Elevated N-terminal Pro-brain Natriuretic Peptide Levels Research Articles

Influence of cigarette smoking on cardiac biomarkers: the Atherosclerosis Risk in Communities (ARIC) Study.

Cigarette smoking has been associated with incident heart failure independent of coronary artery disease (CAD), but the mechanisms linking smoking to cardiac damage are not well understood. This study sought to evaluate the relationship between smoking and N-terminal pro-brain natriuretic peptide (NT-proBNP) and high-sensitivity Troponin T (hs-TnT), which are, respectively, biomarkers of myocardial wall stress and injury, in a large community-based cohort. We examined the association between smoking history and NT-proBNP and hs-TnT in 9649 participants free of overt CAD or heart failure from the Atherosclerosis Risk in Communities (ARIC) Study who attended Visit 4 (1996-1998), as well as the association with change in these biomarkers from Visit 4 to Visit 5 (2011-2013) in 3151 participants. At Visit 4, higher cumulative cigarette exposure, assessed by total pack-years, was associated with elevated levels of NT-proBNP (P < 0.001) and hs-TnT (P = 0.01) among ever smokers in multivariable analyses adjusted for potential confounders. After 15 years of follow-up, participants who were active smokers at Visit 4 had greater incidence of elevated NT-proBNP {adjusted proportion = 48% [95% confidence interval (CI) 41, 54] vs. 35 (95% CI 32, 39); P = 0.006} and hs-TnT [adjusted proportion = 32% (95% CI 26, 38) vs. 23 (95% CI 20, 26); P = 0.021] compared with never smokers, adjusting for baseline and follow-up covariates. In a large community-based cohort free of overt CAD and heart failure, cigarette smoking was associated with biomarkers of myocardial wall stress and injury at baseline as well as with a continued measurable increase in these biomarkers after 15 years of follow-up.

Atrial Cardiopathy and Cryptogenic Stroke: A Cross-sectional Pilot Study

There is increasing evidence that left atrial dysfunction or cardiopathy is associated with ischemic stroke risk independently of atrial fibrillation. We aimed to determine the prevalence of atrial cardiopathy biomarkers in patients with cryptogenic stroke. We included consecutive patients with ischemic stroke enrolled in the New York Columbia Collaborative Specialized Program of Translational Research in Acute Stroke registry between December 1, 2008, and April 30, 2012. Medical records were reviewed and patients with a diagnosis of cryptogenic stroke were identified. Atrial cardiopathy was defined as at least one of the following: serum N-terminal probrain natriuretic peptide (NT-proBNP) level greater than 250 pg/mL, P-wave terminal force velocity in lead V1 (PTFV1) on electrocardiogram (ECG) greater than 5000 µV⋅ms, or severe left atrial enlargement (LAE) on echocardiogram. We compared clinical, echocardiographic, and radiological characteristics between patients with and without atrial cardiopathy. Among 40 patients with cryptogenic stroke, 63% had at least one of the biomarkers of atrial cardiopathy; 49% had elevated NT-proBNP levels, 20% had evidence of increased PTFV1 on ECG, and 5% had severe LAE. Patients with atrial cardiopathy were more likely to be older (76 versus 62 years, P = .012); have hypertension (96% versus 33%, P < .001), hyperlipidemia (60% versus 27%, P = .05), or coronary heart disease (28% versus 0%, P = .033); and less likely to have a patent foramen ovale (4% versus 40%, P = .007). There is a high prevalence of biomarkers indicative of atrial cardiopathy in patients with cryptogenic stroke. Clinical trials are needed to determine whether these patients may benefit from anticoagulation to prevent stroke.

Elevated NT-pro-brain natriuretic peptide level is independently associated with all-cause mortality in HIV-infected women in the early and recent HAART eras in the Women's Interagency HIV Study cohort.

BackgroundHIV-infected individuals are at increased risk of right and left heart dysfunction. N-terminal-pro-brain natriuretic peptide (NT-proBNP), a marker of cardiac ventricular strain and systolic dysfunction, may be associated with all-cause mortality in HIV-infected women. The aim of this study was to determine if elevated levels of NT-proBNP is associated with increased mortality in HIV-infected women.DesignProspective cohort study.Methods and ResultsWe measured NT-proBNP in 936 HIV-infected and 387 age-matched HIV-uninfected women early (10/11/94 to 7/17/97) and 1082 HIV-infected and 448 HIV-uninfected women late (4/1/08 to 10/7/08) in the highly active antiretroviral therapy (HAART) periods in the Women’s Interagency HIV Study. An NT-proBNP >75th percentile was more likely in HIV-infected persons, but only statistically significant in the late period (27% vs. 21%, unadjusted p = 0.03). In HIV-infected participants, NT-proBNP>75th percentile was independently associated with worse 5-year survival in the early HAART period (HR 1.8, 95% CI 1.3–2.4, p<0.001) and remained a predictor of mortality in the late HAART period (HR 2.8, 95% CI 1.4–5.5, p = 0.002) independent of other established risk covariates (age, race/ethnicity, body mass index, smoking, hepatitis C serostatus, hypertension, renal function, and hemoglobin). NT-proBNP level was not associated with mortality in HIV-uninfected women.ConclusionNT-proBNP is a novel independent marker of mortality in HIV-infected women both when HAART was first introduced and currently. As NT-proBNP is often associated with both pulmonary hypertension and left ventricular dysfunction, these findings suggest that these conditions may contribute significantly to adverse outcomes in this population, requiring further definition of causes and treatments of elevated NT-proBNP in HIV-infected women.

