Leptin is Positively Associated with Blood Pressure in African Men with a Low Body Mass Index: The SAfrEIC Study

Abstract

Severe underweight may be a risk factor for hypertension in developing countries, although the manner whereby this occurs is unknown. Leptin is known to exert both beneficial and detrimental vascular effects, and is predictive of poor cardiovascular outcome at high levels, but also at low levels. We explored the relationship between blood pressure and leptin in black men from South Africa with a body mass index (BMI) in the underweight to normal range. We included 113 African men (BMI≤25 kg/m²) and took anthropometric, biochemical and cardiovascular measures. The blood pressure-leptin relationship was then investigated along quintiles of leptin and within BMI stratified median split (20 kg/m²) groups. Blood pressure increased across leptin quintiles 1–3 (p for trend≤0.040), whereas no relationship was observed along quintiles 3 to 5 (p for trend≥0.14) (adjusted for age and waist circumference). Blood pressure was similar in the two BMI median split groups (p≥0.083). In the low BMI group only, blood pressure associated positively with leptin following unadjusted, partial, and full adjustment (systolic blood pressure and diastolic blood pressure: R²=0.20–0.27, β=0.32–0.34, p≤0.009). Decreasing leptin levels are not likely to contribute to hypertension prevalence in the underweight. Rather, in African men with a BMI≤20 kg/m², low leptin levels are positively and independently associated with elevated blood pressure, which is not seen at higher BMI (20–25 kg/m²). Our findings suggest a differential concentration dependent vascular effect of leptin in underweight and normal weight African men.

