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.

I think Dr. Cannell's making an impact internationally. I don't think it's any coincidence that British awareness of D deficiency is rising almost in tandem - but still quite behind - with US reports.

John Cannell and Vitamin D

I have noticed that, thanks to the efforts of Dr John Cannell, many mainstream docs in my area have begun to order Vitamin D tests and supplement when found to be low.

Satellite Maps of the Earth  

Satellite maps of the earth showing UV Sunlight exposure correlate with serum Vitamin D levels, and the farther north, the lower the Vitamin D, and the higher the incidence of Cancer and Multiple Sclerosis in our population.

These NASA space satellite photos of North America color coded for UV sun exposure can be seen on Dr. Grant's Vitamin D Web Site.  Here, you will see a pattern remarkably similar to the incidence of cancer and multiple sclerosis. This is thought to be due to differences in Vitamin D levels. The farther north with less sun exposure and lower Vitamin D levels, there is an increased incidence of cancer and multiple sclerosis.

Diseases Caused by, or Associated With Vitamin D Deficiency:

Again here is the list: Osteoporosis, Hypertension, Cardiovascular disease, Cancer, Depression, Epilepsy, Type One Diabetes, Insulin resistance, Autoimmune Diseases, Migraine Headache, PolyCystic Ovary Disease (PCOS), Musculoskeletal and bone pain, Psoriasis.

Vitamin D deficiency has been reported in 57% of 290 medical inpatients in Massachusetts, 93% of 150 patients with overt musculoskeletal pain in Minnesota, 48% of patients with Multiple Sclerosis, 50% of patients with lupus and fibromyalgia, 42% of healthy adolescents, 40% of African American Women, and 62 % of the morbidly obese, 83% of 360 patients with low back pain in Saudi Arabia, 73% of Austrian patients with Ankylosisng Spondylitis, 58% of Japanese girls with Graves’s Disease, 40% of Chinese adolescent girls, 40-70% of all Finnish medical patients. (the above is from Dr Cannell newsletter)

Low Vitamin D in Florida?

Surprisingly, we have been seeing low vitamin D levels even here in sunny Florida demonstrated by serum 25-OH Vit D blood testing.  These people avoid the sun for fear of skin cancer.

To read a synopsis of Dr John Cannell's excellent work...Vitamin D Deficiency by Jeffrey Dach MD

Jeffrey Dach MD
4700 Sheridan Suite T
Hollywood Fl 33021
954-983-1443
Jeffrey Dach MD
Natural Medicine 101

I have found many of the vitamin D articles that say 50% or 60% or 80% of the people were vitamin D deficient are using cutoffs of 30 or even 20ng/ml. If they were to use 40-50ng/ml as the low, all but a very few would be found to be deficient.

What I don't understand are the people who tell me their doctor put them on 50,000 IU of ergocalciferol and when the level rises, they are told to discontinue it. I know one person who has gone through 3 cycles of vitamin D supplementation. She told me her doctor is puzzled as to why her D keep dropping. This should not happen when information is so easy to access.

I, too, can't understand the desire of physicians to use 50,000 IU of D2, which we know is only 30% as effective as D3. Plus, it uses a prescription and costs more per pill than D3.

A fantastic graph of Disease states and the effects of D can be found at the grassroots website Dr. Cannell referred to in his recent newsletter.

Dr. C Grant developed the graph and with his permission, we've reproduced it and have copies of it hanging in our exam rooms. It's a very powerful tool to use when talking with patients about the important of optimizing D levels.

Actually Labcorp will use either chemoluminescence (081950) or mass spec (500510).  The mass spec is through Esoterica which invented mass spec, so it is probably OK.  If you prefer chemoluminescense, then specify the correct code. (081950).

More vindication:

http://www.sciencedaily.com/releases/2008/12/081201200032.htm
*Preventive Vitamin D Screening Avocated*

In their review article, published in the December, 9, 2008, issue of the Journal of the American College of Cardiology (JACC), the authors issue practical recommendations to screen for and treat low vitamin D levels, especially in patients with risk factors for heart disease or diabetes.

"Vitamin D deficiency is an unrecognized, emerging cardiovascular risk factor, which should be screened for and treated," said James H. O'Keefe, M.D., cardiologist and director of Preventive Cardiology at the Mid America Heart Institute, Kansas City, MO. "Vitamin D is easy to assess, and supplementation is simple, safe and inexpensive."

mikeV

I would of never thought that about  Labcorp and quest. i would of thought that a lab test is a lab test.

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The ironic thing: I've made both Quest and LabCorp lots of money via this newsletter, the website, and by repeatedly telling the press that people need to know their 25(OH)D level, which has contributed to the skyrocketing sales of 25(OH)D blood tests.