Lipoprotein-associated phospholipase A2 (Lp-PLA2) – an enzyme carried in the blood with 'bad' cholesterol – is associated with coronary heart disease risk to about the same extent as high blood pressure and cholesterol, an international study led by Dr Alexander Thompson and Professor John Danesh of the University of Cambridge has found.
The results, published in this week's Lancet, reinforce interest in this enzyme as a potential new therapeutic target for preventing heart disease.
Coronary heart disease is the leading cause of death worldwide, responsible for around 7 million deaths every year (1). Smoking, diabetes, high blood pressure, and high levels of bad cholesterol are known to cause coronary heart disease, but do not entirely explain its incidence.
As a result, there is considerable interest in identifying other risk factors, as this knowledge should help to develop new preventative medicines. For example, large clinical trials are testing new drugs (2) that block Lp-PLA2, an enzyme that is preferentially produced in people whose arteries are more affected by a process known as inflammation - the body's response to damage.
In the current study, the authors looked at how Lp-PLA2 measurements were related to subsequent risk of coronary heart disease, stroke and death in 79,036 participants from 32 prospective studies.
They found that higher levels of Lp-PLA2 in the blood were associated with increased risk of coronary heart disease, stroke and early death. For coronary heart disease, the magnitude of the increased risk associated with higher Lp-PLA2 levels was similar to that due to higher blood pressure or bad cholesterol.
However, "because blood pressure and cholesterol themselves were not as strongly associated with heart disease in this study as has been reported previously", the authors stressed the need for further studies.
The relevance of inflammation to cardiovascular disease is not well understood. Like Lp-PLA2, other blood proteins involved in inflammation such as C-reactive protein and fibrinogen are also associated with the risk of several different major chronic diseases.
However, because Lp-PLA2 levels appear unrelated to these other proteins, the authors stated that Lp-PLA2 measurements could have the potential to provide distinct insight into the relation between inflammation and development of coronary heart disease.
According to Dr Thompson*: "Randomised clinical trials of Lp-PLA2 inhibitors should help establish whether lowering Lp-PLA2 levels can reduce risk of vascular disease".
In an accompanying Comment, Dr Robert S Rosenson, Cardiometabolic Disorders, Mount Sinai School of Medicine, Mount Sinai Heart, New York, USA, echoed this sentiment, saying: "The importance of inhibited activation of these phospholipase A2 pathways on clinical events associated with atherosclerotic vascular disease awaits the results of prospective trials."
Dr John Danesh and Dr Alex Thompson, University of Cambridge, UK. T) +44 (0)1223 741302 E) ajt61@medschl.cam.ac.uk; jd292@medschl.cam.ac.uk
Dr Robert S Rosenson, Cardiometabolic Disorders, Mount Sinai School of Medicine, Mount Sinai Heart, New York, USA. T) +1 212-659-9181 E) robert.rosenson@mssm.edu
For full Article and Comment, see: http://press.thelancet.com/inflamm.pdf
Notes to editors
*Quote direct from Dr Thompson and cannot be found in text of Article
(1) World Health Organization: http://www.who.int/topics/cardiovascular_diseases/en/
(2) Two large clinical trials of a drug that blocks Lp-PLA2 are currently underway. These studies, involving around 15,000 and 11,000 people with heart disease respectively, are expected to be completed in 2012-2014. More information is available on the register of clinical trials: http://clinicaltrials.gov/ct2/show/NCT00799903 and http://clinicaltrials.gov/ct2/show/NCT01000727
Journal
The Lancet