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Roberto Elosua

Publications and source records attributed to Roberto Elosua.

At least 19 recordsLinked to original sources

Aerobic Fitness and Health-Related Phenotypes: A Two-Stage Phenome-Wide Mendelian Randomization Study.

PURPOSE: We investigated potentially causal associations between genetically predicted aerobic fitness and multiple health phenotypes using a two-stage phenome-wide Mendelian randomization (MR) study. METHODS: Genetically determined aerobic fitness, as operationalized by Cai et al., served as the exposure instrument. We screened 712 health-related phenotypes as outcomes using publicly available European-ancestry genome-wide association studies (GWAS) summary statistics from OpenGWAS (Discovery GWAS n > 5000), prioritizing non-UK Biobank/non-FinnGen datasets for Discovery when available and selecting an independent GWAS for validation. Associations were estimated using the MR-Robust Adjusted Profile Score method, controlled for multiple testing (5% false discovery rate) and unaffected by violations of MR assumptions (directional concordance between discovery and validation; no evidence of horizontal pleiotropy across inverse-variance weighted, MR-Egger, weighted-median, and weighted-mode methods; negative control analysis on hair color). RESULTS: We identified 108 discovery associations, of which 34 remained valid and statistically significant after validation. Higher genetically determined aerobic fitness was associated with lower lacunar stroke risk, lower arterial stiffness, higher heart rate variability, lower diastolic blood pressure, more favorable anthropometric measures, lower use of antidiabetic drugs, lower asthma risk, lower C-reactive protein, higher bone mineral density, favorable liver function biomarkers, favorable platelet-related traits, multiple blood count-derived hematological cell indices and counts, as well as higher years of schooling. Adverse associations were confined to atrial fibrillation, valvular heart disease, and systolic blood pressure. CONCLUSIONS: Genetically determined aerobic fitness is linked to a broad pattern of favorable cardiometabolic, inflammatory, musculoskeletal, respiratory, hepatic, and hematological phenotypes, alongside a narrow set of potential cardiovascular hazards.

Humans↗

Validity of an adaptation of the Framingham cardiovascular risk function: the VERIFICA Study.

BACKGROUND: To assess the reliability and accuracy of the Framingham coronary heart disease (CHD) risk function adapted by the Registre Gironí del Cor (REGICOR) investigators in Spain. METHODS: A 5-year follow-up study was completed in 5732 participants aged 35-74 years. The adaptation consisted of using in the function the average population risk factor prevalence and the cumulative incidence observed in Spain instead of those from Framingham in a Cox proportional hazards model. Reliability and accuracy in estimating the observed cumulative incidence were tested with the area under the curve comparison and goodness-of-fit test, respectively. RESULTS: The Kaplan-Meier CHD cumulative incidence during the follow-up was 4.0% in men and 1.7% in women. The original Framingham function and the REGICOR adapted estimates were 10.4% and 4.8%, and 3.6% and 2.0%, respectively. The REGICOR-adapted function's estimate did not differ from the observed cumulated incidence (goodness of fit in men, p = 0.078, in women, p = 0.256), whereas all the original Framingham function estimates differed significantly (p<0.001). Reliabilities of the original Framingham function and of the best Cox model fit with the study data were similar in men (area under the receiver operator characteristic curve 0.68 and 0.69, respectively, p = 0.273), whereas the best Cox model fitted better in women (0.73 and 0.81, respectively, p<0.001). CONCLUSION: The Framingham function adapted to local population characteristics accurately and reliably predicted the 5-year CHD risk for patients aged 35-74 years, in contrast with the original function, which consistently overestimated the actual risk.

Adult↗

Variants at the APOA5 locus, association with carotid atherosclerosis, and modification by obesity: the Framingham Study.

