Simon Murray, MD

This month is American Heart Month. I could begin by telling you that heart disease is the leading cause of death for men, women, and people of most racial and ethnic groups in the United States.

One person dies every 36 seconds in the United States from cardiovascular disease. 

About 655,000 Americans die from heart disease each year

I could also tell you the risk factors for coronary artery disease: LDL cholesterol elevation, diabetes, family history of premature heart disease, hypertension, and smoking. But you already know that or haven't given it much attention.

Maybe you did not consider heart disease a possibility at your age or that your family was immune or perhaps you thought getting heart disease was the natural consequence of aging—None of these are true.

When it comes to evaluating risk, humans are relatively poor at predicting probability. You may be more worried about being bitten by a shark (1/ 370,000,00)

, but forget that the lifetime risk of dying from the cardiac disease is just 1-in-4.

Consider this: research from analysis of the Framingham Heart Study demonstrates multiple important points:

The average lifetime risk of developing cardiovascular disease in Americans was around 52% for men and 39% for women.

Lifetime risk jumped to 69% for men and 50% for women who had two or more cardiovascular risk factors by age 50.

Lifetime risk was just 5% among men and 8% among women who had optimal risk factors for cardiovascular disease at age 50. That meant that they lacked risk factors like being overweight, did not smoke and did not have diabetes, high cholesterol, and high blood pressure.

People in the low-risk group tended to live into their nineties, while those in the higher risk groups died decades earlier.

ust 3% of men and 4% of women in the analysis fell into this very low-risk category at age 50! 

But the Risk of Dying from Cardiac Disease is Declining.

We have done better in our "war against cardiac disease." The death rate from heart disease over the past two decades declined by 18.6% and for coronary heart disease we saw the rate decrease by 31.8%.7 Using a combination of surgery, multiple drugs, and other interventions, we have improved our risk, but at what cost?

The amount of money spent on health care last year in the U.S. was 3.6 trillion dollars, much of it for heart disease. (Consider this: If you spent one dollar per second, it would take you over 32,000 years to spend one trillion dollars.)

In 2019, I had the opportunity to speak to Dr. Dean Ornish, a leading proponent of lifestyle changes to treat and reverse cardiac disease, about his book "Undo It."

 I became interested in his work with Bill Clinton, who had been told after having a heart attack in 1993 that he had a genetic predisposition to having heart disease. There was nothing that could help him.

Ornish worked with him and Clinton's cardiac conditions improved, and he remains vigorous and healthy. Nonetheless, I was dubious that lifestyle could help reverse and prevent heart disease. I also knew there here was little financial incentive for physicians to promote prevention over treatment of illness. Lastly, patients in my experience were often resistant towards at following treatment plans that required major changes in lifestyle, (Even if they did work).

Dr. Ornish is the founder and president of the nonprofit Preventive Medicine Research Institute and a medicine professor at the University of California, San Francisco. He is the author of six books, including Dr. Dean Ornish's Program for Reversing Heart Disease; Eat More, Weigh Less; Love & Survival; The Spectrum, and his most recent book, "Undo It." He has created hundreds of centers around the United States to teach people how to change their lives.

He was convinced that high tech medicine had reached its limitations for treating chronic medical conditions like cardiac disease. Ornish commented that, "As doctors we are trained to act quickly when something bad happens. We call in the calvary for quick fixes, to patch things up, but don't consider how the situation might have been avoided." Someone once told me that, "Bad things happen quickly; good things take time."

As Americans, we don't like things that take time to get results. We want quick cures, and it cost 3.6 trillion dollars last year to follow this course. We were able to reduce death from heart disease by 18%, but what happened to the other 72%?

Dr. Ornish cited his 39 years of research with randomized trials documenting that lifestyle changes could not only treat cardiac disease but could prevent and reverse it at very little cost. 

He noted that 80% of the money spent on health care is for chronic diseases that are mostly preventable. 

In his book, he cited four proven lifestyle choices to prevent cardiac disease.

It seemed a bit too simple for me. But as I learned, there are many proponents of lifestyle management of chronic diseases. And it is not a new idea. Herophilus, a Greek physician who practiced medicine in Alexandria in 300 B.C. defined the art of medicine as a triad consisting of knowledge of the things concerning health, knowledge of things pertaining to disease, and knowledge of neutral things.

Herophilus, who became the most influential anatomist of his time, practiced in Egypt where human dissection was allowed, unlike Greece. Dr. Von Staden, an emeritus scholar at the Institute for Advanced Study told me that Herophilus and other Greek philosophers believed that the knowledge of things concerning health was the most essential part of the art of medicine triad. Von Staden wrote, "Medicine in Hellenistic times, like earlier medicine, is concerned with the dietetics of the health. Indeed at this time the doctrine of health is considered to be not only as important as therapeutics, it seems to be even more important than healing of the sick." 

