Lipid Biomarkers and Coronary Heart Disease: Part I Lipoprotein A [Lp(a)] and Lipoprotein A Associated Phospholipase A (Lp(a)-PLA)
Plaut, David, McLellan, William, Journal of Continuing Education Topics & Issues
There are many risk factors for coronary heart disease (coronary artery disease, CAD). These include genetic factors, diet, high blood pressure as well as a number of biomarkers (serum markers). Cholesterol may have been the first of these and has been followed by several dozen more. One of the intriguing questions for both clinicians and laboratorians is which of these should be measured and when should they be measured (i.e., starting at an early age for everyone, only on those patients with a history of CAD, those suspected of ACS in the ED or after an event such as a stroke or AMI).
For a number of years, there has been interest in some of the lipoproteins including HDL and LDL and their various forms. Lipoprotein A, another of these, has more recently sparked the interest of clinicians and hence, the laboratory. There are now rapid, automated assays for Lipoprotein A [Lp(a)], often called "L P little A" and Lipoprotein A associated phospholipase A (Lp(a)-PLA). This short review touches on some of the material that has made these two markers your clinical staff may have asked about or have ordered and that you are sending out.
For example, a large study (1) found that in a prospective study of 5,888 community-dwelling older adults (65 years of age or older), some 4,000 women and men who were free of vascular disease provided base-line serum samples for analysis for levels of Lp(a) lipoprotein. These subjects were followed for a median of 7.4 years to evaluate the development of stroke and to track deaths from vascular causes and all causes. The men and women were divided into quintile groups (e.g., the lower 20%, etc.) according to the Lp(a) lipoprotein level at base line. The risk of an event was determined for each of the quintiles; the lowest quintile served as the reference group. Compared with this lowest quintile, men in the highest quintile had three times the unadjusted risk of stroke, almost three times the risk of death associated with vascular events, and nearly twice the risk of death from all causes. Adjustment for age, sex, total cholesterol, low-density lipoprotein cholesterol (LDL), and triglycerides, carotid-wall thickness, smoking status, the presence or absence of diabetes and systolic and diastolic hypertension, body-mass index, and other traditional risk factors had little effect on the final assessments. Similar analyses for women, which also included adjustment for estrogen use or non-use, revealed no such relation.
In another study, (2) 490 patients (average age 60.5) who underwent coronary angiography to evaluate chest pain were classified into two groups, a CAD group (n = 256), who had significant stenosis, and a control group (n = 234) who had normal or minimally occluded coronary arteries. The Lp(a) level and mean LDL particle size were significantly correlated (Figure 1.) with the level of stenosis.
A report from India (3) that discussed three groups of patients: non-insulin dependent diabetics (NIDDM) with CAD (Group 1), and without CAD (Group 2), as well as a group of control patients (neither NIDDM or CAD, Group 3) found that Lp(a) concentrations were significantly higher in Group 1 patients when compared with Groups 2 and 3. There was only a weak correlation of the only total cholesterol and low-density cholesterol concentrations with the Lp(a) levels in Group 1, suggesting that these are independent risk factors (Figure 1.). (When two risk factors are independent, there is a better argument to measure both of them than if they are dependent.)
While most of the studies suggest that measurement of Lp(a) is a useful marker of future risk, not all do. For example, in a study of 490 patients (mean: 60.5 [+ or -] 11.5 years old) who underwent coronary angiography to evaluate chest pain were classified into two groups, a CAD group (n = 256), who had significant stenosis observed by coronary antiogram, and a control group (n = 234), who had normal, or minimal, coronary arteries. …