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Cureus May 2024Introduction Type 2 diabetes mellitus (T2DM), a prevalent chronic metabolic disorder, necessitates multifaceted treatment approaches. Emerging studies highlight the...
Retrospective Observational Study on Assessing Sitagliptin and Dapagliflozin as a Fixed-Dose Combination in the Indian Population With Type 2 Diabetes Mellitus: The SIDAXA Study.
Introduction Type 2 diabetes mellitus (T2DM), a prevalent chronic metabolic disorder, necessitates multifaceted treatment approaches. Emerging studies highlight the cardiovascular advantages of sodium-glucose transport protein 2 (SGLT2) and dipeptidyl peptidase 4 (DPP-4) inhibitors in T2DM. This investigation delves into the synergistic effects of the fixed-dose combination (FDC) of sitagliptin and dapagliflozin, offering insights into its safety and efficacy for the Indian population. Methods This real-world, retrospective, observational study spanned 328 cases across 111 Indian centres, evaluating the safety, efficacy, and clinical utilization of the sitagliptin and dapagliflozin FDC in T2DM patients after obtaining ethical approval. Assessments at baseline, week four, and week 12 encompassed hemoglobin A1C (HbA1C), fasting plasma glucose (FPG), postprandial blood glucose (PPBG), low-density lipoprotein cholesterol (LDL-C), systolic blood pressure (SBP), diastolic blood pressure (DBP), and weight change. The statistical analysis was done using Statistical Package for Social Sciences (SPSS) version 29.0.1.0(171) (IBM Corp., Armonk, NY, USA) with a significance level p<0.05. Results Study participants [mean age: 51.14±5.55 years, 77.74% (n=255) males, 22.26% (n=73) females] exhibited prevalent risk factors like sedentary lifestyle (n=167, 50.91%) and smoking (n=147, 44.82%). Comorbidities included hypertension (n=235, 71.65%) and dyslipidaemia (n=139, 42.38%). Metformin (n=282, 85.98%) and sulfonylurea (n=134, 40.85%) were commonly prescribed concomitant oral antidiabetic agents (OADs). FDC administration significantly reduced HbA1c by 1.05 ± 0.83% (p < 0.0001) at week 12. FPG and PPBG showed significant reductions of 22.98 ± 22.23 mg/dL (p < 0.0001), 165.50 ± 37.02 mg/dL and 40.94 ± 36.04 mg/dL (p < 0.0001) at four weeks respectively. By week 12, significant reductions were noted in SBP (14.61±13.98mmHg reduction, p-value <0.0001), DBP (7.80±8.45mmHg reduction, p-value <0.0001), and LDL-C levels (18.14±23.95 mg/dL reduction, p-value <0.0001). In patients with established cardiovascular disease, there was reduction in HbA1c levels by 1.02 ± 0.63% after 12 weeks, with FPG decreasing by 54.52 ± 32.67 mg/dL and PPBG decreasing by 88.73 ± 44.90 mg/dL. Treatment-emergent adverse events included headache, changes in micturition, genital mycotic infection, and nausea and diarrhoea which were mild, transient, and necessitated no treatment discontinuation. Conclusion The FDC of sitagliptin and dapagliflozin significantly improved glycaemic control and lipid profiles in T2DM patients, particularly those with coronary artery disease. It demonstrated a favourable safety profile in the Indian population, signifying its potential as an effective and well-tolerated therapeutic option in patients with established cardiovascular disease.
PubMed: 38910691
DOI: 10.7759/cureus.60815 -
The Korean Journal of Internal Medicine Jun 2024Achieving rapid reduction of low-density lipoprotein cholesterol (LDL-C) levels below 55 mg/dL in patients with acute myocardial infarction (AMI) can be challenging with...
BACKGROUND/AIMS
Achieving rapid reduction of low-density lipoprotein cholesterol (LDL-C) levels below 55 mg/dL in patients with acute myocardial infarction (AMI) can be challenging with statins alone. This single-center, retrospective study aimed to assess the impact of single-dose injection of evolocumab 140 mg on LDL-C levels during the peri-percutaneous coronary intervention (PCI) period in patients with AMI.
METHODS
A total of 95 patients with AMI who underwent PCI were divided into the evolocumab (n = 50) and non-evolocumab (n = 45) groups.
