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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.

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.

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.

Objective— The contribution of human cytomegalovirus (HCMV) to vascular disease may depend on features of the immune response not reflected by the detection of specific antibodies. Persistent HCMV infection in healthy blood donors has been associated with changes in the distribution of NK cell receptors (NKR). The putative relationship among HCMV infection, NKR distribution, subclinical atherosclerosis, and coronary heart disease was assessed. Methods and Results— NKR expression was compared in acute myocardial infarction (AMI) patients ( n =70) and a population-based control sample ( n =209). The relationship between NKR expression and carotid intima-media thickness (CIMT) in controls ( n =149) was also studied. HCMV infection was associated with higher proportions of NKG2C+ and LILRB1+ NK and T-cells. In contrast, only LILRB1+ NK and CD56+ T-cells were found to be increased in AMI patients, independent of age, sex, conventional vascular risk factors, and HCMV seropositivity. Remarkably, LILRB1 expression in NK and T-cells significantly correlated with CIMT in controls. Conclusion— The association of overt and subclinical atherosclerotic disease with LILRB1+ NK and T-cells likely reflects a relationship between the immune challenge by infections and cardiovascular disease risk, without attributing a dominant role for HCMV. Our findings may lead to the identification of novel biomarkers of vascular disease.

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.

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.

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.

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

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.

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 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.

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

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.

Background: Epidemiological evidence of the effects of long-term exposure to air pollu tion on the chronic processes of athero genesis is limited. Objective: We investigated the association of long-term exposure to traffic-related air pollu tion with subclinical atherosclerosis, measured by carotid intima media thickness (IMT) and ankle–brachial index (ABI). Methods: We performed a cross-sectional analysis using data collected during the reexamination (2007–2010) of 2,780 participants in the REGICOR (Registre Gironí del Cor: the Gerona Heart Register) study, a population-based prospective cohort in Girona, Spain. Long-term exposure across residences was calculated as the last 10 years’ time-weighted average of residential nitrogen dioxide (NO2) estimates (based on a local-scale land-use regression model), traffic intensity in the nearest street, and traffic intensity in a 100 m buffer. Associations with IMT and ABI were estimated using linear regression and multinomial logistic regression, respectively, controlling for sex, age, smoking status, education, marital status, and several other potential confounders or intermediates. Results: Exposure contrasts between the 5th and 95th percentiles for NO2 (25 μg/m), traffic intensity in the nearest street (15,000 vehicles/day), and traffic load within 100 m (7,200,000 vehicle-m/day) were associated with differences of 0.56% (95% CI: –1.5, 2.6%), 2.32% (95% CI: 0.48, 4.17%), and 1.91% (95% CI: –0.24, 4.06) percent difference in IMT, respectively. Exposures were positively associated with an ABI of > 1.3, but not an ABI of < 0.9. Stronger associations were observed among those with a high level of education and in men ≥ 60 years of age. Conclusions: Long-term traffic-related exposures were associated with subclinical markers of atherosclerosis. Prospective studies are needed to confirm associations and further examine differences among population subgroups.key words: ankle–brachial index, average daily traffic, cardiovascular disease, exposure assessment, exposure to tailpipe emissions, intima media thickness, land use regression model, Mediterranean diet, nitrogen dioxide

Introduction A chyle fistula is an uncommon complication following abdominal and pancreatic surgery, particularly in the retroperitoneal compartment. It can also appear as a complication of a severe acute pancreatitis. Medical treatment is the initial approach, but resolution is often slow. Somatostatin or octreotide can help in accelerating the resolution of fistulae. Patients and methods Patients developing a chyle fistula (output >100 ml/24 h, normal amylase levels and triglyceride concentrations above 110 mg/dl) associated with pancreatic disorders were treated with oral intake restriction and parenteral nutrition, followed by subcutaneous octreotide 0.1 mg/8 h. Results Four female patients aged 55–80 years, who underwent pancreatic surgery or presented with an acute pancreatitis, were treated. Chyle fistulae ranging from 100 to 2000 ml/24 h were treated with octreotide, being resolved within five to seven days. No recurrence has been found in a 2–4 years follow up. Conclusions We have found that chyle fistula medical treatment is often related to a slow resolution, somatostatin or octreotide administration dramatically reduces its duration. Other previously reported studies have also shown that the quick onset of such treatment can accelerate the whole process, leading to a shorter recovery and lower hospital costs.

