Covassin, Naima

Telomere length (TL) is associated with cardiovascular disease (CVD) and cancer. Obstructive sleep apnea (OSA) is also linked to higher risk of CVD and cancer, and to TL. We investigated the association between TL and risk of major adverse cardiac events (MACE) and cancer in OSA patients. We studied 210 individuals undergoing sleep-related studies between 2000 and 2007. Baseline characteristics and follow-up data (available in 164 subjects) were obtained from clinic records. Incidence rates were calculated for the entire group and by OSA status. Hazard ratios were calculated to estimate effects of OSA and TL on risk of MACE and cancer. In total, 32 individuals (20%) developed MACE and/or cancer during 12.7-year follow-up. The OSA group had a higher likelihood of cancer (16.0 vs. 4.9 events per 1000 person-years, P = 0.044) but no clear evidence of an elevated incidence of MACE (10.8 vs. 4.8 events per 1000 person-years, P = 0.293) compared to the non-OSA group. There was no association between TL and MACE- (HR = 1.01, 95% CI 0.78–1.28), or cancer-risk (HR = 1.18, 95% CI 0.96–1.43). Our study warrants further investigation of any modulating effect of OSA on TL and the risk of MACE and cancer.

Background: Abdominal fat elevates while lower-body (LB) fat diminishes cardiovascular risk. However, molecular mechanisms differentiating the two fat depots are not completely understood. MicroRNA (miRNA) are important regulators of gene expression with widespread effects on several proteins. Objective: To explore miRNA differences between the two fat depots using unbiased next-generation sequencing (NGS) approach. Methods: Total RNA isolated from paired subcutaneous (sc) fat tissue obtained from abdomen (ABD) and LB (femoral) region of 12 healthy subjects (7 male; age: 27 ± 5 years; BMI: 23.5 ± 3.2 kg/m 2 ) was used to quantify miRNA expression. Body fat distribution was determined using dual-energy X-ray absorptiometry and abdominal computed tomography scans. RNA was prepped using the NEBNext small RNA library prep kit and sequenced using Illumina HiSeq 2000. Raw sequence data were processed using CAP-miRSeq pipeline. miRNA expression between the two depots was evaluated using EdgeR. Relationship between miRNA and regional fat depots were examined using Spearman’s correlation. Adjusted or unadjusted P value <0.05 was considered significant. Results: Using NGS, 383 ± 55 known miRNA with ≥5 raw reads were detected in the study samples. Principal component analysis including all miRNAs showed no any clear separation between ABD or LB fat tissue. However, 37 miRNAs were found to have altered expression in the two depots. miR-196a-5p (log2FC=1.138, p<0.001), miR-146b-5p ( log2FC=1.388, p<0.001), miR-1287 ( log2FC=1.059, p<0.001), miR-1247-5p (1.002, p<0.001), and miR-346 (log2FC =-1.240, p=0.002) were among the top five differentially expressed miRNA in ABD Vs. LB fat. Interestingly, ABD fat tissue expression of miR196a-5p (rho=-0.58, p=0.047) and miR146b-5p (rho=0.76, p=0.004) correlated with visceral fat while miR146b-5p (rho=0.66, p=0.02) and miR1287 (rho=0.79, p=0.002) correlated with ABD sc fat. Conclusions: Several miRNAs are differentially expressed between ABD and LB fat tissue which may partly contribute to depot specific alterations in adipose tissue function and consequent cardiometabolic risk. Furthermore, the associations between miRNA and regional fat depots suggest a functional role of these miRNA in fat distribution.

