Jorge Escobedo

CARMELA: assessment of cardiovascular risk in seven Latin American cities.

OBJECTIVE This cross-sectional, population-based observational study using stratified multistage sampling assessed the prevalence of cardiovascular risk factors and carotid plaques and measured carotid intima-media thickness in individuals living in major cities in 7 Latin American countries. PATIENTS AND METHODS The study comprised individuals (n=11,550) aged 25 to 64 years, living in Barquisimeto, Bogota, Buenos Aires, Lima, Mexico City, Quito, and Santiago. Data on anthropometric parameters, blood pressure, fasting glucose, total and high-density lipoprotein cholesterol, triglycerides, carotid intima-media thickness, carotid plaque, and smoking status were collected through household interviews and clinical, biochemical, and sonographic measurements. RESULTS The overall prevalence rates (ranges across cities) were as follows: hypertension (> or = 140/90 mm Hg or pharmacologic treatment), 18% (9%-29%); hypercholesterolemia (total cholesterol > or = 240 mg/dL), 14% (6%-20%); diabetes (glycemia > or = 126 mg/dL or self-reported diabetes), 7% (4%-9%); metabolic syndrome, 20% (14%-27%); obesity (body mass index > or = 30 kg/m2), 23% (18%-27%); smoking, 30% (22%-45%); and plaque, 8% (5%-14%). The mean intima-media thickness was 0.65 mm (0.60-0.74 mm). CONCLUSION The prevalence of hypertension mirrored the world average in 3 cities but was lower in the rest. Hypercholesterolemia was highly prevalent even in countries of different socioeconomic levels. The prevalence of diabetes was similar to that in the developed countries. Tobacco use in women living in Santiago and Buenos Aires was among the worlds highest. Intima-media thickness and carotid plaque prevalences varied widely.

Development of a panel of genome-wide ancestry informative markers to study admixture throughout the americas

Most individuals throughout the Americas are admixed descendants of Native American, European, and African ancestors. Complex historical factors have resulted in varying proportions of ancestral contributions between individuals within and among ethnic groups. We developed a panel of 446 ancestry informative markers (AIMs) optimized to estimate ancestral proportions in individuals and populations throughout Latin America. We used genome-wide data from 953 individuals from diverse African, European, and Native American populations to select AIMs optimized for each of the three main continental populations that form the basis of modern Latin American populations. We selected markers on the basis of locus-specific branch length to be informative, well distributed throughout the genome, capable of being genotyped on widely available commercial platforms, and applicable throughout the Americas by minimizing within-continent heterogeneity. We then validated the panel in samples from four admixed populations by comparing ancestry estimates based on the AIMs panel to estimates based on genome-wide association study (GWAS) data. The panel provided balanced discriminatory power among the three ancestral populations and accurate estimates of individual ancestry proportions (R2>0.9 for ancestral components with significant between-subject variance). Finally, we genotyped samples from 18 populations from Latin America using the AIMs panel and estimated variability in ancestry within and between these populations. This panel and its reference genotype information will be useful resources to explore population history of admixture in Latin America and to correct for the potential effects of population stratification in admixed samples in the region.

Prevalence of the Metabolic Syndrome in Latin America and its association with sub-clinical carotid atherosclerosis: the CARMELA cross sectional study