Comparison of Doppler echocardiographic and tissue Doppler velocity data in beta-thalassaemia major with high and normal NT-proBNP levels of children in the south-east region of Turkey.

It has been reported that N-terminal pro-brain natriuretic peptide (NT-proBNP) is early biomarker of iron- induced cardiomyopathy in β-thalassemia major (β-TM). In this study, we aimed to assess the Doppler echocardiographic, tissue Doppler velocity datas and clinical characteristics in β-TM patients with high and normal NT-proBNP levels who have normal systolic function. Fifty-eight β-TM patients who were on regular transfusion in every 3-4 weeks for more than one year and 20 healthy children were included into the study. According to NT-proBNP levels, β-TM patients are divided in two groups. Group I: the patients with high NT-proBNP levels; Group II: the patients with normal NT-proBNP levels. The mean serum NT-proBNP levels were significantly increased in patients with β-TM compared to control group (P<0.05). The serum ferritin levels were ranged between 676-9,476 ng/mL (mean: 3,716±2,003 ng/mL) in β-TM. No correlation was found between ferritin and NT-pro BNP in patients with β-TM. The mean age and body surface area (BSA) were significantly low in group with high NT-proBNP compared to group with normal NT-proBNP (P<0.01). The mean heart rate, systolic blood pressure (SBP) and diastolic blood pressure (DBP) were elevated, but not significantly in group with high NT-proBNP. Also, the mean ferritin and hemoglobin levels were decreased in this group compared to group with normal NT-proBNP, but statistically not significant. The left ventricular end diastole (LVED) diameters and left ventricular mass index (LVMI) values were found significantly decreased in group with high NT-proBNP compared to other group respectively (P<0.001, P<0,05). Right ventricular early diastolic tricuspid inflow velocity/early diastolic tissue Doppler indices (TDI) tricuspid annular velocity (RV E/E') were found increased in group with high NT-proBNP levels and difference was statistically significant (P<0.05). In addition, NT-pro BNP was found correlated with RV E/E' (r: 0.320). According to our result, elevated NT-proBNP level was correlated with RVE/E', but it was not associated with ferritin level. The serum NT-proBNP level may be increased as a response to increased myocardial workload and decreased hemoglobin level in patients who have an increased need for transfusion.

The significance of serum N-terminal pro-brain natriuretic peptide levels for prognosis of patients in intensive care unit

To assess the significance of elevated serum N-terminal pro-brain natriuretic peptide (NT-proBNP) levels in predicting 30-day mortality rate for patients in intensive care unit (ICU). A retrospective study was conducted. The clinical data of 480 patients admitted to ICU in Tianjin First Center Hospital from June 2012 to October 2013 were studied. The characteristics of patients were recorded, the acute physiology and chronic health evaluationII ( APACHEII) score was calculated, and the routine blood tests, blood biochemistry, and serum NT-proBNP level within 24 hours after admission were determined. Patients were divided into non-survival and survival groups according to 30-day outcome, and the characteristics and clinical parameters were compared between two groups, and single factor analysis affecting prognosis was analyzed. All patients were divided into four groups according to four percentile method as NT-proBNP<280 ng/L (group Q1), 280 ng/L≤NT-proBNP<1 200 ng/L (group Q2), 1 200 ng/L≤NT-proBNP<1 990 ng/L (group Q3), 1 990 ng/L≤NT-proBNP<4 700 ng/L (group Q4). A Cox regression analysis was used to test the independence of the predictors. A receiver operator characteristic curve (ROC curve) was plotted to compare the power of APACHEII score and NT-proBNP in predicting the outcome. Kaplan-Meier analysis was used to assess survival rate among different NT-proBNP patients. By single factor analysis it was shown that age, APACHEII score, creatinine, NT-proBNP and severe infection were those influencing the outcome. NT-proBNP 1 200-4 700 ng/L (groups Q3 and Q4) and APACHEII score>20 were independent risk factors for predicting outcome [relative risk (RR) for group Q3 was 3.624, 95% credibility interval (95%CI) was 1.258-10.138; RR for group Q4 was 5.059, 95%CI was 3.202-9.993; RR for APACHEII score>20 was 2.987, 95%CI was 1.345-5.823]. The area under the ROC curve (AUC) for APACHEII score and serum NT-proBNP was similar, and it was 0.831 (95%CI 0.778-0.884) and 0.876 (95%CI 0.827-0.925), respectively. The cut-off value of NT-proBNP for predicting mortality was 1 250 ng/L. Kaplan-Meier analysis showed that groups of Q2, Q3 and Q4 had lower cumulative survival rate compared with group Q1 (26.5%, 25.4%, 16.2% vs. 29.6%), and group Q4 showed most significant extent of lowering of survival rate (χ(2)=122.920, P<0.05). Elevated NT-proBNP level in ICU patients signify severity of the disease, and it is an independent predictor of death of ICU patients.

