Community-based serum chloride abnormalities predict mortality risk

INTRODUCTION: This population-based study aimed to investigate the prognostic value of ambulatory serum chloride abnormalities, often ignored by physicians. METHODS: The study population included all non-hospitalized adult patients, insured by "Clalit" Health Services in Israel’s southern district, who underwent at least 3 serum chloride tests in community-based clinics during 2005–2016. For each patient, each period with low (≤97 mmol/l), high (≥107 mmol/l) or normal chloride levels were recorded. A Cox proportional hazards model was used to estimate the mortality risk of hypochloremia and hyperchloremia periods. RESULTS: 664,253 serum chloride tests from 105,655 subjects were analyzed. During a median follow up of 10.8 years, 11,694 patients died. Hypochloremia (≤ 97 mmol/l) was independently associated with elevated all-cause mortality risk after adjusting for age, co-morbidities, hyponatremia and eGFR (HR 2.41, 95%CI 2.16–2.69, p<0.001). Crude hyperchloremia (≥107 mmol/L) was not associated with all-cause mortality (HR 1.03, 95%CI 0.98–1.09 p = 0.231); as opposed to hyperchloremia ≥108 mmol/l (HR 1.14, 95%CI 1.06–1.21 p<0.001). Secondary analysis revealed a dose-dependent elevated mortality risk for chloride levels of 105 mmol/l and below, well within the "normal" range. CONCLUSION: In the outpatient setting, hypochloremia is independently associated with an increased mortality risk. This risk is dose-dependent where the lower the chloride level, the higher is the risk.