For certain patient groups, obstructive sleep apnea (OSA) may be associated with cardiovascular disease. At present, physicians determine OSA severity by referring to the apnea-hypopnea index (AHI), which measures the number of cessations (apneas) or reductions (hypopneas) in breathing per hour of sleep. However, standards for categorizing patients as having mild, moderate, or severe sleep apnea are not sufficiently rooted in clinical data. As such, recent studies are delving deeper into evaluating disease subtypes and using data to determine a patient’s risk for cardiovascular disease.

“OSA is a highly prevalent disease, especially with the increase in the prevalence of obesity worldwide,” says Diego R. Mazzotti, PhD. “Based on the pathophysiology of OSA, the respiratory pauses observed during sleep can elicit several physiological responses that can increase the risk of cardiovascular disease.”

Taking a Deeper Look

For a study published in the American Journal of Respiratory and Critical Care Medicine, Dr. Mazzotti and colleagues sought to better define OSA symptom subtypes and how those subtypes relate to prevalent and incident cardiovascular disease.

Dr. Mazzotti and colleagues examined whether prevalence of overall cardiovascular disease and its components (coronary heart disease [CHD], heart failure [HF], and stroke) are linked to OSA symptom subtypes. To establish how cardiovascular risk varies among OSA subtypes, the study included data obtained from the Sleep Heart Health Study—specifically from 1,207 individuals with moderate or severe OSA (AHI greater or equal than 15) —“to confirm that symptom subtypes of OSA are reproducible in an independent community-based cohort in the US,” says Dr. Mazzotti. The study employed Kaplan-Meier survival analysis and Cox proportional hazards models to assess if cardiovascular mortality and the rate of other incident events were different among four symptom subtypes—disturbed sleep, minimally symptomatic, excessively sleepy, and moderately sleepy. The study also compared these rates with those of 2,830 individuals without OSA (AHI less than five).

Examining Key Findings

The study’s findings support the clinical relevance of OSA symptom subtypes, as it demonstrates that they are reproducible and associated with cardiovascular risk. Clinical symptoms aid in identifying subtypes of patients with moderate-severe OSA. Furthermore, symptom-based subtypes might shed light on the risk of prevalent and incident adverse cardiovascular consequences. “Patients might express different symptomatology, and this could be a very important marker of disease progression and inform risk” says Dr. Mazzotti.

Upon examining the results of all subtypes, the excessively sleepy subtype exhibited more than three times increased odds of prevalent HF. The excessively sleepy subtype also showed an increased risk of new cardiovascular disease, CHD, and HF events (hazard ratios, 1.7-2.4). This subtype also demonstrated increased risk for prevalent and incident cardiovascular events when compared with non-OSA individuals. “We show that OSA patients of the excessively sleepy subtype tend to develop cardiovascular disease much earlier than individuals without OSA,” says Dr. Mazzotti.

As such, Dr. Mazzotti noted, “This study highlighted that more specific ways of identifying the excessively sleepy OSA patients are necessary.” (Figure). “For example, excessively sleepy OSA patients have higher scores of the Epworth Sleepiness scale but also much higher prevalence of feeling sleepy during the day, not feeling rested on waking up, and often feeling physically tired. Combined, these symptoms might help physicians to identify the excessively sleepy subtype.”

Assessing Implications

“Physicians should recognize that OSA is not a well-defined, homogenous disease, and paying attention to symptom profiles can be valuable to stratify patients according to their risk for cardiovascular disease,” says Dr. Mazzotti. He adds that clinicians need training on how to identify subtypes at greater risk and how to spot the correlation between multiple sleepiness-related symptoms and an elevated ESS score—a relationship that’s indicative of patients who are more likely to have cardiovascular consequences due to their OSA.


Symptom Subtypes of Obstructive Sleep Apnea Predict Incidence of Cardiovascular Outcomes