Effect of cytochrome p450 polymorphisms on platelet reactivity after treatment with clopidogrel in acute coronary syndrome

Genetic polymorphisms of cytochrome P450 (CYP) isoforms may promote variability in platelet response to clopidogrel. This study was conducted to analyze, in 603 patients with non-ST elevation acute coronary syndromes, the effect of CYP3A4, CYP3A5, and CYP2C19 gene polymorphisms on clopidogrel response and post-treatment platelet reactivity assessed by adenosine diphosphate (ADP)-induced platelet aggregation, vasodilator-stimulated phosphoprotein phosphorylation index, and ADP-induced P-selectin expression. The CYP2C19*2 polymorphism was significantly associated with ADP-induced platelet aggregation, vasodilator-stimulated phosphoprotein phosphorylation index, and ADP-induced P-selectin expression in recessive (p <0.01, p <0.007, and p <0.06, respectively) and codominant (p <0.08, p <0.0001, and p <0.009, respectively) models, but the CYP3A4*1B and CYP3A5*3 polymorphisms were not. The CYP2C19*2 allele carriers exhibited the highest platelet index levels in multivariate analysis (p = 0.03). After covariate adjustment, the CYP2C19*2 allele was more frequent in clopidogrel nonresponders, defined by persistent high post-treatment platelet reactivity (ADP-induced platelet aggregation >70%; p = 0.03). In conclusion, the present data suggest that the CYPC19*2 allele influences post-treatment platelet reactivity and clopidogrel response in patients with non-ST elevation acute coronary syndromes.     

Long-term follow-up after percutaneous treatment of the unprotected left main stenosis in high risk patients not suitable for bypass surgery

Introduction and objectives

Percutaneous coronary intervention is recommended in patients with unprotected left main stenosis non suitable for coronary artery bypass graft. Long-term follow-up of those patients remains uncertain.

Methods

All patients with de novo unprotected left main stenosis treated with stent implantation were consecutively enrolled. Percutaneous coronary intervention was indicated according to the standards of care, taking into account clinical and anatomical conditions unfavorable for coronary artery bypass graft. The primary end point was the occurrence of major adverse cardiac events, a composite of death, nonfatal acute myocardial infarction, or target lesion revascularization.

Results

Of 226 consecutive patients included, 202 (89.4%) were treated with drug-eluting stents. Mean age was 72.1 years, 41.1% had renal dysfunction, and mean Syntax score and EuroSCORE were 28.9 and 7.4, respectively. Angiographic and procedural success was achieved in 99.6% and 92.9% of patients. At 3 years, the rates of major adverse cardiac events, death, nonfatal acute myocardial infarction and target lesion revascularization were 36.2%, 25.2%, 8.4%, 8.0%, respectively. Target lesion revascularization was more frequently observed when ≥2 stents were implanted rather than a single stent (18.5% vs 5.8%, P=.03); and with bare metal stents rather than drug-eluting stents (13.0% vs 7.9%, P=.24). Definite stent thrombosis was observed in 2 patients (0.9%) and probable stent thrombosis in 7 (3.1%). Female sex, impaired left ventricular function, and use of bare metal stents were significantly related with all-cause mortality.

Conclusions

High-risk patients with unprotected left main stenosis treated with percutaneous coronary intervention presented with a high rate of major adverse cardiac events at long-term follow-up. Female sex, impaired left ventricular function, and use of bare metal stents were predictors of poor prognosis.Full English text available from:www.revespcardiol.org     

Diferencias en función del sexo en las características clínicas,tratamiento y mortalidad a 28 días y 7 años de un primer infarto agudo de miocardio. Estudio RESCATE II

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 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.Full English text available from:www.revespcardiol.org/en     

Interleucina 6 y proteína C reactiva ultrasensible para la predicción de la evolución clínica en síndromes coronarios agudos sin elevación del segmento ST

Introduction and objectives

High baseline levels of interleukin-6 and C-reactive protein confer an increased risk of mortality in non-ST-segment elevation acute coronary syndrome. The aim of the study was to determine whether serial measurements of interleukin-6 and high-sensitivity C-reactive protein provide additional information to baseline measurements for risk stratification of non-ST-segment elevation acute coronary syndrome.

