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1.  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.
doi:10.1016/j.ijcard.2011.05.051
PMCID: PMC3395778  PMID: 21704392
Heart failure; Right ventricle; Bucindolol; Mortality; Morbidity
2.  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.
doi:10.1016/j.ijcard.2011.05.003
PMCID: PMC3395759  PMID: 21621285
heart failure; age; Medicare; quality of care; outcomes
3.  Bucindolol, systolic blood pressure, and outcomes in systolic heart failure: a prespecified post hoc analysis of BEST 
BACKGROUND
In the Beta-Blocker Evaluation of Survival Trial (BEST) trial, systolic blood pressure (SBP) ≤120 mm Hg was an independent predictor of poor prognosis in ambulatory patients with chronic systolic heart failure (HF). Because SBP is an important predictor of response to beta-blocker therapy, the BEST protocol had pre-specified a post hoc analysis to determine if the effect of bucindolol varied by baseline SBP.
METHODS
In the BEST, 2706 patients with chronic systolic (left ventricular ejection fraction <35%) HF and New York Heart Association class III (92%) or IV (8%) symptoms and receiving standard background therapy were randomized to receive either bucindolol (n=1354) or placebo (n=1354). Of these, 1751 had SBP ≤120 mm Hg and 955 had SBP >120 mm Hg at baseline.
RESULTS
Among patients with SBP >120 mm Hg, all-cause mortality occurred in 28% and 22% of patients receiving placebo and bucindolol, respectively (hazard ratio when bucindolol was compared with placebo, 0.77; 95% confidence interval, 0.59–0.99; P=0.039). In contrast, among those with SBP ≤120 mm Hg, 36% and 35% of patients in the placebo and bucindolol groups died, respectively (hazard ratio, 0.95; 95% confidence interval, 0.81–1.12; P=0.541). Hazard ratios (95% confidence intervals) for HF hospitalization associated with bucindolol use were 0.70 (0.56–0.89; P=0.003) and 0.82 (0.71–0.95; P=0.008) for patients with SBP >120 and ≤120 mm Hg, respectively.
CONCLUSION
Bucindolol, a nonselective beta-blocker with weak alpha-blocking properties, significantly reduced HF hospitalization in systolic HF patients regardless of baseline SBP. However, bucindolol reduced mortality only in those with SBP >120 mm Hg.
doi:10.1016/j.cjca.2011.07.004
PMCID: PMC3769783  PMID: 21982425
Bucindolol; systolic blood pressure; outcomes; heart failure
4.  In-Hospital Cardiology Consultation and Evidence-Based Care for Nursing Home Residents with Heart Failure 
Objectives
To determine the association between cardiology consultation and evidence-based care for nursing home (NH) residents with heart failure (HF).
Participants
Hospitalized NH residents (n= 646) discharged from 106 Alabama hospitals with a primary discharge diagnosis of HF during 1998–2001.
Design
Observational.
Measurements of Evidence-Based Care
Pre-admission estimation of left ventricular ejection fraction (LVEF) for patients with known HF (n=494), in-hospital LVEF estimation for HF patients without known LVEF (n=452), and discharge prescriptions of angiotensin-converting enzyme inhibitors or angiotensin receptor blockers (ACEIs-or-ARBs) to systolic HF (LVEF <45%) patients discharged alive who were eligible to receive those drugs (n=83). Eligibility for ACEIs-or-ARBs was defined as lack of prior allergy or adverse effect, serum creatinine <2.5 mg/dL, serum potassium <5.5 mEq/L, and systolic blood pressure >100 mm Hg.
Results
Pre-admission LVEF was estimated in 38% and 12% of patients receiving and not receiving cardiology consultation, respectively (adjusted odds ratio {AOR}, 3.49; 95% CI, 2.16–5.66; p <0.001). In-hospital LVEF was estimated in 71% and 28% of patients receiving and not receiving cardiology consultation, respectively (AOR, 6.01; 95% CI, 3.69–9.79; p <0.001). ACEIs-or-ARBs were prescribed to 62% and 82% of patients receiving and not receiving cardiology consultation, respectively (AOR, 0.24; 95% CI, 0.07–0.81; p=0.022).
