Hypercholesterolemia: How Low Can You Go?

Like I discussed with hypertension management in my last blog, my patients get frustrated about the moving target for goals in treating hypercholesterolemia (high cholesterol).  When I started my medical training in the 1980s, we generally looked at total cholesterol and considered it to be high if it was over 240.  Eventually we learned to look at the different components of total cholesterol, as some cholesterol is good (HDL or “high density lipoprotein”), while the rest is bad.  The majority of the bad cholesterol (or “non-HDL cholesterol”) comes from the LDL (“low density lipoprotein”) cholesterol.  Goals for LDL cholesterol have dropped over the last 30 years, from 190, then 160, then 130, then 100, then 70.  In fact, we now know that below 70 is not an absolutely safe level and potent new medicine combinations can achieve levels below 30. 

So why do we keep changing our minds?  Well, medical guidelines follow the data that comes out of clinical trials.  Trials in the 1990s started by testing medications to see if it made sense to treat people with a statin whose total cholesterol level was over 200.  The results were positive—meaning YES, it was beneficial in lowering the risk of bad things happening, like dying or having a heart attack.  Once a new goal is established, further trials are done to see if it is beneficial to treat people whose cholesterol levels aren’t as elevated.

In 2008, a trial called JUPITER found that patients whose LDL was below 130 (the average at study entry was 108) had a significant clinical benefit when started on rosuvastatin (formerly known as Crestor®).  And in the last several years, patients with LDL levels averaging just over 90, who were placed on a new class of medication called PCSK9 inhibitors (brand names Repatha® and Praluent®), were found to benefit when these drugs lowered that number to between 30-60.

So, why does our LDL need to be so low when the lab tests we order indicate that “normal” is about 130.  Unfortunately, lab reference values (normal ranges), sometimes don’t reflect anything more than a population average.  Unlike something such as a potassium level, which is tightly regulated by our bodies—and we can die from a life-threatening heart rhythm when it falls outside a fairly narrow range—cholesterol levels aren’t really regulated.  When we are born, our LDL cholesterol is actually about 50-60, but as we age and are exposed to a “western diet” (no, not an Arizona or California diet, but the general diet eaten throughout the industrialized western world), our LDL levels steadily climb—some people’s more than others, likely related to genetic differences.  So almost all of us have cholesterol levels that are too high for optimal cardiovascular health.  These higher levels lead to clogging up of our arteries.

Our current strategy, therefore, is not to treat the cholesterol because it is high (since that applies to virtually everybody), but to treat the patient whose risk is high: people who have had a heart attack or needed a stent, people with diabetes, people with several risk factors that make for an elevated risk. That decision can be complicated and one that you should discuss with your personal physician, who can weigh your own unique risk profile to help decide if you are a candidate for medication or should just adhere to a healthy diet.  In a later blog, I’ll discuss what it means to eat a healthy diet.

Greg Koshkarian, MD, FACC

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Gregory Koshkarian, MD, FACC