Dyslipidaemia is a well-known risk factor for coronary artery disease (CAD), and managing these high-risk people requires lowering lipid levels as a secondary preventative measure. Additionally, patients with obstructive sleep apnea frequently have dyslipidaemia (OSA). The initial course of treatment for OSA is continuous positive airway pressure (CPAP). Evidence of CPAP's potential lipid-lowering benefits in CAD patients with OSA is, however, lacking. In a group of patients with CAD and concurrent OSA, we investigated the impact of CPAP as an additional therapy to lipid-lowering medicine.

A secondary analysis of the RICCADSA trial, which was carried out in Sweden between 2005 and 2013, was done in this study (Trial Registry: ClinicalTrials.gov; No: NCT 00519597). 244 revascularized CAD patients with non-sleepy OSA (apnea-hypopnea index 15/h, Epworth) were included in this study. Sleepiness CPAP or no-CPAP was randomly assigned to 244 revascularized CAD patients with nonsleepy OSA (apnea-hypopnea index 15/h, Epworth Sleepiness Scale score 10). At baseline and 12 months following randomization, levels of circulating triglycerides (TG), total cholesterol (TC), high-density lipoprotein (HDL), and low-density lipoprotein (LDL) (all in mg/dL) were assessed. The most recent recommendations of the European Cardiology Society and the European Atherosclerosis Society set the ideal TG levels as circulating TG 150 mg/dL and the goal LDL levels at 70 mg/dL. A total of 196 individuals with baseline and 12-month follow-up blood samples available were included (94 randomised to CPAP, 102 to no-CPAP). At baseline, we discovered no significant intergroup differences in the levels of circulating TG, TC, HDL, and LDL.

The percentage of patients with the required TG levels, however, significantly decreased in the CPAP group from 87.2% to 77.2% (p = 0.022), whereas it increased in the no-CPAP group from 84.3% to 88.2%. (n.s.). After a year, both groups' desired LDL values were still low (15.1% vs. 17.2% in the CPAP group and 20.8% vs. 18.8% in the no-CPAP group; n.s.). In a multiple linear regression model, the increase in body mass index, after adjusting for age, sex, and CPAP use (hours/night), predicted the rise in TG levels ( = 4.1; 95% confidence interval (1.0-7.1); p = 0.009). In this group of OSA sufferers with revascularization, CPAP showed no lipid-lowering impact.The rise in TG levels after a year was predicted by a rise in body mass index, indicating that in people with CAD and OSA, independent of CPAP use, lifestyle changes should take precedence.

Low-density lipoprotein (LDL) cholesterol is a well-known risk factor for coronary artery disease (CAD), hence managing these high-risk patients requires lowering lipid levels as a secondary preventative measure [1]. 11.7% of people between the ages of 20 and 39 and 41.2% of adults between the ages of 40 and 64 have increased levels of LDL, according to the National Health and Nutrition Examination Survey [2].

Obstructive sleep apnea (OSA), which affects 9% and 24% of middle-aged men and women, respectively, is another significant public health issue in developed nations [3]. According to the long-term Wisconsin Sleep Cohort research, which was published in 2013 [4], the prevalence estimates for people aged 30 to 70 are significantly greater (17% of women and 34% of males). Moreover, among adult OSA populations, dyslipidemia [5] and obesity [4] coexist. Mechanisms,

Numerous factors, including chronic intermittent hypoxia [6, 7, 8, 9], fragmented sleep [9, 10], and sympathetic overactivity [11], have been theorised to have a role in the dysregulation of lipid profiles in OSA patients. The need for effective therapy is further increased by the independent associations between OSA and dyslipidemia and an increase in all-cause mortality, vascular heart disease, and stroke [12]. The initial course of treatment for OSA is continuous positive airway pressure (CPAP) [13]. According to an observational study conducted over a period of 30 years, OSA patients who received CPAP treatment for more than 5 years were 5.6 times more likely to live [14]. However, there is little proof that CPAP can potentially lower lipid levels in CAD patients who also have OSA. Reduced levels of circulating triglycerides (TG), total cholesterol (TC), and high-density lipoprotein (HDL) were seen in earlier meta-analyses.

