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Our aim was to investigate the associations between B-type natriuretic peptide (NT-proBNP), troponin T (TnT) and C-reactive protein (CRP) and changes in left ventricular function and size after acute coronary syndrome.In 119 patients admitted for non-ST-elevation acute coronary syndrome, echocardiography and blood sampling were performed prior to coronary angiography. Echocardiography was repeated at follow-up after 8 ± 3 months. Left ventricular function was assessed by speckle tracking echocardiography. In 50 patients, infarct size was determined by magnetic resonance imaging. The associations between baseline levels of NT-proBNP, TnT and CRP and myocardial functional recovery, left ventricular intraventricular volumes and infarct size were determined by linear regression.All three biomarkers were associated with myocardial dysfunction at baseline. However, high levels of NT-proBNP were associated with better myocardial recovery, as measured by global longitudinal strain, even after adjusting for other factors potentially influencing myocardial recovery.Elevated levels of NT-proBNP at baseline are independently associated with improved myocardial performance 8 months after non-ST-elevation acute coronary syndrome.

Objectives The purpose of this study was to assess the association between B-type natriuretic peptide (BNP) and N-terminal pro-B-type natriuretic peptide (NT-proBNP) and the incidence of specific cardiovascular events in low-risk patients with stable coronary disease, the incremental prognostic information obtained from these two biomarkers compared with traditional risk factors, and their ability to identify patients who may benefit from angiotensin-converting enzyme (ACE) inhibition. Background The prognostic value of BNPs in low-risk patients with stable coronary artery disease remains unclear. Methods Baseline plasma BNP and NT-proBNP concentrations were measured in 3,761 patients with stable coronary artery disease and preserved left ventricular function participating in the PEACE (Prevention of Events With Angiotensin-Converting Enzyme Inhibition) study, a placebo-controlled trial of trandolapril. Multivariable Cox regression was used to assess the association between natriuretic peptide concentrations and the incidence of cardiovascular mortality, fatal or nonfatal myocardial infarction, heart failure, and stroke. Results The BNP and NT-proBNP levels were strongly related to the incidence of cardiovascular mortality, heart failure, and stroke but not to myocardial infarction. In multivariable models, BNP remained associated with increased risk of heart failure, whereas NT-proBNP remained associated with increased risk of cardiovascular mortality, heart failure, and stroke. By C-statistic calculations, BNP and NT-proBNP significantly improved the predictive accuracy of the best available model for incident heart failure, and NT-proBNP also improved the model for cardiovascular death. The magnitude of effect of ACE inhibition on the likelihood of experiencing cardiovascular end points was similar, regardless of either BNP or NT-proBNP baseline concentrations. Conclusions In low-risk patients with stable coronary artery disease and preserved ventricular function, BNPs provide strong and incremental prognostic information to traditional risk factors.

Coronary artery disease (CAD) is prevalent in patients with type 2 diabetes mellitus (T2DM) and because it is often asymptomatic and extensive in comparison with CAD in subjects without diabetes, it represents a diagnostic challenge. The objective of the study was to investigate the prevalence of CAD in asymptomatic T2DM patients utilizing angiography and to investigate its association with cardiovascular (CV) risk factors, the metabolic syndrome and markers of inflammation.Eighty-two patients with T2DM without symptoms of CAD, and withor=1 CV risk factor (hypertension, dyslipidaemia, premature familial CAD, smoking or microalbuminuria) underwent a diagnostic stress test and coronary angiography irrespective of stress test results. Stenosis detected in the main coronary arteriesor=50% of lumen diameter was categorized as one-, two- or three-vessel disease. Inflammatory markers were analysed in fasting samples.Fifteen men and two women had significant CAD (21%) (1-vessel disease, n=10; 2- or 3-vessel disease, n=7). Patients with 2- or 3-vessel disease were significantly older and had a longer duration of diabetes, but the prevalence of other traditional CV risk factors or the metabolic syndrome was similar among those with 1-vessel and those with 2- or 3-vessel disease. Sensitivity for CAD of the stress test was low (0.35). The mean level of the pro-inflammatory marker interleukin-6 was elevated in patients with 2- to 3-vessel CAD as compared to patients with no or 1-vessel CAD (p0.05).Significant CAD was found in 21% of asymptomatic patients with T2DM withor=1 CV risk factor. Inflammatory markers may be helpful in identifying patients that are likely to have significant CAD, but larger studies are warranted.

