External validation and comparison of six cardiovascular risk prediction models in the Prospective Urban Rural Epidemiology (PURE)-Colombia study.

AIMS: To external validate the SCORE2, AHA/ACC Pooled Cohort Equation (PCE), Framingham Risk Score (FRS), Non-Laboratory INTERHEART Risk Score (NL-IHRS), Globorisk-LAC, and WHO prediction models and compare their discrimination and calibration capacity. METHODS: Validation in individuals aged 40-69 years with at least 10 years follow-up and without baseline use of statins or cardiovascular diseases from the Prospective Urban Rural Epidemiology prospective cohort study (PURE)-Colombia. For discrimination, the C-statistic, and Receiver Operating Characteristic curves with the integrated area under the curve (AUCi) were used and compared. For calibration, the smoothed time-to-event method was used, choosing a recalibration factor based on the integrated calibration index (ICI). In the NL-IHRS, linear regressions were used. RESULTS: In 3,802 participants (59.1% women), baseline risk ranged from 4.8% (SCORE2 women) to 55.7% (NL-IHRS). After a mean follow-up of 13.2 years, 234 events were reported (4.8 cases per 1000 person-years). The C-statistic ranged between 0.637 (0.601-0.672) in NL-IHRS and 0.767 (0.657-0.877) in AHA/ACC PCE. Discrimination was similar between AUCi. In women, higher overprediction was observed in the Globorisk-LAC (61%) and WHO (59%). In men, higher overprediction was observed in FRS (72%) and AHA/ACC PCE (71%). Overestimations were corrected after multiplying by a factor derived from the ICI. CONCLUSIONS: Six prediction models had a similar discrimination capacity, supporting their use after multiplying by a correction factor. If blood tests are unavailable, NL-IHRS is a reasonable option. Our results suggest that these models could be used in other countries of Latin America after correcting the overestimations with a multiplying factor.

Detecting people at high risk of cardiovascular disease and implementing preventive interventions in this population is a key strategy in primary prevention. Recently, new risk calculation tools have been developed, but before their application and routine use in populations different from those where it was developed, it's necessary to validate them. The recommendations for predicting cardiovascular risk in Colombia's guidelines are based on studies with noteworthy limitations. This study involving 3,802 healthy individuals in Colombia supports the recommendation of using these prediction models. The estimation result should be multiplied by a correction factor, because most of the prediction models overestimate cardiovascular risk. For example, the correction factors suggested in women for AHA/ACC PCE and SCORE2 are 0.54 and 0.75, respectively. In men, the correction factors suggested in AHA/ACC PCE and SCORE2 are 0.28 and 0.61, respectively. Therefore, the present study with a contemporary population provides additional evidence to update these recommendations in Colombia and perhaps in Latin America.

Physical Activity and Obesity Risk in Adults in Colombia: The Prospective Urban Rural Epidemiology (PURE) Study.

PURPOSE: This study aimed to investigate longitudinal associations between physical activity levels and obesity in adults in Colombia, where participation in large amounts of light-intensity physical activity is a necessity for many people. METHODS: Participation in moderate- and vigorous-intensity physical activity was assessed from 2005 to 2009, and obesity was assessed from 2011 to 2019 in men and women from the Prospective Urban Rural Epidemiology (PURE) study. Total physical activity level was categorized as low (<600 MET·min·wk -1 ), medium (600-3000 MET·min·wk -1 ), or high (>3000 MET·min·wk -1 ; 600 MET·min·wk -1 is equivalent to 150 min of moderate activity or 75 min of vigorous activity per week). Obesity was defined as body mass index ≥30 kg·m -2 . Analyses were adjusted for age, sex, smoking, socioeconomic status, diet, alcohol, sedentary time, and sleep. RESULTS: The main analysis included 3086 men and women aged 51 ± 9 yr at baseline (mean ± SD). Compared with the low physical activity group, the odds ratio (95% confidence interval) for obesity was 0.67 (0.53-0.85) in the medium physical activity group and 0.78 (0.62-0.98) in the high physical activity group after adjustment for potential confounders. Smoking is probably a major confounder, and it is noteworthy that similar associations were observed in participants who reported never smoking. CONCLUSIONS: The PURE study is the only prospective cohort study in Colombia. The present analysis is important because it suggests that even the busy people of Colombia could substantially reduce their risk of obesity by participating in moderate- and vigorous-intensity physical activity.

