Obesity, diabetes and sleep-disordered breathing (SDB) are considered to be extant and growing public health crises. A wealth of information links these conditions to each other and to increased morbidity, reduced quality of life and death. While managing these conditions that often occur together may be challenging for patients and clinicians, successfully addressing them represents a real opportunity to reduce cardiovascular disease and prevent cardiovascular events.

"It's extremely important we as health care professionals address diabetes, poor sleep and poor sleep hygiene, and obesity as they are modifiable risk factors for cardiovascular disease," says Nishant P. Shah, MD, FACC, a preventive cardiologist at Duke Heart Center, Duke University School of Medicine, in Durham, NC.

"Given that these cardiometabolic conditions are linked to major cardiovascular events, I believe all clinicians need to be mindful of them, whether or not they are subspecialty trained," he adds.

Shah and other experts think a new approach and more focused efforts on prevention are needed to halt their destructive path through the population. Herein are practical steps that clinicians can take to more effectively help their patients with these increasingly common issues.

The Changing Face of Obesity

Our understanding of obesity has changed dramatically in the decade since the American Medical Association (AMA) first recognized it as a disease in 2013. Most professional societies, including the AMA, now recognize obesity to be both relapsing and progressive in nature and requiring continuous effort to control, rather than a behavioral concern related to lack of willpower.

Of the 17.9 million deaths per year from cardiovascular disease, the majority are now considered preventable through interventions that target the risk factors associated with excess body weight, according to a joint position paper developed by the World Heart Federation and World Obesity Federation and released in December 2022.¹

The authors, led by Francisco Lopez-Jimenez, MD, MBA, FACC, from Mayo Clinic (Rochester, MN), emphasize that when it comes to obesity, doing something is vastly better than doing nothing.

"Given the wealth of evidence linking cardiovascular disease with obesity, assessment of cardiovascular risk and aggressive strategies for risk reduction among those living with overweight/obesity should help to reduce the burden of cardiovascular morbidity and mortality in this group," write Lopez-Jimenez, et al.

Shah applauds efforts like this joint position paper for trying to raise awareness and encouraging action on obesity and obesity-related cardiovascular disease.

"Although they can be related to genetics, obesity, hypertension and diabetes are all modifiable risk factors to some extent. In many cases, they can be prevented by just a adopting healthier lifestyle before they develop. Thus, these efforts are important to raise awareness of what we can control,"he says.

Is Weight Loss the Key to Success?

It's not uncommon to see a patient in the clinic with all three issues – obesity, sleep apnea and diabetes. "My approach is usually to see what I can do to target all three, because they are invariably linked, not always in a causal way, but linked in terms of increasing cardiovascular risk," says Shah.

"With that, attending to the obesity is absolutely essential as it often related to the development of diabetes and sleep apnea," he adds.

Managing obesity requires motivation, positive reinforcement and education by the clinician, as well as a strong commitment by the patient who may have to "change how they live their life for the rest of their life," says Shah. "We must be empathetic to the fact that this may not always be easy and support our patients along the way," he adds.

For Garima Sharma, MD, FACC, helping her patients lose weight demands a combination of education and motivation. Sharma is director of cardio-obstetrics at The Johns Hopkins University School of Medicine in Baltimore and president of the ACC Maryland Chapter. Her practice focuses on women's cardiovascular health and prevention.

"In our center, we work to help patients with high cardiometabolic risk understand what they're eating and how they can improve their diet. As well as understand how to take control over their diet, sleep, physical activity, blood pressure and blood sugar," says Sharma.

Additionally, for persons desiring pregnancy, education is provided about the association of suboptimal cardiovascular health and adverse pregnancy outcomes and long-term cardiovascular risks. "There is a strong motivational component where we're really empowering them to take control of their health."

Sharma most often suggests a Mediterranean diet pattern, rich in green leafy vegetables, legumes, fruit and lean meat. But while the preponderance of the data show that a healthy diet is a cornerstone for maintaining good health, the exact parameters of that diet appear to be flexible.

