Analysis of the Association Between Apolipoprotein E Polymorphism and Cardiovascular Risk Factors in an Elderly Population with Longevity

OBJECTIVE: To establish the allelic and genotypic frequencies related to apolipoprotein E (ApoE) polymorphism and association of the genotypes with risk factors and cardiovascular morbidity in an elderly population with longevity. METHODS: We analyzed 70 elderly patients aged 80 years or more who were part of the Projeto Veranópolis. We used the gene amplification technique through the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and cleavage with the restriction enzyme Hha I to identify the ApoE genotypes. The most frequent genotypes were compared considering biological variables and cardiovascular risks and morbidity. RESULTS: The frequencies of the E2, E3, and E4 alleles were 0.05, 0.84, and 0.11, respectively, and of the genotypes were as follows: E3E3 (0.70), E3E4 (0.22), E2E3 (0.06), and E2E2 (0.02). Individuals with the E3E4 had a mean age greater than those with the E3E3. No association was observed between the genotypes and the variables analyzed, except for obesity, which was associated with the E3E3 genotype. Individuals with the E3E4 genotype had high levels of LDL-cholesterol and fibrinogen as compared with those with the E3E3 genotype. CONCLUSION: The results suggest that the E4E4 genotype may be associated with early mortality. A balance between the protective or neutral factors and the cardiovascular risk factors may occur among the individuals with different genotypes, attenuating the negative effects of the E4 allele.

South American Guidelines for Cardiovascular Disease Prevention and Rehabilitation

In this document, the Inter-American Committee of Cardiovascular Prevention and Rehabilitation, together with the South American Society of Cardiology, aimed to formulate strategies, measures, and actions for cardiovascular disease prevention and rehabilitation (CVDPR). In the context of the implementation of a regional and national health policy in Latin American countries, the goal is to promote cardiovascular health and thereby decrease morbidity and mortality. The study group on Cardiopulmonary and Metabolic Rehabilitation from the Department of Exercise, Ergometry, and Cardiovascular Rehabilitation of the Brazilian Society of Cardiology has created a committee of experts to review the Portuguese version of the guideline and adapt it to the national reality. The mission of this document is to help health professionals to adopt effective measures of CVDPR in the routine clinical practice. The publication of this document and its broad implementation will contribute to the goal of the World Health Organization (WHO), which is the reduction of worldwide cardiovascular mortality by 25% until 2025. The study group's priorities are the following: • Emphasize the important role of CVDPR as an instrument of secondary prevention with significant impact on cardiovascular morbidity and mortality; • Join efforts for the knowledge on CVDPR, its dissemination, and adoption in most cardiovascular centers and institutes in South America, prioritizing the adoption of cardiovascular prevention methods that are comprehensive, practical, simple and which have a good cost/benefit ratio; • Improve the education of health professionals and patients with education programs on the importance of CVDPR services, which are directly targeted at the health system, clinical staff, patients, and community leaders, with the aim of decreasing the barriers to CVDPR implementation.

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

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

Air pollution and its impacts on health in Vitoria, Espirito Santo, Brazil

ABSTRACT OBJECTIVE To analyze the impact of air pollution on respiratory and cardiovascular morbidity of children and adults in the city of Vitoria, state of Espirito Santo. METHODS A study was carried out using time-series models via Poisson regression from hospitalization and pollutant data in Vitoria, ES, Southeastern Brazil, from 2001 to 2006. Fine particulate matter (PM10), sulfur dioxide (SO2), and ozone (O3) were tested as independent variables in simple and cumulative lags of up to five days. Temperature, humidity and variables indicating weekdays and city holidays were added as control variables in the models. RESULTS For each increment of 10 µg/m3 of the pollutants PM10, SO2, and O3, the percentage of relative risk (%RR) for hospitalizations due to total respiratory diseases increased 9.67 (95%CI 11.84-7.54), 6.98 (95%CI 9.98-4.17) and 1.93 (95%CI 2.95-0.93), respectively. We found %RR = 6.60 (95%CI 9.53-3.75), %RR = 5.19 (95%CI 9.01-1.5), and %RR = 3.68 (95%CI 5.07-2.31) for respiratory diseases in children under the age of five years for PM10, SO2, and O3, respectively. Cardiovascular diseases showed a significant relationship with O3, with %RR = 2.11 (95%CI 3.18-1.06). CONCLUSIONS Respiratory diseases presented a stronger and more consistent relationship with the pollutants researched in Vitoria. A better dose-response relationship was observed when using cumulative lags in polynomial distributed lag models.

