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1.  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
2.  A Brief Educational Intervention to Improve Healthcare Providers' Awareness of Child Passenger Safety 
Introduction. Motor vehicle crashes are the leading cause of death among US children aged 4–14 years. In theory, health provider counseling about Child Passenger Safety (CPS) could be a useful deterrent. The data about the effectiveness of CPS dissemination is sparse, but existing results suggest that providers are not well informed. Moreover, there is insufficient evidence to determine whether provider counseling about CPS is effective. Methods. We therefore assessed CPS best practice knowledge among 217 healthcare workers at hospitals in seven cities throughout the USA and evaluated the impact of a brief, lunch and learn educational intervention with a five-item questionnaire. Attendees were comprised of physicians, nurses, social workers, pediatric residents, and pediatric trauma response teams. Results. Pre-post survey completion was nearly 100% (216 of 217 attendees). Participation was fairly evenly distributed according to age (18–29, 30–44, and 45+ years). More than 80% of attendees were women. Before intervention, only 4% of respondents (9/216) answered all five questions correctly; this rose to 77% (167/216) (P < 0.001, using a Wilcoxon signed-rank test) after intervention. Conclusion. Future research should consider implementation and controlled testing of comparable educational programs to determine if they improve dissemination of CPS best practice recommendations in the long term.
doi:10.1155/2013/821693
PMCID: PMC3583053  PMID: 23476672
3.  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
4.  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
5.  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
6.  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
7.  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
8.  Using Administrative Databases to Calculate Framingham Scores within a Large Healthcare Organization 
Background and Purpose
Framingham calculators are typically implemented in one-on-one settings to determine if a patient has a high risk of developing cardiovascular disease in the next 10 years. Because health care administrative datasets are including more clinical information, we explored how well administrative data-derived Framingham scores could identify persons who would develop stroke in the following year.
Methods
Using a nested case-control design, we compared all 313 persons who developed a first time stroke at 5 VA Medical Centers with a random sample of 25,361 persons who did not develop a first-time stroke in 2008. We compared Framingham scores and risk using administrative data available at the end of 2007.
Results
Stroke cases had higher risk profile than controls: older age, higher systolic blood pressure and total cholesterol, and more likely to have diabetes, cardiovascular disease (CVD), left ventricular hypertrophy and be on treatment for blood pressure (p<0.05). The mean Framingham generalized CVD score (18.0 vs. 14.5) as well as the mean Framingham stroke specific score (13.2 vs. 10.2) was higher for stroke cases than controls (both p<0.0001). The c-statistic for the generalized CVD score was 0.68, 95% Confidence Interval (CI); 0.65–0.70 and for the stroke score was 0.64, 95% CI; 0.62–0.67.
Conclusions
Persons who develop a stroke in the following year have a worse Framingham risk profile, as determined by administrative data. Future studies should examine how to improve the stroke predictive tools and to identify the appropriate populations and uses for applying stroke risk predictive tools.
doi:10.1161/STROKEAHA.110.603340
PMCID: PMC3125472  PMID: 21546488
Framingham calculator; stroke; administrative database
9.  History of Cancer and Mortality in Community-Dwelling Older Adults 
Cancer epidemiology  2010;35(1):30-36.
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.
doi:10.1016/j.canep.2010.07.011
PMCID: PMC3062071  PMID: 20708995
History of cancer; mortality; propensity score; older adults
10.  Understanding the Reasons for the Underutilization of Pneumococcal Vaccination Among Community-Dwelling Older African Americans 
OBJECTIVES
To understand the potential roles of various patient and provider factors in the underutilization of pneumococcal vaccination among Medicare-eligible older African Americans.
DESIGN
The Cardiovascular Health Study.
SETTING
Four US states.
PARTICIPANTS
795 pairs of community-dwelling Medicare-eligible African American and white adults, ≥65 years, balanced by age and gender.