Genetic variation at the apolipoprotein A5 gene (APOA5) is associated with increased triglyceride concentrations, a risk factor for atherosclerosis. Carotid intimal medial thickness (IMT) is a surrogate measure of atherosclerosis burden. We sought to determine the association of common APOA5 genetic variants with carotid IMT and stenosis. A total of 2,273 Framingham Offspring Study participants underwent carotid ultrasound and had data on at least one of the five APOA5 variants (-1131T>C, -3A>G, 56C>G, IVS3+476G >A, and 1259T>C). Although none of the individual variants was significantly associated with carotid measures, the haplotype defined by the presence of the rare allele of the 56C>G variant was associated with a higher common carotid artery (CCA) IMT compared with the wild-type haplotype (0.75 vs. 0.73 mm; P < 0.05). The rare allele of each of the -1131T >C, -3A>G, IVS3+476G>A, and 1259T>C variants and the haplotype defined by the presence of the rare alleles in these four variants were each significantly associated with CCA IMT in obese participants. These associations remained significant even after adjustment for triglycerides. APOA5 variants were associated with CCA IMT, particularly in obese participants. The mechanism of these associations and the effect modification by obesity are independent of fasting triglyceride levels.

Apolipoprotein A-V↗

Association between well-characterized lipoprotein-related genetic variants and carotid intimal medial thickness and stenosis: The Framingham Heart Study.

OBJECTIVE: To determine the association of well-characterized lipoprotein-related genetic variants with carotid intimal medial thickness (IMT) and stenosis. METHODS: 3380 men and women from the Framingham Offspring Study underwent carotid ultrasound to determine carotid IMT and stenosis>/=25%. We genotyped 12 variants in 10 lipoprotein-related genes known to be associated with significant differences in lipoprotein levels. RESULTS: For most of the variants, there was no association with carotid IMT. In multivariable, sex-specific analyses, the rare allele of the cholesterol ester transfer protein (CETP) TaqIB variant was associated with lower ICA IMT in men. Hypertension was associated with higher ICA IMT only in male carriers of the rare allele of the APOCIII Sst-1 variant (p for the interaction=0.041). In analyses of carotid stenosis in male, carriers of the lipoprotein lipase (LPL) N291S rare variant showed a higher risk of carotid stenosis (OR=2.59, 95% confidence interval: 1.11-6.02, p=0.028) compared to NN genotype. CONCLUSIONS: While there is no evidence for a significant association of several common lipoprotein-related genetic variants with carotid IMT, our results are consistent with the previously reported role of CETP and LPL genetic variants in cardiovascular risk and the possible modulation of the association between hypertension and carotid IMT by APOCIII Sst-1 variant.

Adolescent↗

Circulating oxidized LDL is associated with increased waist circumference independent of body mass index in men and women.

BACKGROUND: Obesity is associated with oxidative stress, and the oxidation of LDL is thought to play a crucial role in the generation of atherosclerotic lesions. OBJECTIVE: The objective was to describe the association of waist circumference (WC) and body mass index (BMI; in kg/m2) with plasma circulating oxidized LDL (ox-LDL) and C-reactive protein (CRP). DESIGN: This cross-sectional study included data for circulating ox-LDL and CRP from a subpopulation of 586 men and women enrolled in a population-based survey conducted in 2000 in Girona, Spain. Multivariate analysis was performed to describe the independent association of WC and BMI with ox-LDL and CRP. RESULTS: Multivariate logistic regression analysis adjusted for lifestyle, educational level, and dietary confounders showed a direct association of WC (quartile distribution) and BMI categories with ox-LDL (P for linear trend = 0.002) and CRP (P for linear trend = 0.004). Subjects in the top quartile of WC and with a BMI > 29.9 were at high risk of elevated circulating concentrations of ox-LDL and CRP. Further adjustment for cardiovascular disease risk factors did not substantially modify these associations. The risk of high ox-LDL concentrations in overweight (BMI = 25.0-29.9) or obese (BMI > or = 30) subjects with a WC < 102 cm (men) or < 88 cm (women) was not significantly different from that in normal-weight subjects with these WCs. In contrast, overweight or obese subjects with higher WCs (WC > or = 102 cm for men and > or = 88 cm for women) were at significantly higher risk of increased ox-LDL. CONCLUSION: High WC was associated with high concentrations of ox-LDL independently of BMI in the study population.

Abdominal Fat↗

Concordance of electrocardiographic patterns and healed myocardial infarction location detected by cardiovascular magnetic resonance.

