Lipid transfers to HDL are predictors of precocious clinical coronary heart disease

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 +/- 33%,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% vs19.5 +/- 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. (C) 2011 Published by Elsevier B.V.

Long-Term Prospective Study of the Influence of Estrone Levels on Events in Postmenopausal Women with or at High Risk for Coronary Artery Disease

Background. The link between endogenous estrogen, coronary artery disease (CAD), and death in postmenopausal women is uncertain. We analyzed the association between death and blood levels of estrone in postmenopausal women with known coronary artery disease (CAD) or with a high-risk factor score for CAD. Methods. 251 postmenopausal women age 50-90 years not on estrogen therapy. Fasting blood for estrone and heart disease risk factors were collected at baseline. Women were grouped according to their estrone levels (<15 and >= 15 pg/mL). Fatal events were recorded after 5.8 perpendicular to 1.4 years of followup. Results. The Kaplan-Meier survival curve showed a significant trend (P = 0.039) of greater all-cause mortality in women with low estrone levels (< 15 pg/mL). Cox multivariate regression analysis model adjusted for body mass index, diabetes, dyslipidemia, family history, and estrone showed estrone (OR = 0.45; P = 0.038) as the only independent variable for all-cause mortality. Multivariate regression model adjusted for age, body mass index, hypertension, diabetes, dyslipidemia, family history, and estrone showed that only age (OR = 1.06; P = 0.017) was an independent predictor of all-cause mortality. Conclusions. Postmenopausal women with known CAD or with a high-risk factor score for CAD and low estrone levels (< 15 pg/mL) had increased all-cause mortality.

Higher incidence of death in multi-vessel coronary artery disease patients associated with polymorphisms in chromosome 9p21

Background: We investigated whether 9p21 polymorphisms are associated with cardiovascular events in a group of 611 patients enrolled in the Medical, Angioplasty or Surgery Study II (MASS II), a randomized trial comparing treatments for patients with coronary artery disease (CAD) and preserved left ventricular function. Methods: The participants of the MASS II were genotyped for 9p21 polymorphisms (rs10757274, rs2383206, rs10757278 and rs1333049). Survival curves were calculated with the Kaplan-Meier method and compared with the log-rank statistic. We assessed the relationship between baseline variables and the composite end-point of death, death from cardiac causes and myocardial infarction using a Cox proportional hazards survival model. Results: We observed significant differences between patients within each polymorphism genotype group for baseline characteristics. The frequency of diabetes was lower in patients carrying GG genotype for rs10757274, rs2383206 and rs10757278 (29.4%, 32.8%, 32.0%) compared to patients carrying AA or AG genotypes (49.1% and 39.2%, p = 0.01; 52.4% and 40.1%, p = 0.01; 47.8% and 37.9%, p = 0.04; respectively). Significant differences in genotype frequencies between double and triple vessel disease patients were observed for the rs10757274, rs10757278 and rs1333049. Finally, there was a higher incidence of overall mortality in patients with the GG genotype for rs2383206 compared to patients with AA and AG genotypes (19.5%, 11.9%, 11.0%, respectively; p = 0.04). Moreover, the rs2383206 was still significantly associated with a 1.75-fold increased risk of overall mortality (p = 0.02) even after adjustment of a Cox multivariate model for age, previous myocardial infarction, diabetes, smoking and type of coronary anatomy. Conclusions: Our data are in accordance to previous evidence that chromosome 9p21 genetic variation may constitute a genetic modulator in the cardiovascular system in different scenarios. In patients with established CAD, we observed an association between the rs2383206 and higher incidence of overall mortality and death from cardiac causes in patients with multi-vessel CAD.

