Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Review
  • Published:

C-reactive protein and Hypertension

Journal of Human Hypertension volume 28, pages 410–415 (2014)Cite this article

Subjects

Abstract

C-reactive protein (CRP), the prototypical acute-phase reactant, is one of the most widely known biomarkers of cardiovascular disease. Circulating levels of CRP are clinically used to predict the occurrence of cardiovascular events and to aide in the selection of therapies based on more accurate risk assessment in individuals who are at intermediate risk. This paper reviews the role of CRP in hypertension. In hypertensive individuals, CRP levels associate with vascular stiffness, atherosclerosis and the development of end-organ damage and cardiovascular events. Data suggest that some anti-hypertensive medications may lower CRP levels in a manner independent of their effect on blood pressure. In individuals who are normotensive at baseline, CRP levels have been shown in multiple cohorts to foretell the development of hypertension on follow-up. Whether genetic variability that influences circulating levels of CRP independent of environmental and behavioral factors can also be used in a similar manner to predict the change in blood pressure and development of hypertension is controversial. In addition to its role as a biomarker, experimental studies have unraveled an active direct participation of CRP in the development of endothelial dysfunction, vascular stiffness and elevated blood pressure. CRP has also been implicated as a mediator of vascular remodeling in response to injury and cardiac remodeling in response to pressure overload. Emerging data may reveal novel vascular inflammatory pathways and identify new targets for treatment of vascular pathology.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Figure 1
Figure 2
Figure 3

Similar content being viewed by others

References

  1. Harrison DG, Guzik TJ, Lob HE, Madhur MS, Marvar PJ, Thabet SR et al. Inflammation, immunity, and hypertension. Hypertension 2011; 57 (2): 132–140.

    Article  CAS  Google Scholar 

  2. Androulakis ES, Tousoulis D, Papageorgiou N, Tsioufis C, Kallikazaros I, Stefanadis C . Essential hypertension: is there a role for inflammatory mechanisms? Cardiol Rev 2009; 17 (5): 216–221.

    Article  Google Scholar 

  3. Hage FG, McCrory MA, Szalai AJ . C-reactive protein and cardiovascular disease: Lessons learned from studying genetically engineered mice. In: Nagasawa S ed C-Reactive Protein – N Res. Nova Publishers: Hauppauge NY, 2008 ISBN: 978-1-60692-237-8..

    Google Scholar 

  4. Emerging Risk Factors C, Kaptoge S, Di Angelantonio E, Lowe G, Pepys MB, Thompson SG et al. C-reactive protein concentration and risk of coronary heart disease, stroke, and mortality: an individual participant meta-analysis. Lancet 2010; 375 (9709): 132–140.

    Article  Google Scholar 

  5. Ridker PM, Danielson E, Fonseca FA, Genest J, Gotto AM Jr, Kastelein JJ et al. Rosuvastatin to prevent vascular events in men and women with elevated C-reactive protein. N Engl J Med 2008; 359 (21): 2195–2207.

    Article  CAS  Google Scholar 

  6. Greenland P, Alpert JS, Beller GA, Benjamin EJ, Budoff MJ, Fayad ZA et al. ACCF/AHA guideline for assessment of cardiovascular risk in asymptomatic adults: a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines. J Am Coll Cardiol 2010; 56 (25): e50–e103.

    Article  PubMed  Google Scholar 

  7. Anderson TJ, Gregoire J, Hegele RA, Couture P, Mancini GB, McPherson R et al. Update of the Canadian Cardiovascular Society guidelines for the diagnosis and treatment of dyslipidemia for the prevention of cardiovascular disease in the adult. Can J Cardiol 2013; 29 (2): 151–167.

    Article  Google Scholar 

  8. Hashimoto H, Kitagawa K, Hougaku H, Etani H, Hori M . Relationship between C-reactive protein and progression of early carotid atherosclerosis in hypertensive subjects. Stroke 2004; 35 (7): 1625–1630.

    Article  CAS  Google Scholar 

  9. Amer MS, Elawam AE, Khater MS, Omar OH, Mabrouk RA, Taha HM . Association of high-sensitivity C-reactive protein with carotid artery intima-media thickness in hypertensive older adults. J Am Soc Hypertens 2011; 5 (5): 395–400.

