Background Although co‐occurrence of sleep disorder with heart failure is known, it is not clear whether that condition is a cause or consequence of heart failure. The present study was conducted as a longitudinal examination of the predictive value of sleep parameters on progression of left ventricular diastolic dysfunction. Methods and Results Four‐hundred fifty‐two subjects were followed for a mean of 34.7 months. An outcome of diastolic dysfunction was defined as increase in early inflow velocity/early diastolic tissue velocity >14. Sleep apnea‐hypopnea index, minimal oxygen saturation, sleep duration, and activity index (physical movement during sleep time, a potential parameter of poor sleep quality) were determined using apnomonitor and actigraphy findings, while heart rate variability was measured with a 24‐hour active tracer device. Sixty‐six of the patients developed diastolic dysfunction during the follow‐up period, with a median time of 25 months. Kaplan–Meier analysis results revealed that those with sleep apnea classified as moderate (apnea‐hypopnea index 15 to <30, P <0.01 versus none) or severe (apnea‐hypopnea index ≥30, P <0.01 versus none), and with a high activity index (Q3 or Q4, P <0.01 versus Q1), but not short sleep duration ( P =0.27) had a significantly greater risk for a diastolic dysfunction event. Results of multivariable Cox proportional hazards regression analysis indicated that moderate to severe sleep apnea after a follow‐up period of 3 years (hazard ratio [HR], 9.26 [95% CI, 1.89–45.26], P <0.01) and high activity index (HR, 1.85 [95% CI, 1.01–3.39], P =0.04) were significantly and independently associated with future diastolic dysfunction. Moreover, significant association of high activity index with the outcome was not confounded by either minimal oxygen saturation or heart rate variability. Conclusions Sleep apnea and physical movement during sleep, but not sleep duration and autonomic nervous dysfunction, are independent important predictors for progression of left ventricular diastolic dysfunction.

Background: Diabetes is an important risk factor of heart failure (HF) and is associated with left ventricular (LV) diastolic dysfunction. However, integrated importance of diabetes and its comorbid conditions, such as altered nocturnal blood pressure (BP) variation, as predictors of diastolic dysfunction is not known in pre-HF period. The present study was conducted as longitudinal examination of the predictive value of nocturnal hypertension profiles on progression of LV diastolic dysfunction in diabetic and non-diabetic patients without heart diseases. Methods: Pre-heart failure 422 subjects (154 diabetes, 268 non-diabetes) were followed for 36.8 ± 18.2 months. The relationships among the patterns of nocturnal hypertension and the outcome of LV diastolic dysfunction, defined as increase in E/e' >14, were investigated in the patients with and without diabetes. Results: The interaction effect of the diabetes status and the patterns of nocturnal hypertension on the hazard rate of the occurrence of E/e'>14 was statistically significant (p=0.017). Kaplan-Meier analysis results revealed that diabetic patients with non-dipper (p=0.016 vs. dipper) and riser (p=0.007 vs. dipper) had a significantly greater risk for a diastolic dysfunction event. Furthermore, multivariable Cox proportional hazards analysis revealed that non-dipper (HR: 3.00; 95% CI: 1.11–8.06, p = 0.029) and riser (HR: 3.58; 95% CI: 1.24–10.35, p = 0.018) patterns were significantly associated with elevated risk of the outcome of LV diastolic dysfunction. In contrast, no similar significant associations were found in non-diabetic patients. Conclusions: During pre-HF periods, nocturnal hypertension is an important predictor for progression of LV diastolic dysfunction in diabetic patients.

[Background] Sleep apnea, a common co-morbid condition of diabetes, has been shown to be associated with established heart failure. However, its role in association of the presence of diabetes in the progression of cardiac diastolic function in pre-heart failure phase is not known. This prospective study is to longitudinally examine the predictive value of sleep apnea and diabetes on progression of left ventricular (LV) diastolic dysfunction in patients without heart disease.[Methods] Among 976 patients registered in HSCAA prospective cohort study, 517 without heart disease (175 type 2 diabetes, 342 non-diabetes) were followed with repeated echocardiography in every 1-3 years for a mean 34.7 months. LV diastolic dysfunction was determined by transmitral early inflow velocity/early diastolic tissue velocity (E/e´) >14. Annual change in E/e’ was calculated by using the slope of the linear regression line calculated from at least 3 echocardiographic measurements. Sleep apnea was determined by an apnomonitor device in conjunction with percutaneous oxygen saturation, and apnea hypopnea index (AHI) was calculated.[Results] Kaplan-Meier analyses revealed that subjects with diabetes or sleep apnea had a significantly (p<0.01) greater risk for LV diastolic dysfunction, with hazards ratio of 2.21 (1.41-3.47) and 2.23 (1.40-3.55), respectively. Subjects with sleep apnea exhibited significantly higher risk for LV diastolic dysfunction in non-diabetic subjects (p<0.01), while showed tendency of higher risk in diabetic subjects (p=0.10). The annual change of E/e’ was significantly and independently associated with both diabetes (β=0.278, p<0.01) and AHI (β=0.138, p<0.01). Finally, ROC analyses revealed that addition of AHI and diabetes to classical risk factors best predicted individuals with fast progression of diastolic dysfunction (annual change of E/e’ >1.0) with an AUC of 0.81.[Conclusions] In patients without heart disease, sleep apnea is an important predictor for progression of LV diastolic dysfunction. Its association is partly confounded, but still independent of the presence of diabetes.