Q-wave myocardial infarction (MI) location is generally based on a pathologic correlation first proposed >50 years ago. Despite the proved reliability of contrast-enhanced cardiovascular magnetic resonance (CE-CMR) imaging to detect and locate infarcted areas, no global study has been conducted with the aim of correlating the electrocardiographic (ECG) patterns of Q-wave MI with infarct location. We studied this correlation in 51 patients with ST-elevation acute coronary syndrome who presented with Q waves or equivalents during MI. Seven preestablished ECG patterns that matched with high specificity to 7 different MI locations as detected by CE-CMR imaging were used to assess its value in clinical practice to locate an infarcted area. There were 4 ECG patterns in the anteroseptal zone (23 patients; septal, apical, and/or anteroseptal, extensive anterior, and limited anterolateral) and 3 ECG patterns in the inferolateral zone (28 patients; lateral, inferior, and inferolateral). In conclusion, (1) the predefined ECG patterns we used matched well (86% global concordance) with their corresponding infarction areas as detected by CE-CMR imaging and have real value in clinical practice, and (2) the RS morphology in lead V(1) is due to lateral MI and the QS morphology in lead aVL is due to mid-anterior and mid-lateral MI. Therefore, the terms posterior and high lateral infarction are incorrect and should be changed to lateral wall and limited anterolateral wall MI.

Electrocardiography↗

Protective effect of the KCNMB1 E65K genetic polymorphism against diastolic hypertension in aging women and its relevance to cardiovascular risk.

The E65K polymorphism in the beta1-subunit of the large-conductance, Ca2+-dependent K+ (BK) channel, a key element in the control of arterial tone, has recently been associated with low prevalence of diastolic hypertension. We now report the modulatory effect of sex and age on the association of the E65K polymorphism with low prevalence of diastolic hypertension and the protective role of E65K polymorphism against cardiovascular disease. We analyzed the genotype frequency of the E65K polymorphism in 3924 participants selected randomly in two cross-sectional studies. A five-year follow-up of the cohort was performed to determine whether cardiovascular events had occurred since inclusion. Estrogen modulation of wild-type and mutant ion channel activity was assessed after heterologous expression and electrophysiological studies. Multivariate regression analyses showed that increasing age upmodulates the protective effect of the K allele against moderate-to-severe diastolic hypertension in the overall group of participants (odds ratio [OR], 0.35; P=0.006). The results remained significant when analyses were restricted to women (OR, 0.18; P=0.02) but not men (OR, 0.46; P=0.09). This effect was independent of the reported acute modulation of BK channels by estrogen. A five-year follow-up study also demonstrated a reduced age- and sex-adjusted hazard ratio of 0.11, 95% CI, 0.01 to 0.79 of K-carriers for "combined cardiovascular disease" (myocardial infarction and stroke) compared with EE homozygotes. Our study provides the first genetic evidence for the different impact of the BK channel in the control of human blood pressure in men and women, with particular relevance in aging women, and highlights the E65K polymorphism as one of the strongest genetic factors associated thus far to protection against myocardial infarction and stroke.

Adult↗

Ambient air pollution is associated with increased risk of hospital cardiac readmissions of myocardial infarction survivors in five European cities.

