Association of Plasma Homocysteine with Self-Reported Sleep Apnea Is Confounded by Age: Results from the National Health and Nutrition Examination Survey 2005-2006
High levels of plasma homocysteine are implicated in the pathogenesis of cardiovascular diseases especially if accompanied by sleep apnea, but a direct pathogenetic link between plasma homocysteine levels and obstructive sleep apnea is debatable. This association can have far-reaching public health implications considering the inverse association between folate and plasma homocysteine. We used data from the 2005-2006 cycle of the National Health and Nutrition Examination Survey (NHANES) to test the hypothesized associations. Of the 4490 subjects included in analysis, 177 reported sleep apnea. Age-standardized and design-effect-corrected prevalence rates were differential across gender, plasma homocysteine, and red cell folate status. Plasma homocysteine was positively correlated with age ( , ). Multivariate analyses using sociodemographic and clinical covariates demonstrated that plasma homocysteine levels retained their respective associations with self-reported sleep apnea in all models except when age was included as a covariate. Our results demonstrate that the claimed association of plasma homocysteine with sleep apnea may be confounded by age. 1. Introduction Obstructive sleep apnea (OSA)—a disorder in which a person frequently stops breathing during sleep—results from an obstruction of the upper airway that occurs because of inadequate motor tone of the tongue and/or airway dilator muscles. In the United States, the prevalence of OSA is estimated to be 3–7% in men and 2–5% in women [1]. In addition, up to 93% of women and 82% of men may already have an undiagnosed moderate to severe OSA [2]. Further, the comorbid occurrence of OSA with obesity is well-recognized: prevalence of OSA is reported to be 41% among patients with a body mass index (BMI) greater than 28？Kg/m2 and as high as 78% in morbidly obese patients who present for bariatric surgery [3, 4]. Of greater interest and importance, however, is the association of OSA with cardiovascular disorders [5]. OSA has been identified as a crucial intermediate factor in the pathophysiology of hypertension, ischemic heart disease, arrhythmias, stroke and diabetes. It has been shown that habitual snorers are at a 2 times higher likelihood of developing type 2 diabetes independently of other covariates [6]. Also, treatment of sleep-disordered breathing is known to improve outcomes after congestive heart failure and stroke [7, 8]. A possible mechanism for the strong correlation between OSA and cardiovascular risk factors is the concomitant association of plasma homocysteine levels with both these
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