Ilan Raymond

NT‐proBNP and the diagnosis of heart failure: a pooled analysis of three European epidemiological studies

Many studies have shown that the B‐type natriuretic peptides (BNP and NT‐proBNP) are proven diagnostic markers for heart failure due to left ventricular systolic dysfunction. The manner in which they are to be used is still being unravelled; most single centre studies have chosen the best concentration of the peptide on ROC analysis as their cut‐point resulting in numerous different values for both BNP and NT‐proBNP appearing in the literature. We report a different approach of defining an age and sex corrected abnormal concentration for NT‐proBNP, derived from normal individuals within a large sample of 3051 subjects pooled from three European epidemiology studies and applying that to the entire population to detect HF and LVD. Three thousand and fifty one subjects were studied. Of these 10% (305) had significant LVD and 3.1% (94) had HF. The median concentrations of NT‐proBNP (IQR) in normals, those with LVD and in heart failure subjects were 20 pg/ml (10.30), 117.3 pg/ml (28.145) and 269.6 pg/ml (54.323), P<0.001, respectively. The area under the ROC curve for NT‐proBNP for the detection of ‘heart failure’ was 0.85 and 0.69 for LVD. NT‐proBNP was an independent predictor of the presence of HF on multivariate analysis. An abnormal NT‐proBNP was defined as being >95th centile for normals, age and sex corrected, and diagnosed HF with a sensitivity of 75% and a negative predictive value of 99%. In an additional analysis in a breathless subgroup of our population, in 30% a raised NT‐proBNP concentration could be explained by HF due to LVD, in another 64% the high BNP level was associated with some other structural of functional cardiac abnormality or renal impairment. We were unable to assign a possible cause to the high NT‐proBNP values in 5.9% of this breathless subgroup of the population. An abnormal NT‐proBNP concentration is an accurate diagnostic test both for the exclusion of HF in the population and in ruling out LVD in breathless subjects. An elevated NT‐proBNP merely indicates the presence of ‘cardio‐renal distress’ and should prompt referral for further investigation.

IGF1 as predictor of all cause mortality and cardiovascular disease in an elderly population.

BACKGROUND IGF1 is believed to influence ageing and development of cardiovascular disease (CVD) through complex mechanisms. Reduced IGF1 levels might be causally associated with conditions accompanying ageing including development of CVD. However, in animal models reduced GH-IGF1 signalling increases lifespan. Reduced IGF1 activity might also be associated with longevity in humans. OBJECTIVE The objective was to investigate if plasma IGF1 levels were associated with all cause mortality, and the development of chronic heart failure (CHF) and a major CV event. PATIENTS AND DESIGN A population based study of 642 individuals, aged 50-89 years. Development of CHF was evaluated in 576 individuals with normal systolic function assessed by echocardiography and without the history of CHF or myocardial infarction. Development of the first major CV event was evaluated in 504 individuals with normal systolic function and without prevalent CVD. Outcomes were ascertained after 5 years using hospital discharge diagnoses. RESULTS Adjustment for risk factors IGF1 values in the fourth quartile versus values below the fourth quartile was associated with increased mortality (n=103), hazard ratio (HR) 1.52 (95% confidence interval (CI) 1.01-2.28; P=0.044). IGF1 in the fourth quartile was also independently associated with risk of development of CHF (n=19), HR 5.02 (95% CI 2.00-12.64; P=0.001) but showed no association with the overall incidence of major CV events (n=58), HR 1.05 (95% CI 0.59-1.90; P=0.861). CONCLUSIONS High IGF1 levels were independently associated with increased all cause mortality and risk of development of CHF, whereas no relation with the overall incidence of CVD was observed.

Biomarkers of endothelial dysfunction are elevated and related to prognosis in chronic heart failure patients with diabetes but not in those without diabetes

Biomarkers of endothelial dysfunction, such as soluble E‐selectin, and von Willebrand factor (vWf) are elevated in patients with chronic heart failure (CHF). The impact of diabetes mellitus (DM) on these biomarkers, and their relation to prognosis remains unknown.

Echocardiographic indices of left ventricular diastolic dysfunction in 647 individuals with preserved left ventricular systolic function

Knowledge about the occurrence of isolated diastolic dysfunction (DD) in the general population is limited.

