Maite Vallejo

Ambient fine particles modify heart rate variability in young healthy adults

Particulate air pollution has been related with cardiopulmonary morbidity and mortality. Recent studies have shown that an increase in particulate matter (PM)2.5 ambient concentrations was associated with a decrease in heart rate variability (HRV) in the elderly with cardiovascular conditions, which could increase the risk of death. In order to assess if this association could also be observed in young adults, we studied 40 young healthy residents of the Mexico City Metropolitan Area (MCMA) who underwent 13 h Holter electrocardiographic and PM2.5 personal monitoring. HRV was evaluated in time domain: the standard deviation of normal RR intervals (SDNN) and the percentage of differences between adjacent normal RR intervals larger than 50 ms (pNN50). In multivariate analysis with mixed effects models, a significant negative association of pNN50 with PM2.5 accumulative exposure was found. An increase in 30 μg/m3 of the average PM2.5 personal exposure in the previous 2 h decreased the pNN50 in 0.08% (P=0.01). This observation revealed an acute effect related to environmental exposure to PM2.5 with regard to HRV in normal youngsters. The long-term health consequences of this association in young healthy adults remain to be clarified.

Age, body mass index, and menstrual cycle influence young women's heart rate variability A multivariable analysis

Heart rate variability (HRV) in women has been related independently to endogenous sex hormones, hormone replacement therapy, menopause, menstrual cycle, body mass index (BMI), and physical conditioning. However, the joint influence of all these factors has not been reported. The present study describes the relation between circadian variation HRV and assesses its association with BMI, age, and menstrual cycle in healthy young women. A multivariable analysis was performed to estimate the predictive variables involved in SDNN, pNN50, and rMSSD profile, using the classification and regression tree (CART) and the logistic regression models. It was found that the first predictive variable was age, which divided women in two groups: >29.5 years old and <29.5 years old. In the case of the SDNN, the second predictive variable was BMI; the highest values were observed in women younger than 23 years old, with a BMI less than 19.82 kg/m2 and during the follicular phase of her menstrual cycle. For pNN50 and rMSSD the second predictive variable was menstrual cycle for women younger than 29.5 years old. Thus, in this group of women, age was a major determinant of cardiac autonomic nervous modulation followed by the BMI. HRV may be better understood using a multivariable analysis that could mimic physiological conditions.

Personal PM2.5 and CO exposures and heart rate variability in subjects with known ischemic heart disease in Mexico City.

Cardiovascular diseases are the main cause of death in Mexico City and have shown a rising trend over the past 20 years. Various epidemiological studies have reported an association between respirable particles and carbon monoxide (CO), with cardiorespiratory outcomes. The purpose of this study was to assess the effect of particulate matter with aerodynamic diameters of less than 2.5 μm (PM2.5), also known as respirable or fine particles and CO on heart rate variability (HRV) in 5-min periods in patients with known ischemic heart disease. 30 patients were selected from the outpatient clinic of the National Institute of Cardiology of Mexico and followed during 11 h, using electrocardiography (ECG) ambulatory electrocardiograms and personal monitors for CO and PM2.5. We calculated frequency-domain measurements using power spectral analysis and assessed the association with pollutants using mixed models analysis in 5-min periods. We found a decrease in HRV measured as high frequency (Ln) (coefficient=−0.008, 95% confidence interval (CI), −0.015, 0.0004) for each 10 μg/m3 (micrograms per cubic meter) increase of personal PM2.5 exposure. We also found a decrease of low (ln) (coefficient=−0.024, 95% CI, −0.041, −0.007) and very low frequencies (ln) (coefficient=−0.034, 95% CI, −0.061, −0.007) for 1 parts per million (p.p.m.) increase in CO personal exposure after adjustment for potential confounding factors. These results show that for this high-risk population, the alteration of the cardiac autonomic regulation was significantly associated with both PM2.5 and CO personal exposures.

