Increased Levels Of Certain Protein Linked To Risk Of Coronary Heart Disease
April 8, 2008
An article published in the open-access journal PLoS Medicinefindsthat there is a link between coronary heart disease and levels ofinterleukin-6 (IL-6), a protein triggered by inflammation thatattracts immune system cells to an injury site. John Danesh(University of Cambridge) and colleagues also suggest that new drugsdesigned to fight vascular disease may target the IL-6 protein.
Coronary heart disease (CHD) is the leading cause of death in adults indeveloped countries. When deposits of plaque, calcium, and othercellular waste products harden against the arterial walls(atherosclerosis), there is an interruption of blood flow through thebody. Blockages in the coronary arteries result in CHD, and myocardialinfarction (heart attack) can occur if plaque breaks off the arterywall and restricts blood flow to the heart.
The research by Danesh and colleagues focuses on atherosclerosis as aninflammatory condition. They work with the premise that the immunesystem responds to injury by creating an area of redness and swelling(inflammation), a process which involves the production of cytokines.Cytokines are proteins that attract immune system cells to an injuredsite, such as an artery wall that has been damaged by atherosclerosis.Inflammation of the damaged artery, due to these cytokines, may furtheraid in the growth of atherosclerotic plaques. Thus, the researchers setout to see if a link could be established between prolonged moderateincreases in a cytokine called interleukin-6 (IL-6) and CHD. If such alink exists, new therapies could be developed that target cytokines inorder to reduce inflammation and slow down atherosclerosis.
Danesh and colleagues analyzed two large-scale studies conductedbetween 1967 and 1991 that included about 25,000 healthy middle-agedpeople - the Reykjavik Study (RS) and the British Regional HeartStudy (BRHS). Over a 20-year period, 2,138 had a first non-fatal heartattack or died from CHD. The researchers had access to the baselineIL-6 levels in these participants and in 4,267 participants who did nothave CHD. Adjusting for a year-to-year consistency of IL-6 levels, theresearchers found that increased long-term IL-6 levels were associatedwith a doubling of the risk for CHD. In a brief meta-analysis, theauthors indicate that their finding is consistent with findings from 15previous relevant studies.
“Long-term IL-6 levels are associated with CHD risk about as stronglyas are some major established risk factors, but causality remainsuncertain. These findings highlight the potential relevance ofIL-6-mediated pathways to CHD,” conclude the authors.
An accompanying perspective by Bruce Neal (George Institute forInternational Health, Sydney, Australia) is included in the same issueof the journal. Neal writes:
“While impressive in their rigour, the findings from this study areprobably rather limited in regard to their clinical implications.Future studies of interventions for the control of vascular diseasemight gain insight into mechanisms of action through assay of IL-6.Likewise, IL-6 could be a target for the development of new chemicalentities designed to modify vascular disease progression.”
“It is now widely accepted that 90% or more of vascular disease can beexplained on the basis of known risk factors, so these new data aboutIL-6 probably have relatively little to add in terms of ourunderstanding of causation. There are also multiple interventions thatmodify these known risks and avert premature death and disability fromvascular disease at low cost. Therefore there is little need for a newand probably costly drug that acts via IL-6. The better application ofproven risk stratification methods and the more efficient delivery ofproven management strategies could already cut a swathe through thecurrent vascular disease burden. These proven strategies should remainthe priority, particularly in developing regions of the world wheremost vascular disease now occurs. A focus on the identification ofpractical strategies for the delivery of existing interventions coulddeliver hugely cost effective global health gains.”
Long-Term Interleukin-6 Levels and Subsequent Risk of CoronaryHeart Disease: Two New Prospective Studies and a Systematic Review
John Danesh, Stephen Kaptoge, Andrea G. Mann, Nadeem Sarwar, AngelaWood, Sara B. Angleman, Frances Wensley, Julian P. T. Higgins, LucyLennon, Gudny Eiriksdottir, Ann Rumley, Peter H. Whincup, Gordon D. O.Lowe, Vilmundur Gudnason
PLoS Medicine (2008). 5(4): e78.
doi:10.1371/journal.pmed.0050078
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About PLoS Medicine
PLoS Medicine is an open access, freely availableinternationalmedical journal. It publishes original research that enhances ourunderstanding of human health and disease, together with commentary andanalysis of important global health issues. For more information, visithttp://www.plosmedicine.org
About the Public Library of Science
The Public Library of Science (PLoS) is a non-profit organizationof scientists and physicians committed to making the world’sscientific and medical literature a freely available public resource.For more information, visit http://www.plos.org
Written by: Peter M Crosta
Copyright: Medical News Today
