Friday, November 19, 2010


When I was in medical school, we were always taught that Coronary Heart Disease ( CAD ) was a degenerative condition, where artery walls accumulate cholesterol and harden with age. This we called atherosclerosis. Then came along the findings that seemed to suggest that atherosclerosis seemed to also be a response to inflammation. There were inflammatory cells found at the sites of the vulnerable plaque. These findings gave rise to the current theory, that atherosclerosis may also be an inflammatory response. Some even suggest that the vulnerability of the plaque, may be due to the inflammation. In fact, there was much work to suggest that " inflammation ", may not be infection, but a response to injury with LDL-Cholesterol. It may be the oxidised LDL-Cholesterol in the plaque that is the cause of the inflammatory response that was noted by the pathologist. Researchers search high and low, to see how they could mark out plaque inflammation. Many of our usual clinical inflammatory markers, like ESR, C reactive proteins, etc, did not quite provide an accurate enough marker. C reactive protein is something we found in patients with SLE, as a marker for the state of activity in SLE and their potential for renal involvement in lupus.
Someone then stumbled on hS-CRP as a marker. hS-CRP stands for highly sensitive, or highly selective C reactive protein. It was essentially micro levels of C reactive protein that can only be detected by very sensitive assay techniques.
" Statins ", a group of drugs very effective in lowering cholesterol, especially LDL-Cholesterol, also seemed to lower hS-CRP.
There in comes the difficulty. Some researchers seemed to feel that hS-CRP is an important risk marker for CAD, while others feel that it is not. The cardiac community seemed rather divided on this. After the publication of the JUPITER trial ( led by the Amercans ) results, suggesting that hS-CRP was very important as a CAD marker and lowering it confers significant benefit on our patients, the FDA review their guidelines and adviced that hS-CRP should be measured to ascertain risk for CAD and that the indication for Rosuvastatin ( the statin used in the JUPITER trial ), should include its ability to lower hS-CRP.
At the recent AHA 2010 meeting in Chicago, Dr Peter Sever presented a re-analysis of the ASCOT trial ( led by the Europeans ) on CAD with the use of Lipitor, and found little benefit in measuring hS-CRP and found that lowering it with Lipitor, did not confer much benefit. They argued that using LDL-cholesterol as a guide to treatment was much better ( what we have always taught ).
So the debate goes on. What is the role of hS-CRP in the management of CAD? Is it useful? Must it be measured in risk assessment? Does lowering hS-CRP alone confer benefit, or is lowering LDL-cholesterol the important thing?
I do not know the answer. But I do know that most labs do not measure hS-CRP well, and the results are so varied that is was difficult to aplly clinically ( at least in my experience in Malaysia ). Measurement of LDL-cholesterol was more consistent, and clinically useful.
Whatever it is, it does look like atherosclerosis is partly a degenerative process, with an inflammatory component, very likely to be due to oxidised LDL-cholesterol as the cause of the inflammation.
I am sure that the debate will go on, between the cardiologist on both sides of the pond.

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