Despite new research, low LDL cholesterol is still key to prevent heart problems and stroke

Tens of millions of Americans use cholesterol-lowering drugs called statins to help reduce their risk of stroke and clinical atherosclerotic cardiovascular disease (ASCVD) – heart disease caused by plaque in the blood vessels.

LDL-C, or the “bad” cholesterol, contributes to fatty build-up in the arteries. Decades of research has shown that high levels of LDL-C, the “bad” cholesterol, can increase one’s risk for heart attack, stroke, and peripheral artery disease. The recent clinical practice guidelines agree with previous guidelines that recommend treating LDL-C to reduce cardiovascular risk.

So, it’s understandable why people may have been surprised by recent news headlines about low LDL-C.

New research published in the journal Neurology, the medical journal of the American Academy of Neurology, suggests that women who have LDL-C levels of 70 mg/dL or lower may be twice as likely to have a hemorrhagic stroke than women with LDL-C levels from 100 to 130 mg/dL. Hemorrhagic strokes, which account for about 15 percent of all strokes but 40 percent of all stroke-related deaths, occur after a brain aneurysm bursts or from a weakened blood vessel leak.

This sounds like big news. Let’s examine the study more closely.

The Women’s Health Study (WHS) is a 20-year observational study of the impact of low-dose aspirin and/or vitamin E in 27,937, mostly white middle-aged women without established heart disease. Less than 4 percent of the study participants – 1,069 women, to be exact – had LDL-C levels less than 70 mg/dL. Those women tended to be younger, more likely to be underweight (body mass index under 17 kg/ m2), more likely to drink alcohol in excess (more than five servings daily), and less likely to be treated with post-menopausal hormone replacement (HRT) therapy after menopause. Over the 20-year span, there were nine hemorrhagic strokes in women with low LDL-C. There were 128 hemorrhagic strokes in the 26,868 women with LDL-C greater than 70 mg/dL.

When researchers compared the hemorrhagic stroke rate with the reference range, they observed a higher risk for hemorrhagic stroke in the low LDL-C group and a higher rate for those with levels greater than 160 mg/dL. Ultimately, they felt that the association between low LDL-C and hemorrhagic stroke was statistically significant but did point out that even though this was a very large study, it was difficult to draw significant clinical conclusions about risk management.

First, it’s important to note that there is no well-established physiologic explanation for why a low LDL-C level would lead to increased bleeding or stroke. In fact, individuals with inherited causes of extremely low LDL-C levels do not have increased stroke risk.

While this study is interesting, there are several limitations. Most notably, this is an observational study, and researchers didn’t specifically examine whether taking medicine to lower LDL-C to less than 70 mg/dL would carry the same risk. In addition, there are several important conditions that may cause both a low LDL-C and hemorrhagic stroke, including high alcohol intake and being underweight. Beyond that, the identification of an uncommon event (nine out of 1,069 women suffered a hemorrhagic stroke) associated with a condition that affects less than 4 percent of the population studied may not have clinical significance.

Here’s the bottom line: This research should not change therapeutic decision-making. If you have or are at risk for ASCVD, your clinical provider will continue to prescribe statins and in some circumstances, other medicine to lower your LDL-C. It’s important that patients do not stop taking medicine to lower their LDL-C. More than 30 years’ worth of clinical evidence supports the use of statin therapy as an effective way to lower cholesterol and reduce one’s risk of heart disease and stroke.

Authors: Douglas Jacoby, MD, is a cardiologist and medical director of the Penn Medicine Center for Preventive Cardiology and Lipid Management and an associate professor of cardiovascular medicine medicine in the Perelman School of Medicine at the University of Pennsylvania. Daniel Soffer, MD, is an internist and lipidologist at the Penn Medicine Center for Preventive Cardiology and clinical associate professor of medicine in the Perelman School of Medicine at the University of Pennsylvania.