Methods

Two hundred and sixteen consecutive patients with non-ST-segment elevation acute coronary syndrome were prospectively included. Blood samples were obtained within 24 h of hospital admission and at 30 days of follow-up. The endpoint was a composite of all-cause death, nonfatal myocardial infarction, or acute decompensated heart failure.

Results

Both interleukin-6 and high-sensitivity C-reactive protein levels decreased from day 1 to day 30, regardless of adverse events (both P<.001). Interleukin-6 levels at 2 time points (interleukin-6 day 1, per pg/mL; hazard ratio=1.006, 95% confidence interval, 1.002-1.010; P=.002 and interleukin-6 day 30, per pg/mL; hazard ratio=1.047, 95% confidence interval, 1.021-1.075; P<.001) were independent predictors of adverse events, whereas high-sensitivity C-reactive protein day 1 and high-sensitivity C-reactive protein day 30 levels were not. Patients with interleukin-6 day 1≤8.24 pg/mL and interleukin-6 day 30≤4.45 pg/mL had the lowest event rates (4.7%), whereas those with both above the median values had the highest event rates (35%). After addition of interleukin-6 day 30 to the multivariate model, C-index increased from 0.71 (95% confidence interval, 0.63-0.78) to 0.80 (95% confidence interval, 0.72-0.86), P=.042, and net reclassification improvement was 0.39 (95% confidence interval, 0.14-0.64; P=.002).

Conclusions

In this population, both interleukin-6 and high-sensitivity C-reactive protein concentrations decreased after the acute phase. Serial samples of interleukin-6 concentrations improved the prognostic risk stratification of these patients.Full English text available from:www.revespcardiol.org/en     

Fracción aminoterminal del propéptido natriurético cerebral y troponina ultrasensible en el dolor torácico agudo de origen incierto. Un subestudio del estudio PITAGORAS

Introduction and objectives

High-sensitivity troponin assays have improved the diagnosis of acute coronary syndrome in patients presenting with chest pain and normal troponin levels as measured by conventional assays. Our aim was to investigate whether N-terminal pro-brain natriuretic peptide provides additional information to troponin determination in these patients.

Methods

A total of 398 patients, included in the PITAGORAS study, presenting to the emergency department with chest pain and normal troponin levels as measured by conventional assay in 2 serial samples (on arrival and 6 h to 8 h later) were studied. The samples were also analyzed in a central laboratory for high-sensitivity troponin T (both samples) and for N-terminal pro-brain natriuretic peptide (second sample). The endpoints were diagnosis of acute coronary syndrome and the composite endpoint of in-hospital revascularization or a 30-day cardiac event.

Results

Acute coronary syndrome was adjudicated to 79 patients (20%) and the composite endpoint to 59 (15%). When the N-terminal pro-brain natriuretic peptide quartile increased, the diagnosis of acute coronary syndrome also increased (12%, 16%, 23% and 29%; P=.01), as did the risk of the composite endpoint (6%, 13%, 16% and 24%; P=.004). N-terminal pro-brain natriuretic peptide elevation (>125 ng/L) was associated with both endpoints (relative risk= 2.0; 95% confidence interval, 1.2-3.3; P=.02; relative risk=2.4; 95% confidence interval, 1.4-4.2; P=.004). However, in the multivariable models adjusted by clinical and electrocardiographic data, a predictive value was found for high-sensitivity T troponin but not for N-terminal pro-brain natriuretic peptide.

Conclusions

In low-risk patients with chest pain of uncertain etiology evaluated using high-sensitivity T troponin, N-terminal pro-brain natriuretic peptide does not contribute additional predictive value to diagnosis or the prediction of short-term outcomes.Full English text available from:www.revespcardiol.org/en.     

El polimorfismo de un solo nucleótido PLAU P141L se asocia con el grado de circulación colateral en pacientes con enfermedad arterial coronaria

Introduction and objectives

Urokinase-type plasminogen activator, which is encoded by the PLAU gene, plays a prominent role during collateral arterial growth. We investigated whether the PLAU P141L (C > T) polymorphism, which causes a mutation in the kringle domain of the protein, is associated with coronary collateral circulation in a cohort of 676 patients with coronary artery disease.