MEASUREMENTS
Data on self-reported race, receipt of pneumococcal vaccination and other key socio-demographic and clinical variables were collected at baseline.
RESULTS
Participants had a mean (±SD) age of 73 (±6) years and 63% were women. Pneumococcal vaccination was received by 22% African Americans and 28% whites (unadjusted odds ratios {OR} for African Americans, 0.75; 95% confidence interval {CI}, 0.60–0.94; P=0.013). This association remained significant despite adjustment for socio-demographic and clinical confounders including education, income, chronic obstructive pulmonary disease and prior pneumonia (OR, 0.74; 95% CI, 0.56– 0.97; P=0.030). However, the association was no longer significant after additional adjustment for the receipt of influenza vaccination (OR, 0.79; 95% CI, 0.59–1.06; P=0.117). A receipt of an influenza vaccination was associated with higher odds of receiving a pneumococcal vaccination (unadjusted OR, 6.43; 95% CI, 5.00–8.28; P<0.001) and the association between race and pneumococcal vaccination lost significance when adjusted for influenza vaccination alone (OR, 0.81; 95% CI, 0.63–1.03; P=0.089).
CONCLUSION
The strong association between the receipt of influenza and pneumococcal vaccinations suggests that patients’ and providers’ attitudes toward vaccination, rather than traditional confounders such as education and income, may help explain the underutilization of pneumococcal vaccination among older African Americans.
doi:10.1111/j.1532-5415.2010.03181.x
PMCID: PMC3058385  PMID: 21143440
Racial variations; pneumococcal vaccination; older adults
11.  Mild hyperkalemia and outcomes in chronic heart failure: A propensity matched study 
International journal of cardiology  2009;144(3):383-388.
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.
doi:10.1016/j.ijcard.2009.04.041
PMCID: PMC2888731  PMID: 19500863
Mild hyperkalemia; heart failure; mortality; hospitalization
12.  Epidemiology of Stroke in Chronic Heart Failure Patients with Normal Sinus Rhythm: Findings from the DIG Stroke Sub-Study 
International journal of cardiology  2009;144(3):389-393.
Background
Little is known about the epidemiology of stroke in chronic systolic and diastolic heart failure (HF) patients in normal sinus rhythm (NSR) receiving angiotensin-converting enzyme (ACE) inhibitors. Because all HF patients in the Digitalis Investigation Group (DIG) trial (N=7788) were in NSR and nearly all were receiving ACE inhibitors, a survey-based stroke sub-study was conducted but its findings have never been published.
Methods
DIG investigators confirmed a total 222 cases of stroke of which 144 had neurological deficit ≥24 hours. We used logistic regression models to determine predictors of incident stroke among all 7788 patients and predictors of neurological deficit ≥24 hours and all-cause mortality among 222 stroke patients.
Results
Age ≥65 years (adjusted odds ratio {AOR}, 1.36; 95% confidence interval {CI}, 1.02–1.80; P=0.035), nonwhite race (AOR, 0.65; 95% CI, 0.42–0.99; P=0.047), hypertension (AOR, 1.46; 95% CI, 1.11–1.94; P=0.008), diabetes mellitus (AOR, 1.37; 95% CI, 1.03–1.82; P=0.030), and cardiomegaly (AOR, 1.39; 95% CI, 1.03–1.86; P=0.030) were independent predictors of stroke. However, among those with stroke, nonwhites had higher odds of neurological deficits ≥24 hours (AOR, 2.86; 95% CI, 1.01–8.07; P=0.047) and death (AOR, 3.28; 95% CI, 1.30–8.30; P=0.012).
Conclusion
Older age, hypertension, diabetes and cardiomegaly were associated with increased incidence of stroke among HF patients with NSR receiving ACE inhibitors. The association of race and stroke, however, was complex. While nonwhite race was associated with decreased risk of stroke, among those with stroke, nonwhite race was associated with increased stroke severity and mortality.
doi:10.1016/j.ijcard.2009.04.035
PMCID: PMC2952701  PMID: 19439379
heart failure; stroke; epidemiology; outcomes; race
13.  Association between hyperuricemia and incident heart failure among older adults: A propensity-matched study 
International journal of cardiology  2009;142(3):279-287.
