Interaction between cardiovascular risk factors and body mass index and 10-year incidence of cardiovascular disease, cancer death, and overall mortality.

The effect of above-normal body mass index (BMI) on health outcomes is controversial because it is difficult to distinguish from the effect due to BMI-associated cardiovascular risk factors. The objective was to analyze the impact on 10-year incidence of cardiovascular disease, cancer deaths and overall mortality of the interaction between cardiovascular risk factors and BMI. We conducted a pooled analysis of individual data from 12 Spanish population cohorts with 10-year follow-up. Participants had no previous history of cardiovascular diseases and were 35-79years old at basal examination. Body mass index was measured at baseline being the outcome measures ten-year cardiovascular disease, cancer and overall mortality. Multivariable analyses were adjusted for potential confounders, considering the significant interactions with cardiovascular risk factors. We included 54,446 individuals (46.5% with overweight and 27.8% with obesity). After considering the significant interactions, the 10-year risk of cardiovascular disease was significantly increased in women with overweight and obesity [Hazard Ratio=2.34 (95% confidence interval: 1.19-4.61) and 5.65 (1.54-20.73), respectively]. Overweight and obesity significantly increased the risk of cancer death in women [3.98 (1.53-10.37) and 11.61 (1.93-69.72)]. Finally, obese men had an increased risk of cancer death and overall mortality [1.62 (1.03-2.54) and 1.34 (1.01-1.76), respectively]. In conclusion, overweight and obesity significantly increased the risk of cancer death and of fatal and non-fatal cardiovascular disease in women; whereas obese men had a significantly higher risk of death for all causes and for cancer. Cardiovascular risk factors may act as effect modifiers in these associations.

Derivation and validation of a set of 10-year cardiovascular risk predictive functions in Spain: the FRESCO Study.

OBJECTIVE: To derive and validate a set of functions to predict coronary heart disease (CHD) and stroke, and validate the Framingham-REGICOR function. METHOD: Pooled analysis of 11 population-based Spanish cohorts (1992-2005) with 50,408 eligible participants. Baseline smoking, diabetes, systolic blood pressure (SBP), lipid profile, and body mass index were recorded. A ten-year follow-up included re-examinations/telephone contact and cross-linkage with mortality registries. For each sex, two models were fitted for CHD, stroke, and both end-points combined: model A was adjusted for age, smoking, and body mass index and model B for age, smoking, diabetes, SBP, total and HDL cholesterol, and for hypertension treatment by SBP, and age by smoking and by SBP interactions. RESULTS: The 9.3-year median follow-up accumulated 2973 cardiovascular events. The C-statistic improved from model A to model B for CHD (0.66 to 0.71 for men; 0.70 to 0.74 for women) and the combined CHD-stroke end-points (0.68 to 0.71; 0.72 to 0.75, respectively), but not for stroke alone. Framingham-REGICOR had similar C-statistics but overestimated CHD risk. CONCLUSIONS: The new functions accurately estimate 10-year stroke and CHD risk in the adult population of a typical southern European country. The Framingham-REGICOR function provided similar CHD prediction but overestimated risk.

Improving interMediAte risk management. MARK study.

