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Thromb Haemost 2013; 110(05): 977-986
DOI: 10.1160/TH13-05-0383
Blood Coagulation, Fibrinolysis and Cellular Haemostasis
Schattauer GmbH

Procoagulant reactivity to laboratory acute mental stress in Africans and Caucasians, and its relation to depressive symptoms: The SABPA Study

Roland von Känel
1   Division of Psychosomatic Medicine, Department of General Internal Medicine, Inselspital, Bern University Hospital and University of Bern, Switzerland
2   Department of Clinical Research, University of Bern, Switzerland
,
Mark Hamer
3   Department of Epidemiology and Public Health, University College London, UK
4   Hypertension in Africa Research Team (HART), Faculty of Health Sciences North West University, Potchefstroom, South Africa
,
Nico T. Malan
4   Hypertension in Africa Research Team (HART), Faculty of Health Sciences North West University, Potchefstroom, South Africa
,
Kobus Scheepers
4   Hypertension in Africa Research Team (HART), Faculty of Health Sciences North West University, Potchefstroom, South Africa
,
Muriel Meiring
5   Department of Haematology and Cell Biology, University of the Free State, Bloemfontein, South Africa
,
Leonè Malan
4   Hypertension in Africa Research Team (HART), Faculty of Health Sciences North West University, Potchefstroom, South Africa
› Author Affiliations
Further Information

Publication History

Received: 11 May 2013

Accepted after major revision: 20 July 2013

Publication Date:
01 December 2017 (online)

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Summary

The risk of cardiovascular disease is dramatically increasing in Africans (black). The prothrombotic stress response contributes to atherothrombotic disease and is modulated by depressive symptoms. We examined coagulation reactivity to acute mental stress and its relation to psychological well-being in Africans relative to Caucasians (white). A total of 102 African and 165 Caucasian school teachers underwent the Stroop Color-Word Conflict test. Circulating levels of von Willebrand factor (VWF) antigen, fibrinogen, and D-dimer were measured before and after the Stroop. Cardiovascular reactivity measures were also obtained. All participants completed the Patient Health Questionnaire-9 and the General Health Questionnaire-28 for the assessment of depressive symptoms and total psychological distress, respectively. After controlling for covariates, resting levels of VWF, fibrinogen, and D-dimer were higher in Africans than in Caucasians (all p-values ≤0.006). Depressive symptoms and psychological distress were not significantly associated with resting coagulation measures. Stress reactivity in VWF (p<0.001) and fibrinogen (p=0.016), but not in D-dimer (p=0.27), were decreased in Africans relative to Caucasians with Africans showing greater reactivity of total peripheral resistance (p=0.017). Depressive symptoms, but not general psychological distress, were associated with greater VWF increase (p=0.029) and greater fibrinogen decrease (p=0.030) in Africans relative to Caucasians. In conclusion, Africans showed greater hypercoagulability at rest but diminished procoagulant reactivity to acute mental stress when compared with Caucasians. Ethnic differences in the vascular adrenergic stress response might partially explain this finding. Depressive symptoms were associated with exaggerated VWF reactivity in Africans relative to Caucasians. The clinical implications of these findings for Africans need further study.

keywords

Cardiovascular disease - coagulation - depression - ethnicity - psychological stress
 

