C. Barrett Bowling

Hypokalemia and Outcomes in Patients with Chronic Heart Failure and Chronic Kidney Disease: Findings from Propensity-Matched Studies

Background—Little is known about the effects of hypokalemia on outcomes in patients with chronic heart failure (HF) and chronic kidney disease. Methods and Results—Of the 7788 patients with chronic HF in the Digitalis Investigation Group trial, 2793 had chronic kidney disease, defined as estimated glomerular filtration rate <60 mL/min per 1.73 m2. Of these, 527 had hypokalemia (serum potassium <4 mEq/L; mild) and 2266 had normokalemia (4 to 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 when hypokalemia was compared with normokalemia, 1.56; 95% CI, 1.25 to 1.95; P<0.0001). Matched hazard ratios (95% CIs) for cardiovascular and HF mortalities and all-cause, cardiovascular, and HF hospitalizations were 1.65 (1.29 to 2.11; P<0.0001), 1.82 (1.28 to 2.57; P<0.0001), 1.16 (1.00 to 1.35; P=0.036), 1.27 (1.08 to 1.50; P=0.004), and 1.29 (1.05 to 1.58; P=0.014), respectively. Among 453 pairs of balanced patients with HF and chronic kidney disease, all-cause mortality occurred in 47% and 38% of patients with mild hypokalemia (3.5 to 3.9 mEq/L) and normokalemia, respectively (matched hazard ratio, 1.31; 95% CI, 1.03 to 1.66; P=0.027). Among 169 pairs of balanced patients with estimated glomerular filtration rate <45 mL/min per 1.73 m2, all-cause mortality occurred in 57% and 47% of patients with hypokalemia (<4 mEq/L; mild) and normokalemia, respectively (matched hazard ratio, 1.53; 95% CI, 1.07 to 2.19; P=0.020). Conclusions—In patients with HF and chronic kidney disease, hypokalemia (serum potassium <4 mEq/L) is common and associated with increased mortality and hospitalization.

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 pathophysiologic processes. Treatment plans target underlying disease mechanisms with the goal of improving disease-related outcomes. Because average glomerular filtrate rates 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 comorbid conditions 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 about the safety and efficacy of recommended interventions often is 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 generally is used to shape rather than dictate treatment decisions. We 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.

Hypokalemia and Outcomes in Patients With Chronic Heart Failure and Chronic Kidney DiseaseCLINICAL PERSPECTIVE

Background—Little is known about the effects of hypokalemia on outcomes in patients with chronic heart failure (HF) and chronic kidney disease. Methods and Results—Of the 7788 patients with chronic HF in the Digitalis Investigation Group trial, 2793 had chronic kidney disease, defined as estimated glomerular filtration rate <60 mL/min per 1.73 m2. Of these, 527 had hypokalemia (serum potassium <4 mEq/L; mild) and 2266 had normokalemia (4 to 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 when hypokalemia was compared with normokalemia, 1.56; 95% CI, 1.25 to 1.95; P<0.0001). Matched hazard ratios (95% CIs) for cardiovascular and HF mortalities and all-cause, cardiovascular, and HF hospitalizations were 1.65 (1.29 to 2.11; P<0.0001), 1.82 (1.28 to 2.57; P<0.0001), 1.16 (1.00 to 1.35; P=0.036), 1.27 (1.08 to 1.50; P=0.004), and 1.29 (1.05 to 1.58; P=0.014), respectively. Among 453 pairs of balanced patients with HF and chronic kidney disease, all-cause mortality occurred in 47% and 38% of patients with mild hypokalemia (3.5 to 3.9 mEq/L) and normokalemia, respectively (matched hazard ratio, 1.31; 95% CI, 1.03 to 1.66; P=0.027). Among 169 pairs of balanced patients with estimated glomerular filtration rate <45 mL/min per 1.73 m2, all-cause mortality occurred in 57% and 47% of patients with hypokalemia (<4 mEq/L; mild) and normokalemia, respectively (matched hazard ratio, 1.53; 95% CI, 1.07 to 2.19; P=0.020). Conclusions—In patients with HF and chronic kidney disease, hypokalemia (serum potassium <4 mEq/L) is common and associated with increased mortality and hospitalization.

