Rigidez carotídea y riesgo de eventos vasculares y mortalidad: el estudio REGICOR / Carotid artery stiffness and risk of vascular events and mortality: the REGICOR study

Introducción y objetivos: Los objetivos son analizar la relación dosis-respuesta de la rigidez de la arteria carótida y la mortalidad y evaluar su capacidad predictiva. Métodos: Estudio de cohorte poblacional que incluyó a 6.468 participantes, con una mediana de seguimiento de 6,5 años. Se evaluaron 6 índices de rigidez. Se identificaron los eventos coronarios y cerebrovasculares y la mortalidad. Resultados: La rigidez carotídea, el coeficiente de Peterson y la velocidad de la onda de pulso (VOP) se asociaron de manera lineal y directa con los eventos cerebrovasculares: aumento del 8% (IC95%, 1-16%) por unidad de rigidez, del 7% (IC95%, 2-13%) cada 10 unidades del coeficiente de Peterson y del 26% (IC95%, 8-48%) por unidad de la VOP. La tensión carotídea se asoció de modo no lineal con el riesgo de enfermedad coronaria: en valores <0,09 unidades, cada aumento de 0,01 unidades se asoció con una disminución de un 16% del riesgo (IC95%, –33 a +6%); por encima de 0,09 unidades, cada incremento de 0,01 unidades se asoció con un aumento de un 16% del riesgo (IC95%, 6-27%). La inclusión de estos índices no mejoró la capacidad predictiva de las funciones de riesgo. Conclusiones: La rigidez carotídea, el coeficiente de elasticidad de Peterson y la VOP tienen una relación lineal y directa con el riesgo de enfermedad cerebrovascular. La tensión (strain) carotídea tiene una relación en U con el riesgo de enfermedad coronaria. Estos índices no contribuyen a mejorar la capacidad predictiva de las funciones de riesgo. (AU)

Introduction and objectives: The aims of this study were to determine the dose-response association of carotid arterial stiffness with vascular outcomes and overall mortality, and to assess their added predictive capacity. Methods: Population-based cohort study including 6468 individuals, with a median follow-up of 6.5 years. Six carotid artery stiffness indices were assessed: strain, stiffness, Peterson elasticity coefficient, compliance coefficient, distensibility coefficient, and pulse wave velocity (PWV). Incident coronary, cerebrovascular, global vascular, and total fatal events were identified. Results: Carotid compliance and distensibility coefficients were not associated with any of the outcomes. Carotid stiffness, Peterson elasticity coefficient, and PWV showed a direct linear relationship to cerebrovascular disease: the risk increased by 8% (95%CI, 1-16) per stiffness unit increase, by 7% (95%CI, 2-13) per 10-unit Peterson elasticity coefficient increase, and by 26% (95%CI, 8-48) per PWV unit increase. Carotid strain showed a nonlinear association with ischemic heart disease. When strain was ≤ 0.09 units, each 0.01-unit increase was associated with a 15% lower risk of coronary events (95%CI,−33 to 6); above 0.09 units, each 0.01 increase in strain was associated with a 16% higher risk of coronary events (95%CI, 6-27). The addition of the stiffness indices did not improve the predictive capacity of validated risk functions. Conclusions: Carotid stiffness, Peterson elasticity coefficient, and PWV have a direct linear association with cerebrovascular disease risk. Carotid strain is not linearly related to U-shaped ischemic heart disease risk. The inclusion of these indexes does not improve the predictive capacity of risk functions. (AU)

Measuring Cardiorespiratory Fitness without Exercise Testing: The Development and Validation of a New Tool for Spanish Adults.

