Jean-Pierre Cambou

Comparison of Thrombolysis Followed by Broad Use of Percutaneous Coronary Intervention With Primary Percutaneous Coronary Intervention for ST-Segment-Elevation Acute Myocardial Infarction : Data From the French Registry on Acute ST-Elevation Myocardial Infarction (FAST-MI)

Background— Intravenous thrombolysis remains a widely used treatment for ST-elevation myocardial infarction; however, it carries a higher risk of reinfarction than primary PCI (PPCI). There are few data comparing PPCI with thrombolysis followed by routine angiography and PCI. The purpose of the present study was to assess contemporary outcomes in ST-elevation myocardial infarction patients, with specific emphasis on comparing a pharmacoinvasive strategy (thrombolysis followed by routine angiography) with PPCI. Methods and Results— This nationwide registry in France included 223 centers and 1714 patients over a 1-month period at the end of 2005, with 1-year follow-up. Sixty percent of the patients underwent reperfusion therapy, 33% with PPCI and 29% with intravenous thrombolysis (18% prehospital). At baseline, the Global Registry of Acute Coronary Events score was similar in thrombolysis and PPCI patients. Time to initiation of reperfusion therapy was significantly shorter in thrombolysis than in PPCI (median 130 versus 300 minutes). After thrombolysis, 96% of patients had coronary angiography, and 84% had subsequent PCI (58% within 24 hours). In-hospital mortality was 4.3% for thrombolysis and 5.0% for PPCI. In patients with thrombolysis, 30-day mortality was 9.2% when PCI was not used and 3.9% when PCI was subsequently performed (4.0% if PCI was performed in the same hospital and 3.3% if performed after transfer to another facility). One-year survival was 94% for thrombolysis and 92% for PPCI (P=0.31). After propensity score matching, 1-year survival was 94% and 93%, respectively. Conclusions— When used early after the onset of symptoms, a pharmacoinvasive strategy that combines thrombolysis with a liberal use of PCI yields early and 1-year survival rates that are comparable to those of PPCI.

β Fibrinogen Gene Polymorphisms Are Associated With Plasma Fibrinogen and Coronary Artery Disease in Patients With Myocardial Infarction The ECTIM Study

Background Polymorphisms of the β fibrinogen gene have been shown to affect plasma fibrinogen levels and the risk of peripheral arterial disease. We now present the results of a detailed analysis of the β fibrinogen gene in relation to plasma fibrinogen and to the severity of coronary artery disease (CAD) in patients with myocardial infarction (MI) in the ECTIM Study. Methods and Results Ten polymorphisms of the β fibrinogen gene, including five new polymorphisms identified by single-strand conformation polymorphism analysis, and one polymorphism in the 3′ flanking region of the α fibrinogen gene were investigated in 565 patients with MI and 668 control subjects. The polymorphisms were in tight linkage disequilibrium and the genotype frequencies were similar in patients with MI and control subjects. In the multivariate analysis, only two polymorphisms, β Hae III (P<.0003) and β-854 (P<.01), were independently associated with plasma fibrinogen. The significant association between β fibrinogen polymorphisms...

Association of Changes in Clinical Characteristics and Management With Improvement in Survival Among Patients With ST-Elevation Myocardial Infarction

CONTEXT The contemporary decline in mortality reported in patients with ST-segment elevation myocardial infarction (STEMI) has been attributed mainly to improved use of reperfusion therapy. OBJECTIVE To determine potential factors-beyond reperfusion therapy-associated with improved survival in patients with STEMI over a 15-year period. DESIGN, SETTING, AND PATIENTS Four 1-month French nationwide registries, conducted 5 years apart (between 1995, 2000, 2005, 2010), including a total of 6707 STEMI patients admitted to intensive care or coronary care units. MAIN OUTCOME MEASURES Changes over time in crude 30-day mortality, and mortality standardized to the 2010 population characteristics. RESULTS Mean (SD) age decreased from 66.2 (14.0) to 63.3 (14.5) years, with a concomitant decline in history of cardiovascular events and comorbidities. The proportion of younger patients increased, particularly in women younger than 60 years (from 11.8% to 25.5%), in whom prevalence of current smoking (37.3% to 73.1%) and obesity (17.6% to 27.1%) increased. Time from symptom onset to hospital admission decreased, with a shorter time from onset to first call, and broader use of mobile intensive care units. Reperfusion therapy increased from 49.4% to 74.7%, driven by primary percutaneous coronary intervention (11.9% to 60.8%). Early use of recommended medications increased, particularly low-molecular-weight heparins and statins. Crude 30-day mortality decreased from 13.7% (95% CI, 12.0-15.4) to 4.4% (95% CI, 3.5-5.4), whereas standardized mortality decreased from 11.3% (95% CI, 9.5-13.2) to 4.4% (95% CI, 3.5-5.4). Multivariable analysis showed a consistent reduction in mortality from 1995 to 2010 after controlling for clinical characteristics in addition to the initial population risk score and use of reperfusion therapy, with odds mortality ratios of 0.39 (95%, 0.29-0.53, P <.001) in 2010 compared with 1995. CONCLUSION In France, the overall rate of cardiovascular mortality among patients with STEMI decreased from 1995 to 2010, accompanied by an increase in the proportion of women younger than 60 years with STEMI, changes in other population characteristics, and greater use of reperfusion therapy and recommended medications.