BACKGROUND: Cardiovascular risk functions fail to identify more than 50% of patients who develop cardiovascular disease. This is especially evident in the intermediate-risk patients in which clinical management becomes difficult. Our purpose is to analyze if ankle-brachial index (ABI), measures of arterial stiffness, postprandial glucose, glycosylated hemoglobin, self-measured blood pressure and presence of comorbidity are independently associated to incidence of vascular events and whether they can improve the predictive capacity of current risk equations in the intermediate-risk population. METHODS/DESIGN: This project involves 3 groups belonging to REDIAPP (RETICS RD06/0018) from 3 Spanish regions. We will recruit a multicenter cohort of 2688 patients at intermediate risk (coronary risk between 5 and 15% or vascular death risk between 3-5% over 10 years) and no history of atherosclerotic disease, selected at random. We will record socio-demographic data, information on diet, physical activity, comorbidity and intermittent claudication. We will measure ABI, pulse wave velocity and cardio ankle vascular index at rest and after a light intensity exercise. Blood pressure and anthropometric data will be also recorded. We will also quantify lipids, glucose and glycosylated hemoglobin in a fasting blood sample and postprandial capillary glucose. Eighteen months after the recruitment, patients will be followed up to determine the incidence of vascular events (later follow-ups are planned at 5 and 10 years). We will analyze whether the new proposed risk factors contribute to improve the risk functions based on classic risk factors. DISCUSSION: Primary prevention of cardiovascular diseases is a priority in public health policy of developed and developing countries. The fundamental strategy consists in identifying people in a high risk situation in which preventive measures are effective and efficient. Improvement of these predictions in our country will have an immediate, clinical and welfare impact and a short term public health effect. TRIAL REGISTRATION: Clinical Trials.gov Identifier: NCT01428934.

Validity Assessment of Low-risk SCORE Function and SCORE Function Calibrated to the Spanish Population in the FRESCO Cohorts.

INTRODUCTION AND OBJECTIVES: To assess the validity of the original low-risk SCORE function without and with high-density lipoprotein cholesterol and SCORE calibrated to the Spanish population. METHODS: Pooled analysis with individual data from 12 Spanish population-based cohort studies. We included 30 919 individuals aged 40 to 64 years with no history of cardiovascular disease at baseline, who were followed up for 10 years for the causes of death included in the SCORE project. The validity of the risk functions was analyzed with the area under the ROC curve (discrimination) and the Hosmer-Lemeshow test (calibration), respectively. RESULTS: Follow-up comprised 286 105 persons/y. Ten-year cardiovascular mortality was 0.6%. The ratio between estimated/observed cases ranged from 9.1, 6.5, and 9.1 in men and 3.3, 1.3, and 1.9 in women with original low-risk SCORE risk function without and with high-density lipoprotein cholesterol and calibrated SCORE, respectively; differences were statistically significant with the Hosmer-Lemeshow test between predicted and observed mortality with SCORE (P < .001 in both sexes and with all functions). The area under the ROC curve with the original SCORE was 0.68 in men and 0.69 in women. CONCLUSIONS: All versions of the SCORE functions available in Spain significantly overestimate the cardiovascular mortality observed in the Spanish population. Despite the acceptable discrimination capacity, prediction of the number of fatal cardiovascular events (calibration) was significantly inaccurate.

Statins for Prevention of Cardiovascular Events in a Low-Risk Population With Low Ankle Brachial Index.

BACKGROUND: Evidence is lacking about the effectiveness of risk reduction interventions in patients with asymptomatic peripheral arterial disease. OBJECTIVES: This study aimed to assess whether statin therapy was associated with a reduction in major adverse cardiovascular events (MACE) and mortality in this population. METHODS: Data were obtained from 2006 through 2013 from the Catalan primary care system's clinical records database (SIDIAP). Patients age 35 to 85 years with an ankle-brachial index ≤0.95 and without clinically recognized cardiovascular disease (CVD) were included. Participants were categorized as statins nonusers or new-users (first prescription or represcribed after at least 6 months) and matched 1:1 by inclusion date and propensity score for statin treatment. Conditional Cox proportional hazards modeling was used to compare the groups for the incidence of MACE (myocardial infarction, cardiac revascularization, and ischemic stroke) and all-cause mortality. RESULTS: The matched-pair cohort included 5,480 patients (mean age 67 years; 44% women) treated/nontreated with statins. The 10-year coronary heart disease risk was low (median: 6.9%). Median follow-up was 3.6 years. Incidence of MACE was 19.7 and 24.7 events per 1,000 person-years in statin new-users and nonusers, respectively. Total mortality rates also differed: 24.8 versus 30.3 per 1,000 person-years, respectively. Hazards ratios were 0.80 for MACE and 0.81 for overall mortality. The 1-year number needed to treat was 200 for MACE and 239 for all-cause mortality. CONCLUSIONS: Statin therapy was associated with a reduction in MACE and all-cause mortality among participants without clinical CVD but with asymptomatic peripheral arterial disease, regardless of its low CVD risk. The absolute reduction was comparable to that achieved in secondary prevention.

