Pulse Wave Amplitude Drops Index: A Biomarker of Cardiovascular Risk in Obstructive Sleep Apnea

Rationale: It is currently unclear which patients with obstructive sleep apnea (OSA) are at increased cardiovascular risk. Objective: To investigate the value of pulse wave amplitude drops (PWAD), reflecting sympathetic activations and vasoreactivity, as a biomarker of cardiovascular risk in OSA. Materials and Methods: PWAD was derived from pulse oximetry-based photoplethysmography signal in three prospective cohorts: HypnoLaus (N=1941), Pays-de-la-Loire Sleep Cohort (PLSC; N=6367) and ISAACC (N=692). PWAD index was the number of PWAD (>30%) per hour during sleep. All participants were divided into subgroups according to the presence/absence of OSA (apnea-hypopnea index [AHI]≥15 or <15/hours) and the median PWAD index. Primary outcome was the incidence of composite cardiovascular events. Results: Using Cox models adjusted for cardiovascular risk factors (hazard ratio [95% confidence interval]), patients with low PWAD index and OSA had a higher incidence of cardiovascular events versus the high PWAD/OSA group and those without OSA in HypnoLaus (2.16[1.07–4.34], p=0.031 and 2.35[1.12-4.93], p=0.024) and PLSC (1.36[1.13–1.63], p=0.001 and 1.44[1.06–1.94], p=0.019), respectively. In ISAACC, the low PWAD/OSA untreated group had a higher cardiovascular event recurrence rate versus the no-OSA group (2.03[1.08–3.81], p=0.028). In PLSC and HypnoLaus, every 10 events/h increase in continuous PWAD index was independently associated with incident cardiovascular events exclusively in OSA patients (HR 0.85[0.73–0.99], p=0.031 and HR 0.91[0.86–0.96], p=<0.001 respectively). This association were not significant in no-OSA and in ISAACC. Conclusions: In OSA patients, a low PWAD index reflecting poor autonomic and vascular reactivity was independently associated with a higher cardiovascular risk.