Jun R. Chiong

Validation and Potential Mechanisms of Red Cell Distribution Width as a Prognostic Marker in Heart Failure

BACKGROUND Adverse outcomes have recently been linked to elevated red cell distribution width (RDW) in heart failure. Our study sought to validate the prognostic value of RDW in heart failure and to explore the potential mechanisms underlying this association. METHODS AND RESULTS Data from the Study of Anemia in a Heart Failure Population (STAMINA-HFP) registry, a prospective, multicenter cohort of ambulatory patients with heart failure supported multivariable modeling to assess relationships between RDW and outcomes. The association between RDW and iron metabolism, inflammation, and neurohormonal activation was studied in a separate cohort of heart failure patients from the United Investigators to Evaluate Heart Failure (UNITE-HF) Biomarker registry. RDW was independently predictive of outcome (for each 1% increase in RDW, hazard ratio for mortality 1.06, 95% CI 1.01-1.12; hazard ratio for hospitalization or mortality 1.06; 95% CI 1.02-1.10) after adjustment for other covariates. Increasing RDW correlated with decreasing hemoglobin, increasing interleukin-6, and impaired iron mobilization. CONCLUSIONS Our results confirm previous observations that RDW is a strong, independent predictor of adverse outcome in chronic heart failure and suggest elevated RDW may indicate inflammatory stress and impaired iron mobilization. These findings encourage further research into the relationship between heart failure and the hematologic system.

Prospective assessment of the occurrence of anemia in patients with heart failure: Results from the Study of Anemia in a Heart Failure Population (STAMINA-HFP) Registry

BACKGROUND Although a potentially important pathophysiologic factor in heart failure, the prevalence and predictors of anemia have not been well studied in unselected patients with heart failure. METHODS The Study of Anemia in a Heart Failure Population (STAMINA-HFP) Registry prospectively studied the prevalence of anemia and the relationship of hemoglobin to health-related quality of life and outcomes among patients with heart failure. A random selection algorithm was used to reduce bias during enrollment of patients seen in specialty clinics or clinics of community cardiologists with experience in heart failure. In this initial report, data on prevalence and correlates of anemia were analyzed in 1,076 of the 1,082 registry patients who had clinical characteristics and hemoglobin determined by finger-stick at baseline. RESULTS Overall (n = 1,082), the registry patients were 41% female and 73% white with a mean age (+/-SD) of 64 +/- 14 years (68 +/- 13 years in community and 57 +/- 14 years in specialty sites, P < .001). Among the 1,076 patients in the prevalence analysis, mean hemoglobin was 13.3 +/- 2.1 g/dL (median 13.2 g/dL); and anemia (defined by World Health Organization criteria) was present in 34%. Age identified patients at risk for anemia, with 40% of patients >70 years affected. CONCLUSIONS Initial results from the STAMINA-HFP Registry suggest that anemia is a common comorbidity in unselected outpatients with heart failure. Given the strong association of anemia with adverse outcomes in heart failure, this study supports further investigation concerning the importance of anemia as a therapeutic target in this condition.

Prospective evaluation of the association between hemoglobin concentration and quality of life in patients with heart failure

BACKGROUND Reduced hemoglobin has been associated with adverse outcomes in heart failure, but the relationship of hemoglobin to health-related quality of life in outpatients with this syndrome has not been well studied. METHODS We used data from the prospective, observational Study of Anemia in a Heart Failure Population Registry, which randomly selected outpatients with heart failure from specialty or community cardiology clinics. Hemoglobin was determined by finger stick at baseline and during medically indicated follow-up visits. Health-related quality of life was assessed using the Kansas City Cardiomyopathy Questionnaire and the Minnesota Living with Heart Failure Questionnaire at 3-month intervals for 12 months. RESULTS Adjusted regression analysis demonstrated a significant, direct, linear relationship between hemoglobin and health-related quality of life from baseline through 12 months follow-up on all Kansas City Cardiomyopathy Questionnaire domains (all P < .001) and the Summary and Physical domains of the Minnesota Living with Heart Failure Questionnaire (all P < .05). Adjusted categorical analysis of the change in Kansas City Cardiomyopathy Questionnaire Clinical scores associated with change in hemoglobin from baseline to 6 months also showed a significant relationship between increasing hemoglobin and improved health status (5.9 +/- 1.8 units for a hemoglobin increase of >or=1 g/dL, 0.7 +/- 1.2 units for change in hemoglobin <1 g/dL, and -2.6 +/- 1.4 units for a >or=1 g/dL decrease in hemoglobin, P < .001). CONCLUSIONS These prospective, observational results indicate that reduced hemoglobin is associated with poorer quality of life in patients with heart failure. Additional studies will be required to establish if this is a cause-and-effect relationship.

