Interleukin 6 polymorphisms are associated with cardiovascular risk factors in premature coronary artery disease patients and healthy controls of the GEA Mexican study.

BACKGROUND AND AIMS: Interleukin-6 (IL-6) is an acute-phase protein that plays an important role in the inflammatory response, vascular inflammation, and atherosclerosis process. The study aimed to establish whether IL-6 gene polymorphisms and IL-6 concentrations are associated with premature coronary artery disease (pCAD) and cardiovascular risk factors. METHODS: The IL-6 concentrations and the rs2069827, rs1800796, and rs1800795 IL-6 polymorphisms were determined in 1150 pCAD patients and 1083 healthy controls (coronary artery calcium equal to zero determined by tomography). RESULTS: The IL-6 polymorphisms studied were not associated with pCAD, but they were associated with cardiovascular risk factors in patients and controls. In controls, under the dominant model, the rs1800795 C allele and the rs2069827 T allele were associated with a low risk of central obesity (OR = 0.401, p = 0.017 and OR = 0.577, p = 0.031, respectively), hypoalphalipoproteinemia (OR = 0.581, p = 0.027 and OR = 0.700, p = 0.014, respectively) and hypertriglyceridemia (OR = 0.575, p = 0.030 and OR = 0.728, p = 0.033, respectively). In pCAD, the rs1800795 C allele was associated with an increased risk of hypoalphalipoproteinemia (OR = 1.370, padditive = 0.025) and increased C-reactive protein (CRP) concentrations (OR = 1.491, padditive = 0.007). pCAD patients had significantly higher serum IL-6 concentrations compared to controls (p = 0.002). In the total population, individuals carrying the rs1800795 GC + CC genotypes had higher levels of IL-6 than carriers of the GG genotype (p = 0.025). In control individuals carrying the C allele (CG + CC), an inverse correlation was observed between IL-6 and HDL-cholesterol levels (p = 0.003). CONCLUSIONS: In summary, the IL-6 polymorphisms were not associated with pCAD, however, they were associated with cardiovascular risk factors in pCAD patients and healthy controls. Individuals carrying the rs1800795 GC + CC genotypes had higher levels of IL-6 than carriers of the GG genotype.

Low HDL-C/ApoA-I index is associated with cardiometabolic risk factors and coronary artery calcium: a sub-analysis of the genetics of atherosclerotic disease (GEA) study.

BACKGROUND: The high-density lipoprotein cholesterol to apolipoprotein A-I index (HDL-C/ApoA-I) may be practical and useful in clinical practice as a marker of atherosclerosis. This study aimed to investigate the association between the HDL-C/ApoA-I index with cardiometabolic risk factors and subclinical atherosclerosis. METHODS: In this cross-sectional sub-analysis of the GEA study, 1,363 individuals, women (51.3%) and men (48.7%) between 20 and 75 years old, without coronary heart disease or diabetes mellitus were included. We defined an adverse cardiometabolic profile as excess adipose tissue metrics, non-alcoholic liver fat measured by non-contrasted tomography, metabolic syndrome, dyslipidemias, and insulin resistance. The population was stratified by quartiles of the HDL-C/Apo-AI index, and its dose-relationship associations were analysed using Tobit regression, binomial, and multinomial logistic regression analysis. RESULTS: Body mass index, visceral and pericardial fat, metabolic syndrome, fatty liver, high blood pressure, and CAC were inversely associated with the HDL-C/ApoA-I index. The CAC > 0 prevalence was higher in quartile 1 (29.2%) than in the last quartile (22%) of HDL-C/ApoA-I index (p = 0.035). The probability of having CAC > 0 was higher when the HDL-C/ApoA-I index was less than 0.28 (p < 0.001). This association was independent of classical coronary risk factors, visceral and pericardial fat measurements. CONCLUSION: The HDL-C/ApoA-I index is inversely associated with an adverse cardiometabolic profile and CAC score, making it a potentially useful and practical biomarker of coronary atherosclerosis. Overall, these findings suggest that the HDL-C/ApoA-I index could be useful for evaluating the probability of having higher cardiometabolic risk factors and subclinical atherosclerosis in adults without CAD.

The dysfunctional adiposity index is a clinical surrogate of pericardial fat in adults without premature CVD: A sub-analysis of the GEA Mexican study control group.