  • References

  • 1 Borissoff JI, Spronk HM, ten Cate H. The haemostatic system as a modulator of atherosclerosis. N Engl J Med 2011; 364: 1746-1760.
    CrossrefPubMedGoogle Scholar
  • 2 von Känel R, Mills PJ, Fainman C. et al. Effects of psychological stress and psychiatric disorders on blood coagulation and fibrinolysis: a biobehavioural pathway to coronary artery disease?. Psychosom Med 2001; 63: 531-544.
    CrossrefPubMedGoogle Scholar
  • 3 Thrall G, Lane D, Carroll D. et al. A systematic review of the effects of acute psychological stress and physical activity on haemorheology, coagulation, fibrinolysis and platelet reactivity: Implications for the pathogenesis of acute coronary syndromes. Thromb Res 2007; 120: 819-847.
    CrossrefPubMedGoogle Scholar
  • 4 von Känel R, Preckel D, Zgraggen L. et al. The effect of natural habituation on coagulation responses to acute mental stress and recovery in men. Thromb Haemost 2004; 92: 1327-1335.
    Article in Thieme ConnectPubMedGoogle Scholar
  • 5 Wirtz PH, Ehlert U, Emini L. et al. Anticipatory cognitive stress appraisal and the acute procoagulant stress response in men. Psychosom Med 2006; 68: 851-858.
    CrossrefPubMedGoogle Scholar
  • 6 Ellins E, Halcox J, Donald A. et al. Arterial stiffness and inflammatory response to psychophysiological stress. Brain Behav Immun 2008; 22: 941-948.
    CrossrefPubMedGoogle Scholar
  • 7 Brydon L, Steptoe A. Stress-induced increases in interleukin-6 and fibrinogen predict ambulatory blood pressure at 3-year follow-up. J Hypertens 2005; 23: 1001-1007.
    CrossrefPubMedGoogle Scholar
  • 8 Strike PC, Magid K, Brydon L. et al. Exaggerated platelet and haemodynamic reactivity to mental stress in men with coronary artery disease. Psychosom Med 2004; 66: 492-500.
    CrossrefPubMedGoogle Scholar
  • 9 von Känel R, Dimsdale JE, Ziegler MG. et al. Effect of acute psychological stress on the hypercoagulable state in subjects (spousal caregivers of patients with Alzheimer's disease with coronary or cerebrovascular disease and/or systemic hypertension. Am J Cardiol 2001; 87: 1405-1408.
    CrossrefPubMedGoogle Scholar
  • 10 Strike PC, Magid K, Whitehead DL. et al. Pathophysiological processes underlying emotional triggering of acute cardiac events. Proc Natl Acad Sci USA 2006; 103: 4322-4327.
    CrossrefPubMedGoogle Scholar
  • 11 Aschbacher K, Roepke SK, von Känel R. et al. Persistent versus transient depressive symptoms in relation to platelet hyperactivation: a longitudinal analysis of dementia caregivers. J Affect Disord 2009; 116: 80-87.
    CrossrefPubMedGoogle Scholar
  • 12 von Känel R, Dimsdale JE, Adler KA. et al. Effects of depressive symptoms and anxiety on haemostatic responses to acute mental stress and recovery in the elderly. Psychiatry Res 2004; 126: 253-264.
    CrossrefPubMedGoogle Scholar
  • 13 Lippi G, Montagnana M, Favaloro EJ. et al. Mental depression and cardiovascular disease: a multifaceted, bidirectional association. Semin Thromb Haemost 2009; 35: 325-336.
    Article in Thieme ConnectPubMedGoogle Scholar
  • 14 Sliwa K, Wilkinson D, Hansen C. et al. Spectrum of heart disease and risk factors in a black urban population in South Africa (the Heart of Soweto Study): a cohort study. Lancet 2008; 371: 915-922.
    CrossrefPubMedGoogle Scholar
  • 15 Pieters M, de Maat MP, Jerling JC. et al. Fibrinogen concentration and its role in CVD risk in black South Africans-effect of urbanisation. Thromb Haemost 2011; 106: 448-456.
