Symptom Subtypes of Obstructive Sleep Apnea Predict Incidence of Cardiovascular Outcomes

Abstract

Rationale: Symptom subtypes have been described in clinical and population samples of patients with obstructive sleep apnea (OSA). It is unclear whether these subtypes have different cardiovascular consequences.Objectives: To characterize OSA symptom subtypes and assess their association with prevalent and incident cardiovascular disease in the Sleep Heart Health Study.Methods: Data from 1,207 patients with OSA (apnea-hypopnea index ≥ 15 events/h) were used to evaluate the existence of symptom subtypes using latent class analysis. Associations between subtypes and prevalence of overall cardiovascular disease and its components (coronary heart disease, heart failure, and stroke) were assessed using logistic regression. Kaplan-Meier survival analysis and Cox proportional hazards models were used to evaluate whether subtypes were associated with incident events, including cardiovascular mortality.Measurements and Main Results: Four symptom subtypes were identified (disturbed sleep [12.2%], minimally symptomatic [32.6%], excessively sleepy [16.7%], and moderately sleepy [38.5%]), similar to prior studies. In adjusted models, although no significant associations with prevalent cardiovascular disease were found, the excessively sleepy subtype was associated with more than threefold increased risk of prevalent heart failure compared with each of the other subtypes. Symptom subtype was also associated with incident cardiovascular disease (P < 0.001), coronary heart disease (P = 0.015), and heart failure (P = 0.018), with the excessively sleepy again demonstrating increased risk (hazard ratios, 1.7-2.4) compared with other subtypes. When compared with individuals without OSA (apnea-hypopnea index < 5), significantly increased risk for prevalent and incident cardiovascular events was observed mostly for patients in the excessively sleepy subtype.Conclusions: OSA symptom subtypes are reproducible and associated with cardiovascular risk, providing important evidence of their clinical relevance.

Keywords: cardiovascular disease; cluster analysis; sleep apnea; sleepiness; symptom subtypes.

Figure 1.

Symptom profile of the identified obstructive sleep apnea symptom subtypes in the Sleep Heart Health Study. The relative differences in symptom burden among subtypes are shown by the color scale, which represents the standardized (z-score) symptom proportion or mean Epworth Sleepiness Scale across groups. Brighter red indicates higher relative symptom burden. ESS = Epworth Sleepiness Scale.

Figure 2.

Unadjusted Kaplan-Meier survival curves indicating the time to incidence of cardiovascular disease (CVD), coronary heart disease (CHD), heart failure, stroke, and death from CVD grouped by obstructive sleep apnea symptom subtype. The log-rank test was used to compare the survival distribution across subtypes. There were suggestive differences in CVD and trending differences in CHD survival curves among symptom subtypes. HF = heart failure.

Figure 3.

Results of the Cox proportional hazards regression models to evaluate the association between obstructive sleep apnea symptom subtypes and incident cardiovascular disease (CVD), coronary heart disease (CHD), heart failure (HF), stroke, and death from CVD. The sample consisted of individuals without the corresponding outcome at the Sleep Heart Health Study baseline visit. Adjusted models included age, sex, body mass index, type 2 diabetes, hypertension, high-density lipoprotein, total cholesterol, triglycerides, apnea–hypopnea index, alcohol use, smoking status, race, ethnicity, and use of lipid-lowering medication as covariates. Pairwise comparisons are performed using each subtype as the reference group. The hazard ratio represented in the x-axis is shown in the log scale. More detailed results are presented in Table 2. The excessively sleepy subtype is the only subtype at increased risk for incident CVD, CHD, and HF. CI = confidence interval; Cox PH = Cox proportional hazards; HR = hazard ratio.

Figure 4.

Unadjusted Kaplan-Meier survival curves indicating the time to incidence of cardiovascular disease (CVD), coronary heart disease (CHD), heart failure (HF), stroke, and death from CVD grouped by obstructive sleep apnea symptom subtype, including the sample of individuals without obstructive sleep apnea (OSA) in the Sleep Heart Health Study. Results of pairwise log-rank tests between each subtype and individuals without OSA are shown below each curve. There were significant differences in survival curves for incident CVD, CHD, and HF, when symptom subtypes were compared with individuals without OSA. In all cases, the excessively sleepy subtype demonstrated the worst survival. For stroke and cardiovascular mortality, the minimally symptomatic and the moderately sleepy subtypes demonstrated worse survival than individuals without OSA.

Figure 5.

Results of the adjusted Cox proportional hazards regression models to evaluate the association between each obstructive sleep apnea symptom subtype and incident cardiovascular disease (CVD), coronary heart disease (CHD), heart failure (HF), stroke, and death from CVD compared with individuals without obstructive sleep apnea (no OSA). The sample consisted of individuals without the corresponding outcome at the Sleep Heart Health Study baseline visit. Models were adjusted for age, sex, body mass index, type 2 diabetes, hypertension, high-density lipoprotein, total cholesterol, triglycerides, alcohol use, smoking status, race, ethnicity, and use of lipid-lowering medication as covariates. Individuals without OSA were used as the reference group. The hazard ratio represented in the x-axis is shown in the log scale. More detailed results are presented in Table E6. The excessively sleepy subtype is at increased risk for incident CVD, CHD, and HF when compared with individuals without OSA. CI = confidence interval.