Atorvastatin and growth, rupture of small unruptured intracranial aneurysm: results of a prospective cohort study

 In case you have an aneurysm, plus whatever your doctor is already doing.

Atorvastatin and growth, rupture of small unruptured intracranial aneurysm: results of a prospective cohort study

Show all authors

Jie Wang*, Jiancong Weng*, Hao Li, ...

First Published April 9, 2021 Research Article 

https://doi.org/10.1177/1756286420987939

Article information

Abstract

Background and aims:

The role of statins in unruptured intracranial aneurysm (UIA) growth and rupture remains ambiguous. This study sought to determine whether atorvastatin is associated with aneurysm growth and rupture in patients harboring UIA <7 mm.

Methods:

This prospective, multicenter cohort study consecutively enrolled patients with concurrent UIA <7 mm and ischemic cerebrovascular disease from four hospitals between 2016 and 2019. Baseline and follow-up patient information was recorded. Because of the strong anti-inflammatory effect of aspirin, patients using aspirin were excluded. Patients taking atorvastatin 20 mg daily were atorvastatin users. The primary and exploratory endpoints were aneurysm rupture and growth, respectively.

Results:

Among the 1087 enrolled patients, 489 (45.0%) took atorvastatin, and 598 (55%) took no atorvastatin. After a mean follow-up duration of 33.0 ± 12.5 months, six (1.2%) and five (0.8%) aneurysms ruptured in atorvastatin and non-atorvastatin groups, respectively. In the adjusted multivariate Cox analysis, UIA sized 5 to <7 mm, current smoker, and uncontrolled hypertension were associated with aneurysm rupture, whereas atorvastatin [adjusted hazard ratio (HR) 1.495, 95% confidence interval (CI) 0.417–5.356, p = 0.537] was not. Of 159 patients who had follow-up imaging, 34 (21.4%) took atorvastatin and 125 (78.6%) took no atorvastatin. Aneurysm growth occurred in five (14.7%) and 21 (16.8%) patients in atorvastatin and non-atorvastatin groups (mean follow-up: 20.2 ± 12.9 months), respectively. In the adjusted multivariate Cox analysis, UIAs sized 5 to <7 mm and uncontrolled hypertension were associated with a high growth rate; atorvastatin (adjusted HR 0.151, 95% CI 0.031–0.729, p = 0.019) was associated with a reduced growth rate.

Conclusions:

We conclude atorvastatin use is associated with a reduced risk of UIA growth, whereas atorvastatin is not associated with UIA rupture.

The trial registry name:

The Clinic Benefit and Risk of Oral Aspirin for Unruptured Intracranial Aneurysm Combined With Cerebral Ischemia

Clinical Trial Registration-URL:

http://www.clinicaltrials.gov

 

Statins: Not the Cure for Heart Disease

All this writing about statistics of statins and not one word about the real cause of heart disease, inflammation in the artery wall. Don't these doctors ever talk to each other or read the current literature? I asked my doctor about this and he told me my cholesterol drug, atorvastatin, was also anti-inflammatory.

World Renowned Heart Surgeon Speaks Out On What Really Causes Heart Disease

Statins: Not the Cure for Heart Disease

Right now, 40 million Americans take statins to lower cholesterol in an attempt to prevent complications of atherosclerosis such as heart disease and stroke. Despite this, heart disease is still the No. 1 cause of death in the U.S., and stroke is the fifth leading cause of death. Patients on high-intensity statin therapy can still have heart attacks, strokes and other vascular issues. Thus, it is important for both the health care provider and the patient to understand the role of statins in heart disease prevention.
One important concept during the health care providers and patient discussion about statins is the statistical term "number needed to treat" — or NNT — meaning the number of patients that must get a specific treatment before one event is prevented.
For the primary prevention of heart disease (preventing the first event), the number of patients that need statin therapy to prevent one death from heart disease is 167. To prevent one heart attack the NNT is 77, and to prevent one stroke 250 patients need to be on a statin. This is based on data from a meta-analysis published in 2010 which had a 4-year follow-up. Review the abstract here. For secondary prevention of heart disease, the NNT is closer to 80 (read more here).
The patient needs to know that being on a statin does not give them a free pass to eat a diet high in cholesterol and saturated fat. This needs to be strongly reinforced by the health care provider at every visit. In fact, diets that are cholesterol-free and low in processed and refined foods (aka, a whole-foods plant-based diet) can markedly reduce serum cholesterol levels to the same degree or better than statin therapy.
A great anecdotal example from the former president of the American College of Cardiology Kim Williams, MD, can be read here. His LDL dramatically reduced by changing to a plant-based diet and he avoided the need for statin therapy completely. Health care providers should place greater emphasis on lifestyle change instead of just prescribing a statin without having the patient commit to dietary changes.
Whether the DASH diet, Mediterranean diet or a whole-foods plant-based diet — as seen in the documentary "Forks Over Knives," which I refer patients to regularly — anything is better than the standard American diet. Practitioners should know, however, that the only diet ever shown to cause regression of atherosclerosis is the whole-foods plant-based diet, as seen on quantitative angiography, which you can read about here and here. While data are limited on mortality benefit and plant-based nutrition, unlike the data for statins, the rates of cardiac events and cardiovascular deaths were near zero with this nutritional approach, even in a high-risk patient population in these small studies.
Statins are not the cure for heart disease, but perhaps diet and lifestyle changes are. Focus on diet and lifestyle changes, including a whole food plant-based diet as an option. As the saying goes: turn off the faucet, do not just mop the floor.
– by Steven Lome, DO, RVT

