Perinatal development and adult blood pressure

A growing body of evidence supports the concept of fetal programming in cardiovascular disease in man, which asserts that an insult experienced in utero exerts a long-term influence on cardiovascular function, leading to disease in adulthood. However, this hypothesis is not universally accepted, hence animal models may be of value in determining potential physiological mechanisms which could explain how fetal undernutrition results in cardiovascular disease in later life. This review describes two major animal models of cardiovascular programming, the in utero protein-restricted rat and the cross-fostered spontaneously hypertensive rat. In the former model, moderate maternal protein restriction during pregnancy induces an increase in offspring blood pressure of 20-30 mmHg. This hypertensive effect is mediated, in part, by fetal exposure to excess maternal glucocorticoids as a result of a deficiency in placental 11-ß hydroxysteroid dehydrogenase type 2. Furthermore, nephrogenesis is impaired in this model which, coupled with increased activity of the renin-angiotensin system, could also contribute to the greater blood pressure displayed by these animals. The second model discussed is the cross-fostered spontaneously hypertensive rat. Spontaneously hypertensive rats develop severe hypertension without external intervention; however, their adult blood pressure may be lowered by 20-30 mmHg by cross-fostering pups to a normotensive dam within the first two weeks of lactation. The mechanisms responsible for this antihypertensive effect are less clear, but may also involve altered renal function and down-regulation of the renin-angiotensin system. These two models clearly show that adult blood pressure is influenced by exposure to one of a number of stimuli during critical stages of perinatal development.

Air pollution and neonatal deaths in São Paulo, Brazil

Air pollution has been associated with health effects on different age groups. The present study was designed to assess the impact of daily changes in air pollutants (NO2, SO2, CO, O3, and particle matter (PM10)) on total number of daily neonatal deaths (those that occur between the first and the 28th days of life) in São Paulo, from January 1998 to December 2000, since adverse outcomes such as neonatal deaths associated with air pollution in Brazil have not been evaluated before. Generalized additive Poisson regression models were used and nonparametric smooth functions (loess) were adopted to control long-term trend, temperature, humidity, and short-term trends. A linear term was used for holidays. The association between air pollutants and neonatal deaths showed a short time lag. Interquartile range increases in PM10 (23.3 µg/m³) and SO2 (9.2 µg/m³) were associated with increases of 4% (95% CI, 2-6) and 6% (95% CI, 4-8), respectively. Instead of adopting a two-pollutant model we created an index to represent PM10 and SO2 effects. For an interquartile range increase in the index an increase of 6.3% (95% CI, 6.1-6.5) in neonatal deaths was observed. These results agree with previous studies performed by our group showing the deleterious effects of air pollutants during the perinatal period. The method reported here represents an alternative approach to analyze the relationship between highly correlated pollutants and public health problems, reinforcing the idea of the synergic effects of air pollutants in public health.

Temperature, air pollution, and mortality from myocardial infarction in São Paulo, Brazil

An increase in daily mortality from myocardial infarction has been observed in association with meteorological factors and air pollution in several cities in the world, mainly in the northern hemisphere. The objective of the present study was to analyze the independent effects of environmental variables on daily counts of death from myocardial infarction in a subtropical region in South America. We used the robust Poisson regression to investigate associations between weather (temperature, humidity and barometric pressure), air pollution (sulfur dioxide, carbon monoxide, and inhalable particulate), and the daily death counts attributed to myocardial infarction in the city of São Paulo in Brazil, where 12,007 fatal events were observed from 1996 to 1998. The model was adjusted in a linear fashion for relative humidity and day-of-week, while nonparametric smoothing factors were used for seasonal trend and temperature. We found a significant association of daily temperature with deaths due to myocardial infarction (P < 0.001), with the lowest mortality being observed at temperatures between 21.6 and 22.6ºC. Relative humidity appeared to exert a protective effect. Sulfur dioxide concentrations correlated linearly with myocardial infarction deaths, increasing the number of fatal events by 3.4% (relative risk of 1.03; 95% confidence interval = 1.02-1.05) for each 10 µg/m³ increase. In conclusion, this study provides evidence of important associations between daily temperature and air pollution and mortality from myocardial infarction in a subtropical region, even after a comprehensive control for confounding factors.

