Death and Disability in Patients with Sleep Apnea - A Meta-analysis

Background:Several studies have been attempting to ascertain the risks of Sleep Apnea Syndrome (SAS) and its morbidity and mortality.Objective:The main objective was to verify whether SAS increases the risk of death; the secondary objective was to evaluate its morbidity in relation to cardiovascular disease and the number of days hospitalized.Methods:A systematic review and a meta-analysis were performed of the published literature. The research focused on studies comparing the number of deaths in patients with untreated SAS and in patients with non-SAS.Results:The meta-analysis was based on 13 articles, corresponding to a total of 13394 participants divided into two groups (non-SAS = 6631; SAS = 6763). The meta-analysis revealed a clear association of SAS with the occurrence of fatal events, where the presence of SAS corresponded to a 61% higher risk of total mortality (OR=1.61; CI: 1.43 - 1.81; p < 0.00001), while the risk of death from cardiac causes was 2.52 times higher in these patients (OR = 2.52; IC: 1.80 - 3.52; p < 0.00001). Similar results were obtained for mortality from other causes (OR = 1.68; CI: 1.08 - 2.61; p = 0.02). Resembling results were obtained in the remaining outcomes: non-fatal cardiovascular events were higher in the SAS group (OR = 2.46; IC: 1.80 - 3.36; p < 0.00001), the average number of days hospitalized was also higher in the SAS group (IV = 18.09; IC: 13.34 - 22.84; p < 0.00001).Conclusion:The results show that untreated SAS significantly increases the risk of death, cardiovascular events and the average number of days hospitalized.

Cost-Effectiveness of High, Moderate and Low-Dose Statins in the Prevention of Vascular Events in the Brazilian Public Health System

Background:Statins have proven efficacy in the reduction of cardiovascular events, but the financial impact of its widespread use can be substantial.Objective:To conduct a cost-effectiveness analysis of three statin dosing schemes in the Brazilian Unified National Health System (SUS) perspective.Methods:We developed a Markov model to evaluate the incremental cost-effectiveness ratios (ICERs) of low, intermediate and high intensity dose regimens in secondary and four primary scenarios (5%, 10%, 15% and 20% ten-year risk) of prevention of cardiovascular events. Regimens with expected low-density lipoprotein cholesterol reduction below 30% (e.g. simvastatin 10mg) were considered as low dose; between 30-40%, (atorvastatin 10mg, simvastatin 40mg), intermediate dose; and above 40% (atorvastatin 20-80mg, rosuvastatin 20mg), high-dose statins. Effectiveness data were obtained from a systematic review with 136,000 patients. National data were used to estimate utilities and costs (expressed as International Dollars - Int$). A willingness-to-pay (WTP) threshold equal to the Brazilian gross domestic product per capita (circa Int$11,770) was applied.Results:Low dose was dominated by extension in the primary prevention scenarios. In the five scenarios, the ICER of intermediate dose was below Int$10,000 per QALY. The ICER of the high versus intermediate dose comparison was above Int$27,000 per QALY in all scenarios. In the cost-effectiveness acceptability curves, intermediate dose had a probability above 50% of being cost-effective with ICERs between Int$ 9,000-20,000 per QALY in all scenarios.Conclusions:Considering a reasonable WTP threshold, intermediate dose statin therapy is economically attractive, and should be a priority intervention in prevention of cardiovascular events in Brazil.

Impact of Light Salt Substitution for Regular Salt on Blood Pressure of Hypertensive Patients

