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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Coffee Consumption Lowers Mortality Risk

The online edition of the Annals of Internal Medicine, July 11, 2017 edition published an article from MJ Gunter using data from the European Prospective Investigation into Cancer and Nutrition that concluded that coffee consumption lowered patient mortality. The study looked at more than 520,000 patients from 10 different countries that were followed for 16.4 years. In a side study they looked at a group of 14, 800 patients and examined the correlation between coffee consumption and biomarkers of liver inflammation, function and health.

Patients who drank the most coffee had statistically significant lower all-cause mortality than individuals who did not consume coffee.  Patients in the highest group of coffee consumption tended to have significantly lower risk for mortality related to digestive diseases. Women coffee drinkers had a lower risk for cerebrovascular disease mortality and circulatory disease mortality but were at higher risk for ovarian cancer related mortality.

The researchers concluded, “Coffee drinking was associated with reduced risk for death from various causes.”

I will enjoy my coffee even more now. If only I could lay off the bagels and donuts that go with it.

PPI Use and Death Risk

In recent weeks we have seen articles linking the long term use of proton pump inhibitors such as Nexium (esomeprazole), Protonix ( Pantoprazole), Aciphex (Rabeprazole), Prilosec ( Omeprazole) with an increased risk of community acquired pneumonia, kidney disease, bone disease, cognitive dysfunction and increased risk of clostridia difficile infection (antibiotic related colitis). These drugs are commonly used short-term for the treatment of ulcers, gastro esophageal reflux disease, Barrett’s Esophagus, upper GI bleeding and H Pylori infections.

Often, after the prescribed treatment period, physicians try to discontinue the use of PPI’s but the patients have a return of their symptoms. With these medications now being sold over the counter, it is very difficult to get a symptomatic individual to curtail therapy even if the long-term risk is daunting.

I often attempt to switch patients to “old fashioned” antacids such as Tums, Rolaids, Mylanta, Gaviscon or even the H2 receptor blockers such as Tagamet and Zantac (Cimetidine and Ranitidine). All too frequently the response is that “my symptoms returned and only get better with the PPI.”

A study published in the British Medical Journal looked at data from the Veterans Administration data base for a period of two years, and selected a representative group of PPI users and non-users. They then followed them for 7-8 years.

Patients taking PPI drugs regularly had a 25% increased risk of death. There was no apparent reason why these medications led to a higher death risk. Further studies will be needed. The conclusion is take them for as short a period of time as possible.

Pneumococcal Vaccine in Development May Fight All Strains of the Disease

Community acquired pneumonia (CAP) plus other infections attributable to the Pneumococcus bacteria account for 15 million infections per year including pneumonia, meningitis and bronchitis. The organism is the leading cause of death in children less than five years old.  Over the last 30 years pharmaceutical companies have developed Pneumovax 23 which covers 23 unique bacteria that cause CAP in adults and Prevnair 13 which covers 13 pneumococcal bacterial strains.  Twelve of the bacteria in Prevnair 13 are identical to the Pneumovax 23 with only one unique bacterial type included.

A group at the State University of New York at Buffalo led by Blaine Pfeifer, specializing in chemical and bacterial engineering; has developed a new approach to pneumococcal vaccination. Working with computer modeling and animals to this point, they have developed a successful vaccine that attacks pathogenic pneumococcal bacteria while leaving the beneficial and non-pathogenic subtypes alone. The vaccine reads proteins on the surface of the bacterial cells and destroys only those that show aggressive activity. The vaccine has been 100% effective against the 12 most virulent pneumococcal bacterial strains existing in animal studies.    The vaccine is being prepared for human testing in the near future.  The preliminary work was discussed in the medical magazine Medical Economics

Generics and Therapeutic Substitution – Safety and Efficacy?

Excuse me for being a “doubting Thomas,” but when I saw articles in JAMA Internal Medicine and commentaries supporting use of generics instead of brand name drugs I asked myself “Where is the proof of equivalent results and safety?”.  Generic substitution implies that the original product is no longer patented and exclusive and another firm is now producing an identical chemical version which produces the same beneficial effects on the patient.  Therapeutic substitution means your pharmaceutical insurance company or pharmacy changes the drug you are prescribed to one in the same drug class. Think of drinking Coca Cola and having the supermarket substitute a comparable brand instead.

The reason for this is simply to spend less money. Many pharmaceutical insurance companies realize if they put an obstacle in your path of obtaining your medication you likely will pay for it independently saving them money.  The authors of the JAMA articles estimate between 2010 and 2012 therapeutic substitution would have saved $73 billion. The out-of-pocket savings to the patient would have amounted to $25 billion.

I’m for saving money and spending less with certain guidelines. However; I want to know that a generic medicine is produced in a factory inspected by the Food and Drug Administration (FDA) at least as frequently as the drugs produced in North American factories. I like to know where the drug was made including country of origin, city, location and the plant’s track record for health and safety. I also want to know the generic medication produces the same drug levels and positive effects as the brand name medication and is made with no more contaminants than the original branded product.

