Thiazide-Associated Hyponatremia and Mortality Risk: A Cohort Study

Area of Science:

• Cardiology
• Nephrology
• Pharmacology

Background:

• Hypertension affects millions globally, with thiazide diuretics being a common treatment.
• Hyponatremia is a known complication of thiazide therapy.
• The mortality risk associated with thiazide-induced hyponatremia in outpatients is not well-established.

Purpose of the Study:

• To investigate the association between early hyponatremia and mortality in outpatients initiating thiazide diuretic treatment.
• To compare mortality rates in patients who develop hyponatremia versus those who do not.

Main Methods:

• Retrospective cohort study utilizing deidentified electronic medical records from the TriNetX network (approx. 93 million patients).
• Included adult patients (40-90 years) with essential hypertension starting thiazide diuretics (2010-2021).
• Propensity score matching was used to compare a hyponatremia cohort (serum sodium ≤135 mmol/L within 6 months) with a control cohort (serum sodium 136-144 mmol/L).

Main Results:

• The hyponatremia cohort exhibited a significantly higher hazard of one-year mortality (HR 1.96; 95% CI, 1.72-2.28; P < 0.001).
• Increased hazards were also observed for sepsis, pneumonia, urinary tract infections, cellulitis, myocardial infarction, stroke, congestive heart failure, ataxia, and hip fracture in the hyponatremia group.

Conclusions:

• Developing early hyponatremia after starting thiazide diuretics is associated with a substantially increased risk of mortality.
• These findings underscore the need for vigilant monitoring of serum sodium levels in patients on thiazide therapy.