Conclusion
In-hospital cardiology consultation was associated with significantly higher odds of LVEF estimation among NH residents with HF. However, it did not translate into higher odds of discharge prescriptions for ACEIs-or-ARBs to NH resident with systolic HF who were eligible for the receipt of these drugs.
doi:10.1016/j.jamda.2011.09.001
PMCID: PMC3750116  PMID: 21982687
heart failure; nursing home residents; cardiology consultation; evidence-based care
5.  Association between smoking and outcomes in older adults with atrial fibrillation 
Tobacco smoking is a risk factor for atrial fibrillation (AF), but little is known about the impact of smoking in patients with AF. Of the 4060 patients with recurrent AF in the Atrial Fibrillation Follow-up Investigation of Rhythm Management (AFFIRM) trial, 496 (12%) reported having smoked during the past two years. Propensity scores for smoking were estimated for each of the 4060 patients using a multivariable logistic regression model and were used to assemble a matched cohort of 487 pairs of smokers and nonsmokers, who were balanced on 46 baseline characteristics. Cox and logistic regression models were used to estimate the associations of smoking with all-cause mortality and all-cause hospitalization, respectively, during over 5 years of follow-up. Matched participants had a mean age of 70 ± 9 years (± S.D.), 39% were women, and 11% were non-white. All-cause mortality occurred in 21% and 16% of matched smokers and nonsmokers, respectively (when smokers were compared with nonsmokers, hazard ratio = HR = 1.35; 95% confidence interval = 95% CI = 1.01–1.81; p = 0.046). Unadjusted, multivariable-adjusted and propensity-adjusted HR (95% CI) for all-cause mortality associated with smoking in the pre-match cohort were: 1.40 (1.13–1.72; p = 0.002), 1.45 (1.16–1.81; p = 0.001), and 1.39 (1.12–1.74; p = 0.003), respectively. Smoking had no association with all-cause hospitalization (when smokers were compared with nonsmokers, odds ratio = OR = 1.21; 95% CI = 0.94–1.57, p = 0.146). Among patients with AF, a recent history of smoking was associated with an increased risk of all-cause mortality, but had no association with all-cause hospitalization.
doi:10.1016/j.archger.2011.05.027
PMCID: PMC3358565  PMID: 21733581
Atrial fibrillation; Smoking; Mortality; Propensity score
6.  Impairment of activities of daily living and incident heart failure in community-dwelling older adults 
European Journal of Heart Failure  2012;14(6):581-587.
Aims
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.
Methods and results
Of the 5795 community-dwelling adults, aged ≥65 years, in the Cardiovascular Health Study, 5511 had data on baseline IADL and were free of prevalent HF. Of these, 1333 (24%) had baseline IADL impairment, defined as self-reported difficulty with one or more of the following tasks: using the telephone, preparing food, performing light and heavy housework, managing finances, and shopping. Propensity scores for IADL impairment, estimated for each of the 5511 participants, were used to assemble a cohort of 1038 pairs of participants with and without IADL impairment who were balanced on 42 baseline characteristics. Centrally adjudicated incident HF occurred in 26% and 21% of matched participants with and without IADL impairment, respectively, during >12 years of follow-up [matched hazard ratio (HR) 1.33; 95% confidence interval (CI) 1.11–1.59; P = 0.002]. Unadjusted and multivariable-adjusted HRs for incident HF before matching were 1.77 (95% CI 1.56–2.01; P < 0.001) and 1.33 (95% CI 1.15–1.54; P < 0.001), respectively. IADL impairment was also associated with all-cause mortality (matched HR 1.19; 95% CI 1.06–1.34; P = 0.004).
Conclusion
Among community-dwelling older adults free of baseline HF, IADL impairment is a strong and independent predictor of incident HF and mortality.
doi:10.1093/eurjhf/hfs034
PMCID: PMC3359859  PMID: 22492539
Instrumental activities of daily living; Incident heart failure; Propensity score
7.  Rheumatic heart disease and risk of incident heart failure among community-dwelling older adults: a prospective cohort study 
Annals of Medicine  2011;44(3):253-261.
Background
Little is known about the association of rheumatic heart disease (RHD) with incident heart failure (HF) among older adults.
Design
Cardiovascular Health Study, a prospective cohort study.