There is controversy whether new biomarkers are able to identify myocardial ischemia in the absence of myonecrosis.We measured NT-pro BNP, NT-pro ANP, ischemia-modified albumin (IMA) and placental growth factor (PlGF) in patients undergoing nuclear stress testing for suspected ischemic heart disease. A thallium scan was used for detection of reversible myocardial ischemia and cardiac troponin T (cTnT) for exclusion of stress-induced myonecrosis. Of 195 patients, 24 with reversible and 62 with no perfusion defect were included in the analysis. Plasma levels were measured before, 18 min and 4 h after stress testing.Of the 86 patients, 52 received an exercise stress and 34 dipyridamol. New myonecrosis indicated by cTnT could be excluded in all patients. Plasma levels of NT-pro BNP and NT-pro ANP before testing were significantly higher in patients who later developed reversible perfusion defects (NT-pro BNP 139.00 (58.25/367.01) pg/mL vs 327.45 (120.50/972.85) pg/mL, p0.05; NT-pro ANP 732.5 (470.0/1220.0) pg/mL vs 1470.0 (694.0/1910.0) pg/mL, p0.05). Plasma levels of NT-pro BNP, NT-pro ANP and PIGF did not change significantly after stress testing, IMA levels rose significantly after 4 h in patients with and without reversible perfusion defects.The elevation of NTpro BNP and NT-pro ANP at baseline may represent the cumulative effect of repeated bouts of myocardial ischemia. A single brief episode of provoked ischemia does not cause a significant increase of the measured biomarkers beside from IMA after exercise stress test potentially indicating skeletal muscle ischemia.

N-terminal-pro-B-type natriuretic peptide (NT-pro-BNP) is well established as a predictor of prognosis in patients with left ventricular dysfunction. Although a similar prognostic significance has been suggested in 1 study of right ventricular failure and idiopathic pulmonary arterial hypertension, NT-pro-BNP has not been assessed as a marker of disease severity in a more heterogenous group of patients with chronic precapillary pulmonary hypertension (PH). Hence, this study assessed plasma NT-pro-BNP and other clinical variables in 61 consecutively recruited patients with various forms of chronic precapillary PH. Right-sided cardiac catheterization and cardiopulmonary exercise testing were performed at baseline, and the prognostic significance of NT-pro-BNP was investigated with a mean follow-up of 25 months. Compared with age-matched controls (n = 10), plasma NT-pro-BNP was significantly greater in those with idiopathic pulmonary arterial hypertension (n = 16), chronic precapillary PH associated with other diseases (n = 26), and chronic thromboembolic disease (n = 19) and was correlated with hemodynamic variables and functional capacity. In 17 medically treated patients, the significant decrease in NT-pro-BNP levels correlated with improved hemodynamics. During follow-up, 15 patients died from cardiopulmonary causes. Baseline NT-pro-BNP was an independent predictor of mortality. Kaplan-Meier survival analysis according to the median value of NT-pro-BNP (168 pmol/L) demonstrated a significantly higher mortality rate in those with supramedian values than in those with low plasma levels (p = 0.010). In conclusion, these findings suggest that in a heterogenous group of patients with chronic precapillary PH, plasma NT-pro-BNP can be used to determine the clinical severity of disease and is independently associated with long-term mortality.