BACKGROUND AND AIM: The Dysfunctional Adiposity Index (DAI) is a clinical surrogate for evaluating adipose tissue functionality and cardiometabolic health. However, its association with Pericardial Fat Volume (PFV) has not been tested. The aim of this study was to evaluate DAI- PFV association, stratified by type 2 diabetes (T2D) status, and identify DAI thresholds for detecting increased PFV among patients without premature CVD. METHODS AND RESULTS: Participants from the GEA-Mexican study underwent a computed tomography scan to measure PFV. Adjusted logistic regression analyses tested the association between DAI and PFV. AUROC curves evaluated DAI's ability to identify elevated PFV (≥57.57 cm³), and the Youden method determined DAI thresholds, along with diagnostic metrics. The study analyzed 997 participants (women: 55%; mean age: 54 ± 9 years; median PFV: 42 cm³ [IQR: 29-58]), with a 13% prevalence of T2D. DAI was positively associated with elevated PFV (OR: 1.33, 95% CI: 1.07-1.70), which was more pronounced among subjects with T2D (OR: 3.01, 95% CI: 1.41-6.40). DAI thresholds were established for all participants (>1.176), individuals without T2D (>1.003), and with T2D (>1.936), yielding sensitivities of 71%, 81%, and 57%, and specificities of 48%, 38%, and 75%, respectively. The adjusted logistic regression tied DAI thresholds to a 1.68-fold elevation in PFV for all, 2.06-fold for those without T2D, and 6.81-fold for those with T2D. CONCLUSION: DAI was positively associated with increased PFV, particularly among participants with T2D. Established DAI thresholds demonstrated good diagnostic values for detecting increased PFV. DAI could serve as an accessible marker to identify PF in clinical settings.

Association of TLR8 Variants in Sex-Based Clinical Differences in Patients with COVID-19.

The host immune response might confer differential vulnerability to SARS-CoV-2 infection. The Toll-like receptor 8 (TLR8), could participated for severe COVID-19 outcomes. To investigated the relationship of TLR8 rs3764879-C/G, rs3764880-A/G, and rs3761624-A/G with COVID-19 outcomes and with biochemical parameters. A cross-sectional study of 830 laboratory-confirmed COVID-19 patients was performed, and classified into mild, severe, critical, and deceased outcomes. The TLR8 rs3764879-C/G, rs3764880-A/G, and rs3761624-A/G polymorphisms were genotyped. A logistic regression analysis was performed to determinate the association with COVID-19. A stratified analysis was by alleles was done with clinical and metabolic markets. In all outcomes, men presented the highest ferritin levels compared to women (P < 0.001). LDH levels were significantly different between sex in mild (P = 0.003), severe (P < 0.001) and deceased (P = 0.01) COVID-19 outcomes. The GGG haplotype showed an Odds Ratio of 1.55 (Interval Confidence 95% 1.05-2.32; P = 0.03) in men. Among patients with severe outcome, we observed that the carriers of the GGG haplotype had lower Ferritin, C-reactive protein and LDH levels than the CAA carriers (P < 0.01). After further stratified by sex, these associations were also seen in the male patients, except for D-dimer. Interestingly, among men patients, we could observe associations between TLR8 haplotypes and Ferritin (P < 0.001), D-dimer (P = 0.04), C-reactive protein, and Lactate dehydrogenase in mild (P = 0.04) group. Our results suggest that even though TLR8 haplotypes show a significant association with COVID-19 outcomes, they are associated with clinical markers in COVID-19 severity.

DNA Methylation of the IL-17A Gene Promoter Is Associated with Subclinical Atherosclerosis and Coronary Artery Disease: The Genetics of Atherosclerotic Disease Mexican Study.

The interleukin-17 (IL-17) has a crucial role during inflammation and has been associated with cardiovascular diseases, but its role in epigenetics is still poorly understood. Therefore, the aim of this study was to evaluate the DNA methylation status of the IL-17A gene promoter to establish whether it may represent a risk factor for subclinical atherosclerosis (SA) or clinical coronary artery disease (CAD). We included 38 patients with premature CAD (pCAD), 48 individuals with SA, and 43 healthy controls. Methylation in the CpG region of the IL-17A gene promoter was assessed via methylation-specific polymerase chain reaction (MSP). Individuals with SA showed increased methylation levels compared to healthy controls and pCAD patients, with p < 0.001 for both. Logistic regression analysis showed that high methylation levels represent a significant risk for SA (OR = 5.68, 95% CI = 2.38-14.03, p < 0.001). Moreover, low methylation levels of the IL-17A gene promoter DNA represent a risk for symptomatic pCAD when compared with SA patients (OR = 0.16, 95% CI = 0.06-0.41, p < 0.001). Our data suggest that the increased DNA methylation of the IL-17A gene promoter is a risk factor for SA but may be a protection factor for progression from SA to symptomatic CAD.

Associations of the CYP7A1 Gene Polymorphisms Located in the Promoter and Enhancer Regions with the Risk of Acute Coronary Syndrome, Plasma Cholesterol, and the Incidence of Diabetes.

