Ambulatory Blood Pressure Monitoring in the Diagnosis and Management of Arterial Hypertension in Current Medical Practice in Algeria

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Current Hypertension Reviews, 2021, 17, 75-82

RESEARCH ARTICLE

ISSN: 1573-4021 eISSN: 1875-6506

Ambulatory Blood Pressure Monitoring in the Diagnosis and Management of Arterial Hypertension in Current Medical Practice in Algeria

BENTHAM SCIENCE

Naima Hammoudi-Bendib1, Leila Manamani2, Souhila Ouabdesselam3, Dalila S. Ouamer3, Sofiane Ghemri1, Laurene Courouve4, Amine Cherif 5, Lamine Mahi6,* and Salim Benkhedda3

1EHS Dr Maouche (CNMS), Algiers, Algeria; 2CHU Ibn Sina, Annaba, Algeria; 3Cardiology Division, Mustapha Hospital Cardiology Oncology Collaborative Research Group (COCRG), Benyoucef Benkhedda University, Algiers, Algeria; 4CEMKA-EVAL, Bourg-la-Reine, France; 5MERINAL Laboratories, Algiers, Algeria; 6AXELYS SANTE DZ, Algiers, Algeria

Abstract: Objective: There are limited data on the management of hypertension (HT) in Algeria. The aim of this study was to assess, in current medical practice, the use and benefits of ambulatory blood pressure monitoring (ABPM) for the diagnosis and management of HT. Methods: A prospective, observational, multicenter study was performed in 2017. Patients aged ≥ 18 years with suspected or treated HT were included. A 24-hour ABPM was performed at baseline A R T I C L E H I S T O R Y in all patients. Therapeutic decision was taken by the physician according to ABPM results and patients were then followed up to 6 weeks.

Received: December 11, 2019 Results: The analysis included 1027 patients (mean age, 51.0 years; women, 61.6%) with treated Revised: February 26, 2020 Accepted: March 03, 2020 HT (37.3%) or suspected HT (62.7%). Major cardiovascular risk factors were diabetes (15.7%) and lipid disorders (7.2%). ABPM was pathological in 55.1% of patients on antihypertensive treatment DOI: and in 60.8% of patients with suspected HT. A therapeutic adjustment or a treatment switch was 10.2174/1573402116666200324144223 performed after pathological ABPM in 37.4% of patients already on antihypertensive treatment and an antihypertensive therapy was initiated in 54.9% of patients with initially suspected HT. Conclusion: This study is the first evaluation of the usefulness of ABPM for the management of HT in Algeria. Our results emphasize that ABPM is a highly valuable method for avoiding the white- coat effect and for detecting patients who are insufficiently treated with antihypertensive drugs. Keywords: Arterial hypertension, ambulatory blood pressure monitoring, office blood pressure, antihypertensive treatment, white coat effect, antihypertensive drugs.

1. INTRODUCTION remain insufficient: 29% in 1999-2000 and 37% in 2003- 2004 in the United States [8]; 37% in 2005-2011 in Italy [9]; The prevalence of arterial hypertension (HT) is 30-40% 38% in 2002 and 50% in 2007 and 2012 in France [10]. In in Algeria [1-3]. In the TAHINA study, the prevalence of HT Algeria, the PACT study performed in 2007 showed that was 23.5% and 34.2% in the age classes 55-59 years and 60- only 23.7% of hypertensive patients were controlled [11]. 64 years, respectively [3]. In Europe, comparable rates of prevalence (30-45%) were reported in 2013 [4]. High blood The definition of the control of BP varies in international pressure (BP) is the main risk factor for cardiovascular dis- guidelines. In the United Kingdom, the objective is treating ease and premature death worldwide [5]. The relationship hypertensive persons aged 60 years or older to a BP < between high BP and fatal coronary artery disease and fatal 150/90 mmHg and hypertensive persons 30-59 years of age stroke is now well established [6]. The increased cardiovas- to a BP < 140/90 mmHg [12]. The European guidelines for cular risk in patients with high BP can be reduced with early the management of HT recommend for diagnosis of HT a diagnosis and antihypertensive treatment [7]. unified BP target < 140/90 mmHg [7]. BP is usually controlled at the doctor’s office but self-monitoring is recom- Hypertension is a chronic condition which is clinically mended to assess the efficacy of antihypertensive treatment silent and the rates of well-controlled hypertensive patients and the achievement of the therapeutic target [13].