BackgroundMetabolic syndrome increases cardiovascular risk. Limited information on its prevalence in Latin America is available. The Cardiovascular Risk Factor Multiple Evaluation in Latin America (CARMELA) study included assessment of metabolic syndrome in 7 urban Latin American populations.MethodsCARMELA was a cross-sectional, population-based, observational study conducted in Barquisimeto, Venezuela; Bogota, Colombia; Buenos Aires, Argentina; Lima, Peru; Mexico City, Mexico; Quito, Ecuador; and Santiago, Chile. The prevalence of metabolic syndrome, defined according to the National Cholesterol Education Program Adult Treatment Panel III (NCEP ATP III), and associated carotid atherosclerosis were investigated in 11,502 participants aged 25 to 64 years.ResultsAcross CARMELA cities, metabolic syndrome was most prevalent in Mexico City (27%) and Barquisimeto (26%), followed by Santiago (21%), Bogota (20%), Lima (18%), Buenos Aires (17%), and Quito (14%). In nondiabetic participants, prevalence was slightly lower but followed a comparable ranking. Overall, 59%, 59%, and 73% of women with high triglycerides, hypertension, or glucose abnormalities, respectively, and 64%, 48% and 71% of men with abdominal obesity, hypertension, or glucose abnormalities, respectively, had the full metabolic syndrome. Prevalence of metabolic syndrome increased with age, markedly so in women. Mean common carotid artery intima-media thickness (CCAIMT) and prevalence of carotid plaque increased steeply with increasing numbers of metabolic syndrome components; mean CCAIMT was higher and plaque more prevalent in participants with metabolic syndrome than without.ConclusionThe prevalence of metabolic syndrome and its components by NCEP ATP III criteria was substantial across cities, ranging from 14% to 27%. CARMELA findings, including evidence of the association of metabolic syndrome and carotid atherosclerosis, should inform appropriate clinical and public health interventions.

Genome-wide association study of type 2 diabetes in a sample from Mexico City and a meta-analysis of a Mexican-American sample from Starr County, Texas

Aims/hypothesisWe report a genome-wide association study of type 2 diabetes in an admixed sample from Mexico City and describe the results of a meta-analysis of this study and another genome-wide scan in a Mexican-American sample from Starr County, TX, USA. The top signals observed in this meta-analysis were followed up in the Diabetes Genetics Replication and Meta-analysis Consortium (DIAGRAM) and DIAGRAM+ datasets.MethodsWe analysed 967 cases and 343 normoglycaemic controls. The samples were genotyped with the Affymetrix Genome-wide Human SNP array 5.0. Associations of genotyped and imputed markers with type 2 diabetes were tested using a missing data likelihood score test. A fixed-effects meta-analysis including 1,804 cases and 780 normoglycaemic controls was carried out by weighting the effect estimates by their inverse variances.ResultsIn the meta-analysis of the two Hispanic studies, markers showing suggestive associations (p < 10−5) were identified in two known diabetes genes, HNF1A and KCNQ1, as well as in several additional regions. Meta-analysis of the two Hispanic studies and the recent DIAGRAM+ dataset identified genome-wide significant signals (p < 5 × 10−8) within or near the genes HNF1A and CDKN2A/CDKN2B, as well as suggestive associations in three additional regions, IGF2BP2, KCNQ1 and the previously unreported C14orf70.Conclusions/interpretationWe observed numerous regions with suggestive associations with type 2 diabetes. Some of these signals correspond to regions described in previous studies. However, many of these regions could not be replicated in the DIAGRAM datasets. It is critical to carry out additional studies in Hispanic and American Indian populations, which have a high prevalence of type 2 diabetes.

Hypertension in seven Latin American cities: the Cardiovascular Risk Factor Multiple Evaluation in Latin America (CARMELA) study.

Background Little information is available regarding hypertension, treatment, and control in urban population of Latin America. Objective We aimed to compare blood pressure (BP) distribution, hypertension prevalence, treatment, and control in seven Latin American cities following standard methodology. Methods The Cardiovascular Risk Factor Multiple Evaluation in Latin America (CARMELA) study was a cross-sectional, epidemiologic study assessing cardiovascular risk factors using stratified multistage sampling of adult populations (aged 25–64 years) in seven cities: Barquisimeto (Venezuela; n = 1848); Bogotá (n = 1553); Buenos Aires (n = 1482); Lima (n = 1652); Mexico City (n = 1720); Quito (n = 1638); and Santiago (n = 1655). The prevalence of hypertension and high normal BP were determined based on 2007 European Society of Hypertension and European Society of Cardiology definitions. Results BP increased with age in men and women; pulse pressure increased mainly in the upper age group. The hypertension prevalence ranged from 9% in Quito to 29% in Buenos Aires. One-quarter to one-half of the hypertension cases were previously undiagnosed (24% in Mexico City to 47% in Lima); uncontrolled hypertension ranged from 12% (Lima) to 41% (Mexico City). High normal BP was also evident in a substantial number of each city participants (≈5–15%). Majority of population has other cardiovascular risk factors despite hypertension; only 9.19% of participants have no risk factors apart from hypertension. Conclusion From 13.4 to 44.2% of the populations of seven major Latin American cities were hypertensive or had high normal BP values. Most hypertensive patients have additional risk factors. Public health programs need to target prevention, detection, treatment, and control of total cardiovascular risk in Latin America.

