Sleep and Cardiovascular Risk: A Causal Relationship?

Dr. Sanja J. Jelic

Dr. Sanja J. Jelic

Sleep is increasingly recognized as an important contributor to health, yet many Americans – particularly women – regularly do not get enough sleep. To learn if inadequate sleep increases their risks of heart disease, Sanja J. Jelic, MD, Division of Pulmonary, Allergy and Critical Care Medicine; Lori J. Mosca, MD, MPH, PhD, and Brooke Aggarwal, EdD, MS, CHES, Division of Cardiology; and Marie-Pierre St-Onge, PhD, Division of Endocrinology, NewYork-Presbyterian/Columbia University Irving Medical Center, have come together to study the relationship between sleep habits and cardiovascular risk factors in three separate, but synergistic, investigative phases.

Marie-Pierre St-Onge, PhD, and Lori J. Mosca, MD, MPH, PhD

Marie-Pierre St-Onge, PhD, and Lori J. Mosca, MD, MPH, PhD

“Sleep restriction today is very prevalent and most people curtail their sleep thinking that it is nothing,” says Dr. Jelic, a pulmonologist and expert in sleep apnea. “They tend to be very cavalier about it. They lead busy lives and have to get things done. However, we think that this lack of sleep does have some negative consequences on cardiovascular health.”

“Multiple studies have found associations between short sleep duration and sleep disorders and heart disease, but the evidence is not quite there yet,” says Dr. Mosca, a vocal leader in women’s heart health for more than two decades. “It’s been a big debate among researchers in the field. We’re not sure if lack of sleep causes the increased risk or if the two are just correlated.”

In 2016, Columbia University was named one of five American Heart Association’s Go Red for Women Strategically Focused Research Network Centers. The Center’s $3.7 million funding supports multifaceted research projects over four years looking at sleep and cardiovascular risk across women’s life stages. “We believe there is substantial evidence suggesting that lack of sleep, poor sleep habits, and poor quality of sleep are risk factors for cardiovascular disease,” says Dr. Mosca, Executive Center Director. “We wanted to study the problem of lack of sleep and sleep patterns in women because they have unique life stages that put them at high risk for abnormal sleep patterns. The study goal is to use three scientific approaches – population-based science, clinical science, and basic science – to determine which women are at risk for sleep problems and to determine if there is a causal relationship with heart problems.”

Population-Based Study

In the first year, the Center’s population-based research project, led by Dr. Brooke Aggarwal, a behavioral scientist in the Division of Cardiology, recruited 500 women between the ages of 20 and 79 to examine sleep patterns and cardiometabolic risk at different stages of life. “We’re looking to see if a woman’s reproductive life stage modifies any relationship that we may find between sleep and cardiovascular health,” says Dr. Aggarwal. “Close relationships are generally thought to be beneficial, but negative relationships might increase the risk of heart disease. One’s perception of social support – such as feeling cared about, valued, and loved – may be more important than the simple presence of a spouse or partner.”

Clinical Trial

In the Center’s second project, participants from the population cohort are being invited to enroll in a clinical trial in which they are asked to restrict their sleep by 90 minutes each night for six weeks; an accelerometer worn on their wrists tracks hours of sleep. Dr. Marie-Pierre St-Onge, a nutrition scientist and obesity researcher, serves as the Principal Investigator of this arm of the study, which is comparing the impact of sleep restriction on diet, exercise habits, amounts of body fat, and cardiometabolic risk factors to baseline sleep patterns to determine if lack of sleep is a causal factor in the development of heart disease. “If the answer is yes, that means we should include lack of sleep as a major lifestyle risk factor in standard screening guidelines for heart disease, just as we include smoking, physical activity, and diet,” says Dr. St-Onge, Center Director, who served as Chair of an American Heart Association major scientific statement on sleep and cardiometabolic risk published in Circulation in November 2016.

Basic Science

Dr. Sanja Jelic is the Principal Investigator of the basic science component examining the molecular changes that occur when premenopausal and menopausal women restrict sleep and how those changes raise the risk of heart disease. All of the women who are enrolled in the clinical project are also enrolled in the basic science project. Dr. Jelic believes that the effect of sleep restriction on endothelial dysfunction can lead to cardiovascular risk. She has developed a novel technique to directly assess abnormal activation of these cells, which she previously used to study obstructive sleep apnea. “The goal here is to see whether sleep deprivation affects vascular function at all and to determine the mechanisms,” she says. “Knowing mechanisms may ultimately lead us to new ways to improve vascular health in people who do not get sufficient sleep.”

Dr. Jelic collects the endothelial cells via a small intravenous catheter similar to a modified blood draw. “We’re currently looking into pathways that regulate inflammation and nitric oxide bioavailability and oxidative stress that may play a key role in vascular dysfunction,” explains Dr. Jelic. “We are also seeking to determine the impact of sleep restriction on endothelial apoptotic rate and repair capacity.”

Dr. Jelic’s preliminary data seems to indicate that some of the molecular pathways are being altered. “It’s well known that lack of sleep alters the activity pathway and affects a person’s ability to make decisions or perform complex tasks or operate machinery,” says Dr. Jelic. “These are mostly behavioral observations. What we are focusing on are hardcore cardiovascular changes that we think are going to be affected by this behavior.”

The researchers emphasize that their work seeks to call attention to the importance of adequate sleep to metabolic and general health. “One of our main motivations is to contribute to the evidence base that will allow for sleep habits and sleep disorders to be routinely screened for in the physician’s office,” says Dr. Mosca. “We all screen for cardiovascular risk factors, such as cholesterol and blood pressure. We often ask about diet and exercise. Given the strong correlation between sleep habits and cardiovascular risk, we want to put this on the radar of every physician to start screening for sleep disorders and poor sleep patterns and refer their patients to pulmonologists – many of whom are sleep specialists – for evaluation and possible treatment.”

Reference Articles
Mosca L, Ouyang P, Hubel CA, Reynolds HR, Allison MA. Go Red for Women Strategically Focused Research Network Centers. Circulation. 2017 Feb 7;135(6):609-11.

Emin M, Wang G, Castagna F, Rodriguez-Lopez J, Wahab R, Wang J, Adams T, Wei Y, Jelic S. Increased internalization of complement inhibitor CD59 may contribute to endothelial inflammation in obstructive sleep apnea. Science Translational Medicine. 2016 Jan 6;8(320):320ra1.

St-Onge MP, Grandner MA, Brown D, Conroy MB, Jean-Louis G, Coons M, Bhatt DL. Sleep Duration and Quality: Impact on Lifestyle Behaviors and Cardiometabolic Health: A Scientific Statement from the American Heart Association. Circulation. 2016 Nov 1;134(18):e367-e386.

For More Information
Dr. Brooke Aggarwal | [email protected]
Dr. Sanja J. Jelic | [email protected]
Dr. Lori J. Mosca | [email protected]
Dr. Marie-Pierre St-Onge | [email protected]