RESULTS
The percentage change of LDL-C level at 1-3 weeks from baseline was 78.4 ± 13.4% reduction in the evolocumab group versus 45.6 ± 22.6% in the non-evolocumab group, with a mean difference of -33.5% between the groups (95% CI: -42.6 to -24.5%; p < 0.001). The achievement rate of LDL-C levels below 55 mg/dL at 1-3 weeks was significantly higher in the evolocumab group than in the non-evolocumab group (97.7% vs. 60.0%, p < 0.001).
CONCLUSIONS
Patients with AMI who received single-dose injection of evolocumab 140 mg during the peri-PCI period had a significantly greater LDL-C reduction and higher proportion of patients achieved the target LDL-C level in the early phase AMI than those who did not receive evolocumab.
PubMed: 38910509
DOI: 10.3904/kjim.2024.080 -
The Journal of Reproduction and... Jun 2024Understanding how stress hormones induce apoptosis in oviductal epithelial cells (OECs) and mural granulosa cells (MGCs) can reveal the mechanisms by which female stress...
Understanding how stress hormones induce apoptosis in oviductal epithelial cells (OECs) and mural granulosa cells (MGCs) can reveal the mechanisms by which female stress impairs embryonic development and oocyte competence. A recent study showed that tissue plasminogen activator (tPA) ameliorates corticosterone-induced apoptosis in MGCs and OECs by acting on its receptors low-density lipoprotein receptor-related protein 1 (LRP1) and Annexin A2 (ANXA2), respectively. However, whether tPA is involved in corticotropin-releasing hormone (CRH)-induced apoptosis and whether it uses the same or different receptors to inhibit apoptosis induced by different hormones in the same cell type remains unknown. This study showed that CRH triggered apoptosis in both OECs and MGCs and significantly downregulated tPA expression. Moreover, tPA inhibits CRH-induced apoptosis by acting on ANXA2 in both OECs and MGCs. While ANXA2 inhibits apoptosis via phosphatidylinositol 3-kinase/protein kinase B (PI3K/Akt) signaling, LRP1 reduces apoptosis via mitogen-activated protein kinase (MAPK) signaling. Thus, tPA used the same receptor to inhibit CRH-induced apoptosis in both OECs and MGCs, however used different receptors to inhibit corticosterone-induced apoptosis in MGCs and OECs. These data helps understand the mechanism by which female stress impairs embryo/oocyte competence and proapoptotic factors trigger apoptosis in different cell types.
PubMed: 38910127
DOI: 10.1262/jrd.2024-028 -
Journal of Advanced Research Jun 2024Atherosclerosis, traditionally considered a lipid-related disease, is now understood as a chronic inflammatory condition with significant global health implications. (Review)
Review
INTRODUCTION
Atherosclerosis, traditionally considered a lipid-related disease, is now understood as a chronic inflammatory condition with significant global health implications.
OBJECTIVES
This review aims to delve into the complex interactions among immune cells, cytokines, and the inflammatory cascade in atherosclerosis, shedding light on how these elements influence both the initiation and progression of the disease.
METHODS
This review draws on recent clinical research to elucidate the roles of key immune cells, macrophages, T cells, endothelial cells, and clonal hematopoiesis in atherosclerosis development. It focuses on how these cells and process contribute to disease initiation and progression, particularly through inflammation-driven processes that lead to plaque formation and stabilization. Macrophages ingest oxidized low-density lipoprotein (oxLDL), which partially converts to high-density lipoprotein (HDL) or accumulates as lipid droplets, forming foam cells crucial for plaque stability. Additionally, macrophages exhibit diverse phenotypes within plaques, with pro-inflammatory types predominating and others specializing in debris clearance at rupture sites. The involvement of CD4 T and CD8 T cells in these processes promotes inflammatory macrophage states, suppresses vascular smooth muscle cell proliferation, and enhances plaque instability.
RESULTS
The nuanced roles of macrophages, T cells, and the related immune cells within the atherosclerotic microenvironment are explored, revealing insights into the cellular and molecular pathways that fuel inflammation. This review also addresses recent advancements in imaging and biomarker technology that enhance our understanding of disease progression. Moreover, it points out the limitations of current treatment and highlights the potential of emerging anti-inflammatory strategies, including clinical trials for agents such as p38MAPK, tumor necrosis factor α (TNF-α), and IL-1β, their preliminary outcomes, and the promising effects of canakinumab, colchicine, and IL-6R antagonists.