    Article  CAS  Google Scholar 

  10. Gomez-Marcos MA, Recio-Rodriguez JI, Patino-Alonso MC, Agudo-Conde C, Gomez-Sanchez L, Rodriguez-Sanchez E et al. Relationships between high-sensitive C-reactive protein and markers of arterial stiffness in hypertensive patients. Differences by sex. BMC Cardiovas Disord 2012; 12: 37.

    Article  CAS  Google Scholar 

  11. Nakhai-Pour HR, Grobbee DE, Bots ML, Muller M, van der Schouw YT . C-reactive protein and aortic stiffness and wave reflection in middle-aged and elderly men from the community. J Hum Hypertens 2007; 21 (12): 949–955.

    Article  CAS  PubMed  Google Scholar 

  12. Conen D, Zeller A, Pfisterer M, Martina B . Usefulness of B-type natriuretic peptide and C-reactive protein in predicting the presence or absence of left ventricular hypertrophy in patients with systemic hypertension. Am J Cardiol 2006; 97 (2): 249–252.

    Article  CAS  Google Scholar 

  13. Iwashima Y, Horio T, Kamide K, Rakugi H, Ogihara T, Kawano Y . C-reactive protein, left ventricular mass index, and risk of cardiovascular disease in essential hypertension. Hypertens Res 2007; 30 (12): 1177–1185.

    Article  CAS  Google Scholar 

  14. Tsioufis C, Dimitriadis K, Andrikou E, Thomopoulos C, Tsiachris D, Stefanadi E et al. ADMA, C-reactive protein, and albuminuria in untreated essential hypertension: a cross-sectional study. Am J Kidney Dis 2010; 55 (6): 1050–1059.

    Article  CAS  PubMed  Google Scholar 

  15. Tonelli M, Sacks F, Pfeffer M, Jhangri GS, Curhan G and Cholesterol and Recurrent Events (CARE) Trial Investigators. Biomarkers of inflammation and progression of chronic kidney disease. Kidney Int 2005; 68 (1): 237–245.

    Article  CAS  Google Scholar 

  16. Shankar A, Sun L, Klein BE, Lee KE, Muntner P, Nieto FJ et al. Markers of inflammation predict the long-term risk of developing chronic kidney disease: a population-based cohort study. Kidney Int 2011; 80 (11): 1231–1238.

    Article  CAS  PubMed  Google Scholar 

  17. Menon V, Greene T, Wang X, Pereira AA, Marcovina SM, Beck GJ et al. C-reactive protein and albumin as predictors of all-cause and cardiovascular mortality in chronic kidney disease. Kidney Int 2005; 68 (2): 766–772.

    Article  CAS  Google Scholar 

  18. deFilippi C, Wasserman S, Rosanio S, Tiblier E, Sperger H, Tocchi M et al. Cardiac troponin T and C-reactive protein for predicting prognosis, coronary atherosclerosis, and cardiomyopathy in patients undergoing long-term hemodialysis. JAMA 2003; 290 (3): 353–359.

    Article  CAS  Google Scholar 

  19. Bazeley J, Bieber B, Li Y, Morgenstern H, de Sequera P, Combe C et al. C-reactive protein and prediction of 1-year mortality in prevalent hemodialysis patients. Clin J Am Soc Nephrol 2011; 6 (10): 2452–2461.

    Article  CAS  PubMed  Google Scholar 

  20. Suleiman M, Khatib R, Agmon Y, Mahamid R, Boulos M, Kapeliovich M et al. Early inflammation and risk of long-term development of heart failure and mortality in survivors of acute myocardial infarction predictive role of C-reactive protein. J Am Coll Cardiol 2006; 47 (5): 962–968.

    Article  Google Scholar 

  21. Anzai T, Yoshikawa T, Shiraki H, Asakura Y, Akaishi M, Mitamura H et al. C-reactive protein as a predictor of infarct expansion and cardiac rupture after a first Q-wave acute myocardial infarction. Circulation 1997; 96 (3): 778–784.