Alcohol and atherosclerosis

Observational studies have attributed a protective effect to alcohol consumption on the development of atherosclerosis and cardiovascular morbidity and mortality. Alcohol intake in the amount of one to two drinks per day results in an estimated 20-40% reduction in cardiovascular events. An additional protective effect, according to major cohort studies, has been attributed to wine, probably due to antioxidant effects and platelet antiaggregation agents. On the other hand, the influence of different patterns of alcohol consumption and environmental factors may explain a great part of the additional effect of wine. Protection may be mediated by modulation of other risk factors, because alcohol increases HDL-C, produces a biphasic response on blood pressure, and modulates the endothelial function, while it neither increases body weight nor impairs glucose-insulin homeostasis. Alcohol may also have a direct effect on atherogenesis. Despite these favorable effects, the current evidence is not enough to justify prescribing alcohol to prevent cardiovascular disease.

Hypertension in Patients with Cancer

There is a known association between chemotherapy and radiotherapy for treatment of cancer patients and development or worsening of hypertension. The aim of this article is to review this association. A literature search was conducted for articles reporting this association on the databases PubMed, SciELO and LILACS between 1993 and 2013. There was a high coprevalence of hypertension and cancer, since both diseases share the same risk factors, such as sedentary lifestyle, obesity, smoking, unhealthy diet and alcohol abuse. The use of chemotherapy and adjuvant drugs effective in the treatment of cancer increased the survival rate of these patients and, consequently, increased the incidence of hypertension. We described the association between the use of angiogenesis inhibitors (bevacizumab, sorafenib and sunitinib), corticosteroids, erythropoietin and non-steroidal anti-inflammatory drugs with the development of hypertension. We also described the relationship between hypertension and carotid baroreceptor injury secondary to cervical radiotherapy. Morbidity and mortality increased in patients with cancer and hypertension without proper antihypertensive treatment. We concluded that there is need for early diagnosis, effective monitoring and treatment strategies for hypertension in cancer patients in order to reduce cardiovascular morbidity and mortality.

The role of secondary hyperparathyroidism in left ventricular hypertrophy of patients under chronic hemodialysis

End-stage renal disease (ESRD) patients frequently develop structural cardiac abnormalities, particularly left ventricular hypertrophy (LVH). The mechanisms involved in these processes are not completely understood. In the present study, we evaluated a possible association between parathyroid hormone (PTH) levels and left ventricular mass (LVM) in patients with ESRD. Stable uremic patients on intermittent hemodialysis treatment were evaluated by standard two-dimensional echocardiography and their sera were analyzed for intact PTH. Forty-one patients (mean age 45 years, range 18 to 61 years), 61% males, who had been on hemodialysis for 3 to 186 months, were evaluated. Patients were stratified into 3 groups according to serum PTH: low levels (<100 pg/ml; group I = 10 patients), intermediate levels (100 to 280 pg/ml; group II = 10 patients) and high levels (>280 pg/ml; group III = 21 patients). A positive statistically significant association between LVM index and PTH was identified (r = 0.34; P = 0.03, Pearson's correlation coefficient) in the sample as a whole. In subgroup analyses, we did not observe significant associations in the low and intermediate PTH groups; nevertheless, PTH and LVM index were correlated in patients with high PTH levels (r = 0.62; P = 0.003). LVM index was also inversely associated with hemoglobin (r = -0.34; P = 0.03). In multivariate analysis, after adjustment for age, hemoglobin, body mass index, and blood pressure, the only independent predictor of LVM index was PTH level. Therefore, PTH is an independent predictor of LVH in patients undergoing chronic hemodialysis. Secondary hyperparathyroidism may contribute to the elevated cardiovascular morbidity associated with LVH in ESRD.

