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ORIGINAL RESEARCH article

Front. Physiol., 18 October 2021
Sec. Respiratory Physiology and Pathophysiology
This article is part of the Research Topic Causes and Consequences of Sleep Apnea: Spotlights on the Roles of Sex and Sex Hormones View all 6 articles

Effect of Maternal Obstructive Sleep Apnea-Hypopnea on 24-Hour Blood Pressure, Nocturnal Blood Pressure Dipping and Arterial Stiffness in Hypertensive Disorders of Pregnancy

\r\nPattaraporn Panyarath,Pattaraporn Panyarath1,2Noa GoldscherNoa Goldscher1Sushmita Pamidi,Sushmita Pamidi1,3Stella S. Daskalopoulou,Stella S. Daskalopoulou3,4Robert GagnonRobert Gagnon5Natalie Dayan,Natalie Dayan3,4Kathleen RaicheKathleen Raiche1Allen OlhaAllen Olha1Andrea Benedetti,Andrea Benedetti3,6R. John Kimoff,*R. John Kimoff1,3*
  • 1Respiratory Division and Sleep Laboratory, McGill University Health Centre, Montreal, QC, Canada
  • 2Division of Respiratory and Respiratory Critical Care Medicine, Department of Internal Medicine, Faculty of Medicine, Prince of Songkla University, Songkhla, Thailand
  • 3Center for Outcomes Research, McGill University Health Centre, Montreal, QC, Canada
  • 4Division of Internal Medicine, McGill University Health Centre, Montreal, QC, Canada
  • 5Maternal-Fetal Medicine, Department of Obstetrics and Gynecology, McGill University Health Centre, Montreal, QC, Canada
  • 6Department of Epidemiology and Biostatistics, McGill University Health Centre, Montreal, QC, Canada

Rationale: Maternal obstructive sleep apnea-hypopnea (OSAH) is associated with hypertensive disorders of pregnancy (HDP). Attenuation of the normal nocturnal blood pressure (BP) decline (non-dipping) is associated with adverse pregnancy outcomes. OSAH is associated with nocturnal non-dipping in the general population, but this has not been studied in pregnancy. We therefore analyzed baseline data from an ongoing RCT (NCT03309826) assessing the impact of OSAH treatment on HDP outcomes, to evaluate the relationship of OSAH to 24-h BP profile, in particular nocturnal BP dipping, and measures of arterial stiffness.

Methods: Women with a singleton pregnancy and HDP underwent level II polysomnography. Patients with OSAH (apnea-hypopnea index (AHI) ≥ 5 events/h) then underwent 24-h ambulatory BP monitoring and arterial stiffness measurements (applanation tonometry, SphygmoCor). Positive dipping was defined as nocturnal systolic blood pressure (SBP) dip ≥ 10%. The relationships between measures of OSAH severity, measures of BP and arterial stiffness were evaluated using linear regression analyses.

Results: We studied 51 HDP participants (36.5 ± 4.9 years, BMI 36.9 ± 8.6 kg/m2) with OSAH with mean AHI 27.7 ± 26.4 events/h at 25.0 ± 4.9 weeks’ gestation. We found no significant relationships between AHI or other OSA severity measures and mean 24-h BP values, although BP was generally well-controlled. Most women were SBP non-dippers (78.4%). AHI showed a significant inverse correlation with % SBP dipping following adjustment for age, BMI, parity, gestational age, and BP medications (β = −0.11, p = 0.02). Significant inverse correlations were also observed between AHI and DBP (β = −0.16, p = 0.01) and MAP (β = −0.13, p = 0.02) % dipping. Oxygen desaturation index and sleep time below SaO2 90% were also inversely correlated with % dipping. Moreover, a significant positive correlation was observed between carotid-femoral pulse wave velocity (cfPWV) and REM AHI (β = 0.02, p = 0.04) in unadjusted but not adjusted analysis.

Conclusion: Blood pressure non-dipping was observed in a majority of women with HDP and OSAH. There were significant inverse relationships between OSAH severity measures and nocturnal % dipping. Increased arterial stiffness was associated with increasing severity of OSAH during REM sleep in unadjusted although not adjusted analysis. These findings suggest that OSAH may represent a therapeutic target to improve BP profile and vascular risk in HDP.

Introduction

Hypertensive disorders of pregnancy (HDP) complicate up to 10% of pregnancies and are a leading cause of maternal and infant morbidity and mortality worldwide (Lo et al., 2013; Seely and Ecker, 2014; Folk, 2018; Shah and Gupta, 2019). HDP are classified by the American College of Obstetricians and Gynecologists (ACOG) into four categories: pre-eclampsia–eclampsia, chronic hypertension, chronic hypertension with superimposed pre-eclampsia, and gestational hypertension. Chronic hypertension is defined as hypertension that develops either pre-pregnancy or at less than 20 weeks’ gestation. Gestational hypertension is defined as blood pressure (BP) higher than 140/90 mmHg diagnosed after 20 weeks of gestation, and pre-eclampsia is characterized by new-onset hypertension with proteinuria or end organ damage symptoms (Roberts et al., 2013).

Nocturnal BP dipping is a reflection of the normal physiologic reduction in sympathetic nervous activity during sleep (O’Brien et al., 2013; Parati et al., 2014). Normally, night-time systolic and diastolic BP are 10–20% lower than daytime BP in non-pregnant women and throughout normal pregnancy (Gupta et al., 2011). However, many patients with HDP demonstrate an absence of nocturnal BP dipping (non-dippers) (Oney and Meyer-Sabellek, 1990; Ayala et al., 1997; Hermida et al., 2000; Gupta et al., 2011). In the general population, non-dipping predicts mortality and cardiovascular events (Lee et al., 2005; Fagard et al., 2009; Gavriilaki et al., 2020). In HDP, an association between BP non-dipping and altered hemodynamic function and fetal growth restriction (FGR) has been reported. Ilic et al. (2017) demonstrated that the prevalence of preterm delivery and FGR was significantly higher in non-dippers compared to dippers (66.7% vs. 16.7% for preterm delivery and 72.4% vs. 24.2% for FGR). Furthermore, the authors found that non-dipping in HDP patients was associated with impaired maternal cardiac function, including reduced left ventricle ejection fraction, velocity of longitudinal systolic function, and cardiac output (Ilic et al., 2017). Targeting factors associated with BP non-dipping could, therefore, potentially contribute to improved maternal and fetal outcomes in HDP.

Obstructive sleep apnea-hypopnea (OSAH) is characterized by repetitive upper airway obstruction during sleep resulting in intermittent hypoxia and sleep fragmentation (American Academy of Sleep Medicine Task Force, 1999). OSAH is associated with sympathetic activation, oxidative stress, systemic inflammation, and endothelial dysfunction, and in the general population is associated with hypertension and increased risk of congestive heart failure, and acute ischemic events (Peppard et al., 2000; Baguet et al., 2012; Phillips and O’Driscoll, 2013). OSAH in the general population is also associated with BP non-dipping (Seif et al., 2014; Torres et al., 2015; Genta-Pereira et al., 2018; Crinion et al., 2019; Cuspidi et al., 2019; Pio-Abreu et al., 2021). The reported prevalence of a non-dipping BP pattern in OSAH is 48–84% and a recent meta-analysis study found that OSAH increases the likelihood of BP non-dipping by 1.5-fold (Cuspidi et al., 2019). Crinion et al. (2019) reported a significant inverse relationship between OSAH severity and the magnitude of nocturnal BP dip (β = −0.29, p = 0.03). On the other hand, randomized, controlled trials have demonstrated that treatment of OSAH with continuous positive airway pressure (CPAP) lowers BP in non-pregnant people with hypertension (Bratton et al., 2015; Patil et al., 2019). Of note, BP non-dipping was identified as a good predictor of BP response to CPAP treatment in people with OSAH (Labarca et al., 2021).

