Atherosclerosis refers to the buildup of fats, cholesterol and other substances in and on your artery walls (plaque), which can restrict blood flow. The plaque can burst, triggering a blood clot. Although atherosclerosis is often considered a heart problem, it can affect arteries anywhere in your body. 

For years, the belief was that plaque builds up, narrowing the artery until such time that the blockage becomes critical. It turns out that while partly true, the final event is a rupture of the plaque leading to a clot formation that blocks the artery causing the heart attack or stroke. This is why clot prevention by blocking platelets with aspirin and Plavix works. 

Before we discuss plaque buildup and clot formation and treatment in detail, I want to discuss something still in the very early stages and still being investigated. This is about how we prevent this process. We know that plaque builds up and the vulnerable portion of this ruptures releasing the lipid core into the artery lumen. This in turn attracts platelets, which stick together and cause the blockage. The million-dollar question is the obvious one: Why today and not two weeks ago? After all, all the risk factors are not changed. 

So, it appears that there are factors that precipitate the vulnerable plaque to rupture. First, it is now clear that atherosclerosis is a chronic inflammatory disease. Plaques are composed of components namely inflammatory cells, smooth muscle cells, a fibrous component of connective tissue and a fat component of lipids. 

Second, endothelial injury plays the inciting role. The endothelium is the innermost layer of cells in an artery. Turbulent blood flow leads to endothelial dysfunction, which inhibits vasodilatory molecules and stimulates production of adhesion molecules and attracts inflammatory cells. These inflammatory cells enter the plaque. These macrophages are activated and secrete enzymes that cause the plaque to rupture. This, in turn, as I had said, leads to clot formation. 

This leads to two questions. One: Can we detect this inflammation? Two: Can we treat it? CRP is an inflammatory marker and is elevated in inflammatory conditions like rheumatoid arthritis, lupus, etc. In atherosclerosis we are talking about micro-inflammation. So, now we can do a test called hs-CRP (high sensitivity CRP), which can detect small amounts of this. This certainly has been shown to predict cardiovascular events. 

As for treatment strategies, at least two anti-inflammatory therapies have been tried. Canakinumab is a monoclonal antibody targeting interleukin-1β. This has been shown to work in inflammatory arthritis. The CANTOS trial showed that canakinumab (150 mg) was superior to a placebo at preventing adverse cardiac events. Even more interesting are the results with colchicine. An old drug, and thus generic, it is used in acute gout. There have been at least three trials using low-dose colchicine as a preventive for cardiovascular disease, all showing benefit. While not yet officially approved, it’s very promising. Stay tuned.

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