Effect of continuous and interval exercise training on the PETCO2 response during a graded exercise test in patients with coronary artery disease

OBJECTIVE: The purpose of this study was to evaluate the following: 1) the effects of continuous exercise training and interval exercise training on the end-tidal carbon dioxide pressure (PETCO2) response during a graded exercise test in patients with coronary artery disease; and 2) the effects of exercise training modalities on the association between PETCO2 at the ventilatory anaerobic threshold (VAT) and indicators of ventilatory efficiency and cardiorespiratory fitness in patients with coronary artery disease. METHODS: Thirty-seven patients (59.7 +/- 1.7 years) with coronary artery disease were randomly divided into two groups: continuous exercise training (n = 20) and interval exercise training (n = 17). All patients performed a graded exercise test with respiratory gas analysis before and after three months of the exercise training program to determine the VAT, respiratory compensation point (RCP) and peak oxygen consumption. RESULTS: After the interventions, both groups exhibited increased cardiorespiratory fitness. Indeed, the continuous exercise and interval exercise training groups demonstrated increases in both ventilatory efficiency and PETCO2 values at VAT, RCP, and peak of exercise. Significant associations were observed in both groups: 1) continuous exercise training (PETCO(2)VAT and cardiorespiratory fitness r = 0.49; PETCO(2)VAT and ventilatory efficiency r = -0.80) and 2) interval exercise training (PETCO(2)VAT and cardiorespiratory fitness r = 0.39; PETCO(2)VAT and ventilatory efficiency r = -0.45). CONCLUSIONS: Both exercise training modalities showed similar increases in PETCO2 levels during a graded exercise test in patients with coronary artery disease, which may be associated with an improvement in ventilatory efficiency and cardiorespiratory fitness.

Regulatory variation in a TBX5 enhancer leads to isolated congenital heart disease

Recent studies have identified the genetic underpinnings of a growing number of diseases through targeted exome sequencing. However, this strategy ignores the large component of the genome that does not code for proteins, but is nonetheless biologically functional. To address the possible involvement of regulatory variation in congenital heart diseases (CHDs), we searched for regulatory mutations impacting the activity of TBX5, a dosage-dependent transcription factor with well-defined roles in the heart and limb development that has been associated with the HoltOram syndrome (hearthand syndrome), a condition that affects 1/100 000 newborns. Using a combination of genomics, bioinformatics and mouse genetic engineering, we scanned approximate to 700 kb of the TBX5 locus in search of cis-regulatory elements. We uncovered three enhancers that collectively recapitulate the endogenous expression pattern of TBX5 in the developing heart. We re-sequenced these enhancer elements in a cohort of non-syndromic patients with isolated atrial and/or ventricular septal defects, the predominant cardiac defects of the HoltOram syndrome, and identified a patient with a homozygous mutation in an enhancer approximate to 90 kb downstream of TBX5. Notably, we demonstrate that this single-base-pair mutation abrogates the ability of the enhancer to drive expression within the heart in vivo using both mouse and zebrafish transgenic models. Given the population-wide frequency of this variant, we estimate that 1/100 000 individuals would be homozygous for this variant, highlighting that a significant number of CHD associated with TBX5 dysfunction might arise from non-coding mutations in TBX5 heart enhancers, effectively decoupling the heart and hand phenotypes of the HoltOram syndrome.

Ischemic heart disease and correlates in adults from Ribeirao Preto, Brazil

OBJECTIVE: To identify the prevalence of ischemic heart disease (IHD) and correlates in an adult population. METHODS: Cross-sectional population-based epidemiological study including a weighted sample of 2,471 adults of both sexes and with age 30 years or older residing in Ribeirao Preto, Southeastern Brazil, in 2007. The Rose Questionnaire was administered, and IHD prevalence was calculated with point estimates and 95% confidence intervals. To identify correlates (sociodemographic, cardiovascular risk factors, and those related to access to health services and to physical activity level), crude and adjusted prevalence ratios were estimated using Poisson regression. RESULTS: IHD prevalence was higher in females than males at all age strata. In the final model, the following variables were independently associated with IHD: work status (PR = 0.54 [0.37; 0.78]); family history of IHD (PR = 1.55 [1.12;2.13]); hypertension (PR = 1.70 [1.18;2.46]); self-reported health status (PR=2.15 [1.40;3.31]); smoking duration (third tertile) (PR=1.73 [1.08;2.76]); adjusted waist circumference (PR=1.79 [1.21;2.65]) and hypertriglyceridemia (PR=1.48 [1.05;2.10]). Linear trend test of PR across self-reported health status categories was statistically significant (p<0.05). CONCLUSIONS: A high prevalence of IHD was found, and the factors associated with the outcome are almost all modifiable and potentially influenced by public policy interventions.

