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High-Circulating Leptin Levels Are Associated with Greater Risk of Hypertension in Men Independently of Body Mass and Insulin Resistance: Results of an Eight-Year Follow-Up Study

Departments of Clinical and Experimental Medicine (F.G., L.D., R.Ia., O.R., D.D.P., R.Ip., P.S.) and Preventive Medical Sciences (E.F.), Federico II University Medical School, 80131 Naples, Italy; Epidemiology and Population Genetics (G.B., A.S.), Institute of Food Science, Consiglio Nazionale delle Ricerche, 83100 Avellino, Italy; and Clinical Sciences Research Institute (F.P.C.), Warwick Medical School, Coventry CV4 7AL, United Kingdom

Address all correspondence and requests for reprints to: Drs. Ferruccio Galletti or Pasquale Strazzullo, Department of Clinical and Experimental Medicine, "Federico II" University Medical School, Via S. Pansini, 5, 80131 Naples, Italy. E-mail: galletti{at}unina.it or strazzul{at}unina.it, respectively.

Background: We previously reported a significant association between plasma leptin (LPT) concentration and blood pressure (BP), which was partly independent of serum insulin levels and insulin resistance. The aims of this study were to detect whether serum LPT levels predict the development of hypertension (HPT) in the 8-yr follow-up investigation of a sample of an adult male population (the Olivetti Heart Study), and to evaluate the role of body mass index (BMI) and insulin resistance in this putative association.

Patients and Methods: The study population was made up of 489 untreated normotensive subjects examined in 1994–1995 (age: 50.1 ± 6.7 yr; BMI: 26.3 ± 2.8 kg/m²; BP: 120 ± 10/78 ± 6 mm Hg; and homeostatic model assessment index: 2.1 ± 1.6).

Results: The HPT incidence over 8 yr was 35%. The participants with incident HPT had similar age but higher BMI (P < 0.001), serum LPT (P < 0.001), and BP (P < 0.01) at baseline. One SD positive difference in baseline serum LPT log was associated at univariate analysis with a 49% higher rate of HPT [95% confidence interval (CI) 22–83; P < 0.001]). In three different models of multivariable logistical regression analysis, LPT was respectively associated with a 41% greater risk to develop HPT (95% CI 15–74; P < 0.001) upon adjustment for age and baseline BP, with a 48% (95% CI 20–81) greater risk when adding the homeostatic assessment model index to the model, and with 33% greater risk (95% CI 6–67; P < 0.02) upon adjustment for BMI.

Conclusions: In this sample of originally normotensive men, circulating LPT level was a significant predictor of the risk to develop HPT over 8 yr, independently of BMI and insulin resistance.