Relationships between cardiometabolic disorders and obstructive sleep apnea: Implications for cardiovascular disease risk

Previous studies have reported the effects of obstructive sleep apnea (OSA) and cardiometabolic disorders on cardiovascular disease (CVD), but associations between cardiometabolic biomarkers and two cardinal features of OSA (chronic intermittent hypoxia and sleep fragmentation) and their interactions on CVD in OSA populations remain unclear. A total of 1727 subjects were included in this observational study. Data on overnight polysomnography parameters, biochemical biomarkers, and anthropometric measurements were collected. Metabolic syndrome (MS), including blood pressure, waist circumference (WC), fasting glucose, triglycerides (TG), and high‐density lipoprotein cholesterol (HDL‐C), was diagnosed based on modified criteria of the Adult Treatment Panel III. WC, mean arterial pressure, TG and low‐density lipoprotein cholesterol (LDL‐C) were independently associated with apnea‐hypopnea index (AHI) after adjustment for confounding factors (β = 0.578, P = 0.000; β = 0.157, P = 0.001; β = 1.003, P = 0.019; and β = 4.067, P = 0.0005, respectively). Furthermore, the interaction analysis revealed joint effects between hypertension, obesity, hyperglycemia, and LDL‐C dyslipidemia and AHI on CVD. The relative excess risks of CVD due to the interactions with OSA were 2.06, 1.02, 0.48, and 1.42, respectively (all P < 0.05). In contrast, we found no independent effect of the microarousal index (MAI) on CVD. However, LDL‐C level and some MS components (WC, TG) were associated with MAI. Our findings indicate that hypoxemia and cardiometabolic disorders in OSA may potentiate their unfavorable effects on CVD. Sleep fragmentation may indirectly predispose patients with OSA to an increased risk of CVD. Thus, cardiometabolic disorders and OSA synergistically influence cardiometabolic risk patterns.     

Association Between Adiposity and Left Ventricular Mass in Children With Hypertension

Left ventricular hypertrophy (LVH) is prevalent among hypertensive children; however, blood pressure (BP) does not predict its presence. The authors conducted a 1‐year prospective cohort study to examine the hypothesis that obesity‐related risk factors are associated with left ventricular mass index (LVMI) in hypertensive children, and the association between adiposity and LVMI is mediated by BP‐dependent and ‐independent pathways. A total of 49 hypertensive children were enrolled: 51% were overweight/obese and 41% had LVH at baseline. Children overweight/obese at baseline and follow‐up had a greater LVMI increase than those of healthy weight at each visit: mean change of 6.4 g/m^2.7 vs 0.95 g/m^2.7. Baseline body mass index z score was independently associated with LVMI change (β=4.08, 1.54–6.61; P=.002). Only pulse pressure and serum aldosterone partially mediated this relationship. Hypertensive youth manifest multiple cardiovascular disease risk factors that worsen over time despite treatment. Of these, adiposity is most associated with LVH and increasing LVMI.     

The interaction between hypertension and obstructive sleep apnea on subjective daytime sleepiness

Hypertension is one of the most common chronic cardiovascular diseases in adults while obstructive sleep apnea (OSA) is the most common type of sleep apnea. It was recently reported that the mean Epworth Sleepiness Scale (ESS) score, measuring subjective daytime sleepiness, was significantly higher in non‐hypertensive subjects than the hypertensive counterparts with moderate to severe obstructive sleep apnea. In the current study, the authors investigated the interaction between hypertension and OSA on daytime sleepiness among 280 subjects recruited from a sleep study. OSA was evaluated with the Apnea‐Hypopnea Index (AHI), and daytime sleepiness was measured with the ESS. Significantly higher mean ESS scores were found for subjects without than those with hypertension (11.3 vs 9.4, P = 0.003) but only a marginally significant difference was discerned for the ESS scores between subjects with AHI ≥15/h and AHI <15/h (P = 0.075). A significant interaction between hypertension and OSA status on daytime sleepiness was observed from the analysis of variance (P = 0.02). The adjusted mean ESS score for the group of normotensive subjects with moderate to severe OSA (13.11) was significantly higher than the other three groups, namely, normotensive subjects with mild OSA (9.35), hypertensive subjects with mild OSA (9.70), and hypertensive subjects with moderate to severe OSA to (9.43). In conclusion, subjective daytime sleepiness of normotensive subjects with moderate to severe OSA was significantly more severe than other subjects.     

