Statin therapy reduces vertebral artery atherosclerotic plaques: a case report with insight from vessel wall magnetic resonance imaging

Introduction

Ischemic stroke remains a leading global health concern, with approximately 20% of cases involving the posterior circulation and up to one-third related to vertebral artery (VA) stenosis (1). The reduction of low-density lipoprotein cholesterol (LDL-C) levels using statins reduces stroke risk and stabilizes atherosclerotic plaques in various vascular territories (2,3). However, there is limited direct evidence for the statin-induced regression of VA plaques, especially when assessed using vessel wall magnetic resonance imaging (VW-MRI). In the present case, long-term statin therapy led to a marked improvement and near-complete resolution of severe VA stenosis and plaques on VW-MRI, highlighting the potential of intensive lipid-lowering therapy to induce significant vascular changes, even in VA atherosclerosis. We present this case in accordance with the CARE reporting checklist (available at https://qims.amegroups.com/article/view/10.21037/qims-2025-1156/rc).

Case presentation

A 65-year-old male presented to our outpatient clinic with symptoms of paresthesia in the right upper extremity. The patient had no history of smoking or alcohol use but had been diagnosed with hypertension and was receiving medication. In addition, the patient had no prior diagnoses of other illnesses, including cerebrovascular disease. At the time of visit, the patient’s lipid profile revealed a total cholesterol (TC) level of 210 mg/dL, triglyceride (TG) level of 128 mg/dL, high-density lipoprotein cholesterol (HDL-C) level of 54 mg/dL, and LDL-C level of 111.8 mg/dL. Brain magnetic resonance imaging was performed to evaluate the possibility of a transient ischemic attack, and severe stenosis in the right proximal VA was identified (Figure 1A).

Figure 1 Severe stenosis of the right vertebral artery was confirmed through multiple imaging studies prior to statin therapy. (A) Neck MRA shows severe stenosis of the right proximal vertebral artery (white arrow). (B,C) Digital subtraction angiography reveals severe stenosis at the same location identified in the neck MRA (black arrow). The degree of stenosis was measured as approximately 80%. These images were acquired using a Siemens AXIOM-Artis system (estimated magnification factor: ×1.37). (D) Vessel wall magnetic resonance imaging with time-of-flight shows the lumen of the right vertebral artery to have a high signal intensity, and the vessel wall appears thickened with iso-signal intensity material (white arrowhead). The left vertebral artery is also visualized with high signal intensity (red arrowhead). (E) On the T2-weighted image, the vascular lumen appears to have a hypo-signal intensity, whereas the plaque shows an overall hyper-signal intensity with areas of mixed hypo-signal intensity inside (white arrowhead). This suggests the presence of a lipid-rich necrotic core within fibrous tissue. The left vertebral artery appears as a low signal intensity structure without evidence of plaque (red arrowhead). (F) On the contrast-enhanced T1-weighted image, an intact fibrous cap is observed as high-signal intensity with enhancement, adjacent to the hypo-signal intensity vascular lumen (white arrowhead). The left vertebral artery with low signal intensity can also be identified (red arrowhead). MRA, magnetic resonance angiography.

Transfemoral cerebral angiography (TFCA) was performed for a more detailed assessment, and the results confirmed approximately 80% narrowing of the vessel lumen (Figure 1B,1C). To further evaluate plaque characteristics, VW-MRI was performed using a Philips Achieva 3T scanner (Philips Healthcare, Best, the Netherlands). For the contrast-enhanced T1-weighted sequences, gadobutrol (Gadovist^®, Schering AG, Berlin, Germany) was administered as the contrast agent. The results showed a massive plaque in the right stenotic lesion, characterized as a stable plaque with an intact fibrous cap and a large necrotic core (Figure 1D-1F).

