|Year : 2019 | Volume
| Issue : 2 | Page : 76-81
A comparative study of central and peripheral arterial parameters in hypertensive patients on angiotensin receptor blockers and calcium channel blockers
Kailas Laxman Rao1, Mohammed Abdul Hannan Hazari2, Bachi Tazneem3, Ahmed Abdul Aziz3, Asiya Mohtesham3, A Afreen3, Kethavath Priyanka3
1 Department of Cardiology, Owaisi Hospital and Research Centre, Deccan College of Medical Sciences, Hyderabad, Telangana, India
2 Department of Physiology, Deccan College of Medical Sciences, Hyderabad, Telangana, India
3 Department of Pharmacy Practice, Deccan School of Pharmacy, Hyderabad, Telangana, India
|Date of Submission||27-Mar-2019|
|Date of Acceptance||30-Apr-2019|
|Date of Web Publication||23-Jul-2019|
Dr. Mohammed Abdul Hannan Hazari
Department of Physiology, Deccan College of Medical Sciences, DMRL “X” Road, Kanchanbagh, Hyderabad - 500 058, Telangana
Source of Support: None, Conflict of Interest: None
Aims: Untreated or inappropriately managed hypertension (HTN) is a significant risk factor for all-cause morbidity and mortality due to its complications. For proper management of HTN, timely diagnosis and classification into appropriate category is crucial. According to hypertensive class category, pharmacological therapy can be initiated according to the national or international guidelines. Various antihypertensive medications have differential effects on peripheral and central arterial parameters. Our study was aimed at comparing the effects of two classes of antihypertensive drugs, i.e., angiotensin receptor blockers (ARBs) and calcium channel blockers (CCBs). Materials and Methods: Hypertensive patients on monotherapy – ARBs (Group 1, n = 35) and CCBs (Group 2, n = 35) – over the age of 18 years, belonging to both genders, were recruited. Results: Heart rate and peripheral and central arterial pressures were lower in Group 2 compared to Group 1; ankle brachial index and carotid-femoral pulse wave velocity were less in Group 1 in comparison with Group 2; but these differences were statistically not significant. Conclusions: We conclude that the two groups of drugs were equally effective in blood pressure reduction, both in central and peripheral arteries.
Keywords: Angiotensin receptor blockers, Blood pressure, Calcium channel blockers, Central arterial pressure, Hypertension, Pulse wave velocity
|How to cite this article:|
Rao KL, Hazari MA, Tazneem B, Aziz AA, Mohtesham A, Afreen A, Priyanka K. A comparative study of central and peripheral arterial parameters in hypertensive patients on angiotensin receptor blockers and calcium channel blockers. J Health Res Rev 2019;6:76-81
|How to cite this URL:|
Rao KL, Hazari MA, Tazneem B, Aziz AA, Mohtesham A, Afreen A, Priyanka K. A comparative study of central and peripheral arterial parameters in hypertensive patients on angiotensin receptor blockers and calcium channel blockers. J Health Res Rev [serial online] 2019 [cited 2019 Aug 20];6:76-81. Available from: http://www.jhrr.org/text.asp?2019/6/2/76/263243
| Introduction|| |
Hypertension (HTN) is a significant risk factor for cardiovascular disease (CVD), which causes morbidity and mortality due to its severe complications if not diagnosed properly and accurately on time. It has been found that various antihypertensive drugs produce variable effects on the central blood pressure (BP) even though the same BP is observed by brachial measurements.,,,, In the present article, we tried to evaluate the efficacy of antihypertensive drugs on the central and peripheral arterial parameters. In hypertensive patients, arterial stiffness (AS) measured with pulse wave velocity is a robust speculation for mortality due to CVDs.,,
The aim of this study was to compare the role of angiotensin receptor blockers (ARBs) and calcium channel blockers (CCBs) by measuring central and peripheral arterial parameters in the management of HTN. The objectives were to measure and compare the differences in arterial parameters in hypertensive individuals on ARBs and CCBs and also to estimate the vascular age and analyze cardiovascular risk.