Background: Cardiorespiratory fitness (CRF) is an important component of overall physical fitness and is associated with numerous health benefits, including a reduced risk of heart disease, diabetes, and obesity. However, direct measurement of CRF is time-consuming and therefore not feasible for screening purposes. Methods: A maximal treadmill exercise test with the Bruce protocol was performed to estimate VO2max in 1047 Spanish men and women aged 17 to 62 years. Weight, height, and heart rate were measured. Leisure-time physical activity (LTPA) was recorded using the Minnesota Leisure Time Physical Activity Questionnaire. A multiple linear regression model was developed to predict exercise-based VO2max. The validity of the model was examined by correlation, concordance, Bland-Altman analysis, cross-validation, and construct validity analysis. Results: There was no significant difference between VO2max obtained by the Bruce protocol (43.56 mL/kg/min) or predicted by the equation (43.59 mL/kg/min), with R2 of 0.57, and a standard error of the estimate of 7.59 mL/kg/min. Pearson's product-moment correlation and Lin's concordance correlation between measured and predicted CRF values were 0.75 and 0.72, respectively. Bland-Altman analysis revealed a significant proportional bias of non-exercise eCRF, overestimating unfit and underestimating highly fit individuals. However, 64.3% of participants were correctly classified into CRF tertile categories, with an important 69.9% in the unfit category. Conclusions: The eCRF equation was associated with several cardiovascular risk factors in the anticipated directions, indicating good construct validity. In conclusion, the non-exercise eCRF showed a reasonable validity to estimate true VO2max, and it may be a useful tool for screening CRF.

Genetic characteristics involved in COVID-19 severity. The CARGENCORS case-control study and meta-analysis.

Pre-existing coronary artery disease (CAD), and thrombotic, inflammatory, or virus infectivity response phenomena have been associated with COVID-19 disease severity. However, the association of candidate single nucleotide variants (SNVs) related to mechanisms of COVID-19 complications has been seldom analysed. Our aim was to test and validate the effect of candidate SNVs on COVID-19 severity. CARGENCORS (CARdiovascular GENetic risk score for Risk Stratification of patients positive for SARS-CoV-2 [COVID-19] virus) is an age- and sex-matched case-control study with 818 COVID-19 cases hospitalized with hypoxemia, and 1636 controls with COVID-19 treated at home. The association between severity and SNVs related to CAD (n = 32), inflammation (n = 19), thrombosis (n = 14), virus infectivity (n = 11), and two published to be related to COVID-19 severity was tested with adjusted logistic regression models. Two external independent cohorts were used for meta-analysis (SCOURGE and UK Biobank). After adjustment for potential confounders, 14 new SNVs were associated with COVID-19 severity in the CARGENCORS Study. These SNVs were related to CAD (n = 10), thrombosis (n = 2), and inflammation (n = 2). We also confirmed eight SNVs previously related to severe COVID-19 and virus infectivity. The meta-analysis showed five SNVs associated with severe COVID-19 in adjusted analyses (rs11385942, rs1561198, rs6632704, rs6629110, and rs12329760). We identified 14 novel SNVs and confirmed eight previously related to COVID-19 severity in the CARGENCORS data. In the meta-analysis, five SNVs were significantly associated to COVID-19 severity, one of them previously related to CAD.

Carotid artery stiffness and risk of vascular events and mortality: the REGICOR study.

INTRODUCTION AND OBJECTIVES: The aims of this study were to determine the dose-response association of carotid arterial stiffness with vascular outcomes and overall mortality, and to assess their added predictive capacity. METHODS: Population-based cohort study including 6468 individuals, with a median follow-up of 6.5 years. Six carotid artery stiffness indices were assessed: strain, stiffness, Peterson elasticity coefficient, compliance coefficient, distensibility coefficient, and pulse wave velocity (PWV). Incident coronary, cerebrovascular, global vascular, and total fatal events were identified. RESULTS: Carotid compliance and distensibility coefficients were not associated with any of the outcomes. Carotid stiffness, Peterson elasticity coefficient, and PWV showed a direct linear relationship to cerebrovascular disease: the risk increased by 8% (95%CI, 1-16) per stiffness unit increase, by 7% (95%CI, 2-13) per 10-unit Peterson elasticity coefficient increase, and by 26% (95%CI, 8-48) per PWV unit increase. Carotid strain showed a nonlinear association with ischemic heart disease. When strain was ≤ 0.09 units, each 0.01-unit increase was associated with a 15% lower risk of coronary events (95%CI,-33 to 6); above 0.09 units, each 0.01 increase in strain was associated with a 16% higher risk of coronary events (95%CI, 6-27). The addition of the stiffness indices did not improve the predictive capacity of validated risk functions. CONCLUSIONS: Carotid stiffness, Peterson elasticity coefficient, and PWV have a direct linear association with cerebrovascular disease risk. Carotid strain is not linearly related to U-shaped ischemic heart disease risk. The inclusion of these indexes does not improve the predictive capacity of risk functions.

