Skip to main content
SpringerLink
Log in

Changes in haemostatic and platelet activation markers in non-dipper hypertensive patients

  • Nephrology – Original Paper
  • Published:
International Urology and Nephrology Aims and scope Submit manuscript

Abstract

Background

Non-dipper hypertensive patients are at increased risk for cardiovascular disease. Coagulation and fibrinolysis activation factors are considered as risk factors for cardiovascular disease. The aim of this study was to examine the relationship between the haemostatic and platelet activation markers and the non-dipping pattern in treated hypertensive patients.

Patients and methods

Seventy-one treated hypertensive patients (53 with essential and 18 with secondary hypertension, due to chronic kidney disease—stage 4), aged 33 to 81 years (30 men), were classified as dippers and non-dippers, according to the presence or absence, respectively, of a decline of nocturnal average systolic blood pressure (BP) by more than 10% of the diurnal BP (non-dipping pattern) on 24-hour ambulatory BP monitoring. Plasma levels of factors VIII and IX, fibrinogen, prothrombin fragment 1 + 2, thrombin–antithrombin complex, protein C, plasmin-alpha-2 antiplasmin complex, D-dimer and platelet factor 4 were measured in all patients.

Results

Thirty-seven patients were classified as dippers and 34 as non-dippers. The percentages of patients with essential and with secondary hypertension were similar in the dippers and in the non-dippers groups (both P = 0.754). Multivariate analysis of variance showed statistically significant differences in all measured variables between dippers and non-dippers (P = 0.043). Plasma levels of factors VIII and IX, fibrinogen, prothrombin fragment 1 + 2, protein C, plasmin-alpha-2-antiplasmin complex, and D-dimers were significantly higher in non-dippers when compared to dippers (P < 0.05 for all). In contrast, there were no significant differences in plasma levels of thrombin–antithrombin complex (P = 0.955) and platelet factor 4 (P = 0.431) between the two groups.

Conclusion

This study provides evidence that non-dipper treated hypertensive patients exhibit alterations in haemostasis, which may affect their cardiovascular risk.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2

Similar content being viewed by others

References

  1. O’Brien E, Sheridan J, O’Malley K (1988) Dippers, non-dippers. Lancet 2:397

    Article  PubMed  Google Scholar 

  2. Farmer CKT, Goldsmith DJA, Cox J, Dallyn P, Kingwood JC, Sharpstone P (1997) An investigation of the effect of advancing uraemia, renal replacement therapy and renal transplantation on blood pressure diurnal variability. Nephrol Dial Transplant 12:2301–2307

    Article  PubMed  CAS  Google Scholar 

  3. Staessen J, Bieniaszewski L, O’Brien E, Gosse P, Hayashi H, Imai Y, Kawasaki T, Otsuka K, Palatini P, Thijs L, Fagard R (1997) Nocturnal blood pressure fall on ambulatory monitoring in a large international database. Hypertension 29:30–39

    PubMed  CAS  Google Scholar 

  4. Routledge F, McFetridge-Durdle J (2007) Nondipping blood pressure patterns among individuals with essential hypertension: a review of the literature. Eur J Cardiovasc Nurs 6:9–26

    Article  PubMed  Google Scholar 

  5. Kanbay M, Turgut F, Uyar ME, Akcay A, Covic A (2008) Causes and mechanisms of nondipping hypertension. Clin Exp Hypertens 30:585–597

    Article  PubMed  Google Scholar 

  6. Verdecchia P, Porcellati C, Schillaci G, Borgioni C, Ciucci A, Battistelli M, Guerrieri M, Gatteschi C, Zampi I, Santucci A, Santucci C, Reboldi G (1994) Ambulatory blood pressure. An independent predictor of prognosis in essential hypertension. Hypertension 24:793–801

    PubMed  CAS  Google Scholar 

  7. Routledge F, McFetridge-Durdle J, Dean CR (2007) Night-time blood pressure patterns and target organ damage: a review. Can J Cardiol 23:132–138

    Article  PubMed  Google Scholar 

  8. Mancia G, De Backer G, Dominiczak A et al (2007) Management of Arterial Hypertension of the European Society of Hypertension; European Society of Cardiology: 2007 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). J Hypertens 25:1105–1187

