Quality of life and chronic heart failure therapy guided by natriuretic peptides: results from the ProBNP Outpatient Tailored Chronic Heart Failure Therapy (PROTECT) study.

BACKGROUND: Heart failure (HF) treatment guided by amino-terminal pro-B type natriuretic peptide (NT-proBNP) may reduce cardiovascular event rates compared to standard-of-care (SOC) management. Comprehensive understanding regarding effect of NT-proBNP guided care on patient-reported quality of life (QOL) remains unknown. METHODS: One hundred fifty-one subjects with HF due to left ventricular systolic dysfunction were randomized to either SOC HF management or care with a goal to reduce NT-proBNP values ≤1000 pg/mL. Effects of HF on QOL were assessed using the Minnesota Living with HF Questionnaire (MLHFQ) quarterly, with change (Δ) in score assessed across study procedures and as a function of outcome. RESULTS: Overall, baseline MLHFQ score was 30. Across study visits, QOL improved in both arms, but was more improved and sustained in the NT-proBNP arm (repeated measures P = .01); NT-proBNP patients showing greater reduction in MLHFQ score (-10.0 vs -5.0; P = .05), particularly in the physical scale of the questionnaire. Baseline MLHFQ scores did not correlate with NT-proBNP; in contrast, ∆MLHFQ scores modestly correlated with ∆NT-proBNP values (ρ = .234; P = .006) as did relative ∆ in MLHFQ score and NT-proBNP (ρ = .253; P = .003). Considered in tertiles, less improvement in MLHFQ scores was associated with a higher rate of HF hospitalization, worsening HF, and cardiovascular death (P = .001). CONCLUSIONS: We describe novel associations between NT-proBNP concentrations and QOL scores among patients treated with biomarker guided care. Compared to SOC HF management, NT-proBNP guided care was associated with greater and more sustained improvement in QOL (Clinical Trial Registration: www.clinicaltrials.govNCT00351390).

Association between anxiety and C-reactive protein levels in stable coronary heart disease patients.

BACKGROUND: Anxiety is highly prevalent among patients with stable coronary heart disease (CHD). However, the biologic effects that may connect these two seemingly unrelated disorders is not well understood. OBJECTIVE: This study aimed for a comprehensive evaluation of anxiety in stable CHD patients, in addition to cardiac biomarkers such as C-reactive protein (CRP), troponin T, and amino-terminal pro-B-type brain natriuretic peptide. METHOD: The study included 43 CHD patients with anxiety disorder and 42 CHD patients without psychiatric disorder given the Structured Clinical Interview for DSM-IV. RESULTS: Regression analyses showed an association between anxiety (anxiety disorder, not otherwise specified) and CRP levels, despite model adjustment for various related demographic and clinical variables. Anxiety was associated with CRP levels. CONCLUSION: There are significant associations between anxiety and CHD risk, with a potential biologic link between anxiety and elevations in a biomarker with powerful prognostic risk, namely CRP. It is not clear whether this association is directly causal or relates to other medical processes among patients with heightened anxiety. The findings suggest that the current focus on depressive disorders with respect to biomarkers and CHD outcomes should be broadened to include anxiety disorders, as well.

Association between major depressive disorder and C-reactive protein levels in stable coronary heart disease patients.

OBJECTIVE: This study aimed for a comprehensive evaluation of major depressive disorder (MDD) in stable coronary heart disease (CHD) patients, excluding all other potential psychiatric comorbidities, and including associations with cardiac biomarkers such as C-reactive protein (CRP), troponin T (TnT), and amino-terminal pro-B-type brain natriuretic peptide (NT-proBNP). METHODS: Cross-sectional study of a consecutive series of 72 stable CHD outpatients (n=30 with MDD, n=42 with no psychiatric disorder). Psychiatric diagnoses were established by using the Structured Clinical Interview for DSM-IV (SCID), and psychiatric assessment was performed on Axis I, Axis III, Axis IV, and Axis V. Regression analyses were performed including CRP, TnT, and NT-proBNP as dependent variables, and MDD, demographics, and comorbid medical conditions as independent variables. RESULTS: Stepwise multiple regression analyses showed a significant association between MDD and CRP (beta=0.262, P=.02), excluding all other demographic and medical variables from the models, except age (beta=0.266, P=.02). In addition, the results described a significant relationship between type II diabetes mellitus and TnT (beta=0.267, P=.02), and age and NT-proBNP levels (beta=0.374, P=.001). CONCLUSION: Major depressive disorder was associated with elevated CRP levels in a consecutive series of stable CHD patients.

Association between C-reactive protein and generalized anxiety disorder in stable coronary heart disease patients.

