Inflammation as a Cause of Heart Attacks and Strokes

Years ago I attended a series of lectures sponsored by the Cleveland Clinic to promote its proprietary lab tests that were geared to detect previously undetectable causes of heart attacks and strokes. A cardiologist at Cleveland Clinic, along with a research nurse out of Emory University Hospital and Medical Center, noted that 50% of the men having heart attacks and strokes were within the recommended life and health guidelines. They didn’t smoke, their blood pressures were controlled, they had lipids within the recommended guidelines and their weight was appropriate – as was their activity level.

They unofficially dubbed it the Supermen study and showed that by reducing “inflammation” they could reduce the number of heart attacks and strokes. They concentrated on periodontal disease and rheumatologic diseases as sources of inflammation. They believed that angina and heart attacks and strokes did not occur because a blood vessel gradually narrowed much like a plumbing pipe clogged with hair and debris. They felt that soft lipid plaque under the surface in vehicles dubbed “foam cells” ruptured through the blood vessel wall into the lumen through the endothelial lining under the direction of inflammation in the body.

This breakthrough into the blood carrying portion of the blood vessel was perceived as a fresh cut or wound which was bleeding. The body’s natural response was to try and stop the bleeding by creating a clot. This clot occurred quickly in a small vessel and every living item downstream, not supplied by a collateral blood vessel, died from lack of oxygen and fuel to function. They treated the identifiable inflammation and felt that statin medications (Lipitor, Zocor, Pravachol, Crestor , Livalo and the generics) had an of- label quality that reduced inflammation as well as lowered the cholesterol.

I bought into that theory and incorporated these blood tests into the patient population most at risk and the appropriate age where prevention would make a major difference. Tests like hsCRP, Myeloperoxidase, Apo-B and others were used for screening. Finding the inflammation and treating it for men who met the definition for entry into the Supermen study was far more difficult. The whole theory of inflammation causing acute cardiac and cerebrovascular events was treated much like climate change, genetically modified foods and even vaccinations with a large degree of community doubt.

Last week at a major European Cardiology meeting the CANTOS (Canakinumab Anti-inflammatory Thrombosis Outcomes Study) showed that by administering an anti- inflammatory medicine for three plus years at an appropriate dosage, we could reduce the number of heart attacks and strokes significantly. Using a monoclonal antibody, “Canakinumab” at 150 mg every third month they treated inflammation and reduced the number of events. The downside was the annual cost of this medicine currently stands at about $200,000 per year making it unavailable for most of us.

The surprising and startling finding was that it reduced lung cancers by 70% and other malignancies as well. The true finding in this study may be its use as a cancer weapon in the future. The study truly opened the door for research into new and less expensive approaches to treating inflammation. It validated inflammation as a pathway to vascular disease. Now we need to find a way to make that treatment affordable to all.

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HDL Cholesterol: The Good Cholesterol Can Go Bad

CholesterolWhen discussing lipids and cholesterol the public, in particular, has been educated to the fact that the cholesterol is divided into several different types based on where it settles in a test tube after being spun in a centrifuge. The good cholesterol or HDL (high density lipoprotein) is said to be healthy and protective while the LDL (low density lipoproteins) are felt to be detrimental to your health. For years now we have been striving to lower the LDL cholesterol by eating correctly, exercising and when necessary taking medications such as statins.  At the same time we are trying to raise our HDL, or protective cholesterol, by exercising.  The higher your HDL cholesterol is, and the lower your LDL cholesterol is, your risks of not having a cardiovascular event improve.

In reality we know that HDL cholesterol carries bad cholesterol away from the blood vessel walls and deposits it in the liver where it is broken down and removed.  HDL is like a convoy of trucks ferrying your cholesterol away from vital places. The LDL cholesterol does just the opposite, carrying unwanted lipids to the vessel walls and depositing them there. 

 Just when we were getting comfortable with this concept, researchers at many institutions were able to break the LDL or bad cholesterol down into even more discrete groups. Apparently the large fluffy type of LDL is now considered beneficial. At the same time they have broken the HDL or protective cholesterol down into smaller divisions with some types being “broken” and causing inflammation in the artery walls leading to heart attacks and strokes. 

 Dr. Stanley Hazen, MD of the Cleveland Clinic’s Lemer Research Institution is one of the cardiologists promoting the concept of existing “broken” HDL which is damaging to our vessels and bodies.  Hazen’s research shows that in people with heart disease, about 1 in 5 HDL particles in the artery wall are dysfunctional.  People who have more of this dysfunctional HDL are at higher risk of heart disease, independent of the well-known risk factors such as age, diabetes, smoking and blood pressure.  This dysfunctional HDL is very hard for a lab to detect. 

 Dr. Hazen was part of a team that developed the MPO or myeloperoxidase blood level as a marker of plaque buildup in artery walls as a result of dysfunctional HDL and other risk elements.   High myeloperoxidase levels are associated with inflammation and damage to the vessel walls resulting in increased risks of heart attack and stroke.  The MPO test is licensed and copyrighted to the Cleveland Clinic and only available through the Cleveland Heart Labs program.

 We offer the Cleveland Heart Lab panel of tests as part of the cardiovascular risk assessment we present to individuals who do not have cardiovascular or cerebrovascular disease.  It is the only panel of tests that offers the Myeloperoxidase Level.  If interested please ask about this panel at your next visit.