Obstructive sleep apnea-hypopnea may develop or worsen over the course of pregnancy, reaching an estimated prevalence of 17–45% of women in the third trimester (Pamidi and Kimoff, 2018). There is increasing evidence that maternal OSAH is associated with a greater risk of HDP (Champagne et al., 2009; Ding et al., 2014; Pamidi et al., 2014; Bourjeily et al., 2017; Li et al., 2018; Liu et al., 2019; Querejeta Roca et al., 2020; Lu et al., 2021) and other adverse pregnancy outcomes, including gestational diabetes mellitus and small for gestational age infants (SGA) (Pamidi et al., 2016). Recent meta-analyses have reported adjusted odds ratios of 1.93–2.38 for the association between OSAH and gestational hypertension (Ding et al., 2014; Pamidi et al., 2014; Li et al., 2018; Liu et al., 2019; Lu et al., 2021). Similarly, OSAH is associated with increased risk for pre-eclampsia (adjusted odds ratios of 2.19–2.63) (Ding et al., 2014; Pamidi et al., 2014; Li et al., 2018; Liu et al., 2019; Lu et al., 2021). The findings from the general adult OSAH population suggest that maternal OSAH may also be associated with non-dipping in HDP, and thus potentially contribute to the links between maternal BP non-dipping and adverse HDP outcomes. However, this has not been directly studied.

Arterial stiffness is a summative indicator of vascular health and an established cardiovascular risk marker in the general population. Previous studies have demonstrated that OSAH in the general population is associated with increased arterial stiffness and that stiffness measures improve with CPAP treatment (Kohler et al., 2013; Vlachantoni et al., 2013; Wons and Kohler, 2015; Lin et al., 2016; Chalegre et al., 2020). Arterial stiffness is increased in HDP and a previous meta-analysis (Hausvater et al., 2012) found significantly higher values for carotid-femoral pulse wave velocity (cfPWV) and augmentation index (AIx) in pre-eclampsia compared with gestational hypertension. Work at our center has also recently shown that changes in arterial stiffness predict subsequent development of pre-eclampsia (Phan et al., 2021). The foregoing observations raise the possibility that maternal OSAH may also be associated with increased arterial stiffness in HDP. However, this has not been directly studied.

The primary aim of this study was therefore to evaluate the relationship of maternal OSAH to 24-h BP and in particular nocturnal BP dipping in women with HDP. We also aimed to evaluate the relationship of OSAH to measures of arterial stiffness in women with HDP with OSAH.

Materials and Methods

Study Design

This is a cross-sectional analysis of baseline data collected from an ongoing pilot randomized controlled trial (RCT) assessing the impact of OSAH treatment on HDP outcomes. The RCT is registered at clinicaltrials.gov (NCT03309826). The primary objective of this study was to evaluate the relationship of maternal OSAH to 24-h BP and in particular, nocturnal BP dipping in women with HDP. The secondary objective was to evaluate the relationship of OSAH to measures of arterial stiffness in women with HDP.

Study Population and Protocol

We recruited women ≥18 years of age with a singleton pregnancy, ≥12 weeks’ gestation diagnosed with hypertension defined by daytime systolic BP ≥ 140 and/or diastolic BP ≥ 90 mmHg or current antihypertensive treatment from our obstetric clinics. Women were excluded if they had current severe pre-eclampsia/eclampsia requiring immediate delivery; chronic kidney disease (serum creatinine >100 mmol/L); another secondary cause of hypertension; active cardiac disease or stroke within the last 3 months; malignancy or other active psychiatric or chronic medical condition; active smoking, alcohol use or illicit drugs; current/recent treatment for OSAH; restless legs syndrome; shift work; travel across time zones in the past month or other active medical sleep disorder. The study was approved by our institutional Research Ethics Board and all participants gave written informed consent.

Potential participants underwent a home level II polysomnography (PSG) to screen for OSAH, which was defined by an apnea-hypopnea index (AHI) ≥5 events/h using AASM research (Chicago) scoring criteria (American Academy of Sleep Medicine Task Force, 1999). Those found to have OSAH then underwent measurement of arterial stiffness, immediately followed by 24-h ambulatory BP monitoring on the same day.

Sleep Measurements

One-night home level II PSG was performed using the Embletta MPR with ST-proxy sleep system (Natus Inc., Mississauga, ON, United States) using our standard techniques (Champagne et al., 2009; Pamidi et al., 2014). A trained sleep technologist installed the recording equipment in the participant’s home. Sleep-wake state, arousals, and periodic limb movements were scored using AASM criteria (Berry et al., 2012), but respiratory events were scored using AASM research (Chicago) criteria (American Academy of Sleep Medicine Task Force, 1999) by a single experienced Registered Polysomnographic Technologist-certified scorer. We applied Chicago scoring criteria as they are more sensitive than AASM 2012 criteria, in that OSAH in pregnancy is characterized predominantly by hypopneas associated with microarousals rather than apneas or frequent desaturations (Champagne et al., 2009; Pamidi et al., 2014).

Participants also completed questionnaires assessing subjective sleep quality [Pittsburgh sleep quality index (PSQI)] (Buysse et al., 1989) and daytime sleepiness [Epworth sleepiness score (ESS)] (Johns, 1991).

Blood Pressure and Heart Rate Measurements

Twenty-four-hour BP and heart rate were measured every 30 min during the daytime (6.00 AM–11.00 PM) and every 1 h at night (11.00 PM–6.00 AM) (Parati et al., 2014) using a validated Spacelabs Inc. device. Mean and standard deviation (SD) were calculated for both BP and heart rate. Heart rate variability was assessed via the coefficient of variability (CoV)–calculated as SD of heart rate divided by mean heart rate X 100. Office BP also was measured using a validated automated device BpTRU (average of last 5 of 6 unattended measurements obtained 1 min apart in the sitting or left lateral decubitus position) (Myers et al., 2014; Magee et al., 2015). In previous studies, BpTRU in non-pregnancy yielded values closely comparable to daytime values from 24-h ambulatory blood pressure monitoring (ABPM) (Myers et al., 2014).

Arterial Stiffness Measurements

Participants underwent arterial stiffness measurement using Applanation tonometry (SphygmoCor; AtCor Medical, Sydney, NSW, Australia) to obtain measurements of cfPWV (central stiffness, main arterial stiffness outcome measure), carotid-radial PWV (crPWV) (peripheral stiffness), wave reflection assessed by AIx, and AIx corrected to a heart rate of 75 bpm (AIx75), as well as central BPs, pulse pressure amplification (PPA) (a measure of the progressive increase in pulse pressure from central to peripheral arteries), and subendocardial viability ratio (SEVR) (an index of myocardial oxygen supply and demand) using our established protocol (Gomez et al., 2016).

Statistical Analysis

Based on BP dipping status on 24-h ABPM measurement, the participants were divided into dippers and non-dippers. The % BP dip was calculated as the difference between daytime and nighttime mean systolic blood pressure (SBP) divided by mean daytime SBP. Positive dipping (dippers) was defined as nocturnal SBP dip ≥ 10%, while <10% dip was defined as non-dipping. We similarly assessed ≥10% dipping for diastolic (DBP) and mean arterial pressure (MAP) (O’Brien et al., 2013; Parati et al., 2014).

