Impact of Lipids and Vascular Damage on Early Atherosclerosis in Adolescents with Parental Premature Coronary Artery Disease.

AIM: To assess the relationship of cardiovascular risk factors (CRFs) with carotid intima media thickness (IMT) in adolescents with a parental history of premature coronary artery disease (PCAD). METHODS: This cross-sectional study included 50 healthy adolescents, aged 14-18 years, both sexes, with a parental history of PCAD, that were compared to 50 controls without this history. Questionnaires regarding information of CRFs were applied. Blood chemistry analyses, included lipid profile, lipoprotein (a), low density lipoprotein (LDL) susceptibility to oxidation, and inflammatory cytokine levels. The IMT was evaluated by ultrasound. RESULTS: The mean age of all participants was 15.9 years. Anthropometric measurements, blood pressure, and lipid profile were similar in both groups. However, the parental history of PCAD group exhibited lower high density lipoprotein cholesterol concentrations, shorter LDL particle oxidation time, and higher lipoprotein (a) levels compared to the control group. IMT was significantly higher in adolescents with a parental history of PCAD compared to controls, (0.53 ± 0.04 mm vs 0.47 ± 0.02 mm, p = 0.001). Among adolescents with a parental history of PCAD, those with ≥ 3 CRFs had significantly higher IMT values (0.56 mm) than those with < 3 CRFs (0.52 mm) and controls (0.48 mm). Multivariable analyses identified that systolic blood pressure and parental history of PCAD explained 26.8% and 16.1% of the variation in IMT. Furthermore, body mass index, LDL-C, ApoB-100, triglycerides and lipoprotein (a) interact with blood pressure levels to explain the IMT values. CONCLUSION: Adolescents with a parental history of PCAD had higher IMT values than the control group, primary explained by systolic blood pressure and the parental inheritance. Adolescents with parental history of PCAD and ≥ 3 CRFs exhibited the highest IMT values. Notably, lipids and systolic blood pressure jointly contribute to explain IMT in these adolescents.

Adipose tissue dysfunction serum markers are associated with high density lipoprotein size and glycation in the early stages of type 2 diabetes.

BACKGROUND: High-density lipoproteins (HDLs) have antiatherogenic properties related to their chemical structure. Adipose tissue (AT) influences HDL reverse cholesterol transport and plasma HDL cholesterol levels. However, whether AT dysfunction affects HDL subpopulations and their glycation in early type 2 diabetes (T2D) is still unknown. OBJECTIVE: To investigate the association of inflammation and AT dysfunction serum markers with the size and glycation of HDLs in normoglycemic, prediabetes, and T2D subjects. METHODS: We assessed HDL particle size and advanced glycation end-product (AGE) content in HDLs isolated from normoglycemic (n = 17), prediabetes (n = 17), and recently T2D-diagnosed (n = 18) subjects. Insulin, adiponectin, and plasminogen activator inhibitor 1 (PAI-1) were determined using the Bio-Rad Multiplex Platform, and free fatty acids (FFAs) and high sensitivity C-reactive protein (hs-CRP) were determined by standard procedures. The AT insulin resistance (ATIR) index and ATIR/adiponectin and adiponectin/leptin ratios were calculated. RESULTS: HDL was progressively smaller (nm) and enriched with AGE (mg-BSA-AGE/mg protein) according to the glucose categories: 8.49 and 7.5 in normoglycemic subjects, 8.44 and 12.4 in prediabetic subjects, and 8.32 and 14.3 in T2D subjects (P = 0.033 and P = 0.009 for size and AGE, respectively). In multivariable regression analysis, the ATIR/adiponectin ratio was inversely associated with HDL size (ß = -0.257, P = 0.046), and the ATIR ratio was directly associated with HDL glycation (ß = 0.387, P = 0.036). In contrast, adiponectin and the adiponectin/leptin ratio were not associated with alterations in HDL particles. Furthermore, HDL size was associated with resistin (ß = -0.348, P = 0.007) and PAI-1 (ß = -0.324, P = 0.004). HDL and AGE were related to insulin concentrations (ß = 0.458, P = 0.015). Analyses were adjusted for age, sex, body mass index, triglycerides, and HDL-cholesterol. CONCLUSION: HDL size was significantly associated with the ATIR/adiponectin ratio and inflammation, whereas glycation was more strongly related to the ATIR index. These findings have important implications for the management and prevention of cardiovascular disease in T2D patients.

Self-reported dietary omega-3 polyunsaturated fatty acids are associated with adipose tissue markers and glucose metabolism in apparently healthy subjects.