Methods

The polymorphism was genotyped in blood samples using a TaqMan-based genotyping assay, and collateral circulation was assessed by the Rentrop method. Multivariate logistic regression models adjusted by clinically relevant variables to estimate odds ratios were used to examine associations of PLAU P141L allelic variants and genotypes with collateral circulation.

Results

Patients with poor collateral circulation (Rentrop 0-1; n = 547) showed a higher frequency of the TT genotype than those with good collateral circulation (Rentrop 2-3; n = 129; P = .020). The T allele variant was also more common in patients with poor collateral circulation (P = .006). The odds ratio of having poorly developed collaterals in patients bearing the T allele (adjusted for clinically relevant variables) was statistically significant under the dominant model (odds ratio =1.83 [95% confidence interval, 1.16-2.90]; P = .010) and the additive model (odds ratio =1.73 [95% confidence interval, 1.14-2.62]; P = .009).

Conclusions

An association was found between coronary collateral circulation and the PLAU P141L polymorphism. Patients with the 141L variant are at greater risk of developing poor coronary collateral circulation.Full English text available from: www.revespcardiol.org/en     

Efecto del tratamiento optimizado con insulina en la reactividad plaquetaria tras el alta de pacientes hiperglucémicos con síndrome coronario agudo

Introduction and objectives

Intensive glucose control with insulin in patients with an acute coronary syndrome reduces platelet reactivity during hospitalization, compared to conventional control. However, the effect of strict, long-term glucose control on platelet reactivity in these patients remains uncertain.

Methods

This is a prospective, randomized trial evaluating the effects of optimized glucose control (target glucose, 80-120 mg/dL) with insulin, compared with conventional control (target glucose, <180 mg/dL), on platelet reactivity after hospital discharge in patients with an acute coronary syndrome and hyperglycemia. The primary endpoint was assessment of platelet aggregation after stimulation with adenosine diphosphate 20 μM at 12-month follow-up.

Results

One hundred four patients were randomized to optimized management (n=53) or conventional management (n=51). There were no differences between groups in baseline characteristics or platelet function. After 12 months of follow-up, blood glucose levels were significantly lower in the optimized treatment group (104 vs 119 mg/dL; P<.001). However, platelet aggregation following adenosine diphosphate 20 μM stimulation showed no differences between the groups (54.2% [14.3%] vs 55.1% [18.3%] respectively; P=.81). There were no significant differences for other platelet function tests.

Conclusions

Long-term optimized glucose control with insulin in patients with an acute coronary syndrome did not result in a reduction in platelet reactivity compared to conventional control.Full English text available from:www.revespcardiol.org/en     

Impacto del tratamiento preventivo con agonistas adrenérgicos β2 de acción larga y glucocorticoides inhalados en la morbimortalidad de 1.543 episodios de exacerbación grave de asma

Background and Objectives

Recent systematic reviews and meta-analyses examining long-acting #b₂-adrenergic agonists (LABA) as maintenance treatment for asthma have shown surprisingly conflicting results. The aim of the present study was to determine the impact, in terms of efficacy and safety, of previous maintenance treatment on severe asthma exacerbations.

Patients and Methods

We retrospectively evaluated the clinical characteristics of exacerbations experienced by 1543 patients with moderate persistent and severe persistent asthma. Drug therapy was as follows: a combination of inhaled LABAs and corticosteroids (493 patients), an inhaled corticosteroid only (456 patients), and no maintenance treatment (594 patients).

Results

Asthmatic patients taking LABAs did not show higher mortality, longer stay in the intensive care unit, longer hospital stay, lower pH, or worse airflow obstruction than the other 2 groups. On the contrary, they had a higher mean (SD) forced expiratory volume in 1 second at discharge (54% [16%]) than patients taking inhaled corticosteroids (48% [19%]) and patients taking no maintenance treatment (48% [20%]) (P=.009). Patients taking no maintenance treatment also had lower mean (SD) pH values (7.37 [0.11]) than patients taking LABAs (7.39 [0.09]) and patients taking inhaled corticosteroids (7.39 [0.08]) (P=.002), and more admissions to the intensive care unit (11.1% vs 6.5% and 7.7%; P=.002 and P=.018, respectively).