Trend and Joinpoint Analysis of Cancer Incidence and 1-Year Mortality in North-East Spain 2005-2020.

Cancer is the second leading cause of death. It is thus essential to examine cancer trends in all regions. In addition, trend data after 2019 and on cancer 1-year mortality are scarce. Our aim was to analyze incidence and 1-year mortality cancer trends in northeastern Spain during 2005-2020. We used the Osona Tumor Registry, which registers cancer incidence and mortality in Osona. The mortality information came from the Spanish Death Index. We analyzed age-standardized incidence rates and 1-year mortality by sex in the population aged > 17 years during 2005-2020. Trends were examined with negative binomial and joinpoint regression. Incidence rates of colorectal, lung and bronchus, and urinary bladder cancer increased annually in females by 2.86%, 4.20%, and 4.56%, respectively. In males, the incidence of stomach and prostate cancer decreased annually by 3.66% and 2.05%, respectively. One-year mortality trends decreased annually for endometrium cancer (-9.0%) and for colorectal cancer in males (-3.1%). From 2019 to 2020, the incidence of cancer decreased, while 1-year mortality increased in both sexes. In a North-Eastern Spanish county, 1-year mortality decreased for endometrium cancer in females and for colorectal cancer in males. Our results suggest a trend of decreasing cancer incidence and increasing cancer mortality as a result of the COVID-19 pandemic.

Analysis of myocardial infarction incidence and case-fatality in the last three decades in the province of Girona.

INTRODUCTION AND OBJECTIVES: Myocardial infarction (MI) incidence and case fatality trends are highly informative but relatively untested at the population level. The objective of this work was to estimate MI incidence and case fatality in the Girona population aged 35-74 years, and to determine their 30-year trends (1990-2019). METHODS: The REGICOR (Girona Heart Registry) monitored MI incidence and case fatality rates from 1990 to 2008. For the period 2008 to 2019, we linked discharges from Girona hospitals (n=4 974 977) and mortality registry (n=70 405) during this period. Our linkage algorithm selected key MI diagnostic codes and removed duplicates. Estimates from the linkage algorithm and the REGICOR registry were compared using chi-square tests for overlapping years (2008-2009). We estimated the annual percent change (APC) of standardized MI incidence and 28-day case fatality, and analyzed their trends using joinpoint regression. RESULTS: MI incidence and case fatality estimates were similar in the linkage algorithm and the REGICOR registry. We observed significant decreasing trends in the incidence of MI. The trend was APC, -0.96% (95% confidence interval (95%CI), -1.4 to -0.53) in women from 1990 to 2019 and -4.2% (95%CI, -5.5 to -3.0) in men from 1994 to 2019. The largest decrease in case fatality was -3.8% (95%CI, -5.1 to -2.5) from 1995 to 2003 in women and -2.4% (95%CI, -2.9 to -1.9) from 1995 to 2004 in men, mainly due to prehospital case fatality declines: -1.8% (95%CI, -2.6 to -1.1) in men and -3.2% (95%CI, -4.6 to -1.8) in women. CONCLUSIONS: In Girona, MI incidence and case fatality decreased between 1990 and 2019. The incidence showed a slow but continuous decrease while case fatality only stabilized in the last decade, particularly in women.

