Author + information
- Rami Doukky, MD, MSc∗,†,‡,§∗ (, )
- Elizabeth Avery, MS∗,§,
- Ashvarya Mangla, MD∗,‡,§,
- Fareed M. Collado, MD‡,
- Zeina Ibrahim, MD†,
- Marie-France Poulin, MD‡,
- DeJuran Richardson, PhD∗,§,‖ and
- Lynda H. Powell, PhD∗,§
- ∗Department of Preventive Medicine, Rush University Medical Center, Chicago, Illinois
- †Division of Cardiology, John H. Stroger, Jr. Hospital of Cook County, Chicago, Illinois
- ‡Division of Cardiology, Rush University Medical Center, Chicago, Illinois
- §Rush Center for Urban Health Equity, Rush University Medical Center, Chicago, Illinois
- ‖Department of Mathematics and Computer Science, Lake Forest College, Lake Forest, Illinois
- ↵∗Reprint requests and correspondence to:
Dr. Rami Doukky, Division of Cardiology, John H. Stroger, Jr. Hospital of Cook County, 1901 West Harrison Street, Suite 3620, Chicago, Illinois 60612.
Objectives This study sought to evaluate the impact of sodium restriction on heart failure (HF) outcomes.
Background Although sodium restriction is advised for patients with HF, data on sodium restriction and HF outcomes are inconsistent.
Methods We analyzed data from the multihospital HF Adherence and Retention Trial, which enrolled 902 New York Heart Association functional class II/III HF patients and followed them up for a median of 36 months. Sodium intake was serially assessed by a food frequency questionnaire. Based on the mean daily sodium intake prior to the first event of death or HF hospitalization, patients were classified into sodium restricted (<2,500 mg/d) and unrestricted (≥2,500 mg/d) groups. Study groups were propensity score matched according to plausible baseline confounders. The primary outcome was a composite of death or HF hospitalization. The secondary outcomes were cardiac death and HF hospitalization.
Results Sodium intake data were available for 833 subjects (145 sodium restricted, 688 sodium unrestricted), of whom 260 were propensity matched into sodium restricted (n = 130) and sodium unrestricted (n = 130) groups. Sodium restriction was associated with significantly higher risk of death or HF hospitalization (42.3% vs. 26.2%; hazard ratio [HR]: 1.85; 95% confidence interval [CI]: 1.21 to 2.84; p = 0.004), derived from an increase in the rate of HF hospitalization (32.3% vs. 20.0%; HR: 1.82; 95% CI: 1.11 to 2.96; p = 0.015) and a nonsignificant increase in the rate of cardiac death (HR: 1.62; 95% CI: 0.70 to 3.73; p = 0.257) and all-cause mortality (p = 0.074). Exploratory subgroup analyses suggested that sodium restriction was associated with increased risk of death or HF hospitalization in patients not receiving angiotensin-converting enzyme inhibitor or angiotensin receptor blocker (HR: 5.78; 95% CI: 1.93 to 17.27; p = 0.002).
Conclusions In symptomatic patients with chronic HF, sodium restriction may have a detrimental impact on outcome. A randomized clinical trial is needed to definitively address the role of sodium restriction in HF management. (A Self-management Intervention for Mild to Moderate Heart Failure [HART]; NCT00018005)
Heart failure (HF) continues to increase in prevalence with an enormous impact on morbidity and mortality (1). The treatment of HF involves both pharmacologic and nonpharmacologic approaches (2). Traditionally, one of the cornerstones of nonpharmacological management in HF has been restricting dietary sodium intake. Data supporting this approach are inconsistent, as some studies have shown benefit (3,4), whereas others demonstrated better outcomes with sodium liberalization (5–7). This controversy has manifested in the American College of Cardiology Foundation (ACCF)/American Heart Association (AHA) guidelines for the management of HF. The 2009 guideline gave sodium restriction in patients with symptomatic HF a Class I recommendation (recommended) to reduce congestive symptoms with Level of Evidence: C (expert consensus) (8). Other societal guidelines issued similar recommendations (9). More recently, the 2013 ACCF/AHA guidelines downgraded the recommendation for sodium restriction to Class IIa (reasonable) with Level of Evidence: C (2).