    Article  PubMed  CAS  Google Scholar 

  9. Redon J, Lurbe E (2008) Nocturnal blood pressure versus nondipping pattern. What do they mean? Hypertension 51:41–42

    Article  PubMed  CAS  Google Scholar 

  10. Turfaner N, Karter Y, Curgunlu A, Ayan F, Mibmanli I, Sipabioglu F (2009) Blunted nocturnal fall in blood pressure in isolated clinical hypertension. Swiss Med Wkly 139:251–255

    PubMed  CAS  Google Scholar 

  11. Staessen J, Thijs L, Fagard R, O’Brien E, Clement D, de Leeuw P, Mancia G, Nachev C, Palatini P, Parati G, Tuomilehto J, Webster J (1999) Predicting cardiovascular risk using conventional vs ambulatory blood pressure in older patients with systolic hypertension. JAMA 282:539–546

    Article  PubMed  CAS  Google Scholar 

  12. Ohcubo T, Hozawa A, Yamaguchi J, Kikuya M, Ohmori K, Michimata M, Matsubara M, Hashimoto J, Hoshi H, Araki T, Tsuji I, Satoh H, Hisamichi S, Imai Y (2002) Prognostic significance of the nocturnal decline in blood pressure in individuals with and without high 24-h blood pressure: the Ohasama study. J Hypertens 20:2183–2189

    Article  Google Scholar 

  13. Dolan E, Stanton A, Thijs L, Hinedi K, Atkins N, McClory S, Den Hond E, McCormack P, Staessen JA, O’Brien E (2005) Superiority of ambulatory over clinic blood pressure measurement in predicting mortality. The Dublin outcome study. Hypertension 46:156–161

    Article  PubMed  CAS  Google Scholar 

  14. Fagard R, Celis H, Thijs L, Staessen J, Clement D, de Buyzere M, de Bacquer D (2008) Daytime and nighttime blood pressure as predictors of death and cause-specific cardiovascular events in hypertension. Hypertension 51:55–61

    Article  PubMed  CAS  Google Scholar 

  15. de la Sierra A, Redon J, Banegas J, Segura J, Parati G, Gorostidi M, de la Cruz J, Sobrino J, Llisterri J, Alonso J, Vinyoles E, Pallarés V, Sarría A, Aranda P, Ruilope L (2009) Prevalence and factors associated with circadian blood pressure patterns in hypertensive patients. Hypertension 53:466–472

    Article  PubMed  Google Scholar 

  16. Merlini PA, Bauer KA, Oltrona L, Ardissino D, Cattaneo M, Belli C, Mannucci PM, Rosenberg RD (1994) Persistent activation of coagulation mechanism in unstable angina and myocardial infarction. Circulation 90:61–68

    PubMed  CAS  Google Scholar 

  17. Thögersen AM, Jansson JH, Boman K, Nilsson TK, Weinehall L, Huhtasaari F, Hallmans G (1998) High plasminogen activator inhibitor and tissue plasminogen activator levels in plasma precede a first acute myocardial infraction in both men and women. Evidence for the fibrinolytic system as an independent primary risk factor. Circulation 98:2241–2247

    PubMed  Google Scholar 

  18. Minnema MC, Peters RJG, de Winter R, Lubbers YPT, Barzegar S, Bauer KA, Rosenberg RD, Hack CE, ten Cate H (2000) Activation of clotting factors XI and IX in patients with acute myocardial infraction. Arterioscler Thromb Vasc Biol 20:2489–2493

    Article  PubMed  CAS  Google Scholar 

  19. Danesh J, Whincup P, Walker M, Thomson A, Rumley A (2001) Fibrin D-Dimer and coronary heart disease. Prospective study and meta-analysis. Circulation 103:2323–2327

    PubMed  CAS  Google Scholar 

  20. Rumley A, Lowe GDO, Sweetnam PM, Yarnell JWG, Ford RP, Factor VIII (1999) von Willebrand factor and the risk of major ischaemic heart disease in the Caerphilly Heart Study. Br J Haematol 105:110–116

    Article  PubMed  CAS  Google Scholar 

  21. Yarnell JWG, Sweetnam PM, Rumley A, Lowe GDO (2000) Lifestyle and hemostatic risk factors for ischemic heart disease. The Caerphilly Study. Arterioscler Thromb Vasc Biol 20:271–279

    Article  PubMed  CAS  Google Scholar 

  22. Lowe GDO, Rumley A, Sweetnam PM, Yarnell JWG (2001) Fibrin D-dimer, markers of goagulation activation and the risk of major ischaemic heart disease in the Caerphilly study. Thromb Haemost 85:822–827

