|Year : 2017 | Volume
| Issue : 3 | Page : 131-136
Circadian blood pressure variation amongst people with chronic kidney diseases: A pilot study in Ibadan
Abiodun M Adeoye1, Yemi R Raji1, Adewole Adebiyi1, Bamidele O Tayo2, Babatunde L Salako1, Adesola Ogunniyi1, Akinlolu Ojo3, Richard Cooper2
1 Department of Medicine, University of Ibadan, Ibadan, Nigeria
2 Department of Public Health Sciences, Loyola University Chicago Stritch School of Medicine, Maywood, IL, USA
3 Department of Medicine, University of Arizona College of Medicine, Tucson, AZ, USA
|Date of Web Publication||30-Oct-2017|
Abiodun M Adeoye
Department of Medicine, College of Medicine, University of Ibadan, Ibadan
Source of Support: None, Conflict of Interest: None
Background: Circadian variation in blood pressure (BP) has been shown to determine cardiovascular events in people with chronic kidney diseases (CKDs). Studies aimed at elucidating the relationship between diurnal variation in BP and cardiovascular disease have yielded conflicting results, and very few of these studies have been conducted on CKD patients in Sub-Saharan Africa, hence the need for this study. Subjects and Methods: Eighty-five adult participants comprising 54 patients with CKD (36 males and 18 females) and 31 hypertensive patients (16 males and 15 females) free of CKD were recruited for 24 h ambulatory BP monitoring and cardiovascular risk factor assessment. Results: Patients with CKD had a higher mean clinic systolic BP (159.8 ± 28.6 vs. 147.9 ± 19.0 mmHg, P = 0.049) and reduced estimated glomerular filtration rate (19.2 ± 18.6 vs. 106.2 ± 30.6, P < 0.0001) when compared with hypertensives free of CKD. The mean 24 h ambulatory SBP (135.9 ± 28.5 vs. 120.3 ± 11.8 mmHg, P = 0.007), diastolic BP (82.6 ± 18.1 vs. 74.8 ± 9.0 mmHg, P = 0.034) and mean arterial pressure (100.9 ± 21.2 vs. 90.6 ± 10.2 mmHg, P = 0.018) were higher amongst CKD patients. Compared with hypertensive without CKD, daytime hypertension (58.9% vs. 21.4, P = 0.001), nocturnal hypertension (80.4% vs. 50.0%, P = 0.004) and non-dippers (92.0% vs. 73.1%, P = 0.026) were commoner in people with CKD. White coat effect was more common amongst hypertensives without CKD (74.2% vs. 38.0%, P = 0.002). The mean left atrial diameter and left ventricular mass index were higher in CKD group. Conclusion: This study highlights the high prevalence of varied phenotypes in circadian rhythm amongst CKD patients. Ambulatory blood pressure monitoring may be useful for early risk stratification of CKD patients. Large longitudinal study is needed to assess the prognostic implication of the findings.
Keywords: Ambulatory blood pressure phenotypes, chronic kidney diseases, left ventricular mass
|How to cite this article:|
Adeoye AM, Raji YR, Adebiyi A, Tayo BO, Salako BL, Ogunniyi A, Ojo A, Cooper R. Circadian blood pressure variation amongst people with chronic kidney diseases: A pilot study in Ibadan. Niger Postgrad Med J 2017;24:131-6
|How to cite this URL:|
Adeoye AM, Raji YR, Adebiyi A, Tayo BO, Salako BL, Ogunniyi A, Ojo A, Cooper R. Circadian blood pressure variation amongst people with chronic kidney diseases: A pilot study in Ibadan. Niger Postgrad Med J [serial online] 2017 [cited 2017 Dec 16];24:131-6. Available from: http://www.npmj.org/text.asp?2017/24/3/131/217404
| Introduction|| |
Chronic kidney disease (CKD) has now been recognised as a global health problem. Worldwide, the incidence of CKD is on the increase; substantial variation is observed amongst ethnic populations. Compared with persons of European descent, Afro-origin populations are prone to renal damage early in life and experience a more rapid course towards end-stage renal diseases (ESRDs). The prevalence of CKD in Africa ranges from 2% to 30.2% depending on the location and study design. In Nigeria, about 38 million people are estimated to be living with CKD. The burden of poverty, cardiovascular diseases (CVDs) and CKD have significantly increased morbidity and mortality in Nigeria. Although close to 90% of patients with CKD could not afford dialysis for more than 3 months in most Nigerian hospitals and mortality could be as high as 87% in most centres, few that could afford renal replacement therapy are still at higher risk of cardiovascular events.,
Hypertension is the most important modifiable risk factor that increases the risk for progression to (ESRD) in Nigeria; therefore, control of blood pressure (BP) could substantially reduce the risk of cardiovascular events and slow the decline of kidney function. While elevated clinic BP increases the risk of CKD, prior studies have shown that diurnal BP variations rather than a single measurement predict cardiovascular events better in people with CKD. Appropriately stratifying CKD patients based on diurnal BP variability can guide the dosing and timing of BP medications and perhaps leads to prevention and reduction of cardiovascular burden amongst patients with CKD.