Extremes of sleep duration and obstructive sleep apnea (OSA) are both associated with hypertension. We aimed to explore whether sleep duration modifies the relationship between OSA and prevalent hypertension, using both objective and subjective measures of total sleep duration. A total of 7107 OSA patients and 1118 primary snorers were included in the study. Hypertension was defined based either on direct blood pressure measures or on diagnosis by a physician. Objective sleep duration was derived by polysomnography and subjective sleep duration was self-reported. Logistic regression models were used to estimate the associations between objective/subjective sleep duration and hypertension prevalence in OSA and primary snorers. Compared with primary snorers, OSA combined with objective sleep duration of 5 to 6 hours increased the odds of hypertension by 45% (odds ratio, 1.45; 95% confidence interval, 1.14–1.84), whereas OSA combined with objective sleep duration <5 hours further increased the odds of hypertension by 80% (odds ratio, 1.80; 95% confidence interval, 1.33–2.42). These results were independent of major confounding factors frequently associated with OSA or hypertension. In stratified analysis by sleep duration, risk of hypertension in those with extremely short sleep (<5 hours) was not significantly different between OSA and primary snorers, whereas odds were significant for OSA in the other 4 sleep duration strata (5–6, 6–7, 7–8, and >8 hours). No significance was evident using subjective sleep duration. We conclude that objective short sleep duration is associated with hypertension in OSA patients. Extremely short sleep duration in itself may actually be even more detrimental than OSA in terms of hypertension risk.

Background Excessive daytime sleepiness ( EDS ), a common symptom among patients with sleep‐disordered breathing, is closely associated with the development of cardiovascular diseases, but its long‐term prognostic value is not completely understood. The aim of this study was to investigate whether EDS would be an independent prognostic factor after myocardial infarction. Methods and Results We prospectively recruited 112 post–myocardial infarction patients. The Epworth Sleepiness Scale was completed before polysomnography, and EDS was defined as a score ≥11. After exclusion of 8 patients who accepted treatment with continuous positive airway pressure, 104 patients were followed up for 48 months. The primary composite end point was major adverse cardiac events. Patients with EDS had higher rates of major adverse cardiac events (48.4% versus 27.4%, χ 2 =5.27, P =0.022) and reinfarction (29.0% versus 5.5%, χ 2 =13.51, P =0.0002) compared with those without EDS . In the Cox proportional hazards model, patients with EDS had 2.15 times (95% confidence interval, 1.08–4.18; P =0.030) higher crude risk of major adverse cardiac events, with prognostic significance persisting after adjusting for age, diabetes mellitus, depression, left ventricular ejection fraction, apnea–hypopnea index, and nocturnal nadir oxygen saturation (hazard ratio: 2.13, 95% confidence interval, 1.04–4.26, P =0.039). Furthermore, among participants with moderate to severe sleep‐disordered breathing, the presence of EDS was associated with higher risk of major adverse cardiac events than those without EDS , after adjusting for age and nadir oxygen saturation (hazard ratio: 3.17, 95% confidence interval, 1.22–7.76, P =0.019). Conclusions EDS may be an independent prognostic factor of adverse outcome in post–myocardial infarction patients with moderate to severe sleep‐disordered breathing. Evaluation of EDS may shed new light on risk stratification and identify treatment responders for this patient population.

Obstructive sleep apnea (OSA) is associated with cardiometabolic diseases. Telomere shortening is linked to hypertension, diabetes mellitus, and cardiovascular diseases. Because these conditions are highly prevalent in OSA, we hypothesized that telomere length (TL) would be reduced in OSA patients. We identified 106 OSA and 104 non-OSA subjects who underwent polysomnography evaluation. Quantitative PCR was used to measure telomere length in genomic DNA isolated from peripheral blood samples. The association between OSA and TL was determined using unadjusted and adjusted linear models. There was no difference in TL between the OSA and non-OSA (control) group. However, we observed a J-shaped relationship between TL and OSA severity: the longest TL in moderate-to-severe OSA [4,918 ± 230 (SD) bp] and the shortest TL in mild OSA (4,735 ± 145 bp). Mean TL in moderate-to-severe OSA was significantly longer than in the control group after adjustment for age, sex, body mass index, hypertension, dyslipidemia, and depression (β = 96.0, 95% confidence interval: 15.4–176.6, P = 0.020). In conclusion, moderate-to-severe OSA is associated with telomere lengthening. Our findings support the idea that changes in TL are not unidirectional processes, such that telomere shortening occurs with age and disease but may be prolonged in moderate-to-severe OSA. NEW & NOTEWORTHY Here, we show that moderate-to-severe obstructive sleep apnea is associated with longer telomeres, independent of age and cardiovascular risk factors, challenging the hypothesis that telomere shortening is a unidirectional process related to age/disease. A better understanding of the mechanisms underlying telomere dynamics may identify targets for therapeutic intervention in cardiovascular aging/other chronic diseases.