Racial/ethnic heterogeneity in associations of blood pressure and incident cardiovascular disease by functional status in a prospective cohort: the Multi-Ethnic Study of Atherosclerosis.

OBJECTIVES:Research has demonstrated that the association between high blood pressure and outcomes is attenuated among older adults with functional limitations, compared with healthier elders. However, it is not known whether these patterns vary by racial/ethnic group. We evaluated race/ethnicity-specific patterns of effect modification in the association between blood pressure and incident cardiovascular disease (CVD) by functional status. SETTING:We used data from the Multi-Ethnic Study of Atherosclerosis (2002-2004, with an average of 8.8 years of follow-up for incident CVD). We assessed effect modification of systolic blood pressure and cardiovascular outcomes by self-reported physical limitations and by age. PARTICIPANTS:The study included 6117 participants (aged 46 to 87; 40% white, 27% black, 22% Hispanic and 12% Chinese) who did not have CVD at the second study examination (when self-reported physical limitations were assessed). OUTCOME MEASURES:Incident CVD was defined as an incident myocardial infarction, coronary revascularisation, resuscitated cardiac arrest, angina, stroke (fatal or non-fatal) or death from CVD. RESULTS:We observed weaker associations between systolic blood pressure (SBP) and CVD among white adults with physical limitations (incident rate ratio (IRR) per 10 mm Hg higher SBP: 1.09 (95% CI 0.99 to 1.20)) than those without physical limitations (IRR 1.29 (1.19, 1.40); P value for interaction <0.01). We found a similar pattern among black adults. Poor precision among the estimates for Hispanic or Chinese participants limited the findings in these groups. The attenuated associations were consistent across both multiplicative and additive scales, though physical limitations showed clearer patterns than age on an additive scale. CONCLUSION:Attenuated associations between high blood pressure and incident CVD were observed for blacks and whites with poor function, though small sample sizes remain a limitation for identifying differences among Hispanic or Chinese participants. Identifying the characteristics that distinguish those in whom higher SBP is associated with less risk of morbidity or mortality may inform our understanding of the consequences of hypertension among older adults

Late systolic central hypertension as a predictor of incident heart failure : the Multi-Ethnic Study of Atherosclerosis

Background: Experimental studies demonstrate that high aortic pressure in late systole relative to early systole causes greater myocardial remodeling and dysfunction, for any given absolute peak systolic pressure. Methods and Results: We tested the hypothesis that late systolic hypertension, defined as the ratio of late (last one third of systole) to early (first two thirds of systole) pressure-time integrals (PTI) of the aortic pressure waveform, independently predicts incident heart failure (HF) in the general population. Aortic pressure waveforms were derived from a generalized transfer function applied to the radial pressure waveform recorded noninvasively from 6124 adults. The late/early systolic PTI ratio (L/ESPTI) was assessed as a predictor of incident HF during median 8.5 years of follow-up. The L/ESPTI was predictive of incident HF (hazard ratio per 1% increase= 1.22; 95% CI= 1.15 to 1.29; P58.38%) was more predictive of HF than the presence of hypertension. After adjustment for each other and various predictors of HF, the HR associated with hypertension was 1.39 (95% CI= 0.86 to 2.23; P=0.18), whereas the HR associated with a high L/E was 2.31 (95% CI=1.52 to 3.49; P<0.0001). Conclusions: Independently of the absolute level of peak pressure, late systolic hypertension is strongly associated with incident HF in the general population

Coronary Artery Surgery Study (CASS): Comparability of 10 year survival in randomized and randomizable patients

