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June 9, 2009JAMA news releases are made available to the public after 3 pm US Central time on the first 4 Tuesdays of each month. The Archives of Journals news releases are made available to the public after 3 pm Central time on Mondays. We also provide a list of previous news releases. THIS WEEK'S CONTENTS
JAMA NEWS RELEASES
(Embargoed for Release: 3 p.m. CT Tuesday, June 9, 2009)
JAMA REPORT (VIDEO SCRIPT)
INFORMATION CONTAINED IN THESE NEWS RELEASES IS PROTECTED BY COPYRIGHT. JOURNAL ATTRIBUTION IS REQUIRED. JOURNALISTS CAN NOW ACCESS EMBARGOED JAMA/ARCHIVES STUDIES ON-LINE. Go to www.jamamedia.org for more information and to apply for access. TV Note: This week's JAMA Report video is on the outcomes of donor stem cell transplantation for patients with leukemia. The report will be fed Tuesday, June 9, from 9:00 - 9:30 a.m. ET and 2:00 - 2:30 p.m. ET, on Galaxy 28 (C-Band), Transponder 19, downlink frequency: 4080 vertical, audio 6.2/6.8. For more information, call 312/464-JAMA. Please Note: The FOR THE MEDIA website now has a search feature to enable media to find previous JAMA/Archives news releases on specific medical topics. This search feature link is located on the home page at www.jamamedia.org EMBARGOED FOR RELEASE UNTIL 3 P.M. (CT), Tuesday, June 9, 2009
Genetically Elevated Levels of Lipoprotein Associated With Increased Risk of Heart Attack
CHICAGO—A genetic analysis of data from three studies suggests that genetically elevated levels of lipoprotein(a) are associated with an increased risk of heart attack, according to a study in the June 10 issue of JAMA. Myocardial infarction (MI; heart attack) remains a leading cause of illness and death despite targeting of low-density lipoprotein (LDL) cholesterol by statin therapy. "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," the authors write. They add that a mendelian (genetics) randomization study could also provide evidence of a causal relationship. "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." Levels of lipoprotein(a) may vary up to a thousand-fold among individuals, and levels are partly determined by variations in the LPA gene coding for the apolipoprotein(a) moiety (any equal part) of lipoprotein(a). The most influential LPA variation is the kringle IV type 2 (KIV-2) size variation. The number of KIV-2 repeats correlates inversely with levels of lipoprotein(a), according to background information in the article. Pia R. Kamstrup, M.D., of Herlev Hospital, Copenhagen University Hospital, Herlev, Denmark, and colleagues examined whether genetically elevated lipoprotein(a) levels are associated with increased risk of MI. Three studies of white individuals from Copenhagen, Denmark, were used: the Copenhagen City Heart Study (CCHS), a general population study with 16 years of follow-up (1991-2007, n = 8,637, 599 MI events); the Copenhagen General Population Study (CGPS), a general population study (2003-2006, n = 29 388, 994 MI events); and the Copenhagen Ischemic Heart Disease Study (CIHDS), a case-control study (1991-2004, n = 2,461, 1,231 MI events). For all participants, plasma lipoprotein(a) levels, lipoprotein(a) KIV-2 size variation genotype, and MIs were recorded from 1976 through July 2007. The researchers found: "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...," they write. "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."
"Nonetheless, final proof of causality still requires randomized clinical trials demonstrating reduced MI risk in response to lipoprotein(a)-lowering therapy."
Editor's Note: Please see the article for additional information, including other authors, author contributions and affiliations, financial disclosures, funding and support, etc. Editorial: Mendelian Randomization — Nature's Randomized Trial in the Post-Genome Era
In an accompanying editorial, George Thanassoulis, M.D., and Christopher J. O'Donnell, M.D., M.P.H., of the National Heart, Lung and Blood Institute's Framingham Heart Study, Framingham, Mass., comment on the findings of Kamstrup and colleagues.