 (Dietetics is the science of applying nutrition principals to aid in preservation of health, and can loosely include exercise. )

Ornish may be one of the most influential modern thought leaders who have connected heart health and emotional health, but he is not the only one.

In a recent article in Psychiatric Times, Dr. Lawson Wulsin and Dr. Juliana Zambrano stated, "Psychosocial factors, especially recurrent depressive symptoms, severe mental illness, and high numbers of adverse childhood experiences, contribute substantially to both the onset and progression of CHD. Its effect size is as strong as that of the traditional CHD risk factors, such as smoking and high cholesterol".

They state, "The most robust psychosocial interventions for CHD are intensive lifestyle medicine programs."

Dr. Ornish has established a nonprofit group to promote and teach his ideas. He reported that 85% of his patients could comply with the program, and he has reduced their health care costs by 50%. Medicare now covers treatment at one of his centers. The affordable health care act mandated even more preventative measures to promote health that are covered by insurance. As Ornish commented to me, it is unfortunate that the programs didn't become popular until they were reimbursable by insurance.

The major point is that many chronic diseases, including cardiac disease, are significantly influenced by our wellness state. Modern medicine is good at intervening once we are sick but has for too long has neglected the simple things that can make a more significant impact on health. These things include following a Mediterranean diet, moderate exercise (150 hours a week), stressing less (Meditation, yoga, turn off the news), loving more (especially loving yourself enough to avoid unhealthy behaviors like smoking, drugs, drinking to excess, and the unhealthy pursuit of wealth, career, fame ). Practicing gratitude is especially helpful at reducing stress. Being kind and forgiving yourself for perceived personality defects will allow you to forgive others. If you seek revenge, you dig two graves.

Change doesn't come quickly. We seek progress, not perfection. Choose to change your life. Learn more about formulating a plan. (Ornish's book 'Undo It' is a good start.) The desire to make a change is a wish, and without a plan is only a dream.

Lastly, learn to do with less. I have had the privilege of spending the final hours of life with hundreds of patients, and not one ever said, "My only regret is that I didn't work more hours and have more money." My father used to say that a man is not wealthy for what he has, but for what he can do without.

1. Centers for Disease Control and Prevention. Underlying Cause of Death, 1999–2018. CDC WONDER Online Database. Atlanta, GA: Centers for Disease Control and Prevention; 2018. Accessed March 12, 2020.

2. Virani SS, Alonso A, Benjamin EJ, Bittencourt MS, Callaway CW, Carson AP, et al. Heart disease and stroke statistics—2020 update: a report from the American Heart Association. Circulation. 2020;141(9):e139–e596.

3. Fryar CD, Chen T-C, Li X. Prevalence of uncontrolled risk factors for cardiovascular disease: United States, 1999–2010 NCHS data brief, no. 103. Hyattsville, MD: National Center for Health Statistics; 2012. Accessed May 9, 2019.

4. Sources: All accidental death information from National Safety Council. Disease death information from Centers for Disease Control and Prevention. Shark fatality data provided by the International Shark Attack File.

5. Sources: All accidental death information from National Safety Council. Disease death information from Centers for Disease Control and Prevention.

6. Sources: All accidental death information from National Safety Council. Disease death information from Centers for Disease Control and Prevention.

7. Lloyd-Jones DM, Leip EP, Larson MG, D'Agostino RB, Beiser A, Wilson PW, Wolf PA, Levy D. Prediction of lifetime risk for cardiovascular disease by risk factor burden at 50 years of age. Circulation. 2006 Feb 14;113(6):791-8. doi: 10.1161/CIRCULATIONAHA.105.548206. Epub 2006 Feb 6. PMID: 16461820.

9. Reverón RR. Herophilus and Erasistratus, pioneers of human anatomical dissection. Vesalius. 2014 Summer;20(1):55-8. PMID: 25181783.

10. Von, S. H. (1989). Herophilus: The art of medicine in early Alexandria: edition, translation, and essays. Cambridge: Cambridge University Press.

Articles

Dr. Simon Murray reflects on the ongoing fight against cardiovascular disease in the US as part of our coverage of American Heart Month. 

Reflecting on The Fight Against Cardiovascular Disease in 2021 with Simon Murray, MD

What is the role of ACE inhibition or angiotensin receptor blockers (ARBs) within regard to the novel coronavirus (COVID-19)?

There has been some dissent lately about the role angiotensin-converting enzyme plays in the COVID-19 infections. The chemistry can be quite confusing, making it easy to see why it has caused controversy.

A very elegant system exists in humans to regulate blood pressure when there are sudden drops in renal blood flow or reduced sodium excretion, which could lead to hypotension. The system is called the renin-angiotensin system (RAS), which keeps us from fainting when we stand up quickly or when we are dehydrated.