Extreme dipping was defined as nocturnal BP dip ≥ 20% and inverse dipping was defined as any increase in BP overnight (Parati et al., 2014). Due to very small numbers (Figure 2A), extreme dippers were included in the dipper group and reverse dippers in the non-dipper group. Comparison of 24-h and office BP measures, as well as arterial stiffness measures between dipper and non-dipper groups was performed using unpaired T-tests. The primary analysis was to evaluate the relationship of OSAH severity to 24-h BP, in particular % nocturnal BP dipping. Linear regression was performed to evaluate the relationship between measures of OSAH severity [AHI; AHI during REM-sleep (REM-AHI); 4% oxygen desaturation index (4%ODI); % time of SpO2 below 90%] and mean 24-h BP. A separate linear regression model was constructed to evaluate the association between OSAH severity measures and % BP dipping. We adjusted for five potential confounding factors, including age, body mass index, gestational age at enrolment, parity, and number of antihypertensive medications in subsequent multiple regression models. For analysis of arterial stiffness, given uncertainty regarding normal arterial stiffness values in pregnancy, participants were divided into high vs. low arterial stiffness using the group median value for cfPWV of 7.2 m/s. Participant characteristics were then compared between high vs. low arterial stiffness groups. The relationship between OSAH severity measures and cfPWV as well as other arterial stiffness measures was also examined using linear regression models. All analyses were carried out using SPSS software, version 27.

Results

Study Participants

Two-hundred and eighty nine potential participants were identified from our obstetrics clinics between November 2017 and January 2021 (Figure 1). Of these, 38 women declined to participate in the study, 184 women were ineligible on the basis of no hypertension at screening, preterm delivery expected within 2 weeks, twin pregnancy, current CPAP treatment, medical co-morbidities, substance use, language barrier, or follow-up at another institution.

FIGURE 1
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Figure 1. Enrollment flow diagram.

There were 67 potentially eligible participants who underwent PSG testing. 16 participants were excluded (five participants with AHI <5 events/h, five participants without 24-h BP data, and six participants failed the first night PSG then refused to repeat). The characteristics of the 51 HDP participants with OSAH who completed the study measurements are shown in Tables 1, 2. Participants were of mean age 36.5 ± 4.9 years, most were obese based on pre-pregnancy BMI and nearly half were Caucasian. The majority of participants were classified as having chronic hypertension (80.4%) and were receiving a single anti-hypertensive medication (64.7%) as well aspirin (82.4%) to reduce pre-eclampsia risk. A minority of participants had gestational diabetes. There was a history of pre-eclampsia in a previous pregnancy in 27.5%. PSG, 24-h ABPM, and arterial stiffness measurements were performed upon recruitment in either the second or third trimester. Most women were diagnosed with mild to moderate obstructive sleep apnea (Table 2). On average, they reported no or mild excessive daytime sleepiness based on ESS, but overall poor subjective sleep quality based on the PSQI (Table 1).

TABLE 1
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Table 1. Patient characteristics stratified by blood pressure dipping status.

TABLE 2
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Table 2. Polysomnography characteristics of participants stratified by blood pressure dipping status.

The cohort was divided into dippers and non-dippers based on systolic BP dipping status. BP non-dipping was observed 40 participants (78.4%). No differences in demographics, subjective daytime sleepiness (ESS) or sleep quality (PSQI) or polysomnographic variables assessing sleep quality or fragmentation or OSAH severity were found between dippers and non-dippers (Tables 1, 2). We also found no significant relationships between % BP dipping and subjective sleepiness or sleep quality or with polysomnographic characteristics reflecting sleep quality and continuity (Supplementary Table 1).

On average, most participants had normal 24-h BP and office BP. As expected, nighttime systolic and diastolic BP was significantly higher in non-dippers than dippers, but there were no other significant differences in 24-h BP or in office BP between dippers and non-dippers (Table 3). Office BP measurements showed a significant positive correlation with the systolic and diastolic values obtained by 24-h ABPM (β = 0.75 and 0.70 for systolic and diastolic BP, respectively; p-value < 0.01). The mean % systolic BP dip in the dippers was 13.7 ± 3.4% vs. 4.1 ± 3.5% for non-dippers. Similarly, the mean % diastolic BP and MAP dip in the dippers and non-dippers were 16.6 ± 5.2% vs. 4.4 ± 5% for diastolic BP dip, and 15.2 ± 4.4% vs. 4.7 ± 4.2% for MAP dip, respectively (Table 3).

TABLE 3
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Table 3. 24-h blood pressure and % blood pressure dipping of participants stratified by blood pressure dipping status.

Association Between Obstructive Sleep Apnea-Hypopnea Severity and 24-H Blood Pressure Measures

No significant relationships were found between AHI or other OSAH severity measures and 24-h SBP, DBP, or MAP values in regression analyses (Table 4). However, AHI showed a significant inverse correlation with % SBP dip following adjustment for age, body mass index, parity, gestational age, and BP medications (β = −0.11, 95% CI = −0.20 to −0.02; p = 0.02) (Table 5 and Figure 2). Similarly, significant inverse correlations were observed between AHI and % DBP dip (β = −0.16, 95% CI = −0.29 to −0.04; p = 0.01) and % MAP dip (β = −0.13, 95% CI = −0.24 to −0.02; p = 0.02) (Table 5 and Figure 2). As shown in Supplementary Tables 2, 3, we found no significant relationships between participants demographics and 24-h BP or % BP dip in regression analyses.

TABLE 4
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Table 4. Regression models for association between 24-h blood pressures and obstructive sleep apnea severity measures.

TABLE 5
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Table 5. Regression models for association between % blood pressure dipping and obstructive sleep apnea severity measures.

FIGURE 2
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Figure 2. Linear regression models demonstrated association between % blood pressure dipping and apnea-hypopnea index. (A) % Systolic blood pressure (SBP) dipping. (B) % Diastolic blood pressure (DBP) dipping. (C) % Mean arterial pressure (MAP) dipping.

In addition, 4% oxygen desaturation index showed a significant inverse correlation with % SBP, DBP and MAP dip in adjusted regression analyses (β = −0.15, 95% CI = −0.23 to −0.06; p < 0.01 for % SBP dip, β = −0.23, 95% CI = −0.35 to −0.11; p < 0.01 for % DBP dip and β = −0.18, 95% CI = −0.30 to −0.09; p < 0.01 for % MAP dip). Moreover, there were significant positive correlations between total sleep time with oxygen saturation <90% and % SBP, DBP and MAP dip in adjusted regression analyses (β = −0.32, 95% CI = −0.57 to −0.07; p = 0.01 for % SBP dip, β = −0.67, 95% CI = −0.99 to −0.34; p < 0.01 for % DBP dip and β = −0.54, 95% CI = −0.82 to −0.26; p < 0.01 for % MAP dip). We also found a positive significant correlation between nadir oxygen saturation and % DBP dip in adjusted regression analysis (β = 0.56, 95% CI = 0.13 to 0.99; p = 0.01) and % MAP dip in unadjusted regression analysis (β = 0.30, 95% CI = 0.03 to 0.58; p = 0.03) but not % SBP dip (Table 5).

Association Between Obstructive Sleep Apnea-Hypopnea Severity and 24-H Heart Rate Measures

There were no significant differences in 24-h, daytime and nighttime heart rate between dippers and non-dippers stratified by SBP, DBP, or MAP dipping status (Supplementary Table 4).

The nocturnal decline in heart rate was small in all groups and did not differ according to dipping status. We also found no significant differences in heart rate variability (CoV) between dippers and non-dippers for 24 h, daytime or nighttime (Supplementary Table 4). No significant relationships were found between AHI or other OSAH severity measures and 24-h, daytime, or nighttime heart rate CoV (Supplementary Table 5).

Association Between Obstructive Sleep Apnea-Hypopnea Severity and Arterial Stiffness Measures

Of the 43 patients who completed arterial stiffness measurement, there were 11 dippers and 32 non-dippers. The mean cfPWV was 7.4 ± 1.2 m/s. The participants were divided into high vs. low central arterial stiffness according to the group median cfPWV at 7.2 m/s. No differences between sleep characteristics for high and low cfPWV groups were observed (Supplementary Table 6).

