Interleukin-6, Fibrin D-Dimer, and Coagulation Factors VII and XIIa in Prediction of Coronary Heart Disease

Introduction: D-dimer, a marker of coagulation activation, has higher levels in blacks than whites and has been variably associated with stroke and coronary heart disease (CHD). Methods: REGARDS recruited 30,239 participants in their homes across the continental US between 2003-07; by design 55% were female, 41% black, and 56% lived in the southeast. In a case-cohort study, D-dimer was measured in 646 participants with incident stroke, 515 with incident CHD, and 1104 in a cohort random sample. D-dimer was log transformed and modeled per 1-unit increase. Cox models were used to determine the HR for vascular disease for D-dimer and the difference in HR (95% CI) by race and vascular disease calculated by bootstrapping with 1000 replicate samples and using the 2.5 and 97.5 percentiles of the distribution (see Table for model variables). Results: Median D-dimer was higher in blacks (0.45 mcg/mL; IQR 0.26, 0.85) than whites (0.38 mcg/mL; IQR 0.23, 0.69); p <0.001. D-dimer was higher with increasing age, female gender, diabetes, hypertension and prebaseline cardiovascular disease (all p <0.05). The table shows the HR of stroke and CHD by baseline D-dimer. In minimally-adjusted models, D-dimer was associated with both stroke and CHD. Accounting for Framingham stroke and CHD risk factors, D-dimer remained associated with CHD (HR 1.45; 95% CI 1.18, 1.79), but was marginally associated with stroke (HR 1.20; 95% CI 0.99, 1.45). The difference in the HR of D-dimer between CHD and stroke was 0.22 in the basic model and 0.25 in the Framingham model, but this difference was of marginal statistical significance (Table). There was no difference in the HRs for stroke or CHD for D-dimer in blacks compared to whites (Table). Discussion: The association of D-dimer with stroke appeared smaller than for CHD with similar associations by race. Findings suggest that hemostasis activation may play a greater role in pathogenesis of CHD than stroke. Further study is needed to confirm these findings and evaluate the association of D-dimer with different stroke subtypes.

Download Full-text

Abstract P075: Influence of Systemic Interleukin-6 on the Inverse Association between Your-Choice American Heart Diet and a 41-Year Mortality Risk from Coronary Heart Disease among Men

Circulation ◽

10.1161/circ.129.suppl_1.p075 ◽

2014 ◽

Vol 129 (suppl_1) ◽

Author(s):

Jun Dai ◽

Anthony J Acton ◽

Robert V Considine ◽

Ruth E Krasnow ◽

Terry Reed

Keyword(s):

Coronary Heart Disease ◽

Heart Disease ◽

Systemic Inflammation ◽

Mortality Risk ◽

Interleukin 6 ◽

Reactive Protein ◽

Chd Risk ◽

Long Term Mortality

Introduction: Whole diet evaluated using dietary pattern is associated with systemic inflammation and coronary heart disease (CHD). Systemic inflammation also contributes to CHD risk. Genetic factors explain variations in whole diet, systemic inflammation, and CHD. However, it is unknown whether systemic inflammation is a mechanism linking whole diet to the long-term mortality risk from coronary heart disease independent of genes. Hypothesis: Systemic inflammation measured as plasma interleukin-6 levels medicates the association between whole diet and long-term mortality risk from coronary heart disease independent of genes. Methods: From the National Heart, Lung, and Blood Institute Twin Study, we included 554 white, middle-aged, veteran male twins (105 monozygotic and 109 dizygotic twin pairs; 65 monozygotic and 61 dizygotic unpaired twins). The twins were not on antihypertensive medication and had diastolic blood pressure below 105 mmHg at baseline (1969-1973) and did not have suspected acute inflammation [plasma levels of interleukin-6 (IL-6) above 10 pg/mL or C-reactive protein above 30 mg/L)]. Usual dietary data at baseline were collected through nutritionist-administered dietary history interview. Your-Choice American Heart Diet (YCARD) score was devised to quantitatively evaluate whole diet. Plasma interleukin-6 and C-reactive protein levels were measured with ELISA. Data on vital status and death causes were collected through death certificates until Dec 31, 2010. A frailty survival model was used to estimate various associations: overall (equivalent to the association in the general population), within-pair (independent of genes and environment common to co-twins), and between-pair (indicating influence of the common factors). We controlled for total caloric intake and known CHD risk factors including body mass index and modified Framingham Risk Score. Results: There were 75 CHD deaths during a 41-year follow-up (median follow-up of 34 years). The adjusted overall association between YCARD score and the CHD mortality risk was negative [partial coefficient for a 10-unit increment in the YCARD score: βo (95% confidence interval (CI)): -0.13 (-0.24, -0.02); hazard ratio (95% CI): 0.88 (0.78, 0.98)]. The partial regression coefficient was -0.02 [95% CI (-0.23, 0.19)] for the within-pair effect of YCARD (βw) and -0.12 [95% CI (-0.26, 0)] for the between-pair effect of YCARD (βb) in relation to CHD mortality risk. Additional adjustment for IL-6 led to a 15.4% reduction in the βo, a 100% increment in the βw, and a 16.7% reduction in the βb. Conclusions: Systemic inflammation measured as interleukin-6 mediates the association between whole diet and long-term coronary heart mortality risk, which is largely through genetic and environmental factors shared between co-twins.

