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Funding Acknowledgements Type of funding sources: Public grant(s) – National budget only. Main funding source(s): CIBERCV of cardiovascular diseases; CIBERESP. OnBehalf REGICOR investigators Background Although myocardial infarction (MI) severity trends are systematically measured with mortality rates, MI incidence trends and the precision of its estimation by linkage of anonymized electronic databases are relatively untested. We validated a linked-data method (LDM) to estimate a population MI incidence and case-fatality, and to analyse the 1990-2016 trends in North-Eastern Spain. Methods LDM consisted of linking MI hospital discharges (n = 4,533,981) and mortality registry data (n = 40,676) for 2008-2016, selecting key MI diagnostic codes. The prospective REGICOR study, including all MI cases in Girona, 1990-2009, was used as the gold standard for validation purposes. Standardized MI cumulated incidence and 28-day case fatality for population aged 35-74 years was calculated, 1990-2016 trends were analysed by linear and joinpoint regression and annual percentage change (APC). Results LDM and REGICOR MI incidence and case-fatality estimates were similar for 2008-09 (Table). LDM MI incidence and case-fatality significantly decreased: APC 1990-2016 [95% CI]) was -1.8 [-2.6;-0.9] in women, and APC 2002-2016 -2.8 [-3.8;-1.8] in men; case-fatality APC 1990-2016 was -4.7% [-5.7;-3.8] in women and APC 1995-2005 -6.5%[-8.5;-4.5] in men. Conclusions LDM in population aged 35-74 reliably estimated MI incidence and case-fatality. MI incidence and case-fatality significantly decreased after 1990. Comparative analysis of REGICOR vs LDM REGICOR 2008-2009 LDM 2008-2009 Estimate 95% CI Estimate 95% CI P-Value Cumulated incidence Men 245.4 228.3; 262.5 239.7 222.5; 256.3 0.626 Women 61.1 52.6; 69.6 58.2 49.9; 66.4 0.626 Overall 28-day case-fatality Men 23.5% 19.7; 27.2 21.3% 17.8; 24.9 0.422 Women 19.3% 6.7; 31.9 17.7% 6.3; 29.1 0.855 In-hospital case-fatality Men 6.9% 4.8; 9.0 5.7% 3.8; 7.6 0.394 Women 5.0% 1.9; 8.2 3.7% 1.0; 6.5 0.540 Pre-hospital case-fatality Men 16.5% 11.8; 21.3 15.6% 11.2; 20.1 0.791 Women 14.2 % 6.6; 21.9 14.0% 6.3; 21.7 0.961 CI Confidence Interval

Background Current evidence shows that single-stage treatment of concomitant choledocholithiasis and cholelithiasis is as effective and safe as two-stage treatment. However, several studies suggest that single-stage approach requires shorter hospitalization time and is more cost-effective than the two-stage approach, even though it requires considerable training. This study aimed to evaluate the implementation of a protocol for managing concomitant choledocholithiasis and cholelithiasis using single-stage treatment. Methods A prospective cohort study of patients diagnosed with cholelithiasis and choledocholithiasis who were treated with the single-stage treatment – transcystic instrumentation, choledocotomy or intraoperative endoscopic retrograde cholangiopancreatography (ERCP) – between September 2010 and June 2017 was assessed. The primary outcomes were complications, hospital stay, operative time and recurrence rate. Results 164 patients were enrolled. 141 (86%) were operated laparoscopically. Preoperatively diagnosed stones were not found by intraoperative imaging or disappeared after “flushing” in 38 patients (23.2%). Surgical approach was transcystic in 45 patients (27.41%), choledochotomy in 74 (45.1%), intraoperative ERCP in 4 (2.4%), and bilioenteric derivation in 3 (1.8%). Mean hospitalization stay was 4.4 days. Mean operative time was 166 min 27 patients (16.5%) had complications and 1 patient was exitus (0.6%). Recurrence rate was 1.2%. Conclusions Single-stage approach is a safe and effective management option for concomitant cholelithiasis and choledocolithiasis. Furthermore, a significant number of common bile duct stones pass spontaneously to duodenum or can benefit from a transcystic approach, with presumable low morbidity and cost-efficiency.

Resumen Antecedentes y objetivos La fibrilacion auricular es la arritmia cronica mas comun. El proposito de este estudio fue determinar la prevalencia de la fibrilacion auricular y su relacion con los factores de riesgo cardiovascular en Espana. Metodologia Estudio transversal a partir de un analisis agrupado de 17.291 individuos aleatorizados reclutados en 6 estudios poblacionales. Resultados La prevalencia de fibrilacion auricular fue de 1,5%. (intervalo de confianza 95%: 1,3-1,7%). Los hombres tuvieron mayor prevalencia que las mujeres (1,9 vs. 1,1%, respectivamente). La prevalencia de fibrilacion auricular se incremento progresivamente con la edad: 0,05% en los menores de 45 anos, 0,5% entre los 45-59 anos, 2,3% entre los 60-74 anos, y 6,3% en los mayores de 75 anos. El porcentaje de individuos que recibia tratamiento anticoagulante fue de 74,3%. Los factores de riesgo asociados significativamente con la arritmia fueron: edad mayor de 60 anos (odds ratio [OR]: 7,6; IC 95%: 5,1-11,2), sexo masculino (OR : 1,8; IC 95%: 1,4-2,4), hipertension arterial (OR : 1,6; IC 95%: 1,2-2,1), obesidad (OR : 1,5; IC 95%: 1,2-2,1), y antecedentes de enfermedad coronaria (OR : 1,9; IC 95%: 1,3-3,0). Conclusion La fibrilacion auricular es una enfermedad frecuente en los individuos de mayor edad mientras que su prevalencia es baja en individuos menores de 60 anos. La mayoria de los individuos con fibrilacion auricular estaban bajo tratamiento anticoagulante. Los factores de riesgo para padecer esta arritmia fueron la edad, el sexo masculino, la hipertension, la obesidad y los antecedentes de enfermedad coronaria.

Background and objectives Atrial fibrillation (AF) is the most common type of arrhythmia. The purpose of this study was to determine the prevalence of atrial fibrillation and its relationship with cardiovascular risk factors in Spain. Methodology Cross-sectional study based on a grouped analysis of 17,291 randomized individuals recruited in 6 population studies. Results The prevalence of atrial fibrillation was 1.5% (95% CI: 1.3–1.7%). Men had a greater prevalence of the disease than women (1.9 vs. 1.1%, respectively). The prevalence of atrial fibrillation progressively increased with age: 0.05% for patients younger than 45 years, 0.5% for those between 45 and 59 years of age, 2.3% for those between 60 and 74 years of age and 6.3% for those older than 75 years. The percentage of individuals who underwent anticoagulant treatment was 74.3%. The risk factors significantly associated with arrhythmia were ages older than 60 years (odds ratio [OR]: 7.6; 95% CI: 5.1–11.2), the male sex (OR: 1.8; 95% CI: 1.4–2.4), arterial hypertension (OR: 1.6; 95% CI: 1.2–2.1), obesity (OR: 1.5; 95% CI: 1.2–2.1) and a history of coronary artery disease (OR: 1.9; 95% CI: 1.3–3.0). Conclusion Atrial fibrillation is a common disease in elderly individuals, while its prevalence is low in individuals younger than 60 years. Most individuals with atrial fibrillation were on anticoagulant treatment. The risk factors for this type of arrhythmia are age, the male sex, hypertension, obesity and a history of coronary artery disease.