Evaluation of Surgical Treatment of Congenital Heart Disease in Patients Aged Above 16 Years

Background: The increasing number of children with evolving congenital heart diseases demands greater preparation of professionals and institutions that handle them. Objective: To describe the profile of patients aged over 16 years with congenital heart disease, who have undergone surgery, and analyze the risk factors that predict hospital mortality. Methods: One thousand five hundred twenty patients (mean age 27 +/- 13 years) were operated between January 1986 and December 2010. We performed a descriptive analysis of the epidemiological profile of the study population and analyzed risk factors for hospital mortality, considering the complexity score, the year in which surgery was performed, the procedure performed or not performed by the pediatric surgeon and reoperation. Results: There was a significant increase in the number of cases from the year 2000. The average complexity score was 5.4 and the septal defects represented 45% of cases. Overall mortality was 7.7% and most procedures (973 or 61.9%) with greater complexity were performed by pediatric surgeons. Complexity (OR 1.5), reoperation (OR 2.17) and pediatric surgeon (OR 0.28) were independent risk factors influencing mortality. Multivariate analysis showed that the year in which the surgery was performed (OR 1.03), the complexity (OR 1.44) and the pediatric surgeon (OR 0.28) influenced the result. Conclusion: There is an increasing number of patients aged 16 years which, despite the large number of simple cases, the most complex ones were referred to pediatric surgeons, who had lower mortality, especially in recent years. (Arq Bras Cardiol 2012;98(5):390-397)

Abnormal function of monoamine oxidase-A in comorbid major depressive disorder and cardiovascular disease: Pathophysiological and therapeutic implications (Review)

The association between major depressive disorder (MDD) and cardiovascular disease (CVD) is among the best described medical comorbidities. The presence of MDD increases the risk of cardiac admissions and mortality and increases healthcare costs in patients with CVD, and similarly, CVD affects the course and outcome of MDD. The potential shared biological mechanisms involved in these comorbid conditions are not well known. However, the enzyme monoamine oxidase-A (MAO-A), which has a key role in the degradation of catecholamines, has been associated with the pathophysiology and therapeutics of both MDD and CVD. Increased MAO-A activity results in the dysregulation of downstream targets of this enzyme and thus affects the pathophysiology of the two diseases. These deleterious effects include altered noradrenaline turnover, with a direct elevation in oxidative stress parameters, as well as increased platelet activity and cytokine levels. These effects were shown to be reversed by MAO inhibitors. Here, a model describing a key role for the MAO-A in comorbid MDD and CVD is proposed, with focus on the shared pathophysiological mechanisms and the potential therapeutic relevance of agents targeting this enzyme.

Genetic and environmental risk factors in congenital heart disease functionally converge in protein networks driving heart development

Congenital heart disease (CHD) occurs in similar to 1% of newborns. CHD arises from many distinct etiologies, ranging from genetic or genomic variation to exposure to teratogens, which elicit diverse cell and molecular responses during cardiac development. To systematically explore the relationships between CHD risk factors and responses, we compiled and integrated comprehensive datasets from studies of CHD in humans and model organisms. We examined two alternative models of potential functional relationships between genes in these datasets: direct convergence, in which CHD risk factors significantly and directly impact the same genes and molecules and functional convergence, in which risk factors significantly impact different molecules that participate in a discrete heart development network. We observed no evidence for direct convergence. In contrast, we show that CHD risk factors functionally converge in protein networks driving the development of specific anatomical structures (e.g., outflow tract, ventricular septum, and atrial septum) that are malformed by CHD. This integrative analysis of CHD risk factors and responses suggests a complex pattern of functional interactions between genomic variation and environmental exposures that modulate critical biological systems during heart development.

Long-Term Follow-Up of Implantable Cardioverter-Defibrillator for Secondary Prevention in Chagas' Heart Disease