    Article  CAS  Google Scholar 

  22. Tommasi S, Carluccio E, Bentivoglio M, Buccolieri M, Mariotti M, Politano M et al. C-reactive protein as a marker for cardiac ischemic events in the year after a first, uncomplicated myocardial infarction. Am J Cardiol 1999; 83 (12): 1595–1599.

    Article  CAS  Google Scholar 

  23. Muir KW, Weir CJ, Alwan W, Squire IB, Lees KR . C-reactive protein and outcome after ischemic stroke. Stroke 1999; 30 (5): 981–985.

    Article  CAS  Google Scholar 

  24. Di Napoli M, Papa F, Bocola V . C-reactive protein in ischemic stroke: an independent prognostic factor. Stroke 2001; 32 (4): 917–924.

    Article  CAS  Google Scholar 

  25. Idicula TT, Brogger J, Naess H, Waje-Andreassen U, Thomassen L . Admission C-reactive protein after acute ischemic stroke is associated with stroke severity and mortality: the ‘Bergen stroke study’. BMC Neurol 2009; 9: 18.

    Article  PubMed  Google Scholar 

  26. Elkind MS, Tai W, Coates K, Paik MC, Sacco RL . High-sensitivity C-reactive protein, lipoprotein-associated phospholipase A2, and outcome after ischemic stroke. Arch Intern Med 2006; 166 (19): 2073–2080.

    Article  CAS  Google Scholar 

  27. Ridker PM, Danielson E, Fonseca FA, Genest J, Gotto AM Jr, Kastelein JJ et al. Reduction in C-reactive protein and LDL cholesterol and cardiovascular event rates after initiation of rosuvastatin: a prospective study of the JUPITER trial. Lancet 2009; 373 (9670): 1175–1182.

    Article  CAS  PubMed  Google Scholar 

  28. Fliser D, Buchholz K, Haller H . Antiinflammatory effects of angiotensin II subtype 1 receptor blockade in hypertensive patients with microinflammation. Circulation 2004; 110 (9): 1103–1107.

    Article  CAS  Google Scholar 

  29. Ridker PM, Danielson E, Rifai N, Glynn RJ . Valsartan, blood pressure reduction, and C-reactive protein: primary report of the Val-MARC trial. Hypertension 2006; 48 (1): 73–79.

    Article  CAS  Google Scholar 

  30. Palmas W, Ma S, Psaty B, Goff DC Jr, Darwin C, Barr RG . Antihypertensive medications and C-reactive protein in the multi-ethnic study of atherosclerosis. Am J Hypertens 2007; 20 (3): 233–241.

    Article  CAS  Google Scholar 

  31. Fulop T, Rule AD, Schmidt DW, Wiste HJ, Bailey KR, Kullo IJ et al. C-reactive protein among community-dwelling hypertensives on single-agent antihypertensive treatment. J Am Soc Hypertens 2009; 3 (4): 260–266.

    Article  PubMed  Google Scholar 

  32. Sesso HD, Buring JE, Rifai N, Blake GJ, Gaziano JM, Ridker PM . C-reactive protein and the risk of developing hypertension. Jama 2003; 290 (22): 2945–2951.

    Article  CAS  Google Scholar 

  33. Wang TJ, Gona P, Larson MG, Levy D, Benjamin EJ, Tofler GH et al. Multiple biomarkers and the risk of incident hypertension. Hypertension 2007; 49 (3): 432–438.

    Article  CAS  Google Scholar 

  34. Dauphinot V, Roche F, Kossovsky MP, Schott AM, Pichot V, Gaspoz JM et al. C-reactive protein implications in new-onset hypertension in a healthy population initially aged 65 years: the Proof study. J Hypertens 2009; 27 (4): 736–743.

    Article  CAS  PubMed  Google Scholar 

  35. Cheung BM, Ong KL, Tso AW, Leung RY, Xu A, Cherny SS et al. C-reactive protein as a predictor of hypertension in the Hong Kong Cardiovascular Risk Factor Prevalence Study (CRISPS) cohort. J Hum Hypertens 2012; 26 (2): 108–116.

