INTRODUCTION Hypertension is more prevalent in patients with chronic kidney disease (CKD) and has a strong risk of cardiovascular disease. Elevated blood pressure leads to decline the kidney function in CKD patients. Therefore, treatment of hypertension plays a central role in the management of CKD. Hypertension accelerates vascular aging which leads to aortic stiffening. Increased arterial stiffness (pulse wave velocity [PWV]) is associated with increased systolic blood pressure (SBP). However antihypertensive drug has achieved better controlling effect on diastolic blood pressure (DBP) than SBP. PWV may remain same or not after the antihypertensive drug therapy, which directly implies SBP response to the treatment [1]. Antihypertensive regimens commonly include angiotensin- converting enzyme (ACE) inhibitor and angiotensin receptor blocker (ARB), calcium channel blocker (CCB), and beta blockers [2]. The mechanism of action of CCB, including amlodipine which inhibits N-type calcium channel and cilnidipine which inhibits both L and N-type calcium channels, in hypertension is due to its inhibition of calcium inux into vascular smooth muscle cells (VMC) that causes relaxation of VMC, decreased after load and systemic blood pressure. Both amlodipine and cilnidipine have signicant impact on blood pressure and arterial stiffness [3-5]. However, amlodipine associated with higher incidence of adverse events like pedal edema leads to discontinuing the treatment. Studies have reported the similar antihypertensive action between amlodipine and cilnidipine [6, 7]. However, cilnidipine is superior in terms of improving articial stiffness and central aortic pressure [8, 9] with greater antiproteinuric effect [10, 11]. There is still a scarcity of clinical trials comparing effects of amlodipine and cilnidipine on arterial stiffness and vascular aging in patients with CKD associated hypertension. Therefore, the present study aimed to assess and compare amlodipine with cilnidipine on hemodynamic parameters of central blood pressure and arterial stiffness in patients with CKD on dialysis and with associated hypertension. METHODS AND MATERIALS Study design: The present prospective study was conducted in the department of Nephrology of Grant Government Medical College and Sir J. J. Group of Hospitals, Mumbai, Maharashtra, India from October 2018 to October 2019. Patients of either sex with CKD on dialysis and with associated hypertension were included in the study. Patient with any known drug allergy, or with any history of systemic illness and presence of pre-existing edema, nephritic syndrome, anaemia was excluded from this study. Study procedure: The complete medical history and demographic details (age, sex, body mass index (BMI), BP) were collected for each patient. Central blood pressure (cBP) and AS were measured ®using the Mobil-O-Graph PWA (I.E.M. GmbH, Stolberg, Germany). A common cuff was centered on the left upper arm. Cuff size was chosen according to the circumference of the ®mid-upper arm. Mobil-O-Graph PWA provides information about peripheral BP, vascular age, augmentation index (AI) and PWV. Patients who were taking either amlodipine or cilnidipine were categorised into group 1 and group 2, respectively. BP and pulse rate value were analysed and the average value was recorded. Statistical analysis: Statistical analysis was performed using Statistical Package for the Social Sciences (SPSS) version 23.0. Analysis of categorical variables using Chi-square test and continuous variables using independent sample t-test was done for the assessment of the level of signicance. A P value <0.05 was considered statistically signicant. RESULTS A total of 87 patients were included and majority of patients were men (n=55). The demographics of enrolled patients are summarized in Table 1. COMPARISON OF HEMODYNAMIC AND VASCULAR PARAMETERS BETWEEN PATIENTS WITH CKD AND ASSOCIATED HYPERTENSION TREATED WITH AMLODIPINE AND CILNIDIPINE Original Research Paper Dr. Geeta Sheth* Associate Professor, Department of Nephrology, Grant Government Medical College and Sir J. J. Group of Hospitals, Mumbai, Maharashtra, India *Corresponding Author X 9GJRA - GLOBAL JOURNAL FOR RESEARCH ANALYSIS Nephrology Background: Hypertension is more prevalent in patients with chronic kidney disease (CKD) and has a strong risk of cardiovascular disease. This study was aimed to assess and compare amlodipine with cilnidipine on hemodynamic parameters of central blood pressure and arterial stiffness in patients with CKD on dialysis and with associated