BACKGROUND: Plasminogen activator inhibitor 1 (PAI-1) and resistin are associated with dysfunctional adipose tissue (AT)-related metabolic complications. The role of dietary eicosapentaenoic (EPA) and docosahexaenoic (DHA) fatty acids in this relationship is unknown. AIM: To investigate the association of EPA and DHA with PAI-1 and resistin, as well as the role of this association on the glucose metabolism of apparently healthy subjects. SUBJECTS AND METHODS: Thirty-six healthy individuals were included. Validated food frequency questionnaires were used to analyse dietary habits. Inflammatory and glucose metabolism markers were quantified. Subcutaneous AT samples were obtained, and adipocyte number, area, and macrophage content were assessed. RESULTS: In 36 subjects aged 56 ± 8 years and with a body mass index of 26 ± 4 kg/m2, logEPA, and logDHA showed significant association with logresistin and a marginal association with PAI-1. Adipocyte number, area, and lognumber of macrophages per adipocyte significantly correlated with PAI-1 but not with logresistin. Although logEPA and logDHA were independently associated with loginsulin, loginsulin resistance, and C-Peptide, the addition of logresistin, but not of PAI-1, into the multivariable model, abolished the associations. CONCLUSIONS: EPA and DHA could modulate glucose metabolism across AT functional states. Our data indicate that this association is independent of other metabolic risk factors.

Effect of dietary chia supplementation on glucose metabolism and adipose tissue function markers in non-alcoholic fatty liver disease subjects / Efecto de la suplementación de la dieta con chía sobre el metabolismo de la glucosa y marcadores de función del tejido adiposo en sujetos con hígado graso no alcohólico

Background: adipose tissue dysfunction is a key factor for diabetes and non-alcoholic fatty liver disease (NAFLD) development. Chia (Salvia hispanica) is an abundant source of omega-3 fatty acids, antioxidants, and fiber which could improve adipose tissue functionality. Aim: to analyze the effect of an isocaloric chia-supplemented diet on glucose metabolism, adipose tissue inflammation, and endothelial function markers in patients with NAFLD and early stages of diabetes. Methods: in 32 patients with previous NAFLD diagnosis, without known diabetes, the effect of a diet supplemented with ground chia (25 g/day/8 weeks) was evaluated. Visceral (VAF) and liver fat, plasma lipids, fatty acids, and cytokine profiles, oral glucose tolerance test (OGTT), insulinogenic index (IGI30), insulin disposition index (DIO), and endothelial progenitor cells (EPC) were analyzed. Before and after eight weeks of diet supplementation. Results: chia supplementation promoted increases in plasma alpha-linolenic acid (75 %) and fiber consumption (55 %), and a higher number of EPC (+126 %). Basal OGTT showed that nine patients had normal OGTT, 17 pre-diabetes, and six newly diagnosed diabetes. In patients with diabetes, chia favored a healthier adipose tissue (VAF -7 %, NAFLD -100 %, adiponectin +47 %, resistin -30 %, IL-6 -44 %, IL-1β -22 %) and upturn glucose metabolism through the improvement of beta-cell function (IGI30 +50 %, DIO +66 %). (AU)

Antecedentes: la disfunción del tejido adiposo es un factor clave para el desarrollo de diabetes e hígado graso no alcohólico (HGNA). La chía (Salvia hispanica) es una fuente abundante de ácidos grasos omega-3, antioxidantes y fibra, que podrían mejorar la funcionalidad del tejido adiposo. Objetivo: analizar el efecto de una dieta isocalórica suplementada con chía sobre el metabolismo de glucosa y los marcadores de inflamación del tejido adiposo y de función endotelial en pacientes con HGNA y etapas tempranas de diabetes. Métodos: en 32 pacientes con diagnóstico previo de HGNA, pero sin diabetes conocida, se evaluó el efecto de una dieta suplementada con chía molida (25 g/día) sobre la grasa visceral (GAV) y hepática, el perfil de lípidos, los ácidos grasos y las citoquinas en plasma, la prueba de tolerancia oral a la glucosa (OGTT), el índice insulinogénico (IGI30), el índice de disposición de insulina (DIO) y las células progenitoras endoteliales (EPC), antes y después de ocho semanas de suplementación. Resultados: la suplementación con chía promovió aumentos en el consumo de ácido alfa-linolénico en plasma (75 %) y fibra de alta viscosidad (55 %) y un mayor número de EPC (+126 %). La OGTT basal mostró que nueve pacientes tenían curva normal, 17 tenían prediabetes y seis, diabetes de recién diagnóstico. En los pacientes con diabetes, la chía favoreció un tejido adiposo más sano (GAV -7 %, NAFLD -100 %, adiponectina +47 %, resistina -30 %, IL-6 -44 %, IL-1β -22 %) y un aumento del metabolismo de la glucosa a través de la mejora de la función de las células beta (IGI30 +50 %, DIO +66 %). (AU)

Effect of dietary chia supplementation on glucose metabolism and adipose tissue function markers in non-alcoholic fatty liver disease subjects.