Left heart disease: a frequent cause of early pulmonary hypertension in systemic sclerosis, unrelated to elevated NT-proBNP levels or overt cardiac fibrosis but associated with increased levels of MR-proANP and MR-proADM: retrospective analysis of a French Canadian cohort

Objectives: Pulmonary hypertension (PH) causes mortality in systemic sclerosis (SSc). Pulmonary arterial hypertension (PAH) and left heart disease (LHD) are frequent causes of PH. Therefore, we studied PAH and LHD in early PH.Method: A total of 432 French Canadian SSc patients were studied retrospectively. All underwent screening for PH. We analysed clinical, serological, and radiographic data from 26 patients with early PH diagnosed by right heart catheterization (RHC). SSc patients with (n = 21) and without PH (n = 19) were prospectively re-evaluated by cardiac magnetic resonance imaging (MRI) and serial measurements of N-terminal pro-brain natriuretic peptide (NT-proBNP) and the haemodynamic biomarkers mid-regional pro-atrial natriuritic peptide (MR-proANP) and mid-regional pro-adrenomedullin (MR-proADM).Results: The most frequent cause of early PH was LHD (58%). PAH was seen in 34% of patients. No association was found between the type of PH and autoantibodies. Early LHD-PH, but not early PAH, was associated with lower NT-proBNP (p = 0.024), but MR-proANP and MR-proADM levels were higher in early LHD-PH than in patients without PH (p = 0.014 and p = 0.012, respectively). Only one patient had abnormal cardiac MRI explaining LHD-PH.Conclusions: Early PH in SSc, like late PH, is heterogeneous and RHC is essential for determining its underlying cause. The most frequent cause of early PH was LHD. Levels of MR-proANP and MR-proADM, but not NT-proBNP, were increased in early LHD-PH, and may be more reliable than NT-proBNP as a biomarker of early PH in this subgroup of patients. Cardiac MRI did not explain LHD-PH. This study is the first to identify a high frequency of LHD in early PH correlating with normal NT-proBNP levels but increased MR-proANP and MR-proADM levels in SSc patients.

Prognostic Value of N-Terminal Pro-Brain Natriuretic Peptide in Outpatients With Hypertrophic Cardiomyopathy

In hypertrophic cardiomyopathy, the plasma levels of N-terminal pro-brain natriuretic peptide (NT-proBNP) correlate with functional capacity. However, their prognostic relevance remains unresolved. We followed up 183 stable outpatients with hypertrophic cardiomyopathy (age 50 ± 17years, 64% men) for 3.9 ± 2.8years after NT-proBNP measurement. The primary end point included cardiovascular death, heart transplantation, resuscitated cardiac arrest, and appropriate implantable cardioverter-defibrillator intervention. The secondary end point (SE) included heart failure-related death or hospitalization, progression to end-stage disease, and stroke. The median NT-proBNP level was 615pg/ml (intertertile range 310 to 1,025). The incidence of the primary end point in the lower, middle, and upper tertiles was 0%, 1.3%, and 2.1% annually, respectively (overall p= 0.01). On multivariate analysis, the only independent predictors of the primary end point were NT-proBNP (hazard ratio for log-transformed values 5.8, 95% confidence interval 1.07 to 31.6; p= 0.04) and a restrictive left ventricular filling pattern (hazard ratio 5.19, 95% confidence interval 1.3 to 21.9; p= 0.02). The NT-proBNP cutoff value of 810pg/ml had the best sensitivity for the primary end point (88%), but the specificity was low (61%). The incidence of the SE in the lower, middle, and upper NT-proBNP tertiles was 4.6%, 12.0%, and 11.2% annually, respectively (overall p= 0.001). An NT-proBNP level of <310pg/ml was associated with a 75% reduction in the rate of SE compared with a level of ≥310pg/ml (hazard ratio 0.25, 95% confidence interval 0.11 to 0.57; p= 0.001), independent of age, left ventricular outflow tract obstruction, or atrial fibrillation. In conclusion, in stable outpatients with hypertrophic cardiomyopathy, plasma NT-proBNP proved a powerful independent predictor of death and heart failure-related events. Although the positive predictive accuracy of an elevated NT-proBNP level was modest, low values reflected true clinical stability, suggesting the possibility of avoiding or postponing aggressive treatment options.