Assessing the efficacy of implantable cardioverter-defibrillators (ICD) in patients with Chagas' heart disease (ChHD) and identifying the clinical predictors of mortality and ICD shock during long-term follow-up. ChHD is associated with ventricular tachyarrhythmias and an increased risk of sudden cardiac death. Although ChHD is a common form of cardiomyopathy in Latin American ICD users, little is known about its efficacy in the treatment of this population. The study cohort included 116 consecutive patients with ChHD and an ICD implanted for secondary prevention. Of the 116 patients, 83 (72%) were men; the mean age was 54 +/- 10.7 years. Several clinical variables were tested in a multivariate Cox model for predicting long-term mortality. The average follow-up was 45 +/- 32 months. New York Heart Association class I-II developed in 83% of patients. The mean left ventricular ejection fraction was 42 +/- 16% at implantation. Of the 116 patients, 58 (50%) had appropriate shocks and 13 (11%) had inappropriate therapy. A total of 31 patients died (7.1% annual mortality rate). New York Heart Association class III (hazard ratio [HR] 3.09, 95% confidence interval 1.37 to 6.96, p = 0.0064) was a predictor of a worse prognosis. The left ventricular ejection fraction (HR 0.972, 95% confidence interval 0.94 to 0.99, p = 0.0442) and low cumulative right ventricular pacing (HR 0.23, 95% confidence interval 0.11 to 0.49, p = 0.0001) were predictors of better survival. The left ventricular diastolic diameter was an independent predictor of appropriate shock (I-ER 1.032, 95% confidence interval 1.004 to 1.060, p = 0.025). In conclusion, in a long-term follow-up, ICD efficacy for secondary sudden cardiac death prevention in patients with ChHD was marked by a favorable annual rate of all-cause mortality (7.1%); 50% of the cohort received appropriate shock therapy. New York Heart Association class III and left ventricular ejection fraction were independent predictors of worse prognosis, and low cumulative right ventricular pacing defined better survival. (C) 2012 Elsevier Inc. All rights reserved. (Am J Cardiol 2012;110:1040-1045)

Inflammation and circulating endothelial progenitor cells in patients with coronary artery disease and residual platelet reactivity

Sao Paulo Research Foundation [FAPESP/05/57710-3]

Cancer-related deaths among different treatment options in chronic coronary artery disease: results of a 6-year follow-up of the MASS II study

Introduction The primary end points of randomized clinical trials evaluating the outcome of therapeutic strategies for coronary artery disease (CAD) have included nonfatal acute myocardial infarction, the need for further revascularization, and overall mortality. Noncardiac causes of death may distort the interpretation of the long-term effects of coronary revascularization. Materials and methods This post-hoc analysis of the second Medicine, Angioplasty, or Surgery Study evaluates the cause of mortality of patients with multivessel CAD undergoing medical treatment, percutaneous coronary intervention, or surgical myocardial revascularization [coronary artery bypass graft surgery (CABG)] after a 6-year follow-up. Mortality was classified as cardiac and noncardiac death, and the causes of noncardiac death were reported. Results Patients were randomized into CABG and non-CABG groups (percutaneous coronary intervention plus medical treatment). No statistical differences were observed in overall mortality (P = 0.824). A significant difference in the distribution of causes of mortality was observed among the CABG and non-CABG groups (P = 0.003). In the CABG group, of the 203 randomized patients, the overall number of deaths was 34. Sixteen patients (47.1%) died of cardiac causes and 18 patients (52.9%) died of noncardiac causes. Of these, seven deaths (20.6%) were due to neoplasia. In the non-CABG group, comprising 408 patients, the overall number of deaths was 69. Fifty-three patients (77%) died of cardiac causes and 16 patients (23%) died of noncardiac causes. Only five deaths (7.2%) were due to neoplasia. Conclusion Different treatment options for multivessel coronary artery disease have similar overall mortality: CABG patients had the lowest incidence of cardiac death, but the highest incidence of noncardiac causes of death, and specifically a higher tendency toward cancer-related deaths. Coron Artery Dis 23:79-84 (C) 2012 Wolters Kluwer Health | Lippincott Williams & Wilkins.

Effect of Complete Revascularization on 10-Year Survival of Patients With Stable Multivessel Coronary Artery Disease MASS II Trial

