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REFLECTIONS
Dyslipidaemia
Dyslipidaemia Global Newsletter #6 2023

SPECIAL POPULATIONS Dyslipidaemia

Aggressive LDL-C lowering and the brain: Impact on risk for dementia and
hemorrhagic stroke: A scientific statement from the American Heart Association.
Goldstein LB, et al. Arterioscler Thromb Vasc Biol. 2023 Oct;43(10):e404-e442.

Lowering LDL-C is associated with reducing ASCVD risk, with no identified lower limit to LDL-C beneath which there is no further
ASCVD risk reduction. LDL-C targets for high- and very high-risk patients have decreased over time. Despite the known benefits
of LDL-C lowering, there is some concern on very low lowering of LDL-C, with some clinical trials suggesting an increased risk for
hemorrhagic stroke or detrimental effect on cognition.

The authors of this scientific statement aimed to evaluate the literature to support or refute the conclusion that aggressive LDL-C
lowering or lipid lowering exerts toxic effects on the brain, leading to cognitive impairment/dementia or hemorrhagic stroke. They
examined 1) the impact of aggressive LDL-C reduction on ASCVD events, including statin and non-statin therapies; 2) consequences
of inadequate LDL-C reduction, including practice gaps in lipid control and unfounded side effect concerns that prevent optimal
management; 3) the blood–brain barrier and lipids; 4) brain metabolism of cholesterol and potential effect of cholesterol-lowering
drugs; 5) ASCVD risk factors and Alzheimer disease; 6) lipid-lowering drugs and the risks of impaired cognition and dementia; 7)
reports of cognitive changes after statins are started; 8) LDL-C and ischemic stroke; 9) LDL-C reduction and hemorrhagic stroke risk;
and finally 10) LDL-C reduction after hemorrhagic stroke.

The authors concluded that the available data consistently show that lowering LDL-C reduces the risk of adverse ASCD-related
events in high-risk populations. Although some older retrospective, case-control, and prospective longitudinal studies suggest that
statins and LDL-C lowering are associated with cognitive impairment or dementia, the majority of observational studies and data from
randomized trials do not support this conclusion. While the authors suggest that additional studies are needed to ensure cognitive
safety over longer periods of time, they agree that contemporary guidelines recommending the risk-stratified attainment of lipid-
lowering goals are reasonable.

The risk of a hemorrhagic stroke associated with statin therapy CLINICAL PEARLS FROM THE FACULTY
in patients without a history of cerebrovascular disease was
found to be small and consistently non-significant. The authors
found no evidence that PCSK9i or ezetimibe increases bleeding
risk. There is no indication from either randomized studies or
Mendelian inheritance studies evaluating patients or populations
with lifelong low LDL-C that they have enhanced vulnerability to
hemorrhagic stroke, and there is little evidence that achieving
very low levels of LDL-C increases that risk. The authors note
that lower LDL-C correlates with lower risk of overall stroke and
stroke recurrence, mostly related to a reduction in ischemic
stroke. They comment that concern about hemorrhagic stroke WATCH
risk should not deter a clinician from treating LDL-C to guideline- DR. SHAWKY DISCUSS THE
recommended risk-stratified targets. RELEVANCE OF THE RESULTS ON
CLINICAL PRACTICE.
Finally, the authors note that data reflecting the risk of
hemorrhagic stroke with statin treatment among patients with a
history of hemorrhagic stroke are not robust. PCSK9 inhibitors CLICK HERE
have not been adequately tested in patients with prior ICH, and FOR THE LINK TO FULL ARTICLE
lipid lowering in this population requires more focused study.

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