25 CAT Coronary Calcium Scoring, Reversing Heart Disease by Jeffrey Dach MD

by Jeffrey Dach MD

Finally Accepted by the AHA 

The AHA (American Heart Association) has steadfastly denied for many years that Coronary Calcium Scoring was a valid marker of heart disease.  Well guess what? They have recanted, and admitted that the amount of calcium in the coronary arteries reliably predicts heart attack risk. This is called the calcium score.(1)

UCLA cardiologist, Dr. Matt Budoff, a long-time champion of the Coronary Calcium Scan, and author of the AHA paper says, "The total amount of coronary calcium (Agatston score) predicts coronary disease events beyond standard risk factors."(1)

Image upper left, courtesy of Wikipedia Rembrandt, The Anatomy Lesson.

Dr. Detrano, in a recent article in NEJM (New England of Medicine), confirms that "The coronary calcium score is a strong predictor of incident coronary heart disease and provides predictive information beyond that provided by standard risk factors". (31)  The Coronary Calcium Score is a precise quantitative tool for measuring and tracking heart disease risk, and is more valuable and accurate than other traditional markers (such as total cholesterol which is practically worthless as a heart disease risk marker).

What is Coronary Artery Disease?  It's Plaque Formation.

Coronary Arteries in Cross Section

Age 20-30 years                          Age 50-70 years

Chart below shows increasing heart attack rate as coronary calcium goes up

Chart Above shows that Calcium Score is Highly Predictive of Heart Attack Risk

What is a Heart Attack?

(image at right courtesy of Wikipedia)

The bifurcations have maximal turbulance and mechanical stress on the vessel wall.  Remember the blood is flowing under pulsatile pressure, and this mechanical pressure and turbulence, over time, causes little stress cracks in the vessel. The cracks appear at sites of maximal stress.  The coronary arteries are a special case because of the extra motion of the cardiac muscle which moves and stretches the coronary arteries every heart beat, especially as the arteries branch off from the aorta which is relatively stationary, while lower down over the surface of the heart, the vessels move vigorously with each heart beat.  Atherosclerosis is essentially the net result of the healing process for these little cracks in the arterial wall resulting from mechanical stress.

William Davis MD,  Advocate of the Coronary Calcium Score

What does Calcium Look Like?
Normal                  Calcified

 
Calcium looks White on the CAT scan (red arrows at right).
(Above) CAT scans of the Coronary Arteries.

The left image shows a normal coronary artery (red arrows), while the right image shows a heavily calcified coronary artery (white line outlined by red arrows) indicating high risk for coronary artery disease and heart attack.

The Track Your Plaque Program, by William Davis MD(2)(3)

1) Quantify plaque with Coronary Calcium Score with CAT scan (or with Electron Beam CT). Obtain your CAT Scan serially, every 12 months to assess response to treatment and lifestyle modification (track your plaque).

2) Use Sophisticated Lipoprotein Panel (Quest-VAP , LabCorp-NMR)(7)(8) to uncover hidden causes of plaque progression. LDL particle size and number, Lipoprotein (a). Repeat every 6 months.

3) The Main Treatment Goal is the reduction in Coronary Artery Calcium Score, and by inference, reduction in plaque volume and reduction in cardiovascular mortality. The cardiology community still awaits the hard data on these results (CHD mortality and CHD events, treatment arm vs no treatment arm).  These numbers have not been published as far as I know.

How to Measure Success in Halting or Reversing Heart Disease Plaque

According to Dr. Davis, calcium score typically increases at an astonishing rate of 30-35% per year without treatment. Therefore, Dr. Davis considers treatment success to be reduction in this rate from 30 to perhaps only a 5-10 per cent increase in calcium score per year.  An absolute reduction in calcium score on follow up scanning is the optimal outcome, which is difficult to achieve even with strict adherance to the Track Your Plaque program, in Dr Davis's experience.

Track Your Plaque Program Details - Attain the Following Targets:

a) Reduction of LDL to 60 mg/dl (LDL should be measured directly, not calculated)

b) Reduction of triglycerides to 60 mg/dl.

c) Raising HDL to 60 mg/dl.

d) Correction of hidden causes of plaque on Lipoprotein profile such as total number of small LDL particles, IDL, and Lp(a).

e) Achieving normal blood pressure (<130/80)  Even a small elevation of blood pressure in diseased arteries can cause increased mortality.  Diseased arteries are fragile and plaque rupture can occur easily.

f) Achieving normal blood sugar (≤100 mg/dl). Diabetes is a high risk factor for heart disease.
 
g) Reduction of C-reactive protein to <1 mg/l

Dietary Modification and Supplements to Attain Above Targets:

Niacin

a) Niacin vitamin B3 (Slo-Niacin Upsher-Smith (44) or Niaspan Kos Pharmaceuticals preferred) 500-1500mg. per day (avoid the no-flush niacin which contains inositol).(6)(44)

Omega 3 Fish Oil

b) Fish oil (Omega 3 oils) 4000 mg per day (providing 1200 mg omega-3 fatty acids). (molecular distilled pharmaceutical grade).(36)

