Background and Purpose: Leptin, an important hormone for body weight regulation, may be involved in the pathogenesis of cardiovascular manifestations of obesity. We tested whether leptin may be an independent risk marker for stroke in a case-referent study. Methods: Definitive acute stroke events, defined by MONICA criteria, were identified from October 1, 1995 to April 30, 1999. Referents without known cardiovascular disease were randomly selected from a population census. Patient characteristics were taken from hospital files and leptin was analyzed in stored samples. Logistic regression analysis was used to determine possible differences in leptin levels between groups. Results: One hundred and thirty-seven cases with ischemic stroke and 69 cases with hemorrhagic stroke were identified. In comparison with referents, male patients with stroke had significantly higher leptin levels. Both male and female stroke patients had increased blood pressure compared with the referents. In multivariate analyses, high leptin levels were associated with both ischemic (OR = 4.89; 95% CI: 1.89–12.62) and hemorrhagic (OR = 3.86; 95% CI: 1.13–13.16) stroke in men, and with ischemic stroke in women (OR = 4.10; 95% CI: 1.45–11.62). The combination of high leptin levels and increased blood pressure (systolic or diastolic) was associated with a strong positive interaction in males with hemorrhagic stroke. Conclusion: Leptin may be an important link for the development of cerebrovascular disease in the insulin resistance syndrome in men.

1.
Wolf PA, Kannel WB, D’Agostino RB: Epidemiology of stroke; in Ginsberg MD, Bogousslavsky J (eds): Cerebrovascular Disease. Pathophysiology, Diagnosis and Management. Malden, Blackwell Science, 1998, vol 2, pp 834–849.
2.
Prevention of stroke by antihypertensive drug treatment in older persons with isolated systolic hypertension. Final results of the Systolic Hypertension in the Elderly Program (SHEP). SHEP Cooperative Research Group. JAMA 1991;265:3255–3264.
3.
MacMahon S, Peto R, Cutler J, Collins R, Sorlie P, Neaton J, Abbott R, Godwin J, Dyer A, Stamler J: Blood pressure, stroke, and coronary heart disease. 1. Prolonged differences in blood pressure: Prospective observational studies corrected for the regression dilution bias. Lancet 1990;335:765–774.
4.
Haffner SM: Epidemiology of hypertension and insulin resistance syndrome. J Hypertens Suppl 1997;15:S25–S30.
5.
Reaven GM: Banting lecture 1988. Role of insulin resistance in human disease. Diabetes 1988;37:1595–1607.
6.
Reaven GM, Lithell H, Landsberg L: Hypertension and associated metabolic abnormalities – the role of insulin resistance and the sympathoadrenal system. N Engl J Med 1996;334:374–381.
7.
Farooqi IS, Jebb SA, Langmack G, Lawrence E, Cheetham CH, Prentice AM, Hughes IA, McCamish MA, O’Rahilly S: Effects of recombinant leptin therapy in a child with congenital leptin deficiency. N Engl J Med 1999;341:879–884.
8.
Rainwater DL, Comuzzie AG, VandeBerg JL, Mahaney MC, Blangero J: Serum leptin levels are independently correlated with two measures of HDL. Atherosclerosis 1997;132:237–243.
9.
Glasow A, Haidan A, Hilbers U, Breidert M, Gillespie J, Scherbaum WA, Chrousos GP, Bornstein SR: Expression of Ob receptor in normal human adrenals: Differential regulation of adrenocortical and adrenomedullary function by leptin. J Clin Endocrinol Metab 1998;83:4459–4466.
10.
Haynes WG, Morgan DA, Walsh SA, Mark AL, Sivitz WI: Receptor-mediated regional sympathetic nerve activation by leptin. J Clin Invest 1997;100:270–278.
11.
Dunbar JC, Hu Y, Lu H: Intracerebroventricular leptin increases lumbar and renal sympathetic nerve activity and blood pressure in normal rats. Diabetes 1997;46:2040–2043.
12.
Shek EW, Brands MW, Hall JE: Chronic leptin infusion increases arterial pressure. Hypertension1998;31:409–414.
13.
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.
14.
Stegmayr B, Asplund K, Wester PO: Trends in incidence, case-fatality rate, and severity of stroke in northern Sweden, 1985–1991. Stroke 1994;25:1738–1745.
15.
Wester P, Radberg J, Lundgren B, Peltonen M: Factors associated with delayed admission to hospital and in-hospital delays in acute stroke and TIA: A prospective, multicenter study. Seek-Medical-Attention-in-Time Study Group. Stroke 1999;30:40–48.