Introduction: Background: adipose tissue dysfunction is a key factor for diabetes and non-alcoholic fatty liver disease (NAFLD) development. Chia (Salvia hispanica) is an abundant source of omega-3 fatty acids, antioxidants, and fiber which could improve adipose tissue functionality. Aim: to analyze the effect of an isocaloric chia-supplemented diet on glucose metabolism, adipose tissue inflammation, and endothelial function markers in patients with NAFLD and early stages of diabetes. Methods: in 32 patients with previous NAFLD diagnosis, without known diabetes, the effect of a diet supplemented with ground chia (25 g/day/8 weeks) was evaluated. Visceral (VAF) and liver fat, plasma lipids, fatty acids, and cytokine profiles, oral glucose tolerance test (OGTT), insulinogenic index (IGI30), insulin disposition index (DIO), and endothelial progenitor cells (EPC) were analyzed. Before and after eight weeks of diet supplementation. Results: chia supplementation promoted increases in plasma alpha-linolenic acid (75 %) and fiber consumption (55 %), and a higher number of EPC (+126 %). Basal OGTT showed that nine patients had normal OGTT, 17 pre-diabetes, and six newly diagnosed diabetes. In patients with diabetes, chia favored a healthier adipose tissue (VAF -7 %, NAFLD -100 %, adiponectin +47 %, resistin -30 %, IL-6 -44 %, IL-1ß -22 %) and upturn glucose metabolism through the improvement of beta-cell function (IGI30 +50 %, DIO +66 %). Conclusions: dietary supplementation with 25 g/day of ground chia may promote a healthier adipose tissue and improve pancreatic ß-cell and endothelial function. Among patients with early metabolic abnormalities, phytochemical properties of chia may retard diabetes progression and advanced stages of liver damage.

Introducción: Antecedentes: la disfunción del tejido adiposo es un factor clave para el desarrollo de diabetes e hígado graso no alcohólico (HGNA). La chía (Salvia hispanica) es una fuente abundante de ácidos grasos omega-3, antioxidantes y fibra, que podrían mejorar la funcionalidad del tejido adiposo. Objetivo: analizar el efecto de una dieta isocalórica suplementada con chía sobre el metabolismo de glucosa y los marcadores de inflamación del tejido adiposo y de función endotelial en pacientes con HGNA y etapas tempranas de diabetes. Métodos: en 32 pacientes con diagnóstico previo de HGNA, pero sin diabetes conocida, se evaluó el efecto de una dieta suplementada con chía molida (25 g/día) sobre la grasa visceral (GAV) y hepática, el perfil de lípidos, los ácidos grasos y las citoquinas en plasma, la prueba de tolerancia oral a la glucosa (OGTT), el índice insulinogénico (IGI30), el índice de disposición de insulina (DIO) y las células progenitoras endoteliales (EPC), antes y después de ocho semanas de suplementación. Resultados: la suplementación con chía promovió aumentos en el consumo de ácido alfa-linolénico en plasma (75 %) y fibra de alta viscosidad (55 %) y un mayor número de EPC (+126 %). La OGTT basal mostró que nueve pacientes tenían curva normal, 17 tenían prediabetes y seis, diabetes de recién diagnóstico. En los pacientes con diabetes, la chía favoreció un tejido adiposo más sano (GAV -7 %, NAFLD -100 %, adiponectina +47 %, resistina -30 %, IL-6 -44 %, IL-1ß -22 %) y un aumento del metabolismo de la glucosa a través de la mejora de la función de las células beta (IGI30 +50 %, DIO +66 %). Conclusiones: la suplementación de la dieta con 25 g/día de chía molida puede promover un tejido adiposo más saludable y mejorar la función endotelial y de las células ß pancreáticas. Entre los pacientes con anomalías metabólicas tempranas, las propiedades fitoquímicas de la chía pueden retrasar la progresión de la diabetes y el desarrollo de etapas avanzadas de daño hepático.

Uric acid is associated with morpho-functional adipose tissue markers in apparently healthy subjects.

BACKGROUND: Studies have focused on the search of novel biomarkers that allow to easily identify dysfunctional adipose tissue (AT). Uric acid (UA) could be produced and reabsorbed by AT. It has been suggested that the increases of UA concentrations participates in AT dysfunction. We investigated the association of UA with morpho-functional adipose tissue markers in apparently healthy subjects. METHODS: Forty apparently healthy individuals were included. Dietary habits and anthropometrical features were evaluated. Circulating concentrations of UA, adiponectin, leptin, and plasminogen activator inhibitor-1 (PAI-1) were quantified. Periumbilical subcutaneous AT samples were obtained and adipocyte number, adipocyte area, and macrophages content were assessed. RESULTS: The present study included 40 healthy subjects (67% women) with an average age of 57 ± 9 y, BMI of 26 ± 4 (kg/m2). UA showed a significant association with the number and mean area of adipocytes, macrophages number, adiponectin, and PAI-1. Although UA was independently associated with the number and mean area of adipocytes, macrophages number, adiponectin into the adjusted multivariable model. CONCLUSION: UA concentrations are associated with morpho-functional adipose tissue markers. Our results underscore the importance of UA as one earlier instigator of adipose tissue dysfunction in subjects without metabolic abnormalities.