Vitamin D

Vitamin D level restored to above 50 ng/ml (Vitamin D3 2000-5,000 u/day), Vitamin K2 also used.  Low vitamin D is associated with increasing arterial calcification and increased heart disease risk. (26)Consumption of calcium tablets by women increases arterial calcification and heart attack risk.(5) Read my previous article on vitamin D which can be found here. (60)

d) Low Glycemic Diet (avoid Fructose Corn Syrup, avoid wheat products), and eliminate wheat products like Shredded Wheat cereal, Raisin Bran, and whole wheat bagels.

e) Consume foods such as raw almonds, walnuts, pecans; olive oil and canola oil. Beneficial for lipoprotein profile.

f) Increasing protein intake, our major building block for body tissues.  Added benefit of protein intake is that it doesn't increase blood sugar.  This is low glycemic nutrition.

g) Wine—Red wines contain resveratrol, (don’t exceed two glasses/ day). Bioflavonoids and anti-oxidants have a strong anti-inflammatory effect.

h) Fiber - Gound flaxseed (2 tbsp/day)-Extra fiber aids in detoxifying liver and the entire body  by interrupting the enterohepatic circulation. Psyllium (metamucil). Regulates bowel movements and has favorable effect on lipoprotein profile.

Vitamin C

Vitamin C (1000–3000 mg/day), is a key player, as it is the vitamin for strong collagen formation, strengthening the arterial wall.  See Linus Pauling's patented protocol which includes Vitamin C and amino acids Proline and Lysine, the two amino acids that act as receptors for Lp(a).  By consuming additional Lysine and Proline, the receptor sites on the Lp(a) and other lipoproteins are covered up and made less sticky, resulting in less deposition in the artery wall.  The vitamin C is important not only for strong collagen formation, a major component of the arterial wall, but also for all other structural elements of the body, for that matter. (37)(52)(53)(54)(55)(56)(57)

Humans have a genetic deficiency in Gulano-Lactone-Oxidase (GLO), the final enzyme step in the manufacture of Vitamin C, and therefore unlike all the other animals who make their own Vitamin C, we cannot make this necessary vitamin.  We share with all other primates this genetic disease, the inability to manufacture vitamin C, producing a vitamin C deficiency state in all humans.(58)

Also see Thomas Levy's two books on Vitamin C. (49)(50)(51)

j) Exercise and weight loss- improves insulin sensitivity, reduces inflammatory markers, reduces blood pressure, improves lipoprotein profile.

Magnesium

k) Magnesium supplementation is inexpensive and safe. Magnesium deficiency due to dietary deficiency or thiazide diuretics for hypertension is common, and is associated increased heart disease risk.  Magnesium reduces blood pressure, relaxes smooth muscle in arteries, and is needed for normal endothelial function.(41)(42)(43)

L-Arginine

L-arginine is converted to nitric oxide, an important substance for arterial health. Research by Furchgott and other showed that nitric oxide (NO) relaxes arterial smooth muscle, dilating coronary arteries by up to 50%.(35)  However, Nitric Oxide (NO) is gone after a few seconds, so it must be replenished at a constant rate to keep the arteries relaxed and open. Lack of NO is associated with constricted arteries, damage to the arterial lining, and accelerated plaque growth. L-arginine shrinks coronary plaque,  corrects "endothelial dysfunction", improves insulin sensitivity, is anti-inflammatory and shrinks plaque.  Dosage: l-arginine 6000 mg twice a day, best taken on an empty stomach.

Reverse Cholesterol Transport and Essential Phospholipid - Phosphatidyl Choline (PC) (38)
(39)

James C. Roberts MD FACC, a practicing invasive cardiologist, lectures extensively on his clinical success with Phosphatidylcholine (IV or in Liposomal Oral Format with EDTA):  Reverse Cholesterol Transport and Metal Detoxification.  A DVD of his lectures is available which describes considerable clinical success with oral EDTA and phosphytidylcholine.  This page contains his DVD lecture material complete with clinical case histories.(61)

Essential Phospholipid is available under trade name Phoschol which increases Lecithin Cholesterol Acyl Transferase activity (LCAT) (Dobiasova M 1988).(40)(40b)  Activating LCAT is beneficial because LCAT is the crucial substance which transports cholesterol from the arterial plaque back to the liver for metabolic breakdown into bile.  This process reverses atherosclerotic plaque formation.  Dosage: 3 softgels Phoschol a day each containing 900 mg PC.(38)(39)

Thyroid Function

Normalize thyroid function. Broda Barnes MD showed that low thyroid function was a significant risk factor for heart disease. This conclusion was based on autopsy data from Graz Austria and detailed in his book, Hypothyroidism the Unsuspected Illness, and his other book, Solved the Riddle of Heart Attacks. Barnes felt that the thyroid lab tests were frequently unreliable, and he used clinical judgement instead. (59)

LipoProtein (a)

All About Reducing Lipoprotein (a)(2)(3)

Lipoprotein little A, also written as Lp(a) is a genetic variant lipoprotein which is associated with a high risk of heart disease, and therefore identification and reduction is essential.  The problem is that the conventional Lipid panels done in your doctor's office do not include Lp(a).  Only the more sophisticated lipoprotein panels such as the VAP (Atherotech) or NMR (Liposcience) panels provide Lp(a) data.

