Association between obstructive sleep apnea severity and endothelial dysfunction in an increased background of cardiovascular burden

Abstract

Summary The objective of the study is to examine whether increasing OSA severity is associated with worsening endothelial function. The design is a cross-sectional examination of the baseline assessment of a multicenter randomized controlled clinical trial examining the effects of oxygen, CPAP therapy, or lifestyle modifications on cardiovascular biomarkers. Participants were recruited from cardiology clinics at four sites. Participants with an Apnea Hypopnea Index (AHI) of 15 to 50 and known cardio/cerebrovascular disease (CVD) or CVD risk factors were included. OSA severity indices (oxygen desaturation index [ODI], AHI, and percent sleep time below 90% oxygen saturation [TST<90]) and a measure of endothelium mediated vasodilatation (Framingham Reactive Hyperemia Index, F-RHI derived from peripheral arterial tonometry, PAT) were assessed. The sample included 267 individuals with a mean AHI of 25.0 ± 8.5 (SD) and mean F-RHI 0.44 ± 0.38. In adjusted models, the slope of the relationship between ODI and F-RHI differed above and below an ODI of 24.6 (p=0.04), such that above an ODI of 24.6 there was a marginally significant decline in the geometric mean of the PAT ratio by 3% (95% CI: (0%, 5%); p=0.05) while below this point, there was a marginally significant incline in the geometric mean of the PAT ratio by 13% (95% CI: (0%, 27%); p=0.05) per 5-unit increase in ODI. A similar pattern was observed between AHI and F-RHI. No relation was noted with TST<90 and F-RHI. There was evidence of a graded decline in endothelial function in association withn higher levels of intermittent hypoxemia.

Association Between Endothelial Function (Assessed on Reactive Hyperemia Peripheral Arterial Tonometry) and Obstructive Sleep Apnea, Visceral Fat Accumulation, and Serum Adiponectin

“…In addition to the present study, endothelial dysfunction was also seen in severe OSA patients in other studies, including 1 that used RH-PAT. [43][44][45] In the present multivariate analysis, severe OSA was related to RHI independently of sex. Therefore, not only sex but also the severity of OSA might have a significant association with endothelial function as reflected by RH-PAT.…”

The Impact of Obstructive Sleep Apnea and Tobacco Smoking on Endothelial Function

“…In a cohort of over 400 men and women in Norway, sampled from a larger population-based study, only women with sleep apnea demonstrated dose-dependent worsening of the reactive hyperemia index compared to their non-apneic counterparts of the same gender [27]. Recently, Seif et al [23] demonstrated a non-linear relationship between OSA severity and endothelial function measured by the Framingham index in a cohort of predominantly male subjects at high cardiovascular risk. Similar to that study, we found a significant association between PAT ratio and OSA severity, in particular intermittent hypoxia, albeit the relationship weakened after adjustment for age and BMI/waist circumference as confounding variables (table 2).…”

“…The PAT probes provided measurement of pulse volume changes in the index fingers of the occluded arm compared to the control arm. PAT ratios (Framingham reactive hyperemia index) were analyzed by standard automated algorithms (Itamar Medical Ltd.) as previously described [19,22,23] and used as the indicator of digital vasomotor response. The natural logarithm of the ratio of pulse amplitude during the 90-120 s post-deflation to that at baseline pulse in the hyperemic finger was calculated and then divided by the same ratio in the control finger.…”

Intermittent Hypoxia Impairs Endothelial Function in Early Preatherosclerosis

“…Additionally, little is known about the activation of EPCs in the central sites of their production and preservation in bone marrow under hypoxic conditions in frame of OSA. One explanation of the above outlined discrepant results concerning endothelial changes and induction of repair pathways under hypoxia seem to be differences in the intensity of hypoxia across various studies, as it is known that the more pronounced the hypoxia is, the faster the vasculopathy proceeds (Seif et al 2013). Our hypothesis is that also the initial stage of vessel pathology determines the extent of vessel disease progression and induction of related pathomechanisms underlying hypoxia.…”