What is the link between CRP and OSAHS?

* The role of inflammation is well established in theories describing atherosclerotic disease. Virtually every step in atherogenesis is believed to involve cytokines and other bioactive molecules and cells that are characteristic of inflammation. Studies have shown that an elevated level of CRP, which is a serum marker of inflammation, in the high-normal range (0.2 to 1.0 mg/dL) in apparently healthy adults increases the relative risk of cardiovascular disease by 1.5.¹

The link between OSAHS and cardiovascular disease is well established in several broad community-based studies. The mechanism in the development of cardiovascular disease is attributed to increased sympathetic activity resulting from sleep deprivation and fragmentation and repetitive hypoxemic events with significant arterial desaturation. These factors are believed to lead to the activation of proinflammatory cytokines.

Although many aspects of the relationship between elevated CRP levels and OSAHS are controversial, there is agreement that many patients with moderate to severe OSAHS have elevated CRP levels. It is also known, however, that CRP concentration is increased in obese patients with insulin resistance. Insulin resistance may occur in association with OSAHS in obese patients. Most of the studies that have identified elevated CRP levels in patients with OSAHS included a significant percentage of obese patients. Therefore, the interpretation that CRP is elevated secondary only to OSAHS and not in response to obesity has been questioned. Two major studies have addressed this question, with conflicting results.

Guilleminault and associates² studied 156 patients with OSAHS, 39 patients with upper airway resistance syndrome, and a control group of 54 persons. Their results showed that only body mass index (BMI) was significantly associated with high CRP values, and they concluded that obesity is a risk factor for elevated CRP levels and not sleep-disordered breathing.

In contrast, Yao and associates³ studied 316 consecutive Asian men to determine whether nonobese patients with a mean BMI of 25.4 had elevated CRP levels associated with OSAHS. Their findings showed that OSAHS is associated with increased levels of CRP in nonobese men. Although the discrepancy between these 2 studies may reflect a difference between Caucasians and Asians, the Japanese study showed a relationship between OSAHS and elevated CRP levels. It would be logical to assume that elevated CRP levels would also be found in a Caucasian population of patients with OSAHS that included a significant number of nonobese patients.

Many other studies also have indicated a strong association between OSAHS and elevated CRP levels.^4,5 In these studies, patients with newly diagnosed OSAHS had significantly higher CRP levels than did patients without OSAHS, when matched for BMI. These elevations are usually seen in patients with moderate to severe OSAHS.

Most of the evidence supports an association between OSAHS and elevated CRP levels with or without associated obesity. Evidence also supports the link between an elevated CRP level and an increased risk of cardiovascular disease. Most of the studies that have evaluat- ed OSAHS treatment--either with continuous positive airway pressure (CPAP) or surgery--have demonstrated a reduction of CRP levels following treatment.

Many studies have shown that CPAP therapy reduces CRP levels, further implicating OSAHS as the cause of elevated CRP levels.⁶ Two studies also have demonstrated a reduction in CRP levels after surgical correction of OSAHS.^7,8 My colleagues and I⁷ studied the effect of surgery for OSAHS on CRP levels. In addition to showing that CRP levels dropped after successful surgery, we also showed that CRP levels fell in patients who improved after surgery but failed to achieve a complete cure. This is evidence that surgical improvement of OSAHS even without cure may have beneficial long-term cardiovascular effects. Even minimally invasive treatment, such as the pillar implant technique, resulted in a reduction in CRP level.

Although studies of the relationship between CRP levels and OSAHS continue, current evidence suggests that OSAHS causes elevated CRP levels and elevated CRP levels translate into an increased risk of cardiovascular disease. Treatment of OSAHS--whether with CPAP, minimally invasive techniques, or surgery--reduces CRP levels and, therefore, likely reduces the risk of cardiovascular disease.

To our readers:

We wish to acknowledge an error that appeared in the April 2007 issue. The article "Hemoptysis: A review of causes, evaluation, and treatment" (pages 139-148) should not have included Figure 4 on page 148. This Figure was originally published in the following article: Swanson KL, Johnson CM, Prakash UBS, et al. Bronchial artery embolization: experience with 54 patients. Chest. 2002;121:789-795. It was presented as Figure 2 on page 791.

We regret the error and extend our apologies to Drs Swanson, Johnson, Prakash, McKusick, Andrews, and Stanson and to Chest.

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Yokoe T, Minoguchi K, Matsuo H, et al. Elevated levels of C-reactive protein and interleukin-6 in patients with obstructive sleep apnea syndrome are decreased by nasal continuous positive airway pressure.

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Friedman M, Bliznikas D, Vidyasagar R, et al. Reduction of C-reactive protein with surgical treatment of obstructive sleep apnea hypopnea syndrome.

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Kinoshita H, Shibano A, Sakoda T, et al. Uvulopalatopharyngoplasty decreases levels of C-reactive protein in patients with obstructive sleep apnea syndrome.

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