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Although age-dependent effects on blood pressure (BP) have been reported, they have not been systematically investigated in large-scale genome-wide association studies (GWASs). We leveraged the infrastructure of three well-established consortia (CHARGE, GBPgen, and ICBP) and a nonstandard approach (age stratification and metaregression) to conduct a genome-wide search of common variants with age-dependent effects on systolic (SBP), diastolic (DBP), mean arterial (MAP), and pulse (PP) pressure. In a two-staged design using 99,241 individuals of European ancestry, we identified 20 genome-wide significant (p≤ 5 10) loci by using joint tests of the SNP main effect and SNP-age interaction. Nine of the significant loci demonstrated nominal evidence of age-dependent effects on BP by tests of the interactions alone. Index SNPs in the EHBP1L1 (DBP and MAP), CASZ1 (SBP and MAP), and GOSR2 (PP) loci exhibited the largest age interactions, with opposite directions of effect in the young versus the old. The changes in the genetic effects over time were small but nonnegligible (up to 1.58 mm Hg over 60 years). The EHBP1L1 locus was discovered through gene-age interactions only in whites but had DBP main effects replicated (p = 8.3 10) in 8,682 Asians from Singapore, indicating potential interethnic heterogeneity. A secondary analysis revealed 22 loci with evidence of age-specific effects (e.g., only in 20 to 29-year-olds). Age can be used to select samples with larger genetic effect sizes and more homogenous phenotypes, which may increase statistical power. Age-dependent effects identified through novel statistical approaches can provide insight into the biology and temporal regulation underlying BP associations. © 2014 The American Society of Human Genetics.

Background: Traffic noise has been associated with prevalence of hypertension, but reports are inconsistent for blood pressure (BP). To ascertain noise effects and to disentangle them from those suspected to be from traffic-related air pollution, it may be essential to estimate people’s noise exposure indoors in bedrooms. Objectives: We analyzed associations between long-term exposure to indoor traffic noise in bedrooms and prevalent hypertension and systolic (SBP) and diastolic (DBP) BP, considering long-term exposure to outdoor nitrogen dioxide (NO2). Methods: We evaluated 1,926 cohort participants at baseline (years 2003–2006; Girona, Spain). Outdoor annual average levels of nighttime traffic noise (Lnight) and NO2 were estimated at postal addresses with a detailed traffic noise model and a land-use regression model, respectively. Individual indoor traffic Lnight levels were derived from outdoor Lnight with application of insulations provided by reported noise-reducing factors. We assessed associations for hypertension and BP with multi-exposure logistic and linear regression models, respectively. Results: Median levels were 27.1 dB(A) (indoor Lnight), 56.7 dB(A) (outdoor Lnight), and 26.8 μg/m3 (NO2). Spearman correlations between outdoor and indoor Lnight with NO2 were 0.75 and 0.23, respectively. Indoor Lnight was associated both with hypertension (OR = 1.06; 95% CI: 0.99, 1.13) and SBP (β = 0.72; 95% CI: 0.29, 1.15) per 5 dB(A); and NO2 was associated with hypertension (OR = 1.16; 95% CI: 0.99, 1.36), SBP (β = 1.23; 95% CI: 0.21, 2.25), and DBP (β⊇= 0.56; 95% CI: –0.03, 1.14) per 10 μg/m3. In the outdoor noise model, Lnight was associated only with hypertension and NO2 with BP only. The indoor noise–SBP association was stronger and statistically significant with a threshold at 30 dB(A). Conclusion: Long-term exposure to indoor traffic noise was associated with prevalent hypertension and SBP, independently of NO2. Associations were less consistent for outdoor traffic Lnight and likely affected by collinearity. Citation: Foraster M, Künzli N, Aguilera I, Rivera M, Agis D, Vila J, Bouso L, Deltell A, Marrugat J, Ramos R, Sunyer J, Elosua R, Basagaña X. 2014. High blood pressure and long-term exposure to indoor noise and air pollution from road traffic. Environ Health Perspect 122:1193–1200; http://dx.doi.org/10.1289/ehp.1307156

We appreciate Kawada’s interest in our study (Rivera et al. 2013). His letter focuses on some limitations of our study, which were already discussed in our article. Kawada notes that the small number of participants with low ankle–brachial index (ABI) provided low power to detect an association; this is a limitation that we acknowledged in our article (Rivera et al. 2013). Kawada also points out that the number of covariates in the model exceeds the common rule of thumb of having at least 10 events per variable. We recognize that, with a small number of cases, one is inevitably faced with the trade-off between including all relevant confounders and keeping the number of covariates to a minimum. However, in our article we provided results from a minimally adjusted model including only five confounders and an interaction term. In this model, the number of events per variable was > 10, and the results were not significantly different from those of the fully adjusted model. Kawada suggests selecting a “higher cut-off value of ABI, such as 1.0” for low ABI given that “an ABI of 0.9–1.0 is also associated with cardiovascular risk (Ono et al. 2003).” The findings of Ono et al. were for patients on hemodialysis due to end-stage renal disease and thus cannot be extrapolated to healthy population samples such as the one considered in our study (i.e., with no history or current signs of cardiovascular disease). We selected a cut-off value of 0.9 for low ABI because of the strong evidence of increased risks of incident cardiovascular disease, morbidity, and mortality in individuals with ABI < 0.9 (Allison et al. 2008; Ankle Brachial Index Collaboration 2008; Lee et al. 2004; McDermott et al. 2005). A cut-off value of 0.9 is also more specific (Lee et al. 2004) and much more common in the literature, which allows comparison with other studies. Kawada’s second argument involves the consideration of multicollinearity in the fully adjusted model (model 2), in which systolic and diastolic blood pressure were included. Systolic and diastolic blood pressure were only moderately correlated (correlation coefficient, 0.62), and according to the variance inflation factor (VIF), there were no multicollinearity problems (VIF was 2.45 for systolic blood pressure and 1.98 for diastolic blood pressure). Kawada points at “contradictory results” in the association between air pollution and carotid intima media thickness (IMT), mainly based on the null and weak associations found by Lenters et al. (2010) between several markers of air pollution [nitrogen dioxide, sulfur dioxide, PM2.5 (particulate matter ≤ 2.5 μm in aerodynamic diameter), black smoke, and traffic intensity] and three indicators of vascular damage (IMT, pulse wave velocity, and augmentation index). We consider, however, that these do not constitute results contradictory to the positive association between air pollution and subclinical markers of atherosclerosis found in the six studies thoroughly discussed in our article (Bauer et al. 2010; Diez Roux et al. 2008; Hoffmann et al. 2007, 2009; Kunzli et al. 2005, 2010) as well as by Wilker et al. (2013). The study by Lenters et al. (2010) involved a cohort of young adults, on average 28 years of age. Exposure to air pollution was estimated at the current address only. As the authors acknowledged, the young age of participants and the exposure misclassification, which resulted from exposure estimated at the current address only, are likely explanations for their mixed results. Finally, we agree with Kawada’s closing remark on the need for longitudinal studies, as we concluded in our article.

Physical activity has been identified as a protective factor against the occurrence and progression of coronary heart disease. The lipoprotein lipase (LPL) HindIII polymorphism has been associated with changes in triglyceride and high density lipoprotein (HDL)-cholesterol levels. We have investigated whether the association between the LPL HindIII genetic polymorphism and lipid levels is modified by physical activity. We have also tested the hypothesis that physical activity may interact with smoking and the LPL HindIII polymorphism to determine an individual's plasma lipid concentrations. A total of 520 men were selected from a representative sample used in a population study conducted in Gerona, Spain. The median value (291 kcal/day) of energy expenditure in leisure-time physical activity of the studied sample was selected as a cut-off to define sedentary or active subjects. Serum HDL-cholesterol was positively and significantly associated with the amount of daily energy expenditure in physical activity, whereas inverse associations were seen between physical activity and triglyceride concentration and with the triglyceride to HDL-cholesterol ratio. These effects were consistent across LPL HindIII genotypes. There was a statistically significant interaction between LPL genotype and smoking on lipid concentrations. No statistically significant differences were observed in lipid levels of active or sedentary non-smokers between H- carriers and H+H+ homozygotes for the LPL HindIII polymorphism. In smokers, sedentary H+H+ homozygotes showed significantly higher triglyceride and lower HDL-cholesterol concentrations than sedentary H- carriers. These differences were smaller and not statistically significant when lipid values of active H+H+ homozygotes were compared with active H- carriers. Among all subgroups, sedentary smokers with the H+H+ genotype had the most adverse lipid profile, which was considerably less adverse in H+H+ smokers who were physically active. These findings suggest that the presence of the H+H+ genotype has a deleterious effect on lipid profile in an adverse environment such as smoking, and that the expenditure of more than 291 kcal/day in physical activity attenuates this effect.

