Statins Reduce Heart Disease Risk, But Probably Not Because They Lower Cholesterol

When cyclists find out that I am a heart doctor, they most frequently ask about cholesterol numbers.

a??a?|My cholesterol is thisa?|What do you think?a??

a??a?|My doctor wants me to take a statina?|But I read that these drugs might lower my functional threshold power 2.014 watts/40km.a??

All this focus on numbers saddens me. Remember, I am a forest guy, not a tree guy. Whata??s more, as a doctor that revels in the adrenaline rush of ablating rogue circuits with technology that would impress even a twenty-something, I find questions about biochemistry drearya??like eating quinoa.

I wish folks would ask me about how to terminate AF with a catheter, or how an (evidenced-based) ICD saved a moma??s life, or perhaps even this: a??Do you do heart surgery?a??

But more often than not people want to know about cholesterol.

Okay. It just so happens that this week brought some very interesting news concerning the treatment of abnormal cholesterol lab values. News that big-picture docs have to like.

Here goes:

The AIM-HIGH trial, a large NIH-sponsored study which tested the addition of the HDL-raising drug Niaspan to a statin drug in patients at high risk of heart disease, was terminated early due to lack of benefit. The trial included patients with low levels of?? HDL (a??gooda?? cholesterol) and well-controlled LDL levels  (a??bada?? cholesterol). Most of the patients enrolled already had manifest heart disease, or they had a cluster of other risk factors, like obesity, diabetes and high blood pressure. These were truly high risk patientsa??a group that would be likely to benefit from higher levels of HDL.

Niaspan worked as intended: it did indeed raise levels of HDL. But the striking finding was that there was not any reduction in heart-related adverse events. The drug simply did not reduce a??harda?? endpoints, like heart attack, stroke and death.?? (In fact, there was a small increase in the number of strokes in the Niaspan group.)

How is this possible?

This finding seems counter-intuitive.  We know that low HDL levels are associated with a higher risk for heart disease; therefore it would seem logical that raising the level of the molecule would confer benefit. But such is not the case with drugs that increase HDL. (A 2006 study called ILLUMINATE revealed that another potent HDL-raising drug, Torcetrapib, actually increased the risk of heart events.)

I see three important lessens in this trial:

(1) Though low HDL levels are associated with a higher risk of heart events, it is clear that raising HDL levels with drugs is not helpful. Heart health doesna??t come from swallowing pills!

(2) The best way to increase HDL levels is through regular and vigorous exercise.

(3) The over-attention to levels of chemicals (medical people call them biomarkers) is problematic. When looking at a study which claims benefits, a reader should ask whether there were actual differences in outcomes. Changing the level of something (like cholesterol, blood sugar, or bone density) may not correspond to actual benefit. Always ask about outcomes.

Let me conclude with a comment about statin drugs. I strongly believe that statins lower the risk of heart-related events through actions on the blood vessel wall. They mitigate inflammation in the blood vessel. We cana??t measure this anti-inflammatory effect, so we measure cholesterol levels. But statins are different than other cholesterol-lowering drugs because they have favorable outcome data. Numerous trials have shown that patients at high heart risk of heart disease that take statins have fewer heart attacks and strokes.

Thata??s enough biochemistry quinoa.

References:

Here is the NIH press release for AIM-HIGH (Atherothrombosis Intervention in Metabolic Syndrome with Low HDL/High Triglycerides: Impact on Global Health)

More complete and academically rigorous accounts can be viewed on Cardiobrief and TheHeart.org.

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