Methods
Of the 4751 community-dwelling adults ≥65 years, free of prevalent HF at baseline, 140 had RHD, defined as self-reported physician-diagnosed RHD along with echocardiographic evidence of left-sided valvular disease. Propensity scores for RHD, estimated for each of the 4751 participants, were used to assemble a cohort of 720, in which 124 and 596 participants with and without RHD respectively were balanced on 62 baseline characteristics.
Results
Incident HF developed in 33% and 22% of matched participants with and without RHD respectively during 13 years of follow-up (hazard ratio when RHD was compared to no-RHD, 1.60; 95% confidence interval, 1.13–2.28; P=0.008). Pre-match unadjusted, multivariable-adjusted and propensity-adjusted hazard ratios (95% confidence intervals) for RHD-associated incident heart failure were 2.04 (1.54–2.71; P<0.001), 1.32 (1.02–1.70; P=0.034) and 1.55 (1.14–2.11; P=0.005) respectively. RHD was not associated with all-cause mortality (HR, 1.09; 95% CI, 0.82–1.45; P=0.568).
Conclusion
RHD is an independent risk factor for incident HF among community-dwelling older adults free of HF, but has no association with mortality.
doi:10.3109/07853890.2010.530685
PMCID: PMC3116996  PMID: 21254894
Heart failure; rheumatic heart disease; older adults
8.  Renin-angiotensin inhibition in systolic heart failure and chronic kidney disease 
The American Journal of Medicine  2012;125(4):399-410.
Background
The role of renin-angiotensin inhibition in older systolic heart failure patients with chronic kidney disease remains unclear.
Methods
Of the 1665 patients, age ≥65 years, with systolic heart failure (ejection fraction <45%) and chronic kidney disease (estimated glomerular filtration rate <60 ml/min/1.73 m2), 1046 received angiotensin-converting enzyme inhibitors or angiotensin receptor blockers. Propensity scores for the receipts 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 over 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=0.045). There was no significant association with heart failure hospitalization (HR, 0.86; 95% CI, 0.72–1.03; p=0.094). Similar mortality reduction (HR, 0.83; 95% CI, 0.70–1.00; p=0.046) occurred in a subgroup of matched patients with estimated glomerular filtration rate <45 ml/min/1.73 m2. Among 171 pairs of propensity-matched patients without chronic kidney disease, the use of these drugs was associated with significant reduction in all-cause mortality (HR, 0.72; 95% CI, 0.55–0.94; p=0.015) and heart failure hospitalization (HR, 0.71; 95% CI, 0.52–0.95; p=0.023).
Conclusions
Discharge prescription of angiotensin-converting enzyme inhibitors or angiotensin receptor blockers was associated with a significant modest reduction in all-cause mortality in older systolic heart failure patients with chronic kidney disease including those with more advanced chronic kidney disease.
doi:10.1016/j.amjmed.2011.10.013
PMCID: PMC3324926  PMID: 22321760
systolic heart failure; chronic kidney disease; angiotensin-converting enzyme inhibitors; angiotensin receptor blockers
9.  Effect of Warfarin on Outcomes in Septuagenarian Patients with Atrial Fibrillation 
The American Journal of Cardiology  2011;109(3):370-377.
Anticoagulation has been shown to reduce ischemic stroke in atrial fibrillation (AF). However, concerns remain regarding their safety and efficacy in those ≥70 years of age who comprise most AF patients. Of the 4060 patients (mean age, 65 years; range, 49–80 years) in the Atrial Fibrillation Follow-up Investigation of Rhythm Management (AFFIRM) trial, 2248 (55% of 4060) were 70–80 years of age, 1901 of whom were receiving warfarin. Propensity score for warfarin use, estimated for each of the 2248 patients, were used to match 227 of the 347 no-warfarin patients (in 1:1, 1:2 or 1:3 sets) with 616 warfarin patients, who were balanced on 45 baseline characteristics. All-cause mortality occurred in 18% and 33% of matched patients receiving and not receiving warfarin, respectively, during up to six (mean, 3.4) years of follow-up (hazard ratio {HR} when warfarin use was compared with its non-use, 0.58; 95% confidence interval {CI}, 0.43–0.77; p<0.001). All-cause hospitalization occurred in 64% and 67% of matched patients receiving and not receiving warfarin, respectively (HR associated with warfarin use, 0.93; 95% CI, 0.77–1.12; p=0.423). Ischemic stroke occurred in 4% and 8% of matched patients receiving and not receiving warfarin, respectively (HR associated with warfarin use, 0.57; 95% CI, 0.31–1.04; p=0.068). Major bleeding occurred in 7% and 10% of matched patients receiving and not receiving warfarin, respectively (HR associated with warfarin use, 0.73; 95% CI, 0.44–1.22; p=0.229). In conclusion, warfarin use was associated with reduced mortality in septuagenarian AF patients but had no association with hospitalization or major bleeding.