Cardiovascular autonomic responses during head-up tilt test in newly diagnosed type 2 diabetes.

BACKGROUND: Autonomic dysfunction is commonly observed in patients with long-standing type 2 diabetes. Previous studies have confirmed the value of both subjectively assessed symptoms and objective measurements of autonomic nervous system function in diagnosing cardiovascular autonomic neuropathy. However, the head-up tilt test (HUTT) has been rarely used to investigate cardiovascular autonomic responses in subjects with high risk of newly diagnosed type 2 diabetes (nT2D). OBJECTIVE: To evaluate autonomic cardiovascular responses through passive orthostatic challenge along the diabetes continuum. METHODS: The study population was stratified as normoglycemic (n = 16), prediabetes (n = 20), and nT2D (n = 20). The prevalence of orthostatic intolerance and autonomic cardiovascular responses was evaluated with the Task Force Monitor during a 30-min passive HUTT. Spectral indices of heart rate and blood pressure variability and baroreceptor effectiveness index (BEI) were calculated through the HUTT. BEI was obtained by the sequence method. RESULTS: There were no differences in the prevalence of orthostatic intolerance or in the indices of heart rate and blood pressure variability among the three groups of study. The BEI was attenuated in the nT2D group in supine rest and throughout HUTT compared with normoglycemic and prediabetes groups. The multivariable linear regression analysis showed that BEI was associated with fasting glucose (ß = - 0.52, p < 0.001) and HbA1c (ß = - 0.57, p  < 0.001) independently of cardiovascular risk factors. CONCLUSION: Cardiovascular autonomic neuropathy, expressed as blunted BEI, is the only abnormal autonomic nervous test detected in nT2D, and it was independently associated with fasting glucose and HbA1c values.

Dysfunctional adiposity index as a marker of adipose tissue morpho-functional abnormalities and metabolic disorders in apparently healthy subjects.

Compared to body mass index, waist circumference (WC), and adiposity measurements, adipose tissue (AT) morpho-functionality evaluations are better predictors of cardiometabolic abnormalities (CA). The present study establishes a dysfunctional adiposity index (DAI) as an early marker of CA based on adipocytes morpho-functional abnormalities. DAI was established in 340 subjects without cardiovascular risk factors selected from a cross-sectional study (n=1600). Then, DAI was calculated in 36 healthy subjects who underwent subcutaneous AT biopsy. The correlation of DAI with adipocyte morphology (size/number) and functionality (adiponectin/leptin ratio) was analyzed. The DAI cut-off point was identified and its independent association with CA was determined in 1418 subjects from the cross-sectional study. The constant parameters to calculate the DAI were [WC/[22.79+[2.68*BMI]]]*[triglycerides (TG, mmol/L)/1.37]*[1.19/high density lipoprotein-cholesterol (HDL-C, mmol/L)] for males, and [WC/[24.02+[2.37*BMI]]]*[TG(mmol/L)/1.32]*[1.43/HDL-C(mmol/L)] for females. DAI correlated with adipocytes mean area, adipocyte number and adiponectin/leptin ratio. DAI ≥1.065 was independently associated with diabetes, non-alcoholic fatty liver disease, subclinical atherosclerosis, and hypertension. The present study highlights that DAI is associated with early CA independently of adiposity and other risk factors. Since DAI is obtained using accessible parameters, it can be easily incorporated into clinical practice for early identification of AT abnormalities in apparently healthy subjects.

Effects of fatty liver on the size and composition of high-density lipoprotein cholesterol subpopulations in adolescents with type 2 diabetes mellitus.

BACKGROUND: Type 2 diabetes mellitus (T2DM) is an emerging disease in the pediatric population. The association between T2DM and non-alcoholic fatty liver disease (NAFLD) has been described. Recent evidence suggests that sizes and composition of high-density lipoprotein (HDL) may be more important that HDL-C levels in predicting coronary heart disease. There is not data regarding the HDL subclasses distribution and composition in T2DM youths with NAFLD. METHODS: This cross-sectional study included 47 adolescents with T2DM and 23 non-diabetic controls of both sexes aged 10 to 18 years. The presence of NAFLD was determined estimated proton density fat fraction (PDFF) by magnetic resonance by spectroscopy. We compared the HDL subclasses distribution (HDL2b, HDL2a, HDL3a HDL3b and HDL3c) and the HDL chemical composition (total protein, triglyceride, phospholipid, cholesteryl esters, and free cholesterol) between the groups of adolescents with T2DM and the control group. RESULTS: Patients with T2DM and NAFLD had a significantly lower proportion HDL2b (P = .040) and a higher proportion of HDL3c (P = .035); higher proportion of TG (P = .032) and a lower CE (P = .002) and FC (P < .001). A negative association was observed between PDFF and the percentages of HDL2b (r2 = -0.341, P = .004) and the average particle size (r2 = -0.327, P = .05), and a positive association with HDL3c subpopulations (r2 = 0.327, P = .015); about composition inside HDL particle, a positive association with PDFF and the TG (r2 = 0.299, P = .013) and negative with CE (r2 = -0.265, P = .030). CONCLUSIONS: In adolescents diagnosed with T2DM, the presence of NAFLD is associated with abnormalities in the distribution of HDL subpopulations and the lipid composition of HDL particles.

