Cardiac Autonomic Dysfunction in Obstructive Sleep Apnea: The Hidden Role of Vitamin D Deficiency

IF 3.5 2区 医学 Q1 MEDICINE, GENERAL & INTERNAL
Huai Heng Loh, Siow Phing Tay, Ai Jiun Koa, Mei Ching Yong, Asri Said, Chee Shee Chai, Natasya Marliana Abdul Malik, Anselm Ting Su, Bonnie Bao Chee Tang, Florence Hui Sieng Tan, Norlela Sukor
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This underscores the importance of identifying modifiable factors to mitigate cardiovascular risks in these patients. A key mechanism linking OSA to heightened cardiovascular risks in CAD is cardiac autonomic dysfunction, characterized by increased sympathetic activity and reduced parasympathetic tone. These alterations can be assessed through heart rate variability (HRV), a well-established predictor of adverse cardiovascular outcomes.</p><p>Patients with OSA often exhibit lower serum 25-hydoxyvitamin D [25(OH)D] levels, with a high prevalence of vitamin D deficiency (VDD) compared to those without OSA [<span>4</span>]. OSA and VDD share overlapping risk factors, with interplay between obesity, hypoxia, reduced vitamin D absorption, inflammation, and effects on upper airway muscle function [<span>4</span>]. VDD is linked to higher cardiovascular risk and mortality and may be associated with poorer HRV [<span>5, 6</span>], although evidence remains limited.</p><p>This study aimed to investigate the role of vitamin D in cardiovascular autonomic function among OSA patients, addressing a critical gap in understanding the interplay between VDD, OSA, and cardiovascular risks. Given the contribution of systemic inflammation and endothelial dysfunction to cardiovascular risks in OSA, we also assessed high-sensitivity C-reactive protein (hsCRP) and brachial artery flow-mediated dilatation (BAFMD) as secondary endpoints, providing complementary insights alongside cardiac autonomic function. The study was conducted in accordance with the principles outlined in the Declaration of Helsinki. Ethical approval was obtained from the Medical Research Ethical Committee of Malaysia (NMRR-21-1472-60812) and UNIMAS Medical Ethics Committee (UNIMAS/TNC(PI)/09-65/01). All patients who fulfilled study criteria were recruited after informed consent obtained. This study was part of a broader research effort, <i>Cardiovascular Impacts of RAAS and Vitamin D in Obstructive Sleep Apnea (CARD-OSA)</i>, which sought to explore the complex roles of renin-angiotensin-aldosterone system and vitamin D in OSA and their broader implications for patient health.</p><p>Designed as a cross-sectional study, it was conducted at a tertiary sleep center from June 2022 to May 2024. Briefly, patients aged ≥18 years with a body mass index (BMI) ≥27.5 kg/m<sup>2</sup>, and confirmed OSA were recruited. The BMI cut-off used, following WHO Asia-Pacific criteria for obesity, aimed to focus on obese individuals, who comprise a high-risk subgroup for both OSA and VDD. Those who were on vitamin D and calcium supplements, had chronic kidney disease, malignancy, cardiac rhythm abnormalities, congestive heart failure, uncontrolled thyroid or parathyroid disease, and pregnancy were excluded from the study.</p><p>Although the study participants were not formally screened for CAD, data on co-morbidities from medical records were documented. All participants underwent assessments for anthropometry, serum 25(OH)D, metabolic parameters, hsCRP, and HRV. Cardiac autonomic function was assessed using Polar H10 strap sensor over 3 min for short-term HRV data, and 24-h Holter monitoring for long-term HRV analysis. Ultrasound of BAFMD was assessed as per protocol [<span>7</span>]. Potential confounders in regression analysis were selected based on established links to HRV and vitamin D status in prior literature and their clinical relevance in OSA.</p><p>The HRV parameters included for analysis and their normal values and ranges are displayed in Tables S1 and S2 respectively. OSA severity was categorized into mild (apnoea-hypopnoea index, AHI 5 to &lt;15/h), moderate (AHI 15 to &lt;30/h), and severe (AHI ≥ 30/h). Vitamin D was categorized based on serum 25(OH)D levels, that is, &lt;20 ng/mL as VDD, and ≥20 ng/mL as non-VDD (nVDD). Normal endothelial function assessed by BAFMD was defined as ≥7.1%, the optimal cut-off for distinguishing individuals with cardiovascular risks [<span>8</span>].</p><p>A total of 797 patients suspected of OSA were screened and 204 (mean age 43.4, 49% males) were recruited (Figure S1). Most patients had severe OSA, with median AHI of 39.0/h (range of AHI 30.1–125.9/h). Demographic data, co-morbidities, metabolic profile, cardiovascular risk markers, and HRV parameters of the study participants are displayed in Table S3. Comparing to those in nVDD group, patients with VDD were younger, consisted mainly of Malay ethnicity and female participants, with lower prevalence of dyslipidemia but higher BMI. Otherwise, there was no significant difference in other co-morbidities and metabolic parameters. Patients with VDD had higher hsCRP (Table S3), and poorer HRV (Table 1) compared with the nVDD group. However, there was no difference in BAFMD.</p><p>Pearson's correlation showed serum 25(OH)D levels were negatively associated with sympathetic nervous system (SNS) index (<i>r</i> = –0.185, <i>p</i> = –0.009) and stress index (<i>r</i> = –0.145, <i>p</i> = 0.041) (Table S4). This association remained significant even after adjusting for confounding factors, as illustrated in the multivariate linear regression analysis (Table S5). The best-fitting models with the highest adjusted <i>R</i><sup>2</sup> were chosen leading to the differences in variables between the two models.