Association of coronary artery calcification with obstructive sleep apnea and obesity in middle-aged men

Background and aimsObstructive sleep apnea (OSA) and obesity are closely associated, and both have been reported to increase the risk of coronary heart disease. Although obesity is known to be associated with coronary artery calcification (CAC), there is limited information on whether OSA is associated with CAC independent of obesity.Methods and resultsA cross-sectional study examined the association between OSA and CAC among 258 healthy men, ages 40–49 years old, randomly selected from a population-based cohort. All individuals underwent overnight polysomnography and electron-beam computed tomography to measure their apnea–hypopnea index (AHI) and degree of CAC. A logistic regression model including potential cardiovascular risk factors excluding body mass index (BMI) showed that the presence of CAC was significantly greater in the fourth quartile versus the first quartile of AHI severity (odds ratio [OR] 2.21, 95% confidence interval [CI] 1.01–4.86). A multivariate linear regression model excluding BMI also showed that AHI was significantly associated with CAC (P = 0.004). However, this association was no longer significant after adjusting for BMI.ConclusionsIn our cross-sectional study, even though both OSA and obesity were positively associated with the presence and extent of CAC, only obesity remained a significant independent contributor after an adjustment for potential cardiovascular risk factors, irrespective of OSA.     

Association of mood disorders with cardiovascular disease risk factors in overweight and obese youth with elevated blood pressure

The American Heart Association defines mood disorders (MDO) as a tier‐II cardiovascular disease risk factor in children. Cross‐sectional analysis of overweight/obese children referred to an obesity hypertension clinic revealed 37% had a MDO (defined by clinical diagnosis or Patient Health Questionnaire‐9/‐A score ≥10), 55% had confirmed hypertension, and 75% left ventricular hypertrophy (LVH). Children with MDOs were older, had greater measures of adiposity, and had a greater prevalence of hypertension (78%) than those without MDOs (42%; P = .04). Hypertensive children were 2.8 times more likely to have a MDO than those without (52% vs 18%; P = .02). Multivariable logistic regression revealed a statistically significant independent association of MDOs with hypertension (Odds Ratio [OR] 6.3, P = .048), but not LVH (LVMI ≥ 51 g/m^2.7; OR 1.13, P = .88). Overall, the prevalence of MDOs in this group of overweight/obese children with elevated blood pressure was well above national averages, suggesting that at‐risk youth, particularly those with confirmed hypertension, should be regularly screened for MDOs.     

Alterations of cholesterol synthesis and absorption in obstructive sleep apnea: Influence of obesity and disease severity

Background and aimsObstructive sleep apnea (OSA) is closely linked to obesity and related adverse metabolic changes, including dyslipidemia. However, it is not clear whether OSA is an independent contributing factor to dyslipidemia, or the observed association is a reflection of a concomitant presence of obesity. Additionally, dyslipidemia is usually evaluated through measurement of parameters of routine lipid status, while more precise evaluation of lipid homeostasis is rarely performed in OSA. In this study, we analyzed markers of cholesterol synthesis and absorption in patients with OSA with respect to the presence of obesity and the disease severity.Methods and resultsThis study enrolled 116 OSA patients. Concentrations of non-cholesterol sterols (NCS), measured by LC-MS/MS, were used as markers of cholesterol synthesis and absorption. Apnea-hypopnea index (AHI) and oxygen saturation (SaO₂) were utilized as markers of OSA severity. Serum lipid status parameters were determined by routine enzymatic methods. Markers of cholesterol synthesis were increased (P = 0.005), whilst markers of cholesterol absorption decreased (P = 0.001) in obese OSA patients. Cholesterol synthesis/absorption ratio was elevated in obese subjects (P < 0.001). Concentration of cholesterol synthesis marker lathosterol was significantly higher in subjects with severe OSA (P = 0.014) and we observed a trend of decreased cholesterol absorption in these patients. AHI was revealed as an independent determinant of lathosterol concentration (P = 0.022).ConclusionsOur results suggest that the presence of obesity and severe forms of OSA is characterized by elevated endogenous cholesterol synthesis. AHI was singled out as an independent determinant of the serum level of cholesterol synthesis marker lathosterol.     