In this study, we investigated the impact of sodium restriction on HF outcomes in patients enrolled in the HART (Heart Failure Adherence and Retention Trial), a behavioral intervention trial that assessed the efficacy of self-management counseling versus education alone in symptomatic HF patients (10). We hypothesized that if sodium restriction was protective, there would be a difference in clinical outcomes and HF symptoms between patients with low versus high sodium intake.
We analyzed data from HART (10), which was a multihospital, partially blinded, behavioral randomized controlled trial, funded by the National Institutes of Health (HL065547). HART assessed the impact of self-management counseling versus education alone on the primary outcome of death or HF hospitalization in patients with symptomatic HF. Details of the intervention, patient enrollment, eligibility, and results of the main trial were reported elsewhere (10,11). The study enrolled from 10 centers in the Chicago, Illinois metropolitan area and the behavioral intervention was conducted by Rush University Medical Center. The trial was approved by the institutional review board of each participating institution and was registered on clinicaltrials.gov (NCT00018005).
Briefly, HART enrolled HF patients with New York Heart Association (NYHA) functional class II or III symptoms, having HF with reduced ejection fraction (HFrEF) or preserved ejection fraction (HFpEF). Reduced systolic function was defined as left ventricular ejection fraction ≤40%. Eligible patients had to have HF symptoms for no less than the prior 3 months and either: 1) ejection fraction ≤40%; or 2) diuretic agent therapy for at least 3 months and ≥1 previous HF hospitalization. This was a null trial; it showed no significant impact of the self-management intervention on the composite of death or HF-related hospitalization (10). For the purpose of the current study, we assessed the impact of sodium intake on HF outcomes in the HART patients over a median follow-up of 36 months.
Sodium intake assessment
A standardized food frequency questionnaire was used to assess sodium intake at baseline and in annual follow-up visits at year 1, 2, and 3 (12). The questionnaire was developed and tested at Stanford University (Stanford, California) and had been used in multiple behavioral HF clinical trials, sponsored by the National Institutes of Health (10–14). The questionnaire queries the intake of 57 commonly consumed food items in the American diet during the course of the preceding week, with particular emphasis on high sodium content meals. Each food item is weighted according to frequency of consumption and sodium content. Based on patients’ responses, estimates of daily sodium intake (milligrams) were calculated after adding an assumed baseline sodium consumption of 1,250 mg/d, derived from essential food items in the American diet (e.g., bread and meats), as detailed in Online Table 1. Because sodium intake can vary, particularly during and after HF hospitalizations, we analyzed sodium intake as a time-dependent variable, averaging intake reported in all study visits preceding the first adverse event of death or HF hospitalization. We elected not to categorize the patients on the basis of a single sodium intake value because sodium consumption tends to vary over time.
Based on the reported average sodium consumption, we divided the cohort into 2 groups: 1) lower sodium intake (<2,500 mg/d), labeled “restricted”; and 2) higher sodium intake (≥2,500 mg/d), labeled “unrestricted”. Recommendations from various clinical societies and existing guidelines were considered in deciding this cutoff value (9).
Clinical and psychosocial data
During baseline and yearly visits, data were gathered on demographics, psychosocial characteristics, medical comorbidities, medication usage and adherence, and NYHA functional class. Socioeconomic status was defined as low if the patient’s annual household income was <$30,000 or if the highest attained education was high school or less. Medication adherence for key HF medications was assessed as the proportion of pills consumed relative to the prescribed amount using electronic pill bottle cap over the course of a month. To uniformly adjust for diuretic agent usage, the dosages of various loop diuretic agents were converted into furosemide dose equivalent (Online Table 2). During each visit, the 6-min walk distance was measured. Depression was defined by self-reported established diagnosis or scoring ≥10 on the Geriatric Depression Screening Scale (15). Chronic kidney disease (CKD) was defined as glomerular filtration rate <60 ml/min/1.73 m2 (Cockcroft-Gault formula) or dialysis therapy. Coronary artery disease was defined as a prior history of coronary revascularization or confirmed myocardial infarction. Quality of life was assessed using health and functioning subscale of the Quality of Life Index, Cardiac Version-IV (modified) (16) and 2 subscales from the 36-Item Short Form Health Survey (SF-36) (17). We indexed the burden of 12 HF symptoms tallied using the cardiopulmonary subscale of the HF Symptom Checklist (modified) (Online Table 3) (18).
