Nocturnal hypertension among primary care Chinese patients who underwent ambulatory blood pressure monitoring: prevalence and associated risk factors

Hing-han Chen 陳慶嫺, Ka-ming Ho 何家銘, Yim-chu Li 李艷珠, Catherine XR Chen 陳曉瑞

HK Pract 2023;45:21-31

Summary

Objective: To study the prevalence and associated risk factors of nocturnal hypertension among primary care Chinese patients who had undergone ambulatory blood pressure monitoring.
Nocturnal hypertension (NHT) increases the risks of cardiovascular events. Isolated NHT was found to be more prevalent among Chinese than among Westerners.
There has been no local data on the prevalence of NHT and its associated risk factors among the Chinese patients managed in Hong Kong’s primary care. To address this knowledge gap, we conducted this study.
Method: This study was a cross-sectional study. Chinese patients who underwent ambulatory blood pressure monitoring (ABPM) from 1/12/2017 to 30/11/2018 and had annual assessment done were recruited. Their demographic data, clinic blood pressure (BP) readings, ABPM result and laboratory data were reviewed. Student’s t-test and analysis of variance were used to analyse continuous variables and the Chi square test was used for categorical data. All statistical tests were two-sided, and a P-value of <0.05 was considered significant.
Results: Among the 162 patients fulfilling the inclusion criteria, 106 were found to have NHT with a period prevalence of 65.4%. Among those with NHT, 17 (10.5%) patients had isolated NHT with normal daytime blood pressure. NHT cases were found to have higher readings of average daytime and night time BP and more NHT cases were non-dippers. A higher proportion of non-dippers were found to have ischaemic heart disease (7.9% vs 0%, p=0.025) and NHT (78.2% vs 44.3%, p<0.001) than the dippers.
Conclusions: Noctornal hypertension is commonly encountered in primary care. Family physicians should have enhanced awareness of the presence of NHT and non-dippers during management of hypertension. Concerted effort should be made to control both daytime and night time BP to target levels and therefore prevent the development of cardiovascular disease.

Keywords: nocturnal hypertension, ambulatory blood pressure monitoring, primary care, risk factor

摘要

目的： 研究接受動態血壓監測的中國基層醫療病人患有夜 間高血壓的患病率及相關危險因素。
簡介： 夜間高血壓(NHT) 會增加心血管疾病的風 險。發現單純的夜間高血壓在中方比在西方更普 遍。在接受基層醫療健康的中國病人中，沒有關於 夜間高血壓患病率及其相關危險因素的本地數據。 為了增加這一方面知識，我們進行了這項研究。
方法： 這是一項橫斷面研究。招募於2017年1月12日 至2018年11月30日接受動態血壓監測(ABPM)並進 行年度評估的中國患者。審閱了他們的人口統計數 據、臨床血壓(BP)讀數、動態血壓監測結果和實驗 室數據。學生t 測試和方差分析用於分析連續變數，Chi平方測試用於分類資料。所有統計測試都是雙面 的，P值<0.05被認為是有意義的。
結果： 在162名符合納入標準的患者中，106人被發 現患有夜間高血壓，患病率為65.4%。在夜間高血壓 患者中，有17名(10.5%)病人患有單純夜間高血壓， 白天血壓正常。夜間高血壓病例的平均白天和夜間 血壓讀數較高，並且更多夜間高血壓病例是沒有血 壓晝夜變動類型的患者。相比血壓俱有晝夜變動的 病人，發現沒有血壓晝夜變動的病人患有缺血性心 臟病(7.9%對0%，p=0.025)和夜間高血壓(78.2%對 44.3%，p<0.001)的比例更高。
結論： 夜間高血壓中基層醫療中很常見。家庭醫生在 高血壓治療過程中應提高對夜間高血壓和血壓沒有晝 夜變動的病人的認識。應共同努力將白天和夜間的血 壓控制在目標水平，從而防止心血管疾病的發展。

關鍵詞： 夜間高血壓，動態血壓監測，基層醫療，風險因素

Introduction

Hypertension (HT) is common in Hong Kong. According to the Population Health Survey 2014/15 conducted by the Department of Health, the total prevalence of HT was 27.7% (25.5% for females and 30.1% for males) among persons aged 15-84.¹ HT contributes substantially to cardiovascular morbidity and mortality, and to all-cause mortality. Due to advances in medical technology, we can evaluate blood pressure (BP) not only during waking period, but also during sleeping time periods. The abnormally high BP in sleeping time is known as nocturnal hypertension (NHT).

Evidence from the literature has shown that the presence of NHT increases the risk of cardiovascular events, namely stroke and coronary events.^2,3 In addition, NHT is associated with poor physical function and cognitive dysfunction in the elderly.⁴ One study among Chinese patients with nondialysis chronic kidney disease (CKD)⁵ showed that nocturnal BP was a significant risk factor for renal events and cardiovascular events among these group of patients. Renal events meant doubling of serum levels of creatinine or end-stage renal disease, which ever occurred first. Furthermore, studies also showed that nocturnal BP was the most important determinant of all the organ damages such as left ventricular hypertrophy, microalbuminuria, carotid intima-media thickness.^2,6-10

Therefore, nocturnal BP level is considered as a stronger predictor of cardiovascular morbidity and total mortality than daytime BP.^8,10-12

I sol a t ed NHT, whi ch i s de f ined a s dayt ime normotension but with nocturnal elevated BP, is found to be more prevalent in Chinese (10.9%) than in Westerners (6.0%) and Eastern Europeans (7.9%).^13,14 However, due to the difficulties to identify the condition, the importance of isolated NHT is frequently overlooked.² Using the daytime clinic BP alone to guide the antihypertensive treatment would therefore render patients with isolated NHT at risk of poor BP control and the subsequent development of cardiovascular complications. Ambulatory blood pressure monitoring (ABPM) has been reported to be a better predictor for health outcomes than BP measured in clinic or at home.^15,16 Some studies showed that both daytime and night time ambulatory systolic BP were better predictors of all-cause and cardiovascular mortality than clinic BP alone.^15,17,18 In addition, it is the only method to offer insights on patterns of nocturnal BP, therefore helps identifying patients with NHT.¹⁹ Having said so, due to limited resources, ABPM service could not be provided for all patients. Usual indications for ABPM include identifying white-coat HT, masked HT, abnormal 24- hour BP patterns and assessment of treatment.²⁰

Concerning the risk factors of NHT, studies have shown that some conditions, such as older age, diabetes, CKD, albuminuria, poor sleep quality such as obstructive sleep apnoea (OSA), insomnia, nocturia, depression, shift-working, etc. are associated with the development of NHT.^{2,8,10,17,19,21,22} Once NHT is identified, chronotherapy is suggested for these patients, by taking hypertensive medication at night to restore the normal circadian rhythm.^10,23 This would be more effective than morning administration, and could improve the overall BP control. This is confirmed by a local study showing that restoring the nocturnal BP dip can improve left ventricular systolic ejection fraction among Chinese patients.²⁴

Up to now, there was no local data on the prevalence of NHT and its associated risk factors among Chinese patients managed in the primary care setting. Locally, a significant proportion of hypertensive patients are managed in primary care and followed up at government General Out-patient Clinics (GOPCs) of the Hospital Authority. In addition, the ABPM service has been available to primary care clinics since 2012 to improve the quality of care. To address this knowledge gap, we conducted this study and hopefully our findings will provide important background information on the prevalence of NHT in Chinese patients who undergo ABPM and explore its associated risk factors.

Methods
Study Design:

Cross-sectional study carried out at public primary care clinics

Subjects:
Inclusion criteria

All adult Chinese patients who underwent ABPM in GOPCs of Kowloon Central Cluster from 1/12/2017 to 30/11/2018 and had annual blood and urine checkup at least once during the study period were included. Patients were referred to have ABPM due to the following indications: suspected white coat HT, poorly controlled or resistant HT or suspected masked HT. All the devices for ABPM had been validated independently by Biomedical Engineering Service Section (BESS) yearly. In these clinics, hypertensive patients were provided with blood and urine checkups at least annually. This 1-year retrieval period was therefore likely to cover all such patients regularly followed up in these clinics. Annual blood checkup for all hypertensive patients included renal function test with creatinine level, fasting glucose and lipid profile. Routine urine checkup included spot urine protein-creatinine ratio (PCR). Urine albumin-creatinine ratio (ACR) would be done if the patients were known to have diabetes mellitus (DM).

Inclusion criteria

1. Patients who were younger than 18-years-old.
2. Patients who were Non-Chinese in ethnicity.
3. Patients who worked night shift. Nurse would ask whether patients had night shift duty before ABPM. Such patients would be identified and excluded.
4. Patients who were intolerant to ABPM or the ABPM data was invalid.
5. Patients who had no blood or urine checkup during the study period.

ABPM and definition of nocturnal hypertension:

ABPM measures patients’ BP during a 24-hour period. ‘ABPM daytime’ and ‘ABPM nighttime’ were defined according to patients’ schedules. ABPM provides a more accurate assessment with respect to clinic BP. A valid ABPM result should have at least 70% of expected measurements.²⁰ The minimum of daytime measurements should not be <20, with a minimum of 7 measurements at night. All patients who underwent ABPM were asked about the sleep time and awake time and these data were entered into ABPM software (cardiovisions 1.16.6). They were advised not to do vigorous exercise. Awake BP readings were measured in 30-minutes interval. Night time readings were measured in 45-60-minutes interval, depending on total number of sleeping hours so minimum of 7 measurements would be achieved at night. Nocturnal dipping status and whether patients got daytime HT were also retrieved from the report. Dipper was defined as the difference between daytime mean systolic pressure and nighttime mean systolic pressure greater than or equal to 10%.²⁵

Determination of variables:

All relevant clinical data were retrieved from the Clinical Management System (CMS) of the Hospital Authority. It included patient demographics such as age, gender, body mass index (BMI), smoking and drinking status; comorbidities such as DM, cardiovascular diseases (including stroke, ischemic heart disease, or peripheral vascular disease), conditions which may affect sleep such as mood problems (including depression, anxiety disorder), benign prostate hypertrophy (BPH) and OSA; laboratory data such as serum creatinine levels, estimated glomerular filtration rate (eGFR), urine ACR or spot urine PCR, serum fasting glucose, lipid profile, clinic BP and current treatment (receiving how many antihypertensive drugs, any bedtime hypertensive drugs) etc. If more than one test had been done, the blood and urine test done closest to the date of ABPM was used for data analysis. For clinic BP, patients were advised to measure BP after at least 10-minutes of rest in the outpatient clinic. The clinic BP reading on date of referring for ABPM was used in data analysis. Obesity was defined as BMI ≥25kg/m2. Microalbuminuria was defined as urine ACR being 2.5 to 30mg/mmol for males and 3.5 to 30mg/ mmol for females. Proteinuria was defined as urine ACR being >30mg/mmol or urine PCR >50mg/mmol for both genders.²⁷ An elevated urine ACR and PCR needed to be confirmed in the absence of urinary tract infection with additional first-void specimens collected during the next 3 to 6 months. CKD was defined as having an eGFR of <60mL/min/1.73m². Patient was considered a smoker if currently smokes or was within the first six months of quitting.

Sample Size Estimation:

According to the literature , the prevalence of isolated NHT was around 10.9% in Chinese population.¹³ Currently there are about 100,000 HT cases in our cluster. Assuming a prevalence of 10.9% patients who performed ABPM having NHT, with 5% margin of error and 95% confidence level, the sample size required is 150 (calculated via the statistic calculator).²⁸ To allow the room for case exclusion (around 30%), a sample size of 230 was decided for this study. Each ABPM case done within this period was assigned with a case number. Random Selection Generator was used to randomly select the case number and recruited into the study.²⁹

Statistical Analysis:

All data were entered and analysed using computer software (Windows version 21.0; SPSS Inc, Chicago [IL], US). Student’s t-test and analysis of variance were used for analysing continuous variables. Chi square test was used for categorical data and if the sample size is small (<5), Fisher's Exact test was used. All statistical tests were two sided, and a P-value of less than 0.05 was considered significant.

Results

A total of 348 cases had performed ABPM during the study period in the GOPCs of the Kowloon Central Cluster (KCC), among which 230 cases were randomly selected for this study. Further review of the data showed 68 cases (29.6%) did not fulfill the inclusion criteria and were therefore excluded. These patients included 1 case who was younger than 18 years old, 1 case that was not Chinese, 17 cases with invalid ABPM result, and 49 cases (21.3%) did not have blood and urine checked during the study period. Thus, the remaining 162 patients (70.4%) fulfilling the inclusion criteria were included into the data analysis.

Figure 1 summarised the flow chart of case recruitment and the ABPM diagnosis of the patients included in this study. From the data, we can see that, among the 162 patients included, 106 cases were found to have NHT, giving a period prevalence of 65.4%. In addition, 17 cases were found to have isolated NHT, with a period prevalence of 10.5%.

Table 1 summarised the demographic characteristics of all patients categorised according to the four ambulatory BP patterns. Basic demographic data revealed that the mean age of these groups of patients was 64.8 +/- 13.4 years old, and 63 were male (38.9%). Patients with sustained HT, isolated NHT and isolated day HT were older than the normotension group, with their mean age being 65.8 +/- 13.3 years, 61.1 +/- 14 years, 67.1 +/- 12.9 years respectively versus 57.5 +/- 12.4 years (p=0.044). Their gender composition, BMI, proportion of smoker and drinkers were comparable.

Table 2 summarised the demographic characteristics of the patients with or without NHT. In summary, they were comparable in terms of age, male-to-female ratio, smoking status, and BMI (all p>0.05).

Table 3 summarised the comorbidities and ABPM reading of patients with or without NHT. Compared with nocturnal normotension group, NHT group was found to have higher proportion with daytime HT (84% vs 69.6%, p=0.043). Not surprisingly, the average night time SBP and DBP were both much higher than the nocturnal normotension group (both p<0.001). In addition, NHT group was found to have fewer dippers (25.5%) than the nocturnal normotension group (60.7%), with p<0.001. The comorbidity rates for stroke, ischemic heart disease (IHD), DM, CKD, mood problem, BPH, OSA were all similar (all p>0.05). Number of antihypertensive medication used and whether patient was on bedtime antihypertensive were not statistically significantly different either (all p>0.05).

Table 4 summarised the comorbidities and ABPM readings of patients categorised according to the four ambulatory BP patterns. The sustained HT group and isolated day HT group were found to have higher proportion with DM (25.8% and 25.6% respectively, vs 0% for isolated NHT and 5.9% for normotension group, p=0.035). Isolated day HT and normotension group were found to have more with dipper (64.1% and 52.9% respectively) whereas isolated NHT group was found to have lowest dipper rate (0%, p<0.001). The lipid profile and comorbidity rates for stroke, IHD, microalbuminuria/proteinuria, CKD, mood problem, BPH, OSA were all similar (all p>0.05).

We further analysed the demo graphics, comorbidities and ABPM reading of patients with or without dipping (Table 5). In summary, they were comparable in terms of age, male-to-female ratio, and BMI (all p>0.05). Non-dippers were found to have higher proportion with IHD (7.9% vs 0%, p=0.025) and NHT (78.2% vs 44.3%, p<0.001) versus the dippers. The comorbidity rates for stroke, DM, CKD, mood problem, BPH, OSA were similar (all p>0.05).

Discussion

Our study revealed that the prevalence of NHT among hypertensive patient undergone ABPM was 65.4%. In primary care, ABPM is usually indicated for suspected whitecoat hypertension or resistant hypertension. The high prevalence of NHT in our study subjects is likely contributed by the patients with resistant hypertension. Among those with NHT, the prevalence of isolated NHT was 10.5%. It was well known that ethnic diversity exists in diurnal BP patterns, possibly due to different genetic background, lifestyle, or both.¹³ In addition, it was noted that patients with isolated NHT were much younger than those with isolated day HT or sustained HT, but was older than those with normotension (Table 1). With regards to the comorbidities, our data indicated that patients with NHT had a higher chance of daytime HT and being non-dippers too (Table 3). These findings should alert physicians to the importance of both daytime and nocturnal BP control and pay particular attentions to the non-dippers. During our daily practice, we usually started once daily dose of antihypertensive to patients and advised the patients to take the medication in the morning. If patients were identified to have NHT, an addition of night time dose of antihypertensive would be advised so as to improve the overall BP control. Similarly, for isolated NHT case, the patient should be advised to take the antihypertensive before the sleep. Indeed, studies had confirmed that taking hypertensive medication at night time could improve the overall BP control and reduce HT complication rate.²³ Therefore, all HT patients should be advised to have both day time and nocturnal BP monitoring either by ABPM or home BP monitoring so that doctors could advise them the treatment as appropriate. In this regard, monitoring clinic BP or daytime home BP alone was considered inadequate. All doctors should also pay special attention to the diurnal patterns of different HT and make all efforts to make sure that both the daytime and night time HT are under control.

Isolated NHT is a very easily missed clinical condition when only daytime BP or clinic BP is monitored. Our study revealed that the prevalence of isolated NHT was 10.5%, which was not low. In addition, all isolated NHT group was found to be non-dipper (Table 4) and the non-dipper cases were found to have higher proportion with IHD (Table 5). As non-dipper had been shown to be associated with higher mortality and cardiovascular events¹², all doctors should pay special attention to the presence of isolated NHT and make every effort to identify them early by using either the ABPM or regular home BP monitoring before sleep. In a recent study comparing self-measured home BP (HBP) and ABPM, the evening BP before sleep was similar between measured by home BP and ABPM. The BP before sleep was on average 10 mmHg lower than daytime BP and close to nocturnal BP.³⁰ Since ABPM might not readily available in some clinic setting, home BP before sleep may be considered as a surrogate of nocturnal BP and suboptimal home BP before sleep could be an indication for ABPM.

