Elevated serum leptin in patients with coronary artery disease: no association with the Trp64Arg polymorphism of the β3-adrenergic receptor

Abstract

BACKGROUND: Serum leptin is associated with the occurrence of cardiovascular risk factors but it is unknown whether leptin is also associated with cardiovascular disease. Another open question is whether the Trp64Arg polymorphism of the b b 3 -adrenergic receptor (b 3 -AR) is a determinant of circulating leptin. OBJECTIVES: We measured serum leptin concentrations in a large group of patients with angiographically assessed coronary artery disease (CAD) and investigated the relationship between the Trp64Arg polymorphism of the b 3 -adrenergic receptor (AR) and serum leptin. PATIENTS AND METHODS: Leptin was measured in the fasting state in 1000 consecutive patients with angiographically con®rmed CAD by radioimmunoassay. The codon 64 TaC polymorphism of the b b 3 -AR gene was analysed by the polymerase chain reactionarestriction fragment length polymorphism (PCRaRFLP) technique. Controls were 1000 age-, gender-and weight-matched subjects without clinical signs of CAD. RESULTS: Serum leptin concentrations were signi®cantly higher in patients with CAD than in those without CAD (median: 6.8 vs 6.1 ngaml, P`0.001). In a multiple regression analysis leptin was found to be a determinant of CAD (P 0.005) along with established risk factors. No differences in serum leptin were observed between wild-type and heterozygous carriers of the Trp64Arg mutation of the b 3 -AR gene, whereas the small group of homozygous carriers had higher leptin due to their higher BMI. In a multiple linear regression analysis, body mass index, gender and fasting insulin were the main signi®cant determinants of serum leptin, whereas the b 3 -AR polymorphism had no effect. CONCLUSIONS: Patients with coronary artery disease exhibit higher serum leptin concentrations than age-and gender-matched controls of comparable BMI, indicating that leptin could contribute to the development of cardiovascular disease, possibly via activation of the sympathetic nervous system. The Trp64Arg variant of the b 3 -adrenoceptor did not in¯uence serum leptin.

Leptin Causes Nitric-Oxide Independent Coronary Artery Vasodilation in Humans.

“…These findings suggest that leptin causes coronary vasodilation at subphysiologic leptin concentrations, but the degree of coronary vasodilation induced by leptin may decrease at or above physiologic leptin concentrations, and this phenomenon may be associated with "leptin resistance" (21). These factors may contribute to the differences seen between epidemiologic studies (19,20) and ours. It is likely that leptin may be used orally as an anti-obesity agent in the near future.…”

“…In addition, it is possible that differences in leptin concentration may contribute to the differing responses of the coronary arteries. In the present study, the baseline leptin concentration was 3.6 ng/ml and did not differ from the values reported ( 5 ng/ml) in the above studies (19,20). Although we showed that leptin-induced coronary vasodilation is not associated with the baseline leptin concentration, the mean body mass index was 24.5 0.8 kg/m 2 , and severely obese patients were not included in the present study.…”

“…Several epidemiologic studies have shown that hyperleptinemia is a risk factor for coronary artery disease (19,20), suggesting that an increased leptin concentration may unfavorably influence the coronary arteries. However, we have demonstrated that acute infusion of leptin dilates the coronary arteries without any significant change in hemodynamic variables or metabolic parameters, suggesting a favorable effect of leptin on the coronary arteries.…”

No Influence of Surgical Stress on Postoperative Leptin Gene Expression in Different Adipose Tissues and Soluble Leptin Receptor Plasma Levels

“…This difference is probably due to the fact that BMI in carcinoma patients was significantly lower than in patients with heart disease. This observation is in line with a recent report of higher plasma leptin concentrations in patients with coronary heart disease compared to a control group [29]. On the other hand, in cancer patients, a tendency of lower leptin levels has been described [30].…”

Association of leptin levels with pathogenetic risk of coronary heart disease and stroke: a meta-analysis

“…revealed that leptin was an independent risk factor for acute myocardial infarction even after adjustment of several cardiovascular risk factors, such as high BMI, blood pressure and hyperinsulinaemia (15). Meanwhile, a later cross-sectional study also demonstrated that serum leptin was a significant determinant of CAD in addition to other established cardiovascular risk factors, such as smoking, age, gender, fasting insulin and BMI, and the capacity of leptin activating the sympathetic nervous system was considered as pivotal role for the significant association (28). Notably, discrepant results observed from these and subsequent studies mainly attributed to different study design, particularly the different treatment for various cardiovascular risk factors.…”