The effect of gender on the prevalence of hypertension in obstructive sleep apnea

doi:10.1016/j.sleep.2008.09.005

Sleep Medicine

Volume 10, Issue 7, August 2009, Pages 759-762

https://doi.org/10.1016/j.sleep.2008.09.005 Get rights and content

Abstract

Background

Obstructive sleep apnea (OSA) causes systemic hypertension. However, there is conflicting data on the effect of gender on susceptibility to hypertension in OSA. Some show no gender differences in the prevalence of hypertension while others report either female or male propensity to have hypertension in the context of OSA. The inconsistencies in the results appear to be due to lack of full range of sleep apnea severity and insufficient number of women in the studies. We examined the effect of gender on prevalent hypertension in a cohort with a large representation of females with OSA.

Methods

A cross-sectional study of a large cohort of subjects referred for sleep disorder evaluation.

Results

The cohort comprised of 736 with OSA and 315 without OSA. OSA was defined as apnea-hypopnea index (AHI) of ⩾5/h. There were 529 men and 207 women in the OSA group with mean ± SD age of 50 ± 13 and 51 ± 14 years, respectively. The control group consisted of 154 men and 161 women with mean ± SD age of 44 ± 15 and 43 ± 14 years, respectively. The AHI in the OSA group varied from 5 to 197 with a median of 24 and a mean of 36 (interquartile range: 11–53). Multiple logistic regression analyses, modeling the association between AHI and hypertension and considering other covariates, showed that odds of hypertension increased with increasing age, BMI, and AHI. There was evidence that men were at higher risk for hypertension than women OR 1.82 (95%CI 1.01, 3.20) at the highest quartile of BMI.

Conclusions

We have shown that the prevalence of hypertension increases with increasing age and severity of OSA, and markedly obese men may have a nearly 2-fold greater risk for hypertension than women in this clinic-based population.

Introduction

Obstructive sleep apnea (OSA) is characterized by recurrent upper airway obstruction during sleep. These episodes are terminated by arousals and are commonly associated with oxygen desaturation. OSA syndrome is a highly prevalent disorder with an estimated prevalence of 4% and 2% in middle-aged adult men and women, respectively [1], [2]. A growing body of evidence shows that OSA syndrome is independently associated with significant cardiovascular morbidity and mortality, including coronary artery disease, heart failure and stroke [3], [4], [5], [6]. The acute hemodynamic and autonomic perturbations that accompany obstructive apneas during sleep, associated with repeated arousals and intermittent hypoxemia, can lead to sustained diurnal hypertension, independent of other known risk factors for hypertension [7], [8]. The prevalence of hypertension in OSA ranges between 30% and 70% [9]. Epidemiological studies [7], [10], clinic-based studies [11], [12], and case-control studies [13] have consistently shown that the risk for hypertension increases with increasing severity of OSA even after correction for several frequently encountered comorbid conditions such as obesity and age. However, the effect of gender on the development of hypertension in OSA has not been entirely elucidated. Population-based studies showed no consistent evidence for gender differences in the prevalence of hypertension in adults with sleep-disordered breathing [7], [10], [14]. Some show no association with gender [7], [10], while another population-based study demonstrated that men were more prone to hypertension than women with OSA [14]. Other studies drawing from a clinic population have shown that females are more prone to endothelial dysfunction [15] and hypertension [16] than males with OSA. The inconsistencies appear to be related to a limited range of severity of OSA and few female subjects in the cohorts.

We undertook this study to address the gaps and inconsistencies in the role of gender susceptibility to hypertension in OSA. In this study, we describe the effect of gender on the prevalence of hypertension in a cohort of sleep clinic patients with a wide range of sleep-disordered breathing severity and a large representation of women.