Women with myocardial infarction (MI) have shown a 28-day survival disadvantage compared with men. However, results were less consistent when considering long-term mortality in 28-day survivors. The aim was to estimate the trends for sex-related differences in the three endpoints considered for this study: (1) 28-day mortality or severe ventricular dysfunction (acute pulmonary oedema or cardiogenic shock) during the hospital stay, (2) 28-day mortality and (3) two-year cardiovascular mortality or non-fatal MI in 28-day survivors after a first MI. A cohort of 3,982 consecutive patients with first Q-wave MI admitted to a university tertiary reference hospital between 1978 and 2007 was followed for 2 years. Short-term prognosis improved in women over the studied period; similar rates were observed in both sexes in the 2000s. After adjusting for age, co-morbidities and anterior location of MI, female sex had an odds ratio = 1.71 (95 % confidence interval [CI] 1.34–2.17) of short-term severe MI or death over the studied period. Overall, sex differences in long-term prognosis remained similar over the studied period (hazard ratio = 1.40; 95 % CI 1.02–1.91). In conclusion, short-term prognosis improved over the past 30 years for first Q-wave MI patients, becoming similar for both men and women in the most recent decade. Long-term prognosis did not improve in either men or women, indicating that secondary prevention should be reinforced to achieve consistent reductions in the number of cardiovascular events.

To investigate comorbid conditions with prognostic influence in non-ST-segment elevation acute coronary syndrome (NSTEACS).The study group consisted of a derivation cohort of 1017 patients (admitted from October 1, 2002, through October 1, 2008) and an external validation cohort of 652 patients (admitted from February 1, 2006, through September 30, 2009). Comorbid conditions, including risk factors and components of the Charlson comorbidity index (ChCI) and coronary artery disease-specific index, were recorded. The main outcome was one-year mortality.During follow-up, 103 patients died. After adjusting for variables associated with NSTEACS characteristics (base model), 5 comorbid conditions predicted mortality: severe or mild renal failure (hazard ratio [HR], 2.9 and HR, 1.6, respectively), dementia (HR, 3.1), peripheral artery disease (HR, 2.0), previous heart failure (HR, 2.6), and previous myocardial infarction (HR, 1.4). A simple comorbidity index (SCI) was developed using these variables, (per point: HR, 1.6; 95% confidence interval, 1.4-1.8; P = .0001). Adding the SCI, Charlson comorbidity index, or coronary artery disease-specific index to the base model resulted in a gain of 6.58%, 5.00%, and 4.04%, respectively, in discriminative ability (P = .001), without significant differences among the 3 indices. In patients with comorbid conditions, the highest risk period was in the first weeks after NSTEACS. The strength of the association between SCI and mortality rate was similar in the external validation cohort (HR, 1.3; 95% confidence interval, 1.1-1.6; P = .001).Renal dysfunction, dementia, peripheral artery disease, previous heart failure, and previous myocardial infarction are the comorbid conditions that predict mortality in NSTEACS. A simple index using these variables proved to be as accurate as the more complex comorbidity indices for risk stratification. In-hospital management of patients with comorbid conditions merits further investigation.

The aims of the study were: to describe the distribution of physical activity practice; to determine the prevalence and trends of sedentary lifestyle in the population aged 35 to 74 years of Girona in the 1995-2005 period; and to identify the variables associated to sedentary lifestyle at the population level.Data from three independent population-based cross-sectional studies undertaken in 1995 (n=1419), 2000 (n=2499), and 2005 (n=5628) were analyzed. Physical activity was measured using the Minnesota Leisure Time Physical Activity questionnaire. Sedentary lifestyle was defined as an energy expenditure in moderate physical activity (4-5.5 METs)675 kcal/week or420 kcal/week in intense PA (≥ 6 METs). Logistic regression was used to determine the variables associated with sedentary lifestyle.The age-standardized prevalence of sedentary lifestyle was 53.8%, 39.5%, and 32.6% in 1995, 2000, and 2005 respectively. The prevalence of sedentary lifestyle has decreased especially in women older than 50 years living in the urban areas. An increase in light and moderate physical activity practice in men older than 50 years and in light physical activity practice in women older than 50 years was observed. Female gender, age, smoking and lower educational level were associated with a higher prevalence of sedentary lifestyle.Prevalence of sedentary lifestyle has decreased in the 1995-2005 period in Girona, especially in women, but is still high. Health promotion programs should include physical activity practice as a key element and should take into account gender and social inequalities.

