Continuous positive airway pressure therapy for patients with obstructive sleep apnea and coronary artery disease

Abstract

Obstructive sleep apnea (OSA) and coronary artery disease (CAD) frequently coexist, forming a bidirectional pathophysiological loop that amplifies cardiovascular risk. Intermittent hypoxemia in OSA patients promotes endothelial dysfunction, systemic inflammation, oxidative stress, and sympathetic activation, thereby accelerating atherogenesis, whereas myocardial ischemia and ventricular dysfunction in CAD patients can further destabilize upper-airway patency and exacerbate OSA. Continuous positive airway pressure (CPAP) is the standard therapy for OSA and reliably restores sleep architecture; however, large randomized trials have reported inconsistent effects on major adverse cardiovascular events, particularly in patients with established CAD. This mini review synthesizes contemporary data on CPAP across diverse OSA–CAD clinical scenarios, delineates patient phenotypes most likely to achieve cardiovascular benefit and identifies contexts in which CPAP provides limited protection. On the basis of these findings, we propose pragmatic recommendations for patient selection, adherence monitoring and optimization of CPAP therapy and highlight key research priorities, including extended follow-up, adherence-enhancing strategies and multimodal interventions. Clarifying the circumstances under which CPAP is cardioprotective will enable more precise management of patients with OSA, with or without concomitant CAD.

Key Words: Obstructive sleep apnea; Coronary artery disease; Continuous positive airway pressure; Major adverse cardiovascular events; Integrated treatment

Core Tip: Obstructive sleep apnea and coronary artery disease often cooccur, each worsening the other. Continuous positive airway pressure (CPAP) improves obstructive sleep symptoms, but large trials have shown mixed cardiovascular benefits. This review highlights patient profiles most likely to benefit from CPAP and offers guidance for integrating CPAP with lifestyle and medical therapy to optimize outcomes.

INTRODUCTION

Obstructive sleep apnea (OSA) and coronary artery disease (CAD) each impose substantial global health burdens[1-3]. OSA affects more than 40% of patients with established CAD, compared with nearly 10%–40% in the general population, and is frequently underdiagnosed owing to nonspecific symptoms and limited cardiovascular screening[4-7]. OSA is a complex disorder characterized by collapse of the upper airway during sleep and leads to intermittent hypoxemia, sleep fragmentation and sympathetic overactivity[8]. These pathophysiological disturbances promote endothelial dysfunction, systemic inflammation, oxidative stress and accelerated atherogenesis[9]. Conversely, myocardial ischemia and impaired ventricular function in CAD can increase upper-airway collapsibility, exacerbating OSA severity and perpetuating a vicious cycle. This bidirectional interaction not only accelerates plaque formation and destabilization but also impairs exercise tolerance, diminishes quality of life and elevates the risk of major adverse cardiovascular events (MACEs), such as myocardial infarction (MI), stroke and cardiovascular death[3].

Continuous positive airway pressure (CPAP) remains the gold-standard treatment for OSA. It prevents apneic episodes, restores normal sleep architecture and alleviates daytime somnolence[10]. In addition to these respiratory benefits, several studies have reported that CPAP can lower blood pressure, improve the left ventricular ejection fraction and reduce N-terminal pro-B-type natriuretic peptide levels, suggesting a potential reduction in cardiovascular risk[11-13]. However, large multicenter randomized trials such as SAVE, RICCADSA, and ISAACC did not demonstrate a significant reduction in cardiovascular events even when CPAP adherence was adequate. In SAVE, patients with moderate-to-severe OSA and established cardiovascular disease (CVD) experienced no significant decrease in MACEs[14]. The RICADSA trial enrolled post-revascularization CAD patients and failed to show a cardiovascular benefit with CPAP[15]. ISAACC focused on acute coronary syndrome (ACS) patients with newly diagnosed OSA and likewise reported no MACE reduction despite high adherence. These null findings have raised questions about patient selection, adherence thresholds and the potential need for combined therapies.