Detection of IS6110 and HupB gene sequences of Mycobacterium tuberculosis and bovis in the aortic tissue of patients with Takayasu’s arteritis

BackgroundTakayasu’s arteritis (TA) is a chronic inflammatory disease affecting the large arteries and their branches; its etiology is still unknown. In individuals suffering from TA, arterial inflammation progresses to stenosis and/or occlusion, leading to organ damage and affecting survival. Relation of TA with Mycobacterium tuberculosis has been known, but there have been only a few systematic studies focusing on this association. The IS6110 sequence identifies the Mycobacterium tuberculosis complex and the HupB establishes the differences between M. tuberculosis and M. bovis. Our objective was to search the presence of IS6110 and HupB genes in aorta of patients with TA.MethodsWe analyzed aorta tissues embedded in paraffin from 5760 autopsies obtained from our institution, we divided the selected samples as cases and controls; Cases: aortic tissues of individuals with Takayasu’s arteritis. Control positive: aortic tissues (with tuberculosis disease confirmed) and control negative with other disease aortic (atherosclerosis).ResultsOf 181 selected aorta tissues, 119 fulfilled the corresponding criteria for TA, TB or atherosclerosis. Thus 33 corresponded to TA, 33 to tuberculosis (TB) and 53 to atherosclerosis. The mean age was 22 ± 13, 41 ± 19, and 57 ± 10, respectively. IS6110 and HupB sequences were detected in 70% of TA tissues, 82% in tuberculosis, and in 32% with atherosclerosis. Important statistical differences between groups with TA, tuberculosis versus atherosclerosis (p = 0.004 and 0.0001, respectively) were found.ConclusionWe identified a higher frequency of IS6110 and HupB genes in aortic tissues of TA patients. This data suggests that arterial damage could occur due to previous infection with M. tuberculosis.

Personal exposure to PM2.5 air pollution and heart rate variability in subjects with positive or negative head-up tilt test.

Particulate matter air pollution has been related to an increase in cardiopulmonary morbidity and mortality especially in susceptible subjects with a known cardiopulmonary disease. Recent studies suggest that PM(2.5) air pollution was associated with changes in heart rate variability (HRV). The purpose of this study was to identify and compare changes in HRV in positive or negative head-up tilt (HUT) participants. Fifty two subjects, 31 women and 21 men, 20-40 years old, underwent PM(2.5) personal monitoring and Holter-ECG monitoring in supine and orthostatic position, during active standing, in indoor and outdoor environments. All measurements were made between 8 and 11 AM in the same geographical location (southeast of Mexico City). Frequency domain indexes were estimated in absolute (ms(2)) and in normalized units (nu) (low frequencies (LF), high frequencies (HF) and low/high frequency ratio (LF/HF)) in 5 min periods by standard methods. Data were transformed into natural logarithmic scale (ln). Comparisons were made between genders and positive and negative HUT subjects. LF were larger and HF were smaller in negative HUT males. Multivariate analysis with GEE models, adjusted for each index, showed a significant decrease of HRV (LFln -0.194 95% CI, -0.4509, 0.0627, and HFln -0.298 95% CI, -0.5553, -0.0401) associated to an increase in PM(2.5) air pollution in positive and negative HUT subjects which was larger for HFln in outdoor environments. PM(2.5) air pollution was associated with changes in HRV in positive and negative HUT subjects without cardiopulmonary disease.

Single Nucleotide Polymorphisms within LIPA (Lysosomal Acid Lipase A) Gene Are Associated with Susceptibility to Premature Coronary Artery Disease. A Replication in the Genetic of Atherosclerotic Disease (GEA) Mexican Study

