Increased proximal sodium reabsorption is associated with increased cardiovascular risk in men

Objective To explore the relationship between fractional lithium excretion (taken as an index of proximal sodium excretion), blood pressure and metabolic risk factors for coronary heart disease in a sample of a general white male population. Design A cross-sectional survey of a sample of a white male working population carried out as part of the Olivetti Heart Study. Setting The Olivetti factory in Pozzuoli, a suburb of Naples, Italy. Participants Five hundred and sixty-seven untreated white male workers aged 21-68 years. Measurements Anthropometry, blood pressure, a blood test to determine the lipid profile, electrolytes, glucose and uric acid levels, a detailed questionnaire and urinary measurements on a fasting timed urine sample after a 300 mg lithium carbonate capsule taken the night before the investigation. Results The fractional excretion of lithium was inversely associated with body weight, body mass index, diastolic blood pressure, serum triglycerides level and serum uric acid level whereas it was positively associated with serum high-density lipoprotein cholesterol level. The greater the percentage of filtered sodium reabsorbed at the proximal tubule the greater the overall metabolic cardiovascular risk. The association was consistent across tertiles of fractional excretion of lithium, was independent of age, smoking, alcohol consumption and sodium excretion (taken as an index of sodium intake) and persisted in multiple regression analysis. Men with high serum triglycerides, high serum uric acid and low serum high-density lipoprotein cholesterol levels and higher blood pressure had significantly lower fractional excretion of lithium (and thus enhanced proximal sodium reabsorption) than did men with a normal metabolic profile (21.8 ± 5.6 versus 26.5 ± 5.1%, P = 0.002). Conclusions The independent association between a cluster of risk factors for cardiovascular disease suggestive of insulin resistance and increased proximal sodium reabsorption at the renal tubule indicates a new feature of the metabolic syndrome that, if causal, could be amenable to intervention.