The Frederiksberg Heart Failure Study: Rationale, Design and Methodology, with Special Emphasis on the Sampling Procedure for the Study Population and Its Comparison to the Background Population

Background/Objective: The aim of the Frederiksberg Heart Failure Study was to describe the epidemiology of heart failure in the general population among persons older than 50 years. This paper describes some aspects of the methodology of this study, especially regarding population sampling. Methods: From 1997 to 2000, a random sample of 1,088 women and men aged 50–89 years from the municipality of Frederiksberg (city of Copenhagen, Denmark) were invited to participate in the study; 764 subjects (70.2%) were examined (57% female). To optimize scientific information across age groups, we used age-stratified sampling, attempting to have at least 150 subjects in each age decade, i.e. 50–59 years (n = 240), 60–69 years (n = 208), 70–79 years (n = 190) and 80–89 years (n = 126). Each participant filled in a questionnaire and was submitted to an echocardiographic examination, an ECG and collection of blood samples. The group of invited subjects (divided into participants and nonparticipants) was compared with the background population with regard to hospital admissions due to cardiovascular diseases and mortality 1 year before and 1 year after sampling. Results: As a result of the sampling strategy, the sampling proportion increased from 2.86% in the age class 50–59 years to 4.43% in the age class 80–89 years, with no evidence of a sex difference. The participation proportion systematically decreased with age, from 75.2% in the age class 50–59 years to 57.5% in the age class 80–89 years, with no sex difference. Both participants and nonparticipants had admission rates for cardiovascular diseases similar to that of the background population during the year before sampling. However, the rate of admission was significantly increased (p = 0.025) during the year after the time of sampling, and this applied equally to participants and nonparticipants. The 1-year mortality rate was increased in the sample after sampling (p = 0.014). However, participants had a 1-year mortality rate very close to that of the background population, whereas nonparticipants had a 1-year mortality rate more than three times higher than that of the participants (p < 0.001). In terms of methodology, the echocardiographic assessment was examined as follows: the interobserver variability between two independent observers in measuring the ejection fraction by means of echocardiography was calculated, and overall agreement was found to be 93.2% (kappa value = 0.786), corresponding to a very good level of agreement. The interobserver coefficient of variation was 4.9%. Conclusion: In this population-based study, the increased mortality and admission rates among nonparticipants suggest that subjects who agree to participate in a study on heart failure are a biased sample, in that they represent relatively healthy subjects. The fact that the participation rate declined with age indicates a systematic age effect in this bias. Standard methods to assess how representative of the corresponding background population a study population is should be agreed upon for future studies.

α-Defensins and outcome in patients with chronic heart failure.

α‐Defensins are part of the innate immune system. Low‐grade inflammation seems to play a crucial role in development and progression of chronic heart failure (CHF). The aims of the present study were to compare plasma levels of α‐defensins in CHF patients and healthy controls and to examine the predictive ability of α‐defensins, alone and combined with N‐terminal pro brain natriuretic peptide (NT‐proBNP), with respect to all‐cause mortality.

Long-term L-Triiodothyronine (T3) treatment in stable systolic heart failure patients: a randomised, double-blind, cross-over, placebo-controlled intervention study

Chronic heart failure (HF) is characterized by reduced serum T3 levels and increased activity of the T3 degrading enzyme deiodinase D3. This may result in an intracellular composition of the cardiomyocyte mimicking that of hypothyroidism. Short‐term T3‐administration to systolic HF patients might be beneficial.

Plasma calprotectin levels reflect disease severity in patients with chronic heart failure

Background: Low-grade inflammation has been associated with cardiovascular disease (CVD) and chronic heart failure (CHF). The aim of the present study was to investigate the potential usefulness of the inflammatory protein calprotectin as a biomarker in CHF. Methods: Plasma calprotectin was measured in 193 CHF patients with left ventricular function <45% and in 100 healthy controls at baseline. Patients with CHF were followed for a median period of 2.6 years according to mortality. Results: The levels of plasma calprotectin were significantly increased in the CHF patients compared to the control group (P < 0.01), primarily due to elevated levels in the patients with New York Heart Association (NYHA) class III and IV. Furthermore, plasma calprotectin was a superior biomarker of high NYHA classes than other parameters reflecting CHF severity, OR 2.2 (1.1–4.3) (P = 0.019). After the follow-up period, 46 patients had died. Plasma calprotectin levels did not predict mortality in CHF patients. Conclusions: Plasma calprotectin is increased in CHF patients, indicating that inflammatory activity is upregulated in CHF and may be associated with the severity of CHF.

Biochemical Cardiac Risk Markers in the General Population, Hypertension and Coronary Artery Disease

Recently there has been a growing interest in risk assessment of individuals, using biochemical markers of cardiac risk, with an increasing focus on a multi‐marker strategy. Natriuretic peptides (BNP and NT‐proBNP) are well‐established markers of increased risk in the general population and in high‐risk groups with hypertension, and coronary heart disease. However, there is at present no indication for routine measurements of natriuretic peptides in the risk assessment of individuals or patients, as there is no evidence for subsequent therapeutic initiatives. Natriuretic peptides are useful when screening for heart failure in symptomatic individuals. However, the use of NT‐proBNP screening for risk or left ventricular systolic dysfunction in the general population is still a matter of debate.