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Circulation. 2018 Aug 14;138(7):712-723. doi: 10.1161/CIRCULATIONAHA.117.029901.

D-Dimer Predicts Long-Term Cause-Specific Mortality, Cardiovascular Events, and Cancer in Patients With Stable Coronary Heart Disease.

Author information

1
National Health and Medical Research Council Clinical Trials Centre, University of Sydney, Australia (J.S., K.P.R., D.E., W.H., A.C.K.).
2
Green Lane Cardiovascular Service, Auckland City Hospital, New Zealand (H.D.W., R.A.S.).
3
Royal Prince Alfred Hospital, Sydney, Australia (D.R.S.).
4
University Heart Centre Hamburg, Germany (T.Z., S.B.).
5
Baker Heart and Diabetes Institute, Melbourne, Australia (P.J.N.).
6
Faculty of Health Sciences and Medicine, Bond University, Gold Coast, Queensland, Australia (P.P.G.).
7
Department of Medicine, University of Otago, Christchurch, New Zealand (J.E.).
8
Department of Epidemiology and Preventive Medicine, Monash University, Melbourne, Australia (A.M.T.).

Abstract

BACKGROUND:

D-dimer, a degradation product of cross-linked fibrin, is a marker for hypercoagulability and thrombotic events. Moderately elevated levels of D-dimer are associated with the risk of venous and arterial events in patients with vascular disease. We assessed the role of D-dimer levels in predicting long-term vascular outcomes, cause-specific mortality, and new cancers in the LIPID trial (Long-Term Intervention with Pravastatin in Ischaemic Disease) in the context of other risk factors.

METHODS:

LIPID randomized patients to placebo or pravastatin 40 mg/d 5 to 38 months after myocardial infarction or unstable angina. D-dimer levels were measured at baseline and at 1 year. Median follow-up was 6.0 years during the trial and 16 years in total.

RESULTS:

Baseline D-dimer levels for 7863 patients were grouped by quartile (≤112, 112-173, 173-273, >273 ng/mL). Higher levels were associated with older age, female sex, history of hypertension, poor renal function, and elevated levels of B-natriuretic peptide, high-sensitivity C-reactive protein, and sensitive troponin I (each P<0.001). During the first 6 years, after adjustment for up to 30 additional risk factors, higher D-dimer was associated with a significantly increased risk of a major coronary event (quartile 4 versus 1: hazard ratio [HR], 1.45; 95% confidence interval, 1.21-1.74), major cardiovascular disease (CVD) event (HR, 1.45; 95% confidence interval, 1.23-1.71) and venous thromboembolism (HR, 4.03; 95% confidence interval, 2.31-7.03; each P<0.001). During the 16 years overall, higher D-dimer was an independent predictor of all-cause mortality (HR, 1.59), CVD mortality (HR, 1.61), cancer mortality (HR, 1.54), and non-CVD noncancer mortality (HR, 1.57; each P<0.001), remaining significant for deaths resulting from each cause occurring beyond 10 years of follow-up (each P≤0.01). Higher D-dimer also independently predicted an increase in cancer incidence (HR, 1.16; P=0.02).The D-dimer level increased the net reclassification index for all-cause mortality by 4.0 and venous thromboembolism by 13.6.

CONCLUSIONS:

D-dimer levels predict long-term risk of arterial and venous events, CVD mortality, and non-CVD noncancer mortality independent of other risk factors. D-dimer is also a significant predictor of cancer incidence and mortality. These results support an association of D-dimer with fatal events across multiple diseases and demonstrate that this link extends beyond 10 years' follow-up.

KEYWORDS:

biomarkers; cardiovascular diseases; cholesterol; coronary disease; fibrin fragment D; hydroxymethylglutaryl-CoA reductase inhibitors; lipids; risk assessment

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