    Article  CAS  Google Scholar 

  36. Lakoski SG, Cushman M, Siscovick DS, Blumenthal RS, Palmas W, Burke G et al. The relationship between inflammation, obesity and risk for hypertension in the Multi-Ethnic Study of Atherosclerosis (MESA). J Hum Hypertens 2011; 25 (2): 73–79.

    Article  CAS  Google Scholar 

  37. Chuang SY, Hsu PF, Chang HY, Bai CH, Yeh WT, Pan HW . C-reactive protein predicts systolic blood pressure and pulse pressure but not diastolic blood pressure: the Cardiovascular Disease Risk Factors Two-Township Study. Am J Hypertens 2013; 26 (5): 657–664.

    Article  CAS  Google Scholar 

  38. Hage FG, Szalai AJ . C-reactive protein gene polymorphisms, C-reactive protein blood levels, and cardiovascular disease risk. J Am Coll Cardiol 2007; 50 (12): 1115–1122.

    Article  CAS  Google Scholar 

  39. Hage FG, Szalai AJ . The role of C-reactive protein polymorphisms in inflammation and cardiovascular risk. Curr Atheroscler Rep 2009; 11 (2): 124–130.

    Article  CAS  Google Scholar 

  40. Carpentier YA, Scruel O . Changes in the concentration and composition of plasma lipoproteins during the acute phase response. Curr Opin Clin Nutr Metab Care 2002; 5 (2): 153–158.

    Article  CAS  Google Scholar 

  41. Dehghan A, Dupuis J, Barbalic M, Bis JC, Eiriksdottir G, Lu C et al. Meta-analysis of genome-wide association studies in >80 000 subjects identifies multiple loci for C-reactive protein levels. Circulation 2011; 123 (7): 731–738.

    Article  CAS  PubMed  Google Scholar 

  42. Wensley F, Gao P, Burgess S, Kaptoge S, Di Angelantonio E, Shah T et al. Association between C reactive protein and coronary heart disease: mendelian randomisation analysis based on individual participant data. BMJ 2011; 342: d548.

    Article  Google Scholar 

  43. Komurcu-Bayrak E, Erginel-Unaltuna N, Onat A, Ozsait B, Eklund C, Hurme M et al. Association of C-reactive protein (CRP) gene allelic variants with serum CRP levels and hypertension in Turkish adults. Atherosclerosis 2009; 206 (2): 474–479.

    Article  CAS  PubMed  Google Scholar 

  44. Davey Smith G, Lawlor DA, Harbord R, Timpson N, Rumley A, Lowe GD et al. Association of C-reactive protein with blood pressure and hypertension: life course confounding and mendelian randomization tests of causality. Arterioscler Thromb Vasc Biol 2005; 25 (5): 1051–1056.

    Article  PubMed  Google Scholar 

  45. Kong H, Qian YS, Tang XF, Zhang J, Gao PJ, Zhang Y et al. C-reactive protein (CRP) gene polymorphisms, CRP levels and risk of incident essential hypertension: findings from an observational cohort of Han Chinese. Hypertens Res 2012; 35 (10): 1019–1023.

    Article  CAS  Google Scholar 

  46. Zhao Y, Wang H, Liu S, Zhao X, Chen Y, Yang Y et al. Association study of CRP gene polymorphism and hypertension in Han Chinese population. Gene 2013; 512 (1): 41–46.

    Article  CAS  Google Scholar 

  47. Hage FG . Hypertension and C-reactive protein. Hypertens Res 2012; 35 (10): 969–971.

    Article  CAS  Google Scholar 

  48. Torzewski J, Torzewski M, Bowyer DE, Frohlich M, Koenig W, Waltenberger J et al. C-reactive protein frequently colocalizes with the terminal complement complex in the intima of early atherosclerotic lesions of human coronary arteries. Arterioscler Thromb Vasc Biol 1998; 18 (9): 1386–1392.

    Article  CAS  Google Scholar 

  49. Vongpatanasin W, Thomas GD, Schwartz R, Cassis LA, Osborne-Lawrence S, Hahner L et al. C-reactive protein causes downregulation of vascular angiotensin subtype 2 receptors and systolic hypertension in mice. Circulation 2007; 115 (8): 1020–1028.