Furthermore, left ventricular hypertrophy (LVH) is the most common target organ damage of hypertension. LVH frequently coexists with hypertension in patient with CKD and this association has been shown to potentiate the incidence of cardiovascular events. Interestingly, LVH is more prevalent and more severe in CKD than in hypertensive patients with normal renal function and predicts subsequent renal function deterioration in people of high cardiovascular risk.,,
Based on the foregoing, there is the need for early detection of modifiable risk factors that predict morbidity and mortality in people with CKD. In Sub-Saharan Africa, little is known about diurnal BP variation amongst CKD patients and there is a large knowledge gap on evidence that comprehensively looks at the left ventricular (LV) function and BP variations in the African population with CKD. In this study, we determined the pattern of diurnal BP variation, LVH and their impact on CVD burden amongst CKD patients with a view to determining the feasibility of a large prospective study that will help in appropriate risk stratification and guide prompt institution of suitable interventions amongst cohorts with CKD.
| Subjects and Methods|| |
This prospective and comparative study was conducted over a period of 6 months from December 2015 to May 2016 following approval by the Joint University of Ibadan (UI)/University College Hospital (UCH) Ethics Committee approval reference number UI/EC/15/0254 dated 23rd November, 2015. Using a prevalence of 33% CVD in CKD  and a study powered at 80% to detect a difference of 10% in the prevalence of cardiovascular events and death amongst CKD cases and controls, the estimated number of participants for the main study is a minimum of 300 participants per group. For this pilot study, 18% of the estimated number of participants for the proposed main study were recruited.
A total of 85 participants comprising 54 patients with CKD and 31 hypertensive patients free of CKD were recruited over 6 months from the Medical Outpatient Department and Owena dialysis unit of the UCH, Ibadan. Using Modification of Diet in Renal Disease 4-variable equation, CKD was defined as estimated glomerular filtration rate (eGFR) <60 ml/min/1.73 m 2. Pre-tested questionnaires were administered on all the participants to obtain information on demographics, aetiology and stages of CKD, duration of disease, onset of dialysis and dialysis vintage, kidney transplantation, lifestyle and medication history. Contact information of the participants and their next of kin was obtained for communication on follow-up. Clinic (office) BP was measured using a standard Omron (HEM711DLX) BP apparatus on the left arm placed at heart level after 5 min rest and using a cuff of appropriate size with the participant in the sitting position and legs uncrossed. Three BP measurements were obtained with a minimum interval of 1 min and average of the last two measurements was used in the present analysis.
All the participants had a 24 h ambulatory BP monitoring done using SpaceLabs ambulatory blood pressure monitoring (ABPM) (SpaceLabs Healthcare, Issaquah, WA, USA) which was placed on the non-dominant arm. Cuff sizes were selected after measuring participants' non-dominant arm circumference. The machine was programmed to read half hourly from 7 am to 10 pm and hourly from 10 pm to 7 am. Measurements were done during week days to allow participants return to the hospital after 24 h for disconnection of the ABPM monitoring machine. Patients were encouraged to proceed with their routine daily activities but to avoid vigorous physical activities and keep motionless at the time of measurement. After 24 h of monitoring, participants returned to our centre to have the device removed. For an ABPM measurement to be considered complete, a participant was required to have at least 10 daytime and 5 night-time SBP and diastolic BP (DBP) measurements.
Anthropometric measurements including height, weight, waist and arm circumferences were obtained. Height was measured without shoes to the nearest centimetre using a ruler attached to the wall, whereas weight was measured to the nearest 0.1 kg on an electronic scale with the participant wearing light outdoor clothing and no shoes. Waist circumference was measured at the narrowest part of the participant's torso (or the minimum circumference between the rib cage and the iliac crest) using an anthropometric measuring tape. The measurement was taken at the end of expiration. Average of three measured waist circumferences recorded to the nearest tenth of a centimetre was obtained for analysis.