Lp(a) and Lipoproteins:

1) Lp(a) is best to measured in (nmol/l), and target  below 75 nmol/l .
2) Lp(a) measured in mg/dl (weight may not be accurate), then target below 30 mg/dl .
3) Measured (not calculated) LDL target 50–60 mg/dl.
4) LDL particle number target (NMR) of 600–700 nmol/l or apoprotein B of 50–60 mg/dl. Reduce small LDL to <10% of total LDL.

Treating Lp(a) with Niacin

Use Niaspan® (Kos Pharmaceuticals) or over-the-counter Slo-Niacin® (Upsher-Smith).
Both are better tolerated than OTC plain niacin, which may cause the hot flushes. Reduce hot flushed by drinking a full glass of water with each gelcap, and some find adding an aspirin tablet to the routine helps to reduce flushing.

Lp(a) and BioIdentical Hormones

Bio-Identical hormones are beneficial for reducing heart disease.  In menopausal females, estrogen preparations such as Bi-Est are used. Estrogens have been shown to reduce coronary artery calcium score.(46)
 
In males over 50, bio-identical testosterone cream may lowers Lp(a) by as much as 25% (William Davis MD).  Medical studies show that optimizing Testosterone levels in aging males can reduce risk of coronary artery disease by 60%. (47)(48)

DHEA can promote weight loss, and improve insulin sensitivity.(45) 

Lp(a) and L-Carnitine

The supplement L-carnitine can be a useful adjunct; 2000–4000 mg per day (1000 mg twice a day) can reduce Lp(a) 7–8%, and occasionally will reduce it up to 20%.

Remember, reduction in calcium score on follow up calcium scan is the goal.
 
What about Statin-Cholesterol Lowering drugs?

Dr Davis admits that the total cholesterol and the LDL cholesterol numbers are of little value in predicting heart disease risk. And he says that the statin drug side effects, ie. muscle pain and weakness, are more common in actual practice than the drug advertising would suggest, making statin drugs difficult to take for the long term.

In my opinion, statin drugs are not recommended for women as explained in my previous article on Statin Drugs for Women, which can be found here (33).  My other article on Statins, Lipitor and the Dracula of Medical Technology can be found here. (34)

What about Calcium Supplements for women to prevent osteoporosis?

Dr Davis points out that women who take calcium tablets have double the risk of heart attacks than those on placebo.(5)

Check out my earlier Heart Disease Reversal Page here. 

Credit and Thanks is given to William Davis MD at the Track Your Plaque Web Site and Blog for the above information.(2)(3)

Jeffrey Dach MD
7450 Griffin Road, Suite 190
Davie, Florida 33314
954-792-4663
http://www.jeffreydachmd.md
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References:

(1) http://circ.ahajournals.org/cgi/content/full/114/16/1761
(Circulation. 2006;114:1761-1791.) AHA Scientific Statement
Assessment of Coronary Artery Disease by Cardiac Computed Tomography
A Scientific Statement From the American Heart Association Committee on Cardiovascular Imaging and Intervention, Council on Cardiovascular Radiology and Intervention, and Committee on Cardiac Imaging, Council on Clinical Cardiology. Matthew J. Budoff, MD, FAHA; Stephan Achenbach, MD; Roger S. Blumenthal, MD, FAHA; J. Jeffrey Carr, MD, MSCE; Jonathan G. Goldin, MD, PhD; Philip Greenland, MD, FAHA; Alan D. Guerci, MD; Joao A.C. Lima, MD, FAHA; Daniel J. Rader, MD, FAHA; Geoffrey D. Rubin, MD; Leslee J. Shaw, PhD; Susan E. Wiegers, MD

(2) http://www.trackyourplaque.com/index.asp
William R. Davis, MD, FACC Heart Disease Reversal Expert Web: www.trackyourplaque.com Dr. Davis is author of Track Your Plaque and founder of the Track Your Plaque website, both of which are devoted to the concept of early detection of heart disease using CT heart scans. He is a vocal advocate of self-empowering strategies to reduce risk of heart disease. He is Medical Director of Milwaukee Heart Scan and practices cardiology in the Milwaukee area. He is a graduate of St. Louis University School of Medicine and obtained his training in medicine and cardiology at the Ohio State University Hospitals and Case-Western Reserve/ MetroHealth Medical Centers.
Track Your Plaque 2600 N. Mayfair Road, Suite 950 Wauwatosa, WI 53226 414-456-1123 414-456-1766

(3) http://heartscanblog.blogspot.com/
William Davis Track Your Plaque Blog

(4) http://atvb.ahajournals.org/cgi/content/full/19/5/1250
Arteriosclerosis, Thrombosis, and Vascular Biology. 1999;19:1250-1256.)
Fish Intake, Independent of Apo(a) Size, Accounts for Lower Plasma Lipoprotein(a) Levels in Bantu Fishermen of Tanzania The Lugalawa Study Santica M. Marcovina; Hal Kennedy; Gabriele Bittolo Bon; Giuseppe Cazzolato; Claudio Galli; Edoardo Casiglia; Massimo Puato; Paolo Pauletto

(5) http://www.bmj.com/cgi/content/full/bmj.39440.525752.BEv1
(Bolland MJ, Barber PA, Doughty RN et al. Vascular events in healthy older women receiving calcium supplementation: randomised controlled trial. Brit Med J BMJ, doi:10.1136/bmj.39440.525752.BE; published 15 January 2008)

Over 5 years, women taking calcium had twice the risk of having a heart attack compared with women taking the placebo; women taking calcium had a 47 percent higher risk of having any one of three "events" (heart attack, stroke or sudden death) than women in the placebo group.