Background: Studies have shown sodium restriction to have a beneficial effect on blood pressure (BP) of hypertensive patients. Objective: To evaluate the impact of light salt substitution for regular salt on BP of hypertensive patients. Methods: Uncontrolled hypertensive patients of both sexes, 20 to 65 years-old, on stable doses of antihypertensive drugs were randomized into Intervention Group (IG - receiving light salt) and Control Group (CG - receiving regular salt). Systolic BP (SBP) and diastolic BP (DBP) were analyzed by using casual BP measurements and Home Blood Pressure Monitoring (HBPM), and sodium and potassium excretion was assessed on 24-hour urine samples. The patients received 3 g of salt for daily consumption for 4 weeks. Results: The study evaluated 35 patients (65.7% women), 19 allocated to the IG and 16 to the CG. The mean age was 55.5 ± 7.4 years. Most participants had completed the Brazilian middle school (up to the 8th grade; n = 28; 80.0%), had a family income of up to US$ 600 (n = 17; 48.6%) and practiced regular physical activity (n = 19; 54.3%). Two patients (5.7%) were smokers and 40.0% consumed alcohol regularly (n = 14). The IG showed a significant reduction in both SBP and DBP on the casual measurements and HBPM (p < 0.05) and in sodium excretion (p = 0.016). The CG showed a significant reduction only in casual SBP (p = 0.032). Conclusions: The light salt substitution for regular salt significantly reduced BP of hypertensive patients.

BNP was Associated with Ischemic Myocardial Scintigraphy and Death in Patients at Chest Pain Unit

Background:Recent studies have suggested that B-type Natriuretic Peptide (BNP) is an important predictor of ischemia and death in patients with suspected acute coronary syndrome. Increased levels of BNP are seen after episodes of myocardial ischemia and may be related to future adverse events.Objectives:To determine the prognostic value of BNP for major cardiac events and to evaluate its association with ischemic myocardial perfusion scintigraphy (MPS).Methods:This study included retrospectively 125 patients admitted to the chest pain unit between 2002 and 2006, who had their BNP levels measured on admission and underwent CPM for risk stratification. BNP values were compared with the results of the MPS. The chi-square test was used for qualitative variables and the Student t test, for quantitative variables. Survival curves were adjusted using the Kaplan-Meier method and analyzed by using Cox regression. The significance level was 5%.Results:The mean age was 63.9 ± 13.8 years, and the male sex represented 51.2% of the sample. Ischemia was found in 44% of the MPS. The mean BNP level was higher in patients with ischemia compared to patients with non-ischemic MPS (188.3 ± 208.7 versus 131.8 ± 88.6; p = 0.003). A BNP level greater than 80 pg/mL was the strongest predictor of ischemia on MPS (sensitivity = 60%, specificity = 70%, accuracy = 66%, PPV = 61%, NPV = 70%), and could predict medium-term mortality (RR = 7.29, 95% CI: 0.90-58.6; p = 0.045) independently of the presence of ischemia.Conclusions:BNP levels are associated with ischemic MPS findings and adverse prognosis in patients presenting with acute chest pain to the emergency room, thus, providing important prognostic information for an unfavorable clinical outcome.

Fatty Acid and Cholesterol Concentrations in Usually Consumed Fish in Brazil

Background: Several studies have demonstrated clinical benefits of fish consumption for the cardiovascular system. These effects are attributed to the increased amounts of polyunsaturated fatty acids in these foods. However, the concentrations of fatty acids may vary according to region. Objective: The goal of this study was to determine the amount of,cholesterol and fatty acids in 10 Brazilian fishes and in a non-native farmed salmon usually consumed in Brazil. Methods: The concentrations of cholesterol and fatty acids, especially omega-3, were determined in grilled fishes. Each fish sample was divided in 3 sub-samples (chops) and each one was extracted from the fish to minimize possible differences in muscle and fat contents. Results: The largest cholesterol amount was found in white grouper (107.6 mg/100 g of fish) and the smallest in badejo (70 mg/100 g). Omega-3 amount varied from 0.01 g/100 g in badejo to 0.900 g/100 g in weakfish. Saturated fat varied from 0.687 g/100 g in seabass to 4.530 g/100 g in filhote. The salmon had the greatest concentration of polyunsaturated fats (3.29 g/100 g) and the highest content of monounsaturated was found in pescadinha (5.98 g/100 g). Whiting and boyfriend had the best omega-6/omega 3 ratios respectively 2.22 and 1.19, however these species showed very little amounts of omega-3. Conclusion: All studied Brazilian fishes and imported salmon have low amounts of saturated fat and most of them also have low amounts of omega-3.