AbstractThe Coronary Artery Surgery Study (CASS) includes 780 patients with mild or moderate stable angina pectoris or asymptomatic survivors of a myocardial infarction who were randomized to either medical or surgical therapy and 1,319 patients who were eligible for randomization but were not randomized (randomizable patients). There were no substantial aggregate differences observed in any of the survival comparisons after 10 years of follow-up study between the randomized and randomizable patients assigned to the medical (79% versus 80%) or surgical (82% versus 81%) groups or in patient subgroups stratified according to coronary artery disease extent and left ventricular ejection fraction.Cox regression analyses were done with independent variables known to be predictors of survival, including surgical versus medical therapy and randomized versus randomizable group, to test the null hypothesis of a mortality difference between medical versus surgical assignment according to group assignment (randomized versus randomizable). In no case did the initial group category enter as a significant predictor of survival. The results in the randomizable group reinforce those in the randomized group with respect to the medical versus surgical comparison.Two subgroups are identified with a significant surgical advantage: 1) patients with proximal left anterior descending coronary artery stenosis ≥70% and an ejection fraction < 0.50, and 2) patients with three vessel coronary artery disease and an ejection fraction < 0.50. In both groups, coronary bypass surgery had a statistically significant beneficial effect on survival (p < 0.05).After a decade of follow-up, the CASS randomizable patients confirm conclusions reached on the basis of the CASS randomized trial

Giardiasis: Impact on child growth

Artículo científico -- Universidad de Costa Rica. Instituto de Investigaciones en Salud, 1986Chronic disorders of the gastrointestinal tract may impair physical growth during infancy and childhood. Growth retardation has been particularly well documented in children with Crohn's disease and coeliac disease in which growth retardation may occur in the absence of gastrointestinal symptoms. Recurrent and persistent infection in infancy and childhood is also associated with growth retardation, the major offenders being infections of the respiratory and gastrointestinal tracts. The pathogenic mechanisms of growth disturbance in chronic disease are poorly understood. Possible candidates include reduced dietary intake as a result of anorexia, food withholding following cultural practice or physician's advice and increased energy expenditure associated with fever and infection. Nutritional deprivation due to intestinal malabsorption is probably a less important factor in inflammatory bowel disease but may be more relevant in coeliac disease and infective disorders of the intestine. Although Giardia is now an established intestinal pathogen its relationship to child growth and development has not been clearly defined. However, giardiasis (1) frequently affects infants and children; (2) is known to cause morphological damage of the small intestine and malabsorption of a variety of nutrients 15 ; (3) is not always a self-limiting infection and may persist for many weeks or months; (4) has been shown to impair physical growth in some individuals with Giardia infection. There is, however, very little population-based data on the effect of Giardia infection on physical growth during infancy and childhood and thus the impact of this parasite at a community level is largely unknown. The parasite may be excreted by apparently asymptomatic individuals and thus before widespread strategies for the control of this infection are introduced the extent of its clinical impact must be established.Universidad de Costa Rica. Instituto de Investigaciones en Salud.UCR::Vicerrectoría de Investigación::Unidades de Investigación::Ciencias de la Salud::Instituto de Investigaciones en Salud (INISA

Renal insufficiency as a predictor of cardiovascular outcomes and mortality in elderly individuals

AbstractObjectivesThis study was designed to evaluate the relationship between elevated creatinine levels and cardiovascular events.BackgroundEnd-stage renal disease is associated with high cardiovascular morbidity and mortality. The association of mild to moderate renal insufficiency with cardiovascular outcomes remains unclear.MethodsWe analyzed data from the Cardiovascular Health Study, a prospective population-based study of subjects, aged >65 years, who had a serum creatinine measured at baseline (n = 5,808) and were followed for a median of 7.3 years. Proportional hazards models were used to examine the association of creatinine to all-cause mortality and incident cardiovascular mortality and morbidity. Renal insufficiency was defined as a creatinine level ≥1.5 mg/dl in men or ≥1.3 mg/dl in women.ResultsAn elevated creatinine level was present in 648 (11.2%) participants. Subjects with elevated creatinine had higher overall (76.7 vs. 29.5/1,000 years, p < 0.001) and cardiovascular (35.8 vs. 13.0/1,000 years, p < 0.001) mortality than those with normal creatinine levels. They were more likely to develop cardiovascular disease (54.0 vs. 31.8/1,000 years, p < 0.001), stroke (21.1 vs. 11.9/1,000 years, p < 0.001), congestive heart failure (38.7 vs. 17/1,000 years, p < 0.001), and symptomatic peripheral vascular disease (10.6 vs. 3.5/1,000 years, p < 0.001). After adjusting for cardiovascular risk factors and subclinical disease measures, elevated creatinine remained a significant predictor of all-cause and cardiovascular mortality, total cardiovascular disease (CVD), claudication, and congestive heart failure (CHF). A linear increase in risk was observed with increasing creatinine.ConclusionsElevated creatinine levels are common in older adults and are associated with increased risk of mortality, CVD, and CHF. The increased risk is apparent early in renal disease

