Fibrinogen and Fibrates- A New Approach to Preventing Heart Attacks

Coronary angiogram of a man

Coronary arteries

This is revisiting a topic I covered earlier in my post Hypertension Maybe Your Blood’s Too Thick. Basically I reviewed the literature on the topic of viscosity of blood possibly leading to high blood pressure. One key protein that is implicated in thickening the blood is fibrinogen. It is involved in the inflammatory pathways and blood clotting. It seems by research that in normal levels it keeps a good balance of helping the immune system and preventing major bleeding while not causing too many clots or inflammation. But when the level is too high is seems to increase the risk for coronary artery disease leading to heart attacks. A 1999 study Eriksson et al. showed that those in the highest 25% of fibrinogen levels had 3 times the risk for coronary artery disease than those in the lowest 25% even after controlling for other coronary artery disease risk factors. Many other studies have shown the same relationship including Onohara 2000, Bolibar 1993, De Luca 2011, Montalescot 1998, Lima et al 2012, and many more. In fact looking closely at the data fibrinogen is likely a more accurate predictor of risk for heart disease than cholesterol.

So one may ask why isn’t my doctor following my fibrinogen level, and if its high why aren’t they treating it? Well before I would have said because we have no known treatment to lower fibrinogen but then I found data showing this is not true. Multiple studies have shown that the pharmaceutical class of drugs referred to as fibrates do decrease fibriongen. This includes drugs such as fenofibrate and gemfibrozil which are usually used to treat a certain type of cholesterol when it is high called triglycerides. They do this pretty well but studies for outcomes did not show a huge benefit therefore they are not commonly used. However, they have never been tested in patients with high fibrinogen, they have only been studied in patients with high cholesterol or triglycerides. As far back as 1999 de la Serna et al. showed that fenofibrate decreased fibrinogen by 15%. In fact there was a study as far back as 1989 by Leschke et al showing that fenofibrate dropped fibrinogen levels from a mean of 300 to 250. They also showed a significant improvement in blood viscosity and using myocardial scintigraphy (a study to look at blood flow to the heart) they showed an improvement in blood flow to areas of the heart that previously were not getting adequate blood flow in all subjects they evaluated. It was however a small study. This drop in fibrinogen is not seen with statin drugs which are the most commonly used cholesterol drugs today.

And then of course there are the always forgotten and neglected natural medications. A 2009 study by Hsia et al. showed that nattokinase (a supplement derived from fermented soy and commonly used in Japan) can decrease fibrinogen levels by 9%. And a recent rat study May 2013 by El-Sayed et al showed curcumin (the ingredient believed to be the main active ingredient of turmeric) can decrease fibrinogen along with multiple other cardiovascular risk factors as well.

There are many more studies, too many to cite them all. Given the vast amount of data we have and considering that it goes back as far as the 1980s it is way overdue to do a study where we take a group of patients with high fibriongen levels and radomize them to fenofibrate (or another fibrate, or curcumin or nattokinase) and see if they get a significant drop in fibriongen. Then more importantly follow them to see if that translates into a significant decrease in the risk for heart attack and/or stroke. Given that fibrinogen is intricately involved in inflammation and blood clot formation it only seems logical that reducing it would translate into huge health benefits. It’s about time to find out if we should be more concerned about our fibrinogen level than our cholesterol.

References

Studies showing relationship of fibrinogen to coronary artery disease

http://www.ncbi.nlm.nih.gov/pubmed/9888868– Eriksson et all.

http://www.ncbi.nlm.nih.gov/pubmed/11129810 – Onohara et al.

http://www.ncbi.nlm.nih.gov/pubmed/8498300 – Bolibar et al.

http://www.ncbi.nlm.nih.gov/pubmed/21080031– De Luca et al.

http://www.ncbi.nlm.nih.gov/pubmed/9717059, Montalescot et al.

http://www.ncbi.nlm.nih.gov/pubmed/23049444, Lima et al.