STUDY OBJECTIVE—The objective of this study was to analyse whether the risk of death within 28 days and three years after a first Q wave myocardial infarction was higher in hospitalised women than in men. DESIGN—Follow up study. PATIENTS AND SETTING—All consecutive first Q wave myocardial infarction patients aged 25 to 74 years (447 women and 2322 men) admitted to a tertiary hospital in Gerona, Spain, from 1978 to 1997 were registered and followed up for three years. MAIN RESULTS—Women were older, presented more comorbidity and developed more severe myocardial infarctions than men. A significant interaction was found between sex and age. Women aged 65-74 had higher early mortality risk than men of the same age (OR 1.62; 95% CI 1.01, 2.66) after adjusting for age, comorbidity and acute complications including heart failure. Women under 65 tended to be at lower risk of early mortality than men (0.45 (95% CI 0.19, 1.04). Three year mortality of 28 day survivors did not differ between sexes. CONCLUSIONS—These data support the idea that the higher 28 day mortality in hospitalised women with a first Q wave myocardial infarction is mainly attributable to the large number of patients aged 65 to 74 years in whom the risk is higher than that in men. Women under 65 with myocardial infarction do not seem to be a special group of risk. Keywords: age factors; heart failure; mortality; myocardial infarction; sex factors; prognosis

Editors' Note: In Writ e Click this week, Drs. Martinez-Selles et al. ask whether in “Advanced interatrial block and ischemic stroke: The Atherosclerosis Risk in Communities Study” an association was seen between advanced interatrial block and dementia. Authors O'Neal et al. respond that an analysis of this question is forthcoming. Dr. Chang brings his …

Introduction: Anthracyclines are cytotoxic antibiotics used in the treatment of lymphomas. Myocardiopathy is a well-known toxicity of anthracyclines, and both acute/subacute and late-onset presentations have been described. Early detection of asymptomatic cardiac dysfunction and identification of biomarkers for anthracycline cardiotoxicity risk may be important to prevent irreversible heart damage. Objective: To prospectively evaluate the incidence, time of appearance and clinico-biological variables associated with the development of myocardiotoxicity in patients with diffuse large B-cell lymphoma (DLBCL) treated with R-CHOP/R-CHOP-like regimens. Patients and Methods: one hundred and sixty six patients with DLBCL from 05/2004 to 05/2014. Excluded: HIV infection (10), treatment without anthracyclines (21) and other causes (5) (Table 1). Left ventricular ejection fraction (LVEF) determined by high resolution echocardiography and the N-terminal brain natriuretic peptide (NT-proBNP) fragment were done prior initiation of treatment, at the end and every 6-12 months thereafter. Myocardiotoxicity was defined as: LVEF 15% if prior LVEF Results: median age 68 years (IQR: 54-75), 51% male, median NT-proBNP 251.8 pg/mL (IQR: 76.2-560.1), median LVEF 64% (IQR: 60-69%) and median FRESCO scale 4.5 (IQR 2.1-7.2). NT-proBNP was correlated with FRESCO scale, but not with LVEF. With a median follow-up of 64.7 months (95% CI 56.4-73.6) 24 cardiac events were observed (5 clinical CHF + normal LVEF, 7 clinical CHF + LVEF low and 12 low LVEF without clinical CHF). Cumulative incidence of myocardiotoxicity was 8.8% at 6 months (95% CI 5.0 to 15.3), 12.3% at 12 months (95% CI 7.6 to 19.6), 14.2% at 24 months (95% CI 9.1 to 21.9) and 17.6% at 5 years (95% CI 11.6 to 26.1). C statistic for myocardiotoxicity was: FRESCO scale 0.7192 (95%CI: 0.6284- 0.8099) and FRESCO scale+NT-proBNP 0.807 (95%CI: 0.7309-0.8832). Competing risks analysis showed a significantly increased cumulative incidence of myocardiotoxicity in patients with NT-proBNP >600 +/- FRESCO >4.5 (Figure 1). Finally, we performed a computational modeling using 12 Bayesian networks to analyze the connections between demographic characteristics, cardiovascular risk factors, treatment, occurrence of cardiotoxicity and death (Figure 2 illustrates one of the networks). Conclusions: myocardiotoxicity induced by anthracyclines remains an important problem in the daily practice. The FRESCO cardiovascular risk function is useful for predictingmyocardiotoxicity and levels of NT-proBNP improved accuracy myocardiotoxicity risk. We propose that patients with NT-proBNP >600 pg/mL or FRESCO > 4.5 should have a specific cardiologic surveillance and follow-up in cardio-oncology units from the start of their anthracyclin-containing chemotherapy. Disclosures No relevant conflicts of interest to declare.

Fundamento La dislipemia, la resistencia a la insulina, la hipertension arterial y la hipertrofia ventricular izquierda son factores de riesgo independientes para la enfermedad cardiaca coronaria. El objetivo del presente estudio fue analizar la relacion entre la masa ventricular izquierda y la presion arterial maxima de esfuerzo con las lipoproteinas plasmaticas y otros parametros metabolicos en pacientes con hipertension arterial esencial Pacientes y metodo Se incluyeron en el estudio 32 varones no diabeticos con una edad media de 46,8 anos (23-66) diagnosticados de novo de hipertension arterial esencial. Se determinaron el colesterol y trigliceridos en las lipoproteinas plasmaticas, la apolipoproteina (apo) B serica, la glucemia e insulinemia en ayunas y despues de una sobrecarga oral con glucosa, la masa ventricular izquierda mediante ecocardiografia bidimensional y se realizo una prueba de esfuerzo en tapiz rodante Resultados El indice de la masa ventricular izquierda se correlaciono con el colesterol total (r = 0,47; p 2 = 0,40), y esta ultima se asocio con el indice de masa corporal y la presion arterial sistolica media (R 2 = 0,36) Conclusiones La asociacion entre la masa ventricular izquierda y la presion arterial sistolica maxima de esfuerzo con diversos marcadores del sindrome de resistencia a la insulina en los pacientes con hipertension arterial esencial implica, independientemente de las cifras de presion arterial, un aumento adicional del riesgo de enfermedad cardiaca coronaria

The aim of the study was to assess the association between fibrinogen and other cardiovascular risk factors. A cross-sectional population-based study in Gerona (Spain) was designed, 1544 subjects (747 men, 797 women) participated. Anthropometric measurements, blood pressure and blood samples were obtained. Fibrinogen was measured by a coagulometric method. Smoking habits, alcohol consumption and physical activity practice were recorded by questionnaires. Fibrinogen was directly related to age, body mass index (BMI) and female gender and inversely to alcohol and moderate-heavy physical activity practice. Fibrinogen was also higher in men and young women who smoked. In the multivariate analysis, age (regression coefficient (RC): 1.33; standard error (SE): 0.13; unit = 1 year), female gender (RC: 12.24; SE: 3.56) and BMI (RC: 1.83; SE: 0.39; unit = 1 kg/m2) were directly associated with fibrinogen, whereas alcohol (RC: -0.04; SE: 0.01; unit = 1 g/d) was inversely associated. A statistically significant interaction between smoking and age was observed. Age was the strongest variable associated with fibrinogen and modifies the association between smoking and fibrinogen; the magnitude of this association increases with age.

Purpose Regular physical activity (PA) is associated with lower risk for several chronic diseases. It is important to validate PA measurement instruments in different populations. The objective was to validate the Minnesota leisure time PA questionnaire among Spanish women. Methods A cross-sectional study with quota sampling was designed. Two PA groups (active, expending less than 301 MET-min x d(-1) in PA, and very active, expending more than 300 MET-min x d(-1)) and two age groups (18-40 and 41-60 yr) were defined. The Minnesota questionnaire was administered to obtain total energy expenditure in leisure time PA (EEPAtotal) and classified according to the intensity of the different types of PA (EEPAheavy, EEPAmoderate, and EEPAlight). The 250 women recruited performed an exercise test to assess fitness. Results Spearman correlation coefficients among EEPAtotal, EEPAheavy, EEPAmoderate, EEPAlight, and fitness were 0.39, 0.51, 0.13, and 0.02, respectively. Multiple linear regression model adjusted by the different EEPAs and age accounted for 46% of fitness variability. Besides age, only EEPAmoderate and EEPAheavy were associated with fitness. Conclusion The Spanish version of the Minnesota questionnaire is a valid instrument for measuring leisure time PA performed in the last year in Spanish women aged 18-60 yr. Moderate and heavy physical activity are adequately assessed whereas light physical activity practice assessment may be questionable.

