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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Hypertension- Maybe Your Blood’s too Thick

BLOOD PRESSURE CHECK

While watching the documentary Forks Over Knives I heard a physician explain that it was possible that a vegan diet may lower blood pressure by lowering the blood viscosity (thickness). He stated this in passing but to me it was earth-shaking. I have had thousands of patients with high blood pressure and am treating it on a daily basis. I have sat through countless lectures on hypertension and still to this day we do not really know what causes it. The leading explanations include increased sympathetic activity (think high adrenaline, anxiety), decrease kidney function with age, increased hormone called angiotensin II, or complex interaction of genetic factors. However all of these fail to really explain why obesity, inactivity and diet raise blood pressure.

When I heard that it could be the viscosity (thickness) of the blood I was overwhelmed by the simplicity of it. If the blood is thicker it will take higher pressures to move it. Think of the pressure needed to move water through a pipe as opposed to oil. Thick liquids are harder to move though pipes so a higher pressure is needed. So maybe that is why we are having such a hard time finding a cause for high blood pressure. Because we view it as the problem. However, high blood pressure may not be a problem at all, but instead is the body’s adaptive response to keep the blood flowing when it gets thicker. The problem may be thick blood. However, none of the medications in my arsenal for hypertension treat high viscosity.

As usual I went to the research to see what foresighted researcher was working on this question. And yet again I found that it was looked at LONG ago. In 1981 in the American Journal of Medicine Dr. Letcher et al. showed a direct relationship between blood pressure and blood viscosity. As the blood gets thicker the blood pressure goes up. And those patients with high blood pressure have high blood viscosity. This correlation was further supported by another study by Dr. Letcher in 1983 published in the journal Hypertension.

It seems armed with this information pharmaceutical companies would have marched forward to find the magic drug to decrease blood viscosity and researchers would be toiling night and day to find the underlying cause of the high viscosity blood. However, that did not happen. Today hypertension drugs mostly act by dilating blood vessels (making the pipe wider) or decreasing the pumping action of the heart to decrease the pressure. This does give health benefits likely because it decreases the shear forces on the walls of the vessels. However, none of these medications fix the underlying issue that the body may have been trying to overcome, pushing thick blood around effectively.

And despite there being a simple test to measure blood viscosity it is rarely used and when it is it is not for hypertensive patients. In fact in all my years of practicing medicine I can only think of one patient who had their blood viscosity checked.

One of the culprits that may be causing this increased blood thickness is fibrinogen, a protein involved in the formation of blood clots. Fibrinogen seems to be closely correlated with blood viscosity and it is logical that blood clotting agents may thicken the blood. Also, it is known that a vegan diet lowers your levels of fibrinogen so this may be the pathway through which a vegan diet lowers blood pressure. Also, smoking is shown to raise fibrinogen levels and smoking raises blood pressure. Also there is a class of cholesterol medications called fibrates that are known to decrease fibrinogen levels and studies have shown that they also lower blood pressure.

I can attest personally to the blood pressure lowering effects of a vegetarian diet. My mother has very high blood pressure (she was 220/110 when she was diagnosed). She is on 4 separate blood pressure medications. I had this tendency as well and would run high even in college, my blood pressure was close to 140. After watching a documentary and hearing a piece on NPR about the conditions at cattle and pig farms and slaughter houses I decided to be vegetarian. Within months my blood pressure came down to an average of about 115.

To leave the question of what causes high blood pressure unanswered when the explanation may be so close at hand and has already been put forth 30 years ago seems negligent. Millions are suffering with high blood pressure and resultant strokes and heart attacks. If we could find the answer and a treatment that fixes the true underlying cause, the potential benefit to society and savings to our healthcare system would be almost impossible to measure.

Here is another great article summing up the research. Well what little there is.