Heart Failure,  Coronary Artery Disease and Cholesterol

Edward Lichten, M.D., P.C.
555 South Old Woodward Avenue
Suite 700

Birmingham, MI 48009 
248.593.9999

Email: drlichten@yahoo.com

 

 
Heart Failure, Coronary Artery Disease and Cholesterol

OVERVIEW:   

Most people may a problem understanding that Heart Failure, Coronary Artery Disease and Elevated Cholesterol are three completely independent disease states. Therefore, a person with heart failure may also show evidence of coronary artery disease or elevated cholesterol. Similarly, evidence of coronary artery disease and subsequent myocardial infarction may occur in a person without elevated cholesterol. Meanwhile, up to half of the individuals having heart attacks may have normal cholesterol.  The following material will look at the cause of each one of these diseases and the natural means by which the severity of the problem can be minimized and possibly normal status restored.

Historical Overview Understand Coronary Artery Disease

Long before there were prescription medications for cholesterol and as early as the turn of the 20th century, there was no discernible coronary artery disease. People died from infections whether it was the pandemic flu of 1919 or pneumonia.  The first report of deaths from coronary artery disease were considered an oddity except by a few.1 Instead, by the end of the 21st century, coronary artery disease would become the number one cause of death in western civilizations.

Coronary Artery disease-CAD is the partial obstruction of the major arteries that bring blood, oxygen and nutrients to the heart muscle.  It is postulated that deposits of cholesterol form plaques that attach to the arteries.  When these plaques break or fall off, they may cause complete obstruction of some part of the coronary artery. The obstruction of blood to the muscle of the heart can cause the myocardial infarction, i.e. heart muscle death. If enough of the heart or the electrical system is affected, then the heart is unable to pump blood and the patient dies.

Heart failure is different in that there are many different disease processes that can weaken the heart enough to cause ‘failure’. Coronary Artery Disease may progressively destroy more and more heart muscle or infection, or a genetic condition or a metabolic condition may occur that leaves the heart muscle just too weak to pump blood. While coronary heart disease is seen primarily in the 40 to 70 year old men, congestive heart failure occurs in the majority of those living into their 80’s. 

Cholesterol is the pre-cursor to many of the bio-identical hormones. It is essential for human survival.  Since the 1920’s, biochemists have used natural and plant based cholesterol to synthesize estrogen, testosterone, DHEA, pregnenolone and progesterone. Even Vitamin D needs cholesterol to function properly.  There are a number of inherited or genetic diseases that result in very high levels of cholesterol related lipids: They are defined by high levels of various cholesterols, high levels of triglycerides and abnormal distributions of large and small chylomicrons that hold the fat.  As some of these rare lipid diseases are associated with increased cardiac mortality, it was logical to expect researchers to associate abnormal levels of cholesterol with the rapid increase in coronary artery disease.

After World War II, Ancel Keys2, a physiologist performed an epidemiologic study of dietary habits and heart disease in countries around the world. He concluded that the cause of heart disease was directly related to the intake of animal fat. However, his study was flawed in that he selected out only 6 of the 22 countries to ‘stratify’ his study.  And as every good mathematician knows, you can prove anything with ‘stratified’ data.

But the doctors and the pharmaceutical companies, in their desire to treat and prevent heart disease, adopted and promoted Ancel Keys’ work.  Medication after medication has been proposed to block fat and treat/cure coronary artery and heart disease, only to be removed, drug after drug from the F.D.A. approved list.  Over the last 25 years, various medications have been suggested as ‘cure alls’ only to be abandomed from use because of unforeseen complications.  The lists includes:

Atromid-S:            Approved in 1975 for the treatment of extremely rare medical conditions where the serum triglycerides normal 100-200 go over 2000.  a large study of 5000 men for 5 years of active drug and one year of follow up showed, under the World Health Organization supervision, a 44% increase in mortality, half from cancer.3

Statins:            Statins were approved in 1987 to treat abnormal lipids-dyslipidemia.  Every one of the statins is reported to have complications of rhadbdomyolysis, a sometime fatal breakdown of muscle tissue. More than 800 cases were reported to the FDA with a watch group asking for the removal of Crestor®. Bayer Pharmaceutical voluntarily removed Baycol® in 1991.4-6

Rezulin®:            Rezulin® was the first troglitazone used to lower insulin resistance in adults with diabetes mellitus. The complications of this medication included liver toxicity. It was removed within 2-3 years of launch and after sales reached almost one billion dollars per year.7

Yet today, with these and their closely related pharmaceutical products still on the market and accounting for billions of dollars of health costs, the people of the United States and Europe still suffer with one of the highest rates of coronary artery deaths in the world. 