Purpose To determine the differences and trends in the prevalence, awareness, treatment and control of cardiovascular risk factors and lifestyle variables across educational level in the 1995−2005 period in a country with a universal free health care system. Methods Data from three consecutive independent population-based surveys were used. Cardiovascular risk factors, lifestyle variables, and self-reported educational level were collected in 9646 individuals ages 35–74 years throughout the decade. Results The prevalence of hypertension and diabetes was inversely associated with education. An increase in the proportion of hypertension and dyslipidemia awareness, treatment, and control in all educational level groups was observed. This increase was greater among the lowest education group, reducing the disparities between groups. The prevalence of lifestyle-related risk factors decreased in the greatest but increased in the lowest education group, widening the disparities between groups. Conclusions A universal free health care system is effective in avoiding inequalities in the diagnosis, treatment, and control of cardiovascular risk factors. However, other social determinants seem to explain the social inequalities in the prevalence of these risk factors and in the adoption of healthy lifestyles.

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

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.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.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.Body mass index is not a useful anthropometric measure to determine the prognosis of patients after a first myocardial infarction.

To determine the effect of age and study period on coronary heart disease (CHD) risk attributable to cardiovascular risk factors.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 cholesterolor = 240 mg/dl, low-density lipoprotein (LDL) cholesterolor = 160 mg/dl, and high-density lipoprotein cholesterol40 mg/dl were the risk factors considered. The composite end-point included myocardial infarction, angina pectoris, and CHD death.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 subjects55 years; for thoseor = 55 years, the PAF for hypertension was 34% (1,61). The decrease observed between 1995 and 2005 in the population's mean LDL cholesterol level reduced that PAF in all age groups.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.

Introduction and objectives To determine the prevalence of acute myocardial infarction (AMI) without classical risk factors, and to ascertain whether affected patients exhibit a higher prevalence of emergent risk factors and whether the presence of specific emergent risk factors influence prognosis at 6 months. Methods The FORTIAM (Factores Ocultos de Riesgo Tras un Infarto Agudo de Miocardio) study is a multicenter cohort study that includes 1371 AMI patients who were admitted within 24 hours of symptom onset. Strict definitions were used for classical risk factors and the concentrations of the following markers were determined: lipoprotein (a) [Lp(a)], oxidized low-density lipoprotein (oxLDL), high-sensitivity C-reactive protein, fibrinogen, homocysteine, and antibody to Chlamydia. The endpoints observed during the 6-month follow-up were death, angina, and re-infarction. Results The prevalence of AMI without classical risk factors was 8.0%. The absence of classical risk factors did not affect the 6-month prognosis. The only emergent risk factors independently associated with a poorer prognosis were the Lp(a) and oxLDL concentrations. Cutpoints were determined using smoothing splines: 60 mg/dL for Lp(a) and 74 U/L for oxLDL. The associated hazard ratios, adjusted for age, sex, and classical risk factors, were 1.40 (95% confidence interval, 1.06-1.84) and 1.48 (95% confidence interval, 1.06-2.06), respectively. Conclusions The proportion of AMI patients without classical risk factors was low and their prognosis was similar to that in other AMI patients. Both oxLDL and Lp(a) concentrations were independently associated with a poorer 6-month prognosis, irrespective of the presence of classical risk factors.

