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Objective: To assess the relationship between osteoprotegerin (OPG) and cardiovascular death, and the pathobiological mechanisms contributing to the association, in acute coronary syndromes (ACS).Design: Prospective observational.Setting: Biomarker substudy of MERLIN-TIMI 36, a randomised, placebo controlled trial of ranolazine in non-ST elevation (NSTE)-ACS.Patients: 4463 patients with NSTE-ACS.Interventions: Ranolazine or placebo.Main Outcome Measures: Incidence of cardiovascular death (CV death); additionally, heart failure (HF), cardiac arrhythmias, in-hospital ischaemia, severe recurrent ischaemia or recurrent myocardial infarction (MI).Results: During a median follow-up of 341 days, 208 patients died of cardiovascular causes. The OPG baseline concentration was strongly associated with both 30 day and 1 year incidence of CV death. After adjustment for conventional risk markers, OPG concentrations (log transformed) remained a significant predictor of CV death by 30 days (HR (95% CI) 2.32 (1.30 to 4.17); p=0.005) and by 1 year (HR 1.85 (1.33 to 2.59); p<0.001). Baseline levels of OPG were also an independent predictor of new or worsening HF at 30 days (HR 2.25 (1.38 to 3.69); p=0.001) and 1 year (HR 1.81 (1.26 to 2.58) p=0.001). By univariable analysis, higher OPG was associated with both early ischaemic and arrhythmic events. Although OPG levels were associated with recurrent MI within 12 months, this association was attenuated and no longer significant after multivariable adjustment.Conclusions: OPG is independently associated with 30 day and 1 year risk of cardiovascular mortality and HF development after NSTE-ACS. As no independent relationship between OPG levels and recurrent ischaemia or MI was observed, myocardial dysfunction may be a more important stimulus for OPG production than ischaemia in ACS. [ABSTRACT FROM AUTHOR]

Background: Echocardiography and B-type natriuretic peptide (BNP) are diagnostic tests for congestive heart failure (CHF), but an emergency diagnosis can be difficult. Objective: To assess the diagnostic performance of BNP testing and echocardiographic assessment of left ventricular systolic function, separately and combined, for the identification of CHF in patients with acute dyspnea. Design: Prospective, multinational, multicenter study. Setting: Patients presenting to emergency departments in seven hospitals between June 1999 and December 2000. Patients: A total of 1,586 patients with acute dyspnea. Main Outcome Measures: Echocardiographic determination of ejection fraction (EF) and point-of care BNP measurement for the diagnosis of CHF. Results: Seven hundred nine of the 1,586 patients underwent echocardiography; 492 patients (69.4%) had a final diagnosis of CHF. Patients with CHF were older (68.5 years vs 61.6 years, p < 0.0001), had a lower EF (39.5% vs 56.1%, p < 0.0001), and a higher BNP (683 pg/mL vs 129 pg/mL, p < 0.0001) than patients without CHF. Area under the receiver operating characteristic (ROC) curve for the diagnosis of CHF was significantly higher for BNP (0.89) than for EF (0.78; area under the ROC curve difference, 0.12; p < 0.0001). The sensitivity of BNP > or = 100 pg/mL for the diagnosis of CHF was 89%, and specificity was 73%. Values for EF < or = 50% had a sensitivity of 70% and a specificity of 77%. Multivariate logistic regression analysis showed that, in combination with clinical, ECG, and chest radiograph data, BNP > or = 100 pg/mL and EF < or = 50% remained independent predictors of CHF (odds ratios, 32.1 and 6.2, respectively). The proportions of patients who were correctly classified were 67% for BNP alone, 55% for EF alone, 82% for the two variables together, and 97.3% when clinical, ECG, and chest radiograph data were added. Conclusion: BNP measurement was superior to two-dimensional echocardiographic determination of EF in identifying CHF, regardless of the threshold value. The two methods combined have marked additive diagnostic value. [ABSTRACT FROM AUTHOR]

Investigates the diagnostic and biological significance of anti-p41 IgM antibodies against Borrelia burgdorferi. Identification of anti-p41 IgM antibodies in patients; Analysis of anti-p41 IgM positive sera for reactivity against Treponema Pallidum; Immobilization of Borrelia afzelii through sera with IgM antibodies.