Could it be that cholesterol was never the cause of heart disease and that these cholesterol lowering medications are just one more liver poison? Could statins only artificially suppress lipid profiles while the real culprit continues to make these cardiac health matters worse?

Understanding Cholesterol

Cholesterol is a necessary part of human existence. From cholesterol in the diet and cholesterol manufactured in the liver originates many of the major hormones that fuel the human endocrine system. Cholesterol begets Pregnenolone, Progesterone, Cortisol, DHEA, Testosterone, Estrone, Estradiol and during pregnancy, Estriol.  Understand that cholesterol is necessary for human life.

If the body is stressed and the adrenals are not working properly from under nutrition or physical exhaustion, the cholesterol levels will physiologically increase to attempt to manufacture more DHEA and cortisol.  If the thyroid is under performing, then the cholesterol levels increase to produce more of the other hormones.  If a woman has polycystic ovaries with an imbalance of testosterone over estrogen, the cholesterol increases. And if the man is low in testosterone or becomes diabetic, his cholesterol increases.

The point is that hypercholesterolemia is a sign that the body’s hormones are not in balance. To treat the symptom, the alleged high cholesterol in the blood, by poisoning the HMG-CoA system, is absolutely ludicrous. Why not understand the cause of the problem, whether it is diet, nutrition or hormones and address that directly?  

Total cholesterol levels up to 300 mg/ml were not considered important until there were pharmaceutical drugs available to lower the levels.  Dr. Lichten does not prescribe cholesterol-lowering medications except to rare individuals with true defined classes of hyperlipidemia. Rather, he will first and foremost treat the cause of the cholesterol as a problem of nutrition and a problem of hormone imbalance.

Understanding Cholesterol’s Role as a Bio-Identical Hormone

Cholesterol is necessary for normal human function. Without cholesterol, the following functions do not occur properly:8

  1. Bile salts, which are necessary for absorption of essential fats and minerals including Vitamin A, D, E and K are derived from cholesterol.
  2. Cholesterol is necessary for vitamin D production.
  3. Cholesterol is incorporated into the inner layers of every cell wall.
  4. Cholesterol is incorporated into the myelin sheath that insulates every large peripheral nerve cell.
  5. Cholesterol is necessary for normal action of circulating T-cells, lymphocytes and Helper B-cells part of the immune system.

In the liver, energy components from the Kreb’s cycle, Acetyl-CoA is metabolized to HMG-CoA and onto cholesterol, which makes Ubiquinone. Ubiquinone is commonly called Co-enzyme Q10.  Co-Q10 is the very important carrier molecule in the oxidation-phosphorylation cycle within the cell that produces energy that powers the cell.  Poisoning the HMG-CoA system can bring down the energy system for the entire body.  One of the complications noted with statins is the loss of adequate levels of Co-enzyme Q10. 

When one of the pharmaceutical companies sought to add Coenzyme Q10 to their statin, it was our governing bodies that stopped this single attempt to correct a wrong. Maybe it was an attempt to not give one company an advantage. Meanwhile, there is no logic in taking a statin drug without massive amounts of Co-Q 10. More about this will be addressed later.

So, why the Hype over “Know your cholesterol level?”

In 1985, the National Cholesterol Education Program (NCEP)9 was created by the National Heart, Lung and Blood Pressure Institute of the Federal Government. The purpose of the NCEP was to raise public cholesterol awareness including cooperative efforts with the American Heart Association. While everyone now knows their blood cholesterol level, the medical science has yet to prove that “lowering your cholesterol will significantly lower your risk of coronary artery or heart disease”.9

The reason for this false dicotomy or fuzzy logic is that the pharmaceutical companies and the university and hospital based physicians have forgotten the basic rule of science. Established more than 150 years ago, the only proof of a theorem relies on the completion of (4) steps.  These steps represent the principles of the Scientific Method10 upon which science is based. The principles are clear:

  1. Make an observation
  2. Collect data
  3. Establish a hypothesis to explain the observations
  4. Accept all challenges to your hypothesis, if it withstands all challenges, then the theory is accepted. Results must be reproducible.