Background: Coronary heart disease (CHD) is the leading cause of mortality worldwide. CHD clusters in families but this familial aggregation remains largely unexplained. ESR1 is a candidate gene for CHD although recent meta-analyses of the rs2234693 variant reported inconsistent evidence for association with myocardial infarction (MI) in men. The objectives of this study were to perform a qualitative and a quantitative assessment of all evidence to date regarding this association. Methods: We performed structured literature searches for studies addressing the association between the ESR1 rs2234693 and CHD. We assessed the quality of these studies collectively and individually according to recently published guidelines on the reporting and interpretation of genetic association studies. We also performed a meta-analysis of all studies to date, including a sample of MI cases and controls from our region. Results: The qualitative assessment indicated that many studies met a low proportion of the criteria proposed by the current guidelines. No significant association between ESR1 rs2234693 and MI was observed in our sample or in the meta-analysis (16 studies; N ∼ 32,000; OR ∼ 1). Strong between-study heterogeneity was largely explained by a quality score based on the quality criteria. Studies that reported significant associations were generally of poorer quality. Conclusion: We confirm the lack of association between the ESR1 rs223469 and CHD, and show that inconsistencies between previous studies is explained by differences in their quality. © 2009 Elsevier Ireland Ltd. All rights reserved.

We conducted a genome-wide association study testing single nucleotide polymorphisms (SNPs) and copy number variants (CNVs) for association with early-onset myocardial infarction in 2,967 cases and 3,075 controls. We carried out replication in an independent sample with an effective sample size of up to 19,492. SNPs at nine loci reached genome-wide significance: three are newly identified (21q22 near MRPS6-SLC5A3-KCNE2, 6p24 in PHACTR1 and 2q33 in WDR12) and six replicated prior observations1, 2, 3, 4 (9p21, 1p13 near CELSR2-PSRC1-SORT1, 10q11 near CXCL12, 1q41 in MIA3, 19p13 near LDLR and 1p32 near PCSK9). We tested 554 common copy number polymorphisms (>1% allele frequency) and none met the pre-specified threshold for replication (P < 10-3). We identified 8,065 rare CNVs but did not detect a greater CNV burden in cases compared to controls, in genes compared to the genome as a whole, or at any individual locus. SNPs at nine loci were reproducibly associated with myocardial infarction, but tests of common and rare CNVs failed to identify additional associations with myocardial infarction risk.

The REACH Registry is the largest worldwide designed to obtain information on cardiovascular risk factor control and preventive treatment in a population who have, or are at risk of having, symptoms of atherothrombosis. The objective of this study is to show the results of cardiovascular events obtained in a sample of the Spanish population at one year follow-up and intervention.The REACH Spain registry is a prospective cohort study of subjects with vascular risk factors (ORF) for atherothrombosis or with symptomatic vascular disease (VD): coronary artery disease (CAD) and/or cerebrovascular disease (CVD) and/or peripheral artery disease (PAD). The main outcome measures were rates of all-cause mortality, cardiovascular (CV) death, and the overall combined CV death, myocardial infarction (MI), or stroke and CV hospitalization at one year follow-up.In Spain 2,516 patients were recruited and 2,252 completed one year follow-up, the mean age was 68,1 (73,8% men), 11,6% of subjects with ORF and 88,5% with VD, 55% with CAD, 33% with CVD and 17% with PAD. The annual rate of all-cause mortality in VD and ORF groups were 3,57% and 1,98% (NS) respectively, while for CV death they were 2,69% and 0,62% (P.05) and for overall combined CV death myocardial infarction (MI), or stroke and CV hospitalization they were 15,34% and 5,47% (P=.0001). The annual rate of CV death for CAD, CVD and PAD groups were 3,47%, 2,78% and 1,46% respectively, and for the overall combined CV death, myocardial infarction (MI) , or stroke and CV hospitalization they were 18,52%, 13,75% and 14,52%. These event rates increased with the number of symptomatic arterial disease locations from 0,1,2 or 3 for CV death (0,62%, 2,46%, 3,55% and 4,32%, respectively P.05) and for overall combined CV death myocardial infarction (MI), or stroke and CV hospitalization (5,50%, 4,18%, 20,59% y 19,40%, respectively P.0001). At one year follow-up, 82,8% of the patients were with at least one antiplatelet drug and 86,2% were receiving lipid-lowering agents.The REACH Spain Registry at one year follow-up in patients with atherothrombotic disease or at risk of having symptoms of atherothrombosis shows a high rate of all-cause mortality and of overall combined major CV events, which is becoming higher as the number of symptomatic arterial disease locations increases.

