C-reactive protein levels and coronary artery disease incidence and mortality in apparently healthy men and women: The EPIC-Norfolk prospective population study 1993-2003

Leiden University, Leyden, South Holland, Netherlands
Atherosclerosis (Impact Factor: 3.99). 09/2006; 187(2):415-22. DOI: 10.1016/j.atherosclerosis.2005.09.023
Source: PubMed


Measurement of C-reactive protein (CRP) levels has been proposed as a useful marker to improve the prediction of future coronary artery disease (CAD) risk, but this notion has been challenged recently.
We performed a prospective case-control study among apparently healthy men and women. The odds ratio (OR) for future CAD incidence was 2.49 (95% CI=2.02-3.08, p for linearity <0.0001) unadjusted, and 1.66 (95% CI=1.31-2.12, p for linearity <0.0001), after adjustment for classical cardiovascular risk factors, for top versus bottom quartile of the CRP distribution. Notably, the risk factor adjusted predictive value was substantially stronger for fatal CAD (OR=2.92, 95% CI=1.83-4.67, p for linearity <0.0001) than for non-fatal CAD (OR=1.25, 95% CI=0.93-1.66, p for linearity=0.06). CRP levels were among the strongest predictors of CAD incidence and mortality. CRP levels remained a statistically significant predictor of future CAD, even after adjustment for the Framingham risk score.
In this British cohort with risk factor levels representative of a contemporary Western population, CRP concentration was among the strongest predictors of CAD incidence and mortality. We suggest that current guidelines on CRP measurement in clinical practice should be based on contemporary and representative populations.

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    • "Regarding CRP, a controversial worldwide debate persists over its participation in CVD. Several retrospective and prospective studies, as well as meta-analyses, have described an association with MI [71, 72, 84, 89, 90], coronary insufficiency [4, 73, 91], cerebrovascular disease [85], and peripheral artery disease [92], behaving as an important mortality predictor [69]. As such, a large portion of scientific opinion supports CRP as a risk marker, in response to the inflammatory process within the atherosclerotic plaque and other previously established CRF [88]. "
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    ABSTRACT: An important etiopathogenic component of cardiovascular disease is atherosclerosis, with inflammation being an essential event in the pathophysiology of all clinical pictures it comprises. In recent years, several molecules implicated in this process have been studied in order to assess cardiovascular risk in both primary and secondary prevention. C-reactive protein is a plasmatic protein of the pentraxin family and an acute phase reactant, very useful as a general inflammation marker. Currently, it is one of the most profoundly researched molecules in the cardiovascular field, yet its clinical applicability regarding cardiovascular risk remains an object of discussion, considered by some as a simple marker and by others as a true risk factor. In this sense, numerous studies propose its utilization as a predictor of cardiovascular risk through the use of high-sensitivity quantification methods for the detection of values <1 mg/L, following strict international guidelines. Increasing interest in these clinical findings has led to the creation of modified score systems including C-reactive protein concentrations, in order to enhance risk scores commonly used in clinical practice and offer improved care to patients with cardiovascular disease, which remains the first cause of mortality at the worldwide, national, and regional scenarios.
    Full-text · Article · Feb 2014
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    • "Moreover, almost half of their patients who had CRP levels >10 mg/L had an infection within 2 weeks prior to their index hospitalization with an MI [21], thus obscuring a direct relation between CRP to diastolic dysfunction following the occurrence of an MI. There are now convincing data that CRP is an independent predictor of future cardiovascular events, including cardiovascular death, MI, stroke, revascularization, the development of peripheral vascular disease, and sudden cardiac death [22] [23] [24] [25] [26]. Early CRP level elevation in AMI was shown to predict higher risk for future HF development, despite apparent clinical stability [3]. "
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    ABSTRACT: An elevated C-reactive protein (CRP) level is associated with adverse outcomes in patients with acute myocardial infarction (AMI). Although CRP levels have been shown to be associated with left ventricular (LV) systolic function and remodeling in AMI, little is known about their relation to early LV diastolic function. We retrospectively studied 173 consecutive patients <75 years of age with first ST-segment elevation MI (STEMI) that was treated by primary percutaneous coronary intervention (PPCI). They had presented within 24h of chest pain onset and their CRP levels were determined within 6h of hospital admission. They all underwent echocardiography within 3 days of admission and were stratified by CRP tertiles. The cut-off points for the CRP tertiles were <2.6mg/L, 2.6-7.9mg/L, and >7.9mg/L. Patients with higher CRP levels had a significantly higher mean mitral inflow E wave velocity (68±16cm/s vs 77±19cm/s vs 76±17cm/s; p=0.02), a higher E/average e' (8.9±1.9 vs 9.8±2.8 vs 10.4±3.2; p=0.02), and a higher systolic pulmonary artery pressure (27±6mmHg vs 30±8mmHg vs 32±10mmHg; p=0.04). Elevated CRP levels were associated with more advanced diastolic dysfunction than normal CRP levels (p=0.04). The admission CRP level was an independent predictor of average E/e' ratio (multivariate analysis). Admission CRP levels are associated with echocardiographic parameters of elevated LV filling pressure in patients with STEMI treated with PPCI.
    Full-text · Article · Nov 2013 · Journal of Cardiology
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    • "shows the distribution of cardiovascular risk factors among cases and controls in the EPIC-Norfolk CAD nested case-control study. As expected and as previously reported [40], cases had more adverse cardiovascular risk profiles than control participants who remained free of disease during follow-up. There was no material difference between circulating IGF-I and IGFBP- 3 levels among cases and controls (Table 3). "
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    ABSTRACT: Although experimental studies have suggested that insulin-like growth factor I (IGF-I) and its binding protein IGFBP-3 might have a role in the aetiology of coronary artery disease (CAD), the relevance of circulating IGFs and their binding proteins in the development of CAD in human populations is unclear. We conducted a nested case-control study, with a mean follow-up of six years, within the EPIC-Norfolk cohort to assess the association between circulating levels of IGF-I and IGFBP-3 and risk of CAD in up to 1,013 cases and 2,055 controls matched for age, sex and study enrolment date. After adjustment for cardiovascular risk factors, we found no association between circulating levels of IGF-I or IGFBP-3 and risk of CAD (odds ratio: 0.98 (95% Cl 0.90-1.06) per 1 SD increase in circulating IGF-I; odds ratio: 1.02 (95% Cl 0.94-1.12) for IGFBP-3). We examined associations between tagging single nucleotide polymorphisms (tSNPs) at the IGF1 and IGFBP3 loci and circulating IGF-I and IGFBP-3 levels in up to 1,133 cases and 2,223 controls and identified three tSNPs (rs1520220, rs3730204, rs2132571) that showed independent association with either circulating IGF-I or IGFBP-3 levels. In an assessment of 31 SNPs spanning the IGF1 or IGFBP3 loci, none were associated with risk of CAD in a meta-analysis that included EPIC-Norfolk and eight additional studies comprising up to 9,319 cases and 19,964 controls. Our results indicate that IGF-I and IGFBP-3 are unlikely to be importantly involved in the aetiology of CAD in human populations.
    Full-text · Article · Aug 2011 · International Journal of Molecular Epidemiology and Genetics
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