Sex Differences in Cardiovascular Disease Risk Factor Prevalence, Morbidity, and Mortality in Colombia: Findings from the Prospective Urban Rural Epidemiology (PURE) Study.

Background: Controversies exist on whether the presence of cardiovascular risk factors and their association with major cardiovascular events (MACE) is different between men and women. Most of the evidence comes from high-income countries, hindering extrapolation of sociocultural and demographic factors of other regions. Objective: To evaluate sex differences in the prevalence of cardiovascular risk factors and the incidence of MACE and diabetes in Colombian adults. Methods: We performed a survival analysis from women and men aged 35-70 belonging to the Prospective Urban Rural Epidemiology-Colombia prospective study. Incidence rates for MACE composite (myocardial infarction, stroke, heart failure, death) and each outcome and diabetes were calculated. Kaplan-Meier curves and log-rank tests were performed. The association between demographic, behavioral, and metabolic variables with MACE and diabetes were evaluated with Cox proportional hazards models. Results: 7,552 participants (50±9.7 years) were included; 64% were women. Women had higher hypertension prevalence, body mass index, levels of total cholesterol, LDL-c, and HDL-c but lower triglycerides levels. Women were more sedentary but fewer smokers or active alcohol consumers and had higher educational levels. After 12-year mean follow-up (SD 2.3), the incidence rate of MACE composite was higher in men [4.2 (3.6-4.9) vs. 3.2 (2.8-3.7) cases per 1000 person-years]. Diabetes had the greatest association with MACE (HR = 2.63 95%CI:1.85;3.76), followed by hypertension (HR = 1.75 95%CI:1.30;2.35), low relative grip strength (HR = 1.53 95%CI:1.15;2.02), smoking (HR = 1.47 95%CI: 1.11;1.93), low physical activity (HR = 1.42 95%CI: 1.03;1.96). When evaluating risk factors by sex, only an increased waist-to-hip ratio was more strongly associated with MACE in men (p-interaction <0.05). Conclusions: The composite MACE outcome was higher in men despite having a lower overall burden of risk factors. The risk factors contribution was similar, leading us to reconsider the need to carrying out differentiated cardiovascular risk prevention and management campaigns, at least in our region.

Waist circumference cut-off points to identify major cardiovascular events and incident diabetes in Latin America: findings from the prospective Urban rural epidemiology study Colombia.

Background: Abdominal obesity (AO) indirectly represents visceral adiposity and can be assessed by waist circumference (WC) measurement. In Latin America, cut-off points for the diagnosis of AO are based on Asian population data. We aim to establish the WC cut-off points to predict major cardiovascular events (MACE) and incident diabetes. Methods: We analyzed data from the cohort PURE study in Colombia. WC cut-off points were defined according to the maximum Youden index. Multivariate logistic regression was used to obtain associations between WC and MACE, diabetes, and cumulative incidence of outcomes visualized using Kaplan-Meier curves. Results: After a mean follow-up of 12 years, 6,580 individuals with a mean age of 50.7 ± 9.7 years were included; 64.2% were women, and 53.5% were from rural areas. The mean WC was 85.2 ± 11.6 cm and 88.3 ± 11.1 cm in women and men, respectively. There were 635 cases of the MACE composite plus incident diabetes (5.25 events per 1,000 person-years). Using a cut-off value of 88.85 cm in men (sensitivity = 0.565) and 85.65 cm in women (sensitivity = 0.558) resulted in the highest value for the prediction of the main outcome. These values were associated with a 1.76 and 1.41-fold increased risk of presenting the composite outcome in men and women, respectively. Conclusions: We defined WC cut-off points of 89 cm in men and 86 cm in women to identify the elevated risk of MACE and incident diabetes. Therefore, we suggest using these values in cardiovascular risk assessment in Latin America.

Insulin Resistance Markers to Detect Nonalcoholic Fatty Liver Disease in a Male Hispanic Population.