Association of obstructive sleep apnea with endothelial function and heart remodeling in hypertension: A cross-sectional study

BackgroundThis study aims to analyze the association of obstructive sleep apnea (OSA) with endothelial function and heart structure in patients with hypertension and lay a clinical foundation for preventing and treating endothelial dysfunction and heart remodeling in patients with hypertension.MethodsA cross-sectional study design was adopted in this study. From April 2020 to April 2021, 143 patients with hypertension were included and classified into two groups according to the severity of OSA: 81 patients with hypertension without OSA [apnea-hypopnea index (AHI) < 5 events/hour] serving as the control group; 62 patients with hypertension with moderate-severe OSA (AHI ≥ 15 events/hour) serving as the OSA group. The endothelial function and heart structure were assessed by flow‐mediated vasodilation (FMD) and transthoracic echocardiography. Logistic regression analyses were conducted to identify factors associated with endothelial dysfunction and heart remodeling.ResultsCompared with the control group, patients with OSA had significantly greater interventricular septal thickness (IVST) and left ventricular posterior wall thickness (LVPWT) (P < 0.05), and FMD exhibited a significant decrease (P < 0.05). Logistic regression analyses demonstrated that gender and AHI were associated with FMD (P < 0.05), and FMD was associated with LVMI (P < 0.05).ConclusionsOSA was associated with endothelial dysfunction and heart remodeling in patients with hypertension. Endothelial dysfunction may be crucial for the development of heart remodeling in patients with hypertension with OSA.     

Gender differences in clinical and polysomnographic features of obstructive sleep apnea: a clinical study of 2827 patients

Purpose

Obstructive sleep apnea (OSA) is underdiagnosed in females due to different clinical presentation. We aimed to determine the effect of gender on clinical and polysomnographic features and identify predictors of OSA in women.

Methods

Differences in demographic, clinical, and polysomnographic parameters between 2052 male and 775 female OSA patients were compared.

Results

In female OSA patients, age (56.1 ± 9.7 vs. 50.4 ± 11.6 years, p < 0.0001) and body mass index (36.3 ± 8.6 vs. 31.8 ± 5.9 kg/m², p < 0.0001) were increased, whereas men had higher waist-to-hip ratio and neck circumference (p < 0.0001). Hypertension, diabetes mellitus, thyroid disease, and asthma were more common in females (p < 0.0001). Men reported more witnessed apnea (p < 0.0001), but nocturnal choking, morning headache, fatigue, insomnia symptoms, impaired memory, mood disturbance, reflux, nocturia, and enuresis were more frequent in women (p < 0.0001).

The indicators of OSA severity including apnea-hypopnea index (AHI) (p < 0.0001) and oxygen desaturation index (p = 0.007) were lower in women. REM AHI (p < 0.0001) was higher, and supine AHI (p < 0.0001) was lower in females. Besides, women had decreased total sleep time (p = 0.028) and sleep efficiency (p = 0.003) and increased sleep latency (p < 0.0001). In multivariate logistic regression analysis, increased REM AHI, N3 sleep, obesity, age, morning headache, and lower supine AHI were independently associated with female gender.

Conclusions

These data suggest that frequency and severity of sleep apnea is lower in female OSA patients, and they are presenting with female-specific symptoms and increased medical comorbidities. Therefore, female-specific questionnaires should be developed and used for preventing underdiagnosis of OSA.