The patient was treated with 40 mg atorvastatin for approximately 18 months. No neurological symptoms recurred during the study. In addition, the patient’s lipid profile improved significantly, with TC, TG, HDL-C, and LDL-C levels decreasing to 136, 66, 56, and 46.8 mg/dL, respectively. Subsequently, the atorvastatin dose was reduced to 10 mg for maintenance.

Three years after the initial diagnosis, a follow-up TFCA was performed to monitor the vascular condition and assess the need for angioplasty. The results showed complete resolution of the stenotic lesion in the right proximal VA, with no abnormalities in distal flow (Figure 2A,2B). In addition, neck magnetic resonance angiography and VW-MRI demonstrated significant improvement, and the previously identified massive plaque and severe stenosis in the right proximal VA were no longer evident (Figure 2C-2F). The follow-up VW-MRI was performed using the same scanner and with the same contrast agent as the initial VW-MRI.

Figure 2 Three years after starting statin therapy, follow-up imaging revealed disappearance of the previously detected right vertebral artery plaque. (A,B) On digital subtraction angiography, the previously observed severe stenosis of the right proximal vertebral artery is no longer present (black arrow), and the distal flow appears normal. These images were acquired using a Siemens AXIOM-Artis system (estimated magnification factor: ×1.37). (C) MRA confirms the improvement of the severe stenosis in the right proximal vertebral artery (white arrow). (D) On vessel wall magnetic resonance imaging with time-of-flight, the iso-signal intensity plaque previously seen is no longer visible (white arrowhead). The left vertebral artery with similar signal intensity can also be seen (red arrowhead). (E) On T2-weighted image, the plaque, which was composed of high-signal intensity and hypo-signal intensity areas, has disappeared (white arrowhead). The left vertebral artery with low signal intensity is observed (red arrowhead). (F) On contrast-enhanced T1-weighted image, the plaque has significantly regressed (white arrowhead). The left vertebral artery with low signal intensity is also observed, showing the same appearance as before (red arrowhead). MRA, magnetic resonance angiography.

Despite complete resolution of stenosis observed in follow-up imaging of the VA, the possibility of arterial dissection could not be entirely ruled out. However, features characteristic of dissection, such as intimal flap, double lumen, and delayed contrast filling, were not observed during TFCA. Furthermore, VW-MRI similarly revealed findings consistent with a lipid-rich necrotic core and fibrous cap, rather than an intimal flap or intramural hematoma. Therefore, the stenosis was determined to be caused by an atherosclerotic plaque rather than dissection.

Subsequently, the patient developed impaired kidney function, leading to discontinuation of statin therapy. Despite this, the patient remained free of neurological symptoms.

Ethical considerations

All procedures performed in this study were in accordance with the ethical standards of the institutional and/or national research committee(s) and with the Declaration of Helsinki and its subsequent amendments. Written informed consent was obtained from the patient for publication of this case report and accompanying images. A copy of the written consent is available for review by the editorial office of this journal.

Discussion

Globally, 7.6 million people are diagnosed with ischemic stroke annually, accounting for approximately 62% of all stroke cases. In addition, 3.3 million people die annually from ischemic stroke, and the associated societal burden continues to increase (4). This underscores the urgent need for the development of effective preventive strategies. Dyslipidemia is a primary risk factor that increases the risk of ischemic stroke by approximately 28% is dyslipidemia (5). Among the various lipid profiles, LDL-C is the most useful indicator of the risk of ischemic stroke, and it is closely associated with one of its etiological subtypes, large artery atherosclerosis. Meta-analyses of randomized trials have shown that each 1 mmol/L reduction in LDL-C level is associated with a 22% decrease in major vascular events (2). Consequently, lowering LDL-C levels can reduce the risk of ischemic stroke, and statins are commonly used medications for lowering the levels. Findings from previous studies, along with the observations in this case report, have shaped clinical practice and reinforced the role of statins in both primary and secondary prevention.