There was no significant difference in the proportion of high cfPWV patients between dippers and non-dippers. Likewise, there was no significant difference in other arterial stiffness measures between dippers and non-dippers except for a higher SEVR with non-dippers (Table 6).

TABLE 6
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Table 6. Arterial stiffness characteristics of participants stratified by blood pressure dipping status.

There were significant relationships between cfPWV and BMI in unadjusted and adjusted regression analyses [β = 0.06 (95% CI = 0.01 to 0.11) and 0.08 (95% CI = 0.02 to 0.13); p = 0.02 and 0.01, respectively] (Table 7 and Supplementary Figure 1). Similarly, a significant positive association between cfPWV and maternal age was observed in adjusted regression analysis. While most measures of OSAH severity did not show significant associations with arterial stiffness measures, we did observe a significant positive correlation between cfPWV and the AHI during REM sleep (REM-AHI) in unadjusted regression analysis (β = 0.02, 95% CI = 0.001 to 0.03; p = 0.04). However, this was no longer significant following adjustment for age, body mass index, gestational age, and parity (β = 0.01, 95% CI = −0.01 to 0.03; p = 0.23) (Table 7 and Figure 3). There were no significant correlations between cfPWV and other OSAH severity measures (Table 7).

TABLE 7
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Table 7. Regression models for association between carotid femoral pulse wave velocity and demographics and obstructive sleep apnea severity measures.

FIGURE 3
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Figure 3. Linear regression model demonstrated association between carotid femoral pulse wave velocity and REM-apnea hypopnea index (REM-AHI).

Significant inverse associations were observed between cfPWV and 24-h BP values in adjusted regression analyses, but cfPWV was not correlated with % nocturnal BP dipping (Supplementary Table 7).

Discussion

Pre-eclampsia affects 2–8% of pregnancies and remains a leading cause of maternal and neonatal mortality (Shah and Gupta, 2019). While previous studies have identified risk factors for progression to pre-eclampsia among women with gestational hypertension, (Florio et al., 2005; Davis et al., 2007; Bellomo et al., 2011; Rana et al., 2012; Melamed et al., 2014; Phan et al., 2021) there is a need to identify risk factors which can be modified to improve adverse maternal and fetal outcomes in women with HDP.

Estimates of the prevalence of OSAH in pregnancy by the third trimester range from 17 to 45% (Pamidi and Kimoff, 2018). Several studies have shown that OSAH is strongly associated with a greater risk of HDP (Champagne et al., 2009; Ding et al., 2014; Pamidi et al., 2014; Bourjeily et al., 2017; Li et al., 2018; Liu et al., 2019; Querejeta Roca et al., 2020; Lu et al., 2021). In keeping with this, in the present study, out of 67 HDP women who initially met eligibility criteria, 56 (83.6%) tested positive for OSAH.

While the high prevalence of OSAH in our pregnant participants with chronic and gestational hypertension supports the link between OSAH and HDP, we did not observe any significant relationships between OSAH severity measures and 24-h BP values. We believe the most likely explanation for the lack of an association between OSAH severity measures and 24-h BP profile is that our participants were on at least one anti-hypertensive medication and were followed regularly by our maternal-fetal medicine specialists with close monitoring of BP control. BP values overall were within the target normal range so that a relationship between OSAH severity and BP level was not evident.

It is well known that a non-dipping BP pattern predicts poor cardiovascular outcomes in non-pregnant patients with hypertension (de la Sierra et al., 2014; Seif et al., 2014; Torres et al., 2015; Genta-Pereira et al., 2018; Crinion et al., 2019; Cuspidi et al., 2019; Pio-Abreu et al., 2021). In HDP patients, BP non-dipping predicts preterm delivery, FGR, and poor maternal cardiac function (Ilic et al., 2017). Thus a nocturnal non-dipping BP pattern would appear to be an important measure for risk stratification in patients with HDP. We found a high proportion (nearly 80%) of BP non-dipping among our HDP patients with OSAH. Previous studies reported that blunting of circadian pattern was more common in pre-eclampsia patients compared to normotensive pregnant women (Oney and Meyer-Sabellek, 1990; Ayala et al., 1997; Hermida et al., 2000; Gupta et al., 2011). In pre-eclampsia patients, the prevalence of systolic and diastolic BP non-dipping was 40 and 65%, respectively, while in normotensive pregnant women, non-dippers were found only 23 and 34.3% for systolic and diastolic BP (Gupta et al., 2011).

Previous studies in the general population indicate that OSAH is associated with BP non-dipping (Seif et al., 2014; Torres et al., 2015; Genta-Pereira et al., 2018; Crinion et al., 2019; Cuspidi et al., 2019; Pio-Abreu et al., 2021). However, the present study is the first to demonstrate that increasing severity of OSAH as reflected by AHI, 4% ODI, and TST < 90%, is associated with decreased nocturnal BP dipping in hypertensive pregnant women. These associations remained significant after adjusting for age, body mass index, parity, gestational age, and BP medications. We found that each 1 event/h increase in AHI was associated with 0.11 and 0.16% reduction in % SBP and DBP dipping, respectively. Similarly, we found each 1 event/h increase in 4% ODI was associated with 0.15 and 0.23% reduction in % SBP and DBP dipping, respectively. The nocturnal hypertension in OSAH participants may be explained by the BP surge at the end of the obstructive respiratory events (Somers et al., 1995).

Recent meta-analyses demonstrate that CPAP treatment improves BP in OSAH with the largest changes being in nocturnal BP values, with restoration of dipping in some studies (Bratton et al., 2015; Patil et al., 2019). The link between OSAH and BP non-dipping in the present study therefore raises the possibility that treatment of OSAH could restore the nocturnal dipping pattern in HDP and thus potentially attenuate the risk for development of pre-eclampsia. The effects of CPAP treatment on 24 h BP are being explored in our ongoing pilot controlled trial (NCT03309826).

Previous studies have shown that arterial stiffness is elevated in patients with OSAH (Kohler et al., 2008; Doonan et al., 2011; Jenner et al., 2017) and one study demonstrated an association between OSAH, increased arterial stiffness and a non-dipping BP pattern in patients with hypertension (odd ratio = 3.03; 95% CI = 1.08–0.35) (Jenner et al., 2017). Evidence from meta-analyses demonstrated that CPAP treatment is associated with improved arterial stiffness in patients with OSAH, (Kohler et al., 2013; Vlachantoni et al., 2013; Wons and Kohler, 2015; Lin et al., 2016; Chalegre et al., 2020) while a recent RCT showed that 6-months CPAP treatment prevented progression of arterial stiffness in patients with moderate-severe OSAH and resistant hypertension (Cardoso et al., 2020).

There is increasing interest in the role of arterial stiffness in HDP (Vlachopoulos et al., 2010; Joyeux-Faure et al., 2018; Theorell-Haglöw et al., 2019). Meta-analysis has shown significant increases in arterial stiffness measurements in women with pre-eclampsia compared with those with gestational hypertension (Hausvater et al., 2012). Recently, we have shown a change point early in the second trimester in carotid femoral pulse wave velocity (cfPWV, the gold standard measure of arterial stiffness) trajectories measured throughout pregnancy in women destined to develop pre-eclampsia vs. those who did not (Phan et al., 2021). However, there has to date been no study on the relationship between OSAH and arterial stiffness in HDP patients.

