June 9, 2009 -- Genetic testing confirms that high levels of a type of cholesterol known as lipoprotein(a) are associated with an increased risk for heart attacks, but the clinical implications of the finding are unclear.
Lipoprotein(a) has long been suspected of contributing to cardiovascular risk. But this new research offers the strongest evidence yet identifying it as an independent risk factor for heart attack.
The study appears in the June 10 issue of the Journal of the American Medical Association.
LDL, HDL, and Lp(a)
But unlike LDL or high-density lipoprotein (HDL), lipoprotein(a) is not routinely measured because it has not been clear if doing so provides additional information about who should be taking cholesterol-lowering drugs.
Lipoprotein(a), also known as Lp(a), consists of LDL cholesterol bound to the protein apolipoprotein(a).
Some people are genetically predisposed to have a lot of lipoprotein(a) and others very little. Because of this, Lp(a) levels can vary greatly from person to person.
This wide genetic variability made lipoprotein(a) an ideal candidate for a new type of research that may offer an alternative to long and expensive randomized trials for identifying risk factors for disease.
Instead of lowering lipoprotein(a) levels with drugs, the researchers assessed genetic variations in the gene that controls Lp(a) levels in the blood of close to 45,000 participants in three large long-term, follow-up studies conducted in Denmark.
They found that heart attack risk increased as lipoprotein(a) levels rose, based upon the underlying genetic code. The association was seen in all three studies.
“These findings are consistent with a causal association of elevated lipoprotein(a) levels with increased (heart attack) risk,” study co-author Borge Nordestgaard, MD, and colleagues write.
Clinical Implications ‘Limited’
Nordestgaard tells WebMD that the findings justify a large, randomized intervention trial designed to target lipoprotein(a).
“It is not clear that this test tells us anything about risk that we don’t already learn from evaluating more established risk factors,” says Christopher O’Donnell, MD, MPH. “At present, it can’t really be used for evaluating treatment decisions.”
And treatment is not necessarily straightforward. Although cholesterol-lowering statin drugs may also lower lipoprotein(a), a prescription-strength formulation of the B vitamin niacin is the only treatment purported to specifically reduce Lp(a).
But it is not known if lowering Lp(a) with prescription niacin protects against heart attacks, and troubling side effects such as skin itching and flushing similar to hot flashes can occur in people who take the drug.
In an editorial published with the study, O’Donnell and colleague George Thanassoulis, MD, write that the clinical implications of the new research “remain quite limited.”
Based on the study findings, they conclude that “as a lifelong cardiovascular risk factor and as a pharmacologic target, LDL is likely much more potent than lipoprotein(a).”
“As a cardiologist, I still look for the traditional risk factors which have been shown to be associated with cardiovascular risk, such as LDL, HDL, blood pressure, and other risk factors obtained through diabetes testing and family history,” O’Donnell tells WebMD. “I don’t think the evidence from this study would support putting Lp(a) on that list.”