Prospective monitoring N-terminal pro-brain natriuretic peptide during natural progression of atherosclerotic renal artery stenosis in elderly

Prognostic values of N-terminal pro-brain natriuretic peptide (NT-proBNP) in myriad diseases have been studied. During the natural progression of atherosclerotic renal artery disease (ARVD) changes of NT-proBNP levels and its significance is not understood. A prospective longitudinal follow-up study was conducted among 61 ARVD patients (77.7±5.2 years old). NT-proBNP was determined at baseline and six month intervals over 25.89±12.44 months and its correlation with death and/or newly occurred CVEs were assessed. Level of NT-proBNP increased from baseline median 210.0pg/mL (25th–75th percentile, 98.0pg/mL–540.0pg/mL) to 900.9pg/mL (25th–75th percentile, 704.5pg/mL–1583.5pg/mL) (p=0.032) at the end of follow-up. Among 44.26% of the cohort (n=27) NT-proBNP level ≥450pg/mL was detected, which 6 deaths happened (22.22% death rate) and CVEs occurred to 62.96% of patients, comparing to 0% death rate (p=0.077) and 8.82% affected by CVEs (p=0.019) in other 55.74% of cohort (n=34) whose NT-proBNP <450pg/mL. Kaplan–Meier analysis showed that NT-proBNP level ≥450pg/mL was a risk factor related to CVEs (HR=3.96, p=0.03). Cox regression analysis found NT-proBNP level ≥450pg/mL was an independent risk factor of CVEs (HR=5.12, p=0.022) after adjustment of body mass index, blood pressure, kidney function. The negative predictive value was 90.9% of NT-proBNP levels ≥450pg/mL for new CVEs. NT-proBNP levels diverge throughout ARVD natural progression in elderly males over 75 years of age. Elevated NT-proBNP level of ≥450pg/mL was predictive for CVEs with 90.9% of negative predictive value.

The prognostic value of N-terminal pro-brain natriuretic peptide in non-ST elevation acute coronary syndromes: a meta-analysis

Precise risk stratification is important in patients with non-ST elevation acute coronary syndromes (NSTE-ACS) on determination for hospitalization and intensity of treatment. A meta-analysis was performed in studies of patients with NSTE-ACS to evaluate the predictive nature of elevated N-terminal pro-brain natriuretic peptide (NT-proBNP). Online searches were conducted using database to identify suitable studies. A summary of relative risks (RRs) for death and myocardial infarction (MI) was calculated using random-effects modeling. We also calculated the pooled sensitivity, specificity, positive predictive value, and negative predictive value. Thirteen studies were included. Elevated NT-proBNP levels were significantly associated with mortality [RR 4.89; 95% confidence interval (CI) 3.85–6.22] and incidence of MI (RR 1.66; 95% CI 1.24–2.22). The sensitivity and specificity for MI was 69.1% (95% CI 66.6%–71.6%) and 43.6% (95% CI 42.9%–44.3%), respectively, along with the positive and negative predictive values for MI of 8.2% (95% CI 7.7%–8.7%) and 95.1% (95% CI 94.6%–95.5%), respectively. Meta-analysis suggests that elevated NT-proBNP levels were associated with an increased risk for MI or death in patients with NSTE-ACS. Normal levels of NT-proBNP are certainly more helpful when selecting NSTE-ACS patients with likelihood for favorable outcomes.

Abstract 8166: Elevated N-Terminal Pro-Brain Natriuretic Peptide Increases the Risk of Recurrent Thromboembolic Events After Acute Pulmonary Embolism

Introduction: N-Terminal Pro-Brain Natriuretic Peptide (NTproBNP) is a predictor of short-term clinical adverse outcome in patients with acute pulmonary embolism (APE), but its long-term prognostic value remains largely undefined. Hypothesis: We assessed the hypothesis that elevated plasma NTproBNP level is associated with recurrent venous thromboembolism (VTE). Methods: On admission, NTproBNP levels were measured in 224 consecutive patients with the first episode of acute pulmonary embolism occurring from January 2005 through October 2010. Patients were categorized to two groups by NTproBNP reference range and followed up at 3, 6, and 12 months and yearly thereafter. The primary end point was symptomatic, recurrent fatal or nonfatal VTE. Results: NTproBNP was elevated in 158 (71%) patients and not elevated in 66 (29%) patients. After a mean follow-up period of 31.0±19.4 months, patients with elevated NTproBNP showed an increased risk of recurrent VTE (20 patients, 12.7%) compared with those not elevated (only 1 patient, 1.5%) ( P =0.009). 6 of 7 deaths related to pulmonary embolism occurred in patients with NTproBNP elevated, compared with patients with NTproBNP normal (1 of 7 deaths, P=0.64). At multivariate analysis stratified by oral anticoagulant treatment duration, elevated NTproBNP was an independent predictor of recurrent VTE (hazard ratio; 10.50; P =0.02). Conclusions: Elevated NTproBNP is associated with the increased risk of VTE recurrence in acute pulmonary embolism patients.

