Is TMAO the New LDL CHOLESTEROL?

Prevention of heart disease has centered on smoking cessation, controlling blood pressure, achieving an appropriate weight, regular exercise, control of blood sugar and control of your cholesterol.  Despite addressing and controlling these items individuals still have heart attacks and strokes and vascular events. Researchers are now directing their attention to a dietary metabolite of red meat called trimethlamine N-oxide or TMAO.

Recent peer reviewed and published studies have shown an association between high blood levels of TMAO and increased risk of all-cause mortality and cardiovascular disease.  A 2017 study published in the Journal of the American Heart Association found a 60% increased risk of a major cardiovascular event and death from all causes in individuals with elevated TMAO.  Other research has linked high TMAO levels to heart failure and chronic kidney disease.

Our bodies make TMAO when choline and L-carnitine are metabolized by our gut bacteria in the microbiome. Red meat is particularly high in L-carnitine.  A study group at the Cleveland Clinic found that red meat raised the TMAO levels more than white meats or non-meat protein. They also discovered that red meat allowed more bacteria in the gut microbiome to be switched to producing TMAO. Of interest was the fact that the amount of fat in the food, particularly saturated fat, made no difference on the TMAO levels obtained.   Stanley Hazen, M.D. PhD, section head of preventive cardiology at the Cleveland Clinic, feels the TMAO pathway is “independent of the saturated fat story.”  The important issue to Dr Hazen is the presence of the gut bacteria to produce the TMAO from foods eaten.

Not all scientists buy into the TMAO theory of cardiovascular disease because of the relatively high level of TMAO found in many fish.  Some experts believe the beneficial effects of omega 3 fatty acids in fish offset the negative effects of TMAO. The leading researcher on TMAO says it is an evolving study and he is supported by experts who believe TMAO is “atherogenic, prothrombotic and inflammatory” per Kim Williams, M.D., chief of cardiology at Rush University Medical Center in Chicago.

There is even a blood test to measure TMAO levels developed by the Cleveland Clinic and available through Quest Labs.  Do not get too excited about asking your physician to order it on your blood because it requires eliminating meat, poultry and fish plus other food items for several days in advance of the test.

For many years researchers at the Cleveland Clinic and Emory University recognized that 50% or more of heart attacks occurred in men who followed all the risk reduction guidelines including stopping smoking, controlling blood pressure and lipids, losing weight and getting active. Perhaps the answer as to why will be in the TMAO research and the solution will be changing the gut bacteria or their ability to convert L-carnitine to TMAO.

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Sunscreen Ingredients are Absorbed says FDA

For years public health officials, dermatologists and primary care physicians have been encouraging people to apply sunscreen before going out into the outdoors to reduce the risk of sunburn and skin cancers.  We are taught to apply it in advance of exposure by about 30 minutes and to reapply it every few hours especially if we are sweating and swimming.   Living in South Florida, sun exposure is a constant problem so we tend to wear long sleeve clothing with tight woven fabrics to reduce sun exposure.  My 15-month old grandson, visiting last weekend was smeared with sunscreen by his well-meaning parents before we went out to the children’s playground nearby.

These precautions seemed reasonable and sensible until an article appeared in JAMA Dermatology recently.  An article authored by M. Mata, PhD. evaluated the absorption of the chemical constituents of sunscreen after applying it as directed four times per day.  The article was accompanied by a supporting editorial from Robert M. Cliff M.D., a former commissioner in the FDA and now with Duke University School of Medicine and K. Shanika, M.D., PhD.

The study applied sunscreen four times a day to 24 subjects. Blood levels were drawn to assess absorption of the sunscreen products avobenzene, oxybenzone and octocrylene.  The results of the blood testing showed that the levels of these chemicals far exceeded the recommended dosages by multiples. The problem is that no one has evaluated these chemicals to see if at those doses it is safe or toxic causing illness?

The editorial accompanying the findings encourages the public to keep using sunscreen but cautions that the FDA and researchers must quickly find out if exposure to these levels is safe for us?  We do know that the chemical oxybenzone causes permanent bleaching and damage to coral reefs in the ocean from small amounts deposited by swimmers coated with sunscreen. The state of Hawaii has actually banned sunscreens containing oxybenzone to protect their coral reefs.

The fact that these chemicals have been approved and are strongly absorbed with no idea of the consequences is solely the result of elected officials wanting “small government” and reducing funding to the oversight organizations responsible for making sure what we use is not toxic.  It is a classic example of greed and profit over public safety.  The research on the safety of these chemicals must be funded and addressed soon. The American Academy of Pediatrics and Dermatology need to advise parents of youngsters whose minds and bodies are in the development and growth stages what is best to do for their children – sooner rather than later.

Lung Cancer Screening is Underutilized

Dr. Jinai Huo of the University of Florida (Go Gators!) presented data to Reuters Health that primary care physicians are under-utilizing the technology available to screen for lung cancer. This is a particularly sore topic to me because my associate and I always screened smokers and heavy past smokers for lung cancer with an annual chest x-ray until the United States Preventive Task Force issued guidelines that it didn’t save lives and was not cost effective.  They said, it cost $200,000 in normal x-rays to find one cancer early and it was deemed not worth it.