But in the last 20 years, a bastard theory called Evidence Based Medicine has become the teaching point for physicians and the public. Evidence based medicine makes no proofs, one only has to perform steps 1, 2 and 3.  Evidence based medicine is nothing more than dogma:  “my drug is better than your drug,” or more often “my drug is better than nothing.” While the true scientist could look at these studies and retort, “neither of your drugs are necessary.” The failure to consider that the doctor would first measure the appropriate hormone laboratory values to determine what was the cause of the underlying disease is the thorn in the ‘fuzzy logic’ studies. Replacing the inherently deficient thyroid or testosterone hormones, for example, corrects the patient’s underlying medical condition and negates statin intervention. 

And that is the point.  Just because cholesterol levels are elevated in coronary artery disease or heart failure does not mean that high cholesterol was in any manner, the cause of the malady.

But, before rejecting the pharmaceutical proof that cholesterol-lowering drugs are beneficial, let us review their Evidence Based Data.

1.                  Heart Protection Study11 in 2002 of 20,536 adults in the England aged 40-80 with high risk for heart disease. Randomized to simvasatin (Zocor®) 40mg daily.  Difference in survival at 6 years was 87.1% for Zocor® versus 85.4% for placebo. But the complications of statins include cognitive impairment, depression and suppression of the immune system and liver dysfunction and muscle changes were not factored into continuation of the drug..

2.                  Prosper study12 2002 of 5804 patients on Pravechol® versus placebo.  Mortality difference of 0.2% not statistically significant.

3.                  ALLHAT13 2003 study of 10,355 on Pravachol® versus placebo. Mortality difference 0.4%. Not statistically significant.

4.                  ASCOT-LLA14 study of 19,342 hypertensive patients on Lipitor®. The study showed a decrease in cardiac mortality but an increase in other mortalities. The statistical difference between groups again was 0.465%. Not significant..

5.                  PROVE-IT15 2004 study of 4,162 patients who had a heart attack or angina randomized to Lipitor® or Pravachol. ® Both groups had small reduction in calculated death rates 2.2% Lipitor® and 3.2% Pravachol® but without a control group.

The point is, there is no great and overwhelming proof that $12 billion dollars in cholesterol lowering drugs are doing anything to improve the health of the American public. In this chapter is listed peer reviewed and published medical studies that address bio-identical hormone deficiencies as the cause of heart failure and coronary artery disease. First, Dr. Lichten states, “Treat the cause”. And, then from a scientific and logical standpoint, the pharmaceutical companies are asked to explain how a statin which lowering cholesterol levels by poisoning the liver really can make mankind live longer and better.  It just does not make sense.

The Truth About Heart Disease

Before there were cholesterol-lowering drugs there was heart disease.  As physicians we need only look back 100 years to see that there was a major problem with heart disease in the form of congestive heart failure causing untold deaths.  The term used was dropsy. The cause of death was hypothyroidism.

In the paper presented at the 1997 meeting of the American Thyroid Association, R, Arem showed what every doctor learned in medical school: that there exists a strong link between abnormal thyroid function, elevated cholesterol, elevated triglyceride levels and heart disease. But what physicians knew in the 1890’s;  that replacement of thyroid medication could prevent and treat ‘dropsy;’ has been lost on the physicians in practice today.  Dropsy is the end stage of hypothyroid induced congestive heart failure.  There is fluid retention that is seen in the lower legs as edema, in the abdominal cavity as ascites, in the lungs as pulmonary edema, and in and around heart as a pericardial effusion. Low thyroid function can also increases the risk of hypertension, increases vascular resistance, and contributes to other complications of heart disease. Treatment then and now with appropriate ‘natural’ thyroid replacement that has the active thyroid molecules, will reduce not only 1) the heart failure and 2) lower the cholesterol and strikingly 3) triglyceride levels, sometimes to normal. Arem16 said so at the American Thyroid Association meeting and said so in his book:  The Thyroid Solution by Ballantine books. 1999.

