Association between sleep apnea-specific hypoxic burden and severity of coronary artery disease.

PURPOSE: Sleep apnea-specific hypoxic burden (SASHB) is a polysomnographic metric that comprehensively measures the degree of nocturnal desaturation caused by obstructive sleep apnea. This research was conducted to elucidate the relationship between SASHB and coronary artery disease (CAD) severity. METHODS: We carried out a prospective study of hospitalized patients with CAD of unstable angina who were expected to undergo invasive coronary angiography at Beijing Anzhen Hospital from February to September 2023. SASHB values were calculated using a self-programmed C + + program. Multivariable logistic regression analysis was applied to identify the association between SASHB and the prevalence of severe CAD, documented by the Gensini Score, and the SYNTAX (Synergy between Percutaneous Coronary Intervention With Taxus and Cardiac Surgery) Score. RESULTS: This study enrolled 137 patients with a median age of 59 years, 96 (70.1%) of whom were male. A total of 125 (91.2%) patients had coronary stenosis of ≥ 50% in at least one location. Patients with a high SASHB of ≥ 18% min/h had a significantly higher Gensini Score (32.0 vs. 18.5, P = 0.002) and SYNTAX Score (14.0 vs. 7.0, P = 0.002) than those with a low SASHB. After adjusting for multiple covariates, a high SASHB was significantly associated with the prevalence of severe CAD, determined by a Gensini Score ≥ 21 (OR 2.67, P = 0.008) or a SYNTAX Score > 22 (OR 4.03, P = 0.016). CONCLUSION: Our findings revealed a robust and independent association between SASHB and CAD severity in patients with unstable angina, highlighting the potential value of SASHB as a predictor of risk and a target for interventions aimed at preventing cardiovascular diseases. TRIAL REGISTRATION: Chinese Clinical Trial Registry No. ChiCTR2300067991 on February 2, 2023.

Sex-specific associations between daytime sleepiness, chronic diseases and mortality in obstructive sleep apnea.

Objective: Excessive daytime sleepiness (EDS) is common in obstructive sleep apnea (OSA) and has been linked to adverse outcomes, albeit inconsistently. Furthermore, whether the prognostic impact of EDS differs as a function of sex is unclear. We aimed to assess the associations between EDS and chronic diseases and mortality in men and women with OSA. Methods: Newly-diagnosed adult OSA patients who underwent sleep evaluation at Mayo Clinic between November 2009 and April 2017 and completed the Epworth Sleepiness Scale (ESS) for assessment of perceived sleepiness (N = 14,823) were included. Multivariable-adjusted regression models were used to investigate the relationships between sleepiness, with ESS modeled as a binary (ESS > 10) and as a continuous variable, and chronic diseases and all-cause mortality. Results: In cross-sectional analysis, ESS > 10 was independently associated with lower risk of hypertension in male OSA patients (odds ratio [OR], 95% confidence interval [CI]: 0.76, 0.69-0.83) and with higher risk of diabetes mellitus in both OSA men (OR, 1.17, 95% CI 1.05-1.31) and women (OR 1.26, 95% CI 1.10-1.45). Sex-specific curvilinear relations between ESS score and depression and cancer were noted. After a median 6.2 (4.5-8.1) years of follow-up, the hazard ratio for all-cause death in OSA women with ESS > 10 compared to those with ESS ≤ 10 was 1.24 (95% CI 1.05-1.47), after adjusting for demographics, sleep characteristics and comorbidities at baseline. In men, sleepiness was not associated with mortality. Conclusion: The implications of EDS for morbidity and mortality risk in OSA are sex-dependent, with hypersomnolence being independently associated with greater vulnerability to premature death only in female patients. Efforts to mitigate mortality risk and restore daytime vigilance in women with OSA should be prioritized.

Overfeeding-induced weight gain elicits decreases in sex hormone-binding globulin in healthy males-Implications for body fat distribution.

OBJECTIVE: Obesity and upper-body fat elevates cardiometabolic risk. However, mechanisms predisposing to upper-body fat accumulation are not completely understood. In males, low testosterone (T) frequently associates with obesity, and estrogen deficiency may contribute to upper-body adiposity. This study examines the effects of overfeeding-induced weight gain on changes in gonadal hormones in healthy males and its association with regional fat depots. METHODS: Twenty-five males (age: 29.7 ± 6.9 years; BMI: 24.7 ± 3.1 kg/m2 ) were overfed for 8 weeks to gain approximately 5% body weight. Changes in total and regional fat depots were assessed using dual-energy x-ray absorptiometry and abdominal computed tomography scans. Circulating T, estrone (E1), 17-ß estradiol (E2), and sex hormone-binding globulin (SHBG) concentrations were measured at baseline and after weight gain. RESULTS: Overfeeding resulted in 3.8 (3.3, 4.9) kg weight gain with increased total body fat. Weight gain did not alter circulating T (p = 0.82), E1 (p = 0.52), or E2 (p = 0.28). However, SHBG decreased (p = 0.04) along with consequent increases in T/SHBG (p = 0.02) and E2/SHBG (p = 0.03) ratios. Importantly, baseline E2/SHBG ratio was inversely associated with increases in upper-body fat mass (ρ = -0.43, p = 0.03). CONCLUSIONS: Modest weight gain does not alter circulating gonadal hormones in males but may increase bioavailability of T and E2 via decreases in SHBG. The association between baseline E2/SHBG and regional fat mass suggests that higher levels of bioavailable E2 may protect from upper-body fat accumulation during overfeeding-induced modest weight gain in healthy males. Our study suggests a complex relationship between adipose tissue, gonadal hormones, and fat accumulation in males.