AIMS: Comprehensive evaluation of major depressive disorder (MDD), anxiety disorder, and MDD in conjunction with anxiety disorder in stable coronary heart disease (CHD) patients, including cardiac biomarkers such as C-reactive protein (CRP), troponin T (TnT), and amino-terminal pro-B-type brain natriuretic peptide (NT-proBNP). METHODS AND RESULTS: Cross-sectional study of a consecutive series of 120 stable CHD outpatients (n = 30 with MDD, n = 30 with anxiety disorder, n = 30 with MDD and anxiety disorder, n = 30 with no psychiatric disorder). Psychiatric diagnoses were established by using the structured clinical interview for DSM-IV (Diagnostic and Statistical Manual of Mental Disorders-IV). Binomial logistic regression analyses using cut-off scores of biomarkers as dependent variables showed associations between CRP and generalized anxiety disorder (GAD) (P = 0.04), and education (P = 0.004), whereas MDD, and MDD and anxiety disorder did not reach the significance level. TnT showed relationships with hyperlipidaemia (P = 0.009), history of obesity or overweight (P = 0.04), and education (P = 0.04). NT-proBNP was associated with type II diabetes (P = 0.005). CONCLUSION: After adjusting for relevant demographic, medical, and psychiatric co-variables, CRP was associated with GAD.

Improvement in structural and functional echocardiographic parameters during chronic heart failure therapy guided by natriuretic peptides: mechanistic insights from the ProBNP Outpatient Tailored Chronic Heart Failure (PROTECT) study.

AIMS: We sought to determine if heart failure (HF) care with a goal to lower N-terminal pro B-type natriuretic peptide (NT-proBNP) concentrations, compared with standard of care (SOC) management, is associated with improvement in echocardiographic parameters of cardiac structure and function. METHODS AND RESULTS: Of 151 subjects with HF due to left ventricular systolic dysfunction (LVSD) prospectively randomized to NT-proBNP-guided vs. SOC HF care, 116 had serial echocardiographic data. Endpoints in this echocardiographic study included the relationship between change in NT-proBNP and LV reverse remodelling, as well as associations between biomarker-guided therapy and measures of diastolic function, right ventricular (RV) size and function, estimates of LV filling pressure and RV systolic pressure (RVSP), and the degree of mitral regurgitation (MR). After a mean of 10 months of study procedures, in adjusted analyses, final NT-proBNP concentrations predicted risk of remodelling [hazard ratio (HR) ↑LV end-diastolic volume index = 1.43, 95% confidence interval (CI) 1.10-1.86, P = 0.007; HR ↑LV end-systolic volume index = 1.54, 95% CI 1.10-1.91, P = 0.01; HR ↓LV ejection fraction (LVEF) = 1.53, 905% CI 1.12-1.89, P = 0.02]. In addition to greater improvement in LVEF and reductions in LV volume, compared with SOC, NT-proBNP-guided patients showed significant decreases in the ratio of early transmitral peak velocity to early diastolic peak annular velocity (E/E'), pulmonary vein peak S velocity, RV fractional area change, RVSP, and MR severity. CONCLUSION: NT-proBNP concentrations may serve as a non-invasive indicator of the state of cardiac structure and function in HF due to LVSD. Multiple, prognostically meaningful echocardiographic variables improved more significantly in patients treated with NT-proBNP-guided care vs. SOC.

Use of amino-terminal pro-B-type natriuretic peptide to guide outpatient therapy of patients with chronic left ventricular systolic dysfunction.

OBJECTIVES: The aim of this study was to evaluate whether chronic heart failure (HF) therapy guided by concentrations of amino-terminal pro-B-type natriuretic peptide (NT-proBNP) is superior to standard of care (SOC) management. BACKGROUND: It is unclear whether standard HF treatment plus a goal of reducing NT-proBNP concentrations improves outcomes compared with standard management alone. METHODS: In a prospective single-center trial, 151 subjects with HF due to left ventricular (LV) systolic dysfunction were randomized to receive either standard HF care plus a goal to reduce NT-proBNP concentrations ≤1,000 pg/ml or SOC management. The primary endpoint was total cardiovascular events between groups compared using generalized estimating equations. Secondary endpoints included effects of NT-proBNP-guided care on patient quality of life as well as cardiac structure and function, assessed with echocardiography. RESULTS: Through a mean follow-up period of 10 ± 3 months, a significant reduction in the primary endpoint of total cardiovascular events was seen in the NT-proBNP arm compared with SOC (58 events vs. 100 events, p = 0.009; logistic odds for events 0.44, p = 0.02); Kaplan-Meier curves demonstrated significant differences in time to first event, favoring NT-proBNP-guided care (p = 0.03). No age interaction was found, with elderly patients benefitting similarly from NT-proBNP-guided care as younger subjects. Compared with SOC, NT-proBNP-guided patients had greater improvements in quality of life, demonstrated greater relative improvements in LV ejection fraction, and had more significant improvements in both LV end-systolic and -diastolic volume indexes. CONCLUSIONS: In patients with HF due to LV systolic dysfunction, NT-proBNP-guided therapy was superior to SOC, with reduced event rates, improved quality of life, and favorable effects on cardiac remodeling. (Use of NT-proBNP Testing to Guide Heart Failure Therapy in the Outpatient Setting; NCT00351390).