Low LDL Cholesterol Linked to Bleeding Strokes

Ask any golfer if you can have too low a golf score and he will think you’re nuts. After all, the lowest score wins in golf. Ask almost any cardiologist if you can have too low LDL cholesterol levels and you are likely to get the same perplexed look. LDL cholesterol has been dubbed “bad” cholesterol. It is perceived as the major culprit in heart disease. Because statins lower LDL cholesterol so well, they are called life savers. But what if low LDL cholesterol levels were linked to hemorrhagic or bleeding strokes?

Please…Do NOT Shoot the Messenger!

We often get angry messages from cardiologists who insist that statins produce few, if any, adverse reactions. They cite the United States Preventive Services Task Force (USPSTF) report published in JAMA (Aug. 23/30, 2022). These experts concluded that statins are not likely to cause serious adverse drug reactions such a muscle pain or diabetes.

Researchers who conduced many statin studies (the Cholesterol Treatment Trialists’ Collaboration or CTTC) published their conclusions about the side effects of statins in The Lancet (Aug. 29, 2022). The essence of their analysis seems to be that reports of statin side effects are mostly imaginary. When people complain of muscle pain, weakness or other musculoskeletal problems they are not caused by statins but could be triggered by negative press reports.

I guess they are referring to people like me, since Terry and I write syndicated newspaper columns in which we do sometimes mention statin side effects. But even a statin enthusiast like Steven Nissen, MD, admits that statins can have side effects.

Dr. Nissen is not just any cardiologist. He has served as President of the American College of Cardiology (ACC) and has been in leadership roles at the Cleveland Clinic for decades. In a paper published in the New England Journal of Medicine (April 13, 2023), Dr. Nissen and his colleagues wrote:

“…7 to 29% of patients report adverse musculoskeletal effects that prevent them from using statins or limit their ability to receive guideline-recommended doses.”

I will, no doubt, infuriate some cardiologists for mentioning a much more serious complication. A reader shared this reaction to a column about low LDL cholesterol and hemorrhagic strokes:

New Research Links Low LDL Cholesterol to Bleeding Strokes:

Q. As a nurse for decades, I have seen numerous episodes of negative statin experiences. Most often, the prescribing physician refuses to entertain the possibility of statins as the cause, though when given a doctor-approved “statin holiday,” many patients become pain-free and resume normal activity.

One patient with a total cholesterol level of 98 read your article on the danger of extremely low cholesterol. The physician’s response was: “The lower, the better.” A short time later the patient died of a hemorrhagic stroke, as your article had warned.

Reactions to statins can ruin lives, even if some doctors refuse to believe the reactions are serious.

A. You have raised one of the most controversial topics in cardiovascular medicine. Most experts are in agreement that lowering LDL cholesterol reduces the risk of ischemic strokes (those caused by blood clots in the brain). But they don’t agree about how using statins to lower LDL cholesterol affects the risk of hemorrhagic strokes (those caused by bleeding in the brain).

The most recent meta-analysis reviewed 33 statin trials (Journal of the American Heart Association, Feb. 20, 2024). The authors reported a small increased relative risk (17 percent) for bleeding strokes among people taking statins to lower their LDL cholesterol.

The authors concluded:

“Our findings confirm and strengthen the existing evidence that LDL‐C–lowering therapies increase the risk of HS [hemorrhagic stroke].”

We would be the first to point out that the absolute risk of a bleeding stroke is quite low. And an accompanying editorial emphasizes that:

“…the fear of HS [hemorrhagic stroke] risk should not preclude statin use if clinically indicated.”

You can learn more about the pros and cons of statins and other ways of managing cardiovascular risk in our eGuide to Cholesterol Control & Heart Health. This online resource can be found under the Health eGuides tab.

Low Cholesterol and Bleeding Strokes

It usually comes as a shock to patients and health professionals to learn that low cholesterol, especially low LDL cholesterol, might have some negative consequences. For decades we have been told that “bad” cholesterol is our enemy. The belief is that LDL cholesterol clogs our arteries and is the primary cause of heart attacks and strokes. There was no concept of too low cholesterol.

We believed that mantra for a long time. Then we talked with Walter Willett, MD, DrPH, MPH. Dr. Willett is arguably one of the world’s foremost epidemiologists and nutrition scientists. At the time we talked with him he was chairman of the Department of Nutrition at the Harvard School of Public Health. Here’s what he said about very low cholesterol levels:

“…in Japan, where cholesterol levels have been low, hemorrhagic stroke rates have been extremely high, so that total cardiovascular mortality has not been very different between the United States and Japan.”

