A study appearing in this week's New England Journal of Medicine confirms that a combination of gene variants previously associated with cholesterol levels does reflect patients' cholesterol levels and can signify increased risk of heart attack, stroke or sudden cardiac death.
Led by researchers from the Massachusetts General Hospital Cardiology Division, the study's findings are a first step towards the ability to identify individuals who might benefit from earlier use of cholesterol-lowering medications and other measures to combat elevated risk.
“The prospect of personalized medicine has received much hype, but until recently, there has been little hard evidence to support the promise,” says Sekar Kathiresan, MD, MGH Director of Preventive Cardiology, the paper's lead author. “We feel that our data provides two insights. First, we provide a foundation for the possibility that a panel of gene variants will eventually be useful in preventive cardiac care. Second, we show that the combination of multiple variants related to cholesterol importantly contribute to the genetic risk for heart attack.”
It is estimated that about half the variation in high-density lipoprotein (HDL) and low-density lipoprotein (LDL) cholesterol levels is inherited, rather than being caused by lifestyle factors such as diet and exercise. While studies have associated several gene variants with cholesterol levels, exactly how those variants impact the risk of cardiovascular disease is unclear. The current study was designed to explore the influence of those variants on the risk of cardiovascular events -- heart attack, stroke or sudden cardiac death -- and whether measuring such variants could help predict risk better than simply measuring HDL and LDL levels.
Since the effects of individual gene variants appears slight, the research team looked at a combination of 9 single-nucleotide polymorphisms (SNPs) previously associated with cholesterol levels. They analyzed data from 5,414 Swedish adults who participated in a major prospective epidemiological study and correlated data -- including standard measurements of HDL and LDL cholesterol and the presence of the 9 gene variants -- with information on the participants' subsequent medical histories available from a registry of information collected on all Swedish citizens. After the initial genotyping of participants not receiving lipid-lowering therapy, participants were assigned a genotype score ranging from 0 to 18, based on how many copies of the unfavorable SNPs they carried. Of the participants who had no cardiovascular events before enrolling in the study, 238 suffered a heart attack, stroke or cardiac death during the subsequent 10.6 years.