Beyond Cholesterol – Part 2

The CVD Trio


English: HDL (Photo credit: Wikipedia)

As noted in Part 1 of this 3-part series – Making Sense of Your Cholesterol Scores – cholesterol measures alone have been insufficient for predicting and preventing cardiovascular events like heart attack and stroke.

Over half of these occur in people with normal cholesterol levels.

As a result, researchers continue to look for other “biomarkers” that may help identify those with continuing cardiovascular risk despite normal cholesterol levels.

In other words, there’s false comfort in thinking that your normal cholesterol reading eliminates your risk for cardiovascular disease – something I discuss in Our Healthcare Sucks.

This has led to studies using other, less well-known markers for identifying elevated cardiovascular risk.

European researchers found elevated triglycerides and low HDL (“good”) cholesterol –  common with abdominal obesity and metabolic syndrome – have been associated with the highest risk of developing coronary artery disease.

Given the increasing prevalence and risks of high blood pressure as you age, combining your cholesterol and triglyceride readings with your blood pressure may give you the most integrated assessment of your cardiac disease risk that’s more complete than any of these variables alone.

Given that half those dying from cardiovascular disease have normal cholesterol levels, it’s clearly in your best interest to look beyond cholesterol for more precise estimates of your true CVD risk so you can seek the healthcare you need to manage your actual risk – and reject that which you don’t need.

Fine-Tuning Your Risk Category

A simple way to convert this information into a quantifiable estimate of your 10-year risk for heart disease based on data from the Framingham Heart Study can be found in the online risk assessment tool provided by the National Cholesterol Education Program at hp2010.nhlbihin.net/atpiii/calculator.asp?usertype=prof.

Entering your age, gender, total and HDL cholesterol, systolic blood pressure, and whether you smoke or not generates a 10-year assessment of your risk for heart disease, including heart attack.

  • A 10% or lower risk is considered low risk,

  • 10-20% intermediate risk, and

  • Over 20% is considered high risk.

If you’re at a 10-20% intermediate risk, you may want to consider additional tests such as those listed below to further refine your risk and possibly avoid more invasive tests and procedures if you are properly reclassified as low risk.

You can also adopt lifestyle behaviors that will lower your risk and avoid unnecessary medical care as well.

Can You say Triglycerides?

Several other blood tests can help better assess your actual risk for many diseases:

  • Triglycerides (TGs) – This blood test is included in a blood lipid profile along with cholesterol levels. Triglycerides are the other major form of blood lipids (fats) most associated with cardiovascular disease and diabetes and are commonly elevated in overweight people and those with pre-diabetes.

Low HDL and high triglycerides is a common combination in the so – called metabolic syndrome that often precedes a diabetes diagnosis .

This combination may be more predictive than LDL cholesterol for cardiovascular risk, especially in women. That’s because elevated triglycerides usually mean a high level of very small LDL particles (called VLDL) as well, and these are most likely to cause plaque.

Triglyceride levels under 150 mg/dL is considered healthy (under 100 is better), while over 500 mg/dL (some suggest over 400) is considered very high risk and cause for treatment with prescription strength fish oil.

If yours is over 150, you should consider supplementing with fish oil (high doses in the 4-10g/day range have been shown to reduce TGs by 30-50%).

Sunshine Makes You Healthy

  • Vitamin D level – This is a somewhat newer indicator for disease that’s increasingly recognized as associated with a broad range of diseases – from heart disease and diabetes to cancer and Alzheimer’s Disease.

The leading researcher at Johns Hopkins on the link between low vitamin D levels and cardiovascular disease cautions that further research is needed, but that it does appear that some populations can better protect against CVD with prudent sun exposure and/or supplementation.

Others have found no such link, but possible benefit in protecting against heart failure in older adults. This does suggest a preventive role for vitamin D in heart disease prevention, even if it’s an indirect one.

A level over 30 ng/dl is considered desirable, with some advocating a level over 50 as being protective.

Male smokers and those with a family history of pancreatic cancer (see below) should keep their level closer to 30 – and no higher than 40 (35 is safer) – than to aggressively pursue a higher blood level reading.

A European study concluded that “An optimal serum concentration of 40-60 nmol/L (equals only 15.4 – 23 ng/dl) for the lowest (prostate) cancer risk.”

This is well below the 30 level considered desirable and casts doubt on what the ideal blood level is, at least for men.

For women, a reading in the 40-50 range is considered protective, although women with a family history of pancreatic cancer may want to avoid such a high reading and try to keep it closer to the 30 ng/dl level.