Aim The rs1412444 and rs2246833 polymorphisms within the LIPA gene were recently found to be significantly associated with coronary artery disease (CAD) in genome-wide association studies in Caucasian and Asian populations. The aim of the present study was to replicate this association in an independent population with a different genetic background. Methods The rs1412444 and rs2246833 polymorphisms of the LIPA gene were genotyped by 5′ exonuclease TaqMan genotyping assays in a sample of 899 Mexican patients with premature CAD, 270 individuals with subclinical atherosclerosis, and 677 healthy unrelated controls. Haplotypes were constructed after linkage disequilibrium analysis. Results Under recessive and additive models, the rs1412444 T and rs2246833 T alleles were associated with an increased risk of premature CAD when compared to controls adjusting for age, gender, BMI, and total cholesterol (OR = 1.53, PRec = 0.0013 and OR = 1.34, PAdd = 5 × 10-4 for rs1412444 and OR = 1.45, PRec = 0.0039 and OR = 1.28, PAdd = 0.0023 for rs2246833). The effect of the two polymorphisms on various metabolic cardiovascular risk factors was analyzed in premature CAD and controls (CAC score = 0). The T alleles in both polymorphisms after adjusting for age, gender, BMI, and medication were associated with hypo-α-lipoproteinemia, hypercholesterolemia, hypertriglyceridemia, metabolic syndrome, and type 2 diabetes mellitus using recessive and additive models. The polymorphisms were in strong linkage disequilibrium and, based on SNP functional prediction software, only the rs1412444 polymorphism seemed to be functional. Conclusions These results indicate that the rs1412444 and rs2246833 of the LIPA gene are shared susceptibility polymorphisms for CAD among different ethnicities.

Single Nucleotide Polymorphisms of the Angiotensin-Converting Enzyme (ACE) Gene Are Associated with Essential Hypertension and Increased ACE Enzyme Levels in Mexican Individuals

Aim To explore the role of the ACE gene polymorphisms in the risk of essential hypertension in Mexican Mestizo individuals and evaluate the correlation between these polymorphisms and the serum ACE levels. Methods Nine ACE gene polymorphisms were genotyped by 5′ exonuclease TaqMan genotyping assays and polymerase chain reaction (PCR) in 239 hypertensive and 371 non- hypertensive Mexican individuals. Haplotypes were constructed after linkage disequilibrium analysis. ACE serum levels were determined in selected individuals according to different haplotypes. Results Under a dominant model, rs4291 rs4335, rs4344, rs4353, rs4362, and rs4363 polymorphisms were associated with an increased risk of hypertension after adjusting for age, gender, BMI, triglycerides, alcohol consumption, and smoking. Five polymorphisms (rs4335, rs4344, rs4353, rs4362 and rs4363) were in strong linkage disequilibrium and were included in four haplotypes: H1 (AAGCA), H2 (GGATG), H3 (AGATG), and H4 (AGACA). Haplotype H1 was associated with decreased risk of hypertension, while haplotype H2 was associated with an increased risk of hypertension (OR = 0.77, P = 0.023 and OR = 1.41, P = 0.004 respectively). According to the codominant model, the H2/H2 and H1/H2 haplotype combinations were significantly associated with risk of hypertension after adjusted by age, gender, BMI, triglycerides, alcohol consumption, and smoking (OR = 2.0; P = 0.002 and OR = 2.09; P = 0.011, respectively). Significant elevations in serum ACE concentrations were found in individuals with the H2 haplotype (H2/H2 and H2/H1) as compared to H1/H1 individuals (P = 0.0048). Conclusion The results suggest that single nucleotide polymorphisms and the “GGATG” haplotype of the ACE gene are associated with the development of hypertension and with increased ACE enzyme levels.

Determinants of Thyrotoxic Cardiomyopathy Recovery

The purpose was to evaluate the effect of the disease duration prior to treatment, thyroid hormones level, or both on the reversibility of dilated cardiomyopathy. Between January 2006 and December 2010, a longitudinal study with a 6 months follow-up was carried on. One hundred and seventy patients with hyperthyroidism were referred to the cardiologist, and 127 had a 6 months followup after antithyroid treatment and were evaluated by echocardiography. Dilated cardiomyopathy reversibility criteria were established according to echocardiographic parameters. Complete reversibility existed when all parameters were met, partial reversibility when LVEF was ≥55% plus two or three other parameters, and no reversibility when LVEF was ≤55% regardless of other parameters. The results showed that echocardiography parameters related to the regression of myocardial mass were associated with a disease duration shorter than 10.38 months. This was the main predictive variable for reversal of dilated cardiomyopathy, followed by β-blocker treatment, and the last predictive variable was the serum level of free triiodothyronine. This study showed that the effect on the myocardium related to thyrotoxicosis was associated with the disease duration before treatment.

