Putting it all together:  There are two major factors in coronary disease, the inflammatory response and that of the amount of the building materials for atherosclerosis—the cholesterol family of compounds.  Misleadingly it is the latter that has all the press and all the treatment.

 Plaque buildup is accelerated with high levels of LDL, but LDL level is not the driving engine, rather it is the inflammatory response within the artery wall (IR).  In other words, LDL is statistically relevant, but not that relevant, while the inflammatory response (IR) is very relevant. The poorly correlated LDL is easy to track:  current LDL level gives a good indication as to LDL levels over the past decade, and it is frequently measured.  On the other hand, current IR is poorly correlated to past levels, and is rarely tested for.  IR testing is both more expensive and rare (his-CRP, SSS proteins levels are two measures of IR).  Moreover, these markers of inflammation are not sufficiently specific:  inflammation in other tissues besides the artery wall will produce elevated CRP and SSS protein level.  Moreover, current high levels of markers doesn’t indicate if the current inflammation is of the sort that is correlated with coronary disease or provide information concerning various past inflammations.  Risk factors measured by inflammation markers, health problems, and cholesterol profile, are mere risk factors; viz., they are not test which affirm a disease. 

 Plaque build up occurs through oxidative damage to LDL, which occurs within the artery walls.   White blood cells play a crucial role through 5-LO, 12-LO, and 15-LO pathways which are involved in the oxidation of LDL (see http://healthfully.org/id9.html).  This process occurs within the artery wall.  Thus the very process of forming plaque is isolated and affecting the blood test.  (see http://healthfully.org/heart/id5.html for a very informative illustration of this process).  High levels of LDL means there is more of it for oxidative process to use in the build of plaque, and a a strongly positive test for the markers of inflammation could be a result of one of the types of infects which indirectly play a role in the white-cell mediated process within the artery wall.  For example gingivitis (gum disease) is correlated with atherosclerosis. There is an industry of lowering LDL because big PhARMA makes billions, and thus we test for cholesterol so that they can sell cholesterol lowering drugs. 

            Many results confirm that IR (inflammation response) is the main culprit: 1) the reduction in LDL level which is dramatic with the use of statins produces only a modest reduction in MI.  2) the use of VIOXX over 2 years resulted in a 200% increase in mortality among the elderly (exposed in the VIGOR study) because it increased the IR.  3) IR has a large body of research articles and its mechanism has been described in detail (see for example http://healthfully.org/heart/id14.html).  4)  the role of tobacco—a pack a day over 20 years results in over a doubling the rate of deaths from MI.(see http://healthfully.org/tobacco/id2.html).  The main cause is the circulation of reactive oxygen from carbon monoxide, which causes the oxidative damage to LDL.  5) Certain infections such as gingivitis are correlated with increased risk.  Point 2) needs further elucidation:  VIOXX and all COX-2 inhibitors--but for aspirin--shut off the mechanism which terminates the inflammatory response in the artery walls:  the inflammation response runs unchecked even when the cause has been removed.  Naproxin also given in the VIGOR increased mortality by 50%.  The elderly who all ready have significant atherosclerosis, COX-2 inhibitors such as VIOXX and Naproxin acceleration it and thus caused in the VIGOR study such a dramatic increase in MIs and deaths.  Points 1) & 2) are particularly dispositive:  modest reduction in MI with dramatic reduction in LDL, while allowing plaque formation to run unchecked produced a dramatic increase in MI.  Lower by drugs LDL is grossly over rated.      

It is not atherosclerosis that causes most of the MI, but rather unstable plaque.  Three imaging study have shown that “Most artery flow disrupting events occur at locations with less than 50% lumen narrowing (~20% stenosis is average).”  http://healthfully.org/heart/id15.html.  However, when the unstable plaque leaks it will reach clog a narrow opening down stream.  With atherosclerosis, this will often be a major coronary or ceberal artery  (see second illustration at http://healthfully.org/heart/id5.html.); without atheroclerosis it will plug a smaller vessel.  Because of this nearly everyone over the age of 40 has unstable plaque, and thus is at risk of a MI or stroke. 

“Atherosclerosis is a common condition in both the developed and developing world and is now recognised to be an inflammatory condition leading to the development of ischaemic heart disease, cerebrovascular disease and peripheral vascular disease”-- British Journal of Anaesthesia 2006 97(6):758-769; doi:10.1093/bja/ael303, G.M. Howard. 

One would hope that a treatment reducing the inflammatory response would be developed.  However, such intervention would negatively affect both resistance to illnesses and infections and increase their severity.  Given the complexity of the immune response, it is not likely that such an approach would in the near future be developed.  Thus like cancer prophylactic measures are the best course.  The best of all interventions are the lifestyle changes:  strenuous exercise,* weight loss, and avoiding tobacco smoke.  To this add avoiding all NSAIDs but for aspirin.

*Strenuous exercise, which gets up the heart rate to about 80% of maximum, stimulates the development of new coronary vessels, and also widens them.  This reduces the risk of a clot blocking a major coronary vessel.