New evidence confirms that high sodium intake among patients with chronic kidney disease (CKD) is associated with worse cardiovascular outcomes -- including congestive heart failure, heart attacks, and stroke.
Compared with CKD patients with the lowest sodium intake, those with the highest were 36% more likely to suffer one of these outcomes (hazard ratio 1.36; 95% CI 1.09-1.70; P=0.007), a team of investigators led by Jiang He, MD, PhD, of Tulane University in New Orleans, La., reported in the Journal of the American Medical Association.
"These findings, if confirmed by clinical trials, suggest that moderate sodium reduction among patients with CKD and high sodium intake may lower cardiovascular disease (CVD) risk," the authors of the prospective cohort study said.
The study suggests that primary care physicians and nephrologists treating patients with CKD should more carefully monitor sodium intake in these patients, and make sure they know the risks associated with too much dietary salt, said Neil Powe, MD, and Kirsten Bibbins-Domingo, MD, PhD, of the University of California, San Francisco, in an accompanying editorial.
"Arguably, physicians inform all patients, particularly those with hypertension and diabetes, about the risks associated with excessive salt intake. However, the high rate of cardiovascular events among patients with CKD may require more concerted attention, including periodic review of salt intake during physician visits," Powe and Bibbins-Domingo said.
While the association between sodium intake and hypertension is well established, the connection between sodium and clinical cardiovascular disease is less clear, especially in patients with CKD, the investigators said.
"To our knowledge, this study is the first to investigate the association between sodium excretion and CVD incidence in a population with CKD. These analyses documented a significantly increased risk of CVD in individuals with the highest urinary sodium excretion independent of several important CVD risk factors, including use of antihypertensive medications, baseline eGFR, and history of CVD," He and colleagues wrote.
"Findings were consistent across subgroups and independent of further adjustment for total caloric intake and systolic blood pressure," the investigators noted.
The study included 3,757 patients with mild to moderate CKD enrolled in the Chronic Renal Insufficiency Cohort (CRIC) study. They were followed from 2003 to 2013. Their average age was 58, and 45% were women.
Urinary sodium excretion, estimated from the mean of three repeated 24-hour urine samples, was used to assess sodium intake. Patients were categorized into four quartiles of sodium excretion, from the lowest (<2,894 mg/24 hours) to the highest (≥4,548 mg/24 hours). The investigators looked for a connection between sodium excretion and a composite of cardiovascular endpoints including congestive heart failure, myocardial infarction (MI), and stroke. The investigators also analyzed each of these outcomes separately.
Over a median 6.8 years of follow-up, 804 composite first CVD events, 575 congestive heart failure events, 305 MI events, and 148 stroke events occurred. From lowest to highest quartile of sodium excretion, the cumulative incidence of composite CVD events was 18.4%, 16.5%, 20.6%, and 29.8% (log-rank P< 0.001).
The cumulative incidence of congestive heart failure in the lowest versus the highest quartile was 13.3% versus 23.2% (log-rank P<0.001). The cumulative incidence of MI was 7.8% versus 10.9% (log-rank P< 0.001). The cumulative incidence of stroke was 2.7% versus 6.4% (log-rank P=0.001).
After adjusting for age, sex, race, and risk factors including hypertension and baseline eGFR, the highest quartile of sodium excretion was significantly associated with greater risk for all endpoints, except MI, when compared with the lowest quartile:
- Composite CVD endpoint: HR 1.36; 95% CI 1.09-1.70; P=0.007).
- Congestive heart failure: HR 1.34; 95% CI 1.03-1.74; P=0.03).
- Stroke: HR 1.81; 95% CI 1.08-3.02; P=0.02).
- MI: HR 1.15; 95% CI 0.79-1.66; P=0.46).
A restricted cubic spline analyses of the association between sodium excretion and composite CVD showed no evidence of a nonlinear association (P=0.11) and indicated a significant linear association (P<0.001).
Limitations of the study included that only three 24-hour urinary specimens were collected, which might not be enough to reflect habitual sodium intake, and that how well urinary sodium excretion approximates dietary sodium intake has not been assessed in CKD patients, the investigators said.
"Although the very low sodium target of 1,500 mg/d for those with kidney disease has been questioned because direct evidence for cardiovascular benefit is lacking, the national target for sodium intake of 2,300 mg/d for the general population has been generally accepted for guidelines, and yet more than 90% of U.S. adults routinely consume sodium in excess of this target," Powe and Bibbins-Domingo said.
The study was funded by the National Institutes of Health
He reported no financial relationships with industry.
Powe and Bibbins-Domingo reported no financial relationships with industry.
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