     

A Hypertensive Response to Exercise Is Prominent in Patients With Obstructive Sleep Apnea and Hypertension: A Controlled Study

Blood pressure (BP) behavior during exercise is not clear in hypertensive patients with obstructive sleep apnea (OSA). The authors studied 57 men with newly diagnosed essential hypertension and untreated OSA (apnea‐hypopnea index [AHI] ≥5) but without daytime sleepiness (Epworth Sleepiness Scale score ≤10), and an equal number of hypertensive controls without OSA matched for age, body mass index, and office systolic BP. All patients underwent ambulatory BP measurements, transthoracic echocardiography, and exercise treadmill testing according to the Bruce protocol. A hypertensive response to exercise (HRE) was defined as peak systolic BP ≥210 mm Hg. Patients with OSA and control patients had similar ambulatory and resting BP, ejection fraction, and left ventricular mass. Peak systolic BP was significantly higher in patients with OSA (197.6±25.6 mm Hg vs 187.8±23.6 mm Hg; P=.03), while peak diastolic BP and heart rate did not differ between groups. Furthermore, an HRE was more prevalent in patients with OSA (44% vs 19%; P=.009). Multiple logistic regression revealed that an HRE is independently predicted by both the logAHI and minimum oxygen saturation during sleep (odds ratio, 3.94; confidence interval, 1.69–9.18; P=.001 and odds ratio, 0.94; confidence interval, 0.89–0.99; P=.02, respectively). Exaggerated BP response is more prevalent in nonsleepy hypertensives with OSA compared with their nonapneic counterparts. This finding may have distinct diagnostic and prognostic implications.     

Influence of high risk of obstructive sleep apnea on adherence to antihypertensive treatment in outpatients

Obstructive sleep apnea (OSA) is a common cause of high blood pressure (BP). Many patients, however, have uncontrolled BP because of nonadherence to antihypertensive medication. The possibility that OSA influences adherence has not been investigated to date. The authors sought to explore the possible association between high risk of OSA and nonadherence. This study was carried out in a hypertension outpatient clinic. Adherence to medication, high risk of OSA, and sleepiness were evaluated in a cross‐sectional study. These variables were identified using the eight‐item Morisky, STOP‐Bang, and Epworth scales, respectively. A total of 416 patients with hypertension were enrolled (32% male, aged 65±11 years). Nonadherence was identified in 71 (17%) individuals. The prevalence of high risk of OSA was 323 (78%) and of somnolence was 136 (33%). High risk of OSA was associated with nonadherence, showing a prevalence ratio (PR) of 2.6 (95% confidence interval [CI], 1.3–5.6) and retained significance after adjustment for sleepiness (PR, 2.3; 95% CI, 1.1–4.9 [P=.011]). Sleepiness was also associated with nonadherence (PR, 1.7; 95% CI, 1.1–2.6 [P=.003]). High risk of OSA and sleepiness are associated with nonadherence. These conditions, if treated, may allow for achieving better outcomes and improvement of adherence to medication.     

Uric acid as a potential mediator of cardiovascular morbidity in obstructive sleep apnea syndrome

Background and aimsObstructive sleep apnea (OSA) is now considered as an independent risk factor for cardiovascular (CV) disease. Although uric acid is increasingly being implicated in CV morbidity and mortality, no study attempted to determine independent role of uric acid in CV morbidity of OSA patients. We aimed to assess the role of serum uric acid as a potential mechanism of CV morbidity in a nonselected cohort of OSA patients.MethodsThis was a cohort study in which patients who had undergone a formal sleep study for diagnosis of OSA were recruited. Included patients were grouped according to apnea–hypopnea index (AHI) as mild, moderate and severe OSA. Patients with AHI < 5 served as control group. Patients were interrogated as to cardiovascular morbid conditions which included prior history and an established diagnosis of coronary artery disease, cerebrovascular accident, congestive heart failure due to coronary artery disease and arrhythmias.Results436 OSA patients included (72 controls, 97 with mild, 75 with moderate, and 192 with severe OSA). The severe group also had higher serum uric acid level compared with the control and other OSA groups. Linear regression showed that the Ln uric acid was positively associated with Ln AHI score. In unadjusted logistic regression, severe OSA was associated with higher odds of a cardiovascular event, OR = 2.81 (1.307–6.041), p = 0.0081 while the other categories of sleep apnea were not. However, severe OSA was no longer significant after adjusting for age, gender, diabetes mellitus status, hypertension status, BMI, and smoking, OR = 1.882 (0.826–4.287), p = 0.1322. Uric acid was significantly higher in those who had a cardiovascular event even in the mild, moderate and severe OSA groups.ConclusionHyperuricemia is strongly associated with cardiovascular disease in OSA patients. This strong relationship persists even after controlling for well-known traditional risk factors for cardiovascular disease.     