BP follows a circadian pattern during the daytime hours

*Address correspondence to this author at the Axelys Santé DZ, 16 Rue des and is minimal after midnight. Moreover, the measurement Pins-16035 Hydra, Algiers, Algeria; E-mail: [email protected] of BP in the physician’s office may induce a transient rise in

BP (“white coat effect”) [14]. Many studies have shown that tion of antihypertensive treatment, no treatment because HT the correlation of end-organ damages associated with hyper- not confirmed, treatment modification or other decision. tension (e.g., left ventricular hypertrophy, proteinuria, serum The secondary endpoints were sociodemographic charac- creatinine, vascular damages) was higher using ambulatory teristics of patients, indications for ABPM (diagnostic aim or blood pressure monitoring (ABPM) compared to office BP therapeutic aim), comorbidities and cardiovascular risk fac- measurement [14]. Therefore, the use of ABPM is recom- tors, ABPM outcomes (daytime and nocturnal), antihyper- mended for HT diagnosis and more particularly in the fol- tensive treatments, treatment modifications after ABPM and lowing situations: suspected “white coat” HT, excessive BP after 6 weeks of follow-up, rates of BP self-monitoring and variability during the same visit or at different visits, suspi- treatment observance (as defined by the Compliance Evalua- cion of hypotensive episodes or suspicion of resistance to tion Test of Girerd et al. [22]). antihypertensive drug treatment [15-21]. It was calculated that the description of the primary end- The objective of this study was to evaluate, in current points with sufficient precision (3%) required sample size of medical practice, the use and benefit of ABPM in the man- at least 966 patients. With a percentage of incomplete or agement of HT in Algeria, both in public and private cardi- unusable data around 10%, a sample size of 1062 patients ology settings. was necessary. It was planned to select 100 centers which included a maximum of 20 patients. 2. MATERIALS AND METHODS Categorical variables were compared by Chi-square test 2.1. Study Design and Patients or Fisher’s exact test and continuous variables by Student’s This was a prospective, observational, national and mul- t-test or Wilcoxon test. Tests were two-sided and a p-value ticentric study performed in public and private settings in lower than 0.05 was considered to be statistically significant. Algeria from February to August 2017. 3. RESULTS Centers were selected with a concern for representativity from a database of cardiologists who practiced in private 3.1. Patient Characteristics offices or in university hospitals. The 69 centers which recruited patients were distributed Patients aged ≥ 18 years who were either hypertensive on the national territory and were representative of the Alge- (defined as office SBP ≥ 140 mmHg or DBP ≥ 90 mmHg) or rian facilities that offer health care services in cardiology. referred for suspected hypertension were included. Patients Thus, among the 48 wilayas (provinces) that divide Algeria, were not included if they