Other studies have indicated that specific subgroups may benefit more clearly. Secondary analyses of previous randomized controlled trials (RCTs) and smaller single-center trials suggest that patients with higher baseline sleepiness, elevated blood pressure or more severe nocturnal hypoxemia may prevent subsequent MACEs with CPAP. In addition, propensity-matched cohort studies and meta-analyses that include real-world adherence data have reported lower incidences of MI and stroke among individuals who use CPAP consistently[16-20]. These conflicting results highlight the need to identify the phenotypic and clinical variables that modulate the efficacy of CPAP in reducing MACEs.

Given these uncertainties, several questions remain unanswered. Why do outcomes differ across major trials? Which patient phenotypes and comorbidity profiles predict meaningful cardiovascular benefit? How should CPAP be combined with pharmacological therapy and lifestyle modification to optimize care for patients with coexisting OSA and CAD? To address these gaps, this review first summarizes the pathophysiological mechanisms linking OSA and CAD. It then critically evaluates evidence from randomized trials and observational studies, including those reporting neutral cardiovascular outcomes and those showing benefit. Finally, we discuss practical considerations for patient selection, adherence strategies and multimodal interventions and propose a research agenda to clarify the role of CPAP in comprehensive cardiovascular management.

PATHOPHYSIOLOGICAL LINKS BETWEEN OSA AND CAD

OSA and CAD share common risk factors such as obesity, hypertension, insulin resistance, smoking, and chronic inflammation, which contribute to their onset and progression[21,22]. However, each condition arises from distinct underlying mechanisms. OSA primarily develops due to upper airway collapsibility, which is influenced by craniofacial anatomy, neuromuscular control deficits, and adipose deposition in the pharyngeal region. Several pathophysiological mechanisms have been proposed to explain how OSA contributes to CAD progression, including intermittent hypoxia (IH), oxidative stress, sympathetic activation, endothelial dysfunction, and systemic inflammation (Figure 1). These interconnected processes create a proatherogenic environment that accelerates cardiovascular damage in OSA patients. CAD, on the other hand, results from chronic vascular injury driven by dyslipidemia, oxidative stress, endothelial dysfunction, and a prothrombotic state, ultimately leading to atherosclerosis and myocardial ischemia[4,21].

Figure 1 Cardiovascular consequences of obstructive sleep apnea. CAD: Coronary artery disease; MACE: Major adverse cardiac events; NO: Nitric oxide; HIF-1α: Hypoxia-inducible factor 1-alpha; OSA: Obstructive sleep apnoea; ROS: Reactive oxygen species.

IH and oxidative stress

IH, a hallmark of OSA, precipitates oxidative stress, a key mediator of vascular dysfunction and atherosclerosis, thereby playing a crucial role in the development of CAD.

During apneic episodes, cyclical patterns of oxygen desaturation followed by reoxygenation trigger an overproduction of ROS, primarily due to mitochondrial dysfunction and nicotinamide adenine dinucleotide phosphate oxidase activation[23]. This surge in oxidative stress undermines the bioavailability of endothelial nitric oxide, elevates the levels of adhesion molecules such as intercellular adhesion molecule-1 and vascular cell adhesion molecule-1 and enhances leukocyte infiltration into the vascular wall, contributing to vascular inflammation[24].

Moreover, IH stimulates the activation of HIF-1α, a transcriptional regulator that significantly increases the expression of proinflammatory cytokines such as interleukin (IL)-6, tumor necrosis factor-alpha (TNF-α), vascular endothelial growth factor, and endothelin-1. These factors collectively exacerbate endothelial dysfunction and promote vascular remodeling[25]. Concurrently, oxidative stress catalyzes the oxidation of low-density lipoprotein (LDL), which promotes macrophage recruitment, foam cell formation, and the development of atherosclerotic plaques[26]. Over time, these processes contribute to plaque instability and substantially increase the risk of ACS[27].

Systemic inflammation

OSA is characterized by chronic, low-grade systemic inflammation, which significantly contributes to the progression of CAD[28]. The frequent cycles of hypoxia and reoxygenation characteristic of OSA activate NF-κB, a critical transcription factor that orchestrates inflammatory responses. This activation of NF-κB stimulates the increased production of inflammatory mediators such as C-reactive protein (CRP), IL-6, TNF-α, and monocyte chemoattractant protein-1, leading to endothelial dysfunction and increased leukocyte adhesion[28].

