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Vol. 74. Issue 5.
Pages 414-420 (May 2021)
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Vol. 74. Issue 5.
Pages 414-420 (May 2021)
Original article
DOI: 10.1016/j.rec.2020.02.011
Analysis of the dose-response relationship of leisure-time physical activity to cardiovascular disease and all-cause mortality: the REGICOR study
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
Albert Claráa,b,c,d, Georgina Berenguerd, Silvia Pérez-Fernándezb,c, Helmut Schröderb,e, Rafel Ramosf,g,h, María Graub,e, Irene R. Déganob,c,i, Alba Fernández-Sanlésb, Jaume Marrugatb,c, Roberto Elosuab,c,i,
Corresponding author

Corresponding author: Instituto Hospital del Mar de Investigaciones Médicas (IMIM), Dr. Aiguader 88, 08003 Barcelona, Spain.
a Servicio de Angiología y Cirugía Vascular, Hospital del Mar, Barcelona, Spain
b Instituto Hospital del Mar de Investigaciones Médicas (IMIM), Barcelona, Spain
c CIBER Enfermedades Cardiovasculares, Barcelona, Spain
d Facultad de Medicina, Universidad Autónoma de Barcelona, Barcelona, Spain
e CIBER Epidemiología y Salud Pública, Barcelona, Spain
f Instituto Universitario de Investigación en Atención Primaria Jordi Gol (IDIAP Jordi Gol), Unidad de Apoyo a la Investigación de Girona, Girona, Spain
g Instituto de Investigación Biomédica de Girona (IdIBGi), Girona, Spain
h Departamento de Ciencias Médicas, Facultad de Medicina, Universidad de Girona, Girona, Spain
i Departamento de Medicina, Facultad de Medicina, Universidad de Vic-Central de Cataluña, Vic, Barcelona, Spain
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Figures (1)
Tables (2)
Table 1. Baseline characteristics of the participants and number of events of interest during the follow-up stratified by quartiles of LTPA in MET-min/d
Table 2. Hazard ratio (95% confidence interval) of the association between LTPA practice from 0 to 400 MET-min/d and all-cause mortality, CVD mortality, and cardiovascular disease morbidity or mortality. The effect size of the association is expressed for each increase of 100 MET-min/d in LTPA
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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.


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.


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.


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.

Physical activity
Cardiovascular disease
Dose-response relationship
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.


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.


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.


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.

Palabras clave:
Actividad física
Enfermedad cardiovascular
Relación dosis-respuesta


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