Section snippets

Study population

The Yale Sleep cohort Study established in 1997, is a prospective observational registry of morbidity and mortality in subjects referred for sleep disorders, as previously described [5]. The current study is a cross-sectional analysis of the cohort in 2001. The subjects underwent at least 2 h of attended sleep and respiratory monitoring, completed a 10-page standardized questionnaire on their sleep and medical history which included questions regarding the diagnosis of hypertension and the use

Results

The characteristics of the study population are shown in Table 1. There were 736 subjects in the OSA group and 315 subjects in the control group. The participants included 529 men and 207 women in the OSA group with mean ± SD age of 50 ± 13 and 51 ± 14 years, respectively. The control group consisted of 154 men and 161 women with mean ± SD age of 44 ± 15 and 43 ± 14 years, respectively. These subjects had been referred with the presumptive diagnosis of sleep-related breathing disorders but were found to

Discussion

We studied a large cohort of individuals, referred to Yale Center for Sleep Medicine, to examine the role of gender on the prevalence of hypertension in patients with OSA syndrome. Our results demonstrate that OSA syndrome is associated with increased prevalence of hypertension in both men and women. However, obese men have higher odds for having hypertension compared to obese females with OSA. There was a significant trend between increasing prevalence of hypertension and increasing severity

Disclosure

No conflict of interest to declare.

Acknowledgments

The study was supported, in part, by a career development award from the Veterans Affairs Health Services Research and Development Service (H.K. Yaggi), a National Research Service Institutional Research Training Grant from the National Institute of Health (T32HL07778) (N. Shah), and Yale Center for Sleep Medicine.