N-terminal pro-brain natriuretic peptide (Nt-proBNP) and high-sensitivity C-reactive protein (hsCRP) are cardiovascular risk markers in various populations, but are not well examined in hypertension. Therefore, we wanted to investigate whether high Nt-proBNP or hsCRP predicted the composite endpoint of cardiovascular death, non-fatal stroke or non-fatal myocardial infarction independently of traditional cardiovascular risk factors and the urine albumin: creatinine ratio (UACR), which is a well established cardiovascular risk factor in hypertension.In 945 hypertensive patients from the LIFE study with electrocardiographic left ventricular (LV) hypertrophy, we measured traditional cardiovascular risk factors including electrocardiography, morning UACR, hsCRP by immunoturbidimetry assay and Nt-proBNP by immunoassay after 2 weeks of placebo treatment. During 55 months' follow-up 80 patients suffered a composite endpoint.HsCRP as well as Nt-proBNP above the median values of 3.0 mg/l and 170 pg/ml, respectively, was associated with a higher incidence of composite endpoint (13.1 versus 3.8%, P0.01, and 11.5 versus 5.4%, P0.01). In Cox regression analyses, standardized log(hsCRP)/SD predicted a composite endpoint [hazard ratio (HR) 1.3 per SD = 0.47 log(mg/l), P0.05] after adjustment for traditional cardiovascular risk factors, but not after further adjustment for UACR. Standardized log(Nt-proBNP)/SD predicted a composite endpoint after adjustment for traditional cardiovascular risk factors [HR 1.9 per SD = 0.49 log(pg/ml), P0.05] as well as after further adjustment for UACR [HR 1.5 per SD = 0.49 log(pg/ml), P0.01]. Log(Nt-proBNP) added significantly to the Cox regression models using traditional cardiovascular risk factors with and without UACR (both P0.001).Nt-proBNP predicted a composite endpoint after adjustment for traditional risk factors, UACR and a history of diabetes or cardiovascular disease and added significantly to the prediction of composite endpoint, whereas hsCRP did not.

Objective: GH deficiency is associated with an increased cardiovascular mortality. Fifty-five patients with adult-onset GH deficiency (AO-GHD) (24 female, 31 male, mean age 49 years) were enrolled in a placebo-controlled double-blind crossover study to investigate the effects of GH therapy on a variety of cardiovascular risk factors representing different aspects of atherogenesis, including apolipo-proteins (Apo A-1, Apo B), markers of subclinical inflammation (high-sensitivity C-reactive protein (CRP) and interleukin-6) and markers of endothelial function (intercellular adhesion molecule-1, von Willebrand factor and sCD40L (a pro-atherogenic factor and marker for plaque destabilization)). Methods: GH therapy was individually dosed to obtain an IGF-I concentration within the normal range for age and sex. GH and placebo were administered for 9 months each, separated by a 4 month washout period. Results: The final mean dose of GH was 50% higher for women and IGF-I increased to the same level in both sexes. Compared with placebo, substitution with GH showed a significant effect on Apo B (mean change −0.15 (−0.22 to −0.08) mg/l) and CRP (−1.8 (−3.3 to −0.3) mg/l). The baseline level of and change in IGF-I during treatment with GH contributed significantly to the improvement in both markers. No effects were found on interleukin-6 or Apo A-1, or on markers of endothelial function. No gender differences were observed for any of the markers at baseline or following intervention. Conclusions: GH substitution to naïve patients with AO-GHD at a low, individually titrated dose aiming at normalizing IGF-I was followed by significant reductions in Apo B and CRP, indicating a positive effect of GH on cardiovascular risk.

Aims: This study was designed to test if the renal excretion of the N-terminal prohormone of the B-type natriuretic peptide (NTproBNP) is modulated by angiotensin-converting enzyme inhibition (ACE-I). Methods: Following 7 days on a sodium-enriched diet and an induction period of 4 days with incremental dosages of enalapril (2.5, 5, 7.5, 10 mg) or placebo, 10 healthy subjects underwent crossover and double-blind treatment with 20 mg enalapril sodium or placebo at 8:00 h. After 4 h (at 12:00 h), 20 ml·kg–1 NaCl 0.9% was infused over 60 min. Hemodynamics were determined and blood and urine were sampled at 8:00, 12:00, 13:00, 14:00, 16:00, and 18:00 h. Angiotensin II (AII), NTproANP, and NTproBNP were determined by radio- and electrochemiluminescence immunoassays. Results: In the whole group, ACE-I led to a lower arterial blood pressure during the fourth day of induction and during the time from 8:00 to 16:00 h, a decrease in AII levels from 8:00 to 14:00 h (p < 0.05), and to a higher cumulative urine output (p < 0.05) in comparison with control. Neither cumulative sodium nor urinary NTproBNP/creatinine excretion were significantly increased after ACE-I. However, a subgroup of 6 volunteers – showing an increase in sodium excretion after ACE-I – also demonstrated lower AII levels at 13:00 h, a higher cumulative urine flow, and a higher urinary NTproBNP/creatinine excretion in comparison with control (all: p < 0.05). Conclusions: This suggests that the renal excretion of NTproBNP is modified by enalapril. However, it remains to be determined if this is a direct effect of ACE-I, the decrease in arterial blood pressure, or other potentially confounding variables like bradykinin or endopeptidase activity.

