Elevated N-terminal pro-B-type Natriuretic Peptide Research Articles

Modeling the Impact of Biomarker-Guided Versus ASCVD Risk-Guided Drug Treatment in US Adults With Stage 1 Hypertension: The National Health and Nutrition Examination Survey, 1999 to 2004.

Guidelines recommend antihypertensive medication for adults with both stage 1 hypertension (systolic blood pressure, 130-139 mm Hg or diastolic blood pressure, 80-89 mm Hg) and 10-year atherosclerotic cardiovascular disease (ASCVD) risk ≥10%. Cardiac biomarkers could facilitate a more targeted approach to the treatment of stage 1 hypertension. We studied 1999 to 2004 National Health and Nutrition Examination Survey participants aged ≥20 years with untreated stage 1 hypertension without heart failure or ASCVD. hs-cTnI (high-sensitivity cardiac troponin I) and hs-cTnT (high-sensitivity cardiac troponin T) and NT-proBNP (N-terminal pro-B-type natriuretic peptide) were measured in stored serum. We used the Pooled Cohort Equations to predict 10-year ASCVD risk. All participants had linked mortality follow-up through December 31, 2019. Overall, 17.5% of US adults (32.2 million) had untreated stage 1 hypertension. Among these 32.2 million persons, 15.7% had ASCVD risk ≥10%, 5.6% had elevated hs-cTnI, 4.7% had elevated hs-cTnT, and 9.5% had elevated NT-proBNP. Among adults aged 65 to 79 years with untreated stage 1 hypertension, 80.5% had ASCVD risk ≥10%, 13.0% had elevated hs-cTnI, 15.2% had elevated hs-cTnT, and 29.4% had elevated NT-proBNP. Less than half of the adults aged ≥80 years with untreated stage 1 hypertension had elevated biomarkers. The cardiovascular disease mortality rates among all adults with untreated stage 1 hypertension and with either ASCVD risk ≥10%, elevated hs-cTnI, elevated hs-cTnT, or elevated NT-proBNP were 7.51, 7.74, 8.75, and 5.87 per 1000 person-years, respectively. Cardiac biomarkers may be more selective for informing risk-based treatment decisions in stage 1 hypertension, particularly among adults aged ≥65 years.

Prognostic Implications of N-Terminal Pro-B-Type Natriuretic Peptide in Patients With Non-ST-Elevation Myocardial Infarction.

Limited data exist regarding the prognostic implications of N-terminal pro-B-type natriuretic peptide (NT-proBNP) in patients with non-ST-elevation myocardial infarction (NSTEMI) who undergo percutaneous coronary intervention (PCI).Methods and Results: Of 13,104 patients in the nationwide Korea Acute Myocardial Infarction Registry-National Institutes of Health, 3,083 patients with NSTEMI who underwent PCI were included in the present study. The primary endpoint was major adverse cardiovascular events (MACE) at 3 years, a composite of all-cause death, recurrent myocardial infarction, unplanned repeat revascularization, and admission for heart failure. NT-proBNP was measured at the time of initial presentation for the management of NSTEMI, and patients were divided into a low (<700 pg/mL; n=1,813) and high (≥700 pg/mL; n=1,270) NT-proBNP group. The high NT-proBNP group had a significantly higher risk of MACE, driven primarily by a higher risk of cardiac death or admission for heart failure. These results were consistent after confounder adjustment by propensity score matching and inverse probability weighting analysis. In patients with NSTEMI who underwent PCI, an initial elevated NT-proBNP concentration was associated with higher risk of MACE at 3 years, driven primarily by higher risks of cardiac death or admission for heart failure. These results suggest that the initial NT-proBNP concentration may have a clinically significant prognostic value in NSTEMI patients undergoing PCI.

Natriuretic Peptides and Prognosis in Patients With Type 2 Diabetes Mellitus and High Risk for Cardiovascular Events

BackgroundThe prognosis of individuals with and without an established heart failure (HF) diagnosis and similarly elevated N-terminal pro-B-type natriuretic peptide (NT-proBNP) levels is not well-known. Methods and ResultsCANVAS (Canagliflozin Cardiovascular Assessment Study) trial participants were stratified according to baseline NT-proBNP quartiles and history of HF at baseline. Adjusted event rates per 1000 patient-years of follow-up for hospitalizations for HF, cardiovascular mortality, and kidney events were assessed, and hazard ratios (HR) were calculated using Cox proportional hazard models. Of the 3507 participants with available NT-proBNP concentrations, 471 (13.4%) had history of HF. The incidence rate per 1000 patient-years for hospitalizations for HF increased across the NT-proBNP quartiles in patients with (0, 2.8, 13.4, and 40.1; P < .001) and without (1.8, 3.1, 6.0, and 19.1; P < .001) HF, with a significantly higher risk in patients with HF compared with those without (with HF, quartile 3 HR 9.28 [interquartile range (IQR) 1.15–75.05]; P = .04; without HF, quartile 4 HR 4.86 [95% CI, 2.08–11.35]; P < .001). A similar higher risk for kidney events was seen in HF patients (with HF, quartile 4 HR 6.94 [95% CI, 2.66–18.08]; P = .001; without HF, quartile 4 HR 4.85 [95% CI, 3.02–7.80]; P = .001). Similar trends were seen for cardiovascular mortality. ConclusionsAmong patients with type 2 diabetes and cardiovascular risk, an elevated NT-proBNP level was associated with worse HF and kidney outcomes in general, regardless of history of HF; however, the presence of a clinical diagnosis of HF at baseline was associated with an incrementally higher risk, particularly in higher NT-proBNP quartiles.