CONCLUSION
This review explores cutting-edge anti-inflammatory interventions, their potential efficacy in preventing and alleviating atherosclerosis, and the role of nanotechnology in delivering drugs more effectively and safely.
PubMed: 38909884
DOI: 10.1016/j.jare.2024.06.016 -
BMC Medical Research Methodology Jun 2024Baseline imbalances have been identified in randomized trials of evolocumab and alirocumab. Our aim was to quantitatively assess (1) the presence of systematic baseline... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Baseline imbalances have been identified in randomized trials of evolocumab and alirocumab. Our aim was to quantitatively assess (1) the presence of systematic baseline differences, and (2) the relationship of baseline differences with effects on low-density lipoprotein-cholesterol (LDL-c) and clinical outcomes in the trials.
METHODS
We performed a meta-epidemiological study. PubMed, Embase, regulatory reports, ClinicalTrials.gov and company websites were searched for trials. Seven baseline characteristics (mean age, LDL-c, BMI, percentage males, diabetics, smokers, and hypertensives) and five outcomes (LDL-c, major adverse cardiac events, serious adverse events, any adverse events, all-cause mortality) were extracted. We calculated (1) range and distribution of baseline imbalances (sign-test), (2) pooled baseline differences and heterogeneity (meta-analysis), (3) differences in SDs around continuous variables (sign-test and pooling), and (4) the relationship of baseline differences with outcomes (meta-regression). The comparisons of PCSK9-inhibitor groups with either placebo or ezetimibe were analysed separately and combined.
RESULTS
We identified 43 trials with 63,193 participants. Baseline characteristics were frequently missing. Many trials showed small baseline imbalances, but some large imbalances. Only baseline BMI showed a statistically significant lower pooled mean for the drug versus placebo groups (MD -0.16; 95% CI -0.24 to -0.09). Heterogeneity in baseline imbalances was present in six placebo- and five ezetimibe-comparisons. Heterogeneity was statistically significant for BMI, males, diabetics and hypertensives in the combined comparisons. There was a statistically significant preponderance for larger SDs in the PCSK9-inhibitor versus control groups (sign-test age 0.014; LDL-c 0.014; BMI 0.049). Meta-regression showed clinically relevant relationships of baseline imbalances in age, BMI and diabetics with the risk of any adverse events and the risk of mortality. Two relationships were statistically significant: A higher mean BMI in the drug versus control group with a decreased risk of mortality (beta - 0.56; 95% CI -1.10 to -0.02), and a higher proportion of diabetics with an increased risk of any adverse events (beta 0.02; 95% 0.01 to 0.04).
CONCLUSIONS
Heterogeneous baseline imbalances and systematically different SDs were present in evolocumab and alirocumab trials, so study groups cannot be assumed to be comparable. These findings raise concerns about the design and conduct of the randomization procedures.
Topics: Humans; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Cholesterol, LDL; Male; Anticholesteremic Agents; Randomized Controlled Trials as Topic; Female; Treatment Outcome; Middle Aged; Hypercholesterolemia; PCSK9 Inhibitors; Aged; Proprotein Convertase 9
PubMed: 38909176
DOI: 10.1186/s12874-024-02260-z -
Journal of Clinical Lipidology Apr 2024Elevated lipoprotein(a) (Lp(a)) is an established risk factor for cardiovascular disease (CVD). To date, the only approved treatment to lower Lp(a) is lipoprotein...
BACKGROUND
Elevated lipoprotein(a) (Lp(a)) is an established risk factor for cardiovascular disease (CVD). To date, the only approved treatment to lower Lp(a) is lipoprotein apheresis (LA). Previous studies have demonstrated that LA is effective in reducing cardiovascular (CV) risk in patients with elevated low-density lipoprotein cholesterol (LDL-C) and/or Lp(a). Here we report our long-term experience with LA and its effectiveness in reducing CVD events in patients with elevated Lp(a).
METHODS
This retrospective open-label, single-center study included 25 individuals with Lp(a) elevation >60 mg/dL and LDL-C < 2.59 mmol/L who had indication for LA. The primary endpoint of this study was the incidence of any CV event (determined by medical records) after initiation of LA.