Assessment of Myocardial Infarction by Cardiac Magnetic Resonance Imaging and Long-Term Mortality

Background: Cardiac magnetic resonance imaging provides detailed anatomical information on infarction. However, few studies have investigated the association of these data with mortality after acute myocardial infarction. Objective: To study the association between data regarding infarct size and anatomy, as obtained from cardiac magnetic resonance imaging after acute myocardial infarction, and long-term mortality. Methods: A total of 1959 reports of “infarct size” were identified in 7119 cardiac magnetic resonance imaging studies, of which 420 had clinical and laboratory confirmation of previous myocardial infarction. The variables studied were the classic risk factors – left ventricular ejection fraction, categorized ventricular function, and location of acute myocardial infarction. Infarct size and acute myocardial infarction extent and transmurality were analyzed alone and together, using the variable named “MET-AMI”. The statistical analysis was carried out using the elastic net regularization, with the Cox model and survival trees. Results: The mean age was 62.3 ± 12 years, and 77.3% were males. During the mean follow-up of 6.4 ± 2.9 years, there were 76 deaths (18.1%). Serum creatinine, diabetes mellitus and previous myocardial infarction were independently associated with mortality. Age was the main explanatory factor. The cardiac magnetic resonance imaging variables independently associated with mortality were transmurality of acute myocardial infarction (p = 0.047), ventricular dysfunction (p = 0.0005) and infarcted size (p = 0.0005); the latter was the main explanatory variable for ischemic heart disease death. The MET-AMI variable was the most strongly associated with risk of ischemic heart disease death (HR: 16.04; 95%CI: 2.64-97.5; p = 0.003). Conclusion: The anatomical data of infarction, obtained from cardiac magnetic resonance imaging after acute myocardial infarction, were independently associated with long-term mortality, especially for ischemic heart disease death.

Sudden Cardiac Death in Brazil: A Community-Based Autopsy Series (2006-2010)

Background: Sudden cardiac death (SCD) is a sudden unexpected event, from a cardiac cause, that occurs in less than one hour after the symptoms onset, in a person without any previous condition that would seem fatal or who was seen without any symptoms 24 hours before found dead. Although it is a relatively frequent event, there are only few reliable data in underdeveloped countries. Objective: We aimed to describe the features of SCD in Ribeirão Preto, Brazil (600,000 residents) according to Coroners’ Office autopsy reports. Methods: We retrospectively reviewed 4501 autopsy reports between 2006 and 2010, to identify cases of SCD. Specific cause of death as well as demographic information, date, location and time of the event, comorbidities and whether cardiopulmonary resuscitation (CPR) was attempted were collected. Results: We identified 899 cases of SCD (20%); the rate was 30/100000 residents per year. The vast majority of cases of SCD involved a coronary artery disease (CAD) (64%) and occurred in men (67%), between the 6th and the 7th decades of life. Most events occurred during the morning in the home setting (53.3%) and CPR was attempted in almost half of victims (49.7%). The most prevalent comorbidity was systemic hypertension (57.3%). Chagas’ disease was present in 49 cases (5.5%). Conclusion: The majority of victims of SCD were men, in their sixties and seventies and the main cause of death was CAD. Chagas’ disease, an important public health problem in Latin America, was found in about 5.5% of the cases.

Relationship between Neutrophil-To-Lymphocyte Ratio and Electrocardiographic Ischemia Grade in STEMI

Background: Neutrophil-to-lymphocyte ratio (NLR) has been found to be a good predictor of future adverse cardiovascular outcomes in patients with ST-segment elevation myocardial infarction (STEMI). Changes in the QRS terminal portion have also been associated with adverse outcomes following STEMI. Objective: To investigate the relationship between ECG ischemia grade and NLR in patients presenting with STEMI, in order to determine additional conventional risk factors for early risk stratification. Methods: Patients with STEMI were investigated. The grade of ischemia was analyzed from the ECG performed on admission. White blood cells and subtypes were measured as part of the automated complete blood count (CBC) analysis. Patients were classified into two groups according to the ischemia grade presented on the admission ECG, as grade 2 ischemia (G2I) and grade 3 ischemia (G3I). Results: Patients with G3I had significantly lower mean left ventricular ejection fraction than those in G2I (44.58 ± 7.23 vs. 48.44 ± 7.61, p = 0.001). As expected, in-hospital mortality rate increased proportionally with the increase in ischemia grade (p = 0.036). There were significant differences in percentage of lymphocytes (p = 0.010) and percentage of neutrophils (p = 0.004), and therefore, NLR was significantly different between G2I and G3I patients (p < 0.001). Multivariate logistic regression analysis revealed that only NLR was the independent variable with a significant effect on ECG ischemia grade (odds ratio = 1.254, 95% confidence interval 1.120–1.403, p < 0.001). Conclusion: We found an association between G3I and elevated NLR in patients with STEMI. We believe that such an association might provide an additional prognostic value for risk stratification in patients with STEMI when combined with standardized risk scores.