Interrelationships among common predictors of cardiovascular diseases in patients of OSA: A large-scale observational study

Background and aimsThe apolipoprotein B/apolipoprotein A-I (ApoB/ApoA-I) and insulin resistance has been recognized as common cardiovascular diseases (CVD) risk factors. However, whether they were biomarkers for 10-year CVD risk in obstructive sleep apnea (OSA) had been rarely studied. Besides, interrelationships between the ApoB/ApoA-I, insulin resistance and OSA remain unclear.Methods and resultsA total of 4010 subjects were finally included. Anthropometric, fasting biochemical, and polysomnographic parameters were collected. 10-year Framingham CVD risk score (FRS) was calculated for each subjects. The relationships between insulin resistance, OSA risk and the ApoB/ApoA-I was evaluated through logistic regressions analysis, restricted cubic spline (RCS) analysis and mediation analysis. ApoB/ApoA-I, HOMA-IR and AHI were all risk factors for high10-year CVD risk as assessed by FRS (odds ratios (OR) = 5.365, 1.094, 1.010, respectively, all P < 0.001)). The fully adjusted OR (95% confidence intervals) for both OSA [1 (reference), 1.308 (1.027–1.665), 1.517 (1.178–1.953), and 1.803 (1.371–2.372)] and insulin resistance [1 (reference), 1.457 (1.173–1.711), 1.701 (1.369–2.113), 2.051(1.645–2.558)] increased from the first to the fourth quartiles of the ApoB/ApoA-I. The RCS mapped a nonlinear dose–effect relationship between the ApoB/ApoA-I and risk of insulin resistance and OSA. Mediation analyses showed HOMA-IR explain 9.7%, 4.7% and 10.8% of the association between apnea-hypopnea index, oxygen desaturation index, micro-arousal index and ApoB/ApoA-I, respectively.ConclusionsOur study revealed that ApoB/ApoA-I, insulin resistance and OSA were risk factors for CVD. Insulin resistance may serve as a potential mediator in OSA-related lipoprotein disorders and further increase CVD risk.     

Mandibular advancement splint titration in obstructive sleep apnoea

Introduction  Mandibular advancement splints (MAS) allowing self-adjustment may be better tolerated, but the optimum titration protocol needs systematic study. Aim  The aims of the study are to assess the effectiveness of a titratable MAS device in consecutive patients with body mass index (BMI) < 35 kg/m² and obstructive sleep apnoea [OSA, apnoea–hypopnoea index (AHI) 10–40/h] and compare two methods of adjustment [self-adjustment or adjustment after polysomnographic (PSG) feedback]. Materials and methods  Twenty-eight patients (24 M, mean age 49 years, mean BMI 27.6 kg/m²) with symptomatic (Epworth Sleepiness score > 8/24, snoring, choking or poor sleep quality) OSA (mean AHI 25.7/h, range 10–46/h) had a MAS set at 70% maximal protrusion and were randomised to subjective self-adjustment for 6 weeks (n = 16) or objective adjustment (n = 12; fixed position for 3 weeks, then PSG based feedback at 3 weeks with self-adjustment instructions). Primary outcome variable (AHI) and OSA symptoms were compared by t tests and chi-squared tests at baseline and after 6 weeks. Resolution of apnoea was defined as AHI < 5/h; improvement was defined as AHI decreased by >50% but still >5/h. Results  The groups had similar baseline demographics, OSA severity and occlusal type. MAS therapy improved or resolved OSA in 20 out of 28 (71%) and was reportedly used nightly by 91% of the objective group and 63% of the subjective group (p = 0.04). MAS were used all night by 75% of the objective group and 69% of the subjective group (p > 0.05). MAS adjustment following PSG feedback did not lower AHI further from 3 weeks (baseline 26.5 ± 12.0/h, 3 weeks 15.3 ± 13.5/h p = 0.01, 6 weeks 11.7 ± 10.0/h, p = 0.11). The overall improvement was similar to that achieved with subjective adjustment (baseline AHI 25.4 ± 7.4/h, 6 weeks 14.3 ± 10.7/h, p = 0.0002). Symptomatic benefit was reported by both groups. Conclusion  In selected patients, titratable MAS improved or resolved OSA in the majority of patients and was well tolerated. PSG-based feedback at 3 weeks allowed objective confirmation of efficacy and increased device use but did not result in greater improvement in AHI or symptoms. Neither titration method was significantly superior for us to provide firm endorsement. However, we recommend a follow-up sleep study to confirm MAS efficacy.     