ABPM request repeated measures of BP. It is reasonable to concern about the possible sleep disturbance secondary to the frequent blood pressure measurement and the sleep disturbance might affect the interpretation of nocturnal BP. In our study, enrolled patients did not particularly complain sleep disturbance caus ed by ABPM. A recent study compared the nocturnal BP between sleep and awake state, showing no significant difference regardless patient was asleep or not.³⁰

As to the aetiology of NHT, it was multifactorial. Some studies had shown that it was commonly encountered with a number of clinical backgrounds, such as autonomic dysfunction, volume overload secondary to salt sensitivity and CKD, poor quality of sleep, disruption of biological circadian rhythms and other factors.¹⁴ However, risk factors proved to be associated with the presence of NHT in other studies, including older age, the presence of diabetes, CKD, albuminuria, or with poor sleep quality^{2,8,10,17,19,21,22} were not significantly different in the dipper versus non-dipper group in our study. The reasons for this discrepancy could be explained by the difference in their racial or ethnic compositions. In addition, the clinic setting was also different, with many of such studies were carried out in secondary care settings whereas our study was carried out in the primary setting. We had to admit that the sample size of our study was relatively small (n=162), which may limit the power to detect the significant difference between the groups. In our recruited patients, only 15 patients were found to have cardiovascular disease (CVD) including IHD and stroke, and even fewer number of patients got OSA, BPH, or mood problem. Indeed, most patients managed in the primary care were relatively more stable with fewer complications and therefore had a lower prevalence of CVD compared with those managed in secondary or tertiary settings. Furthermore, some patients had already received treatment for different comorbidities such as antihypertensive for HT, lipid lowering agent for hyperlipidaemia or continuous positive airway pressure for OSA. Improvement of these conditions might also affect the prevalence of NHT or isolated NHT.

Nocturia due to lower urinary tract symptoms (LUTS) might affect sleep quality than thus affect the nocturnal BP. In our study, only 7 out of 63 male subjects have BPH, which might not affect the interpretation of data. The prevalence of BPH in our study was 11%, this was similar to literature. In a study about LUTS in Chinese male patients, the prevalence of LUTS among men aged beyond age 50 years was 10.66%. Prevalence in age group 50-59 was 8.39%, and 10.61%in age group 60-69, 14.7% in age group >=70.³¹

Strength and limitations of the study

This was the first local study on the prevalence of NHT and its associated risk factors in the primary care setting. In addition, the ABPM readings, the clinical data and the biochemical data were all retrieved from the CMS system of the Hospital Authority, therefore not much human error or recall bias.

However, several limitations existed in this study. First, this was a single cluster study and only patients who had performed ABPM were recruited, therefore selection bias existed. Also, the sample size was small, this might affect the significance of data. In this study, most patients were referred to have ABPM due to the following indications: suspected white coat HT, poorly controlled or resistant HT or suspected masked HT. Therefore, our study findings may not be generalised to other settings or to the general population. Second, 49 case (21.3%) who did not have blood or urine assessments done were excluded, which may affect the genuine prevalence rate of NHT in the study. It is well observed in our daily practice that those patients who do not attend routine blood or urine tests tend to have poor compliance to regular follow up and taking regular medications. Therefore, the exclusion of these groups of patient would likely result in under-estimation of the prevalence rate of NHT. Third, because of the crosssectional nature of our study, we were unable to adjust for other potential unmeasured confounders e.g. quality of sleep during ABPM, frequency of nocturia. Therefore no temporal or causal relationship could be established.

Implications for primary care

Family physicians are at the forefront in the management of HT, and aim to achieve optimal BP control to prevent cardiovascular complications. This study has provided important background information on the high prevalence of NHT among Chinese patients. Physicians should stay alert on it and promote the use of ABPM to identify this group of patients. If patients are identified to have NHT, adding a night time dose of antihypertensive would be advised so as to improve the overall BP control and reduce its complication rate.

Conclusion

In summary, our study suggested that NHT was a common condition, with a period prevalence of 65.4%. NHT cases were found to have a higher reading of average daytime and night time BP and more NHT cases were non-dippers. In addition, non-dipper patients were found to have higher proportion with IHD and NHT than the dippers. Family physicians should enhance the awareness on the presence of NHT and non-dippers during management of HT in daily practice. Concerted effort should be made to bring both the daytime and night time BP down to target level and therefore prevent the development of CVD.

Acknowledgement

I sincerely thank my supervisors Dr. Catherine Chen and Dr. Ken Ho for their continuous encouragement, inspiration, and support during this study. I would also like to thank Mr. Steven Lau, statistical officer of Kwong Wah Hospital, Kowloon Central Cluster for his expert statistical support.

References