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.
doi:10.1016/j.ijcard.2009.01.010
PMCID: PMC2906633  PMID: 19201041
Uric acid; incident heart failure; kidney function; propensity score
14.  Oral Potassium Supplement Use and Outcomes in Chronic Heart Failure: A Propensity-Matched Study 
International journal of cardiology  2009;141(2):167-174.
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.
doi:10.1016/j.ijcard.2008.11.195
PMCID: PMC2900187  PMID: 19135741
Heart failure; potassium supplement; mortality; hospitalization; propensity score
15.  Incident Coronary Revascularization and Subsequent Mortality in Chronic Heart Failure: A Propensity-Matched Study 
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.
doi:10.1016/j.ijcard.2008.10.049
PMCID: PMC2904513  PMID: 19081647
heart failure; revascularization; mortality; outcomes
16.  Uncontrolled Hypertension and Increased Risk for Incident Heart Failure in Older Adults with Hypertension: Findings from a Propensity-Matched Prospective Population Study 
Background
Hypertension is a risk factor for incident heart failure (HF). However, the effect of uncontrolled blood pressure (BP) on incident HF in older adults with hypertension has not been prospectively examined in propensity-matched studies.
Methods
Of the 5795 Cardiovascular Health Study participants, ≥65 years, 2562 with self-reported physician-diagnosed hypertension had no baseline HF. Of these, 1391 had uncontrolled hypertension, defined as systolic BP (SBP) ≥140 (n=1373) or diastolic BP ≥90 mm Hg (n=18). Propensity scores for uncontrolled hypertension, calculated for each participant, were used to assemble a cohort of 1021 pairs of participants with controlled and uncontrolled hypertension who were balanced on 31 baseline characteristics.
Results
Centrally adjudicated incident HF developed in 23% and 26% of participants with controlled and uncontrolled hypertension respectively during 13 years of follow-up (matched hazard ratio {HR} when uncontrolled hypertension was compared with uncontrolled hypertension, 1.39; 95% confidence interval {CI}, 1.12–1.73; P=0.003). HR’s (95% CI’s) for incident HF for those with (n=503) and without (n=1539) chronic kidney disease (CKD) were 1.73 (95% CI, 1.26–2.38; P=0.001) and 1.08 (95% CI, 0.87–1.34; P=0.486) respectively (P for interaction, 0.012). Compared with participants with controlled hypertension, HR’s for incident HF associated with SBP 140–159 and ≥160 mm Hg were 1.06 (95% CI, 0.86–1.31; P=0.572) and 1.58 (95% CI, 1.27–1.96; P<0.0001) respectively.
Conclusions
In community-dwelling older adults with hypertension, those with uncontrolled (versus controlled) BP has increased risk of new-onset HF, which is more pronounced in those with SBP≥160 mm Hg and with CKD.
doi:10.1016/j.jash.2010.02.002
PMCID: PMC2914566  PMID: 20374948
Hypertension; uncontrolled blood pressure; incident heart failure
17.  A history of atrial fibrillation and outcomes in chronic advanced systolic heart failure: a propensity-matched study 
European Heart Journal  2009;30(16):2029-2037.
Aims
Atrial fibrillation (AF)-associated poor outcomes in heart failure (HF) are often attributed to older age, advanced disease, and comorbidity burden of HF patients with AF. Therefore, we examined the effect of AF on outcomes in a propensity-matched study in which patients with and without AF were well balanced on all measured baseline characteristics.