Serial measurements of NT-proBNP are predictive of not-high-dose anthracycline cardiotoxicity in breast cancer patients

Background:The aim of this study was to assess the value of N-terminal pro-brain natriuretic peptide (NT-proBNP) in predicting late cardiotoxicity in patients treated with not-high-dose chemotherapy (NHDC), and to compare the predictive value of NT-proBNP and cardiac troponin I (cTnI).Methods:In 71 patients undergoing NHDC with anthracyclines, NT-proBNP and cTnI levels were measured before and 24 h after each NHDC cycle. Left ventricular (LV) function was assessed by echocardiography at baseline, every two NHDC cycles, at the end of chemotherapy, and at 3-, 6- and 12-month follow-up.Results:During NHDC, only NT-proBNP showed abnormal values. According to NT-proBNP behaviour, patients were divided into two groups: group A (n=50) with normal (n=23) or transiently elevated NT-proBNP levels (n=27), and group B (n=21) with persistently elevated NT-proBNP levels. At follow-up, LV impairment was significantly worse in group B than in group A. %Δ (baseline–peak) NT-proBNP was predictive of LV impairment at 3-, 6- and 12-month follow-up, with a cutoff of 36%.Conclusion:Serial measurements of NT-proBNP may be a useful tool for the early detection of patients treated with NHDC at high risk of developing cardiotoxicity.

Serum A-FABP Is Increased and Closely Associated with Elevated NT-proBNP Levels in Type 2 Diabetic Patients Treated with Rosiglitazone

BackgroundAdipocyte fatty acid-binding protein (A-FABP) has been shown to play important roles in the development of metabolic syndrome, diabetes, and cardiovascular diseases. In this study we investigated the possible role of A-FABP in the development of cardiac dysfunction related to rosiglitazone treatment.Methodology/Principal FindingsA total of 84 patients with newly diagnosed type 2 diabetes were treated with rosiglitazone for 48 weeks. Circulating A-FABP and N-terminal pro-brain natriuretic peptide (NT-proBNP) levels were determined at baseline and repeated at 24 and 48 weeks. After the 48-week rosiglitazone treatment period, serum levels of both A-FABP and NT-proBNP increased progressively and significantly (P<0.01). Serum levels of A-FABP were demonstrated to be positively correlated with gender and waist circumference both at baseline and the end of the study, and with age, body mass index (BMI), total cholesterol (TC), triglyceride (TG), low-density lipoprotein cholesterol (LDL-C), and NT-proBNP at 48 weeks (all P<0.05). In addition, changes in A-FABP were significantly and positively correlated with changes in NT-proBNP (r = 0.239, P = 0.039). Furthermore, multiple stepwise regression analysis showed that the changes in A-FABP were independently and positively associated with changes in NT-proBNP after adjusting for confounding factors (β = 0.320, P = 0.007).Conclusions/SignificanceRosiglitazone-mediated increase of A-FABP is closely associated with the elevation of NT-proBNP, a well-established marker of cardiac dysfunction. The findings of our study imply that A-FABP may mediate the cross-talk between heart and adipose tissue.

NT-proBNP, but not ANP and C-reactive protein, is predictive of paroxysmal atrial fibrillation in patients undergoing pulmonary vein isolation

The purpose of this study is to evaluate the relationship between plasma high-sensitivity C-reactive protein (hs-CRP), atrial natriuretic peptides (ANP), N-terminal-pro-brain natriuretic peptide (NT-proBNP) levels, and the risk and recurrence of atrial fibrillation (AF) after pulmonary vein isolation (PVI) in patients with paroxysmal atrial fibrillation (PAF). Plasma ANP, NT-proBNP, and hs-CRP levels were measured before and 3 months after PVI in 33 patients with PAF and 30 control participants. (1) NT-proBNP levels at baseline were significantly elevated in subjects with PAF compared with control subjects (296.8 ± 272.1 vs. 80.8 ± 69.1 pg/ml), but ANP and hs-CRP levels were normal; NT-proBNP levels normalized 3 months after PVI, but ANP and hs-CRP levels did not change significantly; NT-proBNP levels at baseline in the recurrent group were markedly higher than those in the nonrecurrent AF group (572.7 ± 234.2 vs. 176.8 ± 188.7 pg/ml). (2) Cox stepwise multivariate analysis demonstrated that only elevated NT-proBNP level at baseline was an independent predictor of AF recurrence (p < 0.001) after PVI among 13 variables, such as echocardiographic parameters, plasma ANP, NT-proBNP, and hs-CRP levels. A cutoff value of NT-proBNP ≥ 423.2 pg/ml was a significant risk factor for AF recurrence (p = 0.002). Elevated NT-proBNP level at baseline, but not ANP and hs-CRP, is a sensitive biomarker for early predicting AF recurrence in patients with PAF.