The effect of performing corrections on reported uterine cancer mortality data in the city of São Paulo

Reports of uterine cancer deaths that do not specify the subsite of the tumor threaten the quality of the epidemiologic appraisal of corpus and cervix uteri cancer mortality. The present study assessed the impact of correcting the estimated corpus and cervix uteri cancer mortality in the city of São Paulo, Brazil. The epidemiologic assessment of death rates comprised the estimation of magnitudes, trends (1980-2003), and area-level distribution based on three strategies: i) using uncorrected death certificate information; ii) correcting estimates of corpus and cervix uteri mortality by fully reallocating unspecified deaths to either one of these categories, and iii) partially correcting specified estimates by maintaining as unspecified a fraction of deaths certified as due to cancer of "uterus not otherwise specified". The proportion of uterine cancer deaths without subsite specification decreased from 42.9% in 1984 to 20.8% in 2003. Partial and full corrections resulted in considerable increases of cervix (31.3 and 48.8%, respectively) and corpus uteri (34.4 and 55.2%) cancer mortality. Partial correction did not change trends for subsite-specific uterine cancer mortality, whereas full correction did, thus representing an early indication of decrease for cervical neoplasms and stability for tumors of the corpus uteri in this population. Ecologic correlations between mortality and socioeconomic indices were unchanged for both strategies of correcting estimates. Reallocating unspecified uterine cancer mortality in contexts with a high proportion of these deaths has a considerable impact on the epidemiologic profile of mortality and provides more reliable estimates of cervix and corpus uteri cancer death rates and trends.

Antagonic effect of the inhibition of inducible nitric oxide on the mortality of mice acutely infected with Escherichia coli and Bacteroides fragilis

Sepsis, the leading cause of death in intensive care units, is associated with overproduction of nitric oxide (NO) due to inducible NO synthase (iNOS), responsible for some of the pathologic changes. Aminoguanidine (AG) is a selective iNOS inhibitor with reported inconsistent actions in sepsis. To investigate the influence of iNOS, we studied models of acute bacterial sepsis using acute challenges with aerobic (Escherichia coli) and anaerobic (Bacteroides fragilis) bacteria in the presence of AG. Six-week-old, 23 g, male and female BALB/c and C57Bl/6j mice, in equal proportions, were inoculated (ip) with bacteria in groups of 4 animals for each dose and each experiment in the absence or presence of AG (50 mg/kg, ip, starting 24 h before challenge and daily until day 6) and serum nitrate was measured by chemiluminescence. Both types of bacteria were lethal to mice, with an LD50 of 6 nephelometric units (U) for E. coli and 8 U for B. fragilis. Nitrate production peaked on the second day after E. coli inoculation with 8 and 6 U (P < 0.05), but was absent after non-lethal lower doses. After challenge with B. fragilis this early peak occurred at all tested doses after 24 h, including non-lethal ones (P < 0.05). AG-treated mice challenged with E. coli presented higher survival (P < 0.05) and increased LD50. AG-treated mice challenged with B. fragilis had lower LD50 and higher mortality. Control AG-treated animals presented no toxic effects. The opposite effect of iNOS blockade by AG in these models could be explained by restriction of oxygen for immune cells or an efficient action of NO in anaerobic localized infections. The antagonic role of NO production observed in our bacterial models could explain the reported discrepancy of NO action in sepsis.

Racial inequalities and perinatal health in the southeast region of Brazil

Few studies are available about racial inequalities in perinatal health in Brazil and little is known about whether the existing inequality is due to socioeconomic factors or to racial discrimination per se. Data regarding the Ribeirão Preto birth cohort, Brazil, whose mothers were interviewed from June 1, 1978 to May 31, 1979 were used to answer these questions. The perinatal factors were obtained from the birth questionnaire and the ethnic data were obtained from 2063 participants asked about self-reported skin color at early adulthood (23-25 years of age) in 2002/2004. Mothers of mulatto and black children had higher rates of low schooling (£4 years, 27.2 and 38.0%) and lower family income (£1 minimum wage, 28.6 and 30.4%). Mothers aged less than 20 years old predominated among mulattos (17.0%) and blacks (14.0%). Higher rates of low birth weight and smoking during pregnancy were observed among mulatto individuals (9.6 and 28.8%). Preterm birth rate was higher among mulattos (9.5%) and blacks (9.7%) than whites (5.5%). White individuals had higher rates of cesarean delivery (34.9%). Skin color remained as an independent risk factor for low birth weight (P < 0.001), preterm birth (P = 0.01), small for gestational age (P = 0.01), and lack of prenatal care (P = 0.02) after adjustment for family income and maternal schooling, suggesting that the racial inequalities regarding these indicators are explained by the socioeconomic disadvantage experienced by mulattos and blacks but are also influenced by other factors, possibly by racial discrimination and/or genetics.