</p><p>Our study revealed two key findings: first, OSA patients with VDD exhibit lower HRV and higher hsCRP compared to nVDD patients; second, lower vitamin D concentrations are correlated with poorer HRV, particularly in terms of heightened SNS activation, as evidenced by significantly higher SNS and stress indices. These findings underscore the intricate interplay between vitamin D status and cardiac autonomic function in OSA patients.</p><p>The association between OSA and VDD has been well established, with a bi-directional relationship detailed in previous literature [<span>4</span>]. Although evidence remains inconsistent whether hypovitaminosis D directly contributes to adverse cardiovascular outcomes, several potential pathways have been proposed [<span>9</span>]. These mechanisms include oxidative stress and inflammation, which promote vascular injury, reflected by the higher hsCRP levels observed in the VDD group. Endothelial dysfunction—characterized by impaired nitric oxide availability and vascular reactivity—was not evident in our cohort, whereas dysregulation of cardiac autonomic control was apparent, with poorer HRV indices in VDD patients indicating a shift toward sympathetic predominance and reduced parasympathetic activity.</p><p>Vitamin D influences cardiac tissues and modulates cardiac contractility via calcium metabolism and VDR activity. Low vitamin D levels have also been implicated in structural and ionic channel remodeling, leading to prolonged repolarization intervals and abnormal parasympathetic activity [<span>10</span>]. This aligns with our findings, where serum 25(OH)D levels were significantly associated with HRV parameters, particularly the SNS and stress indices, even after adjusting for confounders, although the low adjusted <i>R</i><sup>2</sup> indicates that the model explains a modest proportion of the variance in HRV. These results suggest that hypovitaminosis D, alongside OSA severity, may partly contribute to elevated cardiovascular risks in OSA patients by increasing SNS activity and disrupting autonomic balance.</p><p>HRV, a non-invasive measure of cardiac autonomic function, reflects fluctuations in SNS and PNS activity. Abnormal HRV is linked to heightened risks of cardiovascular disease and mortality. Reduced HRV, indicative of heightened SNS activity or diminished PNS activity, has been linked to adverse outcomes, including malignant arrhythmias and sudden cardiac death [<span>11</span>]. Short-term HRV assessment, such as those performed in our study, has gained popularity for its ability to predict mortality and ease of artifact handling compared to 24-h recordings, which are more susceptible to inter-individual variability from daily activities [<span>12</span>]. The use of Polar H10 device in our study ensured precise measurement of these indices, further strengthening the reliability of our findings.</p><p>Despite the robustness of our study, several limitations should be noted. First, the cross-sectional design of our study precludes determination of causality between VDD and cardiovascular risks in OSA patients. Second, genetic polymorphisms related to vitamin D, such as those involving vitamin D binding protein and vitamin D receptors, were not investigated due to resource and budget constraints. These genetic factors may further elucidate individual variability in the relationship between vitamin D status and cardiac autonomic function. Third, as our cohort comprised a higher proportion of females (51%) and middle-aged adults, the findings may not be generalizable to the broader OSA population. This may reflect local referral patterns and healthcare-seeking behaviour among women and the middle-aged individuals [<span>13, 14</span>]. In addition, men with OSA and older patients in our setting may have had a greater burden of established cardiovascular complications or advanced organ dysfunction, leading to their exclusion based on our study criteria. Besides, hsCRP and BAFMD measured in our study provide only a partial representation of inflammatory status and endothelial function. The absence of other markers including interleukin-6, tumor necrosis factor-6, and measures of microvascular endothelial function limits a more comprehensive assessment of the pathways linking VDD, inflammation, endothelial health, and cardiac autonomic dysfunction.</p><p>Despite these limitations, this is, to the best of our knowledge, the first study to explore the role of vitamin D in cardiac autonomic function among OSA patients. By excluding individuals receiving vitamin D supplementation, we minimized confounders and ensured that our results more accurately reflect the natural impact of vitamin D status on cardiac autonomic function in this population.</p><p>Moving forward, longitudinal studies are needed to confirm these findings and to evaluate the potential role of vitamin D supplementation in mitigating cardiac autonomic dysfunction and cardiovascular risks in this population. Future research should explore optimal vitamin D thresholds for cardiovascular protection and the impact of supplementation on HRV over time.</p><p>In conclusion, VDD may contribute to the autonomic dysfunction through mechanisms that partially account for the increased cardiovascular risks observed in OSA patients. 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引用次数: 0