Furthermore, these inflammatory pathways are crucial for increasing plaque vulnerability[29]. CRP, IL-6, and TNF-α further aggravate endothelial dysfunction by inhibiting endothelial nitric oxide synthase and encouraging the proliferation and migration of vascular smooth muscle cells, thereby contributing to the instability of atherosclerotic plaques[30,31]. Additionally, the inflammatory environment fosters a prothrombotic state by upregulating plasminogen activator inhibitor, which enhances platelet aggregation and increases the risk of thrombotic events, including MI[32].

Sympathetic activation

In patients with OSA and concurrent CVD, sympathetic activation plays a pivotal role in disease progression. OSA-induced recurrent nocturnal hypoxia and arousals trigger persistent hyperactivity of the sympathetic nervous system, a key driver of CAD pathogenesis[33]. The hypoxia-driven chemoreflex heightens carotid body sensitivity, sustaining sympathetic outflow and elevating circulating catecholamines, notably norepinephrine[34]. This intensified adrenergic activity leads to chronic hypertension, tachycardia, and increased myocardial oxygen demand, placing considerable strain on the cardiovascular system[35].

Over time, chronic sympathetic overactivation fosters adverse cardiac remodeling. Elevated catecholamine levels promote left ventricular hypertrophy by increasing afterload and exerting direct myocardial effects via β1-adrenergic receptor stimulation[36]. Additionally, prolonged sympathetic excitation disrupts cardiac autonomic balance, heightening the risk of malignant arrhythmias, such as ventricular tachycardia, which are prevalent in CAD patients[37]. Concurrently, upregulation of the renin-angiotensin-aldosterone system amplifies vasoconstriction, oxidative stress, and endothelial dysfunction, further accelerating atherosclerosis progression[38]. Collectively, these processes amplify cardiovascular strain and accelerate atherosclerosis in CAD patients.

Sleep fragmentation

Sleep fragmentation, a defining feature of OSA, disrupts sleep homeostasis and heightens cardiovascular risk[39]. This fragmentation dysregulates autonomic nervous system activity, increases blood pressure variability and impairs baroreceptor sensitivity, which predisposes patients to hypertension and endothelial dysfunction[40].

Moreover, fragmented sleep elevates cortisol levels by activating the hypothalamic–pituitary–adrenal axis, driving insulin resistance, dyslipidemia, and obesity, which are key risk factors for CAD[41]. Chronically, it disrupts glucose metabolism by impairing pancreatic beta-cell function and increasing hepatic glucose production, worsening metabolic syndrome[42].

At the molecular level, sleep fragmentation alters circadian gene expression, including BMAL1 and CLOCK, which govern vascular tone and metabolic balance[33]. Disruption of these genes compromises endothelial function, increases arterial stiffness, and promotes a proinflammatory vascular state, accelerating atherosclerosis and CAD progression[43,44]. Collectively, these disruptions from sleep fragmentation amplify cardiovascular and metabolic risks, driving CAD progression.

IMPACT OF CPAP THERAPY IN OSA

OSA is a condition in which the restorative effects of sleep are impaired. One of the primary mechanisms linking OSA to cognitive impairment is the recurrent hypoxia experienced during apneic episodes[45]. Karapin et al[46] reported thatrecurrent apneic pauses with subsequent intermittent brain hypoxia and sleep fragmentation could affect cognitive impairment, potentially causing structural and cerebrovascular damage to the brain.

Moreover, the impact of OSA on neurocognitive health is multifactorial. Beyond hypoxia, sleep fragmentation characterized by frequent nocturnal arousals markedly disrupts sleep quality, leading to excessive daytime sleepiness and fatigue, which can significantly impair patients’ quality of life[47].

As the cornerstone therapy for OSA, CPAP therapy has demonstrated notable benefits beyond symptom control, enhancing functional outcomes and quality of life, as depicted in Figure 2.

Figure 2 Clinical impact of continuous positive airway pressure therapy in patients with obstructive sleep apnea. OSA: Obstructive sleep apnea.

