Biomarkers in stable coronary heart disease, their modulation and cardiovascular risk: the LIPID biomarker study

White, HD; Simes, J; Tonkin, AM; Blankenberg, S; Sullivan, DR; Zeller, T; Colquhoun, DM; Funke-Kaiser, A; Stewart, R; Hunt, D; Kirby, A; Keech, AC; Nestel, P; Hague, W; LIPID study investigators; Thompson, PL; West, M
Abstract
AIMS: In patients with stable coronary heart disease (CHD), we aimed to assess 1. the prognostic power of biomarkers reflecting haemodynamics, micronecrosis, inflammation, coagulation, lipids, neurohumoral activity, and renal function; 2. whether changes in concentrations of these biomarkers over 12 months affected subsequent CHD risk; and 3. whether pravastatin modified the change in biomarker concentrations and this influenced the risk of future events. METHODS: In the LIPID study, 9014 patients were randomised to pravastatin 40 mg or placebo 3-36 months after an acute coronary syndrome. Eight biomarkers were measured at baseline (n=7863) and 12 months later (n=6434). RESULTS: During a median of 6.0 (IQR 5.5-6.5) years follow-up, 1100 CHD-related deaths and nonfatal myocardial infarctions occurred, 694 after biomarker measurement at 12 months. Baseline BNP, CRP, cystatin C, D-dimer, midregional pro-adrenomedullin, and sensitive troponin I predicted recurrent CHD events. In a multivariable model, sensitive troponin I, BNP, and cystatin C had the strongest associations with outcome (P<0.001 for trend). The strongest improvement in risk prediction was achieved by including sensitive troponin I (net reclassification improvement (NRI) 5.5%; P=0.003), BNP (4.3%; P=0.02), history of MI (NRI 7.0%; P<0.001). In landmark analyses, among biomarkers, changes to 12 months in sensitive troponin I (HR 1.32 (1.03-1.70) for T3/T1), BNP (HR 1.37 (1.10-1.69) for Q4/Q1) and Lp-PLA2 (HR 1.52 (1.16-1.97)) improved CHD risk prediction. CONCLUSIONS: Baseline levels and changes in sensitive troponin I, and BNP may have the potential to guide the intensity of secondary prevention therapy. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.
Journal INT J CARDIOL
ISSN 0167-5273
Published 15 Dec 2015
Volume 201
Issue
Pages 499-507
DOI 10.1016/j.ijcard.2015.07.080
Type Journal Article
Sponsorship
NHMRC: 490968