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  • Heart Attacks: Researchers Finally Find “Big Piece Of The Missing Puzzle”

    January 30, 2017: by Bill Sardi

    Although a thrombus (blood clot) in a coronary artery that supplies the heart with oxygenated blood is the most frequent cause of death among men, “its immediate cause has always been wrapped up in mystery.” — Pathologist Paris Constantinides, Journal American Medical Assn.,1964.

    In 1990 an article published in The New York Times stated that cardiologists “had a nagging sense that a big piece of the puzzle of why people have heart attacks was missing…. although doctors conventionally attributed heart attacks to severe narrowing of the heart’s arteries from fatty deposits, they found in studying the coronaries of heart attack victims that the vessels were often relatively clean. And some cardiac patients had none of the known risks, like smoking, diabetes, high blood pressure and high cholesterol.”

    The report went on to say: “Blood clots that plug the heart’s tiny arteries have emerged as the prime culprits in perhaps 80 percent of heart attacks, and smaller clots appear to contribute to the more chronic process of hardening of the arteries, or atherosclerosis. Now cardiologists have collected impressive evidence that the blood of heart attack victims may form clots too readily and stick with unusual tenacity to vessel walls, blocking the arteries of the heart.”

    The New York Times report made reference to pathologist Dr. Paris Constantinides, who over 50 years ago now found that “hardening of the arteries wasn’t the problem… when the clot was removed some of the vessels were still 70-80 percent open” he said.  [New York Times Oct 16, 1990]

    Generally speaking, modern-day cardiologists address blocked coronary arteries as stenosis – narrowing of a blood vessel — and treat it with implantable wire props called stents.  Stent-happy cardiologists abound.

    Twenty-six years after the New York Times report the reason for the clots in coronary arteries has finally been uncovered.

    But there is more to learn before the final piece of the puzzle is revealed.

    Sticky Platelet Syndrome

    Prior to the report in the New York Times a phenomenon called sticky platelet syndrome was first described in 1983.  Blood platelets are a component of blood that halt bleeding by clumping together to seal up breaks in blood vessel walls.  Platelets are what seal up a wound in your skin.

    However, this syndrome was largely ignored in the medical literature till 1995. [Clinical & Applied Thrombosis/ Hemostasis 1998]  However a present-day report says sticky platelet syndrome is still being ignored. [Seminars Thrombosis Hemostasis 2016]

    A report published in 1998 indicated sticky platelet syndrome accounts for 21% of unexplained arterial blockages (acute heart attack and strokes, transient ischemic attacks or TIAs, and retinal and peripheral blood clots) and 13% of unexplained venous blockages (deep vein thrombosis in the legs, retina, and lungs).  The total incidence of clotting related diseases (thrombosis) in 1996 was reported as follows:

    1498 per 100,000 Americans (3,742,000 cases of clotting events — strokes, heart attacks) resulting in 1,990,000 deaths

    Compared to:

    544 cases of cancer per 100,000 Americans (1,359,150 cases) resulting in 554,740 cancer-related deaths.

    All totaled, clotting events are three times more prevalent and four times a deadly than cancer.

    Commonly used blood thinners, Warfarin (Coumadin) or heparin are not effective for sticky platelet syndrome though low-dose aspirin (81 mg) appears to be somewhat effective, thoughproblematic. [Clinical Applied Thrombosis/Hemostasis 1998]

    However, before you reach for an aspirin tablet you should know that a baby aspirin has not been demonstrated to prevent heart attacks among healthy individuals. [FDA Consumer]  And a full-size aspirin tablet can cause bleeding gastric ulcers that kill a few thousand people annually. [FDA Safety of Aspirin]

    It was around this time when sticky platelet syndrome began to be recognized that Dr. James H. Privitera wrote his landmark book entitled: Silent Clots: Life’s Biggest Killers (1997).  Used copies are still available at Amazon.com.

    Lipoprotein(a) and vitamin C and sticky platelets

    Elevated homocysteine and lipoprotein(a) are among the listed causes of clotting events.  Lipoprotein(a) is the protein that seals up breaks in artery walls when vitamin C levels are low and normal repair cannot take place.  Lipoprotein(a) is like a sticky bandage and it attracts blood platelets, the clotting factor in blood.

