Marks Daily Apple
Serving up health and fitness insights (daily, of course) with a side of irreverence.
18 Jan

How Might Inflammation Cause Heart Disease?

Despite its obsessive focus on cholesterol levels as the ultimate arbiter of cardiovascular disease, most of the medical field agrees that plenty of other factors also contribute: tobacco usage, psychosocial stress, activity level, and genetic predispositions. In short, a diverse set of lifestyle and genetic factors are consistently associated with cardiovascular disease. This is accepted in the ancestral health community, just as it’s accepted in the mainstream medical community, but the question remains – why? Why does stress contribute to heart disease? How does smoking tobacco increase the risk of heart disease? Why are both the sedentary and the overtrained at a higher risk for heart disease?

Well, as I’m (and others are) quite fond of saying, inflammation is most likely the ultimate cause of heart disease, and all those factors – even some of the genetic ones – are mediated by inflammation. When you get down to it, any explanation of the links between smoking and heart disease, stress and heart disease, exercise and heart disease, cholesterol and heart disease, and even genetics and heart disease must include inflammation to be accurate. As I’ll briefly discuss in the following post, each of these lifestyle and even genetic factors exert much (if not most) of their influence on heart disease via their effects on inflammation.

Let’s explore the evidence for the inflammatory roots of heart disease and continue our discussion of inflammation.


The most common form of tobacco ingestion is smoking – the inhalation of smoked emitted by the burning of dried tobacco. Now, some would argue that it’s the modern processing of tobacco that makes smoking it so bad for us, and that unprocessed tobacco is more benign and results in less heart disease. Or that it’s the modern diet that makes smoking so harmful (see the traditional Kitavans with their moderate smoking habit and apparent lack of heart disease). That’s probably true on some level, but it’s not really within the scope of today’s post. So when I refer to “smoking,” I mean the kind of mass market cigarettes that smokers in the industrialized world use: your Marlboros, your Camels, your Lucky Strikes. The kind that is linked to heart disease.

Plenty of studies show that inhaling incredibly hot, burnt tobacco plant material acutely increases inflammation, quitting immediately lowers inflammation, and recent review (PDF) of the literature specifically causally connects smoking-related inflammation and heart disease. One study even showed that smoking heaps acute inflammatory stress on atherosclerotic plaque, thus increasing the chance of a rupture. And when your atherosclerotic plaque ruptures, or breaks off, the resulting thrombus can lodge itself in the artery and block the blood flow. That, my friends, is a garden-variety heart attack caused by inflammation. Does it get much more cut and dry than that?

It’s also worth noting that smokeless tobacco ingestion, while far from benign, is associated with lower inflammatory markers and less heart disease than smoking.

Stress and Other Psychosocial Factors

Stress comes in many guises nowadays. While Grok had to deal with a few acute, undoubtedly intense psychological stressors, like facing down an opponent or a large animal bearing imposing claws and teeth, he probably didn’t experience the type of chronic, persistent psychological stress “enjoyed” by modern man. We know that psychosocial stress induces a physiological inflammatory response, and just like chronic exercise, chronic psychosocial stress can probably lead to chronic inflammation.

Studies consistently show that folks with higher amounts of psychosocial stress and depression display elevated C-reactive protein and IL-6 levels, both markers of inflammation. They’re also heavier and more likely to be diabetic, which are absolutely confounding factors, but the inflammation/stress association holds even when you account for the other variables. Teasing out cause and effect is probably impossible, but we know that stress, obesity, heart disease, and inflammation are all linked. A further clue may be found among people with anxiety disorders characterized by a heightened inflammatory response to psychosocial stress; commonly, this population experiences a “pro-inflammatory state” and hypertension, both of which are predictors of future cardiovascular disease. Another study found that certain psychosocial factors, like anger and cynicism, were linked to progression of cardiovascular disease.

For a further look at this, check out “The Great Cholesterol Con” by Malcolm Kendrick, who thinks stress is the primary cause of heart disease. I wouldn’t go that far, but it, along with the inflammatory response it engenders, plays a big role. This review paper attempts to explain how psychosocial stress-induced inflammation might lead to heart disease.


In my recent post on blood lipids, I briefly summarized Chris Masterjohn’s ideas about heart disease. Namely, that heart disease is a problem of macrophages (cells that like to gobble up lipids and other things) in the endothelium (arterial wall) receiving oxidized (damaged) LDL and forming atherosclerotic plaque, which is then vulnerable to rupture. Regular LDL is not the issue; only oxidized LDL gets taken up and turned into plaque. Okay, sounds good (or bad), but how does inflammation figure into all this?

The inflammatory response and subsequent oxidative stress load is ultimately responsible for the oxidation of the LDL, while inflammatory cytokines produced at the atherosclerotic site can weaken and loosen the plaque, thus setting the stage for (and even causing) a rupture. In fact, inflammation is intimately involved in nearly every aspect of heart disease.


That was covered fairly exhaustively yesterday, I think, but I’ll throw down the basics. The right type of exercise in the right quantities lowers systemic inflammation, while too much of the wrong kind (or even too much of the right kind) increases it. Both sedentary living and extreme overtraining (PDF) are linked to inflammation and heart disease, and I think poor management of exercise-related inflammation is the key in both situations.

One way exercise can protect against atherosclerosis (and therefore heart disease) is by increasing shear stress on the arterial walls, which causes the endothelium to become less permeable (less accepting of oxidized LDL particles) and produce more nitric oxide (a potent inhibitor of LDL oxidation). You can think of exercise, then, not just as training for your muscles, but also for your arterial walls. It’s enough of an inflammatory stressor to induce an adaptive response. Of course, too much shear stress can be too inflammatory and might actually cause atherosclerosis to progress.


