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Journal of the American Heart... Jun 2024The association of sleep onset time and duration with cardiometabolic health is not well characterized.
BACKGROUND
The association of sleep onset time and duration with cardiometabolic health is not well characterized.
METHODS AND RESULTS
This study included 6696 adults aged 20 to 80 years from the NHANES (National Health and Nutrition Examination Study) 2015 to 2018. Participants were categorized into 9 groups according to the cross-tabulation of sleep onset time (<22:00 [early], 22:00-23:59 [optimal], and ≥24:00 [late]) and duration (<7 hours [insufficient], 7-8 hours [sufficient], and ≥9 hours [excessive]), with optimal sleep onset time and sufficient duration as the reference. The primary outcomes included hypertension, hypertriglyceridemia, low high-density lipoprotein cholesterol, hyperglycemia, central obesity, and metabolic syndrome. Inappropriate sleep onset time and sleep duration were associated with increased odds of hypertension, hypertriglyceridemia, and metabolic syndrome, especially among participants aged 40 to 59 years. Compared with men reporting optimal onset and sufficient duration, men reporting optimal onset with excessive duration (odds ratio [OR]: 2.01 [95% CI, 1.12-3.58]) and late onset with insufficient duration (OR, 1.74 [95% CI, 1.13-2.68]) had higher odds of metabolic syndrome. Compared with women reporting optimal onset and sufficient duration, women reporting optimal onset and insufficient duration (OR, 1.61 [95% CI, 1.11-2.32]) and early onset and excessive duration (OR, 2.16 [95% CI, 1.30-3.57]) had higher odds of hypertension, and women reporting late onset and excessive duration (OR, 5.64 [95% CI, 1.28-6.77]) were at the highest odds of hypertriglyceridemia.
CONCLUSIONS
Late sleep onset as well as insufficient or excessive sleep duration are associated with adverse cardiometabolic outcomes, particularly in participants aged 40 to 59 years.
Topics: Humans; Middle Aged; Male; Female; Adult; Aged; Metabolic Syndrome; Sleep; Time Factors; Nutrition Surveys; Aged, 80 and over; United States; Young Adult; Cardiometabolic Risk Factors; Hypertension; Cross-Sectional Studies; Cardiovascular Diseases; Risk Assessment; Sleep Duration
PubMed: 38874059
DOI: 10.1161/JAHA.123.034165 -
Frontiers in Immunology 2024Mycobacterium tuberculosis (Mtb) is an intracellular pathogen capable of adapting and surviving within macrophages, utilizing host nutrients for its growth and... (Review)
Review
Mycobacterium tuberculosis (Mtb) is an intracellular pathogen capable of adapting and surviving within macrophages, utilizing host nutrients for its growth and replication. Cholesterol is the main carbon source during the infection process of Mtb. Cholesterol metabolism in macrophages is tightly associated with cell functions such as phagocytosis of pathogens, antigen presentation, inflammatory responses, and tissue repair. Research has shown that Mtb infection increases the uptake of low-density lipoprotein (LDL) and cholesterol by macrophages, and enhances cholesterol synthesis in macrophages. Excessive cholesterol is converted into cholesterol esters, while the degradation of cholesterol esters in macrophages is inhibited by Mtb. Furthermore, Mtb infection suppresses the expression of ATP-binding cassette (ABC) transporters in macrophages, impeding cholesterol efflux. These alterations result in the massive accumulation of cholesterol in macrophages, promoting the formation of lipid droplets and foam cells, which ultimately facilitates the persistent survival of Mtb and the progression of tuberculosis (TB), including granuloma formation, tissue cavitation, and systemic dissemination. Mtb infection may also promote the conversion of cholesterol into oxidized cholesterol within macrophages, with the oxidized cholesterol exhibiting anti-Mtb activity. Recent drug development has discovered that reducing cholesterol levels in macrophages can inhibit the invasion of Mtb into macrophages and increase the permeability of anti-tuberculosis drugs. The development of drugs targeting cholesterol metabolic pathways in macrophages, as well as the modification of existing drugs, holds promise for the development of more efficient anti-tuberculosis medications.