| Materials and Methods|| |
Patients (more than 18 years of age, both genders) treated for HTN with ARBs or CCBs, after at least 3 months of monotherapy, with or without comorbidities such as diabetes mellitus, dyslipidemia, or a past history of ischemic heart disease (IHD), were included in the study. Treatment with ARBs was classified into Group 1 and that with CCBs was classified into Group 2. Patients not on antihypertensive agents under this study and those with morbid obesity, severe pedal edema, stroke, severe left ventricular dysfunction, acute coronary syndrome, cor pulmonale, arrhythmias, and severe peripheral vascular disease; pregnant females; and pediatric patients were excluded from the study. A total of seventy patients were recruited, 35 of which were on ARBs and 35 on CCBs during the 6-month study period.
This study used the principles of pulse wave analysis and polymechano cardiography to calculate the derived central and peripheral BPs and their parameters using commercially available PeriScope™ AoIn ver. 3.0.5 (Genesis Medical Systems, Hyderabad, Telangana, India) which is a multiparameteric, diverse, and noninvasive cardiovascular analysis device.
The patients were assessed for appropriate medical history which is recorded in the data collection forms. It was ensured that patients had not smoked or used caffeine for the past 24 h before recording the readings. 10 h of fasting was observed in most of the patients as the test was being performed in the morning hours in a serene environment. To avoid difficulty and errors in the computation, recordings were taken twice. First, the cuffs were tied to the patients on both the upper and lower limbs over the brachial and tibial arteries. Relevant medical history of smoking, HTN, diabetes, alcoholism, and drug use was collected. All of them were administered either ARBs or CCBs with no other antihypertensive agents.
Central and peripheral arterial parameters were recorded for all the patients according to the selection criteria. Cardiovascular risks were also assessed according to the central arterial parameter measurements.
Proper functioning of the vasculature is maintained by the balance of structural and cellular elements. This is usually disturbed when arterial elasticity is reduced due to aging, HTN, diabetes mellitus, chronic kidney disease, atherosclerosis, and other cardiovascular problems. The reduction in the elasticity of the vessels is referred as AS.
The sum of passive stiffness due to elastin and collagen fiber dysfunction and active stiffness caused due to endothelium dysfunction and alterations of vascular smooth muscle cells is denoted as AS. Increased ankle brachial index (ABI) may lead to increased AS due to medial artery calcification.
Arterial stiffness index
AS index (ASI) is another measure of AS which quantifies the contour of the oscillometric envelope of peripheral pulse waveform. With increasing AS, the arteries become harder to collapse by the application of external pressure. Therefore, with increased AS, the oscillometric envelope becomes much flatter. Hence, ASI indicates this flattening process whereby ASI values are higher for more AS. Usually, it should not be >40 mmHg.
Pulse wave velocities
Each sensor records waveform segment that helps in the measurement of pulse transit time (PTT). Heart-brachial pulse wave velocity (hbPWV) of both upper limbs, heart-ankle PWV (haPWV) of both lower limbs, brachial-ankle PWV of both right and left limb pairs, and effective estimated carotid-femoral PWV measurements are recorded as follows:
Where Lha= Distance (in cm) between the heart and the corresponding ankle
Lhb= Distance (in cm) between the heart and the corresponding brachium
Lba= Distance (in cm) between the corresponding brachium and ankle.
Superficial measurements are calculated as follows:
- Heart-to-brachium distance (Lhb) = Heart to shoulder + shoulder to midpoint of brachial cuff
- Heart-to-ankle distance (Lha) = Heart to midpoint of ankle cuff
- Brachial ankle distance (Lba) = Heart-to-brachium distance + heart-to-ankle distance.
Predicted carotid femoral pulse wave velocity
This is derived using both right and left brachial ankle PWVs described above.
