Person:

Gottlieb, Daniel

Although obstructive sleep apnea (OSA) is known to have a strong familial basis, no genetic polymorphisms influencing apnea risk have been identified in cross-cohort analyses. We utilized the National Heart, Lung, and Blood Institute (NHLBI) Candidate Gene Association Resource (CARe) to identify sleep apnea susceptibility loci. Using a panel of 46,449 polymorphisms from roughly 2,100 candidate genes on a customized Illumina iSelect chip, we tested for association with the apnea hypopnea index (AHI) as well as moderate to severe OSA (AHI≥15) in 3,551 participants of the Cleveland Family Study and two cohorts participating in the Sleep Heart Health Study. Among 647 African-Americans, rs11126184 in the pleckstrin (PLEK) gene was associated with OSA while rs7030789 in the lysophosphatidic acid receptor 1 (LPAR1) gene was associated with AHI using a chip-wide significance threshold of p-value<2×(10^{−6}). Among 2,904 individuals of European ancestry, rs1409986 in the prostaglandin E2 receptor (PTGER3) gene was significantly associated with OSA. Consistency of effects between rs7030789 and rs1409986 in LPAR1 and PTGER3 and apnea phenotypes were observed in independent clinic-based cohorts. Novel genetic loci for apnea phenotypes were identified through the use of customized gene chips and meta-analyses of cohort data with replication in clinic-based samples. The identified SNPs all lie in genes associated with inflammation suggesting inflammation may play a role in OSA pathogenesis.

Background: Previous studies have documented a high prevalence of atrial fibrillation (AF) in individuals with obstructive sleep apnea (OSA). Central sleep apnea (CSA) has been associated with AF in patients with heart failure. However, data from prospective cohorts are sparse and few studies have distinguished the associations of obstructive sleep apnea from CSA with AF in population studies. Methods and Results: We assessed the association of obstructive sleep apnea and CSA with incident AF among 2912 individuals without a history of AF in the SHHS (Sleep Heart Health Study), a prospective, community‐based study of existing (“parent”) cohort studies designed to evaluate the cardiovascular consequences of sleep disordered breathing. Incident AF was documented by 12‐lead ECG or assessed by the parent cohort. obstructive sleep apnea was defined by the obstructive apnea‐hypopnea index (OAHI). CSA was defined by a central apnea index ≥5 or the presence of Cheyne Stokes Respiration. Logistic regression was used to assess the association between sleep disordered breathing and incident AF. Over a mean of 5.3 years of follow‐up, 338 cases of incident AF were observed. CSA was a predictor of incident AF in all adjusted models and was associated with 2‐ to 3‐fold increased odds of developing AF (central apnea index ≥5 odds ratio [OR], 3.00, 1.40–6.44; Cheyne–Stokes respiration OR, 1.83, 0.95–3.54; CSA or Cheyne–Stokes respiration OR, 2.00, 1.16–3.44). In contrast, OAHI was not associated with incident AF (OAHI per 5 unit increase OR, 0.97, 0.91–1.03; OAHI 5 to <15 OR, 0.84, 0.59–1.17; OAHI 15 to <30 OR, 0.93, 0.60–1.45; OAHI ≥30 OR, 0.76, 0.42–1.36). Conclusions: In a prospective, community‐based cohort, CSA was associated with incident AF, even after adjustment for cardiovascular risk factors.

Background: Insufficient sleep duration and obstructive sleep apnea, two common causes of sleep deficiency in adults, can result in excessive sleepiness, a well-recognized cause of motor vehicle crashes, although their contribution to crash risk in the general population remains uncertain. The objective of this study was to evaluate the relation of sleep apnea, sleep duration, and excessive sleepiness to crash risk in a community-dwelling population. Methods: This was a prospective observational cohort study nested within the Sleep Heart Health Study, a community-based study of the health consequences of sleep apnea. The participants were 1745 men and 1456 women aged 40–89 years. Sleep apnea was measured by home polysomnography and questionnaires were used to assess usual sleep duration and daytime sleepiness. A follow-up questionnaire 2 years after baseline ascertained driving habits and motor vehicle crash history. Logistic regression analysis was used to examine the relation of sleep apnea and sleep duration at baseline to the occurrence of motor vehicle crashes during the year preceding the follow-up visit, adjusting for relevant covariates. The population-attributable fraction of motor vehicle crashes was estimated from the sample proportion of motor vehicle crashes and the adjusted odds ratios for motor vehicle crash within each exposure category. Results: Among 3201 evaluable participants, 222 (6.9%) reported at least one motor vehicle crash during the prior year. A higher apnea-hypopnea index (p < 0.01), fewer hours of sleep (p = 0.04), and self-reported excessive sleepiness (p < 0.01) were each significantly associated with crash risk. Severe sleep apnea was associated with a 123% increased crash risk, compared to no sleep apnea. Sleeping 6 hours per night was associated with a 33% increased crash risk, compared to sleeping 7 or 8 hours per night. These associations were present even in those who did not report excessive sleepiness. The population-attributable fraction of motor vehicle crashes was 10% due to sleep apnea and 9% due to sleep duration less than 7 hours. Conclusions: Sleep deficiency due to either sleep apnea or insufficient sleep duration is strongly associated with motor vehicle crashes in the general population, independent of self-reported excessive sleepiness.