O. James Ekundayo

A propensity-matched study of the association of peripheral arterial disease with cardiovascular outcomes in community-dwelling older adults.

The association between peripheral arterial disease (PAD) and outcomes has not been studied in a propensity-matched population of community-dwelling older adults. A public-use copy of the Cardiovascular Health Study (CHS) data was analyzed to test the hypothesis that baseline PAD is associated with increased all-cause mortality and cardiovascular morbidity. Of the 5,795 CHS participants, 5,630 had data on baseline ankle-brachial index, and 767 had PAD, defined as ankle-brachial index <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 period of 7.5 years. Overall, 55% of matched participants died from all causes during 9,958 patient-years of follow-up. All-cause mortality occurred in 61% (rate 8,710/100,000 patient-years) and 50% (rate 6,503/100,000 patient-years) of participants, respectively, with and without PAD (matched hazard ratio for PAD vs no PAD 1.47, 95% confidence interval (CI) 1.23 to 1.76, p <0.0001). Prematch unadjusted, multivariable-adjusted, and propensity-adjusted hazard ratios for PAD-associated all-cause mortality were 2.90 (95% CI 2.61 to 3.21, p <0.0001), 1.53 (95% CI 1.36 to 1.71, p <0.0001), and 1.57 (95% CI 1.39 to 1.78, p <0.0001), respectively. Matched hazard ratios for PAD for incident heart failure and symptomatic PAD were 1.32 (95% CI 1.00 to 1.73, p = 0.052) and 3.92 (95% CI 2.13 to 7.21, p <0.0001), respectively. 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.

Association between hyperuricemia and incident heart failure among older adults: A propensity-matched study

BACKGROUND The association between hyperuricemia and incident heart failure (HF) is relatively unknown. METHODS Of the 5461 community-dwelling older adults, >or=65 years, in the Cardiovascular Health Study without HF at baseline, 1505 had hyperuricemia (baseline serum uric acid >or=6 mg/dL for women and >or=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.

Isolated Systolic Hypertension and Incident Heart Failure in Older Adults A Propensity-Matched Study

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 5795 participants in the public-use copy of the Cardiovascular Health Study data set, 5248 had diastolic blood pressure <90 mm Hg and were free of HF at baseline. Of these, 2000 (38%) had 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 1260 pairs of participants with and without ISH. Matched Cox regression models were used to estimate the association of ISH with incident HF during a mean follow-up of 8.7 years. Matched participants (n=2520) 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 when ISH was compared with no ISH: 1.26; 95% CI: 1.04 to 1.51; P=0.016). Prematch unadjusted, multivariable-adjusted, and propensity-adjusted hazard ratios (95% CIs) for ISH-associated incident HF were, respectively, 1.72 (1.51 to 1.97; P<0.0001), 1.35 (1.18 to 1.56; P<0.0001), and 1.22 (1.04 to 1.44; P=0.016). ISH had no association with all-cause mortality (matched hazard ratio: 1.03; 95% CI: 0.88 to 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.

A history of atrial fibrillation and outcomes in chronic advanced systolic heart failure: A propensity-matched study

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.

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

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

Association of diuretic use and overactive bladder syndrome in older adults: a propensity score analysis

Diuretic 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 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 analysis of variance (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.

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 co-morbidity due to DM alone, has not been well studied in these patients. Of the 7,788 patients with chronic HF in the Digitalis Investigation Group trial, 2,218 had DM. We categorized these patients into those with DM alone (DM-only n = 1,123) and those with both DM and CKD (DM-CKD n = 1,095). Propensity scores for DM-CKD, calculated for each of the 2,218 patients, were used to match 699 pairs of patients with DM-only or DM-CKD. Matched Cox regression models were used to estimate associations between DM-CKD and outcomes. All-cause mortality occurred in 44% (rate 1,648/10,000 person-years) of patients with DM-CKD and 39% (rate 1,349/10,000 person-years of follow-up) of patients with DM-only (hazard ratio when DM-CKD was compared with DM-only 1.34, 95% confidence interval [CI] 1.11 to 1.62, p = 0.003). All-cause hospitalization occurred in 76% (rate 5,799/10,000 person-years) and 73% (rate 4,909/10,000 person-years) of patients with DM-CKD and DM-only, respectively (hazard ratio 1.16, 95% CI 0.99 to 1.36, p = 0.064). Respective hazard ratios for other outcomes were cardiovascular mortality 1.33 (95% CI 1.07 to 1.66, p = 0.010), HF mortality 1.41 (95% CI 1.02 to 1.96, p = 0.040), cardiovascular hospitalization 1.17 (95% CI 0.99 to 1.39, p = 0.064), and HF hospitalization 1.26 (95% CI 1.03 to 1.55, p = 0.026). In conclusion, compared with co-morbidity 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.

Isolated Diastolic Hypotension and Incident Heart Failure in Older Adults

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

Uncontrolled hypertension and increased risk for incident heart failure in older adults with hypertension: findings from a propensity-matched prospective population study.

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. Of the 5795 Cardiovascular Health Study participants, > or =65 years, 2562 with self-reported physician-diagnosed hypertension had no baseline HF. Of these, 1391 had uncontrolled hypertension, defined as systolic BP (SBP) > or =140 (n = 1373) or diastolic BP > or =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. 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 controlled hypertension, 1.39; 95% confidence interval [CI], 1.12 to 1.73; P = .003). HRs (95% CI) for incident HF for those with (n = 503) and without (n = 1539) chronic kidney disease (CKD) were 1.73 (95% CI, 1.26 to 2.38; P = .001) and 1.08 (95% CI, 0.87 to 1.34; P = .486) respectively (P for interaction, .012). Compared with participants with controlled hypertension, HRs for incident HF associated with SBP 140 to 159 and > or =160 mm Hg were 1.06 (95% CI, 0.86 to 1.31; P = .572) and 1.58 (95% CI, 1.27 to 1.96; P < .0001), respectively. In community-dwelling older adults with hypertension, those with uncontrolled (versus controlled) BP have increased risk of new-onset HF, which is more pronounced in those with SBP > or =160 mm Hg and with CKD.

Oral Potassium Supplement Use and Outcomes in Chronic Heart Failure: A Propensity-Matched Study

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, 1327/10,000 person-years) and 802 (rate, 1313/10,000 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). HRs (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.