Andreas P. Kalogeropoulos

Inflammatory Markers and Incident Heart Failure Risk in Older Adults: The Health ABC (Health, Aging, and Body Composition) Study

OBJECTIVES The purpose of this study was to evaluate the association between inflammation and heart failure (HF) risk in older adults. BACKGROUND Inflammation is associated with HF risk factors and also directly affects myocardial function. METHODS The association of baseline serum concentrations of interleukin (IL)-6, tumor necrosis factor-alpha, and C-reactive protein (CRP) with incident HF was assessed with Cox models among 2,610 older persons without prevalent HF enrolled in the Health ABC (Health, Aging, and Body Composition) study (age 73.6 +/- 2.9 years; 48.3% men; 59.6% white). RESULTS During follow-up (median 9.4 years), HF developed in 311 (11.9%) participants. In models controlling for clinical characteristics, ankle-arm index, and incident coronary heart disease, doubling of IL-6, tumor necrosis factor-alpha, and CRP concentrations was associated with 29% (95% confidence interval: 13% to 47%; p < 0.001), 46% (95% confidence interval: 17% to 84%; p = 0.001), and 9% (95% confidence interval: -1% to 24%; p = 0.087) increase in HF risk, respectively. In models including all 3 markers, IL-6, and tumor necrosis factor-alpha, but not CRP, remained significant. These associations were similar across sex and race and persisted in models accounting for death as a competing event. Post-HF ejection fraction was available in 239 (76.8%) cases; inflammatory markers had stronger association with HF with preserved ejection fraction. Repeat IL-6 and CRP determinations at 1-year follow-up did not provide incremental information. Addition of IL-6 to the clinical Health ABC HF model improved model discrimination (C index from 0.717 to 0.734; p = 0.001) and fit (decreased Bayes information criterion by 17.8; p < 0.001). CONCLUSIONS Inflammatory markers are associated with HF risk among older adults and may improve HF risk stratification.

Endothelial Dysfunction, Arterial Stiffness, and Heart Failure

Outcomes for heart failure (HF) patients remain suboptimal. No known therapy improves mortality in acute HF and HF with preserved ejection fraction; the most recent HF trial results have been negative or neutral. Improvement in surrogate markers has not necessarily translated into better outcomes. To translate breakthroughs with potential therapies into clinical benefit, a better understanding of the pathophysiology establishing the foundation of benefit is necessary. Vascular function plays a central role in the development and progression of HF. Endothelial function and nitric oxide availability affect myocardial function, systemic and pulmonary hemodynamics, and coronary and renal circulation. Arterial stiffness modulates ventricular loading conditions and diastolic function, key components of HF with preserved ejection. Endothelial function and arterial stiffness may therefore serve as important physiological targets for new HF therapies and facilitate patient selection for improved application of existing agents.

Incident Heart Failure Prediction in the Elderly The Health ABC Heart Failure Score

