Hi Dr. Davis,

This post touches on a point I've been wondering about.

You write that a drop in CT heart scan score signifies a "huge reduction in risk for plaque rupture, or heart attack."

As I understand it, strictly speaking, the score indicates a reduction in the volume of calcium/plaque in the arteries.

In your books and articles you provide references to the studies which document the statistical correlation between FIXED scores and rupture/heart attack.

My question is this (and you may have answered this question already elsewhere):  Have there been studies that document a statistically significant relationship between a reduction in plaque volume (as opposed to a fixed value) and risk of a CAD event?

A follow up question:  Is the actual reason for the risk reduction due to score reduction actually known?  I can imagine that one reason might be that because the arteries have plaque reduced, they are actually larger in terms of blood flow supported than they were before the plaque was reduced.

My belief, however, is that there could be additional reasons for a reduced plaque over time = less risk correlation.

Thoughts about this?

Thanks.

Great questions.

We do know that, if plaque is permitted to grow (by several measures including angiographic studies, carotid ultrasound, as well as heart scan scores), the likelihood of events escalates along with it. This is known with absolute confidence.  

We also know that reductions in plaque burden are also correlated with reductions in risk, also by just about any measure, though the magnitude of reduction varies, since each approach provides a different persective on plaque composition, all differ on incorporation of the Glagov phenomenon ("remodeling"). More data on event reductions are needed, however. But until recently, genuine bona fide reversal had been elusive.

Lastly, actual examination of tissue that has regressed is very limited. As you can imagine, if someone asked you, having regressed, to allow a sample of artery tissue to be removed, you'd likely not be interested. Thus, the observations are indirect and come from animal studies and observations like intracoronary ultrasound.

Actually, reductions in heart scan scores are a surrogate for inactivation of plaque, removal of inflammatory cells, removal of fat-laden tissue, etc. The reduction  in calcium is a parallel phenomenon that we can see. I also wonder, given the wonderful effects of vit D and possibly K2, whether the reduction in calcium provides benefits of its own, independent of the inactivating effects.

While everyone agrees that reduction of atherosclerotic plaque is a good thing, there are several clinical studies that suggest that reduction of calcium in the plaque may not be good. For example, this study found that culprit stenoses in arteries of patients with stable angina had more calcium than those of patients with unstable angina, which had more calcium than those with acute myocardial infarction. This suggests that plaque accumulation in a specific location may actually be beneficial if it stabilizes the plaque and makes it less likely to rupture.

There is not much data on calcium score reduction because it is so rarely seen. What is needed are long-term studies showing that calcium score reduction does reduce the number of adverse coronary events.

I disagree.

There is a commonly offered argument that calcium stabilizes plaque. I think this is nonsense. There are studies by Renu Virmani and others that demonstrate that the shear and tension forces at the edges of calcified plaque are, in fact, areas of greater stress and thereby risk for plaque rupture.

While intracoronary ultrasound will sometimes show that a small segment of a recently ruptured plaque will involve a non-calcified segment, we are NOT using calcium in a lesion-specific fashion. We use it as an index of total plaque.

I also believe that emerging concepts, such as the influence of vitamin D3 on gamma-carboxyglutamic acid Gla protein in vascular tissue are pointing towards the fact that vascular calcification is part of a regulated, active process that influences plaque activity and rupture potential. (See Johnson et al, Vascular calcification: pathobiological mechanisms and clinical implications. Circulation Research 2006 Nov 2006;99(10):1044-59.)

Increasing calcium scores have been conclusively associated with dramatic increases in coronary events. Likewise, emerging data, including our own, show reducing calcium scores is associated with virtual elimination of events.

Do you have something better?

No, I don't have anything better - I don't argue that an increasing calcium score is good, only that we have nothing more than anecdotal evidence to show that calcium score reduction is beneficial. And, there are other experts in the field that do not agree that it is. The recent torcetrapib clinical trial shows that not all ways of increasing a generally beneficial lipid such as HDL are theraputic. Have you considered documenting the results of your practice, i.e., what percent of your patients show calcium score change in each of several percentage ranges including reductions, and what their follow-up results are in terms of hard cardiac events? That might stimulate interest in a controlled clinical trial to verify your results.

What experts "agree" that a reduction in calcium score is not beneficial? Can you specify who? I know the literature on calcium scoring quite well, and I don't ever recall such a study.

