Shigeru Yamano

Inflammatory Response to Acute Myocardial Infarction Augments Neointimal Hyperplasia After Vascular Injury in a Remote Artery

Objective—Percutaneous coronary intervention (PCI) is currently the most widely accepted treatment for acute myocardial infarction (AMI). It remains unclear, however, whether post-AMI conditions might exacerbate neointimal hyperplasia and restenosis following PCI. Given that both a medial smooth muscle cell lineage and a bone marrow (BM)-derived hematopoietic stem cell lineage are now thought to contribute to neointima formation, the primary aims of the present study were to determine whether AMI augments neointimal hyperplasia at sites of arterial injury, and whether BM-derived cells contribute to that process. Methods and Results—We simultaneously generated models of AMI and arterial injury in the same mice, some of which had received BM transplantation. We found that AMI augments neointimal hyperplasia at sites of femoral artery injury by ≈35% (P<0.05), but that while BM-derived cells contributed to neointimal hyperplasia, they did not contribute to the AMI-related augmentation. Expression of interleukin (IL)-6 mRNA was ≈7-fold higher in the neointimas of mice subjected to both AMI and arterial injury than in those of mice subjected to arterial injury alone. In addition, we observed increased synthesis of tumor necrosis factor (TNF)-&agr; within infarcted hearts and TNF-&agr; receptor type 1 (TNFR1) within injured arteries. Chronic treatment with pentoxifylline, which mainly inhibits TNF-&agr; synthesis, reduced levels of circulating TNF-&agr; and attenuated neointimal hyperplasia after AMI. Conclusions—Conditions after AMI could exacerbate postangioplasty restenosis, not by increasing mobilization of BM-derived cells, but by stimulating signaling via TNF-&agr;, TNFR1 and IL-6.

Carotid Atherosclerosis Is Associated with Brain Atrophy in Japanese Elders

Background: The relation between atherosclerosis and brain atrophy remains unclear in patients with risk factors for cardiovascular diseases. Objective: This study was performed to clarify the relation between brain atrophy and carotid atherosclerosis. Methods: A total of 142 patients (78 women and 64 men, mean age 74 years) with no neurologic disturbances were studied. Brain atrophy was evaluated on the basis of the brain atrophy index (BAI, BAI = brain parenchyma/intracranial space A 100%), calculated by means of digitized computed tomographic scans obtained at the level of the basal ganglia. Carotid atherosclerosis was evaluated on the basis of the plaque score (PS), defined as the sum of all plaque heights in both carotid arteries, intima-media thickness (IMT), and vessel diameter (VD) of the common carotid artery as assessed by ultrasonography. Results: Age negatively correlated with BAI in both men (r = –0.587, p < 0.001) and women (r = –0.724, p < 0.001). PS of the carotid artery also negatively correlated with BAI in men (r = –0.502, p < 0.001) as well as women (r = –0.480, p < 0.001). VD and IMT of the right carotid artery negatively correlated with BAI in women (VD; –0.256, p < 0.05, IMT; –0.216, p < 0.05) but not in men. Other characteristics were unrelated to BAI. Multiple regression analysis showed that age and PS were independent predictors of brain atrophy in both sexes. The percentage of variance of BAI values explained by this model in women (51.9%) was much greater than that in men (35.5%). Conclusion: Carotid atherosclerosis may be a useful morphological index of brain atrophy.

Primary systemic amyloidosis presenting as angina pectoris due to intramyocardial coronary artery involvement: a case report.

Abstract We describe a 76-year-old Japanese woman with primary systemic amyloidosis who presented with angina pectoris associated with ST-segment and T-wave abnormalities resulting from intramyocardial coronary artery amyloidosis. The patient was admitted to our hospital because of dyspnea and pretibial edema 7 years after the diagnosis of variant angina. A diagnosis of primary systemic amyloidosis (AL amyloid protein) was made after examination of gastric and endomyocardial biopsy specimens. The patient died of progressive, uncontrolled heart failure 3 months later. An autopsy study demonstrated only mild-to-moderate atherosclerosis in the epicardial coronary arteries. However, histological examination of the heart revealed diffuse stenoses and obstructions in the intramural coronary arteries by amyloid deposits. This patient had small-vessel coronary disease with ST-segment changes and angina caused by cardiac amyloidosis. A correct diagnosis of ischemic heart disease due to primary amyloidosis is important for estimation of the prognosis and for appropriate management.