OBJECTIVES The study assessed whether varying accessibility of patients with unstable angina (UA) to coronary angiography and revascularization determined differing usages and outcomes. BACKGROUND The appropriate use rate of coronary angiography and revascularization procedures in UA remains to be established. METHODS A total of 791 consecutive patients with UA without previous acute myocardial infarction (AMI) admitted to four reference teaching hospitals (one with tertiary facilities) were followed for six months. End points were six-month mortality and readmission for AMI, UA, heart failure, or severe ventricular arrhythmias. RESULTS Patients admitted to the tertiary hospital were 3.27 (95% confidence interval [CI] 2.32 to 4.62) times more likely to undergo coronary angiography after adjustment for comorbidity and severity than were those admitted to nontertiary facilities (overall six-month use rates 70.1% and 48.3%, respectively). Revascularization procedures were performed in 36.2% of patients in the tertiary hospital and 24.6% in the others (p = 0.0007); adjusted relative risk (RR) 2.37 (95% CI 1.55 to 3.63). Median delay for urgent coronary angiography was shorter in the tertiary hospital (24 h vs. 4 days, p < 0.0002). Six-month mortality and readmission rates were similar in tertiary and nontertiary hospitals: 3.9% versus 5.3% and 16.9% versus 21.2%, respectively. Adjusted RR of death or readmission for the nontertiary hospitals was 1.23 (95% CI 0.57 to 2.67). CONCLUSIONS The use of coronary angiography and revascularization procedures in UA patients with no previous AMI is higher in tertiary than in nontertiary hospitals, but the more selective use of these procedures in nontertiary centers does not imply worse outcome.

The relation between maximum systolic blood pressure (BP) during exercise and left ventricular (LV) mass is controversial. Physical activity also induces LV mass increase. The objective was to assess the relation between BP response to exercise and LV mass in normotensive men, taking into account physical activity practice. A cross-sectional study was performed. Three hundred eighteen healthy normotensive men, aged between 20 and 60 years, participated in this study. The Minnesota questionnaire was used to assess physical activity practice. An echocardiogram and a maximum exercise test were performed. LV mass was calculated and indexed to body surface area. LV hypertrophy was defined as a ventricular mass index ≥134 g/m2. BP was measured at the moment of maximum effort. Hypertensive response was considered when BP was ≥210 mm Hg. In the multiple linear regression model, maximum systolic BP was associated with LV mass index and correlation coefficient was 0.27 (SE 0.07). Physical activity practice and age were also associated with LV mass. An association between hypertensive response to exercise and LV hypertrophy was observed (odds ratio 3.16). Thus, BP response to exercise is associated with LV mass and men with systolic BP response ≥210 mm Hg present a 3-times higher risk of LV hypertrophy than those not reaching this limit. Physical activity practice is related to LV mass, but not to LV hypertrophy.

Background —The aim of this study was to analyze 28-day case fatality trends between 1978 and 1993 among hospitalized acute myocardial infarction (AMI) patients in the REGICOR registry, Gerona, Spain, and relate them to thrombolytic and antiplatelet drug use and changes in patient characteristics. Methods and Results —A total of 2053 consecutive patients 25 to 74 years of age with a first Q-wave AMI admitted to the reference hospital between 1978 and 1993 were registered. Clinical characteristics and patient management were recorded. Four 4-year periods were considered: 1978 to 1981, 1982 to 1985 (prethrombolytic therapy), 1986 to 1989 (thrombolytic and antiplatelet drugs introduced), and 1990 to 1993 (thrombolytic and antiplatelet drugs used routinely). The end point was death at 28 days. Case fatality at 28 days decreased 6% per year between 1978 and 1993. A logistic model adjusted for comorbidity and severity showed the last 3 periods to present a steep decrease in the OR of death at 28 days: 0.86 (95% CI, 0.52 to 1.41), 0.59 (95% CI, 0.35 to 0.99), and 0.40 (95% CI, 0.24 to 0.69), respectively, compared with the first period. After 1986, 85.7% of the 112 lives saved could be attributed to the use of antiplatelet and thrombolytic drugs. Adjusted relative risk reduction was 56.0% for antiplatelet drugs, 34.1% for thrombolytic drugs, and 77.9% for the 2 combined. Conclusions —Our results strongly suggest that new therapies introduced since 1986 have contributed to the decrease in 28-day case fatality of patients admitted with a first Q-wave AMI. This decrease could be attributable mainly to the use of antiplatelet and thrombolytic drugs. These findings should encourage the routine use of thrombolytic and antiplatelet drugs and particularly their combination in the acute phase of AMI.

En Espana, la muerte subita cardiaca constituye un importante problema de salud publica a pesar de que su incidencia es de las mas bajas de los paises industrializados. Actualmente, se calcula que el 12% de las defunciones que se producen de forma natural son subitas y, de estas, el 88% son de origen cardiaco. Ademas, en los pacientes con cardiopatia isquemica es la forma mas frecuente de fallecimiento ( mas del 50% ) , siendo ademas el primer sintoma en el 1926% de los casos. Esta estrecha relacion con la cardiopatia isquemica hace que los factores de riesgo de presentarla se asocien tambien con la aparicion de muerte cardiaca subita. Diversos factores, como la actividad fisica o determinados farmacos y drogas, pueden desencadenar su aparicion. La estrategia mas efectiva para prevenir la muerte cardiaca subita incluye la identificacion de subgrupos de alto riesgo ( pacientes con antecedentes de cardiopatia isquemica, insuficiencia cardiaca, supervivientes a un paro cardiaco extrahospitalario o pacientes que presentan fibrilacion o taquicardia ventricular tras un infarto agudo de miocardio) , asi como el desarrollo de intervencione s terapeuticas eficaces. Dado que la mayoria de las muertes cardiacas subitas estan relacionadas con la cardiopatia isquemica, las medidas de prevencion primaria dirigidas a disminuir las tasas de incidencia y mortalidad por esta causa tambien deberian reducir las primeras. El desarrollo de programas comunitarios basados en la rapida respuesta de un servicio de emergencias o programas de educacion en reanimacion cardiopulmonar en el ambito poblacional ha demostrado tambien ser eficaz debido a que la mayor parte de las muertes subitas cardiacas son extrahospitalarias.

The frequency of coronary heart disease in a community is usually measured by myocardial infarction incidence and mortality rates. The measurement of the prevalence of angina pectoris may, however, become a convenient way of assessing coronary heart disease morbidity in the future. The aim of this study was to determine the prevalence of angina and validity of the Rose questionnaire in the Spanish population aged from 45 to 74 years. A cross-sectional study was conducted in 10,248 subjects (45-74 years), representative of the Spanish population. The WHO Rose questionnaire was used and a construct validation against regional mortality rates and cardiovascular risk factor prevalence was devised. The overall angina prevalence increased with age both in men and women, but was higher in the latter (7.3% and 7.7%, respectively). Angina prevalence also increased with the number of cardiovascular risk factors present and correlated with regional CHD mortality rates (r = 0.66). Sensitivity and specificity results of the Rose questionnaire were low when tested against exercise test (52.9% and 52.1%, respectively). As conclusions, Rose questionnaire is a reliable tool for assessing angina prevalence in the Spanish population which is similar to that of other industrialized countries with higher myocardial infarction morbidity and mortality.

