A new study has found that seeing the build-up of plaque in their own arteries is the incentive patients need to comply with doctor’s orders. The study, conducted at the Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center (LA BioMed) and published in the journal Atherosclerosis, found that patients who see more plaque in their arteries tend to be more likely to stay on statin therapy than those who do not get visual proof of their risk of heart attack.

Cholesterol agents such as statins have been used to reduce cardiac morbidity and mortality, but patients are not inclined to stay on the medication. In most studies, compliance is less than 50% after one year.

Authors of the new study found that over a period of 3.6 years, patients who saw visual proof of more plaque after undergoing an electron beam tomography (EBT) scan of their heart were much more likely to comply with prescribed statin therapy. In fact, compliance among those whose scans found the most plaque exceeded 90%. The study followed more than 1,000 patients, each of whom were scanned and then shown their coronary arteries and the plaque that was present.

“Being able to see the buildup of plaque is one of the best and easiest methods to improve patient’s compliance, not only with cholesterol medications, but with diet and exercise as well,” said Dr. Budoff, a principal investigator at LA BioMed and senior author of the study. “Patients seeing the plaque in their own coronary arteries was a powerful motivator of good behavior persisting over three years.”

Electron beam tomography screening is one of the methods of assessing an individual’s heart attack risk endorsed by the SHAPE (Screening for Heart Attack Prevention and Education) Task Force, of which Budoff is a member. This summer, the SHAPE Task Force will publish a new practice guideline for cardiovascular screening in the asymptomatic at-risk population in the American Journal of Cardiology, calling for non-invasive screening of all asymptomatic men 45-75 and women 55-75 to assess their coronary plaque volume or carotid wall thickness. The SHAPE Task Force estimates that screening the asymptomatic population will prevent more than 90,000 deaths each year.

“Electron beam tomography identifies heart disease early, which gives us the ability to aggressively care for the disease with treatments that work,” said John Duncan, PhD, founder and CEO of ViaScan (Las Colinas, California). “We can alter the pathway from disease to death. By aggressively intervening, we can save lives.”

LA BioMed is one of the largest independent, not-for-profit biomedical research institutes in Los Angeles County. Affiliated with both the David Geffen School of Medicine at UCLA and the Harbor-UCLA Medical Center, the institute has an annual budget of more than $72 million and currently supports more than 1,000 research studies in areas such as cardiology, emerging infections, cancer, women’s health, reproductive health, vaccine research, respiratory physiology, neonatology, molecular biology and genetics.

Coronary heart disease polymorphism-based

New research at the National Institute of Environmental Health Sciences (NIEHS), part of the National Institutes of Health, has found that a common genetic variation makes some people more susceptible to coronary heart disease (CHD). The research indicates that Caucasians with this gene variation are roughly 1.5 times more likely to have a CHD event, such as a heart attack, than those who do not have the gene variation. Gene variations are also known as polymorphisms. About 15% of all Caucasians have this particular polymorphism.

“We found that Caucasians who carry this polymorphism, named K55R, were at significantly higher risk of coronary heart disease, independent of other risk factors, like cigarette smoking, diabetes, and hypertension. We did not observe the same association in African-Americans who had the K55R polymorphism,” said Craig Lee, a researcher at NIEHS and lead author on the study. The study is published in the Volume 15, No. 10 issue of Human Molecular Genetics.

This research showed that Caucasians with the K55R polymorphism had an accelerated breakdown of beneficial fatty acids called epoxyeicosatrienoic acids (EETs), which are known to play a protective role in the cardiovascular system. These fatty acids help to lower blood pressure, prevent blood clotting and fight inflammation.

The K55R polymorphism is a naturally-occurring, inherited variation of EPHX2 – the epoxide hydrolase gene. EPHX2 generates an enzyme that rids the body of beneficial EET fatty acids, as part of normal human metabolism. In people with the K55R polymorphism, this normal process is accelerated and even more of the protective EETs are lost.

“This research builds on a body of evidence suggesting the importance of this gene and its fatty acid products in the cardiovascular system,” said David Schwartz, MD, director of NIEHS. “It also suggests that this metabolic pathway may serve as a useful target for the prevention or treatment of cardiovascular disease.”