Risk of Cause-Specific Death in Individuals With Diabetes: A Competing Risks Analysis.

OBJECTIVE: Diabetes is a common cause of shortened life expectancy. We aimed to assess the association between diabetes and cause-specific death. RESEARCH DESIGN AND METHODS: We used the pooled analysis of individual data from 12 Spanish population cohorts with 10-year follow-up. Participants had no previous history of cardiovascular diseases and were 35-79 years old. Diabetes status was self-reported or defined as glycemia >125 mg/dL at baseline. Vital status and causes of death were ascertained by medical records review and linkage with the official death registry. The hazard ratios and cumulative mortality function were assessed with two approaches, with and without competing risks: proportional subdistribution hazard (PSH) and cause-specific hazard (CSH), respectively. Multivariate analyses were fitted for cardiovascular, cancer, and noncardiovascular noncancer deaths. RESULTS: We included 55,292 individuals (15.6% with diabetes and overall mortality of 9.1%). The adjusted hazard ratios showed that diabetes increased mortality risk: 1) cardiovascular death, CSH = 2.03 (95% CI 1.63-2.52) and PSH = 1.99 (1.60-2.49) in men; and CSH = 2.28 (1.75-2.97) and PSH = 2.23 (1.70-2.91) in women; 2) cancer death, CSH = 1.37 (1.13-1.67) and PSH = 1.35 (1.10-1.65) in men; and CSH = 1.68 (1.29-2.20) and PSH = 1.66 (1.25-2.19) in women; and 3) noncardiovascular noncancer death, CSH = 1.53 (1.23-1.91) and PSH = 1.50 (1.20-1.89) in men; and CSH = 1.89 (1.43-2.48) and PSH = 1.84 (1.39-2.45) in women. In all instances, the cumulative mortality function was significantly higher in individuals with diabetes. CONCLUSIONS: Diabetes is associated with premature death from cardiovascular disease, cancer, and noncardiovascular noncancer causes. The use of CSH and PSH provides a comprehensive view of mortality dynamics in a population with diabetes.

Evaluación de la validez de las funciones SCORE de bajo riesgo y calibrada para población española en las cohortes FRESCO / Validity assessment of low-risk SCORE function and SCORE function calibrated to the Spanish population in the FRESCO cohorts

Introducción y objetivos. Estudiar la validez de la función SCORE original de bajo riesgo sin y con colesterol unido a lipoproteínas de alta densidad y SCORE calibrada en población española. Métodos. Análisis agrupado con datos individuales de 12 estudios de cohorte de base poblacional. Se incluyó a 30.919 participantes de 40-64 años sin enfermedades cardiovasculares en el momento del reclutamiento, que se siguieron durante 10 años para la mortalidad cardiovascular contemplada en el proyecto SCORE. La validez de las funciones se analizó mediante el área bajo la curva ROC (discriminación) y el test de Hosmer-Lemeshow (calibración), respectivamente. Resultados. Se dispuso de 286.105 personas/año. La mortalidad a 10 años por causas cardiovasculares fue del 0,6%. La razón de casos esperados/observados fue de 9,1, 6,5 y 9,1 en varones y de 3,3, 1,3 y 1,9 en mujeres con las funciones SCORE original de bajo riesgo sin y con colesterol unido a lipoproteínas de alta densidad y SCORE calibrada, respectivamente; diferencias estadísticamente significativas con el test de calibración de Hosmer-Lemeshow entre la mortalidad predicha con SCORE y la observada (p < 0,001 en ambos sexos y en todas las funciones). Las áreas bajo la curva ROC con SCORE original fueron 0,68 en varones y 0,69 en mujeres. Conclusiones. Todas las versiones de las funciones SCORE disponibles en España sobreestiman significativamente la mortalidad cardiovascular observada en la población española. A pesar de la aceptable capacidad de discriminación, la predicción del número de acontecimientos cardiovasculares mortales (calibración) fue significativamente imprecisa (AU)