Methods and results
Of the 2708 advanced chronic systolic HF patients in the Beta-Blocker Evaluation of Survival Trial, 653 had a history of AF. Propensity scores for AF were calculated for each patient and were used to assemble a cohort of 487 pairs of patients with and without AF who were balanced on 74 baseline characteristics. Matched Cox regression analyses were used to estimate associations of AF with outcomes during 23 months of mean follow-up. All-cause mortality occurred in 187 (rate, 2046/10 000 person-years of follow-up) and 181 (rate, 1885/10 000 person-years) matched patients with and without AF, respectively [matched hazard ratio (HR) when AF was compared with no-AF 1.03, 95% confidence interval (CI) 0.79–1.33; P = 0.84]. Heart failure hospitalization occurred in 215 (rate, 3171/10 000 person-years) and 184 (rate, 2405/10 000 person-years) matched patients with and without AF, respectively (matched HR when AF was compared with no-AF 1.28, 95% CI 1.00–1.63; P = 0.049). Hazard ratios and 95% CIs for AF-associated HF hospitalization for bucindolol and placebo groups were, respectively, 1.08 (0.81–1.43) and 1.54 (1.17–2.03; P for interaction = 0.09).
Conclusion
A history of AF had no intrinsic association with mortality but was associated with HF hospitalization in chronic systolic HF.
doi:10.1093/eurheartj/ehp222
PMCID: PMC2726959  PMID: 19531579
Heart failure; Atrial fibrillation; Mortality; Hospitalization
18.  A Propensity-Matched Study of the Association of Peripheral Arterial Disease with Cardiovascular Outcomes in Community-Dwelling Older Adults 
The American journal of cardiology  2008;103(1):130-135.
The association between peripheral arterial disease (PAD) and outcomes has not been studied in a propensity-matched population of community-dwelling older adults. We analyzed the public-use copy of the Cardiovascular Health Study (CHS) datasets to test the hypothesis that baseline PAD is associated with increased all-cause mortality and cardiovascular morbidity. Of the 5795 CHS participants, 5630 had data on baseline ankle-brachial index (ABI) and 767 had PAD defined as ABI <0.9. Propensity scores for PAD were calculated for each participant using 66 baseline covariates and were used to match 679 pairs of participants with and without PAD. Matched Cox regression models were used to estimate associations of PAD with outcomes during a median follow up of 7.5 years. Overall, 55% of matched participants died from all causes during 9958 person-years of follow-up. All-cause mortality occurred in 61% (rate, 8710/100,000 person-years) and 55% (rate, 6503/100,000 person-years of follow up) of participants respectively with and without PAD (matched hazard ratio {HR} when PAD was compared with no-PAD, 1.47; 95% confidence interval {CI}, 1.23–1.76; P<0.0001). Pre-match unadjusted, multivariable-adjusted and propensity-adjusted HR (95% CI) for PAD-associated all-cause mortality were 2.90 (2.61–3.21; P<0.0001), 1.53 (1.36–1.71; P<0.0001) and 1.57 (1.39–1.78; P<0.0001) respectively. Matched HR and 95% CI for PAD for incident heart failure and symptomatic PAD were respectively 1.32 (1.00–1.73; P=0.052) and 3.92 (3.92–7.21; P<0.0001). In conclusion, in a propensity-matched well-balanced population of community-dwelling older adults, baseline PAD was associated with increased all-cause mortality and cardiovascular morbidity.
doi:10.1016/j.amjcard.2008.08.037
PMCID: PMC2909744  PMID: 19101243
Peripheral artery disease; mortality; propensity score
19.  Value of Orthopnea, Paroxysmal Nocturnal Dyspnea, and Medications in Prospective Population Studies of Incident Heart Failure 
The American journal of cardiology  2009;104(2):259-264.