The Randomized Intervention with CPAP in Coronary Artery Disease and Obstructive Sleep Apnea (RICCADSA) trial was carried out in Sweden between 2005 and 2013 and the current study is a primary analysis of one of the secondary outcomes. An earlier description of the RICCADSA cohort can be found elsewhere [18]. In a nutshell, persons who had undergone coronary artery bypass grafting (CABG) or percutaneous coronary intervention (PCI) within the previous six months were sequentially asked to participate. Based on the results of the home sleep apnea testing, the CAD patients were divided into two groups: those with OSA (apnea-hypopnea index [AHI] 15/h) and those without OSA (apnea-hypopnea index [AHI] 5/h) (HSAT). The HSAT recordings were made using the Embletta® Portable Digital System device (Embla, Broomfield, CO, USA), as previously detailed in detail [18,19] included two respiratory inductance plethysmography belts, a nasal pressure detector, and pulse oximetry to measure oxygen saturation and heart rate (SpO2). According to standards from 1999, hypopnea was defined as at least a 50% reduction in nasal pressure amplitude and/or thoraco-abdominal movement lasting at least 10 seconds [20]. Apnea was defined as at least a 90% stoppage of airflow. 196 CAD patients from the randomised controlled trial (RCT) arm with nonsleepy OSA (AHI 15/h, ESS score 10) were included in the current protocol (Figure 1). The main trial's 1:1 random assignment was planned with a block size of eight patients (four CPAP, four controls), stratified by gender and revascularization method (PCI/CABG), as previously described [19].

The ESS is a self-rating survey that has eight items that estimate the likelihood of nodding asleep under eight different circumstances [21]. Nonsleepy participants were those who received less than 10 out of a possible 24 points.

As previously stated [19], information about the research population's anthropometrics, smoking habits, medical history, and medications—including the use of lipid-lowering agents—was gleaned from the medical records. Obese participants were those with a body mass index (BMI) more than 30 kg/m2 [22].

After fasting all night, blood samples were taken in the morning using serum tubes and ethylenediaminetetraacetic acid (07:00–08.00 am). At baseline and 12 months following randomization, the levels of circulating total cholesterol (TC), high-density lipoprotein (HDL), low-density lipoprotein (LDL), and triglycerides (TG) (all in mg/dL) were assessed. According to the most recent recommendations of the ECS and the EAS [1], the goal LDL values were set at 70 mg/dL and the desirable TG levels were circulating TG 150 mg/dL.

The descriptive statistics were used to look at the demographic and clinical baseline features of the study sample. The current data's assumed normality for all variables was examined using the Shapiro-Wilk test. Interquartile ranges (IQR) were used to delineate the median values for continuous variables, and numbers and percentages were used to denote categorical variables. For the continuous variables, the Mann-Whitney U test was used to examine between-group differences. To compare the subgroups on the categorical variables, the chi-square test was utilised. The Wilcoxon Signed-Rank test and McNemar's test were used to examine the within-group differences for continuous and categorical data, respectively. A p-value of 0.05 or less was regarded as significant for all two-sided statistical tests. SPSS® 26.0 for Windows® was used to conduct the statistical analysis.

A total of 196 patients who were receiving lipid-lowering therapy and had blood samples accessible at baseline and at the 12-month follow-up were included (94 randomised to CPAP, 102 to no-CPAP) participants assigned to CPAP vs. no-CPAP had comparable demographic and clinical traits, HSAT, and circulating lipid levels at baseline. As part of the secondary cardiovascular prevention guidelines at the time of the study period, statin therapy was initiated in all patients at baseline.

At the 1-year follow-up, all patients were still receiving statin medication. Figure 2 shows that in the intention-to-treat population, there were no significant between-group or within-group variations in the circulating levels of TG, TC, HDL, and LDL levels at 12-month follow-up compared to baseline across the CPAP and no-CPAP groups.

At baseline, both groups had the same desired TG levels. The proportion of patients having the required TG-levels after 12 months did, however, differ significantly between groups (p = 0.048). The CPAP group showed the most notable within-group difference (87.2% at baseline vs. 77.2% after 12 months; p = 0.022). After a year, both groups had similar percentages of participants with low LDL values (15.1% in the CPAP group and 20.8% in the no-CPAP group, respectively), with no discernible within- or between-group variations.

at 1-year follow-up, there was a linear relationship between the changes in TG levels and BMI. In a multiple linear regression model with adjustments for age, sex, and CPAP use (hours/night), the increase in BMI ( = 4.1; 95% confidence interval (1.0-7.1); p = 0.009) predicted the rise in TG levels.In the whole study population that was randomly assigned to get CPAP, the median CPAP usage was 3.8 hours per night (IQR 0.0–6.1 hours per night), and 47 out of 94 participants (or 50%) were considered CPAP adherents. The definition of adherence was at least 4 hours every night for the entire 1-year period. The primary conclusions of the study were unaffected by post-hoc analyses of the patients stratified by CPAP adherence (data not shown).

