Patients with obstructive sleep apnea marked by excessive daytime sleepiness had a greater risk for developing cardiovascular disease than patients with other OSA symptom subtypes, new research finds.
Compared to having OSA without excessive sleepiness, the symptom was associated with a 3-fold greater likelihood of having a diagnosis of heart failure at enrollment and a doubled likelihood of suffering a cardiovascular event during follow-up, according to a report in the American Journal of Respiratory and Critical Care Medicine.
Diego Mazzotti, PhD, of the University of Pennsylvania Perelman School of Medicine, Philadelphia, and colleagues, analyzed data from 1,207 adult (ages 40 years or older) participants in the multicenter Sleep Heart Health Study (SHHS) who had moderate to severe OSA, defined as Apnea-Hypopnea Index (AHI) ≥15 events/hour. Patients were followed for nearly 12 years.
In earlier studies, Mazzotti and colleagues identified specific subtypes of OSA based on clinical symptoms at diagnosis. Their research suggests these subtypes, which include insomnia and excessive daytime sleepiness, represent true underlying disease characteristics.
In an interview with MedPage Today, Mazzotti said the findings show the importance of including patients with excessive daytime sleepiness in studies evaluating OSA treatments.
He noted that the widely publicized Sleep Apnea Cardiovascular Endpoints (SAVE) study, which found no benefit for continuous positive airway pressure (CPAP) therapy in preventing CVD events in patients with OSA, excluded patients with excessive daytime sleepiness.
He said this is the case with most OSA treatment studies because it is considered unethical to withhold treatment from these patients because of their high risk for automobile accidents and other adverse events related to lack of sleep.
Yet, Mazzotti said, "these are exactly the patients who are most likely to benefit from treatment."
Clustering analysis identified four optimal clinical subtypes based on symptoms in individuals with moderate-severe OSA Based on the distribution of observed symptoms, the subtypes were labeled: Disturbed Sleep (n=147, 12.2%), Minimally Symptomatic (n=394, 32.6%), Excessively Sleepy (n=201, 16.7%), and Moderately Sleepy (n=465, 38.5%).
Patients categorized as Excessively Sleepy subtype tended to be younger and have higher BMIs and AHIs compared to other subtypes.
Patients in the Disturbed Sleep subtype were more often female with lower AHIs compared to the Moderately Sleepy subtype.
"Although statistically significant, these differences are relatively small from a clinical standpoint, underscoring the fact that patients with clinically similar disease severity and demographic characteristics present with distinct OSA subtypes," the researchers wrote.
The analysis revealed significant associations between the cardiovascular disease components and heart disease, heart failure and stroke, and Excessive Sleepy subtype, but not the other identified subtypes.
- The Excessively Sleepy subtype was associated with increased risk of prevalent heart failure compared to the Minimally Symptomatic (OR 3.07; 95% CI 1.26-7.46; P=0.013), Disturbed Sleep (OR 3.67; 95% CI 1.03-13.1; P=0.045), and Moderately Sleepy (OR 3.62; 95% CI 1.56-8.41; P=0.003) subtypes, suggesting that symptom subtypes are independent predictors of prevalent HF among patients with moderate-severe OSA.
- The Excessively Sleepy subtype was associated with increased risk of new onset CVD when compared to each of the three other symptom subtypes: the Excessively Sleepy subtype demonstrated hazard ratios of 2.28 (95% CI, 1.53-3.40), when compared to the Minimally Symptomatic subtype (P=0.0001), 2.37 (95% CI, 1.40-4.01), compared to the Disturbed Sleep (P=0.0013), and 2.23 (95% CI, 1.52-3.27), compared to the Moderately Sleepy (P<0.0001).
- Excessively Sleepy was the only subtype at increased risk for prevalent CVD (OR 2.00; 95% CI 1.21- 3.31; P=0.007) when compared to individuals without OSA. Analyses of secondary outcomes found that the Excessively Sleepy was also the only subtype at increased risk for prevalent heart failure (OR 4.64; 95% CI 2.17-9.92; P=0.0001). No other subtypes demonstrated increased risk of prevalent disease relative to patients without OSA for incident CVD.
Given the study's observational design, it was not clear that excessive sleepiness is a causal risk factor for CVD versus a surrogate marker of underlying cardiovascular risk pathways, the researchers concluded.
But they added that, given the strength of the association, excessive sleepiness should be considered in clinical practice.
"At the most basic level, clinicians should recognize that patients with reports of multiple sleepiness-related symptoms and a very high ESS score are more likely to have cardiovascular consequences due to their OSA," they wrote. "The notion of OSA as a heterogeneous disorder is firmly established and should lead to new insights into the ways in which specific patients benefit from treatment, improving efficiency of clinical trials and facilitating personalized medicine approaches."
The Sleep Heart Study and the National Sleep Research Resource was supported by the National Heart, Lung, and Blood Institute.
The researchers declared no relevant relationships with industry related to this study.
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