Risk of upper gastrointestinal bleeding in patients on oral anticoagulant and proton pump inhibitor co-therapy.

BACKGROUND: Proton pump inhibitors (PPIs) are known to reduce the risk of upper gastrointestinal bleeding in patients on oral anticoagulants, and patients are increasingly on oral anticoagulants and PPI co-therapy. However, evidence is lacking on the safety and effectiveness of oral anticoagulants when co-administered with PPIs. METHODS: Among patients initiating oral anticoagulants (warfarin and non-vitamin K antagonist oral anticoagulants [NOACs], i.e. rivaroxaban, dabigatran, apixaban, and edoxaban) during 2013-2017, those concomitantly prescribed PPIs were identified (n = 19,851). The primary endpoint was hospitalization for major upper gastrointestinal bleeding, and secondary endpoints were death and ischemic stroke. RESULTS: During a mean 1.4 years of follow-up, the primary endpoint occurred in 512 (2.58%) patients. Overall, NOACs were associated with lower upper gastrointestinal bleeding risk after adjustment for age, sex, comorbidities and concomitant medications (adjusted hazard ratio 0.78, 95% confidence interval 0.65-0.94), compared to warfarin. There was no significant difference in upper gastrointestinal bleeding risk among the individual NOACs. This trend of reduced risk for upper gastrointestinal bleeding in NOACs compared to warfarin was consistent for both regular and reduced doses, throughout bleeding risk groups, and other subgroup analyses. NOACs were also associated with lower risk of death compared to warfarin. The risk for ischemic stroke was not significantly different among the oral anticoagulants in patients with atrial fibrillation. CONCLUSION: In patients on oral anticoagulant and PPI co-therapy, NOACs were associated with lower risk of upper gastrointestinal bleeding and mortality compared to warfarin, while there was no difference among the oral anticoagulants for stroke prevention. In patients on PPI therapy, NOACs may preferred over warfarin for decreasing risk of upper gastrointestinal bleeding and mortality.

Sex differences in the prognosis of patients with hypertrophic cardiomyopathy.

We investigated sex-related differences in the prognosis of patients with hypertrophic cardiomyopathy (HCM) using the Korea National Health Insurance Service database. From 2010 to 2016, 9524 patients diagnosed with HCM and had more than 1-year follow-up period were analyzed. The primary endpoint was the composite of cardiovascular death or new-onset heart failure (HF) admission. Propensity score-matching analysis was performed to adjust for different baseline characteristics. With a 4.4-years' median follow-up interval (range 2.0-6.6 years) and male predominance (77.6%), women with HCM were older (52.6 ± 9.7 vs. 51.4 ± 9.1, p < 0.001), had lower incomes, more comorbidities based on Charlson comorbidity index. Women with HCM had a higher incidence of the primary endpoint than men (incidence rate: 34.15 vs. 22.83 per 1000 person-years, log-rank p < 0.001). Multivariable Cox analysis showed that female sex was a poor prognostic factor for the primary endpoint (HR 1.43, 95% CI 1.24-1.64, p < 0.001). This was mainly driven by a higher incidence of new-onset HF admission (HR 1.55, 95% CI 1.34-1.80). However, there was no difference in the incidence of cardiovascular death between the sexes. This result was concordant in the propensity score-matched cohort. In conclusion, women with HCM have worse prognosis, which was mainly driven by a higher new-onset HF admission.

Risk of Ischemic Heart Disease and Stroke in Prostate Cancer Survivors: A Nationwide Study in South Korea.

In this study using national health insurance data, we investigated the risk of ischemic heart disease (IHD) and stroke among prostate cancer (PC) survivors compared with the general population, as well as the risk of cardiovascular disease (CVD) according to primary treatment. A total of 48,298 PC patients diagnosed from 2007 to 2013 were included and matched to non-cancer controls. Compared to the general population, PC survivors had a slightly lower risk of IHD (adjusted hazard ratio [aHR] = 0.89, 95% confidence interval [CI] 0.83-0.96) or stroke (aHR 0.90, 95% CI 0.87-0.95). Especially, survivors who underwent surgery had lower risks of IHD (aHR 0.70, 95% CI 0.61-0.80) or stroke (aHR 0.73, 95% CI 0.67-0.81). Compared to survivors in the active surveillance/watchful waiting group, the androgen deprivation therapy (ADT) group had a significantly greater risk of stroke (aHR 1.16, 95% CI 1.02-1.32), but the IHD risk was not significantly elevated (aHR 1.06, 95% CI 0.88-1.29). In conclusion, PC survivors had a slightly lower risk of CVD compared to the general population, which was attributable to self-selection for PSA screening, specifically in the surgery-only group. CVD risk was dependent on treatment received, and attention should be given to patients who receive ADT.

Long-term Effects of high-doSe pitavaStatin on Diabetogenicity in comparison with atorvastatin in patients with Metabolic syndrome (LESS-DM): study protocol for a randomized controlled trial.

