This study assessed the relationship between PDSA and habitual snoring with incident cardiovascular events and all- cause mortality in a large multi-ethnic cohort. Even after adjusting for multiple potential confounders, we observed that PDSA but not habitual snoring is significantly associated with incident cardiovascular events and all-cause mortality. The current study provides further support for sleep apnea as a novel CVD risk factor and the need for clinical trials to define the role of sleep apnea screening and treatment in cardiovascular disease reduction. Although physician-diagnosed sleep apnea and self-reported snoring each provide a limited amount of information on sleep apnea severity, our analyses indicate that PDSA is potentially more informative than snoring in predicting adverse cardiovascular health outcomes. There is likely substantial misclassification in the use of reports of physician-diagnosed sleep apnea. In fact, it is estimated that as many as 85% of individuals with sleep apnea are undiagnosed and untreated (25
). It is likely that those who reported this diagnosis were referred for relatively symptomatic and more severe disease. Thus, PDSA may represent a less sensitive but relatively specific marker of moderate to severe sleep apnea.
While there have been consistent associations between sleep apnea and cardiovascular risk factors/ cardiovascular disease (7
), data on the association between snoring and cardiovascular risk/ cardiovascular diseases have been rather weak and inconsistent other than reports relating snoring to stroke (12
). Our findings show that while the majority of those with PDSA reported snoring (98%), snoring history alone is likely not of sufficient specificity to identify individuals with the most severe overnight physiological stresses who may be at greatest risk for adverse cardiovascular disease and mortality. This observation also is consistent with data from the Sleep Heart Health Study that showed that the highest risk for incident cardiovascular disease, stroke, and mortality is in individuals with moderate to severe sleep apnea (18
). It should be noted that we analyzed a composite outcome, which only included 76 cases of stroke. Given a postulated mechanism whereby snoring per se may cause carotid vessel trauma (27
), it is possible that our analyses were under-powered to detect a unique association between snoring and cerebrovascular events.
We also explored the consistency of associations in men and women, and across race/ethnic groups. Of interest, the point estimates for the relationship between PDSA and incident CVD were similar in men and women but did not reach statistical significance in women due to the lower number of reported PDSA and fewer events. This contrasts with the Sleep Heart Health Study findings which showed much stronger point estimates in men than in women when characterizing exposure using the apnea hypopnea index. This important difference may be explained by the younger age of the women or by the greater predictiveness of a simple report of physician diagnosed sleep apnea compared to an apnea hypopnea index measured at a single time point.
We also explored the consistency of associations across 4 racial/ethnic groups. Although there was limited power to detect subgroup differences, overall similar patterns were seen for Caucasians, Chinese, African Americans and Hispanics, with a suggestion that the highest relative risks for death occurred in Hispanics. Further research of larger samples of women and ethnic minorities are needed to better understand whether population differences exist in vulnerability to sleep apnea-associated CVD.
The biological plausibility of our findings has been well described and includes deleterious effect of sleep apnea and associated hypoxemia on the cardiovascular system through activation of the sympathetic nervous system, oxidative stress, endothelial dysfunction, insulin resistance and dyslipidemia. These mechanisms, in turn, increases risk for hypertension, diabetes mellitus and increased intima media thickness (5
). The results of the current analysis may underestimate the total impact of PDSA on CVD since we adjusted for many of the intermediate risk factors that may be in the causal pathway linking sleep apnea to cardiovascular disease.
The strengths of our study included the large multi ethnic nature of our cohort, rigorous adjudication procedures, availability of cardiovascular risk factors that were included in our models and relatively long follow up period.
Our study had several limitations, notably the lack of objective data on snoring and/sleep apnea severity and the use of a self-reported measure of PDSA. Despite this limitation, our findings were consistent with studies such as the Sleep Heart Health study which used objective diagnosis of sleep apnea. We also had limited power to test for subgroup differences. Although we adjusted for several potential confounders, it is possible that unmeasured residual confounding occurred. In particular, it is possible that individuals reporting a PDSA are individuals who seek medical attention for other medical conditions that we did not assess.
In summary, this study of a large multiethnic cohort showed that PDSA was associated with increased risk for incident CV events and all- cause mortality, with estimates similar across gender and race/ethnic groups. Habitual snoring was not independently associated with either incident CV events or all- cause mortality.