Platelet activating factor acetylhydrolase is associated with cardiac valvular calcification in dialysis patients

Abstract Objectives The cardiovascular mortality risk is greatly increased in patients with chronic kidney disease (CKD), especially in dialysis patients, due to atherosclerosis. Platelet activating factor acetylhydrolase (PAF-AH) is an enzyme that hydrolyzes platelet activating factor (PAF). Valvular calcifications and PAF-AH are associated with atherosclerosis. However, little is known about the status of PAF-AH activity and valvular calcification in dialysis patients. Therefore, the aim of this study was to investigate the status of these parameters in CKD patients. Methods This study included 92 chronic renal failure (CRF) (dialysis group), and 86 CKD patients (non-dialysis group). Echocardiography was performed to assess valvular calcification. Results There was no significant difference between the dialysis and CKD groups in terms of PAF-AH activities. However, when comparisons were stratified according to the presence of valve calcification, higher PAF-AH activity and N-terminal pro-B-type natriuretic peptide (NT-proBNP) levels were evident in patients with calcification compared to those without. Additionally, the CRF group also exhibited elevated PAF-AH and NT-proBNP levels. While elevated NT-proBNP persisted in the CKD group, in contrast, changes in PAF-AH were not significant. Conclusions The results of this study suggest that high PAF-AH and NT-proBNP levels are associated with valvular calcification in dialysis patients. Both biomarkers may be used as a risk factor for calcification. Furthermore, inhibition of PAF-AH activity may be a treatment target to reduce calcification.

Natriuretic peptides, body mass index and heart failure risk: Pooled analyses of SAVOR-TIMI 53, DECLARE-TIMI 58 and CAMELLIA-TIMI 61.

N-terminal pro-B-type natriuretic peptide (NT-proBNP) concentrations are lower in patients with obesity. The interaction between body mass index (BMI) and NT-proBNP with respect to heart failure risk remains incompletely defined. Data were pooled across three randomized clinical trials enrolling predominantly patients who were overweight or obese with established cardiometabolic disease: SAVOR-TIMI 53, DECLARE-TIMI 58 and CAMELLIA-TIMI 61. Hospitalization for heart failure (HHF) was examined across strata of baseline BMI and NT-proBNP. The effect of dapagliflozin versus placebo was assessed for a treatment interaction across BMI categories in patients with or without an elevated baseline NT-proBNP (≥125 pg/ml). Among 24 455 patients, the median NT-proBNP was 96 (interquartile range [IQR]: 43-225) pg/ml and the median BMI was 33 (IQR 29-37) kg/m2, with 68% of patients having a BMI ≥30 kg/m2. There was a significant inverse association between NT-proBNP and BMI which persisted after adjustment for all clinical variables (p < 0.001). Within any range of NT-proBNP, those at higher BMI had higher risk of HHF at 2 years (comparing BMI <30 vs. ≥40 kg/m2 for NT-proBNP ranges of <125, 125-<450 and ≥450 pg/ml: 0.0% vs. 0.6%, 1.3% vs. 4.0%, and 8.1% vs. 13.8%, respectively), which persisted after multivariable adjustment (adjusted hazard ratio [HRadj] 7.47, 95% confidence interval [CI] 3.16-17.66, HRadj 3.22 [95% CI 2.13-4.86], and HRadj 1.87 [95% CI 1.35-2.60], respectively). In DECLARE-TIMI 58, dapagliflozin versus placebo consistently reduced HHF across BMI categories in those with an elevated NT-proBNP (p-trend for HR across BMI = 0.60), with a pattern of greater absolute risk reduction (ARR) at higher BMI (ARR for BMI <30 to ≥40 kg/m2: 2.2% to 4.7%; p-trend = 0.059). The risk of HHF varies across BMI categories for any given range of circulating NT-proBNP. These findings showcase the importance of considering BMI when applying NT-proBNP for heart failure risk stratification, particularly for patients with low-level elevations in NT-proBNP (125-<450 pg/ml) where there appears to be a clinically meaningful absolute and relative risk gradient.

Associations between N-Terminal Pro-B-Type Natriuretic Peptide, Body Fluid Imbalance and Quality of Life in Patients Undergoing Hemodialysis: A Cross-Sectional Study

Natriuretic peptides may be associated with the complex interaction between malnutrition and fluid overload. This study assessed the relationship between N-terminal pro-B-type natriuretic peptide (NT-proBNP), body fluid composition, and quality of life (QOL) domains. A multicenter, cross-sectional study was conducted between 2019 and 2022. The QOL survey of 322 patients undergoing maintenance hemodialysis (227 men and 95 women; mean age, 65 ± 12 years) was conducted using the Kidney Disease QOL-Short Form v. 1.3. The patients in the higher NT-proBNP quartile group were older and had a longer dialysis vintage; lower body mass index, serum albumin, blood urea nitrogen, creatinine, sodium, uric acid, total cholesterol, triglycerides, and hemoglobin levels; lower geriatric nutritional risk index (GNRI), skeretal mascle mass index, and phase angle (PhA); and higher pre- and post-dialysis systolic blood pressure (BP), cardiothoracic index, and C-reactive protein (CRP) (p &lt; 0.05). Multivariate analysis revealed that post-dialysis systolic BP, CRP, and GNRI or PhA were independently associated with NT-proBNP. The higher NT-proBNP group experienced muscle attenuation and/or inflammation and an enlarged left atrium. Consequently, the elevated NT-proBNP by such an imbalance in body fluid composition is associated with lower health-related QOL.

Clinical characteristics and outcomes of patients hospitalized with heart failure with preserved ejection fraction and low NT-proBNP levels.