Introduction and objectives. To assess the validity of the original low-risk SCORE function without and with high-density lipoprotein cholesterol and SCORE calibrated to the Spanish population. Methods. Pooled analysis with individual data from 12 Spanish population-based cohort studies. We included 30 919 individuals aged 40 to 64 years with no history of cardiovascular disease at baseline, who were followed up for 10 years for the causes of death included in the SCORE project. The validity of the risk functions was analyzed with the area under the ROC curve (discrimination) and the Hosmer-Lemeshow test (calibration), respectively. Results. Follow-up comprised 286 105 persons/y. Ten-year cardiovascular mortality was 0.6%. The ratio between estimated/observed cases ranged from 9.1, 6.5, and 9.1 in men and 3.3, 1.3, and 1.9 in women with original low-risk SCORE risk function without and with high-density lipoprotein cholesterol and calibrated SCORE, respectively; differences were statistically significant with the Hosmer-Lemeshow test between predicted and observed mortality with SCORE (P < .001 in both sexes and with all functions). The area under the ROC curve with the original SCORE was 0.68 in men and 0.69 in women. Conclusions. All versions of the SCORE functions available in Spain significantly overestimate the cardiovascular mortality observed in the Spanish population. Despite the acceptable discrimination capacity, prediction of the number of fatal cardiovascular events (calibration) was significantly inaccurate (AU)

Evaluación de la empatía en estudiantes de Medicina / Empathy assessment in medical students

INTRODUCCIÓN Y OBJETIVOS: La empatía es la capacidad de transmitir comprensión hacia las emociones de otros individuos. La empatía de los profesionales sanitarios se ha asociado a mejores resultados clínicos y de relación con el paciente. El objetivo del estudio era conocer el nivel de empatía de los estudiantes de Medicina, y su evolución después de recibir un curso sobre Entrevista Clínica y Comunicación. MÉTODOS: Estudio longitudinal prospectivo con intervención (módulo de Comunicación y Entrevista Clínica de un mes de duración) y sin grupo control. La empatía se midió con el cuestionario Índice de Reactividad Interpersonal (IRI) que tiene 2 dimensiones cognitivas (toma de perspectiva y fantasía) y 2 emocionales (preocupación empática y distrés personal). La empatía percibida se obtuvo mediante autoevaluación del 0 al 10. RESULTADOS: Participaron 136 alumnos, un 72% eran mujeres, con una edad media de 20,3 años. La empatía percibida correlacionó con las dimensiones del IRI, excepto con distrés personal. Después de la intervención educativa se observaron incrementos en los hombres en toma de perspectiva (de 16,5 a 17,8; p = 0,005) y en las mujeres en fantasía (de 15,5 a 16,7; p = 0,001), con aumento en ambos sexos de la empatía percibida autoevaluada (de 6,9 a 7,4 en hombres; p = 0,009 y de 7,4 a 7,8 en mujeres; p < 0,001). No se modificaron las dimensiones emocionales de empatía. CONCLUSIONES: Los estudiantes de Medicina no perciben dentro de la empatía el componente de distrés personal, y después de la formación se incrementaron los niveles de empatía cognitiva y percibida

INTRODUCTION AND OBJECTIVES: Empathy is the capacity to place oneself in another's position and understand his/her emotions. Empathy of health professionals has been associated with better clinical outcomes and relationship with the patients. The aim of the study is to define the level of empathy of Medical students and how does it evolve after following a one-month Clinical Interview and Communication training module. METHODS: The study is a non-control prospective longitudinal study. Second year Medical students have followed Clinical interview and Communication training module during one month. Empathy has been measured through the Interpersonal Reactivity Index (IRI) questionnaire that has 2 cognitive (perspective taking and fantasy) and 2 emotional (empathic concern and personal distress) dimensions. The perceived empathy was self-assessed using a 1-10 points scale. RESULTS: A sample of 136 students participated on this study (72% women, mean age 20.3 years). The perceived empathy correlates with the size of IRI, except personal distress. Post training intervention scores showed a significant increase in perspective taking dimension among men (from 16.5 to 17.8; P=.005) and fantasy among women (from15.5 to 16.7; P=.001), while self-assessed empathy increased in both sexes (from 6.9 to 7.4 in men; P=.009 and from 7.4 to 7.8 in women; P<.001). CONCLUSIONS: Medical students don't perceive personal distress as an empathy component. After receiving clinical interview and training module, cognitive and perceived empathy were significantly increased