Introduction Blood pressure increases in cold periods, but its implications on prevalence of hypertension and on individual progression to hypertension remain unclear. Our aim was to develop a pre-screening test for identifying candidates to suffer hypertension only in cold months among non-hypertensive subjects. Methods We included 95,277 subjects registered on a primary care database from Girona (Catalonia, Spain), with ≥3 blood pressure measures recorded between 2003 and 2009 and distributed in both cold (October–March) and warm (April–September) periods. We defined four blood pressure patterns depending on the presence of hypertension through these periods. A Cox model determined the risk to develop vascular events associated with blood pressure patterns. A logistic regression distinguished those nonhypertensive individuals who are more prone to suffer cold-induced hypertension. Validity was assessed on the basis of calibration (using Brier score) and discrimination (using the area under the receiver operating characteristics). Results In cold months, the mean systolic blood pressure increased by 3.3±0.1 mmHg and prevalence of hypertension increased by 8.2%. Cold-induced hypertension patients were at higher vascular events risk (Hazard ratio=1.44 [95% Confidence interval 1.15–1.81]), than nonhypertensive individuals. We identified age, diabetes, body mass index and prehypertension as the major contributing factors to cold-induced hypertension onset. Discussion Hypertension follows a seasonal pattern in some individuals. We recommend screening for hypertension during the cold months, at least in those nonhypertensive individuals identified as cold-induced hypertensive by this assessment tool.

AIM To determine whether circulating antibodies against oxidized low-density lipoprotein (LDL; OLAB) levels are associated with acute myocardial infarction (AMI) in individuals without classical cardiovascular risk factors. METHODS A case-control study including 34 first AMI patients without classical risk factors (smoking, dyslipidemia, hypertension or diabetes) and 45 population-based healthy controls. RESULTS There were no differences in anthropometric variables between cases and controls. Oxidized LDL levels were similar in both groups. Total cholesterol, LDL cholesterol, apolipoprotein B and physical activity were lower in cases than in controls. OLAB levels were also lower in cases than controls (128 versus 447 U/l, P < 0.001). After adjusting for age, oxidized LDL and physical activity, participants with OLAB levels of 165 U/l or less had a higher risk of AMI (odds ratio, OR = 7.48, 95% confidence interval: 1.57-35.66). When the model was fitted with OLAB as a continuous variable, the natural logarithm (LnOLAB) levels were independently associated with AMI with an OR of 0.40 (95% confidence interval: 0.19-0.86). After adjusting the model by Framingham-risk-adapted score and oxidized LDL, the LnOLAB levels maintained their independent association (OR of 0.43, 95% confidence interval: 0.23-0.79). CONCLUSION First AMI patients without classical risk factors had lower levels of OLAB compared with healthy controls. It is likely that the immunological reaction due to oxidized LDL participates as a preventive factor in the physiopathology of atherosclerosis.

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.

Background The use of validated multivariate cardiovascular predictive models in a population setting is of interest for public health policy makers. We aimed to validate the estimations of the CASSANDRA model (coronary heart disease (CHD) incidence and CHD risk distribution), considering the population changes in age, sex and CHD risk factors prevalence in a 10-year period. Methods We compared the projected CHD incidence estimated with CASSANDRA with that observed in the Girona Heart Registry (REGICOR) for 1995–2004 and 2000–2009 in the population of Girona (Spain) aged 35–74 years. We used official age and sex distributions for this population. Baseline cardiovascular risk factors prevalence and the distribution of cardiovascular risk were obtained from three cross-sectional studies performed in 1995, 2000 and 2005. To validate the future distribution of cardiovascular risk, we tested the yearly CHD risk variance over the study period. Results No significant differences between the estimated and observed annual CHD incidence per 100 000 men were found in 1995–2004 (CASSANDRA=457.8 and REGICOR=420.3, incidence rate ratio (IRR) (95% CI)=0.92 (0.89 to 0.96)) and in 2000–2009 (441.4 and 409.6, respectively, IRR=0.93 (0.90 to 0.96)). However, overpredictions of 18% and 22%, respectively, were observed in women (198.8 and 160.4, IRR=0.82 (0.77 to 0.86), and 197.1 and 152.8, IRR=0.78 (0.74 to 0.83), respectively). No significant differences were found in the CHD risk variance in the three different cross-sectional studies. Conclusions The CASSANDRA model produces valid estimates, particularly in men, of the future burden of disease and in the distribution of cardiovascular risk in individuals aged 35–74 years.

Objectives To assess 1) the association of lipid oxidation biomarkers with 10-year coronary artery disease (CAD) events and subclinical atherosclerosis, and 2) the reclassification capacity of these biomarkers over Framingham-derived CAD risk functions, in a general population. Methods Within the framework of the REGICOR study, 4782 individuals aged between 25 and 74 years were recruited in a population-based cohort study. Follow-up of the 4042 who met the eligibility criteria was carried out. Plasma, circulating oxidized low-density lipoprotein (oxLDL) and oxLDL antibodies (OLAB) were measured in a random sample of 2793 participants. End-points included fatal and non-fatal acute myocardial infarction (AMI) and angina. Carotid intima-media thickness (IMT) in the highest quintile and ankle-brachial index Results Mean age was 50.0 (13.4) years, and 52.4% were women. There were 103 CAD events (34 myocardial infarction, 43 angina, 26 coronary deaths), and 306 subclinical atherosclerosis cases. Oxidized LDL was independently associated with higher incidence of CAD events (HR = 1.70; 95% Confidence Interval: 1.02–2.84), but not with subclinical atherosclerosis. The net classification index of the Framingham-derived CAD risk function was significantly improved when ox-LDL was included (NRI = 14.67% [4.90; 24.45], P = 0.003). No associations were found between OLAB and clinical or subclinical events. The reference values for oxLDL and OLAB are also provided (percentiles). Conclusions OxLDL was independently associated with 10-year CAD events but not subclinical atherosclerosis in a general population, and improved the reclassification capacity of Framingham-derived CAD risk functions.

There is limited prospective evidence at population scale of the impacts of lifestyle and surrogate measures of general and abdominal adiposity on the transition of a metabolically healthy (absence of a metabolic disorder) overweight/obese (MHOO) phenotype to a metabolically abnormal overweight/obese (MAOO) phenotype. Therefore, we determined the relationship between 10-year body mass index (BMI), waist circumferences (WC), waist to height ratio (WHtR), and lifestyle changes and the transition of the MHOO phenotype.We conducted a prospective population-based study of 3,052 male and female Spaniards aged 25-74 years who were followed from 2000 through 2009. Diet and leisure-time physical activity were recorded on validated questionnaires. Weight, height, WC, blood lipids, glycemia, and blood pressure were measured. All variables were obtained at baseline (BL) and follow-up (FL). Participants with a BMI ≥ 25 kg/m(2) and free from hypercholesterolemia, hypertriglyceridemia, diabetes, hypertension, and low HDL and high LDL cholesterol levels were characterized as the MHOO phenotype. A composite healthy lifestyle index (HLI) was constructed by including temporary changes in 3 lifestyle variables (diet, leisure-time physical activity, and smoking).Initially, 20.8% of subjects had the MHOO phenotype; 49.2% of these shifted to MAOO phenotype. In multivariate analysis, changes in BMI, WC, WHtR were positively associated (p = 0.004, p = 0.018, and p = 0.016, respectively) with this transition. One unit increase in the HLI was associated with a 33% lower risk (p = 0.025) to the MAOO phenotype transition after adjusting for age, sex, educational level, and baseline energy intake, BMI, WC, and WHtR.The presence of metabolic disorders in the MHOO phenotype is predicted by an increase in anthropometric surrogate measures of general and abdominal adiposity. In contrast, a healthy lifestyle protects against a transition to the MAOO phenotype.

Anal (EcoA) and rectal endosonography (EcoEAR) is a useful test in the evaluation of patients with anorectal pathology. However, there is no clear consensus on its indications. The aim of this study was to determine the opinion of clinicians regarding the current indications and usefulness of this diagnostic test in daily clinical practice. A cross-sectional observational study was conducted using a survey sent to the services of General surgery in a specific area of Spain. The clinical usefulness of the test was evaluated using an analog scale from 0 (lowest value) to 10 (maximum utility) for each pathology. Of the 47 hospitals, 23 responded to the questionnaire (48.9%). The average number of ultrasounds performed in these centers was 217 per year (standard deviation: 140.1, range 73–450) during the last 3 years. The most common indications for this test were: rectal tumor (85%), anal fistula (80%), and fecal incontinence (70%). This test was suggested more, depending on availability in the hospital itself. In conclusion, anal and rectal endosonography remains a very useful diagnostic clinical test in the opinion of clinicians in general and digestive surgery, especially in the evaluation of patients with anal fistula, fecal incontinence, or rectal tumors.