(6) http://www.upsher-smith.com/legacy/products/sloniacin/sloniacinintro.html
Slo Niacin Upsher Smith

(7) http://www.liposcience.com/
LipoScience NMR Lipiprotein Analysis through LabCorp

(8) http://www.thevaptest.com/
Atherotec VAP Lipid analysis through Quest

(9) http://www.scct.org/news/clinical_consensus_coronary_artery_calcium_scoring.pdf
ACCF/AHA 2007 Clinical Expert Consensus Document on Coronary Artery Calcium Scoring By Computed
Tomography in Global Cardiovascular Risk Assessment and in Evaluation of Patients With Chest Pain
A Report of the American College of Cardiology Foundation Clinical Expert Consensus Task Force (ACCF/AHA Writing Committee to Update the 2000 Expert Consensus
Document on Electron Beam Computed Tomography) Developed in Collaboration With the Society of Atherosclerosis Imaging and Prevention and the Society of Cardiovascular Computed Tomography Journal of the American College of Cardiology Vol. 49, No. 3, 2007

(10) http://archinte.ama-assn.org/cgi/content/full/164/12/1285
Using the Coronary Artery Calcium Score to Predict Coronary Heart Disease Events
A Systematic Review and Meta-analysis Mark J. Pletcher, MD, MPH; Jeffrey A. Tice, MD; Michael Pignone, MD, MPH; Warren S. Browner, MD, MPH. Arch Intern Med. 2004;164:1285-1292. Vol. 164 No. 12, June 28, 2004

Conclusion  The coronary artery calcium score is an independent predictor of coronary heart disease events.

(11) http://www.heartscan.com/
Dr. John Rumberger. Heart Scan 2161 Ygnacio Valley Road Suite #100 Walnut Creek, CA 94598

(12) http://www.heartscan.com/Budoff_EBCT.pdf
Why EBCT? by Matthew Budoff, MD, FACC, FAHA Assoc. Professor of Medicine, Director, Cardiac CT Harbor-UCLA Medical Center, Torrance, CA

(13) http://www.heartscan.com/Clinton_heart_disease.pdf
Clinton Heart Disease Reveals Misconceptions about Testing Colorado Heart & Body Imaging says “Clinton Syndrome” reveals limitations of stress tests and promise of EBT heart scans

(14) http://www.ajronline.org/cgi/content/abstract/95/3/667
American Journal of Roentgenology, Vol 95, 667-672, 1965 by American Roentgen Ray Society
THE SIGNIFICANCE OF CORONARY CALCIFICATION  JOSEPH JORGENS M.D., PH.D.1, WILLIAM J. BOARDMAN M.D.2, SHELDON W. DAMBERG M.D.2, WILLIAM N. KINNEY M.D.2, and ROBERT R. KUNDEL M.D.2

(15) http://www.ajronline.org/cgi/content/full/187/1/73
AJR 2006; 187:73-80 American Roentgen Ray Society
How Predictive Is Breast Arterial Calcification of Cardiovascular Disease and Risk Factors When Found at Screening Mammography?

(16) http://circ.ahajournals.org/cgi/content/full/94/5/1175
(Circulation. 1996;94:1175-1192.)© 1996 American Heart Association, Inc.   Coronary Artery Calcification: Pathophysiology, Epidemiology, Imaging Methods, and Clinical Implications

(17) http://www.sciencedirect.com/science?_ob=ArticleURL&_udi=B6T18-3RTYDN3

Clinical Studies Arterial Calcification and Not Lumen Stenosis Is Highly Correlated with Atherosclerotic Plaque Burden in Humans: A Histologic Study of 723 Coronary Artery Segments Using Nondecalcifying Methodology .

Journal of the American College of Cardiology  Volume 31, Issue 1, January 1998, Pages 126-133

Conclusions. Coronary calcium quantification is an excellent method of assessing atherosclerotic plaque presence at individual artery sites. Moreover, the amount of calcium correlates with the overall magnitude of atherosclerotic plaque burden. This study suggests that the remodeling phenomenon is the likely explanation for the lack of a good predictive value between lumen narrowing and quantification of mural calcification.

(18) http://content.onlinejacc.org/cgi/content/abstract/27/2/285
J Am Coll Cardiol, 1996; 27:285-290 Prognostic value of coronary calcification and angiographic stenoses in patients undergoing coronary angiography R Detrano, T Hsiai, S Wang, G Puentes, J Fallavollita, P Shields, W Stanford, C Wolfkiel, D Georgiou, M Budoff, and J Reed  Saint John's Cardiovascular Research Center, Los Angeles, California, USA.

CONCLUSIONS. Electron beam computed tomographic calcium scores correlate moderately well with angiographic findings. These scores predict coronary heart disease-related events in patients undergoing angiography as well as do the number of angiographically affected arteries.

