Plasma concentrations of D-Dimer predict mortality?

Concentração plasmática de Dímero-D é um preditor de mortalidade?

EDITORIALS

Plasma concentrations of D-Dimer predict mortality?

Concentração plasmática de Dímero-D é um preditor de mortalidade?

Oswaldo T. Greco^I; Rafael L. Greco^II

^IDiretor científico do Instituto de Moléstias Cardiovasculares de S. José do Rio Preto, SP

^IIMédico assistente do IMC. S. José do Rio Preto, SP

^{Correspondência}

Atherosclerosis is characterized by a nonspecific local inflammatory process which is accompanied by a systemic response. Since such an inflammatory response is present at all stages of atherogenesis, a large number of emerging inflammatory biomarkers have been identified during the past decade, which might aid in identifying individuals at high risk for coronary heart disease(CHD).

Fibrin D-Dimer is a major fibrin-specific degradation product that detects cross-linked fibrin resulting from endogenous fibrinolysis. D-Dimer can be considered as a global marker for the direct measurement of ongoing turnover of cross-linked fibrin and for an activation of the haemostatic system without reflecting the changes in fibrinogen and fibrin status. In addition, due to the introduction of ELISA, measurement of D-Dimer is well established in clinical practice as a screening marker of activated coagulation. D-Dimer plays an important role in the detection of hypercoagulable states such as acute symptomatic deep-vein thrombosis, pulmonary embolism or disseminated intravascular coagulation (CVD) having a high negative predictive value.

Taking into account that thrombogenesis is one of the fundamental pathological processes underlying the major complications of atherosclerotic disease, measurement of D-dimer might be useful to identify patients at high risk for future CVD events.

Indeed, in the Physician's Health Study,¹ a strong association between increased D-Dimer concentrations and future myocardial infarction was found in multivariate analysis, after controlling for nonlipid risk factors and Lp(a). However, if total and high-density lipoprotein cholesterol, as well as endogenous t-PA and its primary inhibitor, PAI-1, were included in the analysis, its association was attenuated and no longer statistically significant. Future ischemic events were predicted by D-Dimer levels in a study by Lowe et al.,² but not by other markers of procoagulant activity, such as prothrombin fragment F1+2 and thrombin-antithrombin complex (measures of thrombin generation), or by factor VII coagulant activity. Increased levels of D-Dimer also predicted future CHD events in apparently healthy middleaged participants of a large community-based prospective study.³ Comparison of men in the top tertile with those in the bottom tertile of the baseline fibrin D- Dimer distribution resulted in an odds ratio for CHD of 1.79 (95% CL, 1.36-2.36) after adjustmente for smoking, other classical risk factors, and indicators of socioeconomic status. Subsequent meta-analysis, including this and four other population-based cohorts and two studies in patients with stable CVD, yielded almost the same results: an odds ratio of 1.7 (95% CI,1,3-2,2) was found for subjects with D-Dimer levels in the top tertile compared with those in the bottom. In the Atherosclerosis Risk in Communities study, several haemostatic parameters (t-PA, PAI-1, plasminofen and prothrombin fragment F1+2, D-Dimer) were measured in 326 incident CHD cases during a follow-up of 4.3 years and in a randomly stratified referent cohort of 720 individuals. Among these biomarkers only- D-dimer showed a powerful predicitive value for incident CHD with a RR of 4.21 (95% CI, 1.9-9.6).⁴ Finally, in there more recently published reports the strength of the association between elevated levels of D-Dimer and cardiovascular events was similar to those preciously found in meta-analysis, revealing multivariate-adjusted risk estimates of 1.86(95% CI,1.24-2.80.⁵

We conclude that pulmonary embolism can be exclude in patients who have low clinical probability of pulmonary embolism and negative erythrocyte agglutination D-Dimer test results and that further diagnostic testing is not beneficial to this population. These findings are present in approximately 50% of outpatients and 20% of inpatients with suspected pulmonary embolism.

References

1. Ridker PM, Hennekens CH, Cerskus A, StamplerMJ. Plasma concentrations of cross-linked fibrin degradation product (D-dimer) and the risk of future myocardial infarction among apparently healthy men. Circulation 1994;90:2.236-2.240.

2. Lowe GD, Rumley A, Sweetham PM, et al. Fibrin D-dimer, markers of coagulation activation and the risk of major ischaemic heart disease in the Caerphilly Study. Tromb Haemost 2001;86:822-827.

3. Danesh J, Whincup P, Walker M, et al. Fibrin D-dimer and coronary heart disease: prospective study and meta-analysis. Circulation 2001;103:2.323-2.327

4. Folsom AR, Aleksic N, Park E, et al. Prospective study of fibrinolytic factors and incident coronary heart disease: the Atherosclerosis Risk in. Communities (ARIC) Study. Arterioscler Thromb Vasc Biol 2001;21:611-617

5. Smith A, Patterson C, Yamell J, et al. Which remostatic markers add to the predictive value of conventional risk factors for coronary heart disease and ischemic stroke? The Caerphilly Study. Circulation 2005;112:3.080-3.087.

Recebido: 24/10/2006

Aceito: 25/10/2006

Avaliação: O tema abordado foi sugerido e avaliado pelo editor.

Conflito de interesse: não declarado

Publication Dates

• Publication in this collection
  12 July 2007
• Date of issue
  Dec 2006