A recent study by Milinovic et al[48] involving 87 patients with severe OSA who initiated CPAP therapy revealed that severe OSA patients experienced improvements in OSA-related quality of life and reduced daytime sleepiness following one month of CPAP therapy. This improvement was established in terms of daily functioning, social interactions, emotional well-being, and symptom perception, which emphasizes the benefits of effective OSA treatment for patients’ quality of life.

A study by Benkirane et al[45] reported that CPAP therapy significantly improved subjective sleep quality and cognitive functions, including episodic memory, working memory, verbal fluency, and inhibition, over time after six months of CPAP use. Regular CPAP use not only mitigates the immediate physiological disturbances caused by OSA but also facilitates cognitive recovery and daily functioning, including increased quality of life, reduced daytime sleepiness, and improved mood. These improvements highlight the broader psychosocial benefits of CPAP therapy and emphasize the importance of integrating patient-reported outcomes into the management of OSA.

A study by Velescu et al[49] regarding the impact of CPAP adherence on global cognition via the Montreal cognitive assessment (MoCA), 34 new patients diagnosed with moderate or severe OSA [apnea-hypopnea index (AHI) ≥ 15 events/hour] from the CPAP group were compared with 31 moderate-to-severe OSA patients from the no-CPAP group. At baseline, there were no significant differences in total MoCA scores between the two groups. After one year, an improvement in the total MoCA score of 22.7 ± 3.5 (P < 0.001) was observed for the CPAP group, and the significant difference in the scores between the groups was greater for the delayed recall and attention subtopic (P < 0.001).

CPAP is the gold standard for managing moderate-to-severe OSA. However, adherence to CPAP remains problematic, with many patients either intermittently or permanently discontinuing CPAP use, and the impact of CPAP therapy discontinuation remains unclear. In a study by Wali et al[50], patients with moderate-to-severe OSA who were compliant with CPAP therapy were included. All the subjects underwent a CPAP efficacy assessment, followed by 1 month of closely monitored CPAP usage. The subjects were then randomized into two groups: (1) Complete CPAP withdrawal (NO-CPAP); and (2) Intermittent CPAP use (using the device every other day). Discontinuation of CPAP therapy, whether completely or intermittently, leads to rapid OSA relapse, with age and neck circumference being key predictors of OSA relapse. These findings underscore the impact of CPAP withdrawal and the need for continuous CPAP adherence to effectively manage OSA. Kohler et al[51] reported that CPAP withdrawal led to a recurrence of OSA within a few days and a return of subjective sleepiness and was associated with impaired endothelial function and increased urinary catecholamines, blood pressure, and heart rate.

IMPACT OF CPAP THERAPY IN OSA AND CVD

CPAP is recognized as the first-line therapy for OSA, as noted earlier. A growing body of epidemiological and pathophysiological evidence also confirms a close association between OSA and a broad spectrum of CVDs, including hypertension, coronary atherosclerosis, heart failure, stroke, and malignant arrhythmias[33,52-55]. These links naturally prompt the question of whether CPAP, beyond alleviating respiratory symptoms, might also reduce cardiovascular events—yet definitive evidence remains elusive.

Several clinical scenarios illustrate this knowledge deficit. First, it is still uncertain whether individuals with OSA but no prior history of CVD experience fewer incident cardiovascular events when CPAP therapy is initiated. Second, the extent to which CPAP can lower the burden of MACEs in patients who already harbor both OSA and established CVD has not been resolved. Third, no data are available to indicate whether empirically prescribing CPAP to patients with CVD but without OSA yields any cardiovascular benefit. These unanswered questions have driven successive observational cohorts and RCTs aimed at clarifying the putative cardioprotective effect of CPAP.

Despite considerable investigative effort, randomized trials have not demonstrated any cardioprotective advantage for CPAP in scenario 2 patients with OSA and established CVD or, in scenario 3, the empirical use of CPAP in individuals who have CVD but no OSA.

The multinational SAVE trial enrolled a large cohort of patients with OSA and either coronary or cerebrovascular disease; throughout follow-up, CPAP did not reduce the composite endpoint of cardiovascular death, MI, stroke, or cardiovascular hospitalization, although symptomatic relief was evident[14].

