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• The additive value of biomarkers to clinical risk scores in acute coronary syndrome
  Antonio Tello-Montoliu
  Published on: 17 August 2009

• Published on: 17 August 2009

  The additive value of biomarkers to clinical risk scores in acute coronary syndrome

  • Antonio Tello-Montoliu, Consultant in Cardiology
  • Other Contributors:
    • Francisco Marín, Vanessa Roldán, Gregory YH Lip

  We read with great interest the study by Ang et al1, addressing the value of brain natriuretic peptide (BNP) levels in comparison with the GRACE score for acute coronary syndromes(ACS), and the additional predictive role of BNP on this established risk score. The latter is of great interest for physicians managing ACS patients. Indeed, several new (and sometimes, not-so-new) biomarkers have been studied in relation to their...

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  We read with great interest the study by Ang et al1, addressing the value of brain natriuretic peptide (BNP) levels in comparison with the GRACE score for acute coronary syndromes(ACS), and the additional predictive role of BNP on this established risk score. The latter is of great interest for physicians managing ACS patients. Indeed, several new (and sometimes, not-so-new) biomarkers have been studied in relation to their prognostic role in ACS, and some give prognostic information in relation to new adverse events2. Several biomarkers, like BNP or C-reactive protein (CRP), are currently available in the majority of hospitals and could be readily used in clinical practice. However, except for troponin, neither is currently being used for ACS risk stratification. Do these new biomarkers really offer much additional information? In the study by Ang et al, BNP showed better discriminatory accuracy than the GRACE score, and the combination of both increased risk prediction, but only with a marginal improvement. Our group has investigated the addition of various different biomarkers to the TIMI risk score and its effect on the area under curve (AUC) values (see figure), in a non-ST elevation ACS (nSTEACS) population of 415 patients. These data corroborate the small increases of the AUC value when new biomarkers were added to the clinical risk variables. The figure shows how c-statistic increases after adding different variables into the model, as represented by TIMI risk score. The addition of new biomarkers, such as hs-CRP, NT pro-BNP, and angiogenin (a marker of angiogenic activity) all confer a slight increase of c-statistic. Despite the smaller power of prediction of TIMI risk score in comparison with GRACE scale, these studies are in agreed with others3. Thus, could new biomarkers be useful in current clinical practice? In our opinion, new biomarkers may give greater accuracy to the clinical scores for nSTEACS risk prediction, and add new important information regarding major adverse events, for example, the prediction of death or heart failure by BNP levels. This information would be complementary to troponin or clinical scales. However, more interesting is the possibility of classifying patients in new risk group. For example, Ang et al show how the GRACE- scale high risk group could be reclassified in two new risk groups, representing the 25% of entire population. The new ‘very high risk’ group (high BNP + high GRACE scale) was approximately 6 fold more likely to experience a cardiovascular adverse event at 10 months. Similarly, in a 358 patients admitted with nSTEACS, we found a 2-fold increase of event rate at 6 month follow-up, depending the number of biomarkers elevated (in this case, troponin, hs-CRP and NT pro-BNP), despite the risk group as defined by TIMI risk score4. This finding may be certainly be important given that new high risk groups could be managed more aggressively in terms of drugs and interventions. These results were confirmed by other authors, for example, Wiviott et al5 demonstrate a better outcome of patients (mainly women) who had high BNP and CRP levels and underwent cardiac catheterization unless their troponin levels were low. Nonetheless, not all new biomarkers (for example, placental growth factor6) have been demonstrated their value in risk prediction as convincingly as BNP or CRP levels. The exploration of different biomarkers from several systems implicated in the complex physiopathology of nSTEACS could be interesting and may be highly accurate. Until well-established and highly predictive new biomarkers are available, we suggest that the use of other one biomarker, such as BNP (or NT pro-BNP) and/or hs-CRP levels in current clinical practice could by helpful, by giving more information to the physician regarding the risk of adverse events in patients admitted with nSTEACS. Antonio Tello-Montoliu1 Francisco Marín2 Vanessa Roldán3 Gregory YH Lip4 1 Cardiology Department. Hospital Virgen de la Salud. Toledo (Spain). 2 Cardiology Department. Hospital Virgen de la Arrixaca. Murcia (Spain). 3 Hematology and Oncology Department. Hospital Morales Meseguer. Murcia (Spain). 4 University of Birmingham Centre for Cardiovascular Sciences, City Hospital, Birmingham, England UK REFERENCES 1. Ang DSC, Wei L, Kao MPC, Lang CC, Struthers AD. A comparision between b-type natriuretic peptide, global registry of acute coronary events (GRACE) score and their combination in ACS risk stratification. Heart 2009. In press. 2. Morrow DA, Cannon CP, Jesse RL, Newby LK, Ravkilde J, Storrow AB, et al. National Academy of Clinical Biochemistry Laboratory Medicine Practice Guidelines: clinical characteristics and utilization of biochemical markers in acute coronary syndromes. Clin Chem. 2007;53:552- 74. 3. Westerhout CM, Fu Y, Lauer MS, et al. Short- and long-term risk stratification in acute coronary syndromes. The added value of quantitative ST-segment depression and multiple biomarkers. J Am Coll Cardiol 2006;48:939-947. 4. Tello-Montoliu A, Marín F, Roldán V, Mainar L, López MT, Sogorb F, et al. A multimarker risk stratification approach to non-ST elevation Acute Coronary Syndrome: Implications of Troponin T, CRP, NT pro-BNP and fibrin D-Dimer levels. J Int Med 2007;262:651-8. 5. Wiviott SD, Cannon CP, Morrow DA, Murphy SA, Gibson CM, McCabe CH, et al. Differential expression of cardiac biomarkers by gender in patients with unstable angina/non-ST-elevation myocardial infarction: a TACTICS- TIMI 18 (Treat Angina with Aggastrat and Determine Cost of Therapy with an Invasive or Conservative Strategy-Thrombolysis in Myocardial Infarction 18) substudy. Circulation 2004;109:580-6. 6.- Heeschen C, Dimmeler S, Fichtlscherer S, Hamm CW, Berger J, Simoons ML, et al. Prognostic value of placental growth factor in patients with acute chest pain. JAMA 2004;291:435–41.

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  Conflict of Interest:
  None declared.

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