Joan Sala

Estimación del riesgo coronario en España mediante la ecuación de Framingham calibrada

Rev Esp Cardiol 2003;56(3):253-61 253 Introducción y objetivos. Las ecuaciones de Framingham sobrestiman el riesgo de enfermedad coronaria en los países cuya incidencia es baja. En éstos, la ecuación debería adaptarse para la correcta prevención de la enfermedad coronaria. Se presentan las tablas de riesgo coronario global de Framingham calibradas para la población española. Pacientes y método. Se utilizó el procedimiento de calibración de la ecuación de Framingham, consistente en sustituir la prevalencia de factores de riesgo cardiovascular y la tasa de incidencia de acontecimientos coronarios de Framingham por las de nuestro medio. Se ha usado la ecuación de Framingham, que incluye el colesterol unido a lipoproteínas de alta densidad (cHDL). Se han calculado las probabilidades de acontecimiento a los 10 años y se han elaborado unas tablas con códigos de color y la probabilidad exacta en cada casilla correspondiente a las distintas combinaciones de los factores de riesgo clásicos, para una concentración de cHDL de 35-59 mg/dl. Resultados. Las tasas de acontecimientos coronarios y la prevalencia de factores de riesgo difieren considerablemente entre la población estudiada y Framingham. Valores de cHDL < 35 mg/dl incrementan el riesgo en un 50% y los > 60 mg/dl lo reducen en un 50%, aproximadamente. La proporción de casillas con una probabilidad de acontecimiento coronario a los 10 años superior al 9% es 2,3 veces menor, y la de casillas con una probabilidad > 19% es 13 veces menor en las tablas calibradas que en las originales de Framingham. Conclusiones. La función de Framingham calibrada puede constituir un instrumento para estimar con más precisión el riesgo coronario global en la prevención primaria de esta enfermedad en España. Su uso debe acompañarse de una validación apropiada y se debe trabajar en la elaboración de ecuaciones propias españolas.

High prevalence of cardiovascular risk factors in Gerona, Spain, a province with low myocardial infarction incidence

STUDY OBJECTIVE: To establish the prevalence of main cardiovascular risk factors in the province of Gerona, where the incidence of myocardial infarction is known to be low. DESIGN: This was a cross sectional study of prevalence of cardiovascular risk factors conducted on a large random population sample. SETTING: The province of Gerona, Spain. PARTICIPANTS: Two thousand four hundred and four eligible inhabitants of Gerona aged between 25 and 74 years were randomly selected for a multi-stage sample stratified by age and sex. The following were standardly measured: lipids (total cholesterol, high density, low density, lipoprotein (a) and triglycerides), fibrinogen, basal glycaemia, arterial pressure, anthropometric variables, smoking, history of angina (Rose questionnaire), and a medical history questionnaire. Population measurements were standardised for the world population of 24 to 74 years of age. RESULTS: The participation rate was 72.7% (1748). Total mean cholesterol was 5.69 mmol/l in men and 5.61 mmol/l in women and mean high density cholesterol was 1.22 mmol/l and 1.47 mmol/l, respectively. Median lipoprotein (a) was 0.22 g/l. These three lipids increased significantly with age. Mean fibrinogen was 2.92 g/l in men and 3.09 g/l in women, and was higher in smokers. The prevalence of hypertension (systolic arterial tension > or = 140 mm Hg or diastolic > or = 90 mm Hg or drug treatment) was 31.3% in men and 27.7% in women. The proportion of male smokers was 33.8% and female smokers 22.7%. The proportion of female smokers in the 25-34 year age group exceeded that of the remaining age groups for both men and women. CONCLUSIONS: The prevalence of cardiovascular risk factors in Gerona is relatively high for the low myocardial infarction incidence typical of the area, although similar to that of other Spanish areas. The factors that confer sufficient protection to compensate for the effect of the prevalence of these risk factors remain to be elucidated.