    This author has previously written about lipoprotein(a), which was identified as a major factor in the onset of heart attacks by Linus Pauling and Dr. Matthias Rath described in 1990. [Proceedings National Academy Sciences Dec 1990; Knowledge of Health Aug 5, 2013]

    Elevated lipoprotein(a) blood levels promote blood clots.  In one study about 20% of patients with clots in the veins in their legs were found to have elevated lipoprotein(a) levels. [Blood 2000]

    Unstable arterial plaque that can rupture and induce an acute heart attack was first described in the year 2000. [New England Journal Medicine 2000] Low vitamin C blood levels give rise to unstable arterial plaque that is vulnerable to rupture. [Circulation March 26, 2002]

    Lipoprotein(a) is only found in the blood of animals that do not internally produce their own vitamin C. [Chang Gung Medical Journal 2011]  Statin drugs actually raise lipoprotein(a) levels. [Atherosclerosis Oct 2006]

    It is not beneficial to attempt to lower lipoprotein(a) levels but rather to increase vitamin C intake so lipoprotein(a) never sticks to breaks in wall of coronary arteries.

    Elevated lipoprotein(a) does not fully explain sticky platelet syndrome

    Lipoprotein(a) still does not explain all of the idiopathic heart attacks (those that arise spontaneously without a known cause).

    Because the origin of these heart attacks and strokes went unexplained they were assumed to be hereditary.  But it turns out, sticky platelet syndrome is largely governed by the foods one eats and families learn to like the same foods.  So while this syndrome is passed along family lines, it is familial not genetic (inherited).

    In this modern era of medicine there are still no guidelines for the treatment of sticky platelet syndrome because of a lack of understanding of its origin. [Seminars in Thrombosis & Hemostasis 2016; [Folia Haematologica 1988]

    Given no convincing understanding to the origin of sticky platelet syndrome as no identifiable risk factors are evident, and given that it occurs along family lines, it has remained a mystery, till now

    Lo and behold: gut microbes cause sticky platelet syndrome

    A recently published report says: “We now show that gut microbes, through generation of trimethylamine N-oxide (TMAO), an odorless, colorless, nitrogen-based metabolite produced in the human gut (intestines) directly contributes to blood platelet-induced thrombosis (clotting) potential.”  [Cell March 24, 2016]

    Another report says: “Blood plasma TMAO levels predict subsequent heart attacks and strokes by 3 years.  TMAO reveals a previously unrecognized mechanistic link between specific dietary nutrients, gut microbes, platelet function and clotting risk.” [Cell March 24, 2016]

    A recent study shows patients arriving at an emergency room with chest pain were six times more likely to exhibit elevated TMAO levels and were almost twice as likely to die of a heart attack over a 7-year follow-up period. [European Heart Journal Jan 11, 2017]  Another recent study confirms this doubling of mortal heart attack risk with elevated TMAO levels. [Journal American Heart Association June 2016]

    And more convincingly, TMAO has recently been identified as the agent that induces rupture of arterial plaque. [American Journal Cardiology Nov 1, 2016]

    TMAO is independent of established risk factors for heart attack and stroke such as insulin resistance, mid-section obesity and fatty liver. [Scientific Reports May 27, 2016]

    TMAO is not just a bystander or a minor player in the etiology of life threatening blood clots that induce heart attacks and strokes.  Blood platelet involvement and activation is described as an “essential step in the genesis and propagation of atherothrombotic (blood clotting) complications.”  [Cell Metabolism April 12, 2016]

    Nutrients in foods elevate TMAO levels

    Nutrients such as choline (a B vitamin rich in eggs) and carnitine (an amino acid provided in beef), lecithin (phosphatidylcholine) and betaine are metabolized in the gut (intestines) and converted to TMA (trimethylamine) and then transported to the liver via the portal vein where it is metabolized into TMAO. [Toxins Nov 8, 2016; PLoS One Jan 27, 2017; Nature April 7, 2011]

    Certain foods raise TMAO levels.  Beef as a source of carnitine raises TMAO levels. [Food & Function Sept 14, 2016]

    While eggs are a rich source of choline, consumption of 0, 1, 2, 3 eggs a day was not shown to increase TMAO levels in healthy adults. [Lipids Jan 13, 2017]  Yet in another study, 2 eggs/day did increase TMAO levels. [American Journal Clinical Nutrition Sept 2014]

    While eggs and beef are a source of choline and carnitine, two dietary precursors for TMAO, fish consumption produces far higher circulating TMAO blood levels (46-62 times greater) than eggs and beef. [Molecular Nutrition Food Research Jan 2017]

    While consumption of fish demonstrably raises TMAO levels, in an animal study fish oil (not fish) reduces TMAO induced impaired glucose intolerance and fatty tissue inflammation in high-fat fed mice. [Food & Function April 2015]  So fish oil supplements are not to be feared.