Effects of Ischemic Postconditioning on the Hemodynamic Parameters and Heart Nitric Oxide Levels of Hypothyroid Rats

Background: Ischemic postconditioning (IPost) is a method of protecting the heart against ischemia-reperfusion (IR) injury. However, the effectiveness of IPost in cases of ischemic heart disease accompanied by co-morbidities such as hypothyroidism remains unclear. Objective: The aim of this study was to determine the effect of IPost on myocardial IR injury in hypothyroid male rats. Methods: Propylthiouracil in drinking water (500 mg/L) was administered to male rats for 21 days to induce hypothyroidism. The hearts from control and hypothyroid rats were perfused in a Langendorff apparatus and exposed to 30 min of global ischemia, followed by 120 min of reperfusion. IPost was induced immediately following ischemia. Results: Hypothyroidism and IPost significantly improved the left ventricular developed pressure (LVDP) and peak rates of positive and negative changes in left ventricular pressure (±dp/dt) during reperfusion in control rats (p < 0.05). However, IPost had no add-on effect on the recovery of LVDP and ±dp/dt in hypothyroid rats. Furthermore, hypothyroidism significantly decreased the basal NO metabolite (NOx) levels of the serum (72.5 ± 4.2 vs. 102.8 ± 3.7 μmol/L; p < 0.05) and heart (7.9 ± 1.6 vs. 18.8 ± 3.2 μmol/L; p < 0.05). Heart NOx concentration in the hypothyroid groups did not change after IR and IPost, whereas these were significantly (p < 0.05) higher and lower after IR and IPost, respectively, in the control groups. Conclusion: Hypothyroidism protects the heart from IR injury, which may be due to a decrease in basal nitric oxide (NO) levels in the serum and heart and a decrease in NO after IR. IPost did not decrease the NO level and did not provide further cardioprotection in the hypothyroid group.

Reproducibility of Left Ventricular Mass by Echocardiogram in the ELSA-Brasil

Background: Echocardiography, though non-invasive and having relatively low-cost, presents issues of variability which can limit its use in epidemiological studies. Objective: To evaluate left ventricular mass reproducibility when assessed at acquisition (online) compared to when assessed at a reading center after electronic transmission (offline) and also when assessed by different readers at the reading center. Methods: Echocardiographers from the 6 ELSA-Brasil study investigation centers measured the left ventricular mass online during the acquisition from 124 studies before transmitting to the reading center, where studies were read according to the study protocol. Half of these studies were blindly read by a second reader in the reading center. Results: From the 124 echocardiograms, 5 (4%) were considered not measurable. Among the remaining 119, 72 (61%) were women, mean age was 50.2 ± 7.0 years and 2 had structural myocardial abnormalities. Images were considered to be optimal/ good by the reading center for 110 (92.4%) cases. No significant difference existed between online and offline measurements (1,29 g, CI 95% −3.60-6.19), and the intraclass correlation coefficient between them was 0.79 (CI 95% 0.71-0.85). For images read by two readers, the intraclass correlation coefficient was 0.86 (CI 95% 0.78-0.91). Conclusion: There were no significant drifts between online and offline left ventricular mass measurements, and reproducibility was similar to that described in previous studies. Central quantitative assessment of echocardiographic studies in reading centers, as performed in the ELSA-Brasil study, is feasible and useful in clinical and epidemiological studies performed in our setting.