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This is a retrospective analysis on the data acquired through a multicenter aSAH registry. Between January 2019 and December 2021, a total of 732 aSAH patients had been registered into our database. After excluding 109 patients whose activities at aSAH onset had been unidentifiable, the remaining 623 aSAH patients were dichotomized to 59 patients who sustained aSAH during sleep (Sleep group) and 564 patients who sustained aSAH during daytime activities (Awake group). Two-group comparison of demographic variables and multivariate logistic regression analysis were performed to clarify their clinical characteristics and identify potential risk factors.
The Sleep group exhibited significantly higher frequencies of diabetes (15.5 % vs. 6.4 %, p = 0.01) and antiplatelet use (13.8 % vs. 4.6 %, p=0.004) than the Awake group. Furthermore, multivariate logistic regression analysis showed that diabetes (OR, 3.051; 95 % CI, 1.281-7.268; p = 0.012) and antiplatelet use (OR, 3.640; 95 % CI, 1.422-9.316; p = 0.007) were correlated with aSAH occurring during sleep. There were no significant inter-group differences in the patient outcomes evaluated at discharge.
The current results indicate that risk factors may exist for aSAH occurring during sleep. Further investigations on how comorbidities such as diabetes, antiplatelet use and sleep apnea affect human hemodynamic and hemostatic parameters during sleep is warranted to better understand those relationships.
Sex-specific differences in patients with obstructive sleep apnea-hypopnea syndrome
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Since the early understandings of obstructive sleep apnea (OSA), it has been clear that there are sex-dependent features of the disease. This article reviews our understanding of the sex differences in the epidemiology, pathophysiology, symptom presentation, morbidity/mortality, polysomnogram features, and treatment of OSA. Key concepts include: 2:1 male female prevalence ratio for OSA in the general population; increase in OSA prevalence in women across the menopausal spectrum; greater upper airway collapsibility in men despite inherently larger airways; greater array of sleep-related symptoms in women with OSA which may hinder recognition of the disease; significant impact of OSA on functional status and health-related quality of life in women; milder polysomnographic presentation of OSA in women; and uncertainties on whether there are differential gender susceptibilities to cardiovascular and metabolic complications of OSA or treatment responses. OSA in pregnancy and impact of gender in central sleep apnea syndromes are also explored.
Sleep Apnea and Hypertension: Are There Sex Differences? The Vitoria Sleep Cohort
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All of these factors could suggest a possible increased level of cardiovascular protection and/or a longer required exposure time for the expression of hypertension in women than in men. These data are consistent with a case-controlled study performed by Hedner et al,32 who found an independent association between OSA and hypertension with a dose-response effect in men but not in women and with the results from the cross-sectional study of the Yale Sleep Cohort Study,33 although sex differences were observed only in the highest BMI quartile. The results differ from a recent large database study34 and the Sleep Heart Health Study results,5 which suggested that OSA might predict future hypertension among women but not men.
Evidence from longitudinal studies has reported contradictory results regarding the association between OSA and hypertension. In a previous analysis of the Vitoria Sleep Cohort, the relationship between OSA and the risk of developing hypertension was evaluated and no independent association after adjustment for confounding factors was found. In the present study, a post hoc analysis to assess the association between OSA and incident stage 2 hypertension (systolic BP ≥ 160 mm Hg and/or diastolic BP ≥ 100 mm Hg) was made on the basis of sex differences.
A prospective study was performed over 7.5 ± 0.8 years on a middle-aged general population, which included 1,155 normotensive subjects (43.7% men) who completed the follow-up. BP measurements (at baseline and follow-up) and polygraphy at baseline were performed. Logistic regression models were used to determine the association between the respiratory disturbance index (RDI) and stage 2 hypertension and a recursive partitioning method was used to determine the variables related to the incidence of stage 2 hypertension. The RDI was divided into subgroups (0-2.9, 3-6.9, 7-13.9, and ≥ 14), using the first subgroup as reference.
For men, an RDI ≥ 14 was associated with a significantly increased OR for stage 2 hypertension (OR, 2.54 [95% CI, 1.09-5.95], P = .032). This association was not statistically significant among women (P = .371).
The results suggest an association between moderate and severe OSA, and the incidence of more severe forms of hypertension occurring in men but not in women. However, because this is a community-based study, the women’s population characteristics may differ from women usually seen in sleep-disorders clinics.
Gender differences in the association of sleep apnea and inflammation
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Citation Excerpt :
In contrast, a population-based study has shown that men in the highest AHI tertile have a 3.7-fold risk of hypertension, whereas women in the highest tertile only have a 1.6-fold increased risk (Hedner et al., 2006). Furthermore, men within the highest BMI quartile have been shown to have a twofold higher risk for hypertension than BMI-matched women, independent of sleep apnea (Mohsenin et al., 2009). Another large prospective study reported a significantly increased stroke risk in the highest AHI quartile in men, but not women (Redline et al., 2010).