Topics: Mycobacterium tuberculosis; Cholesterol; Humans; Macrophages; Tuberculosis; Animals; Host-Pathogen Interactions; Antitubercular Agents; Lipid Metabolism
PubMed: 38873598
DOI: 10.3389/fimmu.2024.1402024 -
Frontiers in Immunology 2024The interplay between myeloid cells and T-lymphocytes is critical to the regulation of host defense and inflammation resolution. Dysregulation of this interaction can... (Review)
Review
The interplay between myeloid cells and T-lymphocytes is critical to the regulation of host defense and inflammation resolution. Dysregulation of this interaction can contribute to the development of chronic inflammatory diseases. Important among these diseases is atherosclerosis, which refers to focal lesions in the arterial intima driven by elevated apolipoprotein B-containing lipoproteins, notably low-density lipoprotein (LDL), and characterized by the formation of a plaque composed of inflammatory immune cells, a collection of dead cells and lipids called the necrotic core, and a fibrous cap. As the disease progresses, the necrotic core expands, and the fibrous cap becomes thin, which increases the risk of plaque rupture or erosion. Plaque rupture leads to a rapid thrombotic response that can give rise to heart attack, stroke, or sudden death. With marked lowering of circulating LDL, however, plaques become more stable and cardiac risk is lowered-a process known as atherosclerosis regression. A critical aspect of both atherosclerosis progression and regression is the crosstalk between innate (myeloid cells) and adaptive (T-lymphocytes) immune cells. Myeloid cells are specialized at clearing apoptotic cells by a process called efferocytosis, which is necessary for inflammation resolution. In advanced disease, efferocytosis is impaired, leading to secondary necrosis of apoptotic cells, inflammation, and, most importantly, defective tissue resolution. In regression, efferocytosis is reawakened aiding in inflammation resolution and plaque stabilization. Here, we will explore how efferocytosing myeloid cells could affect T-cell function and vice versa through antigen presentation, secreted factors, and cell-cell contacts and how this cellular crosstalk may contribute to the progression or regression of atherosclerosis.
Topics: Humans; Atherosclerosis; T-Lymphocytes; Myeloid Cells; Animals; Cell Communication; Phagocytosis; Apoptosis; Plaque, Atherosclerotic
PubMed: 38873597
DOI: 10.3389/fimmu.2024.1403150 -
Food Science & Nutrition Jun 2024This research aimed to examine the association between the following Mediterranean-DASH Intervention for Neurodegenerative Delay (MIND) dietary pattern and oxidative...
Association between Mediterranean-dietary approaches to stop hypertension intervention for neurodegenerative delay diet and biomarkers of oxidative stress, metabolic factors, disease severity, and odds of disease in rheumatoid arthritis patients.
This research aimed to examine the association between the following Mediterranean-DASH Intervention for Neurodegenerative Delay (MIND) dietary pattern and oxidative stress indicators, metabolic factors, disease activity, and the odds of disease in patients with rheumatoid arthritis (RA). In this cross-sectional study, we included 101 patients with RA and 101 healthy individuals. The MIND diet score was measured using a semi-quantitative Food Frequency Questionnaire (FFQ) with 147 food items. Total capacity antioxidant (TCA), superoxide dismutase (SOD), glutathione peroxidase (GPX), and malondialdehyde (MDA) serum concentrations were evaluated by ELISA, and the disease severity was measured regarding the disease activity score 28 (DAS-28) criteria. The average score of the MIND diet was substantially lower in the RA subjects than in the healthy people ( < .001). Individuals with a higher MIND diet score had lower odds of RA than those with a low score ( < .001). There was no remarkable link between the MIND diet and oxidative stress factors ( > .05). A reverse association was found between the MIND diet score and disease activity ( < .05). The MIND diet was significantly and negatively correlated with triglycerides, low-density lipoprotein cholesterol, total cholesterol, fasting blood glucose, and hemoglobin A1C. There was a positive association between the diet and high-density lipoprotein cholesterol. The findings indicate that following the MIND diet may decrease disease activity and the odds of RA. Also, high adherence to the MIND diet may improve the lipid profile and blood glucose status in RA patients.
PubMed: 38873478
DOI: 10.1002/fsn3.4055 -
Cureus May 2024Through the ages, infertility, affecting 8% to 12% of couples worldwide, has been a perturbing clinical problem. Approximately 40% to 50% of all infertility cases are...
BACKGROUND
Through the ages, infertility, affecting 8% to 12% of couples worldwide, has been a perturbing clinical problem. Approximately 40% to 50% of all infertility cases are due to 'male factor' infertility. Semen analysis is crucial in routinely evaluating idiopathic male infertility. Studies support the idea that semen parameters are associated with serum lipids and sperm DNA fragmentation (SDF). Therefore, it is possible to evaluate male infertility by serum lipid levels, especially before assisted reproduction technology, and modify it by bringing about lifestyle modifications. This study aimed to measure the correlation of SDF with levels of total cholesterol (TC), triglycerides (TG), very low-density lipoprotein (VLDL), low-density lipoprotein (LDL), and high-density lipoprotein (HDL) among males with abnormal semen parameters.
