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.