The history of thyroid disease and medical treatment unfortunately took a wrong turn in 1939. As Broda Barnes,17 M.D., the leading clinician and researcher in thyroid disease revealed in his book entitled Hypothyroidism, he was approached by the pharmaceutical manufacturers to promote synthetic thyroid, Synthroid®. He allegedly first explained that Synthroid® was an incomplete thyroid containing only T4, whereas Armour thyroid®, also a prescription medication had both thyroxine-T4 and tri-iodothyronine-T3 from the thyroid glands of pigs or beef cattle.  By marketing an incomplete thyroid, Barnes predicted that Synthetic thyroid would wreak havoc on the endocrine system.  The pharmaceutical company took no heed and proceeded to make synthetic thyroid the drug of choice. Doctors today are taught to be adamant that synthetic is better because they have heard this nonsense hundreds of times.   The marketing falsehoods spread about natural or Armour thyroid have obviously been important in the shifting of the vast majority of prescription thyroid to Synthroid 15:1 and away from Armour thyroid.  Yet the medical literature is now replete with the unique functions for T3 in heart disease.

To summarize what Barnes and others have stated about normal thyroid function 70 years ago and appropriate scientifically today:

  1. Normal thyroid function is necessary for health, life and normal fertility.
  2. Appropriate replacement of thyroid necessitates both T4 and T3 in a balance that reestablishes normal body temperature.
  3. Laboratory tests are guidelines, not absolutes, in treating the patients with thyroid disease.
  4.  
Conclusion #1: Check for Hypothyroidism as a Cause of Elevated Cholesterol

Thyroid disease is definitely one of the causes of high cholesterol.  It goes unrecognized and under-diagnosed in individuals with heart disease.  Why worry about lowering cholesterol with some statin when there is an FDA approved thyroid and appropriate laboratory tests to prove there exists a thyroid deficiency concurrently in the first place? Bio-identical, Armour thyroid might not only lower cholesterol and lower blood pressure but there is a 100-year history of it being used to prevent and treat congestive heart failure.  Replacing natural thyroid will not only treat those cold hands and feet, increase mental focus and fix the brittle nails, hair loss and thinning eyebrows, but it by nature of cause-and-effect, might lower cholesterol. Bio-identical thyroid has scientifically proven to be so much more important in the cholesterol-CAD-heart disease continuum than a statin because thyroid replacement treats the cause  Why then not treat hypothyroidism first, recheck the cholesterol and lipid levels and follow up with a diet high in omega-3 fatty acids, appropriate nutraceuticals and instruction to the patient in a change of lifestyle, before deciding to add statins or recheck other parameters?

Is the physician’s concern only the allegedly cholesterol laden plaque in the coronary arteries of 50 and 60 year-old heart attack victims or the epidemic of heart failure seen in both men and women today?

Heart Failure

The incidence of congestive heart failure-CHF in the United States is increasing with more than 500,000 new cases per year. While heart failure occurs in 1% of people at age 50, 5% of people at age 75, it occurs in 25% of people aged 85 and older. Congestive heart failure is the most frequent reason for admission to the hospital under Medicare.18  Could the cause of this increase in admissions be due to misdiagnosed hypothyroidism or the precarious policy of prescribing statins to everyone whose total cholesterol is now only over 200 mg/ml?

Statins may be compounding the problem. A study of 20 patients on Lipitor® showed a 66% occurrence of abnormalities of the diastole or filling stage of the heart. This is a major component of congestive heart failure.19 Could statins do more than block production of necessary Co-enzyme Q-10? A search of the literature finds a double-blind study that established clearly that statins do no good for individuals with CHF.20  There were no demonstrable changes in heart function for those individuals with heart failure placed on high dose statins.   Stephen Sinatra, M.D.21 says in his book, The Sinatra Solution,  that to treat and prevent heart disease one needs to consider bio-identical nutrient replacement: Co-enzyme Q-10, N-acetyl choline and D-ribose.  After organizing Continuing Medical Educational Courses with Dr. Lichten, Dr. Sinatra admits to prescribing more bio-identical hormones for his cardiac patients, specifically, testosterone to men.

Testosterone and Heart Failure

Another missed cause of heart failure is the absence of testosterone.  As men age, there is both a natural drop in testosterone levels and an increase in SHBG that bind up more testosterone. To this double whammy is added the increased estrogen poisoning in our food and the xeno-estrogens of plastics and DDT.  Men, at an alarming rate, are experiencing heart failure at a rate not seen before.  And modern medication with statins and medical diagnostic equipment tests are missing the connection between low testosterone and heart failure and low testosterone and coronary artery disease.

