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.

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.

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.

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.

The comparative effectiveness of angiotensin-converting enzyme inhibitors (ACEIs) versus angiotensin receptor blockers (ARBs) in real-world older heart failure (HF) patients remains unclear. Of the 8049 hospitalized HF patients ≥65 years discharged alive from 106 Alabama hospitals, 4044 received discharge prescriptions of either ACEIs (n=3383) or ARBs (n=661). Propensity scores for ARB use, calculated for each of 4044 patients, were used to match 655 (99% of 661) patients receiving ARBs with 661 patients receiving ACEIs. The assembled cohort of 655 pairs of patients was well-balanced on 56 baseline characteristics. During over 8 years of follow-up, all-cause mortality occurred in 63% and 68% of matched patients receiving ARBs and ACEIs respectively (hazard ratio {HR} associated with ARB use, 0.86; 95% confidence interval {CI}, 0.75–0.99; p=0.031). Among the 956 matched patients with data on left ventricular ejection fraction (LVEF), the association between ARB (versus ACEI) use was significant only in 419 patients with LVEF≥45% (HR, 0.65; 95% CI, 0.51–0.84; p=0.001) but not in the 537 patients with LVEF <45% (HR, 1.00; 95% CI, 0.81–1.23; p=0.999; p for interaction= 0.012). HRs (95% CIs) for HF hospitalization associated with ARBs use were 0.99 (0.86–1.14; p=0.876) overall, 0.80 (0.63–1.03; p=0.080) among those with LVEF≥45% and 1.14 (0.91–1.43; p=0.246) among those with LVEF <45% (p for interaction, 0.060). In conclusion, in older HF patients with preserved LVEF, a discharge prescription of ARBs (versus ACEI) was associated with lower mortality and a trend toward lower HF hospitalization, findings which need replication in other HF populations.

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.

Aims

To test the hypothesis that baseline hypoalbuminaemia is associated with 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, 5450 were free of centrally adjudicated prevalent HF at baseline, and also had data on baseline serum albumin. Of these, 599 (11%) had hypoalbuminaemia, defined as baseline serum albumin levels ≤3.5 mg/dL. Propensity scores for hypoalbuminaemia were calculated for each patient and used to assemble a matched cohort of 582 pairs of participants with and without hypoalbuminaemia, who were well balanced on 58 baseline characteristics. Using Cox regression models, we estimated the association of hypoalbuminaemia with centrally adjudicated incident HF during 9.6 years of median follow-up. Matched participants had a mean (±SD) age of 74 (±6) years, 62% were women, and 16% were African Americans. Incident HF occurred in 25 and 20% of matched participants with and without hypoalbuminaemia, respectively [hazard ratio when hypoalbuminaemia was compared with normoalbuminaemia, 1.40; 95% confidence interval, 1.05–1.85; P = 0.020]. Pre-match unadjusted, multivariable-adjusted, and propensity-adjusted hazard ratios (95% confidence intervals) for incident HF associated with hypoalbuminaemia were 1.33 (1.12–1.58; P = 0.001), 1.33 (1.11–1.60; P = 0.002), and 1.25 (1.04–1.50; P= 0.016), respectively. The combined endpoint of incident HF or all-cause mortality occurred in 59 and 50% of matched participants with and without hypoalbuminaemia, respectively (hazard ratio, 1.33; 95% confidence interval, 1.11–1.61; P= 0.002).

Conclusions

Among community-dwelling older adults without HF, baseline hypoalbuminaemia was associated with increased risk of incident HF during 10 years of follow-up.

Background

Associations between coronary artery disease (CAD) and outcomes in systolic heart failure (HF) and that between coronary artery bypass graft (CABG) and outcomes in patients with HF and CAD have not been examined using propensity-matched designs.

Methods

Of the 2707 patients with advanced chronic systolic HF in the Beta-Blocker Evaluation of Survival Trial (BEST), 1593 had a history of CAD, of whom 782 had prior CABG. Using propensity scores for CAD we assembled a cohort of 458 pairs of CAD and no-CAD patients. Propensity scores for prior CABG in those with CAD were used to assemble 500 pairs of patients with and without CABG. Matched patients were balanced on 68 baseline characteristics.

