA expression and protein levels of glypican-1 and syndecan-4 in cardiac and skeletal muscles during streptozotocin (STZ)-induced diabetes., Methods: Diabetes was induced in male Wistar rats by STZ administration. The rats were assigned to one of the following groups: control (sham injection), after 24 hours, 10 days, or 30 days of STZ administration. Echocardiography was performed in the control and STZ 10-day groups. Western and Northern blots were used to quantify protein and mRNA levels in all groups. Immunohistochemistry was performed in the control and 30-day groups to correlate the observed mRNA changes to the protein expression., Results: In vivo cardiac functional analysis performed using echocardiography in the 10-day group showed diastolic dysfunction with alterations in the peak velocity of early (E) diastolic filling and isovolumic relaxation time (IVRT) indices. These functional alterations observed in the STZ 10-day group correlated with the concomitant increase in syndecan-4 and glypican-1 protein expression. Cardiac glypican-1 mRNA and skeletal syndecan-4 mRNA and protein levels increased in the STZ 30-day group. On the other hand, the amount of glypican in skeletal muscle was lower than that in the control group. The same results were obtained from immunohistochemistry analysis., Conclusion: Our data suggest that membrane proteoglycans participate in the sequence of events triggered by diabetes and inflicted on cardiac and skeletal muscles. more...