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From the Townsend Letter
May 2012

Dr. Mark Houston: A New Perspective on Cardiovascular Disease
Interviewed by Nancy Faass, MSW, MPH

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Cardiovascular diseases continue to be the number one cause of death in the US. Among these conditions, the primary causes of mortality are coronary heart disease, angina, myocardial infarction, stroke, and congestive heart failure (CHF). Unfortunately, we have reached a limit in our treatment of coronary heart disease using traditional medical interventions.

The Coronary Heart Disease Gap
Over the past two decades, the primary approach to treatment has been to target the top 5 risk factors:

  • hypertension
  • dyslipidemia
  • obesity
  • diabetes mellitus (dysglycemia and insulin resistance)
  • smoking

In cardiovascular medicine, we have developed a false sense of security, based on the belief that if we just address these 5 major risk factors, we will be able to prevent most of the incidence of heart attack – but this is simply not the case. The traditional evaluation, prevention, and treatment of these top 5 coronary heart disease (CHD) risk factors still result in a CHD gap. This gap implies that despite aggressive and optimal treatment of these 5 risk factors, we are still missing something. The gap reflects the fact that about 50% of patients will still develop CHD or myocardial infarction despite "normal" levels of these risk factors as presently defined in the medical literature.

There are important details within each of the 5 CHD risk factors that are not being measured by physicians and are thus ignored in the prevention and treatment of CHD. To have more impact on cardiovascular disease, we must now look to the other 395 risk factors and the details within the top 5 risk factors.

Today, some of the most innovative thinking in cardiovascular care is occurring in the fields of functional medicine, metabolic medicine, and integrative practice. This means looking beyond just the major risk factors to identify the risk mediators, underlying causes, and metabolic and functional disorders that are actually inducing cardiovascular disease. We go to the genesis of what is causing the coronary heart disease.

Three Primary Immune Responses
To explain our new perspective on cardiovascular health, I have a simple maxim: Although there are infinite numbers of insults to the vascular system and the heart, the blood vessel has only a finite number of responses to these insults. The three primary biological responses that result in heart and disease are:

  • inflammation
  • oxidative stress
  • autoimmune disease of the vascular wall, vascular endothelium, and heart

Our strategy for diagnosis, prevention, and treatment grows out of this understanding. The first step in treating the individual patient is to identify which of these three finite responses is predominating. Then we backtrack to determine the initial trigger(s) that induced this response, resulting in cardiovascular disease.

This is totally revolutionary thinking in the field of cardiovascular treatment. The advantage to this approach is that, if you can get these three finite responses under control, and then backtrack to identify the initial triggers of these vascular responses, you can be much more effective in preventing, managing, and resolving cardiovascular disease. With this approach, you can address not only 5 risk factors, but as many as 400. We have a solid scientific basis for this perspective, because hundreds of these risk factors have already been identified and documented in the research literature.

Two Primary Forms of Vascular Stress
The next key point is that there are an infinite number of potential insults to the vascular system and the heart, which include any type of adverse event or stressor that you can name. Yet all the insults that trigger cardiovascular compromise can ultimately be grouped into two major categories – either biochemical or biomechanical stressors.

These stressors may be one of the top 5 risk factors, or they could be one of the other 395 factors that we do not talk about. It could be a toxin, some type of chronic infection, or some other environmental issue that we do not ever measure, such as POPS (persistent organic pollutants) or heavy metals.

Biomechanical stressors: These issues include not only elevated blood pressure and stress in the arteries, but also other forms of vascular dysfunction.

Biochemical insults: Examples of these insults include chemicals or toxins to which we are exposed or the result of metabolic disorders reflected in the level of hormones, glucose, oxidized LDL, insulin, and homocysteine. This could be termed our total toxic burden. The list is nearly endless.

A New View of the Vascular System
Another key to cardiovascular disease is vascular biology, which informs our basic understanding of the underlying causes of cardiovascular illness.

The critical understanding here is based on the nature of the vascular endothelium and its function. The endothelium is the layer of cells that line the heart and every blood vessel in the body. This vast network of cells can be considered an entire organ system, one of the largest in the body. This is a single monolayer of cells that essentially separates the blood from the vascular smooth muscle. If the endothelium is healthy, then the blood elements are healthy, avoiding oxidative stress, inflammation, immune dysfunction, adhesion molecules, elevated C-reactive protein, platelet aggregation, proliferation, and growth of the vascular and cardiac smooth muscle with hypertrophy and stiffness, as well as thrombosis.

If the endothelium becomes unhealthy, this communicates down into the vascular smooth muscle and a series of dysfunctional dynamics begins to occur. Basal constriction develops, which increases blood pressure, and causes leakiness in the endothelium with symptoms that can include microalbuminuria, proliferation and growth, foam cells, fatty streaks, and subintimal plaques in the arteries. Endothelial dysfunction is the key to understanding how an individual initially develops cardiovascular disease.