N-Terminal Pro-Brain Natriuretic Peptide and Risk of Cardiovascular Events in a Japanese Community

Few studies have examined the association between natriuretic peptides and the incidence of cardiovascular disease (CVD) in Asian populations. A total of 3104 community-dwelling Japanese individuals aged ≥40 years without history of CVD were followed up for 5 years. A total of 127 CVD events were identified. The age- and sex-adjusted incidence of CVD increased with increasing N-terminal pro-brain natriuretic peptide (NT-proBNP) levels (<55, 55-124, 125-399, and ≥400 pg/mL) at baseline and was significantly higher even in subjects with a modest increase. This association remained robust even after adjustment for other potential risk factors (55-124 pg/mL: multivariate-adjusted hazard ratio=1.85 [95% CI 1.07-3.18], P=0.03; 125-399 pg/mL: 2.98 [95% CI 1.65-5.39], P<0.001; ≥400 pg/mL: 4.54 [95% CI 2.22-9.29], P<0.001). The multivariate-adjusted hazard ratios for the development of total CVD and its subtypes, coronary heart disease and stroke, were significantly increased by a 1 SD increment of the log NT-proBNP concentrations and were nearly equal among CVD subtypes. Similar findings were observed for stroke subtypes of ischemic stroke and intracerebral hemorrhage but not subarachnoid hemorrhage. The effects of the 1 SD increment in log NT-proBNP values were comparable in subjects with and without other cardiovascular risk factors, except for sex. The area under the receiver operating characteristic curve was significantly (P=0.006) increased by adding NT-proBNP values to the model including other potential risk factors. Elevated NT-proBNP levels were shown to be a significant risk factor for the development of CVD and its subtypes in a general Japanese population, independently of other cardiovascular risk factors.

Strain and strain rate echocardiography for evaluation of right ventricular dysfunction in patients with idiopathic pulmonary arterial hypertension

Optimizing the non-invasive imaging of right ventricular (RV) function is of increasing interest for therapy monitoring and risk stratification in patients with idiopathic pulmonary hypertension (IPAH). Therefore, this study evaluated strain and strain rate echocardiography as a tool for comprehensive assessment of RV function and disease severity in IPAH patients. In 30 IPAH patients [WHO functional classes II-IV; mean pulmonary artery pressure (mPAP) 48.8 +/- 12.5 mmHg; pulmonary vascular resistance (PVR) 7.9 +/- 5.3 Wood units] and in 10 matched healthy control subjects' two-dimensional echocardiography, 6-MWD and N-terminal pro-brain natriuretic peptide (NT-proBNP) levels were obtained. In IPAH patients when compared with controls, RV systolic strain (-18.8 +/- 4.3 vs. -34.5 +/- 3.8%, p = 0.0016) and strain rate (-1.6 +/- 0.6 vs. -2.7 +/- 0.5 s(-1), p = 0.018) were significantly altered and correlated significantly with elevated NT-proBNP levels (r = 0.73 and r = 0.62; p < 0.001, respectively) and reduced 6-MWD (r = -0.76 and r = -0.81; p < 0.001). In IPAH patients, reduced strain correlated with both mPAP (r = 0.61, p = 0.01 for strain; and r = 0.55, p = 0.04 for strain rate, respectively), and PVR (r = 0.84, p < 0.001 for strain; and r = 0.67, p < 0.001 for strain rate, respectively). This study gives first comprehensive evidence that strain echocardiography allows accurate non-invasive assessment of RV function and disease severity in patients with IPAH.