BACKGROUND: Ambient air pollution has been associated with increases in acute morbidity and mortality. The objective of this study was to evaluate the short-term effects of urban air pollution on cardiac hospital readmissions in survivors of myocardial infarction, a potentially susceptible subpopulation. METHODS AND RESULTS: In this European multicenter cohort study, 22,006 survivors of a first myocardial infarction were recruited in Augsburg, Germany; Barcelona, Spain; Helsinki, Finland; Rome, Italy; and Stockholm, Sweden, from 1992 to 2000. Hospital readmissions were recorded in 1992 to 2001. Ambient nitrogen dioxide, carbon monoxide, ozone, and mass of particles <10 microm (PM10) were measured. Particle number concentrations were estimated as a proxy for ultrafine particles. Short-term effects of air pollution on hospital readmissions for myocardial infarction, angina pectoris, and cardiac causes (myocardial infarction, angina pectoris, dysrhythmia, or heart failure) were studied in city-specific Poisson regression analyses with subsequent pooling. During follow-up, 6655 cardiac readmissions were observed. Cardiac readmissions increased in association with same-day concentrations of PM10 (rate ratio [RR] 1.021, 95% CI 1.004 to 1.039) per 10 microg/m3) and estimated particle number concentrations (RR 1.026 [95% CI 1.005 to 1.048] per 10,000 particles/cm3). Effects of similar strength were observed for carbon monoxide (RR 1.014 [95% CI 1.001 to 1.026] per 200 microg/m3 [0.172 ppm]), nitrogen dioxide (RR 1.032 [95% CI 1.013 to 1.051] per 8 microg/m3 [4.16 ppb]), and ozone (RR 1.026 [95% CI 1.001 to 1.051] per 15 microg/m3 [7.5 ppb]). Pooled effect estimates for angina pectoris and myocardial infarction readmissions were comparable. CONCLUSIONS: The results suggest that ambient air pollution is associated with increased risk of hospital cardiac readmissions of myocardial infarction survivors in 5 European cities.

Adult↗

Sport practice and the risk of lone atrial fibrillation: a case-control study.

BACKGROUND: Lone atrial fibrillation (LAF) is characterized by the presence of atrial fibrillation in the absence of structural heart disease or other identifiable cause of arrhythmia. In a recent study, we reported sport practice to be more frequent in LAF patients than in the general population. The aim of the study was to determine the association between sport practice and the prevalence of LAF in men. METHODS: An age-matched case-control study was designed. Cases were identified from consecutive patients who attended an outpatient clinic; 51 men with LAF were included, 20 of them with vagal characteristics. Controls were selected from the general population (n=109). A questionnaire to assess former and current sport practice and the number of lifetime hours of sport practice was administered. Conditional logistic regression was used for statistical analysis. RESULTS: The proportion of patients with LAF who reported current sport practice (31%) was higher than that observed in controls (14%). In the logistic regression, current practice of sport was associated with a higher prevalence of LAF (OR=3.13; 95% CI: 1.39-7.05). The practice of more than 1500 lifetime hours of sport appears to be the threshold for the observed association. Current practice of sport with a lifetime practice greater than 1500 h was associated with LAF (OR=2.87; 95% CI: 1.20-6.91). CONCLUSION: In men, the combination of current and prolonged lifetime sport practice is associated with higher risk of LAF.

Adult↗

Association between physical activity, physical performance, and inflammatory biomarkers in an elderly population: the InCHIANTI study.

BACKGROUND: Our aim was to determine the association between physical activity and physical performance, and inflammatory biomarkers in elderly persons. METHODS: One thousand four persons aged 65 years or more, participants in a cross-sectional population-based study, were included. Interviewers collected information on self-reported physical activity during the previous year. Moreover, 841 participants performed a 400-meter walking test to assess physical performance. Plasma concentrations of inflammatory biomarkers were determined. RESULTS: Compared to sedentary men, men practicing light and moderate-high physical activity had a significantly lower erythrocyte sedimentation rate (-0.33 and -0.40 mm/h; p =.023 and p =.006, respectively), fibrinogen level (-43 and -39 mg/dL; p =.001 and p =.004, respectively), and logarithm of C-reactive protein (CRP) (-0.43 and -0.73 mg/L; p =.025 and p <.001, respectively), whereas only those men practicing moderate-high physical activity had a significantly lower uric acid level (-0.57 mg/dL; p =.023), log(interleukin 6) levels (-0.33 pg/mL; p =.014), and log(tumor necrosis factor-alpha) (-0.31 pg/mL; p =.030). In women, those practicing light and moderate-high physical activity had significantly lower uric acid (-0.45 and -0.34 mg/dL; p =.001 and p =.039, respectively) and log(interleukin 6) levels (-0.18 and -0.30 pg/mL; p =.043 and p =.004, respectively); only those women practicing moderate-high physical activity had significantly lower log(CRP) (-0.31 mg/L; p =.020). In women, when the analysis was adjusted for body mass index, the association between physical activity and CRP was no longer significant. Similar findings were observed when we carried these analyses according to physical performance. CONCLUSIONS: Current physical activity practice and performance are associated with inflammatory biomarkers. A significant beneficial association is already observed with light physical activity practice and intermediate performance.