Mean arterial pressure percentage
One more measure for AS/atherosclerosis is the percentage of mean arterial pressure (%MAP). It is the ratio of height of mean arterial pressure from diastolic pressure to the total pulse pressure (PP) expressed in percentage [Figure 1]. If the artery is stenosed, MAP is large. If ABI is >1.2 and %MAP is >40%, it may indicate hardening of the artery.
|Figure 1: Central arterial pulse wave. ©QAMER. Creative Commons Attribution 4.0 International License|
Click here to view
Peripheral blood pressure
BP recorded in the right (brachial artery) upper arm in this study is documented as peripheral BP.
The difference between systolic and diastolic BP (SBP and DBP) is PP, which is measured in mmHg. Force generated by the heart whenever it contracts is represented by this measure. If the resting BP is 140/90 mmHg, then PP is 50 mmHg. PP changes with the arm positioning.
The number of times an individual's heart beats per minute is called heart rate (HR). It is synonymously used with pulse rate. It varies from person to person, but the normal range is 60–100 beats/min.
Central arterial pressures
Central arterial (aortic) pressures in this study were recorded using PeriScope™. These peripheral pressures are derived from peripheral arterial waveforms by validated transfer functions. Aortic systolic pressure (AoSP), aortic diastolic pressure (AoDP), and aortic PP (AoPP) were recorded.
Augmentation pressure and augmentation index
The quantity of pressure added to the systolic pressure peak based on the reflected wave is labeled as augmentation pressure (AP) . Augmentation index (Aix) is the ratio of the AP to AoPP expressed in percentage.
Estimated vascular age
Vascular age was automatically calculated based on PWV by the instrument. Difference (△age) between the chronological and vascular ages was also calculated.
All the statistical analyses were performed using MS Office Excel 2016 and SPSS version 17.0 (SPSS Inc., Chicago, IL, USA). Mean ± standard deviations were calculated for scale variables that were normally distributed, and percentages were calculated for categorical variables. The analyses were done for both central and peripheral arterial parameters to evaluate the level of relativeness in between the two measurements and to correlate their findings and accuracy. Fisher's exact test or Chi-square test was used for analyzing the differences between categorical data. t-test was used for comparing the scale data. Medication adherence was assessed and measured using the Morisky Medication Adherence Scale-8. Central (aortic) and peripheral (brachial) BPs with and/or without comorbidities were analyzed and measured using multivariate logistic analysis. P < 0.05 was considered significant at 95% significance level for two-tailed test.
| Compliance With Ethical Standards|| |
The study was approved by the Institutional Review Board (IRB Reference No. 2017/19/001). All procedures performed were in accordance with the National Ethical Guidelines for Biomedical and Health Research Involving Human Participants (2017).
Written informed consent was obtained from all participants included in the study.
| Results|| |
The average age of the patients in Group 1 (ARBs) was 54.69 ± 13.83 years and in Group 2 (CCBs), it was 51.34 ± 14.13 years; both the groups included same number of patients, i.e., 35 patients. The average height (cm), weight (kg), and body mass index (kg/m2) in Group 1 (ARBs) were 156.9 ± 8.5, 67 ± 13.6, and 27.38 ± 5.72 and in Group 2 (CCBs) were 157.5 ± 8.9, 71.5 ± 10.8, and 28.9 ± 4.69, respectively. All the demographic details of both the groups were similar [Table 1].
Group 1 (ARBs) patients were mostly on telmisartan (n = 32, 91%) and Group 2 patients were mostly on amlodipine (n = 24, 68%). These patients were on monotherapy (either ARB or CCB) for the treatment of HTN at the time of assessment. Patients were on treatment with anti-diabetic medicines, lipid-lowering agents, etc., for associated comorbid conditions.
It was observed that both the groups were having equal number of patients with diabetes (18) which was the major associated comorbidity, whereas the prevalence of IHD was lower in Group 2 (CCBs) [Table 2]. In total, there were eight smokers (Group 1 had three and Group 2 had five) and three alcoholics (Group 1 had two and Group 2 had one).
High level of medication adherence was seen in 42 patients, whereas low level of adherence was seen in three patients [Table 3].
There were similar reductions in BP in both the treatment groups: central AoSPs were 129.47 ± 20.5 versus 123.88 ± 20.46 (P = 0.24) and central AoDPs were 83.36 ± 10.46 versus 80.58 ± 19.38 (P = 0.46). HR, PP, haPWV, hbPWV, ABI, aortic Aix, and ASI were positively correlated with carotid femoral PWV (cfPWV) [Table 4].
The parameters that were lower in Group 1 (ARBs) were right ankle ASI, right ABI (R. ABI), left ABI (L. ABI), and cfPWV. The parameters that were lower in Group 2 (CCBs) were AoSP, AoDP, AoPP, AoAP, Aix, brachial BP (both SBP and DBP), MAP, PP, HR, right brachial ASI (R. Bra. ASI), left brachial ASI (L. Bra. ASI), left ankle ASI (L. Ank. ASI), and △ age, but all with P > 0.05 [Table 4]. There were no statistical differences in medication adherence and comorbidities between both the groups [Table 2] and [Table 3]. Both the classes of drugs were found to be similarly effective on central and peripheral arterial parameters.
| Discussion|| |
The current study explored the effects of CCBs and ARBs in lowering the BP in peripheral arterial segments and central artery (aorta). In addition, stiffness in the vasculature was assessed indirectly by measuring the PWV. We performed the measurements for diagnosing the risk of people who may be suffering with other types of cardiovascular events in future. Patients included in this study were hypertensive of various stages that were on treatment with Group 1 (ARBs) or Group 2 (CCBs). We used PeriScope™ which is based on oscillometric waveform pattern measurements and calculates various central arterial parameters including PWV and ASI, for detecting stiffness of the arteries and their relation with future cardiovascular risks.
It was found that CCBs reduced central SBP more than ARBs, but no major change was observed in brachial BPs with both the classes. This may be due to (1) reduction of arterial reflective power and also due to (2) late arrival time of the reflected wave. Because the HR-adjusted Aix is reduced in CCBs, the first proposition can be proved. Brachial systolic pressure is not effected with the pressure wave while a central (aortic) pressure gets effected. Studies done previously concluded that the ARBs reduce PWV in a positive relationship with cfPWV along with HR and PP, better than CCBs.,
In the present study, we found that parameters which were reduced by CCBs better than ARBs were AoSP, AoDP, AoPP, AP, Aix, peripheral SBP, peripheral DBP, MAP, PP, HR, R. Bra. ASI, L. Bra. ASI, L. Ank. ASI, and the difference between actual age and vascular age. The parameters that were affected by ARBs more than CCBs were R. Ank. ASI, R. ABI, L. ABI, and cfPWV.
Both the classes of drugs were found to be similarly effective on central and peripheral arterial parameters. There were no statistically significant differences in medication adherence and comorbidities between both the groups.
There are studies which reported that CCBs reduce central arterial pressures better than ARBs which may be due to reflex sympathetic activity. Markers of sympathetic activity were observed in CCB group patients such as variations in HR; however, long-acting CCBs do not affect HR but sympathetic activity increases. It was found that CCBs Group patients' 24h mean HR was moderately higher when compared to ARBs Group. Previous studies have depicted that there is a positive relationship of HR with cfPWV.,, Notable changes in catecholamine levels of plasma were observed in CCB patients (amlodipine – 10 mg/day) in contrast with ARB patients (valsartan – 160 mg/day) as described by de Champlain et al. When patients were in standing position, marked variation was observed for the two therapy groups. Catecholamine's significant and supportive part was observed after renal denervation therapy in resistant HTN. Inactivation of nitric oxide and impaired endothelial vasomotion occurs due to the action of catecholamines., Previous studies have suggested that endothelium-derived nitric oxide is an evident mediator in the reduction of PWV., Marked variations were seen in endothelial functioning of HTN patients who were on valsartan 80–160 mg/day and amlodipine 5–10 mg/day therapies for a year, wherein amlodipine had no significant effect on endothelial functioning, while elevated flow-mediated dilation was due to valsartan effect.
This study had few limitations. Convenient sampling was used, and the sample was relatively small to produce the profound results. Moreover, it was a cross-sectional study conducted for a short period of time.
| Conclusions|| |
We conclude that central and peripheral arterial parameters followed similar trends in both the treatment groups. Vascular age and cardiovascular risk estimated from the calculated parameters indicated similar effects. The difference between actual age and vascular age is comparable in both the groups. Although both the drug classes had different mechanism of actions, their impact on HTN was comparable. The study concluded that both classes of drugs were found to be equally effective in reducing HTN. Further follow-up studies, especially prospective studies, will provide significant results with increased sample size and study duration.
The investigators acknowledge the support of staff from the Department of General Medicine and Department of Cardiology, Deccan College of Medical Sciences, and staff of Deccan School of Pharmacy for their efforts in the conduct of this study.
Financial support and sponsorship
The study was supported by the Indian Council of Medical Research (ICMR) (Crossref funder ID: http://dx.doi.org/10.13039/501100001411) through Extramural research grant (IRIS ID: 2012-0836). Received by the Principal investigator - Dr. Mohammed Abdul Hannan Hazari.
Conflicts of interest
KLR declares that he has no conflict of interest. MAHH has received research grants from Indian Council of Medical Research (ICMR) during the conduct of the study. BT declares that she has no conflict of interest. AAA declares that he has no conflict of interest. AM declares that she has no conflict of interest. AA AM declares that she has no conflict of interest. KP declares that she has no conflict of interest.
| References|| |
London GM, Asmar RG, O'Rourke MF, Safar ME; REASON Project Investigators. Mechanism(s) of selective systolic blood pressure reduction after a low-dose combination of perindopril/indapamide in hypertensive subjects: Comparison with atenolol. J Am Coll Cardiol 2004;43:92-9.
Agabiti-Rosei E, Mancia G, O'Rourke MF, Roman MJ, Safar ME, Smulyan H, et al.
Central blood pressure measurements and antihypertensive therapy: A consensus document. Hypertension 2007;50:154-60.
Jiang XJ, O'Rourke MF, Zhang YQ, He XY, Liu LS. Superior effect of an angiotensin-converting enzyme inhibitor over a diuretic for reducing aortic systolic pressure. J Hypertens 2007;25:1095-9.
Dhakam Z, McEniery CM, Yasmin, Cockcroft JR, Brown MJ, Wilkinson IB, et al.
Atenolol and eprosartan: Differential effects on central blood pressure and aortic pulse wave velocity. Am J Hypertens 2006;19:214-9.
Dhakam Z, Yasmin, McEniery CM, Burton T, Brown MJ, Wilkinson IB. A comparison of atenolol and nebivolol in isolated systolic hypertension. J Hypertens 2008;26:351-6.
Blacher J, Guerin AP, Pannier B, Marchais SJ, Safar ME, London GM. Impact of aortic stiffness on survival in end-stage renal disease. Circulation 1999;99:2434-9.
Laurent S, Cockcroft J, Van Bortel L, Boutouyrie P, Giannattasio C, Hayoz D, et al.
Expert consensus document on arterial stiffness: Methodological issues and clinical applications. Eur Heart J 2006;27:2588-605.
Lebrun CE, van der Schouw YT, Bak AA, de Jong FH, Pols HA, Grobbee DE, et al.
Arterial stiffness in postmenopausal women: Determinants of pulse wave velocity. J Hypertens 2002;20:2165-72.
Hendriks EJ, Westerink J, de Jong PA, de Borst GJ, Nathoe HM, Mali WP, et al.
Association of high ankle brachial index with incident cardiovascular disease and mortality in a high-risk population. Arterioscler Thromb Vasc Biol 2016;36:412-7.