Objetivos El objetivo del presente estudio ha sido la identificacion de factores antropometricos y dieteticos que influyen en la concentracion de colesterol HDL en la provincia de Girona. Poblacion y metodos Se diseno un estudio transversal, con un muestreo aleatorio y se incluyeron 798 varones y 852 mujeres. Se recogieron variables antropometricas, se calculo el gasto energetico diario en actividad fisica en el tiempo libre y se administro un cuestionario dietetico que permitio la obtencion de datos nutricionales. Asimismo, se determinaron los lipidos y lipoproteinas. Resultados Se observaron diferencias significativas de los trigliceridos sericos, indice de masa corporal, indice cintura/cadera, valores de glucemia basal y consumo de alcohol entre el tercil superior y el inferior de colesterol HDL en ambos sexos. En los varones, el gasto energenico diario en actividad fisica se asocio significativamente con los valores de colesterol HDL, al igual que el consumo de grasa total y grasa monoinsaturada. En las mujeres, ademas del indice cintura/cadera y la glucemia basal, la vitamina C fue la variable nutricional positivamente relacionada con el colesterol HDL. Conclusiones El consumo moderado de alcohol, el ejercicio fisico, el consumo de vitamina C y la optimizacion del peso corporal aportan una importante contribucion al incremento de la concentracion del colesterol HDL en nuestro medio.

This study was designed to determine the value of automatic corrected QT-interval measurement in Holter tapes in patients after myocardial infarction as a marker of life-threatening ventricular arrhythmias. We compared the corrected QT interval, automatically measured in 24-hour Holter recordings, in two groups of patients after myocardial infarction: group I was composed of 14 patients admitted consecutively to our hospital for documented sustained ventricular tachycardia or out-of-hospital cardiac arrest. Group II consisted of 28 patients with previous myocardial infarction with characteristics similar to those of group I, but without malignant ventricular arrhythmias in the follow-up. The global mean 24-hour corrected QT interval was longer in group I (425 +/- 20 msec) than in those patients after myocardial infarction without arrhythmias (group II) (405 +/- 17 msec; p0.01). Furthermore, a significant proportion of patients of group I (seven of 14) exhibited more peaks of corrected QT longer than 500 msec compared with patients of group II (two of 28; p0.005). A circadian rhythm of corrected QT peaks was observed in group I, having a significantly higher incidence from 11 PM to 11 AM (p0.05). We conclude that automatic corrected QT-interval measurement on Holter electrocardiogram is now available and feasible. Our results suggest that this is a marker for risk assessment of life-threatening ventricular arrhythmias. Large-scale trials are needed to confirm these results and to determine the predictive value of this technique for risk stratification.

[Abstract] Introduction and objectives. In Spain, data based on large population-based cohorts adequate to provide an accurate prediction of cardiovascular risk have been scarce. Thus, calibration of the EuroSCORE and Framingham scores has been proposed and done for our population. The aim was to develop a native risk prediction score to accurately estimate the individual cardiovascular risk in the Spanish population. Methods. Seven Spanish population-based cohorts including middle-aged and elderly participants were assembled. There were 11 800 people (6387 women) representing 107 915 person-years of follow-up. A total of 1214 cardiovascular events were identified, of which 633 were fatal. Cox regression analyses were conducted to examine the contributions of the different variables to the 10-year total cardiovascular risk. Results. Age was the strongest cardiovascular risk factor. High systolic blood pressure, diabetes mellitus and smoking were strong predictive factors. The contribution of serum total cholesterol was small. Antihypertensive treatment also had a significant impact on cardiovascular risk, greater in men than in women. The model showed a good discriminative power (C-statistic = 0.789 in men and C = 0.816 in women). Ten-year risk estimations are displayed graphically in risk charts separately for men and women. Conclusions. The ERICE is a new native cardiovascular risk score for the Spanish population derived from the background and contemporaneous risk of several Spanish cohorts. The ERICE score offers the direct and reliable estimation of total cardiovascular risk, taking in consideration the effect of diabetes mellitus and cardiovascular risk factor management. The ERICE score is a practical and useful tool for clinicians to estimate the total individual cardiovascular risk in Spain. [Resumen] Introducción y objetivos. En España no existen unas cohortes poblacionales suficientemente grandes para hacer predicciones precisas del riesgo cardiovascular. Las ecuaciones de Framingham y EuroSCORE calibradas son las más utilizadas en España. El objetivo es desarrollar la primera ecuación de predicción autóctona para estimar con precisión el riesgo cardiovascular individual en España. Métodos. Análisis conjunto de siete cohortes españolas de población de mediana edad y anciana. La población del estudio —11.800 personas (6.387 mujeres)— aportó un total de 107.915 personas-año de seguimiento y 1.214 eventos cardiovasculares (633 de ellos, mortales). Se efectuó un análisis de regresión de Cox para examinar la contribución de los diferentes factores al riesgo de cualquier evento cardiovascular (mortal y no mortal). Resultados. La edad fue el principal factor de riesgo de eventos cardiovasculares. La presión arterial sistólica, la diabetes mellitus, el tabaquismo y el tratamiento antihipertensivo fueron factores predictivos fuertemente asociados con el riesgo cardiovascular. En cambio, la contribución del colesterol total sérico fue pequeña, especialmente en los mayores de 70 años. El modelo final de riesgo mostró un buen poder discriminatorio (estadístico C = 0,789 en varones y C = 0,816 en mujeres). Conclusiones. ERICE es una nueva ecuación de riesgo cardiovascular genuinamente española obtenida a partir del riesgo concurrente individual de los participantes en varias cohortes. La ecuación ERICE ofrece una estimación directa y fiable del riesgo cardiovascular total teniendo en cuenta factores como la diabetes mellitus y el tratamiento farmacológico de los factores de riesgo cardiovascular, habitualmente no incluidos en otras ecuaciones. Instituto de Salud Carlos III; G03/065 Instituto de Salud Carlos III; PI05/1464 Instituto de Salud Carlos III; RD06/0014/0015

Land-use regression (LUR) models are increasingly used to estimate air pollution exposure in epidemiologic studies. These models use air pollution measurements taken at a small set of locations and modeling based on geographical covariates for which data are available at all study participant locations. The process of LUR model development commonly includes a variable selection procedure. When LUR model predictions are used as explanatory variables in a model for a health outcome, measurement error can lead to bias of the regression coefficients and to inflation of their variance. In previous studies dealing with spatial predictions of air pollution, bias was shown to be small while most of the effect of measurement error was on the variance. In this study, we show that in realistic cases where LUR models are applied to health data, bias in health-effect estimates can be substantial. This bias depends on the number of air pollution measurement sites, the number of available predictors for model selection, and the amount of explainable variability in the true exposure. These results should be taken into account when interpreting health effects from studies that used LUR models.

Sudden death is probably the greatest challenge in modern cardiology. After reviewing its history, we describe the epidemiology of sudden death and its associated diseases. We highlight its physiopathologic aspects, including the factors that act on vulnerable myocardium triggering the final arrhythmia, mainly ventricular fibrillation and, to a lesser extent, bradycardia and sudden death. We emphasize the relevance of acute ischemia, ventricular dysfunction and genetic factors, not only in genetic heart disease, but also as triggers of sudden death in acute and chronic ischemic heart disease. Finally, we describe the best way to identify candidates at risk, discuss how to prevent sudden death, and outline the best approach to managing a patient resuscitated from cardiac arrest. Full English text available from: www.revespcardiol.org

Introduction and objectives There is a paucity of data regarding the differences in the biomarker profiles of patients with obesity, metabolic syndrome, and diabetes mellitus as compared to a healthy, normal weight population. We aimed to study the biomarker profile of the metabolic risk continuum defined by the transition from normal weight to obesity, metabolic syndrome, and diabetes mellitus. Methods We performed a pooled analysis of data from 7 cross-sectional Spanish population-based surveys. An extensive panel comprising 20 biomarkers related to carbohydrate metabolism, lipids, inflammation, coagulation, oxidation, hemodynamics, and myocardial damage was analyzed. We employed age- and sex-adjusted multinomial logistic regression models for the identification of those biomarkers associated with the metabolic risk continuum phenotypes: obesity, metabolic syndrome, and diabetes mellitus. Results A total of 2851 subjects were included for analyses. The mean age was 57.4 (8.8) years, 1269 were men (44.5%), and 464 participants were obese, 443 had metabolic syndrome, 473 had diabetes mellitus, and 1471 had a normal weight (healthy individuals). High-sensitivity C-reactive protein, apolipoprotein B100, leptin, and insulin were positively associated with at least one of the phenotypes of interest. Apolipoprotein A1 and adiponectin were negatively associated. Conclusions There are differences between the population with normal weight and that having metabolic syndrome or diabetes with respect to certain biomarkers related to the metabolic, inflammatory, and lipid profiles. The results of this study support the relevance of these mechanisms in the metabolic risk continuum. When metabolic syndrome and diabetes mellitus are compared, these differences are less marked.