Dr. Davis,

The wizard, hmmm, I mean, Dr. Oz says on Oprah that "we'd rather focus on the plaque itself—because the calcium actually might help stabilize the plaque and reduce the chance of it rupturing."

http://www2.oprah.com/health/yourbody/youdocs/youdocs_faqs_io_10.jhtml

So, there's the proof you asked for.  It was on the Oprah show.

And by the way, Oprah's doc says that Ornish has the answer here:

http://www2.oprah.com/health/yourbody/youdocs/youdocs_faqs_io_11.jhtml

Seriously, this question of the Calcium Score relationship to risk reduction is a key issue and I appreciate your sharing your knowledge about the question.

It will be interesting to see if Anonymous gets back to you with expert reference list you've asked for.

I don’t think there is a study that shows that because calcium reduction is so infrequently seen. I have discussed it with the Director of Preventive Cardiology at a State University Hospital who is of the opinion that calcium reduction may not be beneficial. I suspect that most experts would say that there isn’t enough data to conclude that reduction of calcium is either beneficial or detrimental because most have never seen it.

My point is that several studies show that plaque rupture tends to happen in arteries that have “spotty,” but not extensive calcium, and that coalescence of small calcium deposits into larger deposits reduces the surface area in contact with softer plaque, thereby reducing the extent of the stress risers that can lead to plaque rupture. Quoting from some of these

“…double helical computerized tomography demonstrates that extensive calcium characterizes the coronary arteries of patients with chronic stable angina, whereas a first AMI [acute myocardial infarction] most often occurs in mildly calcified or noncalcified culprit arteries.” Shemesh et. al., American Journal of Cardiology, 1998 Feb 1;81(3):271-5, Comparison of coronary calcium in stable angina pectoris and in first acute myocardial infarction utilizing double helical computerized tomography.

“Acute coronary syndromes are associated with a relative lack of calcium in the culprit stenoses compared with stenoses of patients with stable angina.” Joshua A. Beckman et. al., Arteriosclerosis, Thrombosis, and Vascular Biology. 2001;21:1618, Relationship of Clinical Presentation and Calcification of Culprit Coronary Artery Stenoses.

“The relationship between calcification and clinical events likely relates to mechanical instability introduced by calcified plaque at its interface with softer, noncalcified plaque. In general, as calcification proceeds, interface surface area increases initially, but eventually decreases as plaques coalesce. This phenomenon may account for reports of less calcification in unstable plaque.” Moeen Abedin et. al.,  Arteriosclerosis, Thrombosis, and Vascular Biology. 2004;24:1161, Vascular Calcification - Mechanisms and Clinical Ramifications.  

“In AMI patients, the typical pattern was spotty calcification, associated with a fibrofatty plaque and positive remodeling. In ACS [acute coronary syndrome] patients showing negative remodeling, no calcification was the most frequent observation. Conversely, SAP [stable angina pectoris] patients had the highest frequency of extensive calcification…To the best of our knowledge, the present IVUS study is the first to demonstrate the relationship between calcification patterns, arterial remodeling, and the morphology of plaques within the culprit lesion segment. The major finding is that there is a significant difference in the pattern of coronary calcifications at the culprit lesion segment, particularly with respect to size, number, and length of the deposits, among patients with AMI, UAP [unstable angina pectoris], and SAP. Small calcium deposits were significantly more frequent in the culprit lesion segments in ACS than in SAP patients.” Shoichi Ehara, et. al., Circulation. 2004;110:3424-3429, Spotty Calcification Typifies the Culprit Plaque in Patients With Acute Myocardial Infarction.

Also, there is an MRI study of  the carotid arteries of CAD patients who had been given niacin, lovastatin, and colestipol for 10 years. In comparison with matched, untreated patients, the carotid plaque of the treated patients showed much less lipid but much more calcium than the untreated patients. Xue-Qiao Zhao, Arteriosclerosis, Thrombosis, and Vascular Biology. 2001;21:1623, Effects of Prolonged Intensive Lipid-Lowering Therapy on the Characteristics of Carotid Atherosclerotic Plaques In Vivo by MRI.

It seems that reduction of the “spotty” calcium may reduce the likelihood of plaque rupture, but reduction of coalesced calcium such as is seen in stable angina patients may  increase the surface area of calcium (if the coalesced calcium reverts to spotty deposits) and therefore be detrimental. From the standpoint of evidence-based medicine, the only way to be sure of the effects of calcium reduction is to conduct a clinical trial of patients undergoing such reduction.

In the meantime, Dr. Davis, since you are one of the few cardiologists whose patients are experiencing calcium score reduction, it would be of great benefit if you would document the results of your practice in a quantitative way.