In this study, we did not find significant relationships between overall AHI, oxygen desaturation, or sleep time with SpO2 below 90% and arterial stiffness measures, which contrasts with previous findings in non-pregnant OSAH (Theorell-Haglöw et al., 2019). This discrepancy may be explained in part by the variability of central arterial stiffness during pregnancy in the second to third trimester, particularly if they are destined to develop pre-eclampsia or not (Khalil et al., 2009). However, we did find a significant association between cfPWV and increasing severity of OSAH during REM sleep. Data from several cohort studies have indicated that REM-related OSA in particular is linked to incident hypertension and vascular risk (Mokhlesi et al., 2014; Aurora et al., 2018), which is consistent with the interaction we observed between REM OSAH and arterial stiffness. The significant correlation between REM AHI and cfPWV remained significant after adjustment for age, parity, and weeks of gestation, but not when additionally adjusted for BMI (Table 7). We also found significant relationships between cfPWV and BMI in unadjusted and adjusted regression analyses. This observation is consistent with previous findings in morbidly obese patients that increasing BMI was independently associated with higher cfPWV in women but not in men (Nordstrand et al., 2011). While one interpretation would be that the interaction of REM AHI with cfPWV is solely due to the confounding effect of obesity, the interaction is likely more complex in that obesity will tend to worsen OSAH severity (reduced upper airway caliber due to fat deposition and lung volume-dependent effects, reduced O2 stores with more events meeting desaturation criteria) and in that respect may be part of the mechanistic pathway by which OSAH may alter vascular function.

There are several strengths of our study. OSAH was diagnosed based on complete overnight PSG yielding greater diagnostic accuracy than limited-channel sleep recordings. More importantly, this is the first demonstration of a significant inverse relationship between measures of OSAH severity and 24-h BP or arterial stiffness in HDP patients.

There were some limitations in our study. In that 24-h BP monitoring was performed only after potential participants were determined to have OSAH, we did not have a non-OSAH comparison group. Furthermore, our sample size was limited thus constraining statistical power. While we were unable to demonstrate a significant association between a OSAH severity and 24-h BP, our patient cohort was being closely followed in obstetrical medicine, were all receiving at least one anti-hypertensive medication and BP was controlled and generally within the normal range. Ethical considerations precluded withdrawal of medication for the present study. However, future studies could prospectively evaluate women with a prior HDP no longer requiring medication post-partum but planning a subsequent pregnancy, to longitudinally assess the relationship of OSAH and BP control and nocturnal dipping prior to and over the course of pregnancy. While we found significant correlations in this study between AHI, ODI and % dipping, as well as between arterial stiffness and REM AHI, as shown in Figures 2, 3, these relationships appear to have been influenced by the smaller number of severe patients. These findings suggest that the impact of OSAH and potential benefits of OSAH treatment with respect to vascular risk reduction may be most marked in severe OSAH. However, this remains to be determined across the range of OSAH severity in our ongoing pilot RCT and other interventional studies. Finally, in this study we assessed the relationship between OSAH, BP values, non-dipping and arterial stiffness at a single time point relatively late in pregnancy. Our recent work indicates that in longitudinal follow-up from early to late pregnancy, changes in arterial stiffness may predict subsequent development of pre-eclampsia (Phan et al., 2021). Thus further work is warranted to evaluate the relationships between OSAH, BP profile and arterial stiffness longitudinally over the course of pregnancy and evaluate the association between these changes and maternal and fetal outcomes.

Conclusion

In this cohort, we found BP non-dipping in a majority of women with HDP and OSAH. We observed a significant inverse relationship between OSAH severity and % nocturnal BP dipping. Furthermore, increased arterial stiffness was associated with increasing severity of OSAH during REM sleep in unadjusted although not adjusted analysis. These findings therefore raise the possibility that OSAH may represent a therapeutic target to improve BP profile and vascular function, and thus reduce risk, in HDP. Our ongoing pilot RCT will explore the impact of OSAH treatment on 24 h-BP, arterial stiffness, and other outcomes in HDP patients.

Data Availability Statement

The raw data supporting the conclusions of this article will be made available by the authors, without undue reservation.

Ethics Statement

The studies involving human participants were reviewed and approved by McGill University Health Centre Research Ethics Board. The patients/participants provided their written informed consent to participate in this study.

Author Contributions

PP and NG conducted the study and gathered data in concert with KR, nurse research coordinator. SD provided arterial stiffness measurements. AO scored all PSG studies. PP analyzed the study data. AB provided statistical guidance and support. SP, SD, RG, and ND were co-investigators who contributed to study design, and interpretation. RJK was the principal investigator/editing author and assumes final responsibility for study integrity. All authors contributed to the article and approved the submitted version.

Funding

The Canadian Institutes for Health Research (CIHR). The CIHR grant number is PJT-148763.

Conflict of Interest

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Publisher’s Note

All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.

Acknowledgments

We would like to thank the whole team of the Respiratory Division and Sleep Laboratory, Center for Research Outcomes Evaluation, Department of Obstetrics and Gynecology, Division of Internal Medicine, Department of Epidemiology and Biostatistics at McGill University Health Centre for their support of this study.

Supplementary Material

The Supplementary Material for this article can be found online at: https://www.frontiersin.org/articles/10.3389/fphys.2021.747106/full#supplementary-material

References

American Academy of Sleep Medicine Task Force (1999). Sleep-related breathing disorders in adults: recommendations for syndrome definition and measurement techniques in clinical research. The report of an American Academy of Sleep Medicine Task Force. Sleep 22, 667–689.

Google Scholar

Aurora, R. N., Crainiceanu, C., Gottlieb, D. J., Kim, J. S., and Punjabi, N. M. (2018). Obstructive sleep apnea during REM sleep and cardiovascular disease. Am. J. Respir. Crit. Care Med. 197, 653–660. doi: 10.1164/rccm.201706-1112OC

PubMed Abstract | CrossRef Full Text | Google Scholar

Ayala, D. E., Hermida, R. C., Mojón, A., Fernández, J. R., and Iglesias, M. (1997). Circadian blood pressure variability in healthy and complicated pregnancies. Hypertension 30(Pt 2), 603–610. doi: 10.1161/01.hyp.30.3.603

CrossRef Full Text | Google Scholar

Baguet, J. P., Barone-Rochette, G., Tamisier, R., Levy, P., and Pepin, J. L. (2012). Mechanisms of cardiac dysfunction in obstructive sleep apnea. Nat. Rev. Cardiol. 9, 679–688. doi: 10.1038/nrcardio.2012.141

PubMed Abstract | CrossRef Full Text | Google Scholar

Bellomo, G., Venanzi, S., Saronio, P., Verdura, C., and Narducci, P. L. (2011). Prognostic significance of serum uric acid in women with gestational hypertension. Hypertension 58, 704–708. doi: 10.1161/HYPERTENSIONAHA.111.177212

PubMed Abstract | CrossRef Full Text | Google Scholar

Berry, R. B., Brooks, R., Gamaldo, C. E., Harding, S. M., Marcus, C. L., Vaughn, B. V., et al. (2012). American Academy of Sleep Medicine Manual for the Scoring of Sleep and Associated Events. Version 2. Darien, IL: American Academy of Sleep Medicine.

