Aim: Recent studies have demonstrated that selective sodium–glucose cotransporter 2 inhibitors (SGLT2is) reduce cardiovascular events, although their mechanism remains obscure. We examined the effect of canagliflozin, an SGLT2i, on atherogenesis and investigated its underlying mechanism.

Method: Canagliflozin (30 mg/kg/day) was administered by gavage to streptozotocin-induced diabetic apolipoprotein E-deficient (ApoE^－/－) mice. Sudan IV staining was performed at the aortic arch. Immunostaining, quantitative RT-PCR, and vascular reactivity assay were performed using the aorta. In vitro experiments using human umbilical vein endothelial cells (HUVECs) were also performed.

Result: Canagliflozin decreased blood glucose (P＜0.001) and total cholesterol (P＜0.05) levels. Sudan IV staining showed that 12-week canagliflozin treatment decreased atherosclerotic lesions (P＜0.05). Further, 8-week canagliflozin treatment ameliorated endothelial dysfunction, as determined by acetylcholine-induced vasodilation (P＜0.05), and significantly reduced the expressions of inflammatory molecules such as ICAM-1 and VCAM-1 in the aorta at the RNA and protein levels. Canagliflozin also reduced the expressions of NADPH oxidase subunits such as NOX2 and p22phox in the aorta and reduced urinary excretion of 8-OHdG, suggesting a reduction in oxidative stress. Methylglyoxal, a precursor of advanced glycation end products, increased the expressions of ICAM-1 and p22phox in HUVECs (P＜0.05, both). Methylglyoxal also decreased the phosphorylation of eNOS^Ser1177 and Akt but increased the phosphorylation of eNOS^Thr495 and p38 MAPK in HUVECs.

Conclusion: Canagliflozin prevents endothelial dysfunction and atherogenesis in diabetic ApoE^－/－ mice. Anti-inflammatory and antioxidative potential due to reduced glucose toxicity to endothelial cells might be its underlying mechanisms.

Aim: Glycemic index (GI) and glycemic load (GL) influence postprandi al glucose concentrations and insulin responses. This study aims to ascertain the connection between GI, GL, and carotid atherosclerotic stenosis and cardiovascular disease (CVD) risk factors.

Methods: A total of 669 patients with ischemic stroke within 7 days were enrolled. GI and GL were assessed with a validated food frequency questionnaire from patients. Computed tomography angiography (CTA) was used for the evaluation of carotid atherosclerotic stenosis. Traditional risk factors such as total cholesterol, triglycerides, LDL-C, HDL-C, C-reactive protein, homocysteine, neutrophil to lymphocyte ratio (NLR), fasting plasma glucose, and hemoglobin A1c were measured. GI/GL and its association with CVD risk factors and carotid stenosis were explored with Spearman analysis and multivariable logistic regression, respectively.

Results: The prevalence of carotid stenosis was 63.2% of all 669 participants. The mean value of GI/GL was 49.3/137. Spearman test did not detect significant relationships between GI/GL and CVD risk factors. In multivariable regression models, GI (4^th vs. 1^st quartile, OR=2.11; 95% CI, 1.30–3.42) and GL (4^th vs. 1^st quartile, OR=1.82; 95% CI, 1.12–2.96) were observed a significant association with carotid stenosis after adjustment for major confounding factors. The association between GL and carotid stenosis became more pronounced among yo ungers (4^th vs. 1^st quartile, OR=2.42; 95% CI, 1.13–4.76) and women (4^th vs. 1^st quartile, OR=3.81; 95% CI, 1.45–5.05).

Conclusion: Higher GI and GL were positively associated with a higher degree of carotid stenosis in these Chinese cerebral infarction patients, especially in younger patients and women.

Aim: To construct a risk prediction model for cardiovascular disease (CVD) based on the Suita study, an urban Japanese cohort study, and compare its accuracy against the Framingham CVD risk score (FRS) model.

Methods: After excluding participants with missing data or those who lost to follow-up, this study consisted of 3,080 men and 3,470 women participants aged 30–79 years without CVD at baseline in 1989–1999. The main outcome of this study was incidence of CVD, defined as the incidence of stroke or coronary heart disease. Multivariable Cox proportional hazards models with stepwise selection were used to develop the prediction model. To assess model performance, concordance statistics (C-statistics) and their 95% confidence intervals (CIs) were calculated using a bootstrap procedure. A calibration test was also conducted.

Results: During a median follow-up period of 16.9 years, 351 men and 241 women developed CVD. We formulated risk models with and without electrocardiogram (ECG) data that included age, sex, systolic blood pressure, diastolic blood pressure, high-density lipoprotein cholesterol, non-high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, diabetes mellitus, smoking, and urinary protein as risk factors. The C-statistics of the Suita CVD risk models with ECG data (0.782; 95% CI, 0.766–0.799) and without ECG data (0.781; 95% CI, 0.765–0.797) were significantly higher than that of the FRS model (0.768; 95% CI, 0.750–0.785).

Conclusions: The Suita CVD risk model is feasible to use and improves predictability of the incidence of CVD relative to the FRS model in Japan.