When in Doubt, Pressurize the Snout

Abstract & Commentary

By Barbara A. Phillips, MD, MSPH, Professor of Medicine, University of Kentucky; Director, Sleep Disorders Center, Samaritan Hospital, Lexington. Dr. Phillips serves on the speakers bureaus for Cephalon, Resmed, and Respironics.

Synopsis: CPAP treatment lowered blood pressure and improved metabolic abnormalities in patients with obstructive sleep apnea.

Source: Sharma SK, et al. CPAP for the metabolic syndrome in patients with obstructive sleep apnea. N Engl J Med 2011;365:2277-2286.

This report comes from the All India Institute of Medical Sciences Hospital in New Delhi, India. (Did you know that being Indian is an independent risk factor for sleep apnea?)1 The authors recruited 86 people who met the following inclusion criteria: no previous or current continuous positive airway pressure (CPAP) therapy, moderate or severe obstructive sleep apnea, and excessive daytime sleepiness. Exclusion criteria were previous or current treatment for hypertension, diabetes mellitus, or dyslipidemia, or any evidence of end-organ damage due to these conditions. Patients were randomly assigned to undergo either CPAP or sham CPAP for 3 months, followed by a washout period of 1 month and then crossover to the other intervention for 3 months. (Sham CPAP was basically a CPAP mask with tiny escape holes in it.) The metabolic syndrome was defined according to the National Cholesterol Education Program's Adult Treatment Panel III criteria2 with the cutoff value for defining abdominal obesity of 90 cm for men and 80 cm for women, as recommended by the World Health Organization guidelines for South Asians.3 Individual criteria were each given a score, which were summed; ≥ 3 was considered to indicate the presence of the metabolic syndrome. Participants underwent an assessment at enrollment that was repeated at the beginning and end of each of the two 3-month intervention periods.

All participants underwent overnight polysomnography. Obstructive sleep apnea was defined as an apnea-hypopnea index (AHI) score of 5 or more events per hour, with the severity described as mild for an AHI score of 5 to < 15, moderate for an AHI score of 15 to 30, and severe for an AHI score > 30. Excessive daytime sleepiness was ascertained with the Epworth Sleepiness Scale, with a score > 10 considered to indicate sleepiness. Other measures included anthropomorphic measures, blood pressure, fasting blood glucose, fasting plasma insulin level, glycated hemoglobin level, triglycerides, high-density lipoprotein (HDL) cholesterol, total cholesterol levels, low-density lipoprotein (LDL) cholesterol level, and insulin resistance. In addition, the investigators measured abdominal fat content with a cross-sectional computed tomographic scan, and assessed carotid intima-media thickness with two-dimensional ultrasonography.

Seventy-five of the 86 patients had the metabolic syndrome at the time of recruitment. The cohort was about 90% male, with a mean age of 45. Their mean BMI was about 33 kg/m2. About 20% of them had hypertension and 22% had diabetes. CPAP treatment (compared to sham CPAP) was associated with statistically significant mean decreases in systolic blood pressure (3.9 mmHg), diastolic blood pressure (2.5 mmHg), total cholesterol (13.3 mg/dL), non-HDL cholesterol (13.3 mg/dL), LDL cholesterol (9.6 mg/dL), triglycerides (18.7 mg/dL), glycated hemoglobin (0.2%), and metabolic syndrome score (0.33). There was a statistically significant increase in HDL to total cholesterol ratio for the active CPAP group. The frequency of the metabolic syndrome was reduced after active CPAP therapy compared with sham CPAP; reversal occurred in 11 of 86 patients using CPAP compared with 1 of 86 using sham CPAP. Of the 14 patients whose metabolic syndrome resolved after CPAP therapy, the specific criterion that resolved was blood pressure in five patients; fasting blood glucose in two; triglycerides in two; HDL cholesterol in three; triglycerides and HDL cholesterol in one; and triglycerides, HDL cholesterol, and fasting blood glucose in one. None of the patients showed improvement in abdominal circumference. Weight fell about a third of a kg with CPAP, compared with a gain of about a third of a kg with sham CPAP.

Two patients were CPAP-intolerant, and one could not use sham CPAP. Overall adherence was better with CPAP than with sham CPAP, and was better if CPAP was given first (4.8 hrs/night) than if it were given after placebo CPAP (4.1 hrs/night). Of the 86 patients, 51 used CPAP for an average of at least 5 hours a night. This group had larger reductions in blood pressure as well as greater improvements in metabolic measures than the group that used CPAP less. Adverse events included skin irritation (in 51%), nasal bridge discomfort (44%), nasal congestion (28%), headache (26%), and mask leaks (in 30%). Patients undergoing sham CPAP did not have improvement in sleepiness. Accelerated hypertension developed in one patient who got CPAP therapy first.

Commentary

This well-done, randomized, placebo-controlled trial has demonstrated that CPAP improves blood pressure as well as the metabolic components of the metabolic syndrome. The improvement in blood pressure with CPAP comes as no surprise, as this has been documented before (although with the notable caveat that adherence makes a difference).4,5 The data about CPAP and the metabolic syndrome are more sparse and less consistent,6,7 though several studies had indicated that CPAP use is associated with reduction in insulin resistance.

The authors point out that the improvement in blood pressure and metabolic parameters that resulted from CPAP in these patients are likely to lead to a reduction in cardiovascular risk. But there's a catch: you have to use it. Those individuals using CPAP at least 5 hours per night derived the most benefit from the treatment in this and in other reports. CPAP adherence is notoriously poor, but I'd wager that it's at least as good as long-term adherence to statins. Furthermore, CPAP improves not only blood pressure and metabolic factors, but also alertness, crash risk, and cognitive function.8,9 Every time you urge a patient who is noncompliant with statins to use these pills, which cause no immediately perceptible improvement in symptoms, consider that there is a significant chance that this patient would also benefit from CPAP.

References

1. Udwadia ZF, et al. Prevalence of sleep-disordered breathing and sleep apnea in middle-aged urban Indian men. Am J Respir Crit Care Med 2004;169:168-173.

2. Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults. Executive summary of the third report of the National Cholesterol Education Program (NCEP) expert panel on detection, evaluation, and treatment of high blood cholesterol in adults (Adult Treatment Panel III). JAMA 2001;285:2486-2497.

3. WHO Expert Consultation. Appropriate body-mass index for Asian populations and its implications for policy and intervention strategies. Lancet 2004;363:157-163. [Erratum, Lancet 2004;363:902.]

4. Lozano L, et al. Continuous positive airway pressure treatment in sleep apnea patients with resistant hypertension: A randomized, controlled trial. J Hypertens 2010;28:2161-2168.

5. Campos-Rodriguez F, et al. Effect of continuous positive airway pressure on ambulatory BP in patients with sleep apnea and hypertension: A placebo-controlled trial. Chest 2006;129:1459-1467.

6. Coughlin SR, et al. Cardiovascular and metabolic effects of CPAP in obese males with OSA. Eur Respir J 2007;29:720-727.

7. Mota PC, et al. APAP impact on metabolic syndrome in obstructive sleep apnea patients. Sleep Breath 2011; 15:665-672.

8. Tregear S, et al. Continuous positive airway pressure reduces risk of motor vehicle crash among drivers with obstructive sleep apnea: Systematic review and meta-analysis. Sleep 2010;33:1373-1380.

9. Antic NA, et al. The effect of CPAP in normalizing daytime sleepiness, quality of life, and neurocognitive function in patients with moderate to severe OSA. Sleep 2011;34:111-119.