Plasma level and gene polymorphism of angiotensin-converting enzyme in relation to myocardial infarction.

BackgroundThe angiotensin-converting enzyme (ACE) plays an important role in the production of angiotensin II and the degradation of bradykinin, two peptides involved in cardiovascular homeostasy. Presence of a polymorphism in the ACE gene (ACE Ss) has been postulated from segregation analysis of plasma ACE in families. This putative polymorphism, which strongly affects the plasma and cellular levels of ACE, probably by modulating ACE gene transcription, has not yet been identified at the molecular level; however, an insertion/ deletion polymorphism is present in the 16th intron of the ACE gene (ACE I/D) and appears to be a very good marker for ACE Ss. The biological role of ACE suggests that the ACE gene polymorphism could affect the predisposition to myocardial infarction (MI). Methods and ResultsWe have recently shown, in a large case-control study (ECTIM), that the marker allele D of the ACE gene, which is associated with higher levels of ACE in plasma and cells, was more frequent in male patients with MI than in control subjects, especially in patients considered at low risk. ACE activity has now been measured from frozen aliquots of plasma in a large subsample of the ECTIM study (n=1086). Plasma ACE level did not differ between patients and control subjects in the older age group (≥55 years) but was higher in patients than in control subjects in the younger age group (<55 years); P<.005 after adjustment on ACE I/D and other risk factors. In patients, plasma ACE levels decreased with age (R= −.225, P< 10−4), but in control subjects no such trend was observed. In the low-risk group (ApoB <1.25 mg/dL, body mass index <26 kg/m2, and not treated with hypolipidemic drugs), plasma ACE level was increased in patients when compared with control subjects among homozygotes and heterozygotes for the ACE I allele (P<.015). Analysis of the distribution of plasma ACE by using commingling analysis conditional on the marker genotype ACE I/D enabled us to infer the frequencies and effects of the postulated ACE Ss genotypes. The results suggest that the higher plasma ACE levels in patients than in control subjects in the younger age group were due to a difference in frequency of the postulated S allele (.47 versus.36). ConclusionsThese results extend our previous findings and indicate that plasma ACE level may be a risk factor for MI, independent of the ACE I/D polymorphism.

Impact of Prehospital Thrombolysis for Acute Myocardial Infarction on 1-Year Outcome Results From the French Nationwide USIC 2000 Registry

Background—Limited data are available on the impact of prehospital thrombolysis (PHT) in the “real-world” setting. Methods and Results—Of 443 intensive care units in France, 369 (83%) prospectively collected all cases of infarction (≤48 hours of symptom onset) in November 2000; 1922 patients (median age, 67 years; 73% men) with ST-segment–elevation infarction were included, of whom 180 (9%) received intravenous thrombolysis before hospital admission (PHT). Patients with PHT were younger than those with in-hospital thrombolysis, primary percutaneous interventions, or no reperfusion therapy. Median time from symptom onset to hospital admission was 3.6 hours for PHT, 3.5 hours for in-hospital lysis, 3.2 hours for primary percutaneous interventions, and 12 hours for no reperfusion therapy. In-hospital death was 3.3% for PHT, 8.0% for in-hospital lysis, 6.7% for primary percutaneous interventions, and 12.2% for no reperfusion therapy. One-year survival was 94%, 89%, 89%, and 79%, respectively. In a multivariate analysis of predictors of 1-year survival, PHT was associated with a 0.49 relative risk of death (95% CI, 0.24 to 1.00; P=0.05). When the analysis was limited to patients receiving reperfusion therapy, the relative risk of death for PHT was 0.52 (95% CI, 0.25 to 1.08; P=0.08). In patients with PHT admitted in ≤3.5 hours, in-hospital mortality was 0% and 1-year survival was 99%. Conclusions—The 1-year outcome of patients treated with PHT compares favorably with that of patients treated with other modes of reperfusion therapy; this favorable trend persists after multivariate adjustment. Patients with PHT admitted very early have a very high 1-year survival rate.

