Thanks for finding this interview. I wanted it posted here so that I could add a link to my header.
Coronary Artery Disease, Lipids, Calcium Score, Niacin, Omega-3 Fatty Acids and Vitamin D
William Davis, M.D.
2600 North Mayfair, Suite, #590
Milwaukee, WI 53226
(414) 456-1123 / 414-456-1766 (FAX)
contact@trackyourplaque.com
"Effect of a Combined Therapeutic Approach of Intensive Lipid Management,
Omega-3 Fatty Acid Supplementation, and Increased Serum 25 (OH) Vitamin D
on Coronary Calcium Scores in Asymptomatic Adults,"
Am J Ther, 2008 Dec 15; [Epub ahead of print]. 46916 (3/2009)
Kirk Hamilton: Can you please share with us your educational background and current position?
William Davis: I am a board-certified cardiologist practicing in Milwaukee, Wisconsin. I graduated from
St. Louis University School of Medicine and took my internal medicine training followed by cardiology
fellowship, both at the Ohio State University Hospitals. I also pursued advanced training in coronary
interventions at the Case-Western Reserve University Hospitals in Cleveland, Ohio.
I presently spend most of my time in a preventive cardiology practice, having gotten away from hospital
procedures. I also am founder of the Track Your Plaque program (www.trackyourplaque.com), an intensive
heart disease prevention program, as well as author of the book by the same name.
KH: What got you interested in studying the combination therapy of a statin drug, niacin, omega-3 fatty
acids, diet and vitamin D supplementation in asymptomatic adults?
WD: The program that was described in the published study came about incrementally as part of my efforts to
achieve reductions in CT heart scan scores. Heart scan scores, or “calcium scores,” provide an index of the
quantity of atherosclerotic plaque in the coronary arteries. They quantify plaque and provide an index that can
be tracked over time to assess the success or failure of various preventive efforts. Several studies have
demonstrated that, without preventive efforts, calcium scores can be expected to increase between 15-40% per
year.
We learned a number of years ago (unpublished data) that obtaining conventional lipid values of LDL
cholesterol 60 mg/dl or less, HDL cholesterol 60 mg/dl or greater, and triglycerides 60 mg/dl or less (60-60-60)
was associated with increased likelihood of arresting the increase or reducing heart scan scores. Thus, several of
the strategies employed targeted the 60-60-60 lipid values.
Accordingly, the lipid values in the study showed dramatic changes: total cholesterol was reduced by
24%, LDL was reduced by 41%; TG were reduced by 42% an HDL levels were increased by 19%.
KH: What was the goal of adding niacin to the statin therapy? To raise HDL cholesterol? How much
was given per day? In what form? Was it given in a single dose or divided dose? With meals or away from
meals?
WD: Niacin (vitamin B3) is useful for raising HDL cholesterol, reducing triglycerides, and reducing small
LDL particles. For this study the form of niacin used was prescription extended-release Niaspan® with doses
ranging from 500-1500 mg per day taken once per day. (I generally ask patients to take niacin at dinnertime to
minimize the “hot flush” effect. Outside of study purposes more recently we have used the very similar overthe-
counter Sloniacin® preparation with great success following the same dosing regimen).
KH: Have you noticed any problems with increases in blood sugar levels or elevations in liver enzymes with
either Niaspan® or Sloniacin®? Any drug interactions to watch out for with these nutraceuticals, especially
with common cardiovascular medications?
WD: Increases in blood sugar commonly occur with any form of niacin, including both Niaspan® and
Sloniacin®. Rarely is the rise greater than 5 mg/dl and is usually quite manageable. Increases in liver enzymes
are uncommon, provided the dosing is once per day in the dose range we employed. However, higher doses (not
used in the study), especially 2000 mg per day or greater, do pose about a 5% likelihood of increased liver
enzymes.
Beyond this, niacin preparations have few interactions with other nutritional agents. In fact, niacin
magnifies the benefits of several nutritional agents, such as omega-3 fatty acids from fish oil. The other
undesirable effects of niacin, beyond that of the “flush” and blood sugar increases, are an increase in
homocysteine and uric acid, both fairly modest effects. There are no formal analyses to guide us in knowing
whether these increases are meaningful with regards to effects on atherosclerotic disease or risk, though the net
effect of niacin remains beneficial.
KH: What was the goal of adding omega-3 fatty acids to the statin therapy? What is its biochemistry in
relationship to atherosclerosis? How much was given per day? In what form? Was it given in a single dose or
divided dose? With meals or away from meals?