Inflammation and Vascular Disease

Heart, stethescopeI was privileged to hear Bradley Bale, MD and Amy Doneen, MSN, ARNP talk about the development of coronary artery disease and cerebrovascular disease in patients with low or few cardiac risk factors.  They cited American Heart Association studies looking at groups of men and women between ages 45 and 65 who have their first heart attack or stroke despite being in compliance with suggested lipid and blood pressure guidelines. They pointed out that the first Myocardial Infarct or Stroke occurred in 88% of women who met lipid guidelines and 66 % of men.  These are people who do not smoke, do not have untreated or uncontrolled lipid levels, are not diabetics and who lead an active life style.  They asked “why”?

Dr. Bale and Ms. Doneen work with the well respected cardiovascular Center of Excellence at the Cleveland Clinic program in Ohio, and believe that inflammation is the root of the problem.  They believe that soft plaque composed of lipids and other cells lurks beneath the endothelial cells lining blood vessels. In the presence of inflammatory stimulants, this soft plaque ruptures suddenly through the endothelial level into the blood stream. When it comes in contact with the blood flowing through the vessels the body believes we are bleeding and cut and chemical mediators are released that initiate the formation of a clot. When this clot occurs in a small coronary artery we have a heart attack or myocardial infarction or precipitate a lethal irregular heartbeat. When this clot occurs in the blood vessels of the brain, we have an acute stroke or cerebrovascular accident.

The key to prevention in the so called low risk patient is to detect the inflammation in advance, and treat it. They are firm believers in performing B Mode Duplex ultrasounds of the carotid arteries in the neck to look for the presence of soft plaque beneath the endothelial cell lining. This soft plaque is distinctly different from the safe but calcified plaque we can see on CT scans used for cardiac scoring studies.  They couple this imaging study with a series of complex blood tests which identify inflammation. These include a myeloperoxidase level, the Lp-PLA2 level, the urine microalbumen to creatinine ratio, a F2-IsoPs level and the cardiac specific CRP level.

These tests and studies in combination with a traditional history and exam, sugar and lipid levels and EKG can help us identify those “low risk” patients who actually are high risk for a heart attack or stroke. The cause of the inflammation is often difficult to spot and may be in your mouth with dental or periodontal disease or in your joints with inflammatory arthritis.  Patients with excellent dental hygiene and normal appearing gums may harbor specific inflammatory bacteria that put them at risk. While this seems a bit forward thinking, remember we once questioned the research that showed that bacteria (H Pylori) caused gastric ulcers and intestinal bleeding.

I have begun instituting the inflammatory blood marker panels in my practice. Labs are sent to the Cleveland HeartLab for this purpose. I will be initiating periodic carotid ultrasound studies for the appropriate patients in the coming year.

It is often difficult for clinicians to distinguish snake oil sold for profit from cutting edge science. I have tried to spare my patients from worthless but profit driven products. I am convinced the Cleveland Clinic is just ahead of the rest of us in offering these services and I will make them available to the appropriate patients and will do it in a financially structured manner that does not add out of pocket cost to the patient. It’s not about adding another profitable income stream to the practice. It’s about identifying individuals who shouldn’t have a heart attack or stroke before they do.

Pradaxa: More Concerns. More Myocardial Infarctions?

Pradaxa is part of a new group of anticoagulants (thrombin X inhibitors) that eventually will allow anticoagulation by the pill route without requiring patients to alter their food and medication intake and avoid foods and medications that interfere with the anticoagulant as patients must do with Warfarin. Pradaxa additionally eliminates the need to take blood tests (INR/ PT) to monitor the dosage as one has to do with Warfarin (Coumadin).

There is a large commercial advertising campaign underway on TV and print media to encourage patients with atrial fibrillation to ask their doctors to switch them from Coumadin to Pradaxa (Dabigatrin).  The campaign bases its claims on the RE-LY trial of 18,000 patients at 80 medical centers throughout the world who took the 150 mg dosage and had significantly fewer strokes than patients taking Warfarin.  The original study was criticized because many of the patients in the Warfarin (Coumadin) group were not on enough Warfarin or at a therapeutic PT/INR to prevent embolic strokes so the comparison with Pradaxa may not be valid. Another criticism involved the fact that Pradaxa can cause major bleeding and there is no antidote to stop the bleeding. Patients on Pradaxa who are bleeding are advised to undergo hemodialysis to remove the drug from their system because there are no medications or treatments available to stop Pradaxa related bleeding.

One wonders how the Food and Drug Administration approved this product for general use under these circumstances without conducting further testing?  The issue becomes even more confusing with the addition of data presented by Ken Uchino, MD, and Adrian Hernandez MD, PhD of the Cleveland Clinic in the online version of the Archives of Internal Medicine. They claim that by reviewing the RE-LY data there is a 38% relative increase in the risk of a myocardial infarction (MI) or heart attack in the Pradaxa group. In an accompanying editorial in the same journal, clinicians at the Hadassah- Hebrew University Medical Center in Jerusalem wrote, “The robust finding that Dabigatran is associated with increased rates of MI (heart attack) is alarming and emphasizes the need for continued critical appraisal of new drugs after phase III trials.”

In my practice I generally will not switch to a new or controversial medication until it has been on the US market for at least one year. I make exceptions for orphan drugs, products to treat incurable diseases with no other choices available. The 12 months gives the medical and scientific community a chance to see how the medication performs and what unexpected adverse effects may be associated with it.

Thrombin X inhibitors are the wave of the future. With no way to stop the bleeding, and data on their safety and efficacy still accumulating, they are just not ready for prime time yet.