Mild hyponatremia, hypernatremia and incident cardiovascular disease and mortality in older men: A population-based cohort study

•Low serum sodium even within the normal range and hypernatremia are associated with increased risk of stroke and CVD.•The association between low normal serum sodium and increased stroke and CVD risk is not explained by known CV risk factors.•The presence of mild hyponatremia is not benign.•By contrast no association is seen between serum potassium and risk of CVD.

AimTo examine the association between serum sodium concentration and incident major cardiovascular disease (CVD) outcomes and total mortality in older men.Methods and ResultsA prospective study of 3099 men aged 60-79 years without a history of cardiovascular disease followed up for an average 11 years during which there were 528 major CVD events (fatal coronary heart disease [CHD] and non-fatal MI, stroke and CVD death) and 873 total deaths. A U shaped relationship was seen between serum sodium concentration and major CVD events and mortality. Hyponatremia (<136 mEq/L) and low sodium within the normal range (136-138 mEq/L) showed significantly increased risk of major CVD events and total mortality compared to men within the upper normal range (139-143 mEq/L) after adjustment for a wide range of confounders and traditional risk factors [adjusted HRs 1.55 (1.13,2.12) and 1.40 (1.14,1.72) for major CVD events respectively and 1.30 (1.02,1.66) and 1.30 (1.11,1.53) respectively for total mortality]. Hyponatremia was associated with inflammation, NT-proBNP, low muscle mass and alkaline phosphatase; these factors contributed to the increased total mortality associated with hyponatremia but did not explain the increased risk of CVD events associated with hyponatremia or low normal sodium concentration. Hypernatremia (≥145 mEq/L) was associated with significantly increased risk of CVD events and mortality due to CVD causes.ConclusionMild hyponatremia even within the normal sodium range and hypernatremia are both associated with increased total mortality and major CVD events in older men without CVD which is not explained by known adverse CV risk factors.