WD: Omega-3 fatty acids from fish oil have been part of the clinical program from the start. We have used
fish oil as a nutritional supplement to provide the omega-3 fatty acids, eicosapentaenoic acid (EPA) and
docosahexaenoic acid (DHA), at a minimum EPA + DHA dose of 1200 mg per day, titrated upwards to reduce
triglycerides to 60 mg/dl or less. The average omega-3 dose was 1440 mg per day. Doses were divided in two
with the morning dose with breakfast, evening dose with dinner. Omega-3 fatty acids, while very helpful for
triglyceride reduction and reduction of other triglyceride-containing abnormal lipoprotein particles, are also
beneficial for marked reduction of cardiovascular events. Omega-3 fatty acids have also been shown to facilitate
slowed atherosclerotic plaque growth in studies such as the HATS trial.
KH: What was the goal of adding vitamin D to the statin therapy? What is its biochemistry in relationship to
atherosclerosis? How much was given per day? In what form? Was it given in a single dose or divided dose?
With meals or away from meals?
WD: Vitamin D has been the most recent addition to this program. Prior to vitamin D, our unreported
experience was that reductions in heart scan score of 3-8% were typical, rarely more than that. When we began
advising patients to supplement vitamin D in practice, we started to see dramatic and faster reductions in CT
heart scan scores. with reductions in heart scan scores of up to 64%.
In fact, despite having employed this approach in hundreds of people in clinical practice prior to vitamin
D, the additional benefit of vitamin D supplementation was so substantial that we decided to only report the
data that includes people who had undergone vitamin D supplementation.
Vitamin D was replaced using gelcap forms (for assured absorption, not obtainable with powder-based
tablet forms) as a nutritional supplement at a dose sufficient to maintain a serum level of 25-hydroxy vitamin D
of 50-60 ng/ml, requiring a mean dose of 3590 units per day. Participants were instructed to take their dose in
the morning with meals. Mean serum D3 levels increased 83%.
The mechanism of vitamin D’s action with regards to coronary atherosclerotic plaque is uncertain,
though vitamin D has been shown to exert suppressive effects at several points in the inflammatory pathways
(e.g., suppression of matrix metalloproteinase-9, reduced C-reactive protein), reduction in blood sugar and
enhanced insulin responsiveness, reduced blood pressure via an angiotensin-inhibiting mechanism, and
deficiency has been related in several studies to increased risk of cardiovascular events and cardiovascular
death. It is not clear from the retrospective analysis whether any of these mechanisms were responsible.
KH: What exactly was the diet therapy? What was the major goal of the diet? To reduce inflammation?
Lower lipids? Etc.?
WD: Participants were counseled on the American Heart Association Step II diet with 30% of calories from
fat, =7% from saturated fat. (Interestingly, more recently, though not reflected in this study, we have used a lowcarbohydrate
diet that restricts wheat, cornstarch, and sugar and preliminary results suggest improved results).
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KH: Can you tell us about your study and the basic results?
WD: The published study represented a retrospective analysis of the participants for whom we possessed
complete data, including two serial heart scans (at least 6 months apart), lipid data within 60 days of each heart
scan, and self-reported adherence to all advised treatments. Because the study was retrospective we were able to
choose participants who were reportedly compliant with the program. The data for participants who did not
complete the program or were lost to follow-up were not shown. The study is therefore skewed towards results
that may be better than that achievable in real-life clinical settings. Nonetheless, these observations were simply
meant to represent a proof-of-concept, i.e., a demonstration that it is indeed possible to exert an effect on
coronary calcium scores.
The unique observation in this analysis is that a significant number of participants were able to prevent
any further increase in coronary calcium score from one heart scan to the next, and several achieved substantial
reductions in score. Of the 45 participants, 22 achieved either no change in score or a reduction after a mean
scan interval of 18 months, with a mean score reduction of 14.5%.
KH: Were there any side effects with the therapy? How was the patient compliance?
WD: Our analysis was retrospective and we therefore chose participants who were in full compliance with all
advised treatments. However, outside of the study, the real compliance issue we encounter is with niacin. Using
the extended-release (not slow-release, which has a very long, up to 24-hour pattern of release, a release pattern
that may heighten likelihood of liver toxicity) increases compliance. But even with this preparation, we still
encounter only about 70% compliance, with approximately 30% intolerant of doses >500 mg per day. There
was no liver toxicity in the study participants.
KH: Who is a candidate for your program? How would you use this information clinically?