The aim of this study was to investigate the clinical characteristics and prognosis of patients hospitalized with heart failure with preserved ejection fraction (HFpEF) and low N-terminal pro-B-type natriuretic peptide (NT-proBNP) levels. Seven hundred ninety consecutive patients hospitalized with HFpEF from 2006 to 2017 were enrolled. Clinical characteristics and outcomes were compared between low NT-proBNP group (<300 ng/L) and elevated NT-proBNP group (≥300 ng/L). 108 HFpEF patients (13.7%) presented with low NT-proBNP levels. Age, body mass index, atrial fibrillation, New York Heart Association functional class, and albumin were independent predictors of low NT-proBNP levels in HFpEF patients. During the median follow-up duration of 1103 days, 11 patients (10.2%) in low NT-proBNP group suffered from primary endpoint event. Elevated NT-proBNP group had a higher risk of all-cause death or heart transplantation than low NT-proBNP group (adjusted HR [95%CI]: 2.36 [1.24,4.49], P = .009). Stratified analyses showed that the association between NT-proBNP (elevated NT-proBNP group vs low NT-proBNP group) and risk of all-cause death or heart transplantation was stronger in non-atrial fibrillation patients than in atrial fibrillation patients (P value for interaction = .025). Furthermore, the associations between NT-proBNP and risk of all-cause death or heart transplantation were stronger in younger and male patients than in older and female patients. However, both subgroups only reached borderline significant (P values for interaction = .062 and .084, respectively). Our findings suggest that low NT-proBNP levels were common in patients hospitalized with HFpEF. Patients with HFpEF and low NT-proBNP levels had a better prognosis than those with elevated NT-proBNP levels, particularly in younger, male, and non-atrial fibrillation patients.

Strategic noninvasive multimodal assessment of cardiac performance in patients with heart failure

Abstract Aims We sought to evaluate whether a noninvasive combination assay targeting left ventricular filling pressure (LVFP) would be useful for risk stratification of patients with heart failure (HF). Although abnormal LVFP is inevitably related to HF outcomes, its noninvasive application remains difficult in daily practice. Methods This prospective observational study enrolled consecutive hospitalized HF patients. According to the baseline N-terminal pro-B-type natriuretic peptide (NT-proBNP) and Doppler echocardiographic diastolic assessments, patients were classified into three groups: normal range of both LVFP and NT-proBNP (Group 1), normal range of LVFP but elevated NT-proBNP (Group 2), and elevated LVFP and NT-proBNP (Group 3). The primary endpoints were the composite adverse cardiovascular events. Results Event-free survival in Group 2 (n = 56, mean age of 65.4±12.4) was better than that in Group 3 (n = 45, mean age of 68.5±11.5) but worse than that in Group 1 (n = 123, mean age of 61.4±10.5) (log-rank p &amp;lt;0.001). Cardiopulmonary exercise test (CPET) findings were compatible with these findings. Left atrial strain showed better risk stratification than left atrial volume index. Serial addition of left atrial assessment and CPET in the model incrementally enhanced the predictive power of LVFP-based stratification for adverse events. Conclusions The strategic combination of NT-proBNP, echocardiographic LVFP and left atrial function, and CPET is helpful to predict adverse clinical outcomes in patients with HF. The larger the number of combined cardiac performance indicators, the better the noninvasive risk-stratification was.

Effects of dapagliflozin in heart failure with preserved ejection fraction and chronic obstructive pulmonary disease: an analysis of the DELIVER trial

Abstract Introduction Chronic obstructive pulmonary disease (COPD) is a common comorbidity in heart failure (HF) with preserved ejection fraction (HFpEF) and associated with worse outcomes. Purpose We investigated the relationship between COPD status and outcomes, and the efficacy of dapagliflozin, compared with placebo, according to COPD status in patients with heart failure (HF) with preserved ejection fraction (HFpEF) randomized in DELIVER. Methods A total of 6,263 patients with HF with New York Heart Association functional class II-IV, left ventricular ejection fraction &amp;gt;40%, evidence of structural heart disease, and elevated N-terminal pro–B-type natriuretic peptide levels were randomized to dapagliflozin or placebo. Clinical outcomes and the effect of dapagliflozin, according to COPD status at baseline, were examined. The primary outcome was a composite of cardiovascular death or worsening HF. Results Of the 6,261 patients with data on baseline COPD, 692 (11.1%) had a history of COPD. Compared with patients without COPD, those with COPD were older, more often men and current smokers, and they had a higher BMI, but lower systolic blood pressure. Patients with COPD also had a longer duration of HF, a higher rate of prior HF hospitalization, higher NT-proBNP, and worse NYHA functional class and KCCQ-TSS. The risk of the primary endpoint was higher in patients with COPD compared with those without COPD (adjusted HR: 1.29 (95% CI: 1.09-1.52). The benefit of dapagliflozin on the primary outcome was consistent irrespective of COPD status: no COPD, HR: 0.82 (95% CI: 0.72-0.93); COPD, HR: 0.84 (95% CI: 0.63-1.12) (Pinteraction = 0.92). Consistent effects were observed for HF hospitalization, cardiovascular death, and all-cause mortality (Table). Dapagliflozin, as compared with placebo, increased (improved) the KCCQ-TSS from baseline to 8 months to a similar extent in patients with and without COPD (Pinteraction = 0.75) (Table). Adverse events and treatment discontinuation were not more frequent with dapagliflozin than with placebo irrespective of COPD status. Conclusions COPD is common in patients with HFpEF and associated with worse outcomes. Dapagliflozin reduced the risk of worsening HF or cardiovascular death, and improved symptoms, similarly in patients with and without COPD. In addition, dapagliflozin was safe and well-tolerated, irrespective of COPD status.

