Kihiro Asano

Concurrent Presence of Metabolic Syndrome in Obstructive Sleep Apnea Syndrome Exacerbates the Cardiovascular Risk: A Sleep Clinic Cohort Study

This cross-sectional study was conducted to examine whether the obstructive sleep apnea syndrome (OSAS) is associated with elevation of the pulse wave velocity (PWV) and increase in the plasma levels of C-reactive protein (CRP), both of which are known markers of cardiovascular risk, and also to determine if the concurrent presence of the metabolic syndrome might exacerbate this elevation in the levels of these cardiovascular risk markers in subjects with OSAS. With these objectives, the PWV and serum CRP were measured in 184 subjects attending a sleep clinic. It was found that the PWV and CRP were higher in the subjects with OSAS (n=94) than in those without OSAS (n=90). Furthermore, among the subjects with OSAS, the PWV and CRP were higher in those with the concurrent presence of the metabolic syndrome (n= 41; PWV=1,562±19 cm/s; CRP=1.8±0.2 mg/l) than in those without metabolic syndrome (n=53; PWV=1,432±21 cm/s; CRP=1.2±0.1 mg/l) (p<0.05). A general linear model analysis demonstrated that OSAS and metabolic syndrome were independently associated with elevated PWV and increase of the plasma levels of CRP. OSAS appears to be associated with increased cardiovascular risk, as reflected by both elevated PWV and increase of the plasma CRP. The concurrent presence of metabolic syndrome may exacerbate this increase in cardiovascular risk in subjects with OSAS. Therefore, the concurrent presence of metabolic syndrome may constitute an additive cardiovascular risk factor in subjects with OSAS.

Severe obstructive sleep apnea impairs left ventricular diastolic function in non-obese men

OBJECTIVE To evaluate whether obstructive sleep apnea (OSA) contributes directly to left ventricular (LV) diastolic dysfunction. METHODS Seventy-four non-obese male OSA (apnea hypopnea index (AHI)⩾5/h) patients without cardiac disease, hypertension or diabetes were enrolled. Echocardiography, pulse wave velocity (PWV) measurements and laboratory testing were performed in all patients. LV diastolic function was assessed by the transmitral flow velocity (E/A ratio), and mitral annular velocity (Ea) was derived from tissue Doppler imaging (TDI). RESULTS The E/A ratio and Ea in the severe OSA group (AHI⩾30/h) was significantly lower than those in the mild to moderate OSA group (5⩽AHI<30/h) (P<0.0001), whereas the S/D ratio, an indicator of pulmonary vein flow velocity, in the severe OSA group was significantly higher than that in the mild to moderate OSA group (P=0.04). AHI exhibited a statistically significant inverse correlation with the E/A ratio (r=-0.47, P=0.0001), but not with relative wall thickness (RWT), LV mass index (LVMI) or PWV. RWT, LVMI and PWV exhibited an inverse correlation with the E/A ratio. Multivariate linear regression analysis revealed that severe OSA was independently associated with the E/A ratio even after adjusting for age, insulin resistance, blood pressure, LV geometry, and PWV (β=-0.23, P=0.001). CONCLUSIONS These results indicate that severe OSA itself may contribute directly to LV diastolic dysfunction irrespective of LV geometry, arterial stiffness, obesity and its associated cardiovascular risk factors.

Severe obstructive sleep apnea increases cystatin C in clinically latent renal dysfunction

BACKGROUND Obstructive sleep apnea (OSA) increases the risk of cardiovascular disease (CVD) and has been reported to be associated with chronic kidney disease (CKD). Recent studies have demonstrated that cystatin C is a prognostic biomarker of the risk of death and CVD even in patients without established CKD. METHODS In a cross-sectional study, we enrolled 267 consecutive OSA patients without CKD who had an apnea-hypopnea index (AHI) ≥ 5 events per hour in overnight polysomnography. CKD was defined as an estimated glomerular filtration rate (eGFR) < 60 mL/min/1.73 m(2) according to the modification of diet in renal disease (MDRD) equation (modified for Japanese). Serum cystatin C levels were measured in all patients. RESULTS Cystatin C was significantly correlated with age (r = 0.37), body mass index (BMI) (r = 0.12), AHI (r = 0.17), C-reactive protein (CRP) (r = 0.12), and Brachial-ankle pulse wave velocity (r = 0.18). Logistic regression analysis demonstrated that severe OSA defined by an AHI ≥ 30 events per hour was an independent variable for the highest quartiles of serum cystatin C levels (≥0.88 mg/L) (OR: 2.04, 95% CI: 1.04-4.01, P = 0.04) even after adjustment for age, BMI ≥ 25, hypertension, and diabetes mellitus. CONCLUSIONS This study indicates that severe OSA independently increases serum cystatin C levels in patients without CKD. Cystatin C is considered to be a biomarker that reflects both clinically latent renal dysfunction and cardiovascular risk that are influenced by OSA.

