Habitual snoring may be associated with cardiovascular disease (CVD); however, limited evidence exists among women. We investigated whether frequent snoring is a predictor of coronary heart disease (CHD) and stroke among 42,244 postmenopausal women participating in the Women’s Health Initiative Observational Study. Participants provided self-reported information regarding snoring habits at baseline (1993 to 1998) and were followed up for outcomes through August 2009. Physician adjudicators confirmed CHD (defined as myocardial infarction, CHD death, revascularization procedures, or hospitalized angina) and ischemic stroke. Cox proportional hazards models were used to evaluate whether snoring frequency is a significant predictor of the adjudicated outcomes. We observed 2,401 incident cases of CHD during 437,899 person-years of follow-up. After adjusting for age and race, frequent snoring was associated with incident CHD (hazard ratio [HR] 1.54, 95% confidence interval [CI] 1.39 to 1.70) and stroke (HR 1.41, 95% CI 1.19 to 1.66), and all CVD (HR 1.46, 95% CI 1.34 to 1.60). In fully adjusted models that included CVD risk factors such as obesity, hypertension, and diabetes, frequent snoring was associated with a more modest increase in incident CHD (HR 1.14, 95% CI 1.01 to 1.28), stroke (HR 1.19, 95% CI 1.02 to 1.40), and CVD (HR 1.12, 95% CI 1.01 to 1.24). In conclusion, snoring is associated with a modest increased risk of incident CHD, stroke, and CVD after adjustment for CVD risk factors. Additional studies are needed to elucidate the mechanisms by which snoring might be associated with CVD risk factors and outcomes.
Snoring is a correlate and early symptom of obstructive sleep apnea (OSA). Snoring can also be associated with hypertension, cardiovascular disease (CVD), type 2 diabetes mellitus, and the metabolic syndrome. The current evidence related to snoring has focused primarily on studies of men, relied on cross-sectional studies, and underrepresented women. Habitual snoring occurs among approximately 33% of the general population, and although sleep apnea is more common among men, the prevalence of sleep disturbance and snoring increases among women as they approach and pass through menopause. Emerging evidence suggests this increase in sleep problems could result from aging, weight gain, or menopause-induced hormonal changes, such as decreases in progesterone and estradiol, which might modulate sleep regulation and breathing. Only 1 previous study has prospectively evaluated the associations of snoring with CVD among older women. Although that study also included pre- and perimenopausal women, their findings suggested snoring was associated with a significant increase in CVD. The primary aim of the present study was to determine whether self-reported snoring frequency among postmenopausal women was significantly associated with an increased risk of incident coronary heart disease (CHD), stroke, and all CVD.
Methods
The Women’s Health Initiative is a multicenter national study of 161,808 postmenopausal women who were enrolled in either the clinical trials or observational study. The methods of recruitment, inclusion and exclusion criteria, protocols, and study design have been previously reported. The present study was conducted using longitudinal data from the Women’s Health Initiative-observational study cohort, which included women who were unable or unwilling to participate in the Women’s Health Initiative clinical trials. The Women’s Health Initiative observational study cohort is a multiethnic population of 93,676 women aged 50 to 79 years at baseline from 40 sites around the United States. Women with previous CVD were excluded from the analysis (n = 6,813), as were as those with “do not know” (n = 43,839) or “missing” (n = 780) responses to the snoring question. Recruitment (1993 to 1998) was conducted through mailings to eligible women. All participants were followed up for outcomes through August 2009. All participants provided informed consent, which was approved by the institutional review board of each of the participating study sites.
Snoring was evaluated by self-report at the baseline study visit. The participants were asked, “Over the past 4 weeks, did you snore?” Snoring was measured as “no, not in the past 4 weeks; “yes, less than once a week”; yes, 1 or 2 times a week”; “yes, 3 or 4 times a week”; yes, 5 or more times a week”; or “do not know.” The subjects were classified as nonsnorers, occasional snorers (<1 to 4 times/week), and frequent snorers (≥5 times/week). This variable was analyzed as a categorical variable, with “nonsnoring” as the reference group.
