THE CASE OF THE MISSING LINK
"AN INDEPENDENT RISK FACTOR FOR CORONARY ARTERY DISEASE"

THE CASE:

Jeffrey A., a professional tennis player in excellent health, suffered a devastating heart attack at age 30. There was no family history for heart disease, no abnormality of cholesterol, triglycerides, HDL, or LDL. All coagulation tests were normal, including protein C, protein S and ATIII. Lifestyle was normal for a professional athlete.

What was the defect in his system leading to this event?
What can be done to prevent this in the future?

THE DIAGNOSIS:

The diagnosis is increased blood levels of Lp(a), a lipoprotein made of one molecule of LDL linked by disulfide bonds to a high molecular weight protein, apolipoprotein(a)1. All isoforms of apolipoprotein(a) regardless of size contain a binding domain structurally very similar to plasminogen and may interfere with the fibrinolytic activity of plasmin by competing with plasminogen for binding sites on fibrin1. In addition, by replacing plasminogen on the endothelial cell surface, Lp(a) inhibits the interaction of plasminogen with tissue plasminogen activator (t-PA)2. (Thus, Lp(a) not only interferes with fibrinolysis and promotes thrombosis, but also accelerates atherosclerosis by binding LIPID (LDL) to the vessel wall3,4,5.) Several studies have identified Lp(a) as being one of the most atherogenic of the lipoproteins and have shown that it is an independent risk factor for both coronary heart disease and cerebrovascular disease6.

Patients with Lp(a) >30 mg/dl have a two-to five-fold increased risk of atherosclerosis4. Elevated Lp(a) has been identified as a risk factor for developing premature coronary artery disease, stroke, restenosis after coronary artery bypass surgery, and myocardial infarction1,7,8. It has been reported that approximately one fourth of all heart attacks in men younger than 60 years occurs in those who have inherited high blood concentrations of Lp(a)7. In addition, Lp(a) is the most serious risk factor among the serum lipids and lipoproteins for cerebrovascular disease1,3. Since increased Lp(a) can occur in patients with a normal lipid profile, recent journal articles have suggested that it is time to add the measurement of Lp(a) into cardiovascular risk analysis testing and as a marker of stenotic carotid atheroscerosis7,8,9.

Lp(a) serum levels are relatively constant throughout life but vary widely within populations3. The apo(a) level is inherited as an autosomal dominant trait and evaluation of relatives of patients with high Lp(a) is advisable1. Factors such as diet, exercise, and smoking appear to have little impact on the level of Lp(a)7,9. Niacin, tamoxifen, and estrogen have been reported to be useful in lowering levels9.

Levels of Lp(a) have a wide normal range depending on the method used. HEMEX Laboratories uses an ELISA methodology for measuring serum Lp(a) levels. Fasting samples are preferred. Lp(a) can be ordered by itself or in panels evaluating risk (see back of page). For more information, call HEMEX Laboratories at (602)997-9161 or 1-800-999-2568.

SAMPLE REQUIREMENTS:

Cardiac Risk Screen - Lp(a), von Willebrand Factor Antigen, tPA, Fibrinogen.
2-1 ml aliquots of serum and 2-1 ml aliquots of citrated plasma.

Hereditary Thrombosis Risk Panel - Lp(a), Protein C, Protein S, Antithrombin III, APC Resistance, and PAI-1.
2-1 ml aliquots of serum and 3-1 ml aliquots of citrated plasma.

Send samples frozen.

REFERENCES:

1. Malekpour A, Saber-Tehrani M, Radahd S. Lipoprotein(a): Structure, properties, and clinical interest. Laboratory Medicine 1993;24/1:31-35.

2. Edelberg JM, Pizzo SV. Lipoprotein(a) inhibits plasminogen activation in a template-dependent manner. Blood Coagulation and Fibrinolysis 1991;2:759-764.

3. Jurgens G, Taddei-Peters WC, Koltringer P, Petek W, Chen Q, Greilberger J, Macomber PF, Butman BT, Stead AG, Ransom JH. Lipoprotein(a) serum concentration and apoliprotein(a) phenotype correlate with severity and presence of ischemic cerebrovascular disease. Stroke 1995;26/10:1841-1848.

4. Tsai MY. Findings reveal specific roles of lipoproteins. Clinical Chemistry News 1990;June:9.

5. Willeit J, Kiechl S; Santer P, Oberhollenzer F, Egger G, Jarosch E, Mair A. Lipoprotein(a) and asymptomatic carotid artery disease: Evidence of a prominent role in the evolution of advanced carotid plaques: The Brunek Study. Stroke 1995;26/9:1582-1587.

6. Hervio L, Chapman MJ, Thillet J, Loyau S, Anglés-Cano E. Does apolipoprotein (a) heterogeneity influence lipoprotein (a) effects on fibrinolysis? Blood 1993;82/2:392-397.

7. Lawn RM. Lipoprotein(a) in heart disease. Scientific American. June 1992:54-60.

8. Levine DM. Lipoprotein(a): A genetically determined risk factor for atherosclerotic disease. The Rogosin Institute, The New York Hospital-Cornell Medical Center. 1992.

9. Kahn J. High Lp(a) levels linked to increased risk for stroke. Clinical Chemistry News 1994;14:7.

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