Profile of three Brazilian birth cohort studies in Ribeirão Preto, SP and São Luís, MA

We describe three birth cohort studies, respectively carried out in 1978/79 and 1994 in Ribeirão Preto, a city located in the most developed region of Brazil, and in 1997/98 in São Luís, a city located in a less developed region. The objective of the present report was to describe the methods used in these three studies, presenting their history, methodological design, objectives, developments, and difficulties faced along 28 years of research. The first Ribeirão Preto study, initially perinatal, later encompassed questions regarding the repercussions of intrauterine development on future growth and chronic adult diseases. The subjects were evaluated at birth (N = 6827), at school age (N = 2861), at the time of recruitment for military service (N = 2048), and at 23/25 years of age (N = 2063). The study of the second cohort, which started in 1994 (N = 2846), permitted comparison of aspects of perinatal health between the two groups in the same region, such as birth weight, mortality and health care use. In 1997/98, a new birth cohort study was started in São Luís (N = 2443), capital of the State of Maranhão. The 1994 Ribeirão Preto cohort and the São Luís cohort are in the second phase of joint follow-up. These studies permit comparative temporal analyses in the same place (Ribeirão Preto 1978/79 and 1994) and comparisons of two contrasting populations regarding cultural, economic and sociodemographic conditions (Ribeirão Preto and São Luís).

Social inequality and perinatal health: comparison of three Brazilian cohorts

The objective of the present study was to estimate and compare social inequality in terms of three indicators, i.e., low birth weight (LBW), preterm birth (PTB) and small for gestational age (SGA) birth, in three birth cohorts. Two cohorts were from the city of Ribeirão Preto, where data were collected for all 6748 live born singletons in 1978/79 and for one third of live born singletons (2846) in 1994. The third cohort consisted of 2443 singletons born in São Luís over a period of one year (1997/98). In Ribeirão Preto, LBW and PTB rates increased in all social strata from 1978/79 to 1994. Social inequalities regarding LBW and PTB disappeared since the increase in these rates was more accelerated in the groups with higher educational level. The percentage of SGA infants increased over the study period. Social inequality regarding SGA birth increased due to a more intense increase in SGA births in the strata with lower schooling. In São Luís, in 1997/98 there was no social inequality in LBW or PTB rates, whereas SGA birth rate was higher in mothers with less schooling. We speculate that the more accelerated increase in medical intervention, especially due to the increase in cesarean sections in the more privileged groups, could be the main factor explaining the unexpected increase in LBW and PTB rates in Ribeirão Preto and the decrease or disappearance of social inequality regarding these perinatal indicators in the two cities.

Breathing disorders in congestive heart failure: gender, etiology and mortality

We investigated the relationship between sleep-disordered breathing (SDB) and Cheyne-Stokes respiration (CSR) while awake as well as mortality. Eighty-nine consecutive outpatients (29 females) with congestive heart failure (CHF; left ventricular ejection fraction, LVEF <45%) were prospectively evaluated. The presence of SDB and of CSR while awake before sleep onset was investigated by polysomnography. SDB prevalence was 81 and 56%, using apnea-hypopnea index cutoffs >5 and >15, respectively. CHF etiologies were similar according to the prevalence of SDB and sleep pattern. Males and females were similar in age, body mass index, and LVEF. Males presented more SDB (P = 0.01), higher apnea-hypopnea index (P = 0.04), more light sleep (stages 1 and 2; P < 0.05), and less deep sleep (P < 0.001) than females. During follow-up (25 ± 10 months), 27% of the population died. Non-survivors had lower LVEF (P = 0.01), worse New York Heart Association (NYHA) functional classification (P = 0.03), and higher CSR while awake (P < 0.001) than survivors. As determined by Cox proportional model, NYHA class IV (RR = 3.95, 95%CI = 1.37-11.38, P = 0.011) and CSR while awake with a marginal significance (RR = 2.96, 95%CI = 0.94-9.33, P = 0.064) were associated with mortality. In conclusion, the prevalence of SDB and sleep pattern of patients with Chagas' disease were similar to that of patients with CHF due to other etiologies. Males presented more frequent and more severe SDB and worse sleep quality than females. The presence of CSR while awake, but not during sleep, may be associated with a poor prognosis in patients with CHF.

