Ruth C. Campbell

Intensive vs Standard Blood Pressure Control and Cardiovascular Disease Outcomes in Adults Aged ≥75 Years: A Randomized Clinical Trial

IMPORTANCE The appropriate treatment target for systolic blood pressure (SBP) in older patients with hypertension remains uncertain. OBJECTIVE To evaluate the effects of intensive (<120 mm Hg) compared with standard (<140 mm Hg) SBP targets in persons aged 75 years or older with hypertension but without diabetes. DESIGN, SETTING, AND PARTICIPANTS A multicenter, randomized clinical trial of patients aged 75 years or older who participated in the Systolic Blood Pressure Intervention Trial (SPRINT). Recruitment began on October 20, 2010, and follow-up ended on August 20, 2015. INTERVENTIONS Participants were randomized to an SBP target of less than 120 mm Hg (intensive treatment group, n = 1317) or an SBP target of less than 140 mm Hg (standard treatment group, n = 1319). MAIN OUTCOMES AND MEASURES The primary cardiovascular disease outcome was a composite of nonfatal myocardial infarction, acute coronary syndrome not resulting in a myocardial infarction, nonfatal stroke, nonfatal acute decompensated heart failure, and death from cardiovascular causes. All-cause mortality was a secondary outcome. RESULTS Among 2636 participants (mean age, 79.9 years; 37.9% women), 2510 (95.2%) provided complete follow-up data. At a median follow-up of 3.14 years, there was a significantly lower rate of the primary composite outcome (102 events in the intensive treatment group vs 148 events in the standard treatment group; hazard ratio [HR], 0.66 [95% CI, 0.51-0.85]) and all-cause mortality (73 deaths vs 107 deaths, respectively; HR, 0.67 [95% CI, 0.49-0.91]). The overall rate of serious adverse events was not different between treatment groups (48.4% in the intensive treatment group vs 48.3% in the standard treatment group; HR, 0.99 [95% CI, 0.89-1.11]). Absolute rates of hypotension were 2.4% in the intensive treatment group vs 1.4% in the standard treatment group (HR, 1.71 [95% CI, 0.97-3.09]), 3.0% vs 2.4%, respectively, for syncope (HR, 1.23 [95% CI, 0.76-2.00]), 4.0% vs 2.7% for electrolyte abnormalities (HR, 1.51 [95% CI, 0.99-2.33]), 5.5% vs 4.0% for acute kidney injury (HR, 1.41 [95% CI, 0.98-2.04]), and 4.9% vs 5.5% for injurious falls (HR, 0.91 [95% CI, 0.65-1.29]). CONCLUSIONS AND RELEVANCE Among ambulatory adults aged 75 years or older, treating to an SBP target of less than 120 mm Hg compared with an SBP target of less than 140 mm Hg resulted in significantly lower rates of fatal and nonfatal major cardiovascular events and death from any cause. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT01206062.

Standard versus High-Dose CVVHDF for ICU-Related Acute Renal Failure

The effect of dosage of continuous venovenous hemodiafiltration (CVVHDF) on survival in patients with acute renal failure (ARF) is unknown. In this study, 200 critically ill patients with ARF were randomly assigned to receive CVVHDF with prefilter replacement fluid at an effluent rate of either 35 ml/kg per h (high dosage) or 20 ml/kg per h (standard dosage). The primary study outcome, survival to the earlier of either intensive care unit discharge or 30 d, was 49% in the high-dosage arm and 56% in the standard-dosage arm (odds ratio 0.75; 95% confidence interval 0.43 to 1.32; P = 0.32). Among hospital survivors, 69% of those in the high-dosage arm recovered renal function compared with 80% of those in the standard-dosage arm (P = 0.29); therefore, a difference in patient survival or renal recovery was not detected between patients receiving high-dosage or standard-dosage CVVHDF.

Racial Differences in the Prevalence of Chronic Kidney Disease among Participants in the Reasons for Geographic and Racial Differences in Stroke (REGARDS) Cohort Study

The racial disparity in the incidence of ESRD exemplified by the three- to four-fold excess risk among black compared with white individuals in the United States is not reflected in the prevalence of less severe degrees of impaired kidney function among black compared with white individuals. The four-variable Modification of Diet in Renal Disease study equation was used to evaluate the black-to-white prevalence of impaired kidney function with increasing severity of impairment among participants in the Reasons for Geographic and Racial Differences in Stroke (REGARDS) study, a nationally representative, population-based cohort of individuals who are 45 yr and older. An estimated GFR (eGFR)<60 ml/min per 1.73 m2 was present in 43.3% of the 20,667 REGARDS participants and was slightly less prevalent among black than white patients (33.7 versus 49.9%; prevalence odds ratio 0.51; 95% confidence interval [CI] 0.48 to 0.54). The lower prevalence among black patients was not uniform as eGFR declined. After controlling for other patient characteristics, the black-to-white odds ratio was 0.42 (95% CI 0.40 to 0.46) at an eGFR of 50 to 59 ml/min per 1.73 m2 and increased to 1.73 (95% CI 1.02 to 2.94) at an eGFR of 10 to 19 ml/min per 1.73 m2. The disparity in prevalence of impaired kidney function among white compared with black patients reversed as the severity of impaired kidney function increased. Factors that are responsible for the increasing prevalence of severely impaired kidney function among black patients remain to be determined.