Atrial fibrillation (AF) is the most common clinically significant cardiac arrhythmia. P-wave duration and interatrial blocks (IAB) have been reported to be associated with AF. Our aim was to determine the individual and combined association of P-wave duration and advanced IAB morphology with AF.We designed an age-, sex-, and survey-matched case-control study nested in a population-based cohort (REGICOR: REgistre GIroní del COR). Two different surveys recruited a total of 9380 participants from 1999 to 2005; all participants were invited to a second examination between 2009 and 2013. For the present study, we selected participants aged 25 to 79 years with follow-up through the end of the study. All electrocardiograms were analyzed by 2 observers to determine P-wave duration and morphology (normal, partial, or advanced IAB).The median follow-up was 7.12 years. Eighty participants presented with AF, had a legible baseline electrocardiogram, and were included in the study, along with 160 controls. P-wave duration and the presence of partial or advanced IAB were associated with AF. When P-wave duration and morphology were considered together, only P-wave duration (≥ 110 milliseconds) showed an independent and strong association with AF. The odds ratio for AF of P-wave duration between 110-119, 120-129 and ≥ 130 milliseconds vs110 milliseconds were 5.33; 95%CI, 1.74-16.33, 5.08; 95%CI, 1.73-14.90 and 5.44; 95%CI, 1.95-15.15, respectively.A P-wave longer than 110 milliseconds increases the risk of AF. Advanced IAB morphology did not seem to provide an additional AF risk beyond that of P-wave duration.

Background Diagnosis of unrecognized myocardial infarction (UMI) remains an open question in epidemiological and clinical studies, inhibiting effective secondary prevention of myocardial infarction. We aimed to determine the prevalence and incidence of Q-wave UMI in asymptomatic individuals aged 35 to 74years, and to ascertain the positive predictive value (PPV) of asymptomatic Q-wave to diagnose UMI. Methods Two population-based cross-sectional studies were conducted, in 2000 (with 10-year follow-up) and in 2005. A baseline electrocardiogram was obtained for each participant. Imaging techniques (echocardiography, cardiac magnetic resonance imaging, and myocardial perfusion single-photon emission computerized tomography) were used to confirm UMI in patients with asymptomatic Q-wave. Results The prevalence of confirmed Q-wave UMI in the 5580 participants was 0.18% (95% confidence interval [CI]: 0.10–0.33) and the incidence rate was 27.1 Q-wave UMI per 100,000person-years. The proportion of confirmed Q-wave UMI with respect to all prevalent MI was 8.1% (95% CI: 4.4–14.2). The PPV of asymptomatic Q-wave to diagnose Q-wave UMI was 29.2% (95% CI: 18.2–43.2%) overall, but much higher (75%, 95% CI: 40.9–92.9%) in participants with 10-year CHD risk ≥10%, compared to lower-risk participants. Conclusion Opportunistic identification of asymptomatic Q-waves by routine electrocardiogram overestimates actual Q-wave UMI, which represents 8% to 13% of all myocardial infarction in the population aged 35 to 74years. This overestimation is particularly high in the population at low cardiovascular risk. In epidemiological studies and in clinical practice, diagnosis of a pathologic Q-wave in asymptomatic patients requires detailed analysis of imaging tests to confirm or rule out myocardial necrosis.

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. This project was supported by clinical research grants from the Ministerio de Salud (EC10-84, EC10-83); Spain’s Ministry of Science and Innovation through the Carlos III Health Institute, cofinanced with European Union ERDF funds (Network for Prevention and Health Promotion in primary Care RedIAPP RD12/0005, Programa HERACLES RD12/0042, and Miguel Servet Contract CP12/03287); and by the Departament de Salut, Generalitat de Catalunya, Agency for Health Technology Assessment (AATRM 034/33/02), and Agency for Management of University and Research Grants (2005SGR00577). Drs. Ramos and Garcia-Gil collaborate (without receiving any personal fee) in 2 projects of primary care for the institute IDIAP Jordi Gol funded by AstraZeneca and AMGEN that are unrelated to the present work. Dr. Marrugat has received lecture fees from Ferrer-in-Code; holds a patent with Gendiag SL; and has received payment for development of educational presentations from AstraZeneca.

The American Heart Association has established criteria for the evaluation of novel markers of cardiovascular risk. In accordance with these criteria, we assessed the association between a multi-locus genetic risk score (GRS) and incident coronary heart disease (CHD), and evaluated whether this GRS improves the predictive capacity of the Framingham risk function.Using eight genetic variants associated with CHD but not with classical cardiovascular risk factors (CVRFs), we generated a multi-locus GRS, and found it to be linearly associated with CHD in two population based cohorts: The REGICOR Study (n=2351) and The Framingham Heart Study (n=3537) (meta-analyzed HR [95%CI]: ~1.13 [1.01-1.27], per unit). Inclusion of the GRS in the Framingham risk function improved its discriminative capacity in the Framingham sample (c-statistic: 72.81 vs.72.37, p=0.042) but not in the REGICOR sample. According to both the net reclassification improvement (NRI) index and the integrated discrimination index (IDI), the GRS improved re-classification among individuals with intermediate coronary risk (meta-analysis NRI [95%CI]: 17.44 [8.04; 26.83]), but not overall.A multi-locus GRS based on genetic variants unrelated to CVRFs was associated with a linear increase in risk of CHD events in two distinct populations. This GRS improves risk reclassification particularly in the population at intermediate coronary risk. These results indicate the potential value of the inclusion of genetic information in classical functions for risk assessment in the intermediate risk population group.

The aim of this study was to describe differences in the characteristics and short- and long-term prognoses of patients with first acute myocardial infarction (MI) according to the presence of ST-segment elevation or non-ST-segment elevation. From 2001 and 2003, 2,048 patients with first MI were consecutively admitted to 6 participating Spanish hospitals and categorized as having ST-segment elevation MI (STEMI), non-ST-segment elevation MI (NSTEMI), or unclassified MI (pacemaker or left bundle branch block) according to electrocardiographic results at admission. The proportions of female gender, hypercholesterolemia, hypertension, and diabetes were higher among NSTEMI patients than in the STEMI group. NSTEMI 28-day case fatality was lower (2.99% vs 5.26%, p = 0.02). On multivariate analysis, the odds ratio of 28-day case fatality was 2.23 for STEMI patients compared to NSTEMI patients (95% confidence interval 1.29 to 3.83, p = 0.004). The multivariate adjusted 7-year mortality for 28-day survivors was higher in NSTEMI than in STEMI patients (hazard ratio 1.31, 95% confidence interval 1.02 to 1.68, p = 0.035). However, patients with unclassified MI presented the highest short- and long-term mortality (11.8% and 35.4%, respectively). The excess of short-term mortality in unclassified and STEMI patients was mainly observed in those patients not treated with revascularization procedures. In conclusion, patients with first NSTEMI were older and showed a higher proportion of previous coronary risk factors than STEMI patients. NSTEMI patients had lower 28-day case fatality but a worse 7-year mortality rate than STEMI patients. Unclassified MI presented the worst short- and long-term prognosis. These results support the invasive management of patients with acute coronary syndromes to reduce short-term case fatality.

Introduction and objectives: Modulation of vascular tone is one of the most relevant estrogen effects. A beneficial effect on endothelial function in postmenopausal women has also been proposed for the selective estrogen receptor modulator raloxifene. However, its effects in women with established cardiovascular disease have not been fully elucidated. In addition, recent trials have generated controversy regarding thromboembolic risk with raloxifene use. The aim of the study was to assess the effect of raloxifene on: a) endothelial function and b) coagulation and fibrinolysis pathways. Methods: The MERCED trial was a prospective, randomized clinical trial. Thirty-three postmenopausal women with ischemic heart disease were enrolled in the study. Raloxifene treatment was administered for a 3-month period, according to a double-blind crossover design. Assessment of vascular function and biologic parameters related to coagulation pathways were conducted at various pre-established timepoints. Results: Flow-mediated dilatation was severely impaired in the study population, and raloxifene had no effect on endothelial function. Treatment with raloxifene was associated to decreased levels of fibrinogen (3.41 [3.11-3.74] vs. 3.69 [3.40-4.00], P < .05); prothrombin fragments F 1+2 (0.93 [0.77-1.12] vs. 0.94 [0.78-1.15], P < .05); and plasmin/antiplasmin complexes (211 [166-267] vs. 242 [199-295], P < .01).

