Sleep Apnea and Diabetes Predict Progression of Cardiac Diastolic Dysfunction in Pre-heart Failure Patients: a Prospective Cohort HSCAA Study

Abstract [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.