Equivalent neutrality was observed in the ISAACC study, which randomized patients within 72 hours of ACS after OSA had been diagnosed. During subsequent follow-up, CPAP failed to lower the incidence of MACEs. An observational reference cohort without OSA showed a similar cardiovascular event rate, confirming that CPAP neither improved nor worsened post-ACS prognosis[15].

The RICCADSA trial produced the same negative result. In nearly 250 revascularized CAD patients with OSA, CPAP did not yield a clinically meaningful reduction in MACEs during follow-up[15].

Collectively, these three RCTs provide no evidence that CPAP diminishes cardiovascular risk in patients who already have both CVD and OSA, and they offer no justification for prescribing CPAP empirically to CVD patients who do not meet diagnostic criteria for OSA. Accordingly, in these high-risk populations, the putative cardioprotective effect of CPAP remains unproven.

These disappointing RCT findings have not deterred attempts to establish the value of CPAP in other settings. Using a nationwide claims database of almost 900000 adults with OSA, Mazzotti et al[16] showed that patients who began CPAP had significantly lower all-cause mortality [hazard ratio (HR) = 0.53, 95%CI: 0.52–0.54] and fewer cardiovascular events, including coronary outcomes (HR = 0.90, 95%CI: 0.89–0.91).

Supporting evidence comes from Yang et al[56], who analyzed approximately 5500 OSA patients and reported a modest but significant decrease in CAD events (relative risk = 0.87, 95%CI: 0.78–0.98, P = 0.02) along with a nearly one-quarter reduction in cardiovascular mortality (RR = 0.77, 95%CI: 0.60–0.99, P = 0.04) among those receiving CPAP. Taken together, these large observational datasets strengthen the case that CPAP reduces cardiovascular events in patients with OSA, thereby supporting an affirmative answer to clinical question 1. Figure 3A illustrates the benefits of CPAP across various patient subgroups.

Figure 3 Impact of continuous positive airway pressure therapy on clinical outcomes in patients with obstructive sleep apnea. A: In patients with obstructive sleep apnea without established coronary artery disease (CAD), continuous positive airway pressure (CPAP) therapy reduces the risk of future cardiovascular events. However, in those with preexisting CAD, the prognostic benefit of CPAP remains unproven despite the physiological rationale; B: Among patients already receiving CPAP therapy, continuation is associated with improved survival compared with treatment discontinuation, highlighting the importance of long-term adherence in optimizing patient outcomes. CPAP: Continuous positive airway pressure; CAD: Coronary artery disease; OSA: Obstructive sleep apnea.

Although RCTs have thus far failed to demonstrate a mortality benefit from CPAP, Pépin et al[57] These negative findings may reflect key study limitations—namely, poor nightly adherence, restrictive enrollment criteria, and an insufficient number of fatal events. To address these gaps, the Nationwide Claims Data Lake for Sleep Apnea study examined whether stopping CPAP during the first treatment year influences long-term outcomes. In nearly 90000 adults with OSA, continued CPAP use was associated with a significantly lower risk of incident heart failure than early CPAP termination was (HR 0.77, 95%CI: 0.71–0.82; P < 0.01). These real-world data strengthen the case that sustained CPAP adherence confers meaningful cardiovascular protection beyond symptom relief.

To synthesize disparate findings from individual RCTs, Li et al[19] conducted a meta-analysis that pooled data from 4493 participants with moderate-to-severe OSA and preexisting cardiovascular or cerebrovascular disease. In the overall analysis, CPAP was not associated with a lower risk of major adverse cardiac or cerebrovascular events when average nightly use was < 4 hours. However, in the prespecified adherence subgroup, patients who maintained CPAP for > 4 hours per night exhibited significant reductions in cardiovascular mortality and stroke. These results suggest that any cardioprotective signal from CPAP may be contingent upon sufficient nightly exposure. Figure 3B illustrates the key findings of this study.

