In this study, we found that the ACCI was a significant independent predictor of all-cause mortality in older OSA patients. An ACCI cutoff of 5, identified using ROC curve analysis, could better discriminate the mortality risk of older OSA patients. The Kaplan–Meier survival curve showed the cumulative survival rate of all participants in the low-ACCI group was significantly higher than those in the high-ACCI group. Regardless of sex or OSA severity, a higher ACCI was associated with a higher mortality risk in older OSA patients. Therefore, personalized multidisciplinary treatment, based on comorbidities, may improve the prognosis of older OSA patients.
The ACCI, a comorbidity scoring system, includes age as a factor to the CCI, and can more comprehensively assess the overall condition of the patient and predict the clinical outcome. Especially in older patients, comorbidity can influence the patient’s selection of treatment options. Unfortunately, the ACCI is not widely utilized in clinical practice. Levine et al.reported that the CCI significantly correlated with the physical function subscale of the Short Form–36(rs = − 0.39, P < 0.001) and is a good predictor of the SF-36 physical function score in patients with sleep apnea. Kravitz et al. showed that the CCI is a significant risk factor for coronavirus disease-related hospitalization of patients with sleep apnea (aOR = 1.45, 95% CI 1.19–1.81, P = 0.0006). Tang et al. indicated that, during the 1-year follow-up, the all-cause mortality of OSA patients (age 60.6 ± 9.6 years) was 10.1%, and the CCI (aHR = 1.273, 95% CI 1.050–1.543, P = 0.014) was identified as an independent predictor of all-cause mortality. Thus, these results further confirmed that the long-term prognosis of the patients with sleep apnea in the low-CCI group was better than that of patients in the high-CCI group. The ACCI seems to be a more appropriate prognostic indicator and has been confirmed to have better predictive value in the prognosis of patients with cancer, infection, and postoperative complications. Therefore, we comprehensively analyzed and validated the effects of the ACCI in the prediction of the prognosis of older OSA patients and found that a 1-point increase in the ACCI score would result in a 58.5% increase in the risk of all-cause mortality in the participants.
Besides the ACCI, all-cause mortality was associated with other factors, including TST and MCV in our study, which differed from the results of other studies. Marshall et al. found that the all-cause mortality rate was 33.3% in participants with moderate–severe OSA (6/18) after follow-up for up to 14 years. Moderate–severe OSA was independently associated with a higher mortality risk (aHR = 7.35, 95% CI: 2.40–22.49, P < 0.05). A prospective longitudinal study with an average follow-up duration of 10.5 ± 4.1 years found that age (HR = 1.07, 95% CI 1.06–1.08, P < 0.001), male sex (HR = 1.68, 95% CI 1.24–2.28, P = 0.001), high AHI (HR = 1.01, 95% CI 1.01–1.02, P < 0.001), high periodic limb movement index (HR = 1.014, 95% CI 1.01–1.02, P = 0.002), and low sleep efficiency (HR = 0.949, 95% CI 0.916–0.984, P = 0.004) were significantly associated with increased all-cause mortality. A study in Denmark that included 22,135 OSA patients showed that male sex, age > 40 years, DM, hypertension, and CHD were associated with greater mortality risk. The reasons for the differences in the results of our study with those of earlier studies are as follows: compared to the median follow-up of more than 10 years in other studies, the duration of follow-up in our study was relatively short as the median age in our study population was 66 years, which is not considered advanced age. Mostly, individuals aged about 65 years rarely have comorbidities and are in a good physical health state due to improved living standards. Moreover, we found that 10.7% (126/1183) of participants undertook exercise training to reduce body weight, and 12.6% (149/1183) took TCM products over the last 43 months of follow-up, both of which may have influenced all-cause mortality in our study population. Furthermore, we focused on routine hematological and biochemical indicators during hospitalization as important covariates and found that MCV is an important predictor of all-cause mortality in older OSA patients, which conferred a 4.7% increased risk of mortality for every 1 unit increase in the MCV; this indicator could improve the prognosis of OSA patients by guiding treatment selection.