Too Low Cholesterol?

Dr. Willett went on to add this in response to our question whether cholesterol levels could ever be too low:

“there is indeed some basis for real concern, even though it’s not been absolutely proven that cholesterol levels can be driven down too low.”

Dr. Willett really shocked us when he said that at one time there was even a public health effort to raise cholesterol levels in Japan because of a problem with bleeding strokes.

Seven years before we spoke with Dr. Willett an article was published in the journal Stroke (July, 1993).

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Researchers performed autopsies on men who died in a local hospital in northeast Japan between 1966 and 1984.

The conclusions:

“Among cases of cerebral hemorrhage [bleeding stroke], serum total cholesterol levels were even lower in men with no significant stenosis in either basal or penetrating arteries than in men with stenosis [narrowing] in either type of artery.

“The association of serum cholesterol with pathogenesis varies among stroke types. Elevated serum cholesterol levels were associated with the presence of cortical artery infarction [clot blockage], while low serum cholesterol levels were associated with cerebral hemorrhage [bleeding stroke].”

A meta-analysis involving 23 prospective studies totaling 1,430,141 participants was published in the journal Stroke (July, 2013).

The Conclusions:

“Total cholesterol level is inversely associated with risk of hemorrhagic stroke. Higher level of low-density lipoprotein cholesterol seems to be associated with lower risk of hemorrhagic stroke.”

In other words, low LDL cholesterol was associated with a higher incidence of stroke and conversely, higher levels of LDL cholesterol were linked to a lower likelihood of a bleeding stroke.

Another study confirms this association in women (Neurology, April 10, 2019).

Low LDL Cholesterol and Bleeding Strokes:

The journal Neurology is “The most widely read and highly cited peer-reviewed neurology journal.” It is also highly respected. An intriguing study published online on April 10, 2019 raises some fascinating questions about striving to achieve lowest possible LDL cholesterol levels.

The authors reviewed data collected from the Women’s Health Study. Nearly 28,000 women were followed for almost 20 years.

Results of Low Levels of  LDL Cholesterol:

What they found was that women with LDL cholesterol levels that were lower than 70 mg/dl were more than twice as likely to experience a hemorrhagic stroke as those with LDL cholesterol levels between 100 and 130. The authors acknowledge that the underlying mechanisms behind this life-threatening complication are not completely understood. They go on to say, though, that:

“…it is thought that low cholesterol may result in arterial medial layer smooth muscle cell necrosis [death] and that the impaired endothelium [the inside of blood vessels] may be more susceptible to microaneursyms, which are often found in ICH [brain hemorrhage] patients.”

What About Drugs that Lower LDL Cholesterol?

Most people cannot get their “bad” cholesterol below 70 without medications. The authors note:

“The association between low LDL-C or triglyceride levels and an increased risk of hemorrhagic stroke seen in some studies led to concern that statins may increase the risk of hemorrhagic stroke events. Two large meta-analyses, one only of randomized controlled trials and one of both trials and observational studies, concluded that there was no association between statin use and the risk of ICH [intracerebral hemorrhage or bleeding stroke].”

They go on to note, however:

“The differences between the statin trials and observational studies such as the one presented here may be due to the different questions the studies address. Statin trials are typically only a few years in duration and examine the effect of a pharmaceutical agent that lowers cholesterol on hemorrhagic stroke risk. In contrast, our observational study may reflect the effect of longer-term exposure to very low LDL-C levels (in the absence of cholesterol- lowering treatment) on vessel wall integrity.”

Are Your Concerned About Too Low Cholesterol?

We think of cholesterol a bit like the porridge in the story of Goldilocks and the Three Bears. If you remember this tale, our young lady did not like her porridge too cold or too hot. She preferred porridge that was “just right.” So too cholesterol may need to be neither too low nor too high. The authors noted that high levels of LDL cholesterol (above 160) seemed to be associated with an increased risk of bleeding stroke too, though the results were not statistically significant.

If you would like to read other articles we have written about the complicated issue of too low cholesterol, we invite you to go to these links:

“Is It Risky to Have Low Cholesterol Naturally?

Will Higher Bad LDL Cholesterol Help Older People Live Longer?

Does Low Cholesterol Lead to Strokes?

What do you think about low LDL Cholesterol? Please share your story or thoughts in the comment section below.