Cholesterol-7-alpha hydroxylase (CYP7A1) is a key enzyme in the synthesis of bile salts, and its activity can contribute to determining cholesterol levels and, consequently, the risk of developing coronary atherosclerotic disease. We evaluated whether seven (rs3808607 G/T, rs9297994 G/A, rs10504255 A/G, rs8192870 G/T, rs2081687 C/T, rs1457043 C/T, and rs10107182 C/T) polymorphisms located in the promoter and enhancer regions of the CYP7A1 gene, which have not been sufficiently explored, are candidates of risk markers of acute coronary syndrome (ACS) in the Mexican population. These polymorphisms were determined in a group of 1317 patients with ACS and 1046 control subjects. The results showed that, under different inheritance models, the alleles rs9297994 G, rs10504255 G, rs8192870 T, rs2081687 T, and rs10107182 C were significantly associated with an increased risk of ACS (pC < 0.05). In addition, the incidence of dyslipidemia among patients with ACS, notably high total cholesterol and LDL-cholesterol, and low HDL-cholesterol plasma levels, were more frequent in carriers of the same five risk alleles associated with ACS (p < 0.05). There was also an unexpected increased incidence of type 2 diabetes mellitus (T2DM) in patients with ACS who are homozygous for the rs2081687 T, rs9297944 G, rs10504255 G, and rs10107182 C alleles of the CYP7A1 gene, suggesting that such gene variants enhance the development of coronary complications in patients with diabetes (p < 0.05). In summary, our study demonstrated that five polymorphisms situated in the promoter and enhancer regions of the CYP7A1 gene are associated with the risk of ACS and higher incidences of dyslipidemia and T2DM in Mexican patients with ACS.

MCP-1 rs1024611 Polymorphism, MCP-1 Concentrations, and Premature Coronary Artery Disease: Results of the Genetics of Atherosclerotic Disease (GEA) Mexican Study.

Monocyte chemoattractant protein-1 (MCP-1) participates in the initiation and progression of atherosclerosis. In vitro studies have reported that the MCP-1 rs1024611 polymorphism is associated with increased MCP-1 concentrations. The study aimed to define whether MCP-1 concentrations are associated with premature coronary artery disease (pCAD) and to establish whether variations in the rs1024611 polymorphism increase MCP-1 concentrations. MCP-1 rs1024611 polymorphism was determined in 972 pCAD patients and 1070 control individuals by real-time PCR. MCP-1 concentrations were determined by the Bio-Plex system. In the total population, men had higher MCP-1 concentrations when compared to women (p < 0.001). When stratified by rs1024611 genotypes, higher MCP-1 concentrations were observed in AA individuals compared to GG subjects (p = 0.023). When performing the analysis considering sex, the differences remained significant in women (AA vs. GG, p = 0.028 and GA vs. GG, p = 0.008). MCP-1 concentrations were similar in pCAD patients and controls (p = 0.782). However, the independent analysis of the studied groups showed that in patients with the AA genotype, MCP-1 concentrations were significantly higher when compared to patients with the GG genotype (p = 0.009). Considering that the AA genotype increases MCP-1 concentration, we evaluated whether, in AA genotype carriers, MCP-1 concentrations were associated with pCAD. The results showed that for every ten pg/mL increase in MCP-1 concentration, the risk of presenting pCAD increases by 2.7% in AA genotype individuals. Individuals with the MCP-1 rs1024611 AA genotype present an increase in MCP-1 concentration. In those individuals, increased MCP-1 concentrations increase the risk of presented pCAD.

The DEFB1 gene rs11362 A/G genetic variant is associated with risk of developing CAD: a case-control study.

BACKGROUND: In the present study, we evaluated whether DEFB1 gene polymorphisms are associated with the presence of coronary artery disease (CAD). METHODS: Two rs11362 A/G, and rs1800972 C/G gene polymorphisms of DEFB1 gene were genotyped by 5'exonuclease TaqMan assays in 219 patients with CAD and 522 control individuals. RESULTS: The distribution of rs1800972 C/G polymorphisms was similar in patients with CAD and healthy controls. Nonetheless, under the co-dominant, dominant, recessive, and additive models, the AA genotype of the rs11362 A/G polymorphism was associated with the risk of developing CAD (OR = 1.89 pCCo-Dom = 0.041, OR = 1.46, pCDom = 0.034, OR = 1.69, pCRes = 0.039, and OR = 1.37, pCAdd = 0.012, respectively). In addition, the linkage disequilibrium showed that the 'AG' haplotype was associated with an increased risk of developing CAD (OR = 1.23, p = 0.042). According, with the Genotype-Tissue Expression (GTEx) consortium data, the rs11362 AA genotype is associated with a low mRNA expression of the ß-defensin-1 in tissues, such as artery aorta, artery coronary, heart left ventricle, and heart atrial appendage (p < 0.001). CONCLUSION: This study demonstrates that rs11362 A/G polymorphism of the DEFB1 gene is involved in the risk of developing CAD, and with a low RNA expression of the ß-defensin-1 in heart tissue.

Selection scan in Native Americans of Mexico identifies FADS2 rs174616: Evidence of gene-diet interactions affecting lipid levels and Delta-6-desaturase activity.