    Article in Thieme ConnectPubMedGoogle Scholar
  • 16 Hamer M, Malan L, Schutte AE. et al. Conventional and behavioural risk factors explain differences in sub-clinical vascular disease between black and Caucasian South Africans: the SABPA study. Atherosclerosis 2011; 215: 237-242.
    CrossrefPubMedGoogle Scholar
  • 17 Hamer M, Malan NT, Harvey BH. et al. Depressive symptoms and sub-clinical atherosclerosis in Africans: role of metabolic syndrome, inflammation and sympathoadrenal function. Physiol Behav 2011; 104: 744-748.
    CrossrefPubMedGoogle Scholar
  • 18 Preckel D, von Känel R. Regulation of haemostasis by the sympathetic nervous system: any contribution to coronary artery disease?. Heartdrug 2004; 4: 123-130.
    PubMedGoogle Scholar
  • 19 von Känel R, Dimsdale JE. Effects of sympathetic activation by adrenergic infusions on haemostasis in vivo. Eur J Haematol 2000; 65: 357-369.
    CrossrefPubMedGoogle Scholar
  • 20 von Känel R, Dimsdale JE, Adler KA. et al. Effects of nonspecific beta-adrenergic stimulation and blockade on blood coagulation in hypertension. J Appl Physiol 2003; 94: 1455-1459.
    CrossrefPubMedGoogle Scholar
  • 21 von Känel R, Kudielka BM, Helfricht S. et al. The effects of aspirin and nonselective beta blockade on the acute prothrombotic response to psychosocial stress in apparently healthy subjects. J Cardiovasc Pharmacol 2008; 51: 231-238.
    CrossrefPubMedGoogle Scholar
  • 22 Huisman HW, Schutte AE, Schutte R. et al. Exploring the link between cardiovascular reactivity and end-organ damage in African and Caucasian men: the SABPA study. Am J Hypertens 2013; 26: 68-75.
    CrossrefPubMedGoogle Scholar
  • 23 World Medical Association. Declaration of Helsinki. Ethical principles of medical research involving human subjects. J Indian Med Assoc 2009; 107: 403-405.
    PubMedGoogle Scholar
  • 24 Lip GY, Lowe GD, Rumley A. et al. Increased markers of thrombogenesis in chronic atrial fibrillation: effects of warfarin treatment. Br Heart J 1995; 73: 527-533.
    CrossrefPubMedGoogle Scholar
  • 25 Baker J, Ayenew W, Quick H. et al. High-density lipoprotein particles and markers of inflammation and thrombotic activity in patients with untreated HIV infection. J Infect Dis 2010; 201: 285-292.
    CrossrefPubMedGoogle Scholar
  • 26 Brotman DJ, Girod JP, Posch A. et al. Effects of short-term glucocorticoids on haemostatic factors in healthy volunteers. Thromb Res 2006; 118: 247-252.
    CrossrefPubMedGoogle Scholar
  • 27 Prasad RN, Koh SC, Viegas OA. et al. Effects on haemostasis after two-year use of low dose combined oral contraceptives with gestodene or levonorgestrel. Clin Appl Thromb Haemost 1999; 5: 60-70.
    CrossrefPubMedGoogle Scholar
  • 28 Gebara OC, Jimenez AH, McKenna C. et al. Stress-induced haemodynamic and haemostatic changes in patients with systemic hypertension: effect of verapamil. Clin Cardiol 1996; 19: 205-211.
    CrossrefPubMedGoogle Scholar
  • 29 Geiser F, Conrad R, Imbierowicz K. et al. Coagulation activation and fibrinolysis impairment are reduced in patients with anxiety and depression when medicated with serotonergic antidepressants. Psychiatry Clin Neurosci 2011; 65: 518-525.
    CrossrefPubMedGoogle Scholar
  • 30 Falaschi P, Proietti A, De Angelis C. et al. Effects of mental stress on cardiovascular and endocrine response in Air Force Academy cadets. Neuro Endocrinol Lett 2003; 24: 197-202.
    PubMedGoogle Scholar
  • 31 Imholz BP, Wieling W, van Montfrans GA. et al. Fifteen years experience with finger arterial pressure monitoring: assessment of the technology. Cardiovasc Res 1998; 38: 605-616.
