CPAP Reverses Atherosclerotic Effects of Sleep Apnea

SAO PAULO, Brazil, Sept. 28 -- Treatment of obstructive sleep apnea with continuous positive airway pressure reverses early signs of atherosclerosis, researchers here found.
In a carefully controlled, randomized trial, CPAP therapy reduced carotid intima-media thickness 9% over four months and improved arterial stiffness 10% among men with severe sleep apnea reported in the first October issue of the American Journal of Respiratory and Critical Care Medicine.
These were "remarkable" changes as great as improvements seen in statin trials over six months to a year, said Luciano F. Drager, M.D., of the University of São Paulo here, and colleagues.
Furthermore, the findings provide the first solid evidence of the long-suspected causal link between sleep apnea atherosclerosis, commented T. Douglas Bradley, M.D., and Dai Yumino, M.D., both of the Center for Sleep Medicine and Circadian Biology at the University of Toronto, Canada, in an accompanying editorial.
"Because obstructive sleep apnea affects approximately 10% of the adult population," they wrote, "these results may have important public health implications for prevention of atherosclerotic diseases."
The link has been difficult to prove because the majority of sleep apnea patients have other risk factors for atherosclerosis, including obesity, hypertension, high cholesterol levels, insulin resistance, and hyperglycemia, they said.
Of the 400 consecutive men who had more than 30 apnea and hypopnea events per hour during a polysomnographic sleep test at the Brazilian center, the researchers excluded all but 24 for atherosclerosis risk factors.
The study included only treatment-naïve men 60 or younger with a body mass index no greater than 35 kg/m2 and no diabetes, hypertension, cerebrovascular or heart disease, renal failure, smoking history, or chronic use of any medication.
These participants were randomly assigned to CPAP or no treatment for four months.
On CPAP therapy, the average apnea-hypopnea index dropped to 4.5 events per hour and early vascular markers of atherosclerosis fell as well.
Carotid intima-media thickness improved significantly from baseline to four months in the CPAP group (707 versus 645 µm, P=0.04) whereas it got slightly worse in the control group (732 versus 740 µm). The overall difference between the groups was significant (P=0.02).
Arterial stiffness as measured by carotid-to-femoral artery pulse-wave velocity was unchanged in the control group (10.1 versus 10.3 m/s) but decreased significantly in all CPAP-treated patients (mean 10.4 versus 9.3 m/s, P<0.001). Again, the CPAP group improved significantly compared with controls (P<0.001).
The inflammatory marker C-reactive protein likewise improved only in the CPAP group (3.7 versus 2.0 mg/L, P=0.001, compared with 3.1 versus 3.3 mg/L for controls, P=NS) with a significant difference between groups in favor of CPAP (P<0.001).
The sympathetic activation marker catecholamine showed the same pattern of improvement in the CPAP group (365 versus 205 pg/mL, P<0.001) but not the control group (362 versus 357 pg/mL, P=NS) for an overall significant difference favoring CPAP (P<0.001).
No carotid plaque was observed in any participant, as expected because of the strict exclusion criteria. Carotid diameter did not change significantly with CPAP, likely because of the short study duration, the researchers said.
"These findings were all the more remarkable because there was no concurrent change in weight, lipid levels, or blood pressure," Drs. Bradley and Yumino said.
Early detection of atherosclerosis and subsequent therapeutic intervention can "significantly alter the natural course of cardiovascular disease," suggesting that the findings do have clinical implications, Dr. Drager and colleagues said.
However, the small sample size and highly selected patient population in the study may limit applicability of the findings, Drs. Bradley and Yumino said.
Before sleep apnea "can take its place with traditional atherogenic factors as a target for risk reduction, large-scale randomized trials that will determine whether treatment of obstructive sleep apnea prevents ischemic cardiovascular and cerebrovascular events should be undertaken," the editorialists wrote.
Therefore, it is premature to recommend apnea screening and CPAP treatment as a strategy to prevent atherosclerosis, the editorialists cautioned.
The study was supported by the Fundação de Amparo à Pesquisa do Estado de São Paulo, Conselho Nacional de Desenvolvimento Cientìfico e Tecnológico, and the E.J. Zerbini Foundation. All the CPAP machines were provided by Respironics, a manufacturer of CPAP devices.
The researchers and Dr. Bradley reported no conflicts of interest. Dr. Yumino reported receiving support from an unrestricted research fellowship from Respironics. Primary source: American Journal of Respiratory and Critical Care MedicineSource reference: Drager LF, et al "Effects of Continuous Positive Airway Pressure on Early Signs of Atherosclerosis in Obstructive Sleep Apnea" Am J Respir Crit Care Med 2007; 176: 706-712. Additional source: American Journal of Respiratory and Critical Care MedicineSource reference: Yumino D, Bradley TD "Pathogenesis of Atherosclerosis: Is Obstructive Sleep Apnea the New Kid on the Block?" Am J Respir Crit Care Med 2007; 176: 634-635.