An adaptation of the Framingham coronary heart disease risk function to European Mediterranean areas

Aim: To determine whether the Framingham function accurately predicts the 10 year risk of coronary disease and to adapt this predictive method to the characteristics of a Spanish population. Method and Results: A Framingham function for predicting 10 year coronary deaths and non-fatal myocardial infarction was applied to the population of the province of Gerona, Spain, where the cumulated incidence rate of myocardial infarction has been determined since 1988 by a specific registry. The prevalence of cardiovascular risk factors in this region of Spain was established in 1995 by a cross sectional study on a representative sample of 1748 people. The number of cases estimated by the Framingham function for 10 year coronary deaths and non-fatal myocardial infarction was compared with that observed. The Framingham function estimated 2425 coronary heart disease cases in women and 1181 were observed. In men, 9919 were estimated and 3706 were observed. Recalibrating the Framingham equations to the event rate and the prevalence of the risk factors in Gerona led to estimates very close to the number of cases observed in Gerona men and women. Conclusions: The Framingham function estimates more than doubled the actual risk of coronary disease observed in north east Spain. After calibration, the Framingham function became an effective method of estimating the risk in this region with low coronary heart disease incidence.

Validity of an adaptation of the Framingham cardiovascular risk function: the VERIFICA study

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

Trends in cardiovascular risk factor prevalence (1995-2000-2005) in northeastern Spain

Background High prevalence of cardiovascular risk factors has been observed in Spain along with low incidence of acute myocardial infarction. Our objective was to determine the trends of cardiovascular risk factor prevalence between 1995 and 2005 in the 35-74-year-old population of Gerona, Spain. Design Comparison of cross-sectional studies were conducted in random population samples in 1995, 2000, and 2005 at Gerona, Spain. Methods An electrocardiogram was obtained, along with standardized measurements of body mass index, lipid profile, systolic and diastolic blood pressure, glycaemia, energy expenditure in physical activity, smoking, use of lipid-lowering and antihypertensive medications, and cardiovascular risk. Prevalence of diabetes, hypertension, and obesity was calculated and standardized for age. Results A total of 7571 individuals (52.0% women) were included (response rate 72%). Low-density lipoprotein cholesterol > 3.4 mmol/l (130 mg/dl) (49.7%) and hypertension (39.1%) were the most prevalent cardiovascular risk factors. In 1995, 2000 and 2005, low-density lipoprotein cholesterol decreased in both men and women: 4.05-3.913.55 mmol/l (156-151-137 mg/dl) and 3.84-3.81-3.40 mmol/l (148-147-131 mg/dl), respectively. Increases were observed in lipid-lowering drug use (5.7-6.3-9.6% in men and 4.0-5.8-8.0% in women), controlled hypertension (14.8-35.4-37.7% in men and 21.3-36.9-45.0% in women); (all P-trends < 0.01), and obesity (greatest for men: 17.5-26.0-22.7%, P-trends = 0.020). Prevalence of myocardial infarction or possibly abnormal Q waves in electrocardiogram also increased significantly (3.9-4.7-6.4%, P-trends = 0.018). Conclusions The cardiovascular risk factor prevalence change in Gerona was marked in this decade by a shift of total cholesterol and low-density lipoprotein cholesterol distributions to the left, independent of the increase in lipid-lowering drug use, and better hypertension control with increased use of antihypertensive drugs. Eur J Cardiovasc Prev Rehabil 14:653-659

Prevalence of Symptomatic and Asymptomatic Peripheral Arterial Disease and the Value of the Ankle-brachial Index to Stratify Cardiovascular Risk