Platelet-derived microparticles (PMPs) are considered a marker of platelet activation. They vary considerably in size, and flow cytometry, the predominant method used to assay PMPs, is only detecting larger PMPs (> 0.1 μm). We describe here a method that quantifies the amount of PMP-located GPIIb antigen in detergent-treated platelet-free plasma (PPP) by means of a one-step time-resolved immunofluorometric assay (TR-IFMA). This assay uses a streptavidin-coated microwell plate and two different monoclonal antibodies to GPIIb (CD41), one conjugated to biotin and the other labeled with europium ion. A wide linear range standard curve with low background and a high sensitivity was obtained. Pre-assay ultracentrifugation or filtration of PPP extensively reduced the fluorometric signal, indicating that the GPIIb antigen is mainly particle-located. A strong correlation between the amount of GPIIb and PMP as detected by flow cytometry was found. Consequently, the assay can be used to study PMP-related phenomena and, in contrast to flow cytometry, can be used on frozen samples and is independent of PMP size.

Background The clinical benefit of percutaneous coronary intervention (PCI) in heart transplant recipients (HTRs) with coronary allograft vasculopathy (CAV) has been questioned. We investigated the degree of inflammatory reaction during PCI in CAV compared to patients with native atherosclerosis, and the possible relationship between PCI-induced inflammation and the degree of re-stenosis in these 2 patient groups. Methods In 11 CAV patients and 10 patients with native atherosclerosis, blood samples were drawn before and 24 hours and 6 months after PCI, and analyzed with regard to hsCRP, MCP-1, components of complement activation, von Willebrand factor (vWf), soluble L-selectin and ICAM-1. Quantitative angiography was performed before and after PCI, and at 6-month follow-up. Results Baseline levels of hsCRP, vWf and MCP-1 were significantly elevated and levels of L-selectin and ICAM-1 and activation products of the alternative pathway of the complement system were decreased in CAV patients compared to those with native atherosclerosis. PCI induced significant increases of hsCRP in both groups as well as an increase in vWf in native atherosclerosis, whereas a decrease in L-selectin was observed in native atherosclerosis. Plasma levels of MCP-1 correlated with percent stenosis at follow-up in both groups, whereas a correlation between hsCRP and percent stenosis was evident only in patients with native atherosclerosis. There were no differences in rates of re-stenosis between the 2 groups. Conclusions HTRs with CAV and patients with native atherosclerosis are characterized by different profiles of immune activation and respond differently to PCI. Nevertheless, an inappropriate inflammatory reactivity may predispose to re-stenosis after PCI in both groups of patients, with pre-procedural inflammation being of particular importance in CAV.

Aims Transplant-associated coronary artery disease (TxCAD) is a major cause of post-transplant graft failure. The aim of this study was to investigate a possible role of mannose-binding lectin (MBL) deficiency and complement activation in TxCAD. Methods and results In a prospective study of heart transplant recipients ( n =38) with a follow-up of 5.3±1.3 years (range: 0.9–6.6), angiographically verified TxCAD ( n =6) was correlated to plasma MBL, complement activation, and endothelial activation (soluble E-selectin). MBL deficiency (