All outcomes were adjudicated by trained physicians using medical records and death certificates. The diagnosis and adjudication of the outcomes for the present study have been previously described and outlined in established protocols. Our primary end point was incident CHD, defined as incident myocardial infarction, CHD death, coronary revascularization, including coronary artery bypass grafting and percutaneous transluminal coronary angioplasty, and hospitalized angina. Participants were followed up for first occurrence of the CHD outcome; those who did not develop CHD were censored at the date of death or last contact. We also assessed incident ischemic stroke and total CVD (CHD and ischemic stroke).
The baseline demographic characteristics were assessed by self-completed questionnaire at the initial visit. Race/ethnicity was categorized as white/Caucasian, black/African American, Hispanic/Latina, Asian, and other. The annual household income was categorized into 3 groups: <$20,000, $20,000 to <$50,000, and ≥$50,000. Education was classified as a 4-level variable: less than high school, high school graduate, some college, and college graduate. Marital status was categorized as a binary variable: married or marriage-like relationship and widowed, divorced, separated, or single.
The behavioral risk factors measured in the baseline questionnaire included smoking, alcohol consumption, and physical activity. Smoking was categorized as current smoker, former smoker, or nonsmoker. Alcohol consumption was measured as servings per week, and physical activity was measured as MET-hours per week, estimated from 9 questions related to the expenditure of energy from recreational activity (including walking and mild, occasional, and strenuous activity).
Physical measurements, including height, weight, waist circumference, and systolic and diastolic blood pressure were assessed at the baseline visit by trained and certified staff. Hypertension was defined as systolic blood pressure >140 mm Hg and/or diastolic blood pressure >90 mm Hg and/or the use of antihypertensive medication. Diabetes was defined by self-report of physician-diagnosed diabetes or the use of diabetes medications. Hyperlipidemia was defined as the use of lipid-lowering medications or having been told of having high cholesterol by a physician. Depression was measured at baseline using the Burnam screening algorithm, a measure that includes 6 items from the 20-item Center for Epidemiological Studies Depression scale and 2 items from the National Institute of Mental Health’s Diagnostic Interview Schedule. A cutpoint of 0.06 was used to identify current depressive symptoms.
We restricted the analyses to those women without missing data for the primary exposure and outcome. The distribution of the demographic characteristics, health behaviors, and cardiovascular risk factors was examined across the snoring categories, and the corresponding associations were statistically tested using analysis of variance and chi-square tests.
The person-years of follow-up were determined from enrollment to a cardiovascular event, loss to follow-up, death, or end of the study period (August 2009). Crude event rates were calculated and compared across the snoring categories. The log-rank test was used to determine whether significant differences were present in survival by snoring group. Hazard ratios (HRs) were computed using Cox proportional hazards models for each outcome. The models were assessed for the proportional hazards assumption.
The covariates considered for the models from baseline data included age, race/ethnicity, education, income, marital status, body mass index (BMI), waist-to-hip ratio, sleep duration, hypertension status, diabetes status, smoking status, alcohol consumption, physical activity, depression, hyperlipidemia, and hormone medication use. The final model included only those covariates that were statistically appropriate (p <0.10) and important because of theoretical considerations. Two-way interactions for snoring and BMI were assessed, and stratified analyses were conducted.
Because >50% of participants reported “do not know” for the primary exposure, we excluded these participants from the primary analysis or the “complete case analysis.” Recognizing that this exclusion might have resulted in a selection bias, we conducted a sensitivity analysis using the inverse probability weighting (IPW) method, in which a model for the probability of “nonmissingness” was fit, and the inverse of these probabilities was used as a weight in the complete case analysis. We used SAS, version 9.3 (SAS Institute, Cary, North Carolina) to perform all statistical analyses.
Results
We observed 2,401 incident cases of CHD within 437,890 person-years of follow-up. At baseline, 47% of women reported no snoring, 33% reported occasional snoring, and 20% reported frequent snoring ( Table 1 ). Regarding race/ethnicity, 84.5% of participants were white/Caucasian, 7.5% were black/African American, 3.6% were Hispanic/Latina, 2.8% were Asian, and 1.5% were other. Compared to the overall cohort, women who reported frequent snoring had a greater BMI, more often were current smokers, had a greater systolic and diastolic blood pressure, and had a greater prevalence of diabetes and depression ( Table 1 ).
