A team of experts presume that an accelerated risk of myocardial infraction or heart attack may be traced to genetically increased levels of lipoprotein(a). This suggestion was made through the genetic analysis of three together by Pia R. Kamstrup, MD, of Herlev Hospital, Copenhagen University Hopsital, Herlev, Denmark and colleagues.
Inspite of aiming of low-density lipoprotein cholesterol (LDL) by statin treatment, myocardial infraction (MI) is presumed to be a leading cause of illness and even death. The experts have stated that lipoprotein(a) levels may significantly differ in different people. These levels presumably may to a certain extent depend on the variations in the LPA gene coding for the apolipoprotein(a) moiety of lipoprotein(a).
“The need for identification of additional causal factors, and thus potential new targets for prophylactic treatment, is apparent. Elevated levels of lipoprotein(a) [a LDL particle bound to a plasminogen-like glycoprotein, apolipoprotein(a)] represent such a candidate; however, whether lipoprotein(a) causes MI is unclear. A randomized intervention trial showing that a reduction in lipoprotein(a) levels leads to a reduction in risk of MI would favor causality. Such a study has yet to be conducted,” note the experts. “Simply put, association of elevated levels of lipoprotein(a), as well as association of genetic variation raising levels of lipoprotein(a), with risk of MI would suggest causality.”
Evidently the most dominant LPA variation would be the kringle IV type 2 (KIV-2) size variation. The amount of KIV-2 repeats was believed to be somehow associated with the lipoprotein(a) levels.
For this purpose the experts were believed to have verified if the level of genetically increased lipoprotein(a) may be traced to an elevated risk of heart attack. The data from three studies were stated to have been genetically analyzed by these experts. They had evidently referred to the Copenhagen City Heart Study (CCHS), the Copenhagen General Population Study (CGPS), and the Copenhagen Ischemic Heart Disease Study (CIHDS).
It was noted that, “We observed an increase in risk of MI with increasing levels of lipoprotein(a), as well as with decreasing numbers of lipoprotein(a) KIV-2 repeats associated with elevated levels of lipoprotein(a). The increase in risk of MI associated with genetically elevated levels of lipoprotein(a) was consistently seen in 3 large independent studies… The KIV-2 genotype explained 21 percent and 27 percent of the total lipoprotein(a) concentration variation in the CCHS and the CGPS. Instrumental variable analysis (in which the increase in lipoprotein[a] levels explained by the KIV-2 genotype was related to MI) directly demonstrated that genetically elevated lipoprotein(a) is associated with increased risk of MI, like elevations in plasma lipoprotein(a). These findings are consistent with a causal association of elevated lipoprotein(a) levels with increased MI risk.”
Having said this, it was also noted that randomized clinical trials may be required to demonstrate a causal link between lipoprotein(a)-lowering treatment and the reduced risk of MI.
These findings were presented in the JAMA issue.