Cardiovascular and inflammatory biomarkers for non-invasive detection of coronary artery obstruction and prediction of long-term survival in patients with suspected chronic coronary syndrome

Abstract Introduction and methods: The knowledge about diagnostic and prognostic value of cardiac and inflammatory biomarkers in patients with chronic coronary syndrome (CCS) is limited. To address this, we analyzed serum levels of selected biomarkers in 2536 patients with suspected CCS (35% female) from the Leipzig LIFE Heart Study who were admitted for coronary angiography. The median follow-up was 10 years. The following biomarkers were considered: high sensitive troponin T (hsTNT), N-terminal pro B-type natriuretic peptide (NT-proBNP), copeptin, high sensitive C-reactive protein (hsCRP) and interleukin-6 (IL-6). Patients were stratified according to the angiographic severity of coronary artery disease (CAD): CAD0 (no sclerosis), CAD1 (non-obstructive, i.e., stenosis &amp;lt; 50%), CAD2 (≥ one stenosis ≥ 50%). Group comparison (GC) included GC1: CAD0 + 1 vs. CAD2, GC2: CAD0 vs. CAD1 + 2. Using age-, sex and symptom-based pre-test probability (PTP) table for obstructive CAD (i.e. CAD 2) which was published in the current CCS guidelines, patients were further classified into the following three categories: PTP &amp;lt; 5% (n=559), PTP 5-15% (n=545) and PTP &amp;gt; 15% (n=1432). Results CAD0, CAD1, CAD2 were apparent in 999, 529, and 1008 patients, respectively. Upon adjustment for traditional risk factors (TRF) the levels of hsTNT, NT-proBNP and IL-6 showed significant difference in GC1 (hsTNT: p=2.0x10-10, NT-proBNP: p=0.049, IL6: p=0.030). In GC2 only elevated hsTNT remained significant (p=1.9x10-7). In the ROC analysis only hsTNT slightly improved the AUC for the GC1-comparison in addition to TRF (0.729 with vs 0.712 witt hsTNT, p=0.013). Within the PTP subcategories the following results were obtained: PTP &amp;lt; 5%: AUC 0.747 with vs 0.730 without hsTNT, p=0.017; PTP 5-15 %: AUC 0.636 with vs 0.670 without hsTNT, p&amp;lt;0.001; PTP &amp;gt; 15%: AUC 0.699 with vs 0.677 without hsTNT, p= 0.024). In PTP 5-15% subgroup TropT cut-off value &amp;lt; 3 pg/mL (N= 119 / 23.4%) showed sensitivity of 89.7% and specificity of 73.1% for CAD2 detection. Ten years survival in groups CAD0, CAD1, CAD2 were 88.3%, 77.3%, 72.4%, respectively. In the multivariate analysis elevated hsTNT, NT-proBNP, copeptin and IL-6 remained significant mortality predictors in CAD2 patients with hazard ratios of similar magnitude (i.e. 1.5, 1.3, 1.4 and 1.3 per unit on the log-scale of the parameters, respectively). hsCRP did not reach significance. In the model stratified into tertiles according to the effects of classical risk factors and the joint biomarker levels for except hsCRP, hazard rates were 3.13 (tertile 2 vs 1) and 11.2 (tertile 3 vs 1). Conclusions In the present study hsTNT substantially improved the detection of obstructive CAD particularly in patients with intermediate PTP 5-15%. Furthermore, the studied biomarkers enable fast and precise non-invasive prediction of mortality risk in patients with suspected CCS, allowing tailored primary and secondary CAD prevention in this high-risk group.

Abstract 18200: Prognostic Importance of Serial NT-proBNP Measurements Following High-Risk Mi: The PARADISE-MI Trial

Introduction: N-terminal pro-B-type natriuretic peptide (NT-proBNP) is a potent predictor of heart failure (HF) and death following myocardial infarction (MI). NT-proBNP levels change post MI. Hypothesis: Serial measurements of NT-proBNP add prognostic information. Aims: To investigate the prognostic importance of NT-proBNP two weeks after MI in PARADISE-MI and to identify predictors of week 2 NT-proBNP. Methods: Patients with MI and LVEF ≤40% and/or pulmonary congestion (n=5661) were randomized to sacubitril/valsartan or ramipril. Patients with NT-proBNP measured at week 2 (n=1057) were analyzed. Associations of week 2 NT-proBNP with subsequent clinical outcomes were evaluated with Cox models adjusted for baseline NT-proBNP, age, sex, atrial fibrillation (AF), LVEF, STEMI presentation, BMI, eGFR, high-sensitivity troponin T (hs-cTnT), time from presentation to randomization and treatment assignment. Results: Median NT-proBNP was 1425 [685, 2598] ng/L at week 2, declining 23% (95% CI, 20-26%) from baseline. Patients in the highest NT-proBNP quartile at week 2 (≥2616 ng/L) were older, had lower LVEF and eGFR, higher Killip class, more AF, and higher baseline NT-proBNP (all p≤0.05). Higher NT-proBNP at week 2 was independently associated with greater risk of CV death or incident HF (adjusted HR [aHR] 1.62 per log2; 95% CI, 1.30-2.03), HF hospitalization (aHR 1.96; 95% CI, 1.46-2.62) and all-cause death (aHR 1.86; 95% CI, 1.40-2.47). Higher baseline NT-proBNP and hs-cTnT, longer interval between presentation and randomization and female sex were associated with higher week 2 NT-proBNP levels while sacubitril/valsartan was associated with lower levels (Table). Conclusions: Patients with elevated NT-proBNP two weeks after high-risk MI are at greater risk of subsequent death or incident HF, even after adjusting for baseline level. Higher baseline NT-proBNP and hs-cTnT are predictive of higher week 2 NT-proBNP while sacubitril/valsartan decreases levels.