Searching for positive selection signals across genomes has identified functional genetic variants responding to environmental change. In Native Americans of Mexico, we used the fixation index (Fst) and population branch statistic (PBS) to identify SNPs suggesting positive selection. The 103 most differentiated SNPs were tested for associations with metabolic traits, the most significant association was FADS2/rs174616 with body mass index (BMI). This variant lies within a linkage disequilibrium (LD) block independent of previously reported FADS selection signals and has not been clearly associated with metabolic phenotypes. We tested this variant in two independent cohorts with cardiometabolic data. In the Genetics of Atherosclerotic Disease (GEA) cohort, the derived allele (T) was associated with increased BMI, lower LDL-C levels and a decreased risk of subclinical atherosclerosis in women. Significant gene-diet interactions affected lipid, apolipoprotein and adiponectin levels with differences according to sex, involving mainly total and complex dietary carbohydrate%. In the Genotype-related Effects of PUFA trial, the derived allele was associated with lower Δ-6 desaturase activity and erythrocyte membrane dihomo-gamma-linolenic acid (DGLA) levels, and with increased Δ-5 desaturase activity and eicosapentaenoic acid levels. This variant interacted with dietary carbohydrate% affecting Δ-6 desaturase activity. Notably, the relationship of DGLA and other erythrocyte membrane LC-PUFA indices with HOMA-IR differed according to rs174616 genotype, which has implications regarding how these indices should be interpreted. In conclusion, this observational study identified rs174616 as a signal suggesting selection in an independent linkage disequilibrium block, was associated with cardiometabolic and erythrocyte measurements of LC-PUFA in two independent Mexican cohorts and showed significant gene-diet interactions.

Diabetes subgroups and sociodemographic inequalities in Mexico: a cross-sectional analysis of nationally representative surveys from 2016 to 2022.

Background: Differences in the prevalence of four diabetes subgroups have been reported in Mexico compared to other populations, but factors that may contribute to these differences are poorly understood. Here, we estimate the prevalence of diabetes subgroups in Mexico and evaluate their correlates with indicators of social disadvantage using data from national representative surveys. Methods: We analyzed serial, cross-sectional Mexican National Health and Nutrition Surveys spanning 2016, 2018, 2020, 2021, and 2022, including 23,354 adults (>20 years). Diabetes subgroups (obesity-related [MOD], severe insulin-deficient [SIDD], severe insulin-resistant [SIRD], and age-related [MARD]) were classified using self-normalizing neural networks based on a previously validated algorithm. We used the density-independent social lag index (DISLI) as a proxy of state-level social disadvantage. Findings: We identified 4204 adults (median age: 57, IQR: 47-66, women: 64%) living with diabetes, yielding a pooled prevalence of 16.04% [95% CI: 14.92-17.17]. When stratified by diabetes subgroup, prevalence was 6.62% (5.69-7.55) for SIDD, 5.25% (4.52-5.97) for MOD, 2.39% (1.95-2.83) for MARD, and 1.27% (1.00-1.54) for SIRD. SIDD and MOD clustered in Southern Mexico, whereas MARD and SIRD clustered in Northern Mexico and Mexico City. Each standard deviation increase in DISLI was associated with higher odds of SIDD (OR: 1.12, 95% CI: 1.06-1.12) and lower odds of MOD (OR: 0.93, 0.88-0.99). Speaking an indigenous language was associated with higher odds of SIDD (OR: 1.35, 1.16-1.57) and lower odds of MARD (OR 0.58, 0.45-0.74). Interpretation: Diabetes prevalence in Mexico is rising in the context of regional and sociodemographic inequalities across distinct diabetes subgroups. SIDD is a subgroup of concern that may be associated with inadequate diabetes management, mainly in marginalized states. Funding: This research was supported by Instituto Nacional de Geriatría in Mexico.

The fatal contribution of serine protease-related genetic variants to COVID-19 outcomes.

