A Medical Device Daily Staff Report

The diagnostics sector is scrambling to identify those at greatest risk for heart disease so as to develop refined systems for prevention, but at least one study suggests that one group genetic indicators is not as robust as is hoped.

A research group led by Thomas Morgan, MD, of the department of genetics at the Howard Hughes Medical Institute (Chevy Chase, Maryland), wrote in the April 11 edition of the Journal of the American Medical Association that while several studies have suggested "a genetic basis for atherosclerotic heart disease and acute coronary syndrome" [ACS] most of the data behind those claims have not been validated in studies of "large, well-characterized patient populations."

Matching 811 patients who presented with ACS between 2001 and 2003 at two centers in Kansas City, Missouri, with 650 controls with no history, the researchers checked their genomes "for 85 variants in 70 genes" to evaluate whether these variations were truly predictive of ACS. The two groups "had similar age, sex and body mass index distributions," but the family history of coronary artery disease or infarction was 2.7 times higher in the men in study group than in the controls. The ratio for women in the study group to women in the controls was 2.0. For both sexes, those who had a history of a disease were more likely to smoke or have Type 2 diabetes, although they apparently were "less likely to consume at least one alcoholic drink per month."

Higher cholesterol levels were seen in the study women than in the controls, but the two groups of men exhibited no such difference. Roughly 36% of the study subject had undergone at least one revascularization, but none of those enrolled as controls had.

The authors stated that of the 85 genetic variants they examined, only one, "the –455 promoter variant in beta-fibrinogen, was [even] nominally statistically significant," and that tests for several of the genes they tested "can already be ordered clinically for indicates that explicitly include possible ACS risk."

The findings of this study argue against the outcomes of "several high-profile studies," including those for two haplotypes, or groups of genes.

As an alternate approach, the article recommends an effort to "screen the entire genome [of an unspecified number of subjects] in an unbiased way," and it pointed out that the cost of such tests is dropping as "the field is moving rapidly toward a comprehensive, genome-wide approach."

Contrast-enhanced MRI targets brain veins

Neuroradiologists at the University of Cincinnati (UC; Cincinnati, Ohio) believe a brain imaging approach that combines standard magnetic resonance imaging (MRI) scans with specialized contrast-enhanced techniques could lead to more effective diagnoses in patients with difficult-to-detect blood clots in veins of the brain.

James Leach, MD, reports the findings in the April issue of the American Journal of Neuroradiology. This is the first study to correlate the clinical importance of data gleaned from standard MRI scans and detailed contrast-enhanced imaging techniques in patients with chronic thrombosis in veins of the brain. "Detailed contrast-enhanced techniques produce more defined distinctions between abnormal and normal veins in the membrane around the brain," said Leach, a neuroradiologist and associate professor at UC and principal investigator of the study."Evaluating patients using a combination of imaging tools could give us a better understanding of the disease process."

Researchers say these specialized techniques — known as contrast-enhanced MR venography — produce more clearly defined pictures of difficult-to-detect abnormal flow areas within vessels of the brain which may serve as important warning signs of blocked blood flow that require medical intervention. The enhanced imaging tools can also help identify areas where flow has been partially reestablished after a vessel blockage has occurred. The researchers used these contrast-enhanced techniques, in combination with standard MRI, to evaluate a small subgroup of patients who have clinical and imaging features consistent with what is called partially recanalized chronic dural sinus thrombosis, a condition in the membrane surrounding the brain where blood flow has been partially reestablished in a previously blocked vessel.

Research has shown that cerebral veins partially or fully blocked by a blood clot—with or without treatment—can open spontaneously, open partially or remain blocked. These blockages can stop blood flow to the brain and increase the patient's risk for stroke and other neurological episodes such as chronic headache.

"In cases where the patient has an ongoing partial or full blockage," Leach said, "the blood clot 'organizes' into a more solid lesion, forms connective scar tissue and can develop small vessels in an attempt to restore blood flow. This was very difficult to diagnose correctly using previous techniques."

"We don't fully understand why this happens, but being able to recognize the imaging characteristics of the condition earlier may help us explain patient symptoms—like persistent headache—that otherwise cannot be explained," he adds.

Leach said that additional research may show that this combined approach may one day help physicians formulate better treatment regimens and possibly prevent more serious medical complications for certain patients.