Metabolic control achievement in a population with premature coronary artery disease: results of the genetics of atherosclerotic disease study.

BACKGROUND AND AIMS: To the best of our knowledge, no studies have investigated the metabolic control of patients with premature coronary artery disease (CAD). The present study analyzes the metabolic control, defined as the simultaneous target in blood pressure, low-density lipoprotein cholesterol, non-high-density lipoprotein cholesterol and hemoglobin A1c, as well as the factors associated with its achievement in patients with premature CAD. METHODS: The study included 1206 patients with CAD diagnosed before the age of 55 and 65 years in men and women, respectively. Sociodemographic, clinical and biochemical data were collected to know the prevalence of cardiovascular risk factors, including individual components of metabolic control plus smoking cessation and body mass index (BMI) <25 kg/m2. Non-strict and strict targets were used to evaluate metabolic control. RESULTS: Participants were 54 ± 8 years old, 19.7% were women and had a median CAD evolution of 2.4 years. Non-strict and strict metabolic control was achieved by 18.4% and 6.2% of patients, respectively. Moreover, 79.8% and 67.6% met a composite of three or more cardiovascular risk factor goals using both criteria. BMI <25 kg/m2 was independently associated with 1.734 (95% confidence interval: 1.207-2.492) and 2.541 (95% confidence interval: 1.608-4.014) higher probabilities to meet non-strict or strict metabolic control. CONCLUSION: Our results show that 18.4% and 6.2% of subjects with premature CAD achieved non-strict and strict metabolic control, respectively. BMI <25 kg/m2 was found to be associated with the achievement of metabolic control. Multidisciplinary strategies including healthy lifestyle changes and pharmacological therapies could decrease the socioeconomic and clinical impact of premature CAD.

Control of blood pressure levels in patients with premature coronary artery disease: Results from the Genetics of Atherosclerotic Disease study.

High blood pressure (BP) is the major cardiovascular-risk factor for coronary artery disease (CAD), principally in young patients who have an important and increasing socioeconomic burden. Despite the Seventh Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (JNC-7), recommended BP target <140/90 mm Hg for patients with stable CAD, in 2017 the American College of Cardiology and the American Heart Association (ACC/AHA) updated BP target to <130/80 mm Hg. We aimed to analyze the prevalence of BP control in patients with premature CAD using both criteria. In addition, antihypertensive therapy, lifestyle, clinical, and sociodemographic characteristics of the patients were evaluated in order to identify factors associated with the achievement of BP targets. The present study included 1206 patients with CAD diagnosed before 55 and 65 years old in men and women, respectively. Sociodemographic, clinical, and biochemical data were collected. The results indicate that 85.6% and 77.5% of subjects with premature CAD achieved JNC-7 non-strict and ACC/AHA strict BP target, respectively. Consistently, number of antihypertensive drugs and hypertension duration >10 years were inversely associated with BP targets, whereas total physical activity and smoking were directly associated with BP targets, regardless of BP criteria. Considering that age, gender, and hypertension duration are non-modifiable cardiovascular-risk factors, our results highlight the need for more effective strategies focused on increase physical activity and smoking cessation in young patients with CAD. These healthier lifestyles changes should favor the BP target achievement and reduce the socioeconomic and clinical burden of premature CAD.

Chia (Salvia hispanica)-supplemented diet ameliorates non-alcoholic fatty liver disease and its metabolic abnormalities in humans.

BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) is a public health problem lacking an approved pharmacological treatment. Omega-3 fatty acids have shown to reverse NAFLD. Chia is a seed rich in α-linolenic acid (ALA), antioxidants, and fiber; therefore, it could be useful to treat NAFLD. METHODS: In a single arm experimental design study, the effect of 25 g/day of milled chia was assessed in 25 patients with NAFLD. After two weeks of dietary stabilization (basal condition) and eight weeks of a chia-supplemented isocaloric diet, liver:spleen attenuation index and visceral abdominal fat (VAF) were measured by computed tomography. Lipids, lipoproteins, free fatty acids (FFA), and ALA plasma concentrations were also determined. RESULTS: Dietary chia supplementation induced an increase in plasma ALA concentration (75%) and dietary fiber (55%) consumption. After chia supplementation, VAF (9%), body weight (1.4%), total cholesterol (2.5%), non-high density lipoprotein cholesterol (3.2%), and circulating FFA (8%) decreased. Furthermore, NAFLD regressed in 52% of the treated patients (P < 0.05 for all). CONCLUSIONS: The results of the present study show that 25 g/day of milled chia ameliorates NAFLD. Chia is an accessible vegetal source of omega-3 fatty acids, antioxidants, and fiber, which could have the potential to prevent metabolic abnormalities in NAFLD patients. Considering that there is no pharmacological treatment approved for NAFLD, the findings of the present study suggest that a chia-supplemented diet could be an innovative alternative to control this disease. RETROSPECTIVELY REGISTERED: https://clinicaltrials.gov/show/NCT03942822.

