Cohort profile of BIOMArCS: the BIOMarker study to identify the Acute risk of a Coronary Syndrome—a prospective multicentre biomarker study conducted in the Netherlands

Abstract

PurposeProgression of stable coronary artery disease (CAD) towards acute coronary syndrome (ACS) is a dynamic and heterogeneous process with many intertwined constituents, in which a plaque destabilising sequence could lead to ACS within short time frames. Current CAD risk assessment models, however, are not designed to identify increased vulnerability for the occurrence of coronary events within a precise, short time frame at the individual patient level. The BIOMarker study to identify the Acute risk of a Coronary Syndrome (BIOMArCS) was designed to evaluate whether repeated measurements of multiple biomarkers can predict such ‘vulnerable periods’.ParticipantsBIOMArCS is a multicentre, prospective, observational study of 844 patients presenting with ACS, either with or without ST-elevation and at least one additional cardiovascular risk factor.Methods and analysisWe hypothesised that patterns of circulating biomarkers that reflect the various pathophysiological components of CAD, such as distorted lipid metabolism, vascular inflammation, endothelial dysfunction, increased thrombogenicity and ischaemia, diverge in the days to weeks before a coronary event. Divergent biomarker patterns, identified by serial biomarker measurements during 1-year follow-up might then indicate ‘vulnerable periods’ during which patients with CAD are at high short-term risk of developing an ACS. Venepuncture was performed every fortnight during the first half-year and monthly thereafter. As prespecified, patient enrolment was terminated after the primary end point of cardiovascular death or hospital admission for non-fatal ACS had occurred in 50 patients. A case–cohort design will explore differences in temporal patterns of circulating biomarkers prior to the repeat ACS.Future plans and disseminationFollow-up and event adjudication have been completed. Prespecified biomarker analyses are currently being performed and dissemination through peer-reviewed publications and conference presentations is expected from the third quarter of 2016. Should identification of a ‘vulnerable period’ prove to be feasible, then future research could focus on event reduction through pharmacological or mechanical intervention during such periods of high risk for ACS.Trial registration numberNTR1698 and NTR1106.

<p>High Lipoprotein(a) Levels as a Predictor of Major Adverse Cardiovascular Events in Hospitalized-Acute Myocardial Infarction Patients</p>

“…The structure can bind to fibrin and receptors on endothelial cells which will interfere clot lysis thus increase the tendency of thrombosis. [10][11][12] The oxidative form of Lp(a) can weaken the fibrinolytic system by decreasing the activation of plasminogen, increasing the production of vasodilator inhibitory agents in endothelial cells thus affecting vasodilation. [12][13][14] Lp(a) has also been shown to interact with other molecules in a plethora of pathways related to thrombosis including inhibition of activation of transforming growth factor-β (TGF-β) and platelet activation.…”

“…24 After all, existing epidemiological research to date shows that high Lp(a) levels are independent predictors of CVD risk and MACE. [10][11][12][13][14] This study involved 66 samples taken by consecutive sampling with a total of 53 males (80.3%) and 13 females (19.7%). STEMI (63.6%) was found more than NSTEMI (36.4%).…”

Joint models for longitudinal and time‐to‐event data in a case‐cohort design

“…This also leads to a substantial difference in event rate which is 24% in CCII, compared to 5% in CCI. Both versions of the case-cohort design use 1492 3 indicates the difference between the slope estimates before and after 30 days. The coefficient for the slope after 30 days is given by…”

“…The motivation for the current paper comes from the longitudinal "BIOMarker study to identify the Acute risk of a Coronary Syndrome" (BIOMArCS), in which acute coronary syndrome (ACS) patients were examined in different medical centers in the Netherlands to study the association between (multiple) biomarkers and a recurrent ACS event (primary endpoint). 3,4 Multiple biomarkers were identified to be of interest, measured in blood samples taken regularly during one year of follow-up. A downside of collecting multiple biomarkers is the rising costs due to the numerous biomarker measurements, since costs are associated with the ascertainment of each biomarker measured.…”

High-frequency metabolite profiling and the incidence of recurrent cardiac events in patients with post-acute coronary syndrome

“…BIOMArCS is a multicentre observational study, conducted during 2008-2015 in the Netherlands. Details concerning the study design have been described elsewhere (Oemrawsingh et al 2016). In brief, BIOMArCS enrolled patients who were admitted for ACS, either with or without ST elevation, and who had at least one additional CVD risk factor.…”