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.

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.

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.

Halting the progression of chronic nephropathy.

The incidence of end-stage renal disease (ESRD) is increasing worldwide. In the United States alone, there were 372,000 patients requiring renal replacement therapy in the year 2000 and is expected to rise to 650,000 by the year 2010. The trends in Europe and Japan are forecasted to follow a similar path. These increases represent a significant burden to countries worldwide; not only due to the financial costs of providing ESRD care, but also because of lost productivity and significant morbidity and mortality for the affected patients. There is clearly a pressing need for the aggressive identification and early treatment of patients with nephropathy to prevent progression to ESRD. Research in the last 25 yr has made great advances in the understanding of the progression of chronic renal disease in diabetic and nondiabetic proteinuric nephropathy. There are now effective treatment options that can slow the progression of chronic nephropathies in many individuals, and ongoing research has raised the tantalizing prospect of the reversal of renal disease progression.

A propensity-matched study of low serum potassium and mortality in older adults with chronic heart failure ☆

OBJECTIVE Most HF patients are older adults, yet the associations of low serum potassium and outcomes in these patients are unknown. We studied the effect of low serum potassium in a propensity-matched population of elderly HF patients. METHODS Of the 7788 patients in the Digitalis Investigation Group trial, 4036 were >or=65 years. Of these, 3598 had data on baseline serum potassium and 324 with potassium >or=5 mEq/L were excluded. Remaining patients were categorized into low (<4 mEq/L; n=590) and normal (4-4.9 mEq/L; n=2684) potassium groups. Propensity scores for low-potassium, calculated for each patient, were used to match 561 low-potassium and 1670 normal-potassium patients. Association of low potassium and outcomes were assessed using matched Cox regression analyses. RESULTS Patients had a mean (+/-SD) age of 72 (+/-6) years, 29% were women and 12% were non-whites. Of the 561 low-potassium patients, 500 had low-normal (3.5-3.9 mEq/L) potassium. All-cause mortality occurred in 37% (rate, 1338/10,000 person-years) normal-potassium and 43% (rate, 1594/10,000 person-years) low-potassium patients (hazard ratio {HR} for low-potassium, 1.22; 95% confidence interval {CI}, 1.04-1.44; p=0.014). Low-normal (3.5-3.9 mEq/L) potassium levels had a similar association with mortality (HR, 1.19, 95% CI, 1.00-1.41, p=0.049). Low (HR, 1.10; 95% CI, 0.96-1.25; p=0.175) or low-normal (HR=1.09, 95% CI=0.95-1.25, p=0.229) serum potassium levels were not associated with all-cause hospitalization. CONCLUSIONS In a propensity-matched population of elderly ambulatory chronic HF patients, well-balanced in all measured baseline covariates, low and low-normal serum potassium were associated with increased mortality but had no association with hospitalization.

Prevalence and Characteristics of a Family History of End-Stage Renal Disease among Adults in the United States Population: Reasons for Geographic and Racial Differences in Stroke (REGARDS) Renal Cohort Study

This report describes the prevalence and characteristics of people with a family history of ESRD in a first-degree relative (FH-ESRD). This is a cross-sectional study of individuals in the Reasons for Geographic and Racial Differences in Stroke (REGARDS) cohort, a population-based sample of US residents who are 45 yr and older. FH-ESRD was ascertained at baseline among 12,030 participants of the cohort, and multivariate logistic regression was used to identify characteristics that were independently associated with FH-ESRD. FH-ESRD was reported by 9.5% of participants. Individual characteristics that were independently associated with FH-ESRD included black race (odds ratio [OR] 2.14; 95% confidence interval [CI] 1.82 to 2.53); female gender (OR 1.28; 95% CI 1.08 to 1.51); a history of diabetes (OR 1.22; 95% CI 1.02 to 1.47); a 1-SD change in the log of the C-reactive protein level (OR 1.10; 95% CI 1.01 to 1.19); and World Health Organization body mass index weight categories normal (OR 2.11; 95% CI 0.66 to 6.79), overweight (OR 2.64; 95% CI 0.82 to 8.42), and obese (OR 3.48; 95% CI 1.09 to 11.1) compared with underweight. Black but not white individuals with FH-ESRD were more likely to have an estimated GFR <60 ml/min per 1.73 m(2). There is a high prevalence of FH-ESRD among US adults, and the prevalence of FH-ESRD was higher among lack individuals. Individuals with a positive family history were more likely to have diabetes and to be obese. If confirmed, then these findings suggest that individuals with FH-ESRD may benefit from interventions to improve the detection and treatment of chronic kidney disease risk factors such as diabetes and obesity.

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.