New Genomic Markers Associated With Risk Of Heart Disease And Early Heart Attack

In one of the reports, from the largest ever study of its kind, the Myocardial Infarction Genetics Consortium identified nine precise genes associated with an increased risk of infarction (MI), three of them newly discovered; the investigators said that these nine gene variants “identify 20% of the population at 2.25-fold increased risk for MI.”

This study set out to find “single letter” differences in gene sequences (known as single nucleotide polymorphisms, SNPs) in 26,000 individuals in ten countries in order to explain why the pattern of early onset heart attack is often clustered in families. Using recently developed techniques for comparing an individual’s gene sequences with reference sequences, the researchers found significant associations with risk of early heart attack for common SNPs in nine genetic regions.

One of the investigators, Dr Sekar Kathiresan from the Consortium, said: “Since we already have effective ways to reduce heart-attack risk, individuals at higher genetic risk may benefit from earlier intervention, something that needs to be tested in future studies."

Other studies reported in the journal included one from the Universite Pierre et Marie Curie in Paris which newly identified a new gene cluster (of three genes) as a possible susceptibility site for coronary artery disease. This study, unlike the first, compared individual and reference groups of SNPs (known as haplotypes).

Adding the studies together, the results suggest the identification of several new gene sites (loci) which appear to affect the risk of coronary heart disease and early heart attack. So far, the added risk from any abnormality in these gene sequences seems small, but the genomic association seems clear. Furthermore, there seems no specific theme to the SNPs involved, suggesting that, while the expression (phenotype) of heart disease and infarction may be consistent, the pathways of risk may be multiple at the genetic level.

Speaking on behalf of the European Society of Cardiology, Professor Thomas Lüscher from the University of Zurich in Switzerland agreed that risk stratification via genetic pathways in coronary heart disease is an important future approach, but warned that these latest results reported in Nature Genetics were from case-control and not prospective studies. He said: “The next stage is to confirm the results in a prospective cohort to find out if they really do provide the same sort of prognostic information we already have from the classical risk factors.”

Professor Lüscher added that there is also a need to discover what the SNPs and gene clusters are doing biologically. “We have to find out what’s going on at the cellular level as well,” he said. “Several of the SNPs have been linked to cholesterol metabolism in the liver, but there are some new ones here associated with coronary artery disease and atherosclerosis.

“This is important work but we need further evidence with statistical power and biological plausibility.”

Journal reference:

1. Myocardial Infarction Genetics Consortium. Genome-wide association of early-onset myocardial infarction with single nucleotide polymorphisms and copy number variants. Nature Genetics, 2009; DOI: 10.1038/ng.327

Immunosuppressant Medication May Be Cost-effective For Dry Eye Syndrome

Published reports suggest that the prevalence of dry eye syndrome in older patients ranges from about 15 percent to 34 percent, according to background information in the article. "Patients with dry eye syndrome have more difficulty reading, carrying out professional work, using a computer, watching television and driving compared with those without dry eyes," the authors write. "The burden of dry eye disease from both the prevalence and patient morbidity standpoints makes this a sizeable public health dilemma."

Using data from two randomized clinical trials and Food and Drug Administration files, Melissa M. Brown, M.D., M.N., M.B.A., of the Center for Value-Based Medicine, Flourtown, and the University of Pennsylvania School of Medicine, Philadelphia, and colleagues assessed the comparative effectiveness and cost-effectiveness of eye drops containing a 0.05 percent emulsion of the drug cyclosporine for patients whose moderate to severe dry eye syndrome did not respond to conventional therapy.

When compared with eye drops containing only lubricant, the cyclosporine drops were associated with a 4.3 percent improvement in quality of life, and conferred a 7.1 percent improvement over no treatment. The total direct medical cost associated with the use of this drug was $1,834; however, because 24.5 percent of treated workers will return to full productivity as a result, there is an estimated $1,236 gain associated with treatment, reducing the net cost to $598.

Based on the authors' analysis, the cost to society for treatment with this medication was $34,953 more per quality-adjusted life year (a measure combining the quality and quantity of life) than the lubricant eye drops alone. This is well below the conventional standard of $50,000 per quality-adjusted life year that most would consider cost-effective, they note.

"The use of topical cyclosporine is a cost-effective treatment strategy for a common disease that, when unresponsive to conventional lubricant therapy, causes a marked diminution in quality of life," the authors conclude.

This study was supported by Allergan Inc.; the Center for Value-Based Medicine, Flourtown, Pa.; and the Eye Research Institute,

Journal reference:

1. Melissa M. Brown; Gary C. Brown; Heidi C. Brown; Jonathan Peet; Zachary Roth. Value-Based Medicine, Comparative Effectiveness, and Cost-effectiveness Analysis of Topical Cyclosporine for the Treatment of Dry Eye Syndrome. Archives of Ophthalmology, 2009; 127 (2): 146 DOI: 10.1001/archophthalmol.2008.608