Prospective evaluation of the association between cardiac troponin T and markers of disturbed erythropoiesis in patients with heart failure

BACKGROUND Elevated cardiac troponin T is a well-documented marker of cardiomyocyte damage and poor prognosis in patients with heart failure. We prospectively evaluated the relationship between this marker and hematopoietic disturbances in heart failure. METHODS Data were analyzed from 254 patients in the UNITE-HF Biomarker Registry, a prospective, observational, multicenter study of the clinical and biomarker correlates of anemia in heart failure. Logistic regression modeling assessed relationships between detectable troponin T and indices of hematologic function including anemia and red cell distribution width. RESULTS Anemia (hemoglobin≤12 g/dL) was present in 65 of the 254 study patients, and detectable troponin T was found in 39. Anemia was a significant independent predictor of detectable troponin T in models that considered a number of clinical characteristics including renal function, functional class, heart rate, and systolic blood pressure (odds ratio 2.57, 95% CI 1.09-6.09, P=.032). Likewise, detectable troponin T was directly and independently related to red cell distribution width in similar multivariable analyses (odds ratio 1.36 per unit increase, 95% CI 1.08-1.71, P=.008). CONCLUSIONS Anemia and increasing red cell distribution width were independently associated with elevated troponin T, a marker of cardiomyocyte injury or death in patients with heart failure.

The impact of B-type natriuretic peptide, New York Heart Association classification and depression on quality of life in nonhospitalized heart failure patients.

Healthcare providers should be concerned with improving the quality of life (QOL) of patients with heart failure (HF) because disease-specific QOL is linked to disease progression. The present study investigated the significance of elevated b-type natriuretic peptide (BNP), NYHA classification and depression to HF-related QOL to develop better management strategies. Outpatient subjects with left ventricular systolic dysfunction (n=108; mean age=64.9+/-12) completed the self-administered Minnesota Living with Heart Failure questionnaire and the Center for Epidemiologic Studies Depression Scale. Functional status was measured using the New York Heart Association Classification (NYHA) and BNP concentrations were measured in plasma samples. Multiregression analysis determined that plasma BNP levels did not contribute significantly to the total QOL score while depression (r=0.63, t ratio=7.43, P<.0001) and NHYA class (r=0.47, t ratio=3.31, P<.001) were significant contributors. NYHA III subjects exhibited worse depression scores (II 15+/-7 and III: 22+/-10, P<.001) and elevated plasma BNP (II: 2.0+/-0.5 and III: 2.4+/-0.6, P<.001). Low-cost psychological assessments are recommended to evaluate depression and suggest that those HF patients with NYHA III be closely monitored for depression and reduced QOL.

Agents that stabilise atherosclerotic plaque.

The concept of plaque stabilisation was developed to explain how medications could decrease adverse coronary events without a substantial reduction in the regression of atherosclerosis. With this concept, a comprehensive view of atherosclerosis is now appreciated. A number of imaging modalities are employed to study atherosclerosis; most identify luminal diameter or stenosis, wall thickness and plaque volume. A number of antiatherosclerotic agents have been studied as well to prove this hypothesis. However, the ultimate goal of medical treatment is to cure or prevent diseases caused by atherosclerosis.