had a contraindication to ABPM, 32 of them had at least one study center (Ain Defla, Ain psychiatric disorders or unable to follow the protocol. In Témouchent, Alger, Annaba, Bordj Bou-Arreridj, Béjaïa, order to avoid biases, patients were included consecutively in Blida, Batna, Bouira, Boumerdes, Chlef, Constantine, Djelfa, each center. El Tarf, Guelma, Ghardaïa, Jijel, Mascara, Médéa, Mosta- A 24-hour ABPM was performed at inclusion (visit V1 at ganem, M’Sila, Naama, Oran, Oum El Bouaghi, Sétif, Sidi Bel Abbes, Skikda, Tiaret, Tipaza, Tissemsilt, Tizi Ouzou, Day 0) in all patients. According to the recommendations of Tlemcen). the European Society of Cardiology (ESC) and the European Society of Hypertension (ESH), the diagnostic threshold for The population analysis included 1027 patients with a hypertension is ≥ 130/80 mmHg over 24 h, ≥ 135/85 mmHg majority of women (61.6%) (Table 1). For 383 (37.3%) pa- for the daytime average and ≥ 120/70 mmHg for the night- tients, ABPM was performed with therapeutic aim (treated time average [7]. Patients were considered as “dippers” if HT patients) and for 644 (62.7%) with diagnostic aim (sus- their nocturnal BP falls by >10% of the daytime average BP pected HT). In treated HT patients, the mean (SD) duration value. from diagnosis was 6.6 (6.9) years. Patients with suspected Therapeutic decision was taken by the physician accord- HT were significantly younger than patients with treated HT ing to ABPM results (visit V2 on Day 1). Treated patients (47.7 vs. 56.6 years; p < 0.001). The main comorbidities were then followed up to 6 weeks (visit V3). were diabetes (15.7%) and lipid disorders (7.2%). Mean (SD) office systolic blood pressure (SBP) was 2.2. Study Objectives 145.8 (21.7) and 146.4 (18.1) mmHg in treated and sus- The primary objective was to evaluate, in current medical pected HT patients (p >0.1) and mean (SD) office diastolic practice, the use and benefits of ABPM in the diagnosis and blood pressure (DBP) was 86.2 (11.5) and 87.8 (11.2) management of HT in Algeria. The secondary objectives mmHg (p = 0.042), respectively (Table 1). Office BP pres- were to describe conditions for using ABPM, socio- sure was elevated (SBP ≥ 140 and DBP ≥ 90 mmHg) at in- demographic characteristics of patients, therapeutic strate- clusion visit in 68.7% of patients with treated HT and in gies and hypertensive drug prescribed and BP values with 78.5% of patients with suspected HT. ABPM. At inclusion visit, patients with treated HT received mainly monotherapy (44.5%) and dual therapy (34.6%). The 2.3. Statistical Analysis most frequent antihypertensive classes were angiotensin re- No formal statistical hypothesis was tested, and the statis- ceptor blockers (46.7% of patients), calcium antagonists tical analysis was essentially descriptive. The primary end- (39.7%), thiazide diuretics (34.5%), angiotensin-converting point assessed the medical decision after ABPM: prescrip- enzyme inhibitors (27.2%) and beta-blockers (26.9%). Ambulatory Blood Pressure Monitoring in Algeria Current Hypertension Reviews, 2021, Vol. 17, No. 1 77