Background— Despite the rising heart failure (HF) incidence and aging United States population, there are no validated prediction models for incident HF in the elderly. We sought to develop a new prediction model for 5-year risk of incident HF among older persons. Methods and Results— Proportional hazards models were used to assess independent predictors of incident HF, defined as hospitalization for new-onset HF, in 2935 elderly participants without baseline HF enrolled in the Health ABC study (age, 73.6±2.9 years, 47.9% males, 58.6% whites). A prediction equation was developed and internally validated by bootstrapping, allowing the development of a 5-year risk score. Incident HF developed in 258 (8.8%) participants during 6.5±1.8 years of follow-up. Independent predictors of incident HF included age, history of coronary disease and smoking, baseline systolic blood pressure and heart rate, serum glucose, creatinine, and albumin levels, and left ventricular hypertrophy. The Health ABC HF model had a c -statistic of 0.73 in the derivation dataset, 0.72 by internal validation (optimism-corrected), and good calibration (goodness-of-fit χ2 6.24, P =0.621). A simple point score was created to predict incident HF risk into 4 risk groups corresponding to 20% 5-year risk. The actual 5-year incident HF rates in these groups were 2.9%, 5.7%, 13.3%, and 36.8%, respectively. Conclusion— The Health ABC HF prediction model uses common clinical variables to predict incident HF risk in the elderly, an approach that may be used to target and treat high-risk individuals. Received January 24, 2008; accepted May 19, 2008.Background—Despite the rising heart failure (HF) incidence and aging United States population, there are no validated prediction models for incident HF in the elderly. We sought to develop a new prediction model for 5-year risk of incident HF among older persons. Methods and Results—Proportional hazards models were used to assess independent predictors of incident HF, defined as hospitalization for new-onset HF, in 2935 elderly participants without baseline HF enrolled in the Health ABC study (age, 73.6±2.9 years, 47.9% males, 58.6% whites). A prediction equation was developed and internally validated by bootstrapping, allowing the development of a 5-year risk score. Incident HF developed in 258 (8.8%) participants during 6.5±1.8 years of follow-up. Independent predictors of incident HF included age, history of coronary disease and smoking, baseline systolic blood pressure and heart rate, serum glucose, creatinine, and albumin levels, and left ventricular hypertrophy. The Health ABC HF model had a c-statistic of 0.73 in the derivation dataset, 0.72 by internal validation (optimism-corrected), and good calibration (goodness-of-fit &khgr;2 6.24, P=0.621). A simple point score was created to predict incident HF risk into 4 risk groups corresponding to <5%, 5% to 10%, 10% to 20%, and >20% 5-year risk. The actual 5-year incident HF rates in these groups were 2.9%, 5.7%, 13.3%, and 36.8%, respectively. Conclusion—The Health ABC HF prediction model uses common clinical variables to predict incident HF risk in the elderly, an approach that may be used to target and treat high-risk individuals.

Hospitalization Epidemic in Patients With Heart Failure: Risk Factors, Risk Prediction, Knowledge Gaps, and Future Directions

Patients with heart failure (HF) are hospitalized over a million times annually in the United States. Hospitalization marks a fundamental change in the natural history of HF, leading to frequent subsequent rehospitalizations and a significantly higher mortality compared with nonhospitalized patients. Three-fourths of all HF hospitalizations are due to exacerbation of symptoms in patients with known HF. One-half of hospitalized HF patients experience readmission within 6 months. Preventing HF hospitalization and rehospitalization is important to improve patient outcomes and curb health care costs. To implement cost-effective strategies to contain the HF hospitalization epidemic, optimal schemes to identify high-risk individuals are needed. In this review, we describe the risk factors that have been associated with hospitalization risk in HF and the various multimarker risk prediction schemes developed to predict HF rehospitalization. We comment on areas that represent gaps in our knowledge or difficulties in interpretation of the current literature, representing opportunities for future research. We also discuss issues with using HF readmission rate as a quality indicator.

Epidemiology of incident heart failure in a contemporary elderly cohort: the health, aging, and body composition study.

BACKGROUND The race- and sex-specific epidemiology of incident heart failure (HF) among a contemporary elderly cohort are not well described. METHODS We studied 2934 participants without HF enrolled in the Health, Aging, and Body Composition Study (mean [SD] age, 73.6 [2.9] years; 47.9% men; 58.6% white; and 41.4% black) and assessed the incidence of HF, population-attributable risk (PAR) of independent risk factors for HF, and outcomes of incident HF. RESULTS During a median follow-up of 7.1 years, 258 participants (8.8%) developed HF (13.6 cases per 1000 person-years; 95% confidence interval, 12.1-15.4). Men and black participants were more likely to develop HF. No significant sex-based differences were observed in risk factors. Coronary heart disease (PAR, 23.9% for white participants and 29.5% for black participants) and uncontrolled blood pressure (PAR, 21.3% for white participants and 30.1% for black participants) carried the highest PAR in both races. Among black participants, 6 of 8 risk factors assessed (smoking, increased heart rate, coronary heart disease, left ventricular hypertrophy, uncontrolled blood pressure, and reduced glomerular filtration rate) had more than 5% higher PAR compared with that among white participants, leading to a higher overall proportion of HF attributable to modifiable risk factors in black participants vs white participants (67.8% vs 48.9%). Participants who developed HF had higher annual mortality (18.0% vs 2.7%). No racial difference in survival after HF was noted; however, rehospitalization rates were higher among black participants (62.1 vs 30.3 hospitalizations per 100 person-years, P < .001). CONCLUSIONS Incident HF is common in older persons; a large proportion of HF risk is attributed to modifiable risk factors. Racial differences in risk factors for HF and in hospitalization rates after HF need to be considered in prevention and treatment efforts.