OBJECTIVES To determine the prevalence of ankle-brachial index (ABI)<0.9 and symptomatic peripheral arterial disease (PAD), association with cardiovascular risk factors (CVRF), and impact of adding ABI measurement to coronary heart disease (CHD) risk screening. DESIGN Population-based cross-sectional survey of 6262 participants aged 35-79 in Girona, Spain. METHODS Standardized measurements (CVRF, ABI, 10-year CHD risk) and history of intermittent claudication (IC), CHD, and stroke were recorded. ABI<0.9 was considered equivalent to moderate-to-high CHD risk (> or =10%). RESULTS ABI<0.9 prevalence was 4.5%. Only 0.62% presented low ABI and IC. Age, current smoker, cardiovascular disease, and uncontrolled hypertension independently associated with ABI<0.9 in both sexes; IC was also associated in men and diabetes in women. Among participants 35-74 free of cardiovascular disease, 6.1% showed moderate-to-high 10-year CHD risk; adding ABI measurement yielded 8.7%. Conversely, the risk function identified 16.8% of these participants as having 10-year CHD risk>10%. In participants 75-79 free of cardiovascular disease, the prevalence of ABI<0.9 (i.e., CHD risk> or =10%) was 11.9%. CONCLUSIONS ABI<0.9 is relatively frequent in those 35-79, particularly over 74. However, IC and CHD risk> or =10% indicators are often missing. Adding ABI measurement to CHD-risk screening better identifies moderate-to-high cardiovascular risk patients.

Meta-analyses of the association between cytochrome CYP2C19 loss- and gain-of-function polymorphisms and cardiovascular outcomes in patients with coronary artery disease treated with clopidogrel

Aims To perform a meta-analysis of the association between CYP2C19 loss- and gain-of-function variants and cardiovascular outcomes and bleeding in patients with coronary artery disease treated with clopidogrel, and to explore the causes of heterogeneity between studies. Methods A comprehensive literature search was conducted. A random-effects model was used to summarise the results. In the presence of between-study heterogeneity, a meta-regression analysis was performed to identify study characteristics explaining this heterogeneity. Results Patients who carried a loss-of-function allele, mainly CYP2C19*2, did not present an increased risk of a cardiovascular event, HR =1.23 (95% CI 0.97 to 1.55). Substantial heterogeneity was observed between studies (I2 =35.6), which was partially explained by the study sample size: the pooled HR was higher among studies with a sample size <500 patients (HR =3.55; 95% CI 1.66 to 7.56) and lower among studies with a sample size ≥500 (HR =1.06; 95% CI 0.89 to 1.26). CYP2C19*2 was associated with an increased risk of a stent thrombosis (HR =2.24; 95% CI 1.52 to 3.30). The gain-of-function allele, mainly CYP2C19*17, was associated with a lower risk of cardiovascular events (HR =0.75; 95% CI 0.66 to 0.87) and a higher risk of major bleeding (HR =1.26; 95% CI 1.05 to 1.50). Conclusions Not only CYP2C19 loss-of-function but also gain-of-function alleles should be considered to define the pharmacogenetic response to clopidogrel. The results question the relevance of the CYP2C19 loss-of-function alleles in the prediction of major cardiovascular events beyond stent thrombosis in coronary patients treated with clopidogrel. The gain-of-function variant is associated with a lower risk of cardiovascular events but a higher risk of bleeding.

Validez relativa de la estimación del riesgo cardiovascular a 10 años en una cohorte poblacional del estudio REGICOR

INTRODUCTION AND OBJECTIVES Cardiovascular risk screening requires accurate risk functions. The relative validity of the Framingham-based REGICOR adapted function is analyzed and the population distribution of cardiovascular 10-year cardiovascular events is described by risk group. METHODS A population cohort of 3856 participants recruited between 1995 and 2000, aged 35 to 74 years from Girona without symptoms of cardiovascular diseases, was followed between 2006 and 2009. Standardized laboratory and blood pressure measurements, questionnaires, and case definitions were used. The follow-up combined cross-linkage of our databases with our regional mortality registry, reexamination, and telephone contact with participants. Coronary disease endpoints alone were considered. RESULTS A total of 27 487 person-years were obtained (mean follow-up 7.1 years), and the follow-up was achieved in 97% of participants (120 coronary disease events). Validity was good: the regression coefficients estimated with the cohort data did not differ from those obtained in the original Framingham function. Function calibration was good: the observed incidence of cardiovascular events in the decile groups of risk did not differ from the function prediction (P=.127 in women, and P=.054 in men). The C statistic (discrimination) was 0.82 (95% confidence interval, 0.76-0.88) in women, and 0.78 (95% confidence interval, 0.73-0.83) in men. More than 50% of cardiovascular events occurred in participants whose 10-year risk was 5% to 14.9%. CONCLUSIONS The studied function accurately predicts coronary disease events at 10 years. Risk stratification could be simplified in 4 groups: low (<5%), moderate (5%-9.9%), high (10%-14.9%) and very high (≥15%).