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.

Association of HDL cholesterol and triglycerides with mortality in patients with heart failure

It has been demonstrated that there is an association between serum lipoproteins and survival rate in patients with ischemic cardiomyopathy, as well as in patients with non-ischemic causes of heart failure. We tested the hypothesis of an association between serum lipoprotein levels and prognosis in a cohort of outpatients with heart failure, including Chagas' heart disease. The lipid profile of 833 outpatients with heart failure in functional classes III and IV of the New York Heart Association, with a mean age of 46.9 ± 10.6 years, 655 (78.6%) men and 178 (21.4%) women, was studied from April 1991 to June 2003. The survival rate was estimated by the Kaplan-Meyer's method and the Cox proportional hazards models. Etiology of heart failure was ischemic cardiomyopathy in 171 (21%) patients, Chagas' heart disease in 144 (17%), hypertensive cardiomyopathy in 136 (16%), and other etiologies in 83 (10%). In 299 (36%) patients, heart failure was ascribed to idiopathic dilated cardiomyopathy. Variables significantly associated with mortality were age (hazard ratio, HR = 1.02; 95%CI = 1.01-1.03; P = 0.0074), male gender (HR = 1.77; 95%CI = 1.2-2.62; P = 0.004), idiopathic dilated cardiomyopathy (HR = 1.81; 95%CI = 1.16-2.82; P = 0.0085), serum triglycerides (HR = 0.97; 95%CI = 0.96-0.98; P < 0.0001), and HDL cholesterol (HR = 0.99; 95%CI = 0.99-1.0; P = 0.0280). Therefore, higher serum HDL cholesterol and higher serum triglycerides were associated with lower mortality in this cohort of outpatients with heart failure.

Hypomagnesemia is a risk factor for nonrecovery of renal function and mortality in AIDS patients with acute kidney injury

The objective of the present study was to determine the prevalence of electrolyte disturbances in AIDS patients developing acute kidney injury in the hospital setting, as well as to determine whether such disturbances constitute a risk factor for nephrotoxic and ischemic injury. A prospective, observational cohort study was carried out. Hospitalized AIDS patients were evaluated for age; gender; coinfection with hepatitis; diabetes mellitus; hypertension; time since HIV seroconversion; CD4 count; HIV viral load; proteinuria; serum levels of creatinine, urea, sodium, potassium and magnesium; antiretroviral use; nephrotoxic drug use; sepsis; intensive care unit (ICU) admission, and the need for dialysis. Each of these characteristics was correlated with the development of acute kidney injury, with recovery of renal function and with survival. Fifty-four patients developed acute kidney injury: 72% were males, 59% had been HIV-infected for >5 years, 72% had CD4 counts <200 cells/mm³, 87% developed electrolyte disturbances, 33% recovered renal function, and 56% survived. ICU admission, dialysis, sepsis and hypomagnesemia were all significantly associated with nonrecovery of renal function and with mortality. Nonrecovery of renal function was significantly associated with hypomagnesemia, as was mortality in the multivariate analysis. The risks for nonrecovery of renal function and for death were 6.94 and 6.92 times greater, respectively, for patients with hypomagnesemia. In hospitalized AIDS patients, hypomagnesemia is a risk factor for nonrecovery of renal function and for in-hospital mortality. To determine whether hypomagnesemia is a determinant or simply a marker of critical illness, further studies involving magnesium supplementation in AIDS patients are warranted.