Telomere Length and Risk of Major Adverse Cardiac Events and Cancer in Obstructive Sleep Apnea Patients.

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.

Comparative Expression of Renin-Angiotensin Pathway Proteins in Visceral Versus Subcutaneous Fat.

Body fat distribution contributes to obesity-related metabolic and cardiovascular disorders. Visceral fat is more detrimental than subcutaneous fat. However, the mechanisms underlying visceral fat-mediated cardiometabolic dysregulation are not completely understood. Localized increases in expression of the renin angiotensin system (RAS) in adipose tissue (AT) may be implicated. We therefore investigated mRNA and protein expression of RAS components in visceral versus subcutaneous AT using paired samples from individuals undergoing surgery (N = 20, body mass index: 45.6 ± 6.2 kg/m2, and age: 44.6 ± 9.1 years). We also examined RAS-related proteins in AT obtained from individuals on renin angiotensin aldosterone system (RAAS) targeted drugs (N = 10, body mass index: 47.2 ± 9.3 kg/m2, and age: 53.3 ± 10.1 years). Comparison of protein expression between subcutaneous and visceral AT samples showed an increase in renin (p = 0.004) and no change in angiotensinogen (p = 0.987) expression in visceral AT. Among proteins involved in angiotensin peptide generation, angiotensin converting enzyme (p = 0.02) was increased in subcutaneous AT while chymase (p = 0.001) and angiotensin converting enzyme-2 (p = 0.001) were elevated in visceral fat. Furthermore, visceral fat expression of angiotensin II type-2 receptor (p = 0.007) and angiotensin II type-1 receptor (p = 0.031) was higher, and MAS receptor (p < 0.001) was lower. Phosphorylated-p53 (p = 0.147), AT fibrosis (p = 0.138) and average adipocyte size (p = 0.846) were similar in the two depots. Nonetheless, visceral AT showed increased mRNA expression of inflammatory (TNFα, p < 0.001; IL-6, p = 0.001) and oxidative stress markers (NOX2, p = 0.038; NOX4, p < 0.001). Of note, mRNA and protein expression of RAS components did not differ between subjects taking or not taking RAAS related drugs. In summary, several RAS related proteins are differentially expressed in subcutaneous versus visceral AT. This differential expression may not alter AngII but likely increases Ang1-7 generation in visceral fat. These potential differences in active angiotensin peptides and receptor expression in the two depots suggest that localized RAS may not be involved in differences in visceral vs subcutaneous AT function in obese individuals. Our findings do not support a role for localized RAS differences in visceral fat-mediated development of cardiovascular and metabolic pathology.

Periodic limb movements of sleep are associated with an increased prevalence of atrial fibrillation in patients with mild sleep-disordered breathing.

BACKGROUND: Growing evidence indicates that periodic limb movements of sleep (PLMS) may be related to increased risk of developing cardiovascular disease. However, the association of PLMS with atrial fibrillation (AF) is unclear, especially in patients with sleep-disordered breathing (SDB). This study sought to investigate whether PLMS were associated with increased AF prevalence, independent of established risk factors. METHODS: We performed a cross-sectional study of patients who underwent attended polysomnography at Mayo Clinic from 2011 to 2014. The association of PLMS with AF prevalence was estimated by using logistic regression models. RESULTS: 15,414 patients were studied, 76.3% of individuals with SDB defined by apnea-hypopnea index (AHI) ≥5/h, and 15.3% with a diagnosis of AF. In univariate logistic modelling, individuals with periodic limb movement index (PLMI) ≥30/h had higher odds of AF (odds ratio [OR] 1.96, 95% confidence interval [CI]1.79-2.16, p<0.001) when compared to patients with PLMI <15/h. After multivariate adjustment (for age, race, sex, history of smoking, hypertension, diabetes, coronary artery disease, heart failure, cerebrovascular disease, renal disease, iron deficiency anemia, chronic obstructive pulmonary disease, AHI, arousal index), in mild SDB patients, a PLMI ≥30/h or periodic limb movement arousal index (PLMAI) ≥5/h had significantly higher odds of AF than those with PLMI <15/h (OR 1.21, 95% CI 1.00-1.47, p=0.048) or PLMAI <1/h (OR 1.27, 95% CI 1.03-1.56, p=0.024). CONCLUSIONS: Frequent PLMS are independently associated with AF prevalence in patients with mild SDB. Further studies are needed to better understand the relationship with incident AF.