There are unmet needs for pharmacologic agents beyond current medications, such as statins, to effectively lower low-density lipoprotein cholesterol levels to target goals, especially in patients with very high or extremely high risk. Pharmacological targeting of mRNA represents an emerging, innovative approach with the potential to expand upon current therapies. In RNA-targeted therapeutics, a novel approach is the use of chemically modified oligonucleotides to inhibit the production of target proteins at their sites of gene coding. There are two main classes of RNA-targeted therapeutics: single-stranded antisense oligonucleotides (ASOs) and double-stranded small inhibiting RNAs. ASOs are synthetic molecules with a length of 15–30 nucleotides that are designed specifically to bind to a target mRNA in a sequence-specific manner. Using these agents to inhibit the translation of key regulatory proteins, such as apolipoprotein CIII, apolipoprotein(a), and angiopoietinlike protein 3, has demonstrated treatment efficacy for dyslipidemia. Many cardiovascular outcome trials with ASOs are ongoing. As clinicians, we must carefully monitor the longterm safety and efficacy of this new modality through large clinical trials in the future.

Statins are the cornerstone of the prevention and treatment of atherosclerotic cardiovascular disease (ASCVD). However, even under optimal statin therapy, a significant residual ASCVD risk remains. Therefore, there has been an unmet clinical need for novel lipid-lowering agents that can target low-density lipoprotein cholesterol (LDL-C) and other atherogenic particles. During the past decade, several drugs have been developed for the treatment of dyslipidemia. Inclisiran, a small interfering RNA that targets proprotein convertase subtilisin/kexin type 9 (PCSK9), shows comparable effects to that of PCSK9 monoclonal antibodies. Bempedoic acid, an ATP citrate lyase inhibitor, is a valuable treatment option for the patients with statin intolerance. Pemafibrate, the first selective peroxisome proliferator-activated receptor alpha modulator, showed a favorable benefit-risk balance but the large clinical phase 3 trial (Pemafibrate to Reduce Cardiovascular OutcoMes by Reducing Triglycerides IN patiENts With diabe- Tes [PROMINENT]) was recently stopped due to the underperformance from interim analysis. High dose icosapent ethyl, a modified eicosapentaenoic acid preparation, shows cardiovascular benefits. Evinacumab, an angiopoietin-like 3 (ANGPTL3) monoclonal antibody, reduces plasma LDL-C levels in patients with refractory hypercholesterolemia. Novel antisense oligonucleotides targeting apolipoprotein C3 (apoC3), ANGPTL3, and lipoprotein(a) have significantly attenuated the levels of their target molecules with beneficial effects on associated dyslipidemias. Apolipoprotein A1 (apoA1) is considered as a potential treatment to exploit the athero-protective effects of high-density lipoprotein cholesterol (HDL-C), but solid clinical evidence is necessary. In this review, we discuss the mode of action and clinical outcomes of these novel lipid-lowering agents beyond statins.

Objectives: This study examined the mediating effects of smartphone dependence on the relationship between anxiety and delayed bedtime and analyzed the group differences based on gender and economic difficulties caused by the COVID-19 pandemic among Korean adolescents. Methods: Data from 4254 middle school students living in metropolitan areas and cohabiting with highly educated parents were analyzed using the 2020 Korea Youth Risk Behavior Survey.The participants were divided into four groups based on gender and economic difficulties caused by COVID-19. T-tests, analysis of variance, and Pearson correlation analysis were conducted on each variable. The Baron–Kenny method and Sobel tests were used to verify the mediating effects. Results: Female students showed higher levels of anxiety, smartphone dependence, and delayed bedtime. Groups experiencing economic difficulties due to COVID-19 reported higher levels of anxiety and smartphone dependence. Across all groups, positive correlations were observed between anxiety, smartphone dependence, and delayed bedtime. Smartphone dependence partially mediated the relationship between anxiety and delayed bedtime, except in the group of male students experiencing economic difficulties caused by COVID-19. Conclusion This study confirmed the associations between anxiety, smartphone dependence, and delayed bedtime among adolescents, suggesting the need for interventions related to smartphone use to support the mental health of adolescents in stressful situations.