Vascular Reactions
When insults occur, they trigger a natural biological response in the endothelium that reflect the body's inherent intelligence.

If there is an insult to the artery, the blood vessel essentially says, "I'm going to defend myself from whatever just attacked me." The body mounts the correct response to the insult, a response appropriate to an acute situation.

However, when an exposure becomes chronic, that initial protective response is likely to be harmful. If the delicate vascular system suffers chronic insults repeatedly, that will trigger one or more of the finite responses in the form of oxidative stress, inflammation, or an autoimmune reaction in the vascular tissue. If, for example, the patient goes to work every day and is exposed to a toxin such as mercury, that will eventually cause "a chronic, dysregulated response in the artery." Note that the response is appropriate, so I describe it as the "correct chronic dysregulated response." The vascular system is simply protecting itself, but when those protective efforts occur in a chronic pattern, that creates disease. This dysfunctional response begins decades before the patient develops any clinical symptoms.

The goal is to identify endothelial dysfunction when it is just beginning and treat it aggressively, which can prevent clinical disease from occurring two, three, or four decades later.

Testing for vascular dysfunction – There are a number of effective tests that you can use to identify endothelial dysfunction early in the process. These noninvasive cardiovascular tests have been shown to accurately measure endothelial dysfunction and are currently available. The two that I have found the most useful are:

EndoPAT – A 10-minute test, the EndoPAT provides highly accurate evaluations of endothelial dysfunction. This test tends to be more highly predictive of potential coronary risk than any other risk factor that we can measure.

The HDI – The Hypertension Diagnostic Indicator uses a computerized arterial pulse wave analysis to look at small and large arterial compliance, to directly evaluate endothelial dysfunction and arterial elasticity.

There are other tests on the market, but I think that these two have the best standardization for identifying endothelial dysfunction at an early stage.

Testing for immune reactivity – Once you identify endothelial dysfunction, you want to ask, what is setting off this reaction? Is it a combination of inflammation, oxidative stress, or autoimmune disease? Which one is predominating? You can determine this by administering a brief series of common lab tests to identify which of those three dynamics is the primary problem. For example:

Inflammation – Test for high-sensitivity C-reactive protein, which is probably the single best marker. If the outcome on the lab report is higher than 2, start looking for what might be causing the inflammation. Usually the patient has other symptoms that will help you determine that.

Oxidative stress – There are several markers that you can use here, including serum testing for oxidized LDL cholesterol and numerous other markers in blood and in the urine, MDA, and 8-hydroxyguanosine. Most clinicians in integrative practice are aware of the various oxidative stress markers that can be checked.

Autoimmune reactions – You can measure the immune system and beta cell function, and you can test for ratios of T-cells (T-4 and T-8 helper cells), and levels of regulatory cells, as well as interleukins and TNF a. You are looking for markers that reflect not just inflammation, but also autoimmune disease.

All three of these phenomena cross-communicate with each other: they cross-talk, so when one is activated, that tends to affect the other two as well. These markers will give you an accurate assessment of what you need to do to treat oxidative stress, inflammation, and autoimmune reactions and the insults to the vascular system.

Identifying the initial trigger – Another key point: When you remove a chronic insult, the body is going to become less reactive, as if it were responding, "Now that I don't have to defend myself anymore, I'm going to turn off those reactions." We want to target the inflammation, and we want to identify and remove the upstream cause of the inflammation.

The goal here is to ask, why does the patient have cardiovascular disease? Why does he have the chronic inflammation, oxidative stress, or immune activation that is causing cardiovascular illness? This is the time to backtrack and identify as best you can which of the 400 different risk factors could be causing that disease.

How do you identify the finite causes? This phase calls for careful evaluation. In preparation, this means taking a careful and complete patient history, performing the physical exam, sending out the appropriate labs, and then beginning your analysis.

In the case of the patient with the mercury exposure, your report to the patient might be: "You are being exposed to mercury in your work, so we are going to measure your mercury level. If it is elevated, we will carefully remove the mercury." The first step is to eliminate the exposure. Frequently the inflammation goes away at that point. The C-reactive protein level will go down, and endothelial function will return to normal. This enables you to reduce risk at a much earlier phase, before the patient develops cardiovascular disease.

Integrative Treatment
In developing a treatment plan, you can draw on functional and metabolic medicine, taking an integrative approach. The wise healer uses what is best for his patient, whether that means nutrients or medication, as long as it does not have adverse effects. Treatment is always prescribed in tandem with lifestyle changes, such as weight management and exercise.

