For many patients with resistant hypertension, recurrent atrial fibrillation, type 2 diabetes, heart failure, or chronic kidney disease, clinicians often respond by escalating medications, adjusting treatment targets, or adding specialists. One contributor to persistent cardiometabolic disease that clinicians may overlook is obstructive sleep apnea (OSA).

The diagnostic challenge is that many patients with OSA do not present with the classic symptoms clinicians often associate with the disorder — snoring and excessive daytime sleepiness. Instead, they may show up with difficult-to-control blood pressure, nighttime symptoms, fragmented sleep, or worsening cardiovascular disease.

“Many of these patients are not sleepy,” said Sogol Javaheri, MD, associate physician in the Division of Sleep and Circadian Rhythm Disorders at Brigham and Women’s Hospital in Boston. For patients with high blood pressure, nocturia, or disrupted sleep, “doing a home sleep test is a great next step,” she said.

Moving Beyond the Sleepy Patient 

Javaheri said waking up poorly rested and even having symptoms that resemble insomnia may be clues. In patients with heart failure, persistent orthopnea or paroxysmal nocturnal dyspnea despite optimized treatment may also warrant consideration of underlying sleep apnea.

Virend Somers, MD, PhD, director of the Cardiovascular Facility and the Sleep Facility within Mayo Clinic’s Center for Clinical and Translational Science in Rochester, Minnesota, said clinicians should not dismiss OSA in patients who do not report daytime sleepiness.

“Even in the absence of daytime sleepiness, the nocturnal hypoxemia, intrathoracic pressure changes, and blood pressure surges may contribute to more rapid progression of the cardiovascular or metabolic disease or even resistance to therapy,” Somers said.

Susheel Patil, MD, PhD, director of the Sleep Medicine Program for University Hospitals and assistant professor at Case Western Reserve University School of Medicine in Cleveland, said clinicians should recognize that patients with cardiometabolic disease represent a population at higher risk for OSA, even when symptoms are subtle.

“Patients with these comorbidities are all at risk of OSA,” said Patil, who is also on the board of directors for the American Academy of Sleep Medicine.

Why Untreated OSA Matters for Cardiometabolic Disease

Repeated airway obstruction during sleep can trigger intermittent hypoxia, sympathetic activation, inflammation, and changes in vascular function that may contribute to cardiovascular risk.

For resistant hypertension, Somers said OSA can activate multiple pathways that directly contribute to blood pressure elevation, including impaired endothelial function and activation of the renin-angiotensin-aldosterone system.

“OSA activates a number of mechanisms that would directly contribute to increasing blood pressure,” Somers said.

The relationship with atrial fibrillation may be similarly complex. Episodes of hypoxemia, increased cardiac workload, and autonomic changes during obstructive events can create conditions that promote arrhythmia.

For patients with atrial fibrillation, evaluation may be especially important when rhythm control is the goal. “If the goal is to maintain in sinus rhythm, sleep testing should be performed before cardioversions or ablations to prevent likelihood of recurrence of atrial fibrillation,” Patil said.

What Does Treating OSA Actually Change?

Although OSA is strongly associated with cardiovascular disease, experts say the evidence that treating OSA reduces major cardiovascular events is more complicated.

“Randomized controlled trials have not yet shown that treatment of OSA improves cardiometabolic outcomes,” Patil said.

For clinicians, that does not mean OSA should be ignored. Instead, Patil said treatment goals should focus on improving symptoms and quality of life while recognizing that OSA identifies patients at higher cardiovascular risk.

According to Somers, observational studies consistently show that patients treated for OSA who adhere to therapy have lower cardiovascular risk. “Those people who actually use their therapy for a substantial part of the night, usually more than 4 hours, tend to do better,” Somers said.

He added that some of the highest-risk patients — including those with severe daytime sleepiness or severe nocturnal hypoxemia — have not been well represented in randomized trials, which may make it harder to identify who benefits most.

Javaheri said patients with greater oxygen desaturation during sleep may be more likely to benefit from treatment, particularly those who spend more time with oxygen saturation below 89%.

Who Is Being Missed?

Obesity remains an important risk factor for OSA, but experts say clinicians should not rely on BMI alone.

Somers said patients with normal weight obesity — meaning high body fat despite a normal BMI — may also have sleep apnea and may be overlooked because they do not fit the traditional OSA profile.

Women are another group that may be missed. Somers said women with OSA often present differently, with symptoms such as mood changes, irritability, fatigue, headaches, and depression rather than classic symptoms.

“There are several reports showing that a diagnosis of sleep apnea is often delayed in women,” Somers said. Many screening questionnaires were developed primarily in men, raising concerns that they may not identify all women who could benefit from evaluation, he said.

Integrating Sleep Into Chronic Disease Management

For primary care clinicians managing patients with multiple chronic conditions, sleep evaluation does not need to be a separate conversation from cardiovascular or metabolic care.

He suggested that screening can begin with simple questions such as, “How do you and your partner perceive your sleep?” and “Are you tired during the day?”

Those questions may reveal symptoms patients have normalized or overlooked, such as unintentionally falling asleep after work or needing frequent naps.

The American Heart Association includes sleep as one of the components of Life’s Essential 8, which reflects growing recognition that sleep health is part of overall cardiometabolic health.

Making Evaluation Practical 

One misconception among clinicians and patients is that OSA evaluation always requires an overnight laboratory study.

“Most patients do not require an in-lab study, even if they have cardiometabolic disease,” Javaheri said. The home sleep test is typically sufficient and will result in a lower financial burden for patients when ordered.

But if a sleep clinic assessment is desired, Javaheri recommended not waiting for a sleep clinic appointment before beginning an evaluation. “Given long wait times in sleep clinics, it makes sense to order the home sleep test with concurrent referral to sleep clinic, so the study is done by the time the patient is seen in the sleep clinic,” she said.

“The biggest challenges,” said Patil, “continue to be getting patients to understand that they have sleep apnea and that they should pursue treatment when it’s recommended, particularly when they perceive themselves to be asymptomatic,” he said.

For patients with resistant hypertension, recurrent atrial fibrillation, diabetes, or heart failure, OSA may not be the only explanation for poor disease control. The goal is to recognize sleep as part of cardiometabolic care and to identify the patients who may benefit from evaluation and treatment, Patil said.

Somers reported being a consultant to Jazz Pharmaceuticals, Lilly, GEM Health, Apnimed, iRhythm, Mineralys Therapeutics, and the Sleep Number Advisory Board. Javaheri and Patil reported no relevant conflicts.

Lara Salahi is a health journalist based in Boston.