Abstract

Obstructive sleep apnea (OSA) is a common sleep-breathing disorder, affecting an estimated 9–38% of adults worldwide, with prevalence increasing in parallel with rising obesity rates and aging population [1]. While men are still more likely to be diagnosed with OSA, this condition is becoming more common in women [2]. Coronary artery disease (CAD), a common complication of OSA, is driven by a combination of intermittent hypoxia, metabolic dysfunction, and systemic inflammation, which together accelerate atherosclerosis [3]. This underscores the importance of identifying modifiable factors to mitigate cardiovascular risks in these patients. A key mechanism linking OSA to heightened cardiovascular risks in CAD is cardiac autonomic dysfunction, characterized by increased sympathetic activity and reduced parasympathetic tone. These alterations can be assessed through heart rate variability (HRV), a well-established predictor of adverse cardiovascular outcomes.

Patients with OSA often exhibit lower serum 25-hydoxyvitamin D [25(OH)D] levels, with a high prevalence of vitamin D deficiency (VDD) compared to those without OSA [4]. OSA and VDD share overlapping risk factors, with interplay between obesity, hypoxia, reduced vitamin D absorption, inflammation, and effects on upper airway muscle function [4]. VDD is linked to higher cardiovascular risk and mortality and may be associated with poorer HRV [5, 6], although evidence remains limited.

This study aimed to investigate the role of vitamin D in cardiovascular autonomic function among OSA patients, addressing a critical gap in understanding the interplay between VDD, OSA, and cardiovascular risks. Given the contribution of systemic inflammation and endothelial dysfunction to cardiovascular risks in OSA, we also assessed high-sensitivity C-reactive protein (hsCRP) and brachial artery flow-mediated dilatation (BAFMD) as secondary endpoints, providing complementary insights alongside cardiac autonomic function. The study was conducted in accordance with the principles outlined in the Declaration of Helsinki. Ethical approval was obtained from the Medical Research Ethical Committee of Malaysia (NMRR-21-1472-60812) and UNIMAS Medical Ethics Committee (UNIMAS/TNC(PI)/09-65/01). All patients who fulfilled study criteria were recruited after informed consent obtained. This study was part of a broader research effort, Cardiovascular Impacts of RAAS and Vitamin D in Obstructive Sleep Apnea (CARD-OSA), which sought to explore the complex roles of renin-angiotensin-aldosterone system and vitamin D in OSA and their broader implications for patient health.

