Old Cholesterol Guideline Theme: It’s All About Your LDL Number

When clinical guidelines come out, there are two major levels at which they’re interpreted. The first interpretation is literal, following the guidelines to a tee. However the more important interpretation is the guideline theme. Most docs forget about the specific details over time and apply the general message to their practice. The prior cholesterol guidelines morphed into the following thematic messages:

1. LDL is bad and the higher your LDL level, the greater your risk of heart disease.

2. The higher your individual risk, the lower your LDL target. For example, let’s drop LDL to less than 70 mg/dl in patients with existing heart disease. Not because there’s evidence to do so, but because we’re making an assumption that lower is better.

3. Since LDL is evil and lower LDLs are better, it is ok to use multiple medications to reach your LDL goal if necessary. Forget the cumulative toxicity of all the different medications and the fact that drugs like zetia never had a shred of good evidence suggesting heart protection. Bottom line is LDL is evil and it must be stopped at all costs, even if the cost is your own health in the form of medication side effects.

New Cholesterol Guideline Theme: It’s All About Your Heart Attack Risk

The main recommendation from the guidelines is that individuals who fall into any of the following four categories should be on a statin:

1. Those with existing heart disease
2. Those with LDL levels above 190 mg/dl
3. Those with diabetes aged 40 to 75 years with LDL between 70-189 mg/dL and without existing heart disease
4. Those without heart disease or diabetes, with an LDL between 70-189 mg/dL and an estimated 10-year heart attack risk of above 7.5%

When comparing the old guidelines to this one, the first 3 categories are essentially unchanged. Most doctors would put heart disease patients, diabetics and those with LDLs above 190 mg/dl on statins. There are some advantages to the newer guidelines:

  • The focus of therapy is on statins, which are the default drug of choice. This is a good thing for those who truly need statins and should hopefully avoid cumulative toxicity from multiple drugs.
  • The concept of treating to a specific LDL target number has been eliminated. This is good since it should reduce unnecessary high dose statin therapy to reach low targets which have not been proven to reduce heart attack risk.
  • These guidelines do a better job of highlighting statin adverse side effects which will hopefully make clinicians think twice before pulling the statin trigger
  • Greater overall emphasis on heart attack risk rather than a focus on the LDL number which makes more sense.

What is the major drawback of these guidelines?

The 4th category where individuals who have no risk factors other than a 10-year heart attack risk above 7.5%. This is significantly lower than the prior cutoff of 20% and will result in many more people taking statin medications. My biggest pet peeve with this category is the risk calculator which in my experience is a terrible tool. It’s based on the Framingham Heart Study. Unless you are white, live in Framingham, Massachusetts, and have recreated a 1950s lifestyle, maybe this risk calculator would have some value in estimating heart attack risk. However for the rest of us, it is a pretty useless tool. The data entry points are gender, age, race (you’re either African American or not), total cholesterol, HDL (good cholesterol), systolic blood pressure (top number of your blood pressure), diabetes status, and smoking status.

What’s missing? How about triglycerides, weight or waist circumference, prediabetic blood sugars, and physical activity levels. I have many patients, especially those of Indian and Asian background, who have high triglycerides, abdominal obesity and prediabetic blood sugars, but don’t smoke and have normal blood pressures. They have a condition called metabolic syndrome, caused by insulin resistance, which accounts for a huge burden of global heart disease and this calculator misses it in most cases. In fact, I’ve plugged in the “before” numbers for some of my heart attack patients and this magical calculator spit out a <1% risk of heart disease. Yes, a 60-year-old smoker with high blood pressure will register a high risk score, but you don’t need a medical degree or a risk calculator to figure that out. What about cardiovascular fitness? Why do my 60+ year old lean, aerobically fit patients who eat a healthy diet continue to score as higher risk than my 40-year-old sedentary, obese, computer engineers who eat an unhealthy diet. I’ve already detected plaque and premature arthritis in these patients in their 30s and 40s, so in today’s high-tech world “age,” a key variable for the risk calculator, is much less critical than lifestyle and fitness levels.

So my suggestion is to either dump this calculator completely or fix it by incorporating metrics that reflect today’s heart attack risks, like insulin resistant measures and lifestyle factors, along with stratifying further by ethnicity to acknowledge that our demographics are far more diverse than Framingham. We don’t live in a “black and white” world as this calculator suggests. Ethnic groups such as Asian Indians have a higher risk of heart disease than African Americans, but this calculator dumps them along with other high risk groups in a large white bucket.

Be Skeptical About Guidelines

If there’s anything that these new guidelines tell us is that the whole business of creating guidelines is fraught with errors. Thanks to the old guidelines that were so focused on LDL numbers, we now have a ton of healthy people with isolated elevated LDLs who are taking statins. How about the number of people on high dose statins or multiple drugs to try to achieve ridiculously low LDLs because somehow the message became the higher the risk, the lower you must drive down LDL numbers? Let’s set the cutoff at 70 mg/dl and see what happens. The real problem with guidelines is their lack of nuance. The original guidelines took a disease as complex as heart disease and reduced it down to an LDL number. These guidelines have now reduced heart disease risk for a significant part of the population down to a single risk calculation score. We also need to start incorporating clearer indications for the role of additional tests such as advanced lipid panels that break down LDL into its subcomponents (type B LDL is more plaque-inducing than type A LDL), hsCRP (marker for inflammation), and non-invasive imaging studies of the coronary arteries (EBCT). In my practice I often use these modalities to determine if an individual truly needs to be on life-long statin therapy. This is not a frivolous decision and should not be left up to an erroneous risk calculator. I’ll do a future more detailed post on interpreting lipids. What these guidelines do suggest is that inflammation is the real culprit behind heart disease since the LDL target number hypothesis from the prior guidelines failed. Statins benefit high risk patients who are a victim of inflammation, not elevated LDL levels. More evidence is pointing towards their benefit as more of an anti-inflammatory drug, rather than an LDL-lowering drug. If that’s the case, the foundations of nutrition, exercise, and stress reduction are far more powerful anti-inflammatory agents than statins. Unfortunately our guidelines and medical training continue to offer ineffective advice on succeeding in these critical areas, while continuing to push medication management as our primary weapon against the epidemic of global heart disease.