Elsevier

Atherosclerosis

Volume 208, Issue 2, February 2010, Pages 490-495
Atherosclerosis

The incremental role of obstructive sleep apnoea on markers of atherosclerosis in patients with metabolic syndrome

https://doi.org/10.1016/j.atherosclerosis.2009.08.016Get rights and content

Abstract

Objective

Metabolic syndrome (MS) is associated with subclinical atherosclerosis, but the relative role of obstructive sleep apnoea (OSA) is largely unknown. The main objective of this study is to determine the impact of OSA on markers of atherosclerosis in patients with MS.

Methods

Eighty-one consecutive patients with MS according to the Adult Treatment Panel III underwent a clinical evaluation, polysomnography, laboratory and vascular measurements of carotid intima media thickness (IMT), carotid-femoral pulse wave velocity (PWV) and carotid diameter (CD) in a blind fashion. OSA was defined as an apnoea-hypopnoea index (AHI) ≥15 events/hour. Multiple linear regression was performed to determine the variables that were independently associated with the vascular parameters.

Results

Fifty-one patients (63%) had OSA. No significant differences existed in age, sex, MS criteria, and cholesterol levels between patients with (MS+OSA) and without OSA (MS−OSA). Compared with MS−OSA patients, MS+OSA patients had higher levels of IMT (661 ± 117 vs. 767 ± 140 μm), PWV (9.6 ± 1.0 vs. 10.6 ± 1.6 m/s), and CD (6705 ± 744 vs. 7811 ± 862 μm) (P < 0.001 for each comparison). Among patients with MS+OSA, all vascular parameters were similar in patients with and without daytime sleepiness. The independent parameters associated with IMT, PWV, and CD were AHI, abdominal circumference, and systolic blood pressure (R2 = 0.42); AHI and systolic blood pressure (R2 = 0.38); and AHI, age, abdominal circumference and systolic blood pressure (R2 = 0.45), respectively. The R2 of AHI for IMT, PWV and CD was 0.12, 0.10 and 0.20, respectively.

Conclusions

OSA is very common and has an incremental role in atherosclerotic burden in consecutive patients with MS.

Introduction

Metabolic syndrome (MS) is one of several proatherogenic factors including insulin resistance, dyslipidemia, hypertension, and abdominal obesity in the same individual, resulting in increased cardiovascular risk [1]. Accordingly, previous studies have suggested that MS is associated with increased markers of atherosclerosis [2], [3], [4], [5], [6]. However, MS is not a well-defined pathophysiological entity, and the diagnostic criteria are based on expert opinions [7]. Despite ongoing efforts to elucidate the pathophysiological basis of MS, the multiple underlying risk factors are not completely understood, and so far, the increased cardiovascular risk has only been partly explained [8]. Therefore, the search for additional factors that may increase our current understanding of the pathophysiology of MS is highly desirable.

Obstructive sleep apnoea (OSA) is a common condition in the general population and is characterized by recurrent episodes of partial or complete obstruction of the upper airway during sleep, promoting intermittent hypoxia and frequent arousals from sleep [9]. Because obesity is a common risk factor for both MS and OSA, the co-existence of OSA in patients with MS is expected to be high. Previous studies have reported that OSA is highly prevalent in patients with MS referred to sleep laboratories [10], [11]. However, patients referred to sleep laboratories frequently have complaints about sleep and therefore may not be a representative population of patients with MS.

