Troubled Sleep, Troubled Hearts

Troubled Sleep, Troubled Hearts
By Michael Gibbons

Posted on: March 26, 2009

Science has not yet confirmed to everyone's satisfaction that obstructive sleep apnea (OSA) causes cardiovascular problems, but ample studies show a link between OSA and increased risk for hypertension, stroke, myocardial infarction, coronary artery disease (CAD) and cardiac arrhythmias.

We must, however, before the final word comes down.

That word will come in the form of the monumental Sleep Heart Health Study (SHHS), now in its 12th year. The SHHS is a multi-center cohort study implemented by the National Heart, Lung and Blood Institute in 1996 to determine whether OSA is associated with an increased risk of coronary heart disease, stroke and hypertension - as mounting evidence suggests it is.

Researchers at the SHHS's seven investigative sites are reviewing a decade of data on approximately 6,400 middle-aged OSA patients who have undergone at-home polysomnography along with other tests charting their cardiovascular health.

In the meantime, sleep experts more than suspect a causal link between OSA and heart problems.

"There is more hypertension among untreated apnea patients than among the general population," said Paul Selecky, MD, a pulmonologist and medical director of the six-bed sleep center at Hoag Memorial Hospital, Newport Beach, CA.

Inflamed Blood Vessels
"Cause and effect has not been established yet, but there are certainly links to stroke, hypertension and cardiovascular disease," added Donna Arand, PhD, clinical director of the Kettering Sleep Disorder Center in Kettering, OH.

Published research shows OSA activates the sympathetic nervous system and releases inflammatory cytokines that inflame the blood vessels, Selecky said. Continuous positive airway pressure (CPAP) lowers this inflammation, often within a few days, he said.

Some cardiologists and endocrinologists in Orange County, CA, are so attuned to the presumed association between OSA, heart problems and diabetes that they send patients with difficult-to-manage high blood pressure or diabetes Selecky's way for OSA testing, especially if those patients are chronic snorers who may not have other symptoms and signs of OSA.

"The idea of OSA causing hypertension is based on evidence of a dose-response relationship showing the higher the apnea-hypopnea index (AHI), the greater the increase in blood pressure," Arand emphasized. "That has been shown in a number of studies."

'Fight-or-Flight' Response
When an episode of OSA causes a transient rise in blood pressure, researchers believe it results in increasing activity in the sympathetic nervous system - the "fight-or-flight" response.

"Over time with these transient changes, you start getting sustained increases in sympathetic nervous system activity that researchers believe form the basis of development of hypertension following chronic sleep apnea," Arand said. "But the actual pathophysiology underlying it is not really clear."

Repeated breath stoppages every night for years can starve the heart of oxygen and increase the risk of heart attack or death by 30 percent, according to one poster presentation at the 2007 American Thoracic Society conference in San Francisco. The more severe the OSA, the greater the risk, the study found.

"There is some evidence to make us believe that when sleep apnea is appropriately treated, the risk of heart disease can be lowered," said researcher Neomi Shah, MD, of Yale University.

For 5 years, Shah and colleagues followed 1,123 patients referred for sleep apnea evaluation. Of these, 510 had an AHI greater than 15. After adjusting for traditional CAD risk factors, the researchers associated OSA with a 30 percent increased risk of CAD or death.

A related ATS poster associated sleep apnea with pregnancy-induced diabetes and high blood pressure.

Assorted Studies
National and international studies continue to pour in linking OSA and heart trouble. The ATS conference alone featured several other posters on the topic, such as:

A Spanish study of 60 patients with congestive heart failure (CHF) and OSA found CPAP improves symptoms of CHF. The improvement is greatest in CHF patients with a left ventricular ejection fraction greater than 30 percent.

Echocardiograms taken of more than 2,000 SHHS subjects revealed an association between OSA and hypertrophy and decreased systolic function of the left ventricle.

After adjusting for risk factors like smoking, Australian researchers studying 110 known snorers concluded snoring is a risk factor for carotid artery atherosclerosis.

"Snoring exerts a local, pathogenic influence on arterial plaque formation, possibly via chronic carotid artery wall vibration," they wrote.

Another study of 154 patients at Kings County Hospital Sleep Clinic, part of SUNY-Downstate Medical Center, Brooklyn, NY, found no relationship between AHI and body mass index with increased incidence of premature ventricular arrhythmias (PVC).

Nevertheless, it did find that administering CPAP decreased PVC incidence.

"Reduction in PVCs might be due to the decrease in the transmural pressure," researchers speculated.

SHHS Methodology
Most likely, data linking OSA and cardiovascular risk are valid. But which causes which? That's the question the SHHS, the most comprehensive OSA/cardiac investigation ever done, hopes to answer.

"Previously, we have published 30 or 40 papers documenting cross-sectional associations between OSA and hypertension, increased risk of stroke, sleepiness, etc., after adjusting for other risk factors," said George O'Connor, MD, MS, professor of medicine at Boston University and principal investigator of the Framingham Heart Study, a component of the SHHS.

"But the primary hypothesis for the study, and the major reason for it, was to see whether, prospectively, OSA predicts for cardiovascular disease." That means ruling out "reverse causation," that is, heart disease somehow causing OSA instead of vice versa.

SHHS researchers have entered their final phase of NIH funding.

"We're now in the process of analyzing the outcomes data," O'Connor said. "We basically have nine or 10 years of follow-up data from the initial polysomnography."

They should complete their primary analyses this year, although additional analyses could stretch on for years.

"There are always many more questions to ask of such a rich database," he said. "Will we answer the question in the coming year when we do these prospective outcomes analyses? If the results are clear, we may feel our work is done here. If not, we may continue to look at outcomes for 15 years, not just 10."

Michael Gibbons is senior associate editor at ADVANCE

tattooyu wrote:I truly believe I was on my way to heart problems, and because I'm relatively young (36), I feel therapy has really put me in the right direction. I was having PVCs every single day. Now they only pop up occasionally, if that. I'm still paranoid that years of untreated OSA has already done damage to my heart, and I might still ask my doctor for an echocardiogram. I know the cardio catheter is probably the most accurate way to tell, but the risks of that are too great for me at my age right now. Before therapy, I did start having symptoms similar to CHF which is why I am still wondering how my heart it doing.

Thanks, Rooster! Awesome.