Prognostic value of multiple emerging biomarkers in cardiovascular risk prediction in patients with stable cardiovascular disease
Introduction
New avenues for prevention of cardiovascular disease (CVD) including better diagnosis and risk evaluation are of increasing interest in high-risk groups. In this regard, novel biomarkers such as natriuretic peptides namely atrial natriuretic peptide (ANP) and brain-type natriuretic peptide (BNP) as well as C-reactive protein (CRP) and homocysteine are of interest.
ANP and BNP are vasoactive cardiac peptide hormones with natriuretic, diuretic, and vasodilator activity [1], that could be important diagnostic and prognostic tools for CVD and related mortality in general population and coronary heart disease (CHD) patients [2], [3], [4], [5], [6], [7], [8]. Few studies have simultaneously evaluated the prognostic value of both natriuretic peptides (proANP and proBNP) over and above conventional cardiovascular risk factors, beyond the period of hospitalization after an acute CVD event (MI, left ventricular systolic dysfunction and chronic heart failure) [9], [10]. In addition, newer assays targeting more stable epitopes of ANP, such as mid-regional pro-ANP (MR-proANP) have become available that could offer more refined risk assessment [11]. In clinical practice established tests such as CRP and homocysteine are often considered in CVD risk assessment. CRP is commonly determined using routinely available assays as a systemic inflammatory marker [12]. Although the evidence linking elevated homocysteine and CVD risk is inconsistent [13], [14], recent promising findings from NHANES III and Multi-Ethnic Study of Atherosclerosis (MESA) studies showing significant improvement in risk prediction for future CVD and CHD events in intermediate-risk patients upon addition of homocysteine to the Framingham risk model [15], has re-sparked interest in this marker for CVD risk assessment. The current study, thus, evaluated the comparative prognostic value of four biomarkers (natriuretic peptides MR-proANP and NT-proBNP, CRP and homocysteine) alone and in combination, in addition to conventional risk factors, in patients with stable CVD, in whom information on predictive risk has not been extensively evaluated using emerging biomarkers [9], [16].
Section snippets
Study design
The SU.FOL.OM3 trial is a multicenter, double-blind randomized controlled trial (RCT) that evaluated the separate and combined effects of daily supplementation with B-vitamins, and/or n-3 polyunsaturated fatty acid for prevention of CVD [17]. Participants (45–80 y) were recruited via a nationwide network of 417 cardiologists, neurologists or other physicians. Those meeting the CVD inclusion criteria of a history of ischemic stroke or other coronary event i.e. acute coronary syndrome with or
Results
The study involved 1456 subjects who were diagnosed with either acute coronary syndrome (31%), or acute MI (49.2%) or stroke (19.5%) at 1–12 months (mean: 4 mo) prior to inclusion in the study. Briefly, subjects were randomly assigned to receive either a placebo (23%) or a supplement (omega-3 fatty acids alone (25%), B-vitamins folic acid and B-12 alone (27%) or with omega-3 fatty acids (25%) [17]. The supplementation had no effect on the occurrence of CVD outcomes [17] nor on specific CVD
Discussion
The comparative prognostic value of a panel of emerging biomarkers namely MR-proANP, NT-proBNP, CRP, and homocysteine for predicting cardiovascular risk was evaluated in this relatively large prospective study of stable CVD patients, who had a major CVD event on average 4 months prior to baseline assessment. Although studies have examined the improvement in CVD risk prediction using novel and classic biomarkers [5], [10], [22], [23], [24], [25], most focused on individuals in early stages of
Funding
The SU.FOL.OM3 trial was supported by the French Ministry of Research [R02010JJ]; Ministry of Health (DGS); Sodexo; Candia; Unilever; Danone; Roche Laboratory; Merck EPROVA GS; and Pierre Fabre Laboratory. The funding agencies were not involved in study design, analysis, and interpretation.
Declaration of conflicting interests
The Authors declare that there is no conflict of interest.
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