Inflammation and Increased Risk of Cardiovascular Disease

For years, experts have noted that up to 50% of men who have a heart attack do not have diabetes, high blood pressure, high cholesterol, do not smoke and are active. This has led to an exploration of other causes and risk factors of cardiac and cerebrovascular disease.

In recent years, studies have shown an increased risk of cardiovascular disease in patients with rheumatoid arthritis, in untreated psoriatic arthritis and in severe psoriasis. We can also add atopic eczema to the list of cardiovascular risk factors.

In a publication in the British Medical Journal, investigators noted that patients with severe atopic eczema had a 20% increase risk in stroke, 40 – 50% increase risk of a heart attack, unstable angina, atrial fibrillation and cardiovascular death. There was a 70% increased risk of heart failure. The longer the skin condition remained active the higher their risks.

The study looked at almost 380,000 patients over at least a 5 year period and their outcomes were compared to almost 1.5 million controls without the skin conditions. Data came from a review of medical records and insurance information in the United Kingdom.

It’s clear that severe inflammatory conditions including skin conditions put patients at increased risk. It remains to be seen whether aggressive treatment of the skin conditions with immune modulators and medications to reduce inflammation will reduce the risks?

It will be additionally interesting to see what modalities cardiologists on each side of the Atlantic suggest we should employ for detection and with what frequency? Will it be exercise stress testing or checking coronary artery calcification or even CT coronary artery angiograms? Statins have been used to reduce inflammation by some cardiologists even in patients with reasonable lipid levels? Should we be prescribing statins in men and women with these inflammatory skin and joint conditions but normal lipid patterns?

The correlation of inflammatory situations with increased risk of vascular disease currently raises more questions with few answers at the present time.

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.

Exercise Induced Muscle Soreness May Not Benefit from Regular Use of NSAID’s

The June 11, 2012 issue of MedPage carries coverage of the meeting of the European League Against Rheumatism where work by Matthias Rother, MD, PhD suggested that taking Ketoprofen or even Celecoxib (Celebrex) for exercise induced muscle soreness may not be a great idea.

The study looked at 64 healthy volunteers who were asked to walk down stairs totaling 400 vertical meters – similar to walking all the way down from the top of a 100-story building.  Forty of the volunteers were randomized to take 200 mg of Celebrex or a placebo twice a day. Twenty-four of the participants were randomized to take Ketoprofen or a placebo.

The patients in the Ketoprofen reported no improvement in pain.  In fact, their pain lasted longer (122 hours) than the placebo groups pain (105 hours).  Patients taking the Celecoxib had a mild pain improvement – so mild that it was not felt to be statistically significant.  This led the researchers to conclude that NSAID’s did not provide significant pain relief to justify their use in post-exercise muscle soreness. They went on to say that muscle inflammation and soreness are part of the inflammatory reaction following exercise that is “essential for recovery.”

This was a small study and it is hard to conclude anything. I will still recommend RICE therapy (Rest, Ice, Compression, Elevation) immediately following post injury or exercise.  Celecoxib (Celebrex) did reduce pain by 12- 13%, so, possibly the dosage and frequency of administration of the NSAID needs to be looked at as well. If my patients do not have a medical reason to avoid NSAIDs, they will still be advised to try them for work and exercise related aches and pains.

Statins Reduce Risks, Even in the Lowest Risk Groups

Current guidelines for the use of statins in the USA (Lipitor, Zocor, Crestor, Atoravastatin, Simvastatin, Pravastatin, etc.) call for only treating individuals who have a ten-year risk of major vascular event of at least 20%.

European researchers including Borislava Mihaylova, MSc DPhil, and colleagues on the Cholesterol Treatment and Trialists Collaborators team writing in the Lancet question whether the guidelines should be changed to treat individuals with even lower risks. Their large Meta analysis suggests that statins provide substantial benefits for primary prevention – especially in patients with a 5-10% ten year risk of a major vascular event. They looked at data from 27 trials including over 175,000 participants. When they took into account cost and side effects of statins, such as muscle pain and inflammation, rhabdomyolysis, diabetes and hemorrhagic stroke, they concluded that the benefits still far outweighed the risks. They think that the clear-cut affect on lower risk individuals coupled with the fact that almost 50% of vascular events occur in patients without previous cardiovascular disease necessitates the broadening of USA guidelines for treatment of patients. The researchers go on to hypothesize that as more generic statins enter the market, cost concerns will become far less of a factor in the decision to treat or not treat.

They noted that for each 1 mmol/L reduction in LDL cholesterol, there was a 21% reduction in the relative risk of major vascular events, and all cause death, irrespective of age, baseline LDL or previous cardiovascular disease.

This research makes it clear that there is great value in assessing the statistical cardiovascular risk of each individual and being more aggressive in the use of statins than current national guidelines call for.  Incorporating risk tools such as the Framingham Risk assessment plus looking at newer techniques such as the measurement of carotid artery intimal thickness may be appropriate in the decision to choose a statin or not.