Greater adherence to any of several healthy eating patterns was associated with a lower risk of death from cardiovascular disease, cancer and respiratory disease in a recent prospective cohort study.² These associations were consistent in different racial and ethnic groups. The eating patterns tested included a Mediterranean diet score as well as three other healthy eating indices, one of which was plant-based.

The education aspect, Sharma adds, often can be as simple as having a patient download an app to track their diet. Or sometimes even more effective is having them track their macros, particularly their carbohydrate intake. "Many people simply don't realize they are eating 200 or 250 grams of carbohydrates a day," she says. For an average individual, 100 to 150 grams of carbohydrates a day should be sufficient.

Sharma also advises her patients to use an activity tracker, whether something sophisticated like an Apple Watch or simply a journal to track exercise. Many physicians are using diet and fitness apps themselves, so often it's as simple as sharing what they find useful with patients.

Importantly, health outcomes related to weight loss should be the focus of discussions with patients. "I've never gotten push back from a patient for encouraging weight loss. I'm very careful to take a cardiometabolic approach and draw direct connections between the weight loss and health outcomes," he says.

"I tell patients that if they lose weight, their blood pressure will be lower and it may be possible to reduce or stop some of their meds, and it will be easier to control their glucose." And that their hips and knees may hurt less so they are better able to stay active and play with their grandchildren.

Referral to a multidisciplinary weight clinic, where medications to assist in weight loss or bariatric surgery are considered, is an option for patients who have not been able to lose weight after multiple attempts.

Weight Loss Drugs Return

Anti-obesity medications fell out of pharma company favor after the fen-phen fiasco and the (cannabinoid receptor blocker) rimonabant failure. Now, with the GLP1 receptor agonists (GLP1 RAs), they're making a big comeback. According to analysts at Cowen, sales of weight loss drugs may reach $30 billion by 2030.

Semaglutide (branded by Novo Nordisk as Ozempic for diabetes and at a higher dose as Wegovy for weight loss) mimics the effects of incretin, a hormone secreted from the gastrointestinal tract to signal fullness. The agent has shown good effectiveness, helping overweight and obese patients lose a mean of 15.0% of body weight (–14.9% vs. –2.4% for placebo, for an estimated treatment difference of –12.5 percentage points; p<0.001).³

Another agent, tirzepatide (Mounjaro, Lilly), appears to work even better. In the SURMOUNT-1 trial, overweight and obese participants randomly assigned to different doses of tirzepatide (5, 10 and 15 mg once weekly) lost between 15.0% and 20.9% of body weight at week 72, compared with 3.1% with placebo (p<0.001 for all comparison with placebo).⁴

Tirzepatide was approved by the U.S. Food and Drug Administration for diabetes in 2022 and has been fast-tracked for approval for weight loss.

"Combining significant weight loss with healthy, balanced meals and at least 30 minutes of physical activity on most days will make a big difference in a person's cardiovascular risk," says Shah. Even just a 5% weight loss can improve metabolic markers and cardiovascular risk factors.

Semaglutide and tirzepatide are both subcutaneous injectables, which for some is a deterrent. But the biggest issue now is reimbursement, especially for weight loss alone without a diagnosis of diabetes. Wegovy can cost around $1,400 a month in the U.S., beyond what many patients feel able to pay, particularly for a drug they may need over a long period.

Tirzepatide also can be costly to patients if not covered by insurance. Lower doses of semaglutide (Ozempic) and other GLP1 RAs can be more affordable if covered and are more likely to be covered by payers for patients with diabetes. They also have profound weight loss potential, notes Shah.

"I think cardiologists should be prescribing GLP1 RAs to appropriate patients as there is a lot of cardiovascular benefit too," says Shah. He notes though this can be difficult because of the lack of insurance coverage when prescribed for weight loss alone in patients without diabetes. Hopefully, promising clinical trial data and ongoing conversations with payers will lead to insurance coverage of these drugs for weight loss alone.

Sleep Finally Gets Respect

"A good laugh and a long sleep are the best cures in the doctor's book." - Irish Proverb

Gone are the days when people boast about how little they sleep. Sleep has been solidly established as an important health metric and bragging rights go to those who bag eight or nine hours a night.

