Yaz Litigation: In spite of continued advancements in the management of acute ischemic heart disease, morbidity and mortality due to atherosclerotic vascular disease continue to rise globally. Thus, the impetus for improving our strategies for the prevention and management of atherosclerosis has remained strong. In this regard, laboratory and experimental research describing key processes in the initiation, progression, and destabilization of the atheroma have pointed to novel directions for cardiovascular evaluation and management. In particular, recognition of the role of inflammation in atherothrombosis has directed attention to inflammatory mediators and indicators as potential targets for risk assessment and for treatment.
Epidemiological data have established a well-characterized set of vascular risk factors, including advanced age, tobacco use, obesity, diabetes, hypertension, and dyslipidemia. However, up to one-third of first coronary events occur among individuals without these traditional risk factors. Researchers have thus sought to identify inflammatory indicators that might add to these clinical factors for predicting myocardial infarction and stroke. Candidate markers have included several of the cytokines that promote the recruitment of monocytes in response to endothelial cell dysfunction; intercellular adhesion molecules that mediate the migration of activated monocytes into the subendothelial space; enzymes that might compromise the integrity of the protective fibrous cap, as well as the acute-phase proteins that are produced and released into the systemic circulation in response to inflammatory cytokines. As an amplified and readily quantified inflammatory signal, the prototypical acute- phase reactant C-reactive protein (CRP) has been a focus of clinical investigation to date.
With systemic levels that are dependent on the rate of de novo hepatic production, CRP levels remain stable over long periods of time in the absence of new stimuli. However, in response to acute tissue injury, infection, or other inflammatory stimuli, CRP levels rise several hundred-fold. As such, CRP and its acute-phase counterpart, serum amyloid A, have been useful in following disease activity in chronic inflammatory conditions such as systemic lupus, inflammatory bowel disease, and rheumatoid arthritis. Traditional semiquantitative latex agglutination or standard turbidometric methods have been adequate to evaluate such marked elevation of CRP in these disease processes. In contrast, the development of high-sensitivity assays for CRP (hs-CRP) has now enabled detection of CRP within the normal range for healthy individuals. Further, the introduction of high through-put methods with high analytical sensitivity and reproducibility has provided a simple clinical tool to carefully evaluate the extent of underlying systemic inflammation.
Cross-sectional studies have evaluated the association between elevated levels of CRP and the presence and extent of atherosclerotic vascular disease. Elevated levels of CRP have been demonstrated among patients with acute myocardial ischemia and infarction, as well as among individuals with stable coronary heart disease (CHD). In a cross-sectional survey of 388 British men aged 50 to 69 recruited from general practice registers, Mendall and colleagues demonstrated a 1.5-fold increase in the prevalence of CHD for each doubling in the levels of hs-CRP (95% CI, 1.25-1.92). Nevertheless, such cross-sectional data cannot exclude the possibility of important confounding, nor do they establish a cause-and-effect relationship. For example, blood levels of hs-CRP have been found to increase with age, body-mass index, and tobacco use, as well as in response to myocardial tissue necrosis. In contrast, prospective studies can control for such confounders and have been important in exploring the independent prognostic information offered by inflammatory markers.
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