Introduction and objectives: Modulation of vascular tone is one of the most relevant estrogen effects. A beneficial effect on endothelial function in postmenopausal women has also been proposed for the selective estrogen receptor modulator raloxifene. However, its effects in women with established cardiovascular disease have not been fully elucidated. In addition, recent trials have generated controversy regarding thromboembolic risk with raloxifene use. The aim of the study was to assess the effect of raloxifene on: a) endothelial function and b) coagulation and fibrinolysis pathways. Methods: The MERCED trial was a prospective, randomized clinical trial. Thirty-three postmenopausal women with ischemic heart disease were enrolled in the study. Raloxifene treatment was administered for a 3-month period, according to a double-blind crossover design. Assessment of vascular function and biologic parameters related to coagulation pathways were conducted at various pre-established timepoints. Results: Flow-mediated dilatation was severely impaired in the study population, and raloxifene had no effect on endothelial function. Treatment with raloxifene was associated to decreased levels of fibrinogen (3.41 [3.11-3.74] vs. 3.69 [3.40-4.00], P < .05); prothrombin fragments F 1+2 (0.93 [0.77-1.12] vs. 0.94 [0.78-1.15], P < .05); and plasmin/antiplasmin complexes (211 [166-267] vs. 242 [199-295], P < .01). Conclusions: The present study provides evidence that in postmenopausal women with demonstrated endothelial dysfunction and ischemic heart disease, mid-term treatment with raloxifene does not affect endothelial function. In the MERCED trial, no increased thrombotic risk was observed, but a decreased thrombotic and fibrinolytic activity was observed with raloxifene. Further studies are required to determine whether thrombotic risk is associated with specific clinical characteristics or subgroups of postmenopausal women with cardiovascular disease.

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 ¼1.23 (95% CI 0.97 to 1.55). Substantial heterogeneity was observed between studies (I 2 ¼35.6), which was partially explained by the study sample size: the pooled HR was higher among studies with a sample size

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%.

Introduction and objectives: To determine the effect of opening an on-site diagnostic catheterization facility on 30-day and 2-year mortality rates in patients with myocardial infarction (MI). Methods: The study included 1539 consecutive MI patients aged 25–74 years who were recruited before and after the catheterization laboratory opened in 1998: during 1995–1997 and 1999–2003, respectively. Results: The 641 consecutive MI patients recruited in 1995–1997 had worse 30-day mortality than the 898 recruited between 1999–2003 (11.2% versus 6.35%, respectively; P = .001). The number of coronary angiographies and percutaneous coronary interventions (PCIs) carried out was greater in the second period (19.4% versus 3.3%, and 54.8% versus 23.0%, respectively; P < .001). Two-year survival curves were significantly better in the second period for all-cause and cardiovascular death. The adjusted odds ratio for death at 30 days was 0.58 (95% confidence interval [CI] 0.36–0.95) for the second period compared with the first and the adjusted hazard ratio for cardiovascular death at 2 years for patients still alive at 30 days was 0.62 (95%CI 0.39–0.99). After adjustment for the prescription of statins, angiotensinconverting enzyme inhibitors, beta-blockers and antiplatelet drugs at discharge, the effect observed at 2 years was no longer significant. Conclusions: Opening a new on-site diagnostic catheterization unit significantly increased the 30-day survival of MI patients. However, the increase in 2-year survival of 30-day survivors observed was largely explained by the implementation of better secondary prevention.

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.Two population-based cross-sectional studies were used to develop (n = 4046) and validate (n = 3285) a regression model to predict ABI0.9. The validation dataset was also used to compare the model's predictive capacity to that of ISC screening criteria. The best model to predict ABI0.9 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 ABI0.9 (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%).This model provides accurate ABI0.9 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.

Background and objectives: The value of body mass index in the prognosis of patients with ischemic heart disease is not well defined. The objective of our study was to determine the association of body mass index with classic and emergent cardiovascular risk factors and with intra-hospital and 6-months mortality. Patients and methods: We conducted a prospective, multicenter study with a 6-months follow-up. We included 1063 patients between the ages of 25–75 years old who were consecutively admitted to the hospital within the first 24 hours of the onset of symptoms between years 2001 and 2003. We determined demographic and anthropometric variables, as well as classic and emergent factors of risk, clinical variables and the treatment administered. We carried out a univariate and multivariate analysis. Results: The percentage of patients with overweight or obesity in this population was 73.56%. Overweight and obesity were associated with classical risk factors, except for smoking, and emergent risk factors. Body mass index was not associated with short-or mid-term prognosis.

Objective To determine the effect of age and study period on coronary heart disease (CHD) risk attributable to cardiovascular risk factors. Methods A cohort of cardiovascular disease (CVD)-free randomly participants from Girona (Spain) aged 35–74 years recruited in 1995 and 2000 and followed for an average of 6.9 years. A survey conducted in the same area in 2005 was also used for the analysis. Smoking, hypertension, diabetes, sedentary lifestyle, obesity, total cholesterol ≥ 240 mg/dl, low-density lipoprotein (LDL) cholesterol ≥ 160 mg/dl, and high-density lipoprotein cholesterol Results LDL cholesterol had the highest potential for CHD prevention between 35 and 74 years [42% (95% Confidence Interval: 23,58)]. The age-stratified analysis showed that the population attributable risk (PAF) for smoking was 64% (30,80) in subjects Conclusion Overall, LDL cholesterol levels had the highest potential for CHD prevention. Periodic PAF recalculation in different age groups may be required to adequately monitor population trends.

Treatment of acute myocardial infarction (AMI) has changed considerably in recent years. The objective of this study was to investigate differences in in-hospital mortality and 6-month outcomes after a first AMI between patients who participated in two trials, in 1992-1994 and 2001-2003, respectively.The study involved 1440 consecutive patients with a first AMI who were admitted to four university hospitals during 1992-1994 (the RESCATE-I trial) and 1288 with a first AMI who met the same diagnostic criteria and who were admitted to the same hospitals during 2001-2003 (the RESCATE-II trial). Patient management, in-hospital mortality and 6-month prognosis and outcomes were compared between the two trials.Reperfusion therapy was carried out in 60.7% of patients in the first trial and in 72.6% in the second (P.001). In the RESCATE-II trial, the median door-to-needle time was shorter (41 min vs. 93 min; P.001) and patients more frequently underwent coronary angiography (65.2% vs. 28.1%; P.001) and revascularization (34.9% vs. 8.1%; P.001). In addition, in-hospital mortality was lower in RESCATE-II (7.5% vs. 10.9%; P.001). After adjustment for age, sex, comorbidity, AMI severity and reperfusion therapy, the odds ratio for in-hospital mortality in RESCATE-II compared with the first trial was 0.52 (95% confidence interval, 0.31-0.86). In addition, mortality (1.4% vs. 3.6%; P=.001) and readmissions at 6 months were also lower in RESCATE-II.Both in-hospital and 6-month mortality in patients with a first AMI decreased during the last decade, probably due to more frequent reperfusion and revascularization therapy and better medical treatment.