New Index for Analysis of Polysomnography, ‘Integrated Area of Desaturation’, Is Associated with High Cardiovascular Risk in Patients with Mild to Moderate Obstructive Sleep Apnea

Background: Although obstructive sleep apnea (OSA) severity is evaluated by the apnea-hypopnea index (AHI), the value of AHI in evaluating cardiovascular risks, especially in mild to moderate OSA, is unclear. Objectives: The purpose of this study is to evaluate the validity of a new index, the integrated area of desaturation (IAD), to detect the incidence of cardiovascular events (CVEs) in such patients. Methods: We enrolled 230 consecutive patients with mild to moderate OSA and 354 with severe OSA diagnosed by polysomnography, of whom 53 and 112, respectively, had CVEs. The IAD was calculated by dividing the area of desaturation by total sleep time in polysomnography. C-reactive protein (CRP) was also measured for all patients. Results: In the mild to moderate OSA patients, the mean IAD of the CVEs group was significantly higher than that of the non-CVE group (94.4 ± 82.7 vs. 62.3 ± 50.8, p = 0.001), whereas mean AHI and 3% oxygen desaturation index were similar in both groups. Multivariate analysis demonstrated that the IAD was an independent variable for CVEs (OR 1.006, 95% confidence interval 1.001–1.012, p = 0.031). Moreover, the IAD level of the high CRP group was significantly higher than that of the low CRP group (92.9 ± 84.8 vs. 63.9 ± 54.5, p = 0.009). There was no significant difference in AHI, IAD or other polysomnographic parameters in the severe OSA patients. Conclusions: IAD might be superior to AHI alone in the evaluation of the history of CVEs in mild to moderate OSA patients, and it deserves attention as a possible predictor of future CVEs.

Plasma B-type natriuretic peptide level is associated with left ventricular hypertrophy among obstructive sleep apnoea patients

Objectives To examine whether increased plasma levels of B-type natriuretic peptide (BNP) are associated with cardiac structural and functional abnormalities in obstructive sleep apnoea (OSA) patients, taking into consideration the confounding effect of obesity. Measurements In a cross-sectional study, polysomnography, echocardiography and the measurement of the serum levels of BNP were performed in 235 consecutive subjects (age 52 ± 14 years) visiting our sleep clinic. Left ventricular hypertrophy (LVH) [left ventricular mass index (LVMI) ≥ 125 g/m2 in men, and ≥ 110 g/m2 in women] and cardiac diastolic function (E/A ratio) were determined by echocardiography. Results The LVMI, prevalence rate of LVH and body mass index (BMI) were higher, and the E/A ratio lower in the subjects with severe OSA (apnoea–hypopnoea index ≥ 30/h, n = 146, LVH 80%) than in those with mild to moderate OSA (n = 89, LVH 35%; P < 0.01), although plasma BNP levels were similar in the two groups. Although the log-transformed plasma BNP level showed a negative correlation with BMI, the results of binary logistic regression analysis demonstrated that the quintile value of BNP was an independent significant variable for the identification of LVH (adjusted odds ratio in quintile 5 = 4.01, 95% confidence interval 1.18–13.70, P < 0.01), even after adjusting for obesity and other risk factors. Conclusion An increased likelihood of cardiac structural and functional abnormalities was observed with increasing severity of OSA. Increased plasma levels of BNP do seem to reflect an increased likelihood of LVH in patients with severe OSA.

Efficacy of adaptive-servo ventilation (HEART PAP™) for an elderly patient with chronic heart failure who had Cheyne–Stokes respiration with central sleep apnea

An 82-year-old male patient, who had been diagnosed with chronic heart failure due to dilated cardiomyopathy and combined valvular disease and who had atrial fibrillation with complete atrioventricular block, was admitted to our hospital owing to the exacerbation of chronic heart failure. During admission, the patient became aware of drowsiness during daytime hours and had periodic apnea during sleep. Polysomnography (PSG) revealed Cheyne-Stokes respiration with severe central sleep apnea as evidenced by an apnea-hypopnea index (AHI) of 93.5/h. Nocturnal oxygen therapy failed to sufficiently suppress apnea, and arousal reactions occurred frequently. Therefore, we conducted titration by adaptive-servo ventilation (ASV; HEART PAP™). Consequently, subjective symptoms and respiratory sleep parameters improved. The patient showed excellent adherence to loading the device at home. PSG at 3 months after implementation of HEART PAP™ indicated improvement in the AHI to 13.5/h, and the patient exhibited marked improvements in breathlessness and awareness of drowsiness during daytime hours. HEART PAP™ was found to be a useful device for Cheyne-Stokes respiration with central sleep apnea that is associated with chronic heart failure even for very elderly patients.