Jean-Claude Beer

Relation Between Body Mass Index, Waist Circumference, and Death After Acute Myocardial Infarction

Background— An elevated body mass index (BMI) has been reported to be associated with a lower rate of death after acute myocardial infarction (AMI). However, waist circumference (WC) may be a better marker of cardiovascular risk than BMI. We used data from a contemporary French population-based cohort of patients with AMI to analyze the impact of WC and BMI on death rates. Methods and Results— We evaluated 2229 consecutive patients with AMI. Patients were classified according to BMI as normal, overweight, obese, and very obese (BMI <25, 25 to 29.9, 30 to 34.5, and >35 kg/m2, respectively) and as increased waistline (WC >88/102 cm for women/men) or normal. Half of the patients were overweight (n=1044), and one quarter were obese (n=397) or very obese (n=128). Increased WC was present in half of the patients (n=1110). Increased BMI was associated with a reduced death rate, with a 5% risk reduction for each unit increase in BMI (hazard ratio, 0.95; 95% CI, 0.93 to 0.98; P<0.001). In contrast, WC as a continuous variable had no impact on all-cause death (P=0.20). After adjustment for baseline predictors of death, BMI was not independently predictive of death. The group of patients with high WC but low BMI had increased 1-year death rate. Conclusions— Neither BMI nor WC independently predicts death after AMI. Much of the inverse relationship between BMI and the rate of death after AMI is due to confounding by characteristics associated with survival. This study emphasizes the need to measure both BMI and WC because patients with a high WC and low BMI are at high risk of death.

Impact of Asymmetric Dimethylarginine on Mortality After Acute Myocardial Infarction

Objective—Asymmetrical dimethylarginine (ADMA) is an endogenous competitive inhibitor of nitric oxide (NO) synthases. From a prospective cohort of patients with acute myocardial infarction (MI), we aimed to analyze the predictive value of circulating ADMA concentrations on prognosis. Methods and Results—Blood samples from 249 consecutive patients hospitalized for acute MI <24 hours were taken on admission. Serum levels of ADMA and its stereoisomer, symmetrical dimethylarginine (SDMA), were determined using high-performance liquid chromatography. The independent predictors of ADMA were glomerular filtration rate, female sex, and SDMA (R2=0. 25). Baseline ADMA levels were higher in patients who had died than in patients who were alive at 1 year follow-up (1.23 [0.98 to 1.56] versus 0.95 [0.77 to 1.20] &mgr;mol/L, P<0.001). By Cox multivariate analysis, the higher tertile of ADMA (median [interquartile range]: 1.45 [1.24 to 1.70] &mgr;mol/L) was a predictor for mortality (Hazard Ratio [95% CI], 4.83 [1.59 to 14.71]), when compared to lower tertiles, even when adjusted for potential confounders, such as acute therapy, biological, and clinical factors. Conclusion—Our study suggests that the baseline ADMA level has a strong prognostic value for mortality after MI, beyond traditional risk factors and biomarkers.

Major prognostic impact of persistent microvascular obstruction as assessed by contrast-enhanced cardiac magnetic resonance in reperfused acute myocardial infarction

The aim of this study was to compare the prognostic significance of microvascular obstruction (MO) and persistent microvascular obstruction (PMO) as assessed by cardiac magnetic resonance (CMR) in patients with acute myocardial infarction (AMI). CMR was performed in 184 patients within the week following successfully reperfused first AMI. First-pass images were performed to evaluate extent of MO and late gadolinium-enhanced images to assess PMO and infarct size (IS). Major adverse cardiac events (MACE) were collected at 1-year follow-up. MO and PMO were found in 127 (69%) and 87 (47%) patients, respectively. By using univariate logistic regression analysis, high Global Registry of Acute Coronary Events (GRACE) risk score (odds ratio [OR] 95% confidence interval [CI]: 3.6 [1.8–7.4], p < 0.001), IS greater than 10% (OR [95% CI]: 2.7 [1.1–6.9], p = 0.036), left ventricular ejection fraction less than 40% (OR [95% CI]: 2.4 [1.1–5.2], p = 0.027), presence of MO (OR [95% CI]: 3.1 [1.3–7.3], p = 0.004) and presence of PMO (OR [95% CI]:10 [4.1–23.9], p < 0.001) were shown to be significantly associated with the outcome. By using multivariate analysis, presence of MO (OR [95% CI]: 2.5 [1.0–6.2], p = 0.045) or of PMO (OR [95% CI]: 8.7 [3.6–21.1], p < 0.001), associated with GRACE score, were predictors of MACE. Presence of microvascular obstruction and persistent microvascular obstruction is very common in AMI patients even after successful reperfusion and is associated with a dramatically higher risk of subsequent cardiovascular events, beyond established prognostic markers. Moreover, our data suggest that the prognostic impact of PMO might be superior to MO.