I need reassurance that my patient isn’t receiving a counterfeit product with stolen original labeling, which has been a scam fooling pharmacists and Customs agents for years.   I would additionally like to know that the generic product, or therapeutically substituted product, works as well as the original. We know for example that Levothyroxine generics and substitutions are problematic.  We additionally know that the beta blocker carvidilol (Coreg) has certain unique properties that other beta blockers do not provide making therapeutic substitution for less expensive medications in the beta blocker class problematic.

Once this information is available it should be distributed in package inserts, online and taught in pharmaceutical, nursing and medical school courses as well as CME courses for health care professionals.

There is an abnormally perverse concern that if a pharmaceutical representative takes a health care provider out for a meal and a drink while explaining their product, we will prescribe it even if it is more expensive or doesn’t work as well.  I doubt sincerely that most physicians would do that but do believe if the cost is comparable, or less, and the efficacy is as good, they might choose the product as a viable alternative.

Increased Dementia Risk in Senior Citizens Due to Proton Pump Inhibitors (PPIs)

Brittany Haenisch, PhD of the German Center for Neurodegenerative Diseases in Bonn, has reported in JAMA Neurology, a study from health insurance data suggesting that taking Proton Pump Inhibitors (PPIs) such as Aciphex (omeprazole), Protonix (pantoprazole), Nexium (esomeprazole), and Prevacid (lansoprazole), was associated with a markedly increased risk of developing dementia. The correlation was stronger in men than women with a slightly increased risk for those taking Nexium.

The study, conducted from 2004 through 2011, looked at 73,679 people age 75 years or older and who were free of dementia at “baseline”.  It revealed 29,510 patients (40%) developed dementia and, of these, almost 3,000 (average age of 84) were taking a PPI medication. The authors concluded that avoiding PPIs may prevent dementia.

All of these medicines are now freely sold over the counter not requiring a prescription. Their use has dramatically increased. There is belief from animal studies that PPIs cross the blood brain barrier and effect the production of amyloid and tau protein associated with dementia. In humans, B12 levels can be lowered effecting cognitive ability. None of this data shows a clear cause and effect relationship so we cannot say PPIs hasten the onset or cause dementia. Newer well designed controlled and blinded studies will be needed for this purpose.

In the interim, I will ask my patients to reduce or avoid these medications. We can treat heartburn and indigestion with products such as antacids, weight loss, eating smaller portions and staying upright after those meals, loosening your belt at the waist and avoiding those foods that reduce lower esophageal sphincter muscle pressure leading to reflux.

There will be some with conditions such as Barret’s Esophagus, which is precancerous, and recent bleeding ulcers which require the use of PPIs for eight or more weeks and then switch to Tums, Rolaids, Gaviscon or Carafate. Some patients will need the PPIs for symptom relief beyond eight weeks and they will need to make a tough decision between symptom relief and increased dementia risk while the researchers search for the answer.

High Disability and Death Rates in Bleeds Associated with New Oral Anticoagulants

In the trailer for the movie Jaws 2 they show a swimmer in the ocean with a deep voice saying, “Just when you thought it was safe to go back into the water…” followed by the classic music associated with a shark attack and a big fin approaching the unsuspecting swimmer. I feel much the same way upon reading a Medpage Today online journal review of an article in JAMA Neurology published on December 14, 2015. Jan C. Purrucker, MD and colleagues looked at 61 consecutive patients with non-trauma related cerebral hemorrhages due to the newer oral anticoagulants Pradaxa, Xarelto and Eliquis. Overall there was a death rate of 28% at three months and “two out of 3 survivors had an unfavorable outcome.”

In October of 2015 the FDA approved the use of the antibody fragment idarucizumab (Praxbind) to reverse anticoagulation in patients bleeding from the administration of the oral anticoagulant Pradaxa. There are currently no medications to reverse the bleeding from the drugs Xarelto or Eliquis but we are promised that new products are in development. The article goes on to discuss how physicians have been forced to improvise when patients on these medications show up bleeding. They have tried fresh frozen plasma, 3-factor, 4-factor and activated prothrombin complex concentrates prothrombin complex concentrates, recombinant factor VIIa and cryoprecipitate alone or in combination with marginal success at best.

Despite there being no antidote to these blood thinners, the massive direct to consumer advertising continues on television prime time and magazines as if the products are no more dangerous than an antacid for heartburn. Coumadin or warfarin is the prototype anticoagulant working by inhibiting vitamin K dependent clotting factors. Its effects are reversible with administration of Vitamin K and clotting factors if bleeding occurs. Coumadin requires periodic blood tests (INR) to check on its efficacy and there is a long list of medications and foods that need to be avoided or adjusted while taking it. It is less convenient but safer in the sense that its effects can be reversed with medication.

The newer oral anticoagulants were championed by several studies that suggested that they were more effective in preventing embolic strokes in patients with the heart rhythm atrial fibrillation. Many experts in the field felt that those conclusions were flawed because the Coumadin group was not tightly regulated to keep their INR in a therapeutic non-clotting range thus unfairly biasing the results in favor of the newer agents.

There is no question that the newer agents are more convenient than warfarin treatment, but until there are readily available antidotes, complications seem to be more difficult to limit and control.