We actually sold our chest x-ray unit, let go our certified radiology technician and cancelled a contract with radiologists to read our films because insurers stopped paying for chest x-rays after the USPTF ruling.  Twenty years later that same group said “woops” an error was made. The statistical analysis on that study was done incorrectly and actually screening does save lives and is cost effective.

Today we have the fast low dose CT scanner to screen for lung cancer and screening does save lives according to the data.  Who should be screened?

Current smokers or those who have quit smoking within the last 15 years who are 55 to 77 years old and have a smoking history of 30 packs or more per year (one pack per day for 30 years or 2 packs a day for fifteen years).  Screening should be done on individuals in good health so if a lesion is found they are considered well enough to undergo diagnostic tests and treatment.

Screening is also recommended in those individuals over 50 years old with a twenty (20) pack year smoking history and a family history of lung cancer or lung disease or occupational exposure to items associated with causing cancer such as radon.

I inquire about smoking at each visit and have been fortunate in that few of our patients still smoke so we spend less time on counseling for smoking cessation.  If you fall into one of the screening groups mentioned in this article, and have not been screened, please notify us so we can arrange for the testing which will be a low dose chest CT scan.

American College of Physicians Breast Cancer Screening Guidance

The American College of Physicians released four guidance statements on detection of breast cancer in women with average risk and no symptoms of breast cancer.

  1. Doctors should discuss with their patients the pros and cons of screening with mammography for breast cancer in asymptomatic women with a modest risk of disease between ages 40- 49 years. The potential risks of screening are felt to outweigh the benefits.
  2. Clinicians should screen average risk women aged 50-74 years for breast cancer with mammography every other year.
  3. Clinicians should discontinue breast cancer screening in women aged 75 years or greater with an average risk of breast cancer and a life expectancy of 10 years or less.
  4. Clinical breast examinations SHOULD NOT be used to screen for breast cancer of average risk women of all ages.

These guidance statements DO NOT APPLY to women with a higher risk of breast cancers including those with abnormal screening results in the past, a personal history of breast cancer or a mutation in the BRCA1 or BRCA2 gene.

At the same meeting, data was presented discussing the problems with supplemental whole breast ultrasound in women with dense breasts.  The concern is that all this testing leads to invasive biopsies, over diagnosis and treatment of breast cancer in 1 in 5 patients and complications and increased cost to patients and insurers.  Like most recommendations on breast cancer, and prostate cancer in men, the results and conclusions from following these guidelines will not be apparent until 10 to 15 years from now.

Today’s adult women will either benefit from these suggestions, which have even included no longer teaching adult women how to perform breast self-exam, or they will be the unsuspecting research victims of cost containment. I question the competence of physicians in examining problematic breast disease if they are not being trained how to evaluate a breast and following that with clinical exams. In surgery we usually do not feel a clinician is competent and fully aware of the pitfalls of a procedure until the surgeon has done 200 or more. We additionally know that doing the procedure frequently results in better results than performing a procedure infrequently.

How will that apply if young physicians no longer examine breasts routinely?  How many, and how often, will they need to do an adequate exam to be able to perform when there is a real issue?  Do we actually wish to create a narrow panel of breast experts only at Centers of Excellence who actually know how to examine a breast and use the available imaging modalities safely and effectively?  It seems these ACP recommendations move in that direction.

For several years now I have been a supporter and champion of our community’s Women’s’ Center associated with Boca Raton Regional Hospital. Run by astute future thinking clinicians and researchers, and stocked with state of the art imaging equipment, it provides an option to meet with a counselor, assess your breast cancer risk and enter a screening pathway most individually suited to your personalized needs.  I will continue to support that choice.

Keep Moving for Cardiovascular Benefits

We keep extolling the benefits and virtues of regular exercise and fitness. Some research studies have documented the intensity and duration of exercise programs with cardiovascular events and mortality. Those who do more and are fitter apparently do much better which surprises few of us.

It comes down to the “which came first the chicken or egg “question?  Are people genetically able to exercise at a high level living longer and healthier because they exercise at a high intensity and duration or vice versa?

It is quite comforting to read the recent study in JAMA by Andrea LaCroix, PhD, MPH and colleagues from the University of California, San Diego that shows the benefits of even modest movement and exercise.  The study was conducted under the umbrella of the Women’s Health Initiative and put pedometers and accelerometers on women to measure activity during waking hours.  Light physical activity was defined as less than 3 metabolic equivalents (Walking one mile in about 22 minutes expends about 3 Metabolic Equivalents of Activity).  They noted that for each hour per day increment in light activity there was a 14% lower risk of Coronary Heart Disease and 8% lower risk of cardiovascular disease.

The researchers evaluated 5,861 women with a mean age of 78.5 years. Average follow-up spanned 3.5 years with study members having 570 cardiovascular disease events and 143 coronary heart disease events. The study group was diverse with there being 48.8% Caucasian women, 33.5 % Black women and 17.6% Hispanic women.