"Aside from the issue of sleep apnea, we need to ask our patients about their sleep duration and sleep quality," says Shah. Poor sleep and poor sleep patterns increase the risk of disease, thus good sleep hygiene should be encouraged and part of the conversation with patients. Among the factors impacting sleep nowadays are phones, televisions and too much light in the bedroom, and even exercising too close to bedtime.

About 35% of U.S. adults sleep less than seven hours a night. One in five report excessive daytime sleepiness, and fewer than half report having a good night of sleep every night.⁵

Indeed, the American Heart Association's Life's Simple 7 checklist was expanded last year to include sleep – and not just its duration, but also its timing, regularity, efficiency, satisfaction and impact on daytime alertness – as something essential for optimal cardiovascular health.⁶ Now called Life's Essential 8, the guidance suggests that adults should strive for seven to nine hours a night of sleep.

The change was spurred by the growing body of evidence linking sleep problems to cardiovascular disease. A recent study illustrated the predictive value of adding sleep to the other health metrics.⁵

The investigators prospectively tested the expanded cardiovascular health metric (Life's Simple 7 plus sleep) in 1,920 middle-aged and older adults participating in the MESA Sleep Study and found that adding a multidimensional measure of sleep improved the models' predictive strength for cardiovascular disease events. Participants in the highest vs. lowest tertile of a cardiovascular health score that included sleep duration, insomnia, daytime sleepiness, obstructive sleep apnea and sleep regularity had a 47% lower incident risk for cardiovascular disease.

"The approach to promoting a healthy lifestyle, which traditionally focused heavily on diet and physical activity, should be expanded to encompass behaviors across the 24‐hour period, including sleep," write the study's authors.

When Sleep is Disordered

"Given that we sleep for about a third of our lives, and given that not just sleep apnea, but poor sleep, sleep deprivation and insomnia have been linked to cardiovascular disease and very strongly linked to obesity and diabetes, I think it's important for sleep to be a routine part of the clinical history," says Virend Somers, MD, PhD, FACC.

Somers, the Alice Sheets Marriott Professor of Cardiovascular Medicine, directs the cardiovascular and sleep facilities within the Center for Clinical and Translational Science at Mayo Clinic's campus in Rochester, and has been studying sleep and its importance in heart health for 35 years.

His first article on sleep was published in 1988 and floated the idea that sleep apnea "may" increase sympathetic activity, a hypothesis his lab subsequently confirmed in a landmark paper in 1997.^7,8

Patients should be thoroughly queried about their sleep: its duration and quality, whether they have difficulty falling asleep or staying asleep, and daytime sleepiness for a start, says Somers.

"Asking if they snore is just the first step. I also ask whether the patient's bed partner has ever noticed that they seem to stop breathing during sleep, what we call 'witnessed apneas,' and a whole host of other questions about their sleep," he says.

While the majority of apneics are overweight or obese, normal weight individuals also can suffer from SDB, so it's important to not make assumptions. "We see lean people with obstructive sleep apnea. It's usually because they have an upper airway abnormality, like a small lower jaw, or they have what we call a retrognathia, where the chin is a little more backwards and less pronounced," says Somers.

SDB causes repetitive episodes of nocturnal hypoxemia, sympathetic nervous activation and cortical arousal, according to a recent JACC Focus Seminar that details the pathophysiological abnormalities, as well as its diagnosis and management.⁹ It's common in people with, or at risk for, cardiovascular disease including those who are obese or have hypertension, coronary disease, heart failure or atrial fibrillation.

SDB is a spectrum, including those who are characterized predominantly by obstructive features (repetitive narrowing and closure of the upper airway during sleep; obstructive sleep apnea) or by abnormalities in neuromuscular output without prominent airway collapse (central sleep apnea).

