Search

Evidence regarding the role of chronic low-grade inflammation in the progression of cardiometabolic diseases (CMDs) and cardiometabolic multimorbidity (CMM) is currently limited. This prospective cohort study, utilising data from the UK Biobank, included 273,804 adults aged 40–69 years initially free of CMD at baseline. CMM was defined as the coexistence of two or more CMDs, such as coronary artery disease, type 2 diabetes mellitus, hypertension and stroke. The aggregated inflammation score (INFLA-score), incorporating C-reactive protein, white blood cell count, platelet count and granulocyte-to-lymphocyte ratio, quantified chronic low-grade inflammation. Absolute risks (ARs), hazard ratios (HRs) and 95% confidence intervals (CIs) assessed the association of increased INFLA-score with the risk of CMMs and CMDs. The accelerated failure time model explored the effect of INFLA-score on the time to CMM onset, and a restricted cubic spline characterised the dose-dependent relationship between INFLA-score and CMM risk. After a median follow-up of 166.37 months, 13,755 cases of CMM were identified. In quartiles with increasing INFLA-score levels, CMM ARs were 4.41%, 4.49%, 5.04% and 6.01%, respectively; HR increased by 2%, 15% and 36%, respectively, compared to the lowest quartile. The INFLA-score and CMM risk relationship was nonlinear (P for nonlinear < 0.001), exhibiting a significant risk trend change at a score of 9. For INFLA-score < 9, CMM risk increased by 1.9% for each 1-point increase; for INFLA-score ≥ 9, the risk increased by 5.9% for each 1-point increase. Additionally, a higher INFLA-score was associated with an earlier onset of CMM (P < 0.001). Compared to the first INFLA-score quartile, the AFT model revealed adjusted median times to CMM occurrence were 2.92, 6.10 and 13.19 months earlier in the second, third and fourth quartile groups, respectively. Chronic low-grade inflammation is associated with a higher risk of cardiometabolic multimorbidity and earlier onset among middle-aged and older adults. Monitoring and screening the INFLA-score in adults without CMDs may improve early prevention of CMM. [ABSTRACT FROM AUTHOR]

Background: Insulin resistance (IR) significantly contributes to cardiovascular disease (CVD) development. Triglyceride glucose (TyG) index and triglyceride glucose-body mass index (TyG-BMI) are recognised as convenient proxies for IR. However, their relationship with sudden cardiac arrest (SCA) remains unclear. Methods: This prospective cohort analysis included 355,242 UK Biobank participants with available TyG index and TyG-BMI data and no history of CVD. Cox proportional risk models assessed the association between the TyG index, TyG-BMI and SCA risk. Additionally, Accelerated Failure Time (AFT) models were employed to investigate the timing of SCA onset. The impact of dynamic increases in TyG index and TyG-BMI levels on SCA risk was examined using restricted cubic spline. Results: Over a median follow-up period of 165.4 months (interquartile range 156.5–174 months), 1,622 cases of SCA were recorded. Multivariate Cox regression analysis revealed a 9% increase in SCA risk per standard deviation increase in TyG index (adjusted hazard ratio (aHR) = 1.09, 95% confidence interval (CI) 1.04–1.15) and an 14% increase per standard deviation increase in TyG-BMI (aHR 1.14, 95% CI 1.09–1.2). AFT models indicated earlier median times to SCA occurrence with increasing quintiles of TyG index and TyG-BMI compared to the lowest quintile (P for trend < 0.05). SCA risk was linearly (P = 0.54) and non-linearly (P = 0.007) correlated with gradual increases in TyG index and TyG-BMI levels, respectively. Sex-stratified analyses showed stronger associations in women. Conclusions: Higher TyG index and TyG-BMI levels are associated with an increased SCA risk and earlier onset, particularly in women. [ABSTRACT FROM AUTHOR]