Conclusions

This study did not reveal higher morbidity or mortality in severe asthma exacerbations in patients with moderate persistent or severe persistent asthma who had received inhaled LABAs combined with inhaled corticosteroids. On the contrary, asthma patients who did not use maintenance treatment experienced more severe asthma exacerbations.     

Prognostic influence of loss of blood group A antigen expression in pathologic stage I non-small-cell lung cancer

Introduction

In the scientific literature, contradictory results has been published on the prognostic value of the loss of expression of blood group antigen A (BAA) in lung cancer. The objective of our study was to analyze this fact in our surgical series.

Patients and methods

In a multicenter study, 402 non-small-cell lung cancer (NSCLC) patients were included. All were classified as stage-I according to the last 2009-TNM classification. We analyzed the prognostic influence of the loss of expression of BAA in the 209 patients expressing blood group A or AB.

Results

The 5-year cumulative survival was 73% for patients expressing BAA vs 53% for patients with loss of expression (P=.03). When patients were grouped into stages IA and IB, statistical significance was only observed in stage I-A (P=.038). When we analyzed the survival according to histologic type, those patients with adenocarcinoma and loss of expression of BAA had a lower survival rate that was statistically very significant (P=.003). The multivariate analysis showed that age, gender and expression of BAA were independent prognostic factors.

Conclusions

The loss of expression of blood group antigen A has a negative prognostic impact in stage I NSCLC, especially in patients with adenocarcinoma.     

Factors determining success in percutaneous revascularization of chronic total coronary occlusion: multidetector computed tomography analysis

Introduction and objectives

Percutaneous revascularization of chronic total coronary artery occlusion is a technical challenge and has a lower success rate than other angioplasty procedures. Identification of predictors of failure could lead to better selection of patients with the greatest possibility of success. In this study, we investigate the multidetector computed tomography features associated with failure of percutaneous treatment for chronic total coronary occlusion.

Methods

This is a prospective, single-center study of 69 consecutive patients with chronic total occlusion in whom multidetector computed tomography study was performed before percutaneous coronary revascularization.

Results

Seventy-seven lesions were analyzed. The mean length of the occlusion was 19.9 (14.3) mm and the estimated duration of occlusion was 47 (62) months. The only angiographic factor independently predictive of failure was a severe curve between the plaque and the proximal patent vessel (odds ratio 3.8, 95% confidence interval, 1.2-12; P=.02). On multidetector computed tomography, the only factor predictive of failure was an arc of calcium affecting more than 50% of the vessel circumference in the proximal (P=.04) and middle (P=.03) third of the occlusion.

Conclusions

Multidetector computed tomography identified a variable that cannot be measured by angiography that can predict failure in percutaneous revascularization of chronic total coronary occlusions. In selected cases, this parameter could be useful for preprocedure screening.Full English text available from:www.revespcardiol.org     

Resultados a muy largo plazo tras la implantación de stents liberadores de fármacos en la estenosis de arteria coronaria principal izquierda no protegida: experiencia de un centro

Introduction and objectives

Encouraging results at long-term follow-up have been reported from non-randomized registries and randomized trials following percutaneous coronary intervention with drug-eluting stent implantation for unprotected left main stenosis. However, information on very long-term (>5-year) outcomes is limited. The aim of this study was to assess the very long-term outcomes (6-years) following drug-eluting stent implantation for left main disease.

Methods

All consecutive patients with unprotected left main stenosis electively treated with drug-eluting stent implantation, between March 2002 and May 2005, were analyzed according to the location of the left main lesion (distal bifurcation vs ostial/body).

Results

The study included 149 patients: 113 with distal bifurcation and 36 with ostial/body lesion. Triple-vessel disease was significantly higher in the distal than in the ostial/body group (52.2% vs 33.2%, P=.05). At 6-years of follow-up, the cumulative major adverse cardiovascular event rate was 41.6% (45.1% distal vs 30.6% ostial/body, P=0.1), including 18.8% any death (22.1% distal vs 8.3% ostial/body, P=.08), 3.4% myocardial infarction (3.5% distal vs 2.8% ostial/body, P=1), and 15.4% target lesion revascularization (18.6% distal vs 5.6% ostial/body, P=.06). The composite of cardiac death and myocardial infarction was 10.7% (13.3% distal vs 2.8% ostial/body, P=.1) while the definite/probable stent thrombosis rate was 1.4% (all in the distal group).