doi:10.1016/j.amjcard.2011.09.023
PMCID: PMC3390022  PMID: 22118824
atrial fibrillation; warfarin; mortality; propensity score; older adults
10.  Outcomes in younger and older adults with chronic advanced systolic heart failure: a propensity-matched study 
International Journal of Cardiology  2010;154(2):128-133.
Background
Older age is an independent predictor of all-cause mortality in patients with mild to moderate heart failure (HF). Whether older age is also an independent predictor of mortality in patients with more advanced HF is unknown.
Methods
Of the 2707 Beta-Blocker Evaluation of Survival Trial (BEST) participants with ambulatory chronic HF (New York Heart Association class III/IV and left ventricular ejection fraction <35%), 1091 were elderly (≥65 years). Propensity scores for older age, estimated for each of the 2707 patients, were used to assemble a cohort of 603 pairs of younger and older patients, balanced on 66 baseline characteristics.
Results
All-cause mortality occurred in 33% and 36% of younger and older matched patients respectively during 4 years of follow-up (hazard ratio {HR} associated with age ≥65 years, 1.05; 95% confidence interval {CI}, 0.87—1.27; P=0.614). HF hospitalization occurred in 38% and 40% of younger and older matched patients respectively (HR, 1.01; 95% CI, 0.84–1.21; P=0.951). Among 603 pairs of unmatched and unbalanced patients, all-cause mortality occurred in 28% and 36% of younger and older patients respectively (HR, 1.34; 95% CI, 1.10–1.64; P=0.004) and HF hospitalization occurred in 34% and 40% of younger and older unmatched patients respectively (HR, 1.24; 95% CI, 1.03–1.50; P=0.024).
Conclusion
Significant bivariate associations suggest that older age is a useful marker of poor outcomes in patients with advanced chronic systolic HF. However, lack of significant independent associations suggests that older age per se has no intrinsic effect on outcomes in these patients.
doi:10.1016/j.ijcard.2010.09.006
PMCID: PMC3116091  PMID: 20947188
Age; heart failure; mortality; hospitalization
11.  A Propensity-Matched Study of the Association of Diabetes Mellitus with Incident Heart Failure and Mortality among Community-Dwelling Older Adults 
The American Journal of Cardiology  2011;108(12):1747-1753.
Diabetes mellitus (DM) is a risk factor for incident heart failure (HF) in older adults. However, to what extent this association is independent of other risk factors remains unclear. Of the 5464 community-dwelling adults ≥65 years in the Cardiovascular Health Study without baseline HF, 862 had DM (fasting plasma glucose levels ≥126 mg/dl, or treatment with insulin or oral hypoglycemic agents). Propensity scores for DM were estimated for each of the 5464 participants and were used to assemble a cohort of 717 pairs of participants with and without DM, who were balanced on 65 baseline characteristics. Incident HF occurred in 31% and 26% of matched participants with and without DM, respectively, during over 13 years of follow-up (hazard ratio {HR} when DM was compared with no DM, 1.45; 95% confidence interval {CI}, 1.14–1.86; p=0.003). Among the 5464 pre-match participants, unadjusted and multivariable-adjusted HRs for incident HF associated with DM were 2.22 (95% CI, 1.94–2.55; p<0.001) and 1.52 (95% CI, 1.30–1.78; p<0.001), respectively. All-cause mortality occurred in 57% and 47% of matched participants with and without DM respectively (HR, 1.35; 95% CI, 1.13–1.61; p=0.001). Among matched participants, DM-associated HRs for incident peripheral arterial disease, incident acute myocardial infarction and incident stroke were 2.50 (95% CI, 1.45–4.32; p=0.001), 1.37 (95% CI, 0.97–1.93; p=0.072), and 1.11 (95% CI, 0.81–1.51; p=0.527), respectively. In conclusion, the association of DM with incident HF and all-cause mortality in community-dwelling older adults without HF is independent of major baseline cardiovascular risk factors.
