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Is Leptin Associated with Hypertensive Retinopathy?¹

Departments of Endocrinology and Metabolism (G.U., M.O., I.C.O.) and Internal Medicine (A.S., C.K., T.E., B.K., F.K.), Gulhane School of Medicine, Etlik-Ankara 06018; and Bayindir Medical Center (N.B.), Sogutozu-Ankara 06520, Turkey

Address all correspondence and requests for reprints to: Metin Ozata, M.D., Department of Endocrinology and Metabolism, Gulhane School of Medicine, Etlik-Ankara 06018, Turkey. E-mail: mozata{at}obs.gata.edu.tr

Previous studies have demonstrated that elevated plasma leptin concentrations are associated with essential hypertension. It has also recently been shown that leptin plays a promoting role in angiogenesis, and the vascular endothelium expresses the long form of leptin receptor. Those data led us to hypothesize that leptin might contribute to end-organ damage in hypertension. Thus, in the present study we evaluated the relationship between plasma leptin concentrations and hypertensive retinopathy (HR). One hundred and eleven patients newly diagnosed with essential hypertension [EHT; mean age, 43.5 ± 10.7 yr; body mass index (BMI), 28.1 ± 4.4 kg/m²; male/female ratio, 71/40] and 79 healthy normotensive control subjects (NT; mean age, 43.6 ± 9.2 yr; BMI, 28.2 ± 3.3 kg/m²; male/female ratio, 50/29) were enrolled in the study. For the assessment of retinopathy according to the Keith-Wagener classification, direct and indirect ophthalmoscopy were performed in all subjects after dilatation of the pupils. Plasma leptin levels were significantly higher in EHT (11.8 ± 11.1 ng/mL) than in NT (7.2 ± 5.1ng/mL) (P = 0.003). Plasma leptin concentrations were strongly correlated with BMI in both EHT (r = 0.45; P = 0.001) and NT (r = 0.38; P = 0.001) groups. Plasma leptin in patients with grade 2 HR (24.8 ± 15.8 ng/mL; n = 22) was significantly higher than that in patients with grade 1 HR (16.1 ± 4.9 ng/mL; n = 29; P = 0.001), grade 0 HR (5.1 ± 3.1 ng/mL; n = 60; P = 0.001), and NT (P = 0.001). Plasma leptin in patients with grade 1 HR was also significantly higher than that in patients without retinopathy (P = 0.001) or in NT (P = 0.001). The estimated threshold of plasma leptin concentration for HR was 10.2 ng/mL. This critical leptin level served largely to separate patients with retinopathy from those without retinopathy. In summary, our results show that plasma leptin concentrations increase progressively with higher grades of hypertensive retinopathy even after correction for BMI, suggesting that a critical leptin level is needed for the development of retinopathy. Elevated concentrations of plasma leptin might be secondary to release of leptin by the vascular endothelium damaged by high blood pressure, as an epiphenomenon. However, a pathogenic role for leptin in hypertensive retinopathy cannot be excluded.

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