Las guías europeas de prevención cardiovascular contemplan dos sistemas de evaluación de la evidencia (SEC y GRADE) y recomiendan combinar las estrategias poblacional y de alto riesgo, interviniendo en todas las etapas de la vida, con la dieta como piedra angular de la prevención. La valoración del RCV incorpora los niveles de HDL y los factores psicosociales, una categoría de muy alto riesgo y el concepto edad-riesgo. Se recomienda el uso de métodos cognitivo-conductuales (entrevista motivadora, intervenciones psicológicas), aplicados por profesionales sanitarios, con la participación de familiares de los pacientes, para contrarrestar el estrés psicosocial y reducir el RCV mediante dietas saludables, entrenamiento físico, abandono del tabaco y cumplimiento terapéutico. También se requieren medidas de salud pública, como la prohibición de fumar en lugares públicos o eliminar los ácidos grasos trans de la cadena alimentaria. Otras novedades consisten en desestimar el tratamiento antiagregante en prevención primaria y la recomendación de mantener la PA dentro del rango 130-139/80-85 mmHg en pacientes diabéticos o con RCV alto. Se destaca el bajo cumplimiento terapéutico observado, porque influye en el pronóstico de los pacientes y en los costes sanitarios. Para mejorar la prevención cardiovascular se precisa una verdadera alianza entre políticos, administraciones, asociaciones científicas y profesionales de la salud, fundaciones de salud, asociaciones de consumidores, pacientes y sus familias, que impulse las estrategias poblacional e individual, mediante el uso de toda la evidencia científica disponible, desde ensayos clínicos hasta estudios observacionales y modelos matemáticos para evaluar intervenciones a nivel poblacional, incluyendo análisis de coste-efectividad. Based on the two main frameworks for evaluating scientific evidence-SEC and GRADE-European cardiovascular prevention guidelines recommend interventions across all life stages using a combination of population-based and high-risk strategies with diet as the cornerstone of prevention. The evaluation of cardiovascular risk (CVR) incorporates HDL levels and psychosocial factors, a very high risk category, and the concept of age-risk. They also recommend cognitive-behavioural methods (e.g., motivational interviewing, psychological interventions, led by health professionals and with the participation of the patient's family, to counterbalance psychosocial stress and reduce CVR through the institution of positive habits such as a healthy diet, physical activity, smoking cessation, and adherence to treatment. Additionally, public health interventions-such as smoking ban in public areas or the elimination of trans fatty acids from the food chain-are also essential. Other innovations include abandoning antiplatelet therapy in primary prevention and the recommendation of maintaining blood pressure (BP) within the 130-139/80-85 mmHg range in diabetic patients and individuals with high CVR. Finally, due to the significant impact on patient progress and medical costs, special emphasis is given to the low therapeutic adherence levels observed. In sum, improving cardiovascular prevention requires a true partnership among the political class, public administrations, scientific and professional associations, health foundations, consumer associations, patients and their families. Such partnership would promote population-based and individual strategies by taking advantage of the broad spectrum of scientific evidence available, from clinical trials to observational studies and mathematical models to evaluate population-based interventions, including cost-effectiveness analyses.

Objective The aims of this study were to analyze the dose–response association between leisure time physical activity (PA) practice and myocardial infarction (MI), considering not only the total amount but also the amount of PA at different levels of intensity, and to determine whether these associations were modified by age. Method In a population-based age- and sex-matched case–control study, all first acute MI patients aged 25 to 74 years were prospectively registered in four Spanish hospitals between 2002 and 2004. Controls were randomly selected from population-based samples recruited during the same period of time. The Minnesota PA questionnaire was administered to assess total energy expenditure in PA and in light-, moderate-, and high-intensity PA. Results Finally, 1339 cases and 1339 controls were included. The association between PA and MI likelihood was non-linear, with significantly lower MI odds at low practice levels (≥ 500 MET·min/week), lowest odds around 1500 MET·min/week, and a plateau thereafter. Light- (in subjects older than 64 years), moderate-, and high-intensity PA produced similar benefits. Conclusion Most of the population could reduce their likelihood of MI by engaging in PA at a moderate level of intensity or, in individuals older than 64 years, at a light level of intensity.

Background and objectiveCoronary heart disease (CHD) is the leading cause of death, and smoking its strongest modifiable risk factor. Our aim was to determine the impact of the Spanish 2006 partial smoke-free legislation on acute myocardial infarction (AMI) incidence, hospitalization and mortality rates, and 28-day case-fatality in Girona, Spain.MethodsUsing a population-based registry (the REGICOR Study), we compared population incidence, hospitalization, and mortality rates, and 28-day case-fatality in the pre- and post-ban periods (2002-2005 and 2006-2008, respectively) by binomial regression analysis adjusted for confounding factors. We also analyzed the ban's impact on the outcomes of interest using the AMI definitions of the American Heart Association (AHA)/European Society of Cardiology (ESC) and the World Health Organization (WHO)-Monitoring trends and determinants in cardiovascular diseases (MONICA).ResultsIn the post-ban period, AMI incidence and mortality rates significantly decreased (relative risk [RR] = 0.89; 95% confidence interval [CI] = 0.81-0.97 and RR = 0.82; 95% CI = 0.71-0.94, respectively). Incidence and mortality rates decreased in both sexes, especially in women, and in people aged 65-74 years. Former and non-smokers (passive smokers) showed diminished incidence rates. Implementation of the ban was not associated with AMI case-fatality. Models tended to be more significant with the WHO-MONICA than with the AHA/ESC definition.ConclusionsThe 2006 Spanish partial smoke-free legislation was associated with a decrease in population AMI incidence and mortality, particularly in women, in people aged 65-74 years, and in passive smokers. These results clarify the association between AMI mortality and the enactment of a partial smoke-free legislation and reinforce the effectiveness of smoking regulations in preventing CHD.

Background: The successful implementation of cardiovascular disease (CVD) prevention guidelines relies heavily on primary care physicians (PCPs) providing risk factor evaluation, intervention and patient education. The aim of this study was to ascertain the degree of awareness and implementation of the Spanish adaptation of the European guidelines on CVD prevention in clinical practice (CEIPC guidelines) among PCPs. Methods. A cross-sectional survey of PCPs was conducted in Spain between January and June 2011. A random sample of 1,390 PCPs was obtained and stratified by region. Data were collected by means of a self-administered questionnaire. Results: More than half (58%) the physicians were aware of and knew the recommendations, and 62% of those claimed to use them in clinical practice, with general physicians (without any specialist accreditation) being less likely to so than family doctors. Most PCPs (60%) did not assess cardiovascular risk, with the limited time available in the surgery being cited as the greatest barrier by 81%. The main reason to be sceptical about recommendations, reported by 71% of physicians, was that there are too many guidelines. Almost half the doctors cited the lack of training and skills as the greatest barrier to the implementation of lifestyle and behavioural change recommendations. Conclusions: Most PCPs were aware of the Spanish adaptation of the European guidelines on CVD prevention (CEIPC guidelines) and knew their content. However, only one third of PCPs used the guidelines in clinical practice and less than half CVD risk assessment tools. © 2013 Brotons et al.; licensee BioMed Central Ltd.

Contains fulltext : 128630.pdf (Publisher’s version ) (Open Access) Smoking influences body weight such that smokers weigh less than non-smokers and smoking cessation often leads to weight increase. The relationship between body weight and smoking is partly explained by the effect of nicotine on appetite and metabolism. However, the brain reward system is involved in the control of the intake of both food and tobacco. We evaluated the effect of single-nucleotide polymorphisms (SNPs) affecting body mass index (BMI) on smoking behavior, and tested the 32 SNPs identified in a meta-analysis for association with two smoking phenotypes, smoking initiation (SI) and the number of cigarettes smoked per day (CPD) in an Icelandic sample (N=34,216 smokers). Combined according to their effect on BMI, the SNPs correlate with both SI (r=0.019, P=0.00054) and CPD (r=0.032, P=8.0 x 10(-7)). These findings replicate in a second large data set (N=127,274, thereof 76,242 smokers) for both SI (P=1.2 x 10(-5)) and CPD (P=9.3 x 10(-5)). Notably, the variant most strongly associated with BMI (rs1558902-A in FTO) did not associate with smoking behavior. The association with smoking behavior is not due to the effect of the SNPs on BMI. Our results strongly point to a common biological basis of the regulation of our appetite for tobacco and food, and thus the vulnerability to nicotine addiction and obesity.