Introduction: Serine proteases play a critical role during SARS-CoV-2 infection. Therefore, polymorphisms of transmembrane protease serine 2 (TMPRSS2) and serpine family E member 1 (SERPINE1) could help to elucidate the contribution of variability to COVID-19 outcomes. Methods: To evaluate the genetic variants of the genes previously associated with COVID-19 outcomes, we performed a cross-sectional study in which 1536 SARS-CoV-2-positive participants were enrolled. TMPRSS2 (rs2070788, rs75603675, rs12329760) and SERPINE1 (rs2227631, rs2227667, rs2070682, rs2227692) were genotyped using the Open Array Platform. The association of polymorphisms with disease outcomes was determined by logistic regression analysis adjusted for covariates (age, sex, hypertension, type 2 diabetes, and obesity). Results: According to our codominant model, the GA genotype of rs2227667 (OR=0.55; 95% CI = 0.36-0.84; p=0.006) and the AG genotype of rs2227667 (OR=0.59; 95% CI = 0.38-0.91; p=0.02) of SERPINE1 played a protective role against disease. However, the rs2227692 T allele and TT genotype SERPINE1 (OR=1.45; 95% CI = 1.11-1.91; p=0.006; OR=2.08; 95% CI = 1.22-3.57; p=0.007; respectively) were associated with a decreased risk of death. Similarly, the rs75603675 AA genotype TMPRSS2 had an OR of 1.97 (95% CI = 1.07-3.6; p=0.03) for deceased patients. Finally, the rs2227692 T allele SERPINE1 was associated with increased D-dimer levels (OR=1.24; 95% CI = 1.03-1.48; p=0.02). Discussion: Our data suggest that the rs75603675 TMPRSS2 and rs2227692 SERPINE1 polymorphisms are associated with a poor outcome. Additionally, rs2227692 SERPINE1 could participate in hypercoagulable conditions in critical COVID-19 patients, and this genetic variant could contribute to the identification of new pharmacological targets and treatment strategies to block the inhibition of TMPRSS2 entry into SARS-CoV-2.

The rs4783961 and rs708272 genetic variants of the CETP gene are associated with coronary artery disease, but not with restenosis after coronary stenting / Los polimorfismos rs4783961 y rs708272 del gen CETP son asociados con la enfermedad arterial coronaria y no con la restenosis tras el implante de un stent coronario

Abstract Objective: We evaluated whether cholesteryl ester transfer protein (CETP) gene polymorphisms are associated with the presence of coronary artery disease (CAD) and/or restenosis in patients with coronary stent. Methods: Two polymorphisms of the CETP gene [−971 A/G (rs4783961), and Taq1B A/G (rs708272)] were genotyped by 5'exonuclease TaqMan assays in 219 patients with CAD (66 patients with restenosis and 153 without restenosis) and 607 control individuals. Results: The distribution of polymorphisms was similar in patients with and without restenosis. However, when the whole group of patients (with and without restenosis) was compared to healthy controls, under dominant model, the G allele of the Taq1B A/G polymorphism was associated with increased risk of CAD (odds ratio [OR] = 1.48, pCDom = 0.032). In the same way, under codominant, dominant, and additive models, the A allele of the −971 A/G polymorphisms was associated with an increased risk of developing CAD (OR = 2.03, pCCo-dom = 0.022, OR = 1.83, pCDom = 0.008, and OR = 1.39, pCAdd = 0.011, respectively). In addition, the linkage disequilibrium showed that the "AG" haplotype was associated with increased risk of developing CAD (OR = 1.28, p = 0.03). Conclusion: This study demonstrates that CETP Taq1B A/G and CETP −971 A/G polymorphisms are associated with an increased risk of developing CAD, but no association with restenosis was observed.

Resumen Objetivo: Evaluamos si los polimorfismos del gen CETP están asociados con la presencia de enfermedad arterial coronaria (EAC) y/o restenosis en pacientes con stent coronario. Métodos: En este estudio se genotiparon dos polimorfismos del gen CETP [−971 A/G (rs4783961) y Taq1B A/G (rs708272)] mediante ensayos de 5'exonucleasa TaqMan en 219 pacientes con EAC (66 pacientes con restenosis y 153 sin restenosis), y 607 individuos de control. Resultados: La distribución de polimorfismos fue similar en pacientes con y sin restenosis. Sin embargo, cuando se comparó todo el grupo de pacientes (con y sin restenosis) con controles sanos, bajo el modelo dominante el alelo G del polimorfismo Taq1B A/G se asocia con un mayor riesgo de EAC (OR = 1.48, pCDom = 0.032). De la misma manera, bajo los modelos co-dominante, dominante y aditivo, el alelo A de los polimorfismos −971 A/G se asocia con un mayor riesgo de desarrollar EAC (OR = 2.03, pCCo-dom = 0.022, OR = 1.83, pCDom = 0,008 y OR = 1.39, pCAdd = 0.011, respectivamente). Adicionalmente, el desequilibrio de ligamiento mostró que el haplotipo "AG" se asocia con un mayor riesgo de desarrollar EAC (OR = 1.28, p = 0.03). Conclusión: En resumen, este estudio demuestra que los polimorfismos CETP Taq1B A/G y CETP −971 A/G están asociados con un mayor riesgo de desarrollar CAD, pero no se observó asociación con restenosis.