(19) http://aje.oxfordjournals.org/cgi/content/full/162/5/421
Coronary Artery Calcium Score and Coronary Heart Disease Events in a Large Cohort of Asymptomatic Men and Women Michael J. LaMonte1, Shannon J. FitzGerald1, Timothy S. Church1, Carolyn E. Barlow1, Nina B. Radford2, Benjamin D. Levine3,4, John J. Pippin2, Larry W. Gibbons2, Steven N. Blair1 and Milton Z. Nichaman1

(20) http://content.onlinejacc.org/cgi/content/abstract/49/18/1860
J Am Coll Cardiol, 2007; 49:1860-1870
CLINICAL RESEARCH: CARDIAC IMAGING

Long-Term Prognosis Associated With Coronary Calcification Observations From a Registry of 25,253 Patients. Matthew J. Budoff, MD*,*,1, Leslee J. Shaw, PhD, Sandy T. Liu*, Steven R. Weinstein*, Tristen P. Mosler, Philip H. Tseng*, Ferdinand R. Flores*, Tracy Q. Callister, MD, Paolo Raggi, MD and Daniel S. Berman, MD * Harbor-UCLA Los Angeles Biomedical Research Institute, Torrance, California  Cedars-Sinai Medical Center, Los Angeles, California  EBT Research Foundation, Nashville, Tennessee.  Division of Cardiology and Department of Radiology, Emory University, Atlanta, Georgia.

Objectives: The purpose of this study was to develop risk-adjusted multivariable models that include risk factors and coronary artery calcium (CAC) scores measured with electron-beam tomography in asymptomatic patients for the prediction of all-cause mortality.

Background: Several smaller studies have documented the efficacy of CAC testing for assessment of cardiovascular risk. Larger studies with longer follow-up will lend strength to the hypothesis that CAC testing will improve outcomes, cost-effectiveness, and safety of primary prevention efforts.

Methods: We used an observational outcome study of a cohort of 25,253 consecutive, asymptomatic individuals referred by their primary physician for CAC scanning to assess cardiovascular risk. Multivariable Cox proportional hazards models were developed to predict all-cause mortality. Risk-adjusted models incorporated traditional risk factors for coronary disease and CAC scores.

Results: The frequency of CAC scores was 44%, 14%, 20%, 13%, 6%, and 4% for scores of 0, 1 to 10, 11 to 100, 101 to 400, 401 to 1,000, and >1,000, respectively. During a mean follow-up of 6.8 ± 3 years, the death rate was 2% (510 deaths). The CAC was an independent predictor of mortality in a multivariable model controlling for age, gender, ethnicity, and cardiac risk factors (model chi-square = 2,017, p < 0.0001). The addition of CAC to traditional risk factors increased the concordance index significantly (0.61 for risk factors vs. 0.81 for the CAC score, p < 0.0001). Risk-adjusted relative risk ratios for CAC were 2.2-, 4.5-, 6.4-, 9.2-, 10.4-, and 12.5-fold for scores of 11 to 100, 101 to 299, 300 to 399, 400 to 699, 700 to 999, and >1,000, respectively (p < 0.0001), when compared with a score of 0. Ten-year survival (after adjustment for risk factors, including age) was 99.4% for a CAC score of 0 and worsened to 87.8% for a score of >1,000 (p < 0.0001).

(21) http://content.onlinejacc.org/cgi/content/full/49/3/378

Serial noninvasive monitoring of calcified atherosclerosis using CAC measurement has been proposed as a means of monitoring medical treatment for CAD as well as assessing change in CVD prognosis (58).

The validity of serial coronary calcium measurements as a method to monitor progression of atherosclerosis requires:

1) that progression of coronary calcium has biologic relevance to atherosclerosis activity;
2) that progression of coronary calcium can be detected relative to inter-test variability;
3) that changes in coronary calcium severity have prognostic relevance; and 4) that modification of cardiovascular risk factors modulates the progression of coronary calcium. Each of these points is subsequently discussed.

Biologic Relevance of Coronary Atherosclerosis Progression.  

The extent of coronary calcium found on fast CT is broadly related to plaque burden, but there is a high degree of site-to-site variability in the presence and extent of calcium within any single atherosclerotic plaque. Pathology studies have shown that the extent of coronary calcium within plaques tends to be related to the presence of healed plaque ruptures (59).

Moreover, vulnerable plaques tend to be those with less extensive calcium deposits frequently seen in a spotty distribution (59), a finding supported by intravascular ultrasound studies of patients with acute coronary syndromes (60).

Opposed to Calcium Score

(22) http://circ.ahajournals.org/cgi/content/full/114/5/e83 
Circulation. 2006;114:e83.) Correspondence Response to Letter Regarding Article, "Coronary Artery Calcium: Should We Rely on This Surrogate Marker?" Rita F. Redberg, MD, MSc
Division of Cardiology, University of California, San Francisco, San Francisco, Calif

Drs Schmermund and Erbel take issue with my assertion1 that coronary artery calcium (CAC) scores, as of now, are not reliable predictors of cardiac events. However, they offer no data to refute this statement. First, they correctly note that CAC is related to coronary atherosclerosis. This relation, however, does not mean CAC is a predictor of cardiac events. Indeed, as coronary atherosclerosis is so prevalent, "only a small proportion of persons with atherosclerosis and detectable coronary calcium will eventually develop clinical coronary events."2 Therefore, although levels of coronary calcium and atherosclerosis are associated with increased cardiac events on a population level, the relationship in any individual person is weak. Indeed, calcification may stabilize atherosclerotic lesions and make them less likely to rupture and cause an acute cardiac event.

