Derivation and validation of a set of 10-year cardiovascular risk predictive functions in Spain: The FRESCO Study
Introduction
Prevention of cardiovascular (CV) diseases is a major public health objective (Perk et al., 2012, Reiner et al., 2011). Three main strategies exist to achieve this aim: the population approach, a focus on high-risk individuals, and opportunistic screening. The population approach includes policy initiatives and community interventions to promote healthy lifestyles and environmental changes (Rose, 1985), such as smoking ban legislation (Meyers et al., 2009). High-risk strategies are based on the intensive modification of risk factor exposure in individuals with a high probability of developing CV diseases. Both approaches are considered cost-effective for the primary prevention of these diseases (Emberson et al., 2004).
Opportunistic screening uses CV risk functions – calculations based on a series of characteristics (typically sex, age, and risk factor profile) – to predict an individual's risk of having a CV event, usually within the next 10 years (D'Agostino et al., 2008, Kannel et al., 2004). Risk functions have been developed to assess cardiovascular (Hippisley-Cox et al., 2007, Pencina et al., 2009, Perk et al., 2012, Ridker et al., 2007, Ridker et al., 2008), coronary (Assmann et al., 2002, Lloyd-Jones et al., 2004, Wilson et al., 1998), or stroke risk (Wolf et al., 1991) in different countries and continents; most of them are designed for the population aged 35 to 74 years. The widely used coronary risk functions developed by the Framingham investigators (D'Agostino et al., 2008, Kannel et al., 2004) have been adapted and validated in different populations (D'Agostino et al., 2001), including Spain, where the Framingham-REGICOR adapted function was developed by the REGICOR (Registre Gironí del Cor or Girona Heart Registry) investigators (Marrugat et al., 2003, Marrugat et al., 2007, Marrugat et al., 2011).
In addition to the adaptation and calibration of risk functions validated for different populations, the development of new risk functions is especially relevant for countries with low cardiovascular incidence and mortality. New risk functions should aim for simplicity and consider different ensembles of factors. For example: sex and age provide a reasonable starting-point for considering individual CV risk; the inclusion of non-laboratory variables can be useful for self-appraisal of risk (Gaziano et al., 2008); additional laboratory measurements that could improve the predictive capacity of the function could be incorporated into the clinical settings. Moreover, expanding the upper age limit to 79 years would be wise, particularly in low-incidence, low-mortality southern Europe as life expectancy continues to increase. Finally, another attempt to simplify and facilitate CV prevention has led to the so-called “global risk” prediction, which includes at least coronary heart disease (CHD) and stroke end-points in the same predictive function (D'Agostino et al., 2008).
The objective of the FRESCO study (Función de Riesgo ESpañola de acontecimientos Coronarios y Otros, or “Spanish risk function of coronary and other cardiovascular events”) was to develop and validate for the Spanish population aged 35 to 79 years a set of CHD, stroke, and global CV risk functions of differing complexities that use easily implemented risk factor measurements and can be automatically calculated by electronic medical records systems. In the subset of 35- to 74-year-old participants, the study also compared the performance of these FRESCO functions and the validated Framingham-REGICOR function.
Section snippets
Design and participants
We conducted a pooled analysis of individual data from 11 population cohorts in 7 Spanish regions examined between 1992 and 2005 with similar methods. The component studies (and the associated regions) were: CORSAIB (Rigo Carratala et al., 2005) (Balearic Islands), DRECA-2 (Santos et al., 2009) (Andalusia), MURCIA (Huerta et al., 2010) (Murcia), EMMA (Ramos et al., 2012), REGICOR (Grau et al., 2007), REUS (Cabré et al., 2008), ZONA FRANCA (Alzamora et al., 2010) (Catalonia), NAVARRA and RIVANA (
Results
The 64,824 recruited participants yielded 50,408 eligible subjects (23,289 (46.2%) men and 27,119 (53.8%) women) aged 35 to 79 years who were followed a median of 9.3 years (447,516 person-years). The flow chart of inclusion and first CV event is displayed in Fig. 1.
The derivation and validation cohort characteristics are described in Table 1: no important differences were observed. Participant characteristics and a summary of the CV events are detailed by component cohort and sex in
Discussion
We present a set of valid, simple, and incremental risk functions to predict CHD, stroke, and global CV events at 10 years for a typical southern European population aged 35 to 79 years, using both classic and non-laboratory cardiovascular risk factors. Moreover, we report that the Framingham-REGICOR adapted function has an adequate discrimination capacity but tends to overestimate the risk in the Spanish population.