16.
Hallqvist J, Ahlbom A, Diderichsen F, Reuterwall C: How to evaluate interaction between causes: A review of practices in cardiovascular epidemiology. J Intern Med 1996;239:377–382.
17.
Engeli S, Sharma AM: Role of adipose tissue for cardiovascular-renal regulation in health and disease. Horm Metab Res 2000;32:485–499.
18.
Söderberg S, Olsson T, Eliasson M, Johnson O, Ahrén B: Plasma leptin levels are associated with abnormal fibrinolysis in men and postmenopausal women. J Intern Med 1999;245:533–543.
19.
Mallamaci F, Cuzzola F, Tripepi G, Cutrupi S, Parlango S, Tripepi Z, Zoccali C: Gender-dependent differences in plasma leptin in essential hypertension. Am J Hypertens 2000;13:914–920.
20.
Glaum SR, Hara M, Bindokas VP, Lee CC, Polonsky KS, Bell GL, Miller RJ: Leptin, the obese gene product, rapidly modulates synaptic transmission in the hypothalamus. Mol Pharmacol 1996;50:230–235.
21.
Haynes WG, Sivitz WI, Morgan DA, Walsh SA, Mark AL: Sympathetic and cardiorenal actions of leptin. Hypertension 1997;30:619–623.
22.
Söderberg S, Ahrén B, Jansson JH, Johnson O, Hallmans G, Asplund K, Olsson T: Leptin is associated with increased risk of myocardial infarction. J Intern Med 1999;246:409–418.
23.
Bornstein SR, Licinio J, Tauchnitz R, Engelmann L, Negrao AB, Gold P, Chrousos GP: Plasma leptin levels are increased in survivors of acute sepsis: Associated loss of diurnal rhythm, in cortisol and leptin secretion. J Clin Endocrinol Metab 1998;83:280–283.
24.
Johansson A, Ahrén B, Näsman B, Carlström K, Olsson T: Cortisol axis abnormalities early after stroke – relationships to cytokines and leptin. J Intern Med 2000;247:179–187.
25.
Carlberg B, Asplund K, Hägg E: Factors influencing admission blood pressure levels in patients with acute stroke. Stroke 1991;22:527–530.
26.
Ciccone M, Vettor R, Pannacciulli N, Minenna A, Bellacicco M, Rizzon P, Giorgino R, de Pergola G: Plasma leptin is independently associated with the intima-media thickness of the common carotid artery. Int J Obes Relat Metab Disord 2001;25:805–810.
27.
Bray GA, York DA: Leptin and clinical medicine: A new piece in the puzzle of obesity. J Clin Endocrinol Metab 1997;82:2771–2776.
28.
de Courten M, Zimmet P, Hodge A, Collins V, Nicolson M, Staten M, Dowse G, Alberti KG: Hyperleptinaemia: The missing link in the metabolic syndrome? Diabet Med 1997;14:200–208.
29.
Frühbeck G: Pivotal role of nitric oxide in the control of blood pressure after leptin administration. Diabetes 1999;48:903–908.
30.
Nakata M, Yada T, Soejima N, Maruyama I: Leptin promotes aggregation of human platelets via the long form of its receptor. Diabetes 1999;48:426–429.
31.
Paolisso G, Tagliamonte MR, Galderisi M, Zito GA, Petrocelli A, Carella C, de Divitiis O, Varricchio M: Plasma leptin level is associated with myocardial wall thickness in hypertensive insulin-resistant men. Hypertension 1999;34:1047–1052.
32.
Paolisso G, Manzella D, Ferrara N, Gambardella A, Abete P, Tagliamonte MR, De Lucia D, Furgi G, Picone C, Gentile S, Rengo F, Varricchio M: Glucose ingestion affects cardiac ANS in healthy subjects with different amounts of body fat. Am J Physiol 1997;273:E471–E478.
33.
Considine RV, Sinha MK, Heiman ML, Kriauciunas A, Stephens TW, Nyce MR, Ohannesian JP, Marco CC, McKee LJ, Bauer TL: Serum immunoreactive-leptin concentrations in normal-weight and obese humans. N Engl J Med 1996;334:292–295.
34.
Ruige JB, Dekker JM, Blum WF, Stehouwer CD, Nijpels G, Mooy J, Kostense PJ, Bouter LM, Heine RJ: Leptin and variables of body adiposity, energy balance, and insulin resistance in a population-based study. The Hoorn Study. Diabetes Care 1999;22:1097–1104.
Copyright / Drug Dosage / Disclaimer
Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.
You do not currently have access to this content.