Abstract 17040: Low Serum Leptin Predicts Cardiovascular Disease Mortality in Older Women: The Rancho Bernardo Study

Abstract

Leptin is a neuroendocrine adipocyte-derived hormone that regulates metabolism and energy expenditure. Circulating leptin levels have been associated with CVD morbidity and mortality; however, whether low or high leptin is harmful is not clear. This study examined the prospective association between serum leptin levels and CVD mortality in community-dwelling older adults, and its modulation by sex and age. We hypothesized a U-shaped relationship. Participants included 694 postmenopausal non-estrogen using women and 865 men (median age = 72.4 years) who had serum leptin levels and CVD risk factors evaluated in 1984-87 and were followed for vital status through 2010. During the median 13.5 year follow-up, 533 deaths were attributed to CVD. The association of leptin with CVD mortality differed by sex (p for interaction = 0.06) and there was evidence of a low, but not a high, threshold. After adjusting for CVD risk factors, the risk for CVD mortality was 63% higher for women in the lowest leptin quintile compared to those with higher values; low leptin did not predict CVD death in men (Table 1). The association among women differed by age (p for interaction = 0.08) such that low leptin predicted 2-fold higher risk of CVD death among women age 75+, but was not related to CVD death in younger women. Excluding women with prevalent diabetes increased the risk estimate to 2.55 for women age 75+. Adjusting for or excluding those with prevalent CVD, or adjusting for IL-6 and CRP, did not alter results. In conclusion, low circulating leptin is associated with increased risk of CVD mortality among older women, but not among younger postmenopausal women or men. The association of low leptin with CVD mortality among women of advanced age may be due to residual confounding from low body fat, or low leptin could be a marker of poor health or sarcopenic processes. The absence of an association of high leptin levels with CVD death may be related to the low proportion (<10%) of obese individuals in this population.