Introduction and objectives Two particular polymorphisms, namely PON1-192 and PON2-311, in the genes encoding the antioxidant enzymes paraoxonase-1 (PON1) and paraoxonase-2 (PON2) have been associated with an increased risk of acute myocardial infarction (AMI). However, previous findings have been contradictory. The aim of this study was to investigate the association between the PON1-192 and PON2-311 polymorphisms and their interaction on AMI risk. Methods This case-control study involved 746 consecutive AMI patients and 1796 control subjects without cardiovascular disease, who were randomly selected from the same population from which the patients came. All participants were recruited between 1999 and 2000 from four Spanish autonomous regions. All were assessed for the presence of PON1-192 and PON2-311 and for classical cardiovascular risk factors. Multivariate analysis was carried out using logistic regression modeling. Results The odds ratios (OR) of AMI for patients with the PON1-192 QQ and PON2-311 SS genotypes (who comprised 50% and 66% of the population, respectively) were 1.26 (95% confidence interval [Cl], 1.02-1.55) and 1.25 (95% Cl, 1.04-1.50), respectively, compared with R and C allele carriers. Moreover, in patients with both QQ and SS genotypes, the adjusted OR of AMI increased to 1.41 (95% Cl, 1.13-1.76). Conclusiones Our results indicate that the PON1-192 and PON2-311 polymorphisms were independent risk factors of AMI in our population.

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 © 2007 The European Society of Cardiology

Fundamento y objetivo REACH es el mayor registro mundial disenado para obtener informacion sobre el control de factores de riesgo cardiovascular y tratamiento preventivo en una poblacion con aterotrombosis sintomatica o alto riesgo de desarrollarla. El objetivo del presente estudio es mostrar los resultados obtenidos en la muestra de la poblacion espanola incluida en el registro. Pacientes y metodo Registro de pacientes consecutivos con solo factores de riesgo cardiovascular (SFR) para aterotrombosis o con enfermedad vascular (EV) sintomatica: enfermedad coronaria (EC) y/o cerebrovascular (ECV) y/o arterial periferica (EAP). Se evaluo el control de factores de riesgo cardiovascular y tratamientos antitrombotico e hipolipemiante. Resultados Espana incluyo a 2.515 pacientes: 297 con SFR y 2.218 con EV (un 61,4% con EC,un 36,6% con ECV y un 18,7% con EAP). En los grupos SFR y EV los porcentajes de falta de control de la presion arterial, los valores plasmaticos de glucosa, de colesterol total y de trigliceridos fueron del 76,5 frente al 57,1% (p Conclusiones El control de los factores de riesgo cardiovascular en personas espanolas de alto riesgo o con EV establecida, especialmente EAP, es inadecuado. Mientras que el uso de estatinas es insuficiente, el de medicacion antitrombotica es aceptable en prevencion secundaria,pero bastante deficiente en prevencion primaria.

Background Smoking is a risk factor for coronary heart disease, but it has been associated with better short-term prognosis in hospitalized patients with acute myocardial infarction. The aims of this study were to determine the association between smoking and myocardial infarction 28-day case-fatality in hospitalized patients and at the population level; and, whether smokers presenting with fatal myocardial infarction are more likely to die before reaching a hospital. Design and methods Population-based myocardial infarction registry, carried out in 1997-1998 in seven regions of Spain, used standardized methods to find and analyze suspected myocardial infarction patients (10 654 patients; 7796 hospitalized). Four categories of smoking status were defined: never-smokers, former smokers for more than 1 year, former smokers for less than 1 year, and current smokers. Results The main end-point was 28-day case-fatality, found to be 20.1, 17.1, 15.6, and 8.9%, in the four smoking status categories, respectively, for hospitalized patients; and 37.4, 33.0, 24.5, and 23.2%, respectively, at population level. Hospitalized current smokers had lower age, sex, and comorbidity-adjusted 28-day case-fatality than never-smokers (odds ratio = 0.71; 95% confidence interval: 0.56-0.90). This association held at population level (odds ratio = 0.68; 95% confidence interval: 0.60-0.76), in which former smoking was also associated with lower case-fatality. In fatal cases, recent former smokers presented a lower risk of out-of-hospital death than never-smokers (odds ratio = 0.47; 95% confidence interval: 0.29-0.77), whereas current smoking was marginally associated with out-of-hospital death (odds ratio = 1.22; 95% confidence interval: 0.99-1.50). Conclusions Current smoking is associated with lower 28-day case-fatality in hospitalized myocardial infarction patients. This association held at population level. Among fatal cases, smoking is associated with higher and recent former smoking with lower risk of dying out-of-hospital.

This issue of the journal includes a publication on the adaptation of the Systematic COronary Risk Evaluation (SCORE) to estimate the risk of death from preventable diseases such as cerebrovascular disease (CVD) and coronary heart disease (CHD), among other cardiovascular diseases. 1 The original system was designed to help guide clinicians responsible for the primary prevention of cardiovascular disease and provides risk estimates for non-diabetic patients aged 40-65 years based on sex, age, systolic blood pressure, total cholesterol, and smoking history. The function exists for countries with high and low cardiovascular risk. 2 Three functions are currently available to calculate cardiovascular risk in Spain: the classic Framingham function, which overestimates risk in the Spanish population, 3 a version of this function which was adapted for the Spanish population by the REGICOR (Registre Gironi del Cor) study investigators in collaboration with investigators from the Framingham Heart Study, and which provides estimates whose validity for Spain was shown in the VERIFICA (Validez de la Ecuacion de

Introduction and objectives The incidence of myocardial infarction in Spain is low, and mortality has been decreasing over the last few decades. The objective of this study was to analyze trends in myocardial infarction mortality, incidence, attack rates, and 28-day case-fatality attack rates between 1990 and 1999 in the general population aged 35-74 years in Girona, Spain. Methods The study included all myocardial infarction cases in Girona classified according to the MONICA algorithm. Attack, incidence, mortality rates and case- fatality were calculated. In addition, the annual percentage change in each of these indicators during the study period was also calculated. Results The mean attack rate per 100,000 inhabitants was 258 (95% CI, 249-267) in men and 55 (95% CI, 51- 59) in women. The mean mortality rate per 100,000 was 99 (95% CI, 93-104) in men and 25 (95% CI, 22-28) in women. Significant reductions in attack, incidence and recurrence rates were observed in men aged 35-64 years during the period 1990-1999, but not in men aged 65-74 years, nor in women. Conclusions Myocardial infarction incidence and mortality rates were low in the general population aged 35- 64 years. Rates improved in men aged 35-64 years during the period 1990-1999, but not in those aged 65-74 years, which indicates that a combination of primary and secondary prevention has increased the age at which a myocardial infarction or its recurrence is observed. Rates in women were lower and did not change during the study period.

Introduction and objectives A patient's social circumstances at the time when acute myocardial infarction (AMI) symptoms first appear might influence survival. Our objectives were to study the living conditions, the location where symptoms started, the type of symptoms, and the delay before action was taken in patients with AMI who survived more than one hour, and to analyze the relationship between these variables and mortality in different time periods. Patients and method Population-based observational cohort study carried out in 1997–1998. Main data source: Registre Gironi del Cor (REGICOR). Death certificates provided information on patients who died before they could be included in the register. The patients' demographic characteristics, lifestyle, clinical history, electrocardiographic abnormalities, cardiac enzyme levels, treatment, and diagnosis were recorded. Mortality before and during hospitalization, and overall mortality at 28 days were studied. Results Of the 1,097 patients included, 274 (24.97%) died before reaching hospital, 171 (15.58%) died in hospital, and 652 (59.4%) were alive at 28 days. Mortality was lower in patients who went directly to hospital (OR=0.32, 95% CI, 0.17–0.59). Mortality at 28 days was higher in those with atypical symptoms (OR=5.52, 95% CI, 2.90–10.50), and in those who lived in an institution (OR=9.47, 95% CI, 1.05–84.9). Conclusions In the absence of specially equipped ambulances, AMI patients who went directly to the hospital or who had typical symptoms had a better chance of survival both before hospitalization and at 28 days. In contrast, 28-day mortality was higher in institutionalized patients.

