Comorbid insomnia and sleep apnea (COMISA) and incident cardiovascular risk: a prospective analysis from the HypnoLaus cohort

Background Comorbid insomnia and obstructive sleep apnea (COMISA) is a prevalent and clinically relevant phenotype. While both insomnia and OSA have been individually associated with increased cardiovascular risk, few longitudinal studies have evaluated their combined impact on incident cardiovascular events in the general population. Methods A total of 1860 participants from the CoLaus|PsyCoLaus cohort, originally recruited between 2003 and 2008 and assessed in the HypnoLaus study between 2009 and 2013, were included, all of whom underwent full-night polysomnography and completed the Pittsburgh Sleep Quality Index (PSQI). OSA was defined as an apnea-hypopnea index (AHI) ≥15 events/h. Insomnia symptoms were defined as difficulty initiating or maintaining sleep ≥3 times/week over the past month. Participants were classified into four groups: reference (no insomnia, no OSA), insomnia alone, OSA alone, and COMISA. Incident cardiovascular events (coronary heart disease, myocardial infarction, stroke, or cardiovascular death) were adjudicated by an expert committee over a median follow-up period of 7.92 years [IQR: 6.30–8.77]. Cox regression models were adjusted for demographic, behavioral, and clinical covariates. Findings Compared to the reference group, COMISA was independently associated with an increased risk of incident cardiovascular events (HR 1.78, 95% CI: 1.09–2.92, p=0.021), while no significant association was observed for insomnia (HR 0.59, 95% CI: 0.31–1.11, p=0.10) or OSA alone (HR 1.33, 95% CI: 0.84–2.10, p=0.22). A significant interaction between OSA and insomnia was observed (p = 0.035). Results were consistent in participants without prior cardiovascular events and across alternative definitions of COMISA. Interpretation COMISA, but not OSA or insomnia alone, was associated with increased incident cardiovascular events. These findings highlight the need to identify and treat COMISA as a distinct and high-risk phenotype in cardiovascular prevention strategies. Funding Faculty of Biology and Medicine of Lausanne, Lausanne University Hospital, Swiss National Science Foundation, Leenaards Foundation, GlaxoSmithKline, Ligue Pulmonaire Vaudoise.