Margaret A. Feller

Relation of Baseline Systolic Blood Pressure and Long-Term Outcomes in Ambulatory Patients With Chronic Mild to Moderate Heart Failure

We studied the impact of baseline systolic blood pressure (SBP) on outcomes in patients with mild to moderate chronic systolic and diastolic heart failure (HF) in the Digitalis Investigation Group trial using a propensity-matched design. Of 7,788 patients, 7,785 had baseline SBP data and 3,538 had SBP ≤ 120 mm Hg. Propensity scores for SBP ≤ 120 mm Hg, calculated for each of the 7,785 patients, were used to assemble a matched cohort of 3,738 patients with SBP ≤ 120 and >120 mm Hg who were well-balanced in 32 baseline characteristics. All-cause mortality occurred in 35% and 32% of matched patients with SBPs ≤ 120 and >120 mm Hg respectively, during 5 years of follow-up (hazard ratio [HR] when SBP ≤ 120 was compared to >120 mm Hg 1.10, 95% confidence interval [CI] 0.99 to 1.23, p = 0.088). HRs for cardiovascular and HF mortalities associated with SBP ≤ 120 mm Hg were 1.15 (95% CI 1.01 to 1.30, p = 0.031) and 1.30 (95% CI 1.08 to 1.57, p = 0.006). Cardiovascular hospitalization occurred in 53% and 49% of matched patients with SBPs ≤ 120 and > 120 mm Hg, respectively (HR 1.13, 95% CI 1.03 to 1.24, p = 0.008). HRs for all-cause and HF hospitalizations associated with SBP ≤ 120 mm Hg were 1.10 (95% CI 1.02 to 1.194, p = 0.017) and 1.21 (95% CI 1.07 to 1.36, p = 0.002). In conclusion, in patients with mild to moderate long-term systolic and diastolic HF, baseline SBP ≤ 120 mm Hg was associated with increased cardiovascular and HF mortalities and all-cause, cardiovascular, and HF hospitalizations that was independent of other baseline characteristics.

Renin-angiotensin inhibition in systolic heart failure and chronic kidney disease

BACKGROUND The role of renin-angiotensin inhibition in older patients with systolic heart failure with chronic kidney disease remains unclear. METHODS Of the 1665 patients (aged≥65 years) with systolic heart failure (ejection fraction<45%) and chronic kidney disease (estimated glomerular filtration rate<60 mL/min/1.73 m(2)), 1046 received angiotensin-converting enzyme inhibitors or angiotensin receptor blockers. Propensity scores for the receipt of these drugs, estimated for each of the 1665 patients, were used to assemble a matched cohort of 444 pairs of patients receiving and not receiving these drugs who were balanced on 56 baseline characteristics. RESULTS During more than 8 years of follow-up, all-cause mortality occurred in 75% and 79% of matched patients with chronic kidney disease receiving and not receiving angiotensin-converting enzyme inhibitors or angiotensin receptor blockers, respectively (hazard ratio [HR], 0.86; 95% confidence interval [CI], 0.74-0.996; P=.045). There was no significant association with heart failure hospitalization (HR, 0.86; 95% CI, 0.72-1.03; P=.094). Similar mortality reduction (HR, 0.83; 95% CI, 0.70-1.00; P=.046) occurred in a subgroup of matched patients with estimated glomerular filtration rate less than 45 mL/min/1.73 m(2). Among 171 pairs of propensity-matched patients without chronic kidney disease, the use of these drugs was associated with a significant reduction in all-cause mortality (HR, 0.72; 95% CI, 0.55-0.94; P=.015) and heart failure hospitalization (HR, 0.71; 95% CI, 0.52-0.95; P=.023). CONCLUSION Discharge prescription of angiotensin-converting enzyme inhibitors or angiotensin receptor blockers was associated with a significant modest reduction in all-cause mortality in older patients with systolic heart failure with chronic kidney disease, including those with more advanced chronic kidney disease.