The polypeptide relaxin (RLX) has been suggested to play a role in cardiorenal integration and to be related to the natriuretic peptide system. We hence examined the effects of variations in thoracic blood volume and intravenous volume loading on plasma and urinary RLX levels and associated changes in natriuretic peptide levels in healthy men. Two groups of eight subjects were randomly tilted into a 15° feet-down or a 15° head-down position. Ten volunteers were crossover subjected to an infusion of 15 ml/kg of 0.9% NaCl (over 60 min) or control during an observation period of 10 h. Blood and urine were sampled at timed intervals. RLX, NH2-terminal prohormones of atrial natriuretic peptide (NT-pro-ANP), and NH2-terminal prohormones of brain natriuretic peptide (NT-pro-BNP) were determined by enzyme, radio-, and electrochemoluminescence immunoassays, respectively. NT-pro-ANP levels (in percentage of baseline levels) were higher ( P < 0.05) during the head-down (124 ± 13%) than during the feet-down position (82 ± 6%). NT-pro-BNP and RLX were not affected by tilting. Volume loading induced a short-lasting increase in plasma NT-pro-ANP, a delayed increase in plasma NT-pro-BNP, had no effect on plasma RLX, and induced a parallel increase in urine flow, renal excretion of sodium, RLX, and NT-pro-BNP. It is concluded that variations in thoracic blood volume in healthy men are not associated with variations in plasma RLX. Increased urinary RLX and NT-pro-BNP excretion during volume loading suggest renal production and a possible role of kidney-derived RLX and brain natriuretic peptide in sodium homeostasis in men.

**Department of Cardiology, †Research Institute for Internal Medicine, ‡Section of Clinical Immunology and Infectious Diseases,§Institute of Clinical Biochemistry, Rikshospitalet; ||Department of Cardiology, Aker sykehus, University of Oslo, Oslo, NorwaySummaryBackground: Atherosclerosis is considered to be a chron-ic inflammatory disorder. Several large-scale clinical studiesdemonstrate that markers of inflammation, such as high-sen-sitivity C-reactive protein (hsCRP), fibrinogen, and solubleCD40 ligand, are potent and independent predictors of vas-cular risk.Hypothesis:The study was undertaken to investigate the ef-fect of increasing the statin dose from conventional to aggres-sive treatment on lipids levels, inflammation, and endothelialfunction in patients with coronary artery disease (CAD).Methods: We randomized 97 patients to either 20 mg sim-vastatin or 80 mg atorvastatin. Plasma levels of lipids, hsCRP,fibrinogen, soluble adhesion molecules, and nitric oxide-totalwere analyzed at baseline and after 6 months of treatment.Results: Lipid values were significantly reduced in bothtreatment groups, but with significantly greater reduction inthe aggressively treated group. Furthermore, aggressive statintreatment significantly decreased hsCRP and fibrinogen,while only small reductions were seen in the conventionallytreated group, resulting in significant differences between thetwo treatment groups (p

Objective To compare indicators of systemic inflammatory response in the second trimester in women who developed pre-eclampsia with normal pregnancies. Design Prospective nested case control study derived from a cohort of 2190 pregnant women. Blood samples were obtained at 18 weeks of gestation. The following inflammatory parameters were measured: tumour necrosis factor-α (TNF-α), plasminogen activator inhibitor-1 (PAI-1), interleukin-1β (IL-1β), IL-6, IL-10, microCRP and tissue factor (TF). Setting Institute of Medical Genetics, University of Oslo, and Department of Medical Genetics, Ulleval University Hospital and Departments of Obstetrics and Gynecology, Aker University Hospital, Oslo, Norway. Sample The cases were 71 women who subsequently developed pre-eclampsia. The controls were 71 healthy, pregnant women matched for age, parity and first trimester body mass index (BMI). Methods Venous blood was drawn from fasting subjects into 5 mL test tubes containing EDTA. Samples were analysed for inflammatory parameters : IL-1-β, IL-6, IL-10, TNF-α, PAI-1, TF (ELISA-technique) and CRP (latex-enhanced immunonephelometric assay), strictly according to the manufacturer's recommendation. Main outcome measures The matched case and control subjects were compared by the paired two-tailed Wilcoxon signed rank test. All P values were two-tailed and P < 0.05 was deemed statistically significant. Results We found no differences in plasma concentrations of PAI-1, IL-1β, IL-6, IL-10, microCRP, TNF-α or TF at 18 weeks of gestation between women who subsequently developed pre-eclampsia and matched control women. Conclusion In contrast to findings from women with overt pre-eclampsia, the present study indicates that there are no indications of intensified systemic inflammatory response at 18 weeks of gestation in women who later develop pre-eclampsia.