Síndrome metabólico, lipoproteína(a) y aterosclerosis subclínica en población mexicana / Metabolic syndrome, lipoprotein(a) and subclinical atherosclerosis in Mexican population

Resumen Objetivo: Investigar la asociación del síndrome metabólico y la lipoproteína(a) [Lp(a)] con el riesgo de aterosclerosis subclínica en adultos mexicanos. Método: En 953 mujeres y hombres se evaluaron datos clínicos, bioquímicos y tomográficos de grasa abdominal visceral, subcutánea, hepática y calcio arterial coronario. La Lp(a) se determinó mediante nefelometría y el síndrome metabólico se diagnosticó con los criterios del Adult Treatment Panel III. La asociación independiente de estas variables con el calcio arterial coronario se obtuvo con análisis de regresión logística multivariada. Resultados: La edad, el peso, el índice de masa corporal, la presión arterial sistólica y diastólica, los volúmenes de grasa abdominal, los lípidos, la glucosa, la insulina y el índice de resistencia a insulina fueron significativamente mayores en los sujetos con síndrome metabólico, mientras que la mediana de Lp(a) fue más baja en comparación con los sujetos sin el síndrome (3.7 [rango intercuartílico (RIC): 2.3-9.2 vs. 5.9 [RIC: 2.5-13.1) mg/dl; p < 0.01). El número de componentes y el síndrome metabólico se asociaron inversamente con la Lp(a) elevada (> 30 mg/dl). La presencia de síndrome metabólico se asoció con un riesgo de calcio arterial coronario > 0 (odds ratio [OR]: 2.19; intervalo de confianza del 95% [IC95%]: 1.64-2.94; p < 0.001), independientemente de la Lp(a) elevada. La glucemia > 100 mg/dl (OR: 2.42; IC95%: 1.7-3.4; p < 0.0001) y la presión arterial elevada (OR: 2.14; IC95%: 1.5-3.1; p > 0.0001) se asociaron con calcio arterial coronario > 0. Conclusiones: En población mexicana existe una asociación inversa entre la concentración de Lp(a) y el síndrome metabólico. Este y sus componentes se asociaron positivamente con aterosclerosis subclínica. La elevada prevalencia de obesidad, diabetes, hipertensión arterial, triglicéridos elevados y concentración de colesterol unido a lipoproteínas de alta densidad que caracterizan a la población mexicana pudieran explicar las diferencias con otras poblaciones.

Abstract Objective: To assess the relationship of metabolic syndrome (MetS) and Lp(a) with subclinical atherosclerosis (CAC) in Mexican adults. Method: Clinical, biochemical and tomographic data of visceral, subcutaneous, hepatic abdominal fat and CAC were evaluated in 953 women and men. Lp(a) was determined by nephelometry and MetS was diagnosed according to ATP III criteria. Multivariate logistic regression analysis was performed to determine the independent association of these variables with CAC. Results: Age, weight, body mass index, systolic and diastolic blood pressure, volumes of visceral, subcutaneous and hepatic abdominal fat, lipids, glucose, insulin and HOMA-RI were significantly higher in subjects with MetS. The median Lp(a) was lower in subjects with MetS compared to subjects without MetS (3.7 [IR: 2.3-9.2 vs. 5.9 [IR: 2.5-13.1) mg/dL; p < 0.01). The number of components and the MetS were inversely associated with the elevated Lp(a) (> 30 mg / dL). The presence of MetS was associated with a CAC risk >0 (OR: 2.19, [95% CI (1.64-2.94)]; p < 0.001), independently of elevated Lp(a). The components of MetS that were independently associated with the presence of CAC > 0 UA were glycaemia > 100 mg/dL (OR 2.42, [95% CI (1.7-3.4)]; p < 0.0001) and high blood pressure (OR 2.14 [95% CI (1.5-3.1)]; p < 0.0001). Conclusions: In Mexican population there is an inverse association between Lp(a) levels and MetS. The MetS and its components were associated with subclinical atherosclerosis. The high prevalence of obesity, diabetes, high blood pressure high triglycerides and low HDL-C, characteristics of Mexican population could explain the differences with other populations.

Coronary artery calcium is associated with lpa gene variant RS7765803-C in Mexican mestizo population The GEA Project

ABSTRACT Background: Lipoprotein(a) [Lp(a)] levels are genetically determined; high levels are a risk factor for coronary disease, although their association with coronary artery calcium (CAC) is controversial. Objective: The objective of the study was to assess the association of LPA gene polymorphisms with CAC in a Mexican Mestizo population. Methods: We included 1594 subjects 35-70 years old. Six polymorphisms of the LPA gene were analyzed. CAC score was determined by tomography and Lp(a) serum levels by immunonephelometry. The association of LPA polymorphism with CAC and Lp(a) was evaluated by logistic regression. Results: The prevalence of Lp(a) ≥30 mg/dL was 10%, and of CAC >0 was 26.9%. Three polymorphisms were associated with high Lp(a) levels: rs10455872-G (p = 0.013), rs6907156-T (p = 0.021), and rs7765803-C (p = 0.001). Homozygotes (CC) for the rs7765803 variant compared with the G allele (CG + GG) carriers had higher Lp(a) levels (8.9 [3.3-23.9] vs. 4.9 [2.3-11.2] mg/dL; p = 0.015) and higher prevalence of CAC >0 (36.5% vs. 26.3%, p = 0.045) and were associated with CAC > 0 (odds ratio = 1.7, 95% confidence interval: 1.06-2.7; p < 0.026). The other polymorphisms were not associated with CAC. Conclusions: This is the first study to demonstrate in a Mexican Mestizo population that carriers of the rs7765803-C allele of LPA gene have 2.6 times greater risk for high Lp(a) values and 1.7 times higher risk for coronary artery disease.

