Vol 25, No 1 (2021)
Original paper
Published online: 2021-03-15

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Myeloperoxidase (MPO) and high sensitivity C-reactive protein (hsCRP) as inflammatory biomarkers of endothelial and leukocyte activation in overweight hypertensive patients

Dunja Buljubasic1, Ines Drenjancevic2, Aleksandar Kibel32, Lada Zibar45, Vedrana Vizjak6, Sanja Mandic78, Tatjana Bacun910
Arterial Hypertension 2021;25(1):15-21.

Abstract

Background: Low-grade inflammation mediates the relation between overweight and the development of cardiovascular diseases. The study aimed to examine if myeloperoxidase (MPO) and hsCRP (high-sensitivity C-reactive protein) in overweight hypertensive patients can be used as biomarkers of endothelial and leukocyte activation.

Material and methods: Seventy-five subjects were included in the study; 38 had essential arterial hypertension (AH) and 37 were normotensive controls (NC), subsequently divided into overweight (OW; BMI ≥ 25 kg/m2) and normal weight subgroups (NW; BMI < 25 kg/m2). Body mass index (BMI), inflammatory markers concentrations, association of MPO and hsCRP with AH and/or overweight were assessed.

Results: AH patients had higher MPO (median 132.5 pmol/L, IQR: 53.8–691.9) (p < 0.001), while hsCRP did not significantly differ compared to normotensive controls (NC). NW-AH patients had higher MPO (p = 0.02) than normotensive NW patients. MPO was similar between normotensive patients OW and NW, while hsCRP concentration was significantly higher in the OW (median 1.85 mg/L, IQR: 0.47–7.19) (p = 0.01) compared to NW. OW-AH patients had significantly higher MPO (median 137.4 pmol/L, IQR: 53.80–703.4) (p = 0.002) compared to normotensive NW and OW (p < 0.001) patients, likely reflecting neutrophilic activation in hypertension. Additionaly, OW-AH patients had significantly higher hsCRP (median 1.71 mg/L, IQR: 0.22–14) (p = 0.005) than normotensive NW patients. hsCRP significantly positively correlated with BMI in both AH (r = 0.41, p = 0.009) and NC groups (r = 0.38, p = 0.01), while MPO did not correlate, supporting inflammation in OW, particularly in OW with AH.

Conclusions: All together, the results suggest that inflammation may mediate mutual association of AH and OW, suggesting MPO as inflammatory biomarker for AH and hsCRP for overweight.