"Although this study certainly provides interesting mechanistic insights into the biology of lipoprotein(a) in the context of MI and suggestive evidence regarding the potential benefit of decreasing lipoprotein(a) early in life, clinicians may ask: ‘How will these results affect current approaches for prediction, prevention, and treatment of my patients?' At present, the clinical implications remain quite limited. These results do not provide the necessary evidence that genetic testing of the LPA locus or measurements of plasma lipoprotein(a) have a role in cardiovascular risk stratification or decisions regarding lipid-lowering therapy. Ultimately, despite nature's best efforts to provide causal evidence for lipoprotein(a), only a true randomized controlled trial demonstrating reductions in MI with targeted lipoprotein(a)-lowering therapy can provide the evidence for benefits and risks of an lipoprotein(a)-lowering strategy."
Editor's Note: Please see the article for additional information, including financial disclosures, funding and support, etc. For more information, contact JAMA/Archives media relations at 312/464-JAMA (5262) or e-mail mediarelations{at}jama-archives.org. EMBARGOED FOR RELEASE UNTIL 3 P.M. (CT), Tuesday, June 9, 2009
Dose-Reduction Techniques Associated With Decreased Amount of Radiation Exposure From Cardiac Scans Without Impairing Image Quality
CHICAGO—An intervention that includes techniques to reduce the amount of radiation from cardiac computed tomography angiography (scanning used to diagnose coronary artery disease) was associated with decreasing patient exposure to radiation without significantly changing the quality of the images, according to a study in the June 10 issue of JAMA. Coronary artery disease remains the most frequent cause of death and disability in the developed world and rates are increasing among developing nations. "As the population at risk has increased, national health care systems are under financial pressure to deliver cost-effective diagnosis and risk stratification of symptomatic patients suspected of having coronary ischemia. Noninvasive multislice cardiac computed tomography angiography (CCTA) has emerged since 2000 as a new diagnostic test with the potential to efficiently address this challenge," the authors write. Results from multiple studies suggest that CCTA may definitively exclude the diagnosis of coronary artery disease in a substantial proportion of appropriately selected patients, however radiation dose from this procedure is of concern. Gilbert L. Raff, M.D., of William Beaumont Hospital, Royal Oak, Mich., and colleagues conducted a study to determine whether implementation of an intervention to improve the technique for scan acquisition would be associated with a reduction in the estimated radiation dose from CCTA and what would be the associated effects on image quality. The study included 4,995 patients undergoing CCTA for suspected coronary artery disease at 15 hospital imaging centers, which included small community hospitals and large academic centers; 4,862 patients (97.3 percent) had complete radiation data for analysis. The techniques to reduce radiation dose included minimized scan range, heart rate reduction, electrocardiographic-gated tube current modulation, and reduced tube voltage in suitable patients. The researchers found that compared with the control period, patients' median (midpoint) estimated radiation dose in the follow-up period was reduced by 53.3 percent. An increase in the number of patients receiving the target dose below a certain level (compared with the control period) was achieved at all sites. The increase in the proportion of those reaching the target dose was greatest at low-volume sites (less than 30 scans per month). "Importantly, despite the reduction in the radiation doses, there were no significant changes during the control period compared with follow-up period in median image quality rating or the proportion of diagnostic-quality scans (554/620 patients [89 percent] in the control period vs. 769/835 patients [92 percent] in the follow-up period)," the authors write. The most powerful factors associated with achievement of the target radiation dose were the use of lower tube voltage, which increased from 13 percent to 43 percent of cases, and a site study volume of more than 30 scans per month. Among patient-related variables, reduction in heart rate demonstrated a strong positive association with a decreased radiation dose. "Baseline data obtained in this study support the concern that CCTA testing may result in relatively high radiation doses, but the rapid improvement in radiation dose in the first 3 intervention months demonstrates how use of existing technology and technical methods is associated with dramatically reduced dosages. The dose-reduction program involved an educational aspect at every level in the imaging process. Without a feedback loop of regular dose measurements and reports, similar monitoring of patient preparation, and appropriate imaging protocols and resultant image quality, there would neither be the opportunity to detect dose elevations nor the ability to improve practice," the researchers write.