Measuring the payback of research activities: a feasible ex-post evaluation methodology in epidemiology and public health.

Most ex-post evaluations of research funding programs are based on bibliometric methods and, although this approach has been widely used, it only examines one facet of the project's impact, that is, scientific productivity. More comprehensive models of payback assessment of research activities are designed for large-scale projects with extensive funding. The purpose of this study was to design and implement a methodology for the ex-post evaluation of small-scale projects that would take into account both the fulfillment of projects' stated objectives as well as other wider benefits to society as payback measures. We used a two-phase ex-post approach to appraise impact for 173 small-scale projects funded in 2007 and 2008 by a Spanish network center for research in epidemiology and public health. In the internal phase we used a questionnaire to query the principal investigator (PI) on the outcomes as well as actual and potential impact of each project; in the external phase we sent a second questionnaire to external reviewers with the aim of assessing (by peer-review) the performance of each individual project. Overall, 43% of the projects were rated as having completed their objectives "totally", and 40% "considerably". The research activities funded were reported by PIs as socially beneficial their greatest impact being on research capacity (50% of payback to society) and on knowledge translation (above 11%). The method proposed showed a good discriminating ability that makes it possible to measure, reliably, the extent to which a project's objectives were met as well as the degree to which the project contributed to enhance the group's scientific performance and of its social payback.

Validity for use in research on vascular diseases of the SIDIAP (Information System for the Development of Research in Primary Care): the EMMA study.

INTRODUCTION AND OBJECTIVES: Information in primary care databases can be useful in research, but the validity of these data needs to be evaluated. We sought to analyze the validity of the data used in the EMMA study based on data from the Information System for the Development of Research in Primary Care. METHODS: We compared the prevalence of cardiovascular risk factors observed in EMMA-hypertension, diabetes, hypercholesterolemia (and its treatments), obesity, and smoking-with equivalent data from the Registre Gironí del Cor (REGICOR), a population-based study that uses standardized methodology, in 2000. We also compared the incidence rates of vascular diseases and its association with these risk factors in a 5-year follow-up. RESULTS: We analyzed data from 34 823 participants included in EMMA and 2540 REGICOR2000 study participants aged 35 to 74. The prevalence of risk factors did not differ significantly between the 2 studies, except for the prevalence of former smokers in men, which was higher in REGICOR2000 (24.7% [95% confidence interval, 23.9%-25.5%] vs 30.1% [95% confidence interval, 27.1%-33.1%]), and the proportion of patients with lipid-lowering and antihypertensive therapy, which was higher in EMMA (46.9% vs 32.7% and 8.7% vs 6.3%, respectively). There were no differences between the 2 studies when comparing the incidence of vascular diseases (2.1% in both studies in men and 1.18% [95% confidence interval, 0.7%-1.7%] in REGICOR2000 vs 0.75% [95% confidence interval, 0.64%-0.87%] in EMMA in women) and its association with risk factors. CONCLUSIONS: The prevalence of cardiovascular risk factors and their association with the incidence of vascular disease observed in the EMMA study are consistent with those observed in an epidemiological population-based study with a standardized methodology.

[Analyzing the coronary heart disease mortality decline in a Mediterranean population: Spain 1988-2005]. / 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.

Derivation and validation of REASON: a risk score identifying candidates to screen for peripheral arterial disease using ankle brachial index.