Background: Epidemiological evidence of the effects of long-term exposure to air pollu tion on the chronic processes of athero genesis is limited. Objective: We investigated the association of long-term exposure to traffic-related air pollu tion with subclinical atherosclerosis, measured by carotid intima media thickness (IMT) and ankle–brachial index (ABI). Methods: We performed a cross-sectional analysis using data collected during the reexamination (2007–2010) of 2,780 participants in the REGICOR (Registre Gironí del Cor: the Gerona Heart Register) study, a population-based prospective cohort in Girona, Spain. Long-term exposure across residences was calculated as the last 10 years’ time-weighted average of residential nitrogen dioxide (NO2) estimates (based on a local-scale land-use regression model), traffic intensity in the nearest street, and traffic intensity in a 100 m buffer. Associations with IMT and ABI were estimated using linear regression and multinomial logistic regression, respectively, controlling for sex, age, smoking status, education, marital status, and several other potential confounders or intermediates. Results: Exposure contrasts between the 5th and 95th percentiles for NO2 (25 μg/m), traffic intensity in the nearest street (15,000 vehicles/day), and traffic load within 100 m (7,200,000 vehicle-m/day) were associated with differences of 0.56% (95% CI: –1.5, 2.6%), 2.32% (95% CI: 0.48, 4.17%), and 1.91% (95% CI: –0.24, 4.06) percent difference in IMT, respectively. Exposures were positively associated with an ABI of > 1.3, but not an ABI of < 0.9. Stronger associations were observed among those with a high level of education and in men ≥ 60 years of age. Conclusions: Long-term traffic-related exposures were associated with subclinical markers of atherosclerosis. Prospective studies are needed to confirm associations and further examine differences among population subgroups.key words: ankle–brachial index, average daily traffic, cardiovascular disease, exposure assessment, exposure to tailpipe emissions, intima media thickness, land use regression model, Mediterranean diet, nitrogen dioxide

A mendelian randomization study based on data from multiple cohorts conducted by Karani Santhanakrishnan Vimaleswaran and colleagues re-examines the causal nature of the relationship between vitamin D levels and obesity., Background Obesity is associated with vitamin D deficiency, and both are areas of active public health concern. We explored the causality and direction of the relationship between body mass index (BMI) and 25-hydroxyvitamin D [25(OH)D] using genetic markers as instrumental variables (IVs) in bi-directional Mendelian randomization (MR) analysis. Methods and Findings We used information from 21 adult cohorts (up to 42,024 participants) with 12 BMI-related SNPs (combined in an allelic score) to produce an instrument for BMI and four SNPs associated with 25(OH)D (combined in two allelic scores, separately for genes encoding its synthesis or metabolism) as an instrument for vitamin D. Regression estimates for the IVs (allele scores) were generated within-study and pooled by meta-analysis to generate summary effects. Associations between vitamin D scores and BMI were confirmed in the Genetic Investigation of Anthropometric Traits (GIANT) consortium (n = 123,864). Each 1 kg/m2 higher BMI was associated with 1.15% lower 25(OH)D (p = 6.52×10−27). The BMI allele score was associated both with BMI (p = 6.30×10−62) and 25(OH)D (−0.06% [95% CI −0.10 to −0.02], p = 0.004) in the cohorts that underwent meta-analysis. The two vitamin D allele scores were strongly associated with 25(OH)D (p≤8.07×10−57 for both scores) but not with BMI (synthesis score, p = 0.88; metabolism score, p = 0.08) in the meta-analysis. A 10% higher genetically instrumented BMI was associated with 4.2% lower 25(OH)D concentrations (IV ratio: −4.2 [95% CI −7.1 to −1.3], p = 0.005). No association was seen for genetically instrumented 25(OH)D with BMI, a finding that was confirmed using data from the GIANT consortium (p≥0.57 for both vitamin D scores). Conclusions On the basis of a bi-directional genetic approach that limits confounding, our study suggests that a higher BMI leads to lower 25(OH)D, while any effects of lower 25(OH)D increasing BMI are likely to be small. Population level interventions to reduce BMI are expected to decrease the prevalence of vitamin D deficiency. Please see later in the article for the Editors' Summary, Editors' Summary Background Obesity—having an unhealthy amount of body fat—is increasing worldwide. In the US, for example, a third of the adult population is now obese. Obesity is defined as having a body mass index (BMI, an indicator of body fat calculated by dividing a person's weight in kilograms by their height in meters squared) of more than 30.0 kg/m2. Although there is a genetic contribution to obesity, people generally become obese by consuming food and drink that contains more energy than they need for their daily activities. Thus, obesity can be prevented by having a healthy diet and exercising regularly. Compared to people with a healthy weight, obese individuals have an increased risk of developing diabetes, heart disease and stroke, and tend to die younger. They also have a higher risk of vitamin D deficiency, another increasingly common public health concern. Vitamin D, which is essential for healthy bones as well as other functions, is made in the skin after exposure to sunlight but can also be obtained through the diet and through supplements. Why Was This Study Done? Observational studies cannot prove that obesity causes vitamin D deficiency because obese individuals may share other characteristics that reduce their circulating 25-hydroxy vitamin D [25(OH)D] levels (referred to as confounding). Moreover, observational studies cannot indicate whether the larger vitamin D storage capacity of obese individuals (vitamin D is stored in fatty tissues) lowers their 25(OH)D levels or whether 25(OH)D levels influence fat accumulation (reverse causation). If obesity causes vitamin D deficiency, monitoring and treating vitamin D deficiency might alleviate some of the adverse health effects of obesity. Conversely, if low vitamin D levels cause obesity, encouraging people to take vitamin D supplements might help to control the obesity epidemic. Here, the researchers use bi-directional “Mendelian randomization” to examine the direction and causality of the relationship between BMI and 25(OH)D. In Mendelian randomization, causality is inferred from associations between genetic variants that mimic the influence of a modifiable environmental exposure and the outcome of interest. Because gene variants do not change over time and are inherited randomly, they are not prone to confounding and are free from reverse causation. Thus, if a lower vitamin D status leads to obesity, genetic variants associated with lower 25(OH)D concentrations should be associated with higher BMI, and if obesity leads to a lower vitamin D status, then genetic variants associated with higher BMI should be associated with lower 25(OH)D concentrations. What Did the Researchers Do and Find? The researchers created a “BMI allele score” based on 12 BMI-related gene variants and two “25(OH)D allele scores,” which are based on gene variants that affect either 25(OH)D synthesis or breakdown. Using information on up to 42,024 participants from 21 studies, the researchers showed that the BMI allele score was associated with both BMI and with 25(OH)D levels among the study participants. Based on this information, they calculated that each 10% increase in BMI will lead to a 4.2% decrease in 25(OH)D concentrations. By contrast, although both 25(OH)D allele scores were strongly associated with 25(OH)D levels, neither score was associated with BMI. This lack of an association between 25(OH)D allele scores and obesity was confirmed using data from more than 100,000 individuals involved in 46 studies that has been collected by the GIANT (Genetic Investigation of Anthropometric Traits) consortium. What Do These Findings Mean? These findings suggest that a higher BMI leads to a lower vitamin D status whereas any effects of low vitamin D status on BMI are likely to be small. That is, these findings provide evidence for obesity as a causal factor in the development of vitamin D deficiency but not for vitamin D deficiency as a causal factor in the development of obesity. These findings suggest that population-level interventions to reduce obesity should lead to a reduction in the prevalence of vitamin D deficiency and highlight the importance of monitoring and treating vitamin D deficiency as a means of alleviating the adverse influences of obesity on health. Additional Information Please access these Web sites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.1001383. The US Centers for Disease Control and Prevention provides information on all aspects of overweight and obesity (in English and Spanish); a data brief provides information about the vitamin D status of the US population The World Health Organization provides information on obesity (in several languages) The UK National Health Service Choices website provides detailed information about obesity and a link to a personal story about losing weight; it also provides information about vitamin D The International Obesity Taskforce provides information about the global obesity epidemic The US Department of Agriculture's ChooseMyPlate.gov website provides a personal healthy eating plan; the Weight-control Information Network is an information service provided for the general public and health professionals by the US National Institute of Diabetes and Digestive and Kidney Diseases (in English and Spanish) The US Office of Dietary Supplements provides information about vitamin D (in English and Spanish) MedlinePlus has links to further information about obesity and about vitamin D (in English and Spanish) Wikipedia has a page on Mendelian randomization (note: Wikipedia is a free online encyclopedia that anyone can edit; available in several languages) Overview and details of the collaborative large-scale genetic association study (D-CarDia) provide information about vitamin D and the risk of cardiovascular disease, diabetes and related traits