Evidence is mounting that OSA is an independent contributor to cardiovascular disease mainly in patients with sleep complaints, such as daytime somnolence. For instance, in patients referred to sleep studies, severe OSA was associated with increased risk of myocardial infarction and stroke [12], [13]. In addition, OSA is tightly linked and may aggravate each component of MS [10], [14]. In 1998, the term Syndrome Z was proposed as a condition that includes OSA as an additional MS feature [15]. However, the evidence for this theoretic syndrome is scanty. More recently, a cross-sectional study from the Cleveland Family Sleep Study proposed a model that co-aggregates the presence of OSA with other MS criteria. The authors found that OSA was the second-most important determining factor of Syndrome Z, surpassed only by visceral obesity [16]. Recent evidence in patients with OSA, free of comorbidities like hypertension, diabetes, and smoking, shows that early signs of accelerated atherosclerosis [17] were partially reversed with the standard treatment of OSA with continuous positive airway pressure (CPAP) [18]. Moreover, in patients with hypertension, the presence of OSA has additive effects on markers of subclinical atherosclerosis [19], [20]. Therefore, the present study attempts to elucidate the cardiovascular burden represented by OSA in patients with MS. We evaluated the relative role of OSA on validated markers of atherosclerosis in consecutive patients with MS as well as whether the vascular parameters were similar in patients with and without daytime sleepiness.

Section snippets

Material and methods

We studied consecutive patients with a recent diagnosis of MS recruited from the Heart Institute (InCor). No patient had a previous diagnosis of OSA. All participants underwent a detailed clinical history and physical examination. Body mass index (BMI) was calculated after body weight and height were measured with subjects in light clothing without shoes. Abdominal circumference was measured with a soft tape on standing subjects midway between the lowest rib and the iliac crest. Two blood

Results

We initially invited 100 consecutive patients with MS to participate in the study. Two patients declined to perform the sleep study, 4 patients were smokers, and 16 patients were using one or more medications such as hypoglycemics, fibrates, and statins (some patients had more than one exclusion criterion). Therefore, the total study sample comprised 81 patients with MS. Clinical characteristics including age, sex, race, BMI, abdominal circumference, blood pressure, and number of MS criteria

Discussion

The main findings of the present study include: (1) a high prevalence of OSA in consecutive patients with a recent diagnosis of MS; (2) validated markers of atherosclerosis (carotid IMT, carotid-femoral PWV, and CD) were significantly higher in MS patients with than without OSA; (3) OSA was not associated with increased daytime somnolence in this population. Moreover, in patients with MS+OSA, all parameters of vascular impairment were similar in patients with and without daytime sleepiness; (4)

Acknowledgements

Sources of funding: The study was supported by the FAPESP, the CNPq and Fundação Zerbini.

References (42)

  • A.D. Achimastos et al.

    Arterial stiffness: determinants and relationship to the metabolic syndrome

    Angiology

    (2007)
  • K.G. Alberti et al.

    Metabolic syndrome—a new world-wide definition. A Consensus Statement from the International Diabetes Federation

    Diabetes Med

    (2006)
  • C.H. Saely et al.

    Adult Treatment Panel III 2001 but not International Diabetes Federation 2005 criteria of the metabolic syndrome predict clinical cardiovascular events in subjects who underwent coronary angiography

    Diabetes Care

    (2006)
  • C.M. Ryan et al.

    Pathogenesis of obstructive sleep apnea

    J Appl Physiol

    (2005)
  • S.R. Coughlin et al.

    Obstructive sleep apnoea is independently associated with an increased prevalence of metabolic syndrome

    Eur Heart J

    (2004)
  • A. Gruber et al.

    Obstructive sleep apnoea is independently associated with the metabolic syndrome but not insulin resistance state

    Cardiovasc Diabetol

    (2006)
  • H.K. Yaggi et al.

    Obstructive sleep apnea as a risk factor for stroke and death

    N Engl J Med

    (2005)
  • I. Wilcox et al.

    “Syndrome Z”: the interaction of sleep apnoea, vascular risk factors and heart disease

    Thorax

    (1998)
  • N.L. Nock et al.

    Empirical evidence for “Syndrome Z”: a hierarchical five-factor model of the metabolic syndrome incorporating sleep disturbance measures

    Sleep

    (2009)
  • L.F. Drager et al.

    Early signs of atherosclerosis in obstructive sleep apnea

    Am J Respir Crit Care Med

    (2005)
  • L.F. Drager et al.

    Effects of continuous positive airway pressure on early signs of atherosclerosis in obstructive sleep apnea

    Am J Respir Crit Care Med

    (2007)
  • Cited by (118)

    View all citing articles on Scopus
    View full text