Obesity was classified based on body mass index (BMI) in kg/m 2 as normal (>20 and <25), overweight (>25 and <30), obesity (>30 and <35) and severe obesity (≥35). Abdominal obesity was defined as waist circumference of ≥102 cm in men and ≥88 cm in women. Participants were further categorised as normal risk (men <94 cm; women <80 cm), increased risk (men 94–102 cm; women80–88 cm), or substantially increased risk (men >102 cm; women >88 cm) on the basis of the World Health Organization's standards for increased health risk associated with waist circumference.,
Hypertension was defined as systolic BP (SBP) ≥140 mmHg and/or DBP ≥90 mmHg or being on antihypertensive treatment. Using clinic/office BP and ABPM, we evaluated three phenotype domains: elevated mean clinic and/or daytime BP, diurnal BP patterns and a disparity between clinic hypertension and out-of-clinic hypertension. Elevated clinic BP was defined as mean clinic SBP ≥140 mmHg or DBP ≥90 mmHg; elevated daytime BP as mean daytime SBP ≥135 mmHg or DBP ≥85 mmHg and elevated night-time BP as mean night-time SBP ≥120 mmHg or DBP ≥70 mmHg. Diurnal BP patterns included nocturnal hypertension, isolated nocturnal hypertension and a non-dipping BP pattern. Mismatches between clinical hypertension and out-of-clinic hypertension included white coat hypertension, masked hypertension and masked isolated nocturnal hypertension.
Echocardiographic examination was performed with the participants in partial left lateral decubitus position using a Toshiba Xario (Toshiba Medical Systems Corp) with a 3.5 MHz transducer. Two-dimensional-guided M-Mode measurements were obtained as recommended by the American Society of Echocardiography. LV, septal, posterior wall thickness and cavity dimensions were measured using leading edge convention at both end-diastole and end-systole. LV mass (LVM) was calculated using the formula of Devereux et al. This has been shown to yield LVM closely related to autopsy measurements (r = 0.90) and has good interobserver reproducibility (ρ=0.93) in one study. LV mass was indexed by body surface area and LV hypertrophy was considered present if the LV mass index (LVMI) is ≥115 g/m 2 in males and ≥95 g/m 2 in females. Relative wall thickness (RWT) was calculated as two posterior wall thickness diastole/LV internal diameter diastole. Increased wall thickness was present when RWT >0.43. LV geometry was stratified using LVMI and RWT. Normal geometry – normal LVMI and RWT, concentric remodeling – normal LVMI and increased RWT, eccentric hypertrophy – increased LVMI and RWT <0.43 and concentric hypertrophy – increased LVMI and RWT ≥0.43. Ejection fraction was calculated using the formula of Teichholz.
Inclusion and exclusion criteria
Participants aged 18 years and above with at least Stage II CKD who consented were recruited. Consenting and age-matched hypertensives were recruited as control. Individuals who were <18 years, had kidney transplantation, or refused consent on both arms of the study were excluded from the study.
Data were analysed using the Statistical Package for the Social Sciences for Windows version 22.0 (IBM, Armonk, NY, USA). Estimates were expressed as either mean values (±standard deviation) for continuous variables or proportions (percentage) for categorical variables. Comparison for statistical significance was by independent Student's t-test for continuous variables or Chi-square for categorical variables. The level of significance was set at P ≤ 0.05.
| Results|| |
[Table 1] summarises the baseline characteristics of the participants. The mean age was 52.5 ± 17.4 years. CKD patients had a higher mean clinic SBP (159.8 ± 28.6 vs. 147.9 ± 19.0 mmHg, P = 0.049), serum creatinine (9.12 ± 8.03 vs. 0.94 ± 0.24 mg/dl, P < 0.0001) and lower eGFR (19.2 ± 18.6 vs. 106.2 ± 30.6 ml/min/1.73 m 2, P < 0.0001) compared with hypertensives free of CKD. Mean age and BMI were comparable across groups. As shown in [Table 2] and [Figure 1], mean full-time, daytime and night-time ambulatory SBP, DBP and mean arterial pressure were higher amongst CKD patients. Compared with controls, daytime hypertension (58.9% vs. 21.4, P = 0.001), nocturnal hypertension (80.4% vs. 50.0%, P = 0.004), masked hypertension and non-dippers (92.0% vs. 73.1%, P = 0.026) were more common in people with CKD. White coat effect more common amongst hypertensive without CKD (74.2% vs. 38.0%, P = 0.002). The mean LVMI and left atrial diameter were higher in CKD compared with control [Table 3]. Similarly, 61.9% and 57% of the participants had increased RWT and LVH, respectively.
