[Show abstract][Hide abstract] ABSTRACT: The frequency of resistant hypertension—defined as blood pressure (BP) ≥140/90 mm Hg with proven use of three antihypertensive medications, or as the use of four antihypertensive drug classes regardless of BP—is unknown in low-middle–income countries. Using data from the Brazilian Longitudinal Study of Adult Health, a cohort of 15,105 civil servants aged 35 to 74 years, the authors identified 4116 patients taking treatment for hypertension, 11% of who had resistant hypertension. These participants were more likely to be older, black, less educated, poorer, and obese. The adjusted prevalence ratios (95% confidence intervals) were diabetes, 1.44 (1.20–1.72); glomerular filtration rate (<60 mL/min/1.72 m2), 1.95 (1.60–2.38); albumin-to-creatinine ratio (>300 mg/g), 2.43 (1.70–3.50); carotid-femoral pulse-wave velocity, 1.07 m/s (1.03–1.11 m/s); common carotid intima-media thickness, 2.57 mm (1.64–4.00 mm); left ventricular hypertrophy, 2.08 (1.21–3.57); and atrial fibrillation, 3.55 (2.02–6.25). Thus, the prevalence of resistant hypertension in Brazil is high and associated with subclinical markers of end-organ cardiovascular damage.
Journal of Clinical Hypertension 10/2014; · 2.36 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Funding Information This work was supported by Fundac ß~ ao Zerbini and Fundac ß~ ao de Amparo a Pesquisa (FAPESP 2011/04344-0). Abstract Several techniques to induce renal ischemia have been proposed: clamp, PVA particles, and catheter-balloon. We report the development of a controlled, single-insult model of unilateral renal ischemia/reperfusion (I/R) without contralateral nephrectomy, using a suitable model, the pig. This is a balloon-catheter-based model using a percutaneous, interventional radiology proce-dure. One angioplasty balloon-catheter was placed into the right renal artery and inflated for 120 min and reperfusion over 24 h. Serial serums were sam-pled from the inferior vena cava and urine was directly sampled from the bladder throughout the experiment, and both kidneys were excised after 24 h of reperfusion. Analyses of renal structure and function were performed by hematoxylin–eosin/periodic Acid-Schiff, serum creatinine (SCr), blood urea nitrogen (BUN), fractional excretion of ions, and glucose, SDS-PAGE analysis of urinary proteins, and serum neutrophil gelatinase-associated lipocalin (NGAL). Total nitrated protein was quantified to characterize oxidative stress. Acute tubular necrosis (ATN) was identified in every animal, but only two animals showed levels of SCr above 150% of baseline values. As expected, I/R increased SCr and BUN. Fractional sodium, potassium, chloride, and bicar-bonate excretion were modulated during ischemia. Serum-nitrated proteins and NGAL had two profiles: decreased with ischemia and increased after rep-erfusion. This decline was associated with increased protein excretion during ischemia and early reperfusion. Altogether, these data show that the renal I/R model can be performed by percutaneous approach in the swine model. This is a suitable translational model to study new early renal ischemic biomarkers and pathophysiological mechanisms in renal ischemia.
[Show abstract][Hide abstract] ABSTRACT: A previous study reported that the myosin regulatory light chain interacting protein (MYLIP) protein might serve as a novel therapeutic class for treating dyslipidemia. It contributes to variations in the levels of circulating low-density lipoprotein cholesterol (LDL-C), promoting the degradation of LDL-LDLR, thus limiting absorption. The effect of genetic variation in the MYLIP gene in a disease scenario characterized by mutations in the LDLR gene has not been previously evaluated.
Pharmacogenetics and Genomics 08/2014; · 3.61 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Increases in resting-state heart rate and decreases in its variability are associated with substantial morbidity and mortality, yet contradictory findings have been reported for the effects of the mood and anxiety disorders and of antidepressants. The authors investigated heart rate and heart rate variability in a large cohort from Brazil, using propensity score weighting, a relatively novel method, to control for numerous potential confounders.
American Journal of Psychiatry 08/2014; · 14.72 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Abstract Effective analytical tools are highly desirable for data analysis and for making the biological link between genotypic and phenotypic measures. In family data it is important to reconcile the methods that explain the phenotypic variability through fixed genetic effects and ones that estimate variance components using classical heritability methods. Thus, in this paper, we propose a method based on added-variable plot for polygenic linear mixed models applied to genome wide association studies in family-based designs. Our goal is to be able to discriminate genetic predictor variables in effects due to random polygenic and residual components. We also propose an index to detect influential families for each predictor variable identified with genetic effect. We assess the performance of our proposed method using our own family simulated data and the Genetic Analysis Workshop 17 family simulated data.