Conclusions

At 6-year clinical follow-up, percutaneous coronary intervention with drug-eluting stent implantation for unprotected left main disease was associated with acceptable rates of cardiac death, myocardial infarction and stent thrombosis. Favorable long-term outcomes in ostial/body lesions compared to distal bifurcation lesions were confirmed at long-term clinical follow-up.Full English text available from:www.revespcardiol.org/en     

Importancia de la carga vascular previa en la mortalidad intrahospitalaria y a largo plazo de pacientes con infarto de miocardio y segmento ST elevado

Introduction and objectives

Patients with a current acute coronary syndrome and previous ischemic heart disease, peripheral arterial disease, or cerebrovascular disease are reported to have a poorer outcome than those without these previous conditions. It is uncertain whether this association with outcome is observed at long-term follow-up.

Methods

Prospective observational study, including 4247 patients with ST-segment elevation myocardial infarction. Detailed clinical data and information on previous ischemic heart disease, peripheral arterial disease, and cerebrovascular disease («vascular burden») were recorded. Multivariate models were performed for in-hospital and long-term (median, 7.2 years) all-cause mortality.

Results

One vascular territory was affected in 1131 (26.6%) patients and ≥ 2 territories in 221 (5.2%). The total in-hospital mortality rate was 12.3% and the long-term incidence density was 3.5 deaths per 100 patient-years. A background of previous ischemic heart disease (odds ratio = 0.83; P = .35), peripheral arterial disease (odds ratio = 1.30; P=.34), or cerebrovascular disease (stroke) (odds ratio = 1.15; P = .59) was not independently predictive of in-hospital death. In an adjusted model, previous cerebrovascular disease and previous peripheral arterial disease were both predictors of mortality at long-term follow-up (hazard ratio = 1.57; P < .001; and hazard ratio = 1.34; P = .001; respectively). Patients with ≥ 2 diseased vascular territories showed higher long-term mortality (hazard ratio = 2.35; P < .001), but not higher in-hospital mortality (odds ratio = 1.07; P = .844).

Conclusions

In patients with a diagnosis of ST-segment elevation acute myocardial infarction, the previous vascular burden determines greater long-term mortality. Considered individually, previous cerebrovascular disease and peripheral arterial disease were predictors of mortality at long-term after hospital discharge.Full English text available from: www.revespcardiol.org/en     

Implante percutáneo de la válvula autoexpandible CoreValve en pacientes con estenosis aórtica grave y aorta de porcelana: seguimiento a medio plazo

Introduction and objectives

There is little information on the use of transcatheter aortic valve implantation in patients with severe aortic stenosis and porcelain aorta. The primary aim of this study was to analyze death from any cause after CoreValve^® implantation in patients with severe aortic stenosis, with and without porcelain aorta.

Methods

In this multicenter, observational prospective study, carried out in 3 hospitals, percutaneous aortic valves were implanted in 449 patients with severely calcified aortic stenosis. Of these, 36 (8%) met the criteria for porcelain aorta. The primary end-point was death from any cause at 2 years.

Results

Patients with porcelain aorta more frequently had extracardiac vascular disease (11 [30.6%] vs 49 [11.9%]; P=.002), prior coronary revascularization (15 [41.7%] vs 98 [23.7%]; P=.017), and dyslipidemia (26 [72.2%] vs 186 [45%]; P=.02). In these patients, there was greater use of general anesthesia (15 [41.7%] vs 111 [16.9%]; P=.058) and axillary access (9 [25%] vs 34 [8.2%]; P=.004). The success rate of the procedure (94.4 vs 97.3%; P=.28) and the incidence of complications (7 [19.4%] vs 48 [11.6%]; P=.20) were similar in both groups. There were no statistically significant differences in the primary end point at 24 months of follow-up (8 [22.2%] vs 66 [16%]; P=.33). The only predictive variable for the primary end point was the presence of complications during implantation (hazard ratio=2.6; 95% confidence interval, 1.5-4.5; P=.001).