Darryl Zeldin, MD, a senior investigator at NIEHS, an author on the study, said, “We’ve been studying this pathway in cells and mice for more than a decade, but this study provides the first direct evidence about its importance to coronary heart disease events in humans.”

The researchers genotyped 2,065 participants for 10 known polymorphisms in the EPHX2 gene. The researchers were also able to confirm that there was an increased level of enzyme activity in individuals who had the K55R polymorphism.

“By looking at 10 different polymorphisms, we were able to survey the gene and determine that this one particular variation is related to cardiovascular disease risk in Caucasians,” said Lee. “More research is needed to determine if this finding is applicable to other populations.”

Participants of this study were part of a larger study, the Atherosclerosis Risk in Communities (ARIC) Study, funded by the National Heart, Lung, and Blood Institute. The ARIC study is a long-term study following nearly 16,000 men and women age 45-64 from four diverse communities, including Forsyth County, North Carolina; Jackson, Mississippi; Minneapolis; and Washington County, Maryland. The study, which started in 1987, seeks to investigate and identify cardiovascular disease risk factors in men and women.

MD-CTA accurate for detecting carotid stenosis

MD-CTA (64-slice CT angiography) is highly accurate in detecting and grading extracranial internal carotid artery (ICA) stenoses in which the artery is closed between 70%-90% when compared to color-coded Doppler sonography, power Doppler and B-flow ultrasound, according to a study by researchers from the University of Munich-Grosshadern (Munich, Germany).

For the study, the researchers analyzed 37 patients with 43 known or suspected extracranial ICA stenoses who underwent MD-CTA and vascular ultrasound. The researchers found that “excellent” visualization of vessels was achieved on MD-CTA in all cases. Of the 43 stenoses, 28 were closed between 70%-80%, 10 were closed between 80%-90%, and all were correctly identified with MD-CTA and vascular ultrasound.

According to the researchers, it is important to be able to identify high-grade ICA stenosis to plan the appropriate surgery and therapy.

“Studies have shown that symptomatic patients with high-grade stenoses of the extracranial ICA profit from thromboendarterectomy, an operation that involves opening the artery and removing the occlusion. In addition, the morphology of the stenosis, especially the detection of ulcerated plaques and thrombi, is crucial for the planning of interventional treatment,” said Dirk Andre Clevert, MD, lead author of the study.

“The diagnostic investigation of stenoses for surgical planning should include a combination of MD-CTA and vascular ultrasound, because ultrasound has also gained a high importance as a generally available non-invasive imaging method. For the depiction of ICA segments within the skull, MD-CTA is especially necessary for preoperative planning,” said Clevert.

Endothelial cells and BP consistency

Blood vessels must be able to quickly sense and adapt to increasing and decreasing rates of blood flow in order to maintain consistent blood pressure throughout the body.

The endothelial cells (ECs) lining the vessel wall recognize shear stresses and transduce signals to vascular muscular cells and others in order to modify vessel shape and structure accordingly.

In a study in the May issue of the Journal of Clinical Investigation, William Sessa and colleagues from Yale University (New Haven, Connecticut) show that the protein caveolin-1 (Cav-1) and structures known as caveolae act as sensors along the cell membrane of ECs in order to detect shear stress and help bring about appropriate reactionary remodeling of affected blood vessels.

Caveolae are distinct flask-shaped invaginated structures at the surface of ECs and consist of Cav-1 and other proteins.

Sessa et al. used mice lacking Cav-1 as well as mice over-expressing Cav-1 specifically in ECs. After tying off the left carotid artery in these mice for 14 days, thereby modifying the blood flow, they found that the inside diameter of the ligated vessels was reduced in normal mice but not in Cav-1 deficient mice. In turn, re-expression of Cav-1 in ECs was sufficient to induce this change in Cav-1 deficient mice.

In an accompanying commentary, Michael Lisanti and Philippe Frank from Thomas Jefferson University (Philadelphia) further discuss the Cav-1 regulated signaling pathways in ECs and conclude that “these data suggest that endothelial caveolae and Cav-1 allow arteries to sense, organize, and mediate signal transduction, thereby giving arteries the ability to change their physical properties and to maintain/regulate normal blood flow in the face of altered shear stress conditions.”

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