**Episode Title: "EP313: The Brain and Low Cholesterol"**
**Dr. Auric Bishop:** Welcome, my name's Dr. Auric Bishop. I'm a cardiologist, an author, and a keynote speaker. I'm CEO of the Healthy Heart Network. I'm all about trying to help people live as well as possible for as long as possible. Heart disease is huge in Australia. Every 20 minutes, someone suffers a heart attack. Most of these could probably have been avoided if only we knew what to do. This podcast is all about helping you understand blood pressure, weight, and cholesterol for better health. If you enjoy this podcast, I would be honoured for a five-star review. You can share it with your family and friends. It may well save someone you love.
**Dr. Warwick Bishop:** Hi, my name is Dr. Warwick Bishop, and welcome to my podcast and videocast station. As always, I'm really very grateful that you've taken some time to tune in and have a listen. I hope this is something that you find interesting and informative. It certainly is topical.
What I'd like to share with you today is around an article that came through Medscape, written by Megan Brooks in September 2023. What it does is summarize the American Heart Association's position on aggressive cholesterol lowering and the impact on the brain.
Now, why are we interested in this? Well, the naysayers to the cholesterol hypothesis and those who really want to disregard statins and, if you like, push the barrow of statin side effects and problems have been trying to suggest that by lowering cholesterol, we increase the risk of stroke. So, if you like, causing problems, causing stroke, by trying to reduce problems, reducing the risk of heart attack.
Well, it turns out the American Heart Association has done an extensive review specifically looking at the impact of aggressive or very low LDL (low-density lipoprotein), the so-called bad lipoprotein, lowering on the brain. And I'm going to read most of this out to you because it's really a valuable summary.
It was a published scientific statement from the American Heart Association (AHA) which focused on the impact of aggressive low-density lipoprotein lowering, specifically in the context of dementia and hemorrhagic stroke. Well, of course, we understand dementia is loss of cognitive function, but what's hemorrhagic stroke? Hemorrhagic stroke is where there is a bleed from a blood vessel within the brain rather than a blockage within a blood vessel preventing blood from getting to the brain. A bleed into the brain can be as detrimental and problematic as lack of blood getting to the brain, but they're two slightly different mechanisms.
The naysayers, or the anti-cholesterol lobby, if you like, the anti-cholesterol lowering lobby, have been saying that by lowering cholesterol in the brain, which is such a lipid-rich structure, we run the risk of increased brain bleeds or hemorrhagic stroke. In quotes, "the brain is the body's most cholesterol-rich organ," and some have questioned whether aggressive LDL cholesterol lowering induces abnormal structural and functional changes. This was said by the writing group LEAD, Dr. Larry Goldstein, MD, Chair, Department of Neurology, University of Kentucky, Lexington. He and his co-writers produced a 39-page scientific statement entitled "The Impact on Risk for Dementia and Hemorrhagic Stroke," and that was released in a journal called Atherosclerosis in September of 2023.
Their objective was to evaluate the contemporary evidence that either supports or refutes the conclusion that aggressive LDL cholesterol lowering or lipid lowering exerts toxic effects on the brain leading to cognitive impairment or dementia, or hemorrhagic stroke. The eight-member writing group used literature reviews, references to published clinical and epidemiological studies, clinical and public health guidelines, authoritative statements, and expert opinion to summarize the latest evidence and identify gaps in current knowledge.
Now they reached four main conclusions.
First, the available data consistently show that LDL cholesterol lowering reduces the risk of atherosclerotic cardiovascular disease events in high-risk groups. So importantly, they're saying that by lowering cholesterol, we are reducing heart attacks in these individuals who are truly at high risk. And that's important for us to remember because heart attack is a major killer.
