Cholesterol and Heart Disease: What's the Real Link?

Correlation is not causation.

Posted Aug 22, 2018

The general picture, then, is that the blood cholesterol level is independent of the intake over a wide range” ~Ancel Keys; “The Relation in Man between Cholesterol Levels in the Diet and in the Blood,” Science (1950).

The causal role of cholesterol in the development of heart disease has its origins in the so-called cholesterol hypothesis. This was the idea, championed by Ancel Keys beginning in the 1950s, that elevated blood cholesterol levels were the singular causal agent responsible for the development of atherosclerosis and subsequently cardiovascular disease. As noted above, Keys himself could find no significant link between dietary cholesterol intake and adverse outcomes related to blood cholesterol levels. This despite the fact, that some participants were consuming the equivalent of 3,000 mg of cholesterol per day; the equivalent of about 16 eggs.

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Even Keys recognized there is no association between dietary cholesterol and blood lipids
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In 1952, Keys changed tactics and instead focused on the dietary intake of fat, particularly saturated fat of animal origin. This ultimately, became the dietary saturated fat causes heart disease mantra that still haunts every dinner table in the modern Western world like the ghost of Christmas past (for more detailed discussion on the saturated fat hypothesis, see Food Shaman: The Art of Quantum Food). What is little appreciated, is that the motivation for such inquiry began with a simple observation.

Following World War II, there was a huge increase in the incidence and prevalence of heart disease in the United States. Meanwhile, on the war-ravaged European continent, such an epiphenomenon was distinctly absent. Little considered in the equation at the time, or since, is the striking fact that at this point in history, both the food and the food pathways of the United States were in a period of tremendous transformation. The drive through at the Temple of Convenience was open, and the marketplace and supermarkets were now overflowing with processed and soon to be ultra-processed offerings.

These fundamental changes to the quality of various comestibles was distinctly missing in Europe at the time; although they would proceed to quickly catch up in the decades that followed. This is evidenced by the observations and subsequent recommendations of Ancel Keys at the time. His visit to Crete – primarily during the period of Lent – yielded what has become to be known as the Mediterranean diet. What he observed was a diet based primarily on fresh local ingredients; olive oil, fruits, vegetables, and seafood (the lack of red meat is not particularly surprising on Crete at this time of year given its high population of Orthodox Greek Christians).

Fast-forward to the present where cholesterol reduction, mostly through pharmacological mechanisms like statin medications, is a mainstay of both primary and secondary prevention. The decisions to initiate treatment and adjustment of the dosing regimens are primarily guided by measurable low-density cholesterol, or LDL-C blood levels. This, despite the fact that statin medications are known to have a number of pleiotropic effects; anti-inflammatory being chief among them.

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For the sake of convenience, we have forsaken a foundation in wholesome, quality, real foods
Source: Copyright Red Tail Productions, LLC

Current guidelines assess a number of cardiovascular risk factors and LDL cholesterol is among them. Generally, an LDL-C of 190 mg/dL (milligrams per deciliter) or more alone is enough to award you a statin prescription. Now a recent study has suggested that those individuals with an LDL-C of 160 to 189 mg/dL should also be started on a statin medication. This would currently subject approximately 13% of the population of the United States, or roughly 50 million people, to additional pharmacologic therapy.

What is particularly striking in this study is what is not mentioned. What many people, healthcare providers included, have failed to appreciate is that looking at risk over a ten-year period finds that there is no correlation between LDL cholesterol and adverse cardiovascular outcomes. It is only over much longer time periods, in this particular study the median follow-up was 26.8 years, that the curves based on LDL-C begin to diverge. Interestingly, when looking at all-cause mortality (death from any cause, including cardiovascular disease) there was essentially no difference in the group with an LDL-C < 100 mg/dL versus an LDL-C≥ 190 mg/dL (HR 1.1 (95% CI, 0.93 – 1.3)) over almost 3 decades.

This seems a ridiculously long incubation period if LDL cholesterol were the sole causative agent. It is quite possible, that LDL-C and non-HDL-C (the total cholesterol in all lipoprotein fractions except HDL) levels correlate to consumption of the modern Western diet (for a corollary with sodium, read Salted and Cured).

There is absolutely no doubt that oxidized cholesterol derived from the low-density lipoprotein sub-fractions plays a role in the development of atherosclerotic disease. But if we take as evidence its sole causative role based on the fact that it is present, and a predominant component, of atherosclerotic plaque; then by extension we must also consider other plaque constituents. For example, recognizing the inflammatory cell component of plaques, has led to the understanding of the role of inflammation in a development of atherosclerotic disease.

Recent evidence has confirmed the presence of DNA derived from certain strains of gut bacteria is also present in atherosclerotic plaques found in the coronary arteries of humans with cardiovascular disease. In an attempt to more fully understand the mechanisms by which the many disabilities and diseases we currently confront manifest, we must acknowledge the 800-pound gourmand in the room.

The quality of our dietary choices matter.

The authenticity and naturalness of our foods speaks in a way to our bodies and our gut microbiota (quickly becoming one of the most important arbitrators of health and wellness or disability and disease) in a way that makes artificial categories like calories and percent sat fat irrelevant. Our quantum leap in understanding will only come when we change our perspective from categories to quality. Perhaps then, we may reach the same conclusion as Hippocrates over 2500 years ago, “All disease begins in the gut.”


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