The functions presented here are relatively simple, and some of them could be
Conclusions
The new functions presented here accurately and precisely estimate 10-year risk of stroke and CHD, separately or combined, in a typical southern European population aged 35 to 79 years. In the population subgroup aged 35 to 74 years, the new CHD functions discriminate as well as the Framingham-REGICOR risk function currently used in this age group. On the other hand, Framingham-REGICOR tended to systematically overestimate CHD risk in the validation cohort.
Funding
This work was supported by MARATO TV3 (081630), Instituto de Salud Carlos III — Fondo Europeo de Desarrollo Regional — European Regions Development Funds [Red de Investigación Cardiovascular RD12/0042 (Programa HERACLES); Red RedIAPP RD06/0018; PI081327; PI1101801]; AGAUR [2009 SGR 1195]; CIBER Epidemiología y Salud Pública; and CIBER de Fisiopatología de la Obesidad y la Nutrición. MG was supported by the Instituto de Salud Carlos III — Fondo Europeo de Desarrollo Regional — European Regions
Conflict of interest
The authors declare that they have no conflict of interest.
Acknowledgments
The authors wish to thank Ruth Martí, Susana Tello, Marta Cabañero, Yolanda Ferrer, Sandra Farré, and Esmeralda Gómez for the data management and administrative support, and Elaine Lilly, Ph.D., Writer's First Aid, for the English language revision of the manuscript. We also appreciate the collaboration of the Registre de Mortalitat de Catalunya del Servei d'Informació i Estudis, Departament de Salut, Generalitat de Catalunya (Anna Puigdefàbregas, Gloria Ribas, and Rosa Gispert).
References (38)
- et al.
Laboratory-based versus non-laboratory-based method for assessment of cardiovascular disease risk: the NHANES I follow-up study cohort
Lancet
(2008) - et al.
Cardiovascular risk factors in Spain in the first decade of the 21st century: a meta-analysis with individual data from 11 population-based studies, DARIOS Study
Rev Esp Cardiol
(2011) - et al.
Concept and usefulness of cardiovascular risk profiles
Am. Heart J.
(2004) - et al.
Framingham risk score and prediction of lifetime risk for coronary heart disease
Am. J. Cardiol.
(2004) - et al.
A coronary heart disease risk score based on patient-reported information
Am. J. Cardiol.
(2007) - et al.
Estimación del riesgo coronario en España mediante la ecuación de Framingham calibrada
Rev. Esp. Cardiol.
(2003) - et al.
Validity of the 10-year cardiovascular risk estimate in a population cohort of the REGICOR Study
Rev. Esp. Cardiol.
(2011) - et al.
Validez del Sistema de Información para el Desarrollo de la Investigación en Atención Primaria (SIDIAP) en el estudio de enfermedades vasculares: Estudio EMMA
Rev. Esp. Cardiol.
(2012) - et al.
Prevalencia de factores de riesgo cardiovascular en las Islas Baleares (estudio CORSAIB)
Rev. Esp. Cardiol.
(2005) - et al.
Factores de riesgo cardiovascular en una población rural de Castilla — La Mancha
Rev. Esp. Cardiol.
(1999)
The peripheral arterial disease study (PERART/ARTPER): prevalence and risk factors in the general population
BMC Public Health
Simple scoring scheme for calculating the risk of acute coronary events based on the 10-year follow-up of the prospective cardiovascular Münster (PROCAM) study
Circulation
Metabolic syndrome as a cardiovascular disease risk factor: patients evaluated in primary care
BMC Public Health
Evaluation of the performance of survival analysis models: discrimination and calibration measures
Validation of the Framingham coronary heart disease prediction scores: results of a multiple ethnic groups investigation
JAMA
General cardiovascular risk profile for use in primary care: the Framingham Heart Study
Circulation
R: A Language and Environment for Statistical Computing
Evaluating the impact of population and high-risk strategies for the primary prevention of cardiovascular disease
Eur. Heart J.
Trends in cardiovascular risk factor prevalence (1995–2000–2005) in northeastern Spain
Eur. J. Cardiovasc. Prev. Rehabil.
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A full roster of the FRESCO Investigators can be found at www.regicor.org/fresco_inv.