MCV is a routine parameter in complete blood count examination and is closely associated with the RDW; the RDW-coefficient of variation (CV) is derived from the Eq. (1 standard deviation unit of erythrocyte volumes divided by MCV) × 100%). The RDW is an independent risk factor for not only cardiovascular mortality but also all-cause mortality. A study of a community-dwelling cohort of non-anemic individuals in Taiwan showed that participants with high RDW had an increased all-cause mortality risk (HR = 1.46, 95% CI: 1.17–1.81, P < 0.001) than participants with low RDW during a median follow-up period of 15.9 years. Arbel et al. conducted a community-based cohort study of 225,006 eligible patients aged 40 years or more and found that 21,939 incident cases of a major cardiovascular event and 4,287 deaths were documented during the 6-year follow-up. Compared with patients with an RDW level < 13%, the HR of total mortality gradually increased to 4.57 (95% CI: 3.35–6.24, P < 0.001) and 3.26 (95% CI: 2.49–4.28, P < 0.001) among male and female patients with an RDW of 17% or higher. However, most studies have focused on the RDW rather than the MCV so far. Wu et al., in a large population-based study with a median 6.21-year follow-up duration, found that an elevated MCV significantly increased the cerebrovascular and cardiovascular mortality risk (aHR = 1.42; 95% CI: 1.15–1.76, P < 0.05), and the results of our study match their results as the MCV was associated with an increased risk of all-cause mortality in older OSA patients. In general, OSA is associated with increased all-cause and cardiovascular mortality risks. We preliminarily confirmed that the MVC is associated with all-cause mortality although we could not identify the exact mechanism involving MCV in OSA pathogenesis.
In our study, there was a 25.8% increased risk of all-cause mortality in older OSA patients for every 1 h increase in the TST. Persistent short or long sleep duration in late adulthood was associated with an increased risk of all-cause mortality, and especially of cardiovascular mortality. Soh et al. study showed that, compared with participants with a sleep duration of 7 h, individuals with persistently long sleep duration had an increased risk of all-cause (HR = 1.47, 95% CI: 1.24–1.73, P < 0.05) and cardiovascular mortality (HR = 1.40, 95% CI: 1.04–1.89, P < 0.05). The proportion of long-sleepers increased with age (6–23.7%). A study about sleep duration and chronic diseases among US adults aged 45 and older indicated that short and long sleep durations were significantly associated with the risk of CHD, stroke, and DM after controlling for sex, age, race, and education. The sleep duration had a U-shaped relationship with the leading chronic diseases. Notably, our study population is older (≥ 60 years), with TST maintained at 5.5–7.0 hours (median 7.1 hours). Longer sleep duration and decreased vitality of brain cells can decrease memory in older adults. Moreover, decreased metabolism and age-related changes in blood vessels were noted in older individuals. Prolonged sleep durations could result in increased blood viscosity and an increased risk of stroke in older adults. Moreover, increased sleep durations could further decrease the basal metabolic rate, which will affect the body's metabolism of carbohydrates and increase the risk of DM. CHD, stroke, and DM are the main mortality-associated risk factors among older adults. The OSA patients in this study not only slept for long durations, but also experienced sleep fragmentation and disrupted sleep architecture that reduced the efficacy of restorative processes during sleep and was probably associated with the unfavorable prognosis of OSA patients.
This study was a multicenter, large-sample, prospective, observational cohort study, and we have attempted to comprehensively analyze whether the ACCI plays a crucial role in predicting the all-cause mortality risk of older OSA patients. However, a few limitations need to be mentioned: 1) this cohort study, with a median follow-up of just 43 months, had a relatively short follow-up period compared to other studies; 2) the study population consisted only Asian participants, and the relative homogeneity of the population limits the generalizability of the results; therefore, the findings of this study should be evaluated in other ethnically diverse populations; 3) the all-cause mortality risk of OSA is mediated by a complex process that correlates with multiple factors. We adjusted our analysis for as many related factors as possible; however, there may be other unmeasured confounders; and 4) our study showed that the ACCI has a predictive effect on all-cause mortality from OSA in older adults. Further research into the association between the ACCI or specific comorbidities and other outcomes of OSA is needed.