Designed as a cross-sectional study, it was conducted at a tertiary sleep center from June 2022 to May 2024. Briefly, patients aged ≥18 years with a body mass index (BMI) ≥27.5 kg/m2, and confirmed OSA were recruited. The BMI cut-off used, following WHO Asia-Pacific criteria for obesity, aimed to focus on obese individuals, who comprise a high-risk subgroup for both OSA and VDD. Those who were on vitamin D and calcium supplements, had chronic kidney disease, malignancy, cardiac rhythm abnormalities, congestive heart failure, uncontrolled thyroid or parathyroid disease, and pregnancy were excluded from the study.

Although the study participants were not formally screened for CAD, data on co-morbidities from medical records were documented. All participants underwent assessments for anthropometry, serum 25(OH)D, metabolic parameters, hsCRP, and HRV. Cardiac autonomic function was assessed using Polar H10 strap sensor over 3 min for short-term HRV data, and 24-h Holter monitoring for long-term HRV analysis. Ultrasound of BAFMD was assessed as per protocol [7]. Potential confounders in regression analysis were selected based on established links to HRV and vitamin D status in prior literature and their clinical relevance in OSA.

The HRV parameters included for analysis and their normal values and ranges are displayed in Tables S1 and S2 respectively. OSA severity was categorized into mild (apnoea-hypopnoea index, AHI 5 to <15/h), moderate (AHI 15 to <30/h), and severe (AHI ≥ 30/h). Vitamin D was categorized based on serum 25(OH)D levels, that is, <20 ng/mL as VDD, and ≥20 ng/mL as non-VDD (nVDD). Normal endothelial function assessed by BAFMD was defined as ≥7.1%, the optimal cut-off for distinguishing individuals with cardiovascular risks [8].

A total of 797 patients suspected of OSA were screened and 204 (mean age 43.4, 49% males) were recruited (Figure S1). Most patients had severe OSA, with median AHI of 39.0/h (range of AHI 30.1–125.9/h). Demographic data, co-morbidities, metabolic profile, cardiovascular risk markers, and HRV parameters of the study participants are displayed in Table S3. Comparing to those in nVDD group, patients with VDD were younger, consisted mainly of Malay ethnicity and female participants, with lower prevalence of dyslipidemia but higher BMI. Otherwise, there was no significant difference in other co-morbidities and metabolic parameters. Patients with VDD had higher hsCRP (Table S3), and poorer HRV (Table 1) compared with the nVDD group. However, there was no difference in BAFMD.

Pearson's correlation showed serum 25(OH)D levels were negatively associated with sympathetic nervous system (SNS) index (r = –0.185, p = –0.009) and stress index (r = –0.145, p = 0.041) (Table S4). This association remained significant even after adjusting for confounding factors, as illustrated in the multivariate linear regression analysis (Table S5). The best-fitting models with the highest adjusted R2 were chosen leading to the differences in variables between the two models.

Our study revealed two key findings: first, OSA patients with VDD exhibit lower HRV and higher hsCRP compared to nVDD patients; second, lower vitamin D concentrations are correlated with poorer HRV, particularly in terms of heightened SNS activation, as evidenced by significantly higher SNS and stress indices. These findings underscore the intricate interplay between vitamin D status and cardiac autonomic function in OSA patients.

The association between OSA and VDD has been well established, with a bi-directional relationship detailed in previous literature [4]. Although evidence remains inconsistent whether hypovitaminosis D directly contributes to adverse cardiovascular outcomes, several potential pathways have been proposed [9]. These mechanisms include oxidative stress and inflammation, which promote vascular injury, reflected by the higher hsCRP levels observed in the VDD group. Endothelial dysfunction—characterized by impaired nitric oxide availability and vascular reactivity—was not evident in our cohort, whereas dysregulation of cardiac autonomic control was apparent, with poorer HRV indices in VDD patients indicating a shift toward sympathetic predominance and reduced parasympathetic activity.

