- Research Article
- Open access
- Published:
Inflammatory status, arterial stiffness and central hemodynamics in hypertensive patients with metabolic syndrome
Artery Research volume 3, pages 115–121 (2009)
Abstract
Introduction
Inflammatory state is activated in metabolic syndrome and may explain part of the adverse prognosis of this entity. Arterial stiffness, central blood pressures and wave reflections are independent predictors of cardiovascular risk. This study investigates the relation between low-grade inflammation and arterial stiffness and central hemodynamics in patients with metabolic syndrome.
Methods
We studied 106 consecutive hypertensive patients with metabolic syndrome. Arterial stiffness was assessed by carotid-femoral (c-f) and carotid-radial (c-r) pulse wave velocity (PWV). Central blood pressures were evaluated by pulse wave analysis and heart rate corrected augmentation index (AIx75) was used as a measure of wave reflections. White blood cell count (WBC), high sensitivity C-reactive protein (hsCRP) and fibrinogen were measured as inflammatory markers.
Results
In univariable analysis, PWVc-f correlated with both hsCRP (p < 0.01) and fibrinogen (p < 0.01), while PWVc-r correlated with hsCRP (p = 0.05). Regarding central blood pressures, aortic SBP correlated positively with hsCRP (p < 0.05) and marginally with fibrinogen (p = 0.06) and WBC (p = 0.08). Interestingly, no correlation was found between AIx75 and any of these biomarkers. After adjustment for age, gender, smoking, mean arterial pressure, heart rate, waist circumference, glucose, total and HDL cholesterol, PWVc-f was independently related to hsCRP (p < 0.001) and fibrinogen (p < 0.01), while a marginal independent correlation was also found between PWVc-r and hsCRP (p = 0.06). Furthermore, aortic PP independently associated with fibrinogen (p < 0.05) whereas marginal associations demonstrated between aortic SBP and hsCRP and fibrinogen (p = 0.06 for both).
Conclusion
Inflammatory status is related to arterial stiffness and central blood pressures (but not to augmentation index) in hypertensives with metabolic syndrome. These findings may have implications for increased cardiovascular risk in these patients.
References
Gami AS, Witt BJ, Howard DE, Erwin PJ, Gami LA, Somers VK, et al. Metabolic syndrome and risk of incident cardiovascular events and death: a systematic review and meta-analysis of longitudinal studies. J Am Coll Cardiol 2007;49:403–14.
Schillaci G, Pirro M, Vaudo G, Gemelli F, Marchesi S, Porcellati C, et al. Prognostic value of the metabolic syndrome in essential hypertension. J Am Coll Cardiol 2004;43:1817–22.
Ford E. The metabolic syndrome and C-reactive protein, fibrinogen, and leukocyte count:findings from the Third National Health and Nutrition Examination Survey. Atherosclerosis 2003;168:351–8.
Wannamethee SG, Lowe GDO, Shaper AG, Rumley A, Lennon L, Whincup P. The metabolic syndrome and insulin resistance: relationship to haemostatic and inflammatory markers in older non-diabetic men. Atherosclerosis 2005;181:101–8.
Laurent S, Cockcroft J, van Bortel L, Boutouyrie P, Giannatasio C, Hayoz D, et al. On behalf of the European Network for Non-invasive investigation of Large Arteries. Expert consensus document on arterial stiffness: methodological issues and clinical applications. Eur Heart J 2006;27:2588–605.
Agabiti-Rosei E, Mancia G, O’Rourke MF, Roman MJ, Safar ME, Smulyan H, et al. Central blood pressure measurements and antihypertensive therapy: a consensus document. Hypertension 2007;50:154–60.
van People NM, Westendorp IC, Bots ML, Reneman RS, Hoeks AP, Hofman A, et al. Variables of the insulin resistance syndrome are associated with reduced arterial distensibility in healthy non-diabetic middle-aged women. Diabetologia 2000;43:665–72.
Safar M, Thomas F, Blacher J, Nzietchueng R, Bureau JM, Pannier B, et al. Metabolic syndrome and age-related progression of aortic stiffness. J Am Coll Cardiol 2006;47:72–5.
Protogerou A, Blacher J, Aslangul E, Le Jeunne C, Lekakis J, Mavrikakis M, et al. Gender influence on metabolic syndrome’s effects on arterial stiffness and pressure wave reflections in treated hypertensive subjects. Atherosclerosis 2007;193:151–8.
Scuteri A, Najjar S, Muller D, Andres R, Hougaku H, Metter J, et al. Metabolic syndrome amplifies the age-associated increases in vascular thickness and stiffness. J Am Coll Cardiol 2004;43:1388–95.
Czernichow S, Bertrais S, Blacher J, Oppert JM, Galan P, Ducimetière P, et al. Metabolic syndrome in relation to structure and function of large arteries: a predominant effect of blood pressure. Am J Hypertens 2005;18:1154–60.
Schillaci G, Pirro M, Vaudo G, Mannarino M, Savarese G, Pucci G, et al. Metabolic syndrome is associated with aortic stiffness in untreated essential hypertension. Hypertension 2005;45:1078–82.
