Circulating biomarkers for predicting cardiovascular disease risk; a systematic review and comprehensive overview of meta-analyses

Abstract

Background: Cardiovascular disease is one of the major causes of death worldwide. Assessing the risk for cardiovascular disease is an important aspect in clinical decision making and setting a therapeutic strategy, and the use of serological biomarkers may improve this. Despite an overwhelming number of studies and meta-analyses on biomarkers and cardiovascular disease, there are no comprehensive studies comparing the relevance of each biomarker. We performed a systematic review of meta-analyses on levels of serological biomarkers for atherothrombosis to compare the relevance of the most commonly studied biomarkers.

Methods and findings: Medline and Embase were screened on search terms that were related to "arterial ischemic events" and "meta-analyses". The meta-analyses were sorted by patient groups without pre-existing cardiovascular disease, with cardiovascular disease and heterogeneous groups concerning general populations, groups with and without cardiovascular disease, or miscellaneous. These were subsequently sorted by end-point for cardiovascular disease or stroke and summarized in tables. We have identified 85 relevant full text articles, with 214 meta-analyses. Markers for primary cardiovascular events include, from high to low result: C-reactive protein, fibrinogen, cholesterol, apolipoprotein B, the apolipoprotein A/apolipoprotein B ratio, high density lipoprotein, and vitamin D. Markers for secondary cardiovascular events include, from high to low result: cardiac troponins I and T, C-reactive protein, serum creatinine, and cystatin C. For primary stroke, fibrinogen and serum uric acid are strong risk markers. Limitations reside in that there is no acknowledged search strategy for prognostic studies or meta-analyses.

Conclusions: For primary cardiovascular events, markers with strong predictive potential are mainly associated with lipids. For secondary cardiovascular events, markers are more associated with ischemia. Fibrinogen is a strong predictor for primary stroke.

Figure 1. PRISMA flow diagram.

Figure 2. Plot of the results of meta-analyses on CVD events in populations without pre-existing CVD.

The results of a selection of meta-analyses on CVD events in populations without pre-existing CVD with a result over 1.5 or under 0.66 are graphically represented. Details of the studies are described in Table 1 and Table S1 in File S1. Abbreviations: CRP: C-reactive protein, Apo: apolipoprotein, HDL: high density lipoprotein.

Figure 3. Plot of the results of meta-analyses on CVD events in populations with pre-existing CVD.

The results of a selection of meta-analyses on CVD events in populations with pre-existing CVD with a result over 1.5 or under 0.66 are graphically represented. Details of the studies are described in Table 2 and Table S2 in File S1. Abbreviations: vWF: von Willebrand Factor, (hs)-CRP: (high sensitivity) C-reactive protein, cTnT/I: cardiac troponin T/I, (NT-pro)BNP: (amino terminal prohormone of) brain natriuretic peptide, eGFR: estimated glomerular filtration rate.

Figure 4. Plot of the results of meta-analyses on stroke events in populations without pre-existing CVD.

The results of a selection of meta-analyses on stroke events in populations without pre-existing CVD are graphically represented. Details of the studies are described in Table 3 and Table S3 in File S1.