WD: Candidates for the clinical program include anyone with a heart scan score (coronary calcium score)
above zero, indicating long-term risk for heart attack and development of heart disease. Despite the fact that
coronary heart disease is the number killer of American men and women, we have no readily available tracking
strategy to follow the course of this disease with ease and precision. Standard testing techniques such as EKGs,
stress tests, and cholesterol panels can not be used to precisely track the course of coronary disease. A heart
scan that yields a coronary calcium score can conceivably be used as a tracking mechanism to gauge
progression, stabilization, or regression.
KH: What is the relationship between calcium scores and CRP? Do they correlate?
WD: C-reactive protein (CRP) is an indirect means of gauging inflammatory phenomena, and
inflammatory responses can heighten the risk of atherosclerotic plaque rupture, AKA heart attack. CRP is not a
measure of plaque. However, having both a heart scan score above zero along with increased CRP suggests
potential for plaque inflammation and plaque rupture. Several studies, in fact, have borne this out.
KH: Is a coronary calcium score the most valuable prognosticator for vascular disease?
WD: Our study therefore demonstrates that no change, or even substantial reduction, in coronary calcium
score is possible. This may provide helpful insights in understanding how to best manage the rapidly expanding
number of people who have undergone a heart scan, have a coronary calcium score above zero (suggesting
some degree of cardiovascular event risk), and what treatments might be considered to impact on progression of
the coronary calcium score and cardiovascular risk.
In clinical practice I have found coronary calcium score the preferred method ?? easy, accessible,
inexpensive, with modest radiation exposure (similar to the exposure of a mammogram) ?? of identifying
people with potential for developing heart disease or experiencing a heart attack. It is best applied to men 40
and over, women 50 and over, who are without symptoms and simply desire a gauge of whether silent coronary
atherosclerotic plaque is present or not. Although the scan measures calcium, not plaque directly, calcium has
proven a reliable index of total plaque volume, as well as a predictor of potential for long-term cardiovascular
events.
KH: Are all CT heart scan machines and technology created equal? Do you have an specific guidelines for
clinicians on how to pick out the correct CT scan machine and technology?
WD: There are two CT technologies capable of providing coronary calcium scoring or heart scanning;
electron-beam tomography, EBT, and multi-detector CT, MDCT.
While EBT devices are the original heart scan devices, there are approximately 70 remaining in
operation in the U.S. and remain an excellent choice for heart scanning, providing heart scans with high
accuracy and low radiation exposure, the equivalent of 4 chest x-rays or the same as a mammogram (General
Electric acquired the manufacturer a number of years ago and promptly scrapped it, probably due to the
confusion created in the marketplace by having two competing technologies).
MDCT is the more recent technology that has been widely applied for CT coronary angiography, a
different test that involves x-ray dye and more radiation exposure. However, these devices are also capable of
performing the simpler heart scan, as well. Radiation exposure is higher with this technology, with slightly less
accuracy. For this reason, it is best to look for the newest versions of these devices which have 64 or more
detector rings, often called "64-slice" CT. As the technology evolves, radiation exposure is being reduced and
accuracy improved. The current 64-slice devices can perform a heart scan with acceptable precision at an
approximately 8-10 chest x-rays equivalent of radiation (about 2 mammograms).
KH: Do you have any further comments on this very interesting subject?
WD: This study therefore shows that stopping or reducing coronary calcium scores is feasible. This is
important, as several studies using statin agents only have cast doubt on whether it is possible to have any
impact on the expected increase in coronary calcium scores. The BELLES Trial (Raggi P et al 2005), for
instance, showed that atorvastatin, 80 mg per day, as a high-intensity LDL-reducing treatment vs. pravastatin,
40 mg per day as a low-intensity treatment, showed no difference on slowing the rate of increase of coronary
calcium scores (both treatment groups showing 15% annual increase). Likewise, Schmermund (2006) showed
no difference between atorvastatin, 80 mg per day, vs. atorvastatin, 10 mg per day, with both arms increasing
approximately 25%.
It is not clear from this study, however, whether this will correlate with an impact on cardiovascular
events; this remains to be seen in studies involving a much larger number of participants.
We employ this approach in clinical practice with considerable success. The (anecdotal) incidence of
coronary events is rare in patients following a process similar to that described here that includes lipids
managed to the 60-60-60 targets, along with omega-3 fatty acid supplementation from fish oil, vitamin D
supplementation to a serum level of 25-hydroxy vitamin D to 50 ng/ml. While this study and our clinical
experience suggests that this regimen does not halt the progression of coronary calcium scores in every patient,
I believe that this study brings us a step closer to understanding how this might be achieved in a substantial
proportion of people. |
