High Prevalence of Cerebral Small Vessel Disease on 7T Magnetic Resonance Imaging in Familial Hypercholesterolemia

• Published in: Journal of Atherosclerosis and Thrombosis 2019/12/01, Vol.26(12), pp.1045-1053
• Main Authors: Todate, Yusuke, Uwano, Ikuko, Yashiro, Satoshi, Chida, Ai, Hasegawa, Yutaka, Oda, Tomoyasu, Nagasawa, Kan, Honma, Hiroyuki, Sasaki, Makoto, Ishigaki, Yasushi
• Format: Article
• Language: English
• Subjects: Blood Pressure; Case-Control Studies; Cerebral Small Vessel Diseases - diagnosis; Cerebral Small Vessel Diseases - epidemiology; Cerebral Small Vessel Diseases - etiology; Cholesterol, LDL - blood; Familial hypercholesterolemia; Female; Follow-Up Studies; Humans; Hyperlipoproteinemia Type II - complications; Japan - epidemiology; LDL cholesterol; Magnetic Resonance Imaging - methods; Male; Middle Aged; Neuroimaging; Original; Prevalence; Prognosis; Risk Factors; Stroke; White matter hyperintensity
• ISSN: 1340-3478; 1880-3873
• DOI: 10.5551/jat.48553

Aim: It remains unclear whether elevated low-density lipoprotein cholesterol (LDL-C) is a risk factor for cerebral vascular disease. Familial hypercholesterolemia (FH) is the most appropriate model for understanding the effects of excess LDL-C because affected individuals have inherently high levels of circulating LDL-C. To clarify the effects of hypercholesterolemia on cerebral small vessel disease (SVD), we investigated cerebrovascular damage in detail due to elevated LDL-C using high resolution brain magnetic resonance imaging (MRI) in patients with FH.Methods: Twenty-eight patients with FH and 35 healthy controls underwent 7T brain MRI. The prevalence of SVD and arterial structural changes were determined in each group.Results: The prevalence of periventricular hyperintensity (PVH) was significantly higher (control, 0% vs. FH, 14.2%, p=0.021) and deep white matter intensity tended to be more frequent in FH patients than in controls. The prevalence of SVD in patients with forms of cerebral damage, such as lacunar infarction, PVH, deep white matter hyperintensities (DWMH), microbleeding, and brain atrophy, was significantly higher among FH patients (control, n=2, 5.7% vs. FH, n=7, 25.0%, p＜0.001, chi-square test). The tortuosity of major intracranial arteries and the signal intensity of lenticulostriate arteries were similar in the two groups. In FH patients, as the grade of PVH progressed, several atherosclerosis risk factors, such as body mass index, blood pressure, and triglyceride level, showed ever worsening values.Conclusion: These results obtained from FH patients revealed that persistently elevated LDL-C leads to cerebral PVH. It is necessary in the management of FH to pay attention not only to the development of coronary heart disease but also to the presence of cerebral SVD.