Five-Year Changes in Inflammatory, Metabolic, and Oxidative Biomarkers and 10-Year Cardiovascular Disease Incidence: The REGICOR Cohort Study.

Ischemic cardiovascular diseases (CVD) originate from an imbalance between atherosclerotic plaque formation, instability, and endothelial healing dynamics. Our aim was to examine the relationship between 5-year changes in inflammatory, metabolic, and oxidative biomarkers and 10-year CVD incidence in a population without previous CVD. This was a prospective cohort study of individuals aged 35-74 years (n = 419) randomly selected from 5263 REGICOR participants without CVD recruited in 2005. Biomarkers were measured at baseline and in 2010. Participants were followed up until 2020 for a composite CVD endpoint including coronary artery disease, stroke, and peripheral artery disease. We used Cox regression to analyze the effect of biomarker levels on the occurrence of the composite endpoint, adjusted for traditional CVD risk factors and baseline levels of each biomarker. Individuals with elevated IL-6 or insulin after 5 years had a higher independent risk of CVD at 10 years, compared to those with lower levels. Each rise of 1 pg/mL of IL-6 or 10 pg/mL of insulin increased the 10-year risk of a CVD event by 32% and 2%, respectively. Compared to a model with traditional CVD risk factors only, the inclusion of IL-6 and insulin improved continuous reclassification by 51%. Elevated serum levels of IL-6 and insulin were associated with a higher risk of CVD at 10 years, independently of traditional CVD risk factors.

Asociación de la actividad física con la funcionalidad de las lipoproteínas de alta densidad en una cohorte de base poblacional: el estudio REGICOR / Association of physical activity with high-density lipoprotein functionality in a population-based cohort: the REGICOR study

Introducción y objetivos Determinar la relación dosis-respuesta entre la actividad física en el tiempo libre (AFTL) actual y pasada, total y según su intensidad, y la funcionalidad de las lipoproteínas de alta densidad (HDL). Métodos Se seleccionó a 642 participantes de un estudio poblacional: la edad media era de 63,2 años y el 51,1% eran mujeres. Se incluyeron datos de la visita inicial y de un seguimiento a 4 años. La AFTL se evaluó mediante cuestionarios validados. Se determinó la capacidad de eflujo de colesterol y antioxidante en el seguimiento. Se utilizaron modelos de regresión lineal y aditivos para evaluar la relación dosis-respuesta. Resultados Se observó una relación inversa y lineal entre la AFTL total actual (entre 0-400 MET x min/día) y la capacidad antioxidante de HDL (coeficiente de regresión [beta]: -0,022; IC95%, -0,030; -0,013), con una meseta por encima de este umbral. Se observaron resultados similares para la AFTL de intensidad moderada (beta: -0,028; IC95%, -0,049; -0,007) y vigorosa (beta: -0,025; IC95%, -0,043; -0,007), pero no para AFTL de intensidad ligera. La AFTL en el seguimiento no se asoció con la capacidad de eflujo de colesterol. La AFTL basal no se asoció con la funcionalidad de HDL. Conclusiones La AFTL de intensidad moderada-vigorosa actual se asocia de forma no lineal con una mayor capacidad antioxidante de las partículas de HDL. Se observa un beneficio máximo con dosis intermedias-bajas de AFTL (0-400 MET x min/día). Nuestros resultados concuerdan con las recomendaciones de práctica de AFTL y sugieren una asociación con la funcionalidad de HDL (AU)

