Lipoprotein(a) or Lp(a), is an established risk predictor for heart attack. It not only has a cholesterol component, like LDL (bad lipid), but a pro-thrombotic (blood clotting) component. Lp(a) levels are genetically determined and remain relatively constant over an individual's lifetime. Unfortunately, they are not affected by lifestyle changes or by most drug therapy. High Lp(a) levels increase the risk for developing coronary artery disease as well as cerebral vascular disease. Elevated levels of Lp(a) are thought to work independently, to add to any underlying heart or vascular disease processes.
High Lp(a) levels can occur in individuals with normal cholesterol levels; if so, they do not carry the same cardiovascular risks as high Lp(a) levels in individuals with high LDL levels. According to one review, the relative risk of cardiovascular disease events attributable to elevated Lp(a) is modest (2-fold increase) in subjects with normal LDL cholesterol levels. However, subjects with high LDL levels, such as those with familial hypercholesterolemia who typically present with LDL levels in the 300 mg/dL range, have a 12-fold increase in the risk of heart attack attributable to concomitantly high levels of Lp(a).
Lowering Lp(a), particularly in patients with high LDL levels, would probably reduce cardiovascular risks. Unfortunately, there are almost no treatment options available at this time that can effectively lower Lp(a). Estrogen and niacin are the only two therapies that will effectively do so. Standard doses of estrogen lower Lp(a) by about 50%; niacin (2-4 g/day), by 20% to 30%.
Aggressive LDL-lowering therapy appears to be a more generally effective option, since high LDL levels greatly add to the risk of high Lp(a).
In an analysis of the Lp(a) data in the FATS Trial lowering LDL levels in those with high LDL and high Lp(a) levels dramatically reduced risk. Without treatment, these patients had a 42% risk of a major clinical event, including MI, the need for revascularization, or CV death over the 2.5 year study. When LDL levels were lowered aggressively, even though the Lp(a) levels remained high, the risk of this group was reduced to less than 10%, for a roughly 75% reduction in the risk of a major cardiovascular event (heart attack, angioplasty, bypass surgery, stroke or death).
In conclusion, while Lp(a) (and probably risk) may be modestly lowered with niacin therapy, and with estrogens in women, aggressive lowering of LDL levels appears to be the most reliable way to treat patients at high risk due to elevated Lp(a).
______________________________________________________________
Lp-PLA2
(Lipoprotein-associated phospholipase A2)
(also known as platelet-activating factor acetylhydrolase)
Lp-PLA2 is a marker of inflammation that plays a critical role in heart disease. Data have consistently demonstrated the association of increased levels of Lp-PLA2 with increased risk of coronary heart disease (CHD). Lp-PLA2 may be particularly useful in identifying CHD risk among patients with a baseline low-density lipoprotein less than 130 mg/dl. About one-third of adults have Lp-PLA2 levels less than 200 ng/mL, one-third have levels between 200-265 ng/mL, and one-third have levels above 265 ng/mL.
Overall, studies suggest that measurement of Lp-PLA2 in plasma may be useful in identifying individuals at high risk for cardiac events (heart attack, angina, etc.). It is not known if treating Lp-PLA2 levels to lower them will reduce this risk. For now, if elevated Lp-PLA2 levels are found, lowering LDL levels should be the primary focus, as well as lowering other risk factors for cardiovascular disease.
______________________________________________________________
Homocysteine
The October 23, 2002 issue of the Journal of the American Medical Association throughly addressed the issue of homocysteine and cardiovascular disease. The basic determination is that homocysteine is most likely an independent risk factor for cardiovascular disease but it's contribution is less then the major risk factors. The major risk factors are smoking, diabetes, high cholesterol and high blood pressure.
Homocysteine is an amino acid produced as a normal byproduct of the breakdown of methionine (from proteins), which is an essential amino acid acquired mostly from eating meat. Studies have shown that too much homocysteine in the blood is related to a higher risk of coronary heart disease, stroke and peripheral vascular disease.
There’s plenty of evidence that homocysteine can be kept at moderate, healthy levels if the body has adequate levels of three important B-vitamins: vitamin B-6, vitamin B-12 and folic acid (the synthetic and more easily absorbed version of folate). These B-vitamins convert homocysteine into a harmless substance. However, a lack of any of these three vitamins can increase homocysteine levels, which could prove to be dangerous.
Although evidence for the benefit of lowering homocysteine levels is arriving slowly, patients at high risk should be strongly advised to be sure to get enough folic acid and vitamins B6 and B12 in their diet. Foods high in folic acid include green, leafy vegetables and grain products fortified with folic acid.
Recent studies have shown conflicting results. One study suggested that taking folic acid, B-6 and B-12 after angioplasty decreased the need for repeat angioplasty (N Engl J Med. 2001;345:1593-1600). Still another trial (FACIT -Folate After Coronary Intervention Trial) suggests that taking these vitamins after angioplasty and stenting (STENT) may increase the possibility of the STENT site needing a repeat angioplasty.
Consult your physician before taking these vitamins because they could hide a B-vitamin deficiency, which could lead to nerve damage. Some physicians routinely screen for this deficiency before adding B-vitamins.
Common supplemantal doses are 400-1200 mcg of Folic Acid, 50-500 mcg of B-12 and 10-50 mg of B-6.
It should be noted that smoking raises Homocysteine levels and quitting smoking will lower these levels.