Correlation between C-Reactive Protein in Peripheral Vein and Coronary Sinus in Stable and Unstable Angina

Background: High sensitivity C-reactive protein (hs-CRP) is commonly used in clinical practice to assess cardiovascular risk. However, a correlation has not yet been established between the absolute levels of peripheral and central hs-CRP. Objective: To assess the correlation between serum hs-CRP levels (mg/L) in a peripheral vein in the left forearm (LFPV) with those in the coronary sinus (CS) of patients with coronary artery disease (CAD) and a diagnosis of stable angina (SA) or unstable angina (UA). Methods: This observational, descriptive, and cross-sectional study was conducted at the Instituto do Coração, Hospital das Clinicas, Faculdade de Medicina, Universidade de São Paulo, and at the Hospital Beneficência Portuguesa de Sao Paulo, where CAD patients referred to the hospital for coronary angiography were evaluated. Results: Forty patients with CAD (20 with SA and 20 with UA) were included in the study. Blood samples from LFPV and CS were collected before coronary angiography. Furthermore, analysis of the correlation between serum levels of hs-CRP in LFPV versus CS showed a strong linear correlation for both SA (r = 0.993, p < 0.001) and UA (r = 0.976, p < 0.001) and for the entire sample (r = 0.985, p < 0.001). Conclusion: Our data suggest a strong linear correlation between hs-CRP levels in LFPV versus CS in patients with SA and UA.

Vascular Response of Ruthenium Tetraamines in Aortic Ring from Normotensive Rats

Background: Ruthenium (Ru) tetraamines are being increasingly used as nitric oxide (NO) carriers. In this context, pharmacological studies have become highly relevant to better understand the mechanism of action involved. Objective: To evaluate the vascular response of the tetraamines trans-[RuII(NH3)4(Py)(NO)]3+, trans-[RuII(Cl)(NO) (cyclan)](PF6)2, and trans-[RuII(NH3)4(4-acPy)(NO)]3+. Methods: Aortic rings were contracted with noradrenaline (10−6 M). After voltage stabilization, a single concentration (10−6 M) of the compounds was added to the assay medium. The responses were recorded during 120 min. Vascular integrity was assessed functionally using acetylcholine at 10−6 M and sodium nitroprusside at 10−6 M as well as by histological examination. Results: Histological analysis confirmed the presence or absence of endothelial cells in those tissues. All tetraamine complexes altered the contractile response induced by norepinephrine, resulting in increased tone followed by relaxation. In rings with endothelium, the inhibition of endothelial NO caused a reduction of the contractile effect caused by pyridine NO. No significant responses were observed in rings with endothelium after treatment with cyclan NO. In contrast, in rings without endothelium, the inhibition of guanylate cyclase significantly reduced the contractile response caused by the pyridine NO and cyclan NO complexes, and both complexes caused a relaxing effect. Conclusion: The results indicate that the vascular effect of the evaluated complexes involved a decrease in the vascular tone induced by norepinephrine (10−6 M) at the end of the incubation period in aortic rings with and without endothelium, indicating the slow release of NO from these complexes and suggesting that the ligands promoted chemical stability to the molecule. Moreover, we demonstrated that the association of Ru with NO is more stable when the ligands pyridine and cyclan are used in the formulation of the compound.

Neural Mechanisms and Delayed Gastric Emptying of Liquid Induced Through Acute Myocardial Infarction in Rats