Genetic variation at the beta-fibrinogen locus in relation to plasma fibrinogen concentrations and risk of myocardial infarction. The ECTIM Study.

Increased plasma fibrinogen concentration is a major cardiovascular risk factor. Conflicting results on genetic variations in plasma fibrinogen levels have been reported. Furthermore, whether fibrinogen genotype is associated with the risk of ischemic heart disease has not been studied so far. An HaeIII restriction fragment length polymorphism of the beta-fibrinogen gene was used in a case-control study to investigate the genetic variation at this locus in relation to plasma fibrinogen concentrations and the risk of myocardial infarction (MI). Five hundred thirty-three male patients aged 27-66 years and 648 control subjects were recruited from four World Health Organization MONICA centers in Northern Ireland and in France. The absence of the HaeIII cutting site (H2 allele) was associated with a significant rise in fibrinogen concentrations in both patients and control subjects. The effect of the HaeIII polymorphism on plasma fibrinogen levels did not significantly differ between centers. Fibrinogen levels were higher in smokers than in nonsmokers. The difference between the two groups was larger in subjects with the genotype H2H2 than in those with either genotype H1H1 or H1H2, regardless of the case-control status. However, there was no significant interaction between smoking status and genotype in their effects on variance in fibrinogen levels, whereas fibrinogen levels. HaeIII genotype accounted for approximately 1% of the total variance in fibrinogen levels, whereas smoking and age together explained 7% and 5% in control subjects and patients, respectively. The frequency of the H2 allele was 0.21 in control subjects and 0.19 in patients.(ABSTRACT TRUNCATED AT 250 WORDS)

Impact of Type of Preadmission Sulfonylureas on Mortality and Cardiovascular Outcomes in Diabetic Patients with Acute Myocardial Infarction

BACKGROUND The impact of antidiabetic medications on clinical outcomes in patients developing acute myocardial infarction (MI) is controversial. We sought to determine whether in-hospital outcomes in patients who were on sulfonylureas (SUs) when they developed their MIs differed from that of diabetic patients not receiving SUs and whether clinical outcomes were related to the pancreatic cells specificity of SUs. METHODS AND RESULTS We analyzed the outcomes of the 1310 diabetic patients included in the nationwide French Registry of Acute ST-Elevation and Non-ST-Elevation Myocardial Infarction in 2005. Medications used before the acute episode were recorded. In-hospital complications were analyzed according to prior antidiabetic treatment. Mortality was lower in patients previously treated with SUs (3.9%) vs. those on other oral medications (6.4%), insulin (9.4%), or no medication (8.4%) (P = 0.014). Among SU-treated patients, in-hospital mortality was lower in patients receiving pancreatic cells-specific SUs (gliclazide or glimepiride) (2.7%), compared with glibenclamide (7.5%) (P = 0.019). Arrhythmias and ischemic complications were also less frequent in patients receiving gliclazide/glimepiride. The lower risk in patients receiving gliclazide/glimepiride vs. glibenclamide persisted after multivariate adjustment (odds ratio 0.15; 95% confidence interval 0.04-0.56) and in propensity score-matched cohorts. CONCLUSION In this nationwide registry of patients hospitalized for acute MI, no hazard was associated with the use of SUs before the acute episode. In addition, patients previously receiving gliclazide/glimepiride had improved in-hospital outcomes, compared with those on glibenclamide.

Improved outcome of cardiogenic shock at the acute stage of myocardial infarction: a report from the USIK 1995, USIC 2000, and FAST-MI French Nationwide Registries

AIM The historical evolution of incidence and outcome of cardiogenic shock (CS) in acute myocardial infarction (AMI) patients is debated. This study compared outcomes in AMI patients from 1995 to 2005, according to the presence of CS. METHOD AND RESULTS Three nationwide French registries were conducted 5 years apart, using a similar methodology in consecutive patients admitted over a 1-month period. All 7531 AMI patients presenting ≤48 h of symptom onset were included. The evolution of mortality was compared in the 486 patients with CS vs. those without CS. The incidence of CS tended to decrease over time (6.9% in 1995; 5.7% in 2005, P = 0.07). Thirty-day mortality was considerably higher in CS patients (60.9 vs. 5.2%). Over the 10-year period, mortality decreased for both patients with (70-51%, P = 0.003) and without CS (9-4%, P < 0.001). In CS patients, the use of percutaneous coronary intervention (PCI) increased from 20 to 50% (P < 0.001). Time period was an independent predictor of early mortality in CS patients (OR for death, 2005 vs. 1995 = 0.45; 95% CI: 0.27-0.75, P = 0.005), along with age, diabetes, and smoking status. When added to the multivariate model, PCI was associated with decreased mortality (OR = 0.38; 95% CI: 0.24-0.58, P < 0.001). In propensity-score-matched cohorts, CS patients with PCI had a significantly higher survival. CONCLUSIONS Cardiogenic shock remains a clinical concern, although early mortality has decreased. Improved survival is concomitant with a broader use of PCI and recommended medications at the acute stage. Beyond the acute stage, however, 1-year survival has remained unchanged.