Participation of white adipose tissue dysfunction on circulating HDL cholesterol and HDL particle size in apparently healthy humans.

OBJECTIVE: To use the combined presence of the elevated insulin resistance index in adipose tissue (Adipo-IR) and low values of adiponectin as a marker of dysfunctional adipose tissue, and to analyze its possible association with low values of high-density lipoprotein cholesterol (HDL-C) and small size of HDL particles. RESEARCH DESIGN AND METHODS: The analysis included 253 subjects with functional adipose tissue and 253 with dysfunctional adipose tissue, considering similar gender, age, and body mass index (BMI). Adipo-IR was considered when index values (free fatty acids × insulin concentrations) were ≥75th percentile. Low levels of adiponectin were considered when concentration in serum was <25th percentile (determined by ELISA). HDL size was estimated by a quantitative validated equation. Small HDL size was considered when values were <25th percentile. RESULTS: When comparing subjects with functional adipose tissue with those of dysfunctional adipose tissue, the latter had a higher prevalence of low HDL-C (51.4% vs. 64.0%; p = 0.004) and small HDL (56.9% vs. 67.6%; p = 0.009). Multivariate analysis indicated that independently from other metabolic risk factors, dysfunction of adipose tissue is significantly associated with low HDL-C (OR: 1.624 [CI 95%: 1.100-2.397]) and small HDL (OR: 1.462 [CI 95%: 1.000-2.139]). Adding BMI, waist circumference, and subcutaneous or visceral adipose tissue did not modify the association. CONCLUSIONS: Dysfunction of adipose tissue is associated with a 65 and 50% higher probability of having low HDL-C and small HDL. Identification of dysfunctional adipose tissue could be a useful tool in the clinical setting to prevent the cardiometabolic risk independently from adiposity.

PON1 concentration and high-density lipoprotein characteristics as cardiovascular biomarkers.

INTRODUCTION: Serum paraoxonase 1 (PON1) is now known to be related to cardiovascular diseases (CVD). The aim of this study was to determine the relationship between PON1 concentration and high-density lipoprotein (HDL) subclasses in patients with proven CVD, cardiovascular risk factors but no CVD (CRF), and in healthy controls (control group). MATERIAL AND METHODS: A case-control study was carried out with 69 volunteers from the Mexican Institute of Social Security, Mexico. Clinical parameters, lipid profile, PON1 concentration, PON1 activities (AREase and CMPAase), and HDL subclasses were evaluated. RESULTS: Patients with CVD had significantly higher glucose and lower total cholesterol than the control group had (p < 0.01). AREase activity was not different between the control (122.57 ±30.72 U/ml), CRF (115.81 ±32.81 U/ml), and CVD (109.34 ±29.60 U/ml) groups. PON1 concentration was significantly lower in CVD patients than in CRF and control patients (p < 0.001); a positive correlation was observed between AREase activity and PON1 concentration in the CVD group (Rho = 0.58; p < 0.01). Logistic regression analysis showed that the decrease in PON1 level was associated with the CVD group (RRR = 0.20; 95% CI: 0.09-0.45) but not with the CRF group (RRR = 1.29; 95% CI: 0.89-1.90). Significant differences were observed in HDL 2a and HDL 3a concentrations between the control group and CRF and CVD groups (p < 0.05), but not between the CRF and CVD groups. CONCLUSIONS: Our data suggest that PON1 status and HDL characteristics could be early biomarkers that predict the potential for developing CVD.

Type 2 Diabetes Mellitus is Associated with Carotid Artery Plaques in Patients with Premature Coronary Heart Disease.

BACKGROUND: In subjects without a history of coronary heart disease (CHD), type 2 diabetes mellitus (T2DM) is associated with carotid artery plaques (CAP), which is a better marker than high carotid intima-media thickness (hCIMT) for predicting first or recurrent cardiovascular events. OBJECTIVE: The objective of this study is to analyze the association of T2DM with CAP and hCIMT in premature CHD patients. METHODS: Premature CHD was considered before the age of 55 years in men and before 65 in women. T2DM was defined according to the American Diabetes Association criteria. CAP was defined as a focal structure encroaching the arterial lumen by at least 50% of the surrounding IMT value or with a thickness > 1.5 mm. RESULTS: Among 1196 patients (CHD duration 1.5 years [interquartile range: 0.4-5.6]), 37.2% had T2DM, and 97.8% were on antihypertensive, 94.4% on lipid-lowering, and 97.3% on anti-aggregate treatment. hCIMT prevalence was similar in patients with or without T2DM, whereas CAP prevalence was higher among T2DM patients (17.7% vs. 30.9%; p < 0.001). T2DM showed association with CAP, independently of CHD evolution and glycemic control (odds ratio: 1.57; 95% confidence interval: 1.09-2.26). CONCLUSIONS: T2DM has an independent association with CAP. Early detection of recurrent cardiovascular events, with CAP identification, could be useful to prevent complications in patients with CHD.