Utility of the Seattle Heart Failure Model in Patients With Advanced Heart Failure

OBJECTIVES The aim of this study was to validate the Seattle Heart Failure Model (SHFM) in patients with advanced heart failure (HF). BACKGROUND The SHFM was developed primarily from clinical trial databases and extrapolated the benefit of interventions from published data. METHODS We evaluated the discrimination and calibration of SHFM in 445 advanced HF patients (age 52 +/- 12 years, 68.5% male, 52.4% white, ejection fraction 18 +/- 8%) referred for cardiac transplantation. The primary end point was death (n = 92), urgent transplantation (n = 14), or left ventricular assist device (LVAD) implantation (n = 3); a secondary analysis was performed on mortality alone. RESULTS Patients were receiving optimal therapy (angiotensin-II modulation 92.8%, beta-blockers 91.5%, aldosterone antagonists 46.3%), and 71.0% had an implantable device (defibrillator 30.4%, biventricular pacemaker 3.4%, combined 37.3%). During a median follow-up of 21 months, 109 patients (24.5%) had an event. Although discrimination was adequate (c-statistic >0.7), the SHFM overall underestimated absolute risk (observed vs. predicted event rate: 11.0% vs. 9.2%, 21.0% vs. 16.6%, and 27.9% vs. 22.8% at 1, 2, and 3 years, respectively). Risk underprediction was more prominent in patients with an implantable device. The SHFM had different calibration properties in white versus black patients, leading to net underestimation of absolute risk in blacks. Race-specific recalibration improved the accuracy of predictions. When analysis was restricted to mortality, the SHFM exhibited better performance. CONCLUSIONS In patients with advanced HF, the SHFM offers adequate discrimination, but absolute risk is underestimated, especially in blacks and in patients with devices. This is more prominent when including transplantation and LVAD implantation as an end point.

Incident Heart Failure Prediction in the ElderlyCLINICAL PERSPECTIVE

Background— Despite the rising heart failure (HF) incidence and aging United States population, there are no validated prediction models for incident HF in the elderly. We sought to develop a new prediction model for 5-year risk of incident HF among older persons. Methods and Results— Proportional hazards models were used to assess independent predictors of incident HF, defined as hospitalization for new-onset HF, in 2935 elderly participants without baseline HF enrolled in the Health ABC study (age, 73.6±2.9 years, 47.9% males, 58.6% whites). A prediction equation was developed and internally validated by bootstrapping, allowing the development of a 5-year risk score. Incident HF developed in 258 (8.8%) participants during 6.5±1.8 years of follow-up. Independent predictors of incident HF included age, history of coronary disease and smoking, baseline systolic blood pressure and heart rate, serum glucose, creatinine, and albumin levels, and left ventricular hypertrophy. The Health ABC HF model had a c -statistic of 0.73 in the derivation dataset, 0.72 by internal validation (optimism-corrected), and good calibration (goodness-of-fit χ2 6.24, P =0.621). A simple point score was created to predict incident HF risk into 4 risk groups corresponding to 20% 5-year risk. The actual 5-year incident HF rates in these groups were 2.9%, 5.7%, 13.3%, and 36.8%, respectively. Conclusion— The Health ABC HF prediction model uses common clinical variables to predict incident HF risk in the elderly, an approach that may be used to target and treat high-risk individuals. Received January 24, 2008; accepted May 19, 2008.Background—Despite the rising heart failure (HF) incidence and aging United States population, there are no validated prediction models for incident HF in the elderly. We sought to develop a new prediction model for 5-year risk of incident HF among older persons. Methods and Results—Proportional hazards models were used to assess independent predictors of incident HF, defined as hospitalization for new-onset HF, in 2935 elderly participants without baseline HF enrolled in the Health ABC study (age, 73.6±2.9 years, 47.9% males, 58.6% whites). A prediction equation was developed and internally validated by bootstrapping, allowing the development of a 5-year risk score. Incident HF developed in 258 (8.8%) participants during 6.5±1.8 years of follow-up. Independent predictors of incident HF included age, history of coronary disease and smoking, baseline systolic blood pressure and heart rate, serum glucose, creatinine, and albumin levels, and left ventricular hypertrophy. The Health ABC HF model had a c-statistic of 0.73 in the derivation dataset, 0.72 by internal validation (optimism-corrected), and good calibration (goodness-of-fit &khgr;2 6.24, P=0.621). A simple point score was created to predict incident HF risk into 4 risk groups corresponding to <5%, 5% to 10%, 10% to 20%, and >20% 5-year risk. The actual 5-year incident HF rates in these groups were 2.9%, 5.7%, 13.3%, and 36.8%, respectively. Conclusion—The Health ABC HF prediction model uses common clinical variables to predict incident HF risk in the elderly, an approach that may be used to target and treat high-risk individuals.