The primary outcome was a composite of death or HF hospitalizations, as in HART. Secondary outcomes were cardiac death and HF hospitalization. The median follow-up was 36 months (interquartile range: 27 to 36 months). The outcomes were determined by a blinded adjudication committee (10). All patients or their family members (in the case of death) were contacted every 3 months by telephone to ascertain the occurrence of death or hospitalization. Reports of death were confirmed by medical records, death certificates, or queries from the Social Security Death Index. HF admissions were adjudicated by the presence of shortness of breath, peripheral edema, or chest radiographic evidence of pulmonary edema without an alternative diagnosis. HF admissions were confirmed if the patient responded to HF therapy or had a documented decrease in left ventricular function. Cardiac death was defined as death caused by myocardial infarction, arrhythmias, or pump failure.
Basic statistical methods
The chi-square test was used to compare dichotomous variables, which were expressed as numbers (percentages). The 2-tailed Student t test was used to compare normally distributed continuous variables, which were expressed as mean ± SD. The Wilcoxon test was used to compare skewed continuous data.
Propensity score matching
Because patients were not randomly assigned to sodium restriction, we matched patients according to their propensity to being sodium restricted. Multivariate logistic regression model (propensity model) was fit to calculate the probability of sodium restriction based on 32 baseline variables listed in Table 1. Additionally, 2 interaction terms, “CKD * angiotensin-converting enzyme inhibitor (ACEi) or angiotensin receptor blocker (ARB) use” and “CKD * spironolactone use”, were included in the propensity model to balance the clinical implications of utilizing these agents. The resultant probabilities were then transformed into propensity score logits. Six-minute walk distance and quality of life were not included in the propensity model due to collinearity with NYHA functional class and SF-36 scores. Serum creatinine was not included in propensity model as it was accounted for in CKD status. Obesity was not included due to association with obstructive sleep apnea. Each patient in the sodium-restricted group was then matched, in 1:1 ratio, to a patient in the unrestricted group with a propensity score within a caliper width of 0.2 * SD of the propensity score logits, creating a propensity-matched cohort. Software (Python, Version 2.6.7, Python Software Foundation) was used for propensity matching. The absolute standardized differences in baseline covariates were calculated pre- and post-propensity matching; covariates with >10% difference after matching were considered suboptimally matched.
Kaplan-Meier curves and the log-rank test were used to compare cumulative event rates in the entire cohort and in the propensity-matched cohort. Risk was expressed as hazard ratio (HR) and 95% confidence interval (CI), calculated using univariate and multivariate Cox regression models. To confirm the findings of the propensity-matched analyses in the entire cohort, we analyzed outcomes using multivariate Cox proportional hazards models, adjusting for the calculated propensity scores. The proportional hazards assumption with respect to Cox regression modeling was confirmed using log-minus-log survival plots.
In exploratory, hypothesis-generating analyses, we studied the impact of sodium restriction on the primary outcome in pre-defined subgroups of sex, age, ethnicity (African American vs. others), NYHA functional class (II vs. III), HF with reduced versus preserved ejection fraction, CKD, and the use of key HF medications (ACEi/ARB, spironolactone, β-blocker) before primary outcome events. Using multivariate Cox regression models in the propensity-matched cohort, we tested the impact of an interaction between sodium restriction and each of the aforementioned subgroup strata on the primary outcome. To confirm the results in the entire cohort, subgroup analyses were also performed in the entire cohort using multivariate Cox regression models, adjusted for the propensity scores.
Longitudinal analysis of time-varying outcome measures
Mixed-effects regression modeling in propensity-matched cohort was used to assess the influence of sodium restriction on the trajectory of the time-varying outcomes of 6-min walk distance, cardiopulmonary HF symptoms, quality of life, SF-36 physical function score, SF-36 energy and vitality score, and daily loop diuretic agent dose. Due to its skewed distribution, the 6-min walk distance was analyzed after a logarithmic transformation. The mixed-effects models used the following structure: fixed effects included sodium intake group, time since baseline, sodium group by time interaction, and covariates with >10% absolute standardized difference between the propensity-matched groups (Figure 1); random effects included intercept and time. Due to missing data, by design, from the third-year visit, we analyzed continuous outcome data only over the first 2 years of the study.
Two-tailed p values <0.05 were considered significant. Software systems PASW 18.0 (IBM Corp, Armonk, New York) and SAS version 9.3 (SAS Institute, Cary, North Carolina) were used for statistical analyses.