hypertension. Methods: This was a prospective study conducted between October 2018 and October 2019. Patients of either sex with CKD on dialysis and with associated hypertension and receiving either amlodipine or cilnidipine were included in the study. Mobil-O- ®Graph PWA was used assess peripheral BP, vascular age, augmentation index (AI) and pulse wave velocity (PWV). Results: A total of 87 patients were included (group 1, amlodipine, n=55; group 2, cilnidipine, n=22). The majority of patients were men (n=55). Proportion of patients with normal, average and abnormal vascular age and arterial stiffness was comparable between the treatment groups. However, in amlodipine group, frequency of patients with normal vascular age (42.2% vs 31.8%) was comparatively higher and frequency of patients with average vascular age (32.8% vs 40.9%) was comparatively lower, compared to cilnidipine group. Conclusion: Both amlodipine and cilnidipine showed equal efcacy on hemodynamic parameters of central blood pressure and arterial stiffness in studied population. ABSTRACT KEYWORDS : Augmentation index, blood pressure, cardiovascular, pulse wave VOLUME-9, ISSUE-1, JANUARY-2020 • PRINT ISSN No. 2277 - 8160 • DOI : 10.36106/gjra Dr. Shahid Ansari Senior Registrar, Department of Nephrology, Grant Government Medical College and Sir J.J. Group of Hospitals, Mumbai, Maharashtra, India 10 X GJRA - GLOBAL JOURNAL FOR RESEARCH ANALYSIS The patients were divided into group 1, patients treated with amlodipine (n=65) and group 2, patients treated with cilnidipine (n=22). Table 1: Demographic and clinical characteristics of participants The mean age of patients from group 1 was 53.66 years while the mean age of patients from group 2 was 50.36 years with male predominance in both the groups (60% vs 72.7%). Antihypertensive efcacy of amlodipine and cilnidipine drug therapy was found to be comparable (Figure 1). SBP, systolic blood pressure; DBP, diastolic blood pressure. Figure 1. Antihypertensive efcacy of amlodipine and cilnidipine treatment Proportion of patients with normal, average and abnormal vascular age was comparable between the treatment groups (P=0.675). However, in amlodipine group, frequency of patients with normal vascular age (42.2% vs 31.8%) was comparatively higher and frequency of patients with average vascular age (32.8% vs 40.9%) was comparatively lower, compared to cilnidipine group. Frequency of patients from both the treatment groups was similar when categorized according to small and large arterial stiffness (P = 0.945 and 0.850, respectively). Majority of patients had normal small arterial stiffness in both the groups while average and abnormal levels of large arterial stiffness were commonly observed in both the groups. Mean peripheral BP was comparable between both the groups. The average pulse pressure was slightly higher in patients from cilnidipine group than those from amlodipine group without any signicant difference (P=0.093). Augmentation index was comparatively higher in patients taking cilnidipine (P=0.411) compared to those taking amlodipine (P=0.411). Pulse wave velocity was similar between both the group (P=0.565) (Table 2). DISCUSSION This study assessed and compared vital hemodynamic parameters of central blood pressure and arterial stiffness measured by oscillometric methods in patients with CKD on dialysis and with associated hypertension treated with two types of calcium channel blockers; amlodipine, a L-type Ca channel blocker and cilnidipine, N/L-type Ca channel blocker. Overall observations demonstrated no signicant difference in any of the pulse wave analysis parameters between the two treatment groups indicating similar effect of L-type and N/L- type calcium channel blockers on these patients. To our knowledge, there is no similar study conducted to compare these observations with amlodipine and cilnidipine. However, several past studies have compared amlodipine with cilnidipine on antihypertensive efcacy and incidence of pedal edema in hypertensive individuals. Two studies from Southern part of India demonstrated equal efcacy of cilnidipine and amlodipine in reducing blood pressure in hypertensive individuals [6, 7]. However, cilnidipine being N-type and L-type calcium channel blocker, associated with lower incidence of pedal edema compared to only L-type channel blocked by amlodipine. Table 2: Comparison of parameters between the treatment groups There are few studies which reported cilnidipine is more effective than amlodipine at improving renal function and arterial stiffness [8] and albuminuria and uric acid metabolism [12] in patients with essential hypertension and in hypertensive patients with CKD, respectively. VOLUME-9, ISSUE-1, JANUARY-2020 • PRINT ISSN No. 2277 - 8160 • DOI : 10.36106/gjra Characteristics Total (N= 87) Age (years) 52.83 (12.64) Sex Male, n (%) 55 (63.20) Female, n (%) 32 (36.80) BMI (kg/m2) 22.72 (3.33) Peripheral BP (mmHg) Systole 128 (86-201) Diastole 86 (58-130) Pulse pressure (mmHg) 40 (19-79) Heart rate (bpm) 85.49 (17.30) Arterial BP (mmHg) 105 (76-159) Augmentation Index (%) 25.83 (11.25) Pulse wave velocity (m/s) 7.84 (1.65) Vascular age Normal 34 (39.5) Average 30 (34.9) Abnormal 22 (25.6) Central BP (mmHg) Systole 119.08 (16.89) Diastole 88 (59-132) Arterial stiffness Small arteries 26.19 (10.36) Large arteries 7.84 (1.65) Data shown as media (SD), unless otherwise specied. BMI, body mass index; BP, blood pressure Parameters Group 1 (n=65) Group 2 (n=22) P value Age 53.66 (12.24) 50.36 (13.77) 0.293 Sex, n (%) Male Female 39 (60) 26 (40) 16 (72.7) 6 (27.3) 0.319 BMI 22.44 (3.33) 23.55 (3.28) 0.177 Vascular age, n (%) Normal Average Abnormal 27 (42.2) 21 (32.8) 16 (25) 7 (31.8) 9 (40.9) 6 (27.3) 0.675 Small arterial stiffness, n (%) 37 (56.9) 23 (35.4) 5 (7.7) 13 (59.1) 7 (31.8) 2 (9.1) 0.945Normal Average Abnormal Large arterial stiffness, n (%) Normal 18 (27.7) 7 (31.8) Average 25 (38.5) 7 (31.8) 0.850 Abnormal 22 (33.8) 8 (36.4) Peripheral BP Systole Diastole 128.35 (20.81) 87.92 (14.15) 132.77 (15.50) 86.31 (10.20) 0.364 0.626 Pulse pressure 41.41 (12.49) 46.45 (10.39) 0.093 Heart rate 89.94 (17.11) 90.09 (17.42) 0.150 Arterial BP 106.32 (15.70) 107.63 (11.95) 0.721 Augmentation Index 25.24 (11.63) 27.54 (10.12) 0.411 Pulse wave velocity 7.88 (1.64) 7.70 (1.69) 0.656 Central BP Systole 118.68 (18.29) 120.27 (12.15) 0.704 Diastole 86.48 (25.50) 88.54 (10.52) 0.713 Data shown as mean (SD), unless otherwise specied. BMI, body mass index; BP, blood pressure Malleshappa P. revealed that urinary albumin excretion was signicantly reduced by administration of the cilnidipine in hypertensive CKD patients [13]. He also suggested that early treatment of cilnidipine in hypertensive CKD patients with low- grade albuminuria may prevent cardiovascular disease. A prospective randomized trial demonstrated by Zaman et al. compared the effects of amlodipine and cilnidipine on blood pressure, heart rate, proteinuria, and lipid prole in hypertensive patients [10]. Both the drugs showed signicantly reduced SBP and DBP. Unlike amlodipine, pulse rate and urinary protein excretion were decreased in cilnidipine group. Also, in cilnidipine group patients with diabetes showed reduce serum triglyceride. A multi-centre study at Japan demonstrated that cilnidipine had greater antiproteinuric effects than amlodipine when used in combination with a renin-angiotensin system (RAS) inhibitor to treat hypertensive patients [14]. Therefore, cilnidipine showed higher antioxidant activity than amlodipine when used in combination therapy. Similar study done by Fujita et al. showed superior effect of cilnidipine in preventing progression of proteinuria more potently than that with amlodipine in hypertensive CKD patients concomitantly with RAS therapy [11]. A randomized trial conducted in hypertensive patients with CKD reported reduction of ambulatory blood pressure and heart rate in the cilnidipine group compared with the control CCBs group. Furthermore, the results showed that cilnidipine is superior to the control CCBs in improving left ventricular hypertrophy [15]. One open labeled study evaluated the effects of amlodipine and cilnidipine on PWV and augmentation pressures in hypertensive patients [9]. Cilnidipine showed signicantly higher improvement in aortic blood pressure and aortic augmentation pressure as well as markers of arterial stiffness including PWV and augmentation index compared with amlodipine. However, this study showed that the cilnidipine has a similar antihypertensive action to the amlodipine, but is superior in terms of improving arterial stiffness and central aortic pressures. The present study assessed hemodynamic parameters of central blood pressure and arterial stiffness in CKD patients associated with hypertension using cilnidipine and amlodipine. However, there was no signicant difference in the markers of arterial stiffness and central blood pressure between both the groups. Both cilnidipine and amlodipine have shown similar effect in reducing blood pressure in patients with CKD and associated with hypertension. 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