Isolated Diastolic Hypotension and Incident Heart Failure in Older Adults

Aging is often associated with increased systolic blood pressure and decreased diastolic blood pressure. Isolated systolic hypertension or an elevated systolic blood pressure without an elevated diastolic blood pressure is a known risk factor for incident heart failure in older adults. In the current study, we examined whether isolated diastolic hypotension, defined as a diastolic blood pressure <60 mm Hg and a systolic blood pressure ≥100 mm Hg, is associated with incident heart failure. Of the 5795 Medicare-eligible community-dwelling adults age ≥65 years in the Cardiovascular Health Study, 5521 were free of prevalent heart failure at baseline. After excluding 145 individuals with baseline systolic blood pressure <100 mm Hg, the final sample included 5376 participants, of whom 751 (14%) had isolated diastolic hypotension. Propensity scores for isolated diastolic hypotension were calculated for each of the 5376 participants and used to match 545 and 2348 participants with and without isolated diastolic hypotension, respectively, who were balanced on 58 baseline characteristics. During >12 years of median follow-up, centrally adjudicated incident heart failure developed in 25% and 20% of matched participants with and without isolated diastolic hypotension, respectively (hazard ratio associated with isolated diastolic hypotension: 1.33 [95% CI: 1.10–1.61]; P=0.004). Among the 5376 prematch individuals, multivariable-adjusted hazard ratio for incident heart failure associated with isolated diastolic hypotension was 1.29 (95% CI: 1.09–1.53; P=0.003). As in isolated systolic hypertension, among community-dwelling older adults without prevalent heart failure, isolated diastolic hypotension is also a significant independent risk factor for incident heart failure.

Impact of diabetes mellitus on outcomes in patients with acute myocardial infarction and systolic heart failure

To determine independent associations of diabetes mellitus with outcomes in a propensity‐matched cohort of patients with acute myocardial infarction (AMI) and systolic heart failure (HF).

Impairment of activities of daily living and incident heart failure in community‐dwelling older adults

Instrumental activities of daily living (IADLs) are tasks that are necessary for independent community living. These tasks often require intact physical and cognitive function, the impairment of which may adversely affect health in older adults. In the current study, we examined the association between IADL impairment and incident heart failure (HF) in community‐dwelling older adults.

Warfarin Use and Outcomes in Patients With Advanced Chronic Systolic Heart Failure Without Atrial Fibrillation, Prior Thromboembolic Events, or Prosthetic Valves

Warfarin is often used in patients with systolic heart failure (HF) to prevent adverse outcomes. However, its long-term effect remains controversial. The objective of this study was to determine the association of warfarin use and outcomes in patients with advanced chronic systolic HF without atrial fibrillation (AF), previous thromboembolic events, or prosthetic valves. Of the 2,708 BEST patients, 1,642 were free of AF without a history of thromboembolic events and without prosthetic valves at baseline. Of these, 471 patients (29%) were receiving warfarin. Propensity scores for warfarin use were estimated for each patient and were used to assemble a matched cohort of 354 pairs of patients with and without warfarin use who were balanced on 62 baseline characteristics. Kaplan-Meier and Cox regression analyses were used to estimate the association between warfarin use and outcomes during 4.5 years of follow-up. Matched participants had a mean age ± SD of 57 ± 13 years with 24% women and 24% African-Americans. All-cause mortality occurred in 30% of matched patients in the 2 groups receiving and not receiving warfarin (hazard ratio 0.86, 95% confidence interval 0.62 to 1.19, p = 0.361). Warfarin use was not associated with cardiovascular mortality (hazard ratio 0.97, 95% confidence interval 0.68 to 1.38, p = 0.855), or HF hospitalization (hazard ratio 1.09, 95% confidence interval 0.82 to 1.44, p = 0.568). In conclusion, in patients with chronic advanced systolic HF without AF or other recommended indications for anticoagulation, prevalence of warfarin use was high. However, despite a therapeutic international normalized ratio in those receiving warfarin, its use had no significant intrinsic association with mortality and hospitalization.

