Differential Expression of Cardiac Biomarkers by Gender in Patients With Unstable Angina/Non–ST-Elevation Myocardial Infarction: A TACTICS-TIMI 18 (Treat Angina with Aggrastat and determine Cost of Therapy with an Invasive or Conservative Strategy–Thrombolysis In Myocardial Infarction 18) Substudy

Background—Diagnosis of coronary artery disease in women is more difficult because of lower specificity of symptoms and diagnostic accuracy of noninvasive testing. We sought to examine the relationship between gender and cardiac biomarkers in patients with unstable angina (UA)/non–ST-segment elevation myocardial infarction (NSTEMI). Methods and Results—In the TACTICS-TIMI 18, OPUS-TIMI 16, and TIMI 11 studies, baseline samples were analyzed in the Thrombolysis In Myocardial Infarction (TIMI) biomarker core laboratory. We examined the relationship between gender and elevated biomarkers. Of 1865 patients from TACTICS-TIMI 18, 34% were women. Fewer women had elevated creatine kinase-MB or troponins, whereas more had elevated high-sensitivity C-reactive protein or brain natriuretic peptide. Presence of ST-segment deviation and TIMI risk scores were not significantly different. This pattern was confirmed in TIMI 11 and OPUS-TIMI 16. The prognostic value of the markers in TACTICS-TIMI 18 was similar in women and men. When a multimarker approach was examined, a greater proportion of high-risk women were identified. Marker-positive patients of both genders had improved outcome with an invasive strategy; however, marker-negative women appeared to have improved outcomes with a conservative strategy. Conclusions—In patients with UA/NSTEMI, there was a different pattern of presenting biomarkers. Men were more likely to have elevated creatine kinase-MB and troponins, whereas women were more likely to have elevated C-reactive protein and brain natriuretic peptide. This suggests that a multimarker approach may aid the initial risk assessment of UA/NSTEMI, especially in women. Further research is necessary to elucidate whether gender-related pathophysiological differences exist in presentation with acute coronary syndromes.

[1]  E. Antman,et al.  C-Reactive Protein Is a Potent Predictor of Mortality Independently of and in Combination With Troponin T in Acute Coronary Syndromes: A TIMI 11A Substudy , 1998 .

[2]  E. Braunwald,et al.  Ability of minor elevations of troponins I and T to predict benefit from an early invasive strategy in patients with unstable angina and non-ST elevation myocardial infarction: results from a randomized trial. , 2001, JAMA.

[3]  E. Antman,et al.  C-reactive protein is a potent predictor of mortality independently of and in combination with troponin T in acute coronary syndromes: a TIMI 11A substudy. Thrombolysis in Myocardial Infarction. , 1998, Journal of the American College of Cardiology.

[4]  M. Sabatine,et al.  The prognostic value of B-type natriuretic peptide in patients with acute coronary syndromes. , 2001, The New England journal of medicine.

[5]  H. White,et al.  Troponin concentrations for stratification of patients with acute coronary syndromes in relation to therapeutic efficacy of tirofiban , 1999, The Lancet.

[6]  P. Ridker,et al.  Inflammation, aspirin, and the risk of cardiovascular disease in apparently healthy men. , 1997, The New England journal of medicine.

[7]  P. Ridker,et al.  C-reactive protein and prognosis after percutaneous coronary intervention. , 2002, European heart journal.

[8]  A. Siegbahn,et al.  Markers of myocardial damage and inflammation in relation to long-term mortality in unstable coronary artery disease. FRISC Study Group. Fragmin during Instability in Coronary Artery Disease. , 2000, The New England journal of medicine.

[9]  J. Hollander,et al.  B-Type Natriuretic Peptide and Clinical Judgment in Emergency Diagnosis of Heart Failure: Analysis From Breathing Not Properly (BNP) Multinational Study , 2002, Circulation.

[10]  E. Braunwald,et al.  Influence of race, sex, and age on management of unstable angina and non-Q-wave myocardial infarction: The TIMI III registry. , 1996 .

[11]  E. Antman.  TIMI 11B. Enoxaparin versus unfractionated heparin for unstable angina or non-Q-wave myocardial infarction: a double-blind, placebo-controlled, parallel-group, multicenter trial. Rationale, study design, and methods. Thrombolysis in Myocardial Infarction (TIMI) 11B Trial Investigators. , 1998, American heart journal.

[12]  L. Wallentin,et al.  Is early invasive treatment of unstable coronary artery disease equally effective for both women and men? FRISC II Study Group Investigators. , 2001, Journal of the American College of Cardiology.

[13]  F. Harrell,et al.  Cardiac Troponin T Levels for Risk Stratification in Acute Myocardial Ischemia , 1996 .