Major risk factors for the appearance of white-matter lesions on MRI in hypertensive patients with controlled blood pressure

Purpose Blood pressure (BP), age, and reduced renal function are major risk factors for white-matter lesions (WMLs) in the general population. However, it remains unclear whether or not the BP itself or other parameters related to the BP are associated with WMLs in hypertensive patients with well-controlled BP. We investigated the relationships of the presence of WMLs with the central systolic BP (cSBP) and estimated glomerular filtration rate (eGFR) in treated hypertensive patients. Method We studied 185 hypertensive patients with median duration of hypertension, 10.0 years, whose BP is controlled to SBP and diastolic BP (DBP) of 139 ± 17 and 79 ± 10 mmHg, respectively. We measured cSBP and brain magnetic resonance imaging (MRI) was examined within 2 weeks after last BP and biological measurements. Results Patients with higher-grade WMLs, as assessed by the presence of Scheltens deep white-matter hyperintensity (SDWMH) in the frontal (grade 0–2 vs 3–6) and parietal areas (grade 0–2 vs 3–6) where small arteries are affected at earlier stage of hypertension, as well as that of Fazekas deep white-matter hyperintensity (FDWMH) (grade 2–3 vs 0–1) and Fazekas periventricular hyperintensity (FPVH) (grade 1–3 vs 0) were older, had higher serum creatinine levels, a longer duration of hypertension, and lower eGFR values. The grade of the WMLs was not associated with either the cSBP or the brachial SBP. In logistic regression analyses after adjustment for age, sex, cSBP, and hypertension duration, showed significant association between eGFR and WMLs. The patients with lower eGFR (<60 mL/minute/1.73 m2) tended to have higher grade WMLs. The odds ratio was 2.87 for FDWMH (P = 0.017), 1.99 for FPVH (P = 0.131), and 2.33 for SDWMH in the parietal area (P = 0.045). Conclusion Presence of WMLs was associated with eGFR, but not with either the brachial SBP or cSBP in hypertensive patients with well-controlled BP.

Comparison between Angiotensin-Converting Enzyme Inhibitors and Angiotensin Receptor Blockers on the Risk of Stroke Recurrence and Longitudinal Progression of White Matter Lesions and Silent Brain Infarcts on MRI (CEREBRAL Study): Rationale, Design, and Methodology

Objectives Patients with a history of ischemic stroke are known to develop new ischemic stroke. While asymptomatic, the presence and progression of silent brain infarcts and white matter lesions on magnetic resonance imaging are associated with an increased risk of future strokes. Both angiotensin-converting enzyme inhibitors and angiotensin II receptor blockers are recommended for the primary and secondary prevention of stroke, but there are no direct comparisons of angiotensin-converting enzyme inhibitors versus angiotensin II receptor blockers regarding their cerebroprotective effects, including their effect on asymptomatic cerebral lesions detected by magnetic resonance imaging. Methods Elderly (65 years or older) patients with essential hypertension who underwent cerebral magnetic resonance imaging and were found to have any cerebral ischemic lesions, such as cerebral infarction, silent brain infarct, or white matter lesion, were enrolled in this CEREBRAL study. Patients who agreed to participate were enrolled in the randomized controlled trial portion. Patients who did not agree to participate in the randomized controlled trial were enrolled in the cohort study portion. After two-years of angiotensin-converting enzyme inhibitor or angiotensin II receptor blockers treatment, follow-up magnetic resonance imaging examination will be performed. The primary end-point is the composite of (1) occurrence of a fatal or nonfatal cerebrovascular event or (2) progression of cerebrovascular lesions as evaluated by magnetic resonance imaging, including white matter lesions or silent brain infarcts. After enrollment, cognitive function was evaluated, if possible, using the Mini-Mental State Examination. Conclusions Our study will clarify whether angiotensin-converting enzyme inhibitors or angiotensin II receptor blockers are more effective for preventing primary and recurrence of ischemic stroke, including the progression of asymptomatic cerebral lesions on magnetic resonance imaging, in elderly hypertensive patients.