Vitamin D influences cardiac tissues and modulates cardiac contractility via calcium metabolism and VDR activity. Low vitamin D levels have also been implicated in structural and ionic channel remodeling, leading to prolonged repolarization intervals and abnormal parasympathetic activity [10]. This aligns with our findings, where serum 25(OH)D levels were significantly associated with HRV parameters, particularly the SNS and stress indices, even after adjusting for confounders, although the low adjusted R2 indicates that the model explains a modest proportion of the variance in HRV. These results suggest that hypovitaminosis D, alongside OSA severity, may partly contribute to elevated cardiovascular risks in OSA patients by increasing SNS activity and disrupting autonomic balance.

HRV, a non-invasive measure of cardiac autonomic function, reflects fluctuations in SNS and PNS activity. Abnormal HRV is linked to heightened risks of cardiovascular disease and mortality. Reduced HRV, indicative of heightened SNS activity or diminished PNS activity, has been linked to adverse outcomes, including malignant arrhythmias and sudden cardiac death [11]. Short-term HRV assessment, such as those performed in our study, has gained popularity for its ability to predict mortality and ease of artifact handling compared to 24-h recordings, which are more susceptible to inter-individual variability from daily activities [12]. The use of Polar H10 device in our study ensured precise measurement of these indices, further strengthening the reliability of our findings.

Despite the robustness of our study, several limitations should be noted. First, the cross-sectional design of our study precludes determination of causality between VDD and cardiovascular risks in OSA patients. Second, genetic polymorphisms related to vitamin D, such as those involving vitamin D binding protein and vitamin D receptors, were not investigated due to resource and budget constraints. These genetic factors may further elucidate individual variability in the relationship between vitamin D status and cardiac autonomic function. Third, as our cohort comprised a higher proportion of females (51%) and middle-aged adults, the findings may not be generalizable to the broader OSA population. This may reflect local referral patterns and healthcare-seeking behaviour among women and the middle-aged individuals [13, 14]. In addition, men with OSA and older patients in our setting may have had a greater burden of established cardiovascular complications or advanced organ dysfunction, leading to their exclusion based on our study criteria. Besides, hsCRP and BAFMD measured in our study provide only a partial representation of inflammatory status and endothelial function. The absence of other markers including interleukin-6, tumor necrosis factor-6, and measures of microvascular endothelial function limits a more comprehensive assessment of the pathways linking VDD, inflammation, endothelial health, and cardiac autonomic dysfunction.

Despite these limitations, this is, to the best of our knowledge, the first study to explore the role of vitamin D in cardiac autonomic function among OSA patients. By excluding individuals receiving vitamin D supplementation, we minimized confounders and ensured that our results more accurately reflect the natural impact of vitamin D status on cardiac autonomic function in this population.

Moving forward, longitudinal studies are needed to confirm these findings and to evaluate the potential role of vitamin D supplementation in mitigating cardiac autonomic dysfunction and cardiovascular risks in this population. Future research should explore optimal vitamin D thresholds for cardiovascular protection and the impact of supplementation on HRV over time.

In conclusion, VDD may contribute to the autonomic dysfunction through mechanisms that partially account for the increased cardiovascular risks observed in OSA patients. This highlights the importance of VDD screening in this high-risk population, potentially guiding risk stratification and integrative management strategies.

The authors declare no conflicts of interest.

