Lipoprotein(a):
What it is, why it's important, and why you need to know if you've
got it!
At 53, Ginnie lived her life walking on eggshells. At age 49, she had to undergo urgent coronary bypass surgery. Her conventional lipid panel prior to bypass revealed fairly bland numbers: LDL cholesterol 133 mg/dl, HDL 46 mg/dl, triglycerides 141 mg/dl—nothing that might have signaled heart disease risk as a young woman.
Ginnie’s physician told her the usual. “Cut the fat in your diet, lose some weight. Here’s a prescription for Zocor®. That’s all we can do. You have heart disease because it’s genetic. It’s in your family. ” And, indeed, Ginnie’s entire immediate family had similar experiences, all in their 40s and 50s, including her younger brother.
When Ginnie came to us, it was clear that she’d lost hope. She
believed that a future of more heart attack and procedures was
inevitable. It was “genetic”, after all.
We submitted Ginnie’s blood for lipoprotein analysis. As
expected, several important abnormalities were uncovered: 90%
of her LDL was of the small size variety; HDL was nearly
completely in the small category, meaning she had virtually no
effective HDL; increased intermediate-density lipoprotein,
signifying an inability to clear blood fats after meals; and a
severe elevation of lipoprotein(a) of 201 nmol/l.
It was clear that her disease did indeed have genetic
components, but they were clearly correctable.
You’d expect Ginnie to be dismayed at hearing that she had
multiple hidden genetic causes for heart disease. But the exact
opposite happened: Ginnie was elated. She now understood that,
while her risk was largely genetic, it was also
identifiable—and treatable. Her one regret: That the causes
weren’t identified before bypass surgery.
If you’ve got coronary plaque, you need to know why. If you don’t, how can you ever hope to gain control over it?
A missing piece in many people’s heart disease prevention program is lipoprotein(a), or Lp(a). If you have it, it can pose special risk for heart disease. If you don’t, great—since it’s a genetic factor, it’ll never have to be checked again. But if you do have Lp(a), the treatment effort is specific. In other words, just eating better, exercising, and taking a cholesterol drug just won’t cut it.
Cholesterol makes you blind!
Cholesterol can’t literally make you blind. But as an indicator
of hidden heart disease, cholesterol can leave you in the dark,
just as it did with Ginnie and her doctor. Cholesterol-mania
may cause you to be blind to all the other causes of heart
disease, some of which are more important than cholesterol.
Can heart attack occur with low cholesterol? Sure can. Can you
celebrate your 95th birthday, outlive all your neighbors and
never have a heart attack despite high cholesterol? Absolutely.
Can you suffer a debilitating or fatal heart attack with
“normal” cholesterol? It happens 1,152 times every day across
the U.S. (American Heart Association, 2004 Update).
Yet most of the time your doctor makes a myopic attempt to
decide whether you have heart disease by looking only at
cholesterol. Most people with coronary disease don’t have one
cause but five, six, or more reasons. High cholesterol is just
one of them.
Lipoprotein(a)—a terrible but fascinating human trait
Lipoprotein (a), or Lp (a) (read “L–P little a”) is a powerful and underappreciated cause of heart disease. Up to 20% of people with heart disease will have increased Lp (a). It can lead to heart attacks early in life, sometimes in your 40s or 50s. Lp (a) is not only a direct cause of plaque growth and plaque rupture (heart attack), but it also magnifies the dangers of all other abnormalities, especially LDL cholesterol and LDL particle number, and small LDL.1
Evolutionarily, Lp(a) may have been intended to be a protective
molecule.2 However, when blood levels of Lp(a) are increased—a
genetically determined characteristic—then Lp(a) is
particularly prone to adhere to the arterial wall and grow
atherosclerotic plaque. Structurally, Lp(a) bears marked
resemblance to a blood clotting protein, plasminogen. Some
investigators have therefore speculated that Lp(a) triggers
blood clot formation in addition to its plaque-promoting
properties. Lp(a) may thereby pose special risk for blood clot
when a plaque ruptures.
Lp(a) is a feature unique to humans, Old World primates, and
hedgehogs. Lower animals lack this molecule. This has
hampered research efforts, since the usual animal models for
heart disease, like mice and rabbits, can’t be used (unless
human genes are implanted into them).
Considerable controversy still surrounds Lp(a) and its role in
heart disease. One source of confusion in Lp(a) research is
that, although it causes heart disease, not all Lp(a) does so.
Some does, some does not. The difference seems to be particle
size.
Lp(a) is really an LDL cholesterol particle with an additional protein called apoprotein a (apo(a)). The apo(a) component varies tremendously in size. Recent data suggest that the smaller the apo(a), the more powerfully it contributes to coronary plaque.3,4 Just as the appreciation of LDL particle size has lagged 20 years behind information on cholesterol, so has the recognition of size variability of Lp(a) only recently emerged into the light. Thus far, 34 different sub-types of Lp(a) based on variable apo(a) size have been identified.
Lp(a) particles bind to the arterial wall and plaque like Velcro. Once within plaque, the apo(a) can dissociate and wreak its own special damage. Inflammation seems to be an especially potent trigger of apo(a) activity within plaque.5
Lp(a) poses risk for heart disease when levels are increased and when the particle is small. Unfortunately, size measurement of Lp(a) and apo(a) are not available except in research settings. It will likely become an available measure in future, however.
Do you have Lp(a)?
Unlike most other lipoproteins which can be tricky to obtain, Lp(a) can be measured by most clinical laboratories. However, the test remains unstandardized 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 not 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.)
However, treatment of Lp(a) doesn’t end there. Two other issues need to be addressed:
 |
Want to read the rest of this Track Your Plaque Special Report?
Already a member? CLICK HERE to log-in. |
Copyright 2006, Track Your Plaque.