Multiple Biomarkers for the Prediction of First Major Cardiovascular Events and Death

Section of Endocrinology, Diabetes, Nutrition, Boston University, Boston, Massachusetts, United States
New England Journal of Medicine (Impact Factor: 55.87). 12/2006; 355(25):2631-9. DOI: 10.1056/NEJMoa055373
Source: PubMed


Few investigations have evaluated the incremental usefulness of multiple biomarkers from distinct biologic pathways for predicting the risk of cardiovascular events.
We measured 10 biomarkers in 3209 participants attending a routine examination cycle of the Framingham Heart Study: the levels of C-reactive protein, B-type natriuretic peptide, N-terminal pro-atrial natriuretic peptide, aldosterone, renin, fibrinogen, D-dimer, plasminogen-activator inhibitor type 1, and homocysteine; and the urinary albumin-to-creatinine ratio.
During follow-up (median, 7.4 years), 207 participants died and 169 had a first major cardiovascular event. In Cox proportional-hazards models adjusting for conventional risk factors, the following biomarkers most strongly predicted the risk of death (each biomarker is followed by the adjusted hazard ratio per 1 SD increment in the log values): B-type natriuretic peptide level (1.40), C-reactive protein level (1.39), the urinary albumin-to-creatinine ratio (1.22), homocysteine level (1.20), and renin level (1.17). The biomarkers that most strongly predicted major cardiovascular events were B-type natriuretic peptide level (adjusted hazard ratio, 1.25 per 1 SD increment in the log values) and the urinary albumin-to-creatinine ratio (1.20). Persons with "multimarker" scores (based on regression coefficients of significant biomarkers) in the highest quintile as compared with those with scores in the lowest two quintiles had elevated risks of death (adjusted hazard ratio, 4.08; P<0.001) and major cardiovascular events (adjusted hazard ratio, 1.84; P=0.02). However, the addition of multimarker scores to conventional risk factors resulted in only small increases in the ability to classify risk, as measured by the C statistic.
For assessing risk in individual persons, the use of the 10 contemporary biomarkers that we studied adds only moderately to standard risk factors.

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    • "Efforts have subsequently been made to identify new predictors of coronary artery disease (CAD)[123] as 20% of coronary events occur in the absence of traditional risk factors.[4] To determine whether there are psychological risk factors for CAD has been a challenge for evidence-based medicine, however, it is not prudent to affirm that they do not affect it pathogenesis, since depression and psychological stress have been associated with increased risk of CAD.[56789] Denollet et al. proposed that there is a type-D or “distressed” personality that describes individuals with high levels of negative affectivity (NA) and social inhibition (SI). "
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    ABSTRACT: Background: Type-D personality has been identified as a risk factor for general and cardiac mortality in patients with coronary artery disease (CAD). Dobutamine-atropine stress echocardiography (DASE) is an established method for non-invasive evaluation of myocardial ischemia in patients with CAD. The objective of this study was to evaluate the prevalence of type-D personality and its association with the occurrence of myocardial ischemia as assessed by DASE. Methods: This case-control study enrolled 306 patients (61 ± 9.6 years, 57.8% female) who were referred by physicians to assessment of myocardial ischemia. Before undergoing DASE, the patients answered the type-D scale, which identifies type-D personality. Results: Type-D personality was identified in 106 patients (34.6%). DASE was positive for myocardial ischemia in 32.4% (99) of 306 participants there was no significant association between type-D personality and ischemic changes on DASE (P = 0.941; odds ratio: 0.98; confidence interval 95%: 0.57-1.69). Chest pain was the only clinical variable with statistically significant prevalence in type-D personality patients (77.4% vs. 57.0%; P < 0.001). Conclusions: Type-D personality was not a significant risk factor for the presence of ischemic changes on DASE. Patients with type-D personality tended to complain more frequently of chest pain than non-type-D patients.
    International journal of preventive medicine 07/2014; 5(7):895-899.
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    • "Regarding the association of CRP and BNP as prognostic markers, an investigation of the Framingham Offspring Study which compared C-statistic between models with traditional risk factors only and with the addition of a multi-marker score that included both hs-CRP and BNP found that only BNP led to a to a small increase in the ability of the model in discriminating between death and survival in older adults [48]. On the other hand, CRP and NT-proBNP, a precursor of BNP, were independently related to CV and overall mortality and a score formed by the two biomarkers plus three others substantially improved the predictive ability over conventional risk factors in a population of older adults with mean age of 71 years [49]. "
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    PLoS ONE 09/2013; 8(9):e75809. DOI:10.1371/journal.pone.0075809 · 3.23 Impact Factor
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    • "It is worth noting that the presence of a strong association between risk factor and the outcome assessed does not necessarily mean that the risk factor provides a base for an effective predictive rule. Wang et al39have shown that, in individual risk assessment, the use of ten biomarkers added only a discrete discriminatory capacity to the classical risk factors, with practically overlapping ROC curves and similar c indices (0.76 versus 0.77). "
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