Based on the observed rate of the primary outcome in HART (36.4%), we calculated, post-hoc, that the available propensity-matched cohort provided the study 80% power to detect ≥37% difference in the rate of the primary outcome based on the chi-square test (2-tailed α = 0.05).
Sodium intake data were available for 833 of 902 (92%) subjects enrolled in HART. The median sodium intake was 3,336 mg/d (interquartile range: 2,701 to 4,237 mg/d; range 1,250 to 15,678 mg/d). Based on the mean sodium intake before primary outcome events (death or HF hospitalization), patients were classified into restricted (n = 145 [17.4%]) and unrestricted (n = 688 [82.6%]) sodium intake groups. The baseline characteristics of the study groups are summarized in Table 1. Notably, sodium-restricted patients were more frequently women and were more likely to have CKD, prior stroke, been treated with a β-blocker, and received higher doses of loop diuretic agents.
During a median follow-up of 36 months, there were 163 (19.6%) deaths, 105 (12.6%) cardiac deaths, and 199 (23.9%) HF hospitalizations; 303 (36.4%) subjects had ≥1 events of death or HF hospitalization. As presented in Table 2, sodium-restricted patients had a borderline significant increase in the rate of death or HF hospitalization (p = 0.054) and statistically significant increase in HF hospitalizations (p = 0.033). The rates of death and cardiac death were similar between the study groups (Table 2).
A total of 130 (90%) of the restricted sodium intake patients could be propensity matched to unrestricted patients, resulting in a propensity-matched cohort of 260 patients (130 sodium restricted, 130 sodium unrestricted). After matching, there was no significant difference in the mean propensity score between the matched groups (p = 0.956) and the balance between the study groups markedly improved, as none of the baseline characteristics were significantly different (Table 1). The propensity-matched groups were also well balanced in baseline characteristics not included in the propensity model, such as body mass index, systolic blood pressure, quality of life, 6-min walk distance, and serum creatinine. The absolute standardized differences between the propensity-matched groups was <10% for the majority of baseline covariates (Figure 1).
In the propensity-matched cohort, there were 89 (34.2%) events of death or HF hospitalization during follow-up. As illustrated in Figure 2 and Table 2, sodium restriction was associated with a statistically significant increase in the rates of death or HF hospitalization (42.3% vs. 26.2%; HR: 1.85; 95% CI: 1.21 to 2.84; p = 0.004) and HF hospitalization (32.3% vs. 20.0%; HR: 1.82; 95% CI: 1.11 to 2.96; p = 0.015), a statistically nonsignificant increase in the rate of cardiac death (10.8% vs. 6.9%; HR: 1.62; 95% CI: 0.70 to 3.73; p = 0.257), and a trend toward increased risk of all-cause mortality (18.5% vs. 10.8%; HR: 1.62; 95% CI: 0.94 to 3.53; p = 0.074). To ensure that these findings were not confounded by suboptimally matched baseline covariates, we analyzed the risk of adverse events after adjusting for covariates with post-matching absolute standardized difference >10% (stroke, β-blocker use, tobacco use, serum sodium, spironolactone use, lung disease, diabetes, NYHA class III, statin use, atrial fibrillation, ACEi/ARB use). After adjustment, sodium restriction continued to be associated with increased risk of death or HF hospitalization (adjusted HR: 1.72; 95% CI: 1.12 to 2.65; p = 0.014) and HF hospitalization (adjusted HR: 1.68; 95% CI: 1.02 to 2.75; p = 0.040), and nonsignificant increase in the risk of cardiac death (p = 0.319) and all-cause mortality (p = 0.123), as shown in Table 2.
The findings of the propensity-matched analyses were confirmed in the entire cohort. As presented in Table 2, after adjusting for propensity scores, sodium restriction was associated with a significant increase in the rates of death or HF hospitalization (HR: 1.37; 95% CI: 1.01 to 1.86; p = 0.042) and HF hospitalization (HR: 1.44; 95% CI: 1.002 to 2.06; p = 0.049), but there was no significant increase in the rate of cardiac death (p = 0.928) or all-cause mortality (p = 0.448).