| Variable | Overall (n = 42,244) | Snoring Frequency (times/wk) | p Value | ||
|---|---|---|---|---|---|
| 0 (n = 19,886) | <1–4 (n = 13,734) | ≥5 (n = 8,624) | |||
| Age (yrs) | 62.6 (7.2) | 62.8 (7.5) | 62.3 (7.0) | 62.5 (7.0) | <0.001 |
| Race | |||||
| Black/African American | 7.5% | 6.3% | 7.2% | 11.0% | <0.001 |
| White/Caucasian | 84.5% | 87.0% | 84.7% | 78.6% | |
| Hispanic/Latina | 3.6% | 2.5% | 4.1% | 5.6% | |
| Asian | 2.8% | 2.8% | 2.5% | 3.1% | |
| Other | 1.5% | 1.5% | 1.4% | 1.8% | |
| Education | |||||
| Less than high school | 4.4% | 3.2% | 4.5% | 6.8% | <0.001 |
| High school graduate | 15.1% | 13.3% | 15.9% | 18.2% | |
| Some college | 35.6% | 33.9% | 36.6% | 37.8% | |
| College graduate | 44.9% | 49.6% | 43.0% | 37.2% | |
| Income (% annual household) | |||||
| <$20,000 | 12.4% | 11.1% | 10.5% | 18.1% | <0.001 |
| $20,000–$49,999 | 40.6% | 38.6% | 40.8% | 44.6% | |
| ≥$50,000 | 47.1% | 50.3% | 48.6% | 37.3% | |
| Marital status | |||||
| Married or partnered | 71.1% | 69.5% | 78.3% | 63.5% | <0.001 |
| Single/divorced/widowed | 28.9% | 30.5% | 21.7% | 36.5% | |
| Body mass index (kg/m 2 ) | 27.2 ± 5.9 | 25.5 ± 12.1 | 27.7 ± 5.8 | 30.3 ± 6.8 | <0.001 |
| Systolic blood pressure (mm Hg) | 125.9 ± 17.7 | 124.1 ± 17.7 | 126.6 ± 17.4 | 128.9 ± 17.4 | <0.001 |
| Diastolic blood pressure (mm Hg) | 74.9 ± 9.3 | 74.0 ± 9.2 | 75.4 ± 9.2 | 76.3 ± 9.6 | <0.001 |
| Hyperlipidemia ∗ | 9.4% | 8.0% | 10.4% | 11.3% | <0.001 |
| Diabetes mellitus | 3.1% | 2.1% | 3.1% | 5.4% | <0.001 |
| Smoker | |||||
| Never | 52.2% | 54.7% | 51.1% | 48.3% | <0.001 |
| Past | 42.2% | 41.0% | 43.1% | 43.5% | |
| Current | 5.6% | 42.7% | 5.8% | 8.2% | |
| Alcohol (servings/wk) | 2.6 ± 5.3 | 2.6 ± 5.1 | 2.9 ± 5.4 | 2.4 ± 5.4 | 0.036 |
| Depression † | 10.5% | 8.7% | 10.3% | 15.0% | <0.001 |
| Physical activity (MET-hrs/wk) | 14.4 ± 14.8 | 16.3 ± 15.7 | 13.7 ± 13.8 | 10.46 ± 13.0 | <0.001 |
| Women’s Health Initiative Insomnia Rating Scale ‡ | 6.6 ± 4.5 | 6.2 ± 4.4 | 6.6 ± 4.3 | 7.4 ± 4.7 | <0.001 |
∗ Defined as individuals taking lipid-lowering medications and who had been told by a physician that they had high cholesterol.
† Center for Epidemiological Studies Depression scale/Diagnostic Interview Schedule.
‡ Higher numbers indicate greater level of sleep disturbance.
