ASSOCIATION BETWEEN CRP AND CARDIOVASCULAR DISEASES – A REVIEW
MARIA KURIAN
BDS
SAVEETHA DENTAL COLLEGE
Abstract:
The aim of this review is to assess the relationship between C reactive protein and cardiovascular diseases. Cardiovascular disease (CVD) is currently the leading cause of death and disability in the developed world, and will soon overtake infectious disease as the pre-eminent cause of death worldwide. A substantial body of evidence has suggested that four modifiable risk factors — smoking, diabetes, hypertension and hyperlipidemia account for a significant proportion of CVD, and that reduction of these risk factors leads to reduction in morbidity and mortality. Interleukin-6 (IL-6) and C-reactive protein (CRP) are markers of systemic vascular inflammation that herald atherothrombosis and may have important interrelationships with traditional cardiovascular risk factors. Although markers of systemic inflammation may have a role in the development of hypertension, supportive clinical data remain limited. IL-6 and CRP were measured from baseline bloods. After multivariate adjustment and strong confounding by body mass index, IL-6 was found weakly associated and CRP strongly associated with hypertension risk.
Introduction:
Inflammatory processes have important roles in the etiology of coronary heart disease (CHD),(1,2) but the mechanisms underlying this relationship are poorly understood. Several studies have shown that elevated plasma levels of fibrinogen, C-reactive protein (CRP), and interleukin-6 (IL-6) are associated with the risk of CHD and the severity of atherosclerosis.(3-6) Whether these molecules play a causative role, or simply act as markers of the acute phase reaction, is debatable.(7) High blood pressure (HBP) is one of the most important risk factors for cardiovascular–renal disease. In spite of its high health impact, primary prevention of HBP is partly hampered because of a limited knowledge of HBP risk factors. (8) C-reactive protein has been shown to be associated to HBP in a few well-controlled studies.(9,10,11) On the other hand, results from studies on the association between interleukin-6 (IL-6) and HBP have been contradictory.(12,13) The interplay between the inflammatory process, cardiovascular risk factors, and atherothrombosis is complex.(14) Despite evolving theories regarding IL-6 and CRP in the central mechanisms of inflammation and atherogenesis,(15) there exists a paucity of data coherently relating clinical cardiovascular risk factors with circulating levels of systemic vascular inflammatory markers in healthy individuals. A strong and consistent association between clinical manifestations of atherothrombotic disease and baseline CRP levels has been described in epidemiological studies of patients with acute myocardial ischemia(16) or myocardial infarction,(17,18) stable and unstable angina pectoris,(19) and myocardial infarction or recurrent ischemia among those hospitalized with angina pectoris.(20,21)
C-REACTIVE PROTEIN:
C-reactive protein (CRP), an acute-phase reactant, is an indicator of underlying systemic inflammation and a novel plasma marker for atherothrombotic disease. The recent use of highly sensitive CRP assays, with international reference standards set by the World Health Organization (WHO),(22) has enhanced the usefulness of CRP as a reliable predictor of cardiovascular events. Large prospective studies in apparently healthy subjects confirmed the prognostic relevance of CRP to (1) the risk of cardiovascular disease in men,(23) women,(24,25) and the elderly(26,27); (2) the risk of fatal coronary disease among smokers with multiple risk factors for atherosclerosis(28); (3) the development of peripheral vascular disease(29); and (4) the risk of coronary heart disease (CHD) in a large cohort of initially healthy middle-aged men.(30) The synthesis of CRP by the liver is largely regulated by IL-6. Although the activated leukocyte is widely assumed to be the major source of circulating IL-6, with additional contributions from fibroblasts and endothelial cells(31)
INFLAMMATORY MARKERS:
In an effort to better identify patients at high risk for cardiovascular events, several markers of risk have been proposed for use in screening, including homocysteine and fibrinogen levels, fibrinolytic capacity, and levels of apolipoprotein A-I, apolipoprotein B-100, and Lp(a) lipoprotein. However, the clinical value of many of these markers has been limited because of inadequate standardization of assay conditions, inconsistency of prospective data, or lack of evidence of significant improvement in the prediction of risk over that afforded by standard lipid screening alone. With the recognition that atherosclerosis is an inflammatory process, several plasma markers of inflammation have also been evaluated as potential tools for prediction of the risk of coronary events. Among them are markers of systemic inflammation produced in the liver, such as high-sensitivity C-reactive protein (hs-CRP) and serum amyloid A; cytokines such as interleukin-6; and adhesion molecules such as soluble intercellular adhesion molecule type 1 (sICAM-1). However, as with other proposed predictors of the risk of cardiovascular events, the prognostic value of these markers of inflammation remains uncertain.
DISCUSSION:
There has been much interest in the prognostic significance of raised levels of C-reactive protein in patients with angina,(32) with the proposal that it points to release of IL-6 by activated
macrophages in an unstable plaque.(33) More recently, however, the observations that raised concentrations of CRP in healthy subjects predicted the incidence of CHD over a period of years(34,35,36) have suggested a role for inflammation in the initiation of atherosclerosis as well as in the precipitation
of an acute event. The synthesis of CRP is predominantly under the control of IL-6(37) which in turn has been assumed to originate largely from activated leukocytes, either in the vessel wall itself or at a remote site of infection.(38,39) The correlations between these antibody titers and concentrations of fibrinogen, TNF-a, and IL-6 were weaker and generally insignificant. In addition to their associations with insulin resistance syndrome variables, elevated levels of CRP and of cytokines were associated with a series of indicators of endothelial dysfunction. Tracy et al have previously reported associations of levels of CRP with a variety of measures of procoagulant activity and fibrinolysis,(40) and have suggested that these represent consequences either of inflammation in underlying atherothrombotic disease or of inflammatory cells activated by products of ongoing coagulation processes.
Conclusion:
CHD is the leading cause of death and disability in developed nations and is increasing rapidly in the developing world. Up to half of all events associated with CHD are reported to occur in apparently healthy individuals who have few or none of the traditional risk factors, including dyslipidemia. As a result, attention has increasingly turned to the role of other factors, such as inflammation, in the development of atherosclerosis and CHD. In conclusion, CRP levels seem to be correlated with levels of heart disease risk. In fact, CRP seems to predict cardiovascular risk at least as well as cholesterol levels do, thus enabling early diagnosis of CVDs and may provide new directions for prevention of cardiovascular events.
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