Results

All-cause mortality occurred in 33% and 24% of matched patients with and without CAD respectively, during 26 months of median follow-up (hazard ratio {HR} when CAD was compared with no-CAD, 1.41; 95% confidence interval {CI}, 1.11–1.81; P=0.006). HR's (95% CIs) for CAD-associated cardiovascular mortality, HF mortality, and sudden cardiac death (SCD) were 1.53 (1.17–2.00; P=0.002), 1.44 (0.92–2.25; P=0.114) and 1.76 (1.21–2.57; P=0.003) respectively. CAD had no association with hospitalization. Among matched patients with HF and CAD, all-cause mortality occurred in 32% and 39% of those with and without prior CABG respectively (HR for CABG, 0.77; 95% CI, 0.62–0.95; P=0.015).

Conclusions

In patients with advanced chronic systolic HF, CAD is associated with increased mortality, and in those with CAD, prior CABG seems to be associated with reduced all-cause mortality but not SCD.

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.

Background

Many national surveys have found substantial differences in self-reported overall health (SROH) between Spanish-speaking Hispanics and other racial/ethnic groups. However, because cultural and language differences may create measurement bias, it is unclear whether observed differences in SROH reflect true differences in health.

Objectives

This study uses a cross-sectional survey to investigate psychometric properties of the SF-36v2 for subjects across four racial/ethnic and language groups. Multi-group latent variable modeling was used to test increasingly stringent criteria for measurement equivalence.

Subjects

Our sample (N = 1281) included 383 non-Hispanic whites, 368 non-Hispanic blacks, 206 Hispanics interviewed in English and 324 Hispanics interviewed in Spanish recruited from outpatient medical clinics in two large urban areas.

Results

We found weak factorial invariance across the four groups. However, there was no strong factorial invariance. The overall fit of the model was substantially worse (change in CFI > .02, RMSEA change > .003) after requiring equal intercepts across all groups. Further comparisons established that the equality constraints on the intercepts for Spanish-speaking Hispanics were responsible for the decrement to model fit.

Conclusions

Observed differences between SF-36v2 scores for Spanish speaking Hispanics are systematically biased relative to the other three groups. The lack of strong invariance suggests the need for caution when comparing SF-36v2 mean scores of Spanish-speaking Hispanics with those of other groups. However, measurement equivalence testing for this study supports correlational or multivariate latent variable analyses of SF-36v2 responses across all four subgroups, since these analyses require only weak factorial invariance.

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.

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.

Background

The impact of gender on major natural history endpoints in heart failure (HF) has not been examined in a propensity-matched study.

Methods

Of the 7788 chronic systolic and diastolic HF patients in the Digitalis Investigation Group trial 1926 were women. Propensity scores for female gender were used to assemble a cohort of 1669 pairs of men and women who were well-balanced on 32 measured baseline characteristics. Matched hazard ratios (HR) and 95% confidence intervals (CI) for outcomes associated with female gender were calculated using stratified Cox regression models.

Results

All-cause mortality occurred in 36% (rate, 1256/10,000 person-years) and 30% (rate, 1008/10,000 person-years) of matched men and women respectively during 5 years of follow up (HR when women were compared with men, 0.82, 95% CI, 0.72–0.94, P=0.004). Female gender was also associated with reduced cardiovascular mortality (matched HR, 0.85; 95% CI, 0.73–0.99, P=0.037) and a trend toward reduced non-cardiovascular mortality (matched HR, 0.73; 95% CI, 0.53–1.00; P=0.053). All-cause hospitalization occurred in 67% (rate, 4003/10,000 person-years) and 65% (rate, 3762/10,000 person-years) matched male and female patients respectively (HR for women, 1.03, 95% CI, 0.93–1.15, P=0.538). Female gender was not associated with cardiovascular or HF hospitalization but was associated with hospitalization due to unstable angina pectoris (matched HR, 1.38; 95%CI, 1.11–1.72; P=0.003) and stroke (matched HR, 0.65; 95%CI, 0.46–0.92; P=0.014).

Conclusions

In patients with chronic HF, female gender has a significant independent association with improved survival but has no association with all-cause, cardiovascular, or HF hospitalizations.

Aim

To determine if the association between hyperuricaemia and poor outcomes in heart failure (HF) varies by chronic kidney disease (CKD).

