Analysis of myocardial infarction incidence and case-fatality in the last three decades in the province of Girona.

INTRODUCTION AND OBJECTIVES: Myocardial infarction (MI) incidence and case fatality trends are highly informative but relatively untested at the population level. The objective of this work was to estimate MI incidence and case fatality in the Girona population aged 35-74 years, and to determine their 30-year trends (1990-2019). METHODS: The REGICOR (Girona Heart Registry) monitored MI incidence and case fatality rates from 1990 to 2008. For the period 2008 to 2019, we linked discharges from Girona hospitals (n=4 974 977) and mortality registry (n=70 405) during this period. Our linkage algorithm selected key MI diagnostic codes and removed duplicates. Estimates from the linkage algorithm and the REGICOR registry were compared using chi-square tests for overlapping years (2008-2009). We estimated the annual percent change (APC) of standardized MI incidence and 28-day case fatality, and analyzed their trends using joinpoint regression. RESULTS: MI incidence and case fatality estimates were similar in the linkage algorithm and the REGICOR registry. We observed significant decreasing trends in the incidence of MI. The trend was APC, -0.96% (95% confidence interval (95%CI), -1.4 to -0.53) in women from 1990 to 2019 and -4.2% (95%CI, -5.5 to -3.0) in men from 1994 to 2019. The largest decrease in case fatality was -3.8% (95%CI, -5.1 to -2.5) from 1995 to 2003 in women and -2.4% (95%CI, -2.9 to -1.9) from 1995 to 2004 in men, mainly due to prehospital case fatality declines: -1.8% (95%CI, -2.6 to -1.1) in men and -3.2% (95%CI, -4.6 to -1.8) in women. CONCLUSIONS: In Girona, MI incidence and case fatality decreased between 1990 and 2019. The incidence showed a slow but continuous decrease while case fatality only stabilized in the last decade, particularly in women.

Single-stage approach for the management of choledocolithiasis with concomitant cholelithiasis. Implementation of a protocol in a secondary hospital.

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.

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

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

Analysis of the Association Between Electrocardiographic P-wave Characteristics and Atrial Fibrillation in the REGICOR Study.

INTRODUCTION AND OBJECTIVES: 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. METHODS: 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). RESULTS: 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 vs < 110 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. CONCLUSIONS: 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.

Prevalence and incidence of Q-wave unrecognized myocardial infarction in general population: Diagnostic value of the electrocardiogram. The REGICOR study.

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.

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

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

New myocardial infarction definition affects incidence, mortality, hospitalization rates and prognosis.

AIMS: 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. DESIGN: Population-based cohort of 4170 consecutive myocardial infarction patients aged 35-74 years from Girona (Spain) recruited between 2002 and 2009. METHODS: 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. RESULTS: 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%). CONCLUSIONS: 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.

Sex-based differences in clinical features, management, and 28-day and 7-year prognosis of first acute myocardial infarction. RESCATE II study.

INTRODUCTION AND OBJECTIVES: To analyze sex-based differences in clinical characteristics, management, and 28-day and 7-year prognosis after a first myocardial infarction. METHODS: Between 2001 and 2003, 2042 first myocardial infarction patients were consecutively registered in 6 Spanish hospitals. Clinical characteristics, management, and 28-day case-fatality were prospectively recorded. Seven-year vital status was also ascertained by data linkage with the National Mortality Index. RESULTS: The registry included 449 women and 1593 men with a first myocardial infarction. Compared with men, women were older, had a higher prevalence of hypertension and diabetes, and were more likely to receive angiotensin-converting enzyme (ACE) inhibitors but were less likely to receive beta-blockers or thrombolysis. No differences were observed in use of invasive procedures. More women had non-ST-segment elevation and unclassified myocardial infarction than men (37.9% vs 31.3% and 9.8% vs 6.1%, respectively; both P<.001). Case-fatality at 28 days was similar in women and men (5.57% vs 4.46%; P=.39). After multivariate adjustment, the odds ratio of 28-day mortality for men was 1.06 (95% confidence interval: 0.49-2.27; P=.883) compared with women. After multivariate adjustment, men had higher 7-year mortality than women, hazard ratio 1.93 (95% confidence interval: 1.46-2.56; P<.001). CONCLUSIONS: There are demographic and clinical differences between men and women with a first myocardial infarction. The short-term prognosis of a first myocardial infarction in this century is similar in both sexes. However, the long-term vital prognosis after a first myocardial infarction is worse in men than in women. These results are observed in both ST-segment elevation myocardial infarction and non-ST-segment elevation myocardial infarction events.

Validation of a population coronary disease predictive system: the CASSANDRA model.

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.

Relationship of lipid oxidation with subclinical atherosclerosis and 10-year coronary events in general population.

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 <0.9 were considered indicators of subclinical atherosclerosis. 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.

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

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

Determinants of the transition from a cardiometabolic normal to abnormal overweight/obese phenotype in a Spanish population.

PURPOSE: 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. METHODS: 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). RESULTS: 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. CONCLUSIONS: 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.

Oxidized low-density lipoprotein antibodies in myocardial infarction patients without classical risk factors.

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.

Association between long-term exposure to traffic-related air pollution and subclinical atherosclerosis: the REGICOR study.

BACKGROUND: Epidemiological evidence of the effects of long-term exposure to air pollution on the chronic processes of atherogenesis is limited. OBJECTIVE: We investigated the association of long-term exposure to traffic-related air pollution 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/m3), 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.

Impact of a partial smoke-free legislation on myocardial infarction incidence, mortality and case-fatality in a population-based registry: the REGICOR Study.

BACKGROUND AND OBJECTIVE: Coronary 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. METHODS: Using 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). RESULTS: In 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. CONCLUSIONS: The 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.

Sex-related differences in prognosis after myocardial infarction: changes from 1978 to 2007.

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.

Assessment of the value of a genetic risk score in improving the estimation of coronary risk.

BACKGROUND: 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. METHODS AND RESULTS: 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. CONCLUSIONS: 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.

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

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

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

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