Key words

African ethnicity - hypertension - leptin - low BMI

• References

• 1 Twagirumukiza M, De Bacquer D, Kips JG, de Backer G, Stichele RV, Van Bortel LM. Current and projected prevalence of arterial hypertension in sub-Saharan Africa by sex, age and habitat: an estimate from population studies. J Hypertens 2011; 29: 1243-1252
• 2 Wilson PW, D’Agostino RB, Sullivan L, Parise H, Kannel WB. Overweight and obesity as determinants of cardiovascular risk: the Framingham experience. Arch Intern Med 2002; 162: 1867-1872
• 3 Tesfaye F, Nawi NG, Van Minh H, Byass P, Berhane Y, Bonita R, Wall S. Association between body mass index and blood pressure across three populations in Africa and Asia. J Hum Hypertens 2007; 21: 28-37
• 4 Montagu CT, Prins JB, Sanders L, Digby JE, O’Rahilly S. Depot – and sex-specific differences in human leptin mRNA expression: implications for the control of regional fat distribution. Diabetes 1997; 46: 342-347
• 5 Ostlund Jr RE, Yang JW, Klein S, Gingerich R. Relation between plasma leptin concentration and body fat, gender, diet, age, and metabolic covariates. J Clin Endocrinol Metab 1996; 81: 3909-3913
• 6 Friedman JM. Leptin at 14 y of age: an ongoing story. Am J Clin Nutr 2009; 89: 973S-979S
• 7 Wolk R, Somers VK. Leptin and vascular function: Friend or foe?. Eur Heart J 2006; 27: 2263-2265
• 8 Schutte AE, Schutte R. Leptin: A cardiovascular perspective. JEMDSA 2012; 17: 72-76
• 9 Nakagawa K, Higashi Y, Sasaki S, Oshima T, Matsuura H, Chayama K. Leptin causes vasodilation in humans. Hypertens Res 2002; 25: 161-165
• 10 Matsuda K, Teragawa H, Fukuda Y, Nakagawa K, Higashi Y, Chayama K. Leptin causes nitric-oxide independent coronary artery vasodilation in humans. Hypertens Res 2003; 26: 147-152
• 11 Shek EW, Brands MW, Hall JE. Chronic leptin infusion increases arterial pressure. Hypertension 1998; 31: 409-414
• 12 Carlyle M, Jones OB, Kuo JJ, Hall JE. Chronic cardiovascular and renal actions of leptin: role of adrenergic activity. Hypertension 2002; 39: 496-501
• 13 Mark AL, Agassandian K, Morgan DA, Liu X, Cassell MD, Rahmouni K. Leptin signaling in the nucleus tractus solitarii increases sympathetic nerve activity to the kidney. Hypertension 2009; 53: 375-380
• 14 Galletti F, D’Elia L, Barba G, Siani A, Cappuccio FP, Farinaro E, Iacone R, Russo O, De Palma D, Ippolito R, Strazzullo P. 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. J Clin Endocrinol Metab 2008; 93: 3922-3926
• 15 Söderberg S, Ahrén B, Stegmayr B, Johnson O, Wiklund PG, Weinehall L, Hallmans G, Olsson T. Leptin is a risk marker for first-ever hemorrhagic stroke in a population-based cohort. Stroke 1999; 30: 328-337
• 16 Ku IA, Farzaneh-Far R, Vittinghoff E, Zhang MH, Na B, Whooley MA. Association of low leptin with cardiovascular events and mortality in patients with stable coronary artery disease: the Heart and Soul Study. Atherosclerosis 2011; 217: 503-508
• 17 Marfell-Jones M, Olds T, Stewart A, Carter JEL. International Standards for Anthropometric Assessment. Potchefstroom, South Africa: ISAK 2006; 32-89
• 18 Matthews DR, Hosker JP, Rudenski AS, Naylor BA, Treacher DF, Turner RC. Homeostasis model assessment: insulin resistance and beta-cell function from fasting plasma glucose and insulin concentrations in man. Diabetologia 1985; 28: 412-419
• 19 Cockcroft DW, Gault MH. Prediction of creatinine clearance from serum creatinine. Nephron 1976; 16: 31-41
• 20 SAL Shea, Hilton MF, Orlova C, Ayers RT, Mantzoros CS. Independent circadian and sleep/wake regulation of adipokines and glucose in humans. J Clin Endocrinol Metab 2005; 90: 2537-2544
• 21 Floras JS. Blood pressure variability: a novel and important risk factor. Can J Cardiol 2013; 29: 557-563
• 22 Westerhof BE, Gisolf J, Stok WJ, Wesseling KH, Karemaker JM. Time-domain cross-correlation baroreflex sensitivity: performance on the EUROBAVAR data set. J Hypertens 2004; 22: 1371-1380
• 23 Baecke JA, Burema J, Frijters JE. A short questionnaire for the measurement of habitual physical activity in epidemiological studies. Am J Clin Nutr 1982; 36: 936-942
• 24 American Diabetes Association . Diagnosis and classification of diabetes mellitus. Diabetes Care 2011; 34: S62-S69
• 25 Thrift AG, Srikanth V, Fitzgerald SM, Kalyanram K, Kartik K, Hoppe CC, Walker KZ, Evans RG. Potential roles of high salt intake and maternal malnutrition in the development of hypertension in disadvantaged populations. Clin Exp Pharmacol Physiol 2010; 37: e78-e90
• 26 Laurent S, Cockcroft J, Van Bortel L, Boutouyrie P, Giannattasio C, Hayoz D, Pannier B, Vlachopoulos C, Wilkinson I, Struijker-Boudier H. European Network for Non-invasive Investigation of Large Arteries . Expert consensus document on arterial stiffness: methodological issues and clinical applications. Eur Heart J 2006; 27: 2588-2605
• 27 Bonyhay I, Jokkel G, Kollai M. Relation between baroreflex sensitivity and carotid artery elasticity in healthy humans. Am J Physiol 1996; 271: H1139-H1144
• 28 Barba G, Russo O, Siani A, Iacone R, Farinaro E, Gerardi MC, Russo P, Della Valle E, Strazzullo P. Plasma leptin and blood pressure in men: graded association independent of body mass and fat pattern. Obes Res 2003; 11: 160-166
• 29 Takizawa H, Ura N, Saitoh S, Wang L, Higashiura K, Takagi S, Takada M, Togashi N, Nakano M, Hayashi Y, Shimamoto K. Gender difference in the relationships among hyperleptinemia, hyperinsulinemia, and hypertension. Clin Exp Hypertens 2001; 23: 357-368
• 30 Shankar A, Xiao J. Positive relationship between plasma leptin level and hypertension. Hypertension 2010; 56: 623-628
• 31 Allison MA, Ix JH, Morgan C, McClelland RL, Rifkin D, Shimbo D, Criqui MH. Higher leptin is associated with hypertension: the Multi-Ethnic Study of Atherosclerosis. J Hum Hypertens 2013; 27: 617-622
• 32 Kramer CK, von Mühlen D, Barrett-Connor E. Does leptin predict incident hypertension in older adults?. Clin Endocrinol (Oxf) 2010; 73: 201-205
• 33 Leyva F, Godsland IF, Ghatei M, Proudler AJ, Aldis S, Walton C, Bloom S, Stevenson JC. Hyperleptinemia as a component of a metabolic syndrome of cardiovascular risk. Arterioscler Thromb Vasc Biol 1998; 18: 928-933
• 34 Wannamethee SG, Tchernova J, Whincup P, Lowe GD, Kelly A, Rumley A, Wallace AM, Sattar N. Plasma leptin: associations with metabolic, inflammatory and haemostatic risk factors for cardiovascular disease. Atherosclerosis 2007; 191: 418-426
• 35 Schutte R, Huisman HW, Schutte AE, Malan NT. Leptin is favourably associated with vascular function in obese Caucasians, but not in obese Africans. J Hum Hypertens 2005; 19: 933-939
• 36 Wang H, Necheles J, Birne JS, Li Z, Xing H, Tang G, Christoffel KK, Brickman WJ, Zimmerman D, Wang X. Association of adipokines with blood pressure in rural Chinese adolescents. J Hum Hypertens 2012; 26: 493-501
• 37 Mohammed MM, Myers DS, Sofola OA, Hainsworth R, Drinkhill MJ. Vasodilator effects of leptin on canine isolated mesenteric arteries and veins. Clin Exp Pharmacol Physiol 2007; 34: 771-774
• 38 Galletti F, D’Elia L, De Palma D, Russo O, Barba G, Siani A, Miller MA, Cappuccio FP, Rossi G, Zampa G, Strazzullo P. Hyperleptinemia is associated with hypertension, systemic inflammation and insulin resistance in overweight but not in normal weight men. Nutr Metab Cardiovasc Dis 2012; 22: 300-306
• 39 Wolk R, Berger P, Lennon RJ, Brilakis ES, Johnson BD, Somers VK. Plasma leptin and prognosis in patients with established coronary atherosclerosis. J Am Coll Cardiol 2004; 44: 1819-1824
• 40 Elkan AC, Håkansson N, Frostegård J, Cederholm T, Hafström I. Rheumatoid cachexia is associated with dyslipidemia and low levels of atheroprotective natural antibodies against phosphorylcholine but not with dietary fat in patients with rheumatoid arthritis: a cross-sectional study. Arthritis Res Ther 2009; 1: R37