Search

Sodium-glucose cotransporter 2 inhibitors (SGLT2is) reduce the risk of heart failure progression and mortality rates. Moreover, osmotic diuresis induced by SGLT2 inhibition may result in an improved heart failure prognosis. Independent of conventional diuretics in patients with type 2 diabetes (T2D) and chronic heart failure, especially in patients with heart failure with preserved ejection fraction (HFpEF), it is unclear whether SGLT2i chronically reduces estimated plasma volume (ePV). As a subanalysis of the CANDLE trial, which assessed the effect of canagliflozin on N-terminal pro-brain natriuretic peptide (NT-proBNP), we examined the change (%) in ePV over 24 weeks of treatment based on the baseline level associated with diuretic usage. In the CANDLE trial, nearly all patients were clinically stable (NYHA class I-II), with approximately 70% of participants presenting a baseline phenotype of HFpEF. A total of 99 (42.5%) patients were taking diuretics (mostly furosemide) at baseline, while 134 (57.5%) were not. Relative to glimepiride, canagliflozin significantly reduced ePV without worsening renal function in patients in both groups: -4.00% vs. 1.46% (p = 0.020) for the diuretic group and -6.14% vs. 1.28% (p < 0.001) for the nondiuretic group. Furthermore, canagliflozin significantly reduced serum uric acid without causing major electrolyte abnormalities in patients in both subgroups. The long-term beneficial effect of SGLT2i on intravascular congestion could be independent of conventional diuretic therapy without worsening renal function in patients with T2D and HF (HFpEF predominantly). In addition, the beneficial effects of canagliflozin are accompanied by improved hyperuricemia without causing major electrolyte abnormalities., (© 2022. The Author(s), under exclusive licence to The Japanese Society of Hypertension.)

The present prospective observational study was conducted to examine the differences in longitudinal associations of the conventional risk factors for cardiovascular disease (CVD) with arterial stiffness and with abnormal pressure wave reflection using repeated measurement data. In 4016 healthy middle-aged (43 ± 9 years) Japanese men without CVD at baseline, the conventional risk factors for CVD, brachial-ankle pulse wave velocity (brachial-ankle PWV) and radial augmentation index (rAI) were measured annually over a 9-year period. Mixed-model linear regression analysis demonstrated a significant independent positive longitudinal association of the mean blood pressure with both the brachial-ankle PWV (estimate = 5.51, standard error = 0.30, P < 0.01) and the rAI (estimate = 0.19, standard error = 0.02, P < 0.01). On the other hand, the serum levels of glycohemoglobin, low-density lipoprotein cholesterol and triglycerides showed longitudinal associations only with the brachial-ankle PWV and not the rAI. In addition, while the radial AI was found to show a significant longitudinal association with the brachial-ankle PWV, the inverse association was not significant. In conclusion, the conventional risk factors for CVD showed heterogeneous longitudinal associations with arterial stiffness and/or abnormal pressure wave reflection. Elevated blood pressure showed independent longitudinal associations with both arterial stiffness (macrovascular damage) and abnormal pressure wave reflection, suggesting that BP is also longitudinally associated, at least in part, with microvascular damage. On the other hand, abnormal glucose metabolism and dyslipidemia showed independent longitudinal associations with only arterial stiffness (macrovascular damage).

The score based on the office systolic blood pressure, age, fasting blood glucose level, and estimated glomerular filtration rate (SAGE score) has been proposed as a useful marker to identify elevated values of carotid-femoral pulse wave velocity (PWV). The present cross-sectional study was conducted to examine whether the SAGE score is also a useful marker to identify subjects with elevated brachial-ankle PWV values in Japanese subjects with hypertension. We measured the brachial-ankle PWV and calculated the SAGE score in a total of 1019 employees of a Japanese company with hypertension and 817 subjects with hypertension derived from a multicenter study cohort. The analyses in this study were based on data from these two study groups as well as on a composite population of the two (n = 1836). The receiver operating characteristic curve analysis showed that the area under the curve to identify subjects with brachial-ankle PWV values of ≥1800 cm/s was over 0.70 in each of the three study groups. Even after adjustments, a SAGE score ≥7 had a significant odds ratio for identifying subjects with brachial-ankle PWV values ≥1800 cm/s in the 1836 study subjects from the composite occupational and multicenter study cohort (odds ratio = 2.1, 95% confidence interval = 1.4-3.0, P < 0.01). Thus, in Japanese subjects with hypertension, the SAGE score may be a useful marker for identifying subjects with elevated brachial-ankle PWV values.