Breast-feeding, weaning and the diarrhoeal syndrome in a Guatemalan Indian village

libro (capítulo) -- Universidad de Costa Rica. Instituto de Investigaciones en Salud, 1976Prospective studies in Mayan Indian children living in their natural setting were carried out from 1964 through 1974; observations began at birth and extended at least throughout the first three years of life. Adequate growth and survival were characteristic of exclusively breast-fed infants in the first months of life. Despite the high rate of infection, children exhibited a considerable resistance to intestinal protozoa, enterobacteriaceae and enteric viruses. Resistance against colonic invaders is attributed to the bifidus flora, and that against agents acting in the small bowel, to specific antibodies present in colostrum and milk. Diarrhoeal disease was least in this period and increased with weaning to reach maximum peaks at the time of weaning. The protracted weaning consisted of progressive administration of foods of low biological value given under deficient sanitary conditions. The nutrient value of the diet as a function of the child's weight was adequate in protein but in most cases it was markedly deficient in calories. Infectious diseases, particularly diarrhoea, were found associated with pronounced reductions in the already deficient calorie intake. Infection and infectious disease were common particularly during the first 6 to 18 months of life. Weight loss was a frequent finding during and after episodes of disease. The consequence of the malnutrition-infection interaction is a marked stunting of growth, clearly evident from examination of the growth curves of village children.Nutrient intake did not correlate with growth velocity. By contrast, the duration of breast-feeding was strongly associated with growth in the linear segment of the curve, while in the period of faster growth the correlation was inverse. On the other hand, morbidity was inversely correlated with calorie and protein intake and this was more obvious in the second than in the first year of life. The data indicate that infection is one of the leading factors associated with reduced calorie (and protein) intakes during the critical period of onset of malnutrition and mortality in childhood. By preventing infection, particularly diarrhoea, the food intake, nutrition and growth of children could be significantly improved.Diarrhoeal diseases still rank among the leading reported causes of childhood morbidity and mortality in nations where malnutrition and deficient hygiene prevail. The inter-American investigation of childhood mortality by the Pan American Health Organization revealed that malnutrition frequently underlies deaths due to diarrhoea and other communicable diseases (Puffer & Serrano 1973). This interrelation was recognized as a syndrome, 'weanling diarrhoea', many years ago in infants and small children (Gordon et al. 1963). The interdependence of weanling diarrhoea with the particular pattern of weaning is evident from the varying age of occurrence of the peak of diarrhoea in various geographical regions. Weanling diarrhoea appears early with early weaning and late when breast-feeding is prolonged. In early diarrhoea the probability of severe malnutrition and premature death and other sequelae is greater than when weaning is late. Prolonged weaning, nevertheless, is associated with malnutrition and mortality. Numerous investigations have failed to show conclusively a satisfactory aetiological explanation for the endemic diarrhoeas, although epidemiologicalUniversidad de Costa RicaUCR::Vicerrectoría de Investigación::Unidades de Investigación::Ciencias de la Salud::Instituto de Investigaciones en Salud (INISA

Urinary Metal Levels and Coronary Artery Calcification: Longitudinal Evidence in the Multi-Ethnic Study of Atherosclerosis (MESA)

