Vascular Calcification: Friend or Foe?

“Am I growing bone in my arteries!?” The patient exclaimed, as I explained that the coronary narrowing had a lot of calcium. It has always struck me as a peculiar phenomenon and one that keeps me puzzled as I plow through the endless frames of IVUS analysis. It reminds me, in some ways, of those strange Teratoma tumors that have teeth or bone growing in them. Grey-scale IVUS studies, in the past, have shown us that larger arcs of calcium occur in more stable disease. Recent studies, have shown that spotty calcification on CT angiography may infer a more vulnerable plaque type. We all know that “calcium scoring” can improve the prediction of a future cardiovascular event over and above Framingham risk. This is because calcification accounts for up to 20% of the actual plaque burden and is therefore a surrogate for the amount of atheroma lurking in the vessel wall. The current consensus is that large amounts of calcium can identify a vulnerable patient rather than a vulnerable plaque. Should we not, therefore, stop the hunt for vulnerable plaques and just get on with treating the vulnerable patient earlier and more adequately? In the UK we often see “normal coronaries” documented in the notes following “diagnostic” angiography. Yet, this is without any idea of the actual plaque burden within the vessel wall or the presence of calcium. In some ways the patient was right. A large number of in-vitro studies have shown that osteoblastic-like cells and bone morphogenetic proteins are involved in the process of vascular calcification. Calcification is first seen in the lipid core of the atheroma, next to inflammatory cells. The basic mechanism is still under dispute but seems to stem from a mixture of vascular smooth muscle cell apoptosis and macrophage synthesis of collagenous proteins, these both act as a base for hydroxyapatite deposition. If you go back further in the evolution of vascular calcification, it may all just boil down to the usual suspect: endothelial dysfunction. It has been shown that healthy endothelium protects against this by expressing matrix GLA protein, a potent vitamin-K dependent inhibitor of vascular calcification. Although this process is probably happening in me, as I type (those famous west of Scotland genetics in action!) How should we react, as Cardiologists, to vascular calcification? Some see it as a stabiliser of the gruel that is forming during inflammatory atherosclerosis. As the process burns out, calcium becomes more predominant and may reduce the “rupture risk”. Although this is plausible, there is a counter argument that calcified vessels are more fragile as seen in the balloon angioplasty era; where dissections always occurred next to the calcium spot. Perhaps neither argument is correct. I believe that certain types of calcification and the location in the plaque is more important than the process itself. As suggested above, calcification cannot be characterised on angiography. Calcification is also associated with reduced myocardial blood flow in the absence of a luminal stenosis, possibly via alternative mechanisms, such as reduced vasomotion. This gets back to my ongoing theme that the angiogram should not be used on its own to detect or treat coronary artery disease. Sure, if you want to see and treat only stenoses, then great. However, if you wonder what you may be missing, you should consider IVUS, FFR and CT as adjuncts to the overall treatment strategy. The information from these additional techniques may answer the following important questions: Why treat a stenosis if it may not be physiologically or compositionally significant? Why not ensure optimum medical care for plaques with a large plaque burden but no significant luminal stenosis? Why deploy a stent when it may not expand properly due to unseen constrictive calcium arcs? Why do we need a luminal stenosis to say that there is significant coronary artery disease? When will we realise that the angiogram has reached its limits and continued reliance on it may be why (despite all our other advances) we are still failing to perfect the treatment of atherosclerosis? How about we switch from our obsession with percentage stenosis to instead quote: percentage calcification; plaque burden; percentage composition and physiological significance, before we just bang a stent in and hope for the best? I am interested in your thoughts on this. In summary, I think calcification may hold the key to plaque vulnerability, it could be our friend in diagnosis and treatment, if we look for it adequately. Unfortunately, it will continue to be our foe if we choose to ignore it completely.