Download Full-text

Coagulation Factors II, V, IX, X, XI, and XII, Plasminogen, and α-2 Antiplasmin and Risk of Coronary Heart Disease

Journal of Atherosclerosis and Thrombosis ◽

10.5551/jat.3673 ◽

2010 ◽

Vol 17 (4) ◽

pp. 402-409 ◽

Cited By ~ 13

Author(s):

Kazumasa Yamagishi ◽

Nena Aleksic ◽

Peter J Hannan ◽

Aaron R Folsom

Keyword(s):

Coronary Heart Disease ◽

Heart Disease ◽

Coagulation Factors

Download Full-text

Interleukin-6-174G>C polymorphism and risk of coronary heart disease in west of Scotland coronary prevention study (WOSCOPS)

ACC Current Journal Review ◽

10.1016/s1062-1458(02)00774-2 ◽

2002 ◽

Vol 11 (5) ◽

pp. 28 ◽

Cited By ~ 1

Author(s):

F. Basso ◽

G.D.O. Lowe ◽

A. Rumley

Keyword(s):

Coronary Heart Disease ◽

Heart Disease ◽

Interleukin 6 ◽

Prevention Study ◽

Scotland Coronary Prevention Study

Download Full-text

C-reactive protein levels and common polymorphisms of the interleukin-1 gene cluster and interleukin-6 gene in patients with coronary heart disease

European Journal of Immunogenetics ◽

10.1111/j.1365-2370.2004.00476.x ◽

2004 ◽

Vol 31 (5) ◽

pp. 207-213 ◽

Cited By ~ 66

Author(s):

G. Latkovskis ◽

N. Licis ◽

U. Kalnins

Keyword(s):

Coronary Heart Disease ◽

Heart Disease ◽

Gene Cluster ◽

Interleukin 6 ◽

Interleukin 1 ◽

C Reactive Protein ◽

Protein Levels ◽

Reactive Protein

Download Full-text

Predictive value of the Wells score combined with D-dimer level in identifying acute pulmonary embolism in patients with coronary heart disease with chest pain

Chinese Medical Journal ◽

10.1097/cm9.0000000000000988 ◽

2020 ◽

Vol 133 (18) ◽

pp. 2253-2255

Author(s):

Jing Wang ◽

Xiao-Yan Wu ◽

Ying Liang ◽

Wei Guo

Keyword(s):

Coronary Heart Disease ◽

Pulmonary Embolism ◽

Heart Disease ◽

Chest Pain ◽

Predictive Value ◽

Acute Pulmonary Embolism ◽

Wells Score ◽

D Dimer

Download Full-text

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

European Journal of Cardiovascular Prevention & Rehabilitation ◽

10.1097/hjr.0b013e3280e129d0 ◽

2007 ◽

Vol 14 (5) ◽

pp. 638-645 ◽

Cited By ~ 18

Author(s):

Margaret May ◽

Debbie A. Lawlor ◽

Rita Patel ◽

Ann Rumley ◽

Gordon Lowe ◽

...

Keyword(s):

Coronary Heart Disease ◽

Heart Disease ◽

Plasminogen Activator ◽

Tissue Plasminogen Activator ◽

Von Willebrand Factor ◽

Incident Coronary Heart Disease ◽

Tissue Plasminogen ◽

Von Willebrand ◽

Willebrand Factor ◽

D Dimer

Background Associations of three markers of thrombotic tendency, von Willebrand factor, tissue plasminogen activator antigen and fibrin D-dimer, with coronary heart disease have been reported in meta-analyses. It is not known, however, whether findings are generalizable to older women. Design Prospective cohort of 3582 women aged 60-79 years randomly selected from 23 towns without evidence of cardiovascular disease at entry into the British Women's Heart and Health Study. Methods Women were followed for 4.7 years for incident coronary heart disease. Cox proportional hazard models were used to compare the hazard ratio of coronary heart disease per doubling for each thrombotic factor. Results In models adjusting for age and town only there was no association between von Willebrand factor or D-dimer and incidence of coronary heart disease, but there was a positive association of tissue plasminogen activator: coronary heart disease hazard ratio per doubling was 1.37 (95% confidence interval: 1.08-1.75). Adjustment for potential confounders (socio-economic position, smoking, lung function, physical activity, alcohol consumption, body mass index, waist-to-hip ratio) attenuated association to 1.20 (0.92-1.58). Further adjustment for risk factors that may be part of the same pathophysiological process linking tissue plasminogen activator to coronary heart disease (high density lipoprotein cholesterol, triglycerides, blood pressure, fasting glucose, insulin, C-reactive protein, fibrinogen) attenuated the hazard ratio to 1.05 (0.79-1.40). Conclusion In older women, tissue plasminogen activator was associated with incident coronary heart disease, but does not appear to be an independent risk factor for coronary heart disease as the association was attenuated by adjustment for confounding and other metabolic and vascular risk factors. Eur J Cardiovasc Prev Rehabil 14:638-645 © 2007 The European Society of Cardiology

Download Full-text