Physical activity improves one's lipid profile and increases physical fitness. The present study was aimed at determining the association of amount and intensity of leisure time physical activity with serum lipid profile and physical fitness. A total of 537 healthy men aged 20-60 years were recruited in a quota sampling frame for measurement of physical activity energy expenditure at two different levels. The Minnesota Leisure Time Physical Activity Questionnaire was administered. Serum lipid and lipoprotein levels were measured, and all participants were given an exercise test. Physical activities with an intensity greater than 7 kcal/minute were significantly associated (p < 0.01) with a higher level of high density lipoprotein (HDL) cholesterol and a lower atherogenic index (total cholesterol:HDL cholesterol). Independently of other confounding variables, each average 100 kcal/day expended in leisure time physical activity with an intensity greater than 7 kcal/minute during the previous year was associated with an increase of 2.09 mg/dl (0.054 mmol/liter) in HDL cholesterol and a decrease of 0.23 in atherogenic index. However, only physical activity with an intensity greater than 9 kcal/minute was associated with decreases in total cholesterol, non-HDL cholesterol, and log(triglycerides). Better physical fitness was associated with physical activities of intensities above 5 kcal/minute. There is a threshold in the intensity of exercise associated with serum lipid profile (7 kcal/minute) and physical fitness (5 kcal/minute). Above the former threshold, the relation between amount of physical activity and lipid levels is linear for total cholesterol, HDL cholesterol, non-HDL cholesterol, and atherogenic index and is logarithmic for triglycerides.

In DNA methylation, methyl groups are covalently bound to CpG dinucleotides. However, the assumption that methyl groups are not lost during routine DNA extraction has not been empirically tested. To avoid nonbiological associations in DNA methylation studies, it is essential to account for potential batch effect bias in the assessment of this epigenetic mechanism. Our purpose was to determine if the DNA isolation method is an independent source of variability in methylation status. We quantified Global DNA Methylation (GDM) by luminometric methylation assay (LUMA), comparing the results from 3 different DNA isolation methods. In the controlled analysis (n = 9), GDM differed slightly for the same individual depending on extraction method. In the population analysis (n = 580) there were significant differences in GDM between the 3 DNA isolation methods (medians, 78.1%, 76.5% and 75.1%; p

The aim of this study is to develop and validate a shorter version (VREM) of the Spanish version of the Minnesota leisure time Physical Activity Questionnaire (CAFM), in order to have a shorter physical activity questionnaire to be used in Primary Care.Descriptive study of validation of a new physical activity measurement questionnaire. 200 patients older than 50, who visited one of 5 primary care centers in Barcelona for any reason were selected, with age-sex Catalonia's distribution. Two phases: first, VREM construction through items reduction. Second, validity of VREM against CAFM (gold standard) and test-retest reliability of VREM were analyzed, using kappa index and the intraclass correlation coefficient (ICC).6 items were included in the VREM: Walking, Gardening, Sport/dancing, Climbing stairs, Shopping walking and Cleaning house. The interview using VREM lasted 5 minutes (standard deviation 2). Agreement between both questionnaires, using 4 levels of physical activity, was 95.5% (kappa=0.93). Test-retest reliability of the questionnaire was 92.5% (kappa=0.88). Using a continuous outcome in metabolic energy turnover (MET), VREM also proved to be valid and reliable (ICC=0.95 and ICC=0.96 respectively).This short version of CAFM has shown good validity and reliability in people ≥50 years.

Left ventricular hypertrophy (LVH) is the adaptative mechanism of the heart to systolic overload of the left ventricle. Nevertheless, LVH plays a role in some complications, such as cardiac arrhythmias. Patients with LVH are more likely to develop ventricular arrhythmias than the hypertensive population without LVH. Further, the relation between left ventricular mass and ventricular arrhythmias is graded and continuous. The arrhythmias described in hypertensive patients with LVH are usually isolated premature ventricular contractions. The presence of electrocardiographic criteria of LVH represents a risk of higher incidence of sudden death, especially in men. The risk is even greater in the presence of ventricular arrhythmias. The presence of late potentials has been recently characterized as more related to ventricular arrhythmias than LVH. Antihypertensive drugs that can reduce LVH also have a beneficial effect on cardiovascular morbility and mortality.

Differences between European countries in coronary heart disease mortality were initially described in the 20th century, and albeit less dramatic than first reported, these differences remain substantial. Three main hypotheses have been proposed to explain the so-called "Mediterranean paradox": a) underestimation of coronary heart disease mortality due to methodological flaws; b) the "lag time" hypothesis, and c) the traditional Mediterranean diet and lifestyle. In this manuscript we present and discuss another possible explanation for the Mediterranean paradox related to the higher prevalence and and incidence of stable atheromatous plaques in this area.

Sudden death is probably the greatest challenge in modern cardiology. After reviewing its history, we describe the epidemiology of sudden death and its associated diseases. We highlight its physiopathologic aspects, including the factors that act on vulnerable myocardium triggering the final arrhythmia, mainly ventricular fibrillation and, to a lesser extent, bradycardia and sudden death. We emphasize the relevance of acute ischemia, ventricular dysfunction and genetic factors, not only in genetic heart disease, but also as triggers of sudden death in acute and chronic ischemic heart disease. Finally, we describe the best way to identify candidates at risk, discuss how to prevent sudden death, and outline the best approach to managing a patient resuscitated from cardiac arrest. Full English text available from:www.revespcardiol.org.

Women with myocardial infarction (MI) have shown a 28-day survival disadvantage compared with men. However, results were less consistent when considering long-term mortality in 28-day survivors. The aim was to estimate the trends for sex-related differences in the three endpoints considered for this study: (1) 28-day mortality or severe ventricular dysfunction (acute pulmonary oedema or cardiogenic shock) during the hospital stay, (2) 28-day mortality and (3) two-year cardiovascular mortality or non-fatal MI in 28-day survivors after a first MI. A cohort of 3,982 consecutive patients with first Q-wave MI admitted to a university tertiary reference hospital between 1978 and 2007 was followed for 2 years. Short-term prognosis improved in women over the studied period; similar rates were observed in both sexes in the 2000s. After adjusting for age, co-morbidities and anterior location of MI, female sex had an odds ratio = 1.71 (95 % confidence interval [CI] 1.34–2.17) of short-term severe MI or death over the studied period. Overall, sex differences in long-term prognosis remained similar over the studied period (hazard ratio = 1.40; 95 % CI 1.02–1.91). In conclusion, short-term prognosis improved over the past 30 years for first Q-wave MI patients, becoming similar for both men and women in the most recent decade. Long-term prognosis did not improve in either men or women, indicating that secondary prevention should be reinforced to achieve consistent reductions in the number of cardiovascular events.

Fundamentos: con el fin de disponer de una versión breve y en español del Cuestionario de Actividad Física en el tiempo libre de Minnesota (CAFM) para poder utilizarlo en atención primaria, el objetivo de este trabajo es presentar la elaboración de la versión reducida (VREM) y su validación. Métodos: Estudio descriptivo de validación del cuestionario, realizada en cinco centros de Atención Primaria de Barcelona. Se seleccionaron 200 sujetos igual o mayores de 50 años que consultaron por cualquier motivo, con una distribución por edad y sexo similar a la de la población de Cataluña . Dos fases: primera, se construyó el VREM mediante reducción del número de ítems. Segunda, se evaluó su validez de criterio respecto al CAFM (referencia) y la fiabilidad test-retest mediante el índice kappa y el coeficiente de correlación intraclase (CCI). Resultados: Los 6 ítems incluidos en el VREM fueron: caminar, trabajar el huerto, hacer deporte o bailar, subir escaleras, ir a comprar a pie y limpiar la casa. La duración de la entrevista mediante el VREM fue de 5 minutos (desviación estándar 2). La validez de criterio entre ambos cuestionarios, usando 4 categorías de actividad física, fue del 95,5% (kappa=0,93). La fiabilidad test-retest del cuestionario fue del 92,5% (kappa=0,88). Usando un resultado continuo en forma de metabolic energy turnover (MET) el VREM también mostró una alta validez y fiabilidad (CCI=0,95 y CCI=0,96 respectivamente). Conclusiones: La versión reducida del CAFM es válida y fiable en población mayor o igual a 50 años.