Background: Nonalcoholic fatty liver disease (NAFLD) is one of the leading causes of chronic liver disease and is closely associated with cardiometabolic disorders, being insulin resistance (IR) the common pathogenic mechanism. The triglycerides/glucose (TyG) index and triglycerides/HDL-c (TG/HDL) ratio are markers correlated with IR. We compared the capacity of these two indexes, alongside IR, to detect NAFLD. Methods: In a cross-sectional cohort study, we examined 263 active military personnel from the Colombian Air Force, aged between 29 and 54 years. Anthropometric measurements and biochemical determinations (glycemia, lipid profile, and insulin) were obtained, and ultrasound studies were performed to evaluate the presence of NAFLD. HOMA-IR index was calculated as (fasting insulin (µIU/mL) × fasting glucose (mmol/L)/22.5), the TyG index as Ln (triglycerides (mg/dL) × fasting glucose (mg/dL)/2), and the TG/HDL ratio as (triglycerides (mg/dL)/HDL-c (mg/dL)). Results: NAFLD ultrasound criteria were met in 70 individuals (26.6%). Subjects with NAFLD had significantly higher values of HOMA-IR (2.55 ± 1.36 vs. 1.51 ± 0.91), TyG (9.17 ± 0.53 vs. 8.7 ± 0.51), and TG/HDL (6.6 ± 4.54 vs. 3.52 ± 2.32) compared to those without NAFLD (p < 0.001). A TyG cutoff point of 8.92 showed an AUC of 0.731, while cutoff points of 3.83 for TG/HDL and 1.68 for HOMA-IR showed an AUC of 0.766 and 0.781, respectively. Conclusion: Our study shows that novel and lower-cost markers of IR are useful for detecting NALFD, with a performance comparable to the HOMA-IR index. These markers should be used as the first step when screening patients for NAFLD.

Ethnic Differences in the Prevalence of Hypertension in Colombia: Association With Education Level.

BACKGROUND: A higher prevalence of hypertension is reported among Afro-descendants compared with other ethnic groups in high-income countries; however, there is a paucity of information in low- and medium-income countries. METHODS: We evaluated 3,745 adults from 3 ethnic groups (552 White, 2,746 Mestizos, 447 Afro-descendants) enrolled in the prospective population-based cohort study (PURE)-Colombia. We assessed associations between anthropometric, socioeconomic, behavioral factors, and hypertension. RESULTS: The overall prevalence of hypertension was 39.2% and was higher in Afro-descendants (46.3%) than in Mestizos (37.6%) and Whites (41.5%), differences that were due to the higher prevalence in Afro-descendant women. Hypertension was associated with older age, increased body mass index, waist circumference and waist-to-hip ratio, independent of ethnicity. Low education was associated with hypertension in all ethnic groups, and particularly in Afro-descendants, for whom it was the factor with the strongest association with prevalence. Notably, 70% of Afro-descendants had a low level of education, compared with 52% of Whites-26% of Whites were university graduates while only 7% of Afro-descendants were. We did not find that education level alone had a mediator effect, suggesting that it is not a causal risk factor for hypertension but is an indicator of socioeconomic status, itself an important determinant of hypertension prevalence. CONCLUSIONS: We found that a higher prevalence of hypertension in Colombian Afro-descendants than other ethnic groups. This was principally associated with their lower mean educational level, an indicator of lower socioeconomic status.

Plasma Levels of Myonectin But Not Myostatin or Fibroblast-Derived Growth Factor 21 Are Associated with Insulin Resistance in Adult Humans without Diabetes Mellitus.

BACKGROUND: Myokines are a group of protein mediators produced by skeletal muscle under stress or physical exertion. Even though their discovery and effects in cell culture and animal models of disease have elicited great enthusiasm, very little is known about their role in human metabolism. We assessed whether plasma concentrations of three known myokines [myonectin, myostatin, and fibroblast-derived growth factor 21 (FGF-21)] would be associated with direct and indirect indicators of insulin resistance (IR) in individuals who did not have a diagnosis of diabetes. METHODS: We studied 81 adults of both sexes comprising a wide range of body adiposity and insulin sensitivity. All participants underwent a thorough clinical assessment and a 5-point oral glucose tolerance test with calculation of multiple IR and insulin sensitivity indices. Twenty-one of them additionally underwent a hyperinsulinemic-euglycemic clamp with determination of steady-state whole-body insulin-stimulated glucose disposal ("M"). We compared plasma myokine concentrations across quartiles of IR indices and clinical IR surrogates, and explored the correlation of each myokine with the M-value. RESULTS: Plasma myonectin levels increased monotonically across quartiles of the incremental area under the insulin curve (higher values indicate more IR) (p-trend = 0.021) and decreased monotonically across quartiles of the insulin sensitivity index (ISI - higher values indicate less IR) (p-trend = 0.012). After multivariate adjustment for other relevant determinants of IR (body mass index, age, and sex), the negative association of myonectin with ISI persisted (standardized beta = -0.235, p = 0.023). Myostatin was not associated with any clinical IR indicator or direct IR index measure. In multivariate analyses, FGF-21 showed a trend toward a positive correlation with glucose disposal that did not reach statistical significance (standardized beta = 0.476, p = 0.091). CONCLUSION: The secretion of myonectin may constitute an attempt at a compensatory mechanism against IR in humans.

