Update on Selected Markers Used in Risk Assessment for Vascular Disease

Clinical Laboratory Science, Winter 2004 by Carreiro-Lewandowski, Eileen

The ATP III recommends that lipoprotein testing should occur in all adults starting at the age of 20, and repeated at five year intervals. It recommends that an initial panel include all four tests (total cholesterol, LDL, HDL, and triglycerides) and testing be performed on fasting samples. In the event a sample is procured from a non-fasting individual, only the HDL and total cholesterol can be considered. If the total cholesterol values are > or =200 mg/dL or HDL is

The report also proposes a multifaceted approach to reducing the risk of CHD, depending on the individual's assessed category of risk. These include lipid-lowering substances, such as prescription medications, use of plant sterols, and diets with increased soluble fiber, along with 'therapeutic lifestyle changes' (TLC) such as weight reduction, increased physical activity, and a TLC diet consisting of 35% of daily calories from fat, mostly from unsaturated sources.

Lower levels of long chain omega-3 polyunsaturated fatty acids found in fish are associated with an increased risk of sudden death among survivors of myocardial infarction.7 While findings remain inconclusive, sufficient data lead to a statement by the American Heart Association recommending the inclusion of fish in a healthy diet.8 Concerns as to the purity of the fatty acids and the risk of adverse effects related to high levels of mercury and other accumulated products in some fish may place additional testing burden in the domain of the clinical laboratory.

NONLIPID MARKERS

Inflammatory markers

Atherosclerosis as an inflammatory response has been previously well established.9,10 Major factors associated with promoting atherosclerosis are also associated with increased risk of inflammation and endothelium dysfunction. These include adverse level and type of lipoproteins, cigarette smoking, hypertension, insulin resistance associated with an increased glucose/diabetes, and the metabolic syndrome as previously mentioned. Recent interest has focused on the potential use of a number of inflammatory related analytes in an attempt to identify either risk factors, defined as the measurement of substances that may lead to atherosclerosis, or risk markers, described as analytes produced as a consequence of the disease process itself (Table 6). While the difference in the terminology may seem minor, the classification of a substance as either a risk factor or marker may cause significant changes in patient treatment and care.

Regardless of its use in risk assessment, whether for detection of atherosclerosis, related processes, or any other so called blood markers, e.g., so called 'tumor markers', the predictive value and clinical utility of any laboratory test is influenced by a number of key factors. These include: 1) analytical specificity and sensitivity; 2) assay associated total error; 3) ability to standardize assay methods and associated calibration material; 4) diagnostic efficiency for identifiable select populations; 5) independence from other risk factors or markers; 6) the relationship between the analyte and its clinical endpoint; and 7) acceptable assay cost and availability. One test that has recently received considerable study is high-sensitivity C-reactive protein (hs-CRP).

CRP is an early acute phase reactant. It increases in response to active infections, systemic inflammatory processes, or trauma. Lower levels of CRP are evident in chronic inflammatory situations, such as that associated with atherosclerotic processes or its development. Traditional assays lacked the sensitivity to monitor changes in chronic inflammation, and as a result, hs-CRP assays were developed. Acute inflammatory changes are associated with increased levels of hs-CRP (