doi:10.1016/j.amjcard.2011.07.046
PMCID: PMC3324944  PMID: 21943936
heart failure; diabetes mellitus; mortality; older adults; propensity-matched
12.  Intrinsic Association of Widowhood With Mortality in Community-Dwelling Older Women and Men: Findings From a Prospective Propensity-Matched Population Study 
Objectives.
Widowhood is associated with increased mortality. However, to what extent this association is independent of other risk factors remains unclear. In the current study, we used propensity score matching to design a study to examine the independent association of widowhood with outcomes in a balanced cohort of older adults in the United States.
Methods.
We used public-use copies of the Cardiovascular Health Study data obtained from the National Heart, Lung, and Blood Institute. Of the 5,795 community-dwelling older men and women aged 65 years and older in Cardiovascular Health Study, 3,820 were married and 1,436 were widows or widowers. Propensity scores for widowhood, estimated for each of the 5,256 participants, were used to assemble a cohort of 819 pairs of widowed and married participants who were balanced on 74 baseline characteristics. The 1,638 matched participants had a mean (± standard deviation) age of 75 (±6) years, 78% were women, and 16% African American.
Results.
All-cause mortality occurred in 46% (374/819) and 51% (415/819) of matched married and widowed participants, respectively, during more than 11 years of median follow-up (hazard ratio associated with widowhood, 1.18; 95% confidence interval, 1.03–1.36; p = .018). Hazard ratios (95% confidence intervals) for cardiovascular and noncardiovascular mortalities were 1.07 (0.87–1.32; p = .517) and 1.28 (1.06–1.55; p = .011), respectively. Widowhood had no independent association with all-cause or heart failure hospitalization or incident cardiovascular events.
Conclusions.
Among community-dwelling older adults, widowhood was associated with increased mortality, which was independent of confounding by baseline characteristics and largely driven by an increased noncardiovascular mortality. Widowhood had no independent association with hospitalizations or incident cardiovascular events.
doi:10.1093/gerona/glr144
PMCID: PMC3252210  PMID: 21903611
Widowhood; Spousal loss; Mortality; Hospitalization; Older adults
13.  Isolated diastolic hypotension and incident heart failure in older adults 
Hypertension  2011;58(5):895-901.
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 over 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% confidence interval, 1.10–1.61; p=0.004). Among the 5376 pre-match individuals, multivariable-adjusted hazard ratio for incident heart failure associated with isolated diastolic hypotension was 1.29 (95% confidence interval, 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.
doi:10.1161/HYPERTENSIONAHA.111.178178
PMCID: PMC3390027  PMID: 21947466
aging; blood pressure; diastolic; heart failure; pulse pressure
14.  Relationship between Stage of Kidney Disease and Incident Heart Failure in Older Adults 
American Journal of Nephrology  2011;34(2):135-141.
Background
The relationship between stage of chronic kidney disease (CKD) and incident heart failure (HF) remains unclear.
Methods
Of the 5,795 community-dwelling adults ≥65 years in the Cardiovascular Health Study, 5,450 were free of prevalent HF and had baseline estimated glomerular filtration rate (eGFR: ml/min/1.73 m2) data. Of these, 898 (16%) had CKD 3A (eGFR 45–59 ml/min/1.73 m2) and 242 (4%) had CKD stage ≥3B (eGFR <45 ml/min/1.73 m2). Data on baseline proteinuria were not available and 4,310 (79%) individuals with eGFR ≥60 ml/min/1.73 m2 were considered to have no CKD. Propensity scores estimated separately for CKD 3A and ≥3B were used to assemble two cohorts of 1,714 (857 pairs with CKD 3A and no CKD) and 557 participants (148 CKD ≥3B and 409 no CKD), respectively, balanced on 50 baseline characteristics.