Conclusions

In patients with aortic stenosis and porcelain aorta unsuitable for surgery, percutaneous implantation of the CoreValve^® self-expanding valve prosthesis is safe and feasible.Full English text available from: www.revespcardiol.org/en     

Factors associated with knowledge and control of arterial hypertension in the Canary Islands

Introduction and objectives

To analyze the factors associated with knowledge and control of hypertension in the adult population of the Canary Islands (18-75 years).

Methods

We recruited a random sample of the general population aged ≥18 years. Hypertension was defined as systolic/diastolic blood pressure ≥140/90 mmHg or known hypertension (self-declared, or controlled hypertension <140/90 mmHg). The bivariate association of known and controlled hypertension with age, sex, anthropometry, serum lipids, medication, and lifestyle was corroborated by adjusting a multivariate logistic model.

Results

We included 6675 participants. The prevalence of hypertension was higher in men (40% vs 31%, P<.001), who also had a lower frequency of treated and controlled hypertension. Female sex (P<.001), age ≥55 years (P<.001), obesity (P<.001), and diabetes (P<.001) were associated with known hypertension. The modifiable factors that, in spite of treatment, increased the risk of poor control of hypertension were alcohol consumption (>30 g/day, odds ratio [OR]=2.4, P<.001; >15-≤30 g/day, OR=2, P=.009; >5-≤15, g/day, OR=1.83, P=.004), obesity (body mass index ≥30, OR=2, P=.003; >24.9-<30, OR=1.7, P=.024), serum cholesterol >250 mg/dL (OR=1.6, P=.006) and elevated heart rate (>80 bpm, OR=1.45, P=.045; >70-≤80 bpm, OR=1.36, P=.038).

Conclusions

The awareness of hypertension increases with frequent use of the health system and with factors associated with known hypertension: female sex, age, underlying health problems. The modifiable factors associated with poor control of known hypertension are alcohol consumption, obesity, elevated heart rate, and hypercholesterolemia.Full English text available from:www.revespcardiol.org     

High on-treatment platelet reactivity by ADP and increased risk of MACE in good clopidogrel metabolizers

High on-treatment platelet reactivity (HPR) by ADP, which primarily reflects the effect of thienopyridines, has been found to be an independent predictor of ischemic events in patients with acute coronary syndrome (ACS) on dual antiplatelet therapy. CYP2C19*2 is associated with HPR by ADP. The aim of our study was to evaluate if high on-clopidogrel platelet reactivity (HPR) by ADP is associated with an increased risk of major adverse coronary events (MACE) after ACS independent of CYP2C19*2 allele, i.e. whether genotyping patients for CYP2C19*2 polymorphism is sufficient to identify those to be switched to novel antiplatelets. A total of 1187 patients were included (CYP2C19 *1/*1 n?=?892; *1/*2 n?=?264; *2/*2 n?=?31); 76 MACE (CV death and non-fatal MI) were recorded in non-carriers of CYP2C19*2 (8.5%) and 39 in carriers of CYP2C19*2 (13.2%). At the landmark analysis in the first 6 months, HPR by ADP and CYP2C19*2 allele were both significantly and independently associated with MACE [HPR by ADP: HR?=?2.0 (95% CI 1.2–3.4), p?=?0.01; CYP2C19*2 allele: HR?=?2.3 (95% CI 1.3–3.9), p?=?0.003]. At the land mark analysis from 7 to 12 months, only HPR by ADP remained significantly associated with the risk of MACE [HPR by ADP: HR?=?2.7 (95% CI 1.4–5.3), p?=?0.003; CYP2C19*2: HR?=?0.8 (95% CI 0.2–1.1), p?=?ns]. CYP2C19*2 allele and HPR by ADP are both independently associated with an increased risk of MACE in the first 6 months after ACS. HPR by ADP is associated with an increased risk until 12 months of follow-up. Therefore, both phenotype and genotype are clinically relevant for the evaluation of the antiplatelet effect of clopidogrel and for the prognostic stratification of ACS patients.     