High prevalence of diabetes and impaired fasting glucose in urban Latin America: the CARMELA Study

Aims  Cardiovascular risk is increased with glucose metabolism abnormalities. Prevalence data can support public health initiatives required to address this risk. The Cardiovascular Risk Factor Multiple Evaluation in Latin America (CARMELA) study was designed to estimate the prevalence of Type 2 diabetes, impaired fasting glucose and related risk factors in seven urban Latin American populations.

The effect of obesity on quality of life in patients with diabetes and coronary artery disease

BACKGROUND Obesity increases the risk of type 2 diabetes and coronary artery disease (CAD). Because all 3 conditions may reduce quality of life, the extent to which obesity, diabetes, and CAD independently affect quality of life is uncertain. METHODS Patients with type 2 diabetes and documented CAD participating in the Bypass Angioplasty Revascularization Investigation 2 Diabetes trial at 45 clinical sites in the United States and Canada were studied in a cross-sectional analysis of baseline data. Quality of life was assessed with the Duke Activity Status Index, the energy/fatigue and health distress scales from the Medical Outcome Study, and overall self-rated health status. RESULTS Higher body mass index was significantly associated with worse scores on all 4 quality of life scales, even after adjustment for the severity of diabetes and CAD and other comorbid conditions. Use of insulin, angina, and current smoking were also associated with significantly lower quality of life on all 4 scales, independent of other factors. CONCLUSIONS Obesity is associated with significantly reduced quality of life in patients with diabetes and CAD, independent of comorbid conditions.

Prognostic Impact of the Presence and Absence of Angina on Mortality and Cardiovascular Outcomes in Patients With Type 2 Diabetes and Stable Coronary Artery Disease: Results from the BARI 2D (Bypass Angioplasty Revascularization Investigation 2 Diabetes) Trial

OBJECTIVES The purpose of this analysis was to assess in patients with type 2 diabetes and stable coronary artery disease (CAD) whether the risk of all-cause mortality and cardiovascular events varied according to the presence or absence of angina and angina equivalent symptoms. BACKGROUND Data on the prognostic value of symptoms in these patients are limited. METHODS Post-hoc analysis was performed in 2,364 patients with type 2 diabetes and documented CAD enrolled in the BARI 2D (Bypass Angioplasty Revascularization Investigation 2 Diabetes) trial to determine the occurrence of death and composite of death, myocardial infarction, and stroke during a 5-year follow-up according to cardiac symptoms at baseline. RESULTS There were 1,434 patients with angina (A), 506 with angina equivalents (E), and 424 with neither of these (N). The cumulative death rates (total 316) were 12% in A, 14% in E, and 10% in N (p = 0.3), and cardiovascular composite rates (total 548) were 24% in A, 24% in E, and 21% in N (p = 0.5). Compared with N, the hazard ratios adjusted for confounders were not different for death in A (1.11; 99% CI: 0.81 to 1.53) and E (1.17; 99% CI: 0.81 to 1.68) or for cardiovascular events in A (1.17; 99% CI: 0.92 to 1.50) and E (1.11; 99% CI: 0.84 to 1.48). CONCLUSIONS Whatever their symptom status, patients with type 2 diabetes and stable CAD were at similar risk of cardiovascular events and death. These findings suggest that these patients may be similarly managed in terms of risk stratification and preventive therapies. (Bypass Angioplasty Revascularization Investigation 2 Diabetes [BARI 2D]; NCT00006305).