Results
During 13 years of follow-up, centrally-adjudicated incident HF occurred in 19, 24 and 38% of pre-match participants without CKD (reference), with CKD 3A [unadjusted hazard ratio (HR) 1.40; 95% confidence interval (CI) 1.20–1.63; p < 0.001] and with CKD ≥3B (HR 3.37; 95% CI 2.71–4.18; p < 0.001), respectively. In contrast, among matched participants, incident HF occurred in 23 and 23% of those with CKD 3A and no CKD, respectively (HR 1.03; 95% CI 0.85–1.26; p = 0.746), and 36 and 28% of those with CKD ≥3B and no CKD, respectively (HR 1.44; 95% CI 1.04–2.00; p = 0.027).
Conclusions
Among community-dwelling older adults, CKD is a marker of incident HF regardless of stage; however, CKD ≥3B, not CKD 3A, has a modest independent association with incident HF.
doi:10.1159/000328905
PMCID: PMC3136373  PMID: 21734366
Chronic kidney disease; Heart failure
16.  Impact of diabetes mellitus on outcomes in patients with acute myocardial infarction and systolic heart failure 
European Journal of Heart Failure  2011;13(5):551-559.
Aims
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).
Methods and results
In the Eplerenone Post-Acute Myocardial Infarction Heart Failure Efficacy and Survival Study (EPHESUS) trial, hospitalized AMI patients complicated by left ventricular ejection fraction ≤40% and symptoms of HF receiving standard therapy were randomized 3–14 days post-AMI to receive eplerenone 25–50 mg/day (n = 3319) or placebo (n = 3313). Of the 6632 patients, 2142 (32%) had a history of diabetes, who were older and sicker. Using propensity scores for diabetes, we assembled a cohort of 1119 pairs of patients with and without diabetes who were balanced on 64 baseline characteristics. Incident fatal or nonfatal recurrent AMI occurred in 136 (12%) and 87 (8%) of matched patients with and without diabetes, respectively, during 2.5 years of follow-up [hazard ratio (HR) when diabetes was compared with no-diabetes, 1.61; 95% confidence interval (CI), 1.23–2.10; P = 0.001]. Diabetes was associated with nonfatal AMI (HR, 1.68; 95% CI, 1.23–2.31; P = 0.001) but not with fatal AMI (HR, 1.42; 95% CI, 0.88–2.28; P = 0.146). Hazard ratios (95% CIs) for the association of diabetes with all-cause mortality, cardiovascular mortality, all-cause hospitalization, and cardiovascular hospitalization were 1.12 (0.93–1.37; P = 0.224), 1.11 (0.90–1.37; P = 0.318), 1.13 (1.00–1.27; P = 0.054), and 1.20 (1.01–1.44; P = 0.042), respectively.
Conclusion
In post-AMI patients with systolic HF, diabetes mellitus is a significant independent risk factor for recurrent short-term nonfatal AMI, but had no association with fatal AMI.
doi:10.1093/eurjhf/hfr009
PMCID: PMC3079464  PMID: 21393298
Diabetes; Recurrent myocardial infarction
17.  Relation of Baseline Systolic Blood Pressure and Long-Term Outcomes in Ambulatory Patients with Chronic Mild to Moderate Heart Failure 
The American journal of cardiology  2011;107(8):1208-1214.