Introduction and objectives To determine the dose-response association between current and past leisure-time physical activity (LTPA), total and at different intensities, and high-density lipoprotein (HDL) functionality parameters. Methods Study participants (n=642) were randomly drawn from a large population-based survey. Mean age of the participants was 63.2 years and 51.1% were women. The analysis included data from a baseline and a follow-up visit (median follow-up, 4 years). LTPA was assessed using validated questionnaires at both visits. Two main HDL functions were assessed: cholesterol efflux capacity and HDL antioxidant capacity, at the follow-up visit. Linear regression and linear additive models were used to assess the linear and nonlinear association between LTPA and HDL functionality. Results Total LTPA at follow-up showed an inverse and linear relationship between 0 and 400 METs x min/d with HDL antioxidant capacity (regression coefficient [beta]: −0.022; 95%CI, −0.030, −0.013), with a plateau above this threshold. The results were similar for moderate (beta: −0.028; 95%CI, −0.049, −0.007) and vigorous (beta: −0.025; 95%CI, −0.043, −0.007), but not for light-intensity LTPA. LTPA at follow-up was not associated with cholesterol efflux capacity. Baseline LTPA was not associated with any of the HDL functionality parameters analyzed. Conclusions Current moderate and vigorous LTPA showed a nonlinear association with higher HDL antioxidant capacity. Maximal benefit was observed with low-intermediate doses of total LTPA (up to 400 METs x min/d). Our results agree with current recommendations for moderate-vigorous LTPA practice and suggest an association between PA and HDL functionality in the general population (AU)

Women with familial hypercholesterolemia phenotype are undertreated and poorly controlled compared to men.

Familial hypercholesterolemia (FH) is an autosomal dominant disease that has a prevalence of approximately 1/250 inhabitants and is the most frequent cause of early coronary heart disease (CHD). We included 1.343.973 women and 1.210.671 men with at least one LDL-c measurement from the Catalan primary care database. We identified 14.699 subjects with Familial hypercholesterolemia-Phenotype (FH-P) based on LDL-c cut-off points by age (7.033 and 919 women, and 5.088 and 1659 men in primary and secondary prevention, respectively). Lipid lower therapy (LLT), medication possession ratio (MPR) as an indicator of adherence, and number of patients that reached their goal on lipid levels were compared by sex. In primary and secondary prevention, 69% and 54% of women (P = 0.001) and 64% and 51% of men (P = 0.001) were on low-to-moderate-potency LLT. Adherence to LLT was reduced in women older than 55 years, especially in secondary prevention (P = 0.03), where the percentage of women and men with LDL-c > 1.81 mmol/L were 99.9% and 98.9%, respectively (P = 0.001). Women with FH-P are less often treated with high-intensity LLT, less adherent to LLT, and have a lower probability of meeting their LDL-c goals than men, especially in secondary prevention.

Association of physical activity with high-density lipoprotein functionality in a population-based cohort: the REGICOR study.

INTRODUCTION AND OBJECTIVES: To determine the dose-response association between current and past leisure-time physical activity (LTPA), total and at different intensities, and high-density lipoprotein (HDL) functionality parameters. METHODS: Study participants (n=642) were randomly drawn from a large population-based survey. Mean age of the participants was 63.2 years and 51.1% were women. The analysis included data from a baseline and a follow-up visit (median follow-up, 4 years). LTPA was assessed using validated questionnaires at both visits. Two main HDL functions were assessed: cholesterol efflux capacity and HDL antioxidant capacity, at the follow-up visit. Linear regression and linear additive models were used to assess the linear and nonlinear association between LTPA and HDL functionality. RESULTS: Total LTPA at follow-up showed an inverse and linear relationship between 0 and 400 METs x min/d with HDL antioxidant capacity (regression coefficient [beta]: -0.022; 95%CI, -0.030, -0.013), with a plateau above this threshold. The results were similar for moderate (beta: -0.028; 95%CI, -0.049, -0.007) and vigorous (beta: -0.025; 95%CI, -0.043, -0.007), but not for light-intensity LTPA. LTPA at follow-up was not associated with cholesterol efflux capacity. Baseline LTPA was not associated with any of the HDL functionality parameters analyzed. CONCLUSIONS: Current moderate and vigorous LTPA showed a nonlinear association with higher HDL antioxidant capacity. Maximal benefit was observed with low-intermediate doses of total LTPA (up to 400 METs x min/d). Our results agree with current recommendations for moderate-vigorous LTPA practice and suggest an association between PA and HDL functionality in the general population.