|Figure 1: Twenty-four hour blood pressure parameters in the study groups|
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|Table 2: Comparisons of blood pressure variations between chronic kidney diseases participants and hypertensives free of chronic kidney disease|
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|Table 3: Comparisons of echocardiographic parameters between chronic kidney diseases participants and hypertensives free of chronic kidney disease|
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| Discussion|| |
In the current study, compared with controls, four out of five CKD patients had nocturnal hypertension and were non-dippers; 62% had isolated nocturnal hypertension and a third had white coat effects. Participants with CKD had higher mean clinic SBP, ambulatory full time systolic and DBP and LVMI.
Circadian BP variations amongst people with CKD have been associated with major cardiovascular events and progression of renal insufficiency. Studies differ on the prevalence of circadian BP variations. The frequencies of nocturnal hypertension and non-dippers in our study sample were far higher than reported by Nakai et al.; in that report, 45% of participants were non-dippers, whereas Wang et al. reported a frequency of 21% isolated nocturnal hypertension. Wang et al. further found that kidney survival rates were significantly worse amongst those with poor dipping status and isolated hypertension. The discrepancies in the findings may be explained by age; our participants were older than their cohort, mean age 52 year versus 44 years in study by Wang et al. Furthermore, the threshold for definition of hypertension in ABPM for native Africans has yet to be defined. Study has shown that threshold for African-Americans is higher than those for Caucasians which will lower the prevalence of various ABPM phenotypes. Despite these possible explanations for discrepancies, our findings have shown that CKD patients were potential candidates for major cardiovascular events.
LVH, a synonym of increased LV mass, is an independent risk factor for sudden cardiac death. In this study, the mean LV mass and frequency of LVH were higher amongst the people with CKD. Similar to our finding, Paoletti et al. found high LVH in CKD, especially those non-dialysed and that independent LV geometry, LVH is a strong predictor of the risk of poor CV and renal outcomes.
In Framingham study, after multivariable adjustment, left atrial enlargement remained a significant predictor of stroke in men and death in both sexes. The relation of LA enlargement to stroke and death appears to be partially mediated by LV mass., In our study, left atrial enlargement coexisted with increased LV mass which may potentiate the risk of major cardiovascular events amongst people with CKD. Whether the increased LV mass mediated the left atrial enlargement was not the objective of the study.
From the foregoing, the reasons for high mortality in our patients with CKD may be more than late presentation to the hospital and dialysis vintage but also lack of appropriate assessment of ABPM BP phenotypes and early identification of those at risk of sudden cardiac death.
There are several strengths of the current pilot study. It is feasible in our community to execute studies on ABPM without altering the daily activities of the participants. Our study appears to be the first of its kind in Nigeria, a representative of native black-African population to comprehensively look at the ambulatory BP phenotypes and LV mass and functions in patients with CKD. Furthermore, this study has objectively shown a clear indication for chronotherapy. Previous studies on the participant were done on hypertensives based on clinic BP measurements.
However, the small, non-random sample size and cross-sectional study design are clear limitations to generalizability and causal effect of our findings. Despite this, our sample size is sufficient for a pilot study and the findings have shown a clear feasibility of large-scale longitudinal studies on people with CKD. In addition, our findings compared well with a large cohort from Hygia project.
| Conclusion|| |
This study highlights the high prevalence of ABPM phenotypes amongst individuals with CKD. Nocturnal hypertension and increased LV mass were prominent amongst patients with CKD. There is a need for larger longitudinal studies to assess the prognostic implications of our findings for risk stratification and possibly determine the effectiveness of chronotherapy amongst native African population.
I want to appreciate Dr. Temitope Bello, Dr. Oladimeji Adebayo, Miss. Aderonmu Olajumoke and Mr. Mayowa Olatedun, for their roles in the collection and entry data from the participants. Our appreciation also goes to all the participants for their cooperation in making this pilot study a success.
Financial support and sponsorship
This work was supported by the National Institutes of Health grant from the NIDDK (K24 DK062234) to Akinlolu Ojo.
Conflicts of interest
There are no conflicts of interest.
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[Table 1], [Table 2], [Table 3]