Secondly, Schmermund and Erbel argue that CAC scores add prognostic information "over and above" cardiovascular risk factors. I respectfully disagree. The great majority of cardiac events that CAC predicts3–5 are soft events—revascularizations and unstable angina. Use of such soft events as end points may be misleading. As stated in the 2000 American College of Cardiology/American Heart Association Expert Consensus document, the test result itself often determines who undergoes these procedures, and it is improper to include them as events predicted by the test.6 In addition, the high rate of revascularization after CAC testing is of concern, because no data show any benefit of revascularization in asymptomatic patients.7

Thirdly, the studies cited include no data regarding the best proof of incremental predictive value, an increase in area under the receiver operator characteristic curve for risk prediction from CAC testing that is incremental to Framingham Risk Scoring (FRS).

Finally, they seem to suggest that calcification does not correlate with cardiac events in people taking statins, but that calcification does correlate in others. Although this hypothesis is interesting, it remains untested. 

We are fairly skilled at cardiac risk prediction. FRS remains the reference standard, and no test, CAC included, has been shown to significantly increase the accuracy of FRS. More importantly, additional tests such as evaluation of CAC levels have not been shown to lead to better patient outcomes. Risk factors in FRS, including high blood pressure and cholesterol levels, indisputably may be lowered to reduce cardiovascular risk. CAC cannot be treated, even if lowering CAC were shown to reduce cardiovascular risk. On one point, we are in agreement: We clearly need more epidemiological and clinical trial data on the use of CAC.

(23) http://www.pubmedcentral.nih.gov/pagerender.fcgi?artid=458849&pageindex=1
Br Heart J. 1974 May; 36(5): 499–506.  PMCID: PMC458849
Incidence and significance of coronary artery calcification. J H McCarthy and F J Palmer
Circulation. 2001;104:412.) Clinical Investigation and Reports

Long-Term Prognostic Value of Coronary Calcification Detected by Electron-Beam Computed Tomography in Patients Undergoing Coronary Angiography. Paul C. Keelan, MB; Lawrence F. Bielak, DDS, MPH; Khalid Ashai, MD; Lama S. Jamjoum, PhD, MPH; Ali E. Denktas, MD; John A. Rumberger, MD, PhD; Patrick F. Sheedy, II, MD; Patricia A. Peyser, PhD; Robert S. Schwartz, MD From the Division of Cardiovascular Diseases (P.C.K., K.A., A.E.D., J.A.R., R.S.S.) and Diagnostic Radiology (P.F.S.), Mayo Clinic, Rochester, Minn, and Department of Epidemiology (L.F.B., L.S.J., P.A.P.), University of Michigan, Ann Arbor, Mich. Dr Rumberger is currently Professor of Medicine in the Department of Cardiology, Ohio State University, Columbus.

(24) http://circ.ahajournals.org/cgi/content/abstract/104/4/412
Correspondence to Robert S. Schwartz, MD, FACC, Division of Cardiovascular Diseases, Mayo Clinic, Rochester, MN 55905.

Conclusions— In patients undergoing angiography, CAC extent on EBCT is highly predictive of future hard cardiac events and adds valuable prognostic information.

(25) http://tech.snmjournals.org/cgi/content/full/36/1/18
Journal of Nuclear Medicine Technology Volume 36, Number 1, 2008 18-24
Cardiac CT: Indications and Limitations*Susanna Prat-Gonzalez, Javier Sanz and Mario J. Garcia The Zena and Michael A. Wiener Cardiovascular Institute, Mount Sinai School of Medicine, New York, New York

Calcium Scoring The most widely used measure of calcium burden is the calcium score (often known as the Agatston score), which is based on the radiographic density–weighted volume of plaques with attenuation values of greater than 130 HUs. The presence of coronary calcification is a robust predictor (for a calcium score of >100, the risk ratio = 1.88) of adverse cardiovascular events, and the prognostic value of coronary calcium burden has been clearly established (7).

Although the utility of screening asymptomatic individuals remains controversial, several studies have indicated that the calcium score provides prognostic information independent of conventional risk factors. In a recently published study, a calcium score of greater than 300 was associated with a significant increase in cardiac events compared with that determined by a clinical score alone (8), supporting the notion that a high calcium score can modify predicted risk; this is especially true for patients in the intermediate-risk category, for whom clinical decision making is most difficult. Patients determined to be at low risk by clinical criteria, however, appear to derive minimal additional prognostic benefit from calcium scoring. These conclusions are represented in a clinical consensus document recently issued by the American College of Cardiology and the American Heart Association (9).

(26) http://circ.ahajournals.org/cgi/content/abstract/96/6/1755
(Circulation. 1997;96:1755-1760.)