Association of obstructive sleep apnea with arterial stiffness and nondipping blood pressure in patients with hypertension

Whether sex influences the association of obstructive sleep apnea (OSA) with markers of cardiovascular risk in patients with hypertension is unknown. In this study, 95 hypertensive participants underwent carotid‐femoral pulse wave velocity, 24‐hour ambulatory blood pressure monitoring, echocardiogram, and polysomnography after a 30‐day standardized treatment with hydrochlorothiazide plus enalapril or losartan. OSA was present in 52 patients. Compared with non‐OSA patients, pulse wave velocity values were higher in the OSA group (men: 11.1±2.2 vs 12.7±2.4 m/s, P=.04; women: 11.8±2.4 vs 13.2±2.2 m/s, P=.03). The proportion of diastolic dysfunction was significant in men and women with OSA. Compared with non‐OSA patients, nondipping systolic blood pressure in OSA was higher in men (14.3% vs 46.4%) and in women (41.4% vs 65.2%). OSA was independently associated with pulse wave velocity (β=1.050; P=.025) and nondipping systolic blood pressure (odds ratio, 3.03; 95% confidence interval, 1.08–8.55; P=.035) in the regression analysis. In conclusion, OSA is independently associated with arterial stiffness and nondipping blood pressure in patients with hypertension regardless of sex.     

Blood pressure and glucose control and the prevalence of albuminuria and left ventricular hypertrophy in patients with hypertension and diabetes

We investigated association between blood pressure and glucose control and the prevalence of albuminuria and left ventricular hypertrophy (LVH) in patients with hypertension and diabetes. Our study participants were treated patients with both diseases, enrolled in a China nationwide registry. The 773 patients were classified into four groups according to the control status of hypertension (systolic/diastolic blood pressure [BP] ≤140/90 mm Hg) and diabetes (HbA1c <7.0%): both uncontrolled (n = 208), only diabetes (n = 175) or hypertension controlled (n = 172), and both controlled (n = 218). Albuminuria was defined as a urinary albumin‐to‐creatinine ratio of ≥30 mg/g. LVH was assessed by the electrocardiogram Cornell product method. Antihypertensive therapy was not different between the four groups (P ≥ .48). The use of insulin alone or insulin plus oral antidiabetic agents was significantly higher than those with both diseases controlled (P ≤ .02). Patients with controlled hypertension and diabetes had a significantly (P < .0001) lower prevalence of albuminuria (odds ratio 0.22, 95% confidence interval 0.11‐0.43) than those with both diseases uncontrolled. Intensive BP control to <130/80 mm Hg was associated with lower risks of albuminuria in all patients (P = .001) and patients with HbA1c <7.0% (P = .048). Intensive glycemic control to HbA1c <6.5% was also associated with a significantly lower risk of albuminuria in all patients (P = .01), but not those with controlled BP (P = .43). Similar trends were observed for LVH, but statistical significance was not achieved on either intensive control condition (P ≥ .07). In patients with hypertension and diabetes, blood pressure and glucose control were associated with a lower prevalence of albuminuria and LVH, especially when achieving a more stringent target.     