Abstract 18410: Correlation Between Body Mass Index and NT-proBNP Levels in Heart Failure With Preserved Ejection Fraction: Implications for Clinical Outcomes

Introduction: N-terminal pro B type natriuretic peptide (NT-proBNP) is associated with increased cardiovascular events in heart failure with preserved ejection fraction (HFpEF). Adiposity is inversely correlated with NT-proBNP. It remains unclear whether obese HFpEF patients exhibit disproportionate outcomes with lower NT-proBNP. Hypothesis: We aimed to study the relationship between NT-proBNP and BMI in the Johns Hopkins University (JHU) HFpEF cohort to identify patient characteristics with increased NT-proBNP in obese HFpEF patients, adjusting for the inverse relation between NT-proBNP and BMI. Methods: We identified 338 individuals from June 2013 to November 2022. Univariate linear regression was performed between NT-proBNP and BMI. The cohort was split based on the median BMI and studentized residuals from NT-proBNP-BMI relationship (low BMI high BNP [Group 1] high BMI high BNP [Group 2] low BMI low BNP [Group 3] high BMI low BNP [Group 4]). Kruskal-Wallis test or Chi-square test was used to compare groups. Results: The median BMI of the cohort was 37kg/m 2 , and with every 1kg/m 2 increase in the BMI, the cut-off for elevated NT-proBNP reduced by 4 pg/ml. High BMI HFpEF patients were younger, predominantly female, and on diuretics (p&lt;0.05 for all), independent of their NT-proBNP levels. Group 4 patients performed better on the 6-minute walk test (240±136 m), had better renal function (eGFR: 68.7±27.3), and less left ventricular (LV) hypertrophy and only mild diastolic dysfunction on echocardiography. Surprisingly, Group 2 resembled Group 1 despite having 70% reduced median NT-proBNP (1898[1047,4409] vs 574[207,1322], p&lt;0.0001). Both “high BNP” groups exhibited lower event free survival for all -cause mortality(p=0.0001) and HF-hospitalization(p&lt;0.05). Conclusions: NT-proBNP is predictive of clinical outcomes in HFpEF even in the presence of obesity. BMI adjusted NT-proBNP may be useful in the diagnosis and prognosis of HFpEF.

Abstract 12796: N-Terminal Pro-B-Type Natriuretic Peptide Levels for Determining Long Term Prognosis in Patients With Non-ST-Elevation Myocardial Infarction (NSTEMI); a Systematic Review and Meta-Analysis

Introduction: The utilization of the biomarker N-Terminal Pro-B-Type Natriuretic Peptide (NT-proBNP) holds diagnostic value for identifying heart failure and acute coronary syndromes. However, its long-term prognostic significance in patients with non-ST-elevation Myocardial Infarction (NSTEMI), a subtype of acute coronary syndromes, remains inadequately explored. Hypothesis: This meta-analysis aims to investigate the correlation between NT-proBNP levels and the subsequent occurrence of adverse clinical outcomes in individuals with NSTEMI. Methods: A systematic search was conducted on PubMed, Google Scholar, Science Direct, Cochrane, and Embase, encompassing articles published until June 2023. The highest recorded NT-proBNP value was utilized for analysis, considering a follow-up duration of at least 30 days. Odds ratios (OR) were synthesized using the random-effects DerSimonian-Laird model, with statistical significance set at a p-value &lt;0.05. Results: The study involved 8 articles, comprising a total of 7,921 patients, of whom 7,161 were diagnosed with NSTEMI. The analysis examined the relationship between NT-proBNP levels and clinical outcomes in NSTEMI patients over an average follow-up period of 19.85 months. Elevated NT-proBNP levels exhibited a significant association with increased odds of Major Adverse Cardiac Events (MACE) [OR 2.56, 95% CI: 1.58-3.53, I2=94.06%, p&lt;0.001], all-cause mortality [OR 2.54, 95% CI: 0.53-4.55, I2=76.96%, p=0.01], and myocardial infarction (MI) [OR 1.10, 95% CI: 0.56-1.63, I2=0.00%, p&lt;0.001]. Conclusions: The elevated NT-proBNP levels in patients with NSTEMI are significantly associated with long-term adverse cardiovascular outcomes. Consequently, NT-proBNP can serve as a valuable tool for assessing the risk of unfavorable cardiac events. However, further extensive investigations are warranted to validate these results on a larger scale.

N-Terminal Pro-B Type Natriuretic Peptide as a Predictive Biomarker of Bronchopulmonary Dysplasia or Death Due to Bronchopulmonary Dysplasia in Preterm Neonates: A Systematic Review and Meta-Analysis.

Emerging evidence suggests the clinical utility of N terminal pro B type natriuretic peptide (NT-proBNP) in multiple cardiac and pulmonary abnormalities both in adult and pediatric populations. To date, however, there is no consensus regarding its efficacy for the prediction and severity of bronchopulmonary dysplasia in premature neonates. The objective of the present meta-analysis was to determine differences in NT-proBNP among neonates that develop BPD or die from BPD and to evaluate if there is relative information on the diagnostic accuracy of the method. We conducted a systematic search according to the PRISMA guidelines and looked into Medline (1966-2023), Scopus (2004-2023), Clinicaltrials.gov (2008-2023), EMBASE (1980-2023), Cochrane Central Register of Controlled Trials CENTRAL (1999-2022) and Google Scholar (2004-2023) together with the reference lists from included studies. The potential risk of bias encountered in our study was evaluated using the QUADAS -2 tool. Finally, a total of 9 studies met the eligibility criteria, comprising 1319 newborns, from which 397 developed BPD and 922 were unaffected controls. The results retrieved from our meta-analysis showed that newborns suffering from BPD had notably elevated NT-proBNP levels after birth when compared with healthy neonates (SMD 2.57, 95% CI 0.41, 4.72). The summary effect of the AUC meta-analysis showed that NT-proBNP was very accurate in detecting neonates at risk of developing severe BPD or dying from the disease (AUC -0.16, 95% CI -0.23, -0.08). No studies reported data relevant to the sensitivity and/or specificity of the method in diagnosing BPD. Serum NT-proBNP levels represent a potential future biomarker with great diagnostic validity for the prediction of BPD complicating preterm deliveries. The limited amount of studies included and the significant variations in cutoff values and timing of measurement still restrict the application of NT-proBNP as an established clinical biomarker for BPD. The design of larger prospective studies will provide a more representative number of participants and will address the discrepancies in existing literature.

