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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Is Aspirin Resistance A True Entity?

Aspirin

Aspirin has been a recognized agent to inhibit platelet function and prevent clotting.  We use it to prevent heart attacks and strokes. It’s used in individuals who have a transient ischemic attack or mini-stroke to prevent a future major stroke. It’s also used as a component of the therapy in patients who have stents put in arteries to relieve arterial blockages.

Despite the use of the aspirin, either alone or in concert with other medications, a certain percentage of patients do have the heart attack or stroke we are hoping to avoid. Scientists have postulated that a number of these patients have a condition called aspirin resistance. They believe aspirin may not work in them due to genetic factors that affect the way aspirin works. The belief is so strong that certain labs now offer genetic assays to assess whether you are a patient with aspirin resistance.

Garret A. FitzGerald, MD, and associates from the University of Pennsylvania published their research in the online section of Circulation: Journal of the American Heart Association which questions the existence of aspirin resistance at all. They recruited 400 healthy non-smoking participants between the ages of 18- 55 to measure the response to the ingestion of a traditional 325 mg regular aspirin or an enteric coated version.  They were able to use several different well accepted measures of aspirins anti-platelet effects to divide the group into aspirin responders and non-responders. They basically found that the non-responders were primarily individuals who received enteric coated aspirin. When you tested their blood in the laboratory with regular non-coated aspirin, or tested them with non-coated aspirin, they suddenly became responders.  FitzGerald and colleagues concluded that “pseudo resistance is caused by delayed and reduced absorption of coated aspirins.”

Doctors and pharmacists have encouraged the use of “coated” aspirin to offset aspirin’s tendency to irritate the lining of the stomach and duodenum and initiate gastrointestinal bleeding. Based on this paper it seems reasonable to suggest to patients that they use regular uncoated aspirin to achieve the desired anti-platelet effect if the patient is not high risk for intestinal bleeding.