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1.  Low Hemoglobin and Recurrent Falls in U.S. Men and Women: Prospective findings from the REasons for Geographic and Racial Differences in Stroke (REGARDS) Cohort 
There are few data available on low hemoglobin levels and incident falls in the general U.S. population.
Of 30,239 Black and white U.S. adults ≥ 45 years old in the population-based REasons for Geographic and Racial Differences in Stroke (REGARDS) study, 16,782 had hemoglobin measured at baseline and follow-up data on falls. Hemoglobin was categorized by 1.0 g/dL increments relative to the World Health Organization cut-point for anemia (13.0 g/dL for men, 12.0 g/dL for women). Recurrent falls, defined as ≥2 falls in the 6 months following baseline were assessed during a telephone interview.
Recurrent falls occurred in 3.9% of men and 4.8% of women. Compared to those with a hemoglobin 1 to 2 g/dL above the anemia cut-point the multivariable adjusted odds ratios (OR; 95% confidence interval [CI]) for recurrent falls associated with hemoglobin levels ≥ 3g/dL, 2 to <3 g/dL, and 0 to 1 g/dL above the cut-point, and 0 to <1 g/dL and ≥1 g/dL below the cut-point were 0.73 (0.45–1.19), 0.84 (0.57–1.24), 1.29 (0.88–1.90), 1.32 (0.0.80–1.2.18) and 2.12 (1.23–3.63), respectively, among men (linear trend p<0.001) and 1.59 (1.10–2.3), 1.24 (0.95–1.62), 1.42(1.11–1.81), 1.28 (0.91–1.80) and 1.76 (1.13–2.74), respectively, among women (linear trend p=0.45; quadratic trend p=0.016).
Among men, lower hemoglobin was associated with an increased risk for recurrent falls. While our findings suggest an increased risk for recurrent falls at both lower and higher hemoglobin levels among women, these findings should be confirmed in subsequent studies.
PMCID: PMC3640699  PMID: 23328832
falls; hemoglobin; gender
2.  Nondisease-Specific Problems and All-Cause Mortality in the REasons for Geographic and Racial Differences in Stroke (REGARDS) Study 
Problems that cross multiple domains of health are frequently assessed in older adults. We evaluated the association between six of these nondisease-specific problems and mortality among middle-aged and older adults.
Prospective, observational cohort
U.S. population sample
Participants included 23,669 black and white US adults ≥ 45 years of age enrolled in the REasons for Geographic and Racial Differences in Stroke (REGARDS) study.
Nondisease-specific problems included cognitive impairment, depressive symptoms, falls, polypharmacy, impaired mobility and exhaustion. Age-stratified (<65, 65-74, and ≥ 75 years) hazard ratios for all-cause mortality were calculated for each problem individually and by number of problems.
Among participants < 65, 65-74, ≥ 75 years old, one or more nondisease-specific problems occurred in 40%, 45% and 55% of participants, respectively. Compared to those with none of these problems the multivariable adjusted hazard ratios and 95% confidence intervals for all-cause mortality associated with each additional nondisease-specific problem was 1.34 (1.23–1.46), 1.24 (1.15–1.35) and 1.30 (1.21–1.39), among participants < 65, 65 – 74 years, ≥ 75 years of age, respectively.
Nondisease-specific problems were associated with mortality across a wide age spectrum. Future studies should determine if treating these problems will improve survival and identify innovative healthcare models to address multiple nondisease-specific problems simultaneously.
PMCID: PMC3656135  PMID: 23617688
nondisease-specific problems; geriatrics; mortality
3.  Correlates of ADL difficulty in a large hemodialysis cohort 
Needing assistance with activities of daily living (ADL) is an early indicator of functional decline and has important implications for individuals’ quality of life. However, correlates of need for ADL assistance have received limited attention among patients undergoing maintenance hemodialysis (HD). A multi-center cohort of 742 prevalent HD patients was assessed 2009–2011 and classified as frail, pre-frail and non-frail by the Fried frailty index (recent unintentional weight loss, reported exhaustion, low grip strength, slow walk speed, low physical activity). Patients reported need for assistance with four ADL tasks and identified contributing symptoms/conditions (pain, balance, endurance, weakness, other). Nearly one in five patients needed assistance with one or more ADL. Multivariable analysis showed increased odds for needing ADL assistance among frail (odds ratio [OR], 11.35; 95% CI, 5.50–23.41; P < 0.001) and pre-frail (OR, 1.93; (95% CI, 1.01–3.68; P = 0.046) compared with non-frail patients. In addition, the odds for needing ADL assistance were lower among blacks compared with whites and were higher among patients with diabetes, lung disease, and stroke. Balance, weakness, and “other” (frequently dialysis-related) symptoms/conditions were the most frequently named reasons for ADL difficulty. In addition to interventions such as increasing physical activity that might delay or reverse the process of frailty, the immediate symptoms/conditions to which individuals attribute their ADL difficulty may have clinical relevance for developing targeted management and/or treatment approaches.
PMCID: PMC3887518  PMID: 24118865
Activities of daily living; frailty; hemodialysis; symptoms/conditions
4.  Effects of enalapril in systolic heart failure patients with and without chronic kidney disease: Insights from the SOLVD Treatment trial 
International journal of cardiology  2012;167(1):151-156.