Trends in hypertension prevalence, awareness, treatment, and control among US adults 80 years and older, 1988-2010.

The authors examined trends in systolic blood pressure (SBP) and diastolic blood pressure (DBP) and the prevalence, awareness, treatment, and control of hypertension in 1988–1994 (n=1164), 1999–2004 (n=1,026), and 2005–2010 (n=1048) among US adults 80 years and older in serial National Health and Nutrition Examination Surveys. Hypertension was defined as SBP ≥140 mm Hg, DBP ≥90 mm Hg, or use of antihypertensive medication. Awareness and treatment were defined by self‐report and control as SBP/DBP<140/90 mm Hg. Mean SBP decreased from 147.3 mm Hg to 140.1 mm Hg and mean DBP from 70.2 mm Hg to 59.4 mm Hg between 1988–1994 and 2005–2010. The prevalence, awareness, and treatment of hypertension each increased over time. Controlled hypertension increased from 30.4% in 1988–1994 to 53.1% in 2005–2010. The proportion of patients taking 3 classes of antihypertensive medication increased from 7.0% to 30.9% between 1988–1994 and 2005–2010. Increases in awareness, treatment, and control of hypertension and antihypertensive polypharmacy have been observed among very old US adults.

Impact of Chronic Kidney Disease on Activities of Daily Living in Community-Dwelling Older Adults

BACKGROUND 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. METHODS 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 m(2) 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. RESULTS 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 ratios (95% CIs) 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 m(2)) 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. CONCLUSION In community-dwelling older adults, CKD is associated with IADL and BADL decline.

Community Mobility Among Older Adults With Reduced Kidney Function: A Study of Life-Space

BACKGROUND Life-Space Assessment captures community mobility and social participation and quantifies the distance, frequency, and independence obtained as an older adult moves through his or her environment. Reduced estimated glomerular filtration rate (eGFR) is associated with decline in activities of daily living among older adults, but less is known about the association of eGFR with restrictions in mobility. STUDY DESIGN Prospective observational cohort study. SETTING & PARTICIPANTS Community-dwelling Medicare beneficiaries from the University of Alabama at Birmingham Study of Aging who had serum creatinine measured during a baseline in-home study visit and completed at least one telephone follow-up (N = 390). PREDICTOR eGFR ≥ 60, 45-59, and <45 mL/min/1.73 m(2). OUTCOME Life-space mobility trajectory. MEASUREMENTS Life-space mobility was evaluated by telephone every 6 months for up to 4.5 years using the previously validated Life-Space Assessment. Scores using this tool range from 0-120 (higher scores indicate greater mobility). RESULTS Mean age of the 390 participants was 77.6 ± 5.8 (SD) years, 41% were African American, 50.5% were women; 30.0% had eGFR of 45-59 mL/min/1.73 m(2), and 20.2% had eGFR < 45 mL/min/1.73 m(2). Age-, race-, and sex-adjusted mean baseline life-space mobility scores were 64.8(95% CI, 62.0-67.6), 63.8 (95% CI, 60.3-67.4), and 58.3 (95% CI, 53.8-62.7) among those with eGFR categories ≥ 60, 45-59, and <45 mL/min/1.73 m(2), respectively. Compared with those with eGFRs ≥ 60 mL/min/1.73 m(2), a more rapid decline in life-space mobility was found among those with eGFRs < 45 mL/min/1.73 m(2), though this did not reach statistical significance (P=0.06); a similar effect was not seen among those with eGFRs of 45-59 mL/min/1.73 m(2) (P=0.3). LIMITATIONS Urinary albumin or longitudinal measures of eGFR were not available. CONCLUSIONS eGFR < 45 mL/min/1.73 m(2) was associated with a trend toward a more rapid decline in life-space mobility among community-dwelling older adults. Findings should be confirmed in a larger population.

Effects of enalapril in systolic heart failure patients with and without chronic kidney disease: insights from the SOLVD Treatment trial.