Results of fractional flow reserve measurement to evaluate nonculprit coronary artery stenoses in patients with acute coronary syndrome

Introduction and objectives

Multivessel disease is usually present in almost half of patients with acute coronary syndromes. Angiography is insufficiently accurate to decide on coronary revascularization in moderate nonculprit lesions. There is some debate about the usefulness of fractional flow reserve assessed by intracoronary pressure wire in acute coronary syndromes. We studied the results of using fractional flow reserve values to decide whether to perform coronary revascularization of nonculprit angiographically moderate lesions in patients with acute coronary syndrome and multivessel disease.

Methods

The fractional flow reserve was used to decide whether to revascularize angiographically moderate nonculprit lesions in a cohort of consecutive patients with acute coronary syndromes recruited in 2 centers.

Results

One hundred and seven patients were included. Based on fractional flow reserve values, 81 patients (75.7%) were not revascularized. All lesions studied were revascularized in 26 patients (24.3%). Patient characteristics of the nontreated group and treated group were, respectively, diseased vessels, 1.3 (0.7) vs 1.4 (0.6) (P<.4); fractional flow reserve-studied lesions, 1.2 (0.5) vs 1.1 (0.4) (P=.3); stenosis, 46.1 (8.3)% vs 47.9 (10.3)% (P=.4); fractional flow reserve, 0.86 (0.1) vs 0.70 (0.1) (P<.005). After 1 year of follow-up, no significant differences in major cardiovascular events were observed between groups. There no deaths or nonfatal myocardial infarctions attributable to fractional flow reserve -deferred lesions. Coronary revascularization of the studied lesions was performed in 3 nontreated group patients (3.7%) due to disease progression.

Conclusions

Fractional flow reserve assessed by intracoronary pressure wire is useful in deciding whether to revascularize angiographically moderate nonculprit lesions in patients with acute coronary syndrome and multivessel disease.Full English text available from:www.revespcardiol.org     

Improved outcomes and complications of atrial fibrillation catheter ablation over time: learning curve, techniques, and methodology

Introduction and objectives

The outcomes of atrial fibrillation ablation procedures vary widely between different centers. Our objective was to analyze the results and complications of this procedure in our center and identify factors predicting the efficacy and safety of atrial fibrillation ablation.

Methods

In total, 726 atrial fibrillation ablation procedures were performed in our center between 2002 and 2009. Beginning in January 2008, a protocol for anticoagulation and conscious sedation was systematically applied. Outcomes and complications could therefore be compared in 2 well-differentiated groups: group A included 419 procedures performed prior to 2008 and group B included 307 procedures completed after 2008 using the new protocol.

Results

During an average follow-up of 8.7 months, 60.9% of patients were arrhythmia-free after one or repeat procedures. After only 1 procedure, the success rate was 41% and significantly higher in group B (51.6% vs 35.2% in group A; P=.001). There were 31 major complications (4.2%), 26 in group A (6.2%) and 5 in group B (1.6%) (P=.002). The implementation of the new protocol was an independent predictor of the absence of complications (odds ratio=0.406; 95% confidence interval, 0.214-0.769; P<.006).

Conclusions

Systematic application of an anticoagulation and conscious sedation protocol is associated with improved results and fewer complications of atrial fibrillation ablation. Factors not evaluated in the present study, such as operator experience and ongoing improvements in atrial fibrillation ablation technology, could have influenced these findings.Full English text available from:www.revespcardiol.org     

Actitud y eficacia de los cardiólogos frente al tabaquismo de los pacientes tras un síndrome coronario agudo

Introduction and objectives

Smoking is one of the most prevalent risk factors in acute coronary syndrome patients. The aim of this study was to assess the attitudes of cardiologists to the smoking habits of these patients

Methods

A prospective multicenter registry of acute coronary syndrome patients. The primary endpoint was defined as smoking abstinence and the secondary endpoint as the incidence of all-cause mortality or nonfatal myocardial infarction.

Results

The study population included 715 patients; 365 were current smokers. During follow-up (median, 375,0 days [interquartile range, 359.3-406.0 days]), 110 patients (30.6%) received smoking cessation support (19.7% at hospital discharge and 37.6% at month 3), specialized units and varenicline being the strategies most frequently used. No clinical differences were observed between patients who received smoking cessation support and those who did not, except for a higher prevalence of previous coronary heart disease in those who received support. In the multivariate analysis, the only variable independently associated with receiving smoking cessation support was previous coronary heart disease (odds ratio =3.16; 95% confidence interval, 1.64-6.11; P<.01). The abstinence rate was 72.3% at month 3 and 67.9% at 1 year; no differences were observed between the patients who received smoking cessation support and those who did not. During follow-up, a nonsignificant trend toward a lower incidence of the secondary endpoint was observed among the patients who were smokers at the time of acute coronary syndrome and who achieved abstinence (P=.07).

