Chinese Medical Journal 2010;123(1):18-22
Relationship of daytime blood pressure and severity of obstructive sleep apnea among Chinese: a multi-center investigation in China
Background Epidemiologic studies have shown an independent and definite association between obstructive sleep apnea (OSA) and hypertension. This study aimed to define the association between daytime blood pressure and severity of OSA in Chinese population in mainland of China.
Methods Twenty university hospital sleep centers in mainland of China were invited by the Chinese Medical Association (CMA) to participate in this epidemiologic study and 2297 consecutive patients (aged 18–85 years; 1981 males and 316 females) referred to these twenty sleep centers for evaluation of OSA between January 2004 and April 2006 were prospectively enrolled. Nocturnal polysomnography was performed in each patient, and disease severity was assessed based on the apneahypopnea index (AHI). These patients were classfied into four groups: nonapneic control (control, n=257) with AHI ≤5 episodes/hour; mild sleep apnea (mild, n=402) with AHI >5 and ≤15 episodes/hour; moderate sleep apnea (moderate, n=460) with AHI >15 and ≤30 episodes/hour and severe sleep apnea (severe, n=1178) with AHI >30 episodes/hour. Daytime blood pressure measurements were performed under standardized conditions in each patient at 10 a.m. in office on the day of referring to sleep centers for getting average value. All the patients were requested to quit medications related to blood pressure for three days before the day of assessing.
Results Both daytime systolic blood pressure and diastolic blood pressure values were significantly related to AHI positively (r = 0.201 and 0.276, respectively; both P values <0.001) and to nadir nocturnal oxygen saturation negatively (r = –0.215 and –0.277, respectively; both P values <0.001), which were the parameters of OSA severity. In two special designed mean plots, means of daytime systolic and diastolic blood pressure increased gradually with increasing AHI. Beyond AHI of 61–65, this increasing trend reached a plateau.
Conclusions The results showed that OSA severity was associated with daytime blood pressure until AHI of 61–65, providing evidence for early OSA management, especially in OSA patients with concomitant hypertension.
As a cause of hypertension,1 obstructive sleep apnea (OSA) has been drawing more attention in recent years. Observational and longitudinal population epidemiologic studies showed an independent and definite association between OSA and hypertension.2,3 OSA promotes hypertension pathogenesis,4 which makes OSA the most important cause of drug-resistant hypertension.5 Furthermore, long-term treatment for OSA with continuous positive airway pressure (CPAP) has been shown to reduce concomitant higher blood pressure.6,7 The seventh report of the Joint National Committee (National Heart, Lung, and Blood Institute Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure) has identified OSA as an important identifiable cause of hypertension.8
Chen and He9 have published an epidemiologic article among Chinese in 2007 which has comparable results with some previous studies.10-16 In this previously published article, we have reported the prevalence of hypertension with concomitant OSA in continental China being 49.3%. However, the systematic research confirming the association between OSA severity and daytime blood pressure in mainland of China is still lacking. Twenty university hospital sleep centers in mainland of China were organized by the Sleep Breath Disorder Group of Society of Respiratory Medicine, Chinese Medical Association (CMA), to participate in this epidemiologic study. The aim of this study was to elucidate the hypothesized relationships between OSA severity and the daytime blood pressure value.
Between January 2004 and April 2006, 2297 consecutive patients (aged 18–85 years; 1981 males and 316 females) referred to these centers were enrolled in this study. To each subject, physician epidemiologists or trained staff explained the study protocol and the informed consent was obtained.
Nocturnal polysomnography was performed in sleep centers for measurement of respiratory effort, flow, and oxygen saturation. The apneahypopnea index (AHI: i.e., average number of apneic events plus hypopneic events per hour of sleep), the lowest and mean nocturnal oxygen saturation were obtained. Apnea was defined as a cessation in airflow for at least 10 seconds; and hypopnea was defined as a decrease in the amplitude of respiratory flow signal of at least 50% for a minimum of 10 seconds followed by either a decrease in oxygen saturation of 4% or signs of physiological arousal. And disease severity was assessed by AHI. The study population was classified into four groups: nonapneic control (control, n=257) with AHI ≤5; mild sleep apnea (mild, n=402) with AHI >5 and ≤15; moderate sleep apnea (moderate, n=460) with AHI >15 and ≤30; and severe sleep apnea (severe, n=1178) with AHI >30.17
Patients’ height, weight, neck, hip, and waist circumference were measured. Their body mass index (BMI, calculated as weight in kilogram divided by square of height in meter) and waist to hip ratio were calculated.
Blood pressure measurements
To each patient, daytime blood pressure measurements were performed four times consecutively under standardized conditions at 10 a.m. in the clinic office on the day of referring to sleep centers, and the final value was the average of four individual pressure measurements. All the patients were requested to quit medications related to blood pressure for three days before the day of assessing.
SPSS 11.5 software package was used for statistical analysis and figure drawing. One way analysis of variance (ANOVA) was used for whole difference and Bonferroni post hoc multiple comparisons were used for differences between groups. Linear correlation analysis and linear fitting were performed for influential power estimating. Chi-square test was used for the comparisons of ratios. Unless otherwise stated, values were reported as mean ± standard deviation (SD), and P <0.05 was considered statistically significant.
Descriptive analysis results
Table 1 summarizes the characteristics of the population, 1981 of men and 316 of women.
Table 1. Anthropometric, sleep, and blood pressure data in 2297 patients attending sleep centers
As shown in Table 2, unadjusted systolic and diastolic blood pressure significantly increased with AHI (all P values intra and inter groups <0.001) increasing in control, mild, moderate and severe groups.
