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.