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Original Investigation |

Sodium Excretion and the Risk of Cardiovascular Disease in Patients With Chronic Kidney Disease

Katherine T. Mills, PhD1; Jing Chen, MD1,2; Wei Yang, PhD3; Lawrence J. Appel, MD4; John W. Kusek, PhD5; Arnold Alper, MD2; Patrice Delafontaine, MD2; Martin G. Keane, MD6; Emile Mohler, MD7; Akinlolu Ojo, MD, PhD8; Mahboob Rahman, MD9,10; Ana C. Ricardo, MD11; Elsayed Z. Soliman, MD12; Susan Steigerwalt, MD13; Raymond Townsend, MD5; Jiang He, MD, PhD1,2 ; for the Chronic Renal Insufficiency Cohort (CRIC) Study Investigators
[+] Author Affiliations
1Department of Epidemiology, Tulane University School of Public Health and Tropical Medicine, New Orleans, Louisiana
2Department of Medicine, Tulane University School of Medicine, New Orleans, Louisiana
3Department of Biostatistics and Epidemiology, University of Pennsylvania Perelman School of Medicine, Philadelphia
4Welch Center for Prevention, Epidemiology, and Clinical Research, Johns Hopkins University, Baltimore, Maryland
5Division of Kidney, Urologic, and Hematologic Diseases, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland
6Department of Medicine, Temple University School of Medicine, Philadelphia, Pennsylvania
7Department of Medicine, University of Pennsylvania Perelman School of Medicine, Philadelphia
8Department of Medicine, University of Michigan, Ann Arbor
9Division of Nephrology and Hypertension, Case Western Reserve University, University Hospitals Case Medical Center, Cleveland, Ohio
10Louis Stokes Cleveland VA Medical Center, Cleveland, Ohio
11Department of Medicine, University of Illinois at Chicago, Chicago
12Department of Internal Medicine-Cardiology, Wake Forest School of Medicine, Winston-Salem, North Carolina
13Department of Medicine, St John’s Health System, Detroit, Michigan
JAMA. 2016;315(20):2200-2210. doi:10.1001/jama.2016.4447.
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Published online

Importance  Patients with chronic kidney disease (CKD) are at an increased risk of cardiovascular disease (CVD) compared with the general population. Prior studies have produced contradictory results on the association of dietary sodium intake with risk of CVD, and this relationship has not been investigated in patients with CKD.

Objective  To evaluate the association between urinary sodium excretion and clinical CVD events among patients with CKD.

Design, Setting, and Participants  A prospective cohort study of patients with CKD from 7 locations in the United States enrolled in the Chronic Renal Insufficiency Cohort Study and followed up from May 2003 to March 2013.

Exposures  The cumulative mean of urinary sodium excretion from three 24-hour urinary measurements and calibrated to sex-specific mean 24-hour urinary creatinine excretion.

Main Outcomes and Measures  A composite of CVD events defined as congestive heart failure, stroke, or myocardial infarction. Events were reported every 6 months and confirmed by medical record adjudication.

Results  Among 3757 participants (mean age, 58 years; 45% women), 804 composite CVD events (575 heart failure, 305 myocardial infarction, and 148 stroke) occurred during a median 6.8 years of follow-up. From lowest (<2894 mg/24 hours) to highest (≥4548 mg/24 hours) quartile of calibrated sodium excretion, 174, 159, 198, and 273 composite CVD events occurred, and the cumulative incidence was 18.4%, 16.5%, 20.6%, and 29.8% at median follow-up. In addition, the cumulative incidence of CVD events in the highest quartile of calibrated sodium excretion compared with the lowest was 23.2% vs 13.3% for heart failure, 10.9% vs 7.8% for myocardial infarction, and 6.4% vs 2.7% for stroke at median follow-up. Hazard ratios of the highest quartile compared with the lowest quartile were 1.36 (95% CI, 1.09-1.70; P = .007) for composite CVD events, 1.34 (95% CI, 1.03-1.74; P = .03) for heart failure, and 1.81 (95% CI, 1.08-3.02; P = .02) for stroke after multivariable adjustment. Restricted cubic spline analyses of the association between sodium excretion and composite CVD provided no evidence of a nonlinear association (P = .11) and indicated a significant linear association (P < .001).

Conclusions and Relevance  Among patients with CKD, higher urinary sodium excretion was associated with increased risk of CVD.

Figures in this Article


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Figure 1.
Cumulative Kaplan-Meier Estimates of Cardiovascular Diseases According to Quartile of Calibrated 24-Hour Urinary Sodium Excretion

Because participants who only had urinary sodium excretion measurements after an outcome occurred were excluded from the analysis for that outcome, there are slightly fewer people at time = 0 years for each individual outcome compared with the 3757 participants described in Table 1, who contributed to at least 1 outcome but not necessarily all of them.

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Figure 2.
Multiple-Adjusted Hazard Ratios and 95% Confidence Intervals of Cardiovascular Diseases Associated With Calibrated 24-Hour Urinary Sodium Excretion

Hazard ratios were adjusted for age, sex, race, clinic site, education, waist circumference, lean body mass index, body mass index, cigarette smoking, alcohol drinking, physical activity, low-density lipoprotein cholesterol, glucose, history of cardiovascular disease, antidiabetic medications, lipid-lowering medications, diuretics, renin-angiotensin system blocking agents, other antihypertensive medications, urinary creatinine excretion, and baseline estimated glomerular filtration rate.

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