Predictors of Major Adverse Cardiovascular Events in Patients With Moderate Aortic Stenosis: Implications for Aortic Valve Replacement.

Although the prognosis and management of severe aortic stenosis has been extensively studied, the risk stratification and outcomes of patients with moderate aortic stenosis remain elusive. This study included 674 patients from the Cleveland Clinic Health System with moderate aortic stenosis (aortic valve area, 1-1.5 cm2; mean gradient, 20-40 mm Hg; and peak velocity <4 m/s) and an NT-proBNP (N-terminal pro-B-type natriuretic peptide) level within 3 months of index diagnosis. The primary outcome of major adverse cardiovascular events (defined as the composite outcome of progression to severe aortic stenosis requiring aortic valve replacement, heart failure hospitalization, or death) was extracted from the electronic medical record. The mean age was 75.3±12 years, and 57% were men. During a median follow-up of 316 days, the composite end point occurred in 305 patients. There were 132 (19.6%) deaths, 144 (21.4%) heart failure hospitalizations, and 114 (16.9%) patients underwent aortic valve replacement. Elevated NT-proBNP (1.41 [95% CI, 1.01-1.95]; P=0.048), diabetes (1.46 [95% CI, 1.08-1.96]; P=0.01), elevated averaged mitral valve E/e' ratio (hazard ratio, 1.57 [95% CI, 1.18-2.10]; P<0.01), and presence atrial fibrillation at the time of index echocardiogram (hazard ratio, 1.83 [95% CI, 1.15-2.91]; P=0.01) were each independently associated with an increased hazard for the composite outcome and when taken collectively, each of these factors incrementally increased risk. These results further elucidate the relatively poor short-medium term outcomes and risk stratification of patients with moderate aortic stenosis, supporting randomized trials assessing the efficacy of transcatheter aortic valve replacement in this population.

Independent and joint associations between the triglyceride-glucose index and NT-proBNP with the risk of adverse cardiovascular events in patients with diabetes and acute coronary syndrome: a prospective cohort study

BackgroundElevated triglyceride-glucose (TyG) index and N-terminal pro-B-type natriuretic peptide (NT-proBNP) are independently associated with increased risk of major adverse cardio-cerebral events (MACCEs) in diabetic patients with the acute coronary syndrome (ACS), but have not been evaluated jointly. We sought to investigate the independent and joint association of the TyG index and NT-proBNP with MACCEs risk.MethodsData from 5046 patients with diabetes and ACS were recorded in the Cardiovascular Center Beijing Friendship Hospital Database Bank between 2013 and 2021, including measurements of fasting triglycerides, plasma glucose, and NT-proBNP. The TyG index was calculated as Ln (fasting triglycerides [mg/dL] × fasting plasma glucose [mg/dL]/2). Associations of the TyG index and NT-proBNP with MACCEs risk were assessed using flexible parametric survival models.ResultsDuring 13589.9 person-years of follow-up, 985 incident MACCEs of the 5046 patients (65.6 years of age and 62.0% men) were observed. Elevated TyG index (HR: 1.18; 95% CI 1.05‒1.32 per 1 unit increase) and NT-proBNP categories (HR: 1.95; 95% CI: 1.50‒2.54 for > 729 pg/ml compared to < 129 pg/ml) were independently associated with MACCEs risk in the fully adjusted model. According to the joint categories of the TyG index and NT-proBNP, patients with the TyG index > 9.336 and NT-proBNP > 729 pg/ml were at the highest risk of MACCEs (HR: 2.45; 95% CI 1.64‒3.65) than the ones with TyG index < 8.746 and NT-proBNP < 129 pg/ml. The test for interaction was not significant (Pinteraction = 0.49). Incorporating these two biomarkers into the established clinical model, the Global Registry of Acute Coronary Events (GRACE) risk score, resulted in a significant improvement in risk stratification.ConclusionsThe TyG index and NT-proBNP were independently and jointly associated with the risk of MACCEs in patients with diabetes and ACS, suggesting that patients with both markers elevated should be aware of the higher risk in the future.

470-P: Elevated NT-ProBNP Is Associated with Significant CT Left Anterior Descending Coronary Artery Calcification Score in T2DM