METHODS
A cross-sectional analytical study was conducted in the infertility clinic of a tertiary care hospital. A total of 106 infertile males with abnormal semen analysis as per the WHO criteria (2010) were enrolled in the study. After routine semen analysis, SDF was studied using the comet assay. The serum fasting lipid profile was analyzed using the spectrophotometric kit in the autoanalyzer. The relationship of SDF with serum lipid profile parameters was analyzed.
RESULTS
Out of 106 infertile men, 52% (n = 55) had severe SDF. A modest positive correlation was observed between SDF (percentage of DNA in comet tail) and serum lipid values (serum TG, serum LDL, and serum VLDL).
CONCLUSIONS
Our study is novel in its research on the correlation between SDF and serum lipid values. Based on the findings of our study, it can be concluded that a significant level of SDF was observed in men with high levels of serum TG, LDL, and VLDL. This provokes a potential relationship between sperm DNA integrity and serum lipid profile, which warrants further research.
PubMed: 38872655
DOI: 10.7759/cureus.60243 -
Cureus May 2024Background The increasing incidence of type 2 diabetes (T2D) in India underscores the pressing need for effective management strategies. Meeting the American Diabetes...
Background The increasing incidence of type 2 diabetes (T2D) in India underscores the pressing need for effective management strategies. Meeting the American Diabetes Association (ADA) ABC targets for diabetes (glycated hemoglobin (HbA1c), blood pressure, and serum low-density lipoprotein cholesterol (LDL-C)) is crucial for effectively managing T2D, as it reflects the optimal control of key metabolic parameters. Insulin resistance (IR) and impaired beta cell function (BCF) have been found to have a significant impact on glycemic control, lipid metabolism, and hypertension, contributing to the complex cardiovascular risk profile of patients with T2D. This study aimed to explore the association between ABC targets for diabetes, IR, BCF, and dyslipidemia in a cross-sectional cohort of T2D patients. Methods This retrospective study examined data from 681 T2D patients with comorbid hypertension and dyslipidemia. The patients were part of a one-year online lifestyle intervention program for diabetes management at the Freedom from Diabetes Clinic in Pune, India, between January 2021 and December 2022. Baseline data (at the time of enrollment in the program) on medical history and anthropometric and biochemical parameters were retrospectively extracted from medical records and used to assess ABC targets and other clinical parameters. The ABC targets for diabetes include three goals: an HbA1c level of less than 7.0%, a blood pressure level of less than 140/90 mmHg, and an LDL-C level of less than 100 mg/dL. Homeostatic Model Assessment of Insulin Resistance (HOMA-IR), Homeostatic Model Assessment of Beta Cell Function (HOMA-B), and Quantitative Insulin Sensitivity Check Index (QUICKI) were calculated using standard formulas. Results Cross-sectional analysis at baseline showed that 152 (22.3%) participants met all three ABC targets, 306 (45.0%) and 183 (26.8%) participants met two or one targets, respectively, and 40 (5.9%) did not meet any of the ABC targets. Participants meeting all three targets showed significantly lower IR, higher sensitivity (HOMA-IR, median 2.1; QUICKI, median 0.34), higher BCF (HOMA-B, median 62.9), and healthier lipid profiles (mg/dL) (total cholesterol, median 126; triglycerides, median 114; and non-high-density lipoprotein (HDL), median 84) than those who did not meet any of the ABC targets (HOMA-IR, median 3.4; QUICKI, median 0.31; HOMA-B, median 31.7; total cholesterol, median 221; triglycerides, median 187; and non-HDL, median 182) (p < 0.01). A significant association was observed between lower BMI (< 25 kg/m), lower IR (HOMA-IR <2.5), and meeting all three ABC targets (p < 0.01). No significant association was observed between the duration of diabetes and ABC target status (p > 0.1). Lower IR was identified as a predictor of achievement of all three ABC targets (p < 0.01). Conclusion This study highlights the significance of meeting ABC targets for diabetes in relation to not only a better lipid profile but also lower IR and higher BCF. These preliminary findings provide novel insights into the interplay between IR, BCF, dyslipidemia, and meeting ABC targets in an Indian T2D population. These findings highlight the need for effective diabetes management strategies and improved patient outcomes, considering factors such as BMI and IR indices.
PubMed: 38872654
DOI: 10.7759/cureus.60268 -
Scientific Reports Jun 2024Simple and practical tools for screening high-risk new-onset diabetes after percutaneous coronary intervention (PCI) (NODAP) are urgently needed to improve post-PCI...