Personal exposure to particulate matter less than 2.5 μm in Mexico City: a pilot study

This study was aimed to describe the personal exposure of permanent residents in Mexico Citys Metropolitan Area (MCMA) to particulate matter of less than 2.5 μm diameter (PM2.5) during their daily activities. A total of 40 healthy volunteers (30 women and 10 men) with sedentary activities were included. All of them carried a PM2.5 personal monitor during 13 h and registered their activities in a written diary that classified them in indoor and outdoor microenvironments in each 30 min period. All sample collections started at 0900 hours, and even though measurements were obtained during the rainy season (April–August 2002), the relative humidity was less than 70%. The data were categorized and evaluated under the following criteria: morning and afternoon exposure, indoor and outdoor activities, and geographical location. The descriptive analysis showed that the overall outdoor median concentration of PM2.5 (89.50 μg/m3) was higher than the indoor one (67.55 μg/m3). PM2.5 concentrations in the morning to early afternoon were more elevated than in the late afternoon, suggesting a circadian-like behavior. In the indoor microenvironment, the highest concentration occurred in the subway (106.2 μg/m3) followed by school (93.27 μg/m3), and the lowest at home (53.1 μg/m3). The outdoor microenvironment with the highest concentrations was the public transportation (bus) (99.95 μg/m3), while the automobile had the lowest (64.9 μg/m3). The geographical zone with the highest concentration was the Center city area (87.87 μg/m3), and the one with the lowest concentration was the northeast area of the city (50 μg/m3). All the differences were statistically significant (P<0.05). Multivariate analysis corroborated that PM2.5 concentrations are mainly determined by geographical locations and hour of the day, but not by the type of microenvironment. The inclusion of covariables in the multivariable analysis ensures a more accurate estimation and prediction of the real PM2.5 concentrations. In conclusion, PM2.5 personal exposure of healthy adult permanent residents of MCMA is usually higher than recommended by the international standards in outdoor and even in indoor microenvironments. Particulate matter personal exposure varies in relation to hour of the day, daily activities and microenvironments.

Association of angiotensin II type 1-receptor gene polymorphisms with the risk of developing hypertension in Mexican individuals.

Introduction: Hypertension is a complex disease in which a significant interaction between genetic and environmental factors takes place. The renin–angiotensin system plays an important role regulating blood pressure to maintain homeostasis and vascular tone. In the present work, the role of angiotensin II type 1-receptor (AGTR1) gene polymorphisms as susceptibility markers for hypertension was evaluated. Materials and methods: Five polymorphisms in the AGTR1 gene were genotyped by 5′ exonuclease TaqMan genotyping assays in 239 hypertensive and 371 non-hypertensive individuals. Results: A similar distribution of rs275651, rs275652, rs275653, and rs5183 polymorphisms was observed in both studied groups. Different distribution of rs5182 genotypes was observed between the studied groups (p = 0.016). According to the co-dominant model, individuals with rs5182 CC genotype have a 1.83-fold increased risk of developing hypertension (p = 0.009). Polymorphisms were distributed in two blocks: block 1 included the rs275651, rs275652, and rs275653 polymorphisms, whereas block 2 included the rs5183 and rs5182 polymorphisms. Individuals with hypertension showed increased frequency of ‘CA’ haplotype of block 2 when compared to non-hypertensive individuals (p = 0.015, odds ratio = 1.33). Conclusion: The results suggest that the rs5182 gene polymorphism could be involved in the risk of developing hypertension in Mexican individuals.