Angiotensin-converting enzyme inhibitors improve outcomes in systolic heart failure (SHF). However, doubts linger about their effect in SHF patients with chronic kidney disease (CKD).
In the Studies of Left Ventricular Dysfunction (SOLVD) Treatment trial, 2569 ambulatory chronic HF patients with left ventricular ejection fraction ≤35% and serum creatinine level ≤2.5 mg/dL were randomized to receive either placebo (n=1284) or enalapril (n=1285). Of the 2502 patients with baseline serum creatinine data, 1036 had CKD (estimated glomerular filtration rate <60 ml/min/1.73 m2).
Overall, during 35 months of median follow-up, all-cause mortality occurred in 40% (502/1252) and 35% (440/1250) of placebo and enalapril patients, respectively (hazard ratio {HR}, 0.84; 95% confidence interval {CI}, 0.74–0.95; p=0.007). All-cause mortality occurred in 45% and 42% of patients with CKD (HR, 0.88; 95% CI, 0.73–1.06; p=0.164), and 36% and 31% of non-CKD patients (HR, 0.82; 95% CI, 0.69–0.98; p=0.028) in the placebo and enalapril groups, respectively (p for interaction=0.615). Enalapril reduced cardiovascular hospitalization in those with CKD (HR, 0.77; 95% CI, 0.66–0.90; p<0.001) and without CKD (HR, 0.80; 95% CI, 0.70–0.91; p<0.001). Among patients in the enalapril group, serum creatinine elevation was significantly higher in those without CKD (0.09 versus 0.04 mg/dL in CKD; p=0.003) during first year of follow-up, but there was no differences in changes in systolic blood pressure (mean drop, 7 mmHg, both) and serum potassium (mean increase, 0.2 mEq/L, both).
Enalapril reduces mortality and hospitalization in SHF patients without significant heterogeneity between those with and without CKD.
PMCID: PMC3395757  PMID: 22257685
enalapril; heart failure; chronic kidney disease
5.  Impact of Chronic Kidney Disease on Activities of Daily Living in Community-Dwelling Older Adults 
Although chronic kidney disease (CKD) is associated with poor physical function, less is known about the longitudinal association between CKD and the decline of instrumental activities of daily living (IADL) and basic activities of daily living (BADL) among community-dwelling older adults.
Participants were part of the prospective observational University of Alabama at Birmingham Study of Aging (n = 357). CKD was defined as an estimated glomerular filtration rate less than 60 mL/min/1.73 m2 using the Modification of Diet in Renal Disease equation. Primary outcomes were IADL and BADL decline defined as an increase in the number of activities for which participants reported difficulty after 2 years. Forward stepwise logistic regression was used to determine associations of baseline CKD and functional decline.
Participants had a mean age of 77.4 (SD = 5.8) years, 41% were African American, and 52% women. IADL decline occurred in 35% of those with CKD and 17% of those without (unadjusted odds ratio, 2.62, 95% confidence intervals [95% CI], 1.59–4.30, p < .001). BADL decline occurred in 20% and 7% of those with and without CKD, respectively (unadjusted odds ratio, 3.37; 95% CI, 1.73–6.57; p < .001). Multivariable-adjusted odds ratio's (95% CI’s) for CKD-associated IADL and BADL decline were 1.83 (1.06–3.17, p =.030) and 2.46 (1.19–5.12, p = .016), respectively. CKD Stage ≥3B (estimated glomerular filtration rate <45 mL/min/1.73 m2) was associated with higher multivariable-adjusted odds of both IADL (3.12, 95% CI, 1.38–7.06, p = .006) and BADL (3.78, 95% CI, 1.36–9.77, p = .006) decline.
In community-dwelling older adults, CKD is associated with IADL and BADL decline.
PMCID: PMC3110910  PMID: 21459762
Activities of daily living; Chronic kidney disease; Functional decline
6.  Geographic Variation in CKD Prevalence and ESRD Incidence in the United States: Results From the Reasons for Geographic and Racial Differences in Stroke (REGARDS) Study 
It is not known whether geographic differences in the prevalence of chronic kidney disease (CKD) exist and are associated with end-stage renal disease (ESRD) incidence rates across the US.
Study Design
Cross-sectional and ecologic.
Setting & Participants
White (n=16,410) and black (n=11,109) participants from across the continental US in the population-based Reasons for Geographic and Racial Differences in Stroke (REGARDS) study.
Geographic region, defined by the 18 Networks of the US ESRD Network Program.
Outcomes & Measurements
Albuminuria, defined as an albumin-creatinine ratio ≥30 mg/g and reduced estimated glomerular filtration rate (eGFR), defined as levels <60 ml/min/1.73m2, were measured in the REGARDS study. ESRD incidence rates were obtained from the US Renal Data System.
