Emin DEMİREL, Serkan GÖKASLAN, Çiğdem ÖZER GÖKASLAN, Sefa ÇELİK

Role of aortic stiffness and inflammation in the etiology of young-onset hypertension

Background/aim: Young-onset hypertension is a form of condition diagnosed in patients aged below 40. Cytokines such as interleukin(IL)-6 and also MCP-1 may play a role in the development of arterial hypertension. Aortic stiffness can be detected by measuring pulsewave velocity (PWV). We aimed to explore the relationship between inflammation and aortic stiffness and investigate their roles in theetiology of young-onset hypertension.Materials and methods: We enrolled 16 patients diagnosed with young-onset hypertension and 16 volunteers without hypertension.The plasma levels of MCP-1 and IL-6 were determined using an enzyme-linked immunosorbent assay and quantitative enzyme-linkedimmunoassay, respectively. Carotid-femoral PWV was measured using an arteriograph device.Results: Compared with those in normotensive controls, the plasma levels of IL-6 and MCP-1 and the PWV values were significantlyhigher in patients with young-onset hypertension (P < 0.001). PWV values were also positively correlated with the levels of MCP-1 andIL-6. However, no statistically significant difference was noted in intima-media thickness between the two groups (P = 0.224).Conclusion: In this study, increased PWVs and the levels of inflammation markers were associated with aortic stiffness and inflammationin patients with young-onset hypertension, suggesting they have a role in the etiology of hypertension.

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1. Alwan A. Global Status Report on Noncommunicable Diseases 2010. Geneva, Switzerland: World Health Organization; 2011.
2. Ejima Y, Hasegawa Y, Sanada S, Miyama N, Hatano R et al. Characteristics of young-onset hypertension identified by targeted screening performed at a university health check-up. Hypertension Research 2006; 29 (4): 261-267
3. Burt VL, Whelton P, Roccella EJ, Brown C, Cutler JA et al. Prevalence of hypertension in the US adult population. Results from the Third National Health and Nutrition Examination Survey, 1988–1991. Hypertension 1995; 25 (3): 305-313.
4. Colhoun HM, Dong W, Poulter NR. Blood pressure screening, management and control in England: results from the health survey for England 1994. Journal of Hypertension 1998; 16 (6): 747-752.
5. McCarron RM, Wang L, Siren AL, Spatz M, Hallenback JM. Monocyte adhesion to cerebromicrovascular endothelial cells derived from hypertensive and normotensive rats. American Journal of Physiology 1994; 267 (6 Pt 2): H2491-H2497.
6. Liu Y, Liu T, McCarron RM, Spatz M, Feuerstein G et al. Evidence for activation of endothelium and monocytes in hypertensive rats. American Journal of Physiology 1996; 270 (6 Pt 2): H2125-31.
7. Chae CU, Lee RT, Rifai N, Ridker PM. Blood pressure and inflammation in apparently healthy men. Hypertension 2001; 38 (3): 399-403.
8. Luther JM, Gainer JV, Murphey LJ, Yu C, Vaughan DE et al. Angiotensin II induces interleukin-6 in humans through a mineralocorticoid receptor-dependent mechanism. Hypertension 2006; 48 (6): 1050-1057.
9. Chamarthi B, Williams GH, Ricchiuti V, Srikumar N, Hopkins PN et al. Inflammation and hypertension: the interplay of interleukin-6, dietary sodium, and the renin-angiotensin system in humans. American Journal of Hypertension 2011; 24 (10): 1143-1148.
10. O’Hayre M, Salanga CL, Handel TM, Allen SJ. Chemokines and cancer: migration, intracellular signalling and intercellular communication in the microenvironment. Biochemical Journal 2008; 409 (3): 635-649.
11. Stumpf C, Raaz D, Klinghammer L, Schneider M, Schmieder RE et al. Platelet CD40 contributes to enhanced monocyte chemoattractant protein 1 levels in patients with resistant hypertension. European Journal of Clinical Investigation 2016; 46 (6): 564-571.
12. Hansson GK, Libby P. The immune response in atherosclerosis: a double-edged sword. Nature Reviews Immunology 2006; 6 (7): 508-519.
