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

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.

Evaluation of Lenticulostriate Arteries Changes by 7 T Magnetic Resonance Angiography in Type 2 Diabetes.

AIM: Progress in neuroimaging techniques allows us to investigate the microvasculature characteristics including lenticulostriate arteries (LSA), which are closely associated with lacunar infarction. Because ischemic stroke is a more critical health problem in East Asian than in other populations, in order to clarify pathological changes underlying cerebral small vessel disease (SVD), we projected an imaging analysis of LSA using high-resolution brain magnetic resonance imaging (MRI) in middle-aged Japanese subjects with type 2 diabetes. METHODS: Twenty-five subjects with type 2 diabetes and 25 non-diabetic control subjects underwent 7 Tesla (7 T) brain MRI. The prevalences of SVD and LSA structural changes were determined in each group. RESULTS: SVD prevalence did not differ significantly between the type 2 diabetes and control groups. The average numbers of stems, as well as numbers of branches, of LSA were significantly smaller in diabetic subjects than non-diabetic control subjects. The signal intensity of LSA was markedly decreased, indicating reduced blood flow in type 2 diabetes. CONCLUSION: In spite of the prevalence of SVD being similar, structural changes and decreased signal intensity of LSA were highly detected in diabetic subjects compared with non-diabetic controls, suggesting that 7 T MRA enables us to determine LSA impairment prior to the development of SVD. Early detection of LSA impairment allows us earlier interventions aimed at the prevention of atherosclerotic events.

Association of Advanced Glycation End Products with coronary Artery Calcification in Japanese Subjects with Type 2 Diabetes as Assessed by Skin Autofluorescence.

AIM: Advanced glycation end products (AGE) are considered to be among the critical pathogenic factors involved in the progression of diabetic complications. Skin autofluorescence (AF), a noninvasive measurement of AGE accumulation, has been recognized as a useful and convenient marker for diabetic vascular diseases in Caucasians. This study aimed to evaluate the association of tissue AGE, assessed using skin AF, with coronary artery calcification in Japanese subjects with type 2 diabetes. METHODS: In total, 122 Japanese subjects with type 2 diabetes enrolled in this cross-sectional study underwent multi-slice computed tomography for total coronary artery calcium scores (CACS) estimation and examination with a skin AF reader. RESULTS: Skin AF positively correlated with age, sex, diabetes duration, pulse wave velocity, systolic blood pressure, serum creatinine, and CACS. In addition, skin AF results negatively correlated with BMI, eGFR, and serum C-peptide concentration. According to multivariate analysis, age and systolic blood pressure showed strong positive correlation and eGFR showed negative correlation with skin AF values. Multiple linear regression analyses revealed a significant positive correlation between skin AF values and logCACS, independent of age, sex, diabetes duration, HbA1c, BMI, IMT, and blood pressure. However, skin AF showed no association with serum levels of AGE, such as Nε-(carboxymethyl) lysine and 3-deoxyglucosone. CONCLUSION: Skin AF results positively correlated with CACS in Japanese subjects with type 2 diabetes. This result indicates that AGE plays a role in the pathogenesis of diabetic macrovascular disease. Measurement of skin AF values may be useful for assessing the severity of diabetic complications in Japanese subjects.