Active Serum Vitamin D Levels Are Inversely Correlated With Coronary Calcification

Karol E. Watson, MD; Marla L. Abrolat, MD; Lonzetta L. Malone, BS; Jeffrey M. Hoeg, MD; Terry Doherty, BA; Robert Detrano, MD, PhD; ; Linda L. Demer, MD, PhD
Circulation. 2008;117:503-511.)

Vitamin D Deficiency and Risk of Cardiovascular Disease. Thomas J. Wang, MD; Michael J. Pencina, PhD; Sarah L. Booth, PhD; Paul F. Jacques, DSc; Erik Ingelsson, MD, PhD; Katherine

Background— Vitamin D receptors have a broad tissue distribution that includes vascular smooth muscle, endothelium, and cardiomyocytes. A growing body of evidence suggests that vitamin D deficiency may adversely affect the cardiovascular system, but data from longitudinal studies are lacking.

Methods and Results— We studied 1739 Framingham Offspring Study participants (mean age 59 years; 55% women; all white) without prior cardiovascular disease. Vitamin D status was assessed by measuring 25-dihydroxyvitamin D (25-OH D) levels. Prespecified thresholds were used to characterize varying degrees of 25-OH D deficiency (<15 ng/mL, <10 ng/mL). Multivariable Cox regression models were adjusted for conventional risk factors. Overall, 28% of individuals had levels <15 ng/mL, and 9% had levels <10 ng/mL. During a mean follow-up of 5.4 years, 120 individuals developed a first cardiovascular event. Individuals with 25-OH D <15 ng/mL had a multivariable-adjusted hazard ratio of 1.62 (95% confidence interval 1.11 to 2.36, P=0.01) for incident cardiovascular events compared with those with 25-OH D 15 ng/mL. This effect was evident in participants with hypertension (hazard ratio 2.13, 95% confidence interval 1.30 to 3.48) but not in those without hypertension (hazard ratio 1.04, 95% confidence interval 0.55 to 1.96). There was a graded increase in cardiovascular risk across categories of 25-OH D, with multivariable-adjusted hazard ratios of 1.53 (95% confidence interval 1.00 to 2.36) for levels 10 to <15 ng/mL and 1.80 (95% confidence interval 1.05 to 3.08) for levels <10 ng/mL (P for linear trend=0.01). Further adjustment for C-reactive protein, physical activity, or vitamin use did not affect the findings.

Conclusions— Vitamin D deficiency is associated with incident cardiovascular disease. Further clinical and experimental studies may be warranted to determine whether correction of vitamin D deficiency could contribute to the prevention of cardiovascular disease.

(27) http://content.onlinejacc.org/cgi/content/abstract/19/6/1167
J Am Coll Cardiol, 1992; 19:1167-1172
Fluoroscopic coronary artery calcification and associated coronary disease in asymptomatic young men
TH Loecker, RS Schwartz, CW Cotta, and JR Hickman Jr

Clinical Sciences Division, U.S. Air Force School of Aerospace Medicine, Brooks Air Force Base, San Antonio, Texas.

Little is known about the diagnostic significance of coronary artery calcification detected fluoroscopically in apparently healthy young men. This study compared the presence of fluoroscopically detected coronary artery calcification with angiographic coronary artery disease in asymptomatic male military aircrew undergoing noninvasive cardiac screening tests and coronary arteriography for occupational indications. Of 1,466 men screened with coronary fluoroscopy, 613 underwent coronary arteriography because of one or more abnormal noninvasive test results. The mean age (+/- SD) of all subjects screened was 40.2 +/- 5 years (range 26 to 65). Significant coronary artery disease (greater than or equal to 50% diameter stenosis) was found in 104 of the 613 subjects with arteriograms (16.9% disease prevalence). Overall sensitivity and specificity for coronary artery calcification detection of significant disease, based only on those subjects undergoing arteriography, were 66.3% and 77.6%, respectively. For measurable disease (mild plus significant), sensitivity was 60.6% and specificity 85.9%. Positive and negative predictive values were 37.7% and 91.9%, respectively, for significant disease. For measurable disease, positive and negative predictive values were 68.9% and 80.9%, respectively.

In these asymptomatic young men, a fluoroscopic examination negative for coronary artery calcification indicated a low risk of significant coronary artery disease, whereas a positive test result (calcification present) substantially increased the likelihood of angiographically significant coronary artery disease.

(28) http://diabetes.diabetesjournals.org/cgi/content/abstract/51/6/1949
Diabetes 51:1949-1956, 2002

Lipoprotein Subclasses and Particle Sizes and Their Relationship With Coronary Artery Calcification in Men and Women With and Without Type 1 Diabetes. Helen M. Colhoun1, James D. Otvos2, Mike B. Rubens3, M. R. Taskinen4, S. Richard Underwood3, and John H. Fuller1 1 Royal Free and University College

(29) http://jcem.endojournals.org/cgi/content/full/88/10/4525

Low-Density Lipoprotein Size and Cardiovascular Disease: A Reappraisal, CLINICAL REVIEW 163: CARDIOVASCULAR ENDOCRINOLOGY 4 Frank M. Sacks and Hannia Campos
Harvard School of Public Health, Department of Nutrition, Boston, Massachusetts 02115

Because the classical lipid risk factors by no means perfectly predict CHD in patients, lipoprotein subfractionation has the potential to improve risk prediction.