Introduction and objectives Analysis of the effect of treatment in observational studies is complex due to differences between treated and nontreated patients. Calculating the probability of receiving treatment conditioned on relevant covariates (propensity score [PS]) has been proposed as a method to control for these differences. We report an application of PS to assess the association between reperfusion treatment and 28-day case fatality in patients with acute myocardial infarction (AMI). Method We describe the procedure used to calculate PS for receiving reperfusion treatment, and different strategies to analyze the association between PS and case fatality with regression modeling and matching. Data were from a population-based registry of 6307 patients with AMI in Spain during 1997–98. Results The PS for reperfusion was calculated in 5622 patients. In the multivariate analysis, reperfusion was associated with lower case fatality (OR=0.59; 95% confidence interval [95% CI], 0.46–0.77). When PS was included as a covariate, this association became non-significant (OR=0.76; 95% CI, 0.57–1.01). In the subgroup of matched patients with a similar PS (n=3138), treatment was not associated with case fatality (OR=0.95; 95% CI, 0.72–1.26). When the influence of cases with missing data on PS was controlled for, reperfusion treatment was associated with lower fatality (OR=0.66; 95% CI, 0.55–0.80). Conclusions Calculating propensity score is a method that controls for differences between treated and nontreated patients. This score has limitations when matching is incomplete and when data are missing. Results of the present example suggest that reperfusion treatment reduces AMI case fatality.

Our aim was to determine the prevalence of diabetes mellitus in the 25-to-74-year-old population in the province of Gerona, Spain. History of known diabetes mellitus was recorded, and fasting glycemia was measured in venous blood. The 1997 diagnostic criteria of the American Diabetes Association were used. Crude prevalence of known diabetes mellitus was 10.0%, and age-standardized prevalence was 7.7% (95% confidence interval [CI], 7.3%-8.1%). Crude prevalence of impaired fasting glucose was 8.6%, and age-standardized prevalence was 7.6% (95% CI, 7.25%-8.1%). Crude prevalence of known diabetes mellitus combined with diabetes mellitus according to glycemia value (total prevalence of diabetes mellitus) was 13.0%, and age-standardized prevalence was 10.0% (95% CI, 9.6%-10.5%). A higher prevalence in men and an increase in prevalence with age were observed. The figures are different from those of other studies in Spain.

The objectives were to analyse whether cardiovascular risk factors appear simultaneously in the population and to determine whether it depends on age. The participants belong to a random sample of individuals 25-74 years of age, representative of the non-diabetic population free of coronary heart disease of the province of Gerona, Spain, studied during 1994-1996. Exploratory factor analysis was used to assess clustering of cardiovascular risk factors and confirmatory factor analysis to compare clus- tering among age groups (25-54 and 55-74). Results: In the 25-54 age group, we observed in both sexes the Central Metabolic Syndrome factor, which included glucose, lipids, and waist-to-hip ratio, and Metabolic Hypertension factor, which included systolic and di- astolic blood pressures, waist-to-hip ratio, low-den- sity lipoproteins, glycaemia, and triglycerides. In the 55-74 age group we observed in both sexes the Cen- tral Metabolic Syndrome factor, with the same com- position as in younger subjects, and Isolated Hypertension factor, composed only of systolic and diastolic blood pressures. In both sexes, the v 2 value for the model of the combined age groups was higher than the sum of v 2 values of the best models for each age group separately (p < 0.01), which indicates that both sexes presented factor structures that differed by age group. Conclusions: The Central Metabolic Syn- drome factor was common to all four sex and age groups studied. In younger subjects blood pressure was related to lipids, obesity, and glycaemia, sug- gesting the existence of a Metabolic Hypertension factor, while systolic and diastolic blood pressures were found to be the only significant variables in the hypertension factor after 54 years.

Background and objectives: The myocardial infarction (MI) incidence rate, prognosis and hospi- talisation rate in the population 65 and over are rarely studied. We sought to determine MI hospital- isation and incidence rates, and 28-day case-fatality, in the 65 year and older population, and to analyse whether their management and prognosis differed from that of younger patients. Methods: All residents in Gerona (Spain) older than 24 years with suspected fatal or non-fatal MI were investigated and included in a population registry. Results: MI mortality, inci- dence, and case-fatality dramatically increased with age after 64. Smoking, thrombolysis, antiplatelet and betablocker drug use, coronary angiograms, and coronary revascularisation decreased with age. The risk of death of patients between 75 and 84 years (OR: 4.15, 95% confidence interval, CI: 1.70-10.15) and between 85 and 94 years (OR: 4.68, 95% CI: 1.62-13.52) was higher than in the 34-64 years age group, independently of any patient characteristic. Conclusions: The magnitude of the impact of MI in the elderly at population and hospital levels is sub- stantially higher than in those younger than 65 years of age. After this age patients receive less treatments and procedures than their younger counterparts.

Aim: The hypothesis that patients with hyperglycaemia during admission, regardless of previous diagnosis of diabetes, have worse prognosis than those with normal glucose values is controversial. The objective was to assess the role of hyperglycaemia on short-term mortality after myocardial infarction (MI). Methods and Results: A cohort study nested in a prospective registry of MI patients in the reference hospital of Gerona, Spain was performed. All consecutive MI patients under 75 were registered between 1993 and 1996. Patient and clinical characteristics, including previous diagnosis of diabetes, glycaemia on admission and in the next four days, were recorded. Patients with glycaemia on admission or four day mean glycaemia >6.67 mmol/l were considered hyperglycaemic. The main outcome measure was mortality at 28 days. Of 662 patients with MI included, 195 (29.7%) had previously known diabetes mellitus, but 457 (69.0%) had glycaemia >6.67 mmol/l on admission. Patients with hyperglycaemia on admission were older, more often female, more frequently had a previous diagnosis of diabetes, developed more complications, and had higher 28 day mortality. The effect of admission glycaemia >6.67 mmol/l on 28 day mortality was independent of major confounding factors, particularly previous diagnosis of diabetes (OR=4.20, 95% confidence intervals 1.18 to 14.96). Conclusions: Higher 28 day mortality was observed among MI patients with glycaemia on admission >6.67 mmol/l compared with patients with lower levels, independently of major confounding variables and, particularly, previous diagnosis of diabetes. This early, simple, and inexpensive marker of bad prognosis after MI should prompt the application of more aggressive treatment of MI and risk factors and, probably, of glycaemia during admission.

To analyse differences in myocardial infarction incidence, mortality and hospitalization rates, 28-day case-fatality and two-year prognosis using two myocardial infarction case definitions: the classical World Health Organization definition (1994) and the European Society of Cardiology/American College of Cardiology definition (2000), which added cardiac troponin as a diagnostic biomarker.Population-based cohort of 4170 consecutive myocardial infarction patients aged 35-74 years from Girona (Spain) recruited between 2002 and 2009.Incidence, mortality rates standardized to the European population and 28-day case-fatality were calculated. To estimate the association between case definition and prognosis, Cox models were fitted.Use of the 2000 European Society of Cardiology/American College of Cardiology definition significantly increased myocardial infarction incidence per 100,000 population (238.3 vs. 274.5 in men and 54.1 vs. 69.7 in women). Applying this definition decreased the 28-day case-fatality rate from 26.9% to 23.4% in men, and from 31.0% to 24.1% in women. In the acute phase, patients diagnosed only by increased troponins were significantly less treated with thrombolysis (34.4% vs. 2.0%), angiotensin-converting enzyme inhibitors (71.7% vs. 65.0%) and percutaneous coronary intervention (41.1% vs. 31.7%). Case-fatality at 28 days was significantly better in cases diagnosed only by troponin increase (0.2 % vs. 9.7%), but two-year cardiovascular mortality was higher (7.5% vs. 3.7%).Inclusion of cardiac troponins in myocardial infarction diagnosis increased annual incidence and decreased case-fatality. Diagnosis based only on increased troponins was associated with worse outcome. This group of patients at high risk of death should receive aggressive secondary prevention therapy.