Epidemiology and cost of advanced heart failure.

The public health impact and the need to intervene upon the worsening heart failure (HF) epidemic are currently a matter of national interest. The greater than

Dietary Sodium Intake in Heart Failure

39 billion annual cost of caring for the 5.8 million patients living with HF in the United States places a considerable burden on the health care system. In 2006, HF was a contributing factor in more than 250,000 deaths. HF is the primary cause of more than 1 million and a contributing cause for more than 3 million hospitalizations. Because of lack of uniform definition, defining advanced HF precisely and, in turn, specifically assessing its epidemiology are difficult. However, with availability of more therapeutic options available for patients with advanced HF, the need to precisely define this entity is becoming ever more important. In general, patients with advanced HF have an extremely high mortality and morbidity and poor health status and quality of life. With the aging of the population and the worsening risk factor profile at large, for example, diabetes mellitus and obesity, the current epidemiological trends in advanced HF will likely get worse. Newer medical and device therapies as well as regenerative techniques hold considerable promise for these patients in future.

Serum Resistin Concentrations and Risk of New Onset Heart Failure in Older Persons: The Health, Aging, and Body Composition (Health ABC) Study

Dietary sodium restriction is arguably the most frequent self-care behavior recommended to patients with heart failure (HF)1,2 and is endorsed by all HF guidelines.2–10 However, the data on which this recommendation is drawn are modest, and the limited trials conducted have produced inconsistent findings. Americans consume ≈3700 mg sodium daily,11 whereas the US Department of Agriculture and the Department of Health and Human Services recommend 2300 mg daily intake for the general population, with a stricter recommendation of 1500 mg/d for those >50 years of age, blacks, or individuals with hypertension, diabetes mellitus, or chronic kidney disease.12 According to a recent report from the National Health and Nutrition Examination Survey, although 47.6% of persons aged ≥2 years meet the criteria to limit daily sodium intake to 1500 mg, the usual intake for 98.6% of those persons was >1500 mg; in 88.2% of the remaining population, daily intake was greater than the recommended <2300 mg.13 The American Heart Association now recommends sodium intake of 1500 mg/d for all Americans,14 similar to the recommendation by the Institute of Medicine.15 Interestingly, and paradoxically, the suggested 1500 mg daily sodium intake for the general population is less than the limit proposed for HF patients by most guidelines, which appears as a contradiction. Whether this contradiction suggests inconsistent policy or a limited understanding of sodium homeostasis in the HF versus non-HF state is debatable. Sodium homeostasis physiology is altered in HF as opposed to healthy individuals and those with hypertension, and may partially explain these incongruous recommendations. This review summarizes the studies assessing the effects of sodium restriction in HF, highlighting knowledge gaps and future directions. Excessive sodium intake is associated with fluid retention. Therefore, all HF management guidelines recommend sodium restriction. In 2005, …