    Google Scholar 

  23. Lowe GDO, Sweetnam PM, Yarnell JWG, Rumley A, Rumley C, Bainton D, Ben-Shlomo Y (2004) C-reactive protein, fibrin D-dimer, and risk of ischemic heart disease. The Caerphilly and Speedwell studies. Arterioscler Thromb Vasc Biol 24:1957–1962

    Article  PubMed  CAS  Google Scholar 

  24. Smith A, Patterson C, Yarnell J, Rumley A, Ben-Shlomo Y, Lowe GDO (2005) Which hemostatic markers add to the predictive value of conventional risk factors for coronary heart disease and ischemic stroke? The Caerphilly Study. Circulation 112:3080–3087

    Article  PubMed  Google Scholar 

  25. Yarnell J, McCrun E, Rumley A, Patterson C, Salomaa V, Lowe GDO, Evans A (2005) Association of European population levels of thrombotic and inflammatory factors with risk of coronary heart disease: the MONICA Optional Haemostasis Study. Eur Heart J 26:332–342

    Article  PubMed  Google Scholar 

  26. Morange PE, Bickel C, Nicaud V, Schnabel R, Rupprecht HJ, Peetz D, Lackner KJ, Cambien F, Blankenberg S, Tiret L (2006) Haemostatic factors and the risk of cardiovascular death in patients with coronary artery disease. The AtheroGene Study. Arterioscler Thromb Vasc Biol 26:2793–2799

    Article  PubMed  CAS  Google Scholar 

  27. Ardissino D, Merlini PA, Bauer KA, Galvani M, Ottani F, Franchi F, Bertocchi F, Ronsenberg RD, Mannucci PM (2003) Coagulation activation and long- term outcome in acute coronary syndromes. Blood 102:2731–2735

    Article  PubMed  CAS  Google Scholar 

  28. Folsom AR, Wu KK, Shahar E, Davis CE (1993) Association of hemostatic variables with prevalent cardiovascular disease and asymptomatic carotid artery atherosclerosis. The Atherosclerosis Risk in Communities (ARIC) Study. Arterioscler Thromb 13:1829–1836

    Article  PubMed  CAS  Google Scholar 

  29. Folsom AR, Wu KK, Rosamond WD, Sharrett R, Chambless LE (1997) Prospective study of hemostatic factors and incidence of coronary heart disease. The Atherosclerosis Risk in Communities (ARIC) Study. Circulation 96:1102–1108

    PubMed  CAS  Google Scholar 

  30. Folsom AR, Rosamond WD, Shahar E, Cooper LS, Aleksic N, Nieto J, Rasmussen ML, Wu KK (1999) Prospective study of markers of hemostatic function with risk of ischemic stroke. The Atherosclerosis Risk in Communities (ARIC) Study. Circulation 100:736–742

    PubMed  CAS  Google Scholar 

  31. Folsom AR, Aleksic N, Park E, Salomaa V, Juneja H, Wu KK (2001) Prospective study of fibrinolytic factors and incident coronary heart disease. The Atherosclerosis Risk in Communities (ARIC) Study. Artrerioscler Thromb Vasc Biol 21:611–617

    Article  CAS  Google Scholar 

  32. Folsom AR, Chambless LE, Ballantyne CM, Coresh J, Heiss G, Wu KK, Boerwinkle E, Mosley TH, Sorlie P, Diao G, Sharrett R (2006) An assessment of incremental coronary risk prediction using C-reactive protein and other novel risk markers. The Atherosclerosis Risk in Communities (ARIC) Study. Arch Intern Med 166:1368–1373

    Article  PubMed  CAS  Google Scholar 

  33. O’Brien E, Coats A, Owens P, Petrie J, Padfield PL, Littler WA, de Swiet M, Mee F (2000) Use and interpretation of ambulatory blood pressure monitoring: recommendations of the British hypertension society. BMJ 320:1128–1134

    Article  PubMed  Google Scholar 

  34. von Känel R, Jain S, Mills PJ, Nelesen RA, Adler KA, Hong S, Perez CJ, Dimsdale JE (2004) Relation of nocturnal blood pressure dipping to cellular adhesion, inflammation and hemostasis. J Hypertens 22:2087–2093