(30) http://www.masson.fr/masson/portal/bookmark?
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Low-Density Lipoprotein Size and Cardiovascular Disease: A Reappraisal …Frank M. Sacks and Hannia Campos

The small, dense LDL phenotype and the risk of coronary heart disease: epidemiology, patho-physiology and therapeutic aspects.

Lamarche B, Lemieux I, Després JP. Department of Food Sciences and Nutrition, Laval University, Ste-Foy, Québec, Canada.

More than decade ago, several cross-sectional studies have reported differences in LDL particle size, density and composition between coronary heart disease (CHD) patients and healthy controls.

Three recent prospective, nested case-control studies have since confirmed that the presence of small, dense LDL particles was associated with more than a three-fold increase in the risk of CHD. The small, dense LDL phenotype rarely occurs as an isolated disorder. It is most frequently accompanied by hypertriglyceridemia, reduced HDL cholesterol levels, abdominal obesity, insulin resistance and by a series of other metabolic alterations predictive of an impaired endothelial function and increased susceptibility to thrombosis. Whether or not the small, dense LDL phenotype should be considered an independent CHD risk factor remains to be clearly established. The cluster of metabolic abnormalities associated with small, dense LDL particles has been referred to as the insulin resistance-dyslipidemic phenotype of abdominal obesity.

Results from the Québec Cardiovascular Study have indicated that individuals displaying three of the numerous features of insulin resistance (elevated plasma insulin and apolipoprotein B concentrations and small, dense LDL particles) showed a remarkable increase in CHD risk. Our data suggest that the increased risk of CHD associated with having small, dense LDL particles may be modulated to a significant extent by the presence/absence of insulin resistance, abdominal obesity and increased LDL particle concentration.

We suggest that the complex interactions among the metabolic alterations of the insulin resistance syndrome should be considered when evaluating the risk of CHD associated with the small, dense LDL phenotype. From a therapeutic standpoint, the treatment of this condition should not only aim at reducing plasma triglyceride levels, but also at improving all features of the insulin resistance syndrome, for which body weight loss and mobilization of abdominal fat appear as key elements.

Finally, interventions leading to reduction in fasting triglyceride levels will increase LDL particle size and contribute to reduce CHD risk, particularly if plasma apolipoprotein B concentration (as a surrogate of the number of atherogenic particles) is also reduced.

(31) http://content.nejm.org/cgi/content/short/358/13/1336
NEJM Volume 358:1336-1345  March 27, 2008  Number 13

Coronary Calcium as a Predictor of Coronary Events in Four Racial or Ethnic Groups
Robert Detrano, M.D., Ph.D., Alan D. Guerci, M.D., J. Jeffrey Carr, M.D., M.S.C.E., Diane E. Bild, M.D., M.P.H., Gregory Burke, M.D., Ph.D., Aaron R. Folsom, M.D., Kiang Liu, Ph.D., Steven Shea, M.D., Moyses Szklo, M.D., Dr.P.H., David A. Bluemke, M.D., Ph.D., Daniel H. O'Leary, M.D., Russell Tracy, Ph.D., Karol Watson, M.D., Ph.D., Nathan D. Wong, Ph.D., and Richard A. Kronmal, Ph.D.

ABSTRACT Background In white populations, computed tomographic measurements of coronary-artery calcium predict coronary heart disease independently of traditional coronary risk factors. However, it is not known whether coronary-artery calcium predicts coronary heart disease in other racial or ethnic groups.

Methods We collected data on risk factors and performed scanning for coronary calcium in a population-based sample of 6722 men and women, of whom 38.6% were white, 27.6% were black, 21.9% were Hispanic, and 11.9% were Chinese. The study subjects had no clinical cardiovascular disease at entry and were followed for a median of 3.8 years.

Results There were 162 coronary events, of which 89 were major events (myocardial infarction or death from coronary heart disease). In comparison with participants with no coronary calcium, the adjusted risk of a coronary event was increased by a factor of 7.73 among participants with coronary calcium scores between 101 and 300 and by a factor of 9.67 among participants with scores above 300 (P<0.001 for both comparisons). Among the four racial and ethnic groups, a doubling of the calcium score increased the risk of a major coronary event by 15 to 35% and the risk of any coronary event by 18 to 39%. The areas under the receiver-operating-characteristic curves for the prediction of both major coronary events and any coronary event were higher when the calcium score was added to the standard risk factors.

Conclusions The coronary calcium score is a strong predictor of incident coronary heart disease and provides predictive information beyond that provided by standard risk factors in four major racial and ethnic groups in the United States. No major differences among racial and ethnic groups in the predictive value of calcium scores were detected.

(32) http://www.nytimes.com/2008/03/12/business/12cnd-scan.html?_r=2&ex=1363060800&en=eb1946f44367ac59&ei=5088&partner=rssnyt&emc=rss&oref=slogin&oref=slogin
Medicare to Keep Paying for Heart Scans  By REED ABELSON Published: March 12, 2008