Prevalencia y extensión de la calcificación arterial coronaria en población mexicana asintomática cardiovascular: estudio Genética de la Enfermedad Aterosclerosa / Prevalence and extent of coronary artery calcification in an asymptomatic cardiovascular Mexican population: Genetics of Atherosclerotic Disease study

Resumen: Objetivo: La prevalencia de calcificación arterial coronaria (CAC), marcador específico de aterosclerosis, no es conocida en México. Nuestro objetivo fue investigar la prevalencia y extensión de CAC y su asociación con factores de riesgo cardiovascular en población mexicana. Métodos: La CAC fue medida por tomografía computarizada multidetector en individuos asintomáticos que participaron en el estudio Genética de la Enfermedad Aterosclerosa. Los factores de riesgo cardiovascular y los medicamentos fueron registrados. Resultados: La muestra incluyó 1,423 individuos (49.5% hombres), con una edad de 53.7 ± 8.4 años. Los portadores de CAC mostraron prevalencias más altas de dislipidemia, diabetes, hipertensión y otros factores de riesgo. La prevalencia de CAC > 0 unidades Agatston fue de 27%, significativamente más alta en hombres (40%) que en mujeres (13%). Los valores medios del puntaje de CAC aumentaron consistentemente con la edad y fueron más altos en hombres que en mujeres en todos los grupos etarios. La edad y el c-LDL elevado se asociaron de manera independiente con la prevalencia de CAC > 0 en hombres y mujeres, mientras que la presión arterial sistólica en las mujeres, y el incremento de la edad en ambos géneros mostró una asociación independiente con la severidad de CAC. Conclusiones: En población mexicana la prevalencia y la extensión de CAC fueron mucho más altas en hombres que en mujeres y aumentaron consistentemente con la edad. Los predictores independientes de la prevalencia de CAC fueron la edad y el c-LDL.

Abstract: Objective: The prevalence of coronary artery calcification (CAC), a specific marker of atherosclerosis, is unknown in Mexico. Our aim was to investigate the prevalence and quantity of CAC and their association with cardiovascular risk factors in a Mexican population. Methods: CAC was measured by multidetector computed tomography in asymptomatic subjects who participated in the Genetics of Atherosclerotic Disease study. Cardiovascular risk factors and medication were recorded. Results: The sample included 1,423 individuals (49.5% men), aged 53.7 ± 8.4 years. Those with CAC showed a higher prevalence of dyslipidaemia, diabetes, hypertension, and other risk factors. The prevalence of CAC > 0 Agatston units was significantly higher among men (40%) than among women (13%). Mean values of CAC score increased consistently with increasing age and were higher in men than women in each age group. Age and high low density lipoprotein cholesterol were independently associated with prevalence of CAC > 0 in men and women, while increasing systolic blood pressure in women and age in both genders showed an independent association with CAC extension. Conclusions: In the Mexican population the prevalence and extent of CAC were much higher in men than in women, and strongly increased with age. Independent predictors of CAC prevalence were age and low density lipoprotein cholesterol (LDL-C).

Association of Adiponectin with Subclinical Atherosclerosis in a Mexican-Mestizo Population.

BACKGROUND AND AIMS: Adiponectin (ADPN) is a cardioprotective adipocytokine, and its association with atherosclerosis development is controversial. The aim of the present study was to assess the association of low ADPN plasma levels with the presence of subclinical atherosclerosis in a Mexican-Mestizo population without history of diabetes or coronary artery disease (CAD). METHODS: In 818 subjects (53.4 ± 9 years; 49.9% women) anthropometry, subcutaneous and visceral adipose tissue, lipids, glucose, C-reactive protein (CRP), insulin, and ADPN levels were determined. Carotid artery intima-media thickness (CIMT) was measured with ultrasound in B mode and the sex-age specific value higher than 75th percentile defined the presence of subclinical atherosclerosis. Low ADPN was considered when plasma concentrations were lower than 25th percentile (8.67 µg/mL in women, 5.30 µg/mL in men). RESULTS: Prevalence of low ADPN was 43.6% (42.9% in women and 44.4% in men; p = 0.66) and elevated CIMT (eCIMT) was 23.8% (25.8% in women and 21.9% in men; p = 0.184). In addition to their higher prevalence of low ADPN, subjects with eCIMT had higher values of body mass index, blood pressure, total cholesterol, triglycerides, glucose, insulin, and CRP. Multivariate analysis revealed that independent of these factors, low ADPN was associated with eCIMT (OR [95% CI]: 1.505 [1.051-2.153]). CONCLUSIONS: In the studied population, low adiponectin concentrations are associated with a higher prevalence of subclinical atherosclerosis, independent of traditional cardiovascular risk factors.