Objectives: This study examined the mediating effects of smartphone dependence on the relationship between anxiety and delayed bedtime and analyzed the group differences based on gender and economic difficulties caused by the COVID-19 pandemic among Korean adolescents. Methods: Data from 4254 middle school students living in metropolitan areas and cohabiting with highly educated parents were analyzed using the 2020 Korea Youth Risk Behavior Survey.The participants were divided into four groups based on gender and economic difficulties caused by COVID-19. T-tests, analysis of variance, and Pearson correlation analysis were conducted on each variable. The Baron–Kenny method and Sobel tests were used to verify the mediating effects. Results: Female students showed higher levels of anxiety, smartphone dependence, and delayed bedtime. Groups experiencing economic difficulties due to COVID-19 reported higher levels of anxiety and smartphone dependence. Across all groups, positive correlations were observed between anxiety, smartphone dependence, and delayed bedtime. Smartphone dependence partially mediated the relationship between anxiety and delayed bedtime, except in the group of male students experiencing economic difficulties caused by COVID-19. Conclusion This study confirmed the associations between anxiety, smartphone dependence, and delayed bedtime among adolescents, suggesting the need for interventions related to smartphone use to support the mental health of adolescents in stressful situations.

Objectives: This study examined the mediating effects of smartphone dependence on the relationship between anxiety and delayed bedtime and analyzed the group differences based on gender and economic difficulties caused by the COVID-19 pandemic among Korean adolescents. Methods: Data from 4254 middle school students living in metropolitan areas and cohabiting with highly educated parents were analyzed using the 2020 Korea Youth Risk Behavior Survey.The participants were divided into four groups based on gender and economic difficulties caused by COVID-19. T-tests, analysis of variance, and Pearson correlation analysis were conducted on each variable. The Baron–Kenny method and Sobel tests were used to verify the mediating effects. Results: Female students showed higher levels of anxiety, smartphone dependence, and delayed bedtime. Groups experiencing economic difficulties due to COVID-19 reported higher levels of anxiety and smartphone dependence. Across all groups, positive correlations were observed between anxiety, smartphone dependence, and delayed bedtime. Smartphone dependence partially mediated the relationship between anxiety and delayed bedtime, except in the group of male students experiencing economic difficulties caused by COVID-19. Conclusion This study confirmed the associations between anxiety, smartphone dependence, and delayed bedtime among adolescents, suggesting the need for interventions related to smartphone use to support the mental health of adolescents in stressful situations.

Objectives: This study examined the mediating effects of smartphone dependence on the relationship between anxiety and delayed bedtime and analyzed the group differences based on gender and economic difficulties caused by the COVID-19 pandemic among Korean adolescents. Methods: Data from 4254 middle school students living in metropolitan areas and cohabiting with highly educated parents were analyzed using the 2020 Korea Youth Risk Behavior Survey.The participants were divided into four groups based on gender and economic difficulties caused by COVID-19. T-tests, analysis of variance, and Pearson correlation analysis were conducted on each variable. The Baron–Kenny method and Sobel tests were used to verify the mediating effects. Results: Female students showed higher levels of anxiety, smartphone dependence, and delayed bedtime. Groups experiencing economic difficulties due to COVID-19 reported higher levels of anxiety and smartphone dependence. Across all groups, positive correlations were observed between anxiety, smartphone dependence, and delayed bedtime. Smartphone dependence partially mediated the relationship between anxiety and delayed bedtime, except in the group of male students experiencing economic difficulties caused by COVID-19. Conclusion This study confirmed the associations between anxiety, smartphone dependence, and delayed bedtime among adolescents, suggesting the need for interventions related to smartphone use to support the mental health of adolescents in stressful situations.

Background: The prognostic consequences of transient hemodynamic deterioration due to cardiac displacement, which is most severe during left circumflex artery (LCX) grafting in off-pump coronary artery bypass surgery (OPCAB) are unknown. This study aimed to investigate the association between mixed venous oxygen saturation (SvO2) < 60% during LCX grafting and the occurrence of composite of morbidity endpoints. Methods: Data of patients who underwent elective OPCAB between January 2010 and December 2019 were reviewed. Logistic regression analysis was performed to detect risk factors for the composite of morbidity endpoints, defined as 30-day or in-hospital mortality, postoperative myocardial infarction, prolonged mechanical ventilation > 24 h, cerebrovascular accident, and acute kidney injury. Results: Among 1,071 patients, the composite of morbidity endpoints occurred in 303 (28%) patients. SvO2 < 60% during LCX grafting was significantly associated with the composite of morbidity (OR: 2.72, 95% CI [1.60, 4.61], P < 0.001) along with advanced age, chronic kidney disease, ratio of early mitral inflow velocity to mitral annular early diastolic velocity, and EuroSCORE II. Other major hemodynamic variables including the cardiac index were not associated with the outcome. Additional regression analysis revealed pre-operative anemia as a predictor of SvO2 < 60% during LCX grafting (OR: 2.09, 95% CI [1.33, 3.29], P = 0.001). Conclusions A decrease in SvO2 < 60%, albeit confined to the period of cardiac displacement, was associated with a 2.7-fold increased risk of detrimental outcomes after OPCAB, implying the prognostic importance of this transient deterioration in oxygen supply-demand balance.