Angiotensinogen is a protein formed in the liver and activated when renin, an enzyme secreted by the kidney in response to a drop in renal blood flow, cleaves it. The resulting protein is called Angiotensin 1, which has no known function except as an intermediary in the process of maintaining blood pressure. Angiotensin 1 is converted by angiotensin-converting enzyme-1 or ACE1 in the lung into angiotensin II.

Angiotensin II can act on the adrenal to produce the hormone aldosterone, which increases sodium retention and promotes potassium excretion. Angiotensin II will bind a specific receptor in the heart, lung, and blood vessels called the AT1 receptor. There are 3 other receptors-AT2, AT3, AT4-but their roles remain unknown.

Once bound to AT1, angiotensin II causes vasoconstriction, fluid and sodium retention, stimulation of aldosterone, and cardiac stimulation. Free, unbound angiotensin II has direct proinflammatory properties in lung tissue.

There is a second angiotensin-converting enzyme called ACE2 that had remained rather obscure in literature until 2002 when it turned out to be the point of entry for SARS virus to enter lung cells.

The 2 angiotensin-converting enzymes, ACE1 and ACE2, are analogs of each other and structurally very similar. ACE2 protein exists as a soluble form but mainly resides on the epithelial surface of the lung, intestine, and heart. Not much was known about ACE2 until the SARS epidemic, but much has been learned since.

ACE2 plays a counterregulatory role in the classical RAS and causes vasodilation, reduction in sodium, and reduced levels of angiotensin II. It does so by reducing angiotensin II levels and converting angiotensin II into angiotensin (1,7), which are vasodilators. ACE2 levels are generally 200 times higher than ACE1 levels.

It also has a negative effect on aldosterone. The 2 proteins ACE1 and ACE2 each have very different actions on the RAS.

Chronic overactivity of the RAS is felt to be one cause of hypertension. It became logical to look for drugs to interfere with this system. In the late 70’s and 1980’s a class of drugs were developed called angiotensin-converting enzyme inhibitors after the discovery that cobra snakes have a large amount of angiotensin in their venom. The way that cobra snakes kill their prey is by causing shock from hypotension.

ACE inhibitors block the conversion of angiotensin 1 to angiotensin II by inhibiting ACE1. The inhibitors were not felt to have any role in blocking ACE2. But a few years later, the second class of drugs was developed, which blocked the action of angiotensin II further upstream at by preventing angiotensin II from binding to specific receptor sites on the blood vessel and heart.

These are ARBS, which have been shown to reduce the symptoms of congestive heart failure, lower blood pressure and protect the kidney from high blood pressure. They are often the first-line drugs used to treat these conditions.

And I said before: the role of ACE2 remained obscure until 2002, prior to the discovery that it binds SARS virus avidly and served as the point of entry of the virus into the cells that lined the surface of the lung.

Why is this important? We know that SARS-COV-2 is bound to ACE2 and serves as a portal of entry of the SARS-COV2 virus into cells-just as it was for the SARS and probably the MERS viruses. Theoretically, anything with increased ACE2 levels could make patients more susceptible to infection with coronavirus, and make their cases more severe.

A letter to the editor in The Lancet described the observation that Chinese patients who had high blood pressure or diabetes and who were taking ACE inhibitors and ARBS had worse outcomes, with more severe infections and more deaths.

The article implied that ARBS and ACE inhibitors elevated ACE2 levels and that increased ACE2 facilitated more viral penetration into lung tissue. The paper concluded that taking these medicines could increase the number and severity of infections. The authors suggested that people should stop taking these medications. On face value, it seemed like a logical conclusion.

For several days after publication, there was a firestorm of confusion about whether or not to take ACE inhibitors or ARBs. The European Society of Cardiology and several leading American cardiology societies all refuted the findings in The Lancet. They suggested that patients should continue their medications and that there was no proof that the COVID-19 infection was adversely affected by inhibition of the RAS. There is evidence that these medicines might make infections better.

It is complicated, but it has already been demonstrated that viral pneumonia improved faster when the patients were taking ACE inhibitors.

Did The Lancet article consider that the patients who did worse either had diabetes, hypertension, or obesity? That triad is part of the metabolic syndrome and would make any sick person worse, because the metabolic syndrome can produce the “cytokine storm” that generates damage to lung tissue.

I was drawn into this debate by several patients who had the quickly popularizing article. A few days later, when institutions refuted the findings, I saw more controversy stir.

This episode is an example of the ongoing issue we have during this pandemic-in which public announcements or declarations on the virus are later retracted. People in authority are making statements and decisions without certain and evidenced knowledge. The most present fact in this debate is that story is rapidly developing.

Of course, as we see the virus rapidly spread and take more lives, it is understandable to see people react quickly, rather than rationally.

Simon Murray, MD, is an internist based in Princeton, NJ. The piece reflects his views, not necessarily those of the publication.

Simon Murray, MD

Articles

Reflecting on The Fight Against Cardiovascular Disease in 2021 with Simon Murray, MD

ACE Inhibitors & ARBs: Wading Into the Unknown of COVID-19