Free thyroxine (FT4) and cholesterol were measured in 400 dogs with either suspected hypothyroidism or dermatological signs such that hypothyroidism needed to be ruled out. Hypothyroidism was diagnosed in 68 dogs from the history, physical examination and stated lower reference limit (

Aortic stenosis (AS) and atherosclerosis share similarities when it comes to risk factors and disease progression. Like in other heart diseases, we hypothesized that biomarkers like high-sensitive troponin T (hsTnT), N-terminal-pro-brain-natriuretic-peptide (NT-proBNP) and high-sensitive C-reactive protein (hsCRP) could be useful in risk stratification.A total of 136 patients (57% men, mean age 74 years), referred for evaluation of AS (valve area 0.62 cm(2), left ventricular ejection fraction 64%) were consecutively enrolled in the study. The relationship between hsTnT, hsCRP and NT-proBNP, different echocardiographic parameters of AS and cardiac function were investigated as well as their relation to all-cause mortality.In contrast to hsCRP, hsTnT and NT-proBNP were individually correlated with prognosis. Regression analysis identified diabetes and the combination of hsTnT and NT-proBNP as significant predictors of all-cause mortality. When analyzing patients without surgery separately, only the combination of hsTnT and NT-proBNP were identified as a significant predictor of all-cause mortality in multivariable analysis.The combination of NT-proBNP and hsTnT came out as the strongest predictor of outcome irrespective of surgical treatment or not and could be of particular interest in risk-stratification in AS-patients. The results should be confirmed in prospective studies both in symptomatic and asymptomatic patients.

Approximately 30% of patients treated with cardiac resynchronization therapy (CRT) do not respond. We evaluated response to CRT at six and 12 months, tested a novel response criterion and evaluated different clinical and echocardiographic predictors of response.Eighty one patients were enrolled. A definition of response to CRT was predefined as a combination of 1) a reduction of LV end-systolic volume of ≥10% and 2) either an improvement in NYHA class by ≥1 or an increase in peak oxygen consumption of ≥1 ml/kg/min. Pre-and postoperatively at six and 12 months we also evaluated the most commonly employed definitions of response in our material: NYHA class, quality of life, left ventricular (LV) performance and functional capacity. After six and 12 months of CRT, 42 (52%) and 48 patients (59%) were responders, respectively. Employing different criteria, response ranged from 33-96% and 31-94% at six and 12 months, respectively. In our material a large pre-operative interventricular motion delay (IVMD) was a predictor of response to CRT (p0.05).Fifty two percent and 59% were responders to CRT at six months and one year given a predefined novel endpoint. Different response criteria to CRT gave response rates ranging from 33-96% and 31-94% at six and 12 months, respectively. A large IVMD predicts response to CRT at six and 12 months.

Predicting response to cardiac resynchronization therapy (CRT) is challenging. Highly sensitive cardiac troponin T (hsTnT) might predict response to CRT and identify patients at a high risk of experiencing severe cardiovascular events. We investigated whether baseline levels of hsTnT were associated with response to CRT and with severe cardiovascular events after long-term follow-up.Eighty-one consecutive patients were included according to the current guidelines for CRT. Biochemical, functional, and clinical parameters were assessed at baseline and at 3, 6, and 12 months of follow-up; and mortality/cardiac transplantation after 46 ± 6 months of follow-up was investigated. Cardiac magnetic resonance imaging and echocardiography were used to assess left ventricular function including viability and remodeling.Seventy-five patients completed 12 months of follow-up; and after a follow-up of 46 ± 6 months, a total of 15 patients died, 13 of these from cardiovascular causes, and 7 underwent heart transplantation. Baseline hsTnT15 ng/L predicted response to CRT and was associated with a more favorable outcome with regard to severe cardiovascular events. Multivariate analysis found that presence of transmural scar tissue/fibrosis on magnetic resonance imaging and use of statins were independently associated with higher concentrations of hsTnT at baseline. There was a strong correlation between hsTnT and N-terminal pro-B-type natriuretic peptide levels.Highly sensitive TnT levels were elevated in the majority of heart failure patients who were scheduled for CRT. The HsTnT levels predicted response to CRT as well as long-time survival.