Product-limit survival estimates were assessed, and the log-rank test results indicated significant differences in the survival rate when stratified by snoring group (p <0.001). Cox proportional hazards models adjusted for age and race indicated a 54% increased risk of CHD among frequent snorers and a 27% increased risk among occasional snorers, with similar hazard ratios observed for stroke and CVD ( Table 2 ). In the fully adjusted models, adjusted for age, race, education, BMI, waist-to-hip ratio, smoking, alcohol consumption, physical activity, depression, hypertension, diabetes, and hyperlipidemia, the positive associations for frequent snoring and cardiovascular outcomes were attenuated but still significant, with an approximate 14% increased risk of CHD, 19% increased risk of stroke, and 12% increased risk of CVD ( Table 2 ). BMI, hypertension, and diabetes were the key drivers of this attenuation, and models including these covariates and sociodemographic data are presented in Table 3 . Because BMI is a strong confounder of the association between snoring and coronary disease, we tested for an interaction by obesity status, which was significant (p = 0.024). In the stratified analysis, frequent snoring was a significant predictor of CHD among overweight and obese women in the age- and race-adjusted models (HR 1.29, 95% confidence interval [CI] 1.07 to 1.54 for overweight; HR 1.33, 95% CI 1.10 to 1.61 for obese), but not normal weight women (HR 1.19, 95% CI 0.93 to 1.52). These associations were attenuated and no longer statistically significant in the fully adjusted models ( Figure 1 ).
| Snoring Frequency | Patients (n) | Person-yrs | Model Adjusted for Age, Race | Model Fully Adjusted † | ||||
|---|---|---|---|---|---|---|---|---|
| HR | 95% CI | p Value | HR | 95% CI | p Value | |||
| CHD ‡ | ||||||||
| Frequent | 609 | 86,227 | 1.54 | 1.39–1.70 | <0.001 | 1.14 | 1.01–1.28 | 0.038 |
| Occasional | 814 | 143,209 | 1.27 | 1.16–1.39 | <0.001 | 1.12 | 1.01–1.24 | 0.032 |
| None (referent) | 978 | 208,454 | 1.00 | Referent | Referent | 1.00 | Referent | Referent |
| CVD § | ||||||||
| Frequent | 790 | 84,671 | 1.46 | 1.34–1.60 | <0.001 | 1.12 | 1.01–1.24 | 0.031 |
| Occasional | 1,103 | 141,122 | 1.25 | 1.16–1.36 | <0.001 | 1.11 | 1.01–1.21 | 0.026 |
| None (referent) | 1,354 | 205,547 | 1.00 | Referent | Referent | 1.00 | Referent | Referent |
| Ischemic stroke | ||||||||
| Frequent | 232 | 95,307 | 1.41 | 1.19–1.66 | <0.001 | 1.19 | 1.02–1.40 | 0.030 |
| Occasional | 349 | 153,389 | 1.29 | 1.11–1.50 | <0.001 | 1.15 | 0.96–1.38 | 0.140 |
| None (referent) | 412 | 220,697 | 1.00 | Referent | Referent | 1.00 | Referent | Referent |
∗ All analyses conducted among disease-free cohort; total numbers reflect this difference by outcome.
† Model adjusted for age, race, education, income, smoking, physical activity, alcohol intake, depression, diabetes, high blood pressure, BMI, waist-to-hip ratio, hyperlipidemia.
‡ Total CHD outcomes included myocardial infarction, CHD death, coronary artery bypass grafting, percutaneous transluminal coronary angioplasty, or hospitalized angina.
§ CVD outcomes included myocardial infarction, CHD death, coronary artery bypass grafting, percutaneous transluminal coronary angioplasty, hospitalized angina, and ischemic stroke.
| Model | Snoring Frequency | HR | 95% CI | p Value |
|---|---|---|---|---|
| 1 | ||||
| Frequent | 1.46 | 1.15–1.40 | <0.001 | |
| Occasional | 1.27 | 1.32–1.63 | <0.001 | |
| None (referent) | 1.00 | Referent | Referent | |
| 2 | ||||
| Frequent | 1.28 | 1.14–1.43 | <0.001 | |
| Occasional | 1.19 | 1.08–1.31 | <0.001 | |
| None (referent) | 1.00 | Referent | Referent | |
| 3 | ||||
| Frequent | 1.33 | 1.19–1.48 | <0.001 | |
| Occasional | 1.19 | 1.08–1.31 | <0.001 | |
| None (referent) | 1.00 | Referent | Referent | |
| 4 | ||||
| Frequent | 1.41 | 1.27–1.57 | <0.001 | |
| Occasional | 1.25 | 1.13–1.37 | <0.001 | |
| None (referent) | 1.00 | Referent | Referent | |
| 5 | ||||
| Frequent | 1.21 | 1.08–1.36 | <0.001 | |
| Occasional | 1.15 | 1.04–1.27 | 0.008 | |
| None (referent) | 1.00 | Referent | Referent |
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