Variabilidad en el manejo hospitalario del infarto agudo de miocardio en España. Estudio IBERICA (Investigación, Búsqueda Específica y Registro de Isquemia Coronaria Aguda)*

Introduccion y objetivos Los datos sobre el manejo de los pacientes con infarto agudo de miocardio (IAM) que llegan a un hospital en Espana no garantizan la exhaustividad en el registro. El objetivo de este trabajo es conocer las caracteristicas y el manejo de los pacientes con IAM que llegan a todos los hospitales de distintas areas de 8 comunidades autonomas espanolas. Metodos El estudio IBERICA es un registro poblacional de IAM entre 25 y 74 anos de edad realizado en ocho comunidades autonomas espanolas. Para este trabajo se incluyeron los casos de IAM que llegaron vivos al hospital durante 1997. Se recogen las caracteristicas, tratamiento y evolucion a los 28 dias del episodio. Se realizo un analisis descriptivo y se calculo el coeficiente de variacion. Resultados Se registraron 4.041 casos de IAM: el 79,9% eran varones y la edad media fue de 61,1 anos. El 10,9% (IC del 95%: 9,9-11,9%) no ingresaron en una unidad de cuidados intensivos cardiologicos, existiendo una gran variabilidad entre las zonas (coeficiente de variacion del 53%). Existe tambien una gran variabilidad en la realizacion e indicacion de tecnicas diagnosticas y terapeuticas invasivas y no invasivas, asi como en el tratamiento farmacologico empleado: unicamente la utilizacion de antiagregantes (91,5%) y trombolisis (41,8%) presenta un coeficiente de variacion Conclusion Las caracteristicas de los pacientes varian entre las zonas estudiadas. Las diferencias geograficas en el manejo y pronostico sugieren que puede existir desigualdades en la atencion al enfermo con IAM en Espana.

Análisis de la disminución de la mortalidad por enfermedad coronaria en una población mediterránea: España 1988-2005

INTRODUCTION AND OBJECTIVES To examine the extent to which the decrease in coronary heart disease mortality rates in Spain between 1988 and 2005 could be explained by changes in cardiovascular risk factors and by the use of medical and surgical treatments. METHODS We used the previously validated IMPACT model to examine the contributions of exposure factors (risk factors and treatments) to the main outcome, changes in the mortality rates of death from coronary heart disease, among adults 35 to 74 years of age. Main data sources included official mortality statistics, results of longitudinal studies, national surveys, randomized controlled trials, and meta-analyses. The difference between observed and expected coronary heart disease deaths in 2005 was then partitioned between treatments and risk factors. RESULTS From 1988 to 2005, the age-adjusted coronary heart disease mortality rates fell by almost 40%, resulting in 8530 fewer coronary heart disease deaths in 2005. Approximately 47% of the fall in deaths was attributed to treatments. The major treatment contributions came from initial therapy for acute coronary syndromes (11%), secondary prevention (10%), and heart failure (9%). About 50% of the fall in mortality was attributed to changes in risk factors. The largest mortality benefit came from changes in total cholesterol (about 31% of the mortality fall) and in systolic blood pressure (about 15%). However, some substantial gender differences were observed in risk factor trends with an increase in diabetes and obesity in men and an increase in smoking in young women. These generated additional deaths. CONCLUSIONS Approximately half of the coronary heart disease mortality fall in Spain was attributable to reductions in major risk factors, and half to evidence-based therapies. These results increase understanding of past trends and will help to inform planning for future prevention and treatment strategies in low-risk populations.