Update on Selected Markers Used in Risk Assessment for Vascular Disease

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

ABBREVIATIONS: ATPIII = Third Report of the Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III); CHD = coronary heart disease; CVD = cardiovascular vascular disease; ET-1 = Endothelin 1; HDL = high density lipoprotein cholesterol; HRT = hormone replacement therapy; Hs-CRP = high-sensitivity C-reactive protein; LDL = low density lipoprotein cholesterol; NO = nitric oxide; PAF = potent platelet-activating factor; TG = triglycerides; TLC = therapeutic lifestyle changes.

INDEX TERMS: coronary heart disease.

Clin Lab Sci 2004;17(1):43

INTRODUCTION

The current Focus section includes three articles associated with updates on various cardiac markers. The initial article, entitled, "Update on Selected Markers Used in Risk Assessment for Vascular Disease" by Eileen Carreiro-Lewandowski, provides information on selected markers used in preventative medicine for identifying and establishing treatment plans for patients at increased risk of vascular disease. Alan Wu, from Hartford Hospital, CT and a well-known authority in cardiac marker utilization, authors the second article providing essential information on troponin assay issues. The last article, written by Debra Faubion, provides information regarding BNP testing.

LEARNING OBJECTIVES

1. Define endothelium dysfunction.

2. Describe the interrelationship of endothelium dysfunction and CVD.

3. Discuss the LDL, total cholesterol, HDL, and triglyceride levels recommended in the Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III) guidelines.

4. Describe the major risk factors, exclusive of LDL levels and existing CHD, that may modify LDL therapeutic goals.

5. List the conditions defining the metabolic syndrome.

6. List the guidelines for lipoprotein testing.

7. Discuss the apparent relationship of omega-3 fatty acid levels and sudden death.

8. Compare and contrast the terms "risk factor" and "risk marker".

9. List the key factors that influence the predictive value and clinical utility of blood test markers.

10. Discuss the use of hs-CRP as an indicator of CHD.

11. List several inflammatory markers, excluding hs-CRP, that may be used to indicate possible risk of CVD.

12. Discuss some of the recent findings in non-inflammatory CVD testing.

Vascular disease, including that leading to heart disease, stroke, or other thrombotic related disorders, continues to plague the public at alarming rates. The estimated annual costs of cardiovascular disease in the USA and Canada are $298 billion and $20 billion, respectively.1 More recently, atherosclerosis development and progression have been strongly linked to inflammatory processes. The term "cardiovascular vascular disease" (CVD) often represents a myriad of symptoms affecting multiple vascular territories including major arteries associated with the heart and brain, and most likely other organs such as the kidneys, plus the peripheral circulation.2 It is estimated that transient ischemic attacks, whether cardiac, cerebrovascular, renal, or vascular, have not been included in many major studies, and the real incidence of vascular disease is much higher than reported. A constellation of lipid and nonlipid risk factors, including those referred to as the 'metabolic syndrome', clearly links development of diabetes mellitus and CVD. One of the risk factors, obesity, has reached epidemic proportions in the U.S., further contributing to the incidence of CVD. Laboratory markers are increasingly important in identifying those individuals at greatest risk of CVD and determining treatment modalities for these patients.

ENDOTHELIAL DYSFUNCTION AND CVD

The endothelium is a single-cell lining covering the internal surface of blood vessels, cardiac valves, and body cavities. Vascular homeostasis is maintained by a balance of vasoactive substances (Table 1) released by the endothelium. This balance maintains vasomotion, smooth muscle proliferation, thrombosis, inflammation, coagulation, fibrinolysis, and oxidation. Endothelium dysfunction occurs when one or more of these functions is disrupted, and the careful balance between these vasoactive substances is disturbed. Generally, the imbalance is associated with either diminished availability or production of nitric oxide (NO), which mediates the vasodilatory action of acetylcholine and maintains vascular smooth muscle tone. Nitric oxide opposes the actions of vasoconstricting peptides such as angiotension-II, norepinephrine, serotonin, and endothelin-1 (ET-1), and inhibits platelet and leukocyte activation. An imbalance of the effectiveness of any of these endothelium derived substances can also cause endothelial dysfunction.

Endothelial dysfunction has been implicated in the pathogenesis and clinical course of all known CVD and is associated with future risk of adverse CVD events.3 Endothelium injury occurs in response to the same risk factors connected to CVD development. Conditions associated with impaired endothelial function include atherosclerosis, hypercholesterolemia, hypertension, increased homocysteine levels, vasculitis, pre-eclampsia, metabolic syndrome, diabetes, active and passive cigarette smoking, ischemia-reperfusion, post menopause, infections, depression, lack of physical activity, obesity, renal failure, the aging process, and congestive heart failure. Adverse changes in lipoproteins associated with CVD, including small-dense, low-density lipoproteins, are also linked to impaired endothelial function.