Deciphering the Genetic Crosstalk between Microglia and Oligodendrocyte Precursor Cells during Demyelination and Remyelination Using Transcriptomic Data.

Demyelinating disorders show impaired remyelination due to failure in the differentiation of oligodendrocyte progenitor cells (OPCs) into mature myelin-forming oligodendrocytes, a process driven by microglia-OPC crosstalk. Through conducting a transcriptomic analysis of microarray studies on the demyelination-remyelination cuprizone model and using human samples of multiple sclerosis (MS), we identified molecules involved in this crosstalk. Differentially expressed genes (DEGs) of specific regions/cell types were detected in GEO transcriptomic raw data after cuprizone treatment and in MS samples, followed by functional analysis with GO terms and WikiPathways. Additionally, microglia-OPC crosstalk between microglia ligands, OPC receptors and target genes was examined with the NicheNet model. We identified 108 and 166 DEGs in the demyelinated corpus callosum (CC) at 2 and 4 weeks of cuprizone treatment; 427 and 355 DEGs in the remyelinated (4 weeks of cuprizone treatment + 14 days of normal diet) compared to 2- and 4-week demyelinated CC; 252 DEGs in MS samples and 2730 and 12 DEGs in OPC and microglia of 4-week demyelinated CC. At this time point, we found 95 common DEGs in the CC and OPCs, and one common DEG in microglia and OPCs, mostly associated with myelin and lipid metabolism. Crosstalk analysis identified 47 microglia ligands, 43 OPC receptors and 115 OPC target genes, all differentially expressed in cuprizone-treated samples and associated with myelination. Our differential expression pipeline identified demyelination/remyelination transcriptomic biomarkers in studies using diverse platforms and cell types/tissues. Cellular crosstalk analysis yielded novel markers of microglia ligands, OPC receptors and target genes.

Cholesterol and Hypertension Treatment Improve Coronary Risk Prediction but Not Time-Dependent Covariates or Competing Risks.

Background and Aims: Cardiovascular (CV) risk functions are the recommended tool to identify high-risk individuals. However, their discrimination ability is not optimal. While the effect of biomarkers in CV risk prediction has been extensively studied, there are no data on CV risk functions including time-dependent covariates together with other variables. Our aim was to examine the effect of including time-dependent covariates, competing risks, and treatments in coronary risk prediction. Methods: Participants from the REGICOR population cohorts (North-Eastern Spain) aged 35-74 years without previous history of cardiovascular disease were included (n = 8470). Coronary and stroke events and mortality due to other CV causes or to cancer were recorded during follow-up (median = 12.6 years). A multi-state Markov model was constructed to include competing risks and time-dependent classical risk factors and treatments (2 measurements). This model was compared to Cox models with basal measurement of classical risk factors, treatments, or competing risks. Models were cross-validated and compared for discrimination (area under ROC curve), calibration (Hosmer-Lemeshow test), and reclassification (categorical net reclassification index). Results: Cancer mortality was the highest cumulative-incidence event. Adding cholesterol and hypertension treatment to classical risk factors improved discrimination of coronary events by 2% and reclassification by 7-9%. The inclusion of competing risks and/or 2 measurements of risk factors provided similar coronary event prediction, compared to a single measurement of risk factors. Conclusion: Coronary risk prediction improves when cholesterol and hypertension treatment are included in risk functions. Coronary risk prediction does not improve with 2 measurements of covariates or inclusion of competing risks.

Usefulness of Cardiac Computed Tomography in Coronary Risk Prediction: A Five-Year Follow-Up of the SPICA Study (Secure Prevention with Imaging of the Coronary Arteries).