Aged↗

[Analysis with the propensity score of the association between likelihood of treatment and event of interest in observational studies. An example with myocardial reperfusion].

INTRODUCTION AND OBJECTIVES: Analysis of the effect of treatment in observational studies is complex due to differences between treated and nontreated patients. Calculating the probability of receiving treatment conditioned on relevant covariates (propensity score [PS]) has been proposed as a method to control for these differences. We report an application of PS to assess the association between reperfusion treatment and 28-day case fatality in patients with acute myocardial infarction (AMI). METHOD: We describe the procedure used to calculate PS for receiving reperfusion treatment, and different strategies to analyze the association between PS and case fatality with regression modeling and matching. Data were from a population-based registry of 6307 patients with AMI in Spain during 1997-98. RESULTS: The PS for reperfusion was calculated in 5622 patients. In the multivariate analysis, reperfusion was associated with lower case fatality (OR = 0.59; 95% confidence interval [95% CI]: 0.46-0.77). When PS was included as a covariate, this association became non- significant (OR = 0.76; 95% CI: 0.57-1.01). In the subgroup of matched patients with a similar PS (n = 3138), treatment was not associated with case fatality (OR = 0.95; 95% CI: 0.72-1.26). When the influence of cases with missing data on PS was controlled for, reperfusion treatment was associated with lower fatality (OR = 0.66; 95% CI: 0.55-0.80). CONCLUSIONS: Calculating propensity score is a method that controls for differences between treated and nontreated patients. This score has limitations when matching is incomplete and when data are missing. Results of the present example suggest that reperfusion treatment reduces AMI case fatality.

Adult↗

Short-term (28 days) prognosis between genders according to the type of coronary event (Q-wave versus non-Q-wave acute myocardial infarction versus unstable angina pectoris).

The type of acute coronary syndrome may account for different prognoses between men and women after myocardial infarction. This study assessed gender differences in 28-day mortality rates for first or recurrent Q-wave and non-Q-wave myocardial infarctions and unstable angina by using data from 5 registries that included 20,836 patients (24.8% women). Mortality rates were higher in women with first Q-wave myocardial infarction but not in the other patients after adjusting for confounding variables.

Adult↗

Association of APOE genotype with carotid atherosclerosis in men and women: the Framingham Heart Study.

The aim of this study was to determine the association between APOE genotype and carotid atherosclerosis, defined as intimal-medial thickness (IMT) and stenosis, and to assess if other cardiovascular risk factors modify this association. A total of 1,315 men and 1,408 women from the Framingham Offspring Study underwent carotid ultrasound during examination cycle 6 and had complete data on APOE genotype. Three APOE genotype groups were defined: APOE2 (including E2/E2, E3/E2 genotypes), APOE3 (E3/E3), and APOE4 (including E4/E3, E4/E4 genotypes). Carotid IMT and the presence of carotid stenosis > 25% were determined by ultrasonography. In women, the APOE2 group was associated with lower carotid IMT (0.67 vs. 0.73 mm) and lower prevalence of stenosis (odds ratio = 0.49; 95% confidence interval = 0.30-0.81) compared with the APOE3 group. In men, APOE genotype was not associated with carotid IMT or stenosis in the whole group; however, diabetes modified the association between APOE genotype and carotid IMT (P for interaction = 0.044). Among men with diabetes, the APOE4 group was associated with a higher internal carotid artery IMT (1.22 mm) than the APOE3 group (0.90 mm) or the APOE2 group (0.84 mm). The E2 allele was associated with lower carotid atherosclerosis in women, and the E4 allele was associated with higher internal carotid IMT in diabetic men.

Apolipoproteins E↗

Acute myocardial infarction population incidence and in-hospital management factors associated to 28-day case-fatality in the 65 year and older.