Abstract Image

阻塞性睡眠呼吸暂停的心脏自主神经功能障碍:维生素D缺乏的隐藏作用。
阻塞性睡眠呼吸暂停(OSA)是一种常见的睡眠呼吸障碍,全球约有9-38%的成年人受其影响,其患病率与肥胖率上升和人口老龄化同步上升。虽然男性仍然更容易被诊断为阻塞性睡眠呼吸暂停,但这种情况在女性中越来越普遍。冠状动脉疾病(CAD)是OSA的常见并发症,由间歇性缺氧、代谢功能障碍和全身性炎症共同驱动,这些因素共同加速动脉粥样硬化的发生。这强调了确定可改变因素以减轻这些患者心血管风险的重要性。将OSA与冠心病心血管风险增加联系起来的一个关键机制是心脏自主神经功能障碍,其特征是交感神经活动增加和副交感神经张力降低。这些改变可以通过心率变异性(HRV)来评估,HRV是一种公认的心血管不良结局的预测因子。OSA患者通常表现出较低的血清25-羟基维生素D [25(OH)D]水平,与无OSA患者相比,维生素D缺乏症(VDD)的患病率较高。OSA和VDD具有重叠的危险因素,肥胖、缺氧、维生素D吸收减少、炎症和上呼吸道肌肉功能影响[4]之间存在相互作用。VDD与较高的心血管风险和死亡率有关,并可能与较差的HRV有关[5,6],尽管证据仍然有限。本研究旨在探讨维生素D在OSA患者心血管自主功能中的作用,解决VDD、OSA和心血管风险之间相互作用的关键空白。考虑到全身性炎症和内皮功能障碍对OSA患者心血管风险的影响,我们还评估了高敏c反应蛋白(hsCRP)和肱动脉血流介导的扩张(BAFMD)作为次要终点,提供了与心脏自主神经功能互补的见解。这项研究是按照《赫尔辛基宣言》所概述的原则进行的。获得了马来西亚医学研究伦理委员会(NMRR-21-1472-60812)和UNIMAS医学伦理委员会(UNIMAS/TNC(PI)/09-65/01)的伦理批准。所有符合研究标准的患者在获得知情同意后被招募。这项研究是一项更广泛的研究工作的一部分,RAAS和维生素D对阻塞性睡眠呼吸暂停(CARD-OSA)的心血管影响,该研究旨在探索肾素-血管紧张素-醛固酮系统和维生素D在OSA中的复杂作用及其对患者健康的更广泛影响。该研究是一项横断面研究,于2022年6月至2024年5月在一家三级睡眠中心进行。简而言之,招募年龄≥18岁、体重指数(BMI)≥27.5 kg/m2且确诊为OSA的患者。根据世卫组织亚太地区肥胖标准,BMI临界值的使用旨在关注肥胖个体,这些个体包括阻塞性睡眠呼吸暂停和室性阻塞性睡眠呼吸暂停的高风险亚组。那些服用维生素D和钙补充剂、患有慢性肾病、恶性肿瘤、心律异常、充血性心力衰竭、甲状腺或甲状旁腺疾病不受控制以及怀孕的人被排除在研究之外。虽然研究参与者没有正式筛查冠心病,但医疗记录中的合并症数据被记录下来。所有参与者都接受了人体测量、血清25(OH)D、代谢参数、hsCRP和HRV的评估。使用Polar H10腕带传感器评估心脏自主功能,短期HRV数据超过3分钟,长期HRV分析使用24小时动态心电图监测。根据方案[7]对BAFMD的超声进行评估。回归分析的潜在混杂因素是根据先前文献中HRV和维生素D状态的确定联系及其在OSA中的临床相关性来选择的。用于分析的HRV参数及其正常值和范围分别显示在表S1和表S2中。OSA严重程度分为轻度(呼吸暂停-低通气指数,AHI 5 ~ 15/h)、中度(AHI 15 ~ 30/h)和重度(AHI≥30/h)。根据血清25(OH)D水平对维生素D进行分类,即≤20 ng/mL为VDD,≥20 ng/mL为非VDD (nVDD)。BAFMD评估的内皮功能正常定义为≥7.1%,这是区分心血管风险个体的最佳临界值。共筛查797例疑似OSA患者,共招募204例(平均年龄43.4岁,49%为男性)(图S1)。大多数患者有严重的OSA, AHI中位数为39.0/h(范围为30.1-125.9 /h)。研究参与者的人口统计数据、合并症、代谢谱、心血管危险指标和HRV参数显示在表S3中。与nVDD组相比,VDD患者更年轻,主要由马来族和女性参与者组成,血脂异常患病率较低,但BMI较高。 除此之外,其他合并症和代谢参数没有显著差异。与nVDD组相比,VDD患者的hsCRP较高(表S3), HRV较差(表1)。然而,在BAFMD方面没有差异。Pearson相关分析显示血清25(OH)D水平与交感神经系统(SNS)指数(r = -0.185, p = -0.009)和应激指数(r = -0.145, p = 0.041)呈负相关(表S4)。如多元线性回归分析(表S5)所示,即使在调整了混杂因素后,这种关联仍然显著。选择调整R2最高的最佳拟合模型,导致两种模型之间的变量存在差异。