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).

Prevalencia y asociación de la calcificación valvular aórtica con factores de riesgo y aterosclerosis coronaria en población mexicana / Aortic valve calcification prevalence and association with coronary risk factors and atherosclerosis in Mexican population

Resumen: Objetivo: La prevalencia de calcificación valvular aórtica (CVA) tiene influencia importante de la etnia y se desconoce en población mexicana. Nuestro objetivo fue investigar la prevalencia de CVA y sus asociaciones con factores de riesgo cardiovascular y calcificación arterial coronaria (CAC). Método: En 1,267 sujetos (53% mujeres) sin enfermedad coronaria conocida y con edad de 35 a 75 años, la CVA y la CAC se evaluaron mediante tomografía computada multidetector, utilizando el método de Agatston. Los factores de riesgo cardiovascular se documentaron en todos los participantes. Las asociaciones de CVA con CAC y factores de riesgo se estimaron usando el análisis de regresión logística múltiple. Resultados: La prevalencia global de CVA y CAC fue del 19.89% y del 26.5%, respectivamente. Ambas condiciones aumentaron con la edad y se encontraron con mayor frecuencia en hombres (25.5 y 37.1%, respectivamente) que en mujeres (14.9 y 13%, respectivamente). La CVA se observó en únicamente el 8.5% de los sujetos sin CAC, mientras que en aquellos con CAC 1-99, 100-399 y > 400 unidades Agatston, las prevalencias fueron del 36.8, 56.8 y 84%, respectivamente. El análisis de regresión logística múltiple ajustado por edad, género, obesidad, inactividad física, hipertensión, dislipidemia y valores altos de insulina, mostró que la presencia de CAC (RM [IC95%]: 3.23 [2.26-4.60]), obesidad (1.94 [1.35-2.79]), género masculino (1.44 [1.01-2.05]) y edad (1.08 [1.03-1.10]), fueron predictores independientes y significativos de la CVA. Conclusiones: La prevalencia de CVA es alta y se asocia significativamente con factores de riesgo aterosclerótico y CAC en población mexicana.

Abstract: Objetive: The prevalence of aortic valve calcification (AVC), strongly influenced by ethnicity, is unknown in Mexican population. The aim of this study was to investigate the prevalence of AVC and its associations with cardiovascular risk factors and coronary artery calcification (CAC), in Mexican subjects. Methods: In 1,267 subjects (53% women) without known coronary heart disease, aged 35 to 75 years, AVC and CAC were assessed by multidetector-computed tomography using the Agatston score. Cardiovascular risk factors were documented in all participants. The associations of AVC with CAC and risk factors were assessed by multivariable logistic regression analyses. Results: The overall prevalence of AVC and CAC was 19.89% and 26.5%, respectively. AVC and CAC increased with age and were found more frequently in men (25.5% and 37.1%, respectively) than in women (14.9% and 13.0%, respectively). AVC was observed in only 8.5% of subjects wit-hout CAC, while those with CAC 1-99, 100-399, and > 400 Agatston units had AVC prevalences of 36.8%, 56.8%, and 84.0%, respectively. The multivariable logistic regression analyses, adjusted for age, gender, obesity, physical inactivity, hypertension, dyslipidemia and high insulin levels, showed that the presence of CAC (OR [CI95%]: 3.23 [2.26-4.60]), obesity (1.94 [1.35-2.79]), male gender (1.44 [1.01-2.05]) and age (1.08 [1.03-1.10]), were significant independent predictors of AVC. Conclusion: Prevalence of AVC is high and significantly associated with atherosclerotic risk factors and CAC in this Mexican population.

Exceso de peso y síndrome metabólico en adolescentes de la Ciudad de México / Obesity or overweight and metabolic syndrome in Mexico City teenagers

Objetivo: Conocer la prevalencia del síndrome metabólico y sus componentes en una muestra de adolescentes de la Ciudad de México. Diseño: Se efectuó un estudio transversal en 772 varones y 1,078 mujeres de 12 a 16 años edad, en ocho escuelas secundarias de la Ciudad de México seleccionadas al azar. Métodos: Se realizaron medidas antropométricas, lípidos y lipoproteínas, Apo-AI y B, glucosa e insulina. Resultados: La prevalencia del síndrome metabólico fue de 12.5%, 11.5% en los varones y 13.5% en las mujeres (p = ns). La concentración baja de colesterol en las HDL fue el componente del síndrome metabólico más frecuente (38%), seguido de triglicéridos elevados (25.5%), hipertensión arterial (19.2%), obesidad central (11.8%) y glucosa en ayuno elevada (1.7%). Excepto por la hipertrigliceridemia, 28.2% en las mujeres y 21.6% en los varones (p < 0.001), la prevalencia de los componentes del síndrome metabólico fue similar en ambos géneros. Conclusiones: La prevalencia elevada de componentes bioquímicos y fisiológicos del síndrome metabólico, asociada con el sobrepeso y la obesidad en los adolescentes de la Ciudad de México, incrementa el riesgo en este grupo de la población de desarrollar de manera prematura ateroesclerosis coronaria y diabetes mellitus.

