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

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.

• Authors: Andrew M Tonkin, Stefan Blankenberg, Adrienne Kirby, Tanja Zeller, David M Colquhoun, Anne Funke-Kaiser, Wendy Hague, David Hunt, Anthony C Keech, Paul Nestel, Ralph Stewart, David R Sullivan, Peter L Thompson, Malcolm West, Harvey D White, John Simes, LIPID study investigators
• Journal: International journal of cardiology (Int J Cardiol) Vol. 201 Pg. 499-507 (Dec 15 2015) ISSN: 1874-1754 [Electronic] Netherlands
• PMID: 26318511 (Publication Type: Journal Article, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Chemical References

• Biomarkers
• Cystatin C
• Fibrin Fibrinogen Degradation Products
• Hydroxymethylglutaryl-CoA Reductase Inhibitors
• Peptide Fragments
• Troponin I
• Troponin T
• fibrin fragment D
• Natriuretic Peptide, Brain
• Adrenomedullin
• C-Reactive Protein
• 1-Alkyl-2-acetylglycerophosphocholine Esterase
• Pravastatin

Topics

• 1-Alkyl-2-acetylglycerophosphocholine Esterase (blood)
• Adrenomedullin (blood)
• Adult
• Aged
• Biomarkers (blood)
• C-Reactive Protein (metabolism)
• Coronary Artery Disease (blood, drug therapy, metabolism)
• Cystatin C (blood)
• Female
• Fibrin Fibrinogen Degradation Products (metabolism)
• Humans
• Hydroxymethylglutaryl-CoA Reductase Inhibitors (administration & dosage, pharmacology)
• Male
• Middle Aged
• Natriuretic Peptide, Brain (blood)
• Peptide Fragments (blood)
• Pravastatin (administration & dosage)
• Predictive Value of Tests
• Prognosis
• Risk Factors
• Troponin I (blood, metabolism)
• Troponin T (blood, metabolism)