    CrossrefPubMedGoogle Scholar
  • 32 Wesseling KH, Jansen LR, Settels JJ, Schreuder JJ. Computation of aortic flow from pressure in humans using a nonlinear, three-element model. J Appl Physiol 1993; 74: 2566-2573.
    CrossrefPubMedGoogle Scholar
  • 33 Harms MP, Wesseling KH, Pott F. et al. Continuous stroke volume monitoring by modelling flow from non-invasive measurement of arterial pressure in humans under orthostatic stress. Clin Sci 1999; 97: 291-301.
    CrossrefPubMedGoogle Scholar
  • 34 Jansen JR, Schreuder JJ, Mulier JP. et al. A comparison of cardiac output derived from the arterial pressure wave against thermodilution in cardiac surgery patients. Br J Anaesth 2001; 87: 212-222.
    CrossrefPubMedGoogle Scholar
  • 35 Pruessner JC, Kirschbaum C, Meinlschmid G. et al. Two formulas for computation of the area under the curve represent measures of total hormone concentration versus time dependent change. Psychoneuroendocrinology 2003; 28: 916-931.
    CrossrefPubMedGoogle Scholar
  • 36 Levey AS, Bosch JP, Lewis JB. et al. A more accurate method to estimate glomerular filtration rate from serum creatinine: a new prediction equation. Modification of Diet in Renal Disease Study Group. Ann Intern Med 1999; 130: 461-470.
    PubMedGoogle Scholar
  • 37 Sharpe PC. Biochemical detection and monitoring of alcohol abuse and abstinence. Ann Clin Biochem 2001; 38: 652-664.
    CrossrefPubMedGoogle Scholar
  • 38 Heil DP. Predicting activity energy expenditure using the Actical® Activity Monitor. Res Q Exercise Sport 2006; 77: 64-80.
    CrossrefPubMedGoogle Scholar
  • 39 Meiring M, Badenhorst PN, Kelderman M. Performance and utility of a cost-effective collagen-binding assay for the laboratory diagnosis of Von Willebrand disease. Clin Chem Lab Med 2007; 45: 1068-1072.
    CrossrefPubMedGoogle Scholar
  • 40 Kroenke K, Spitzer RL, Williams JB. The PHQ-9: validity of a brief depression severity measure. J Gen Intern Med 2001; 16: 606-613.
    CrossrefPubMedGoogle Scholar
  • 41 Goldberg DP, Hillier VF. A scaled version of the General Health Questionnaire. Psychol Med 1979; 9: 139-145.
    CrossrefPubMedGoogle Scholar
  • 42 Fibrinogen Studies Collaboration. Kaptoge S, White IR, Thompson SG. et al. Associations of plasma fibrinogen levels with established cardiovascular disease risk factors, inflammatory markers, and other characteristics: individual participant meta-analysis of 154,211 adults in 31 prospective studies: the fibrinogen studies collaboration. Am J Epidemiol 2007; 166: 867-879.
    CrossrefPubMedGoogle Scholar
  • 43 Lee KW, Lip GY. Effects of lifestyle on haemostasis, fibrinolysis, and platelet reactivity: a systematic review. Arch Intern Med 2003; 163: 2368-2392.
    CrossrefPubMedGoogle Scholar
  • 44 Dubin R, Cushman M, Folsom AR. et al. Kidney function and multiple haemostatic markers: cross sectional associations in the multi-ethnic study of atherosclerosis. BMC Nephrol 2011; 12: 3
    CrossrefPubMedGoogle Scholar
  • 45 Jern C, Eriksson E, Tengborn L. et al. Changes of plasma coagulation and fibrinolysis in response to mental stress. Thromb Haemost 1989; 62: 767-771.
    Article in Thieme ConnectPubMedGoogle Scholar
  • 46 Hamer M, Gibson EL, Vuononvirta R. et al. Inflammatory and haemostatic responses to repeated mental stress: individual stability and habituation over time. Brain Behav Immun 2006; 20: 456-569.
    CrossrefPubMedGoogle Scholar