The free oxygen radicals test (FORT) to assess circulating oxidative stress in patients with acute myocardial infarction.

BACKGROUND AND AIM Reactive oxygen species (ROS) play an important role in the pathogenesis of many diseases including cardiovascular diseases. Several methods have been developed for the direct or indirect measurement of oxygen free radical and its by-products. The current study was designed to validate the new free oxygen radicals test (FORT) and to investigate the potential relationships between ROS and clinical or biological factors in male patients with acute myocardial infarction (AMI). METHODS We analysed FORT values in samples from 66 patients with AMI. RESULTS FORT values ranged from 324 to 1198 FORT units, with a median value of 581 (494-754) FORT units. In univariate analysis, FORT values were positively related only to LVEF <40% (p=0.005), levels of CRP (r=0.438, p<0.001) and peak CK (r=0.274, p=0.028). Multiple linear regression analysis showed that CRP (p=0.023), LVEF <40% (p<0.001) and the presence of diabetes (p=0.039) were independent predictors of serum FORT values. This statistical model can explain 45% of the variance in FORT values (R(2)=0.45). CONCLUSIONS The FORT is a simple tool to assess circulating ROS in routine clinical practice. Oxidative conditions such as inflammation and diabetes are the major determinants of FORT values in patients with AMI.

Impact of chronic oral anticoagulation on management and outcomes of patients with acute myocardial infarction: data from the RICO survey

Objective: To determine the prevalence of chronic oral anticoagulant drug treatment (COA) among patients with acute myocardial infarction (AMI) and its impact on management and outcome. Methods: All patients with ST segment elevation AMI on the RICO (a French regional survey for AMI) database were included in this analysis. COA was defined as continuous use ⩾ 48 hours before AMI. Results: Among the 2112 patients with ST elevation myocardial infarction (STEMI), 93 (4%) patients were receiving COA. These patients were older and more likely to have a history of hypertension, diabetes and prior myocardial infarction than patients without COA. In addition, fewer patients who received COA underwent reperfusion therapy or received an antiplatelet agent (aspirin/thienopyridines). Moreover, patients receiving COA experienced a higher incidence of in-hospital major adverse events (death, recurrent myocardial infarction or major bleeding, p  =  0.005). Multivariate analysis showed that only ejection fraction, current smoking and multiple vessel disease, but not COA, were independent predictive factors for major adverse events. In contrast, COA was an independent predictive factor for heart failure when adjusted for age, diabetes, creatinine clearance, reperfusion, heparin and glycoprotein IIb/IIIa inhibitors (odds ratio 2.06, CI 95% 1.23 to 3.43, p  =  0.005). Conclusion: In this population based registry, patients with STEMI with prior use of COA constituted a fairly large group (4%) with an overall higher baseline risk profile than that of patients without COA. Fewer in the COA group received reperfusion therapy or aggressive antithrombotic treatment and they experienced more adverse in-hospital outcomes. Thus, further studies are warranted to develop specific management strategies for this high risk group.

Beneficial effects of direct call to emergency medical services in acute myocardial infarction.