Conclusions

Use of smoking cessation support strategies is limited in acute coronary syndrome patients and is more widespread among those with previous coronary heart disease.Full English text available from:www.revespcardiol.org     

La presión arterial ambulatoria nocturna se asocia al remodelado auricular y la activación neurohormonal en pacientes con fibrilación auricular idiopática

Introduction and objectives

Hypertension is a risk factor for atrial fibrillation. Activation of the renin-angiotensin-system seems to be involved in atrial enlargement, with release of atrial and brain natriuretic peptides. The aim of this study was to evaluate the relationship between ambulatory blood pressure and levels of natriuretic peptides, with left atrial size in normotensives with idiopathic atrial fibrillation.

Methods

This was a cross-sectional study in patients with idiopathic atrial fibrillation. The following measurements were recorded during the course of the study: office and 24-h ambulatory blood pressure, atrial and brain natriuretic peptides, plasma renin, aldosterone, and angiotensin-converting enzyme.

Results

Forty-eight patients (mean age 55 [10] years; 70.6% male) were included in the study. Mean office sitting blood pressure values were 132.49 (14.9)/80.96 (9.2) mmHg. Mean 24-h ambulatory systolic and diastolic blood pressure values were 121.10 (8.3)/72.11 (6.8) mmHg (daytime, 126.8 [9.7]/77.58 [7.9] mmHg; nighttime, 114.56 [11.6]/68.6 [8.8] mmHg). A clear trend towards increased left atrial size with higher ambulatory blood pressure values was noted, which was statistically significant for nighttime values (r=0,34; P=.020 for systolic and r=0,51; P=.0001 for diastolic). A significant correlation between atrial natriuretic peptide and nighttime systolic (r=0,297; P=.047) and diastolic (r=0,312; P=.037) blood pressure was observed. Significant correlations were also observed between left atrial size and atrial natriuretic peptide levels (r=0,577; P<.0001) and brain natriuretic peptide levels (r=0,379; P=.012).

Conclusions

Nighttime blood pressure is associated with left atrial size and the release of natriuretic peptides in normotensive patients with idiopathic atrial fibrillation.Full English text available from:www.revespcardiol.org/en     

Metabolic syndrome in Spain: prevalence and coronary risk associated with harmonized definition and WHO proposal. DARIOS study

Introduction and objectives

To update the prevalence of metabolic syndrome and associated coronary risk in Spain, using the harmonized definition and the new World Health Organization proposal (metabolic premorbid syndrome), which excludes diabetes mellitus and cardiovascular disease.

Methods

Individual data pooled analysis study of 24 670 individuals from 10 autonomous communities aged 35 to 74 years. Coronary risk was estimated using the REGICOR function.

Results

Prevalence of metabolic syndrome was 31% (women 29% [95% confidence interval, 25%-33%], men 32% [95% confidence interval, 29%-35%]). High blood glucose (P=.019) and triglycerides (P<.001) were more frequent in men with metabolic syndrome, but abdominal obesity (P<.001) and low high-density lipoprotein cholesterol (P=.001) predominated in women. Individuals with metabolic syndrome showed moderate coronary risk (8% men, 5% women), although values were higher (P<.001) than in the population without the syndrome (4% men, 2% women). Women and men with metabolic syndrome had 2.5 and 2 times higher levels of coronary risk, respectively (P<.001). Prevalence of metabolic premorbid syndrome was 24% and the increase in coronary risk was also proportionately larger in women than in men (2 vs 1.5, respectively; P<.001).

Conclusions

Prevalence of metabolic syndrome is 31%; metabolic premorbid syndrome lowers this prevalence to 24% and delimits the population for primary prevention. The increase in coronary risk is proportionally larger in women, in both metabolic syndrome and metabolic premorbid syndrome.Full English text available from:www.revespcardiol.org