Unique Strategies for Lipoprotein(a) Reduction

Lipoprotein(a), or Lp(a), can be among the most frustrating causes of coronary atherosclerotic plaque. Sometimes treatment of this genetic pattern can be simple and straightforward. Other times it can test even the most patient and persistent. Lp(a) is by no means a rare pattern. Of everyone with a heart scan score above zero, 1 in 5 (20%) will have it.

There is fairly broad consensus that increasing Lp(a) does, indeed, increase risk for heart attack and stroke. A review (meta-analysis) of 27 studies examining the effects of increased Lp(a) concluded that persons in the highest third of Lp(a) levels in the population carry a 70% increased risk for heart disease (Danesh J et al 2000). In the Track Your Plaque experience, increased levels of Lp(a) are a significant risk for increasing heart scan scores. Lp(a) is also unique in that it amplifies the dangers of other patterns, such as LDL cholesterol, low HDL, small LDL, and increased C-reactive protein (a measure of inflammation). In the 1100-participant Italian Longitudinal Study on Aging, for instance, the combination of Lp(a) ≥20 mg/dl and LDL≥140 mg/dl increased heart attack risk by a factor of 2.75; the combination of Lp(a) ≥20 mg/dl and type II diabetes increased risk by a factor 6.65 (Solfrizzi V et al 2002). A 1997 University of Utah study of 170 participants, all of whom had established coronary disease, determined that having a total/HDL ratio >5.8 along with two or more non-lipid risk factors such as smoking, hypertension, diabetes, smoking, or high homocysteine, escalated risk an amazing 122-fold (Hopkins PN et al 1997).

Niacin is the mainstay of Lp(a) treatment, followed by testosterone in men, estrogen in women. Sometimes, spectacular results are obtained with just niacin. In others, adding testosterone or estrogen may be required. In others, both treatments fail to yield the effects we desire, or there are reasons that prevent full use of either treatment.

For this reason, here we survey the possibilities for treatment of Lp(a). We have tried some of these unique therapies, others we have not. (We do specify which.) We cannot pretend to have all the answers to the Lp(a) dilemma. It is, undoubtedly, a sometimes frustrating genetic pattern that tests everyone’s resourcefulness and patience. Hopefully, this report will not just suggest some potential therapies for readers, but also trigger interest in exploring new treatments.
 

A quick Lp(a) review

Lp(a) is really an LDL cholesterol particle bound to an additional protein called apoprotein(a) (apo(a)). LDL cholesterol particles, just like VLDL and IDL, each contain one apoprotein B molecule (apo B). The apo(a) particle binds to the LDL particle via apo B, and they do so through two linked sulfur molecules, the so-called “disulfide linkage.”

The apo(a) component of Lp(a) varies tremendously in size from one individual to the next. Studies are in wide agreement that, the smaller the apo(a), the more powerfully it contributes to coronary plaque. Thus far, 34–45 different sub-types of Lp(a) based on variable apo(a) size have been identified.

To add even further to the complexity of Lp(a), the size of the LDL particle can vary, also. It means that people with small LDL particles also have small LDL in Lp(a); people with big LDL particles have big LDL in Lp(a). Some early data, in addition to the Track Your Plaque experience, suggest that small apo(a) in combination with small LDL particles may be the most atherosclerosis-causing of all.

For additional basic discussion of Lp(a), please also see these Special Reports on the Track Your Plaque website:

Lipoprotein(a): What it is, why it's important, and why you need to know if you've got it!
Lipoprotein(a) Checklist
 

Measuring Lp(a)

Lp(a) can be measured by most clinical laboratories. It therefore does not necessitate the special arrangements often necessary to obtain other lipoprotein testing (i.e., NMR, Berkeley, VAP).

However, the test is not standardized and may vary tremendously from lab to lab. This can cause great confusion if you use more than one laboratory for your blood work. It’s therefore important to stick to the same laboratory every time you have Lp(a) checked to eliminate this source of confusion.

Ideally, the laboratory you or your doctor chooses measures Lp(a) in nmol/L, which is a measure of Lp(a) particle number and is less influenced by the variable size of Lp(a) particles. If your measure is in mg/dl or mg/L—measures of weight—then it may be affected by particle size and may not accurately reflect your true risk. But even a weight measure is better than nothing if you don’t have a choice. In future, as laboratories adopt standardized means of measurement, we will likely be able to routinely measure both quantity of particles in nmol/l and Lp(a) particle size (or apo(a) particle size).

What’s a desirable value for Lp(a)? As with LDL cholesterol, this is the toughest question of all. However, some guidelines: If measured in nmol/l, then 75 nmol/l or less is desirable. In mg/dl, 30 mg/dl or less is desirable. (However, because of the lack of standardization, “normal” values in your laboratory may vary, depending on the means of measurement; discuss with your doctor. Also, to convert mg/L to mg/L, divide the mg/L value by 10. A very crude conversion of mg/dl to nmol/L can be obtained by multiplying by 2.5; however, this is only an approximation, since it ignores the fact that Lp(a) particles vary in size and weight.)

One important issue to keep in mind when discussing treatment of Lp(a) is that the magnitude of reduction in Lp(a) is highly dependent on the starting level: the higher the starting level, the greater the percentage reduction in Lp(a) achieved with various treatments; the lower the starting Lp(a), the smaller the percentage reduction. This holds true with virtually all treatments for high Lp(a).

Another issue will emerge as you peruse these treatments: They are frustratingly variable in effect from one person to another, one study to another. Treatment X will work great in one study, not at all in another. This variation plagues all Lp(a) experiences due to its genetic variability from one group of people to another, one race to another, and the varied methods of measurement. Nonetheless, we will try and distill some wisdom out of this hodgepodge.
 

The standard Track Your Plaque approach to Lp(a)

Want to read the rest of this Track Your Plaque Special Report? Already a member? CLICK HERE to log-in. Want to become a member? CLICK HERE Want to learn more about the benefits of membership? CLICK HERE

Copyright 2008, Track Your Plaque.