Objectives: We investigated the impact of an emergency medical services call on the management of acute myocardial infarction, considering time intervals for intervention and revascularization procedures. Methods: Data were prospectively collected from January 2001 to October 2002 from 531 patients hospitalized for myocardial infarction with ST segment elevation and a pre-hospital delay of less than 24 h. Results: Only 26% of patients called the emergency medical services at the onset of symptoms (n=140). Other patients (n=391, 74%) called another medical contact. Baseline characteristics and cardiovascular history were similar in the two groups, except for the percutaneous coronary intervention history (10% in the emergency medical services group versus 4% in the other medical contact group, P<0.05). Time intervals from the onset of symptoms of myocardial infarction to call or to medical intervention, as well as the time interval from medical intervention to hospital admission were significantly shorter in the emergency medical services group. The early reperfusion rate was also significantly greater in the emergency medical services group (77%) compared with the other medical contact group (64%), mainly because of a greater incidence of primary percutaneous coronary intervention (36 versus 26%, P<0.03, respectively). Multivariate analysis adjusted for sex and age showed that less than three medical care providers [odds ratio (OR) 5.042, P<0.001], percutaneous coronary intervention history (OR 2.462, P<0.05), as well as rhythmic disorders (OR 2.105, P<0.05) and complete atrioventricular block (OR 2.757, P<0.05) were independent predictors of emergency medical services care. Conclusion: This study demonstrated that a call to the emergency medical services is underutilized by patients with symptoms of myocardial infarction, and documented the beneficial effects of an emergency medical services call by reducing pre-hospital delays and increasing early revascularization therapies.

Comparative epidemiology of stroke and acute myocardial infarction: the Dijon Vascular Project (DIVA)

Background: Despite a common pathophysiological mechanism (ie, atherosclerosis) and similar vascular risk factors, few reliable studies have compared the epidemiology of stroke and acute myocardial infarction (AMI). Methods: All first ever cases of stroke and AMI in Dijon, France (151 846 inhabitants) from 2001 to 2006 were prospectively recorded. The 30 day case fatality rates (CFRs) and vascular risk factors were assessed in both groups. Results: Over the 6 years, 1660 events (1020 strokes and 640 AMI) were recorded. Crude incidence of stroke was higher than that of AMI (112 vs 70.2/100 000/year; p<0.001). With regard to sex, the relative incidence of stroke compared with AMI was 0.88 (95% CI 0.60 to 1.29; p = 0.51) in women <65 years and 2.32 (95% CI 1.95 to 2.75; p<0.001) in those >65 years whereas it was 0.60 (95% CI 0.42 to 0.86; p<0.001) in men below 55 years, 1.01 (0.81 to 1.24, p = 0.96) in those between 55 and 75 years and 2.01 (95% CI 1.48 to 2.71; p<0.001) at 75 years and older. CFRs at 30 days were similar for stroke and AMI (9.80% vs 9.84%; p = 0.5). Hyperglycaemia (>7.8 mmol/l) at onset was significantly associated with higher CFR in both stroke and AMI patients. The prevalence of male sex, hypercholesterolaemia and diabetes was higher in AMI patients whereas hypertension was more frequent in stroke patients. Conclusion: These findings will help health care authorities to evaluate future needs for stroke and AMI services, and to develop secondary prevention strategies.

Impact of obesity on the prognostic value of the N-terminal pro-B-type natriuretic peptide (NT-proBNP) in patients with acute myocardial infarction

Objective To examine the influence of obesity on the predictive value of the pro-B-type natriuretic peptide (NT-proBNP) assay in acute myocardial infarction. Design Prospective observational study. Setting All intensive care units in one region of France. Patients 2217 consecutive patients admitted for an acute myocardial infarction matched with respect to age, gender, Killip class and renal function. Main outcome measure Cardiovascular death at one year. Results There were three groups (according to body mass index (BMI): obese, overweight and normal) of 739 matched patients. Median levels of NT-proBNP were considerably lower in high BMI patients, by about 20% in overweight and by 60% in obese patients, compared with normal BMI patients. An inverse relationship between the propeptide values and BMI was found in the overall study population (r=−0.20, p<0.0001), and for both genders. In multivariate linear regression, BMI as a continuous variable was a predictor of the log NT-proBNP level, even when adjusted for potential confounders. CV mortality at 1-year follow-up was similar for the three BMI groups (p=0.691). In multivariate logistic regression analysis, log NT-proBNP predicted mortality in normal (OR (95% CI) 3.48 (2.00 to 6.12)) and overweight (OR (95% CI) 3.96 (1.95 to 8.06)) patients, even when adjusted for confounders (GRACE risk score, left ventricular ejection fraction). However, in obese patients, propeptide levels failed to retain their independent prognostic value (OR (95% CI) 1.34 (0.86 to 2.08)). Conclusions In this large population of patients with myocardial infarction, circulating NT-proBNP levels were considerably lower in obese patients; the significance of the propeptide level as an independent prognostic factor is severely compromised.