Table 1. Patient characteristics at inclusion visit.

ABPM with Therapeutic ABPM with Diagnostic Overall Population - P-value Aim (n = 383) Aim (n = 644) (n = 1027)

Women, n (%) 223 (58.2) 410 (63.7) 633 (61.6) 0.08

Age (years), mean (SD) 56.6 (13.0) 47.7 (12.7) 51.0 (13.5) <0.001

Age classes (years), n (%) - - - -

18-29 9 (2.3) 51 (7.9) 60 (5.9) <0.001

30-59 210 (54.8) 477 (74.3) 687 (67.0) -

≥ 60 164 (42.8) 114 (17.8) 278 (27.1) -

Missing 0 2 2 -

BMI (kg/m2) - - - -

Mean (SD) 28.6 (4.4) 28.2 (4.4) 28.3 (4.4) >0.1

> 30 (obesity), n (%) 123 (44.7) 170 (27.0) 293 (29.2) -

Missing 34 62 96 -

Smoking, n (%) 22 (5.9) 41 (6.5) 63 (6.3) >0.1

Missing 8 14 22 -

Diabetes, n (%) 107 (27.9) 54 (8.4) 161 (15.7) <0.001

Lipid disorders, n (%) 49 (12.8) 25 (3.9) 74 (7.2) <0.001

Pregnancy, n (%) 22 (5.7) 24 (3.7) 46 (4.5) >0.1

Myocardial Infarction, n (%) 8 (2.2) 3 (1.1) 11 (1.7) >0.1

Missing 11 367 378 -

Office BP (mmHg) - - - -

SBP, mean (SD) 145.8 (21.7) 146.4 (18.1) 146.2 (19.5) >0.1

DBP, mean (SD) 86.2 (11.5) 87.8 (11.2) 87.2 (11.3) 0.042

SBP ≥ 140 and DBP ≥ 90, n (%) 244 (68.7) 479 (78.5) 723 (74.9) <0.001

Missing 28 34 62 -

Heart rate (bpm), mean (SD) 77.0 (11.0) 80.8 (11.7) 79.4 (11.6) <0.001

Missing 53 82 135 -

Abbreviations: BMI, body mass index; BP, blood pressure; bpm, beats per min, DBP, diastolic blood pressure; SBP, systolic blood pressure.

3.2. 24-h ABPM Outcomes and Therapeutic Strategies in 69.3% of patients with newly diagnosed HT (Fig. 1). Anti- hypertensive treatments consisted of angiotensin receptor Daytime ABPM was pathological in 55.1% of patients blockers (55.3%), calcium inhibitors (44.7%) and thiazide with treated HT and in 60.8% of patients with suspected HT diuretics (44.2%) in patients already treated for HT. Patients (p = 0.08) (Table 2). According to nocturnal ABPM, non- previously suspected for HT were prescribed angiotensin re- dipper patients were 38.2% and 40.7%, respectively. ceptor blockers (50.0%) and ACE inhibitors (28.4%) (Fig. 2). Antihypertensive therapy was initiated at visit V2 after Comparable findings were observed 6 weeks after 24-h ABPM in 54.9% of patients with suspected HT; in pa- ABPM. Indeed, antihypertensive treatment was continued in tients with known HT at inclusion, antihypertensive treat- 85.0% of all patients of the overall population and was ment was continued in 60.5% of them and was changed changed in 13.8% of patients (Table 2). When treatment was (dose adjustment or switch) in 37.4% (Table 2). Therapeutic changed at 6 weeks in patients treated at inclusion (n=38 strategy was based on monotherapy regimen in 35.8% of patients), thiazide diuretics were more frequently prescribed patients who benefited from ABPM with therapeutic aim and (39.5%); for patients suspected of hypertension at inclusion 78 Current Hypertension Reviews, 2021, Vol. 17, No. 1 Hammoudi-Bendib et al.

Table 2. ABPM outcomes and medical decisions.

ABPM with Therapeutic ABPM with Diagnostic Overall Population P-value Aim (n = 383) Aim (n = 644) (n = 1027)

Daytime ABPM, n (%) - - - -

Normal 167 (44.9) 245 (39.2) 412 (41.3) 0.08

Pathological 205 (55.1) 380 (60.8) 585 (58.7) -

Missing 1 0 1 -

Nocturnal ABPM, n (%) - - - -

Dipper 225 (61.8) 365 (59.3) 590 (60.3) >0.1

Non-dipper 139 (38.2) 250 (40.7) 389 (39.7) -

Missing 9 10 19 -

Medical decision at V2, n (%) - - - -

Treatment initiation 4 (1.0) 351 (54.9) 355 (34.8) <0.001

Treatment continuation 231 (60.5) 0 231 (22.6) -

Treatment change 143 (37.4) 0 143 (14.0) -

No treatment 4 (1.0) 288 (45.1) 292 (28.6) -

Missing 0 5 5 -

Medical decision at V3, n (%)a - - - -

Treatment continuation 265 (87.5) 263 (82.7) 528 (85.0) 0.015

Treatment change 38 (12.5) 48 (15.1) 86 (13.8) -

No treatment 0 7 (2.2) 7 (1.1) -

Missing 0 12 12 -

Note: aFor patients with V3 visit (n=303 and n=330, respectively).