    Article  CAS  PubMed  Google Scholar 

  50. Wang CH, Li SH, Weisel RD, Fedak PW, Dumont AS, Szmitko P et al. C-reactive protein upregulates angiotensin type 1 receptors in vascular smooth muscle. Circulation 2003; 107 (13): 1783–1790.

    Article  CAS  Google Scholar 

  51. Kusche-Vihrog K, Urbanova K, Blanque A, Wilhelmi M, Schillers H, Kliche K et al. C-reactive protein makes human endothelium stiff and tight. Hypertension 2011; 57 (2): 231–237.

    Article  CAS  Google Scholar 

  52. Li X, Yang G, Zhao G, Wu B, Edin ML, Zeldin DC et al. Rosuvastatin attenuates the elevation in blood pressure induced by overexpression of human C-reactive protein. Hypertens Res 2011; 34 (7): 869–875.

    Article  CAS  PubMed  Google Scholar 

  53. Hage FG, Oparil S, Xing D, Chen YF, McCrory MA, Szalai AJ . C-reactive protein-mediated vascular injury requires complement. Arterioscler Thromb Vasc Biol 2010; 30 (6): 1189–1195.

    Article  CAS  PubMed  Google Scholar 

  54. Xing D, Hage FG, Chen YF, McCrory MA, Feng W, Skibinski GA et al. Exaggerated neointima formation in human C-reactive protein transgenic mice is IgG Fc receptor type I (Fc gamma RI)-dependent. Am J Pathol 2008; 172 (1): 22–30.

    Article  CAS  PubMed  Google Scholar 

  55. Wang D, Oparil S, Chen YF, McCrory MA, Skibinski GA, Feng W et al. Estrogen treatment abrogates neointima formation in human C-reactive protein transgenic mice. Arterioscler Thromb Vasc Biol 2005; 25 (10): 2094–2099.

    Article  CAS  Google Scholar 

  56. Zhang R, Zhang YY, Huang XR, Wu Y, Chung AC, Wu EX et al. C-reactive protein promotes cardiac fibrosis and inflammation in angiotensin II-induced hypertensive cardiac disease. Hypertension 2010; 55 (4): 953–960.

    Article  CAS  Google Scholar 

  57. Nagai T, Anzai T, Kaneko H, Mano Y, Anzai A, Maekawa Y et al. C-reactive protein overexpression exacerbates pressure overload-induced cardiac remodeling through enhanced inflammatory response. Hypertension 2011; 57 (2): 208–215.

    Article  CAS  Google Scholar 

  58. Ridker PM, Thuren T, Zalewski A, Libby P . Interleukin-1beta inhibition and the prevention of recurrent cardiovascular events: rationale and design of the Canakinumab Anti-inflammatory Thrombosis Outcomes Study (CANTOS). Am Heart J 2011; 162 (4): 597–605.

    Article  CAS  Google Scholar 

  59. Ridker PM . Testing the inflammatory hypothesis of atherothrombosis: scientific rationale for the cardiovascular inflammation reduction trial (CIRT). J Thromb Haemost 2009; 7 (Suppl 1): 332–339.

    Article  CAS  Google Scholar 

  60. Couzin-Frankel J . Cardiovascular disease. Massive trials to test inflammation hypothesis. Science 2012; 337 (6099): 1158.

    Article  Google Scholar 

Download references

Acknowledgements

This work was supported, in part, by a Veterans Affairs Biomedical Laboratory Research & Development Service Merit Award and an American Heart Association NCRP Scientist Development Grant 0930098N. Grant support from Novartis Pharmaceuticals.

Author information

Authors and Affiliations

  1. Division of Cardiovascular Disease, University of Alabama at Birmingham, Birmingham, AL, USA

    F G Hage

  2. Section of Cardiology, Birmingham Veterans Affairs Medical Center, Birmingham, AL, USA

    F G Hage

Authors
  1. F G Hage
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to F G Hage.

Ethics declarations

Competing interests

The author declares no conflict of interest.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Hage, F. C-reactive protein and Hypertension. J Hum Hypertens 28, 410–415 (2014). https://doi.org/10.1038/jhh.2013.111

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/jhh.2013.111

Keywords

This article is cited by

Search

Advanced search

Quick links