Life Extension Magazine August 2009
Understanding Risk Factors for Heart Disease
Part I: Lipids and C-Reactive Protein
By Dr. William Davis
A return-to-basics discussion about the tests that predict risk for heart disease—and what nutritional supplements help correct them
Well before coronary heart disease itself gets underway, so-called risk factors for heart disease declare themselves. Atherosclerotic plaque initiates and grows for good reason. Risk factors identify some of those reasons.
This is the role of risk factors: To provide an indication that potential for atherosclerosis is present.
If you’ve become a bit confused about this conversation over the past few years, you are not alone. Controversy over the importance of risk factors, the overselling of cholesterol drugs, and the emergence of newly identified risk factors for heart disease has made this a rapidly changing, and often difficult to follow, discussion.
The understanding of risk factors for heart disease has come a long way since the 1940s, when it was not at all clear just what aspects of diet, lifestyle, or genetics lay behind the disease. Even cigarette smoking was still being advertised as a healthy habit: “Camels: Smoked by more doctors than any other brand!”
But, even after nearly 60 years of research and heated debate, there is not uniform agreement on what causes heart disease. We’ve zigzagged around the role of diet, cholesterol, and fats, while newly appreciated phenomena like inflammation, genetic factors, and vitamin D deficiency emerge and even further transform the discussion.
We might regard it as 60 years of confusion—or 60 years of wisdom gained. Despite the controversies and persistent uncertainties, surely there are some nuggets of wisdom to be learned.
Risk factors: One at a time
Let’s begin with the four common values present on the standard lipid panel.
LDL cholesterol has become a frequent fixture in the modern lexicon, a topic as common as money and the weather. It has also proven to be the number one most profitable entity—ever—for the drug industry. While this flood of revenue has driven enormous research (and marketing) efforts, it has also served to muddy the waters of truth, since much research behind LDL cholesterol is drug industry-driven and paid-for.
LDL cholesterol is one of the four values provided on any standard cholesterol panel. It is meant to reflect the amount of cholesterol present in the low-density fraction of lipoprotein blood particles (as opposed to those in the high-density fraction, or HDL). It is the basis for most conventional predictions of heart disease risk, since it has been statistically connected to occurrence of heart attack and is recoverable from atherosclerotic plaque when examined.
It is often called "bad" cholesterol, since the higher the LDL, the greater the likelihood of cardiovascular events like heart attack, an observation documented repeatedly from the Framingham Study to other populations.2-4 Despite the controversies the drug industry has created by its overenthusiastic marketing of the LDL-reducing statin drugs, reduction of LDL cholesterol, whether with statin drugs, diet, fibers like oat bran or ground flaxseed, or other strategies (see below) has been confidently tied to reduction in heart attack.5
But there are some limitations.
While LDL is a predictor of heart disease, it is far from a perfect predictor. High LDL cholesterol doesn’t always mean risk for heart disease; low LDL cholesterol doesn’t necessarily mean low risk for heart disease. Most people are unaware that LDL cholesterol is a calculated value, not measured. It is obtained by subtracting measured HDL and triglycerides from total cholesterol, based on an equation developed in the 1960s by Dr. William Friedewald at the National Institute of Health. Because it is calculated, LDL is frequently inaccurate, not uncommonly under- or over-estimating the true value by 50% or more when compared to more accurate measures (like apoprotein B or LDL particle number obtained through lipoprotein testing).6 Nonetheless, calculated LDL is, at least, a reasonable starting place to gauge risk, meaning, the lower the LDL, the better.
Several foods and supplements can be used to reduce LDL cholesterol:
All of these strategies reduce the entire range of LDL cholesterol particles, big and small. However, there are also strategies that reduce the most dangerous small LDL preferentially. That will be a topic for future discussion.
Total cholesterol is a source of great confusion, but one that seemingly has cast an indelible impression on the minds of most Americans.
That’s because the conversation on the dangers of high cholesterol—in both the blood as well as in diet—was the focus of early conversations dating back to the 1950s and 1960s. Back then, you had high cholesterol or you didn’t; the discussion did not include the various sub-fractions of cholesterol like LDL and HDL. It was just total cholesterol.
But total cholesterol is (and always has been) a composite value, a combination of undesirable fractions (LDL and triglycerides), as well as desirable (HDL). Does high total cholesterol therefore represent high LDL cholesterol (bad) or high HDL cholesterol (good), or some combination? Does low total cholesterol signify low LDL cholesterol or low HDL cholesterol? Total cholesterol is a flawed value that often clouds the significance of cholesterol issues, rather than clarifying it.
There is no doubt that total cholesterol does, in a broad population, correlate with heart attack and other cardiovascular events.9 Total cholesterol >240 mg/dl, for instance, carries a three-fold increased risk of cardiovascular events compared to people with total cholesterol <210 mg/dl.2 However, total cholesterol is a miserably inaccurate value when applied to a specific individual, whose total cholesterol can mean a number of different things. We’ve all known someone with high cholesterol who has never suffered any evidence of heart disease, or someone with low cholesterol who has. Cholesterol is a flawed measure of hidden heart disease in any specific individual at any one point in time. This flawed measure is also the value often cited by critics of the lipid hypothesis—and they’re right.
Clouding the issue further is the early concern that cholesterol in foods will increase blood cholesterol—makes sense, doesn’t it? However, this phenomenon has since been shown to exert only modest blood cholesterol-increasing potential.10 Dietary cholesterol, because of inefficient absorption, does not appreciably impact on blood cholesterol.
High-density lipoproteins (HDL)
Subtract the cholesterol contained in LDL, along with the cholesterol in the very low-density lipoprotein fraction (VLDL, represented by triglycerides) and you’re left with HDL cholesterol. But the cholesterol from HDL is different.
Greater levels of HDL are protective because this particle removes cholesterol from vessel walls and carries it to the liver for disposal, a processed called “reverse cholesterol transport,” sort of like traffic flowing in the opposite lane. For this reason, HDL is often called "good" cholesterol.
Plenty of studies have demonstrated, beyond any doubt, that the higher the HDL, the less the risk for heart attack and other cardiovascular events. While we need more clinical data on the benefits of increasing HDL (or, perhaps, its reverse cholesterol transport capacity, or some fraction of HDL), studies like the VA-HIT show that cardiovascular events are reduced 11% for every 5 mg/dl increase in HDL (with the drug gemfibrozil, in this study).11
More than high LDL, low HDL values are common in people with heart attacks and heart disease. In fact, even the Framingham Study has determined that, more than LDL, low HDL is a better predictor of future heart attack.12 Unfortunately, due to the dominance of statin cholesterol drugs to reduce LDL, HDL is often neglected in clinical practice.
The most important fraction of the HDL family is large HDL, sometimes called “HDL 2b,” the most active in removing cholesterol (“reverse cholesterol transport”). The large fraction is commonly deficient when total HDL is less than or equal to 60 mg/dl. Treatments that increase total HDL tend to shift particles towards the large fraction, as well.
Both total and large (HDL2b) HDL can be increased with: