Analysis finds a significant increased risk of CVD with high urinary sodium excretion

Patients with chronic kidney disease who had high urinary sodium excretion had an increased risk of cardiovascular disease compared with those with a low urinary sodium excretion, according to a prospective cohort study.

Lead researcher Katherine T. Mills, PhD, of the Tulane University School of Public Health and Tropical Medicine in New Orleans, and colleagues published their results online in JAMA on May 24.

The researchers noted that approximately 11 percent of the U.S. population has chronic kidney disease, which is associated with an increased risk of end-stage renal disease, cardiovascular disease and all-cause mortality.

In this analysis, the researchers evaluated 3,757 participants from the Chronic Renal Insufficiency Cohort (CRIC) study, an ongoing, multicenter, prospective cohort study of adults between 21 and 74 years old who had mild to moderate chronic kidney disease.

At baseline, the researchers obtained self-reported sociodemographic and lifestyle characteristics, medical history, current medication use and responses to a food frequency questionnaire. Participants attended annual clinic visits and received telephone calls every six months between in-person visits.

Participants were also asked to collect 24-hour urine specimens at baseline and the first two annual follow-up visits. The researchers measured urinary sodium and potassium levels using flame emission spectrophotometry. They measured urinary creatinine on a BioTek Plate Reader ELx808 using a Jaffe reaction with a colorimetric end point and reagents from Sigma-Aldrich.

The mean age of participants was 58 years old, and 45 percent were women.

After a median follow-up period of 6.8 years, there were 804 composite cardiovascular disease events, including 575 cases of congestive heart failure, 305 MIs and 148 strokes.

The cumulative incidence of composite cardiovascular disease events was 174 in the lowest quartile of calibrated sodium excretion, 159 in the second lowest quartile, 198 in the second highest quartile and 273 in the highest quartile. The cumulative incidence was 18.4 percent, 16.5 percent, 20.6 percent and 29.8 percent, respectively.

The cumulative incidence of cardiovascular events in the highest quartile of calibrated sodium excretion compared with the lowest was 23.2 percent versus 13.3 percent for heart failure, 10.9 percent versus 7.8 percent for MI and 6.4 percent versus 2.7 percent for stroke.

“These analyses documented a significantly increased risk of [cardiovascular disease] in individuals with the highest urinary sodium excretion independent of several important [cardiovascular disease] risk factors, including use of antihypertensive medications, baseline eGFR, and history of [cardiovascular disease],” the researchers wrote. “Findings were consistent across subgroups and independent of further adjustment for total caloric intake and systolic blood pressure. However, [cardiovascular disease] risk was not significantly different among participants with a urinary sodium excretion of 4547 mg/24 hours or less. These findings, if confirmed by clinical trials, suggest that moderate sodium reduction among patients with [chronic kidney disease] and high sodium intake may lower [cardiovascular disease] risk.”

The researchers cited a few limitations of the study, including that they could not compare clinical outcomes among patients with urinary sodium excretion less than 2,300 mg sodium per day or less than 1,500 mg sodium per day, which are the recommended low sodium targets.

They also collected only three 24-hour urinary specimens, which may not accurately reflect habitual intake. In addition, they said unmeasured or unadjusted factors may have been present, the degree to which urinary sodium excretion approximates dietary sodium intake has not been assessed in patients with chronic kidney disease and total energy intake had substantial missing values.