The Cholesterol Conundrum
Because aggressively reducing patients’ LDL cholesterol has failed to prevent many cardiovascular events, there’s been renewed effort over the past decade to find better ways to “risk-stratify” patients – especially those at “moderate risk” using the conventional Framingham Risk Score (FRS).
The FRS has been found satisfactory for identifying people at high and low risk for cardiovascular disease, but not as good for differentiating those at moderate risk.
These represent most of the unexpected heart attacks, cardiac arrests, and strokes – about half of which occur in people with normal cholesterol levels.
Even in low and high risk groups, the FRS tends to overstate risk in low risk and understate risk in high risk groups.
This may have something to do with what the FRS excludes (like metabolic syndrome – see Part 2 of this post) and suggests a need for more precise risk screening tools. Additional approaches to assessing cardiovascular disease risk are therefore required, some of which follow.
Know Your Cholesterol RATIOS
More important than absolute cholesterol levels is the ratio of HDL (“good” cholesterol that clears dangerous small LDL particles that easily oxidize, or turn rancid, to form plaque in your artery walls) to either LDL or total cholesterol.
Medical science now recognizes that there’s more involved than simplistic total and LDL cholesterol levels – though much of it has still to reach those laboring in our healthcare trenches.
These largely quantitative measures are a good starting point, but fail to capture the qualitative differences in how LDL and HDL cholesterol actually interact.
It’s these qualitative differences that may explain why so many people are still dying from heart attacks, sudden death, and strokes despite low LDL levels.
Hopefully, this newfound appreciation – still not reflected in mainstream medical practice – will encourage doctors to revisit some treatment assumptions as well (see Our Healthcare Sucks for more on this).
Many doctors, for example, have been reluctant to add fish oil to statin regimens for fear that it will dampen their cholesterol-lowering effects.
While it’s true that fish oil doesn’t lower cholesterol like it does triglycerides, the EPA fatty acids in fish oil have been shown to reduce the oxidation of small LDL cholesterol particles – the most dangerous kind.
This helps the “good” HDL cholesterol to remove these LDL particles before they oxidize, which is crucial since HDL doesn’t work to remove oxidized LDL particles. The EPA in fish oil appears to improve your HDL’s ability to remove excess LDL cholesterol from your bloodstream.
So while it doesn’t lower your LDL or increase your HDL per se, fish oil may increase your HDL’s efficiency by preventing more LDL particles from oxidizing and leaving them available for your HDL to remove before they oxidize and form dangerous plaque.
In other words, it improves your HDL quality independent of any effect on its quantity level in your bloodstream.
WHICH Cholesterol Ratio?
There are a number of alternative ways to evaluate your cholesterol levels that attempt to get at these important qualitative characteristics of your cholesterol. Different ratios are used by different clinicians, so discuss with your physician which may be most relevant to your risk status.
Here are the most commonly employed ratios, starting with the ratio of HDL to LDL:
HDL:LDL over .3 is considered healthy (Example: HDL of 45 and LDL of 110 = .418; over .4 is desirable);
LDL:HDL under 2.5 is considered protective (Example: LDL of 100 and HDL of 50 = 2.0, while an LDL of 150 and HDL of 40 = 3.75 would be a warning sign);
Total cholesterol:HDL under 3.2 – 3.5 is considered healthy. This ratio is easier to use because it’s more common, but it’s less precise than the LDL:HDL ratio.
Examples: Total cholesterol of 210 divided by HDL of 40 = a high-risk 5.25, while total cholesterol of 220 and HDL of 70 = 3.14, considered desirable despite the higher 220 total cholesterol level. The increase in HDL between these two examples more than offsets the lesser increase in unhealthy LDL levels, meaning more HDL is available to better clear out excess LDL cholesterol particles from your bloodstream;
HDL:Total cholesterol –This is the mirror image of the above, with readings over 24% considered protective. Examples: HDL = 40 and TC = 200 for a less-than-optimal 20% reading, meaning you should try to increase your protective HDL and/or lower your TC. An HDL of 50 divided by a 200 TC would yield a 25% result, over the 24% target to qualify as protective, though just barely;
Triglycerides:HDL – Triglyceride (TG) fats are increasingly recognized for their predictive role for not just diabetes, but for cardiac disease as well.
These two measures usually go hand-in-hand, particularly for those with metabolic syndrome – high triglycerides and low HDL is a common combination that usually suggests pre-diabetes and increased cardiovascular risk;
The target here is under 2.0. Examples: TG = 150 and HDL = 40 for a 3.75 ratio, well above the 2.0 or under target. Lowering TGs and/or raising HDL would reduce this risk profile. TGs of 120 and HDL of 65 would yield a 1.85 ratio and be considered protective;
Non-HDL Cholesterol – Another risk refinement due to the fact that half of heart attacks and cardiac arrests occur with normal LDL cholesterol levels.
“Non-HDL cholesterol” is total cholesterol minus HDL, which should be under 130 mg/dL for those at high-risk (see below).
According to the folks at Johns Hopkins:
“The resulting value measures not only LDL cholesterol, but also cholesterol contained in metabolic ‘remnants’ of very low-density lipoproteins (VLDL), the main carriers of triglycerides…
“Studies have shown that non-HDL cholesterol is better than LDL cholesterol alone at predicting cardiovascular risk, especially in people (like diabetics) with elevated triglycerides.”