The Phospholipid Linoleoylglycerophosphocholine as a Biomarker of Directly Measured Insulin Resistance.

BACKGROUND: Plasma concentrations of some lysophospholipids correlate with metabolic alterations in humans, but their potential as biomarkers of insulin resistance (IR) is insufficiently known. We aimed to explore the association between plasma linoleoylglycerophosphocholine (LGPC) and objective measures of IR in adults with different metabolic profiles. METHODS: We studied 62 men and women, ages 30 to 69 years, (29% normal weight, 59% overweight, 12% obese). Participants underwent a 5-point oral glucose tolerance test (5p-OGTT) from which we calculated multiple indices of IR and insulin secretion. Fifteen participants additionally underwent a hyperinsulinemic-euglycemic clamp for estimation of insulin-stimulated glucose disposal. Plasma LGPC was determined using high performance liquid chromatography/time-of-flight mass spectrometry. Plasma LGPC was compared across quartiles defined by the IR indices. RESULTS: Mean LGPC was 15.4±7.6 ng/mL in women and 14.1±7.3 ng/mL in men. LGPC did not correlate with body mass in-dex, percent body fat, waist circumference, blood pressure, glycosylated hemoglobin, log-triglycerides, or high density lipoprotein cholesterol. Plasma LGPC concentrations was not systematically associated with any of the studied 5p-OGTT-derived IR indices. However, LGPC exhibited a significant negative correlation with glucose disposal in the clamp (Spearman r=-0.56, P=0.029). Despite not being diabetic, participants with higher plasma LGPC exhibited significantly higher post-challenge plasma glucose excursions in the 5p-OGTT (P trend=0.021 for the increase in glucose area under the curve across quartiles of plasma LGPC). CONCLUSION: In our sample of Latino adults without known diabetes, LGPC showed potential as a biomarker of IR and impaired glucose metabolism.

Hemoglobina glicosilada y su relación con la fracción de eyección del ventriculo izquierdo en pacientes diabéticos tipo 2 y un primer infarto agudo de miocardio / Relationship between glycated haemoglobin and left ventricule ejection fraction in diabetes type 2 patients on their first acute myocardial infarction / Relação da hemoglobina glicada com a fração de ejeção do ventrículo esquerdo em pacientes diabéticos tipo 2 e um primeiro infarto agudo do miocárdio

Introducción: Dentro del espectro de las enfermedades cardiovasculares, la enfermedad isquémica del corazón se encuentra dentro de las dos patologías con mayor tasa de discapacidad y mortalidad. La Diabetes Mellitus tipo 2 es uno de los factores asociados a peor pronóstico en sujetos con esta enfermedad. Hoy en día se conoce que sobre el miocardio en isquemia, la hiperglicemia aumenta el estrés oxidativo, la hipoxia y por ende su necrosis. Objetivo: Establecer si existe una relación entre los niveles de hemoglobina glicosilada de pacientes diabéticos tipo 2 con un primer infarto agudo de miocardio y la función del ventrículo izquierdo intrahospitalaria, medida por la fracción de eyección. Materiales y Métodos: Estudio observacional en el que se realizó la caracterización de 36 pacientes con diabetes mellitus tipo 2 y un primer episodio de IAM hospitalizados en el Hospital Militar Central. Resultados: Con el test de exactitud de Fischer se obtuvo que los pacientes diabéticos tipo 2 con primer infarto agudo de miocardio y valores de hemoglobina glicosilada por encima de 8,5% presentaron una tendencia a tener fracciones de eyección por debajo de 50% (P= 0,019). Conclusiones: Se necesitan más estudios en los que se evalúen poblaciones más grandes de pacientes para lograr representar todo el espectro de valores de hemoglobina glicosilada y con ello, establecer un punto de corte más exacto a partir del cual sea válido sospechar una disminución de la función ventricular izquierda en el escenario de diabetes mellitus tipo 2 y un primer infarto agudo de miocardio.

Introduction: In the wide range of cardiovascular disease, ischemic heart disease is one of the mayor two pathologies that contribute with the greater disability and mortality rates. Type 2 Diabetes Mellitus is known to be one of the mayor risk factors associated with a worst prognosis among subjects who suffer from ischemic heart disease. Hyperglycemia augments oxidative stress in the ischemic myocardium and thus the hypoxemia and extent of necrosis. Objective: To establish if there is a relationship between glycosylated hemoglobin levels and admissions left ventricular function, measured by ejection fraction, in type 2 diabetic patients suffering from a first acute myocardial infarction. Materials and Methods: Observational study in which we characterized 36 type 2 diabetic patients suffering from a first acute myocardial infarction, hospitalized in The Hospital Militar Central. Results: Using Fischer’s exact test we found that that type 2 diabetics suffering from a first acute myocardial infarction and with glycosylated hemoglobin levels above 8.5% had a tendency to present an ejection fraction below 50% (P= 0.019). Conclusions: Larger studies are needed in order to include all the possible values of glycosylated hemoglobin, so a more accurate cut off point from which a valid suspicion of deteriorated left ventricular function can be made, in the setting of type 2 diabetics with a first acute myocardial infarction.

Introdução: Das doenças cardiovasculares, a doença isquêmica do coração e uma das duas patologias com maior taxa de discapacidade e mortalidade. A Diabetes Mellitus tipo 2 é um dos fatores associados ao pior prognóstico em pessoas com esta doença. Atualmente é conhecido que a hiperglicemia aumenta o estresse oxidativo, a hipóxia e a necroses no miocárdio isquêmico. Objetivo: Estabelecer se existe uma relação entre os níveis de hemoglobina glicada de pacientes diabéticos tipo 2 com um primeiro infarto agudo do miocárdio (IAM) e a função do ventrículo esquerdo, segundo a fração de ejeção. Materiais e Métodos: Estudo observacional, no qual foi feita a caracterização de 36 pacientes com Diabetes Mellitus tipo 2 e um primeiro IAM, hospitalizados no Hospital Militar Central. Resultados: Com o teste de Fischer, obteve-se uma tendência a frações de ejeção abaixo do 50% nos pacientes diabéticos tipo 2 com um primeiro IAM, e níveis de hemoglobina glicada acima de 8,5% (P= 0,019). Conclusões: Precisam-se mais estudos que avaliem um maior número de pacientes, com o fim de representar tudo o espetro de valores da hemoglobina glicada, estabelecendo um ponto de corte mais exato a partir do qual se possa suspeitar uma diminuição da função ventricular esquerda nos pacientes com diabetes mellitus tipo 2 e um primeiro IAM.

El adipocito como órgano endocrino. Implicaciones fisiopatológicas y terapéuticas / Adipose tissue as an endocrine organ. Pathophysiological and therapeutic implications

El concepto de tejido adiposo como el sitio de almacenamiento del exceso de energía ha cambiado en la última década y en la actualidad éste se reconoce como un tejido con alta actividad metabólica y como un órgano endocrino importante, capaz de establecer comunicación con el resto del cuerpo mediante la síntesis y la liberación de moléculas activas llamadas adipoquinas, las cuales actúan localmente y a distancia por medio de efectos autocrinos, paracrinos y endocrinos. También están implicadas en el control de la ingesta de alimentos, en el balance de energía, en el peso corporal, en la homeostasis de glucosa, en el metabolismo lipídico, en la angiogénesis, en la fibrinólisis, en los procesos pro y anti-inflamatorios, en el desarrollo sexual y en la reproducción. Todas estas sustancias tienen un papel clave en la patogénesis del síndrome metabólico, integrado por un grupo de factores de riesgo de origen metabólico que se acompañan a su vez de un riesgo aumentado de diabetes mellitus tipo 2 y de enfermedades cardiovasculares, de prevalencia cada vez mayor en el mundo y considerados actualmente como una pandemia. Una mejor comprensión de la función endocrina del tejido adiposo y de su papel en la patogénesis de estas enfermedades conducirá al desarrollo de una terapéutica más racional para estos desórdenes. Este artículo pretende integrar el conocimiento acerca de la fisiología del tejido adiposo con su papel en las patologías asociadas y con las posibles opciones terapéuticas para su prevención y tratamiento. Palabras clave: tejido adiposo, citoquinas, inflamación, resistencia a la insulina.