Fibrates and fibriongen

http://www.ncbi.nlm.nih.gov/pubmed/10460070 – de la Serna et al

http://www.ncbi.nlm.nih.gov/m/pubmed/2731478/– Leschke et al

Natural supplements and fibrinogen

http://www.ncbi.nlm.nih.gov/pubmed/19358933– Hsia et al

http://www.omicsonline.org/efficacy-of-curcumin-in-reducing-risk-of-cardiovascular-disease-in-high-fat-diet-fed-rats-1948-593X.1000082.php?aid=16486– El Sayed et al.

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Back Pain- There has got to be a better option

Back pain

Chronic back pain is one of the most common and debilitating medical issues and study that was published in JAMA showed that it is increasing. In 1996 the rate was about 4% and by 2006 it was up to 10% of people over the age of 21. This likely has many factors contributing including the increasing rates of obesity, more sedentary life styles and overall poor health and diet. And despite how common and debilitating this problem is the treatments have changed very little over the last couple decades. Still to this day we treat with physical therapy and pain medications and if that doesn’t work the next option is surgery. And the number of patients for whom all three of these fail is immense. Daily in my practice I encounter at least one patient with chronic intractable back pain that is still intolerable despite all the efforts by the medical community. So have we tried everything?

Of course eating a healthier diet, getting more exercise and losing weight are all proven ways to prevent and/or treat back pain. But these are of course much bigger issues that we all are struggling with. And of course exercising when you have crippling back pain can be near impossible for even the most motivated individual. This leads to a vicious cycle of less activity, more pain, which means even less activity, causing more weight gain and more pain. So if one does not want to resort to surgery (which a study in 2009 Spine showed little benefit at 1 to 2 years followup) then they are left with physical therapy and nonsteroidal anti-inflammatory medications such as ibuprofen and opiate pain medications. Physical therapy likely does have benefit and has almost no harmful side effects so should be tried by everyone with back pain. However, ibuprofen and other nonsteroidal anti-inflammatory medications are well-known to cause kidney problems and stomach and intestinal ulcers. I have had many patients with life threatening stomach bleeds and some who even had to have part of their stomach removed due to long-term use of ibuprofen for back pain. And as for opiate pain medications, they are sedating, decrease mental clarity, can be addictive and due to tolerance often lose their effect over time. They are a blessing to those who need them, but everyone in medicine is agreed that we would gladly get rid of opiate pain medications if we had an alternative. Some resort to spinal injections of steroids or pain medications. These often have short effect with little long-term benefit and can be very expensive.

So have any safer treatment modalities been tested? Well indeed they have. Multiple articles have looked at Vitamin D for people with back pain. A 2009 article in the Journal of the American Board of Family Medicine showed a clear improvement in back pain in those given vitamin D. Again in 2003 Spine showed 95% of back pain patients reported improvement when given vitamin D. The Scandinavian Journal of Primary Care in 2011 also showed this benefit along with many others. Yet have any large randomized trials of vitamin D for back pain been done? Not that I know of. And despite all the evidence above it is still not standard practice (in fact it is hardly ever done) to check vitamin D levels in back pain patients.

And that’s not all. There was a randomized trial in the journal European Review Medical Pharmacology 2000 that showed a statistically significant improvement as compared to placebo with Vitamin B12. But of course the sample was small, only 60, which only makes it that much more impressive that they reached statistical significance. But a larger trial needs to be done.

Then there is omega 3 fish oils, well-known to have an anti-inflammatory effect. In 2006 in the journal Surgical Neurology a controlled trial showed a 59% reduction in nonsteroidal anti-inflammatory medication (such as ibuprofen) use and a 60% reported improvement in pain with omega 3s.

And then there are the copious herbal supplements used for inflammation and joint pain. I already reviewed the literature for turmeric in a previous post and it is still growing daily. There is also an herbal supplement called Boswellia. In a 2003 article in Phytomedicine in a controlled study it was found to have a statistically significant and impressive improvement in arthritis related knee pain. It has not been studied in back pain specifically that I know of but the causes of joint pain and back pain are very closely linked.