Purpose The purpose of this study was to determine whether circulating N-terminal pro-atrial natriuretic peptide (N-ANP) levels predict left ventricular hypertrophy in the general population after adjustment for relevant risk factors.Method and Results In a population-based sample of 3287 subjects aged 25–85 years, circulating N-ANP was measured in a subgroup of 389 subjects. Left ventricular mass and ejection fraction were determined by two-dimensional guided M-mode echocardiography. Left ventricular hypertrophy was defined as height adjusted mass above 145·5g.m−1and 125·4g.m−1, in men and women, respectively. Fifty-one subjects with left ventricular hypertrophy had significantly higher N-ANP levels than controls (1075 vs 763pmol.l−1;P<0·0001). A gradually increasing prevalence of left ventricular hypertrophy over increasing 500pmol.l−1intervals of N-ANP was observed (1·8 to 64·3%; (Chi-squaredPfor trend <0·001). N-ANP was an independent predictor of left ventricular hypertrophy after adjustment for ejection fraction, body mass index, hypertension, valvular disease, a history of myocardial infarction, gender, and age. The adjusted odds ratio for left ventricular hypertrophy was 1·79 (95% CI 1·04–3·07) for a 500pmol.l−1increase in N-ANP. A substantial proportion of subjects with elevated N-ANP levels had combined left ventricular hypertrophy and left ventricular dysfunction.Conclusion These results suggests that N-ANP is an independent predictor of left ventricular hypertrophy in the general population. N-ANP determination is, however, poorly suited to distinguish between subjects with isolated left ventricular hypertrophy and left ventricular dysfunction with or without left ventricular hypertrophy. [ABSTRACT FROM PUBLISHER]

OBJECTIVES--(a) To assess the relation between plasma concentrations of proatrial natriuretic factor (1-98) and non-invasively derived indices of left ventricular systolic and diastolic performance and (b) to assess the potential confounding effect of renal function and age on this relation in patients with acute myocardial infarction. DESIGN--Cross sectional comparison of biochemical and echocardiographic indices of cardiac function. SETTING--Norwegian central hospital. PATIENTS--Sixty four patients with acute myocardial infarction. MAIN OUTCOME MEASURES--Relation between plasma proatrial natriuretic factor (1-98) concentrations and echocardiographic indices of left ventricular systolic function as assessed by univariate and multivariate linear regression analysis. Sensitivity and specificity of plasma proatrial natriuretic factor (1-98) concentration as a measure of left ventricular systolic and diastolic dysfunction. RESULTS--Plasma proatrial natriuretic factor (1-98) concentrations were significantly related to left ventricular ejection fraction (r = -0.33; P = 0.008), age (r = 0.43; P < 0.001), and creatinine clearance (r = - 0.53; P < 0.001). In a multivariate model left ventricular ejection fraction and creatinine clearance were both independently related to plasma values. The mean concentration of proatrial natriuretic factor (1-98) was significantly higher in patients with an ejection fraction of < 40% than in those with an ejection fraction of > or = 40% (1876 (1151) v 1174 (530) pmol/l; P = 0.03) and in patients with an abnormal transmitral E/A ratio ( < 0.65 or > 1.65, where E/A is ratio of peak early filling velocity to peak atrial component) compared with those with a normal ratio (1572 (895) v 1137 (523) pmol/l, respectively; P = 0.02). When patients were subdivided according to the median concentration of proatrial natriuretic factor (1192 pmol/l) the sensitivity and specificity were 89% and 56% respectively for detecting a left ventricular ejection fraction of < 40% and 75% and 61% respectively for detecting an abnormal E/A ratio. Concentrations below the median had a negative predictive value of 97% in excluding an ejection fraction of < 40% and of 84% in excluding an abnormal E/A ratio. CONCLUSION--These results suggest that soon after myocardial infarction left ventricular ejection fraction and indices of renal function are independently related to plasma concentrations of proatrial natriuretic factor (1-98). Plasma concentrations of proatrial natriuretic factor (1-98) seem to reflect renal and cardiac performance rather than specific haemodynamic variables assessed by noninvasive methods. Plasma proatrial natriuretic factor (1-98) measurements may be a useful screening tool to identify patients with normal cardiac function soon after myocardial infarction. [ABSTRACT FROM PUBLISHER]