El Feghali R, Topouchian J, Pannier B, Asmar R. Ageing and blood pressure modulate the relationship between metabolic syndrome and aortic stiffness in never-treated essential hypertensive patients. A comparative study. Diabetes Metab 2007;33:183–8.
Mulè G, Cottone S, Mongiovi R, Cusimano P, Mezzatesta G, Seddio G, et al. Influence of the metabolic syndrome on aortic stiffness in never treated hypertensive patients. Nutr Metab Cardiovasc Dis 2006;16:54–9.
Vyssoulis GP, Pietri PG, Karpanou EA, Vlachopoulos CV, Kyvelou SM, Spanos P, et al. Differential impact of metabolic syndrome on arterial stiffness and wave reflections: Focus on distinct definitions. Int J Cardiol; 2008 [Epub ahead of print].
Plantinga Y, Ghiadoni L, Magagna A, Giannarelli C, Penno G, Pucci L, et al. Peripheral wave reflection and endothelial function in untreated essential hypertensive patients with and without the metabolic syndrome. J Hypertens 2008;26:1216–22.
Vlachopoulos C, Dima I, Aznaouridis K, Vasiliadou C, Ioakeimidis N, Aggeli C, et al. Acute systemic inflammation increases arterial stiffness and decreases wave reflections in healthy individuals. Circulation 2005;112:2193–200.
Yasmin McEniery C, Wallace S, Mackenzie I, Cockcroft J, Wilkinson I. C-reactive protein is associated with arterial stiffness in apparently healthy individuals. Arterioscler Thromb Vascul Biol 2004;24:969–74.
Pietri P, Vyssoulis G, Vlachopoulos C, Zervoudaki A, Gialernios T, Aznaouridis K, et al. Relationship between low-grade inflammation and arterial stiffness in patients with essential hypertension. J Hypertens 2006;24:2231–8.
Mahmud A, Feely J. Arterial stiffness is related to systemic inflammation in essential hypertension. Hypertension 2005;46:1118–22.
Vlachopoulos C, Pietri P, Aznaouridis K, Vyssoulis G, Vasiliadou C, Bratsas A, et al. Relationship of fibrinogen with arterial stiffness and wave reflections. J Hypertens 2007;25:2110–6.
Tomiyama H, Koji Y, Yambe M, Kohki M, Shiina K, Gulnisa Z, et al. Elevated C-reactive protein augments increased arterial stiffness in subjects with metabolic syndrome. Hypertension 2005;45:997–1003.
Ferreira I, Boreham C, Twisk J, Gallagher A, Young I, Murray L, et al. Clustering of metabolic syndrome risk factors and arterial stiffness in young adults:the Northern Ireland Young Hearts Project. J Hypertens 2007;25:1009–20.
Wildman R, Mackey R, Bostom A, Thompson T, Sutton-Tyrrell K. Measures of obesity are associated with vascular stiffness in young and older adults. Hypertension 2003;42:468–73.
Castell JV, Gomez-Lechon MJ, David M, Fabra R, Trullenque R, Heinrich PC. Acute-phase response of human hepatocytes: regulation of acute-phase protein synthesis by interleukin-6. Hepatology 1990;12:1179–86.
Wang C-H, Li S-H, Weisel R, Fedak P, Dumont A, Szmitko P, et al. C-reactive protein upregulates angiotensin type 1 receptors in vascular smooth muscle. Circulation 2003;107:1783–90.
Pasceri V, Willerson JT, Yeh ET. Direct proinflammatory effect of C-reactive protein on human endothelial cells. Circulation 2000;102:2165–8.
Clapp B, Hirschfield G, Storry C, Gallimore JR, Stidwill R, Singer M, et al. Inflammation and endothelial function. Direct vascular effects of human C-reactive protein on nitric oxide bioavailability. Circulation 2005;111:1530–6.
Tsioufis C, Dimitriadis K, Selima M, Thomopoulos C, Mihas C, Skiadas I, et al. Low-grade inflammation and hypoadiponectinaemia have an additive detrimental effect on aortic stiffness in essential hypertensive patients. Eur Heart J 2007;28:1162–9.
Schumacher W, Cockcroft J, Timpson NJ, McEniery CM, Gallacher J, Rumley A, et al. Association between C-reactive protein genotype, circulating levels and aortic pulse wave velocity. Hypertension 2009;53:150–7.
Vlachopoulos C, Terentes-Printzios D, Dima I, Aznaouridis K, Stefanadis C. Polymorphims of inflammatory markers/mediators and arterial stiffness. Hypertension 2009;53:e39.
Lund T, Osterud B. Fibrinogen increases lipopolysaccharide-induced tumor necrosis factor-a and interleukin-8 release, and enhances tissue factor activityin monocytes in a modified whole blood system. Blood Coagul Fibrinolysis 2001;12:667–75.
Wilkinson IB, MacCallum H, Cockcroft JR, Webb DJ. Inhibition of basal nitric oxide synthesis increases aortic augmentation index and pulse wave velocity in vivo. Br J Clin Pharmacol 2002;53:189–92.
