How did doctors miss this impending cardiac event? It seems that the body’s defence mechanisms eluded existing medical technology. As you may have read before (Blog post: Blocked Pipework in Our Hearts), our arteries detect that a growing atherosclerotic plaque can reduce blood flow to the intended tissues, so the artery wall expands outwards in an attempt to maintain the diameter of the artery through which blood flows. This process is referred to as positive remodelling or ‘Glagov remodelling’, named after the late Professor Seymour Glagov who demonstrated this phenomenon. Standard angiography – where a dye is administered into the patient’s coronary arteries and X-ray imaging is used to visualise arterial blood flow – will only reveal significant blockages or narrowing of arteries. But if an artery has remodelled considerably to maintain blood flow, atherosclerotic plaques will not be detected in spite of how large they may be. In fact, up to 75% of ruptured atherosclerotic plaques, which have significantly reduced or blocked blood flow, exhibit positive remodelling .
Once the plaque reaches the ‘Glagovian’ limit of blocking 40% of the cross-sectional area of the artery, expansion can no longer occur so further plaque growth only serves to block blood flow, otherwise referred to as negative remodelling . This is when arterial disease will be detected by angiography. As described previously, smooth muscle cells from the artery wall move into the developing plaque and create a layer on top full of smooth muscle cells and collagen produced by these cells, called the fibrous cap. When this cap becomes extremely thin and weak, due to proteins produced by macrophages (the main inflammatory cell) breaking it down, the cap ruptures and can trigger the appearance of a blood clot. If a blood clot does not appear, the ruptured cap will heal itself with the further production of collagen from the smooth muscle cells. The plaque may undergo several cycles of rupture and repair without any blood clots and subsequent symptoms appearing. And it is this process that determines the speed at which the transition from positive to negative remodelling occurs. If the plaque is permitted to grow with the gradual intrusion of lipids and inflammatory cells, the transition may take decades. However repeating cycles of rupture and repair will rapidly increase the rate at which the plaque grows, thus a seemingly harmless plaque can suddenly present a major threat within months or even weeks. This chain of events was most likely responsible for the sudden and unforeseen demise of Tim Russert.
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