BackgroundSodium-glucose cotransporter 2 (SGLT2) inhibitors are reported to have BP-lowering effect in addition to blood glucose-lowering effect, however, its mechanism is still unknown. This study aimed to investigate the mechanism of blood pressure (BP) lowering effects of SGLT2 inhibitors using 24-h urinary collection in obese type 2 diabetes patients.MethodsTwenty patients with type 2 diabetes (age 48.2 ± 10.7 years, BMI 33.0 ± 4.9 kg/m2) were enrolled. Urine volume, 24-h urinary glucose and sodium excretion, and BP at baseline and 2 weeks and 6 months after administration were measured. Body weight, glycosylated hemoglobin, and BP were evaluated before and 1, 3, and 6 months after SGLT2 inhibitor administration. We evaluated the changes in urine volume and urinary excretion of glucose and sodium as well as correlations among urine volume and urinary sodium glucose excretion at 2 weeks and 6 months after administration of the SGLT2 inhibitors. Furthermore, we investigated the correlations between changes in BP and urinary excretion of sodium and glucose at the same time.ResultsTwo weeks after administration, systolic BP (SBP) significantly decreased (128.5 ± 11.0 to 123.2 ± 9.8 mmHg, P = 0.0314), but diastolic BP (DBP) did not (74.4 ± 10.4 to 73.4 ± 8.5 mmHg, P = 0.5821). The decreased SBP significantly correlated with increased urinary glucose excretion (R = −0.62, P = 0.0073), but not increased urinary sodium excretion. At 6 months, SBP (118.6 ± 11.0 mmHg, P = 0.0041) and DBP (68.4 mmHg, P = 0.0363) significantly decreased. The decreased SBP significantly correlated with increased urinary sodium excretion (R = −0.60, P = 0.0014), but not increased urinary glucose excretion.ConclusionsSGLT2 inhibitors significantly decreased SBP after 1 month and DBP after 6 months in obese patients with type 2 diabetes. The main mechanism of the BP-lowering effect may be plasma volume reduction by osmotic diuresis at 2 weeks and by natriuresis at 6 months after SGLT2 inhibitor administration.

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There are few reports on the long-term clinical outcome after percutaneous coronary intervention (PCI) in patients with stable coronary artery disease (CAD) complicated with frailty. This novel study investigated the association between pre-PCI frailty and long-term clinical outcomes in elderly patients aged 65 years or older with stable CAD who underwent elective PCI. We assessed 239 consecutive patients aged 65 years or older with stable CAD who underwent successful elective PCI at Kagoshima City Hospital between January 1st, 2017 and December 31st, 2020. Frailty was retrospectively assessed using the Canadian Study and Aging Clinical Frailty Scale (CFS). Based on the pre-PCI CFS, patients were divided into two groups: the non-frail (CFS < 5) and the frail (CFS ≥ 5) group. We investigated the association between pre-PCI CFS and major adverse cardiovascular events (MACEs) defined as the composite of all-cause death, non-fatal myocardial infarction, non-fatal stroke, and heart failure requiring hospitalization. Additionally, we assessed the association between pre-PCI CFS and major bleeding events defined as Bleeding Academic Research Consortium (BARC) type 3 or 5 bleeding. The mean age was 74.8 ± 7.0 years, and 73.6% were men. According to the pre-PCI frailty assessment, 38 (15.9%) and 201 (84.1%) were classified as frail and non-frail groups, respectively. During a median follow-up of 962 (607–1284) days, 46 patients developed MACEs and 10 patients developed major bleeding events. Kaplan–Meier curves showed a significantly higher incidence of MACE in the frail group compared to those in the non-frail group (Log-rank p < 0.001). Even in multivariate analysis, pre-PCI frailty (CFS ≥ 5) was independently associated with MACE (HR 4.27, 95% CI 1.86–9.80, p-value: < 0.001). Additionally, the cumulative incidence of major bleeding events was significantly higher in the frail group than in the non-frail group (Log-rank p = 0.001). Pre-PCI frailty was an independent risk factor for MACE and bleeding events in elderly patients with stable CAD who underwent elective PCI.