OBJECTIVES--To assess whether the reduction in left ventricular dilatation after acute myocardial infarction obtained by early administration of angiotensin converting enzyme inhibitors depends on continuous treatment. DESIGN--Prospective observational and cross sectional study of withdrawal of randomised treatment with enalapril or placebo. PATIENTS--106 patients on 6 months trial treatment after an acute myocardial infarction. MAIN OUTCOME MEASURES--Left ventricular volumes and ejection fraction as assessed by echocardiography and circulating proatrial natriuretic factor (1-98) before and 4-6 weeks after withdrawal of treatment. RESULTS--There were no significant changes (mean (SD)) in left ventricular systolic (0.7 (4.7) ml/m2) and diastolic (0.4 (6.6) ml/m2) volume indices, ejection fraction (-0.9 (6)%), and proatrial natriuretic factor (172 (992) pmol/l) after withdrawal of enalapril. The significantly lower left ventricular volumes observed with 6 months of enalapril therapy after acute myocardial infarction, as compared with placebo, were maintained 6 weeks after drug withdrawal. CONCLUSION--The results show that the benefit of 6 months of enalapril treatment initiated early after myocardial infarction is maintained for at least 6 weeks after drug withdrawal, suggesting that the treatment effect on left ventricular structure is not reversed by changes in loading conditions caused by subsequent drug withdrawal. [ABSTRACT FROM PUBLISHER]

OBJECTIVE--To evaluate the prognostic significance of plasma N-terminal pro-atrial natriuretic factor (1-98) concentrations measured in the subacute phase after acute myocardial infarction, and to compare the predictive value of measurement of N-terminal pro-atrial natriuretic factor (1-98) with the measurement of atrial natriuretic factor (99-126) and with clinical assessment of the degree of heart failure. DESIGN--Prospective observational. SETTING--Norwegian central hospital. PATIENTS--139 patients (mean (SD) age 66.9 (11.1) years, 71.2% males) with acute myocardial infarction. Patients in cardiogenic shock or with severe heart failure (New York Heart Association class IV) were excluded. MAIN OUTCOME MEASURE--Cardiovascular death within 12 months. RESULTS--During the follow up period 15 patients died. In a univariate Cox proportional hazards model N-terminal pro-atrial natriuretic factor (1-98) was significantly related to mortality (p = 0.0003). In a multivariate model the prognostic value of N-terminal pro-atrial natriuretic factor (1-98) was better than that of atrial natriuretic factor (99-126) and clinical assessment of heart failure (N-terminal pro-atrial natriuretic factor (1-98), p = 0.0003; atrial natriuretic factor (99-126), p = 0.4513; heart failure, p = 0.0719). The odds ratio estimate of patients in whom plasma concentrations of N-terminal pro-atrial natriuretic factor (1-98) were greater than 2000 pmol/l was 25 (95% confidence interval 2.8-225.0) compared with patients with plasma concentrations less than 1000 pmol/l. CONCLUSIONS--These results suggest that determination of plasma N-terminal pro-atrial natriuretic factor (1-98) in the subacute phase of myocardial infarction may provide clinically relevant prognostic information that is superior to that obtained from atrial natriuretic factor (99-126) measurements and clinical evaluation. [ABSTRACT FROM PUBLISHER]

Abstract Background Cardiovascular disease is prevalent and frequently unrecognized in patients with chronic obstructive pulmonary disease (COPD). NT-proBNP is an established risk factor in patients with heart failure. NT-proBNP may also be released from the right ventricle. Thus serum NT-proBNP may be elevated during acute exacerbations of COPD (AECOPD). The prognostic value of NT-proBNP in patients hospitalized with AECOPD is sparsely studied. Our objective was to test the hypothesis that NT-proBNP independently predicts long term mortality following AECOPD. Methods A prospective cohort study of 99 patients with 217 admissions with AECOPD. Clinical, electrocardiographic, radiological and biochemical data were collected at index and repeat admissions and analyzed in an extended survival analysis with time-dependent covariables. Results Median follow-up time was 1.9 years, and 57 patients died during follow-up. NT-proBNP tertile limits were 264.4 and 909 pg/mL, and NT-proBNP in tertiles 1 through 3 was associated with mortality rates of 8.6, 35 and 62 per 100 patient-years, respectively (age-adjusted log-rank p Conclusions NT-proBNP is a strong and independent determinant of mortality after AECOPD.