RESULTS
Mean LA treatment duration was 7.1 years (min-max: 1-19 years). Median Lp(a) was reduced from 95.0 to 31.1 mg/dL after LA (-67.3 %, p < 0.0001). Mean LDL-C was reduced from 1.85 to 0.76 mmol/L after LA (-58.9 %, p < 0.0001). Prior LA, 81 CV events occurred in total (0.87 events/patient/year). During LA, 49 CV events occurred in total (0.24 events/patient/year; -0.63, p = 0.001). Yearly major adverse cardiac event (MACE) rate was reduced from 0.34 to 0.006 (-0.33, p = 0.0002). Similar results were obtained when considering only individuals with baseline LDL-C below 1.42 mmol/L.
CONCLUSION
In this observational study of a heterogeneous CV high-risk cohort with elevated Lp(a), LA reduced Lp(a) levels and was paralleled by a decrease in CV events and MACE. We recommend LA for patients with high Lp(a) who still have CV events despite optimal lipid-lowering medication and lifestyle changes.
PubMed: 38908966
DOI: 10.1016/j.jacl.2024.04.134 -
Diabetes Research and Clinical Practice Jun 2024To examine the real effects of imeglimin on glycemic control and other metabolic factors in patients with type 2 diabetes (T2DM).
OBJECTIVE
To examine the real effects of imeglimin on glycemic control and other metabolic factors in patients with type 2 diabetes (T2DM).
METHODS
A retrospective longitudinal study was conducted based on a chart review. We recruited patients with T2DM who took imeglimin continuously for at least 3 months. Data on various metabolic parameters were collected at the first prescription of imeglimin and at 3, 6 and 12 months after the initiation of imeglimin. Statistical comparisons were performed using paired t-tests.
RESULTS
68 patients were eligible for this study. HbA1c decreased by 0.7 % at 3 months, 1.1 % at 6 months and 1.0 % by 12 months after the initiation of imeglimin. The decreases in HbA1c were observed regardless of age, gender, body mass index, duration of diabetes, renal function and concomitant use of hypoglycemic agents. There were also significant decreases in body weight, low-density lipoprotein-cholesterol (LDL-C), high-density lipoprotein-cholesterol (HDL-C) and non-HDL-C during imeglimin treatment.
CONCLUSIONS
This is the first report showing the long-term effects of imeglimin in a real-world setting. We confirmed the glucose-lowering effects of imeglimin in a real-world clinical setting. Furthermore, favorable effects of imeglimin on body weight and serum lipids were also suggested.
PubMed: 38908549
DOI: 10.1016/j.diabres.2024.111752 -
Journal of Cardiothoracic Surgery Jun 2024Long non-coding RNAs (lncRNAs) are abundant and closely related to the occurrence and development of human diseases. LncRNAs are known to play a key role in many...
BACKGROUND
Long non-coding RNAs (lncRNAs) are abundant and closely related to the occurrence and development of human diseases. LncRNAs are known to play a key role in many cardiovascular diseases. The purpose of this study was to investigate the effect of the RNA component of mitochondrial RNA-processing endoribonuclease (RMRP) on the degree of coronary artery lesions and prognosis in patients with coronary artery disease (CAD).
METHODS
Patients who underwent coronary angiography (CAG) and dynamical-single photon emission computed tomography (D-SPECT) were selected as study subjects, and the results of CAG were reviewed, and the patients were grouped according to SYNTAX score. Evaluate the factors affecting SYNTAX scores. The follow-up analysis was conducted, and the endpoint events were major adverse cardiovascular events (MACEs). Kaplan-Meier method was used to estimate the survival rate, and multivariate Cox regression was used to analyze the relationship between RMRP and MACEs.
RESULTS
The expression level of serum RMRP in patients with CAD was significantly higher than that in healthy people. Multivariate Logistic regression analysis showed that age, low-density lipoprotein cholesterol (LDL-C), RMRP and rest left ventricular ejection fraction (LVEF) were independent factors that affected SYNTAX scores. There were 19 cases of MACEs in the high RMRP group and 9 cases in the low RMRP group, and there was a significant difference in the MACE free survival curve between the two groups. Multivariate Cox regression analysis showed that age, SYNTAX score, rest LVEF and RMRP were risk factors for MACEs.
CONCLUSIONS
Serum RMRP is a key factor affecting the degree of coronary artery disease and prognosis in CAD patients.