We appreciate Kawada’s interest in our study (Rivera et al. 2013). His letter focuses on some limitations of our study, which were already discussed in our article. Kawada notes that the small number of participants with low ankle–brachial index (ABI) provided low power to detect an association; this is a limitation that we acknowledged in our article (Rivera et al. 2013). Kawada also points out that the number of covariates in the model exceeds the common rule of thumb of having at least 10 events per variable. We recognize that, with a small number of cases, one is inevitably faced with the trade-off between including all relevant confounders and keeping the number of covariates to a minimum. However, in our article we provided results from a minimally adjusted model including only five confounders and an interaction term. In this model, the number of events per variable was > 10, and the results were not significantly different from those of the fully adjusted model. Kawada suggests selecting a “higher cut-off value of ABI, such as 1.0” for low ABI given that “an ABI of 0.9–1.0 is also associated with cardiovascular risk (Ono et al. 2003).” The findings of Ono et al. were for patients on hemodialysis due to end-stage renal disease and thus cannot be extrapolated to healthy population samples such as the one considered in our study (i.e., with no history or current signs of cardiovascular disease). We selected a cut-off value of 0.9 for low ABI because of the strong evidence of increased risks of incident cardiovascular disease, morbidity, and mortality in individuals with ABI < 0.9 (Allison et al. 2008; Ankle Brachial Index Collaboration 2008; Lee et al. 2004; McDermott et al. 2005). A cut-off value of 0.9 is also more specific (Lee et al. 2004) and much more common in the literature, which allows comparison with other studies. Kawada’s second argument involves the consideration of multicollinearity in the fully adjusted model (model 2), in which systolic and diastolic blood pressure were included. Systolic and diastolic blood pressure were only moderately correlated (correlation coefficient, 0.62), and according to the variance inflation factor (VIF), there were no multicollinearity problems (VIF was 2.45 for systolic blood pressure and 1.98 for diastolic blood pressure). Kawada points at “contradictory results” in the association between air pollution and carotid intima media thickness (IMT), mainly based on the null and weak associations found by Lenters et al. (2010) between several markers of air pollution [nitrogen dioxide, sulfur dioxide, PM2.5 (particulate matter ≤ 2.5 μm in aerodynamic diameter), black smoke, and traffic intensity] and three indicators of vascular damage (IMT, pulse wave velocity, and augmentation index). We consider, however, that these do not constitute results contradictory to the positive association between air pollution and subclinical markers of atherosclerosis found in the six studies thoroughly discussed in our article (Bauer et al. 2010; Diez Roux et al. 2008; Hoffmann et al. 2007, 2009; Kunzli et al. 2005, 2010) as well as by Wilker et al. (2013). The study by Lenters et al. (2010) involved a cohort of young adults, on average 28 years of age. Exposure to air pollution was estimated at the current address only. As the authors acknowledged, the young age of participants and the exposure misclassification, which resulted from exposure estimated at the current address only, are likely explanations for their mixed results. Finally, we agree with Kawada’s closing remark on the need for longitudinal studies, as we concluded in our article.

Physical activity has been identified as a protective factor against the occurrence and progression of coronary heart disease. The lipoprotein lipase (LPL) HindIII polymorphism has been associated with changes in triglyceride and high density lipoprotein (HDL)-cholesterol levels. We have investigated whether the association between the LPL HindIII genetic polymorphism and lipid levels is modified by physical activity. We have also tested the hypothesis that physical activity may interact with smoking and the LPL HindIII polymorphism to determine an individual's plasma lipid concentrations. A total of 520 men were selected from a representative sample used in a population study conducted in Gerona, Spain. The median value (291 kcal/day) of energy expenditure in leisure-time physical activity of the studied sample was selected as a cut-off to define sedentary or active subjects. Serum HDL-cholesterol was positively and significantly associated with the amount of daily energy expenditure in physical activity, whereas inverse associations were seen between physical activity and triglyceride concentration and with the triglyceride to HDL-cholesterol ratio. These effects were consistent across LPL HindIII genotypes. There was a statistically significant interaction between LPL genotype and smoking on lipid concentrations. No statistically significant differences were observed in lipid levels of active or sedentary non-smokers between H- carriers and H+H+ homozygotes for the LPL HindIII polymorphism. In smokers, sedentary H+H+ homozygotes showed significantly higher triglyceride and lower HDL-cholesterol concentrations than sedentary H- carriers. These differences were smaller and not statistically significant when lipid values of active H+H+ homozygotes were compared with active H- carriers. Among all subgroups, sedentary smokers with the H+H+ genotype had the most adverse lipid profile, which was considerably less adverse in H+H+ smokers who were physically active. These findings suggest that the presence of the H+H+ genotype has a deleterious effect on lipid profile in an adverse environment such as smoking, and that the expenditure of more than 291 kcal/day in physical activity attenuates this effect.

STUDY OBJECTIVE—The objective of this study was to analyse whether the risk of death within 28 days and three years after a first Q wave myocardial infarction was higher in hospitalised women than in men. DESIGN—Follow up study. PATIENTS AND SETTING—All consecutive first Q wave myocardial infarction patients aged 25 to 74 years (447 women and 2322 men) admitted to a tertiary hospital in Gerona, Spain, from 1978 to 1997 were registered and followed up for three years. MAIN RESULTS—Women were older, presented more comorbidity and developed more severe myocardial infarctions than men. A significant interaction was found between sex and age. Women aged 65-74 had higher early mortality risk than men of the same age (OR 1.62; 95% CI 1.01, 2.66) after adjusting for age, comorbidity and acute complications including heart failure. Women under 65 tended to be at lower risk of early mortality than men (0.45 (95% CI 0.19, 1.04). Three year mortality of 28 day survivors did not differ between sexes. CONCLUSIONS—These data support the idea that the higher 28 day mortality in hospitalised women with a first Q wave myocardial infarction is mainly attributable to the large number of patients aged 65 to 74 years in whom the risk is higher than that in men. Women under 65 with myocardial infarction do not seem to be a special group of risk. Keywords: age factors; heart failure; mortality; myocardial infarction; sex factors; prognosis

AIMS Differences in the management and organization of health services may account for some of the variability in myocardial infarction case fa tality in different geographic areas. The 28-day outcome was compared i n two regions with similar myocardial infarction incidence and mortality rates that had opposing patients in the use of coronary angiography an d coronary revascularization. METHODS AND RESULTS The 28-day case fatality of patients aged 35 to 64 years with myocardial infarction, surviving the first hour post-admission to hospitals with coronary care units, was compared in the population of myocardial infarction registries of Toulouse, France and Gerona, Spain. Patient characteristics were similar. In Toulouse, 93% of the 819 registered patients underwent coronary angiography compared with only 6% of the 454 in Gerona. Among hospitalized patients 28-day case fatality was 4.3% and 9.3% in Toulouse and Gerona, respectively (P=0.0003). Rates of thrombolysis and beta-blocker use were higher in Toulouse, although severity indicators were similar to those of Gerona. A model adjusted for these variables showed that the risk of death was 1.90 (95% confidence interval: 1.17-3.07) in Gerona patients compared with those of Toulouse. CONCLUSIONS Routine angiography use is associated with better 28-day myocardial infarction prognosis than restrictive use. However, the optimum proportion of myocardial infarction patients who have to receive angiography procedures remains unclear.

Aims There is increasing evidence that paraoxonase, an HDL-linked enzyme, exerts its effect by removing lipid-peroxidation products. We have conducted a case-control study in Gerona, Spain, to find out whether paraoxonase1 polymorphism at codon 192 (Q and R alleles) is associated with increased risk of coronary heart disease, and how diabetes mellitus, associated with high oxidative risk, influences such an association. Methods and Results One hundred and fifty six consecutive myocardial infarction patients and 310 age- and sex-matched control subjects were studied. There were no differences in the distribution of genotype and allele frequencies between patients and controls. The odds ratios for diabetes and dyslipaemia in control and patients stratified by genotype group were compared. Whereas dyslipaemic status was significantly related to myocardial infarction in QQ homozygotes and R carriers, diabetes mellitus was significantly associated with myocardial infarction only in R-carrier subjects. In logistic regression analysis, diabetic R carriers demonstrated a more than two and a half-fold increase in myocardial infarction risk compared with non-diabetic R carriers (OR: 2·65, P