It is well known that a mechanism of action of statins is the inhibition of 3-hydroxy-3-methylglutaryl coenzyme A reductase, which suppresses cholesterol synthesis (6). In addition, statins exert pleiotropic effects by suppressing the production of isoprenoid intermediates. These effects contribute to the stabilization and reduction of atherosclerotic plaques (7,8). Furthermore, these pleiotropic effects of statins represent a key mechanism that may explain plaque regression in the present case and are the primary phenomena of interest in this report. The efficacy of statins has been demonstrated not only in stroke prevention but also in coronary heart disease, where they have been incorporated into clinical guidelines and have shown favorable outcomes in real-world clinical practice (9,10). In cases of stroke associated with large artery atherosclerosis, statin therapy significantly reduced the risk of stroke recurrence (11). Similarly, in the present case, statin therapy was initiated to prevent stroke.

The beneficial effects of statins on atherosclerotic plaques have been objectively demonstrated using VW-MRI. The characteristics of plaques identified on VW-MRI are closely correlated with histopathological findings, demonstrating the effectiveness of this imaging technique in evaluating treatment responses in atherosclerotic plaques (12,13). Moreover, studies utilizing VW-MRI have shown that lowering LDL-C levels reduces the lipid content within plaques, inducing plaque regression, and ultimately stabilizing the plaques (14-16). Besides, the therapeutic effects of statins on atherosclerotic plaques in the carotid and intracranial arteries have been confirmed using VW-MRI (17,18). However, there is limited evidence regarding the efficacy of statins on atherosclerotic plaques in the VA, and no studies have objectively confirmed their effects using VW-MRI.

The VA supplies blood to the posterior circulation, including the cerebellum, brainstem, and the inferior and posterior cerebral hemispheres. Posterior circulation infarctions account for approximately one-fifth of all ischemic strokes (1), with 25–33% attributed to vertebrobasilar artery stenosis. Atherosclerotic plaque rupture and distal embolization are important mechanisms (19), implying that plaque stabilization in the VA could prevent stroke. However, the effect of statins on VA plaques remains unclear. Although the stabilization of atherosclerotic plaques is expected to reduce the risk of infarction due to VA stenosis, some studies suggest that the effects of statin therapy on the VA may be minimal (20). This may be attributed to differences in the composition of the vascular wall and the lack of sympathetic innervation, making the VA more vulnerable to hypertension and vascular aging (21,22). Compared to other cranial arteries, the VA may show a reduced response to statin treatment.

However, the present case suggests a different perspective. As demonstrated in the patient in this report statin therapy can effectively contribute to plaque regression, even in patients with VA atherosclerotic plaques causing stenosis. This challenges the notion that VA plaques are resistant to statin treatment and highlights the potential role of intensive lipid-lowering therapy in the management of posterior circulation atherosclerosis.

A notable limitation of this case was the relatively lower image quality observed in the follow-up VW-MRI compared to the initial study. This was likely attributable to patient motion and variability in slice positioning during image acquisition. As a result, the delineation of vessel wall boundaries appeared less distinct, potentially affecting diagnostic clarity. Nonetheless, the regression of the previously noted atherosclerotic plaque, including the disappearance of the lipid-rich necrotic core, could still be reliably assessed. We acknowledge this as a technical limitation and have reflected it accordingly in the interpretation of our findings.

Taken together, this case suggests the therapeutic potential of statins even in vascular territories traditionally considered less responsive to treatment. It also indicates that VW-MRI is a useful tool for monitoring the dynamic changes of atherosclerotic plaques.

Conclusions

This case demonstrates that long-term statin therapy can induce significant regression of VA atherosclerotic plaques, as confirmed by serial vessel wall magnetic resonance imaging and angiography. The complete resolution of stenosis following long-term statin administration suggests that posterior circulation atherosclerosis may respond more favorably to lipid-lowering therapy than previously assumed. These observations underscore the clinical utility of vessel wall imaging in monitoring treatment response in vertebrobasilar disease. Further studies are warranted to clarify the broader implications of statin therapy in this vascular territory and to establish standardized imaging-based strategies for follow-up.

