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

TY - JOUR

T1 - Biomarkers in stable coronary heart disease, their modulation and cardiovascular risk: The LIPID biomarker study

AU - Tonkin, Andrew M

AU - Blankenberg, Stefan

AU - Kirby, Adrienne

AU - Zeller, Tanja

AU - Colquhoun, David M

AU - Funke-Kaiser, Anne

AU - Hague, Wendy

AU - Hunt, David

AU - Keech, Anthony C

AU - Nestel, Paul

AU - Stewart, Ralph

AU - Sullivan, David R

AU - Thompson, Peter L

AU - West, Malcolm

AU - White, Harvey D

AU - Simes, John

AU - LIPID Study Investigators

N1 - Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

PY - 2015/12/15

Y1 - 2015/12/15

N2 - 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 - 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.

KW - 1-Alkyl-2-acetylglycerophosphocholine Esterase/blood

KW - Adrenomedullin/blood

KW - Adult

KW - Aged

KW - Biomarkers/blood

KW - C-Reactive Protein/metabolism

KW - Coronary Artery Disease/blood

KW - Cystatin C/blood

KW - Female

KW - Fibrin Fibrinogen Degradation Products/metabolism

KW - Humans

KW - Hydroxymethylglutaryl-CoA Reductase Inhibitors/administration & dosage

KW - Male

KW - Middle Aged

KW - Natriuretic Peptide, Brain/blood

KW - Peptide Fragments/blood

KW - Pravastatin/administration & dosage

KW - Predictive Value of Tests

KW - Prognosis

KW - Risk Factors

KW - Troponin I/blood

KW - Troponin T/blood

U2 - 10.1016/j.ijcard.2015.07.080

DO - 10.1016/j.ijcard.2015.07.080

M3 - SCORING: Journal article

C2 - 26318511

VL - 201

SP - 499

EP - 507

JO - INT J CARDIOL

JF - INT J CARDIOL

SN - 0167-5273

ER -