The HRs for sodium restriction were consistently >1.0 in all subgroups, indicating increased risk (Figure 3). Notably, there was a significant interaction between sodium restriction and ACEi/ARB use (interaction p = 0.021). This was confirmed when we tested for this interaction in the entire cohort adjusting for propensity scores (interaction p = 0.009). This finding indicates a differential effect of sodium restriction, in that those who are not treated with an ACEi/ARB agent had a significantly increased risk of adverse outcome, whereas those treated with an ACEi/ARB had no significant increase in risk (Figure 3). Furthermore, there was a trend toward a significant interaction between sodium restriction and NYHA class (interaction p = 0.138), in that sodium restriction was associated with a significantly greater hazard of adverse outcome in patients with NYHA class II symptoms, whereas the association was weaker in class III patients (Figure 3).
Time-varying HF outcome measures
In the propensity-matched study groups, there were no significant baseline differences in the mean 6-min walk distance, quality of life score, SF-36 physical function score, SF-36 energy and vitality score, cardiopulmonary HF symptoms index, and loop diuretic agents daily dose (Table 1). As illustrated in Figure 4, during 2 years of follow-up, there was no significant difference between the study groups in the trajectory of change in 6-min walk distance, quality of life, physical function, energy and vitality, HF cardiopulmonary symptoms, and loop diuretic agent dosage (group * time interaction p values ≥0.242).
Because sodium intake in the unrestricted group spanned a wide range, we analyzed outcomes among patients who had moderate sodium intake (2,500 to 3,999 mg/d, n = 440) versus those with high sodium intake (≥4,000 mg/d, n = 248), adjusting for propensity scores. There was a nonsignificant increase in the risk of death or HF hospitalization among the high versus moderate sodium intake patients (HR: 1.07; 95% CI: 0.80 to 1.42; p = 0.642).
Patients with missing sodium intake data
In all, 69 (7.6%) patients failed to complete the food frequency questionnaire, thus lacked sodium intake data. As compared with patients with available sodium intake data, they were more commonly African American (p = 0.012), less likely to be married (p = 0.047), and poorly adherent (mean, 15%) to key HF medical therapies (Online Table 4). These subjects had higher rates of death or HF hospitalization, all-cause mortality, and cardiac and noncardiac death (all p values ≤0.001), but had similar rates of HF hospitalization (p = 0.903) (Online Table 5).
In these analyses of data from HART, there was no demonstrable evidence that dietary sodium restriction is associated with lower rate of death or HF hospitalization. In fact, dietary sodium restriction was associated with increased risk of adverse outcomes, particularly HF hospitalization. Although the increase in the rates of cardiac death and all-cause mortality among sodium-restricted patients were not statistically significant due to limitation in statistical power, the HRs of these events were commensurate with that of HF hospitalizations. Moreover, sodium restriction was not associated with a discernable impact on 6-min walk distance, quality of life, physical function, energy and vitality, or cardiopulmonary symptoms. These findings were not confounded by difference in diuretic agent utilization. Given the observational nature of this hypothesis-generating study, a causal effect of sodium restriction cannot be established. Nonetheless, our findings challenge the present convention and press the need for multicenter randomized trial to definitively address the role of sodium restriction in HF management.
For decades, dietary sodium restriction has been the cornerstone of HF management alongside medical therapy. The data supporting this recommendation are thin, leading to inconsistent guidelines from various professional societies (9). A considerable body of published reports indicates that sodium restriction is associated with detrimental hemodynamic and neurohormonal changes, such as decrease in cardiac index and renal perfusion and activation of the renin-angiotensin-aldosterone system and sympathetic activity (9,19,20). Although some studies have shown benefit with sodium restriction (3,4), others have reported better outcomes with sodium liberalization (5–7). Our study provides quality, multicenter observational evidence that low sodium intake may worsen HF outcomes, in agreement with single-center clinical trials (5–7).
It is plausible that increased event rates observed in the sodium-restricted group are due to reverse causality bias, such that sicker patients were more compliant with dietary restriction. The aforementioned explanation of our findings is unlikely given our systematic propensity matching according to wide range of plausible confounders, achieving well-balanced groups in terms of key surrogate measures of HF severity and outcome, such as 6-min walk, quality of life, physical functioning, medication adherence, and others. Moreover, patients were well matched in serum albumin, hemoglobin, body mass index, systolic blood pressure, kidney function, congestive HF symptoms and signs, and diuretic agent use; thus malnutrition, hypotension (end-stage HF), kidney disease, and fluid status were unlikely confounders to low sodium intake. For added rigor, we performed post-matching adjustment for any residual difference between the matched groups. Importantly, dietary sodium intake data in this cohort were not completely observational, because dietary sodium restriction was a major element of the intervention and control arms of HART (10,11).