[Prevalence and extent of coronary artery calcification in an asymptomatic cardiovascular Mexican population: Genetics of Atherosclerotic Disease study]. / Prevalencia y extensión de la calcificación arterial coronaria en población mexicana asintomática cardiovascular: estudio Genética de la Enfermedad Aterosclerosa.

OBJECTIVE: The prevalence of coronary artery calcification (CAC), a specific marker of atherosclerosis, is unknown in Mexico. Our aim was to investigate the prevalence and quantity of CAC and their association with cardiovascular risk factors in a Mexican population. METHODS: CAC was measured by multidetector computed tomography in asymptomatic subjects who participated in the Genetics of Atherosclerotic Disease study. Cardiovascular risk factors and medication were recorded. RESULTS: The sample included 1,423 individuals (49.5% men), aged 53.7±8.4 years. Those with CAC showed a higher prevalence of dyslipidaemia, diabetes, hypertension, and other risk factors. The prevalence of CAC>0 Agatston units was significantly higher among men (40%) than among women (13%). Mean values of CAC score increased consistently with increasing age and were higher in men than women in each age group. Age and high low density lipoprotein cholesterol were independently associated with prevalence of CAC>0 in men and women, while increasing systolic blood pressure in women and age in both genders showed an independent association with CAC extension. CONCLUSIONS: In the Mexican population the prevalence and extent of CAC were much higher in men than in women, and strongly increased with age. Independent predictors of CAC prevalence were age and low density lipoprotein cholesterol (LDL-C).

Microalbuminuria and its Association with Subclinical Atherosclerosis in the Mexican Mestizo population: the GEA study.

BACKGROUND: Microalbuminuria is an early marker of atherosclerosis. Ethnic differences for both conditions have been reported. We studied microalbuminuria prevalence and its association with coronary artery calcification as an early atherosclerosis marker in a Mexican-Mestizo population free of diabetes and hypertension (healthy), as well as in hypertensive and diabetic subjects. METHODS: In 1,472 adults (53.3 ± 9.4 years old, 50.3% women), anthropometric measurements, fasting blood glucose, and lipid profile were determined. A spot urine sample was used to quantify the albumin-to-creatinine ratio and to define microalbuminuria (20-200 mg/g in men, and 30-300 mg/g in women). A coronary artery calcification score was obtained by electron-beam computed tomography and subclinical atherosclerosis was defined as a score > 0. RESULTS: Overall microalbuminuria prevalence was 9.3% (5.4% in healthy, 11.6% in obese, 12% in hypertensive, and 25% in diabetic subjects). Compared to "healthy" subjects without microalbuminuria, those with microalbuminuria had a ∼3-fold higher prevalence of coronary artery calcification > 0, while normal-high albumin-to-creatinine ratio (OR: 1.8; p < 0.05) and microalbuminuria (OR: 2.6; p < 0.001) was independently associated with coronary artery calcification > 0 only among diabetic subjects. CONCLUSIONS: Microalbuminuria and high-normal albumin-to-creatinine ratio were independently associated with subclinical atherosclerosis, suggesting that they may confer a higher risk of future cardiovascular events.

Adipose tissue dysfunction increases fatty liver association with pre diabetes and newly diagnosed type 2 diabetes mellitus.

BACKGROUND: To evaluate the role of adipose tissue function on the association of fatty liver (FL) with impaired fasting glucose (IFG) or newly diagnosed type 2 diabetes mellitus (nT2D). METHODS: In 1264 subjects, computed tomography was used to evaluate FL and elevated visceral adipose tissue (VAT). Fasting plasma glucose, <5.6, 5.6-6.9 and ≥7 mmol/l, were used to defined normoglycemic (NG), IFG or nT2D, respectively. Elevated free fatty acids, low serum adiponectin levels and adipose tissue insulin resistance (Adipo-IR), were used as markers of adipose tissue dysfunction. RESULTS: Compared to NG subjects, those with IFG or nT2D had higher prevalence of FL and elevated VAT. FL was found to be independently associated with IFG and nT2D. Adipo-IR increased the association between FL and IFG [OR: 2.46 (95% I.C.: 1.73-3.49) to 5.42 (3.11-9.41)], whereas low adiponectin levels had a higher effect on the FL and nT2D association [OR: 4.26 (2.18-8.34) to 8.53 (2.96-24.55)]. CONCLUSION: Fatty liver was independently associated with IFG and nT2D. Our results indicate for the first time, that adipose tissue dysfunction increases these associations.