Introduction:
Obstructive and central sleep apnea (SA) induce sleep fragmentation and associates with HTN and cardiovascular diseases (CVDs). Sleep fragmentation is known to increase stress. Further, heightened stress-associated neurobiological metabolism (particularly amygdalar activity - AmygA), potentiates atherosclerosis. However, it is unknown: 1) whether SA increases AmygA in humans, or 2) whether AmygA mediates the link between SA and its CV consequences (HTN and CVD).
Hypothesis:
SA associates with higher AmygA which in turn associates with hypertension (HTN) and myocardial infarction (MI).
Methods:
We studied a cohort of 36424 participants within the Partners Biobank. Diagnoses of MI and sleep apnea and relevant clinical data were obtained from International Statistical Classification of Diseases and Related Health Problems (ICD-10) codes. A subset of 1520 patients provided clinically indicated 18F-fluorodeoxyglucose positron emission tomography/computed tomography imaging. AmygA was measured using validated measures.
Results:
Of 36424 participants, 6596 (18.1%) had SA, 20881(57.3%) had HTN and 4033 (11.1%) had MI. OSA significantly associated with HTN (OR [95%CI]: 3.2 [2.95, 4.48], p<0.0001) and MI (1.30 [1.21, 1.41], p<0.001) in multivariable models. SA associated with AmygA (β [95%CI]: 0.183 [0.058, 0.337], p=0.006). AmygA associated with HTN (1.18 [1.02, 1.38], p= 0.028). Further, AmygA associated with MI (1.28 [1.11, 1.46], p=0.0005). Moreover, AmygA mediated the association between SA and HTN and between SA and MI (p<0.05 for both, figs 1a and 1b).
Conclusion:
Our findings suggest that SA increases the risk of HTN & MI via a mechanism that involves heightened amygdalar activity. This potential mechanism may inform novel treatments.