Then there there are the more hands on approaches to back pain such as accupuncture, massage and chiropractic work such as manipulation. Each of these actually has a surprising amount of research on each, however these studies are fraught with one main problem, a lack of a good placebo. There really is no control group in these studies as there is no good placebo for massage, or manipulation. There is a sham procedure used to be a placebo for accupuncture that is pretty good as a placebo but still likely not completely inert. However, of the three, accupuncture definitely has the strongest evidence supporting it. A review of studies in 2008 by Cochran and another great review of 11 randomized controlled trials in 2013 in the Clinical Journal of Pain showed a clearly statistically significant benefit of accupuncture. As for physical therapy, massage and chiropractic manipulation the data is not as impressive but mostly because it is of much worse quality. The initial study in 1996 of chiropractic care by Assendelft showed no significant benefit. A 1998 article in New England Journal of Medicine showed little benefit for physical therapy or chiropractic care. However, mostly the lack of benefit seen was in large part due to poor quality studies. Personally I don’t think it has been proven one way or the other and I feel likely both have some benefit but not significantly so. Likely we will never know as studying these is extremely difficult given the lack of a good control group and reliance on patient follow up and cooperation which will be highly reliant on the severity of the patient’s pain. However, I would highly support massage either way as it seems to fix everything and anyone who suffers wtih chronic back pain deserves a good massage.

Chronic back pain has been plaguing our lives for as long as we have walked upright. And as we live longer and have less active lives and live those lives with more pounds on board the problem will only get worse. We need new treatments desperately. Vitamins, omega 3 fish oils, accupuncture and herbal supplements offer treatments that are far less toxic than the medications used today and may allow a patient to delay or hopefully avoid surgery. And these supplements are far cheaper than many of the medications and certainly cheaper than spinal injections. These need to be studied immediately to offer doctors other options for their patients. And if even one of these is found to be as effective as nonsteroidal anti-iflammatory medications such as ibuprofen the savings to the medical system could easily be in the billions.

Turmeric- Nature’s Ibuprofen, But WAY Better

Turmeric Root

Turmeric Root

Turmeric (a plant often used as a spice that can be found in any grocery store) is likely the most common herbal supplement I recommend to my patients. Non steroidal anti inflammatory drugs (such as ibuprofen, advil, motrin, aleve, aspirin) are some of the most commonly used drugs, both by physicians and over the counter. However, their serious side effects are well known and feared by physicians. They are one of the leading causes of stomach and intestinal ulcers and can cause kidney failure. They are usually safe is short courses but for people with chronic pain it becomes a real problem.

Turmeric however has been used in traditional Indian (Ayurvedic) and Chinese medicine for hundreds (possibly thousands) of years for its pain relieving and anti-inflammatory qualities. A study was done in 2011 in the journal Inflammation that looked at the anti-inflammatory capability of turmeric vs ginger vs indomethacin (a strong non-steroidal anti- inflammatory drug) in treating arthritis in rats. Turmeric actually did BETTER than both of them. And by quite a bit. Its anti-inflammatory capability was 10% better.

And ironically turmeric not only does NOT cause stomach ulcers but actually has been shown to suppress H pylori (a bacteria well know to cause stomach ulcer) and even decrease the risk for stomach and colon cancer in animal studies.

The anti-inflammatory compound that seems to be doing the work in Turmeric is called curcumin. Unlike many herbal supplements LOTS of data already exists on the effects of turmeric, how, and where it acts in the body. Given that it has been used for centuries by traditional Ayurvedic and Chinese medicine doctors a safety record has already been well established. In fact the longest known living population on earth in Okinawa, Japan eats tons of Turmeric traditionally and drink tea made from it. Okinawa has an average life expectancy of 81.2 years as compared to 76.8 in the United States. Also Okinawa has the lowest rates of heart disease, cancer, and stroke.

So we have plant that is cheap, can treat arthritis or any other inflammatory condition, and its main “side effects” would actually be a decreased risk for cancer, heart attack and stroke and increased life expectancy. Oh yeah, and some studies show it may decrease the risk for Alzheimer’s dementia as well.

Despite this impressive record very few physicians know any of this. This needs to be studied and sanctioned as an acceptable treatment now.