Both systolic and diastolic blood pressure values were significantly related to AHI (r=0.201 and 0.276, respectively; both P values<0.001) and to nadir nocturnal oxygen saturation (r = –0.215 and –0.277, respectively; both P values<0.001).
Taking AHI as an independent variable and systolic and diastolic values as dependent variables, we performed linear fitting. Two equations were as follows: Systolic blood pressure (mmHg) = 0.1301 × AHI (episodes/hour) + 123.535 (F=96.79, P <0.001); Diastolic blood pressure (mmHg) = 0.1197 × AHI (episodes/hour) + 78.0949 (F=188.66, P <0.001).
Similar results were found with nadir nocturnal oxygen saturation: Systolic blood pressure (mmHg) = –0.2533 × nadir nocturnal oxygen saturation (%) + 146.896 (F=111.52, P <0.001); Diastolic blood pressure (mmHg) = –0.2190× nadir nocturnal oxygen saturation (%) + 98.5448 (F=191.10, P <0.001).
AHI cutoff points of every 5 were used, and the population was classified into 17 small groups with AHI: 0–5, 6–10, 11–15, 16–20, 21–25, 26–30, 31–35, 36–40, 41–45, 46–50, 51–55, 56–60, 61–65, 66–70, 71–75, 76–80, 81–. The mean plots of daytime systolic (Figure 1) and diastolic (Figure 2) blood pressure versus small groups taken as order of increased AHI were drawn.
Figure 1. Mean plot of systolic blood pressure versus AHI.
From the plots, means of systolic and diastolic values increased gradually and small fluctuations could be seen. But after the cutoff of 61–65, increasing curve reached a plateau or even dropped slightly though no statistical evidence could be provided.
OSA associated with accompanying daytime sleepiness affects 3% to 7% of adult men and 2% to 5% of adult women in the general population. The health risk in OSA patients is the strong association with acute cardiovascular events such as stroke, myocardial infarction and nocturnal sudden death, and chronic conditions such as coronary artery disease, heart failure, and especially, systemic hypertension.2-4 The association between presence of elevated blood pressure values and severity of OSA has been confirmed in some large cross-sectional studies.3,18 In the largest of those cross-sectional studies, an elevated odds ratio for hypertension was found in subjects with OSA after adjusting for demographics, anthropometric measurements, alcohol consumption and smoking.3
In Table 2, unadjusted systolic and diastolic blood pressure values significantly increased with AHI increasing in the control, mild, moderate and severe groups. From the results, a clear dose-effect was demonstrated: the more apneas per hour of sleep, the higher the blood pressure values, and both systolic and diastolic blood pressure values were significantly related to AHI. According to our data, for each additional apneic event per hour of sleep, mean systolic and diastolic blood pressure values would increase 0.1301 and 0.1197 mmHg. It means that, compared with control group, daytime systolic and diastolic blood pressure values will be at least 3.2525 (0.1301 × 25) and 2.9925 (0.1197 × 25) mmHg higher for severe group. The similar senses were seen when we made the analysis with the nadir nocturnal oxygen saturation, like some previous results in England.2
In previous longitudinal population studies, OSA increased the risk for increased blood pressure at follow-up, and the odds ratios for the presence of incident hypertension at follow-up were 1.42, 2.03, and 2.89 with an AHI of <5, 5 to 15, and >15 events per hour at baseline, respectively. A clear dose-effect was demonstrated: the more apneas per hour of sleep, the higher the chance for becoming hypertensive.2 But in our study, we found that after the cutoff of 61–65, the increasing daytime blood pressure values reach a plateau or even drop slightly though we could not provide statistical evidence (Figure 1 and Figure 2). These results are not found previously because no epidemiologists classified groups in this way before. However, these results may not be isolated. In our cell and tissue level studies,19-22 we found inflammatory status of endothelial cells goes up to the peak levels and then turns down to the minimum with the intermittent hypoxia/reoxygenation (IH/ROX) frequencies increasing continuously, which may contribute to the reason that the inflammation does not come from IH phase but the ROX phase. Of course, our epidemiologic discoveries need further studies to confirm and further researches to explain the reasons.
Because of hypoxemia, hypercapnia, absence of lung inflation, microarousals at the end of apneic episodes, excess sympathetic activation and vasoactive factor releasing, the nocturnal blood pressure dipping diminishes and daytime hypertension develops. OSA also causes acute nocturnal surges in blood pressure which can prolong the daytime period. Sharing common pathogenetic pathway, factors that resulted in persistent daytime hypertension in OSA patients include sympathetic activity increasing, renin-angiotensin- aldosterone system dysfunction, endothelial function damaging, vascular resistance increasing, systemic inflammation, oxidative stress, metabolic dysregulation, atherosclerosis and vascular injury. Because of these reasons, there is an essential interaction between OSA severity and daytime blood pressure.23,24 From our data, OSA severity was associated with the higher blood pressure values until AHI of 61–65. OSA patients are often unaware of the associated symptoms, including snoring, breathing pauses, daytime sleepiness, cognitive dysfunction, impaired performance and damaged health-related quality of life. The cost effectiveness of early OSA management increases with OSA severity,25 and primary physicians across every related medical field should be sufficiently knowledgeable to identify those suffering from the disease. Therefore, this article provides evidence for early OSA management, especially in OSA patients with concomitant hypertension.
Acknowledgement: We are grateful to the information and correction from Prof. Ambrose A. Chiang, Division of Pulmonary and Critical Care Medicine in Duke University Medical Center, USA.
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