The study’s results and message was clear. Keep moving. Even modest exercise is beneficial in reducing heart attack and stroke risk.

Scientific Reports, Media Reports and Ambiguity

Last week I read an article in a peer reviewed journal citing the benefits of a few eggs per week as part of a low carbohydrate dietary intervention for Type II Diabetes.  The information was so meaningful about a controversial food source of protein that I decided to write about it in my blog and pass it along to my patients.  Three days later the American Heart Association and American College of Cardiology discussed the increased risk of cardiovascular events and mortality in individuals consuming three or more eggs regularly. They talked about the detrimental cholesterol being concentrated in the yolk making egg white omelets look healthier than traditional omelets.

In the early 1970’s a VA study was published showing that veterans over 45 years of age who took an aspirin a day had fewer heart attacks and strokes and survived them better than those who don’t.  Fast forward almost 50 years and we have different recommendations for people who have never had an MI or CVA or evidence of cardiovascular disease compared to secondary prevention in individuals who have known coronary artery disease, cerebrovascular disease or diabetes. Throw in the controversial discussions of aspirin preventing colorectal adenomas from developing, aspirin preventing certain types of skin cancers and today’s report that suggests it may prevent liver cancer. Now three studies suggest that in older individuals (70 or greater) the risk of bleeding negates the benefits of cardio and cerebrovascular protection and aspirin may not actually prevent heart attacks and strokes in that age group.

We then turn to statins and prevention of heart attacks and numerous articles about not prescribing them to older Americans.  I saw articles on this topic covered by CNN, the Wall Street Journal, ARP Journal, AAA magazine and in several newsletters published by major national medical centers.  In each piece they caution you to talk to your doctor before stopping that medicine.

I am that seventy year old patient they all talk about.  I have never smoked. I exercise modestly on a regular basis, getting my 10,000 or more steps five or more days a week.  I battle to keep my weight down and find it difficult to give up sweets and bread when so many other of life’s pleasures are no longer available due to age and health related suggestions.

There are clearly no studies that look at patients who took a statin for 15 years and aspirins for over 20 years, stopped them and then were followed for the remainder of their lives.   How will they fare compared to patients who never took them?

I have this discussion every day with my patient’s pointing out the current guidelines and trying to individualize the suggestions to their unique lifestyle and issues. On a personal level, I still have no idea what the correct thing is to do even after discussing it with my doctors.  How can I expect my patients to feel any differently?

Sleep Apnea and Cognitive Impairment

Convincing a patient to undergo a sleep analysis for obstructive sleep apnea is a difficult task. During our history taking session, we ask about excessive snoring, periods of not breathing while asleep, daytime sleepiness and we look at the patient’s body habitus, weight and height. Often, the patient’s spouse or partner has complained about their snoring keeping them up. Most of the time, when I ask about this the response is, “Why go for an evaluation if I am not going to wear that mask anyway?  I have a friend who has a CPAP mask and I am just not going to do that.”

Obstructive sleep apnea and periods of apnea (not breathing) results in the lung blood vessel blood pressure rising.  We call it pulmonary hypertension.  It is different from systemic arterial essential hypertension in that traditional blood pressure medicines do not lower the pulmonary pressures.

If you examine our heart and lung anatomy you realize that the very non-muscular right side of the heart, primarily the right ventricle, pumps blood a short distance to the lungs to exchange gases and removing wasteful gases in exchange for oxygen. That oxygen rich blood returns to the left side of the heart where the very muscular left ventricle pumps it out to the body.

When the body’s systemic blood pressure rises the left side of the heart has to work harder. The muscular left ventricle is much more suited for that task than the right ventricle is suited to pump against pulmonary vessel hypertension.  The result is the right heart fails much sooner than the left side and the treatment options and medications are far less successful.  This explanation to patients is often received, digested and dismissed as hypothetical and down the road.

This week the American Academy of Neurology received a presentation by a group at the Mayo Clinic in Rochester that showed that patients with untreated sleep apnea produced an increased amount of tau protein deposition in the brain. Tau protein deposition is associated with Alzheimer’s disease.  The researchers, led by Diego Z. Carvalho, MD, are not sure if more Tau protein accumulates in brains of people with untreated sleep apnea or if Tau protein accumulation actually leads to sleep apnea?  That research is ongoing.

The lesson is that sleep apnea is something that needs to be diagnosed and treated. I am a fan of referring patients’ to sleep evaluation centers where that is the primary disease state reviewed.

While sleep apnea is one of the abnormalities evaluated, there are many other disorders of sleep that can be recognized and treated to improve patient sleep. At home sleep monitors are available as well but may be limited in diagnosing sleep apnea alone.

If you are determined to have obstructive sleep apnea then treatment choices include weight loss, laser treatment of the uvula, dental appliances to open up your airways, adjustments to your sleep position and many types of facial and nasal CPAP devices.

Most of my patients who try a CPAP mask require 8-12 weeks to adjust to it. Once adjusted to it, their quality of sleep is so good that I rarely have to convince them to keep using it.