That’s because of evidence from a 2009 study in the U.S. that high vitamin D levels in those who don’t receive much sun exposure – meaning they get their vitamin D from diet and supplementation – may be at increased risk for pancreatic cancer.

Your best source, therefore, is limited sun exposure – 10-15 minutes a day for light-skinned people – without sun block protection. This is the primary source of vitamin D production in the human body.

Much of the U.S., however, is in low sun exposure northern latitude regions – especially above the line connecting San Francisco and Philadelphia – accounting for a wider incidence of vitamin D deficiency than previously realized.

Fear of skin cancer with sun exposure and declining cholesterol levels (necessary for vitamin D production in the body) are also likely contributors to vitamin D insufficiency.

This is especially true for older people and those with darker skin pigmentation who need more sun exposure to produce necessary amounts of vitamin D. The overweight and obese are also at risk, as vitamin D is fat-soluble and can be stored in excess fat in the body that makes it less available where needed.

Winter sun exposure declines for non-skiers and may require added supplementation to maintain an even blood level year-round, which may be even more important than the absolute level of vitamin D.


  • IL-6/CRP – These are measures of inflammation that may indicate risk for a broad range of chronic diseases.

For cardiovascular disease, elevated inflammation may indicate plaque instability that could lead to a clot-caused heart attack or stroke.

CRP (C-reactive protein) is a protein produced by the liver in response to toxic cytokines produced by tissue injury, inflammation, infection, and adipose (fat) tissue – especially visceral belly fat.

The problem with the CRP test is it measures acute as well as chronic inflammation, so an elevated level may reflect a passing cold or flu rather than a chronic condition.

Another lab test to test for chronic inflammation is called IL-6 (Interleukin-6). This is sometimes recommended due to the high false positives with the CRP test and has been shown to be more predictive of fatal heart attack and stroke in patients over 70, as well as in women.

A study examining the role of these inflammatory markers in longevity among older adults found that CRP was associated with longevity for men but not women, while IL-6 was relevant to both men and women.

If either is elevated, it’s wise to get another one after a month or two to monitor your inflammatory trend.

For CRP:

  • Under 1.0 mg/L is low risk,

  • 1-3 mg/L moderate risk, and

  • >3 mg/L high risk;

The thresholds for IL-6 are:

  • 9 pg/mL for low risk,

  • 1.9-3.19 pg/mL for moderate risk, and

  • > 3.19 pg/mL is high risk.

If you get a CRP test, you can refine your Framingham Risk Score – if you’re in the moderate risk range of 10% to 20% 10-year risk category – at reynoldsriskscore.org.

Research shows that about half those in the intermediate risk category were reclassified into higher or lower risk categories using this tool, which requires your CRP lab test results to modify your risk score.

Other research has found that 13% of those classified as “intermediate risk” were reclassified as “low risk”, while only 3% were reclassified as “high risk”.

This means a net 10% of people were reclassified to a low risk category where they will not be subjected to unnecessary testing or procedures they might have undergone as “intermediate risk” patients.

The problem is that most obese people, and many who are overweight, have elevated CRP levels – fat is pro-inflammatory, especially in women. This doesn’t necessarily, by itself, indicate elevated risk of cardiovascular disease.

Why You SHOULD Fine-Tune
Your Cardiac Profile

Those considered intermediate risk are likely to receive unnecessary cardiac studies and procedures, making them prime candidates for fine-tuning their risk profile to be certain they don’t receive expensive and often risky medical interventions they don’t truly need.

Normal CRP levels have been found to result in a lowering of CVD risk classification from intermediate to low-risk for some people.

In other words, CRP or IL-6 lab tests may help your doctor refine your true CVD risk and avoid the need for more invasive, risky, and expensive cardiac procedures.

Conversely, you may be prescribed a more aggressive treatment if your risk classification is increased.

Including one of these inflammation tests to fine-tune your CVD risk profile is a prudent way to determine how aggressive to be in your lifestyle and medication management regimens.

However, if you choose the CRP test, insist on a second one if it reclassifies you into a higher-risk category due to its high rate of false positives discussed earlier.

Finally, your insurance – whether Medicare or private – is unlikely to completely cover the costs for this fine-tuning process. Only you can decide if assuring you get only the medical care you need – no more and no less – is worth whatever it may cost you out-of-pocket.

My next post will close out this series on cholesterol and other cardiac disease risk factors.

Until then, please feel free to comment below on your own experiences with cholesterol and other markers for cardiovascular disease.

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John Lynch: John Lynch was founder and CEO of Medical Diagnostics, Inc. - twice named to Business Week's "Best Small Companies" in America. He's since founded MedSmart Members to publish consumer health education publications.
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