Methods and results

Of the 2645 systolic HF patients in the Beta-Blocker Evaluation of Survival Trial with data on baseline serum uric acid, 1422 had hyperuricaemia (uric acid ≥6 mg/dL for women and ≥8 mg/dL for men). Propensity scores for hyperuricaemia, estimated for each patient, were used to assemble a matched cohort of 630 pairs of patients with and without hyperuricaemia who were balanced on 75 baseline characteristics. Associations of hyperuricaemia with outcomes during 25 months of median follow-up were examined in all patients and in those with and without CKD (estimated glomerular filtration rate of <60 mL/min/1.73 m2). Hyperuricaemia-associated hazard ratios (HRs) and 95% confidence intervals (CI) for all-cause mortality and HF hospitalization were 1.44 (1.12–1.85, P = 0.005) and 1.27 (1.02–1.58, P = 0.031), respectively. Hazard ratios (95% CIs) for all-cause mortality among those with and without CKD were 0.96 (0.70–1.31, P = 0.792) and 1.40 (1.08–1.82, P = 0.011), respectively (P for interaction, 0.071), and those for HF hospitalization among those with and without CKD were 0.99 (0.74–1.33, P = 0.942) and 1.49 (1.19–1.86, P = 0.001), respectively (P for interaction, 0.033).

Conclusion

Hyperuricaemia has a significant association with poor outcomes in HF patients without CKD but not in those with CKD, suggesting that hyperuricaemia may predict poor outcomes when it is primarily a marker of increased xanthine oxidase activity, but not when it is primarily due to impaired renal excretion of uric acid.

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.

Aims

Obesity is paradoxically associated with survival benefit in patients with chronic heart failure (HF). However, obesity complicates the management of diabetes mellitus (DM), which is common in HF. Yet, little is known about the impact of obesity in HF patients with DM. Therefore, we examined the association between obesity and outcomes in propensity-matched cohorts of HF patient with and without DM.

Methods and results

Of the 7788 participants with chronic mild to moderate HF in the Digitalis Investigation Group trial, 7379 were non-cachectic [body mass index (BMI) ≥20 kg/m2] at baseline. Of these, 2153 (29%) had DM, of whom 798 (37%) were obese (BMI ≥30 kg/m2). Of the 5226 patients without DM, 1162 (22%) were obese. Propensity scores for obesity were used to separately assemble 636 pairs of obese and non-obese patients with DM and 770 pairs of obese and non-obese patients without DM, who were balanced on 32 baseline characteristics. Among matched patients with DM, all-cause mortality occurred in 38 and 39% of obese and non-obese patients, respectively [hazard ratio (HR) when obesity was compared with no obesity 0.99; 95% confidence interval (CI) 0.80–1.22; P = 0.915]. Among matched patients without DM, all-cause mortality occurred in 23 and 27% obese and non-obese patients, respectively (HR associated with obesity 0.77; 95% CI 0.61–0.97; P = 0.025).

Conclusion

In patients with chronic mild to moderate HF and DM, obesity confers no paradoxical survival benefit. Whether intentional weight loss may improve outcomes in these patients needs to be investigated in future prospective studies.

Background

The association between a history of cancer and mortality has not been studied in a propensity-matched population of community-dwelling older adults.

Methods

Of the 5795 participants in the Cardiovascular Health Study, 827 (14%) had self-reported physician-diagnosed cancer at baseline. Propensity scores for cancer were used to assemble a cohort of 789 and 3118 participants with and without cancer respectively who were balanced on 45 baseline characteristics. Cox regression models were used to determine the association between cancer and all-cause mortality among matched patients, and to identify independent predictors of mortality among unmatched cancer patients.

Results

Matched participants had a mean (SD) age of 74 (6) years, 57% were women, 10% were African Americans, and 38% died from all causes during 12 years of follow-up. All-cause mortality occurred in 41% and 37% of matched participants with and without a history of cancer respectively (hazard ratio when cancer was compared with no-cancer, 1.16; 95% confidence interval, 1.02–1.31; P=0.019). Among those with cancer older age, male gender, smoking, lower than college education, fair-to-poor self-reported health, coronary artery disease, diabetes mellitus, chronic kidney disease, left ventricular hypertrophy, increased heart rate, low hemoglobin and low baseline albumin were associated with increased risk of mortality

Conclusions

Among community-dwelling older adults, a history of cancer was associated with increased mortality and among those with cancer, several socio-demographic variables and morbidities predicted mortality. These findings suggest that addressing traditional risk factors for cardiovascular mortality may help improve outcomes in older adults with a history of cancer.

Background

Compared with serum potassium levels 4–5.5 mEq/L, those <4 mEq/L have been shown to increase mortality in chronic heart failure (HF). Expert opinions suggest that serum potassium levels >5.5 mEq/L may be harmful in HF. However, little is known about the safety of serum potassium 5–5.5 mEq/L.

Methods

Of the 7788 chronic HF patients in the Digitalis Investigation Group trial, 5656 had serum potassium 4–5.5 mEq/L. Of these, 567 had mild hyperkalemia (5–5.5 mEq/L) and 5089 had normokalemia (4–4.9 mEq/L). Propensity scores for mild hyperkalemia were used to assemble a balanced cohort of 548 patients with mild hyperkalemia and 1629 patients with normokalemia. Cox regression models were used to estimate hazard ratios (HR) and 95% confidence intervals (CI) for association between mild hyperkalemia and mortality during a median follow-up of 38 months.

Results

All-cause mortality occurred in 36% and 38% of matched patients with normokalemia and mild hyperkalemia respectively (HR, 1.07; 95% CI, 0.90–1.26; P= 0.458). Unadjusted, multivariable-adjusted, and propensity-adjusted HRs for mortality associated with mild hyperkalemia were 1.33 (95% CI, 1.15–1.52; P<0.0001), 1.16 (95% CI, 1.01–1.34; P=0.040) and 1.13 (95% CI, 0.98–1.31; P=0.091) respectively. Mild hyperkalemia had no association with cardiovascular or HF mortality or all-cause or cardiovascular hospitalization.

Conclusion

Serum potassium 4–4.9 mEq/L is optimal and 5–5.5 mEq/L appears relatively safe in HF. Despite lack of an intrinsic association, the bivariate association of mild-hyperkalemia with mortality suggests that it may be useful as a biomarker of poor prognosis in HF.

Background

Transatlantic differences in outcomes after acute myocardial infarction (AMI) have not been examined in propensity-matched studies.

Methods

In the Eplerenone Post-Acute Myocardial Infarction Heart Failure Efficacy and Survival Study (EPHESUS), there were significant imbalances in baseline characteristics between patients from North America (n=858) and Europe (n=4646). Propensity scores for North America were calculated for each patient based on 64 baseline characteristics, and were then used to assemble 298 pairs of propensity-matched patients who were well-balanced on all measured baseline covariates. Matched Cox regression models were used to estimate transatlantic differences in outcomes during a mean follow-up of 16 months.

Results

There was no transatlantic difference in all-cause mortality (matched hazard ratio {HR}, 1.00; 95% confidence interval {CI}, 0.64–1.57; P=1.000). All-cause hospitalization occurred in 175 (rate, 8974/10,000 person-years) and 137 (rate, 5249/10,000 person-years) patients respectively from North America and Europe (matched HR when North America was compared with Europe, 1.89; 95% CI, 1.41–2.52; P<0.0001). Matched HRs (95% CIs) for cardiovascular and non-cardiovascular hospitalization for North America were respectively 1.35 (0.92–1.97; P=0.125) and 1.89 (1.31–2.72; P<0.0001). Among 5504 pre-match patients, unadjusted, multivariable-adjusted, and propensity-adjusted HRs for all-cause hospitalization for North America were 1.52 (95% CI, 1.38–1.68; P<0.0001), 1.16 (95% CI, 1.02–1.31; P=0.020), 1.41 (95% CI, 1.17–1.70; P<0.0001).

Conclusion

Despite major transatlantic differences in baseline characteristics, there was no difference in post-AMI mortality. The increased non-cardiovascular hospitalization in North America may in part be due to transatlantic differences in patient preferences and access to care.

Background

The association between hyperuricemia and incident heart failure (HF) is relatively unknown.