13. Zhang Y, Agnoletti D, Protogerou AD, Topouchian J, Wang JG et al. Characteristics of pulse wave velocity in elastic and muscular arteries: a mismatch beyond age. Journal of Hypertension 2013; 31 (3): 554-559.
14. Yu WC, Chuang SY, Lin YP, Chen CH. Brachial-ankle vs carotid-femoral pulse wave velocity as a determinant of cardiovascular structure and function. Journal of Human Hypertension 2008; 22 (1): 24-31.
15. Kass DA. Ventricular arterial stiffening: integrating the pathophysiology. Hypertension 2005; 46 (1): 185-193.
16. Mancia G, Fagard R, Narkiewicz K, Redon J, Zanchetti A et al. 2013 ESH/ESC guidelines for the management of arterial hypertension: the Task Force for the management of arterial hypertension of the European Society of Hypertension (ESH) and of the European Society of Cardiology (ESC). Journal of Hypertension 2013; 31 (7): 1281-1357.
17. Zhang Y, Agnoletti D, Xu Y, Wang JG, Blacher J et al. Carotid-femoral pulse wave velocity in the elderly. Journal of Hypertension 2014; 32 (8): 1572-1576.
18. Townsend RR, Wilkinson IB, Schiffrin EL, Avolio AP, Chirinos JA et al. Recommendations for improving and standardizing vascular research on arterial stiffness: a scientific statement from the American Heart Association. Hypertension 2015; 66 (3): 698-722.
19. Nambi V, Chambless L, Folsom AR, He M, Hu Y et al. Carotid intima-media thickness and presence or absence of plaque improves prediction of coronary heart disease risk: The ARIC (Atherosclerosis Risk In Communities) study. Journal of the American College of Cardiology 2010; 55 (15): 1600-1607.
20. Nichols WW, Pepine CJ, O’Rourke MF. Carotid-artery intima and media thickness as a risk factor for myocardial infarction and stroke. New England Journal of Medicine 1999; 340 (22): 1762-1763.
21. Ikeda N, Kogame N, Iijima R, Nakamura M, Sugi K. Impact of carotid artery ultrasound and ankle-brachial index on prediction of severity of SYNTAX score. Circulation Journal 2013; 77 (3): 712-716.
22. Cheng KS, Mikhailidis DP, Hamilton G, Seifalian AM. A review of the carotid and femoral intima-media thickness as an indicator of the presence of peripheral vascular disease and cardiovascular risk factors. Cardiovascular Research 2002; 54 (3): 528-538.
23. Touboul PJ, Hennerici MG, Meairs S, Adams H, Amarenco P et al. Mannheim carotid intima-media thickness consensus (2004-2006). An update on behalf of the Advisory Board of the 3rd and 4th Watching the Risk Symposium, 13th and 15th European Stroke Conferences, Mannheim, Germany, 2004, and Brussels, Belgium, 2006. Cerebrovascular Diseases 2007; 23 (1): 75-80.
24. Laurent S, Boutouyrie P, Asmar R, Gautier I, Laloux B et al. Aortic stiffness is an independent predictor of all-cause and cardiovascular mortality in hypertensive patients. Hypertension 2001; 37 (5): 1236-1241.
25. Virdis A, Schiffrin EL. Vascular inflammation: a role in vascular disease in hypertension? Current Opinion in Nephrology and Hypertension 2003;12 (2): 181-187.
26. Hilgers KF. Monocytes/macrophages in hypertension. Journal of Hypertension 2002; 20 (4): 593-596.
27. Li JJ, Fang CH, Huio RT. Is hypertension an inflammatory disease? Medical Hypotheses 2005; 64 (2): 236-240.
28. Kranzhöfer R, Schmidt J, Pfeiffer CAH, Hagl S, Libby P et al. Angiotensin induces inflammatory activation of human vascular smooth muscle cells. Arteriosclerosis, Thrombosis, and Vascular Biology 1999; 19 (7): 1623-1629.
29. Schieffer B, Schieffer E, Hilfiker-Kleiner D, Hilfiker A, Kovanen PT et al. Expression of angiotensin II and interleukin 6 in human coronary atherosclerotic plaques: potential implications for inflammation and plaque instability. Circulation 2000; 101 (12): 1372-1378.