我们的研究揭示了两个关键发现:首先,与nVDD患者相比,OSA合并VDD患者表现出较低的HRV和较高的hsCRP;其次,较低的维生素D浓度与较差的HRV相关,特别是在SNS激活增强方面,SNS和应激指数显著升高。这些发现强调了OSA患者维生素D状态与心脏自主神经功能之间复杂的相互作用。OSA和VDD之间的关联已经得到了很好的确立,在之前的文献[4]中详细描述了这种双向关系。尽管维生素D缺乏症是否直接导致不良心血管结果的证据仍不一致,但已经提出了几种潜在的途径。这些机制包括氧化应激和炎症,它们促进血管损伤,反映在VDD组观察到较高的hsCRP水平。内皮功能障碍(以一氧化氮可用性和血管反应性受损为特征)在我们的队列中并不明显,而心脏自主控制的失调是明显的,VDD患者的HRV指数较差,表明交感神经占优,副交感神经活动减少。维生素D通过钙代谢和VDR活性影响心脏组织并调节心脏收缩力。低维生素D水平也与结构和离子通道重塑有关,导致复极间隔延长和副交感神经活动异常[10]。这与我们的研究结果一致,即使在调整混杂因素后,血清25(OH)D水平与HRV参数,特别是SNS和应激指数显着相关,尽管调整后的低R2表明该模型解释了HRV方差的适度比例。这些结果表明,维生素D缺乏症和OSA严重程度可能通过增加SNS活动和破坏自主神经平衡,在一定程度上导致OSA患者心血管风险升高。HRV是一种对心脏自主神经功能的无创测量,反映了SNS和PNS活动的波动。HRV异常与心血管疾病和死亡率增加有关。HRV降低,表明SNS活动增强或PNS活动减弱,与不良结局有关,包括恶性心律失常和心源性猝死[11]。与24小时记录相比,短期HRV评估,如在我们的研究中进行的评估,因其预测死亡率的能力和人工制品处理的便利性而受到欢迎,而24小时记录更容易受到来自日常活动的个体间差异的影响。在我们的研究中使用Polar H10设备确保了这些指标的精确测量,进一步加强了我们研究结果的可靠性。尽管我们的研究具有稳健性,但仍应注意到一些局限性。首先,我们研究的横断面设计排除了确定OSA患者VDD与心血管风险之间的因果关系。其次,由于资源和预算的限制,没有研究与维生素D相关的遗传多态性,例如涉及维生素D结合蛋白和维生素D受体的遗传多态性。这些遗传因素可能进一步阐明维生素D状态与心脏自主神经功能之间关系的个体差异。第三,由于我们的队列包括较高比例的女性(51%)和中年人,研究结果可能无法推广到更广泛的OSA人群。这可能反映了当地妇女和中年人的转诊模式和求医行为[13,14]。此外,在我们的研究中,患有OSA的男性和老年患者可能有更大的心血管并发症或晚期器官功能障碍的负担,导致他们根据我们的研究标准被排除在外。此外,我们研究中测量的hsCRP和BAFMD仅能部分反映炎症状态和内皮功能。缺乏其他标志物,包括白细胞介素-6、肿瘤坏死因子-6和微血管内皮功能的测量,限制了对VDD、炎症、内皮健康和心脏自主神经功能障碍联系途径的更全面评估。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
Journal of Evidence‐Based Medicine
Journal of Evidence‐Based Medicine MEDICINE, GENERAL & INTERNAL-
CiteScore
11.20
自引率
1.40%
发文量
42
期刊介绍: The Journal of Evidence-Based Medicine (EMB) is an esteemed international healthcare and medical decision-making journal, dedicated to publishing groundbreaking research outcomes in evidence-based decision-making, research, practice, and education. Serving as the official English-language journal of the Cochrane China Centre and West China Hospital of Sichuan University, we eagerly welcome editorials, commentaries, and systematic reviews encompassing various topics such as clinical trials, policy, drug and patient safety, education, and knowledge translation.
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