Predisposing Factors and Consequences of Elevated Biomarker Levels in Long-Distance Runners Aged ≥55 Years

Cardiac biomarkers play an important role in the diagnosis of cardiovascular disease. Elevated levels can be seen in the context of strenuous exercise. We studied this phenomenon in senior endurance runners. We included 185 participants (61.1 +/- 5 years; 29% women) at a 30-km cross-country race who were self-reportedly in excellent health. Before and after the race, the creatinine, N-terminal pro-brain natriuretic peptide (NT-proBNP), and troponin T were analyzed, and participation in the number of previous races and the race duration were recorded. NT-proBNP increased from 53 ng/L (interquartile range 31 to 89) to 121 ng/L (interquartile range 79 to 184) and troponin T from undetectable to 0.01 microg/L (interquartile range 0.01 to 0.04). The independent predictors of a large NT-proBNP increase were (1) greater levels present at baseline, (2) a greater increase in creatinine (both p <0.001), (3) older age (p = 0.01), and (4) a longer race duration (p <0.05). Troponin T elevation was independently predicted by (1) older age (p = 0.01), (2) a greater increase in creatinine, and (3) participation in fewer previous races (both p <0.05). Of the 15 runners with an elevated (>194 ng/L) baseline NT-proBNP level (8.1% of 185), 4 were found to have serious cardiovascular disease (2.2% of whole sample). Of these 4 patients, 1 died from sudden cardiac death within months after the race. In conclusion, biomarker elevation occurs commonly in senior runners. A high baseline NT-proBNP is predictive of a large release during exercise, suggesting that the factors that control the at rest levels also determine its release with exertion. Troponin T elevation was seen in less-experienced participants. A small group of very ill runners were identified by NT-proBNP analysis.

Chromogranin-A and N-Terminal Pro-Brain Natriuretic Peptide: An Excellent Pair of Biomarkers for Diagnostics in Patients With Neuroendocrine Tumor

For the last decade chromogranin-A (CgA) has been a well-established marker for neuroendocrine tumor (NET), and N-terminal pro-brain natriuretic peptide (NT-proBNP) has been a useful marker for left ventricular dysfunction. This study examined the diagnostic value of CgA and NT-proBNP for carcinoid heart disease (CHD), and their prognostic value for overall survival in NET patients. Serum samples were obtained and cardiac ultrasound studies performed in 102 NET patients. The criterion for mild and severe CHD was tricuspid regurgitation stage I/II and III/IV, respectively. Proportional odds and Cox proportional hazards models were constructed respectively to identify the association between CHD and overall survival with patient characteristics and the two markers. Severe CHD was found in 15 (15%) of 102 patients, 13 of whom had elevated NT-proBNP levels. In the univariate proportional odds model CHD was correlated with age (P = .007), CgA (P = .002), and NT-proBNP (P < .001), whereas in the multivariate model NT-proBNP and CgA were significantly associated with CHD (P < .001 and P = .01). In the univariate Cox models, age (P = .04), sex (P = .03), CgA (P = .003), and NT-proBNP (P = .04) were related to overall survival, and in the multivariate model CgA and NT-proBNP remained significantly related to overall survival (P = .002 and P = .04, respectively). NT-proBNP and CgA are very important markers in the diagnosis of CHD in patients with NET. Furthermore, patients with elevated NT-proBNP in addition to elevated CgA levels showed worse overall survival than patients with elevated CgA alone.

THIS MONTH IN Anesthesiology

Etomidate, has limited clinical utility due to suppression of adrenocortical steroid synthesis. The first etomidate analogue, (R)-3-methoxy-3-oxopropyl1-(1-phenylethyl)-1H-imidazole-5-carboxylate (MOC-etomidate), was designed to be susceptible to ultra-rapid metabolism to reduce this effect. MOC-etomidate potently enhanced γ-aminobutyric acid type A receptor function and demonstrated first-order metabolism in human liver homogenates with an in vitro half-life of 4.4 min compared with &gt; 40 min for etomidate. A rapid, brief loss of righting reflex and minimal hemodynamic changes were observed in rats without adrenocortical suppression MOC-etomidate, is rapidly metabolized, ultra–short-acting, and does not produce prolonged adrenocortical suppression and maintains the favorable pharmacologic properties of etomidate. See the accompanying Editorial View on page 229 Blood transfusion may have an adverse effect on long-term health. A prospective observational study assessed long-term survival in patients undergoing coronary artery surgery who received a perioperative allogeneic blood transfusion. Health outcomes of 1,841 consecutive patients with isolated nonemergency first-time coronary artery surgery and survival &gt; 60 days after surgery were determined. Of the 1,062 patients transfused, 266 died (mean follow-up of 8.1 yr). A new malignant condition was recorded on the death certificate of 27% of patients who were transfused, compared with 43% who were not. Transfusion of blood products was not associated with long-term survival. Patients undergoing coronary artery surgery who have received moderate amounts of blood (≤ 6 units) should be reassured that they are unlikely to experience a reduction in long-term survival.To assess the prognostic value of elevated brain natriuretic peptide (BNP) or N -terminal pro-brain natriuretic peptide (NT-proBNP) levels in predicting mortality and major adverse cardiovascular events (MACE), a meta-analysis was performed of studies in patients undergoing noncardiac surgery using unrestricted MEDLINE and EMBASE searches. Preoperative BNP elevation was significantly associated with an increased risk of short-term MACE (&lt; 43 days postsurgery), all cause mortality, and cardiac death. Elevated NT-proBNP levels were also predictive. Preoperative BNP elevation was also significantly associated with an increased risk of long-term MACE (&gt; 6 months) and all cause mortality. These data suggest that elevated BNP and NT-proBNP levels may identify patients undergoing major noncardiac surgery at high risk of cardiac events.Growing evidence suggests that microvascular dysfunction is the key element of the pathogenesis of septic shock. This retrospective study assessed the outcome and muscle tissue oxygenation (Sto2) of septic shock patients after early resuscitation using early goal-directed therapy. Sto2was monitored in septic shock patients using a tissue spectrometer. No difference was observed between groups with the exception of pulse oximetry saturation (Spo2; 94% vs. 97%, P = 0.04). The Sto2values were significantly lower in nonsurvivors than in survivors (73% vs. 84%, P = 0.02). Further investigations are required to determine if correction of an impaired level of Sto2improves patient outcomes.Clonidine added to intermediate or long-acting local anesthetics for single-shot nerve blocks prolongs duration by about 2 h. Side effects may limit its usefulness.A process-dissociation procedure, which corrected for guessing, was used to determine if more accurate results of auditory memory could be obtained.The perioperative implications of adults with congenital heart disease undergoing noncardiac surgery are reviewed.Intravenous infusion tests have limited utility for predicting analgesia in chronic pain patients.