Prediabetes is not an independent risk factor for incident heart failure, other cardiovascular events or mortality in older adults: Findings from a population-based cohort study

BACKGROUND Whether prediabetes is an independent risk factor for incident heart failure (HF) in non-diabetic older adults remains unclear. METHODS Of the 4602 Cardiovascular Health Study participants, age≥65 years, without baseline HF and diabetes, 2157 had prediabetes, defined as fasting plasma glucose (FPG) 100-125 mg/dL. Propensity scores for prediabetes, estimated for each of the 4602 participants, were used to assemble a cohort of 1421 pairs of individuals with and without prediabetes, balanced on 44 baseline characteristics. RESULTS Participants had a mean age of 73 years, 57% were women, and 13% African American. Incident HF occurred in 18% and 20% of matched participants with and without prediabetes, respectively (hazard ratio {HR} associated with prediabetes, 0.90; 95% confidence interval {CI}, 0.76-1.07; p=0.239). Unadjusted and multivariable-adjusted HRs (95% CIs) for incident HF associated with prediabetes among 4602 pre-match participants were 1.22 (95% CI, 1.07-1.40; p=0.003) and 0.98 (95% CI, 0.85-1.14; p=0.826), respectively. Among matched individuals, prediabetes had no independent association with incident acute myocardial infarction (HR, 1.02; 95% CI, 0.81-1.28; p=0.875), angina pectoris (HR, 0.93; 95% CI, 0.77-1.12; p=0.451), stroke (HR, 0.86; 95% CI, 0.70-1.06; p=0.151) or all-cause mortality (HR, 0.99; 95% CI, 0.88-1.11; p=0.840). CONCLUSIONS We found no evidence that prediabetes is an independent risk factor for incident HF, other cardiovascular events or mortality in community-dwelling older adults. These findings question the wisdom of routine screening for prediabetes in older adults and targeted interventions to prevent adverse outcomes in older adults with prediabetes.

Baseline characteristics, quality of care, and outcomes of younger and older Medicare beneficiaries hospitalized with heart failure: Findings from the Alabama Heart Failure Project ☆ ☆☆

BACKGROUND Most studies of heart failure (HF) in Medicare beneficiaries have excluded patients age <65 years. We examined baseline characteristics, quality of care, and outcomes among younger and older Medicare beneficiaries hospitalized with HF in the Alabama Heart Failure Project. METHODS Of the 8049 Medicare beneficiaries discharged alive with a primary discharge diagnosis of HF in 1998-2001 from 106 Alabama hospitals, 991 (12%) were younger (age <65 years). After excluding 171 patients discharge to hospice care, 7867 patients were considered eligible for left ventricular systolic function (LVSF) evaluation and 2211 patients with left ventricular ejection fraction <45% and without contraindications were eligible for angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) therapy. RESULTS Nearly half of the younger HF patients (45% versus 22% for ≥65 years; p<0.001) were African American. LVSF was evaluated in 72%, 72%, 70% and 60% (overall p<0.001) and discharge prescriptions of ACE inhibitors or ARBs were given to 83%, 77%, 75% and 75% of eligible patients (overall p=0.013) among those <65, 65-74, 75-84 and ≥85 years respectively. During 9 years of follow-up, all-cause mortality occurred in 54%, 61%, 71% and 80% (overall p<0.001) and hospital readmission due to worsening HF occurred in 65%, 60%, 55% and 48% (overall p<0.001) of those <65, 65-74, 75-84 and ≥85 years respectively. CONCLUSION Medicare beneficiaries <65 years with HF, nearly half of whom were African American generally received better quality of care, had lower mortality, but had higher re-hospitalizations due to HF.

