TY - JOUR
T1 - Biomarkers in stable coronary heart disease, their modulation and cardiovascular risk: The LIPID biomarker study
AU - Tonkin, A.M.
AU - Blankenberg, S.
AU - Kirby, A.
AU - Zeller, T.
AU - Colquhoun, D.M.
AU - Funke-Kaiser, A.
AU - Hague, W.
AU - Hunt, D.
AU - Keech, A.C.
AU - Nestel, P.
AU - Stewart, R.
AU - Sullivan, D.R.
AU - Thompson, Peter
AU - West, M.
AU - White, H.D.
AU - Simes, J.
PY - 2015/12/15
Y1 - 2015/12/15
N2 - © 2015 Elsevier Ireland Ltd.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.
AB - © 2015 Elsevier Ireland Ltd.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.
U2 - 10.1016/j.ijcard.2015.07.080
DO - 10.1016/j.ijcard.2015.07.080
M3 - Article
C2 - 26318511
SN - 0167-5273
VL - 201
SP - 499
EP - 507
JO - International Journal of Cardiology
JF - International Journal of Cardiology
ER -