BACKGROUND: The diabetogenic action of statins remains a concern, particularly in patients at high risk for diabetes receiving intensive statin therapy. Despite the risk of diabetes with statin use being considered a potential class effect, recent studies have suggested that pitavastatin exerts neutral or favorable effects on diabetogenicity. However, no randomized trial has compared the long-term effects of pitavastatin with those of other statins on glycemic control in populations at high risk for diabetes. Hence, we aim to assess the long-term effects of pitavastatin in comparison with atorvastatin on glucose metabolism in patients with metabolic syndrome (MetS). METHODS/DESIGN: The Long-term Effects of high-doSe pitavaStatin on Diabetogenicity in comparison with atorvastatin in patients with Metabolic syndrome (LESS-DM) trial is a prospective, randomized, open-label, active control clinical trial of patients with MetS. We plan to randomize 500 patients with MetS (1:1) to receive high-dose pitavastatin (4 mg) or atorvastatin (20 mg) daily for 24 months. The primary endpoint will be the change in hemoglobin A1c after statin treatment. Secondary endpoints will include the following: (1) changes in biochemical markers, including insulin, C-peptide, homeostasis model assessment of insulin resistance and insulin secretion, and adiponectin; (2) changes in imaging parameters, including carotid elasticity metrics and indices of cardiac function; and (3) the incidence of clinical events, including new-onset diabetes and cardiovascular disease. DISCUSSION: In this trial, we will explore whether pitavastatin 4 mg does not disturb glucose metabolism in patients with MetS. It will also provide mechanistic information on statin type-dependent diabetogenic effects and surrogate data regarding vascular and cardiac changes achieved by intensive statin therapy. TRIAL REGISTRATION: ClinicalTrials.gov, NCT02940366 . Registered on 19 October 2016.

Vitamin C prevents stress-induced damage on the heart caused by the death of cardiomyocytes, through down-regulation of the excessive production of catecholamine, TNF-α, and ROS production in Gulo(-/-)Vit C-Insufficient mice.

It is thought that vitamin C has protective roles on stress-induced heart damage and the development of cardiovascular diseases, but its precise role and mechanisms are unclear. In the present study, we investigated the specific mechanisms by which vitamin C leads to protecting the heart from stress-induced damage in the Gulo(-/-) mice which cannot synthesize vitamin C like humans. By exposure to stress (1h/day), the heartbeat and cardiac output in vitamin C-insufficient Gulo(-/-) mice were definitely decreased, despite a significant increase of adrenaline (ADR) and noradrenaline (NA) production. A change of cardiac structure caused by the death of cardiomyocytes and an increased expression of matrix metalloprotease (MMP)-2 and -9 were also found. Moreover, lipid peroxidation and the production of tumor necrosis factor-alpha (TNF-α) in the heart were increased. Finally, all vitamin C-insufficient Gulo(-/-) mice were expired within 2 weeks. Interestingly, all of the findings in vitamin C-insufficient Gulo(-/-) mice were completely prevented by the supplementation of a sufficient amount of vitamin C. Taken together, vitamin C insufficiency increases the risk of stress-induced cardiac damage with structural and functional changes arising from the apoptosis of cardiomyocytes.

Identification of N-methyl-D-aspartate receptor subunit in human periodontal ligament fibroblasts: potential role in regulating differentiation.

BACKGROUND: Periodontal ligament fibroblasts (PDLFs), which can be differentiated into osteoblasts, are crucial cells for the regeneration of the periodontal tissue. Although N-methyl-D-aspartate (NMDA) receptors were reported to be involved in bone formation by affecting osteoblasts, the existence and function of NMDA receptors in PDLFs have not been confirmed. The purpose of this study was to examine the expression of NMDA receptors and their role in human PDLFs. METHODS: Human PDLFs were cultured and evaluated to identify the subunits of NMDA receptors (NR) by reverse transcription-polymerase chain reaction, Western blot analysis, and immunocytochemistry. Then, the cells were assigned to four different groups: a control media group, a control media with NMDA receptor antagonist group, a differentiation media group, and a differentiation media with NMDA receptor antagonist group. Cell proliferation assay, alkaline phosphatase (ALP) activity analysis, and mineralization assay were performed to determine whether NMDA receptors affected the function of PDLFs. RESULTS: NR1, NR2B, and NR2D were detected in human PDLFs. There was no statistically significant difference in proliferation among the groups. However, the NMDA receptor antagonist-treated group showed a significant reduction in ALP activity (P <0.05). Moreover, the NMDA receptor antagonist-supplemented group presented no mineralization. CONCLUSIONS: This study revealed the existence of NMDA receptors in human PDLFs and specified their subunits. Moreover, NMDA receptors had a significant influence on the differentiation and mineralization of human PDLFs but did not affect their proliferation. These results suggest that NMDA receptors may play an important role in the differentiation and mineral tissue formation of human PDLFs.

Surface characteristics of orthodontic materials and their effects on adhesion of mutans streptococci.

OBJECTIVE: To test the hypothesis that there are no significant differences in the adhesion of mutans streptococci (MS) to various orthodontic materials based on their surface characteristics. MATERIALS AND METHODS: Surface roughness (SR) and surface free energy (SFE) characteristics were investigated for nine different orthodontic materials (four orthodontic adhesives, three bracket raw materials, hydroxyapatite blocks, and bovine incisors) using confocal laser scanning microscopy and sessile drop method. Each material, except the bovine incisors, was incubated with whole saliva or phosphate-buffered saline for 2 hours. Adhesion assays were performed by incubating tritium-labeled MS with each material for 3 or 6 hours. RESULTS: Orthodontic adhesives had higher SFE characteristics and lower SR than bracket materials. Orthodontic adhesives showed a higher MS retaining capacity than bracket materials, and MS adhesion to resin-modified glass ionomer and hydroxyapatite was highest. Extended incubation time increased MS adhesion, while saliva coating did not significantly influence MS adhesion. SFE, specifically its dispersive and polar components, was positively correlated with MS adhesion, irrespective of saliva coating. CONCLUSIONS: The hypothesis is rejected. This study suggests that SFE characteristics play an important role in the initial MS adhesion to orthodontic materials.