Effects of rosiglitazone on serum paraoxonase activity and metabolic parameters in patients with type 2 diabetes mellitus

Human serum paraoxonase contributes to the anti-atherogenic effect of high-density lipoprotein cholesterol (HDL-C) and has been shown to protect both low-density lipoprotein cholesterol (LDL-C) and HDL-C against lipid peroxidation. We investigated the effects of rosiglitazone on paraoxonase activity and metabolic parameters in patients with type 2 diabetes mellitus [50 patients (30 males, 20 females); mean±SD age: 58.7±9.2 years, body mass index: 28.2±4.1'kg/m2], in whom glucose control could not be achieved despite treatment with metformin, sulphonylurea, and/or insulin. The patients were given 4'mg/day rosiglitazone for 3 months in addition to their usual treatment. Serum paraoxonase activity, malondialdehyde, homocysteine, and lipid profile were measured at the time of initiation and at the end of therapy with rosiglitazone. After rosiglitazone therapy, serum levels of HDL-C, apolipoprotein A-1, and paraoxonase activity increased significantly (P<0.05) and malondialdehyde, homocysteine, lipoprotein(a), and glucose levels decreased significantly (P<0.05), but no significant changes in levels of total cholesterol and apolipoprotein B were observed. Triglyceride levels also increased significantly (P<0.05). Rosiglitazone treatment led to an improvement in glycemic control and to an increase in paraoxonase activity and HDL-C levels. Although rosiglitazone showed favorable effects on oxidant/antioxidant balance and lipid profile, further studies are needed to determine the effect of rosiglitazone on cardiovascular risk factors and cardiovascular morbidity and mortality.

Vitamin D and Kidney disease: what we know and what we do not know

Vitamin D deficiency is common in the chronic kidney disease (CKD) population. CKD has been recognized as a significant public health problem and CKD patients are at increased risk of total and cardiovascular morbidity and mortality. There are increasing epidemiological data suggesting that vitamin D deficiency may play a role in overall morbidity and mortality associated with CKD. The vitamin D hormonal system is classically implicated in the regulation of calcium homeostasis and bone metabolism but there is ample evidence to support the claim that extra renal conversion of 25(OH)D to 1.25(OH)2 has significant biological roles beyond those traditionally ascribed to vitamin D. Based on the current state of evidence this review intends to give an update on novel biological and clinical insights with relevance to the steroid hormone vitamin D specifically in patients with kidney disease.

Why do we need randomized and epidemiological studies on cardiovascular disease? Evidence-based cardiology VII

Over the last two decades the results of randomized clinical studies, which are powerful aids for correctly assessing therapeutical strategies, have consolidated cardiological practice. In addition, scientifically interesting hypotheses have been generated through the results of epidemiological studies. Properly conducted randomized studies without systematic errors and with statistical power adequate for demonstrating moderate and reasonable benefits in relevant clinical outcomes have provided reliable and strong results altering clinical practice, thus providing adequate treatment for patients with cardiovascular disease (CVD). The dissemination and use of evidence-based medicine in treating coronary artery disease (CAD), heart failure (HF), and in prevention will prevent hundreds of thousands of deaths annually in developed and developing countries. CVD is responsible for approximately 12 million deaths annually throughout the world, and approximately 60% of these deaths occur in developing countries. During recent years, an increase in mortality and morbidity rates due to CVD has occurred in developing countries. This increase is an indication that an epidemiological (demographic, economical, and health-related) transition is taking place in developing countries and this transition implies a global epidemic of CVD, which will require wide-ranging and globally effective strategies for prevention. The identification of conventional and emerging risk factors for CVD, as well as their management in high-risk individuals, has contributed to the decrease in the mortality rate due to CVD. Through a national collaboration, several multi-center and multinational randomized and epidemiological studies have been carried out throughout Brazil, thus contributing not only to a generalized scientific growth in different Brazilian hospitals but also to the consolidation of an increasingly evidence-based clinical practice.

Progression of Blood Pressure and Cardiovascular Outcomes in Hypertensive Patients in a Reference Center

Background: Hypertension is a public health problem, considering its high prevalence, low control rate and cardiovascular complications. Objective: Evaluate the control of blood pressure (BP) and cardiovascular outcomes in patients enrolled at the Reference Center for Hypertension and Diabetes, located in a medium-sized city in the Midwest Region of Brazil. Methods: Population-based study comparing patients enrolled in the service at the time of their admission and after an average follow-up of five years. Participants were aged ≥18 years and were regularly monitored at the Center up to 6 months before data collection. We assessed demographic variables, BP, body mass index, risk factors, and cardiovascular outcomes. Results: We studied 1,298 individuals, predominantly women (60.9%), and with mean age of 56.7±13.1 years. Over time, there was a significant increase in physical inactivity, alcohol consumption, diabetes, dyslipidemia, and excessive weight. As for cardiovascular outcomes, we observed an increase in stroke and myocardial revascularization, and a lower frequency of chronic renal failure. During follow-up, there was significant improvement in the rate of BP control (from 29.6% to 39.6%; p = 0.001) and 72 deaths, 91.7% of which were due to cardiovascular diseases. Conclusion: Despite considerable improvements in the rate of BP control during follow-up, risk factors worsened and cardiovascular outcomes increased.