In CAD patients with OSA who were already using lipid-lowering medication, the current investigation discovered no extra effect of CPAP therapy on the circulating levels of lipids after 12 months. Both CPAP and no-CPAP groups maintained the desired LDL values, and this was unrelated to the severity of OSA at baseline or CPAP adherence. Additionally, we noticed a decline in the percentage of patients who had the target TG levels, which suggests a deterioration. AHI at baseline, CPAP adherence, age, and sex were all significant predictors of the increase in TG levels in a multiple linear regression model; however, the rise in BMI was the sole significant predictor.

In patients with revascularized CAD who also have nonsleepy OSA, this trial is the first RCT, as far as we are aware, to assess the impact of CPAP intervention as an additional treatment to lipid-lowering medicine. The effects of CPAP were previously discussed by Huang et al. [17] in a small group of 65 non-obese persons with recently diagnosed CAD who were using standardised lipid-lowering medication. The authors said that CPAP had no impact on blood lipid levels, which is consistent with our findings. Furthermore, we found no change in the percentage of patients with the appropriate TG and LDL values following CPAP therapy. Clinically significant is the drop in the proportion of patients with the optimal TG levels during CPAP therapy and its correlation with the rise in BMI.

Except for the study by Phillips et al. [28], in which reductions in the total cholesterol and triglyceride levels have been demonstrated after 2 months of CPAP treatment, the RCTs in non-cardiac cohorts with concurrent OSA [23,24,25,26,27,28] have also shown no significant changes in circulating lipid levels. Furthermore, a prior meta-analysis by Xu et al. [15] that comprised six RCTs and 741 participants revealed a substantial but slight decline in TC without any changes in the other parameters. Another meta-analysis by Lin et al. [16] with 699 participants showed lesser decreases in TG and HDL as well as lower levels of TC after CPAP therapy. Therefore, no effect has been seen on circulating LDL levels, the most critical goal, particularly in the secondary cardiovascular prevention models [1].

According to earlier studies, systemic inflammation, oxidative distress, endothelial dysfunction, and atherosclerosis are considered to be the major mechanisms of chronic intermittent hypoxia [29]. The hormone-sensitive lipoprotein activity in adipose tissue, which initiates lipolysis, has also been hypothesised to be modulated by enhanced sympathetic system activation [30]. Additionally, Trammell et al. [31] shown in a mouse model that fragmented sleep is associated with a dysfunctional lipid pathway. Recent research by Martinez-Ceron et al. [32] showed a significant correlation between severe OSA and dyslipidemia, which may be brought on by fragmented sleep and elevated sympathetic activity. Although these postulated processes provide a compelling justification for anticipating favourable outcomes from the use of CPAP to treat OSA, our research did not demonstrate any appreciable impact on the levels of circulating lipids as a supplement to drugs that decrease cholesterol. It is clear that lifestyle changes should take precedence in adults with CAD and OSA, regardless of CPAP treatment, as evidenced by a slight decline in the proportion of patients with the desired TG levels, which can be explained by the rise in BMI at the 1-year follow-up, as well as the continued low proportion of patients with the desired LDL levels despite medication.

The effects of lifestyle changes on the severity of OSA and the metabolic abnormalities in individuals with OSA are still being investigated, although preliminary findings are encouraging [33]. Furthermore, pharyngoplasty with barbed sutures may enhance the metabolic profile of individuals with OSA, even though CPAP is advised as the first therapeutic option for those with OSA [34,35].

Notably, these findings hold true for CAD patients who exhibit the nonsleepy OSA phenotype. Since randomising people with the "sleepy phenotype" would not be morally acceptable, patients with the "sleepy" phenotype were excluded from the current analysis in order to analyse the effect of CPAP on circulating levels of lipids in a more scientific manner (risk for traffic and work accidents). It will be further examined in the complete RICCADSA cohort to determine whether or not the response to CPAP treatment differs between OSA patients with the "sleepy" phenotype and "nonsleepy" lipid profiles.

There are three main weaknesses in the current study. First off, the sample size may not be sufficient to confirm the additional effect of CPAP on the lipid profiles because the power estimate for the main RICCADSA trial was conducted for the primary outcomes (combined of major cardiovascular and cerebrovascular events) [19] and not for the secondary outcomes. Second, neither the general community nor other clinical groups of OSA sufferers may be assumed to apply our findings. Third, the ESS score used to classify patients as "nonsleepy" was less than 10, which may not be accurate in a CAD population. The Multiple Sleep Latency Test [36] is an objective test that is widely used in clinical cohorts, although it is a time- and money-consuming tool.