Statistical Applications in Genetics and Molecular Biology 06/2014; 13(3):359-78. · 1.52 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Refractory angina is a severe form of coronary artery disease (CAD) characterized by persistent angina despite optimal medical therapy. Obstructive sleep apnea (OSA) and depression are common in patients with stable CAD and may contribute to a poor prognosis. We hypothesized that OSA and depression are more common and more severe in patients with refractory angina than in patients with stable CAD.
We used standardized questionnaires and full polysomnography to compare consecutive patients with well-established refractory angina versus consecutive patients with stable CAD evaluated for coronary artery bypass graft surgery.
Patients with refractory angina (n=70) compared with patients with stable CAD (n=70) were similar in respect to sex distribution (male: 61.5% vs 75.5%; p=0.07), body mass index (29.5±4 kg/m2 vs 28.5±4 kg/m2; p=0.06) and were older (61±10 yr vs 57±7 yr; p=0.013), respectively. Patients with refractory angina had significantly more symptoms of daytime sleepiness (Epworth: 12±6 vs 8±5; p<0.001), had higher depression symptom scores (Beck: 19±8 vs 10±8; p<0.001) despite greater use of antidepressants, had higher apnea-hypopnea index (AHI: 37±30 events/h vs 23±20 events/h, p=0.001), higher proportion of oxygen saturation <90% during sleep (8%±13 vs 4%±9, p=0.04) and a higher proportion of severe OSA (AHI ≥30 events/h: 48% vs 27%; p=0.009) than patients with stable CAD. OSA (p=0.017), depression (p<0.001), higher Epworth (p=0.007) and lower sleep efficiency (p=0.016) were independently associated with refractory angina in multivariate analysis.
OSA and depression are independently associated with refractory angina and may contribute to poor cardiovascular outcome.
[Show abstract][Hide abstract] ABSTRACT: Polymorphisms in the LPA gene were associated with coronary artery disease (CAD). However, there are differences in the allelic frequencies, Lp(a) levels, and significant association with CAD according to ethnic groups. In this scenario, the main aim of this study was to assess the influence of the LPA polymorphisms on coronary lesions in Brazilian patients.
1,394 consecutive patients submitted to coronary angiography to study suggestive CAD and twenty coronary segments were scored. Genotyping for the LPA rs10455872 and rs3798220 polymorphisms were performed by high resolution melting analysis.
The frequencies of the rs10455872 G and rs3798220 C variant alleles were 6.4% and 6.2%, respectively. LPA rs10455872 G variant allele was associated with higher odds ratio of having coronary lesions in an adjusted model (OR = 2.02, 95%CI = 1.10-3.72, p = 0.02). Scores of coronary lesions (extension, severity, and Gensini scores) were significantly different among rs10455872 genotype groups. Coronary lesions was not associated with LPA rs3798220 (OR = 1.09, 95%CI = 0.67-1.76, p = 0.73) and scores of coronary lesions were not different among rs3798220 genotypes.
We confirmed the association of the LPA rs10455872 with CAD in a large sample of Brazilian patients. For the LPA rs3798220, our finding is consistent with studies which showed the lack of this genetic association.
Lipids in Health and Disease 04/2014; 13(1):74. · 2.31 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Health interventions aimed at smoking cessation can clearly have
a significant impact on public health around the globe. Even though
the health benefits of quitting smoking are indisputable, research
indicates that smoking cessation is associated with an increase in
the prevalence of overweight. In this scenario, the present study
evaluated the weight gain among patients participating in a smoking
cessation intervention in order to find possible predictor variables.
International journal of cardiology 01/2014; · 6.18 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Many important complex diseases are composed of a series of phenotypes, which makes the disease diagnosis and its genetic dissection difficult. The standard procedures to determine heritability in such complex diseases are either applied for single phenotype analyses or to compare findings across phenotypes or multidimensional reduction procedures, such as principal components analysis using all phenotypes. However each method has its own problems and the challenges are even more complex for extended family data and categorical phenotypes. In this paper, we propose a methodology to determine a scale for complex outcomes involving multiple categorical phenotypes in extended pedigrees using item response theory (IRT) models that take all categorical phenotypes into account, allowing informative comparison among individuals. An advantage of the IRT framework is that a straightforward joint heritability parameter can be estimated for categorical phenotypes. Furthermore, our methodology allows many possible extensions such as the inclusion of covariates and multiple variance components. We use Markov Chain Monte Carlo algorithm for the parameter estimation and validate our method through simulated data. As an application we consider the metabolic syndrome as the multiple phenotype disease using data from the Baependi Heart Study consisting of 1,696 individuals in 95 families. We adjust IRT models without covariates and include age and age squared as covariates. The results showed that adjusting for covariates yields a higher joint heritability (ĥ2=0.53) than without co variates (ĥ2=0.21) indicating that the covariates absorbed some of the error variance.