Acknowledgments

None.

Footnote

Reporting Checklist: The authors have completed the CARE reporting checklist. Available at https://qims.amegroups.com/article/view/10.21037/qims-2025-1156/rc

Funding: The study was supported by “Research Base Construction Fund Support Program” funded by Jeonbuk National University in 2025.

Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://qims.amegroups.com/article/view/10.21037/qims-2025-1156/coif). The authors have no conflicts of interest to declare.

Ethical Statement: The authors are accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved. All procedures performed in this study were in accordance with the ethical standards of the institutional and/or national research committee(s) and with the Declaration of Helsinki and its subsequent amendments. Written informed consent was obtained from the patient for publication of this case report and accompanying images. A copy of the written consent is available for review by the editorial office of this journal.

Open Access Statement: This is an Open Access article distributed in accordance with the Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International License (CC BY-NC-ND 4.0), which permits the non-commercial replication and distribution of the article with the strict proviso that no changes or edits are made and the original work is properly cited (including links to both the formal publication through the relevant DOI and the license). See: https://creativecommons.org/licenses/by-nc-nd/4.0/.

References

1. Markus HS, van der Worp HB, Rothwell PM. Posterior circulation ischaemic stroke and transient ischaemic attack: diagnosis, investigation, and secondary prevention. Lancet Neurol 2013;12:989-98. [Crossref] [PubMed]
2. Baigent C, Blackwell L, Emberson J, Holland LE, Reith C, Bhala N, Peto R, Barnes EH, Keech A, Simes J, Collins R. Efficacy and safety of more intensive lowering of LDL cholesterol: a meta-analysis of data from 170,000 participants in 26 randomised trials. Lancet 2010;376:1670-81. [Crossref] [PubMed]
3. Kim JS. Role of Blood Lipid Levels and Lipid-Lowering Therapy in Stroke Patients with Different Levels of Cerebral Artery Diseases: Reconsidering Recent Stroke Guidelines. J Stroke 2021;23:149-61. [Crossref] [PubMed]
4. Global, regional, and national burden of stroke and its risk factors, 1990-2019: a systematic analysis for the Global Burden of Disease Study 2019. Lancet Neurol 2021;20:795-820. [Crossref] [PubMed]
5. Benjamin EJ, Muntner P, Alonso A, Bittencourt MS, Callaway CW, Carson AP, et al. Heart Disease and Stroke Statistics-2019 Update: A Report From the American Heart Association. Circulation 2019;139:e56-e528. [Crossref] [PubMed]
6. Endo A, Kuroda M, Tsujita Y. ML-236A, ML-236B, and ML-236C, new inhibitors of cholesterogenesis produced by Penicillium citrinium. J Antibiot (Tokyo) 1976;29:1346-8. [Crossref] [PubMed]
7. Oesterle A, Laufs U, Liao JK. Pleiotropic Effects of Statins on the Cardiovascular System. Circ Res 2017;120:229-43. [Crossref] [PubMed]
8. Vaughan CJ, Gotto AM Jr, Basson CT. The evolving role of statins in the management of atherosclerosis. J Am Coll Cardiol 2000;35:1-10. [Crossref] [PubMed]
9. Amarenco P, Kim JS, Labreuche J, Charles H, Abtan J, Béjot Y, et al. A Comparison of Two LDL Cholesterol Targets after Ischemic Stroke. N Engl J Med 2020;382:9. [Crossref] [PubMed]