Harley SL, Sturge J, Powell JT. Regulation by fibrinogen and its products of intercellular adhesion molecule-1 expression in human saphenous vein endothelial cells. Arterioscler Thromb Vasc Biol 2003;163:2285–9.
Guo M, Sahni SK, Sahni A, Francis CW. Fibrinogen regulates the expression of inflammatory chemokines through NF-kappa B activation of endothelial cells. Thromb Heamost 2004;92:858–66.
Feinbloom D, Bauer KA. Assessment of hemostatic risk factors in predicting arterial thrombotic events. Arterioscler Thromb Vasc Biol 2005;25:2043–53.
Greenfield JR, Samaras K, Campbell LV, Jenkins AB, Kelly PJ, Spector TD, et al. Physical activity reduces genetic susceptibility to increased central systolic pressure augmentation: a study of female twins. J Am Coll Cardiol 2003;42:264–70.
Maple-Brown L, Piers L, O’Rourke M, Celermajer D, O’Dea K. Central obesity is associated with reduced peripheral reflection in Indigenous Australians irrespective of diabetes status. J Hypertens 2005;23:1403–7.
Laurent S, Cockcroft J, Van Bortel L, Boutouyrie P, Giannattasio C, Hayoz D, et al. on behalf of the European Network for Non Invasive Investigation of Large Arteries. Abridged version of the expert consensus document on arterial stiffness. Artery Res 2007;1:2–12.
Vlachopoulos C, Stefanadis C. In: Laurent S, Cockcroft J, editors. Central aortic blood pressure. 1st ed. France: Elsevier; 2008. p 13–25.
Nichols WW, O’Rourke MF, editors. McDonald’s blood flow in arteries. 4th ed. London: Edward Arnold; 1998. pp.170–222, 284–315, 347–395, 450–476.
Williams B, Lacy P, Thom S, Cruickshank K, Stanton A, Collier D, et al. CAFE Investigators; Anglo-Scandinavian Cardiac Outcomes Trial Investigators; Cafe Steering Committee and Writing Committee. Differential impact of blood pressure-lowering drugs on central aortic pressure and clinical outcomes. Principal results of the conduit artery function evaluation (CAFE) study. Circulation 2006;113:1213–25.
Agata J, Nagahara D, Kinoshita S, Takagawa Y, Moniwa N, Yoshida D, et al. Angiotensin II receptor blocker prevents increased arterial stiffness in patients with essential hypertension. Circ J. 2004;68:1194–8.
Di Napoli M, Papa F. Angiotensin-converting enzyme inhibitor is associated with reduced concentration of C-reactive protein in patients with first-ever ischemic stroke. Stroke 2003;34:2922–9.
Fliser D, Buchholz K, Haller H. for the European Trial on Olmesartan and Pravastatin in Inflammation and Atherosclerosis (EUTOPIA) investigators. Antiiflammatory effects of angiotensin II subtype 1 receptor blockcade in hypertensive patients with microinflammation. Circulation 2004;110:1103–7.
Fogari R, Zoppi A, Lazzari P, Preti P, Mugellini A, Corradi L, et al. ACE inhibition but not angiotensin II antagonism reduces plasma fibrinogen and insulin resistance in overweight hypertensive patients. J Cardiovasc Pharmacol 1998;32:616–20.
Vyssoulis GP, Marinakis AG, Aznaouridis KA, Karpanou EA, Arapogianni AN, Cokkinos DV, et al. The impact of third-generation beta-blocker antihypertensive treatment on endothelial function and the prothrombotic state: effects of smoking. Am J Hypertens 2004;17:582–9.
Devaraj S, Chan E, Jialal I. Direct demonstration of an antiinflammatory effect of simvastatin in subjects with the metabolic syndrome. J Clin Endocrinol Metab 2006;91:4489–96.
Ridker P, Cushman M, Stampfer MJ, Tracy R, Hennekens C. Inflammation, aspirin and the risk of cardiovascular disease in apparently healthy men. N. Engl J Med 1997;336:973–9.
Pitsavos C, Panagiotakos DB, Chrysohoou C, Kavouras S, Stefanadis C. The associations between physical activity, inflammation, and coagulation markers, in people with metabolic syndrome: the ATTICA study. Eur J Cardiovasc Prev Rehabil 2005;12:151–8.
Giugliano D, Ceriello A, Esposito K. The effects of diet on inflammation. Emphasis on the metabolic syndrome. J Am Coll Cardiol 2006;48:677–85.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
This is an open access article distributed under the CC BY-NC license. https://doi.org/creativecommons.org/licenses/by/4.0/
About this article
Cite this article
Pietri, P., Vlachopoulos, C., Aznaouridis, K. et al. Inflammatory status, arterial stiffness and central hemodynamics in hypertensive patients with metabolic syndrome. Artery Res 3, 115–121 (2009). https://doi.org/10.1016/j.artres.2009.09.001
Received:
Revised:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1016/j.artres.2009.09.001