    When healthy foods turn out to induce TMAO and sticky platelets

    Dietary fiber derived from carbohydrate-rich foods such as potatoes, grains, beans, cereals, produce “resistant starches” (resist digestion), particularly when these cooked foods are cooled. Misdirected health coaches suggest doubling of so-called resistant starches in the diet in order to control weight.

    “Resistant starch has the potential to become the next hot nutrition trend,” says an author of the American Dietetic Association’s Guide To Better Digestion.” [Prevention]

    However, diets high in resistant starch increase blood plasma levels of TMAO, the gut toxin that is associated with increased risk for heart attacks and cardiovascular death. [British Journal Nutrition Dec 2016]

    Nutritionists circle their wagons in defense of foods that raise TMAO

    The community of nutritionists is not ready to accept TMAO as a problematic agent in cardiovascular health and claims kidney disease may be the underlying cause. [Trends Endocrinology Metabolism Feb 2017]  Most certainly, elevated TMAO levels are associated with chronic kidney disease. [Kidney International May 2016]

    The fact that as TMAO levels increase the degree of kidney dysfunction worsens suggests TMAO is a cause not just a marker of kidney failure. [PLoS One Jan 11, 2016]

    TMAO slows bile acid regulation and disposal. Bile if made from cholesterol in the liver.  TMAO then travels in the bloodstream where its detrimental actions can contribute to heart failure, atherosclerosis and kidney disease. [Current Opinion Lipidology April 2016]

    B vitamins have recently been shown to reduce circulating TMAO levels. [Molecular Nutrition Food Research Aug 28, 2016]

    The most striking effect in negating the adverse effects of TMAO was recently demonstrated in an animal study.

    TMAO reduces bile production in the liver that then indirectly results in a marked increase in arterial fatty plaque.  An increase in TMAO blood levels paralleled a change in the balance of two families of gut bacteria (Firmicutes/ Bacteroidetes).  This undesirable effect was reversed by supplementation with the red wine molecule resveratrol in genetically prone laboratory animals.  [mBio April 5, 2016] An extensive report is available at ResveratrolNews.com.

    Who will monitor TMAO levels?

    TMAO blood levels are not currently a part of a standard CBC (complete blood count).  Which medical specialist will be upon to monitor TMAO levels and prescribe corrective therapy?  Cardiologists were trained and are paid to implant stents, insert catheters into the heart and inflate a balloon to break up clots, to perform coronary artery bypass surgery, not to become gut bacteria specialists.  It may be the moment patients take things into their own hands until the practice of modern medicine catches up with its own science.

    Given that resveratrol pills inhibit TMAO, diminish platelet clumping, reduce inflammation [Indian Journal Biochemistry Biophysics Feb 2013; Platelets Aug 2005], and may be the safest and most effective pain reliever ever [ResveratrolNews.com Dec 28, 2015], resveratrol may serve as a safe alternative to aspirin. [Nutraceuticals World April 15, 2010]

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One Response to “Heart Attacks: Researchers Finally Find “Big Piece Of The Missing Puzzle””

  1. Andy Miller Says:
    February 2nd, 2017 at 1:15 am

    Bill, this is a welcome summary of an important topic — the research community seems to accept TMAO as a useful prognostic marker. On the other hand, there is far more skepticism about its interpretation as a causative agent of disease produced mainly by the gut micro-biome, the hypothesis flogged by the Hazen group at the Cleveland Clinic. For example, the 2017 review by Jonsson & Bäckhed, doi=10.1038/nrcardio.2016.183 , states “Although a number of studies have pointed to an association between plasma levels of choline, TMAO, and CVD, available data are still inconsistent.”

    While I share some skepticism about nutritionists, they seem to have a lock on this debate. You cite the report by Cho et al. (2017) showing that any fish in the diet will dominate the TMAO level in the blood of healthy young men. That report also mentions that, unlike eggs and red meat, this TMAO is contained in the fish itself, requiring no processing by the gut micro-biome and liver — the TMAO appears promptly in the blood. Isn’t there something “fishy” about the emphasis on the gut micro-biome? Is the Cleveland group leary of trying to swim against the established healthful reputation of fish in the diet? Their new review article (doi=10.1016/j.trsl.2016.07.007) contains no mention of fish consumption, only fish oil. It seems unlikely that fish oil contains much TMAO, because rancid fish oil doesn’t smell so fishy, while TMAO decomposes to TMA, which apparently is the main odorant that is characteristic of degrading seafood.

    I’m more attracted by the hypothesis that some CVD patients have either an inability to clear TMAO, or an enhanced vulnerability to its effects that is not shared by most of the population. Lets not throw choline out with the bathwater — it’s an essential nutrient for most people, especially pregnant women.

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