Search

Aims Observational studies have suggested strong associations between sleep duration and many cardiovascular diseases (CVDs), but causal inferences have not been confirmed. We aimed to determine the causal associations between genetically predicted sleep duration and 12 CVDs using both linear and nonlinear Mendelian randomization (MR) designs. Methods and results Genetic variants associated with continuous, short (≤6 h) and long (≥9 h) sleep durations were used to examine the causal associations with 12 CVDs among 404 044 UK Biobank participants of White British ancestry. Linear MR analyses showed that genetically predicted sleep duration was negatively associated with arterial hypertension, atrial fibrillation, pulmonary embolism, and chronic ischaemic heart disease after correcting for multiple tests (P  <   0.001). Nonlinear MR analyses demonstrated nonlinearity (L-shaped associations) between genetically predicted sleep duration and four CVDs, including arterial hypertension, chronic ischaemic heart disease, coronary artery disease, and myocardial infarction. Complementary analyses provided confirmative evidence of the adverse effects of genetically predicted short sleep duration on the risks of 5 out of the 12 CVDs, including arterial hypertension, pulmonary embolism, coronary artery disease, myocardial infarction, and chronic ischaemic heart disease (P  <   0.001), and suggestive evidence for atrial fibrillation (P  <   0.05). However, genetically predicted long sleep duration was not associated with any CVD. Conclusion This study suggests that genetically predicted short sleep duration is a potential causal risk factor of several CVDs, while genetically predicted long sleep duration is unlikely to be a causal risk factor for most CVDs. [ABSTRACT FROM AUTHOR]

Background Drug memories that associate drug-paired stimuli with the effects of abused drugs contribute to relapse. Exposure to drug-associated contexts causes consolidated drug memories to be in a labile state, during which manipulations can be given to impair drug memories. Although substantial evidence demonstrates the crucial role of neuronal signaling in addiction, little is known about the contribution of astrocyte-neuron communication. Methods Rats were trained for cocaine-induced conditioned place preference (CPP) or self-administration and microinjected with the glycogen phosphorylation inhibitor 1,4-dideoxy-1,4-imino-D-arabinitol into the basolateral amygdala (BLA) immediately after retrieval. The concentration of lactate was measured immediately after retrieval via microdialysis, and the CPP score and number of nosepokes were recorded 24 hours later. Furthermore, we used antisense oligodeoxynucleotides to disrupt the expression of astrocytic lactate transporters (monocarboxylate transporters 1 and 2) in the BLA after retrieval, tested the expression of CPP 1 day later, and injected L-lactate into the BLA 15 minutes before retrieval to rescue the effects of the oligodeoxynucleotides. Results Injection of 1,4-dideoxy-1,4-imino-D-arabinitol into the BLA immediately after retrieval prevented the subsequent expression of cocaine-induced CPP, decreased the concentration of lactate in the BLA, and reduced the number of nosepokes for cocaine self-administration. Disrupting the expression of monocarboxylate transporters 1 and 2 in the BLA also caused subsequent deficits in the expression of cocaine-induced CPP, which was rescued by pretreatment with L-lactate. Conclusions Our results suggest that astrocyte-neuron lactate transport in the BLA is critical for the reconsolidation of cocaine memory. [ABSTRACT FROM AUTHOR]

Study Objectives: Observational studies suggest associations between insomnia and cardiovascular diseases (CVDs), but the causal mechanism remains unclear. We investigated the potential causal associations between insomnia and CVDs by a combined systematic meta-review and meta-analysis of observational and Mendelian randomization (MR) studies., Methods: We searched PubMed, Web of Science, and Embase for English-language articles from inception to 7/11/2023. Two reviewers independently screened the articles to minimize potential bias. We summarized the current evidence on the associations of insomnia with coronary artery disease (CAD), atrial fibrillation (AF), heart failure (HF), myocardial infarction (MI), hypertension (HTN), and stroke risk by combining meta-analyses of observational and MR studies., Results: Four meta-analyses of observational studies and 9 MR studies were included in the final data analysis. A systematic meta-review of observational studies provided strong evidence that insomnia is an independent risk factor for many CVDs, including AF, MI, and HTN. A meta-analysis of MR studies revealed that insomnia may be potentially causally related to CAD (odds ratio (OR)=1.14, 95% confidence interval (CI)=1.10-1.19, I 2 =97%), AF (OR=1.02, 95% CI=1.01-1.04, I 2 =94%), HF (OR=1.04, 95% CI=1.03-1.06, I 2 =97%), HTN (OR=1.16, 95% CI=1.13-1.18, I 2 =28%), large artery stroke (OR=1.14, 95% CI=1.05-1.24, I 2 =0%), any ischemic stroke (OR=1.09, 95% CI=1.03-1.14, I 2 =60%), and primary intracranial hemorrhage (OR=1.16, 95% CI=1.05-1.27, I 2 =0%). No evidence suggested that insomnia is causally associated with cardioembolic or small vessel stroke., Conclusions: Our results provide strong evidence supporting a possible causal association between insomnia and CVD risk. Strategies to treat insomnia may be promising targets for preventing CVDs., (© 2024 American Academy of Sleep Medicine.)