Prospective population studies of incident heart failure (HF) are often limited by difficulties in assembling a HF-free cohort. We used public-use copies of the Cardiovascular Health Study (CHS) datasets to determine sensitivity, specificity, and positive and negative predictive values (PPV and NPV) of orthopnea and paroxysmal nocturnal dyspnea (PND), with and without the use of medications used in CHS HF criteria (diuretics plus digoxin or vasodilators) in the diagnosis of prevalent HF and in the assembly of a relatively HF-free population. Of the 5771 community-dwelling older adults ≥65 years, 803 had orthopnea, 660 had PND, 1075 had either symptom, 388 had both symptoms, 547 were using HF medications, and 4315 had neither symptom nor were using HF medications. Definite HF was centrally adjudicated in 272 participants. The sensitivity, specificity, PPV and NPV (95% confidence intervals) for either orthopnea or PND were 52% (46%–58%), 83% (82%–84%), 13% (11%–15%) and 97% (97%–98%) respectively, and those for either orthopnea or PND or use of HF medications were 77% (72%–82%), 77% (76%–79%), 14% (13%–16%) and 99% (98%–99%) respectively. In conclusion, only <20% of those with either orthopnea or PND had definite HF, which limits their usefulness in the diagnosis of prevalent HF in the community. However, nearly 99% (NPV) of those with neither symptom nor using HF medications also did not have HF, which may be useful as a simple and inexpensive tool in assembling a relatively HF-free cohort for prospective population studies of incident HF.
doi:10.1016/j.amjcard.2009.03.025
PMCID: PMC2787196  PMID: 19576357
Orthopnea; paroxysmal nocturnal dyspnea; medications; heart failure; diagnosis; population studies
20.  A Propensity-Matched Study of Outcomes of Chronic Heart Failure in Younger and Older Adults 
The majority of heart failure patients are older adults and most heart failure-related adverse events occur in these patients. However, the independent association of age and outcomes in chronic heart failure is not clearly determined. We categorized 7788 ambulatory chronic heart failure patients who participated in the Digitalis Investigation Group trial as younger and older using the cutoff of 65 years. Propensity scores for age were calculated for each patient and used to match 2381 older patients with 2381 younger patients. The impact of age on mortality and hospitalization during a median 40 months of follow-up was assessed using matched Cox regression methods. All-cause mortality occurred in 877 older patients versus 688 younger patients (hazard ratio when older age was compared with younger age (HR) = 1.26, 95% confidence interval (CI) = 1.12–1.41, p <0.0001). Older patients, when compared with propensity-matched younger patients, also had significantly higher mortality rates due to cardiovascular causes (HR = 1.14; 95% CI = 1.00–1.30, p = 0.044) and worsening heart failure causes (HR = 1.32; 95% CI = 1.07–1.62, p = 0.009). No significant association was found between age and hospitalization due to all causes (HR = 1.08; 95% CI = 0.99–1.18, p = 0.084) and cardiovascular causes (HR = 1.03; 95% CI = 0.93–1.13, p = 0.622). However, hospitalization due to heart failure was significantly increased in older patients (HR = 1.14; 95% CI = 1.01–1.28, p = 0.041). In ambulatory chronic heart failure patients, older age although associated with increased mortality was not associated with increased hospitalizations except for those due to worsening heart failure.