Abstract Background A high-sensitivity cardiac troponin T (hs-cTnT) concentration above the 99th percentile (i.e. 14 ng/L) is common during Acute Exacerbation of Chronic Obstructive Pulmonary Disease (AECOPD) and associated with increased mortality. The objective of the study was to identify factors associated with hs-cTnT levels during AECOPD. Methods We included 99 patients with AECOPD on admission. As 41 patients had one or more repeat admissions, there were 202 observations in the final analysis. We recorded clinical and biochemical data, medication, spirometry, chest radiographs, and ECGs. The data were analysed for cross-sectional and longitudinal associations using ordinary least square as well as linear mixed models with the natural logarithm of hs-cTnT as the dependent variable. Results Mean age at inclusion was 71.5 years, mean FEV1/FVC was 45%, and median hs-cTnT was 27.0 ng/L. In a multivariable model there was a 24% increase in hs-cTnT per 10 years increase in age (p Conclusion Age, arterial hypertension, tachycardia, and serum creatinine are independently associated with the level of hs-cTnT on admission for AECOPD.

Abstract Background Obstructive sleep apnea (OSA) is a common yet underdiagnosed condition. The aim of our study is to test whether prediabetes and type 2 diabetes are associated with obstructive sleep apnea (OSA) in extremely obese (BMI ≥ 40 kg/m2) subjects. Methods One hundred and thirty seven consecutive extremely obese patients (99 females) from a controlled clinical trial [MOBIL-study (Morbid Obesity treatment, Bariatric surgery versus Intensive Lifestyle intervention Study) (ClinicalTrials.gov number NCT00273104)] underwent somnography with Embletta® and a 2-hour oral glucose tolerance test (OGTT). OSA was defined by an apnea-hypopnea index (AHI) ≥ 5 events/hour. Patients were categorized into three groups according to criteria from the American Diabetes Association: normal glucose tolerance, pre-diabetes and type 2 diabetes. Multiple logistic regression analysis was used to identify possible determinants of OSA. Results The patients had a mean (SD) age of 43 (11) years and a body mass index (BMI) of 46.9 (5.7) kg/m2. Males had significantly higher AHI than females, 29 (25) vs 12 (17) events/hour, p < 0.001. OSA was observed in 81% of men and in 55% of women, p = 0.008. Twenty-nine percent of subjects had normal glucose tolerance, 42% had pre-diabetes and 29% had type 2 diabetes. Among the patients with normal glucose tolerance 33% had OSA, while 67% of the pre-diabetic patients and 78% of the type 2 diabetic patients had OSA, p < 0.001. After adjusting for age, gender, BMI, high sensitive CRP and HOMA-IR, both pre-diabetes and type 2 diabetes were still associated with OSA, odds ratios 3.18 (95% CI 1.00, 10.07), p = 0.049 and 4.17 (1.09, 15.88), p = 0.036, respectively. Mean serum leptin was significantly lower in the OSA than in the non-OSA group, while other measures of inflammation did not differ significantly between groups. Conclusions Type 2 diabetes and pre-diabetes are associated with OSA in extremely obese subjects. Trial registration MOBIL-study (Morbid Obesity treatment, Bariatric surgery versus Intensive Lifestyle intervention Study) (ClinicalTrials.gov number NCT00273104)

Abstract Background Cardiac Troponin T (cTnT) elevation during exacerbations of chronic obstructive pulmonary disease (COPD) is associated with increased mortality the first year after hospital discharge. The factors associated with cTnT elevation in COPD are not known. Methods From our hospital's database, all patients admitted with COPD exacerbation in 2000–03 were identified. 441 had measurement of cTnT performed. Levels of cTnT ≥ 0.04 μg/l were considered elevated. Clinical and historical data were retrieved from patient records, hospital and laboratory databases. Odds ratios for cTnT elevation were calculated using logistic regression. Results 120 patients (27%) had elevated cTnT levels. The covariates independently associated with elevated cTnT were increasing neutrophil count, creatinine concentration, heart rate and Cardiac Infarction Injury Score (CIIS), and decreasing hemoglobin concentration. The adjusted odds ratios (95% confidence intervals in parentheses) for cTnT elevation were 1.52 (1.20–1.94) for a 5 × 106/ml increase in neutrophils, 1.21 (1.12–1.32) for a 10 μmol/l increase in creatinine, 0.80 (0.69–0.92) for a 1 mg/dl increase in hemoglobin, 1.24 (1.09–1.42) for a 10 beats/minute increase in heart rate and 1.44 (1.15–1.82) for a 10 point increase in CIIS. Conclusion Multiple factors are associated with cTnT elevation, probably reflecting the wide panorama of comorbid conditions typically seen in COPD. The positive association between neutrophils and cTnT elevation is compatible with the concept that an exaggerated inflammatory response in COPD exacerbation may predispose for myocardial injury.