I believe that you are confusing two phenomena.  

Tissue characterization of specific plaque locations that are prone to rupture (or have ruptured) examined by techniques such as intracoronary ultrasound, is distinct from the concept of using coronary calcium scoring as a surrogate measure of total plaque volume.

I believe that lipid-laden, calcium-poor plaques do tend to identify sites more prone to rupture. I have witnessed this myself in many intracoronary ultrasound procedures personally performed.

This is different from using calcium as an index of plaque. While we are uncertain of the relationship of calcium to total plaque in people who have experienced calcium score reduction, all circumstantial evidence points towards dramatic regression of lipid laden plaque, regression of inflammatory cell composition, replacement by fibrous tissue matrix, reduction of oxidative capacity, reduction of  matrix metalloproteinase content, in other words, all the factors that trigger plaque rupture.  

Though just my suspicion, I believe that the initial relative composition of calcium to plaque of 20% is likely increased, meaning calcium occupies more of total plaque volume. In other words, my suspicion is that, if calcium regresses, total plaque volume has regressed even MORE.

We plan to publish our data this spring. We had planned to publish our experience much sooner, but the addition of vitamin D to the program has boosted success so much that we decided to start over again around 2 years ago.

hm... bookmarked style )

so great, your arteries are cleared up but you'll get cancer and die from all of those ct scans.
lovely.

Dr. Davis, two things check out this web site http://www.traceminerals.com/research/synx.html it appears to have some good data on Metabolic Syndrome-X:
I would like to share some good data that I have had by following the TYP program, I was diagnosed with type 2 diabetes Feb. 15 and after that I got my second heart scan, over 600 (my age 57) a 43% increase in 18 Mo. Not good needless to say, than I found TYP in march of this year I started slowly following and implementing a TYP plan,
Background
In February I did not feel well and I went to the doctor(2/15) I had lost 12 lbs my % body fat was going up  the muscles in my stomach were sore at times I was so thirsty I could not stand it and my eye site was changing. Needless to say I was diagnosed as a type II diabetic   glucose 344 A1C 11.2, was prescribed new medications for both the diabetic condition( Januvia 100mg 1X per day actoPlus Met 2X per day 15mg 850mg) along with cholesterol ( Advicor 20/1000 ). I started a life style changing program.
Life style changes
Modified eating program- went to a low GI high Vegetable protein including soy no or almost no Fats, eat as much as I want .(needless to say I have changed this plan)
Quit smoking
Increased exercise- walking on treadmill 7%grade 3.75mph from 30 min. to 30 min twice a day
My Medications were changed Advicor 20/1000; Lisinopril-hydrochlorothiazide tablets 10-12.5 mg and a 325mg aspirin
April started on the TYP plan, my Glucose average was way up, my total cholesterol number was 100 but my LDL-P was 1015 and my small LDL-P was 913 along with a HDL-C of 30  went on the TYP program
Had my Vitamin D checked -it was low , had my DHEA checked it was low, had my Magnesium checked it was low, after my discussion with you came off Lisinopril , ( we are seeing were this settles out to pick the right med's) stopped talking all diabetic med's added two other supplements R-ALA , PGX Fiber Blend (instead of oatmeal too many carbs) along with Vit D, Magnesium, DHEA , 15 grams of soy protein Fish oil, healthy Fats, no wheat products, Dark chocolates L-Arginine.   I have had a additional blood test for these items (Vit D magnesium, DHEA) adjusted supplements body fat down to less than 14% WHAT A DIFFERENCE, in the last 11 days  my fasting glucose numbers are between 84 and 103 that’s normal, before they were above 125 solidly Diabetic (since Feb even with diabetic medications) my doctor has never seen this much improvement without medication, on someone that had a 12 week ave of over 340.I do not know who is more anxious to see my next lipid profile me or my doctor  . I'am scheduled in three weeks.
Needless to say i also beleive that very few people can just take one pill and be cured. I hope i'am alive when they do find the magic cure (and i think they will) but right now the TYP plan is the best game in town. Eugene

Thus, the idea that a statin drug to reduce LDL will cure heart disease is completely folly. It does happen--but rarely. I think I've seen it happen twice. Much more commonly, a program that addresses all the causes of coronary plaque yields far superior benefits.

I knoe a lot about the Cholesterol!
LDL particles vary in size and density, and studies have shown that a pattern that has more small dense LDL particles, called Pattern B, equates to a higher risk factor for coronary heart disease!!My grandpa died for this reason, I think that it was terrible!!