Aims &amp; Objectives: Establish the relationship between N-terminal Pro B-type natriuretic peptide (NT-ProBNP) &amp; CT-Coronary calcium score (CAC) in patients with T2DM. Methodology: Between Oct'19 &amp; Dec'19, 62 asymptomatic T2DM patients, aged 18-75yrs, irrespective of A1c, on regular F/U who had NT-ProBNP ≥ 125pg/ml (Group-G1) &amp; who had undergone CAC &amp; 2D-Echocardiogram (2D) were retrospectively analysed &amp; compared to 62 T2DM patients (Group-G2) with corresponding NT-ProBNP &amp;lt; 125 along with CAC &amp; 2D. Cardio-renal (CR) biomarkers &amp; CAC were compared at the point NT-ProBNP ≥ 125 for Gr-1 with Gr-2. Patients with only preserved ejection fraction (EF) were included. Patients were receiving standard glucose lowering, lipid lowering &amp; BP lowering therapy optimised for CR biomarkers (BMI, HbA1c, Systolic-BP, Diastolic-BP, Lipid profile, highly sensitive C-reactive protein {HSCRP}, Creatinine, urine microalbumin/creatinine ratio {UACR}). Exclusion: low-EF, H/O of IHD, recent (&amp;lt;6mths) hospitalisation &amp;/or coronary intervention. Data analysis: SPSS version 26 &amp; represented as Mean ± 2(SD) with 95% Cl. Pearson co-relation was used &amp; p-value &amp;lt;0.05 was considered significant (S). Results: There was a S difference between Gr-1 &amp; Gr-2 in mean Age yrs (Gr1: 64.35 ± 6.874yrs Vs Gr2: 61.15 ± 6.840, p-0.010), BMI kg/m2 (Gr1: 32.25 ± 5.59 Vs Gr2: 29.66 ± 4.81, p-0.007), NT-ProBNP pg/ml (Gr1: 167.31 ± 159.46 Vs Gr2: 33.98 ± 20.64, p-0.000) &amp; CAC score HU {LAD: Gr1: 286.35 ± 376.83 Vs Gr2: 167.63 ± 234.47, p-0.0393). Total CAC between both groups (Gr1: 471.13 ± 622.81 Vs Gr2: 420.92 ± 659.77, p-0.6638) remained non-significant. There was also no difference seen in SBP, DBP, Lipid Profile (TC, LDL, TG, HDL, Apo B), hs-CRP, serum creatinine, eGFR &amp; UACR. Conclusion: NT-ProBNP ≥125 is related to greater CAC in LAD &amp; may represent an ischemic signal requiring optimal cardiovascular risk factor management inT2DM patients. These patients are older &amp; have a greater BMI. Disclosure V.Gupta: None. V.Teli: None.

450-P: N-Terminal Pro-B Type Natriuretic Peptide Concentrations in Diabetic Cardiomyopathy—Baseline Data from the ARISE-HF Trial

Background: Diabetic Cardiomyopathy (DbCM) is a form of Stage B heart failure (HF). Concentrations of N-terminal pro-B type natriuretic peptide (NT-proBNP) may predict risk for HF progression in persons with DbCM. The ARISE-HF study (NCT04083339) is evaluating efficacy of AT-001, a highly selective aldose reductase inhibitor (AT-001) to improve exercise tolerance in affected patients. The aim of this analysis was to assess association between baseline NT-proBNP and cardiac status in type 2 diabetes participants with DbCM. Methods: Impaired exercise tolerance and baseline characteristics were evaluated in 679 patients with DbCM as a function of NT-proBNP at enrollment. Results: Median NT-proBNP in the overall study population was 71 ng/L (IQR 35-133). Baseline characteristics were similar across NT-proBNP concentrations, however, participants with higher NT-proBNP had higher left atrial volume (p&amp;lt;0.001) and higher right ventricular systolic pressure (p=0.04) on baseline echocardiogram. Higher NT-proBNP concentrations were associated with reduced physical activity reflected in lower PASE Score and a worse functional capacity reflected in lower peak VO2 (p&amp;lt;0.001) (Table 1). Conclusion: Among patients with DbCM, elevated NT-proBNP is associated with echocardiographic abnormalities and worse cardiac functional capacity and inversely associated with activity. Disclosure J.Butler: Consultant; Abbott,, Amgen, Applied Therapeutics, Array, Astra Zeneca, Bayer,, Boehringer Ingelheim, Bristol Myers Squibb, CVRx, G3 Pharma,, Impulse Dynamics, Innolife, Janssen, LivaNova, Luitpold, Medtronic, Merck, Novartis, NovoNordisk, Relypsa, Roche, Sequana Medical, Vifor, Speaker's Bureau; Novartis, Boehringer Ingelheim-Lilly, Astra Zeneca, Janssen. F.Zannad: Advisory Panel; BMS, Novo Nordisk, Pfizer Inc., Servier Laboratories, Other Relationship; Applied Therapeutics Inc., Bayer Inc., Boehringer Ingelheim and Eli Lilly Alliance, Merck &amp; Co., Inc., Novartis. J.L.Januzzi: Consultant; Boehringer Ingelheim Inc., Janssen Pharmaceuticals, Inc., AstraZeneca, Research Support; Applied Therapeutics Inc., Abbott, Roche Diagnostics, Novartis, Innolife Co., Ltd. S.Del prato: Advisory Panel; Abbott Diagnostics, Altimmune, Amarin Corporation, Applied Therapeutics Inc., Eli Lilly and Company, Merck &amp; Co., Inc., Novo Nordisk A/S, Vertex Pharmaceuticals Incorporated, Novartis, Consultant; A. Menarini Diagnostics, Research Support; AstraZeneca, Boehringer Ingelheim International GmbH, Speaker's Bureau; AstraZeneca, Boehringer Ingelheim International GmbH, Eli Lilly and Company, Merck &amp; Co., Inc., Novo Nordisk A/S, Sanofi. J.Ezekowitz: Advisory Panel; Applied Therapeutics Inc. N.E.Ibrahim: None. C.S.Lam: Other Relationship; Actelion, Alleviant Medical, Allysta Pharma, Amgen, AnaCardio, Applied Therapeutics, AstraZeneca, Bayer, Boehringer-Ingelheim, Boston Scientific, Cytokinetics, Darma Inc, EchoNous Inc, Eli Lilly, Impulse Dynamics, Intellia Therapeutics, Ionis Pharmaceutical, Janssen Research &amp; Development LLC, Medscape/WebMD Global LLC, Merck, Novartis, Novo Nordisk, Prosciento Inc, Radcliffe Group Ltd, Recardio Inc, ReCor Medical, Roche Diagnostics, Sanofi, Siemens Healthcare Diagnostics, Us2.ai. R.Perfetti: None. J.Rosenstock: Advisory Panel; Applied Therapeutics Inc., Boehringer Ingelheim Inc., Eli Lilly and Company, Novo Nordisk, Oramed Pharmaceuticals, Sanofi, Zealand Pharma A/S, Intarcia Therapeutics, Inc., Hanmi Pharm. Co., Ltd., Research Support; Applied Therapeutics Inc., Boehringer Ingelheim Inc., Eli Lilly and Company, Merck &amp; Co., Inc., Novartis, Novo Nordisk, Pfizer Inc., Sanofi, Intarcia Therapeutics, Inc. W.Tang: Consultant; Sequana Medical NV, Cardiol Therapeutics, Genomics plc, Zehna Therapeutics LLC, Renovacor, Boston Scientific Corporation, Kiniksa Pharmaceuticals Inc, WhiteSwell Inc, CardiaTec Biosciences Inc, Other Relationship; American Board of Internal Medicine, Springer Nature, Research Support; National Heart, Lung, and Blood Institute. A.Urbinati: None.