The answer to heart failure is right there in every heart cell.  The heart is a muscle that must beat billions of times in a lifetime. It never stops to rest.  So these heart cells are the most finely tuned energy machines in the entire human body.  They are irreplaceable. And they are in tune to testosterone. The heart has more testosterone receptors than any other muscle in the body. 22 Actually, the heart has more dihydrotestosterone receptors.23  Why would it be so sensitive to testosterones if it weren’t the most important connection the heart has to the total body’s function?  Being strong, healthy and virile is the only way that nature can assure reproduction of the human race.

Now, we know that it is a fact that testosterone allows a man or woman to run faster.  Ben Johnson was a top-notch athlete who became the Olympic gold metal sprinter with supplementary testosterone.  Women runs like Florence Griffith Joiner won races at speeds never achieved previously only to die of heart problems from allegedly using performance-enhancing steroids.  In the cases of athletes and normal people alike, testosterone for men offers improved cardiac function in all measurable cardiac parameters.  Testosterone improves heart muscle pumping capacity and requires less energy to do so.  Testosterone should be of primary importance in treating older men with heart failure.24 And as the following will show, starting testosterone early may prevent the development of other heart problems.

Testosterone is an anabolic steroid.  It can make new and bigger muscles as to what bodybuilders can attest.  The same applies to those weak and flabby heart muscles. But to make new muscles, the body needs protein, minerals, vitamins and essential fats. These are called nutraceuticals. In Chapter 14 is listed the necessary supplements and how much Dr. Lichten prefers to prescribe. 

Note that a number of Dr. Lichten’s testosterone deficient patients both with and without diabetes have recorded a 100 point drop in total cholesterol that persists month after month while on testosterone replacement.

3.            Beyond sexual function regulation, male steroids are operative in several physiologic homeostatic systems including the cardiovascular system. By ways of specific androgen receptors, testosterone can mediate cardiomyocyte trophicity, in physiologic states as in diseases involving cardiac hypertrophy. Androgenic hormones also regulate pathologic levels of inflammatory cytokines as 11-6 or TNF, in advanced heart failure. They also mediate vascular resistance with, in vitro and in vivo, proved coronary vasodilatation. Reduced free testosterone serum levels (age-mediated or in premature coronary artery disease patients (CAD) promote a pro-atherogenic lipid profile expressed as HDL-cholesterol decrease and up-regulation of triglycerides levels). The latter observation has relevant clinical significance for evaluation and treatment of CAD disease. As most of normal and diseased cardiovascular system functions are influenced by androgens, we can foresee an increasing interest for further evaluation of their physiologic implications as well as for large and rigorous studies of their therapeutic potential in two leading disabling pathologies, CAD and heart failure.49

 4.            CONCLUSIONS: Short-term intra-coronary administration of testosterone, at physiological concentrations, induces coronary artery dilatation and increases coronary blood flow in men with established coronary artery disease.50

ESTRADIOL and heart disease in women is the subject of Chapter 9.  The W.H.I. statements must be considered limited to oral Prempro® since scientific and physiologic studies show estradiol dilates coronary arteries; a very positive effect.

1.            CONCLUSIONS: Physiological levels of 17beta-estradiol acutely and selectively potentiate endothelium-dependent vasodilatation in both large coronary conductance arteries and coronary microvascular resistance arteries of postmenopausal women. This effect may contribute to the reduction in cardiovascular events observed with estrogen replacement therapy.51

Final Conclusions

Within this chapter, the material presented has shown a direct correlation between the bio-identical hormone levels and symptoms of cardiac disease.  The author has also suggested that each patient have baseline laboratoryt measurements:

  1. Vitamin D
  2.  IGF-1
  3. Thyroxine (T4); Tri-iodothyronine (T3)
  4. DHEA-sulfate, morning cortisol
  5. Fasting insulin, Hemoglobin A1c
  6. Total Testosterone, total Estradiol and Sex Hormone Binding Globulin

plus the

  1. Complete blood count
  2. Metabolic panel
  3. Lipid panel: fasting
  4. Prostate Specific Antigen

A form to order these tests appear in the Appendix-LABTESTS

The final point to be made about cholesterol is that it cannot form plaques until it is oxidized.  Oxidization is what rust is to metal; oxidation leaves the cholesterol foam cell, rough and sticky.  Another term for these oxidative changes is an inflammatory response.  Inflammatory responses occur because of excess insulin, smoking, drinking, drugs and bad food that damage the cells. Therefore, the treatment for all anti-inflammatory processes is to use anti-oxidant supplements and for all men, testosterone. Be aware that testosterone is overwhelmingly the most potent anti-oxidant for men and can offer a profoundly positive improvement in his cardiac, coronary and lipid parameters.52

 

References

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1   Barnes, Broda. Hypothyroidism: The unsuspected illness 1939. Harper-Collins.160-1.
2   Keys, Ansel. Atherosclerosis. A problem in the new public health Journal of Mt. Sinai Hospital. 1953; 20: 118-39.
3  WHO study: increased deaths from Atromid S: Atromid website.
4  Baycol removed from market: Baycol website.
5    Request for Crestor to be removed from market. See Crestor Petition to the FDA to remove the cholesterol-lowering drug rosuvastatin (CRESTOR) from the market (HRG Publication #1693)
6 Statin Safety: An Overview and Assessment of the Data—2005The American Journal of Cardiology, Volume 97, Issue 8, Pages S6-S26 H. Bays6 
FDA request that Rezulin be withdrawn.
http://www.fda.gov/bbs/topics/NEWS/NEW00721.html
9   http://www.vivo.colostate.edu/hbooks/pathphys/digestion/smallgut/absorb_lipids.html10  
10.  v"MsoNormal" style="text-align: justify; text-indent: 0in; margin-left: 0in"> 6. http://en.wikipedia.org/wiki/Scientific_method
11 Ravnskov U. Statins as the new aspirin.  British Medical Journal 2002;324:789
12 MRC/BHF Heart Protection Study of cholesterol lowering with simvastatin in 20,536 high-risk individuals: a randomized placebo-controlled trial. Lancet 2002 Jul 6;360(9326):7-22.
13 PROSPER Study. The Lancet, Volume 361, Issue 9363, Pages 1135-1136
14 Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT). JAMA. 2002;288:2981-2997
15 Hennekens CH. The ALLHAT-LLT and ASCOT-LLA trials: are the discrepancies more apparent than real? Current Atherosclerotic Report 2004;6(1):9-11
16 http://www.suite101.com/article.cfm/womens_thyroid_disease/35085
in patients with chronic systolic heart failure. Journal Cardiac Failure. 2007; 13(1); 1-7
17 Barnes, Broda. Hypothyroidism: The unsuspected illness 1939. Harper-Collins.
18Krumholz HM. Readmission after hospitalization for congestive heart failure among Medicare beneficiaries. Archives of Internal Medicine.1997; 57(1):99-104
19 Langsjoen, PH. Treatment of statin adverse effects with supplemental Coenzyme Q10 and statin drug
discontinuation. BioFactors  2005: 25; 147–152
20 Krum H. Double-blind, randomized, placebo-controlled study of high-dose HMG CoA reductase inhibitor therapy on ventricular remodeling, pro-inflammatory cytokines and neurohormonal parameters. Journal of Cardiac Failure. 207;13(1):1-7
21 Sinatra, Stephen. The Sinatra Solution. Basic health 2005.
22 Shippen E. The Testosterone Syndrome. 1999. M. Evans & Co.
23 Sheridan PJ. The heart contains receptors for dihydrotestosterone but not testosterone: Possible role in sex differential in coronary heart disease  The Anatomical Record. 1989; 223(4): 414-9
24
Pugh PJ. Testosterone treatment for men with chronic heart failure.
Heart 2004;90:446-447
25 Phillips GB. The association of hypotestosteronemia with coronary artery disease in men. Arteriosclerosis and Thrombosis, 1994;14; 701-706,
26. Welch RD et al. Prognostic value of a normal or nonspecific initial electrocardiogram in acute myocardial infarction. JAMA 2001 Oct 24 286 1977-1984