 

Atorvastatin enhances kainate-induced gamma oscillations in rat hippocampal slices

And why would studying oscillations of dead rat brain give any useful information? This should have been laughed out of existence. Or is the rat alive but able to virtually slice its' brain?
http://onlinelibrary.wiley.com/doi/10.1111/ejn.13322/abstract

1. ChengZhang Li^1,†,
2. JianGang Wang^1,†,
3. Jianhua Zhao²,
4. Yali Wang¹,
5. Zhihua Liu¹,
6. FangLi Guo¹,
7. XiaoFang Wang¹,
8. Martin Vreugdenhil^3,4 and
9. ChengBiao Lu^1,*

DOI: 10.1111/ejn.13322

This article is protected by copyright. All rights reserved.

Issue

European Journal of Neuroscience

Accepted Article (Accepted, unedited articles published online and citable. The final edited and typeset version of record will appear in future.)

Additional Information(Show All)

Author InformationPublication History

1. This article has been accepted for publication and undergone full peer review but has not been through the copyediting, typesetting, pagination and proofreading process, which may lead to differences between this version and the Version of Record. Please cite this article as doi: 10.1111/ejn.13322

SEARCH

Search Scope

Search String

• Advanced >
• Saved Searches >

ARTICLE TOOLS

• Get PDF (710K)
• Save to My Profile
• E-mail Link to this Article
• Export Citation for this Article
• Get Citation Alerts

Share

• Abstract
• Cited By

Get PDF (710K)

Keywords:

• Hippocampus;
• pyramidal neurons;
• interneurons;
• PKA ;
• ERK ;
• PI3K

Abstract

Atorvastatin has been shown to affect cognitive functions in rodents and humans. However, the underlying mechanism is not fully understood. Because hippocampal gamma oscillations (γ, 20-80 Hz) are associated with cognitive functions, we studied the effect of atorvastatin on persistent kainate-induced γ oscillation in the CA3 area of rat hippocampal slices. The involvement of NMDA receptors and multiple kinases was tested before and after administration of atorvastatin. Whole-cell current-clamp and voltage-clamp recordings were made from CA3 pyramidal neurons and interneurons before and after atorvastatin application. Atorvastatin increased γ power by ~50% in a concentration-dependent manner, without affecting dominant frequency. Whereas atorvastatin did not affect intrinsic properties of both pyramidal neurons and interneurons, it increased the firing frequency of interneurons but not that of pyramidal neurons. Furthermore, whereas atorvastatin did not affect synaptic current amplitude, it increased the frequency of spontaneous IPSCs, but did not affect the frequency of spontaneous EPSCs. The atorvastatin-induced enhancement of γ oscillations was prevented by pretreatment with the PKA inhibitor H89, the ERK inhibitor U0126, or the PI3K inhibitor wortmanin, but not by the NMDA receptor antagonist D-AP5. Taken together, these results demonstrate that atorvastatin enhanced the kainate-induced γ oscillation by increasing interneuron excitability, with an involvement of multiple intracellular kinase pathways. Our study suggests that the classical cholesterol-lowering agent atorvastatin may improve cognitive functions compromised in disease, via the enhancement of hippocampal γ oscillations.

This article is protected by copyright. All rights reserved.

Get PDF (710K)