Professor Hamburg's lecture focuses on understanding what is happening to the endothelium in patients with diabetes. The many previous cohort studies have shown that vascular dysfunction predicts cardiovascular disease and that it really reflects an early event in the pathogenesis of therosclerosis, myocardial dysfunction, hypertension, and stroke. According to her own studies and the recent researches reveal that there is a particular association between diabetes mellitus and microvascular dysfunction reflected by abnormal Peripheral Arterial Tonometry ratio and reactive hyperemia. And further, she carried out a series of studies using the ability to collect endothelial cells from patients to show that endothelial phenotype is altered in patients with diabetes, with loss of insulin signaling, loss of nitric oxide, and activation of inflammation. And it is suggested that this is a platform to understand how interventions might benefit the endothelial cells in patients with diabetes at cardiovascular standpoint.

Background: To investigate factors associated with the maximal intima-media thickness (max-IMT) of the carotid artery, particularly plaques of an max-IMT of >1.5 mm, in a geographically coherent population in Japan. Methods: A total of 1,073 residents underwent carotid artery ultrasonography during the health screening conducted in Tochigi Prefecture, Japan, from October 2015 to March 2019. The observable visual field of max-IMT was evaluated in 929 participants without stroke or coronary artery disease. The results of a self-administered questionnaire survey examining risk factors for vascular disease were assessed, and factors associated with a max-IMT of >1.5 mm were analyzed. Results: Overall, 15.1% of the participants had a max-IMT of >1.5 mm. There were more elderly male patients and hypertensive patients (47.9% vs. 30.8%) in the max-IMT >1.5-mm group than in the max-IMT ≤1.5-mm group. The prevalence of dyslipidemia and diabetes mellitus was higher in the max-IMT >1.5-mm group than in the max-IMT ≤1.5-mm group. Logistic regression analysis after adjusting for age and sex revealed that hypertension (odds ratio, 1.54; 95% confidence interval, 1.05-2.26; p = 0.0284) was the sole predictor of a max-IMT of >1.5 mm. Conclusion: Among residents in a relatively high stroke-related mortality region, hypertension was associated with a max-IMT of >1.5 mm. For prevention of stroke, screening tests, including carotid artery ultrasonography, must be employed for arteriosclerosis in patients with hypertension.

Background: A systematic review and meta-analysis was conducted to assess the most effective treatment (long-term administration of calcium channel blockers [CCBs] with and without any form of long-acting nitrates [nitrates]) for reducing the incidence of major adverse cardiac events (MACEs) in patients with vasospastic angina (VSA).

Methods: We comprehensively searched MEDLINE (PubMed) and Japan Medical Abstracts Society (ICHUSHI) databases in August 2020 for eligible studies examining the impact of any CCBs with and without nitrates on MACEs in patients with VSA angiographically diagnosed using intracoronary provocation tests. MACE was defined as a composite of cardiac death, nonfatal myocardial infarction, unstable angina, admission due to medically resistant chest pain, and operation of an implantable cardioverter-defibrillator.

Results: Among the 10,278 studies, five studies (four from Japan and one from South Korea) reporting hazard ratios by adjusting the baseline factors using the Cox proportional hazard model and propensity-score matched analysis were selected. In total, 3,640 patients treated with CCBs (any CCBs without nitrates group; n = 2,104) and CCBs plus nitrates (CCBs plus nitrates group, n = 1,536) for a mean follow-up duration of 32-70.5 months were enrolled. MACEs occurred in 323 (8.9%) patients. The CCBs plus nitrates group had a higher risk of MACEs than the any CCBs without nitrates group (risk ratio, 1.51; 95% confidence interval, 1.13-2.01; heterogeneity I² = 42.9%; p = 0.13) in the random-effects model.

Conclusions: Long-term use of CCBs with nitrates did not improve the prognosis in Japanese and South Korean patients with VSA compared to that with long-term use of any CCBs without nitrates.

Background and aims: Fluvastatin is reported to have a stronger influence on vessel walls than other statins; however, it is unclear whether there is a significant difference between the clinical effect of fluvastatin and that of other statins on arterial stiffness. The present study tested whether fluvastatin has a more beneficial effect on arterial stiffness, inflammatory biomarkers, and oxidative stress than other statins.

Methods: The study included 80 patients who had been on cholesterol-lowering therapy for more than 12 months. Brachial-ankle pulse wave velocity (baPWV), carotid artery intima-media thickness (IMT), high sensitivity C-reactive protein (hs-CRP), and malondialdehyde-modified low density lipoprotein (MDA-LDL) were measured before and after (at 3, 6, and 12 months) switching from atorvastatin (n=25), pravastatin (n=30), or non-statin therapy (n=25) to fluvastatin.

Results: LDL-cholesterol increased after switching from atorvastatin to fluvastatin, but not from pravastatin. After 12 months of fluvastatin treatment, baPWV was significantly decreased by 9%, 16%, and 19% in the atorvastatin, pravastatin, and non-statin groups, respectively. The hs-CRP level decreased significantly by 16%, 24%, and 48% in each group, respectively. The max IMT showed a significant decrease in the pravastatin and non-statin groups after fluvastatin treatment. Stepwise regression analysis showed that the change in hs-CRP was a significant determinant of the change in baPWV (F=9.13, p=0.005), and that baPWV was significantly correlated with hs-CRP (r=0.43, p=0.003).

Conclusions: Fluvastatin has a more favorable influence on arterial stiffness than atorvastatin or pravastatin, due to its anti-inflammatory effect. Therefore, lipid-lowering therapy with fluvastatin may better prevent cardiovascular events than atorvastatin or pravastatin.

Background: Flow-mediated dilation (FMD) measurement and reactive hyperemia-peripheral arterial tonometry (RH-PAT) are established methods for assessing vascular endothelial function. Recently, the Japan Society for Vascular Failure proposed a new definition for the values of FMD (≥7.0%, normal; 7.0%> and ≥4.0%, borderline; 4.0%≥, abnormal) and reactive hyperemia index (RHI) measured using RH-PAT (≥2.10, normal; 2.10≥ and >1.67, borderline; 1.67≥, abnormal). This study aimed to assess the clinical significance of FMD and RHI in coronary artery disease (CAD) based on the new definition. Methods: We performed simultaneous FMD and RH-PAT measurements in 131 patients undergoing coronary angiography for suspected CAD. The patients were divided into subgroups according to the normal, borderline, and abnormal values of FMD and RHI in the new definition. Results: No significant correlation was found between the FMD and RHI values in the overall patients. In the normal FMD/normal RHI, normal FMD/abnormal RHI, abnormal FMD/normal RHI, and abnormal FMD/abnormal RHI groups, the prevalence of multivessel CAD was 0%, 25%, 36%, and 56% (P=0.038), respectively. Furthermore, multivessel CAD was observed in 17% of patients in the borderline FMD/borderline RHI group, and the prevalence showed a significant difference among the normal FMD/normal RHI, borderline FMD/borderline RHI, and abnormal FMD/abnormal RHI groups (P=0.006). Multivariate logistic regression analysis showed that abnormal FMD/abnormal RHI was an independent predictor of multivessel CAD (odds ratio: 3.172, 95% confidence interval: 1.012-7.336, P=0.042). Conclusions: The evaluation of simultaneously measured FMD and RHI values based on the new definition would be advantageous for predicting the severity of CAD.