N‐terminal Pro‐brain Natriuretic Peptide in the Elderly with Myocardial Infarction

The myocardial infarction (MI) results in the change of the levels of N-terminal pro-brain natriuretic peptide (NT-proBNP) in blood. In addition, attention is paid to the dependence of NT-proBNP levels on the patients' age. However, the behavior of natriuretic peptide levels has not been recognized well enough in the elderly with MI treated with invasive methods. The aim of the study was to estimate the effect of age on NT-proBNP levels in patients with first MI, and treated with primary percutaneous coronary intervention (PCI) with complete coronary revascularization. One hundred and sixty-one consecutive patients with first ST-elevation MI, and treated with primary PCI with stent implantation (occlusion in infarct-related artery was the patient's only lession) were included. Determination of NT-proBNP level and echocardiography were performed on the 4th-5th day of MI. Thirty-seven patients (23%) aged>or=65 y were considered as a study group. The NT-proBNP levels were nearly 4-fold higher in older patients than in younger patients. Only systolic and diastolic dysfunction, mitral regurgitation, troponin T levels, and glomerular filtration rate (GFR) were independent risk factors of the occurrence of elevated NT-proBNP concentration above median. The patients' age was not a factor independently affecting the increase of NT-proBNP level above the median in patients with first MI and treated successfully with primary PCI. Independently associated elevated levels of NT-proBNP were as follows: presence of diastolic dysfunction, mitral regurgitation, left ventricular systolic dysfunction, troponin T concentration, and GFR.

Preoperative Plasma N-Terminal Pro-Brain Natriuretic Peptide Concentration and Perioperative Cardiovascular Risk in Elderly Patients

The prediction of perioperative cardiovascular complications is important in the medical management of patients undergoing noncardiac surgery. Several indices have been developed, but a simpler, more practical and accurate method is needed. The purpose of this study was to determine whether the N-terminal pro-brain natriuretic peptide (NT-proBNP) concentration before operation can be used to predict perioperative cardiovascular complications in elderly patients undergoing noncardiac surgery. The study group comprised 279 patients older than 60 years who were scheduled for elective surgery. The plasma NT-proBNP concentration, clinical cardiac indices and left ventricular ejection fraction were measured prior to operation. The postoperative cardiac outcomes were followed and predictors for postoperative cardiac risk were identified. Cardiovascular complications occurred in 25 patients (9.0%). Age, the incidence of prior ischemic heart disease or congestive heart failure, and the plasma NT-proBNP concentration were significantly higher in patients with perioperative cardiovascular complications than in those without. Using receiver operating characteristic analysis to predict perioperative cardiovascular events, a cut-off value of 201 pg/ml was identified as the optimal predictor of perioperative complications, showing a sensitivity of 80.0% and specificity of 81.1%. Multivariate analysis revealed that NT-proBNP >201 pg/ml (odds ratio (OR) 7.6, 95% confidence interval (CI) 2.2-26.6, p=0.003) and revised cardiac index > or =2 (OR 6.3, 95% CI 1.7-23.8, p=0.007) were independent predictors for perioperative cardiovascular complications. Elevated NT-proBNP levels are independently associated with an increase in the risk of perioperative cardiovascular complications in elderly patients undergoing noncardiac and nonvascular operations.