27Univesity of Iowa. Well & Good Issue 1. 2000.
28 Hoffmann, U. MDCT in early triage of patients with acute chest pain. American Journal Roentgenol. 2006; 187(5):1240-7
29Kondos GT. et al. Electron-beam tomography coronary artery calcium and cardiac events: a 37-month follow-up of 5635 initially asymptomatic low- to intermediate-risk adults. Circulation. 2003 May 27;107(20):2571-6.
30Newman TB. Carcinogenicity of Lipid lowering drugs Journal of the American Medical Association. 1996; 275(1): 2755-60
31Sacks FM. The effect of pravastatin on coronary events  New England Journal of Medicine 1996; 385: 1001-9
32 Green JJ et al. Calcitrol modulation of cardiac contractile performance via protein kinase C. Journal of Molecular and Cell Cardiology. 2006; 41(2): 350-9
33 Zittermann A et al. Vitamin D insufficiency in congestive heart failure: why and what to do about it?  Heart Failure Review. 2006; 11(1): 25-33.
34Goodwin KD et al. Preventing oxidative stress in rats with aldosteronism by calcitrol and dietary calcium and magnesium supplements. American Journal Medicine Science. 2006; 332(4): 73-8
35 Ortlepp JR et al. The vitamin D receptor gene variant is associated with the prevalence of type 2 diabetes mellitus and coronary artery disease. Diabetic Medicine.2001; 18(10): 842-5.
36 Fazio S et al. A preliminary study of the use of growth hormone in dilated cardiomyopathy. New England Journal of Medicine. 1996; 28(3334(13):809-14
37  LeCorvoisier P et al. Cardiac effects of growth hormone treatment in chronic heart failure: A meta-analysis. Journal of Clinical Endocrinology 2007; 92(1): 180-5
38 Itoh E et al. Metabolic disorders in adult growth hormone deficiency: A study of 110 patients sat a single institute in Japan. Endocrinology Journal. 206; 53(4): 539-45
39 Ceda GP. Clinical implications of the reduced activity of the GH-IGF-1 axis in older men. Journal of Endocrinology Investigation. 2005;28(11 Supp): 96-100
7.       Fazio S et al. A preliminary study of the use of growth hormone in dilated cardiomyopathy. New England Journal of Medicine. 1996; 28(3334(13):809-14
40 Schmidt-Ott UM et al. Thyroid hormone and heart failure. Current Heart Failure Report. 2006; 3(3): 114-9
41 Bunevicius R. Depression and thyroid axis function in coronary artery disease: impact of cardiac impairment and gender. Clinical Cardiology 2006; 29(4): 170-4
42 Walsh JP. Subclinical thyroid dysfunction as a risk factor for cardiovascular disease. Arch Internal Medicine. 2005; 165(21):2451-2
43 Jankowska EA. Anabolic deficiency in men with chronic heart failure: prevalence and detrimental impact on survival. Circulation 2006: 114(17):1829-37
44 Nakamura S. Possible association of heart failure status with synthetic balance between aldosterone and dehydroepiandrosterone in human heart. Circulation. 2004; 110(13):1787-93
45Thijs L et al. Are low dehydroepiandrosterone sulphate levels predictive for cardiovascular diseases? A review of prospective and retrospective studies. Acta Cardiology 2003; 58(5): 403-10
46 Lainscak M et al. Metabolic disturbances in chronic heart failure: a case for the ‘macho’ approach with testosterone?!  European Journal Heart Failure. 2007; (1):2-3
47 Malkin CJ. The effect of testosterone on insulin sensitivity in men with heart failure. 2007 European Journal of Heart Failure. 2007;(1):44-50
48 Smith AM. The influence of sex hormones on pulmonary vascular reactivity: possible vasodilator therapies for the treatment of pulmonary hypertension. Curr Vasc Pharmacol. 2006; 4(1):9-15
49 Smeets L. Heart and Androgens. Rev Med Liege 2004;59(7-8):439-44
50Webb CM. Effects of testosterone on coronary vasomotor regulation in men with coronary heart disease. Circulation 1999; 100(16): 1690-6
51 Gilligan DM et al. Effects of physiological levels of estrogen on coronary vasomotor function in postmenopausal women. Circulation. 1994; 89(6): 2545-51
52 Barud W. Inverse relationship between total testosterone and anti-oxidized low density lipoprotein antibody levels in ageing males. Atherosclerosis. 2002; 164(2):283-8