doi:10.1016/j.archger.2008.06.009
PMCID: PMC2685163  PMID: 18692914
Heart failure; mortality; hospitalization; propensity score; older adults
21.  Association of diuretic use and overactive bladder syndrome in older adults: a propensity score analysis 
Diuretics use and overactive bladder syndrome are common in older adults. However, the relationship between the two has not been well studied. Data were collected by self-administered questionnaires including the Urge Urinary Distress Inventory (Urge-UDI) and the Urge Incontinence Impact Questionnaire (Urge-IIQ), and by outpatient chart abstraction. Patients (n = 172) had a mean age of 79 ± 7.5 (± S.D.), 76% were women, and 48% were African Americans; 76% had hypertension, 32% had heart failure, and 66% were receiving diuretics (57% loop diuretics). Overall, 72%, 68%, and 73% of patients respectively reported urinary frequency, urgency and urge incontinence. Diuretic use was associated with increased frequency (81% versus 55% non-diuretic; odds ratio = OR = 3.48; 95% confidence interval = CI = 1.73–7.03) and urgency (74% versus 57% non-diuretic; OR = 2.17; 95% CI = 1.11–4.24) but not with incontinence (OR = 1.74; 95% CI = 0.87–3.50). When adjusted for propensity scores, diuretic use had independent associations with frequency (adjusted OR = 3.09; 95% CI = 1.20–7.97) and urgency (adjusted OR = 2.50; 95% CI = 1.00–6.27). In addition to frequency and urgency, loop diuretic use was also associated with incontinence (OR = 2.54; 95% CI = 1.09–5.91), which lost significance after propensity adjustment (adjusted OR = 1.88; 95% CI = 0.57–6.17). Overall summary mean Urge-IIQ score was 1.83 ± 0.85 (±S.D.) with 1.75 ± 0.86, 1.68 ± 0.76, and 2.03 ± 0.88, respectively for no-diuretic, non-loop, and loop-diuretic patients (one-way ANOVA p = 0.063). Overactive bladder symptoms were common among ambulatory older adults and were associated with diuretic use, and had stronger associations with loop diuretic use.
doi:10.1016/j.archger.2008.05.002
PMCID: PMC2720316  PMID: 18752858
Diuretic use; overactive bladder; quality of life; propensity score; older adults
22.  Isolated Systolic Hypertension and Incident Heart Failure in Older Adults: A Propensity-Matched Study 
Hypertension  2009;53(3):458-465.
The association between isolated systolic hypertension (ISH) and incident heart failure (HF) has not been prospectively studied in a propensity-matched population of ambulatory older adults. Of the 5,795 participants in the public-use copy of the Cardiovascular Health Study (CHS) dataset, 5248 has diastolic blood pressure <90 mm Hg and were free of HF at baseline. Of these, 2000 (38%) has ISH, defined as average seated systolic blood pressure ≥ 140 mm Hg. Propensity scores for baseline ISH were calculated for each participant (based on 64 baseline covariates), and were used to match 1,260 pairs of participants with and without ISH. Matched Cox regression models were used to estimate association of ISH with incident HF during a mean follow-up of 8.7 years. Matched participants (n=2,520) had a mean (±SD) age of 74 (±6) years, 60% were women, 16% were nonwhites, 18% developed new-onset HF, and 35% died. Incident HF developed in 20% (rate, 242/10,000 person-years) and 16% (rate, 194/10,000 person-years) of participants with and without ISH respectively (matched hazard ratio {HR} when ISH was compared with no-ISH, 1.26; 95% confidence interval {CI}, 1.04–1.51; P=0.016). Pre-match unadjusted, multivariable-adjusted and propensity-adjusted HRs (95% CI) for ISH-associated incident HF were respectively 1.72 (1.51–1.97; P<0.0001), 1.35 (1.18–1.56; P<0.0001) and 1.22 (1.04–1.44; P=0.016). ISH had no association with all-cause mortality (matched HR, 1.03; 95% CI, 0.88–1.19; P=0.732). In conclusion, in a propensity-matched cohort of community-dwelling older adults who were well-balanced in 64 baseline covariates, ISH was associated with increased risk of incident HF but had no association with all-cause mortality.
doi:10.1161/HYPERTENSIONAHA.108.119792
PMCID: PMC2887759  PMID: 19188527
Heart failure; isolated systolic hypertension; mortality; coronary artery disease; cerebrovascular disease; propensity score
23.  Effects of Diabetes Mellitus in Patients with Heart Failure and Chronic Kidney Disease: A Propensity-Matched Study of Multimorbidity in Chronic Heart Failure 
International journal of cardiology  2009;134(3):330-335.
Background
Chronic kidney disease (CKD) and diabetes mellitus (DM) are common comorbidities in heart failure (HF) and each is associated with poor outcomes. However, the effects of multimorbidity related to having both CKD and DM compared to CKD alone have not been well studied in a propensity-matched population of chronic HF patients.