Familial hypercholesterolemia, a genetic variant that reduces the activity of LDL receptors and increases the susceptibility of LDL to oxidation, is famously linked to increased rates of heart disease. This doesn’t actually increase the inflammatory response, but it does mean that folks with FH are generally more vulnerable to oxidative damage from the inflammatory response, simply by virtue of their LDL particles spending more time in the blood.

There is another genetic predisposition that directly alters the inflammatory response and appears to increase the chance of developing heart disease (and other diseases): a single nucleotide polymorphism (SNP, remember those?) that changes the amount of IL-6 (interleukin-6, an inflammatory cytokine that I’ve mentioned before) secreted during the inflammatory response (PDF). People with this SNP secrete more inflammatory IL-6 than people without it, and they tend to have higher rates of cardiovascular disease.

I hope this was helpful, and that it drives home just how important – vital, really – the management of inflammation is to heart health. Hopefully now you have something to hand out when people raise eyebrows at your insistence that inflammation is the real cause of heart disease, rather than “cholesterol” or “all that bacon.” They may not all listen or read what you give them, but someone will. And who knows? You might just change a person’s life.

You want comments? We got comments:

Imagine you’re George Clooney. Take a moment to admire your grooming and wit. Okay, now imagine someone walks up to you and asks, “What’s your name?” You say, “I’m George Clooney.” Or maybe you say, “I’m the Clooninator!” You don’t say “I’m George of George Clooney Sells Movies Blog” and you certainly don’t say, “I’m Clooney Weight Loss Plan”. So while spam is technically meat, it ain’t anywhere near Primal. Please nickname yourself something your friends would call you.

  1. Thanks for the inflammation post, it’s something people should be more aware of. I just wanted to add something for you to think about, if you are doing full body natural movement in alignment (not running on a elliptical trainer or treadmill,that is not natural) you don’t need to do CV workouts, in fact CV can cause more damage to the arteries if you are not in alignment (it’s a matter of blood geometry). Optimal blood geometry and having your muscles at the correct length are extremely important to CV health and decreasing inflammation. If your alignment is off, turbulent flow is created (just like with smoking and stress) the blood cells then scar the inside of your blood vessels and your body repairs the area by patching it up with cholesterol, which leads to plaque.

    Barbara wrote on January 22nd, 2012
  2. Mark’s guidelines for healthy living are spot on, but if you are suffering from a disease that involves chronic inflammation (sarcoidosis, rheumatoid arthritis, inflammatory bowel disease, etc) you may need to remove the source of infection that is causing the inflammation (ie: gum disease). I am being treated for chronic inflammation with the Marshall Protocol. But it is not a quick fix.

    sean wrote on January 23rd, 2012
  3. While this article, like most on this site, is in general very good, the point about stress is quite off the mark. So far in fact that it is a terribly outdated view when the medical research is examined. One only has to look at the award to Warren and Marshall (not the same referenced in the Marshall Protocol) of the Nobel Prize in 2005 for the discovery that peptic ulcers were caused by bacteria living in the stomach, something which the medical community previously believed impossible and so attributed the cause of the illness to the vague term “stress”.

    Stress has been used this way by the medical and wider community for decades. Stress is nothing more than a causal dumping ground for occurances which can’t be otherwise explained by the state of medical research at the time.

    Thinking of stress in this way is dangerous, as it takes the focus away from examining other aspects of lifestyle and diet, that will inevitably be revealed in time to be responsuible for the condition being observed. Far better that we state that the cause of a certain condition is unknown at present, than lump it in with the vague and unhelpful term “stress”.

    If past advancement in research is any indicator (and it most certainly is) then one would expect that by the middle of this century, the concept of stress will be resigned to the area of medical curiosity and ridicule with which we hold the likes of medieval blood-letting. Let’s face it, it’s about as useful.

    Jeff wrote on January 24th, 2012
  4. just found the site and am going through the 1st 7 emails. I enjoyed good health until suddenly 5 years ago went into a-fib and got some heart failure as a result. My 100 hr/wk job certainly contributed. anyway, long story short…I’m on the usual collection of heart meds and an attempt to cure the afib by going inside the heart failed because I have scar tissue throughout my atria – possibly due to Rheumatic fever I had as a kid. I’m taking 4g high DHA fish oil and 2000 units D3 daily and trying to get my diet over to the anti-inflammatory side. I’m not inclined to quickly start shedding prescribed drugs but am looking for guidance on how to improve my long term outlook and what to look for specifically to work with my doctors to reduce some of the meds over time. My BP and cholesterol numbers have been great for years…they’re not the source of the problem, but how do I reduce scar tissue buildup in my heart? Any help GREATLY appreciated

    Mike wrote on January 25th, 2012
  5. My Husband has been on the Primal diet for several months, had a blockage and stent placed in heart 2 years ago . . . recently had his blood work done and doctor is freaking out about 131 LDL, 84 HDL; Triglycerides 68 and now is adamant about going veg/grain again. Any resources or helpful links/words???

    Sue OBryan wrote on July 16th, 2012
  6. Speaking of inflammation as the real cause of heart disease, here is an article written by a surgeon who has been practicing for at least 25 years and operated on over 5,000 patients with heart disease. Some things may sound quite familiar to the Primal community here!

    Kevin Grokman wrote on January 23rd, 2014

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