Reduced right ventricular ejection fraction and increased mortality in chronic systolic heart failure patients receiving beta-blockers: Insights from the BEST trial

BACKGROUND Right ventricular ejection fraction (RVEF) < 20% is an independent predictor of poor outcomes in patients with advanced chronic systolic heart failure (HF). The aim of this study was to examine if the adverse effect of abnormally reduced RVEF varies by the receipt of beta-blockers. METHODS In the Beta-Blocker Evaluation of Survival Trial (BEST), 2708 patients with chronic advanced HF and left ventricular ejection fraction < 35%, receiving standard background therapy with renin-angiotensin inhibition, digoxin, and diuretics, were randomized to receive bucindolol or placebo. Of these 2008 had data on baseline RVEF, and 14% (146/1017) and 13% (125/991) of the patients receiving bucindolol and placebo respectively had RVEF < 20%. RESULTS Among patients in the placebo group, all-cause mortality occurred in 33% and 43% of patients with RVEF ≥ 20% and < 20% respectively (unadjusted hazard ratios {HR}, 1.33; 95% confidence intervals {CI}, 0.99-1.78; p = 0.055 and adjusted HR, 0.99; 95% CI, 0.71-1.37; p = 0.934). Among those receiving bucindolol, all-cause mortality occurred in 28% and 49% of patients with RVEF ≥ 20% and < 20% respectively (unadjusted HR, 2.15; 95% CI, 1.65-2.80; p < 0.001 and adjusted HR, 1.50; 95% CI, 1.08-2.07; p = 0.016). These differences were statistically significant (unadjusted and adjusted p for interaction, 0.016 and 0.053 respectively). CONCLUSIONS In ambulatory patients with chronic advanced systolic HF receiving renin-angiotensin inhibition, digoxin, and diuretics, RVEF < 20% had no intrinsic association with mortality. However, in those receiving additional therapy with bucindolol, RVEF < 20% had a significant independent association with increased risk of mortality.

Right ventricular ejection fraction <20% is an independent predictor of mortality but not of hospitalization in older systolic heart failure patients

BACKGROUND Reduced right ventricular ejection fraction (RVEF) is associated with poor outcomes in patients with chronic systolic heart failure (HF). Although most HF patients are older adults, little is known about the relationship between low RVEF and outcomes in older adults with systolic HF. METHODS Of the 2008 Beta-Blocker Evaluation of Survival Trial (BEST) participants with systolic HF (left ventricular ejection fraction ≤ 35%) 822 were ≥ 65 years and had data on baseline RVEF estimated by gated-equilibrium radionuclide ventriculography. Using RVEF ≥ 40% (n = 308) as reference, we examined association of RVEF 30-39% (n = 214), 20-29% (n = 206) and <20% (n = 94) with outcomes using Cox regression models. RESULTS All-cause mortality occurred in 36%, 40%, 39% and 56% of patients with RVEF ≥ 40%, 30-39%, 20-29% and <20% respectively. Compared with RVEF ≥ 40%, unadjusted hazard ratios (HR) and 95% confidence intervals (CI) for all-cause mortality associated with RVEF 30-39%, 20-29% and <20% were 1.19 (0.90-1.57; P = 0.220), 1.13 (0.84-1.51; P = 0.423) and 1.97 (1.43-2.73; P<0.001) respectively. Respective multivariable-adjusted HRs (95% CIs) for all-cause mortality were 1.19 (0.88-1.60; P = 0.261), 1.00 (0.73-1.39; P = 0.982) and 1.70 (1.14-2.53; P = 0.009). Adjusted HRs (95% CIs) associated with RVEF <20% (versus ≥ 40%) for cardiovascular mortality and HF mortality were 1.79 (1.17-2.76; P = 0.008) and 1.97 (1.02-3.83; P = 0.045) respectively. RVEF had no independent association with sudden cardiac death, all-cause or HF hospitalization. CONCLUSIONS Abnormally low RVEF is a significant independent predictor of mortality, but not of HF hospitalization, in older adults with systolic HF.