Impact of glycemic control strategies on the progression of diabetic peripheral neuropathy in the Bypass Angioplasty Revascularization Investigation 2 Diabetes (BARI 2D) Cohort.

OBJECTIVE The Bypass Angioplasty Revascularization Investigation 2 Diabetes (BARI 2D) trial demonstrated similar long-term clinical effectiveness of insulin-sensitizing (IS) versus insulin-providing (IP) treatments for type 2 diabetes on cardiovascular outcomes in a cohort with documented coronary artery disease. We evaluated the effects of randomized glycemic control strategy (IS vs. IP) on the prevalence and incidence of diabetic peripheral neuropathy (DPN). RESEARCH DESIGN AND METHODS DPN (defined as Michigan Neuropathy Screening Instrument [MNSI] clinical examination score >2) was assessed at baseline and yearly for 4 years. DPN prevalence and incidence were compared by intention-to-treat modeling by logistic generalized estimating equation models for prevalence and Kaplan-Meier estimates and Cox regression models for incidence rates. RESULTS Results are reported for 2,159 BARI 2D participants (70% males) with valid baseline and at least one follow-up MNSI score (mean age 62 ± 9 years, mean HbA1c 7.7 ± 1.6%, diabetes duration 10 ± 9 years). There were no differences in the prevalence of DPN between the IS and the IP groups throughout the 4 years of follow-up. In 1,075 BARI 2D participants with no DPN at baseline, the 4-year cumulative incidence rate of DPN was significantly lower in the IS (66%) than in the IP (72%) strategy group (P = 0.02), which remained significant after adjusting for the in-trial HbA1c (P = 0.04). In subgroup analyses, IS strategy had a greater benefit in men (hazard ratio 0.75 [99% CI 0.58–0.99], P < 0.01). CONCLUSIONS Among patients with type 2 diabetes followed for up to 4 years during BARI 2D, a glycemic control therapy with IS significantly reduced the incidence of DPN compared with IP therapy and may add further benefit for men.

Health Status After Treatment for Coronary Artery Disease and Type 2 Diabetes Mellitus in the Bypass Angioplasty Revascularization Investigation 2 Diabetes Trial

Background Health status is a key outcome for comparing treatments, particularly when mortality does not differ significantly.Background— Health status is a key outcome for comparing treatments, particularly when mortality does not differ significantly. Methods and Results— Bypass Angioplasty Revascularization Investigation 2 Diabetes (BARI 2D) randomized 2368 patients with type 2 diabetes mellitus and stable ischemic heart disease to (1) prompt revascularization versus medical therapy and (2) insulin sensitization versus insulin provision. Randomization was stratified by the intended method of revascularization, coronary artery bypass graft surgery or percutaneous coronary intervention. The Duke Activity Status Index and RAND Energy, Health Distress, and Self-Rated Health scales were assessed at study entry and annually thereafter; linear mixed models were used to evaluate the effect of randomized treatment on these measures. Health status improved significantly from baseline to 1 year (P<0.001) in each randomized treatment group. Compared with medical therapy, prompt revascularization was associated with significantly greater improvements in Duke Activity Status Index (1.32 points; P<0.001), Energy (1.36 points; P=0.02), and Self-rated Health (1.77 points; P=0.007) but not Health Distress (−0.47; P=0.46). These treatment effects were largely maintained over 4 years of follow-up. The effect of revascularization on the Duke Activity Status Index was significantly larger in the subgroup of patients intended for coronary artery bypass graft surgery compared with the subgroup intended for percutaneous coronary intervention. Health status did not differ significantly on any of the 4 measures between the insulin provision and insulin sensitization strategies. Conclusions— Prompt coronary revascularization was associated with small yet statistically significant improvements in health status compared with initial medical therapy among patients with diabetes mellitus and stable ischemic heart disease. Clinical Trial Registration— http://www.clinicaltrials.gov. Unique identifier: NCT00006305.