Associations of Cardiac Biomarkers With Peripheral Artery Disease and Peripheral Neuropathy in US Adults Without Prevalent Cardiovascular Disease.

NT-proBNP (N-terminal pro-B-type natriuretic peptide), high-sensitivity cardiac troponin T (hs-troponin T), and high-sensitivity cardiac troponin I (hs-troponin I) are increasingly being recommended for risk stratification for a variety of cardiovascular outcomes. The aims of our study were to establish the prevalence and associations of elevated NT-proBNP, hs-troponin T, and hs-troponin I with lower extremity disease, including peripheral artery disease (PAD) and peripheral neuropathy (PN), in the US general adult population without known cardiovascular disease. We also assessed whether the combination of PAD or PN and elevated cardiac biomarkers was associated with an increased risk of all-cause and cardiovascular mortality. We conducted a cross-sectional analysis of the associations of NT-proBNP, hs-troponin T, and hs-troponin I with PAD (based on ankle-brachial index <0.90) and PN (diagnosed by monofilament testing) in adult participants aged ≥40 years of age without prevalent cardiovascular disease in NHANES (National Health and Nutrition Examination Survey) 1999 to 2004. We calculated the prevalence of elevated cardiac biomarkers among adults with PAD and PN and used multivariable logistic regression to assess the associations of each cardiac biomarker, modeled using clinical cut points, with PAD and PN separately. We used multivariable Cox proportional hazards models to assess the adjusted associations of cross categories of clinical categories of each cardiac biomarker and PAD or PN with all-cause and cardiovascular mortality. In US adults aged ≥40 years, the prevalence (±SE) of PAD was 4.1±0.2% and the prevalence of PN was 12.0±0.5%. The prevalence of elevated NT-proBNP (≥125 ng/L), hs-troponin T (≥6 ng/L), and hs-troponin I (≥6 ng/L for men and ≥4 ng/L for women) was 54.0±3.4%, 73.9±3.5%, and 32.3±3.7%, respectively, among adults with PAD and 32.9±1.9%, 72.8±2.0%, and 22.7±1.9%, respectively, among adults with PN. There was a strong, graded association of higher clinical categories of NT-proBNP with PAD after adjusting for cardiovascular risk factors. Clinical categories of elevated hs-troponin T and hs-troponin I were strongly associated with PN in adjusted models. After a maximum follow-up of 21 years, elevated NT-proBNP, hs-troponin T, and hs-troponin I were each associated with all-cause and cardiovascular mortality, with higher risks of death observed among adults with elevated cardiac biomarkers plus PAD or PN compared with elevated biomarkers alone. Our study establishes a high burden of subclinical cardiovascular disease defined by cardiac biomarkers in people with PAD or PN. Cardiac biomarkers provided prognostic information for mortality within and across PAD and PN status, supporting the use of these biomarkers for risk stratification among adults without prevalent cardiovascular disease.

Subclinical Cardiovascular Disease in US Adults With and Without Diabetes.

Background We characterized the burden and prognostic value of subclinical cardiovascular disease (CVD) assessed by cardiac biomarkers among adults with and without diabetes in the general US population. Methods and Results We measured hs-cTnT (high-sensitivity cardiac troponin T) and NT-proBNP (N-terminal pro-B-type natriuretic peptide) in stored serum samples from the 1999 to 2004 National Health and Nutrition Examination Survey. Among US adults without a history of CVD (n=10 304), we estimated the prevalence of elevated hs-cTnT (≥14 ng/L) and NT-proBNP (≥125 pg/mL) in those with and without diabetes. We examined the associations between elevated hs-cTnT and NT-proBNP with all-cause and CVD mortality after adjustment for demographics and traditional CVD risk factors. The crude prevalence of subclinical CVD (elevated hs-cTnT or NT-proBNP) was ≈2 times higher in adults with (versus without) diabetes (33.4% versus 16.1%). After age adjustment, elevated hs-cTnT, but not elevated NT-proBNP, was more common in those with diabetes, overall and across age, sex, race and ethnicity, and weight status. The prevalence of elevated hs-cTnT was significantly higher in those with longer diabetes duration and worse glycemic control. In persons with diabetes, elevated hs-cTnT and NT-proBNP were independently associated with all-cause mortality (adjusted hazard ratio [HR], 1.77 [95% CI, 1.33-2.34] and HR, 1.78 [95% CI, 1.26-2.51]) and CVD mortality (adjusted HR, 1.54 [95% CI, 0.83-2.85] and HR, 2.46 [95% CI, 1.31-4.60]). Conclusions Subclinical CVD affects ≈1 in 3 US adults with diabetes and confers substantial risk for mortality. Routine testing of cardiac biomarkers may be useful for assessing and monitoring risk in persons with diabetes.