D-dimer, a biomarker of coagulation, is higher in blacks than in whites and has been associated with stroke and coronary heart disease (CHD). It was our objective to assess the association of higher D-dimer with stroke and CHD in blacks and whites. REGARDS recruited 30,239 black and white participants across the contiguous US and measured baseline D-dimer in stroke (n=646) and CHD (n=654) cases and a cohort random sample (n=1,104). Cox models adjusting for cardiovascular risk factors determined the hazard ratio (HR) for increasing D-dimer for cardiovascular disease with bootstrapping to assess the difference in HR for CHD versus stroke by race. D-dimer was higher with increasing age, female sex, diabetes, hypertension, pre-baseline cardiovascular disease and higher C-reactive protein (CRP). Accounting for cardiovascular risk factors, each doubling of D-dimer was associated with increased stroke (hazard ratio [HR] 1.15; 95 % confidence interval [CI] 1.01, 1.31) and CHD (HR 1.27; 95 % CI 1.11, 1.45) risk. The difference in the HR between CHD and stroke was 0.20 (95 % CI >0.00, 0.58) for blacks and 0.02 (95 % CI –0.30, 0.27) for whites. CRP mediated 22 % (95 % CI 5 %, 41 %) of the association between D-dimer and CHD and none of the association with stroke. Higher D-dimer increased the risk of stroke and CHD independent of cardiovascular risk factors and CRP, with perhaps a stronger association for CHD versus stroke in blacks than whites. These findings highlight potential different pathophysiology of vascular disease by disease site and race suggesting potential further studies targeting haemostasis in primary prevention of vascular disease.
Keywords
Continental population groups -
coronary disease -
D-dimer -
epidemiology stroke
References
1
Bhatia M,
Rothwell PM.
A systematic comparison of the quality and volume of published data available on novel risk factors for stroke versus coronary heart disease. Cerebrovasc Dis 2005; 20: 180-186.
2
Gliksman M,
Wilson A.
Are hemostatic factors responsible for the paradoxical risk factors for coronary heart disease and stroke?. Stroke 1992; 23: 607-610.
5
Danesh J,
Whincup P,
Walker M.
et al. Fibrin D-dimer and coronary heart disease: prospective study and meta-analysis. Circulation 2001; 103: 2323-2327.
6
May M,
Lawlor DA,
Patel R.
et al. Associations of von Willebrand factor, fibrin D-dimer and tissue plasminogen activator with incident coronary heart disease: British Women’s Heart and Health cohort study. Eur J Cardiovasc Prevent Rehabil 2007; 14: 638-645.
7
Tzoulaki I,
Murray GD,
Lee AJ.
et al. Relative value of inflammatory, hemostatic, and rheological factors for incident myocardial infarction and stroke: the Edinburgh Artery Study. Circulation 2007; 115: 2119-2127.
8
Zakai NA,
Katz R,
Jenny NS.
et al. Inflammation and hemostasis biomarkers and cardiovascular risk in the elderly: the Cardiovascular Health Study. J Thromb Haemost 2007; 05: 1128-1135.
9
Folsom AR,
Delaney JA,
Lutsey PL.
et al. Associations of factor VIIIc, D-dimer, and plasmin-antiplasmin with incident cardiovascular disease and all-cause mortality. Am J Hematol 2009; 84: 349-353.
10
Lutsey PL,
Wassel CL,
Cushman M.
et al. Genetic admixture is associated with plasma hemostatic factor levels in self-identified African Americans and Hispanics: the Multi-Ethnic Study of Atherosclerosis. J Thromb Haemost 2012; 10: 543-549.
11
Lutsey PL,
Cushman M,
Steffen LM.
et al. Plasma hemostatic factors and endothelial markers in four racial/ethnic groups: the MESA study. J Thromb Haemost 2006; 04: 2629-2635.
12
Howard G,
Cushman M,
Kissela BM.
et al. Traditional risk factors as the underlying cause of racial disparities in stroke: lessons from the half-full (empty?) glass. Stroke 2011; 42: 3369-3375.
13
Howard VJ,
Cushman M,
Pulley L.
et al. The reasons for geographic and racial differences in stroke study: objectives and design. Neuroepidemiol 2005; 25: 135-143.
14
Howard VJ,
Kleindorfer DO,
Judd SE.
et al. Disparities in stroke incidence contributing to disparities in stroke mortality. Ann Neurol 2011; 69: 619-627.
15
Gillett SR,
Boyle RH,
Zakai NA.
et al. Validating laboratory results in a national observational cohort study without field centers: the Reasons for Geographic and Racial Differences in Stroke cohort. Clin Biochem 2014; 47: 243-246.
16
Safford MM,
Brown TM,
Muntner PM.
et al. Association of race and sex with risk of incident acute coronary heart disease events. J Am Med Assoc 2012; 308: 1768-1774.
17
Luepker RV,
Apple FS,
Christenson RH.
et al. Case definitions for acute coronary heart disease in epidemiology and clinical research studies: a statement from the AHA Council on Epidemiology and Prevention; AHA Statistics Committee; World Heart Federation Council on Epidemiology and Prevention; the European Society of Cardiology Working Group on Epidemiology and Prevention; Centers for Disease Control and Prevention; and the National Heart, Lung, and Blood Institute. Circulation 2003; 108: 2543-2549.
19
Kulathinal S,
Karvanen J,
Saarela O.
et al. Case-cohort design in practice - experiences from the MORGAM Project. Epidemiol Perspect Innovat 2007; 04: 15.
20
Cushman M,
Judd SE,
Howard VJ.
et al. N-terminal pro-B-type natriuretic peptide and stroke risk: the reasons for geographic and racial differences in stroke cohort. Stroke 2014; 45: 1646-1650.
21
Zakai NA,
Judd SE,
Alexander K.
et al. ABO blood type and stroke risk: the REasons for Geographic And Racial Differences in Stroke Study. J Thromb Haemost 2014; 12: 564-570.
24
Pearson TA,
Blair SN,
Daniels SR.
et al. AHA Guidelines for Primary Prevention of Cardiovascular Disease and Stroke: 2002 Update: Consensus Panel Guide to Comprehensive Risk Reduction for Adult Patients Without Coronary or Other Atherosclerotic Vascular Diseases. American Heart Association Science Advisory and Coordinating Committee Circulation 2002; 106: 388-391.
25
Agarwal S,
Hachamovitch R,
Menon V.
Current trial-associated outcomes with warfarin in prevention of stroke in patients with nonvalvular atrial fibrillation: a meta-analysis. Arch Intern Med 2012; 172: 623-633.
26
Kumar G,
Goyal MK.
Warfarin versus Aspirin for Prevention of Stroke in Heart Failure: A Meta-analysis of Randomized Controlled Clinical Trials. J Stroke Cerebrovasc Dis 2013; 22: 1279-1287.
28 Force USPST. Aspirin for the prevention of cardiovascular disease: U. S. Preventive Services Task Force recommendation statement.. Ann Intern Med 2009; 150: 396-404.