"The importance of radiation-reduction techniques must be emphasized during physician and technologist training and physicians should demonstrate technical mastery of these methods before certification to oversee CCTA scanning."
Editor's Note: Please see the article for additional information, including other authors, author contributions and affiliations, financial disclosures, funding and support, etc. For more information, contact JAMA/Archives media relations at 312/464-JAMA (5262) or e-mail mediarelations{at}jama-archives.org. EMBARGOED FOR RELEASE UNTIL 3 P.M. (CT), Tuesday, June 9, 2009
Donor Stem Cell Transplantation Associated With Survival Benefit For Patients With Leukemia
CHICAGO—An analysis of previous studies indicates that allogeneic stem cell transplantation (SCT) (stem cells from a compatible donor) is associated with significant overall and relapse-free survival benefit among adult patients with intermediate- and poor-risk but not good-risk acute myeloid leukemia in first complete remission, compared with nonallogeneic SCT therapies, according to an article in the June 10 issue of JAMA. The optimal curative treatment of acute myeloid leukemia (AML) in first complete remission (CR1) is uncertain. While more than 70 percent of younger adult patients with newly diagnosed AML will enter a CR1 after initial (induction) chemotherapy, a substantial number subsequently experience disease relapse, according to background information in the article. "Allogeneic SCT after myeloablative conditioning [high-dose radiation and/or chemotherapy given to destroy normal and cancerous cells in the bone marrow prior to infusion of donor stem cells] is a curative treatment option for younger patients with AML in CR1. However, concerns regarding allogeneic SCT–related toxicity, and questions regarding its benefit, limit its use for patients who have attained an initial remission," the authors write. John Koreth, M.B.B.S., D.Phil., of the Dana Farber Cancer Institute, Boston, and colleagues conducted a meta-analysis to quantify relapse-free survival (RFS) and overall survival benefit of allogeneic SCT for AML in CR1 overall, and also for good-, intermediate-, and poor-risk AML. The researchers conducted a search for articles on trials evaluating allogeneic SCT vs. nonallogeneic SCT therapies (autologous [donor and recipient are the same person] SCT, consolidation chemotherapy, or both) for AML in CR1. The researchers identified 24 trials that met criteria for inclusion in the analysis, which included 6,007 patients (5,951 patients in RFS analyses and 5,606 patients in overall survival analyses); 3,638 patients were analyzed by cytogenetic (abnormalities in the composition of the chromosomes) risk (547, 2,499, and 592 with good-, intermediate-, and poor-risk AML, respectively). "Our primary finding is that the totality of the prospective trial data indicates statistically significant RFS and overall survival benefit with allogeneic SCT for adult AML in CR1. This conclusion is supported by a variety of sensitivity and subgroup analyses... . Additionally, our analyses indicate that allogeneic SCT benefit likely varies by AML cytogenetic risk. We document significant RFS and overall survival benefit for allogeneic SCT in intermediate- and poor-risk AML, and a lack of significant RFS or overall survival benefit for good-risk AML," the authors write.
"While enrollment in therapeutic trials is to be encouraged, our findings provide evidence to guide clinical decision making and future trial design."
Editor's Note: Please see the article for additional information, including other authors, author contributions and affiliations, financial disclosures, funding and support, etc. For more information, contact JAMA/Archives media relations at 312/464-JAMA (5262) or e-mail mediarelations{at}jama-archives.org.
JAMA REPORTS
VIDEO: Windows Media | Quicktime
HIGHER RISK TRANSPLANT PROCEDURE FOUND TO BE WORTH IT FOR MANY PATIENTS WITH A FORM OF ACUTE LEUKEMIA
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