Google Scholar

Bourjeily, G., Danilack, V. A., Bublitz, M. H., Lipkind, H., Muri, J., Caldwell, D., et al. (2017). Obstructive sleep apnea in pregnancy is associated with adverse maternal outcomes: a national cohort. Sleep Med. 38, 50–57. doi: 10.1016/j.sleep.2017.06.035

PubMed Abstract | CrossRef Full Text | Google Scholar

Bratton, D. J., Gaisl, T., Wons, A. M., and Kohler, M. (2015). CPAP vs mandibular advancement devices and blood pressure in patients with obstructive sleep apnea: a systematic review and meta-analysis. JAMA 314, 2280–2293. doi: 10.1001/jama.2015.16303

PubMed Abstract | CrossRef Full Text | Google Scholar

Buysse, D. J., Reynolds, C. F. III, Monk, T. H., Berman, S. R., and Kupfer, D. J. (1989). The Pittsburgh sleep quality index: a new instrument for psychiatric practice and research. Psychiatry Res. 28, 193–213. doi: 10.1016/0165-1781(89)90047-4

CrossRef Full Text | Google Scholar

Cardoso, C. R. L., Roderjan, C. N., Cavalcanti, A. H., Cortez, A. F., Muxfeldt, E. S., and Salles, G. F. (2020). Effects of continuous positive airway pressure treatment on aortic stiffness in patients with resistant hypertension and obstructive sleep apnea: a randomized controlled trial. J. Sleep Res. 29, e12990. doi: 10.1111/jsr.12990

PubMed Abstract | CrossRef Full Text | Google Scholar

Chalegre, S. T., Lins-Filho, O. L., Lustosa, T. C., França, M. V., Couto, T. L. G., Drager, L. F., et al. (2020). Impact of CPAP on arterial stiffness in patients with obstructive sleep apnea: a meta-analysis of randomized trials. Sleep Breath. 25, 1195–1202. doi: 10.1007/s11325-020-02226-7

PubMed Abstract | CrossRef Full Text | Google Scholar

Champagne, K., Schwartzman, K., Opatrny, L., Barriga, P., Morin, L., Mallozzi, A., et al. (2009). Obstructive sleep apnoea and its association with gestational hypertension. Eur. Respir. J. 33, 559–565. doi: 10.1183/09031936.00122607

PubMed Abstract | CrossRef Full Text | Google Scholar

Crinion, S. J., Ryan, S., Kleinerova, J., Kent, B. D., Gallagher, J., Ledwidge, M., et al. (2019). Nondipping nocturnal blood pressure predicts sleep apnea in patients with hypertension. J. Clin. Sleep Med. 15, 957–963. doi: 10.5664/jcsm.7870

PubMed Abstract | CrossRef Full Text | Google Scholar

Cuspidi, C., Tadic, M., Sala, C., Gherbesi, E., Grassi, G., and Mancia, G. (2019). Blood pressure non-dipping and obstructive sleep apnea syndrome: a meta-analysis. J. Clin. Med. 8:1367. doi: 10.3390/jcm8091367

PubMed Abstract | CrossRef Full Text | Google Scholar

Davis, G. K., Mackenzie, C., Brown, M. A., Homer, C. S., Holt, J., McHugh, L., et al. (2007). Predicting transformation from gestational hypertension to preeclampsia in clinical practice: a possible role for 24 hour ambulatory blood pressure monitoring. Hypertens. Pregnancy 26, 77–87. doi: 10.1080/10641950601147952

PubMed Abstract | CrossRef Full Text | Google Scholar

de la Sierra, A., Gorostidi, M., Banegas, J. R., Segura, J., de la Cruz, J. J., and Ruilope, L. M. (2014). Nocturnal hypertension or nondipping: which is better associated with the cardiovascular risk profile? Am. J. Hypertens. 27, 680–687. doi: 10.1093/ajh/hpt175

PubMed Abstract | CrossRef Full Text | Google Scholar

Ding, X. X., Wu, Y. L., Xu, S. J., Zhang, S. F., Jia, X. M., Zhu, R. P., et al. (2014). A systematic review and quantitative assessment of sleep-disordered breathing during pregnancy and perinatal outcomes. Sleep Breath. 18, 703–713. doi: 10.1007/s11325-014-0946-4

PubMed Abstract | CrossRef Full Text | Google Scholar

Doonan, R. J., Scheffler, P., Lalli, M., Kimoff, R. J., Petridou, E. T., Daskalopoulos, M. E., et al. (2011). Increased arterial stiffness in obstructive sleep apnea: a systematic review. Hypertens. Res. 34, 23–32. doi: 10.1038/hr.2010.200

PubMed Abstract | CrossRef Full Text | Google Scholar

Fagard, R. H., Thijs, L., Staessen, J. A., Clement, D. L., De Buyzere, M. L., and De Bacquer, D. A. (2009). Night-day blood pressure ratio and dipping pattern as predictors of death and cardiovascular events in hypertension. J. Hum. Hypertens. 23, 645–653. doi: 10.1038/jhh.2009.9

PubMed Abstract | CrossRef Full Text | Google Scholar

Florio, P., D’Aniello, G., Sabatini, L., Severi, F. M., Fineschi, D., Bocchi, C., et al. (2005). Factor II: C activity and uterine artery Doppler evaluation to improve the early prediction of pre-eclampsia on women with gestational hypertension. J. Hypertens. 23, 141–146. doi: 10.1097/00004872-200501000-00024

PubMed Abstract | CrossRef Full Text | Google Scholar

Folk, D. M. (2018). Hypertensive disorders of pregnancy: overview and current recommendations. J. Midwifery Womens Health 63, 289–300. doi: 10.1111/jmwh.12725

PubMed Abstract | CrossRef Full Text | Google Scholar

Gavriilaki, M., Anyfanti, P., Nikolaidou, B., Lazaridis, A., Gavriilaki, E., Douma, S., et al. (2020). Nighttime dipping status and risk of cardiovascular events in patients with untreated hypertension: a systematic review and meta-analysis. J. Clin. Hypertens. (Greenwich) 22, 1951–1959. doi: 10.1111/jch.14039

PubMed Abstract | CrossRef Full Text | Google Scholar

Genta-Pereira, D. C., Furlan, S. F., Omote, D. Q., Giorgi, D. M. A., Bortolotto, L. A., Lorenzi-Filho, G., et al. (2018). Nondipping blood pressure patterns predict obstructive sleep apnea in patients undergoing ambulatory blood pressure monitoring. Hypertension 72, 979–985. doi: 10.1161/HYPERTENSIONAHA.118.11525

PubMed Abstract | CrossRef Full Text | Google Scholar

Gomez, Y. H., Hudda, Z., Mahdi, N., Hausvater, A., Opatrny, L., El-Messidi, A., et al. (2016). Pulse pressure amplification and arterial stiffness in low-risk, uncomplicated pregnancies. Angiology 67, 375–383. doi: 10.1177/0003319715590056

PubMed Abstract | CrossRef Full Text | Google Scholar

Gupta, H. P., Singh, R. K., Singh, U., Mehrotra, S., Verma, N. S., and Baranwal, N. (2011). Circadian pattern of blood pressure in normal pregnancy and preeclampsia. J. Obstet. Gynaecol. India 61, 413–417. doi: 10.1007/s13224-011-0062-3

PubMed Abstract | CrossRef Full Text | Google Scholar

Hausvater, A., Giannone, T., Sandoval, Y. H., Doonan, R. J., Antonopoulos, C. N., Matsoukis, I. L., et al. (2012). The association between preeclampsia and arterial stiffness. J. Hypertens. 30, 17–33. doi: 10.1097/HJH.0b013e32834e4b0f

PubMed Abstract | CrossRef Full Text | Google Scholar

Hermida, R. C., Ayala, D. E., Mojón, A., Fernández, J. R., Alonso, I., Silva, I., et al. (2000). Blood pressure patterns in normal pregnancy, gestational hypertension, and preeclampsia. Hypertension 36, 149–158. doi: 10.1161/01.hyp.36.2.149

CrossRef Full Text | Google Scholar

Ilic, A., Ilic, D. J., Tadic, S., Stefanovic, M., Stojsic-Milosavljevic, A., Pavlovic, K., et al. (2017). Influence of non-dipping pattern of blood pressure in gestational hypertension on maternal cardiac function, hemodynamics and intrauterine growth restriction. Pregnancy Hypertens. 10, 34–41. doi: 10.1016/j.preghy.2017.05.003