Currently, the understanding of the cyclic GMP‐AMP synthase (cGAS)‐stimulator of interferon genes (STING) pathway's involvement in efficient immunotherapy mainly revolves around the role of mitochondria or nucleus modulation. Nonetheless, the role of endoplasmic reticulum (ER) stress in activating the cGAS‐STING mechanism to boost immunity against tumors remains essentially unexplored. Herein, novel findings demonstrating that ER stress can be used as a strategy for stimulating the cGAS‐STING pathway, thereby augmenting the immune response against cancer, are presented. To accomplish this objective, ER‐targeting p‐methylbenzene sulfonamide‐tailored IR780 (p‐780) is synthesized and it is loaded into CaO2 nanoparticles, which are further functionalized with distearoyl phosphoethanolamine‐polyethylene glycol（DSPE‐PEG）‐biotin to form PEG/CaO2@p‐780 NPs. The disruption of calcium homeostasis, coupled with the heightened levels of reactive oxygen species (ROS) mediated by p‐780, along with hyperpyrexia, collectively contributes to the amplification of endoplasmic reticulum (ER) stress. This cascade of events effectively triggers the cGAS‐STING pathway and, in parallel, facilitates the degradation of the programmed cell death 1 ligand 1 (PD‐L1) protein. In addition, oxygen released through CaO2 decomposition is expected to promote p‐780–mediated phototherapy, while reversing the immunosuppressive tumor microenvironment associated with hypoxia. Furthermore, DSPE‐PEG‐biotin facilitates tumor site‐specific drug delivery through active targeting mediated by the biotin receptor. Collectively, PEG/CaO2@p‐780 nanoparticles successfully activate systemic antitumor immunity by enhancing ER stress. [ABSTRACT FROM AUTHOR]

Background: Diabetic individuals often encounter various sleep-related challenges. Although the association between sleep duration and atrial fibrillation (AF) have been explored, the association of other sleep traits with the incidence of AF remains unclear. A comprehensive understanding of these traits is essential for a more accurate assessment of sleep conditions in patients with diabetes and the development of novel AF prevention strategies. Methods: This study involved 23,785 patients with diabetes without any pre-existing cardiovascular disease, drawn from the UK Biobank. Sleep behaviour traits examined encompassed sleep duration, chronotype, insomnia, snoring and daytime sleepiness. Sleep duration was categorised into three groups: low (≤ 5 h), proper (6–8 h) and long (≥ 9 h). We assessed associations using multivariate Cox proportional risk regression models. Furthermore, four poor sleep behaviours were constructed to evaluate their impact on the risk of new-onset AF. Results: Over a mean follow-up period of 166 months, 2221 (9.3%) new cases of AF were identified. Short (hazard ratio (HR), 1.28; 95% confidence interval (CI) 1.10–1.50) and long sleep durations (HR 1.16; 95% CI 1.03–1.32) consistently exhibited an elevated risk of AF compared to optimal sleep duration. Early chronotype, infrequent insomnia and daytime sleepiness were associated with 11% (HR 0.89; 95% CI 0.82–0.97), 15% (HR 0.85; 95% CI 0.77–0.95) and 12% (HR 0.88; 95% CI 0.81–0.96) reduced risk of new-onset AF, respectively. However, no significant association was found between snoring and the incidence of AF (HR 0.99; 95% CI 0.91–1.07). Conclusions: In diabetic populations, sleep duration, chronotype, insomnia and daytime sleepiness are strongly associated with AF incidence. An optimal sleep duration of 6–8 h presents the lowest AF risk compared to short or long sleep duration. Additionally, poor sleep patterns present a greater risk of new-onset AF in women than in men. [ABSTRACT FROM AUTHOR]