    Article  Google Scholar 

  35. Henskens LH, Kroon AA, van Oostenbrugge RJ, Haest RJ, Lodder J, de Leeuw PW (2008) Different classifications of nocturnal blood pressure dipping affect the prevalence of dippers and nondippers and the relation with target-organ damage. J Hypertens 26:691–698

    Article  PubMed  CAS  Google Scholar 

  36. Peirdomenico SD, Lapenne D, Gugliemi MD, Constantini F, Romano F, Schiavone C, Cuccurullo F, Mezzetti A (1997) Arterial disease in dipper and nondipper hypertensive patiens. Am J Hypertens 10:511–518

    Article  Google Scholar 

  37. Cuspidi C, Macca G, Sampieri L, Fusi V, Severgini B, Michev I, Salerno M, Margini F, Zanchetti A (2001) Target organ damage and non-dipping pattern defined by two sessions of ambulatory blood pressure monitoring in recently diagnosed essential hypertensive patients. J Hypertens 19:1539–1545

    Article  PubMed  CAS  Google Scholar 

  38. Desideri G, Cipollone F, Valeri L, Grassi D, Necozione S, Croce G, Passacquale G, Garofalo A, Lippi C, Mezzetti A, Ferri C (2007) Enhanced plasma soluble CD40 ligand levels in essential hypertensive patients with blunted nocturnal blood pressure decrease. Am J Hypertens 20:70–76

    Article  PubMed  CAS  Google Scholar 

  39. Alioglou E, Turk UO, Bicak F, Tengiz I, Atila D, Barisik V, Ercan E, Akin M (2008) Vascular endothelial functions, carotid intima-media thickness, and soluble CD40 ligand levels in dipper and nondipper essential hypertensive patients. Clin Res Cardiol 97:457–462

    Article  Google Scholar 

  40. Cuspidi C, Michev I, Meani S, Valerio C, Betrazzoli G, Margini F, Zanchetti A, Non-dipper treated hypretensive patients do not have increased cardiac structural alterations. Cardiovasc Ultrasound. doi: 10.1186/1476-7120-1-1

  41. Lee KW, Blann AD, Lip GYH (2005) High pulse pressure and nondipping circadian blood pressure in patients with coronary artery disease: relationship to thrombogenesis and endothelial damage/dysfunction. Am J Hypertens 18:104–115

    Article  PubMed  Google Scholar 

  42. Soylu A, Yazici M, Duzenli MA, Tokac M, Ozdemir K, Gok H (2009) Relation between abnormalities in circadian blood pressure rhythm and target organ damage in normotensives. Circ J 73:899–904

    Article  PubMed  Google Scholar 

  43. Cuspidi C, Meani S, Salerno M, Valerio C, Fusi V, Severgini B, Lonati L, Margini F, Zanchetti A (2004) Cardiovascular target organ damage in essential hypertensives with or without reproducible nocturnal fall in blood pressure. J Hypertension 22:273–280

    Article  CAS  Google Scholar 

  44. Parati G, Staessen JA (2007) Day-night blood pressure variations: mechanisms, reproducibility and clinical relevance. J Hypertens 25:2377–2380

    Article  PubMed  CAS  Google Scholar 

  45. Boggia J, Li Y, Thijs L, Hansen TW, Kikuya M, Björklund-Bodegärd K, Richart T, Ohkubo T, Kuznetsova T, Torp-Pedersen C, Lind L, Ibsen H, Iamai Y, Wang J, Sandoya E, O’Brien E, Staessen JA (2007) Prognostic accuracy of day versus night ambulatory blood pressure: o cohort study. Lancet 370:1219–1229

    Article  PubMed  Google Scholar 

  46. Tracy RP, Arnold AM, Ettinger W, Fried L, Meilahn E, Savage P (1999) The relation of fibrinogen and factors VII and VIII to incident cardiovascular disease and death in the elderly. Results from the Cardiovascular Health Study. Arterioscler Thromb Vasc Biol 19:1776–1783

    Article  PubMed  CAS  Google Scholar 

  47. Bank I, Libourel EJ, Middeldorp S, Hamulyák K, van Pampus ECM, Koopman MMW, Prins MH, van der Meer J, Büller HR (2005) Elevated levels of FVIII:C within families are associated with an increased risk for venous and arterial thrombosis. J Thromb Haemost 3:79–84