Specific profile and referral bias of rehabilitated patients after an acute coronary syndrome.

PURPOSE Cardiac rehabilitation after acute coronary syndrome is an important but underused therapeutic intervention. The aim of the French nationwide PREVENIR survey was to improve knowledge on the management of cardiovascular risk factors, especially during cardiac rehabilitation after acute coronary syndrome. The purpose of this study was to specify the characteristics of patients referred to cardiac rehabilitation. METHODS The survey was performed in 77 of 501 (15.4%) public or private French coronary care units. All French regions were involved. All the patients admitted to the hospital during January 1998 who survived an acute coronary syndrome were included in the survey. Data on rehabilitation practice were collected from patient medical records, either during an outpatient consultation or from the patient and the general practitioner during the 6-month follow-up period. RESULTS Of the 1394 patients included in the study (779 with myocardial infarction and 615 with unstable angina), only 310 (22%) underwent cardiac rehabilitation. Significant differences in patient characteristics were found between the cardiac rehabilitation and non-cardiac rehabilitation groups, respectively, in terms of gender (82% male vs 68%; P <.001), age younger than 65 years (56% vs 39%; P <.001), type of acute coronary syndrome (75% myocardial infarction vs 50%; P <.001), left ventricular ejection fraction less than 35% (6% vs 13%; P <.0004), and prevalence of percutaneous intervention (54% vs 46%; P <.02). Two risk factors were more common in the rehabilitated group: dyslipidemia (52% vs 44%; P <.02) and current smoking (51% vs 37%; P <.0001). In the multivariate analysis, female gender (odds ratio [OR], 0.6; 95% confidence interval [CI], 0.44-0.87) and older age (>75 years vs. <65 years; OR, 0.40; 95% CI, 0.3-0.7) predicted decreased cardiac rehabilitation prescription. Conversely, previous history of dyslipidemia (OR,1.4; 95% CI, 1.04-1.8), post-myocardial infarction (OR, 2.8; 95% CI, 2.13-3.89), and a percutaneous intervention (OR,1.9; 95% CI, 1.3-2.7) predicted increased cardiac rehabilitation prescription. Severe left ventricular impairment (< or =35% vs >50%) was not an independent factor for cardiac rehabilitation prescription. At 6-month follow-up assessment, rehabilitation patients had a lower rate of hypertension (18% vs 27%), elevated low-density lipoprotein cholesterol (54% vs 62%), and continued smoking (34% vs 50%). CONCLUSIONS The results of the PREVENIR survey underscore the low level of cardiac rehabilitation prescription in France, and the relative exclusion of women and elderly people. Among the risk factors, dyslipidemia and current smoking are more frequent among rehabilitated patients. These findings may help to modify the strategy for using cardiac rehabilitation after acute coronary syndrome, although it is an effective intervention for secondary prevention.

Major impact of admission glycaemia on 30 day and one year mortality in non-diabetic patients admitted for myocardial infarction: results from the nationwide French USIC 2000 study

Objective: To analyse the short and long term prognostic significance of admission glycaemia in a large registry of non-diabetic patients with acute myocardial infarction. Methods: Assessment of short and long term prognostic significance of admission blood glucose in a consecutive population of 1604 non-diabetic patients admitted to intensive care units in France in November 2000 for a recent (⩽ 48 hours) myocardial infarction. Results: In-hospital mortality, compared with that of patients with admission glycaemia below the median value of 6.88 mmol/l (3.7%), rose gradually with each of the three upper sextiles of glycaemia: 6.5%, 12.5% and 15.2%. Conversely, one year survival decreased from 92.5% to 88%, 83% and 75% (p < 0.001). Admission glycaemia remained an independent predictor of in-hospital and one year mortality after multivariate analyses accounting for potential confounders. Increased admission glycaemia also was a predictor of poor outcome in all clinical subsets studied: patients without heart failure on admission, younger and older patients, patients with or without reperfusion therapy, and patients with or without ST segment elevation. Conclusion: In non-diabetic patients, raised admission blood glucose is a strong and independent predictor of both in-hospital and long term mortality.