BACKGROUND AND OBJECTIVES: The myocardial infarction (MI) incidence rate, prognosis and hospitalisation rate in the population 65 and over are rarely studied. We sought to determine MI hospitalisation and incidence rates, and 28-day case-fatality, in the 65 year and older population, and to analyse whether their management and prognosis differed from that of younger patients. METHODS: All residents in Gerona (Spain) older than 24 years with suspected fatal or non-fatal MI were investigated and included in a population registry. RESULTS: MI mortality, incidence, and case-fatality dramatically increased with age after 64. Smoking, thrombolysis, antiplatelet and betablocker drug use, coronary angiograms, and coronary revascularisation decreased with age. The risk of death of patients between 75 and 84 years (OR: 4.15, 95% confidence interval, CI: 1.70-10.15) and between 85 and 94 years (OR: 4.68, 95% CI: 1.62-13.52) was higher than in the 34-64 years age group, independently of any patient characteristic. CONCLUSIONS: The magnitude of the impact of MI in the elderly at population and hospital levels is substantially higher than in those younger than 65 years of age. After this age patients receive less treatments and procedures than their younger counterparts.

Adult↗

The role of age in cardiovascular risk factor clustering in non-diabetic population free of coronary heart disease.

UNLABELLED: The objectives were to analyse whether cardiovascular risk factors appear simultaneously in the population and to determine whether it depends on age. The participants belong to a random sample of individuals 25-74 years of age, representative of the non-diabetic population free of coronary heart disease of the province of Gerona, Spain, studied during 1994-1996. Exploratory factor analysis was used to assess clustering of cardiovascular risk factors and confirmatory factor analysis to compare clustering among age groups (25-54 and 55-74). RESULTS: In the 25-54 age group, we observed in both sexes the Central Metabolic Syndrome factor, which included glucose, lipids, and waist-to-hip ratio, and Metabolic Hypertension factor, which included systolic and diastolic blood pressures, waist-to-hip ratio, low-density lipoproteins, glycaemia, and triglycerides. In the 55-74 age group we observed in both sexes the Central Metabolic Syndrome factor, with the same composition as in younger subjects, and Isolated Hypertension factor, composed only of systolic and diastolic blood pressures. In both sexes, the chi2 value for the model of the combined age groups was higher than the sum of chi2 values of the best models for each age group separately (p < 0.01), which indicates that both sexes presented factor structures that differed by age group. CONCLUSIONS: The Central Metabolic Syndrome factor was common to all four sex and age groups studied. In younger subjects blood pressure was related to lipids, obesity, and glycaemia, suggesting the existence of a Metabolic Hypertension factor, while systolic and diastolic blood pressures were found to be the only significant variables in the hypertension factor after 54 years.

Adult↗

Regional variability in population acute myocardial infarction cumulative incidence and mortality rates in Spain 1997 and 1998.

BACKGROUND: Myocardial infarction (MI) incidence and mortality display a high geographic variation. AIMS: The objective of the present study was to analyze MI mortality, cumulative incidence rate variability in seven regions of Spain from 1997 to 1998. METHODS AND RESULTS: Standardized methods were used to identify, find, register, and classify MI cases that were classified as definite, possible, insufficient-data MI, and non-MI. The total population of the seven monitored regions was 7,364,682 inhabitants. Of the 11,256 cases fulfilling eligibility criteria to investigate, 10,660 were selected to calculate MI rates: 6554 (61.5%) non-fatal definite MI, 1179 (11.1%) fatal definite MI, 1859 (17.4%) fatal possible MI, 1068 (10.0%) fatal cases with insufficient data. The IBERICA 25-74 years age-standardized cumulative incidence rates for men and women, were 207 (range: 175-252) and 45 (range: 36-65) per 100,000, respectively. The age-standardized mortality rates for men and women, were 73 (range: 62-94) and 20 (range: 13-29) per 100,000, respectively. Age-standardized case-fatality was 31.4 and 24.2% in men aged 25-74 and 35-64 years, respectively, and 32.7 and 27.0%, respectively, in women. CONCLUSIONS: MI cumulative incidence and mortality rates are low compared with other industrialized countries but, vary considerably among regions in a Mediterranean country like Spain.

Adult↗