Background: Hypertensive disorders of pregnancy is associated with increased risk of cardiovascular disease later in life, but studies suggest that women with previous hypertensive disorders of pregnancy are not aware of this. Little is known about how these women perceive the condition and the associated long-term risks., Objectives: This study aims to examine and synthesize qualitative evidence on the perceptions and awareness of women with hypertensive disorders of pregnancy following perceived cardiovascular disease risk., Methods: Computer searches of Pub Med, Embase, Web of Science, Cochrane Library, CINAHL, CNKI, Wanfang database, Vip and SinoMed for all qualitative studies that met the inclusion criteria. The time frame for the search was from the establishment of the database to April 2024. Literature quality was assessed using the Australian Joanna Briggs Institute Centre for Evidence-Based Health Care Qualitative Research quality assessment criteria, and results were summarised and integrated using a pooled integration approach., Results: Eleven studies that fulfilled the inclusion criteria and quality assessment were included in the meta synthesis. Three themes were identified during the analysis: (1)Factors affecting perceived cardiovascular risk in women with hypertensive disorders of pregnancy; (2)Women with hypertensive disorders of pregnancy use different strategies to cope with cardiovascular risk; (3)Needs and expectations for coping with cardiovascular disease risk., Conclusions: Both women with hypertensive disorders of pregnancy and healthcare providers lack knowledge of the link between hypertensive disorders of pregnancy and cardiovascular risk. Healthcare professionals should establish a multidimensional support model, pay timely attention to postpartum women's psycho-emotional and risk awareness, and give individualised health education to promote health behaviour change. At the same time, professionals should be given standardised training and personalised follow-up services to reduce the incidence of cardiovascular disease in the future., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Aim: The purpose of this paper is to explore sex-based differences in cardiovascular health (CVH) and the incidence of type 2 diabetes mellitus (T2DM) among women at different menopausal stages and men., Methods: A prospective cohort study was conducted, involving 126,818 participants without pre-existing T2DM from the UK Biobank. CVH was assessed using the Life's Essential 8. Absolute risks (ARs) and hazard ratios (HRs) were separately employed to assess the association between increased CVH and T2DM risk. The Accelerated Failure Time model assessed the impact of CVH on the time to T2DM onset., Results: Over a mean follow-up of 168 months, 4,315 cases of T2DM were documented. In men, each one-point increase in CVH was associated with a 0.268% decrease in AR and a 6.4% decrease in HR for T2DM. In premenopausal, perimenopausal and postmenopausal women, each unit increase in CVH resulted in a 0.105%, 0.180% and 0.166% decrease in AR and a 7.7%, 5.2% and 6.4% decrease in HR of T2DM. The adjusted median time to T2DM onset was delayed by 12.46, 9.83, 11.5 and 21.43 months in the highest quintile of men, premenopausal, perimenopausal and postmenopausal women, respectively, compared with the lowest CVH quintile., Conclusions: As CVH improved, the reduction in AR for T2DM was more prominent in men than in women. HR trends for CVH and T2DM were similar in men and postmenopausal women. Increased CVH delayed the onset of T2MD in both men and women, with the most significant delay observed in postmenopausal women., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Endocrine Society. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com. See the journal About page for additional terms.)

Background: Although the beneficial properties of vitamin D in anti-inflammation and immunity-modulation are promising in the management of inflammatory bowel disease (IBD), data were limited for the critical IBD prognosis. The association between serum vitamin D levels and the risk of bowel resection in individuals with IBD remains largely unknown., Materials and Methods: The authors performed a longitudinal cohort study among 5474 individuals with IBD in the UK Biobank. Serum 25-hydroxyvitamin D [25(OH)D] was measured using direct competitive chemiluminescent immunoassay. Bowel resection events were ascertained via national inpatient data. Multivariable-adjusted Cox proportional hazard regression was used to examine the association between serum 25(OH)D and bowel resection risk, presented with hazard ratios (HRs) and 95% CIs. Restricted cubic spline (RCS) was used to evaluate dose-response associations., Results: During a mean follow-up of 13.1 years, the authors documented 513 incident bowel resection cases. Compared to participants with vitamin D deficiency, nondeficient participants showed a significantly reduced bowel resection risk in IBD (HR 0.72, 95% CI: 0.59-0.87, P =0.001), Crohn's disease (CD, HR 0.74, 95% CI: 0.56-0.98, P =0.038), and ulcerative colitis (UC, HR 0.73, 95% CI: 0.57-0.95, P =0.020). When comparing extreme quintiles of 25(OH)D level, participants with IBD showed a 34% reduced risk of bowel resection (95% CI: 11-51%, P =0.007) and participants with UC showed a 46% reduced risk (95% CI: 19-64%, P =0.003), while this association was not significant in CD (HR 0.93, 95% CI: 0.59-1.45, P =0.740). Linear dose-response associations were observed using the RCS curve (all P -nonlinearity>0.05)., Conclusion: Increased serum level of 25(OH)D is independently associated with reduced bowel resection risk in IBD. This association was significant in UC but may not be stable in CD. Vitamin D deficiency is a risk factor for bowel resection in individuals with IBD, and may be an effective metric in predicting and risk-screening surgical events., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc.)