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.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.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 [CI], 1.02-1.55) and 1.25 (95% CI, 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% CI, 1.13-1.76).Our results indicate that the PON1-192 and PON2-311 polymorphisms were independent risk factors of AMI in our population.

The REACH Registry is the largest worldwide registry designed to obtain information on cardiovascular risk factor control and preventive treatment in a population who have, or are at high risk of having, symptoms of atherothrombosis. The objective of this study is to show the results obtained in a sample of the Spanish population included in that registry.Registry of consecutive patients who have risk factors only (RFO) for atherothrombosis or who have symptomatic vascular disease (VD): coronary heart disease (CHD) and/or cerebrovascular disease (CVD) and/or peripheral artery disease (PAD). Cardiovascular risk factor control and the use of antithrombotic and lipid lowering therapy were evaluated.In Spain 2,515 patients were recruited; 297 had RFO and 2,218 had VD: 61.4% with CHD, 36.6% with CVD and 18.7% with PAD. The rates of noncontrolled blood pressure, glycemia, total cholesterol and triglyceride levels in the RFO group compared to those of the VD group were: 76.5% vs 57.1% (p0.005), 61.6% vs 30.9% (p0.005), 55.7% vs 41.3% (p0.005) and 45.5% vs 35.1% (p0.005), respectively. The antiplatelet therapy rate in these two groups was 44.1% vs 86.5% (p0.005), the anticoagulant therapy rate was 11.4% vs 12.6% (no significant difference) and statin therapy rate was 65.2% vs 65.6% (no significant difference). Significant differences were found among the CHD, CVD and PAD groups as regards noncontrolled blood pressure rate (49.8%. 57.1% and 67.1%, respectively p0.005), total cholesterol control rate (41.3%, 48.2% and 50.2% respectively, p0.005) as well as antiplatelet therapy rate (86.5%. 83.2% and 81.6% respectively p0.005) and statin therapy rate (78.2%. 51.9% and 57.8% respectively p0.005).Cardiovascular risk factor control in subjects at high risk of atherothrombosis or who have established VD is poor. It is poorer in primary prevention and in PAD patients. Whilst the use of statins is insufficient, the use of antithrombotic medication is acceptable in secondary prevention but considerably lacking in primary prevention.

Both mortality due to cerebrovascular disease in individuals aged under 85 years and mortality due to acute myocardial infarction (AMI) are lower in women than men. In contrast, the age-adjusted 28-day case fatality rate after a first AMI is 20% higher in women, particularly in countries where the incidence of AMI is low. In Spain, the case fatality rate is elevated in women hospitalized for a first AMI, but not in those with other forms of coronary heart disease. The pattern of mortality observed after symptom onset, which shows that death is delayed in women, suggests that the mechanism of death is different in the two sexes. The substantial variation that exists in the way results are adjusted and presented make it very difficult to compare the findings of different studies. Relative to men, women with AMI are 10 years older, reach hospital one hour later on average, more frequently have a comorbid condition (mainly diabetes and hypertension), progress to a more serious clinical state, and have a higher adjusted 28-day mortality risk. Moreover, the treatment given to women during the acute phase is less aggressive. A change in healthcare workers' attitudes is needed so that women with acute coronary syndromes can be identified earlier, thereby increasing the use of diagnostic and therapeutic procedures to a level that corresponds to the greater severity of AMI observed in women at presentation.

Background Most studies that have analysed the effect of secondary prevention of coronary heart disease come from hospitals. Those that are community-based have been conducted mainly by nurses and follow-up was generally too short to show impact on cardiovascular events. Methods This is a multi-centre randomised controlled clinical trial in which patients in the intervention group received periodic postal reminders to see their general practitioner every three months during a 3-year follow-up. General practitioners reinforced healthy lifestyle recommendations to patients and reviewed drug therapies at these quarterly intervals. Patients in the control group received usual care. Results A total of 983 patients aged 30–79 were included. During the 3-year follow-up, 67 patients died and 156 experienced a non-fatal cardiovascular event. The event rates and all-cause mortality were similar in the intervention and control groups (24.0% and 23.5%, and 8.1% and 9.9%, respectively). Improvement in quality of life was similar in both groups. Blood pressure and high-density lipoprotein cholesterol were more frequently within recommended levels in the intervention group than in controls: odds ratio 1.63, 95% confidence interval 1.05–2.51, and odds ratio 2.61, 95% confidence interval 1.32–5.18, respectively. Conclusions Intensive secondary prevention conducted by general practitioners may improve long-term blood pressure control and increase high-density lipoprotein cholesterol in patients with stable coronary disease.