Artificial neural network models for predicting 1-year mortality in elderly patients with intertrochanteric fractures in China

The mortality rate of older patients with intertrochanteric fractures has been increasing with the aging of populations in China. The purpose of this study was: 1) to develop an artificial neural network (ANN) using clinical information to predict the 1-year mortality of elderly patients with intertrochanteric fractures, and 2) to compare the ANN's predictive ability with that of logistic regression models. The ANN model was tested against actual outcomes of an intertrochanteric femoral fracture database in China. The ANN model was generated with eight clinical inputs and a single output. ANN's performance was compared with a logistic regression model created with the same inputs in terms of accuracy, sensitivity, specificity, and discriminability. The study population was composed of 2150 patients (679 males and 1471 females): 1432 in the training group and 718 new patients in the testing group. The ANN model that had eight neurons in the hidden layer had the highest accuracies among the four ANN models: 92.46 and 85.79% in both training and testing datasets, respectively. The areas under the receiver operating characteristic curves of the automatically selected ANN model for both datasets were 0.901 (95%CI=0.814-0.988) and 0.869 (95%CI=0.748-0.990), higher than the 0.745 (95%CI=0.612-0.879) and 0.728 (95%CI=0.595-0.862) of the logistic regression model. The ANN model can be used for predicting 1-year mortality in elderly patients with intertrochanteric fractures. It outperformed a logistic regression on multiple performance measures when given the same variables.

Aspirin plus calcium supplementation to prevent superimposed preeclampsia: a randomized trial

Preeclampsia is an important cause of maternal and perinatal morbidity and mortality. Previous studies have tested calcium supplementation and aspirin separately to reduce the incidence of preeclampsia but not the effects of combined supplementation. The objective of this study was to investigate the effectiveness of aspirin combined with calcium supplementation to prevent preeclampsia in women with chronic hypertension. A double-blind, placebo-controlled randomized clinical trial was carried out at the antenatal clinic of a large university hospital in São Paulo, SP, Brazil. A total of 49 women with chronic hypertension and abnormal uterine artery Doppler at 20-27 weeks gestation were randomly assigned to receive placebo (N = 26) or 100 mg aspirin plus 2 g calcium (N = 23) daily until delivery. The main outcome of this pilot study was development of superimposed preeclampsia. Secondary outcomes were fetal growth restriction and preterm birth. The rate of superimposed preeclampsia was 28.6% lower among women receiving aspirin plus calcium than in the placebo group (52.2 vs 73.1%, respectively, P=0.112). The rate of fetal growth restriction was reduced by 80.8% in the supplemented group (25 vs 4.8% in the placebo vs supplemented groups, respectively; P=0.073). The rate of preterm birth was 33.3% in both groups. The combined supplementation of aspirin and calcium starting at 20-27 weeks of gestation produced a nonsignificant decrease in the incidence of superimposed preeclampsia and fetal growth restriction in hypertensive women with abnormal uterine artery Doppler.

Mortality rate after open Roux-in-Y gastric bypass: a 10-year follow-up

The prevalence of obesity has increased to epidemic status worldwide. Thousands of morbidly obese individuals undergo bariatric surgery for sustained weight loss; however, mid- and long-term outcomes of this surgery are still uncertain. Our objective was to estimate the 10-year mortality rate, and determine risk factors associated with death in young morbidly obese adults who underwent bariatric surgery. All patients who underwent open Roux-in-Y gastric bypass surgery between 2001 and 2010, covered by an insurance company, were analyzed to determine possible associations between risk factors present at the time of surgery and deaths related and unrelated to the surgery. Among the 4344 patients included in the study, 79% were female with a median age of 34.9 years and median body mass index (BMI) of 42 kg/m2. The 30-day and 10-year mortality rates were 0.55 and 3.34%, respectively, and 53.7% of deaths were related to early or late complications following bariatric surgery. Among these, 42.7% of the deaths were due to sepsis and 24.3% to cardiovascular complications. Male gender, age ≥50 years, BMI ≥50 kg/m2, and hypertension significantly increased the hazard for all deaths (P<0.001). Age ≥50 years, BMI ≥50 kg/m2, and surgeon inexperience elevated the hazard of death from causes related to surgery. Male gender and age ≥50 years were the factors associated with increased mortality from death not related to surgery. The overall risk of death after bariatric surgery was quite low, and half of the deaths were related to the surgery. Older patients and superobese patients were at greater risk of surgery-related deaths, as were patients operated on by less experienced surgeons.