Developing The Utility Of Blood Biomarker Associations Beyond Population Sample Linkage To Events In Cardiovascular Patients

West et al. 1 report a small, well designed post hoc nested case–control sample from the LIPID trial of pravastatin.2 This was completed in low risk subjects with documented coronary disease in the form of a previous confirmed acute coronary syndrome (ACS). This additional report examines biomarker linkage over a relatively short time frame of 2–3 years and highlights two measurements perhaps not intuitively linked to the biology of coronary disease progression. The conditional logistic regression analysis shows a significant linkage association following point analysis for N-terminal brain natriuretic peptide (NT-BNP) and tissue metalloproteinase-1 (TIMP-1). TIMP-1 has been linked to cardiovascular events in low risk patients previously, in patients with less well confirmed coronary disease.3 Its re-affirmation here as a population predictor of events in this group of patients is of value. Similarly for NT-BNP, which is frequently presumed to be linked to cardiac events largely via the presence of association with ventricular dilatation, remodelling, or ventricular ‘dysfunction’ (not factors intuitively present even in patients with a confirmed yet uncomplicated ACS), this is not the first report to link it to coronary outcomes even in the absence of overt ventricular impairment.4 More interestingly, in this report there was a significant linkage expressed by both markers to subsequent emergent stroke disease.5 Both NT-BNP (indirectly) and TIMP-1 (directly) can be linked, at least theoretically, to structural change within the heart, be it myocytic, functional (i.e. linked to dynamic contractile changes), geometric (fixed changes in cardiac shape or wall thickness), or within the connective tissue support structure.6,7 Both are of course linked in the biology of hypertension and/or hypertensive heart disease and vascular atherosclerosis,8.9 but this … *Corresponding author. Tel: +44 121 507 4476/5080, Fax: +44 121 554 4083, Email: Robert.macfadyen{at}swbh.nhs.uk