10. Tramacere I, Boncoraglio GB, Banzi R, Del Giovane C, Kwag KH, Squizzato A, Moja L. Comparison of statins for secondary prevention in patients with ischemic stroke or transient ischemic attack: a systematic review and network meta-analysis. BMC Med 2019;17:67. [Crossref] [PubMed]
11. Amarenco P, Benavente O, Goldstein LB, Callahan A 3rd, Sillesen H, Hennerici MG, Gilbert S, Rudolph AE, Simunovic L, Zivin JA, Welch KM. Results of the Stroke Prevention by Aggressive Reduction in Cholesterol Levels (SPARCL) trial by stroke subtypes. Stroke 2009;40:1405-9. [Crossref] [PubMed]
12. Cai J, Hatsukami TS, Ferguson MS, Kerwin WS, Saam T, Chu B, Takaya N, Polissar NL, Yuan C. In vivo quantitative measurement of intact fibrous cap and lipid-rich necrotic core size in atherosclerotic carotid plaque: comparison of high-resolution, contrast-enhanced magnetic resonance imaging and histology. Circulation 2005;112:3437-44. [Crossref] [PubMed]
13. Takaya N, Cai J, Ferguson MS, Yarnykh VL, Chu B, Saam T, Polissar NL, Sherwood J, Cury RC, Anders RJ, Broschat KO, Hinton D, Furie KL, Hatsukami TS, Yuan C. Intra- and interreader reproducibility of magnetic resonance imaging for quantifying the lipid-rich necrotic core is improved with gadolinium contrast enhancement. J Magn Reson Imaging 2006;24:203-10. [Crossref] [PubMed]
14. Alkhalil M, Chai JT, Choudhury RP. Plaque imaging to refine indications for emerging lipid-lowering drugs. Eur Heart J Cardiovasc Pharmacother 2017;3:58-67. [Crossref] [PubMed]
15. Du R, Cai J, Zhao XQ, Wang QJ, Liu DQ, Leng WX, Gao P, Wu HM, Ma L, Ye P. Early decrease in carotid plaque lipid content as assessed by magnetic resonance imaging during treatment of rosuvastatin. BMC Cardiovasc Disord 2014;14:83. [Crossref] [PubMed]
16. Mujaj B, Bos D, Selwaness M, Leening MJG, Kavousi M, Wentzel JJ, van der Lugt A, Hofman A, Stricker BH, Vernooij MW, Franco OH. Statin use is associated with carotid plaque composition: The Rotterdam Study. Int J Cardiol 2018;260:213-8. [Crossref] [PubMed]
17. Brinjikji W, Lehman VT, Kallmes DF, Rabinstein AA, Lanzino G, Murad MH, Mulvagh S, Klaas J, Graff-Radford J, DeMarco KJ, Huston Iii J. The effects of statin therapy on carotid plaque composition and volume: A systematic review and meta-analysis. J Neuroradiol 2017;44:234-40. [Crossref] [PubMed]
18. Chung JW, Cha J, Lee MJ, Yu IW, Park MS, Seo WK, Kim ST, Bang OY. Intensive Statin Treatment in Acute Ischaemic Stroke Patients with Intracranial Atherosclerosis: a High-Resolution Magnetic Resonance Imaging study (STAMINA-MRI Study). J Neurol Neurosurg Psychiatry 2020;91:204-11. [Crossref] [PubMed]
19. Cloud GC, Markus HS. Vertebral Artery Stenosis. Curr Treat Options Cardiovasc Med 2004;6:121-7. [Crossref] [PubMed]
20. Sim JE, Song HN, Choi JU, Lee JE, Baek IY, Cho HH, Kim JH, Chung JW, Kim GM, Park HJ, Bang OY, Seo WK. The effect of intensive statin therapy in non-symptomatic intracranial arteries: The STAMINA-MRI sub-study. Front Neurol 2023;14:1069502. [Crossref] [PubMed]
21. Roth W, Morgello S, Goldman J, Mohr JP, Elkind MS, Marshall RS, Gutierrez J. Histopathological Differences Between the Anterior and Posterior Brain Arteries as a Function of Aging. Stroke 2017;48:638-44. [Crossref] [PubMed]
22. Cipolla MJ, Liebeskind DS, Chan SL. The importance of comorbidities in ischemic stroke: Impact of hypertension on the cerebral circulation. J Cereb Blood Flow Metab 2018;38:2129-49. [Crossref] [PubMed]