Simple and practical tools for screening high-risk new-onset diabetes after percutaneous coronary intervention (PCI) (NODAP) are urgently needed to improve post-PCI prognosis. We aimed to evaluate the risk factors for NODAP and develop an online prediction tool using conventional variables based on a multicenter database. China evidence-based Chinese medicine database consisted of 249, 987 patients from 4 hospitals in mainland China. Patients ≥ 18 years with implanted coronary stents for acute coronary syndromes and did not have diabetes before PCI were enrolled in this study. According to the occurrence of new-onset diabetes mellitus after PCI, the patients were divided into NODAP and Non-NODAP. After least absolute shrinkage and selection operator regression and logistic regression, the model features were selected and then the nomogram was developed and plotted. Model performance was evaluated by the receiver operating characteristic curve, calibration curve, Hosmer-Lemeshow test and decision curve analysis. The nomogram was also externally validated at a different hospital. Subsequently, we developed an online visualization tool and a corresponding risk stratification system to predict the risk of developing NODAP after PCI based on the model. A total of 2698 patients after PCI (1255 NODAP and 1443 non-NODAP) were included in the final analysis based on the multicenter database. Five predictors were identified after screening: fasting plasma glucose, low-density lipoprotein cholesterol, hypertension, family history of diabetes and use of diuretics. And then we developed a web-based nomogram ( https://mr.cscps.com.cn/wscoringtool/index.html ) incorporating the above conventional factors for predicting patients at high risk for NODAP. The nomogram showed good discrimination, calibration and clinical utility and could accurately stratify patients into different NODAP risks. We developed a simple and practical web-based nomogram based on multicenter database to screen for NODAP risk, which can assist clinicians in accurately identifying patients at high risk of NODAP and developing post-PCI management strategies to improved patient prognosis.
Topics: Humans; Percutaneous Coronary Intervention; Nomograms; Male; Female; Middle Aged; Risk Factors; Aged; Diabetes Mellitus; Internet; China; Risk Assessment; Prognosis; Acute Coronary Syndrome; ROC Curve
PubMed: 38871809
DOI: 10.1038/s41598-024-64430-9 -
Journal For Immunotherapy of Cancer Jun 2024The sustained effectiveness of anti-programmed cell death protein-1/programmed death-ligand 1 treatment is limited to a subgroup of patients with advanced nasopharyngeal...
BACKGROUND
The sustained effectiveness of anti-programmed cell death protein-1/programmed death-ligand 1 treatment is limited to a subgroup of patients with advanced nasopharyngeal carcinoma (NPC), and the specific biomarker determining the response to immunotherapy in NPC remains uncertain.
METHODS
We assessed the associations between pre-immunotherapy and post-immunotherapy serum lipoproteins and survival in a training cohort (N=160) and corroborated these findings in a validation cohort (N=100). Animal studies were performed to explore the underlying mechanisms. Additionally, the relationship between high-density lipoprotein-cholesterol (HDL-C) levels and M1/M2-like macrophages, as well as activated CD8+T cells in tumor tissues from patients with NPC who received immunotherapy, was investigated.
RESULTS
The lipoproteins cholesterol, HDL-C, low-density lipoprotein-cholesterol, triglycerides, apolipoprotein A-1 (ApoA1), and apolipoprotein B, were significantly altered after immunotherapy. Patients with higher baseline HDL-C or ApoA1, or those with increased HDL-C or ApoA1 after immunotherapy had longer progression-free survival, a finding verified in the validation cohort (p<0.05). Multivariate analysis revealed that baseline HDL-C and elevated HDL-C post-immunotherapy were independent predictors of superior PFS (p<0.05). Furthermore, we discovered that L-4F, an ApoA1 mimetic, could inhibit tumor growth in NPC xenografts. This effect was associated with L-4F's ability to polarize M2-like macrophages towards an M1-like phenotype via the activation of mitogen-activated protein kinase (MAPK) p38 and nuclear factor-κB (NF-κB) p65, thereby alleviating immunosuppression in the tumor microenvironment. Importantly, in patients with NPC with high plasma HDL-C levels, the number of M2-like macrophages was significantly decreased, while M1-like macrophages and activated CD8+T cells were notably increased in those with high HDL-C levels.
CONCLUSION
Higher baseline HDL-C levels or an increase in HDL-C post-immunotherapy can enhance immunotherapeutic responses in patients with NPC by reprogramming M2-like macrophages towards the M1 phenotype. This suggests a potential role for prospectively exploring ApoA1 mimetics as adjuvant agents in combination with immunotherapy.