In terms of nutrient therapy, it is important to know which nutrients have been scientifically validated and which can be used in combination with other nutrients. It is even more vital to know which nutrients can be used in combination with the medications that have been shown to reduce heart attacks and congestive heart failure.

Once you have made the diagnosis and you have a good idea of what the patient's issues are, you can develop a treatment program. This provides an opportunity to offer truly integrative care.

Advanced disease – When your patients have advanced vascular disease, start them on the appropriate drugs as well as a good nutrient protocol with antioxidants and anti-inflammatories and an integrative lifestyle management program. The goal is to treat the arteries, but also the heart.

Less involved conditions – For patients whose condition is less severe, you might not need drugs at all. You may simply want to prescribe an integrative treatment program using nutrients and antioxidants. The severity of the patient's condition will determine your choice of initial therapies.

The good news is that we now have excellent clinical studies in the peer-reviewed medical literature which identify the nutrients that can be used to treat high blood pressure, dyslipidemia, obesity, and diabetes mellitus. The research also indicates other nutrients that are effective in the treatment of congestive heart failure, coronary heart disease, and a range of risk factors. Review articles have been published that provide lists of nutrients and a range of treatment options.

Functional Cardiology
It is important that we begin identifying people in their teenage years and early 20s who have developed vascular disease. We know from autopsy data for Korean War vets and Vietnam vets that many people just 18 to 20 years old already had extensive coronary heart disease. A functional perspective on cardiovascular disease could potentially change the treatment of vascular conditions and heart disease and ultimately reshape medical training.

New Book
All of this information and much more is now published in Dr. Houston's new book, released on February 6, 2012: What Your Doctor May Not Tell You About Heart Disease. The book can be obtained on Amazon, through the publisher directly (Grand Central Publishing, NY), or in your local book stores.

Upcoming Workshop
Institute for Functional Medicine International Conference: A New Era in Preventing, Managing, and Reversing Cardiovascular and Metabolic Dysfunction; May 31–June 3, 2012, Scottsdale, Arizona. For more information see Functional

More Upcoming Workshops
Orlando, April 22, 1–5 p.m. Prevention Medicine Annual Conference (ACPM).
San Francisco, March 22–23. A4M/FAARM; Westin St. Francis Hotel.
Phoenix, April 20–29. A4M/FAARM; Sheraton Phoenix Downtown.
Orlando, May 18. A4M/FAARM Annual Conference; hotel location TBA.
Scottsdale, AZ, May 30–June 3. IFM Annual Conference; Westin Kierland.
San Diego, September 15. Restorative Medical Conference; hotel location TBA.
Chicago, September 21–23. A4M/FAARM; hotel location TBA; see website.
Tampa, October 12–14. A4M/FAARM; hotel TBA; see website.
Atlanta, November 2–4. A4M/FAARM; hotel TBA; see website.
Las Vegas, December 14–16. A4M/FAARM Hotel TBA; see website.

Books: Best-selling books by Dr. Houston include The Handbook of Hypertension (Wiley-Blackwell; 2009), Vascular Biology in Clinical Medicine (Hanley and Belfus; 2002), and What Your Doctor May Not Tell You About Hypertension (Time-Warner Books; 2003).

Online Resources: Integrative protocols are available at under "Supplement Recommendations" and also at Journal articles available at no cost on nutraceutical therapies can be accessed by searching PubMed for Houston MC.

Nancy Faass is a writer and editor in San Francisco who has worked on more than 40 books for publishers that include Elsevier, Harper, McGraw-Hill, Mosby, New Harbinger, New World Library, North Atlantic, and others. Director of The Writers' Group, her work includes writing for the Web, and work on articles and white papers. For more information, see

Dr. Mark HoustonDr. Mark C. Houston graduated from Vanderbilt Medical School, completed his internship and residency at the University of California at San Francisco, and then returned to Vanderbilt University and Medical Center, where he continues to teach and practice. Dr. Houston is triple-board certified by the American Board of Internal Medicine (1977), by the American Society of Hypertension (ASH) as a specialist in clinical hypertension (FASH; 2000), and by the American Board of Anti-Aging Medicine (ABAAM) (2000). He also holds a master of science degree in human nutrition (2003). Dr. Houston is on the consulting editorial board or is a consulting reviewer for more than 20 major US medical journals. He serves as chair of the medical advisory board of the American Nutraceutical Association (ANA), and editor-in-chief of its journal (JANA). Dr. Houston has presented more than 10,000 lectures on hypertension nationally and internationally, and published over 175 articles and scientific abstracts in peer-reviewed medical journals as well as textbook chapters, handbooks, and films. He has also completed over 70 clinical research studies in hypertension, hyperlipidemia, and cardiovascular disease.



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