Factors affecting the management of outcome in elderly patients with acute myocardial infarction particularly with regard to reperfusion : Data from the french regional RICO survey

Background: Acute myocardial infarction (AMI) in elderly patients is often unrecognized and associated with poor prognosis. Objectives: To investigate management and efficacy of reperfusion therapy to the elderly patients with AMI. Methods: From the January 1, 2001 to October 31, 2002, 964 patients with AMI were included in the French regional RICO survey. The patients were divided into three groups: younger (<70 years old), elderly (70–79 years old) and very elderly (≧80 years old). Results: Distribution of groups was 56, 27, and 16%, respectively. The longest time delay to first request for medical attention was found in the very elderly group (30 and 55 vs. 90 min, respectively, p < 0.05). Rate of lysis fell significantly with increasing age (35, 22 and 9%, respectively, p < 0.001) but the time delay to lysis was similar for the 3 groups. The proportion of patients who benefited from primary percutaneaous transluminal coronary angioplasty decreased with age (21, 15, 11%, respectively, p < 0.001), but time delay to balloon angioplasty was similar and no difference in mortality rate was observed between the three groups after reperfusion. The incidence of in-hospital cardiovascular events (cardiogenic shock and recurrent myocardial infarction/ischemia) and in-hospital mortality increased with age (5, 13, 17%, respectively, p < 0.001). Moreover, multivariate analysis showed that only ejection fraction and Killip >1 were independent predictive factors for in-hospital cardiovascular mortality, respectively (OR 5.15, 95% CI 2.08–12.74, p < 0.0001 and OR 3.81, 95% CI 1.90–7.65, p < 0.0001), whereas age, sex, diabetes and anterior location were not significant. Conclusion: Our data in an unselected population indicate that very elderly patients were characterized by increased pre-hospital delays and less frequent utilization of reperfusion therapy, although no difference in the mortality in reperfused patients could be observed between the three age groups.

Atrial Fibrillation Is Associated with a Marker of Endothelial Function and Oxidative Stress in Patients with Acute Myocardial Infarction

Background Atrial fibrillation (AF), whether silent or symptomatic, is a frequent and severe complication of acute myocardial infarction (AMI). Asymmetric dimethylarginine (ADMA), an endogenous eNOS inhibitor, is a risk factor for endothelial dysfunction. We addressed the relationship between ADMA plasma levels and AF occurrence in AMI. Methods 273 patients hospitalized for AMI were included. Continuous electrocardiographic monitoring (CEM) ≥48 hours was recorded and ADMA was measured by High Performance Liquid Chromatography on admission blood sample. Results The incidence of silent and symptomatic AF was 39(14%) and 29 (11%), respectively. AF patients were markedly older than patients without AF (≈ 20 y). There was a trend towards higher ADMA levels in patients with symptomatic AF than in patients with silent AF or no AF (0.53 vs 0.49 and 0.49 μmol/L, respectively, p = 0.18,). After matching on age, we found that patients with symptomatic AF had a higher heart rate on admission and a higher rate of patients with LV dysfunction (28% vs. 3%, p = 0.025). Patients who developed symptomatic AF had a higher ADMA level than patients without AF (0.53 vs. 0.43 μmol/L; p = 0.001). Multivariate logistic regression analysis to estimate symptomatic AF occurrence showed that ADMA was independently associated with symptomatic AF (OR: 2.46 [1.21–5.00], p = 0.013) beyond history of AF, LVEF<40% and elevated HR. Conclusion We show that high ADMA level is associated with the occurrence of AF. Although no causative role can be concluded from our observational study, our work further supports the hypothesis that endothelial dysfunction is involved in the pathogenesis of AF in AMI.