(n=48 patients), changes led mainly to the prescription of ABPM was pathological in 55.1% of treated hypertensive angiotensin receptor blockers (45.8%). patients and there was a new diagnosis of HT in 60.8% of patients with suspicion of HT. ABPM is considered by inter- Self-monitoring of BP was reported for 3.1% national guidelines as the most accurate method for confirm- (n=32/1026) of patients attending visit V2 and 22.7% ing a diagnosis of hypertension [7, 24]. Guidelines from the (n=144/633) in patients attending Visit V3. European Society of Cardiology (ESC)/European Society of Patients who attended visit V3 and completed observance Hypertension (ESH) recommend to base the diagnosis of questionnaire (n=277; 43.8%) were classified as “good com- hypertension on repeated office BP measurements or out-of- pliant” (49.6%), “minor noncompliant” (41.6%) and “non- office BP measurement with ABPM and/or home blood compliant” (8.8%) according to Compliance Evaluation Test. pressure monitoring in order to detect white-coat and masked hypertension and monitor BP control [7]. In our cohort, 4. DISCUSSION 68.7% of patients with treated HT and 78.5% of patients with suspected HT had abnormal office BP pressure at inclu- This national observational study assessed the modalities of use and benefits of 24-h ABPM for the diagnosis and sion. However, only 55.1% and 60.8% of patients had daytime ABPM that was considered to be pathological, respec- management of HT in Algerian cardiology settings. In this tively. These results highlight the dual interest of ABPM: cohort, the mean age was 51.0 years and there was a majority first, ABPM allows transforming a suspicion of HT into a of women. As expected, patients were younger when HT was firm diagnosis; second, it allows not treating people who do suspected and older when HT was already treated. Diabetes not have true hypertension [24]. and lipid disorders were the main factors of cardiovascular risks. These characteristics are consistent with a study per- The high rate of uncontrolled treated patients is not spe- formed in 2017 on 3622 patients in the area of Blida (North cific to the Algerian population or to our cohort and is re- of Algeria) [23]. ported in many studies [8-11]. The efficacy of antihyperten- Ambulatory Blood Pressure Monitoring in Algeria Current Hypertension Reviews, 2021, Vol. 17, No. 1 79

A. ABPM with therapeutic aim (n=383) 50 44.5 45.5 45 42.4

40 36.9 35.8 34.6 35

25 Patients (%)

20 17.5

13.4 15 12.1

10 8.6 6.7 5 1.1 000.8 0 Monotherapy 2 drugs 3 drugs 4 drugs 5 drugs

Treatment at V1 (n=383) With treatment at V2 (n=371) Change at V3 (n=38)

B. ABPM with diagnostic aim (n=644)

80 69.3 70

60 55.3

38.3 40 Patients (%)

30 25.6

6.4 10 4.6 0.6 0 0 Monotherapy 2 drugs 3 drugs 4 drugs

With treatment at V2 (n=348) Change at V3 (n=48)

Fig. (1). Therapeutic strategies before and after ABPM according to (A) therapeutic or (B) diagnostic aim. (A higher resolution / colour version of this figure is available in the electronic copy of the article). sive treatment is dependent on both compliance to treatment cardiovascular mortality, silent cerebrovascular damage, and therapeutic strategy. Thus, Bramley et al. reported that progression of renal damage cardiovascular risk and this among HT patients treated with monotherapy or fixed-dose parameter has to be considered in cardiovascular risk stratifi- combination therapy, only 43% with high treatment compli- cation [14]. However, the classification of patients as dippers ance achieved BP control compared with 34% and 33% with or non-dippers should be cautious after a unique 24-h ABPM medium and low treatment compliance, respectively [25]. because this status varies frequently from day to day and therefore is considered to be poorly reproducible over time Nocturnal records of ABPM reported a high rate of non- [27]. dipper patients both in patients with treated HT (38.2%) and in patients with suspected HT (40.7%). These rates are com- The main therapeutic strategy after ABPM was mainly parable to those reported in other studies including patients based on monotherapy for patients with suspicion of HT and with essential hypertension [26]. Non-dipper patients are bitherapy or monotherapy for patients already treated for HT. considered at increased risk for left ventricular hypertrophy, The use of monotherapy in newly diagnosed patients is con- 80 Current Hypertension Reviews, 2021, Vol. 17, No. 1 Hammoudi-Bendib et al. A. ABPM with therapeutic aim (n=383)

60 55.3

50 46.7 44.2 44.7

39.5 39.7 40 34.5 31.6 27.0 27.2 28.9 30 26.9 26.4 21.1 Patients (%) 20 18.4

10 5.0 4.6 5.3

0 Methyldopa Beta blockers ACE inhibitors Thiazide Calcium ARBs diuretics inhibitors

Treatment at V1 (n=383) With treatment at V2 (n=371) Change at V3 (n=38)

B. ABPM with diagnostic aim (n=644)

50.0 50 45.8

40 35.4

28.4 30 27.1 27.1

21.3 20.7 Patients (%) 20 14.4 12.5 10

1.7 0.2 0 1.1 0.5 0 0.2 0 0 Methyldopa Beta blockers ACE inhibitors Thiazide Calcium ARBs diuretics inhibitors

Treatment at V1 (n=644) With treatment at V2 (n=348) Change at V3 (n=48) Fig. (2). Therapeutic classes prescribed before and after ABPM according to (A) therapeutic or (B) diagnostic aim (ARBs, angiotensin receptor blockers; ACE, angiotensin-converting enzyme). (A higher resolution / colour version of this figure is available in the electronic copy of the article). formed to recommendations [12]. Combinations of two blocker to improve kidney outcomes. If the goal BP is not drugs and more were frequent in patients already treated at achieved within one month, the dose of the initial drug the inclusion due to the duration of the disease. In the gen- should be increased or a second drug should be added [12]. eral population, including diabetic patients, guidelines rec- In our cohort, angiotensin receptor blockers, calcium inhibi- ommend initial antihypertensive treatment with thiazide-type tors and thiazide diuretics in patients already treated at inclu- diuretic, calcium channel blocker, angiotensin-converting sion and angiotensin receptor blockers for patients with enzyme inhibitor or angiotensin receptor blocker [12]. In the newly diagnosed HT were the most frequent treatments. population with chronic kidney disease, initial or add-on In patients who attended visit V3 (after 6 weeks), treat- antihypertensive treatment should include an angiotensin- ment was changed in only 15% of the newly diagnosed pa- converting enzyme inhibitor or an angiotensin receptor tients. In patients previously treated with antihypertensive Ambulatory Blood Pressure Monitoring in Algeria Current Hypertension Reviews, 2021, Vol. 17, No. 1 81 drugs, the use of ABPM allowed adapting or modifying ACKNOWLEDGMENTS treatment in more than one third of them (treatment was un- changed in the remaining two thirds). Compliance Evalua- The authors wish to thank Meriem Aouchar, Faiza Ait- tion Test completed at visit V3 suggested that compliance Belkacem and Ines Chabane for their participation in the could be further improved for better control of BP. These management and the analysis of the study and Francis results on treatment compliance were however comparable to Beauvais for his help in writing of the manuscript. those of the French study of Girerd et al. who reported 39% of “good compliant”, 53% of “minor noncompliant” and 8% REFERENCES of “noncompliant” [22]. [1] Benkhedda B, Chibane A, Temmar M, et al. 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