Background-The importance of complete revascularization remains unclear and contradictory. This current investigation compares the effect of complete revascularization on 10-year survival of patients with stable multivessel coronary artery disease (CAD) who were randomly assigned to percutaneous coronary intervention (PCI) or coronary artery bypass graft (CABG). Methods and Results-This is a post hoc analysis of the Second Medicine, Angioplasty, or Surgery Study (MASS II), which is a randomized trial comparing treatments in patients with stable multivessel CAD, and preserved systolic ventricular function. We analyzed patients who underwent surgery (CABG) or stent angioplasty (PCI). The survival free of overall mortality of patients who underwent complete (CR) or incomplete revascularization (IR) was compared. Of the 408 patients randomly assigned to mechanical revascularization, 390 patients (95.6%) underwent the assigned treatment; complete revascularization was achieved in 224 patients (57.4%), 63.8% of those in the CABG group and 36.2% in the PCI group (P = 0.001). The IR group had more prior myocardial infarction than the CR group (56.2% X 39.2%, P = 0.01). During a 10-year follow-up, the survival free of cardiovascular mortality was significantly different among patients in the 2 groups (CR, 90.6% versus IR, 84.4%; P = 0.04). This was mainly driven by an increased cardiovascular specific mortality in individuals with incomplete revascularization submitted to PCI (P = 0.05). Conclusions-Our study suggests that in 10-year follow-up, CR compared with IR was associated with reduced cardiovascular mortality, especially due to a higher increase in cardiovascular-specific mortality in individuals submitted to PCI.

Eating behavior and nutritional status in patients who underwent coronary angioplasty

Introduction: The identification of stages of dietary change and the factors affecting food choices can direct more effective nutritional intervention against coronary heart disease progression. Objective: Identify the stages of change of eating behavior and its relation with nutritional status, food consumption and previous cardiovascular events in patients who underwent coronary angioplasty. Methods: A cross-sectional study with 200 hospitalized patients from a specialized cardiology hospital, after elective coronary angioplasty. They were applied an algorithm that identifies the provision of change of eating habits for a healthier pattern. Variables measured were stages of change of eating behavior, nutritional status, food consumption and cardiovascular events (previous myocardial infarction or angioplasty). It was realized comparison of averages by analysis of variance or Student's test and Chi-square test for qualitative variables. Value of significance was taken at 5%. Results: The patients were classified in the following stages: 36% maintenance, 26% preparation, 17% precontemplation, 12% action and 9% contemplation. It was observed higher cardiovascular events in maintenance/action group (p = 0.04), higher consumption of calories (p = 0.04), meat/eggs (p = 0.01) and sweets (p = 0.03) in preparation stage, comparing to maintenance group, and no association between nutritional status and stages of change (p = 0.13), although 62% of the individuals in maintenance stage were overweight. Conclusions: This work contributed to identifying the stages of change and conditions that favor changes in eating pattern. Even patients that classified themselves into the maintenance stage need to adjust their eating habits in order to reach a healthy weight.

Cost-Effectiveness Analysis for Surgical, Angioplasty, or Medical Therapeutics for Coronary Artery Disease 5-Year Follow-Up of Medicine, Angioplasty, or Surgery Study (MASS) II Trial

Background-The Second Medicine, Angioplasty, or Surgery Study (MASS II) included patients with multivessel coronary artery disease and normal systolic ventricular function. Patients underwent coronary artery bypass graft surgery (CABG, n = 203), percutaneous coronary intervention (PCI, n = 205), or medical treatment alone (MT, n = 203). This investigation compares the economic outcome at 5-year follow-up of the 3 therapeutic strategies. Methods and Results-We analyzed cumulative costs during a 5-year follow-up period. To analyze the cost-effectiveness, adjustment was made on the cumulative costs for average event-free time and angina-free proportion. Respectively, for event-free survival and event plus angina-free survival, MT presented 3.79 quality-adjusted life-years and 2.07 quality-adjusted life-years; PCI presented 3.59 and 2.77 quality-adjusted life-years; and CABG demonstrated 4.4 and 2.81 quality-adjusted life-years. The event-free costs were $9071.00 for MT; $19 967.00 for PCI; and $18 263.00 for CABG. The paired comparison of the event-free costs showed that there was a significant difference favoring MT versus PCI (P<0.01) and versus CABG (P<0.01) and CABG versus PCI (P<0.01). The event-free plus angina-free costs were $16 553.00, $25 831.00, and $24 614.00, respectively. The paired comparison of the event-free plus angina-free costs showed that there was a significant difference favoring MT versus PCI (P=0.04), and versus CABG (P<0.001); there was no difference between CABG and PCI (P>0.05). Conclusions-In the long-term economic analysis, for the prevention of a composite primary end point, MT was more cost effective than CABG, and CABG was more cost-effective than PCI.