Hemostatic implications of endothelial cell apoptosis in obstructive sleep apnea

Patients with obstructive sleep apnea (OSA) are at increased risk of atherothrombosis independent of the Framingham risk factors. Studies on hemostasis factors in OSA are scarce and inconsistent. We sought to understand the variation in atherothrombotic propensity as a function of apoptotic circulating endothelial cells (CECs) in OSA by investigating the relationship between CEC apoptosis and plasma levels of hemostatic factors tissue factor (TF) and von Willebrand Factor (vWF) in apneic subjects. Apoptotic CECs were detected by flow cytometry in 35 male subjects free of cardiovascular diseases (AHI range 8–43) and 12 healthy male controls (AHI range 2–5) before and after 8 weeks of nasal continuous positive airway pressure (nCPAP). Quantitative determination of TF and vWF was performed using an enzyme-linked immunosorbent assay (ELISA) kit. The mean levels of TF (66.78 ± 41.59 pg/ml) and vWF (189.70 ± 69.24 IU/dl) were significantly higher in OSA patients compared with those in healthy subjects (42.83 ± 14.18 pg/ml; and 124.48 ± 31.43 IU/dl). Apoptotic CECs were elevated in patients with OSA and correlated strongly with TF and vWF levels (p = 0.02 and p < 0.001; respectively). There were no correlations between TF, vWF and apnea hypopnea index, or arousal index. Only the percentage of time spent <90% oxygen saturation was inversely associated with TF (r = 0.38; p = 0.02). Following nCPAP therapy, there was significant decrease in TF levels that correlated with decrease in apoptotic CECs. In patients with OSA, increased prothrombotic factors are strongly determined by apoptotic CECs. Treatment with nCPAP may alleviate the coagulation propensity.     

Therapeutic effect of laparoscopic sleeve gastrectomy on obstructive sleep apnea and relationship of type 2 diabetes in Japanese patients with severe obesity

Aims/IntroductionObstructive sleep apnea (OSA) is among the most important obesity‐related diseases, and offers the potential for accelerated the early onset and progression of type 2 diabetes. The aim of the present study was to clarify the therapeutic effect of laparoscopic sleeve gastrectomy on OSA in severely obese Japanese patients, and to find correlations between OSA improvements and β‐cell function (BCF).Materials and MethodsBetween September 2013 and December 2019, 61 patients who underwent laparoscopic sleeve gastrectomy were enrolled. The apnea–hypopnea index (AHI) was used to diagnose OSA. The tongue area, uvula area and other parameters were measured using cone‐beam computed tomography. Regarding BCF parameters, the homeostasis model assessment of β‐cell function, insulinogenic, Matsuda and disposition indexes were used to evaluate the improvement in BCF. Improvement of OSA was defined as AHI <15.ResultsThe improvement rate of OSA was 51.8% (29/56). The change in AHI was significantly correlated with the excess weight loss percentage (ρ = 0.501), changes in tongue area (ρ = 0.350) and uvula area (ρ = 0.341). Multivariate analysis showed that preoperative AHI and postoperative hemoglobin A1c were independent prognostic factors of OSA non‐improvement. The homeostasis model assessment of β‐cell function (P < 0.001), the insulinogenic index (P < 0.001) and the disposition index (P = 0.019) of patients with AHI of <15 were significantly higher than those in patients with AHI of ≥15.ConclusionsLaparoscopic sleeve gastrectomy is a promising procedure for severely obese patients with OSA. BCF recovery was found to be significantly higher in patients with OSA improvement.     

Association between sleep apnea severity and blood coagulability: treatment effects of nasal continuous positive airway pressure

A prothrombotic state may contribute to the elevated cardiovascular risk in patients with obstructive sleep apnea (OSA). We investigated the relationship between apnea severity and hemostasis factors and effect of continuous positive airway pressure (CPAP) treatment on hemostatic activity. We performed full overnight polysomnography in 44 OSA patients (mean age 47±10 years), yielding apnea–hypopnea index (AHI) and mean nighttime oxyhemoglobin saturation (SpO₂) as indices of apnea severity. For treatment, subjects were double-blind randomized to 2 weeks of either therapeutic CPAP (n=18), 3 l/min supplemental nocturnal oxygen (n=16) or placebo–CPAP (<1 cm H₂O) (n=10). Levels of von Willebrand factor antigen (VWF:Ag), soluble tissue factor (sTF), D-dimer, and plasminogen activator inhibitor (PAI)-1 antigen were measured in plasma pre- and posttreatment. Before treatment, PAI-1 was significantly correlated with AHI (r=0.47, p=0.001) and mean nighttime SpO₂ (r=−0.32, p=0.035), but these OSA measures were not significantly related with VWF:Ag, sTF, and D-dimer. AHI was a significant predictor of PAI-1 (R ²=0.219, standardized β=0.47, p=0.001), independent of mean nighttime SpO2, body mass index (BMI), and age. A weak time-by-treatment interaction for PAI-1 was observed (p=0.041), even after adjusting for age, BMI, pre-treatment AHI, and mean SpO₂ (p=0.046). Post hoc analyses suggested that only CPAP treatment was associated with a decrease in PAI-1 (p=0.039); there were no changes in VWF:Ag, sTF, and D-dimer associated with treatment with placebo–CPAP or with nocturnal oxygen. Apnea severity may be associated with impairment in the fibrinolytic capacity. To the extent that our sample size was limited, the observation that CPAP treatment led to a decrease in PAI-1 in OSA must be regarded as tentative.     