The second main conclusion was this: although some older retrospective case-control and prospective longitudinal studies suggest that statins and LDL-C lowering are associated with cognitive impairment or dementia, i.e., some memory loss, loss of cognitive function, the preponderance of observational studies and data from randomized trials— and I'll repeat that, from randomized trials— do not support this conclusion, at least among trials with medium follow-up, up to six years. The group says additional studies are needed to ensure cognitive safety over longer periods of time. For now, contemporary guidelines recommending the risk-stratified attainment of lipid lowering goals are reasonable. They conclude.
That's what the writing group said. So at this stage, although there were some early case-control reports where there may have been changes in cognitive function, larger observational studies and importantly randomized control trials do not bear that out.
So point one: lowering cholesterol does reduce the risk of heart attack. Two: there is no clear evidence that lowering LDL cholesterol drives either dementia or hemorrhagic stroke.
Point number three: the risk for hemorrhagic stroke associated with statin therapy in patients without a history of cerebrovascular disease is small and consistently non-significant. The writing group found no evidence that PCSK9 inhibitors—these are agents that are very powerful cholesterol-lowering drugs—or ezetimibe, a drug often used in combination with statins, increases bleeding risk. Further, there is no indication that patients or populations with lifelong low LDL cholesterol have enhanced vulnerability to hemorrhagic stroke. And there is little evidence that achieving very low levels of LDL cholesterol increases that risk.
What is clear, the writing group says, is that lower LDL cholesterol levels correlate with lower risk of overall stroke and stroke recurrence. This is related predominantly to a reduction in ischemic stroke, or the stroke that's associated with plaque buildup in the arteries leading to a blocked artery and therefore lack of blood to the brain. In quotes, "Concern about hemorrhagic stroke risk should not deter a clinician from treating LDL cholesterol to guideline-recommended risk stratified targets," as said by the writing group.
So first of all, lowering those LDL cholesterol levels does reduce the risk of heart attacks. Secondly, there is no clear-cut data to suggest progression of dementia. Thirdly, there is no clear data to support the risk of increased chance of a hemorrhagic stroke or a bleed into the brain. And this is even across populations who have genetically very low LDL cholesterol levels.
Fourth, the group notes that data reflecting the risk of hemorrhagic stroke with statin therapy among patients with a history of hemorrhagic stroke are not robust. PCSK9 inhibitors, these powerful agents we use in combination with statins, have not been adequately tested in patients with prior intracranial hemorrhage, so we can't really make long-term assessments about that. Lipid lowering in these populations requires more focused study.
So, in the setting of people with high risk of heart attack, we know that lowering cholesterol will reduce their risk, and consistently that's been the case. We know there's no signal or clear-cut demonstrable marker of increased risk of dementia. There is no clear-cut indicator or marker for increased likelihood of hemorrhagic stroke. We do know that there is space for more long-term studies, particularly with using the non-statin cholesterol-lowering agents.
Now, importantly, this research received no commercial funding, and the disclosures of all the people involved point to them being an extremely unbiased group and, of course, it's representing the position of the American Heart Association.
Well, anyone on a cholesterol-lowering agent who has any concerns about their cognitive function, their risk of dementia, or their risk of hemorrhagic stroke, I think this offers some reassurance. What we do know is that people are all different. And in my own practice, I'm aware of patients who have come and told me that without question, they have issues with their cholesterol-lowering medication. For example, forgetfulness. For example, clouded cognition. And for those individuals, we have to deal with them on a case-by-case basis, as everyone is a little bit different.
In general, though, I hope the American Heart Association position on aggressive lipid lowering was something that you found interesting. I'm going to leave it for now. Again, thank you so much for tuning in. If you have any queries or questions, drop us a note at info at drwarwickbishop.online, and I'm open to any suggestions for future podcasts as well.
For now, goodbye, and I hope you live as well as possible for as long as possible. Take care.
Did you know that coronary artery disease kills one in four people? So most of us are likely to carry some risk or know someone who does. If you're interested in finding out more about how to evaluate that risk, check out www.virtualheartcheck.com.au. It will give you information about risk and what else can be done to be even more precise.