Frequency of Werner helicase 1367 polymorphism and age-related morbidity in an elderly Brazilian population

Werner syndrome (WS) is a premature aging disease caused by a mutation in the WRN gene. The gene was identified in 1996 and its product acts as a DNA helicase and exonuclease. Some specific WRN polymorphic variants were associated with increased risk for cardiovascular diseases. The identification of genetic polymorphisms as risk factors for complex diseases affecting older people can improve their prevention, diagnosis and prognosis. We investigated WRN codon 1367 polymorphism in 383 residents in a district of the city of São Paulo, who were enrolled in an Elderly Brazilian Longitudinal Study. Their mean age was 79.70 ± 5.32 years, ranging from 67 to 97. This population was composed of 262 females (68.4%) and 121 males (31.6%) of European (89.2%), Japanese (3.3%), Middle Eastern (1.81%), and mixed and/or other origins (5.7%). There are no studies concerning this polymorphism in Brazilian population. These subjects were evaluated clinically every two years. The major health problems and morbidities affecting this cohort were cardiovascular diseases (21.7%), hypertension (83.7%), diabetes (63.3%), obesity (41.23%), dementia (8.0%), depression (20.0%), and neoplasia (10.8%). Their prevalence is similar to some urban elderly Brazilian samples. DNA was isolated from blood cells, amplified by PCR and digested with PmaCI. Allele frequencies were 0.788 for the cysteine and 0.211 for the arginine. Genotype distributions were within that expected for the Hardy-Weinberg equilibrium. Female gender was associated with hypertension and obesity. Logistic regression analysis did not detect significant association between the polymorphism and morbidity. These findings confirm those from Europeans and differ from Japanese population.

Effect of air pollution on diabetes and cardiovascular diseases in São Paulo, Brazil

Type 2 diabetes increases the risk of cardiovascular mortality and these patients, even without previous myocardial infarction, run the risk of fatal coronary heart disease similar to non-diabetic patients surviving myocardial infarction. There is evidence showing that particulate matter air pollution is associated with increases in cardiopulmonary morbidity and mortality. The present study was carried out to evaluate the effect of diabetes mellitus on the association of air pollution with cardiovascular emergency room visits in a tertiary referral hospital in the city of São Paulo. Using a time-series approach, and adopting generalized linear Poisson regression models, we assessed the effect of daily variations in PM10, CO, NO2, SO2, and O3 on the daily number of emergency room visits for cardiovascular diseases in diabetic and non-diabetic patients from 2001 to 2003. A semi-parametric smoother (natural spline) was adopted to control long-term trends, linear term seasonal usage and weather variables. In this period, 45,000 cardiovascular emergency room visits were registered. The observed increase in interquartile range within the 2-day moving average of 8.0 µg/m³ SO2 was associated with 7.0% (95%CI: 4.0-11.0) and 20.0% (95%CI: 5.0-44.0) increases in cardiovascular disease emergency room visits by non-diabetic and diabetic groups, respectively. These data indicate that air pollution causes an increase of cardiovascular emergency room visits, and that diabetic patients are extremely susceptible to the adverse effects of air pollution on their health conditions.

A time series analysis of meteorological factors and hospital outpatient admissions for cardiovascular disease in the Northern district of Guizhou Province, China

Findings on the effects of weather on health, especially the effects of ambient temperature on overall morbidity, remain inconsistent. We conducted a time series study to examine the acute effects of meteorological factors (mainly air temperature) on daily hospital outpatient admissions for cardiovascular disease (CVD) in Zunyi City, China, from January 1, 2007 to November 30, 2009. We used the generalized additive model with penalized splines to analyze hospital outpatient admissions, climatic parameters, and covariate data. Results show that, in Zunyi, air temperature was associated with hospital outpatient admission for CVD. When air temperature was less than 10°C, hospital outpatient admissions for CVD increased 1.07-fold with each increase of 1°C, and when air temperature was more than 10°C, an increase in air temperature by 1°C was associated with a 0.99-fold decrease in hospital outpatient admissions for CVD over the previous year. Our analyses provided statistically significant evidence that in China meteorological factors have adverse effects on the health of the general population. Further research with consistent methodology is needed to clarify the magnitude of these effects and to show which populations and individuals are vulnerable.