Discriminative value of serum amyloid A and other acute-phase proteins for coronary heart disease

doi:10.1016/S0021-9150(01)00607-4

Atherosclerosis

Volume 160, Issue 2, February 2002, Pages 471-476

https://doi.org/10.1016/S0021-9150(01)00607-4 Get rights and content

Abstract

We studied the value of serum amyloid A (SAA), a first-class acute-phase protein, as a marker for coronary heart disease (CHD) in a middle-aged male population. In a working population of 16 307 men (age, 35–59 years), 446 cases had a history of CHD or prominent Q:QS waves on electrocardiogram. For each case, two matched controls were investigated. SAA, measured by immunonephelometry, was correlated with other acute-phase proteins, cardiovascular risk factors, and infectious serology markers. SAA concentrations were significantly higher in the cases than in controls (P<0.05) and correlated with serum C-reactive protein (CRP) (r=0.61), plasma fibrinogen (r=0.39), serum haptoglobin (r=0.26), and body mass index (r=0.13) (P<0.001). Serum CRP is a better marker for CHD than SAA, which showed discriminative power only in a univariate model comparing highest versus lowest tertile (odds ratio, 1.39; 95% confidence interval, 1.03–1.87). Neither SAA nor other acute-phase proteins correlated with Chlamydia pneumoniae immunoglobulin (Ig)G, Helicobacter pylori IgG and IgA, and cytomegalovirus IgG. In conclusion, although SAA has a discriminative value for CHD, serum CRP is to be preferred as a first-class acute-phase reactant for detection of the disease.

Introduction

Serum amyloid A (SAA) and C-reactive protein (CRP) are positive acute-phase proteins, levels of which may increase from 100-fold to over 1000-fold following inflammatory stimulus. Their hepatic synthesis is induced by cytokines such as interleukin-6 (IL-6) [1]. SAA and CRP are both called ‘first-class’ acute-phase reactants because they are the most sensitive plasma proteins indicating inflammatory activity [1]. Since the physiological serum level of SAA is approximately ten times higher than that of CRP, it might be easier to detect slightly elevated SAA than CRP [1]. Recent studies indicate that SAA is the most sensitive non-invasive biochemical marker for allograft rejection [2].

Recent evidence suggests that low-grade inflammation contributes importantly to the initiation and the progression of atherosclerosis [3], [4], [5]. Specifically, slightly elevated levels of CRP have been associated with coronary heart disease (CHD) [6], [7], [8], [9] and have been found to predict future cardiovascular risk among apparently healthy subjects [10], [11], [12], [13]. Published data for SAA, on the other hand, are scanty. Elevated SAA levels have been observed in subjects at risk for developing future CHD [12], [13] as well as in patients with coronary and peripheral vascular disease [8], [9], [14], [15], [16]. It has also been proposed that the low-grade inflammation in atherosclerosis might be attributed to underlying infections with bacterial and viral pathogens such as Chlamydia pneumoniae, Helicobacter pylori, and cytomegalovirus [17], [18].

Our objective was to compare serum SAA with CRP concentration as a marker for coronary heart disease in an apparently healthy working population. The first-class acute-phase proteins were correlated with classical cardiovascular risk factors, other acute-phase reactants (fibrinogen, haptoglobin), and antibody titers against infectious agents that have been associated with the atherosclerotic process.

Section snippets

Study subjects

The investigation was approved by the Ethical Committee of the Ghent University Hospital. Middle-aged Caucasian males, employed in 24 Belgian companies, were invited to participate in a health-screening program at the worksite. A total of 16 307 Caucasian men, aged 35–59 years, volunteered and gave informed consent. Data on socio-economic characteristics, smoking habits, alcohol intake, physical activity, diabetes status and medical history were collected by self-administered, detailed

Results

Table 1 compares cardiovascular risk factors between cases and controls. Log-normal distributions were observed for SAA. In the cases, SAA concentrations were higher than in the controls (P<0.05). More significantly, serum CRP levels were also higher in the cases than in controls (P<0.0001).

Table 2 depicts the Pearson correlation analysis between acute-phase proteins and quantitative risk factors for CHD in the control group. SAA positively correlated with serum CRP, plasma fibrinogen, serum

Discussion

In a middle-aged, male, working population, we found that SAA concentrations are higher among subjects with history of CHD and correlate with other markers of inflammation CRP, fibrinogen and haptoglobin. Unlike CRP and other acute-phase proteins, however, SAA did not correlate with the negative acute-phase reactant HDL cholesterol.

SAA can be considered as an apolipoprotein since it binds to HDL particles and has been proposed to modulate the metabolism of the lipoprotein [1], [2]. Inflammatory

Acknowledgements

This study was supported by grant number 7.000.998 from ‘Levenslijn’ (Fund for Scientific Research, Belgium). Reagents for SAA determination were kindly provided by Dade Behring.

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¹: Unfortunately deceased during the course of this study.

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Discriminative value of serum amyloid A and other acute-phase proteins for coronary heart disease

Abstract

Introduction

Section snippets

Study subjects

Results

Discussion

Acknowledgements

Atherosclerosis

Atherosclerosis

Atherosclerosis

J. Immunol. Methods

Am. J. Cardiol.

Serum amyloid A (SAA): a concise review of biology, assay methods and clinical usefulness

Clin. Chem. Lab. Med.

Atherosclerosis — an inflammatory disease

New Engl. J. Med.

Inflammation, atherosclerosis, and cardiovascular risk: an epidemiologic view

Blood. Coag. Fibrinol.

The prognostic value of C-reactive protein and serum amyloid A protein in severe unstable angina

New Engl. J. Med.

Association of fibrinogen, C-reactive protein, albumin, or leukocyte count with coronary heart disease: meta-analyses of prospective studies

J. Am. Med. Assoc.

Systemic inflammatory parameters in patients with atherosclerosis of the coronary and peripheral arteries

Arterioscler. Thromb. Vasc. Biol.

Inflammatory markers in men with angiographically documented coronary heart disease

Clin. Chem.

Inflammation, aspirin, and the risk of cardiovascular disease in apparently healthy men

New Engl. J. Med.

C-reactive protein, a sensitive marker of inflammation, predicts future risk of coronary heart disease in initially healthy middle-aged men. Results from the MONICA (Monitoring Trends and Determinants in Cardiovascular Disease) Augsburg Cohort Study, 1984 to 1992

Circulation

C-reactive protein and other markers of inflammation in the prediction of cardiovascular disease in women

New Engl. J. Med.

Low grade inflammation and coronary heart disease: prospective study and updated meta-analyses

Br. Med. J.