[14]  Dose-ranging trial of enoxaparin for unstable angina: results of TIMI 11A. The Thrombolysis in Myocardial Infarction (TIMI) 11A Trial Investigators. , 1997, Journal of the American College of Cardiology.

[15]  David A Morrow,et al.  Future of Biomarkers in Acute Coronary Syndromes Moving Toward a Multimarker Strategy , 2003, Circulation.

[16]  E. Braunwald,et al.  Benefit of an early invasive management strategy in women with acute coronary syndromes. , 2002, JAMA.

[17]  V. Gökhan Cin,et al.  The prognostic value of serum troponin T in unstable angina. , 1996, International journal of cardiology.

[18]  C. Vassanelli,et al.  [Comparison of early invasive and conservative strategies in patients with unstable coronary syndromes treated with the glycoprotein IIb/IIIa inhibitor tirofiban]. , 2001, Italian heart journal. Supplement : official journal of the Italian Federation of Cardiology.

[19]  E. Braunwald,et al.  Outcome and profile of women and men presenting with acute coronary syndromes: a report from TIMI IIIB. TIMI Investigators. Thrombolysis in Myocardial Infarction. , 1997, Journal of the American College of Cardiology.

[20]  R. Califf,et al.  N‐Terminal Pro‐Brain Natriuretic Peptide and Other Risk Markers for the Separate Prediction of Mortality and Subsequent Myocardial Infarction in Patients With Unstable Coronary Artery Disease: A Global Utilization of Strategies To Open occluded arteries (GUSTO)‐IV Substudy , 2003, Circulation.

[21]  Eorge,et al.  CARDIAC-SPECIFIC TROPONIN I LEVELS TO PREDICT THE RISK OF MORTALITY IN PATIENTS WITH ACUTE CORONARY SYNDROMES , 2000 .

[22]  A. Jaffe,et al.  Gender Differences in C-Reactive Protein Concentrations - Confirmation with Two Sensitive Methods , 2002, Clinical chemistry and laboratory medicine.

[23]  A. Skene,et al.  Oral glycoprotein IIb/IIIa inhibition with orbofiban in patients with unstable coronary syndromes (OPUS-TIMI 16) trial. , 2000, Circulation.

[24]  F. Harrell,et al.  Cardiac troponin T levels for risk stratification in acute myocardial ischemia. GUSTO IIA Investigators. , 1996, The New England journal of medicine.

[25]  E. Antman,et al.  Cardiac troponin I for stratification of early outcomes and the efficacy of enoxaparin in unstable angina: a TIMI-11B substudy. , 2000, Journal of the American College of Cardiology.

[26]  E. Antman,et al.  The TIMI risk score for unstable angina/non-ST elevation MI: A method for prognostication and therapeutic decision making. , 2000, JAMA.

[27]  A. Rebuzzi,et al.  The prognostic value of C-reactive protein and serum amyloid a protein in severe unstable angina. , 1994, The New England journal of medicine.

[28]  D. Levy,et al.  Impact of age and sex on plasma natriuretic peptide levels in healthy adults. , 2002, The American journal of cardiology.

[29]  J. Kaski,et al.  C-reactive protein in patients with chronic stable angina: differences in baseline serum concentration between women and men. , 2000, European heart journal.

[30]  B. Lindahl,et al.  Risk stratification in unstable coronary artery disease--exercise test and troponin T from a gender perspective. FRISC-Study Group. Fragmin during InStability in Coronary artery disease. , 1997, Journal of the American College of Cardiology.

[31]  F Van de Werf,et al.  Sex, clinical presentation, and outcome in patients with acute coronary syndromes. Global Use of Strategies to Open Occluded Coronary Arteries in Acute Coronary Syndromes IIb Investigators. , 1999, The New England journal of medicine.

[32]  Nader Rifai,et al.  Multimarker Approach to Risk Stratification in Non-ST Elevation Acute Coronary Syndromes: Simultaneous Assessment of Troponin I, C-Reactive Protein, and B-Type Natriuretic Peptide , 2002, Circulation.

[33]  C. Cannon,et al.  Differences between men and women in the management of unstable angina pectoris (The GUARANTEE Registry). The GUARANTEE Investigators. , 1999, The American journal of cardiology.

[34]  G. Diamond,et al.  Incremental value of exercise electrocardiography and thallium-201 testing in men and women for the presence and extent of coronary artery disease. , 1995, American heart journal.

[35]  P. Ridker,et al.  C-reactive protein and other markers of inflammation in the prediction of cardiovascular disease in women. , 2000, The New England journal of medicine.