The aggregate findings from the completed trials are summarized in Figure 4. Although randomized evidence thus far fails to support the use of CPAP for the primary or secondary prevention of CVD, these neutral RCTs are not the final word for cardiovascular outcomes. More recent population-based studies—stratified by adherence—indicate that clinically meaningful benefits may surface in specific patient subgroups. Consequently, the minimum nightly adherence required for therapeutic efficacy deserves renewed scrutiny, and further rigorously designed investigations are essential to define the cardiovascular impact of CPAP at a time when both CVD and OSA are increasingly prevalent.

Figure 4 Impact of continuous positive airway pressure therapy on cardiovascular outcomes and symptom relief across different obstructive sleep apnea and cardiovascular disease patient profiles. CPAP: Continuous positive airway pressure; CVD: Cardiovascular disease; OSA: Obstructive sleep apnea.

INTEGRATED TREATMENT APPROACHES FOR OSA AND CAD

Observational studies have indicated that CPAP therapy may improve intermediate cardiovascular risk factors, such as blood pressure and myocardial ischemia, in patients with OSA and CAD. However, its long-term impact on MACEs remains inconclusive. Large RCTs, including SAVE, RICCADSA, and ISAACC, have not demonstrated a significant reduction in MACEs compared with standard care, particularly in populations with suboptimal CPAP adherence averaging less than 4 hours per night[12,14,15]. In contrast, certain post hoc analyses and recent observational data suggest that CPAP may confer cardiovascular benefits in select subgroups, such as patients exhibiting pronounced heart rate responses to respiratory events or those maintaining high adherence to therapy[16,56,58]. The heterogeneity of these findings underscores the limitations of CPAP monotherapy in the complex clinical context of OSA coexisting with CAD. Common comorbid conditions—including obesity, hypertension, and diabetes—may attenuate the individual effects of CPAP on cardiovascular outcomes[14]. Additionally, inconsistencies in endpoint definitions, challenges in blinding and placebo control in CPAP trials, and the limited duration of follow-up complicate the interpretation of existing evidence[16,56]. These considerations raise important clinical questions regarding the potential advantages of integrated treatment strategies. Combining CPAP with established CAD management approaches—such as statin therapy, antiplatelet agents, optimized blood pressure control, and lifestyle modification—may offer synergistic benefits[56]. Moreover, individualizing treatment by identifying patient subgroups more likely to benefit, such as those with mild OSA, high treatment adherence, or marked vascular inflammation, could be pivotal in enhancing cardiovascular prognosis.

Multimodal treatment strategies

Effective management of patients with OSA and CAD demands an integrated, multimodal approach that simultaneously addresses both conditions to optimize outcomes. CPAP therapy, the cornerstone of OSA treatment, should be paired with lifestyle modifications to enhance its impact on CAD. A comprehensive framework integrating sleep apnea therapies with cardiovascular pharmacologic treatment and lifestyle optimization is essential for improving outcomes in this high-risk population (Figure 5).

Figure 5 Integrated therapeutic strategies for managing patients with comorbid obstructive sleep apnea and coronary artery disease. Effective treatment of obstructive sleep apnea (OSA)–coronary artery disease overlap requires a dual-pronged approach targeting both conditions. Management of OSA includes consistent use of continuous positive airway pressure (CPAP) therapy for ≥ 4 hours per night, with mandibular advancement devices or upper airway surgery considered in cases of CPAP intolerance. Cardiovascular risk factors should be concurrently addressed through antiplatelet therapy, blood pressure control, lipid and glucose management, and avoidance of non-selective beta-blockers. Lifestyle interventions—including diet, weight control, and physical activity—are essential to optimize long-term outcomes. Multidisciplinary collaboration further reinforces the effectiveness and sustainability of integrated care. CAD: Coronary artery disease; CPAP: Continuous positive airway pressure; OSA: Obstructive sleep apnea; MAD: Mandibular advancement devices.