PubMed Abstract | CrossRef Full Text | Google Scholar

Jenner, R., Fatureto-Borges, F., Costa-Hong, V., Lopes, H. F., Teixeira, S. H., Marum, E., et al. (2017). Association of obstructive sleep apnea with arterial stiffness and nondipping blood pressure in patients with hypertension. J. Clin. Hypertens. (Greenwich) 19, 910–918. doi: 10.1111/jch.13008

PubMed Abstract | CrossRef Full Text | Google Scholar

Johns, M. W. (1991). A new method for measuring daytime sleepiness: the Epworth sleepiness scale. Sleep 14, 540–545. doi: 10.1093/sleep/14.6.540

PubMed Abstract | CrossRef Full Text | Google Scholar

Joyeux-Faure, M., Tamisier, R., Borel, J. C., Millasseau, S., Galerneau, L. M., Destors, M., et al. (2018). Contribution of obstructive sleep apnoea to arterial stiffness: a meta-analysis using individual patient data. Thorax 73, 1146–1151. doi: 10.1136/thoraxjnl-2018-211513

PubMed Abstract | CrossRef Full Text | Google Scholar

Khalil, A., Jauniaux, E., Cooper, D., and Harrington, K. (2009). Pulse wave analysis in normal pregnancy: a prospective longitudinal study. PLoS One 4:e6134. doi: 10.1371/journal.pone.0006134

PubMed Abstract | CrossRef Full Text | Google Scholar

Kohler, M., Craig, S., Nicoll, D., Leeson, P., Davies, R. J., and Stradling, J. R. (2008). Endothelial function and arterial stiffness in minimally symptomatic obstructive sleep apnea. Am. J. Respir. Crit. Care Med. 178, 984–988. doi: 10.1164/rccm.200805-717OC

PubMed Abstract | CrossRef Full Text | Google Scholar

Kohler, M., Craig, S., Pepperell, J. C. T., Nicoll, D., Bratton, D. J., Nunn, A. J., et al. (2013). CPAP improves endothelial function in patients with minimally symptomatic OSA: results from a subset study of the MOSAIC trial. Chest 144, 896–902. doi: 10.1378/chest.13-0179

PubMed Abstract | CrossRef Full Text | Google Scholar

Labarca, G., Schmidt, A., Dreyse, J., Jorquera, J., Enos, D., Torres, G., et al. (2021). Efficacy of continuous positive airway pressure (CPAP) in patients with obstructive sleep apnea (OSA) and resistant hypertension (RH): systematic review and meta-analysis. Sleep Med. Rev. 58, 101446. doi: 10.1016/j.smrv.2021.101446

PubMed Abstract | CrossRef Full Text | Google Scholar

Lee, K. W., Blann, A. D., and Lip, G. Y. (2005). High pulse pressure and nondipping circadian blood pressure in patients with coronary artery disease: relationship to thrombogenesis and endothelial damage/dysfunction. Am. J. Hypertens. 18, 104–115. doi: 10.1016/j.amjhyper.2004.09.003

PubMed Abstract | CrossRef Full Text | Google Scholar

Li, L., Zhao, K., Hua, J., and Li, S. (2018). Association between sleep-disordered breathing during pregnancy and maternal and fetal outcomes: an updated systematic review and meta-analysis. Front. Neurol. 9:91. doi: 10.3389/fneur.2018.00091

PubMed Abstract | CrossRef Full Text | Google Scholar

Lin, X., Chen, G., Qi, J., Chen, X., Zhao, J., and Lin, Q. (2016). Effect of continuous positive airway pressure on arterial stiffness in patients with obstructive sleep apnea and hypertension: a meta-analysis. Eur. Arch. Otorhinolaryngol. 273, 4081–4088. doi: 10.1007/s00405-016-3914-8

PubMed Abstract | CrossRef Full Text | Google Scholar

Liu, L., Su, G., Wang, S., and Zhu, B. (2019). The prevalence of obstructive sleep apnea and its association with pregnancy-related health outcomes: a systematic review and meta-analysis. Sleep Breath. 23, 399–412. doi: 10.1007/s11325-018-1714-7

PubMed Abstract | CrossRef Full Text | Google Scholar

Lo, J. O., Mission, J. F., and Caughey, A. B. (2013). Hypertensive disease of pregnancy and maternal mortality. Curr. Opin. Obstet. Gynecol. 25, 124–132. doi: 10.1097/GCO.0b013e32835e0ef5

PubMed Abstract | CrossRef Full Text | Google Scholar

Lu, Q., Zhang, X., Wang, Y., Li, J., Xu, Y., Song, X., et al. (2021). Sleep disturbances during pregnancy and adverse maternal and fetal outcomes: a systematic review and meta-analysis. Sleep Med. Rev. 58, 101436. doi: 10.1016/j.smrv.2021.101436

PubMed Abstract | CrossRef Full Text | Google Scholar

Magee, L. A., Pels, A., Helewa, M., Rey, E., and von Dadelszen, P. (2015). The hypertensive disorders of pregnancy (29.3). Best Pract. Res. Clin. Obstet. Gynaecol. 29, 643–657. doi: 10.1016/j.bpobgyn.2015.04.001

PubMed Abstract | CrossRef Full Text | Google Scholar

Melamed, N., Ray, J. G., Hladunewich, M., Cox, B., and Kingdom, J. C. (2014). Gestational hypertension and preeclampsia: are they the same disease? J. Obstet. Gynaecol. Can. 36, 642–647. doi: 10.1016/S1701-2163(15)30545-4

CrossRef Full Text | Google Scholar

Mokhlesi, B., Finn, L. A., Hagen, E. W., Young, T., Hla, K. M., Van Cauter, E., et al. (2014). Obstructive sleep apnea during REM sleep and hypertension. results of the Wisconsin Sleep Cohort. Am. J. Respir. Crit. Care Med. 190, 1158–1167. doi: 10.1164/rccm.201406-1136OC

PubMed Abstract | CrossRef Full Text | Google Scholar

Myers, M. G., Kaczorowski, J., Dawes, M., and Godwin, M. (2014). Automated office blood pressure measurement in primary care. Can. Fam. Phys. 60, 127–132.

Google Scholar

Nordstrand, N., Gjevestad, E., Dinh, K. N., Hofsø, D., Røislien, J., Saltvedt, E., et al. (2011). The relationship between various measures of obesity and arterial stiffness in morbidly obese patients. BMC Cardiovasc. Disord. 11:7. doi: 10.1186/1471-2261-11-7

PubMed Abstract | CrossRef Full Text | Google Scholar

O’Brien, E., Parati, G., Stergiou, G., Asmar, R., Beilin, L., Bilo, G., et al. (2013). European Society Of Hypertension position paper on ambulatory blood pressure monitoring. J. Hypertens. 31, 1731–1768. doi: 10.1097/HJH.0b013e328363e964

PubMed Abstract | CrossRef Full Text | Google Scholar

Oney, T., and Meyer-Sabellek, W. (1990). Variability of arterial blood pressure in normal and hypertensive pregnancy. J. Hypertens. Suppl. 8, S77–S81.

Google Scholar

Pamidi, S., and Kimoff, R. J. (2018). Maternal sleep-disordered breathing. Chest 153, 1052–1066.