  • 47 Freyschuss U, Hjemdahl P, Juhlin-Dannfelt A. et al. Cardiovascular and sympathoadrenal responses to mental stress: influence of beta-blockade. Am J Physiol 1988; 255: H1443-H1451.
    PubMedGoogle Scholar
  • 48 Muldoon MF, Herbert TB, Patterson SM. et al. Effects of acute psychological stress on serum lipid levels, haemoconcentration, and blood viscosity. Arch Intern Med 1995; 155: 615-620.
    CrossrefPubMedGoogle Scholar
  • 49 Zgraggen L, Fischer JE, Mischler K. et al. Relationship between haemoconcentration and blood coagulation responses to acute mental stress. Thromb Res 2005; 115: 175-183.
    CrossrefPubMedGoogle Scholar
  • 50 Palermo A, Bertalero P, Pizza N. et al. Decreased fibrinolytic response to adrenergic stimulation in hypertensive patients. J Hypertens Suppl 1989; 7: S162-S163.
    CrossrefPubMedGoogle Scholar
  • 51 de Boer D, Ring C, Wood M. et al. Time course and mechanisms of mental stress-induced changes and their recovery: hematocrit, colloid osmotic pressure, whole blood viscosity, coagulation times, and haemodynamic activity. Psychophysiology 2007; 44: 639-649.
    CrossrefPubMedGoogle Scholar
  • 52 Cash JD, Lind AR, McNicol GW. et al. Fibrinolytic and forearm blood flow responses to intravenous adrenaline in healthy subjects. Lif Sci 1969; 8: 207-213.
    PubMedGoogle Scholar
  • 53 Steptoe A, Kunz-Ebrecht S, Rumley A. et al. Prolonged elevations in haemostatic and rheological responses following psychological stress in low socioeconomic status men and women. Thromb Haemost 2003; 89: 83-90.
    Article in Thieme ConnectPubMedGoogle Scholar
  • 54 Righini M, Perrier A, De Moerloose P. et al. D-Dimer for venous thromboembolism diagnosis: 20 years later. J Thromb Haemost 2008; 6: 1059-1071.
    CrossrefPubMedGoogle Scholar
  • 55 Frasure-Smith N, Lespérance F. Depression and cardiac risk: present status and future directions. Heart 2010; 96: 173-176.
    CrossrefPubMedGoogle Scholar
  • 56 Mayr FB, Spiel AO, Leitner JM. et al. Racial differences in endotoxin-induced tissue factor-triggered coagulation. J Thromb Haemost 2009; 7: 634-640.
    CrossrefPubMedGoogle Scholar
  • 57 Lutsey PL, Cushman M, Steffen LM. et al. Plasma haemostatic factors and endothelial markers in four racial/ethnic groups: the MESA study. J Thromb Haemost 2006; 4: 2629-2635.
    CrossrefPubMedGoogle Scholar
  • 58 Gader A, Bahakim H, Awadalla S. et al. Ethnic variations in the haemostatic system: comparison between Arabs, Westerners (Europeans and Americans), Asians and Africans. Blood Coagul Fibrinolysis 1995; 6: 537-542.
    CrossrefPubMedGoogle Scholar
  • 59 Sukhu K, Poovalingam V, Mahomed R. et al. Ethnic variation in von Willebrand factor levels can influence the diagnosis of von Willebrand disease. Clin Lab Haematol 2003; 25: 247-249.
    CrossrefPubMedGoogle Scholar
  • 60 Lovallo WR. Do low levels of stress reactivity signal poor states of health?. Biol Psychol 2011; 86: 121-128.
    CrossrefPubMedGoogle Scholar
  • 61 Sporn LA, Marder VJ, Wagner DD. Inducible secretion of large, biologically potent von Willebrand factor multimers. Cell 1986; 46: 185-190.
    CrossrefPubMedGoogle Scholar
  • 62 Kamarck TW, Lovallo WR. Cardiovascular reactivity to psychological challenge: conceptual and measurement considerations. Psychosom Med 2003; 65: 9-21.
    CrossrefPubMedGoogle Scholar
  • 63 Lenting PJ, van Schooten CJ, Denis CV. Clearance mechanisms of von Willebrand factor and factor VIII. J Thromb Haemost 2007; 7: 1753-1760.
    PubMedGoogle Scholar