Maternal adiposity as an independent risk factor for pre‐eclampsia: a meta‐analysis of prospective cohort studies

Studies investigating the association between maternal adiposity and risk of pre‐eclampsia showed contradictory results. Therefore, we performed a meta‐analysis of prospective cohort studies to estimate the effect of maternal adiposity on pre‐eclampsia. We reviewed 1,286 abstracts and finally included 29 prospective cohort studies with 1,980,761 participants and 67,075 pre‐eclampsia events. We pooled data with a random‐effects model, and obtained risk estimates for five predetermined bodyweight groups: low, normal‐weight (reference), overweight, obese and severely obese. In the cohort studies that unadjusted for pre‐eclampsia risk factors, the pooled unadjusted relative risks (RR) with 95% confidence intervals (95%CI) for pre‐eclampsia of overweight, obese and severely obese women were 1.58 (95% CI 1.44–1.72, P < 0.001), 2.68 (95% CI 2.39–3.01, P < 0.001) and 3.12 (95% CI 2.24–4.36, P < 0.001), respectively. In those cohorts that adjusted for pre‐eclampsia risk factors, the pooled unadjusted RRs for pre‐eclampsia of overweight, obese and severely obese women were 1.70 (95% CI 1.60–1.81, P < 0.001), 2.93 (95% CI 2.58–3.33, P < 0.001) and 4.14 (95% CI 3.61–4.75, P < 0.001), respectively. Sensitivity analysis showed maternal adiposity was associated with increased risk of pre‐eclampsia in both nulliparous and multiparas women. In conclusion, overweight or obese pregnant women have a substantially increased risk of pre‐eclampsia, and maternal adiposity is an independent risk factor of pre‐eclampsia.     

Prevalence of sleep apnea and cardiovascular risk factors in patients with hypertension in a day hospital model

Introduction: To identify patients at risk for obstructive sleep apnea (OSA) syndrome at a specialized hypertension center, we administered questionnaires and used respiratory polygraphy (RP). Results: We studied 168 patients (64.8% men and 35.2% women). Patients’ body mass index (BMI) was 34.7 ± 6.79 and Epworth Sleepiness Scale (ESS) scores were 8.01 for male and 8.92 for women (p = 0.69). RP recordings revealed AHI (Apnea-Hypopnea Index) of 18.03 ± 15.7, an ODI (Oxygen Desaturation Index) of 18.6 ± 15.2, and a time oxygen saturation <90% (%) of 20.8 ± 24.3. Around 44% of patients had an AHI of >15 events/h, and continuous positive airway pressure (CPAP) was recommended to 69 patients (41.07%). Pulse wave velocity (PWV) showed high values in AHI > 15/h (p = 0.050), and carotid intima-media thickness (IMT) did not correlate with AHI > 15; right IMT: 0.83 ± 1.3 versus 0.78 ± 0.13 mm (p = 0.41) and 0.82 ± 0.16 versus 0.78 ± 0.19 mm (p = 0.40). However, we find correlation with carotid plaque (p = 0.046). The ACC/AHA calculator revealed a gradual increase in the risk of cardiovascular events: 8.7% with AHI < 5/h, and 30.3% in severe OSA. Conclusions: In hypertension (HT) patients, RP revealed a high prevalence of OSA associated with carotid artery disease, high PWV, and increased cardiovascular risk.