Topics: Humans; Coronary Artery Disease; RNA, Long Noncoding; Male; Female; Prognosis; Middle Aged; Coronary Angiography; Aged; Tomography, Emission-Computed, Single-Photon; Biomarkers; Retrospective Studies
PubMed: 38907341
DOI: 10.1186/s13019-024-02870-0 -
Lipids in Health and Disease Jun 2024The ratio of non-high-density lipoprotein cholesterol (non-HDL-c) to high-density lipoprotein cholesterol (HDL-c) (NHHR) is a novel comprehensive lipid index. The aim of...
PURPOSE
The ratio of non-high-density lipoprotein cholesterol (non-HDL-c) to high-density lipoprotein cholesterol (HDL-c) (NHHR) is a novel comprehensive lipid index. The aim of this study was to investigate the relationship between the NHHR and the prevalence of hyperuricaemia (HUA) in the adult population of the U.S.
METHODS
This cross-sectional study collected data from the National Health and Nutrition Examination Survey (NHANES) (2007-2018). HUA was defined as a serum uric acid (SUA) concentration ≥ 7 mg/dL in men and ≥ 6 mg/dL in women. Multivariate logistic regression models and the restricted cubic spline (RCS) method were applied to examine the relationship between the NHHR and the risk of developing HUA. Subgroup analyses and interaction tests were also performed.
RESULTS
The prevalence of HUA increased with increasing NHHR values (9.01% vs. 13.38% vs. 17.31% vs. 25.79%, P < 0.001). The NHHR was independently correlated with the risk of developing HUA (OR = 1.10, 95% CI: 1.05-1.16; P < 0.001). Furthermore, the risk of developing HUA was significantly greater among individuals with the highest NHHR quartile than among those with the lowest NHHR quartile (OR = 1.94, 95% CI: 1.62-2.33; P < 0.001). This relationship was consistent across subgroups. According to the RCS analysis, an inverted U-shaped relationship existed between the NHHR and the risk of developing HUA.
CONCLUSIONS
The NHHR was closely associated with an increased risk of developing HUA. Further studies on the NHHR could be beneficial for preventing and treating HUA.
Topics: Humans; Hyperuricemia; Female; Male; Cholesterol, HDL; Middle Aged; Adult; Cross-Sectional Studies; Uric Acid; Nutrition Surveys; Risk Factors; Prevalence; Aged; Cholesterol, LDL; Logistic Models
PubMed: 38907262
DOI: 10.1186/s12944-024-02171-4 -
Lipids in Health and Disease Jun 2024Presently, the majority of investigations primarily evaluate the association between lipid profiles and asthma. However, few investigations explore the connection...
BACKGROUND
Presently, the majority of investigations primarily evaluate the association between lipid profiles and asthma. However, few investigations explore the connection between lipids and mortality related to the disease. This study aims to explore the association of serum lipids with all-cause mortality within asthmatic adults.
METHODS
The investigation included 3233 eligible patients with asthma from the NHANES (2011-2018). The potential associations were explored using three Cox proportional hazards models, restricted cubic splines (RCS), threshold effect models, and CoxBoost models. In addition, subgroup analyses were conducted to investigate these associations within distinct populations.
RESULTS
After controlling all covariables, the Cox proportional hazards model proved a 17% decrease in the probability of death for each increased unit of low-density lipoprotein-cholesterol (LDL-C) (mmol/L). Yet, there was no association seen between blood high-density lipoprotein cholesterol (HDL-C), total cholesterol, or triglyceride and all-cause mortality in asthmatics. The application of RCS and threshold effect models verified an inverse and linear association of LDL-C with all-cause mortality. According to the results from the CoxBoost model, LDL-C exhibited the most substantial impact on the follow-up status of asthmatics among the serum lipids.
CONCLUSION
Our investigation concluded that in American asthmatic populations, LDL-C levels were inversely and linearly correlated with mortality. However, no independent relationship was found between triglycerides, total cholesterol, or HDL-C and mortality.
Topics: Humans; Asthma; Male; Female; Middle Aged; Proportional Hazards Models; Adult; Cholesterol, LDL; Cholesterol, HDL; Triglycerides; Cohort Studies; Lipids; Aged; Risk Factors
PubMed: 38907251
DOI: 10.1186/s12944-024-02179-w