[Show abstract][Hide abstract] ABSTRACT: The use of the anthropometric indices of adiposity, especially body mass index and waist circumference in the prediction of diabetes mellitus has been widely explored. Recently, a new body composition index, the body adiposity index was proposed. The aim of this study was to compare the effectiveness of body mass index, waist circumference, and body adiposity index in the risk assessment for type 2 diabetes mellitus.
PLoS ONE 01/2014; 9(6):e100223. · 3.53 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Aortic stiffness is associated with increased cardiovascular mortality. However, the determinants of aortic stiffness progression are not fully established. This study evaluated the predictive value of blood pressure (BP) response to cold pressor test (CPT) in the progression of carotid-femoral pulse wave velocity (PWV) in men and women.
A total of 408 individuals (165 men, 243 women) from Vitoria, Brazil, underwent BP evaluation, clinical and laboratorial investigations, and CPT and PWV assessment. Five years later, the studied individuals were re-evaluated, except for the CPT.
In men, 5-year PWV change correlated inversely with baseline PWV (P < 0.001) and directly with BP response to CPT (P < 0.05) and 5-year BP change (P < 0.05). In women, 5-year PWV change correlated inversely with baseline PWV (P < 0.001) and directly with age (P < 0.01), glycemia (P < 0.05) and 5-year BP change (P < 0.05) but not with BP response to CPT. Further linear regression analysis showed that 5-year PWV change was associated with baseline PWV, systolic BP response to CPT, and 5-year systolic BP change in men and with baseline PWV, age, glycemia, and 5-year systolic BP change in women.
BP response to CPT was a predictor of PWV progression in men after 5 years of follow-up. These findings provide further insights into the pathophysiologic mechanisms of arterial stiffness, suggesting that elevated sympathetic reactivity may be a predisposing factor for future increases in aortic stiffness, at least in men.
American Journal of Hypertension 11/2013; · 3.67 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: -The present study addressed the hypothesis that the activity of dipeptidyl peptidase IV (DPPIV), an enzyme that inactivates peptides that possess cardioprotective actions, correlates with adverse outcomes in heart failure (HF). The therapeutic potential of DPPIV inhibition in preventing cardiac dysfunction was also investigated.
-Measurements of DPPIV activity in blood samples obtained from 190 HF patients and 42 controls demonstrated that patients with HF exhibited an increase of approximately 130% in circulating DPPIV activity compared with healthy subjects. Furthermore, an inverse correlation was observed between serum DPPIV activity and left ventricular LV ejection fraction in HF patients. Similarly, radiofrequency LV ablation-induced HF rats displayed higher DPPIV activity in the plasma (~50%) and heart tissue (~3.5 fold) compared with sham-operated rats. Moreover, positive correlations were observed between the plasma DPPIV activity and LV end-diastolic pressure (LVEDP) and lung congestion. Two days after surgery, one group of LV ablation-induced HF rats was treated with the DPPIV inhibitor sitagliptin (40 mg/kg, twice daily) for six weeks, whereas the remaining rats were administered water. Hemodynamic measurements demonstrated that radiofrequency LV-ablated rats treated with sitagliptin exhibited a significant attenuation of HF-related cardiac dysfunction, including LVEDP, systolic performance and chamber stiffness. Sitagliptin treatment also attenuated cardiac remodeling and cardiomyocyte apoptosis and minimized pulmonary congestion.
-Collectively, the results presented herein associate circulating DPPIV activity with poorer cardiovascular outcomes in human and experimental HF. Moreover, the results demonstrate that long-term DPPIV inhibition mitigates the development and/or progression of HF in rats.
[Show abstract][Hide abstract] ABSTRACT: The Brazilian Longitudinal Study for Adult Health (ELSA-Brasil) is a multicenter prospective cohort of civil servants designed to assess the determinants of chronic diseases, especially cardiovascular diseases and type 2 diabetes. The present article describes the main design and implementation points of the ELSA-Brasil biobank project. Economic, political, logistical and technological aspects of this study are characterized. Additionally, it discusses the final biorepository protocol and the facilities implemented to achieve this objective. The design and implementation process of the ELSA-Brasil biobank took three years to be performed. Both the central and local biobanks were built according to the best biorepository techniques, using different technological solutions for the distinct needs expected in this study.