Background and Purpose— Genetic variation influences risk of intracerebral hemorrhage (ICH). Hypertension (HTN) is a potent risk factor for ICH and several common genetic variants (single nucleotide polymorphisms [SNPs]) associated with blood pressure levels have been identified. We sought to determine whether the cumulative burden of blood pressure-related SNPs is associated with risk of ICH and pre-ICH diagnosis of HTN. Methods— We conducted a prospective multicenter case–control study in 2272 subjects of European ancestry (1025 cases and 1247 control subjects). Thirty-nine SNPs reported to be associated with blood pressure levels were identified from the National Human Genome Research Institute genomewide association study catalog. Single-SNP association analyses were performed for the outcomes ICH and pre-ICH HTN. Subsequently, weighted and unweighted genetic risk scores were constructed using these SNPs and entered as the independent variable in logistic regression models with ICH and pre-ICH HTN as the dependent variables. Results— No single SNP was associated with either ICH or pre-ICH HTN. The blood pressure-based unweighted genetic risk score was associated with risk of ICH (OR, 1.11; 95% CI, 1.02–1.21; P =0.01) and the subset of ICH in deep regions (OR, 1.18; 95% CI, 1.07–1.30; P =0.001), but not with the subset of lobar ICH. The score was associated with a history of HTN among control subjects (OR, 1.17; 95% CI, 1.04–1.31; P =0.009) and ICH cases (OR, 1.15; 95% CI, 1.01–1.31; P =0.04). Similar results were obtained when using a weighted score. Conclusion— Increasing numbers of high blood pressure-related alleles are associated with increased risk of deep ICH as well as with clinically identified HTN.

Questionnaires are frequently used for measuring physical activity. The aim of this study was to validate the Spanish version of the Minnesota Leisure Time Physical Activity Questionnaire (MLTPAQ) in Spanish men. Healthy men (n = 187) aged 20-60 years were recruited. The MLTPAQ was administered to assess the quantity (total activity metabolic index) and quality (heavy, moderate, and light) of physical activity performed in the last year, quarter, month, and week. Fitness was assessed with an exercise test. Spearman's correlation coefficients between the total activity metabolic index and exercise test duration, time to maximal theoretical heart rate, and caloric intake were 0.57, 0.46, and 0.40, respectively. The intraclass correlation coefficients between the total activity metabolic indexes in the last year and in the last quarter, month, and week were 0.62, 0.46, and 0.35, respectively. In multiple linear regression, the heavy, moderate, and light activity metabolic index, age, body mass index, and basal heart rate explained 40% of the variability of time to the maximum theoretical heart rate. The Spanish version of the MLTPAQ is a valid instrument to measure the quantity and quality of physical activity performed in the last year (also in periods shorter than 1 year) by Spanish men aged 20-60 years. Only heavy physical activity is related to cardiorespiratory fitness.

Background— Coronary artery calcification (CAC) detected by computed tomography is a noninvasive measure of coronary atherosclerosis, which underlies most cases of myocardial infarction (MI). We sought to identify common genetic variants associated with CAC and further investigate their associations with MI. Methods and Results— Computed tomography was used to assess quantity of CAC. A meta-analysis of genome-wide association studies for CAC was performed in 9961 men and women from 5 independent community-based cohorts, with replication in 3 additional independent cohorts (n=6032). We examined the top single-nucleotide polymorphisms (SNPs) associated with CAC quantity for association with MI in multiple large genome-wide association studies of MI. Genome-wide significant associations with CAC for SNPs on chromosome 9p21 near CDKN2A and CDKN2B (top SNP: rs1333049; P =7.58×10 −19 ) and 6p24 (top SNP: rs9349379, within the PHACTR1 gene; P =2.65×10 −11 ) replicated for CAC and for MI. Additionally, there is evidence for concordance of SNP associations with both CAC and MI at a number of other loci, including 3q22 ( MRAS gene), 13q34 ( COL4A1/COL4A2 genes), and 1p13 ( SORT1 gene). Conclusions— SNPs in the 9p21 and PHACTR1 gene loci were strongly associated with CAC and MI, and there are suggestive associations with both CAC and MI of SNPs in additional loci. Multiple genetic loci are associated with development of both underlying coronary atherosclerosis and clinical events.

Contains fulltext : 97601.pdf (Publisher’s version ) (Closed access) Abdominal aortic aneurysm (AAA) is a common cause of morbidity and mortality and has a significant heritability. We carried out a genome-wide association discovery study of 1866 patients with AAA and 5435 controls and replication of promising signals (lead SNP with a p value < 1 x 10(-5)) in 2871 additional cases and 32,687 controls and performed further follow-up in 1491 AAA and 11,060 controls. In the discovery study, nine loci demonstrated association with AAA (p < 1 x 10(-5)). In the replication sample, the lead SNP at one of these loci, rs1466535, located within intron 1 of low-density-lipoprotein receptor-related protein 1 (LRP1) demonstrated significant association (p = 0.0042). We confirmed the association of rs1466535 and AAA in our follow-up study (p = 0.035). In a combined analysis (6228 AAA and 49182 controls), rs1466535 had a consistent effect size and direction in all sample sets (combined p = 4.52 x 10(-10), odds ratio 1.15 [1.10-1.21]). No associations were seen for either rs1466535 or the 12q13.3 locus in independent association studies of coronary artery disease, blood pressure, diabetes, or hyperlipidaemia, suggesting that this locus is specific to AAA. Gene-expression studies demonstrated a trend toward increased LRP1 expression for the rs1466535 CC genotype in arterial tissues; there was a significant (p = 0.029) 1.19-fold (1.04-1.36) increase in LRP1 expression in CC homozygotes compared to TT homozygotes in aortic adventitia. Functional studies demonstrated that rs1466535 might alter a SREBP-1 binding site and influence enhancer activity at the locus. In conclusion, this study has identified a biologically plausible genetic variant associated specifically with AAA, and we suggest that this variant has a possible functional role in LRP1 expression. 9 p.

Background— After age, sex is the most important risk factor for coronary artery disease (CAD). The mechanism through which women are protected from CAD is still largely unknown, but the observed sex difference suggests the involvement of the reproductive steroid hormone signaling system. Genetic association studies of the gene-encoding Estrogen Receptor α ( ESR1 ) have shown conflicting results, although only a limited range of variation in the gene has been investigated. Methods and Results— We exploited information made available by advanced new methods and resources in complex disease genetics to revisit the question of ESR1 's role in risk of CAD. We performed a meta-analysis of 14 genome-wide association studies (CARDIoGRAM discovery analysis, N=≈87 000) to search for population-wide and sex-specific associations between CAD risk and common genetic variants throughout the coding, noncoding, and flanking regions of ESR1 . In addition to samples from the MIGen (N=≈6000), WTCCC (N=≈7400), and Framingham (N=≈3700) studies, we extended this search to a larger number of common and uncommon variants by imputation into a panel of haplotypes constructed using data from the 1000 Genomes Project. Despite the widespread expression of ERα in vascular tissues, we found no evidence for involvement of common or low-frequency genetic variation throughout the ESR1 gene in modifying risk of CAD, either in the general population or as a function of sex. Conclusions— We suggest that future research on the genetic basis of sex-related differences in CAD risk should initially prioritize other genes in the reproductive steroid hormone biosynthesis system.

Background and Aims: Long-term exposure to traffic-related noise may increase blood pressure levels and induce hypertension, especially at night-time; however the evidence is still heterogeneous. B...

Background and aims: Traffic-related air pollution causes cardiovascular disease and death. Most evidence relates to short-term exposure causing acute effects like myocardial infarction and stroke....

A B S T R A C T Introduction and objectives: The treatment and control of cardiovascular risk factors both play key roles in primary prevention. The aim of the present study is to analyze the proportion of primary prevention patients aged 35-74 years being treated and controlled in relation to their level of coronary risk. Methods: Pooled analysis with individual data from 11 studies conducted in the first decade of the 21st century. We used standardized questionnaires and blood pressure measures, glycohemoglobin and lipid profiles. We defined optimal risk factor control as blood pressure