We studied the impact of baseline systolic blood pressure (SBP) on outcomes in mild to moderate chronic systolic and diastolic heart failure (HF) patients in the Digitalis Investigation Group trial using propensity-matched design. Of the 7788 patients, 7785 had baseline SBP data and 3538 had SBP ≤120 mm Hg. Propensity scores for SBP ≤120 mm Hg, calculated for each of the 7785 patients, were used to assemble a matched cohort of 3738 patients with SBP ≤120 and >120 mm Hg who were well-balanced on 32 baseline characteristics. All-cause mortality occurred in 35% and 32% of matched patients with SBP ≤120 and >120 mm Hg respectively during 5 years of follow-up (hazard ratio {HR} when SBP ≤120 was compared with >120 mm Hg, 1.10; 95% confidence interval {CI}, 0.99–1.23; p=0.088). HRs (95% CIs) for cardiovascular and HF mortality associated with SBP ≤120 mm Hg were 1.15 (1.01–1.30; p=0.031) and 1.30 (1.08–1.57; p=0.006). Cardiovascular hospitalization occurred in 53% and 49% of matched patients with SBP ≤120 and >120 mm Hg respectively (HR for SBP ≤120 was compared with >120 mm Hg, 1.13; 95% CI, 1.03–1.24; P=0.008). HRs (95% CIs) for all-cause and HF hospitalization associated with SBP ≤120 mm Hg were 1.10 (1.02–1.194; p=0.017) and 1.21 (1.07–1.36; p=0.002). In conclusion, in patients with mild to moderate chronic systolic and diastolic HF, baseline SBP ≤120 mm Hg was associated with increased cardiovascular and HF mortality and all-cause, cardiovascular and HF hospitalization that was independent of other baseline characteristics.
doi:10.1016/j.amjcard.2010.12.020
PMCID: PMC3072746  PMID: 21296319
heart failure; systolic blood pressure; mortality; hospitalization
18.  Evidence of a “Heart Failure Belt” in the Southeastern United States 
The American journal of cardiology  2011;107(6):935-937.
The Southeastern region of the United States is known as the “Stroke Belt” because of the excess stroke mortality in this region as compared to the rest of the country. However, whether a similar geographic variation in heart failure mortality exists is unknown. Using the CDC WONDER’s publicly-available compressed mortality data files and the 2000 United States population as the standard, we estimated age-adjusted heart failure and stroke mortality rates per 100,000 for individuals of all ages, both sexes and all races during 1979–1998 in the United States, and mapped them at the state level. The age-adjusted heart failure mortality rate for the six contiguous Southeastern states (Alabama, Arkansas, Mississippi, Oklahoma, Louisiana, and Georgia) was 31.0/100,000, which was 69% higher than the national rate of 18.3/100,000. This geographic disparity was similar among African Americans (32.9/100,000 in the Southeast versus 21.7/100,000 nationally) and whites (30.8/100,000 in the Southeast versus 18.1/100,000 nationally). These findings suggest that in addition to the “Stroke Belt”, the Southeastern region of the United States may also be burdened by a “Heart Failure Belt”. To better understand the causes of the excess stroke mortality in the “Stroke Belt”, the National Institutes of Health has funded the REasons for Geographic and Racial Differences in Stroke (REGARDS) study (N=30,239, over half from the Southeastern region), which provide a unique opportunity to study the underlying causes of excess heart failure mortality in the “Heart Failure Belt”.
doi:10.1016/j.amjcard.2010.11.012
PMCID: PMC3057326  PMID: 21247536
heart failure; mortality; southeastern states
19.  Warfarin Use and Outcomes in Patients with Advanced Chronic Systolic Heart Failure without Atrial Fibrillation, Prior Thromboembolic Events, or Prosthetic Valves 
The American journal of cardiology  2010;107(4):552-557.
Warfarin is often used in systolic heart failure (HF) patients 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 advanced chronic systolic HF patients without atrial fibrillation (AF), previous thromboembolic events or prosthetic valves. Of the 2708 BEST patients, 1642 were free of AF, without history of thromboembolic events and without prosthetic valves at baseline. Of these, 471 (29%) patients 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 (SD) age of 57 (13) years with 24% women and 24% African Americans. All-cause mortality occurred in 30% of matched patients in both groups receiving and not receiving warfarin (hazard ratio, 0.86; 95% confidence interval, 0.62–1.19; P=0.361). Warfarin use was not associated with cardiovascular mortality (hazard ratio, 0.97; 95% confidence interval, 0.68–1.38; P=0.855) or HF hospitalization (hazard ratio, 1.09; 95% confidence interval, 0.82–1.44; P=0.568). In conclusion, in chronic advanced systolic HF patients without AF or other recommended indications for anticoagulation, the prevalence of warfarin use was relatively high. However, despite therapeutic INR among those receiving warfarin, its use had no significant intrinsic association with mortality and hospitalization.
doi:10.1016/j.amjcard.2010.10.012
PMCID: PMC3053576  PMID: 21185004
heart failure; warfarin; mortality; hospitalization

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