Background: In pathological situations, such as acute myocardial infarction, disorders of motility of the proximal gut can trigger symptoms like nausea and vomiting. Acute myocardial infarction delays gastric emptying (GE) of liquid in rats. Objective: Investigate the involvement of the vagus nerve, α 1-adrenoceptors, central nervous system GABAB receptors and also participation of paraventricular nucleus (PVN) of the hypothalamus in GE and gastric compliance (GC) in infarcted rats. Methods: Wistar rats, N = 8-15 in each group, were divided as INF group and sham (SH) group and subdivided. The infarction was performed through ligation of the left anterior descending coronary artery. GC was estimated with pressure-volume curves. Vagotomy was performed by sectioning the dorsal and ventral branches. To verify the action of GABAB receptors, baclofen was injected via icv (intracerebroventricular). Intravenous prazosin was used to produce chemical sympathectomy. The lesion in the PVN of the hypothalamus was performed using a 1mA/10s electrical current and GE was determined by measuring the percentage of gastric retention (% GR) of a saline meal. Results: No significant differences were observed regarding GC between groups; vagotomy significantly reduced % GR in INF group; icv treatment with baclofen significantly reduced %GR. GABAB receptors were not conclusively involved in delaying GE; intravenous treatment with prazosin significantly reduced GR% in INF group. PVN lesion abolished the effect of myocardial infarction on GE. Conclusion: Gastric emptying of liquids induced through acute myocardial infarction in rats showed the involvement of the vagus nerve, alpha1- adrenergic receptors and PVN.

Role of microRNAs 221/222 on Statin Induced Nitric Oxide Release in Human Endothelial Cells

Background: Nitric oxide (NO) has been largely associated with cardiovascular protection through improvement of endothelial function. Recently, new evidence about modulation of NO release by microRNAs (miRs) has been reported, which could be involved with statin-dependent pleiotropic effects, including anti-inflammatory properties related to vascular endothelium function. Objective: To evaluate the effects of cholesterol-lowering drugs including the inhibitors of cholesterol synthesis, atorvastatin and simvastatin, and the inhibitor of cholesterol absorption ezetimibe on NO release, NOS3 mRNA expression and miRs potentially involved in NO bioavailability. Methods: Human umbilical vein endothelial cells (HUVEC) were exposed to atorvastatin, simvastatin or ezetimibe (0 to 5.0 μM). Cells were submitted to total RNA extraction and relative quantification of NOS3 mRNA and miRs -221, -222 and -1303 by qPCR. NO release was measured in supernatants by ozone-chemiluminescence. Results: Both statins increased NO levels and NOS3 mRNA expression but no influence was observed for ezetimibe treatment. Atorvastatin, simvastatin and ezetimibe down-regulated the expression of miR-221, whereas miR-222 was reduced only after the atorvastatin treatment. The magnitude of the reduction of miR-221 and miR-222 after treatment with statins correlated with the increment in NOS3 mRNA levels. No influence was observed on the miR-1303 expression after treatments. Conclusion: NO release in endothelial cells is increased by statins but not by the inhibitor of cholesterol absorption, ezetimibe. Our results provide new evidence about the participation of regulatory miRs 221/222 on NO release induction mediated by statins. Although ezetimibe did not modulate NO levels, the down-regulation of miR-221 could involve potential effects on endothelial function.

Hypotensive Response Magnitude and Duration in Hypertensives: Continuous and Interval Exercise

Background: Although exercise training is known to promote post-exercise hypotension, there is currently no consistent argument about the effects of manipulating its various components (intensity, duration, rest periods, types of exercise, training methods) on the magnitude and duration of hypotensive response. Objective: To compare the effect of continuous and interval exercises on hypotensive response magnitude and duration in hypertensive patients by using ambulatory blood pressure monitoring (ABPM). Methods: The sample consisted of 20 elderly hypertensives. Each participant underwent three ABPM sessions: one control ABPM, without exercise; one ABPM after continuous exercise; and one ABPM after interval exercise. Systolic blood pressure (SBP), diastolic blood pressure (DBP), mean arterial pressure (MAP), heart rate (HR) and double product (DP) were monitored to check post-exercise hypotension and for comparison between each ABPM. Results: ABPM after continuous exercise and after interval exercise showed post-exercise hypotension and a significant reduction (p < 0.05) in SBP, DBP, MAP and DP for 20 hours as compared with control ABPM. Comparing ABPM after continuous and ABPM after interval exercise, a significant reduction (p < 0.05) in SBP, DBP, MAP and DP was observed in the latter. Conclusion: Continuous and interval exercise trainings promote post-exercise hypotension with reduction in SBP, DBP, MAP and DP in the 20 hours following exercise. Interval exercise training causes greater post-exercise hypotension and lower cardiovascular overload as compared with continuous exercise.