OBJECTIVES The study assessed whether varying accessibility of patients with unstable angina (UA) to coronary angiography and revascularization determined differing usages and outcomes. BACKGROUND The appropriate use rate of coronary angiography and revascularization procedures in UA remains to be established. METHODS A total of 791 consecutive patients with UA without previous acute myocardial infarction (AMI) admitted to four reference teaching hospitals (one with tertiary facilities) were followed for six months. End points were six-month mortality and readmission for AMI, UA, heart failure, or severe ventricular arrhythmias. RESULTS Patients admitted to the tertiary hospital were 3.27 (95% confidence interval [CI] 2.32 to 4.62) times more likely to undergo coronary angiography after adjustment for comorbidity and severity than were those admitted to nontertiary facilities (overall six-month use rates 70.1% and 48.3%, respectively). Revascularization procedures were performed in 36.2% of patients in the tertiary hospital and 24.6% in the others (p = 0.0007); adjusted relative risk (RR) 2.37 (95% CI 1.55 to 3.63). Median delay for urgent coronary angiography was shorter in the tertiary hospital (24 h vs. 4 days, p < 0.0002). Six-month mortality and readmission rates were similar in tertiary and nontertiary hospitals: 3.9% versus 5.3% and 16.9% versus 21.2%, respectively. Adjusted RR of death or readmission for the nontertiary hospitals was 1.23 (95% CI 0.57 to 2.67). CONCLUSIONS The use of coronary angiography and revascularization procedures in UA patients with no previous AMI is higher in tertiary than in nontertiary hospitals, but the more selective use of these procedures in nontertiary centers does not imply worse outcome.

The aim of this study was to assess the clinical course of unstable angina and the prognostic value of clinical and electrocardiographic variables measured during admission in a prospective, multicenter cohort study with 6-month follow-up. The population corresponds to 4 general teaching hospitals in Catalonia, Spain. The clinical course was analyzed in 839 consecutive patients aged up to 80 years with primary unstable angina, without myocardial infarction or previous coronary bypass. The main outcome measures were cardiac mortality and nonfatal myocardial infarction. Patients involved in the present analysis belonged to the Resources Used in Acute Coronary Syndromes and Delays in Treatment (RESCATE) study. Six-month overall mortality, cardiac mortality, and nonfatal myocardial infarction rates were 4.6%, 4.1%, and 3.9%, respectively. Six-month cardiac mortality or myocardial infarction rate did not differ among clinical forms of presentation. Peripheral artery disease (RR 3.5, 95% confidence interval [CI] 1.88 to 6.50, p = 0.0001), ST-T-wave electrocardiographic changes on admission (RR 2.22, 95% CI 1.13 to 4.36, p = 0.0203), and age >65 years (RR 1.74, 95% CI 1.04 to 2.91, p = 0.0356) independently predicted 6-month cardiac mortality or nonfatal myocardial infarction. Their positive predictive values were 21%, 10%, and 11%, respectively, whereas their negative predictive value was ≥93% in all cases. Prevalences were 9%, 70%, and 41%, respectively. In this prospective study, patients with unstable angina without prior myocardial infarction have a relatively low, although not negligible, 6-month severe complication rate. Stratification risk can easily be established with clinical and electrocardiographic characteristics measured during admission. Their absence almost rules out future adverse events, while their presence does not necessarily imply bad prognosis.

Background —The aim of this study was to analyze 28-day case fatality trends between 1978 and 1993 among hospitalized acute myocardial infarction (AMI) patients in the REGICOR registry, Gerona, Spain, and relate them to thrombolytic and antiplatelet drug use and changes in patient characteristics. Methods and Results —A total of 2053 consecutive patients 25 to 74 years of age with a first Q-wave AMI admitted to the reference hospital between 1978 and 1993 were registered. Clinical characteristics and patient management were recorded. Four 4-year periods were considered: 1978 to 1981, 1982 to 1985 (prethrombolytic therapy), 1986 to 1989 (thrombolytic and antiplatelet drugs introduced), and 1990 to 1993 (thrombolytic and antiplatelet drugs used routinely). The end point was death at 28 days. Case fatality at 28 days decreased 6% per year between 1978 and 1993. A logistic model adjusted for comorbidity and severity showed the last 3 periods to present a steep decrease in the OR of death at 28 days: 0.86 (95% CI, 0.52 to 1.41), 0.59 (95% CI, 0.35 to 0.99), and 0.40 (95% CI, 0.24 to 0.69), respectively, compared with the first period. After 1986, 85.7% of the 112 lives saved could be attributed to the use of antiplatelet and thrombolytic drugs. Adjusted relative risk reduction was 56.0% for antiplatelet drugs, 34.1% for thrombolytic drugs, and 77.9% for the 2 combined. Conclusions —Our results strongly suggest that new therapies introduced since 1986 have contributed to the decrease in 28-day case fatality of patients admitted with a first Q-wave AMI. This decrease could be attributable mainly to the use of antiplatelet and thrombolytic drugs. These findings should encourage the routine use of thrombolytic and antiplatelet drugs and particularly their combination in the acute phase of AMI.

Objectives. The aim of the present study was to ascertain whether the degree of accessibility to coronary angiography and revascularization results in differing usages or outcomes, or both, in the setting of a high coverage national health system. Background. The selective use of coronary angiography and revascularization procedures in the management of acute myocardial infarction (MI) remains controversial. Methods. A cohort of 1,460 consecutive patients with a first MI admitted to four referral teaching hospitals (one with tertiary facilities) were followed up for 6 months after admission. Only patients initially admitted to each of the study hospitals were retained for analysis in the original hospital’s cohort. End points were 6-month mortality and readmission for reinfarction, unstable angina, heart failure or severe ventricular arrhythmia. Results. Patients admitted to the tertiary hospital were more likely to undergo coronary angiography (adjusted relative risk 4.22, 95% confidence interval [CI] 3.37 to 5.45) than those admitted to the nontertiary sites (use rate: 22.1% for nontertiary care, 55.5% for tertiary care). Revascularization procedures were performed in 21.2% of patients in the tertiary hospital and in 8.3% in the nontertiary hospitals (p < 0.0001). Median delay for emergency coronary angiography was shorter in the tertiary hospital (within 1 vs. 2 days, p < 0.0001). Six-month mortality or readmission rates were similar (23.7% and 24.7% for tertiary and nontertiary care, respectively). After adjustment for comorbidity and disease severity, the relative risk of death or readmission for the tertiary hospital was 1.03 (95% CI 0.69 to 1.53) times that of the nontertiary hospitals. Conclusions. Selective use of coronary angiography and revascularization procedures may be as effective as less restricted use in the management of acute MI.

Background and objectiveCoronary heart disease (CHD) is the leading cause of death, and smoking its strongest modifiable risk factor. Our aim was to determine the impact of the Spanish 2006 partial smoke-free legislation on acute myocardial infarction (AMI) incidence, hospitalization and mortality rates, and 28-day case-fatality in Girona, Spain.MethodsUsing a population-based registry (the REGICOR Study), we compared population incidence, hospitalization, and mortality rates, and 28-day case-fatality in the pre- and post-ban periods (2002-2005 and 2006-2008, respectively) by binomial regression analysis adjusted for confounding factors. We also analyzed the ban's impact on the outcomes of interest using the AMI definitions of the American Heart Association (AHA)/European Society of Cardiology (ESC) and the World Health Organization (WHO)-Monitoring trends and determinants in cardiovascular diseases (MONICA).ResultsIn the post-ban period, AMI incidence and mortality rates significantly decreased (relative risk [RR] = 0.89; 95% confidence interval [CI] = 0.81-0.97 and RR = 0.82; 95% CI = 0.71-0.94, respectively). Incidence and mortality rates decreased in both sexes, especially in women, and in people aged 65-74 years. Former and non-smokers (passive smokers) showed diminished incidence rates. Implementation of the ban was not associated with AMI case-fatality. Models tended to be more significant with the WHO-MONICA than with the AHA/ESC definition.ConclusionsThe 2006 Spanish partial smoke-free legislation was associated with a decrease in population AMI incidence and mortality, particularly in women, in people aged 65-74 years, and in passive smokers. These results clarify the association between AMI mortality and the enactment of a partial smoke-free legislation and reinforce the effectiveness of smoking regulations in preventing CHD.