Free Leptin Is Associated With Masked Hypertension in Nonobese Subjects

Abstract

Abstract-The aim of the study was to investigate whether diverse clinical blood pressure phenotypes are associated with free leptin surrogates, as reflected by plasma leptin, human soluble leptin receptor, and their ratio (ie, free leptin index) in nonobese normoglycemic subjects. Three separate clinic blood pressure measurements and ambulatory blood pressure monitoring were implemented to divide 494 subjects (aged 44Ϯ5 years; 272 men; body mass index: Ͻ30 kg/m 2 ) into hypertensives (nϭ166), white-coat hypertensives (nϭ82), masked hypertensives (nϭ66), and normotensives (nϭ180). Participants underwent echocardiography, while, from fasting venous blood samples, metabolic profile, plasma leptin, and its receptor levels were assessed. Hypertensives and masked hypertensives demonstrated higher levels of log (10)(leptin) and log (10)(free leptin index), as well as lower levels of log (10)(human soluble leptin receptor) with respect to normotensives. White-coat hypertensives had similar free leptin surrogates compared with normotensives. Younger age, 24-hour systolic and diastolic blood pressures, 24-hour heart rate, and left ventricle mass index were common correlates of free leptin surrogates. After adjustment for confounders, masked hypertensive and hypertensive with respect to normotensive phenotype were associated with log (10)(leptin) with odds ratios (95% CIs) of 1.31 (1.12 to 3.80) and 1.26 (1.09 to 2.24), respectively, log (10)(human soluble leptin receptor) with 0.65 (0.53 to 0.78) and 0.69 (0.57 to 0.84), respectively, and log (10)(free leptin index) with 2.46 (1.32 to 7.23) and 1.84 (1.26 to 3.73), respectively (PϽ0.05 for all of the cases). Free leptin surrogates are associated with masked hypertension in nonobese normoglycemic subjects. Free leptin is almost equally increased in masked and sustained hypertension, suggesting a similar leptin-related vascular impairment. ncreased leptin levels have been independently associated with cardiovascular diseases 1 and risk factors such as obesity, insulin resistance, type 2 diabetes mellitus, 2 as well as with blood pressure (BP) levels even below the clinically defined hypertensive cutoff value. 3,4 Leptin may be implicated on the perpetuation of systemic inflammation given its modulator effect on C-reactive protein 5 and its structural and functional resemblance to proinflammatory cytokines like interleukin 6. 6 Because between hypertension and systemic inflammation there is an established reciprocal pathophysiological link, 7 hyperleptinemia might be implicated on the adverse hemodynamic regulation beyond the centrally obesity-mediated mechanisms of leptin resistance. 8 Although in vivo studies supported the notion that chronic hemodynamic actions of leptin are likely attributable to widespread sympathoactivation of metabolically active tissues and not to the vasculature to increase vasomotor tone, 9 in vitro evidence suggested that leptin at concentrations higher than the physiologically relevant level may exert adverse effects on the vasculature by periphe...

Association of resistin and adiponectin with different clinical blood pressure phenotypes

“…This is the first study to systematically examine the association of different BP clinical phenotypes with adipokines having an opposite physiological effect on cardiometabolic risk factors; we have previously used a similar design to test the association of free leptin with clinical BP phenotypes. 23 In addition, we have shown that higher levels of Res and lower levels of Adp are observed among prehypertensive and masked hypertensive subjects with respect to their normotensive counterparts matched for age, sex and body mass index. 24,25 The healthy offspring of hypertensive subjects are characterized by hyperresistinemia and hypoadiponectinemia, suggesting that the latter 'circulating duo' may precede and contribute to the development of hypertension, rather than being secondary to the increased BP.…”

Adipokines and blood pressure control

“…Recent clinical studies examined free leptin index (ratio between the concentration of leptin and the soluble leptin receptor in plasma) as an indicator of pre-hypertensive status (termed masked hypertension) in nonobese subjects [16]. Results demonstrated that the free leptin index may provide prognostic value towards hypertension and cardiovascular events.…”

Adiposity, leptin and stress reactivity in humans

“…The relationship between leptin and SNS activity in humans is less clear. Elevated plasma leptin levels have been reported in patients with hypertension, compared to normotensive individuals (Thomopoulos et al, 2009). Similarly, cross-sectional studies have found positive associations between circulating leptin and sympathetic activity indexed by blood pressure, heart rate and heart rate variability in obese and lean normotensive humans (Bravo et al, 2006; Flanagan et al, 2007; Ma et al, 2009), and a recent prospective analyses of 489 normotensive men showed that individuals with high serum leptin levels had a 33% increased risk of developing hypertension over 8 years, independent of BMI (Galletti et al, 2008).…”