Accurate identification of individuals at high coronary risk would reduce acute coronary syndrome incidence and morbi-mortality. We analyzed the effect on coronary risk prediction of adding coronary artery calcification (CAC) and Segment Involvement Score (SIS) to cardiovascular risk factors. This was a prospective cohort study of asymptomatic patients recruited between 2013-2017. All participants underwent a coronary computed tomography angiography to determine CAC and SIS. The cohort was followed-up for a composite endpoint of myocardial infarction, coronary angiography and/or revascularization (median = five years). Discrimination and reclassification of the REGICOR function with CAC/SIS were examined with the Sommer's D index and with the Net reclassification index (NRI). Nine of the 251 individuals included had an event. Of the included participants, 94 had a CAC = 0 and 85 a SIS = 0, none of them had an event. The addition of SIS or of SIS and CAC to the REGICOR risk function significantly increased the discrimination capacity from 0.74 to 0.89. Reclassification improved significantly when SIS or both scores were included. CAC and SIS were associated with five-year coronary event incidence, independently of cardiovascular risk factors. Discrimination and reclassification of the REGICOR risk function were significantly improved by both indexes, but SIS overrode the effect of CAC.

Standardized Comparison of Cardiovascular Risk Factors Prevalence in Spanish Women and Men Living with HIV and in the General Population.

People living with HIV (PLWH) have an increased risk of cardiovascular (CV) disease, likely due to a higher prevalence of CV risk factors. We compared the age-standardized prevalence and management of CV risk factors in PLWH to that of the general population in Spain. Blood pressure, lipid, glucose, and anthropometric profiles were cross-sectionally compared along with the treatment of hypertension, dyslipidemia, and diabetes in a general population cohort and a PLWH cohort. Prevalence rates were standardized by the direct method by 10-year age groups in European standard populations and stratified by gender. We included 47,593 individuals aged 35 to 74 years, 28,360 from the general population cohort and 19,233 from the PLWH cohort. Compared to the general population, PLWH had a higher concentration of triglycerides (>35 mg/dL in women and >26 mg/dL in men) and a higher prevalence of smoking (>23% and >17%) and diabetes (>9.9% and >8.5%). The prevalence of treated diabetes, hypertension, and dyslipidemia were up to three-fold lower in both women and men living with HIV. There was a significant difference in PLWH compared to the general population in the lipid, glucose, and anthropometric profile. In addition, PLWH were less often treated for diagnosed diabetes, hypertension, and dyslipidemia.

Análisis de la relación dosis-respuesta de la actividad física recreativa con los eventos cardiovasculares y la mortalidad por todas las causas: el estudio REGICOR / Analysis of the dose-response relationship of leisure-time physical activity to cardiovascular disease and all-cause mortality: the REGICOR study

Introducción y objetivos La práctica de actividad física (AF) es un factor protector contra las enfermedades cardiovasculares y la mortalidad. Sin embargo, el patrón de esta relación aún no está claro. El objetivo de este estudio es evaluar la relación de la AF recreativa con los eventos cardiovasculares y la mortalidad total en una población española. Métodos Cohorte prospectiva de 11.158 individuos de la población general. La AF recreativa se evaluó mediante un cuestionario validado y se identificaron los casos mortales y los eventos cardiovasculares en el seguimiento (mediana, 7,24 años). La asociación entre la AF recreativa y los eventos de interés se analizó mediante modelos aditivos generalizados multivariados. Resultados Se observó una relación no lineal entre la AF recreativa y la mortalidad total y los eventos cardiovasculares. La AF moderada-vigorosa se asoció con estos efectos beneficiosos, pero no la AF ligera. Se identificó un umbral en 400 MET-min/día; por debajo de este, cada aumento de 100 MET-min/día se asociaba con una reducción del riesgo de mortalidad total del 16% (HR=0,84; IC95%, 0,77-0,91), del riesgo de mortalidad cardiovascular del 27% (HR=0,73; IC95%, 0,61-0,87) y del de eventos cardiovasculares del 12% (HR=0,88; IC95%, 0,79-0,99). Por encima de 400 MET-min/día no se observó un beneficio adicional. Conclusiones Existe una relación inversa y no lineal de la AF recreativa de intensidad moderada-vigorosa con la enfermedad cardiovascular y la mortalidad. Los beneficios ya se observan a bajos niveles de AF, con un beneficio máximo a niveles que corresponden a 3-5 veces las recomendaciones actuales. (AU)

