The Truth About Cholesterol

We've all heard the mantra: keep LDL levels – the “bad” cholesterol – down, and the “good” HDL cholesterol up. But thanks in part to the ubiquity of statins, such as Lipitor, which allow us to simply pop a pill to limit LDL production in the body, we've recently adopted tunnel vision when thinking about managing cholesterol. LDL levels are all we seem to care about now, as we strive for lower and lower numbers at each visit to the doctor's office. However, I think we're missing the bigger picture by focusing solely on LDL. First, it's made us reliant on medication to solve a problem that can many times be addressed with changes in diet and exercise regimes. Once someone starts Lipitor treatment, they'll be taking it for life, and if LDL levels don't quite get as low as they should, it's all too easy to solve the problem by increasing the dose. When patients first begin Lipitor treatment, physicians typically prescribe the lowest possible amount, 10mg. However, dosing can go as high as 80mg, which begs the question: Do higher doses of the drug really improve outcomes?

Second, the LDL value doesn't tell the whole story. After all, some people that have low LDL levels, still develop heart disease. When your doctor orders a standard lipid panel, LDLs are measured along with other lipids, such as high-density lipoprotein (HDL) cholesterol and triglycerides. What role do these other types of lipids play in cardiovascular health?

Let's start with the first question: Do higher doses of the drug really improve outcomes? This idea popped into my mind while reading a recent study in PLoS One that looked at LDL levels in patients diagnosed with familial hypercholesterolemia, a genetic predisposition to high levels of “bad” cholesterol. Caused by specific DNA mutations on a small region of chromosome 19, familial hypercholesterolemia drastically increases the chances that a person will develop heart disease. In fact, studies estimate that 85% of men with this mutation will have a heart attack by the age of 60.

The PLoS study found that only a minority of people with hypercholesterolemia brought their LDL levels down to recommended values, even when using statins. According to the authors, doctors were being too cautious with Lipitor dosing, and felt that higher doses would help patients reach their LDL targets.

Blood....beginning....to....boil.....

I know this isn't the first time I've climbed up on my soapbox saying “more medication is not always the answer”, but I wanted to find proof. Lo and behold, I came across a good study from the New England Journal of Medicine that calculated the risk of a major cardiovascular event depending on whether people were taking low- or high-doses of Lipitor (10 or 80 mg, respectively).

statin_b
statin_b

Take a look at Figure 1: Higher doses of Lipitor only made a big difference in risk when HDL levels were low. As HDL levels rose, the difference in height between the light- and dark-green bars went down. This means that if a person can get his or her “good” cholesterol high enough, higher doses of Lipitor will NOT necessarily decrease the risk of having a cardiovascular event.

This finding ties in well with the second question: What role do these other numbers play in cardiovascular health? From the NEJM study, we've seen that high HDL levels – which are a good thing – trump higher doses of Lipitor in preventing heart disease. But can adequate levels of “good” cholesterol also counterbalance the cardiovascular risk when “bad”cholesterol levels are high?

In a word, yes. Take a look at Figure 2: as HDL level increased, the risk of a cardiovascular

event decreased. But more surprising, if HDL and LDL levels were both high (above 55 and 100 mg/dL, respectively), a person had nearly equal risk of a major cardiovascular event as someone who had good LDLs (<70 mg/dL) but bad HDLs (<38 mg/dL)!

Similar evidence is mounting that high triglyceride levels are also an independent risk factor for heart disease. In fact, one study showed that even when people with a history of heart problems used statins to lower their LDLs to acceptable levels, slight increases in triglyceride levels significantly increased the chance they'd have another cardiovascular event.

So there is evidence that the other lipids in the blood (HDL and triglycerides) are equally important in predicting heart health. So is it possible to raise your HDL, or lower your triglyceride, levels? You bet. Studies have shown that simple, endurance exercise training significantly decreases triglyceride levels and raises HDL levels in many people.

I'm not saying that diet and exercise changes will work for everyone. But statins shouldn't be viewed as the magic bullet, either. As more studies on the science of exercise emerge, we'll begin to move past the notion that exercise simply burns calories, and deepen our understanding of the complex interactions of physical activity and metabolism.