Topics: Humans; Nasopharyngeal Carcinoma; Tumor-Associated Macrophages; Immunotherapy; Animals; Female; Male; Cholesterol, HDL; Mice; Middle Aged; Phenotype; Tumor Microenvironment; Nasopharyngeal Neoplasms; Adult
PubMed: 38871480
DOI: 10.1136/jitc-2023-008146 -
Indian Heart Journal Jun 2024Defining lipid goals solely on low-density lipoprotein-cholesterol (LDL-C) levels in Indian population may cause misclassification due to high prevalence of...
BACKGROUND
Defining lipid goals solely on low-density lipoprotein-cholesterol (LDL-C) levels in Indian population may cause misclassification due to high prevalence of hypertriglyceridemia and small dense LDL-C particles. International guidelines now recommend Apoliporotein-B (Apo-B) and non-high-density lipoprotein-cholesterol (non-HDL-C) levels as alternative targets. In this study, we used a cross-sectional representative population database to determine Apo-B and non-HDL-C cut-offs corresponding to identified LDL-C targets and compared them to international guidelines.
METHODS
A community-based survey carried out in urban Delhi and adjacent rural Ballabhgarh provided lipid values for 3047 individuals. The Spearman correlation coefficient was used to evaluate the degree of relationship between Apo-B and LDL-C and non-HDL-C. Cut-off values for Apo-B and non-HDL-C were established using receiver operator curve analysis correlating with guideline-recommended LDL-C targets.
RESULTS
Spearman's rank correlations between Apo-B and LDL-C (0.82) and non-HDL-C and LDL-C (0.93) were significant (p < 0.05). Proposed corresponding cut-off values for LDL-C of 55, 70,100,130 and 160 mg/dl for Apo-B and non-HDL-C in our population were 75.3, 75.5, 91.3, 107.6, 119.4 mg/dL and 92.5,96.5, 123.5, 154.5, 179.5 mg/dL respectively. However, in those with triglycerides >150 mg/dl the corresponding Apo-B and non-HDL-C values were 85.1, 92.7, 103.5, 117.5 and 135 mg/dL and 124.5, 126.5, 147.5, 167.5 and 190.5 mg/L respectively.
CONCLUSION
Based on this study we provide Apo-B and non-HDL cut-offs corresponding to target LDL-C values in Indian patients with and without high triglycerides. It is noted that in individuals with triglycerides ≥ 150 mg/dl, the Apo-B levels are much higher than the values recommended by guidelines.
PubMed: 38871221
DOI: 10.1016/j.ihj.2024.06.003 -
Journal of Cardiology Jun 2024The impact of very low baseline levels of low-density lipoprotein cholesterol (LDL-C) on patients with coronary artery disease remains unclear.
BACKGROUND
The impact of very low baseline levels of low-density lipoprotein cholesterol (LDL-C) on patients with coronary artery disease remains unclear.
METHOD
We enrolled 39,439 patients of the pooled population from the CREDO-Kyoto registries Cohorts 1, 2, and 3. The study population consisted of 33,133 patients who had undergone their first coronary revascularization. We assessed the risk for mortality and cardiovascular events according to quintiles of the baseline LDL-C levels.
RESULTS
Patients in the very low LDL-C quintile (<85 mg/dL) had more comorbidities than those in the other quintiles. Lower LDL-C levels were strongly associated with anemia, thrombocytopenia, and end-stage renal disease. The cumulative 4-year incidence of all-cause death increased as LDL-C levels decreased (very low: 19.4 %, low: 14.5 %, intermediate: 11.1 %, high: 10.0 %, and very high: 9.2 %; p < 0.001), which was driven by both the early and late events. After adjusting for baseline characteristics, the adjusted risks of the very low and low LDL-C quintiles relative to the intermediate LDL-C quintile remained significant for all-cause death (very low: HR 1.29, 95 % CI 1.16-1.44, p < 0.001; low: HR 1.15, 95 % CI 1.03-1.29, p = 0.01). The excess adjusted risks of the lowest LDL-C quintile relative to the intermediate LDL-C quintile were significant for clinical outcomes such as cardiovascular death (HR 1.17, 95 % CI 1.01-1.35), non-cardiovascular death (HR 1.35, 95 % CI 1.15-1.60), sudden death (HR 1.44, 95 % CI 1.01-2.06), and heart failure admission (HR 1.11 95 % CI 1.01-1.22), while there was no excess risk for the lowest LDL-C quintile relative to the intermediate LDL-C quintile for myocardial infarction and stroke.
CONCLUSIONS
Lower baseline LDL-C levels were associated with more comorbidities and a significantly higher risk of death, regardless of cardiovascular or non-cardiovascular causes, in patients who underwent coronary revascularization.
PubMed: 38871119
DOI: 10.1016/j.jjcc.2024.05.011