BACKGROUND: The recommendation of screening with ankle brachial index (ABI) in asymptomatic individuals is controversial. The aims of the present study were to develop and validate a pre-screening test to select candidates for ABI measurement in the Spanish population 50-79 years old, and to compare its predictive capacity to current Inter-Society Consensus (ISC) screening criteria. METHODS AND RESULTS: Two population-based cross-sectional studies were used to develop (n = 4046) and validate (n = 3285) a regression model to predict ABI < 0.9. The validation dataset was also used to compare the model's predictive capacity to that of ISC screening criteria. The best model to predict ABI < 0.9 included age, sex, smoking, pulse pressure and diabetes. Assessment of discrimination and calibration in the validation dataset demonstrated a good fit (AUC: 0.76 [95% CI 0.73-0.79] and Hosmer-Lemeshow test: χ(2): 10.73 (df = 6), p-value = 0.097). Predictions (probability cut-off value of 4.1) presented better specificity and positive likelihood ratio than the ABI screening criteria of the ISC guidelines, and similar sensitivity. This resulted in fewer patients screened per diagnosis of ABI < 0.9 (10.6 vs. 8.75) and a lower proportion of the population aged 50-79 years candidate to ABI screening (63.3% vs. 55.0%). CONCLUSION: This model provides accurate ABI < 0.9 risk estimates for ages 50-79, with a better predictive capacity than that of ISC criteria. Its use could reduce possible harms and unnecessary work-ups of ABI screening as a risk stratification strategy in primary prevention of peripheral vascular disease.

Análisis de la disminución de la mortalidad por enfermedad coronaria en una población mediterránea: España 1988-2005 / Analyzing the coronary heart disease mortality decline in a mediterranean population: Spain 1988-2005

Introducción y objetivos. Examinar el grado en que la disminución de las tasas de mortalidad por cardiopatía isquémica en España entre 1988 y 2005 podría explicarse por cambios en los factores de riesgo cardiovascular y por el uso de tratamientos médicos y quirúrgicos. Métodos. Se utilizó el modelo IMPACT previamente validado para combinar y analizar datos de las tendencias en la prevalencia de factores de riesgo y el uso y la efectividad de tratamientos cardiacos basados en la evidencia, entre varones y mujeres adultos de 35-74 años de edad. Las principales fuentes de datos incluyeron estadísticas oficiales de mortalidad, resultados de estudios longitudinales, encuestas nacionales, ensayos clínicos aleatorizados y metaanálisis. La diferencia entre las muertes coronarias observadas y esperadas en 2005 se distribuyó entre los tratamientos y los factores de riesgo. Resultados. Desde 1988 a 2005, la tasa de mortalidad ajustada por edad cayó un 40%, y hubo 8.530 muertes menos en 2005. Aproximadamente el 47% de la caída en la mortalidad se ha atribuido a los tratamientos. Los abordajes que contribuyeron en mayor medida fueron el tratamiento en fase aguda de los síndromes coronarios (11%), la prevención secundaria (10%) y el tratamiento de la insuficiencia cardiaca (9%). El 50% de la reducción de la mortalidad se ha atribuido a cambios en los factores de riesgo. El mayor beneficio en la mortalidad viene de los cambios en el colesterol total (cerca de un 31% de la caída de la mortalidad) y de la presión arterial sistólica (cerca de un 15%). Pero se observaron importantes diferencias entre sexos en las tendencias de los factores de riesgo: se incrementó la diabetes mellitus y la obesidad entre los varones y la prevalencia del consumo de tabaco entre las mujeres jóvenes, lo cual produjo muertes adicionales. Conclusiones. Aproximadamente la mitad del descenso en la mortalidad coronaria en España se ha atribuido a la reducción de los principales factores de riesgo y la otra mitad, a los tratamientos basados en la evidencia. Estos resultados incrementan la comprensión de tendencias pasadas y ayudarán a planificar futuras estrategias preventivas y de tratamientos en poblaciones con bajo riesgo (AU)

Introduction and objectives. To examine the extent to which the decrease in 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 (AU)