Methods

Of the 5461 community-dwelling older adults, ≥65 years, in the Cardiovascular Health Study without HF at baseline, 1505 had hyperuricemia (baseline serum uric acid ≥6 mg/dL for women and ≥7 mg/dL for men). Using propensity scores for hyperuricemia, estimated for each participant using 64 baseline covariates, we were able to match 1181 pairs of participants with and without hyperuricemia.

Results

Incident HF occurred in 21% and 18% of participants respectively with and without hyperuricemia during 8.1 years of mean follow-up (hazard ratio {HR} for hyperuricemia versus no hyperuricemia, 1.30; 95% confidence interval {CI}, 1.05–1.60; P=0.015). The association between hyperuricemia and incident HF was significant only in subgroups with normal kidney function (HR, 1.23; 95% CI, 1.02–1.49; P=0.031), without hypertension (HR, 1.31; 95% CI, 1.03–1.66; P=0.030), not receiving thiazide diuretics (HR, 1.20; 95% CI, 1.01–1.42; P=0.044), and without hyperinsulinemia (HR, 1.35; 95% CI, 1.06–1.72; P=0.013). Used as a continuous variable, each 1 mg/dL increase in serum uric acid was associated with a 12% increase in incident HF (HR, 1.12; 95% CI, 1.03–1.22; P=0.006). Hyperuricemia had no association with acute myocardial infarction or all-cause mortality.

Conclusions

Hyperuricemia is associated with incident HF in community-dwelling older adults. Cumulative data from our subgroup analyses suggest that this association is only significant when hyperuricemia is a marker of increased xanthine oxidase activity but not when hyperuricemia is caused by impaired renal elimination of uric acid.

The impact of baseline systolic blood pressure (SBP) on outcomes in advanced chronic systolic heart failure (HF) patients has not been studied using propensity-matched design. Of the 2706 Beta-Blocker Evaluation of Survival Trial (BEST) participants with chronic HF, New York Heart Association class III–IV symptoms and left ventricular ejection fraction ≤35%, 1751 had SBP ≤120 (median, 108; range, 70–120) mm Hg and 955 had SBP >120 (median, 134; range 121–192) mm Hg. Propensity scores for SBP >120 mm Hg, calculated for each patient, were used to assemble a matched cohort of 545 pairs of patients with SBP ≤120 and >120 mm Hg, who were balanced on 65 baseline characteristics. Matched Cox regression models were used to estimate associations between SBP ≤120 mm Hg and outcomes over 4 years of follow-up. Matched participants had a mean (±SD) age of 62 (±12) years, 24% were women and 24% were African American. HF hospitalization occurred in 38% and 32% of patients with SBP ≤120 and >120 mm Hg respectively (hazard ratio when SBP ≤120 was compared with SBP >120 mm Hg, 1.33; 95% confidence interval, 1.04 1.69; P=0.023). All-cause mortality occurred in 28% and 30% of matched patients with SBP ≤120 and >120 mm Hg respectively (hazard ratio when SBP ≤120 was compared with SBP >120 mm Hg, 1.13; 95% confidence interval, 0.86 1.49; P=0.369). In conclusion, in patients with advanced chronic systolic HF, baseline SBP ≤120 mm Hg is associated with increased risk of HF hospitalization, but had no association with all-cause mortality.

Background

Hypokalemia is common in heart failure (HF) and is associated with increased mortality. Potassium supplements are commonly used to treat hypokalemia and maintain normokalemia. However, their long-term effects on outcomes in chronic HF are unknown. We used a public-use copy of the Digitalis Investigation Group (DIG) trial dataset to determine the associations of potassium supplement use with outcomes using a propensity-matched design.

Methods

Of the 7788 DIG participants with chronic HF, 2199 were using oral potassium supplements at baseline. We estimated propensity scores for potassium supplement use for each patient and used them to match 2131 pairs of patients receiving and not receiving potassium supplements. Matched Cox regression models were used to estimate associations of potassium supplement use with mortality and hospitalization during 40 months of median follow-up.