Introduction and objectives Regular leisure-time physical activity (LTPA) has been consistently recognized as a protective factor for cardiovascular diseases (CVD) and all-cause mortality. However, the pattern of this relationship is still not clear. The aim of this study was to assess the relationship of LTPA with incident CVD and mortality in a Spanish population. Methods A prospective population-based cohort of 11 158 randomly selected inhabitants from the general population. LTPA was assessed by a validated questionnaire. Mortality and CVD outcomes were registered during the follow-up (median: 7.24 years). The association between LTPA and outcomes of interest (all-cause mortality and cardiovascular disease) was explored using a generalized additive model with penalized smoothing splines and multivariate Cox proportional hazard models. Results We observed a significant nonlinear association between LTPA and all-cause and CVD mortality, and fatal and nonfatal CVD. Moderate-vigorous intensity LTPA, but not light-intensity LTPA, were associated with beneficial effects. The smoothing splines identified a cutoff at 400 MET-min/d. Below this threshold, each increase of 100 MET-min/d in moderate-vigorous LTPA contributed with a 16% risk reduction in all-cause mortality (HR, 0.84; 95%CI, 0.77-0.91), a 27% risk reduction in CVD mortality (HR, 0.73; 95%CI, 0.61-0.87), and a 12% risk reduction in incident CVD (HR, 0.88; 95%CI, 0.79-0.99). No further benefits were observed beyond 400 MET-min/d. Conclusions Our results support a nonlinear inverse relationship between moderate-vigorous LTPA and CVD and mortality. Benefits of PA are already observed with low levels of activity, with a maximum benefit around 3 to 5 times the current recommendations. (AU)

Analysis of the dose-response relationship of leisure-time physical activity to cardiovascular disease and all-cause mortality: the REGICOR study.

INTRODUCTION AND OBJECTIVES: Regular leisure-time physical activity (LTPA) has been consistently recognized as a protective factor for cardiovascular diseases (CVD) and all-cause mortality. However, the pattern of this relationship is still not clear. The aim of this study was to assess the relationship of LTPA with incident CVD and mortality in a Spanish population. METHODS: A prospective population-based cohort of 11 158 randomly selected inhabitants from the general population. LTPA was assessed by a validated questionnaire. Mortality and CVD outcomes were registered during the follow-up (median: 7.24 years). The association between LTPA and outcomes of interest (all-cause mortality and cardiovascular disease) was explored using a generalized additive model with penalized smoothing splines and multivariate Cox proportional hazard models. RESULTS: We observed a significant nonlinear association between LTPA and all-cause and CVD mortality, and fatal and nonfatal CVD. Moderate-vigorous intensity LTPA, but not light-intensity LTPA, were associated with beneficial effects. The smoothing splines identified a cutoff at 400 MET-min/d. Below this threshold, each increase of 100 MET-min/d in moderate-vigorous LTPA contributed with a 16% risk reduction in all-cause mortality (HR, 0.84; 95%CI, 0.77-0.91), a 27% risk reduction in CVD mortality (HR, 0.73; 95%CI, 0.61-0.87), and a 12% risk reduction in incident CVD (HR, 0.88; 95%CI, 0.79-0.99). No further benefits were observed beyond 400 MET-min/d. CONCLUSIONS: Our results support a nonlinear inverse relationship between moderate-vigorous LTPA and CVD and mortality. Benefits of PA are already observed with low levels of activity, with a maximum benefit around 3 to 5 times the current recommendations.