PAULA MUNIZIn the lull of sleep, when the body relaxes and prepares to let you enter the world of dreams, suddenly the air will not go down the throat. Totally unaware of this, the sleeper wakes just enough to breathe in a good gulp of air. This is what happens dozens of times a night to those who suffer from obstructive sleep apnea. This intermittent lack of air causes a series of health problems and, according to the group of Dr Dalva Poyares, from the Federal University of São Paulo (Unifesp), is responsible for structural and functional changes in the heart. Researchers are now looking to reverse these effects and find a cheap and efficient diagnostic marker to detect obstructive sleep apnea, a problem that in São Paulo affects a third of the population. The research is part of a project developed and coordinated by Dr. Sergio Tufik, director of the Sleep Institute, one of the Research, Innovation and Dissemination Centers (Cepid) funded by FAPESP and a global reference in sleep disturbances.
“When a person has apnea they make all the breathing movements but the air doesn’t enter”, says Dalva. The result is negative pressure within the thorax that reduces the return of blood from the lung to the right side of the heart and prevents it filling entirely, forcing the left atrium to contract more. This cardiac heart muscle-building alters the structure of the left atrium to the point of reducing the volume of blood pumped.
The effect had not been detected until now because previous studies used conventional echocardiographs with bidimensional images. “This examination uses parameters in two dimensions to measure the parts of the heart”, explains Dalva, “but the result is not very accurate because the organ has irregular shapes”. With more detailed, three dimensional echocardiography, carried out by echocardiography doctor, Wercules Oliveira, the group from Unifesp managed to detect an increase in the atrium that, although it is not outside the spectrum considered normal, is typical of patients with apnea. This characteristic may explain at least part of the cardiovascular problems common in those who suffer from this nocturnal respiratory difficulty.
An enlarged left atrium had already been pointed out by the Framingham study, an American cardiovascular epidemiology project, as being associated with a greater incidence of cerebral vascular accidents and an indicator of an increase in mortality. The Unifesp study, published at the end of 2009 in Heart, evaluated 56 patients recently diagnosed to be suffering from apnea and showed that part of the functioning of the left atrium may be re-established with the use of CPAP, an apparatus attached to a mask that pumps air into the nose and regularizes the breathing during sleep and should be used every night by those who have apnea. The finding underlines the part apnea plays in the development of cardiac difficulties and highlights the effectiveness of the CPAP as treatment not only for mitigating the lack of air and making sleep more constant and restorative, but also to counteract the consequences of apnea in the organism.
The experiment carried out at the Sleep Institute limited the use of the CPAP to 24 weeks, enough to improve the emptying capacity of the left atrium, but not to diminish the contractive strength of the atrium and reduce it to its normal size. “We still don’t know if it’s possible to reverse the change in shape. It may be necessary to extend the use of the CPAP to a year”, says Dalva.
It is an advance, but one difficulty remains: detecting sleep apnea. The definitive examination is polysomnography, in which the patient sleeps linked up to apparati that measure parameters like respiration and brain and heart activity. But many people who suffer from hypertension, coughs and depression, for example, end up consulting doctors of various specialties without any of them perceiving that the problems are related to the quality of their sleep. There is also no simple and cheap examination that can be done by any doctor, but Dalva’s group may be on the point of resolving this deficiency.
They measured substances linked to oxidative stress, a characteristic of apnea, in the blood of 75 patients and 75 healthy volunteers. The results, published this year in Chest, indicate the amino acid, cysteine, as a possible marker of the disease. The more serious the apnea, the higher the concentration of cysteine in the blood. “It’s the only substance, of those we examined, whose high levels are only related to apnea and not to hypertension, obesity or other factors that are common in those with apnea”, states Dalva.
The discovery was made almost by accident. Cysteine is part of the metabolism of the homocysteine, an amino acid that it was already known was linked to cardiovascular problems. “But no one pays attention to cysteine”, says biologist, Vânia D’Almeida, also from Unifesp. She is one of the authors of the work in Chest and since 1997 she has been studying the homocysteine (see Pesquisa FAPESP nº 60). Alterations in cysteine levels were a surprise in the PhD thesis of Juliana Perry, whose tutors were Tufik and Vânia, which was published in 2007 in Respiratory Physiology & Neurobiology. In a model that reproduces the intermittent lack of air of those with apnea, rats exposed to a low oxygen concentration – with 10% oxygen instead of the normal 21% – and deprived of sleep, have more cysteine in the blood than normal. The idea of measuring this parameter in human beings came from this.
Now it is necessary to examine people with apnea in the initial phase when there are still no symptoms. “We need to know if cysteine is just a marker of the progression of the disease or if it can serve as early diagnosis”, says Vânia. A good database would be the Episono, but only homocysteine was measured in more than a thousand study participants. “We need to reanalyze the samples to measure the cysteine, in addition to repeating the doses with the volunteers who took part in the study”, plans Vânia. They are not vague plans. The subject has already been discussed with Tufik, who declared: “We need this for yesterday.”
CINTRA, F. et al. Cysteine: A potential biomarker of obstructive sleep apnea. Chest. on-line jul. 2010.
OLIVEIRA, W. et al. Impact of continuous positive airway pressure teatment on left atrial volume and function in patients with obstructive sleep apnea assessed by real-time three-dimensional echocardiography. Heart. v. 95, n. 22, p. 1.872-8. nov. 2009.