In exploratory subgroups analyses, sodium restriction appeared to be particularly detrimental in the small subgroup of patients not being treated with ACEi/ARB, suggesting that renin-angiotensin-aldosterone system blockade may mitigate the neurohormonal effects of sodium restriction (9). This is also consistent with the neurohormonal studies demonstrating activation of the renin-angiotensin-aldosterone system in sodium-restricted patients (9,19,20). It is also notable that sodium restriction was detrimental among patients with NYHA class II symptoms, but had a minimal effect on those with class III symptoms. This observation is somewhat consistent with that of Lennie et al (5), who reported in an observational cohort that sodium restriction (<3,000 mg/d) was associated with higher event rates of death or cardiac hospitalizations among patients with class I to II symptoms but lower event rates among those with class III to IV symptoms. It is plausible that excessive sodium restriction in euvolemic class II patients has led to activation of the renin-angiotensin-aldosterone system causing deterioration of HF, whereas sodium restriction may have value in keeping hypervolemic class III patients from further fluid retention. The ACEi/ARB and NYHA class subgroup analyses suggest that the observed findings in the entire cohort were mediated through neurohormonal modulation rather than unrecognized confounders.
The study cohort is composed of outpatients with chronic symptomatic HF. Therefore, the investigation provides no insight on the impact of sodium restriction in patients with acute decompensated HF, patients with severe class IV symptoms, or those with minimal class I symptoms. Additionally, the study provides no information on the effect of “sodium binges” on HF outcome. Furthermore, 7.6% of HART patients lacked sodium intake data; these patients were poorly compliant to key HF therapies and had poor cardiac and noncardiac outcomes. They seem to represent challenging HF patients with more fundamental compliance problems than sodium restriction, thus their outcomes were not solely dependent on their sodium intake.
We lacked data on implantable devices and plasma B-type natriuretic peptide levels; these are potentially important covariates. We also lacked caloric intake data, which may confound patients’ outcomes. However, we matched the patients based on surrogates for nutritional status, such as serum albumin and physical functioning, and ensured excellent match in body mass index. Determining sodium intake from food frequency questionnaire rather than gold standard 24-h urinary sodium (9,21), small sample size, and nonrandomized design are notable limitations.
In patients with chronic HF, low dietary sodium intake (<2,500 mg/d) does not seem to reduce the risk of death or HF hospitalization compared with higher sodium intake (≥2,500 mg/d). Low sodium intake seems to be associated with increased risk of HF hospitalization. Our findings support further downgrade of the ACCF/AHA sodium restriction recommendation in patients with chronic HF to class IIb (efficacy less well established, conflictive evidence), and press the need for multicenter randomized trial to definitively address the role of sodium restriction in HF management.
COMPETENCY IN MEDICAL KNOWLEDGE: Despite limited and conflicting data, sodium restriction is generally recommended for patients with chronic HF. In this observational study of patients enrolled in HART, we demonstrated that sodium restriction (<2,500 mg/d) was associated with increased risk of the composite endpoint of death or HF hospitalizations and HF hospitalization. Sodium restriction was not associated with improved quality of life, physical functioning, 6-min walk distance, or symptoms.
TRANSLATIONAL OUTLOOK: These findings further question the value of sodium restriction in the management of patients with chronic symptomatic HF, and pressing the need for multicenter randomized trials to definitively address this matter.
The authors sincerely thank Guillaume Lambert, PhD, for his contribution in the propensity score matching.
The Heart Failure Adherence and Retention Trial (NCT00018005) was funded by the National Heart, Lung, and Blood Institute (NHLBI) (HL065547). This study is part of the Rush Center for Urban Health Equity, which is funded by the NHLBI, grant number 1P50HL105189-01. Dr. Doukky has served on the advisory board for and received research funding from Astellas Pharma. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose.
- Abbreviations and Acronyms
- American College of Cardiology Foundation
- angiotensin-converting enzyme inhibitor
- American Heart Association
- angiotensin receptor blocker
- confidence interval
- chronic kidney disease
- heart failure
- hazard ratio
- New York Heart Association
- 36-Item Short Form Health Survey
- Received July 14, 2015.
- Accepted August 6, 2015.
- American College of Cardiology Foundation
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