Over the last 15 years, many studies have established an association of sleep apnea with inflammation and metabolic aberrations. However, no controlled studies have examined potential gender effects in this association. We recruited 120 middle-aged, predominantly non-obese mild-to-moderate sleep apneics and controls (62 males, 58 females). All participants underwent a clinical history, physical examination, and 1-night 8-h polysomnography recording and provided a single fasting blood sample for assessment of interleukin-6 (IL-6), tumor necrosis factor receptor 1 (TNFR1), C-reactive protein (CRP), leptin, and adiponectin levels. Among non-sleep apneics, females had higher levels of TNFR1 (p = 0.01), CRP (p = 0.005), leptin (p < 0.001), and adiponectin (p < 0.001) compared to males, independent of age and body mass index. When analyzed separately by gender, sleep apneic men had elevated TNFR1 (p = 0.04), CRP (p = 0.06) and IL-6 (p = 0.11) relative to control men; in sleep apneic females, only CRP was elevated (p = 0.04). Furthermore, CRP was associated with apnea severity in a dose–response manner (p-linear = 0.04 in both genders) and was independently associated with comorbid hypertension in apnea (p-linear = 0.005 for women; p-linear = 0.09 for men). In conclusion, although women have naturally higher levels of inflammatory and metabolic markers than men, sleep apneic men appear to have a more severe inflammatory profile compared to women. Our findings suggest that these markers should be analyzed and interpreted separately in men and women, and that a single measure of plasma CRP appears to be a clinically-useful marker of apnea severity and comorbid cardiovascular morbidity.
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OSAS, a frequently neglected, yet frequent comorbidity in T2DM, is associated with obesity, metabolic syndrome and central fat. OSAS is better documented in males, and this study explored novel gender dimorphisms in T2DM.
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There was a gender dimorphism in glucose control (worse in females), apolipoprotein B100 (higher in females), with apoB100/apoA1 and log(TG)/HDL-C sexually dimorphic. There was also a marked gender dimorphism in GAD65 positivity, higher (+793%) in OSAS[+] females vs. males. There were clear sexual dimorphisms in macro-/microangioathies, regarding stroke, retinopathy and polyneuropathy. OSAS was not sexually dimorphic regarding age; education; and diabetes duration. There was a significant dimorphism in ethnicity. There were no gender-specific dimorphisms related to OSAS in anthropometrics, nor in hypertension, insulin sensitivity, or hyperbolic product loss rate.
We report a series of novel OSAS-related sexual dimorphisms, concerning GAD65 auto-antibodies; polyneuropathy; atherogenic dyslipidemia [all increased in females]; diabetic retinopathy; North-Caucasian ethnicity; metabolic control; and TIA/stroke prevalence [all lower in females]. These findings raise challenging questions regarding the reciprocal pathophysiology between obstructive sleep disorders and cardiometabolic risk in T2DM.
Endothelial dysfunction and hypertension in obstructive sleep apnea - Is it due to intermittent hypoxia?
2013, Journal of Cardiovascular Disease Research
Obstructive sleep apnea (OSA) is a prevalent disorder causing hypertension. Endothelial dysfunction appears to underlie development of hypertension. It is not known whether hypoxia during sleep is necessarily the prerequisite process for endothelial dysfunction and hypertension in OSA. We therefore examined the relationship between endothelial-dependent vasodilatory capacity, hypoxia and circulating angiogenesis inhibitors in OSA.
We studies 95 subjects with and without OSA and hypertension. Endothelial-dependent vasodilation was assessed using brachial artery flow-mediated vasodilation method (FMD). Plasma angiogenesis inhibitors, endoglin (sEng) and fms-like tyrosine kinase-1 (sFlt-1), were measured using ELISA. The apnea–hypopnea indexes were 41 ± 5 and 48 ± 4 events/hr in normotensive OSA (N-OSA) and hypertensive OSA (H-OSA), respectively, indicating severe OSA. The sleep time spent with SaO₂ < 90% (T < 90%) were 34 ± 8 and 40 ± 9 min, respectively. FMD was markedly impaired in H-OSA (8.0% ± 0.5) compared to N-OSA (13.5% ± 0.5, P < 0.0001), H-non-OSA (10.5% ± 0.8, P < 0.01), and N-non-OSA (16.1% ± 1.0, P < 0.0001). There was no correlation between T < 90% and FMD. Both OSA groups had elevated levels of sFlt-1 (62.4 ± 5.9 and 63.9 ± 4.7 pg/ml) compared to N-non-OSA (32.1 ± 6.5, P = 0.0008 and P = 0.0004, respectively) and H-non-OSA (41.2 ± 7.0, P < 0.05 and P = 0.03, respectively). In contrast, sEng was only elevated in H-OSA (4.20 ± 0.17 ng/ml) compared with N-OSA (3.64 ± 0.14, P = 0.01) and N-non-OSA (3.48 ± 0.20, P = 0.01). There was a modest but statistically significant inverse correlation between sEng and FMD in only H-OSA group (r = −0.38, P < 0.05).
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Original ArticleThe effect of gender on the prevalence of hypertension in obstructive sleep apnea

Abstract

Background

Methods

Results

Conclusions

Introduction

Section snippets

Study population

Results

Discussion

Disclosure

Acknowledgments

Am J M

Lancet

Chest

Am heart J

The occurrence of sleep-disordered breathing among middle-aged adults

N Engl J Med

Epidemiology of obstructive sleep apnea: a population health perspective

Am J Respir Crit Care Med

Sleep-disordered breathing and cardiovascular disease

Circulation

Obstructive sleep apnea as a risk factor for stroke and death

N Eng J Med

Prospective study of the association between sleep-disordered breathing and hypertension

N Engl J Med

Obesity, sleep apnea, and hypertension

Hypertension

Obstructive sleep apnea and hypertension: epidemiology, mechanisms and treatment effects

Minerva Medica

Association of sleep-disordered breathing, sleep apnea, and hypertension in a large community-based study

JAMA

Association of hypertension and sleep-disordered breathing

Arch Intern Med

Original Article
The effect of gender on the prevalence of hypertension in obstructive sleep apnea