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References

  1. Lewington S, Clarke R, Qizilbash N, et al. Prospective Studies Collaboration. Age-specific relevance of usual blood pressure to vascular mortality: a meta-analysis of individual data for one million adults in 61 prospective studies. Lancet. 2002; 360(9349): 1903–1913.
  2. Jelaković B, Željković-Vrkić T, Pećin I, et al. Arterijska hipertenzija u Hrvatskoj.Rezultati EH-UH studije. Acta Med Croatica. 2007; 61: 287–92.
  3. Boos CJ, Lip GYH. Is hypertension an inflammatory process? Curr Pharm Des. 2006; 12(13): 1623–1635.
  4. Kakar P, Lip GYH. Towards understanding the aetiology and pathophysiology of human hypertension: where are we now? J Hum Hypertens. 2006; 20(11): 833–836.
  5. Sinisalo J, Paronen J, Mattila KJ, et al. Relation of inflammation to vascular function in patients with coronary heart disease. Atherosclerosis. 2000; 149(2): 403–411.
  6. Schwedler SB, Kuhlencordt PJ, Ponnuswamy PP, et al. Native C-reactive protein induces endothelial dysfunction in ApoE-/- mice: implications for iNOS and reactive oxygen species. Atherosclerosis. 2007; 195(2): e76–e84.
  7. Libby P. Inflammation in atherosclerosis. Nature. 2002; 420(6917): 868–874.
  8. Steffel J, Lüscher TF. Predicting the development of atherosclerosis. Circulation. 2009; 119(7): 919–921.
  9. Kim JS, Kang TS, Kim JB, et al. Significant association of C-reactive protein with arterial stiffness in treated non-diabetic hypertensive patients. Atherosclerosis. 2007; 192(2): 401–406.
  10. Souza JR, Oliveira RT, Blotta MH, et al. Serum levels of interleukin-6 (Il-6), interleukin-18 (Il-18) and C-reactive protein (CRP) in patients with type-2 diabetes and acute coronary syndrome without ST-segment elevation. Arq Bras Cardiol. 2008; 90(2): 86–90.
  11. Venugopal SK, Devaraj S, Yuhanna I, et al. Demonstration that C-reactive protein decreases eNOS expression and bioactivity in human aortic endothelial cells. Circulation. 2002; 106(12): 1439–1441.
  12. Hein TW, Singh U, Vasquez-Vivar J, et al. Human C-reactive protein induces endothelial dysfunction and uncoupling of eNOS in vivo. Atherosclerosis. 2009; 206(1): 61–68.
  13. Guan H, Wang P, Hui R, et al. Adeno-associated virus-mediated human C-reactive protein gene delivery causes endothelial dysfunction and hypertension in rats. Clin Chem. 2009; 55(2): 274–284.
  14. Calabro P, Chang DW, Willerson JT, et al. Release of C-reactive protein in response to inflammatory cytokines by human adipocytes: linking obesity to vascular inflammation. J Am Coll Cardiol. 2005; 46(6): 1112–1113.
  15. Mendall MA, Patel P, Ballam L, et al. C reactive protein and its relation to cardiovascular risk factors: a population based cross sectional study. BMJ. 1996; 312(7038): 1061–1065.
  16. Norman PE, Powell JT. Vitamin D, shedding light on the development of disease in peripheral arteries. Arterioscler Thromb Vasc Biol. 2005; 25(1): 39–46.
  17. Klinke A, Nussbaum C, Kubala L, et al. Myeloperoxidase attracts neutrophils by physical forces. Blood. 2011; 117(4): 1350–1358.
  18. Schindhelm RK, van der Zwan LP, Teerlink T, et al. Myeloperoxidase: a useful biomarker for cardiovascular disease risk stratification? Clin Chem. 2009; 55(8): 1462–1470.
  19. Abu-Soud HM, Hazen SL. Nitric oxide is a physiological substrate for mammalian peroxidases. J Biol Chem. 2000; 275(48): 37524–37532.
  20. Eiserich JP, Baldus S, Brennan ML, et al. Myeloperoxidase, a leukocyte-derived vascular NO oxidase. Science. 2002; 296(5577): 2391–2394.
  21. Sung KC. High sensitivity C-reactive protein as an independent risk factor for essential hypertension. Am J Hypertens. 2003; 16(6): 429–433.
  22. Bautista LE, López-Jaramillo P, Vera LM, et al. Is C-reactive protein an independent risk factor for essential hypertension? J Hypertens. 2001; 19(5): 857–861.
  23. Shafi Dar M, Pandith AA, Sameer AS, et al. hs-CRP: A potential marker for hypertension in Kashmiri population. Indian J Clin Biochem. 2010; 25(2): 208–212.
  24. Bautista LE, Vera LM, Arenas IA, et al. Independent association between inflammatory markers (C-reactive protein, interleukin-6, and TNF-alpha) and essential hypertension. J Hum Hypertens. 2005; 19(2): 149–154.
  25. Van der Zwan LP, Scheffer PG, Dekker JM, et al. Hyperglycemia and oxidative stress strengthen the association between myeloperoxidase and blood pressure. Hypertension. 2010; 55(6): 1366–1372.
  26. Yudkin JS, Stehouwer CD, Emeis JJ, et al. C-reactive protein in healthy subjects: associations with obesity, insulin resistance, and endothelial dysfunction: a potential role for cytokines originating from adipose tissue? Arterioscler Thromb Vasc Biol. 1999; 19(4): 972–978.
  27. Hingorani AD, Cross J, Kharbanda RK, et al. Acute systemic inflammation impairs endothelium-dependent dilatation in humans. Circulation. 2000; 102(9): 994–999.
  28. Bautista LE, Atwood JE, O'Malley PG, et al. Association between C-reactive protein and hypertension in healthy middle-aged men and women. Coron Artery Dis. 2004; 15(6): 331–336.
  29. Sesso HD, Buring JE, Rifai N, et al. C-reactive protein and the risk of developing hypertension. JAMA. 2003; 290(22): 2945–2951.
  30. Fabijanić D, Banić M, Kardum D. C-reaktivni protein u procjeni kardiovaskularnog rizika. Liječ Vjesn. 2006; 128: 167–74.
  31. Hak AE, Stehouwer CD, Bots ML, et al. Associations of C-reactive protein with measures of obesity, insulin resistance, and subclinical atherosclerosis in healthy, middle-aged women. Arterioscler Thromb Vasc Biol. 1999; 19(8): 1986–1991.
  32. Mitu F, Rezuş E, Banu C, et al. Inflammatory markers in hypertensive patients and influence of some associated metabolic risk factor. Rev Med Chir Soc Med Nat Iasi. 2014; 118(3): 631–636.
  33. Lakoski SG, Cushman M, Siscovick DS, et al. The relationship between blood pressure and C-reactive protein in the Multi-Ethnic Study of Atherosclerosis (MESA). J Am Coll Cardiol. 2005; 46(10): 1869–1874.
  34. Pankow J, Folsom A, Cushman M, et al. Familial and genetic determinants of systemic markers of inflammation: the NHLBI family heart study. Atherosclerosis. 2001; 154(3): 681–689.
  35. Sonnenberg GE, Krakower GR, Kissebah AH. A novel pathway to the manifestations of metabolic syndrome. Obes Res. 2004; 12(2): 180–186.
  36. Ridker PM. High-sensitivity C-reactive protein: potential adjunct for global risk assessment in the primary prevention of cardiovascular disease. Circulation. 2001; 103(13): 1813–1818.