Among these integrated components, lifestyle modification plays a foundational role in both improving OSA control and reducing cardiovascular risk. For example, a 20% decrease in body mass index (BMI) has been correlated with a 57% reduction in the AHI, improving sleep quality and alleviating cardiovascular strain, as demonstrated in a meta-analysis of 27 studies/32 treatment arms[58]. Regular physical activity (e.g., 150 minutes/week of moderate exercise) lowers blood pressure and improves endothelial function, whereas smoking cessation reduces vascular inflammation and plaque progression, which are key CAD risk factors[59]. Together, these changes not only enhance CPAP efficacy but also decrease the likelihood of CAD events such as MI and unstable angina.

Pharmacological interventions play a complementary role and should be tailored to each patient’s CAD profile. Antihypertensive drugs (e.g., ACE inhibitors) control blood pressure to reduce coronary artery stress, statins lower LDL cholesterol to stabilize atherosclerotic plaques (target LDL cholesterol < 70 mg/dL in CAD), and antiplatelet agents (e.g., aspirin 81 mg/day) prevent thrombotic events such as MI, aligning with standard CAD management[59]. Regular monitoring, such as quarterly lipid panels and blood pressure checks, ensures that these therapies remain effective, with adjustments made for comorbidities such as diabetes or renal impairment.

Combination therapy using CPAP and standard pharmacological agents for CAD may yield synergistic benefits beyond those achieved by either approach alone. According to the HIPARCO randomized clinical trial, in patients with OSA and resistant hypertension, 12 weeks of CPAP therapy significantly reduced both mean and diastolic 24-hour blood pressure compared with controls. Additionally, CPAP markedly improved nocturnal blood pressure patterns, contributing to more effective overall blood pressure control[60].

CPAP therapy offers additive cardiovascular benefits when combined with agents such as statins and aspirin by independently reducing systemic inflammation and improving endothelial function[61-63]. These complementary mechanisms may yield superior outcomes in patients with OSA and CAD compared with pharmacotherapy alone. For example, by reducing systemic inflammation, CPAP can potentiate the anti-inflammatory effects of statins, leading to greater reductions in high-sensitivity CRP levels[64]. Similarly, by improving endothelial function and attenuating platelet activation, CPAP may restore aspirin responsiveness in patients with OSA-related aspirin resistance. Further research is needed to elucidate the roles of endothelial dysfunction and aspirin resistance in the relationship between CPAP treatment and cardiovascular outcomes[65].

Nonselective beta-blockers should be avoided in OSA patients, as they may worsen upper airway obstruction, impair insulin sensitivity, and are associated with increased cardiovascular risk and mortality in this population. However, selective beta-blockers such as carvedilol and nebivolol are less likely to exacerbate insulin resistance, and either agent has shown meaningful efficacy in managing blood pressure in OSA patients[66,67].

For patients with severe OSA with an AHI ≥ 30 or poor CPAP tolerance, alternative treatments can further support CAD management. Mandibular advancement devices increase upper airway patency, leading to an approximate 50% reduction in the AHI, from 41.0 ± 20.1 to 19.6 ± 17.1 events per hour, indicating that these devices constitute a viable alternative for patients with suboptimal CPAP adherence[68]. Surgical options, such as tonsillectomy or nasal septoplasty, address anatomical obstructions, enhance oxygenation and potentially lower the nocturnal ischemic burden, as recommended by the Australasian Sleep Association’s 2024 guidelines[69]. These interventions mitigate OSA-related hypoxic stress, indirectly protecting coronary health.

Achieving these benefits requires a collaborative, multidisciplinary framework. Cardiologists optimize CAD therapies, pulmonologists fine-tune OSA interventions, and nutritionists guide weight loss and dietary adjustments (e.g., a Mediterranean diet to lower LDL). Telemonitoring technologies, such as CPAP adherence trackers, can facilitate this teamwork by providing real-time data for joint decision-making[70]. This integrated approach not only improves quality of life and survival but also comprehensively addresses the intertwined pathophysiology of OSA and CAD.