"When you take the time to carefully ask about sleep, you often find a complex set of circumstances," says Somers. An example is a woman with disturbed sleep because of hot flashes together with disruptive snoring and insomnia. Her sleep should be considered a risk factor and she should be referred to a sleep specialist because she may benefit from treatment for sleep apnea or perhaps behavioral therapy for insomnia or medication to help her sleep.

Sometimes all that's needed to improve sleep apnea is a special device that prevents a patient from sleeping on his or her back, says Somers. Current therapy for obstructive sleep apnea includes weight loss, exercise, mandibular devices (which stop the lower jaw from falling backwards) and continuous positive airway pressure (CPAP) therapy. These improve daytime sleepiness.

While epidemiological and observational data strongly indicate that sleep apnea can cause and worsen heart disease and that treating apnea can potentially improve cardiovascular outcomes, this has yet to be shown in randomized clinical trials. In particular, CPAP, notes Somers, has not been shown to improve cardiovascular outcomes.

This may be related, he suggests, to patients often using the device only a few hours a night, affecting the ability to see clear benefit from treating sleep apnea in a randomized trial; benefit has been suggested in patients who use CPAP four or more hours a night. Also, the patients at especially high risk, with the most severe nocturnal hypoxia and who have daytime sleepiness, generally have been excluded from the trials.

The cardiovascular community is increasingly recognizing the importance of sleep to cardiovascular health. In fact, the most read and most talked about article in JACC in 2022 was about a study conducted in Somers' lab that showed young healthy participants who sleep only four hours a night have a higher daily calorie intake, by about 300 calories, and preferential increase, by more than 10%, in visceral fat.¹⁰

Cardiometabolic conditions, such as obesity, diabetes and SDB, are now all part of the purview of the cardiovascular clinician to reduce the risk of cardiovascular disease and events in their patients. They should be part of every patient visit and referrals made as needed to a sleep specialist for sleep apnea or an endocrinologist for better glucose control. Or perhaps for consideration of one of the new drugs that effect both glucose control and weight loss, which may incidentally improve cardiovascular outcomes.

References

1. Lopez-Jimenez F, Almahmeed W, Bays H, et al. Obesity and cardiovascular disease: mechanistic insights and management strategies. A joint position paper by the World Heart Federation and World Obesity Federation. Eur J Prev Cardiol 2022;29:2218-37.
2. Shan Z, Wang F, Li Y, et al. Healthy eating patterns and risk of total and cause-specific mortality. JAMA Intern Med 2023;183:142-53.
3. Wilding JPH, Batterham RL, Calanna S, et al. Once-weekly semaglutide in adults with overweight or obesity. N Engl J Med 2021;384:989-1002.
4. Jastreboff AM, Aronne LJ, Ahmad NN, et al. Tirzepatide once weekly for the treatment of obesity. N Engl J Med 2022;387:205-26.
5. Makarem N, Castro‐Diehl C, St‐Onge M, et al. Redefining cardiovascular health to include sleep: Prospective associations with cardiovascular disease in the MESA sleep study. J Am Heart Assoc 2022;11:e025252.
6. Lloyd-Jones DM, Allen NB, Anderson CAM, et al. Life's Essential 8: Updating and enhancing the American Heart Association's construct of cardiovascular health: A presidential advisory From the American Heart Association. Circulation 2022;146:e18-e43.
7. Somers VK, Mark AL, Abboud FM. Sympathetic activation by hypoxia and hypercapnia--implications for sleep apnea. Clin Exp Hypertens A 1988;10 Suppl 1:413-422.doi:10.3109/10641968809075998
8. Somers VK, Dyken ME, Clary MP, Abboud FM. Sympathetic neural mechanisms in obstructive sleep apnea. J Clin Invest 1995;96:1897-1904.
9. Cowie MR, Linz D, Redline S, Somers VK, Simonds AK. Sleep disordered breathing and cardiovascular disease: JACC state-of-the-art review. J Am Coll Cardiol 2021;78:608-24.
10. Covassin N, Singh P, McCrady-Spitzer SK, et al. Effects of experimental sleep restriction on energy intake, energy expenditure, and visceral obesity. J Am Coll Cardiol 2022;79:1254-65.