According to the National Cholesterol Education Program, non-HDL cholesterol should be less than 30 points above your target LDL cholesterol level. Examples:
One Last Cholesterol Ratio
Cholesterol Ratio – One final cholesterol measure is called simply your cholesterol ratio. This is calculated by subtracting your HDL from your total cholesterol and dividing that by your HDL.
For those with established coronary heart disease (CHD), the goal is a cholesterol ratio of 2.5 or less.
Women & Seniors…Say What?
Generally speaking, total cholesterol is over-emphasized in general medical practice today, especially among older patients in whom elevated cholesterol is less dangerous and even protective over 80-85 years of age.
For women, the U.S. Preventive Services Task Force recommends cholesterol testing only be done if they are at high risk for coronary heart disease.
A study in the Journal of the American Geriatrics Society actually found for men and women over age 60 that total cholesterol levels over the usual 200 cut-off point were protective and that elevated levels were not reached until 240 for men and 258 for women.
The respected Worst Pills, Best Pills recommends people over 70 not consider medication unless their total cholesterol is over 300.
What About HDL?
As a rule, HDL is under-emphasized because it’s harder to treat (higher is better with HDL).
HDL should be over 40 for men and over 50 for women to be considered healthy, assuming your Non-HDL level is below your target; an HDL level over 60 is even better.
Some people respond better to tangible targets than to vague notions of “lowering your cholesterol”. Converting good intentions into a quantifiable goal may help you muster the energy needed to put your good intentions into practice.
Total cholesterol/HDL will be used in this example to illustrate this point.
Let’s say you’re overweight with a BMI of 29 – fast approaching obesity at a BMI of 30 and over – and total cholesterol of 260 and HDL of 40.
For men, an HDL of 40 is borderline too low (<40), while for women – who have higher HDL levels to start with – HDL under 50 is considered too low to do its job of removing excess LDL cholesterol before it forms plaque that may block your arteries and/or blood vessels.
A total cholesterol of 260 and HDL of 40 gives you a Total Cholesterol:HDL reading of 6.5 (260 ÷ 40 = 6.5) – well over the 5.0 considered average risk for men and way above the 4.4 considered average for women.
According to the Framingham Heart Study, here’s how these levels translate into relative risk for heart disease in men and women:
A man with a reading of 6.5 could be expected to have a roughly 33% higher risk of heart disease than average, while a woman with the same reading would have a roughly 80% increased risk compared to average (these are pro-rated estimates and are imprecise, but should give a ballpark idea of relative risk).
You can reduce your risk by either lowering your total cholesterol, raising your HDL, or some combination of the two. For example, getting your total cholesterol down to 220 in this example, and your HDL up to 55, would lower your ratio to 4.0 – below average risk for both men and women.
Since the best way to increase your HDL is with more physical activity, focusing on raising your HDL is a healthier primary target than merely lowering your total cholesterol – which too often relies solely on medications that pose risks of side effects and disease causation.
LDL Cholesterol Is Your Greatest Concern
In terms of LDL cholesterol, your optimal target depends on how many risk factors you have besides your LDL cholesterol level. It also depends on the size of your LDL particles. The smaller the average size of your LDL particles, the more likely they are to form dangerous plaque that narrows your blood flow passages.
Unfortunately, standard cholesterol tests don’t measure particle size, though there are more expensive cholesterol tests that do. Your health insurance, however, most likely won’t cover this higher cost unless you’re at high risk and confirm coverage in advance.
The more risk factors, the lower your LDL should be. Here are the 5 key risk factors as outlined by the National Cholesterol Education Program (NCEP):
Age – Men ≥ 45 years, women ≥ 55 years;
Hypertension – Blood pressure ≥140/90 or on hypertensive medication(s);
Low HDL cholesterol – < 40 mg/dL (NCEP doesn’t indicate this, but for women, < 50 mg/dL is considered low HDL); and
Family history of premature coronary heart disease (CHD in male first degree relative < 55 years or female first degree relative < 65 years).
The following table lists LDL targets based on your number of risk factors:
Although the NCEP Guidelines don’t include it, most physicians now recognize diabetes as another CHD risk equivalent placing you in the high risk category.
For those with the highest CHD risk (CVD and diabetes and additional risk factors), the general consensus now is to target an LDL level below 70 mg/dL and an HDL target greater than 60 mg/dL.
Those at the low-risk end of the spectrum, however, should think twice before agreeing to take medications – despite the current promotion of statin drugs for people with normal cholesterol levels.
That’s because all medications, including statin drugs that effectively lower cholesterol levels (and inflammation), have side effects. These include an increase in your risk for diabetes and other complications that may outweigh any marginal benefit for low-risk populations.
Stay tuned for Part 2 on Triglycerides and other risk assessment measures of which you should be aware.
And feel free to weigh in below with your own thoughts and observations.
 Health After 50, Johns Hopkins Medicine, July 2009.  Biomarkers of Inflammation and Malnutrition Associated with Early Death in Healthy Elderly People, Journal of the American Geriatrics Society, Volume 56, Number 5, May 2008, pp. 840-846(7).