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Table of Contents
ORIGINAL ARTICLE
Year : 2021  |  Volume : 3  |  Issue : 2  |  Page : 72-76

Effect of antihypertensive drugs on circadian variation of blood pressure measured by ambulatory blood pressure monitoring in controlled hypertensive individuals


1 Associate Professor, Department of Medicine, MGM Medical College, Aurangabad, Maharashtra, India
2 Postgraduate Resident, Department of Medicine, MGM Medical College, Aurangabad, Maharashtra, India

Date of Submission11-Jan-2021
Date of Decision10-Feb-2021
Date of Acceptance08-Apr-2021
Date of Web Publication22-Nov-2021

Correspondence Address:
Dr. Rohit Jacob Manoj
Postgraduate Resident, Department of Medicine, MGM Medical College, Aurangabad
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/ACCJ.ACCJ_1_21

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  Abstract 


Background: Rewinding back a 100 years ago, Riva Rocci introduced the meticulous way of measuring blood pressure (BP) in clinical practice. With recent years, ambulatory BP monitoring came into existence which is still not used routinely in the management of hypertension. This thought led to the commencement of our study to analyze the variations in ambulatory BP recording over a 24-h cycle. Objectives: The objectives of the study are to determine the BP differences throughout the circadian cycle and to analyze the variations in circadian rhythm due to various antihypertensive drugs. Methods: On the first visit to the Medicine Outpatient Department, patient's medical history was recorded. Three readings of office BP were recorded using a sphygmomanometer. The patient was then provided with the ambulatory BP monitoring device, sent home and asked to follow-up after 24 h and the report was recorded. Results: On comparing the nocturnal pattern among candidates taking single versus combination drug, the dip was found to be in 31.7% in patients on single drug compared to 38.6% combination therapy. The surge in BP was seen in 56.8% of patients on single-drug therapy compared to 43.3% patients on combination drug therapy. Conclusion: Single-drug therapy for hypertension did not show a significant nocturnal pattern compared to the combination drug therapy for hypertension. The presence of the risk factors such as obesity smoking, dyslipidemia, diabetes mellitus, hypothyroidism, family history, and chronic kidney disease showed a presence of dipping and nondipping pattern in BP.

Keywords: Ambulatory, blood pressure, circadian, dipping, hypertension, nocturnal


How to cite this article:
Nikalje A, Manoj RJ. Effect of antihypertensive drugs on circadian variation of blood pressure measured by ambulatory blood pressure monitoring in controlled hypertensive individuals. Ann Clin Cardiol 2021;3:72-6

How to cite this URL:
Nikalje A, Manoj RJ. Effect of antihypertensive drugs on circadian variation of blood pressure measured by ambulatory blood pressure monitoring in controlled hypertensive individuals. Ann Clin Cardiol [serial online] 2021 [cited 2022 May 28];3:72-6. Available from: http://www.onlineacc.org/text.asp?2021/3/2/72/336214




  Introduction Top


Hypertension is the most common noncommunicable disease in India, with largest contribution to the burden of disease strength.[1],[2] Ambulatory BP monitoring, over the years, has provided information regarding different varieties of hypertension. However, the advent of ambulatory BP monitoring is still not used routinely in the management of hypertension.

Never has a study been conducted in India to analyze the effect of various antihypertensive agents on ambulatory blood pressure (BP). This thought led to the commencement of our study to analyze the variations in ambulatory BP recording in individuals who are apparently controlled hypertensives.

The aim of the study is to determine the efficacy of various antihypertensive drugs on the circadian rhythm of BP.

The objectives of the study are to determine the BP differences throughout the circadian cycle and to analyze the variations in circadian rhythm due to various antihypertensive drugs.


  Methods Top


The study was conducted among 310 Office-controlled hypertensive patients attending the Medicine Outpatient Department in a private hospital. The study was an observational cross-sectional hospital-based study conducted over a span of 2 years dating from October 2018 to September 2020 after taking permission from the Institutional Ethics Committee (ECRHS/2018/05 dated October 05, 2018).

Any candidate >18 years of age and with a history of Hypertension since at least 1 month was included in the study. Pregnant women, shift workers, chronic alcoholics (alcohol intake >80 mL/day), chronic smokers (>20 cigarettes/day), bodybuilders, morbid obese individuals, and patients with cardiovascular disorders such as ischemic heart disease, congestive cardiac failure, stroke, and cardiac arrhythmias were excluded from the study.

In this study, we observed the variation in Ambulatory BP recordings among Office controlled hypertensive individuals.

  1. On the first visit to the Medicine Outpatient Department (OPD), patient's medical history, antihypertensive drug history, various demographic parameters were recorded
  2. The BP was measured with a sphygmomanometer
  3. Three readings of systolic and diastolic BP were taken, each 20 min apart and its mean was taken as the office recorded BP
  4. The patient was then provided with the ambulatory BP monitoring device, sent home, and asked to follow-up after 24 h to the Medicine OPD
  5. Patient was asked to follow his daily routine and daily medication intake as usual during this span of time
  6. After 24 h, the ABPM machine was detached from the patient and the reports were recorded.


The study methodology is illustrated in [Flowchart 1].



The collected data were compiled in MS Excel Sheet. For analysis of this data, SPSS (Statistical Software, Mumbai, Maharashtra, India) version 22nd was used. Qualitative data were represented in form of frequency and percentages and Fischer's t-test was used to test the significance of the obtained results.


  Results Top


A total of 310 hypertensive patients fulfilling the inclusion criteria and willing to be part of the study were included and evaluated in detail. The mean age of the patients was found to be 48.93 ± 11.48 years. Among 310 participants, 180 (58.06%) were male and 130 (41.93%) were female hypertensives (male preponderance) [Figure 1] and [Figure 2].
Figure 1: Gender distribution versus nocturnal pattern

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Figure 2: Nocturnal pattern distribution among genders

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The prevalence of hypertension in different age groups is 2.90% (9/310) among 18–30 years, 22.58% (70/310) among 31–40 years, 31.6% (98/310) among 41–50 years, 26.12% (81/310) among 51–60 years, and 16.45% (51/310) among more than 60 years age [Figure 3].
Figure 3: Age versus nocturnal pattern

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On risk factor assessment, it was found that the most common risk factor of hypertension pertaining to our study is dyslipidemia (42.90%) [Figure 4].
Figure 4: Prevalence of risk factors

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The nocturnal pattern of variation in BP is categorized under three headings:

  • Surge (nocturnal elevation or <10% drop in BP)
  • Normal (night time dip in BP ≥10% of daytime BP)
  • Dip (nocturnal drop in BP >20% of daytime BP).


Surge of BP was seen in 96 males and 63 females and dip in BP is seen in 62 males and 45 females.

Out of 310 candidates enrolled, 126 candidates were on a single antihypertensive drug [Table 1]. The most used single antihypertensive drug observed during our study was amlodipine 25.39% (32/126) and telmisartan 16.66% (21/126).
Table 1: Nocturnal pattern of single-drug treatment with the duration of intake

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The most used combination antihypertensives by the study population were a combination of angiotensin receptor blocker and calcium channel blockerss (for example, telmisartan and amlodipine, telmisartan and cilnidipine, and telmisartan and nifedipine) in 26.31% (30/114) population.

However, many patients were taking two antihypertensive drugs at different time intervals. For example, a patient was on telmisartan with hydrochlorothiazide (combination–once a day) as one combination and was also on cilnidipine (twice a day). Hence, the once/twice/thrice a day dosing could not be applied here. The following charts and tables describe the nocturnal pattern with respect to the combination drugs irrespective of the dosing pattern [Figure 5].
Figure 5: Nocturnal pattern in blood pressure variation in single-drug treatment and combination drug treatment

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[Table 2] summarizes the effect of combination drug treatment on nocturnal pattern of Blood Pressure.
Table 2: Nocturnal pattern of combination drug treatment

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On comparing the nocturnal pattern among candidates taking single versus combination drug, the dip was found to be in 31.7% in patients on single drug compared to 38.6% combination therapy. The normal pattern was found in 11.5% of single-drug therapy compared to 18.1% in combination drug therapy. The surge in BP was seen in 56.8% patients on single-drug therapy compared to 43.3% patients on combination drug therapy.

However, with the above observations, it cannot be concluded that combination drug therapy has better hypertensive control than single drug therapy as many confounding factors still play a role in BP control. The statistical analysis, as shown below, states the P = 6.029, which suggests that there is no significant association between the nocturnal pattern of BP and the number of antihypertensive drugs prescribed


  Discussion Top


The present hospital based observational study analyses the BP variation due to various antihypertensive drugs. Moreover, our study also discusses the prevalence of common risk factors and its association with the nocturnal variation pattern of BP.

A North Indian study demonstrated a higher prevalence of Hypertension among females than males.[3] A study done in Delhi and adjoining rural areas of Haryana showed the prevalence to be 4.17% (males) and 2.84% (females) in the age group 25–34 years which increased to 22.9% (males) and 32.9% (females) in the age group 55–64 years.[4]

The present study also incorporates the fact that as age advances, the prevalence of hypertension also increases. However, the prevalence of hypertension above 50 years of age was found to be low. This may be attributed to the fact that only controlled hypertensive individuals were considered in the present study. As age advances, the prevalence of multiple comorbidities increase thus, increasing the risk of uncontrolled hypertension. Hence, many individuals remain in the submerged portion of the iceberg.

Another fact to be noted is that family history of hypertension was an important risk factor found in the present study, accounting to nearly 34.83% of the study population. Many Indian Epidemiological studies have demonstrated significant association between obesity and hypertension. For every 10% increase in weight, a rise of 6.5 mm Hg in systolic pressure was observed in the Framingham study.[5] Studies such as the Bombay Executive Study[6] and the Chennai Urban Population Study[7] have established obesity and overweight as an independent comorbidity associated with hypertension.

In all the patients, we have assessed the BP in the daytime and nighttime. We found a significant higher mean of systolic BP during the day (124.27 ± 13.75) compared with during the night (114 ± 16.9), similarly, the diastolic BP was statistically higher during daytime (81.96 ± 10.11) compared to the nighttime (80.12 ± 10.43).

Hypertension contributes to a major proportion of world disease morbidity and mortality[8] and amounts for 6% of death worldwide.[9]

However, the most important aim of antihypertensive therapy should be complete control of BP. In the present study, it was found that single drug treatment was used more commonly among Hypertensive patients of <2 years duration.

A new developing hypothesis states that hypertensive individuals with a surge nocturnal pattern may have a worse prognosis than majority of the individuals with a normal dipping pattern. Uzu et al.[10] reported a similar observation in their study.

Variation in Blood pressure through a 24 hour cycle is one of the most commonly discussed topic with reference to Hypertension. Achieving a complete control of blood pressure with a less than 10% dip during night hours is the ideal scenario. However, obtaining this level of control permanently is nearly impossible due to various confounding factors affecting blood pressure widely.

Some crucial factors include kidney function, Left Ventricular Mass index, age, demographic factors and many others. Seo et al.[11] showed that raised Urea and Creatinine was commonly associated with non dippers and the possible reasons for the same included old age and long duration of Hypertension. Muxfeldt et al.[12] showed that the LV mass index gradually increased from the extreme dippers to the dippers and the nondippers, and were followed by the reverse dippers. Thus obtaining complete control of Blood Pressure with just Antihypertensives may be a task difficult to achieve.

The percentage of nondipping pattern was found among 14.2% of hypertensives. Di Iorio et al.,[13] in their study, observed 29.8% of nondippers in a hypertensive population.

In the present study, we have found a less incidence of the dip and surge in the patients treated with combination of drug therapy compared to the patients on single drug therapy for hypertension. Similar findings are reported by various authors, presenting the benefits of the combination therapy over the monotherapy,[14] and some showed a mixed relation.


  Conclusion Top


Hypertension treatment progressed with technological developments and new insights each year. However, determining each hypertensive patient's requirement has become a rhetorical comment as the care given for hypertension is more generic as of today. The use of Ambulatory BP Monitoring is not only capable of predicting cardiovascular events but also of delivering a tailored approach to each patient and of treating each, taking into account their individual variability. Overweight individuals are at higher risk of the developing complications compared to the normal BMI hypertensives. Study also adds that combination therapy is beneficial to control the hypertension with minimal surge and dip pattern compared to single-drug therapy.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
  References Top

1.
GBD 2013 Risk Factors Collaborators, Forouzanfar MH, Alexander L, Anderson HR, Bachman VF, Biryukov S, et al. Global, regional, and national comparative risk assessment of 79 behavioural, environmental and occupational, and metabolic risks or clusters of risks in 188 countries, 1990-2013: A systematic analysis for the Global Burden of Disease Study 2013. Lancet 2015;386:2287-323.  Back to cited text no. 1
    
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Travasso C. High blood pressure is the leading health risk factor in India, finds study. BMJ 2015;351:h5034.  Back to cited text no. 2
    
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Malhotra P, Kumari S, Kumar R, Jain S, Sharma BK. Prevalence and determinants of hypertension in an un-industrialised rural population of North India. J Hum Hypertens 1999;13:467-72.  Back to cited text no. 3
    
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Chadha SL, Shukla DK, Singh N. Urban – rural differences in the prevalence of hypertension and its risk factors. Cardiol Today 2001;5:237-40.  Back to cited text no. 4
    
5.
Garrison RJ, Kannel WB, Stokes J 3rd, Castelli WP. Incidence and precursors of hypertension in young adults: The Framingham Offspring Study. Prev Med 1987;16:235-51.  Back to cited text no. 5
    
6.
Anand MP, Bakhle DS, Ajay S. Smoking and hypertension: Indian scenario. J Assoc Physicians India 1990;38:283-4.  Back to cited text no. 6
    
7.
Deepa R, Shantarani CS, Pradeepa R, Mohan V. Is the rule of halves in hypertension still valid? Evidence from the Chennai urban population study. J Assoc Physicians India 2003;51:153-7.  Back to cited text no. 7
    
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Kain HK, Hinman AT, Sokolow M. Arterial blood pressure measurements with a portable recorder in hypertensive patients. I. Variability and correlation with “casual” pressures. Circulation 1964;30:882-92.  Back to cited text no. 8
    
9.
Murray CJ, Lopez AD. Global mortality, disability, and the contribution of risk factors: Global Burden of Disease Study. Lancet 1997;349:1436-42.  Back to cited text no. 9
    
10.
Uzu T, Kazembe FS, Ishikawa K, Nakamura S, Inenaga T, Kimura G. High sodium sensitivity implicates nocturnal hypertension in essential hypertension. Hypertension 1996;28:139-42.  Back to cited text no. 10
    
11.
Di Iorio A, Marini E, Lupinetti M, Zito M, Abate G. Blood pressure rhythm and prevalence of vascular events in hypertensive subjects. Age Ageing 1999;28:23-8.  Back to cited text no. 11
    
12.
Hermida RC, Ayala DE, Fontao MJ, Mojón A, Fernández JR. Chronotherapy with valsartan/amlodipine fixed combination: Improved blood pressure control of essential hypertension with bedtime dosing. Chronobiol Int 2010;27:1287-303.  Back to cited text no. 12
    
13.
Mathur P, Kadavath S, Marsh JD, Mehta JL. Chronotherapy for hypertension: Improvement in patient outcomes with bedtime administration of antihypertensive drugs. Eur Heart J 2020;41:4577-9.  Back to cited text no. 13
    
14.
Hermida RC, Smolensky MH. Chronotherapy of hypertension. Curr Opin Nephrol Hypertens 2004;13:501-5.  Back to cited text no. 14
    


    Figures

  [Figure 1], [Figure 2], [Figure 3], [Figure 4], [Figure 5]
 
 
    Tables

  [Table 1], [Table 2]



 

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