Leptin in Relation to Hypertension: The Role of Obesity in the Insulin Resistance Atherosclerosis Study (IRAS)
Background: Leptin, a protein secreted by adipose tissue, has actions that may affect blood pressure via energy balance, insulin sensitivity and/ or the central nervous system. Purpose: The purpose of this abstract is to evaluate the association between leptin level and blood pressure in the multi-center, tri-ethnic Insulin Resistance Atherosclerosis Study (IRAS) population. Methods: IRAS participants (n=1507) were age 40-69 years; 56% female; mean body mass index (BMI)= 29 kg/m2; and 39% hypertensive. Main exposure: multi species leptin radioimmunoassay was used to quantify leptin concentrations (Linco Research Inc., St. Louis, MO; range 0-122.19ng/ml). Main outcome: Main outcome was hypertension (Yes/No), defined as a systolic >=140mm Hg and/ or a diastolic reading of >=90mm Hg or taking antihypertensive medication. Analysis: Logistic regression was used to analyze the relationship between leptin and hypertension, while adjusting for age, dietary fat, gender, activity, ethnicity and clinic. Final models evaluated the role of obesity. Results: The proportion of individuals that were hypertensive by quartile was 28%, 40%, 40% and 49%, respectively. The odds of being hypertensive was 1.60 (p=0.0001) times higher for every 16ng/ml (1 SD) change in leptin after adjusting for age, gender, dietary fat, ethnicity and clinic site, and energy expended (n=1507). The role of BMI (leptin*BMI) was considered, resulting in a reduction of leptin’s effect on hypertension (p=0.02 for the interaction term). The overall odds ratio for being hypertensive per 16ng/ml (1 SD) change was 1.80 (p=0.04) with an attenuation of the effect as BMI increased (estimated OR for BMI of 22, 27 and 32 was 1.23, 1.14, and 1.05 respectively). Analysis were repeated excluding those with diabetes (n=999) and results were essentially unchanged. Conclusion: Increased leptin is associated with increased occurrence of hypertension and its effect is attenuated by increasing BMI. Future work is necessary to confirm and explain these results.