Revista de saude publica 06/2013; 47 Suppl 2:72-8. · 1.01 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The ELSA (Estudo Longitudinal de Saúde do Adulto - Brazilian Longitudinal Study for Adult Health) is a multicenter cohort study which aims at the identification of risk factors associated with type 2 diabetes and cardiovascular diseases in the Brazilian population. The paper describes the strategies for the collection, processing, transportation, and quality control of blood and urine tests in the ELSA. The study decided to centralize the tests at one single laboratory. The processing of the samples was performed at the local laboratories, reducing the weight of the material to be transported, and diminishing the costs of transportation to the central laboratory at the Universidade de São Paulo Hospital. The study included tests for the evaluation of diabetes, insulin resistance, dyslipidemia, electrolyte abnormalities, thyroid hormones, uric acid, hepatic enzyme abnormalities, inflammation, and total blood cell count. In addition, leukocyte DNA, urine, plasma and serum samples were stored. The central laboratory performed approximately 375,000 tests.
Revista de saude publica 06/2013; 47 Suppl 2:63-71. · 1.01 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: BACKGROUND: Null genotypes of glutathione S-transferase (GST) exhibit the absence of enzymatic activity and are associated with increased cardiovascular risk. Recent reports have related both lower and higher urinary sodium excretion (USE) to higher cardiovascular risk. Here we investigate the impact of GSTM1 and GSTT1-null polymorphisms on USE in a Brazilian population. METHODS: We cross-sectionally evaluated 1,308 subjects from the city of Vitoria, Brazil, based on clinical history, physical examination, anthropometry, analysis of laboratory parameters, measurement of USE, and GST polymorphisms genotyping. RESULTS: The frequency of GST M1, T1, and double-deletion polymorphisms was 51%, 22%, and 11%, respectively. Individuals with the GSTM1-null genotype had lower USE than those with the non-null genotype (92.1±52.3 vs. 102.8 ± 6 0.7 mEq/12h; P < 0.001). Linear regression analysis adjusted for confounding factors revealed that the GSTM1-null genotype was independently associated with USE (P = 0.001). In addition, diastolic blood pressure and triglyceride levels were higher in GSTM1-null individuals than in non-null individuals in the highest tertile of USE. Finally, the presence of GSTT1-null or double-deleted genotypes did not influence USE or affect the interactions between USE and the variables studied. CONCLUSIONS: Deletion of GSTM1 was associated with low USE and modulated the interaction between sodium intake and blood pressure in Brazilian subjects. These novel findings may provide a new unexplored link between sodium regulation and GST homeostasis.
American Journal of Hypertension 05/2013; · 3.67 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: BACKGROUND: According to hypertension guidelines, the recommended electrocardiographic (ECG) diagnostic criteria for left ventricular hypertrophy (LVH) are the Sokolow-Lyon and Cornel voltage criteria, both with general acceptance by primary care physicians. However, it was recently reported that the R-wave voltage in lead aVL (RaVL) was as good as other more complicated and time-consuming ECG criteria to detect LVH in hypertensive patients. Therefore, our aim was to investigate if the ability of the RaVL to identify echocardiographic left ventricular hypertrophy (ECHO-LVH) could be translated to the general population, a more realistic assessment of its utility in a nonreferral setting. METHODS: 682 participants (43.5 % males), aged between 27 and 72 years from the urban population of Vitoria, ES, Brazil, were enrolled. We investigated the association of ECHO-LVH (LV mass >51 g/Ht(2.7)) with several ECG voltage measurements: Sokolow-Lyon and Cornel criteria, S-wave voltage in lead V3 (SV3) and RaVL. RESULTS: The RaVL showed the best positive correlation with LV mass indexed to Ht(2.7), superior to both Cornell and Sokolow-Lyon criteria and was not influenced by gender. Analysis of the ROC curves showed that the RaVL depicted a significant superior performance in relation to all the other measurements in the ability to detect ECHO-LVH. SV3 was not correlated with LV mass. Thus, it seems that most of Cornell's performance depends on its simplified version, that is, RaVL. CONCLUSION: We have shown that the simple and single assessment of RaVL presented a greater diagnostic ability in detecting ECHO-LVH in the general population, signaling its value mainly as a screening tool.
Clinical Research in Cardiology 05/2013; · 3.67 Impact Factor