Study Objectives: This study aimed to determine the associations between accelerometer-measured sleep durations and the risks of incident cardiovascular disease (CVD) and CVD-related mortality., Methods: A total of 92,261 participants (mean age: 62.4±7.8 years, 56.4% female) were included in UK Biobank between 2013 and 2015. Average daily sleep durations were measured using wrist-worn accelerometers over a seven-day period. Sleep durations were categorized as <7 hours/day, 7-9 hours/day (reference), and >9 hours/day. The incidence of CVD and CVD-related mortality were ascertained by hospital records and death registries., Results: During a median follow-up period of 7.0 years, a total of 13,167 participants developed CVD, and 1,079 participants died of CVD. Compared with a sleep duration 7-9 hours/day, an accelerometer-measured sleep duration <7 hours/day but not >9 hours/day was associated with higher risks of incident CVD (HR 1.06, 95% CI: 1.02-1.10), CVD-related mortality (HR 1.29, 95% CI: 1.14-1.47), coronary heart disease (HR 1.11, 95% CI: 1.03-1.19), myocardial infarction (HR 1.14, 95% CI: 1.03-1.27), heart failure (HR 1.20, 95% CI: 1.08-1.34), and atrial fibrillation (HR 1.15, 95% CI: 1.07-1.24). A curvilinear dose‒response pattern was observed between accelerometer-measured sleep durations and incident CVD (Poverall<0.001), with L-shaped associations found for incident CVD and CVD-related mortality., Conclusions: An accelerometer-measured sleep duration <7 hours/day but not >9 hours/day was associated with elevated risks of incident CVD and CVD-related mortality. Maintaining adequate sleep may help promote cardiovascular health., (© The Author(s) 2024. Published by Oxford University Press on behalf of Sleep Research 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.)

Background: Emerging evidence has linked childhood maltreatment with cardiovascular disease risk; however, the association between childhood maltreatment and cardiac arrhythmias remains unclear. Moreover, any genetic predispositions to atrial fibrillation (AF), a common cardiac arrhythmia associated with an elevated risk of stroke, heart failure, and mortality, that modify such associations have been undocumented. Purpose: To examine the associations between childhood maltreatment and incident arrhythmias, and whether a genetic predisposition to arrhythmias modifies these associations. Methods: This prospective analysis included 151,741 participants from the UK Biobank (mean age 55.8 years, 43.4% male). Childhood maltreatment, including five types, was measured using the Childhood Trauma Screener (CTS). Incident arrhythmias (AF, ventricular arrhythmias [VA], and bradyarrhythmia [BA]) were documented through linked hospital admission and death registry. Weighted AF genetic risk score was calculated. Cox proportional hazard models were conducted to test for associations between childhood maltreatment and incident arrhythmias. Results: During a median follow-up of 12.21 years (interquartile range, 11.49-12.90 years), 6,588 AF, 2,093 BA, and 742 VA events occurred. Compared with the absence of childhood maltreatment, having 3-5 types of childhood maltreatment was associated with an increased risk of incident AF (HR, 1.23; 95%CI 1.09-1.37), VA (HR, 1.39; 95%CI 1.03-1.89), and BA (HR, 1.32; 95%CI 1.09-1.61) after adjusting demographic, socioeconomic and lifestyle factors. The associations between cumulative type of childhood maltreatment and the risk of AF ( P overall  < .001; P nonlinear  = .674) and BA ( P overall  = .007; P nonlinear  = .377) demonstrated a linear pattern. There was a gradient association between childhood maltreatment and AF risks across the intermediate and high genetic risk groups (both P trend  < .05) but not within the low genetic risk group ( P trend  = .378), irrespective of non-significant interaction effect ( P interaction  = .204). Conclusion: Childhood maltreatment was associated with higher risks of incident arrhythmias, especially AF and BA. Genetic risk of AF did not modify these associations.