    Article  PubMed  CAS  Google Scholar 

  48. Lijfering WM, Veeger NJGM, Brouwer JLP, van der Meer J (2007) The risk of venous and arterial thrombosis in hyperhomocysteinemic subjects may be a result of elevated factor VIII levels. Haematologica 92:1703–1706

    Article  PubMed  CAS  Google Scholar 

  49. Lowe GDO (2001) Factor IX and thrombosis. Br J Haematol 115:507–513

    Article  PubMed  CAS  Google Scholar 

  50. Miller GJ, Ireland HA, Cooper JA, Bauer KA, Morrissey JH, Humphries SE, Esnouf MP (2008) Relationship between markers of activated coagulation, their correlation with inflammation, and association with coronary heart disease (NPHSII). J Thromb Haemost 6:259–267

    PubMed  CAS  Google Scholar 

  51. Danesh J, Collins R, Appleby P, Peto R (1998) Association of fibrinogen, C-reactive protein, albumin, or leukocyte count with coronary heart disease. JAMA 279:1477–1482

    Article  PubMed  CAS  Google Scholar 

  52. Fibrinogen Studies Collaboration (2005) Plasma fibrinogen level and the risk of major cardiovascular diseases and nonvascular mortality. JAMA 294:1799–1809

    Article  Google Scholar 

  53. Aono Y, Ohkubo T, Kikuya M, Hara A (2007) Kondo t, Obara T, Metoki H, Inoue R, Asayama K, Shintani Y, Hashimoto J, Totsune K, Hoshi H, Satoh H, Izumi SI, Imai Y, Plasma fibrinogen, ambulatory blood pressure, and silent cerebrovascular lesions. The Ohasama Study. Arterioscler Thromb Vasc Biol 27:963–968

    Article  PubMed  CAS  Google Scholar 

  54. Rugman FP, Jenkins JA, Duguid JK, Maggs PB, Hay CR (1994) Prothrombin fragment F1 + 2: correlations with cardiovascular risk factors. Blood Coagul Fibrinolysis 5:335–340

    PubMed  CAS  Google Scholar 

  55. Mercuri F, Giacomello R, Puglisi F, Colaone R, Fabbro D, Menegon MG, Ceriello A, Gonano F, Damante G, Factor V (2000) Leiden increases plasma F1 + 2 levels both in normal and deep venous thrombosis subjects. Haematologica 85:386–389

    PubMed  CAS  Google Scholar 

  56. Gouin-Thibault I, Arkam R, Nassiri S, de la Tourette A, Conard J, Horellou MH, Elalamy I, Samama MM (2002) Markers of activated coagulation in patients with factor V Leiden and/or G20210A prothrombin gene mutation. Thromb Res 107:7–11

    Article  PubMed  CAS  Google Scholar 

  57. Cushman M, Lemaitr RN, Kuller LH, Psaty BM, Macy EM, Sharrett AR, Tracy RP (1999) Fibrinolytic activation markers predict myocardial infraction in the elderly. The Cardiovascular Health Study. Atheroscler Thromb Vasc Biol 19:493–498

    Article  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Haematology Laboratory, General Hospital of Xanthi, Ephessou 68, 67100, Xanthi, Greece

    Athanasia Agorasti

  2. Department of Nephrology, University General Hospital of Alexandroupolis, Democritus University of Thrace, Alexandroupolis, Greece

    Efthimia Mourvati & Ploumis Passadakis

  3. Technological Institute of Kavala, Kavala, Greece

    Theodoros Trivellas

  4. Department of Internal Medicine, University General Hospital of Alexandroupolis, Democritus University of Thrace, Alexandroupolis, Greece

    Vasilios Papadopoulos

  5. Department of Haematology, University General Hospital of Alexandroupolis, Democritus University of Thrace, Alexandroupolis, Greece

    Ioanna Bazntiara & Anna Christoforidou

Authors
  1. Athanasia Agorasti
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Efthimia Mourvati
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Theodoros Trivellas
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Vasilios Papadopoulos
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Ioanna Bazntiara
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Anna Christoforidou
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Ploumis Passadakis
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Athanasia Agorasti.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Agorasti, A., Mourvati, E., Trivellas, T. et al. Changes in haemostatic and platelet activation markers in non-dipper hypertensive patients. Int Urol Nephrol 44, 523–533 (2012). https://doi.org/10.1007/s11255-011-9926-9

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11255-011-9926-9

Keywords

Search

Navigation