Results

All-cause mortality occurred in 818 (rate, 1327/10000 person-years) and 802 (rate, 1313/10000 person-years) patients respectively receiving and not receiving potassium supplements (hazard ratio {HR} when potassium supplement use was compared with nonuse, 1.05; 95% confidence interval {CI}, 0.94–1.18; P=0.390). All-cause hospitalizations occurred in 1516 (rate, 4777/10,000 person-years) and 1445 (rate, 4120/10,000 person-years) patients respectively receiving and not receiving potassium supplements (HR, 1.15; 95% CI, 1.05–1.26; P=0.004). HR (95% CI) for hospitalizations due to cardiovascular causes and worsening HF were respectively 1.19 (95% CI, 1.08–1.32; P=0.001) and 1.27 (1.12–1.43; P<0.0001).

Conclusion

The use of potassium supplements in chronic HF was not associated with mortality. However, their use was associated with increased hospitalization due to cardiovascular causes and progressive HF.

Introduction

Ischemic heart disease (IHD) is common in heart failure (HF), yet the association between incident coronary revascularization and mortality in these patients has not been examined in a propensity-matched study.

Methods

In the Digitalis Investigation Group trial, 2853 patients without coronary revascularization and 120 patients with coronary revascularization during the first three years were alive at the end of three years. We used propensity scores to match 119 and 357 patients with and without coronary revascularization. Matched Cox regression models were used to estimate hazard ratio (HR) and 95% confidence interval (CI) for mortality during the fourth year of follow-up, for all patients and by the mean left ventricular ejection fraction (LVEF) of 35%.

Results

Coronary revascularization was associated with higher mean LVEF (36 % versus 32 %; p<0.0001) and prevalence of angina pectoris (48% versus 32%; p<0.0001) but fewer prior myocardial infarction (80% versus 87%; p=0.023), all of which were balanced post-match. All-cause mortality occurred in 5.9% and 6.2% patients respectively with and without coronary revascularization (HR for coronary revascularization, 0.95; 95% CI, 0.39–2.32; p=0.910). HR for mortality associated with coronary revascularization for patients with LVEF ≤35% and >35% were respectively 1.34 (95% CI, 0.48–3.71; p=0.578) and 0.61 (95% CI, 0.13–2.87; p=0.532).

Conclusion

Chronic HF patients with IHD receiving coronary revascularization were more likely to have angina and higher LVEF. However, in a balanced propensity-matched cohort, there was no association between coronary revascularization and mortality. The LVEF-associated variation in mortality needs to be prospectively studied.

Background

Little is known about the effects of hypokalemia on outcomes in patients with chronic heart failure (HF) and chronic kidney disease (CKD).

Methods and Results

Of the 7788 chronic HF patients in the Digitalis Investigation Group trial, 2793 had CKD, defined as estimated glomerular filtration rate (eGFR) <60 ml/min/1.73 m2. Of these, 527 had hypokalemia (serum potassium <4 mEq/L) and 2266 had normokalemia (4–4.9 mEq/L). Propensity scores for hypokalemia were used to assemble a balanced cohort of 522 pairs of patients with hypokalemia and normokalemia. All-cause mortality occurred in 48% and 36% of patients with hypokalemia and normokalemia respectively during 57 months of follow-up (matched hazard ratio {HR} when hypokalemia was compared with normokalemia, 1.56, 95% confidence interval {CI}, 1.25–1.95; P<0.0001). Matched HR’s (95% CI’s) for cardiovascular and HF mortalities, and all-cause, cardiovascular and HF hospitalizations were 1.65 (1.29–2.11; P<0.0001), 1.82 (1.28–2.57; P<0.0001), 1.16 (1.00–1.35; P=0.036), 1.27 (1.08–1.50; P=0.004) and 1.29 (1.05–1.58; P=0.014) respectively. Among 453 pairs of balanced patients with HF and CKD, all-cause mortality occurred in 47% and 38% of patients with mild hypokalemia (3.5–3.9 mEq/L) and normokalemia respectively (matched HR, 1.31, 95% CI, 1.03–1.66; P=0.027). Among 169 pairs of balanced patients with eGFR <45 ml/min/1.73 m2, all-cause mortality occurred in 57% and 47% of patients with hypokalemia (<4 mEq/L) and normokalemia respectively (matched HR, 1.53, 95% CI, 1.07–2.19; P=0.020).

Conclusions

In patients with HF and CKD, hypokalemia is common and associated with increased mortality and hospitalization.