Objective: Growing evidence indicates that exposure to metals are risk factors for cardiovascular disease (CVD). We hypothesized that higher urinary levels of metals with prior evidence of an association with CVD, including non-essential (cadmium , tungsten, and uranium) and essential (cobalt, copper, and zinc) metals are associated with baseline and rate of change of coronary artery calcium (CAC) progression, a subclinical marker of atherosclerotic CVD. Methods: We analyzed data from 6,418 participants in the Multi-Ethnic Study of Atherosclerosis (MESA) with spot urinary metal levels at baseline (2000-2002) and 1-4 repeated measures of spatially weighted coronary calcium score (SWCS) over a ten-year period. SWCS is a unitless measure of CAC highly correlated to the Agatston score but with numerical values assigned to individuals with Agatston score=0. We used linear mixed effect models to assess the association of baseline urinary metal levels with baseline SWCS, annual change in SWCS, and SWCS over ten years of follow-up. Urinary metals (adjusted to μg/g creatinine) and SWCS were log transformed. Models were progressively adjusted for baseline sociodemographic factors, estimated glomerular filtration rate, lifestyle factors, and clinical factors. Results: At baseline, the median and interquartile range (25th, 75th) of SWCS was 6.3 (0.7, 58.2). For urinary cadmium, the fully adjusted geometric mean ratio (GMR) (95%Cl) of SWCS comparing the highest to the lowest quartile was 1.51 (1.32, 1.74) at baseline and 1.75 (1.47, 2.07) at ten years of follow-up. For urinary tungsten, uranium, and cobalt the corresponding GMRs at ten years of follow-up were 1.45 (1.23, 1.71), 1.39 (1.17, 1.64), and 1.47 (1.25, 1.74), respectively. For copper and zinc, the association was attenuated with adjustment for clinical risk factors; GMRs at ten years of follow-up before and after adjustment for clinical risk factors were 1.55 (1.30, 1.84) and 1.33 (1.12, 1.58), respectively, for copper and 1.85 (1.56, 2.19) and 1.57 (1.33, 1.85) for zinc. Conclusion: Higher levels of cadmium, tungsten, uranium, cobalt, copper, and zinc, as measured in urine, were associated with subclinical CVD at baseline and at follow-up. These findings support the hypothesis that metals are pro-atherogenic factors.The Multi-Ethnic Study of Atherosclerosis (MESA) is supported by contracts 75N92020D00001, HHSN268201500003I, N01-HC-95159, 75N92020D00005, N01-HC-95160, 75N92020D00002, N01-HC-95161, 75N92020D00003, N01-HC-95162, 75N92020D00006, N01-HC-95163, 75N92020D00004, N01-HC-95164, 75N92020D00007, N01-HC-95165, N01-HC-95166, N01-HC-95167, N01-HC-95168 and N01-HC-95169 from the National Heart, Lung, and Blood Institute, and by grants UL1-TR-000040, UL1-TR-001079, and UL1-TR-001420 from the National Center for Advancing Translational Sciences (NCATS). This publication was developed under the Science to Achieve Results (STAR) research assistance agreements, No. RD831697 (MESA Air) and RD-83830001 (MESA Air Next Stage), awarded by the U.S Environmental Protection Agency (EPA). It has not been formally reviewed by the EPA. The views expressed in this document are solely those of the authors and the EPA does not endorse any products or commercial services mentioned in this publication. Dr. Maria Tellez-Plaza was supported by grants PI15/00071 and PI22/00029 from the Strategic Action for Health Research, Instituto de Salud Carlos III and the Spanish Ministry of Science and Innovation, and co-funded with European Funds for Regional Development (FEDER). The opinions and views expressed in this article are those of the authors and do not necessarily represent the official position of the Instituto de Salud Carlos III (Spain). Work in the authors? laboratories is also supported in part by NIH grants P42ES023716, P42ES010349, P42ES033719, P30ES009089, T32ES007322, R01ES029967, R01HL155576. The authors thank the other investigators, the staff, and the participants of the MESA study for their valuable contributions. A full list of participating MESA investigators and institutions can be found at http://www.mesa-nhlbi.org. This paper has been reviewed and approved by the MESA Publications and Presentations Committee.N

Early anti-pseudomonal acquisition in young patients with cystic fibrosis: Rationale and design of the EPIC clinical trial and observational study,

The primary cause of morbidity and mortality in patients with cystic fibrosis (CF) is progressive obstructive pulmonary disease due to chronic endobronchial infection, particularly with Pseudomonas aeruginosa (Pa). Risk factors for and clinical impact of early Pa infection in young CF patients are less well understood

Initial Pseudomonas aeruginosa treatment failure is associated with exacerbations in cystic fibrosis

The risk of pulmonary exacerbation following Pseudomonas aeruginosa (Pa) acquisition in children with cystic fibrosis (CF) is unknown