Aim: To know the metabolic syndrome and its components prevalence in Mexico City adolescents sample. Design: A cross-sectional survey was conducted in 772 men and 1078 women, 12 to 16 years old, from 8 randomly selected public junior high schools in Mexico City. Methods: Anthropometric variables, lipids, lipoproteins, Apo AI and B, glucose and insulin were determined. Results: Prevalence of metabolic syndrome was 12.5%, 11.15% in men and 13.5% en women (p ns). The most frequently metabolic syndrome component found in México City adolescents was low HDL-C levels (38%), followed by hypertriglyceridemia (25.5%), hypertension (19.2%), central obesity (11.8%) and elevated fasting glucose (1.7). Except by the hypertriglyceridemia, higher in woman than in men, 28.2% vs. 21.6%, p < 0.001, the prevalence of metabolic syndrome components was similar between males and females. Conclusions: The high prevalence of biochemical and physiological factors of metabolic syndrome, associated with overweight and obesity in Mexico City adolescents, increases the risk of premature development of coronary atherosclerosis and diabetes mellitus in this population.

Blood pressure and associated cardiovascular risk factors in adolescents of Mexico City / Tensión arterial y su asociación con factores de riesgo cardiovascular en adolescentes de

OBJECTIVE: To determine the prevalence of high blood pressure and associated cardiovascular risk factors in Mexican adolescents. METHODS: A cross-sectional study was conducted in 770 male and 1076 female students (12 to 16 years old) from eight randomly selected high schools in Mexico City. Anthropometry, blood pressure and fasting lipids and lipoproteins were measured. RESULTS: Blood pressure levels were adjusted for age, gender, and height. The prevalence rates of hypertension (systolic blood pressure (SBP) and/or diastolic (DBP) > or =95th percentile), and pre-hypertension (SBP or DBP > or =90th but <95th percentile) were 10.6 and 10%, respectively. Compared to normotensive subjects, those with high blood pressure showed a significantly higher prevalence of obesity, overweight, and dyslipidemia. A stepwise multiple regression analysis showed that waist (18.3%), Tanner stage (4.7%), age (2.1%), gender (0.6%), and body mass index (BMI, 0.3%) accounted for 26% of the variance in SBP; whereas BMI (8.7%), age (4.8%), Tanner stage (1.7%), waist (0.4%), and gender (0.4%) accounted for 15.9% of the variance in DBP. CONCLUSIONS: These results reveal a high prevalence of high blood pressure in adolescents living in Mexico City. Prehypertensive and hypertensive subjects showed a higher prevalence of cardiovascular risk factors, suggesting that, as adults, these adolescents will be at a higher risk of developing cardiovascular disease.

Alteraciones de las lipoproteínas de alta y baja densidad en pacientes coronarios con C-LDL en meta pero C-HDL y triglicéridos anormales / High and low density lipoprotein abnormalities in coronary patients with LDL-C at target and uncontrolled HDL-C and triglycerides

OBJECTIVE: To investigate the high density lipoprotein (HDL) subclasses distribution and chemical composition, as well as low density lipoprotein (LDL) size and LDL oxidation, in coronary male patients treated with statins, that had LDL-cholesterol levels at target (< 100 mg/dL), but whose HDL-cholesterol (< 40 mg/dL) and triglycerides (TG > or = 150 mg/dL) levels were abnormal. The control group was formed by statin treated coronary male patients with LDL-C below 100 mg/dL and normal HDL-C and TG levels. MATERIAL AND METHODS: HDL subclasses and LDL size were determined by gradient gel electrophoresis. LDL susceptibility to oxidation was determined by measuring lag phase duration, after adding the oxidant agent. RESULTS: Compared with the control group (n = 35), patients with low HDL-C + high TG (n = 34) showed significantly lower proportions of large HDL and higher proportions of small HDL particles. In addition, these patients had abnormal HDL composition, smaller LDL size, and higher LDL susceptibility to oxidation (p < 0.05 for all). CONCLUSIONS: Coronary patients with optimal LDL-C levels on statin therapy but with low HDL-C and high TG, have HDL and LDL abnormalities that have been shown to be associated with a higher risk of new coronary events.