BACKGROUND 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). METHODS 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 ≤ 2.5mg/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 m(2)). RESULTS 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 mm Hg, both) and serum potassium (mean increase, 0. /L, both). CONCLUSIONS Enalapril reduces mortality and hospitalization in SHF patients without significant heterogeneity between those with and without CKD.

Incident ESRD and Treatment-Resistant Hypertension: The Reasons for Geographic and Racial Differences in Stroke (REGARDS) Study

BACKGROUND Studies suggest that treatment-resistant hypertension is common and increasing in prevalence among US adults. Although hypertension is a risk factor for end-stage renal disease (ESRD), few data are available for the association between treatment-resistant hypertension and ESRD risk. STUDY DESIGN Prospective cohort study. SETTING & PARTICIPANTS We analyzed data from 9,974 REGARDS (Reasons for Geographic and Racial Differences in Stroke) Study participants treated for hypertension without ESRD at baseline. PREDICTOR Treatment-resistant hypertension was defined as uncontrolled blood pressure (BP) with concurrent use of 3 antihypertensive medication classes including a diuretic or use of 4 or more antihypertensive medication classes including a diuretic regardless of BP. OUTCOME Incident ESRD was identified by linkage of REGARDS Study participants with the US Renal Data System. MEASUREMENTS During a baseline in-home study visit, BP was measured twice and classes of antihypertensive medication being taken were determined by pill bottle inspection. RESULTS During a median follow-up of 6.4 years, there were 152 incident cases of ESRD (110 ESRD cases among 2,147 with treatment-resistant hypertension and 42 ESRD cases among 7,827 without treatment-resistant hypertension). The incidence of ESRD per 1,000 person-years for hypertensive participants with and without treatment-resistant hypertension was 8.86 (95% CI, 7.35-10.68) and 0.88 (95% CI, 0.65-1.19), respectively. After multivariable adjustment, the HR for ESRD comparing hypertensive participants with versus without treatment-resistant hypertension was 6.32 (95% CI, 4.30-9.30). Of participants who developed incident ESRD during follow-up, 72% had treatment-resistant hypertension at baseline. LIMITATIONS BP, estimated glomerular filtration rate, and albuminuria assessed at a single time. CONCLUSIONS Individuals with treatment-resistant hypertension are at increased risk for ESRD. Appropriate clinical management strategies are needed to treat treatment-resistant hypertension in order to preserve kidney function in this high-risk group.

Impairment of activities of daily living and incident heart failure in community‐dwelling older adults

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.

Short-Term Risk of Serious Fall Injuries in Older Adults Initiating and Intensifying Treatment With Antihypertensive Medication

Background—Antihypertensive medication use has been associated with an increased risk of falls in some but not all studies. Few data are available on the short-term risk of falls after antihypertensive medication initiation and intensification. Methods and Results—We examined the association between initiating and intensifying antihypertensive medication and serious fall injuries in a case-crossover study of 90 127 Medicare beneficiaries who were ≥65 years old and had a serious fall injury between July 1, 2007, and December 31, 2012, based on emergency department and inpatient claims. Antihypertensive medication initiation was defined by a prescription fill with no fills in the previous year. Intensification was defined by the addition of a new antihypertensive class, and separately, titration by the addition of a new class or increase in dosage of a current class. Exposures were ascertained for the 15 days before the fall (case period) and six 15-day earlier periods (control periods). Overall, 272, 1508, and 3113 Medicare beneficiaries initiated, added a new class of antihypertensive medication or titrated therapy within 15 days of their serious fall injury. The odds for a serious fall injury was increased during the 15 days after antihypertensive medication initiation (odds ratio, 1.36 [95% confidence interval, 1.19–1.55]), adding a new class (odds ratio, 1.16 [95% confidence interval, 1.10–1.23]), and titration [odds ratio, 1.13 [95% confidence interval, 1.08–1.18]). These associations were attenuated beyond 15 days. Conclusions—Antihypertensive medication initiation and intensification was associated with a short-term, but not long-term, increased risk of serious fall injuries among older adults.