Leptin and altitude in the cardiovascular diseases

Objective: The lower mortality from coronary ischemic disease in populations living at high altitude has been related to an increase of high‐density lipoprotein (HDL)‐cholesterol at altitude. Leptin has been proposed as a cardiovascular risk factor. We investigated whether leptin varies according to the altitude at which people live. Research Methods and Procedures: This was a cross‐sectional study of the first 889 people enrolled in a cohort study in the Canary Islands, Spain. The relationship among serum leptin, altitude, obesity, and other cardiovascular risk factors was analyzed by bivariate and multivariate tests. Results: Leptin levels showed an inverse correlation to altitude expressed in meters (r = −0.10). Obese subjects had this leptin‐altitude association (r = −0.19), but they also had a direct correlation of leptin to HDL‐cholesterol (r = 0.27) and an inverse correlation of leptin to the total cholesterol‐to‐HDL‐cholesterol ratio (r = −0.34), triglycerides (r = −0.29), apolipoprotein B (r = −0.21), and glycemia (r = −0.19). Nonobese subjects had only the leptin‐altitude association (r = −0.11). The final regression model included altitude as predictor. Other associated variables were gender, physical activity, BMI, age, smoking (reducing leptin independently of BMI), alcohol, heart rate, and income. Discussion: Serum leptin level decreases when altitude increases, and this association could help to explain the lower cardiovascular mortality rate at high altitude. However, because in obese subjects there is a direct association of leptin with HDL‐cholesterol and an inverse association with the lipid atherogenic fractions, we suggest the hypothesis of different roles for bound and free leptin, with free leptin being a cardiovascular protective factor in obese people.