Methods
Of the 7788 ambulatory chronic HF patients in the Digitalis Investigation Group trial, 3527 had CKD, of whom 1095 had DM. Based on the absence or presence of DM, patients were categorized into CKD-only and CKD-DM. Propensity scores for CKD-DM were calculated for each patient and were used to match 987 pairs of CKD-only and CKD-DM patients. Hazard ratios (HR) and 95% confidence intervals (CI) comparing CKD-DM patients with CKD-only patients were estimated using matched Cox regression models.
Results
All-cause mortality occurred in 47.0% (rate, 1783/10000 person-years) of CKD-DM patients and 39.6% (rate, 1414/10000 person-years of follow-up) of CKD-only patients (HR when CKD-DM is compared with CKD-only, 1.25; 95% CI, 1.07–1.46; p=0.006). All-cause hospitalization occurred in 75.4% (rate, 5710/10000 person-years) and 67.8% (rate, 4213/10000 person-years) of CKD-DM and CKD-only patients respectively (HR, 1.32; 95% CI, 1.15–1.52; p<0.0001). Respective HR and 95% CI for other outcomes were: cardiovascular mortality (1.27; 1.06–1.52; p=0.009), HF mortality (1.34; 1.04–1.72; p=0.025); cardiovascular hospitalization (1.29; 1.12–1.49; p=0.001) and HF hospitalization (1.37; 1.16–1.63; p<0.0001).
Conclusions
Compared with comorbidity due to CKD alone, multimorbidity with CKD and DM was associated with poor outcomes in chronic HF patients.
doi:10.1016/j.ijcard.2008.12.089
PMCID: PMC2720313  PMID: 19178965
heart failure; chronic kidney disease; diabetes mellitus; mortality
24.  Multimorbidity due to Diabetes Mellitus and Chronic Kidney Disease and Outcomes in Chronic Heart Failure 
Diabetes mellitus (DM) and chronic kidney disease (CKD) are common in patients with chronic heart failure (HF) and are associated with poor outcomes. However, the impact of multimorbidity due to DM and CKD on outcomes, relative to comorbidity due to DM alone, has not been well studied in these patients. Of the 7788 patients with chronic HF in the Digitalis Investigation Group trial, 2218 had DM. We categorized these patients into those with DM alone (DM-only; n=1123) and those with both DM and CKD (DM-CKD; n=1095). Propensity scores for DM-CKD, calculated for each of the 2218 patients, were used to match 699 pairs of DM-only and DM-CKD patients. Matched Cox regression models were used to estimate associations between DM-CKD and outcomes. All-cause mortality occurred in 44% (rate, 1648/10000 person-years) of DM-CKD patients and 39% (rate, 1349/10000 person-years of follow-up) of DM-only patients (hazard ratio when DM-CKD was compared with DM-only, 1.34; 95% confidence interval {CI}, 1.11–1.62; p=0.003). All-cause hospitalization occurred in 76% (rate, 5799/10000 person-years) and 73% (rate, 4909/10000 person-years) of DM-CKD and DM-only patients respectively (hazard ratio, 1.16; 95% CI, 0.99–1.36; p=064). Respective hazard ratios (95% CI) for other outcomes were: cardiovascular mortality (1.33; 1.07–1.66; p=0.010), HF mortality (1.41; 1.02–1.96; p=0.040), cardiovascular hospitalization (1.17; 0.99–1.39; p=0.064) and HF hospitalization (1.26; 1.03–1.55; p=0.026). In conclusion, compared to comorbidity due to DM alone, the presence of multimorbidity due to DM and CKD was associated with increased mortality and morbidity in patients with chronic HF.
doi:10.1016/j.amjcard.2008.08.035
PMCID: PMC2659144  PMID: 19101236
heart failure; multimorbidity; diabetes; chronic kidney disease; outcomes

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