Effect of Dorsomorphin Homolog 1 (DMH1) against Diabetic Dyslipidemia in Streptozotocin-induced Diabetic Rats

Dyslipidemia is usually observed in both types of diabetes and, particularly, “atherogenic dyslipidemic triad” is strongly linked to a higher risk of adverse cardiovascular outcome. On the other hand, bone morphogenetic proteins (BMP) are a group of wide variety of proteins which were found overexpressed and implicated in contribution and acceleration of atherosclerotic calcification. So, the present study aimed to assess effect of DMH1, a selective BMP inhibitor, in a rat model of diabetic-induced dyslipidemia. Methods: STZ-induced diabetes in Wistar rats was used as a model to assess the antihyperlipidemic effect of DMH1(5mg/kg) for a period of 8 weeks. Rats were divided intonormal control (C=10), diabetic control (DC=10), diabetic+vehicle (DV=10) and diabetic DMH1-treated rats (DT=10). Fasting blood glucose (FBG) level was measured on weekly bases. Then, at the end of the experiment, rats were anesthetized and blood samples were collected for the determination of total cholesterol (TC), triglyceride (TG), LDL and HDL levels using the appropriate ELISA assay. Results: FBG levels for all diabetic groups were significantly high, during the experiment period, compared to the control (P< 0.001). While dyslipidemia was remarkable in the diabetic non-treated groups, DMH1 treatment showed a significant decrease in TC (P< 0.001), TG (P< 0.05) and LDL levels (P< 0.001) compared to the non-treated groups (DC & DV). Concurrently, HDL levels for DT group were significantly increased compared to DC or DV groups (P< 0.01). Conclusion: The present experiment showed that DMH1 possessed encouraging activityagainst dyslipidemia in STZ-induced diabetic rats. Our results are promoting for more interest and investigation regarding antihyperlipidemic effect of DMH1 and BMP/Smad pathway in further experimental studies.

Association of Blood Pressure with Cardiovascular Outcome and Mortality: Results from the KNOW-CKD Study

Background Optimal BP control is a major therapeutic strategy to reduce adverse cardiovascular events and mortality in patients with CKD. We studied the association of BP with adverse cardiovascular outcome and all-cause death in patients with CKD. Methods Among 2,238 participants from the KoreaN cohort study for Outcome in patients With CKD, 2,226 patients with baseline BP measurements were enrolled. Main predictor was SBP categorized by 5 levels: &lt;110, 110-119, 120-129, 130-139, and ≥140 mmHg. Primary endpoint was a composite outcome of all-cause death or incident cardiovascular events. We primarily used marginal structural models using averaged and the most recent time-updated SBPs. Results During a median follow-up of 10233.79 person-years (median 4.60 years), the primary composite outcome occurred in 240 (10.8%) participants, with a corresponding incidence rate of 23.5 (95% CI, 20.7–26.6) per 1,000 patient-years. Marginal structural models with averaged SBP showed a U-shaped relationship with the primary outcome. Compared to time-updated SBP of 110–119 mmHg, hazard ratios (95% CI) for &lt;110, 120–129, 130–139, and ≥140 mmHg were 2.47 (1.48–4.11), 1.29 (0.80–2.08), 2.15 (1.26–3.69), and 2.19 (1.19–4.01), respectively. Marginal structural models with the most recent SBP also showed similar findings. Conclusions In Korean patients with CKD, there was a U-shaped association of SBP with the risk of adverse clinical outcome. Our findings highlight the importance of BP control and suggest a potential hazard of SBP &lt;110 mmHg.

Abstract 15583: Cardiovascular Computed Tomography Aortic Valve Calcification, Myocardial Fibrosis and Adverse Outcome Following Transcatheter Aortic Valve Replacement

Introduction: There is evidence to suggest that subtype of aortic stenosis (AS), degree of myocardial fibrosis (MF) and level of aortic valve calcification (AVC) are associated with adverse cardiac outcome in AS. Since little is known about their respective contribution, we sought to investigate their relative importance and interplay as well as association with adverse cardiac events. Methods: 100 consecutive patients with severe AS and indication for transfemoral transcatheter aortic valve replacement (TAVR) were prospectively enrolled between January 2017 and October 2018. Patients underwent transthoracic echocardiography, multi detector computed tomography (MDCT) and left ventricular endomyocardial biopsy at the time of TAVR. Results: The final study cohort consisted of 92 patients with completed study protocol comprising of 39 (42.4 %) normal ejection fraction high gradient (NEFHG), 13 (14.1 %) low EF high gradient (LEFHG), 25 (27.2 %) low EF (flow) low gradient (LEFLG) and 15 (16.3 %) paradoxical low flow low gradient (PLFLG) AS. The high gradient phenotype (NEFHG and LEFHG) showed the largest amount of AVC (807 ± 421; 813 ± 281 mm 3 respectively) as compared to the low gradient phenotype (LEFLG and PLFLG; 503 ± 326; 555 ± 594 mm 3 respectively, p<0.05). Conversely, MF was most prevalent in low output phenotypes (LEFLG>LEFHG>PLFLG>HEFHG, p<0.05). This was paralleled by larger cardiovascular mortality within 400 days post TAVR (LEFLG n=7>PLFLG n=4>LEFHG n=2>NEFHG n=1). Within LEFLG AS, patients with larger AVC (>476.8 mm 3 ) had larger MF (40.2%) and higher cardiovascular mortality (n=5) as compared to patients with less AVC (≤476.8 mm 3 , 17.1% MF, p=0.027, cardiovascular mortality n=2). Conclusion: MF is associated with adverse cardiovascular outcome following TAVR which is most prevalent in low ejection fraction situations. Within the low ejection fraction low gradient subtype large AVC was associated with high amounts of MF and adverse cardiovascular outcome.