Aims We evaluated the relationship between elevated serum uric acid (SUA) and mortality as well as cardiac allograft vasculopathy (CAV) among 184 heart transplant (HTx) recipients. We also measured inflammatory, neurohormonal, and oxidative stress markers to explore pathophysiological mechanisms. Methods and results There were 28 (15%) deaths, patients with SUA ≥502 µmol/L (upper quartile) at 1 year post-HTx had an increased risk of total mortality (adjusted HR 2.21, P = 0.03) and cardiac mortality (adjusted HR 4.38, P = 0.03). Elevated SUA was a significant risk factor for development of moderate/severe angiographic CAV (adjusted HR 4.79, P = 0.01). A smaller decline in SUA (

Background N-terminal probrain natriuretic peptide (NT-proBNP) and C-reactive protein (CRP) are useful in risk stratification of patients with congestive heart failure. They could also be markers of distinctly altered hormonal and immunological milieus, but the combined prognostic value of these biomarkers in heart transplant (HTx) recipients has not been assessed previously. Methods We sought to assess the individual and combined value of NT-proBNP and CRP as markers of acute rejection, cardiac allograft vasculopathy (CAV) and all-cause mortality in HTx recipients. We evaluated 101 patients for acute rejection and 210 patients for CAV and all-cause mortality. Patients evaluated for rejection had serial endomyocardial biopsies and plasma sampling performed during the first year postHTx. All other patients had plasma samples taken upon inclusion at an annual visit. Median follow-up for CAV and all-cause mortality was 2.2 years and 5.4 years, respectively. Results Altogether, 1131 biopsy procedures were performed, and increased NT-proBNP and CRP levels were not useful markers of acute cellular rejection. In total, 78 (37%) patients developed CAV, and 39 (19%) patients died. Neither biomarker was a predictor of CAV, but both were independent predictors of mortality. When combining both biomarkers, elevated levels of both NT-proBNP and CRP identified patients at highest risk for CAV (HR 2.10, P=0.01) and all-cause mortality (HR 3.14, P=0.01). Conclusions In HTx recipients, NT-proBNP and CRP are not useful as markers of acute cellular rejection during the first year postHTx, but combined analysis adds significantly to their predictive value for development of CAV and all-cause mortality.

The purpose of this study was to assess the association between B-type natriuretic peptide (BNP) and N-terminal pro-B-type natriuretic peptide (NT-proBNP) and the incidence of specific cardiovascular events in low-risk patients with stable coronary disease, the incremental prognostic information obtained from these two biomarkers compared with traditional risk factors, and their ability to identify patients who may benefit from angiotensin-converting enzyme (ACE) inhibition.The prognostic value of BNPs in low-risk patients with stable coronary artery disease remains unclear.Baseline plasma BNP and NT-proBNP concentrations were measured in 3,761 patients with stable coronary artery disease and preserved left ventricular function participating in the PEACE (Prevention of Events With Angiotensin-Converting Enzyme Inhibition) study, a placebo-controlled trial of trandolapril. Multivariable Cox regression was used to assess the association between natriuretic peptide concentrations and the incidence of cardiovascular mortality, fatal or nonfatal myocardial infarction, heart failure, and stroke.The BNP and NT-proBNP levels were strongly related to the incidence of cardiovascular mortality, heart failure, and stroke but not to myocardial infarction. In multivariable models, BNP remained associated with increased risk of heart failure, whereas NT-proBNP remained associated with increased risk of cardiovascular mortality, heart failure, and stroke. By C-statistic calculations, BNP and NT-proBNP significantly improved the predictive accuracy of the best available model for incident heart failure, and NT-proBNP also improved the model for cardiovascular death. The magnitude of effect of ACE inhibition on the likelihood of experiencing cardiovascular end points was similar, regardless of either BNP or NT-proBNP baseline concentrations.In low-risk patients with stable coronary artery disease and preserved ventricular function, BNPs provide strong and incremental prognostic information to traditional risk factors.