30. Lee DL, Sturgis LC, Labazi H, Osborne JB Jr, Fleming C et al. Angiotensin II hypertension is attenuated in interleukin-6 knock out mice. American Journal of Physiology Heart and Circulatory Physiology 2006; 290 (3): H935-940.
31. Ikeda U, Ikeda M, Oohara T, Ohuchi A, Kamitani T et al. Interleukin 6 stimulates growth of vascular smooth muscle cells in a PDGF-dependent manner. American Journal of Physiology 1991; 260 (Pt 2): H1713-1717.
32. Rossi D, Zlotnik A. The biology of chemokines and their receptors. Annual Review of Immunology 2000; 18: 217-242.
33. Okada M, Matsumori A, Ono K, Furukawa Y, Shioi T et al. Cyclic stretch upregulates production of interleukin-8 and monocyte chemotactic and activating factor/monocyte chemoattractant protein-1 in human endothelial cells. Arteriosclerosis, Thrombosis, and Vascular Biology 1998; 18 (6): 894-901.
34. Wung BS, Cheng JJ, Chao YJ, Lin J, Shyy YJ et al. Cyclical strain increases monocyte chemotactic protein-1 secretion in human endothelial cells. American Journal of Physiology 1996; 270 (4 Pt 2): H1462-1468.
35. Sheikine Y, Hansson GK. Chemokines and atherosclerosis. Annals of Medicine 2004; 36 (2): 98-118.
36. Schutte AE, Schutte R, Huisman HW, van Rooyen JM, Fourie CM et al. Are behavioural risk factors to be blamed for the conversion from optimal blood pressure to hypertensive status in Black South Africans? A 5-year prospective study. International Journal of Epidemiology 2012; 41 (4): 1114-1123.
37. Vlachopoulos C, Aznaouridis K, Stefanadis C. Prediction of cardiovascular events and all-cause mortality with arterial stiffness: a systematic review and meta-analysis. Journal of the American College of Cardiology 2010; 55 (13): 1318-1327.
38. Ben-Shlomo Y, Spears M, Boustred C, May M, Anderson SG et al. Aortic pulse wave velocity improves cardiovascular event prediction: an individual participant meta-analysis of prospective observational data from 17,635 subjects. Journal of the American College of Cardiology 2014; 63 (7): 636-646.
39. Blacher J, Asmar R, Djane S, London GM, Safar ME. Aortic pulse wave velocity as a marker of cardiovascular risk in hypertensive patients. Hypertension 1999; 33(5): 1111-1117.
40. Mitchell GF, Parise H, Benjamin EJ, Larson MG, Keyes MJ et al. Changes in arterial stiffness and wave reflection with advancing age in healthy men and women: the Framingham Heart Study. Hypertension 2004; 43 (6): 1239-1245.
41. Tomiyama H, Arai T, Koji Y, Yambe M, Motobe K et al. The age-related increase in arterial stiffness is augmented in phases according to the severity of hypertension. Hypertension Research 2004; 27 (7): 465-470.
42. Benetos A, Asamopouolos C, Bureau JM, Temmar M, Labat C et al. Determinants of accelerated progression of arterial stiffness in normotensive subjects and in treated hypertensive subjects over a 6-year period. Circulation 2002; 105 (10): 1202- 1207.
43. Stein JH, Korcarz CE, Hurst RT, Lonn E, Kendall CB et al. Use of carotid ultrasound to identify subclinical vascular disease and evaluate cardiovascular disease risk: a consensus statement from the American Society of Echocardiography Carotid Intima-Media Thickness Task Force. Endorsed by the Society for Vascular Medicine. Journal of the American Society of Echocardiography 2008; 21 (2): 93-111.
44. Mancini GB, Dahlof B, Diez J. Surrogate markers for cardiovascular disease: structural markers. Circulation 2004; 109 (25 Suppl 1): IV22-30.
45. Roman MJ, Saba PS, Pini R, Spitzer M, Pickering TG et al. Parallel cardiac and vascular adaptation in hypertension. Circulation 1992; 86 (6): 1909-1918.
46. Grobbee DE, Bots ML. Carotid artery intima-media thickness as an indicator of generalized atherosclerosis. Journal of Internal Medicine 1994; 236 (5): 567-573.
47. Van Bortel LM. What does intima-media thickness tell us? Journal of Hypertension 2005; 23 (1): 37-39.