For whites, the Network-specific prevalence of albuminuria ranged from 8.4% (95% CI, 3.3%–13.5%) in Network 15 to 14.8% (95% CI, 8.0%–21.6%) in Network 3, and reduced eGFR ranged from 4.3% (95% CI, 2.0%–6.6%) in Network 4 to 16.7% (95% CI, 12.7%–20.7%) in Network 7. For blacks, the prevalence of albuminuria ranged from 12.1% (95% CI, 8.7%–15.5%) in Network 5 to 26.5% (95% CI, 16.7%–36.3%) in Network 4, and reduced eGFR ranged from 6.7% (95% CI, 5.0%–8.4%) in Network 17/18 to 13.4% (95% CI, 7.8%–19.1%) in Network 12. The Spearman correlation coefficients for the prevalence of albuminuria and reduced eGFR with Network-specific ESRD incidence rates were 0.49 and 0.24, respectively, for whites and 0.29 and 0.25, respectively, for blacks.
There were few cases of albuminuria and reduced eGFR in some geographic regions.
In the US, substantial geographic variations in the prevalence of albuminuria and reduced eGFR exist but were only modestly correlated with ESRD incidence, suggesting the CKD burden may not explain the geographic variation in ESRD incidence.
PMCID: PMC3659181  PMID: 23228944
7.  Impairment of activities of daily living and incident heart failure in community-dwelling older adults 
European Journal of Heart Failure  2012;14(6):581-587.
Instrumental activities of daily living (IADLs) are tasks that are necessary for independent community living. These tasks often require intact physical and cognitive function, the impairment of which may adversely affect health in older adults. In the current study, we examined the association between IADL impairment and incident heart failure (HF) in community-dwelling older adults.
Methods and results
Of the 5795 community-dwelling adults, aged ≥65 years, in the Cardiovascular Health Study, 5511 had data on baseline IADL and were free of prevalent HF. Of these, 1333 (24%) had baseline IADL impairment, defined as self-reported difficulty with one or more of the following tasks: using the telephone, preparing food, performing light and heavy housework, managing finances, and shopping. Propensity scores for IADL impairment, estimated for each of the 5511 participants, were used to assemble a cohort of 1038 pairs of participants with and without IADL impairment who were balanced on 42 baseline characteristics. Centrally adjudicated incident HF occurred in 26% and 21% of matched participants with and without IADL impairment, respectively, during >12 years of follow-up [matched hazard ratio (HR) 1.33; 95% confidence interval (CI) 1.11–1.59; P = 0.002]. Unadjusted and multivariable-adjusted HRs for incident HF before matching were 1.77 (95% CI 1.56–2.01; P < 0.001) and 1.33 (95% CI 1.15–1.54; P < 0.001), respectively. IADL impairment was also associated with all-cause mortality (matched HR 1.19; 95% CI 1.06–1.34; P = 0.004).
Among community-dwelling older adults free of baseline HF, IADL impairment is a strong and independent predictor of incident HF and mortality.
PMCID: PMC3359859  PMID: 22492539
Instrumental activities of daily living; Incident heart failure; Propensity score
8.  Managing Older Adults With CKD: Individualized Versus Disease-Based Approaches 
The last decade has seen the evolution and ongoing refinement of a disease-oriented approach to chronic kidney disease (CKD). Disease-oriented models of care assume a direct causal association between observed signs and symptoms and underlying disease pathophysiology. Treatment plans target underlying disease mechanisms with the goal of improving disease-related outcomes. Because average levels of glomerular filtrate rate (GFR) tend to decrease with age, CKD becomes increasingly prevalent with advancing age, and those who meet criteria for CKD are disproportionately elderly. However, several features of geriatric populations may limit the utility of disease-oriented models of care. In older adults, complex comorbidity and geriatric syndromes are common, signs and symptoms often do not reflect a single underlying pathophysiologic process, there can be substantial heterogeneity in life expectancy, functional status and health priorities, and information on the safety and efficacy of interventions is often lacking. For all these reasons, geriatricians have tended to favor an individualized patient-centered model of care over more traditional disease-based approaches. An individualized approach prioritizes patient preferences and embraces the notion that observed signs and symptoms often do not reflect a single unifying disease process, and instead reflect the complex interplay between many different factors. This approach emphasizes modifiable outcomes that matter to the patient. Prognostic information related to these and other outcomes is generally used to shape rather than dictate treatment decisions. We herein argue that an individualized patient-centered approach to care may have more to offer than a traditional disease-based approach to CKD in many older adults.
PMCID: PMC3261354  PMID: 22189037
elderly; disease-oriented; individualized; patient-centered; kidney disease
9.  Relationship between Stage of Kidney Disease and Incident Heart Failure in Older Adults 
American Journal of Nephrology  2011;34(2):135-141.
The relationship between stage of chronic kidney disease (CKD) and incident heart failure (HF) remains unclear.
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.
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).
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.
PMCID: PMC3136373  PMID: 21734366
Chronic kidney disease; Heart failure
10.  Hypokalemia and Outcomes in Patients with Chronic Heart Failure and Chronic Kidney Disease: Findings from Propensity-Matched Studies 
Circulation. Heart failure  2010;3(2):253-260.
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).
In patients with HF and CKD, hypokalemia is common and associated with increased mortality and hospitalization.
PMCID: PMC2909749  PMID: 20103777

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