To the Editor: Patients with hypercholesterolemia, even with additional risk factors, may not during a lifetime develop coronary artery disease (CAD) ([1][1]). These observations suggest that protective mechanisms may balance those directly related to hypercholesterolemia and delay, or even abolish

Background—Inflammation and matrix degradation may play a pathogenic role in chronic heart failure (CHF), and therefore, we examined whether thalidomide, a drug with potential immunomodulating and matrix-stabilizing properties, could improve left ventricular (LV) function in patients with CHF secondary to idiopathic dilated cardiomyopathy (IDCM) or coronary artery disease (CAD).Methods and Results—Fifty-six patients with CHF and an LV ejection fraction (LVEF) Conclusions—Although our results must be confirmed in larger studies that also examine the effects on morbidity and mortality, our findings suggest a role for thalidomide in the management of CHF in addition to traditional cardiovascular medications.

Circulating B-type natriuretic peptide (BNP) is a strong predictor of survival in patients with acute coronary syndromes and in patients with congestive heart failure. Whether circulating BNP levels are predictive of long-term survival in patients with angiographically documented, clinically stable coronary artery disease is unknown. We studied 186 patients with stable angina pectoris and angiographic evidence of significant coronary artery disease. Patients with a recent myocardial infarction, electrocardiographic evidence of ongoing ischemia, anginal pain at rest, or symptomatic congestive heart failure were excluded from the study. During a follow-up of 7.4 years, 23 patients died. By Cox proportional-hazards regression, patient age (p = 0.031), pathologic Q waves on the electrocardiogram (p = 0.037), left ventricular ejection fraction (p = 0.016), and plasma BNP (p = 0.008) were significantly associated with long-term survival. In a stepwise forward multivariate model, BNP (p = 0.005) provided prognostic information above and beyond conventional risk markers. In patients with clinically stable, angiographically documented coronary artery disease, plasma BNP levels are independently related to long-term survival.

ObjectivesThis study was initiated to determine whether heart transplant recipients (HTRs) with cardiac allograft vasculopathy (CAV) have increased levels of high-sensitivity C-reactive protein (hsCRP) and to examine whether an increase in hsCRP after heart transplantation predicts the development of CAV. Furthermore, the effect of pravastatin on plasma levels of hsCRP in HTRs was investigated.BackgroundThe relationship between CAV and hsCRP, as well as the effect of statins on hsCRP in HTRs, has not been well established.MethodsOn referral for their annual angiographic control study, 150 consecutive HTRs (mean 6.5 years since transplantation) were included. Plasma levels of hsCRP were measured before angiography and compared with patients with (n = 52) and without (n = 98) CAV. In 49 of these patients, we additionally analyzed hsCRP in blood samples stored from their six-month visit after the transplantation procedure. Furthermore, in a randomized, crossover study, hsCRP was analyzed in 17 male HTRs before and after six weeks of treatment with 20 mg pravastatin.ResultsMedian levels of CRP were elevated among patients with CAV compared with those with normal angiograms [3.86 (1.78 to 7.00) vs. 1.08 (0.72 to 2.13) mg/l, p < 0.001]. Prospectively evaluated hsCRP levels from six months to follow-up were significantly higher among those who developed CAV compared with those with normal angiograms [+2.76 (1.56 to 5.00) vs. +0.07 (−0.57 to 0.41) mg/l, p < 0.001]. On multivariate analysis, the increase in hsCRP was the only significant predictor of CAV. Six weeks of treatment with pravastatin significantly reduced hsCRP levels by 25%, without any relation to changes in lipid values.ConclusionsElevated plasma levels of CRP are associated with angiographic evidence of CAV, and the increase in hsCRP is a strong predictor of development of CAV. Statin treatment reduces levels of hsCRP and should be used in HTRs, regardless of their lipid levels.

There have been very few reports on rhythmic variation in thyroid hormone concentrations with a periodicity of 4-6 weeks. In an attempt to evaluate whether such a rhythm is a general phenomenon we studied ten healthy male students with weekly blood samples over 12 weeks for T4, T3 and TSH. No rhythmicity could be demonstrated.