Google Scholar

Pamidi, S., Marc, I., Simoneau, G., Lavigne, L., Olha, A., Benedetti, A., et al. (2016). Maternal sleep-disordered breathing and the risk of delivering small for gestational age infants: a prospective cohort study. Thorax 71, 719–725. doi: 10.1136/thoraxjnl-2015-208038

PubMed Abstract | CrossRef Full Text | Google Scholar

Pamidi, S., Pinto, L. M., Marc, I., Benedetti, A., Schwartzman, K., and Kimoff, R. J. (2014). Maternal sleep-disordered breathing and adverse pregnancy outcomes: a systematic review and metaanalysis. Am. J. Obstet. Gynecol. 210, 52.e1–52.e14. doi: 10.1016/j.ajog.2013.07.033

PubMed Abstract | CrossRef Full Text | Google Scholar

Parati, G., Stergiou, G., O’Brien, E., Asmar, R., Beilin, L., Bilo, G., et al. (2014). European Society of Hypertension practice guidelines for ambulatory blood pressure monitoring. J. Hypertens. 32, 1359–1366. doi: 10.1097/HJH.0000000000000221

PubMed Abstract | CrossRef Full Text | Google Scholar

Patil, S. P., Ayappa, I. A., Caples, S. M., Kimoff, R. J., Patel, S. R., and Harrod, C. G. (2019). Treatment of adult obstructive sleep apnea with positive airway pressure: an American Academy of Sleep Medicine Systematic Review, meta-analysis, and GRADE assessment. J. Clin. Sleep Med. 15, 301–334. doi: 10.5664/jcsm.7638

PubMed Abstract | CrossRef Full Text | Google Scholar

Peppard, P. E., Young, T., Palta, M., and Skatrud, J. (2000). Prospective study of the association between sleep-disordered breathing and hypertension. N. Engl. J. Med. 342, 1378–1384. doi: 10.1056/NEJM200005113421901

PubMed Abstract | CrossRef Full Text | Google Scholar

Phan, K., Schiller, I., Dendukuri, N., Gomez, Y. H., Gorgui, J., El-Messidi, A., et al. (2021). A longitudinal analysis of arterial stiffness and wave reflection in preeclampsia: identification of changepoints. Metabolism 120:154794. doi: 10.1016/j.metabol.2021.154794

PubMed Abstract | CrossRef Full Text | Google Scholar

Phillips, C. L., and O’Driscoll, D. M. (2013). Hypertension and obstructive sleep apnea. Nat. Sci. Sleep 5, 43–52. doi: 10.2147/NSS.S34841

PubMed Abstract | CrossRef Full Text | Google Scholar

Pio-Abreu, A., Moreno, H. Jr., and Drager, L. F. (2021). Obstructive sleep apnea and ambulatory blood pressure monitoring: current evidence and research gaps. J. Hum. Hypertens. 35, 315–324. doi: 10.1038/s41371-020-00470-8

PubMed Abstract | CrossRef Full Text | Google Scholar

Querejeta Roca, G., Anyaso, J., Redline, S., and Bello, N. A. (2020). Associations between sleep disorders and hypertensive disorders of pregnancy and materno-fetal consequences. Curr. Hypertens. Rep. 22:53. doi: 10.1007/s11906-020-01066-w

PubMed Abstract | CrossRef Full Text | Google Scholar

Rana, S., Powe, C. E., Salahuddin, S., Verlohren, S., Perschel, F. H., Levine, R. J., et al. (2012). Angiogenic factors and the risk of adverse outcomes in women with suspected preeclampsia. Circulation 125, 911–919. doi: 10.1161/CIRCULATIONAHA.111.054361

PubMed Abstract | CrossRef Full Text | Google Scholar

Roberts, J. M., August, P. A., Bakris, G., Barton, J. R., Bernstein, I. M., Druzin, M., et al. (2013). Hypertension in pregnancy. Report of the American College of Obstetricians and Gynecologists’ task force on hypertension in pregnancy. Obstet. Gynecol. 122, 1122–1131. doi: 10.1097/01.AOG.0000437382.03963.88

CrossRef Full Text | Google Scholar

Seely, E. W., and Ecker, J. (2014). Chronic hypertension in pregnancy. Circulation 129, 1254–1261. doi: 10.1161/CIRCULATIONAHA.113.003904

PubMed Abstract | CrossRef Full Text | Google Scholar

Seif, F., Patel, S. R., Walia, H. K., Rueschman, M., Bhatt, D. L., Blumenthal, R. S., et al. (2014). Obstructive sleep apnea and diurnal nondipping hemodynamic indices in patients at increased cardiovascular risk. J. Hypertens. 32, 267–275. doi: 10.1097/HJH.0000000000000011

PubMed Abstract | CrossRef Full Text | Google Scholar

Shah, S., and Gupta, A. (2019). Hypertensive disorders of pregnancy. Cardiol. Clin. 37, 345–354. doi: 10.1016/j.ccl.2019.04.008

PubMed Abstract | CrossRef Full Text | Google Scholar

Somers, V. K., Dyken, M. E., Clary, M. P., and Abboud, F. M. (1995). Sympathetic neural mechanisms in obstructive sleep apnea. J. Clin. Invest. 96, 1897–1904. doi: 10.1172/JCI118235

PubMed Abstract | CrossRef Full Text | Google Scholar

Theorell-Haglöw, J., Hoyos, C. M., Phillips, C. L., Yee, B. J., Melehan, K. L., Liu, P. Y., et al. (2019). Associations between obstructive sleep apnea and measures of arterial stiffness. J. Clin. Sleep Med. 15, 201–206. doi: 10.5664/jcsm.7616

PubMed Abstract | CrossRef Full Text | Google Scholar

Torres, G., Sánchez-de-la-Torre, M., Martínez-Alonso, M., Gómez, S., Sacristán, O., Cabau, J., et al. (2015). Use of ambulatory blood pressure monitoring for the screening of obstructive sleep apnea. J. Clin. Hypertens. (Greenwich) 17, 802–809. doi: 10.1111/jch.12619

PubMed Abstract | CrossRef Full Text | Google Scholar

Vlachantoni, I. T., Dikaiakou, E., Antonopoulos, C. N., Stefanadis, C., Daskalopoulou, S. S., and Petridou, E. T. (2013). Effects of continuous positive airway pressure (CPAP) treatment for obstructive sleep apnea in arterial stiffness: a meta-analysis. Sleep Med. Rev. 17, 19–28. doi: 10.1016/j.smrv.2012.01.002

PubMed Abstract | CrossRef Full Text | Google Scholar

Vlachopoulos, C., Aznaouridis, K., and Stefanadis, C. (2010). Prediction of cardiovascular events and all-cause mortality with arterial stiffness: a systematic review and meta-analysis. J. Am. Coll. Cardiol. 55, 1318–1327. doi: 10.1016/j.jacc.2009.10.061

PubMed Abstract | CrossRef Full Text | Google Scholar

Wons, A. M., and Kohler, M. (2015). Established vascular effects of continuous positive airway pressure therapy in patients with obstructive sleep apnoea-an update. J. Thorac. Dis. 7, 912–919. doi: 10.3978/j.issn.2072-1439.2015.03.06

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Keywords: obstructive sleep apnea-hypopnea, 24-h blood pressure, nocturnal blood pressure dipping, hypertensive disorders of pregnancy, arterial stiffness

Citation: Panyarath P, Goldscher N, Pamidi S, Daskalopoulou SS, Gagnon R, Dayan N, Raiche K, Olha A, Benedetti A and Kimoff RJ (2021) Effect of Maternal Obstructive Sleep Apnea-Hypopnea on 24-Hour Blood Pressure, Nocturnal Blood Pressure Dipping and Arterial Stiffness in Hypertensive Disorders of Pregnancy. Front. Physiol. 12:747106. doi: 10.3389/fphys.2021.747106

Received: 25 July 2021; Accepted: 21 September 2021;
Published: 18 October 2021.

Edited by:

Vincent Joseph, Laval University, Canada

Reviewed by:

Jyoti Watters, University of Wisconsin–Madison, United States
Frederic Roche, Université Jean Monnet, France

Copyright © 2021 Panyarath, Goldscher, Pamidi, Daskalopoulou, Gagnon, Dayan, Raiche, Olha, Benedetti and Kimoff. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

*Correspondence: R. John Kimoff, john.kimoff@mcgill.ca

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