Prevalence and Associated Factors of Resistant Hypertension among Patients with Chronic Kidney Disease: An Example from Cameroon

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In sub-Saharan Africa, data are scarce.Nansseu JRN, et al. in a systematic review found a prevalence of RAH of 12.1% in the general population [20].This prevalence was 12.8% in patients with CKD in Ghana [21].In Cameroon a study reported that only 23% of all individuals with HTN at the community level were aware of their status, only 46% of those aware were on treatment, among which only 25% achieved expected target BP levels [22].So BP control remains Background Hypertension (HTN) is a major public health problem around the world [1].One billion adults suffer from it, a figure which could reach 1.5 billion in 2025 [2,3].In 13.7% to 14.7% of cases blood pressure (BP) is not controlled despite adequate treatment [4,5].This uncontrolled BP may be pseudo-resistance to treatment or true resistant hypertension [6].Resistant arterial hypertension (RAH) is defined as uncontrolled BP despite the use of three classes of antihypertensive drugs, including at least one diuretic, or controlled BP under four or more antihypertensive drugs [7].The prevalence of RAH ranged from 12 to 19.7% in America [8,9], Spain [10] and in Asia [9].Factors such as, advanced age, obesity, longer duration of HTN, dyslipidemia, diabetes, cardiovascular disease and chronic

International Journal of Nephrology and Kidney Failure
Open Access Journal a challenge in large part due to inappropriate treatment.Moreover, HTN is the leading cause of CKD affecting 1 in 3 patients with CKD, and their coexistence is associated with increased cardiovascular morbidity and mortality [23].No study, to the best of our knowledge has looked at the prevalence and associated factors of RAH in patients with CKD in Cameroon.

Study setting and participants
We conducted a cross-sectional study, from 10 th December 2020 to 30 th May 2021 in the nephrology outpatient's unit of the Douala General Hospital (DGH), and the Douala Laquintinie hospital (DLH).These are the two main referral centers for patients with CKD in the Littoral region.The study was authorized by the General Manager of the DGH and the Director of the DLH.Ethical approval was obtained from the Douala University Ethics Committee n° 2584.
We included patients over 18 years of age, with HTN and CKD stage 2 to 5 not on dialysis (ND), and followed up for at least one month as outpatient at the nephrology unit of the two hospitals.We excluded those who refused to participate.Once their consent was obtained, we collected socio demographic and clinical data such as: age, sex, and major cardiovascular risk factor such as diabetes, dyslipidemia, obesity, smoking, history of cardiopathy, antihypertensive treatment, weight and height for the calculation of body mass index (BMI).BP was measured, using an OMRON® electronic blood pressure monitor only in patients on 3 class of antihypertensive drugs including at least one diuretic: (they were left to rest for 15 minutes, then we took their BP in both arms three times, with two minutes' intervals between each measurement).Those with office BP ≥ 140/90 mmhg, benefited from a home BP self-measurement over three days and the average of the 18 values was calculated and considered.

Definition of operational terms
Hypertension: was considered in any patient on antihypertensive treatment.
Resistant hypertension: was considered in any patient on 4 antihypertensive drugs including one diuretic or a patient on 3 antihypertensive drugs including one diuretic for one month who presented with office BP ≥ 140/90 mmhg and home BP ≥ 135/85 mmhg after home self-measurement.Chronic kidney disease: was defined and classified according to the KDIGO 2012 criteria [23].
Diabetes: was considered in a patient with a known history of diabetes or any patient on antidiabetic treatment.
Obesity: Body mass index greater than or equal to 30 kg/m² [24].

Statistical analysis
Data analysis was done using the statistical package software SPSS 25.0.Fischer exact and Chi-2 tests were used to assess the association between variables.Quantitative variables were expressed by mean (standard deviation), and qualitative ones by frequency and percentages.Logistic regression analysis was used to look for associated factors.A p value <0.05 was considered statistically significant.

Prevalence of RAH and characteristics of the study population
A total of 194 patients were included.The overall prevalence of RAH was 26.29% (51/194) (Figure 1).In our study population, 62.89% (122/194) were male.The mean age was 61.89 (13.13)

Discussion
The aim of this study was to determine the prevalence and associated factors of RAH in patients with CKD followed in nephrology consultations of two referral hospitals in Douala-Cameroon.Our study participants were more male (62.89%), their mean age was 61.89 (13.13) years and 34.54% had CKD stage 3a.The prevalence on RAH was 26.29%, and associated factors were age >60 years, CKD stage 5, presence of diabetes, dyslipidemia, obesity and smoking.Up to 62.89% of the participants were men.Our results are similar to most studies carried out in patients with CKD [15,25,26].Furthermore, the mean age was 61.89 years similar to that found by Thomas G, et [27,28].Age and male gender are known risk factors for CKD and Hypertension [29].
About 36.59%(71/194) had stage 4 and 5 of CKD.Oluyumbo R, et al. in Nigeria in 2017 found a prevalence which was high than ours 30.6% (grade 4) and 28.6% (grade 5) [30].This could be explained by the silent course of the disease and late referrals of patients with CKD in nephrology in our context [30,31].
The prevalence of RAH among patients with CKD varies between studies [7,15,25,32].We found a prevalence of 26.29% in the present study.Tanner et al. in USA, and De Nicola et al. in Italy found a similar prevalence of 30.5% and 22.9% respectively [15,33].However, studies in Spain and China reported lower prevalence of 13.3% and 11.1% respectively [7,32].This could be explained first by their larger sample size, the study population and the difference in treatment protocole: contrary to us they included only hypertensive patients with CKD stage 1 to 4 and it is known that RAH is most frequent in patients with CKD stage 5 [21,34].
In our study, the prevalence of RAH increased with the stage of CKD.It was 18.37%, for stage 3, 46.67%, for CKD stage 4 and 65.85% for stage 5.These results are similar to those found in the literature.In Switzerland in 2018, Viazzi F, et al. found similar results, 37.3% for stage 3 and 62.7% for stages 4 and 5 [35].Also, Ayisi-Boateng NK, et al. in Ghana in 2020 had prevalence of 15.8% for a GFR >60 ml/ min/m², 24.9% for a GFR between 45-59 ml/min/m², and 33.4% for a GFR <45ml/min/m² [21].Hypertension in CKD is caused either by an excess of intravascular volume or by excessive activation of the reninangiotensin-aldosterone system in relation to the state of sodium/ volume balance [36].Among these are increased activity of the sympathetic nervous system, increased endothelin production, decreased availability of endothelium-derived vasodilators/ endothelial dysfunction, structural changes of the arteries, renal ischemia [29,34].All these mechanisms increase with the stage of CKD making HTN more severe and difficult to control with the severity of CKD [34,36].

Figure 1 :
Figure 1: Prevalence of resistant arterial hypertension in the study population (N=194).

Table 2 :
Associated factors with resistant arterial hypertension in multivariate analysis.