Importance of screening and early diagnosis

Early identification of OSA in patients with CAD, and vice versa, is pivotal for improving outcomes and preventing complications such as MI or unstable angina. Routine screening for OSA should be standard in CAD care, particularly for high-risk patients with obesity (BMI ≥ 30 kg/m²), hypertension, or treatment-resistant hypertension, which are conditions that increase CAD severity[71]. The STOP-BANG questionnaire, with a score ≥ 4 indicating high OSA risk, offers a practical bedside tool, achieving a sensitivity of 94% to 96% for moderate-to-severe OSA (AHI ≥ 15)[72,73]. Similarly, the Epworth sleepiness scale (ESS) assesses daytime sleepiness (a score > 10 suggests excessive sleepiness), identifying patients warranting further evaluation[74]. Confirmatory testing with polysomnography (PSG), the gold standard, or home sleep apnea testing (HSAT) should follow, with PSG detecting the AHI with 95% accuracy and the HSAT providing a cost-effective alternative for uncomplicated cases[18].

Conversely, patients diagnosed with OSA should undergo thorough cardiovascular screening for CAD, especially if they present with symptoms such as exertional chest pain, dyspnea, or palpitations—red flags for underlying coronary pathology[75]. Noninvasive tests, such as coronary artery calcium scoring, can detect subclinical CAD, with prevalence estimates suggesting that 40%–60% of OSA patients have significant coronary atherosclerosis[76,77]. This bidirectional screening ensures timely detection of both conditions, enabling integrated management that mitigates hypoxic stress on the coronary arteries and improves long-term quality of life. By addressing OSA and CAD concurrently, clinicians can reduce the progression of atherosclerosis and improve patient prognosis.

Monitoring and evaluating treatment efficacy

Sustained monitoring of CPAP adherence and cardiovascular health is critical to maximize treatment efficacy in patients with OSA and CAD. Research indicates that CPAP use of at least 4 hours per night for optimal benefit significantly reduces blood pressure and improves endothelial function, key factors in CAD management[78]. Adherence below this threshold, which is common in trials such as the SAVE (3.3 hours/night), often yields limited cardiovascular gains, underscoring the need for regular compliance checks via CPAP device telemetry[79]. Follow-up care should extend beyond CPAP to include comprehensive cardiovascular assessments. Monthly blood pressure monitoring targets values below 130/80 mmHg to reduce coronary strain, whereas quarterly lipid panels ensure that LDL cholesterol remains < 70 mg/dL, stabilizing coronary plaques[80-82]. Echocardiography or strain imaging, performed annually, evaluates left ventricular function (e.g., global longitudinal strain), a marker of CAD progression responsive to CPAP[83]. Symptom evaluation, i.e., daytime sleepiness (via ESS) and fatigue, provides patient-reported outcomes, with mean ESS scores demonstrating a significant reduction following CPAP treatment. Studies have shown that ESS scores decline from 16.4 to 7.0 after two months and from 15.2 to 6.0 after one year, indicating sustained improvement in daytime alertness[84].

Long-term monitoring focuses on preventing MACEs, such as MI or revascularization, and typically requires at least five years of follow-up to capture late outcomes[54]. Therapeutic adjustments—such as optimizing CPAP settings or revisiting cardiovascular medications—should be guided by trends in clinical parameters and individual patient response. When residual cardiovascular risk factors persist despite good CPAP adherence, clinicians may consider intensifying pharmacologic treatment as part of a coordinated care strategy. This dynamic and individualized approach reinforces the long-term effectiveness of integrated OSA–CAD management.

CONCLUSION

Although large RCTs have not demonstrated a significant reduction in major cardiovascular events with CPAP therapy in patients with OSA and CAD, this should not preclude its use. CPAP remains recommended for alleviating daytime sleepiness and improving quality of life. Importantly, patients who maintain good adherence to CPAP therapy (≥ 4 hours per night) may derive cardiovascular benefits, particularly those at high risk or with overt cardiovascular manifestations. The use of CPAP should be individualized and integrated with standard CAD treatments, including statins, beta-blockers, and risk factor management. In summary, while CPAP is not a definitive cure, it constitutes a critical component of a comprehensive management strategy aimed at optimizing cardiovascular health and enhancing patient quality of life.

ACKNOWLEDGEMENTS

We gratefully acknowledge the patients and their families for their participation and trust, which made this study possible. We also extend our appreciation to the Heart and Metabolic Innovations Research Team and Vietnam Society of Sleep Medicine for their collaborative spirit and valuable contributions to this research.