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.Population-based observational cohort study carried out in 1997-1998. Main data source: Registre Gironí 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.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).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.

Objective: The characteristics of the 36 item Medical Outcome Short Form Health Study Survey (SF-36) questionnaire, designed as a generic indicator of health status for the general population, allow it to be self-administered or used in personal or telephone interviews. The main objective of the study was to compare the telephone and self-administered modes of SF-36 for a population from Girona (Spain). Methods: A randomized crossover administration of the questionnaire design was used in a cardiovascular risk factor survey. Of 385 people invited to participate in the survey, 351 agreed to do so and were randomly assigned to two orders of administration (i.e., telephone-self and self-telephone); 261 completed both questionnaires. Scores were compared between administration modes using a paired t test. Internal consistency and agreement between modalities were analyzed by respectively applying Chronbach's alpha and intraclass correlation coefficients. The effect of the order of administration on the test-retest difference was analyzed by one-way ANOVA for repeated measurements. Results: Physical function, physical role and social functioning received significantly lower scores when the self-administered questionnaire was used prior to the telephone survey. When the initial survey was conducted by telephone, all Chronbach's alpha coefficients (except social functioning) scored over 0.70 in the self-administered modality. The intraclass correlation coefficient ranged from 0.41 to 0.83 for the telephone-self order and from 0.32 to 0.73 for the self-telephone order. No clinically significant effect was observed for the order of application. Conclusions: The results of the present study suggest that the telephone-administration mode of SF-36 is equivalent to and as valid as the self-administered mode.

The type of acute coronary syndrome may account for different prognoses between men and women after myocardial infarction. This study assessed gender differences in 28-day mortality rates for first or recurrent Q-wave and non–Q-wave myocardial infarctions and unstable angina by using data from 5 registries that included 20,836 patients (24.8% women). Mortality rates were higher in women with first Q-wave myocardial infarction but not in the other patients after adjusting for confounding variables.

[Abstract] Background: Myocardial infarction (MI) incidence and mortality display a high geographic variation. Aims: The objective of the present study was to analyze MI mortality, cumulative incidence rate variability in seven regions of Spain from 1997 to 1998. Methods and Results: Standardized methods were used to identify, find, register, and classify MI cases that were classified as definite, possible, insufficient-dataMI, and non-MI. The total population of the seven monitored regions was 7,364,682 inhabitants. Of the 11,256 cases fulfilling eligibility criteria to investigate, 10,660 were selected to calculate MI rates: 6554 (61.5%)non-fatal definite MI, 1179 (11.1%)fatal definite MI, 1859 (17.4%)fatal possible MI, 1068 (10.0%)fatal cases with insufficient data. The IBERICA 25–74 years age-standardized cumulative incidence rates for men and women, were 207 (range: 175–252) and 45 (range: 36–65) per 100,000, respectively. The age-standardized mortality rates for men and women, were 73 (range: 62–94) and 20 (range: 13–29) per 100,000, respectively. Age-standardized case-fatality was 31.4 and 24.2% in men aged 25–74 and 35–64 years, respectively, and 32.7 and 27.0%, respectively, in women. Conclusions: MI cumulative incidence and mortality rates are low compared with other industrialized countries but, vary considerably among regions in a Mediterranean country like Spain. Cataluña. Comissió Interdepartamental de Recerca i Innovació Tecnològica; CIRIT/2001 SGR 00408 Instituto de Salud Carlos III; FIS 96/0026-01 to 05 Instituto de Salud Carlos III; FIS 97/1270 Instituto de Salud Carlos III; FIS 98/1535