Naidu MU, Reddy BM, Yashmaina S, Patnaik AN, Rani PU. Validity and reproducibility of arterial pulse wave velocity measurement using new device with oscillometric technique: A pilot study. Biomed Eng Online 2005;4:49.
Kahkashan N, Arifuddin MS, Hazari MA, Sultana S, Fatima F, Anees S. Variation in carotid-femoral pulse wave velocity, augmentation pressure and augmentation index during different phases of menstrual cycle. Ann Med Physiol 2018;2:27-32.
Nichols WW, O'Rourke MF. McDonald's Blood Flow in Arteries: Theoretical, Experimental and Clinical Principles. 5th
ed. London, United Kingdom: Arnold; 2005.
Matsui Y, Eguchi K, O'Rourke MF, Ishikawa J, Miyashita H, Shimada K, et al.
Differential effects between a calcium channel blocker and a diuretic when used in combination with angiotensin II receptor blocker on central aortic pressure in hypertensive patients. Hypertension 2009;54:716-23.
Oh GC, Lee HY, Chung WJ, Youn HJ, Cho EJ, Sung KC, et al.
Comparison of effects between calcium channel blocker and diuretics in combination with angiotensin II receptor blocker on 24-h central blood pressure and vascular hemodynamic parameters in hypertensive patients: Study design for a multicenter, double-blinded, active-controlled, phase 4, randomized trial. Clin Hypertens 2017;23:18.
Noll G, Wenzel RR, Shaw S, Lüscher TF. Calcium antagonists and sympathetic nerve activation: Are there differences between classes? J Hypertens Suppl 1998;16:S17-24.
de Champlain J, Karas M, Assouline L, Nadeau R, LeBlanc AR, Dubé B, et al.
Effects of valsartan or amlodipine alone or in combination on plasma catecholamine levels at rest and during standing in hypertensive patients. J Clin Hypertens (Greenwich) 2007;9:168-78.
Albaladejo P, Copie X, Boutouyrie P, Laloux B, Déclère AD, Smulyan H, et al.
Heart rate, arterial stiffness, and wave reflections in paced patients. Hypertension 2001;38:949-52.
Papaioannou TG, Protogerou A, Papamichael C, Mathioulakis D, Tsangaris S, Karatzis E, et al.
Experimental and clinical study of the combined effect of arterial stiffness and heart rate on pulse pressure: Differences between central and peripheral arteries. Clin Exp Pharmacol Physiol 2005;32:210-7.
Williams B, Lacy PS; CAFE and the ASCOT (Anglo-Scandinavian Cardiac Outcomes Trial) Investigators. Impact of heart rate on central aortic pressures and hemodynamics: Analysis from the CAFE (Conduit Artery Function Evaluation) study: CAFE-heart rate. J Am Coll Cardiol 2009;54:705-13.
Symplicity HTN-1 Investigators. Catheter-based renal sympathetic denervation for resistant hypertension: Durability of blood pressure reduction out to 24 months. Hypertension 2011;57:911-7.
Miyagawa K, Ohashi M, Yamashita S, Kojima M, Sato K, Ueda R, et al.
Increased oxidative stress impairs endothelial modulation of contractions in arteries from spontaneously hypertensive rats. J Hypertens 2007;25:415-21.
Spieker LE, Hürlimann D, Ruschitzka F, Corti R, Enseleit F, Shaw S, et al.
Mental stress induces prolonged endothelial dysfunction via endothelin-A receptors. Circulation 2002;105:2817-20.
Kinlay S, Creager MA, Fukumoto M, Hikita H, Fang JC, Selwyn AP, et al.
Endothelium-derived nitric oxide regulates arterial elasticity in human arteries in vivo
. Hypertension 2001;38:1049-53.
Hirooka Y, Kimura Y, Sagara Y, Ito K, Sunagawa K. Effects of valsartan or amlodipine on endothelial function and oxidative stress after one year follow-up in patients with essential hypertension. Clin Exp Hypertens 2008;30:267-76.
[Table 1], [Table 2], [Table 3], [Table 4]