gender and hypertension management: a sub-analysis of the i-insyst survey
TRANSCRIPT
ORIGINAL ARTICLE
Blood Pressure, 2011; 20: 69–76
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Gender and hypertension management: A sub-analysis of the I-inSYST survey
PATRICIA VAN DER NIEPEN & DIERIK VERBEELEN
Department of Nephrology and Hypertension, Universitair Ziekenhuis Brussel, Brussels, Belgium
Abstract Hypertension is a major risk factor for cardiovascular disease, which is the leading cause of death in women. Aim. To evaluate blood pressure control, prevalence of concomitant cardiovascular risk factors, subclinical and clinical organ dam-age, and treatment according to gender. Methods. 11,562 patients (49% women) from the cross-sectional I-inSyst survey in primary care were included. Results. Blood pressure control in women (21.8%) and men (21.2%) was similar, despite a slightly older age (64.9 vs 63 years, p � 0.0001). Women had less concomitant cardiovascular risk factors and organ damage, with the exception of diabetes, cerebrovascular and renal disease, than men. They received more antihypertensive drugs than men (1.7 � 0.9 vs 1.5 � 0.9, p � 0.0001). Diuretics were more (45% vs 36.5%, p � 0.0001), calcium-channel blockers (26% vs 29%, p � 0.003) and angiotensin-converting enzyme inhibitors (20% vs 22%, p � 0.02) were less commonly pre-scribed in women than in men. Different clinical factors (i.e. age, duration of hypertension, smoking) in women and men were associated with blood pressure control, but gender itself was not. Conclusions. In this group of treated hypertensive patients, blood pressure control in women and men was not different. Women had a lower prevalence of most cardiovas-cular risk factors, subclinical and clinical organ damage. Antihypertensive drug treatment varied according to gender.
Key Words: Blood pressure control , guidelines , hypertension , gender , treatment
Introduction
Hypertension is a major, but potentially modifi able risk factor for cardiovascular (CV) disease morbidity and mortality, both in women and in men (1,2). CV disease (CVD) is the leading cause of death in women worldwide (3 – 5). Yet several studies have shown that women are less treated than men and that physicians do not actually perceive CV risk in women (2,6). This gender disparity is stated to contribute to the difference in CVD mortality (7).
Guidelines on the management of hypertension recommend targeting at least a systolic blood pres-sure (SBP) � 140 mmHg and a diastolic blood pres-sure (DBP) � 90 mmHg, which will generally be attained using two or more antihypertensive agents (8). Individuals with hypertension frequently cluster other CV risk factors, which not only adds to their overall CV risk (9) but also infl uences blood pressure
Correspondence: Patricia Van der Niepen, Department of Nephrology and HyperBelgium. Tel: � 32 2 477 60 55. Fax: � 32 2 477 62 30. E-mail: hemovnnp@uz
(Received 19 June 2010 ; accepted 23 September 2010 )
ISSN 0803-7051 print/ISSN 1651-1999 online © 2011 Scandinavian FoundatDOI: 10.3109/08037051.2010.532304
(BP) control rate (10). Target BP and choice of the fi rst-line antihypertensive class therefore depend on the presence of concomitant CV risk factors and comorbidity conditions present in the patient (11).
In spite of the strong benefi cial data of both epide-miological and intervention studies, less than 50% of hypertensive individuals are being treated to goal (12,13). Signifi cant gender differences in levels of BP control have been reported, but the data on the asso-ciation of gender with BP control are confl icting (14).
In this study, we analysed the data from the I-inSYST survey (15), a large cross-sectional survey on the management of hypertension in Belgium, to determine, among patients with treated hyperten-sion, the gender difference in BP control, prevalence of other CV risk factors, subclinical organ damage, established CV and renal disease, treatment and factors associated with BP control.
tension, Universitair Ziekenhuis Brussel, Laarbeeklaan 101, B-1090 Brussels, brussel.be
ion for Cardiovascular Research
70 P. Van der Niepen & D. Verbeelen
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Methods
We performed a sub-analysis of women and men who participated in the I-inSYST survey. The meth-odology of the I-inSyst study was described in detail in the referent manuscript (15).
Study sample
From December 2003 to June 2004, 994 primary care physicians throughout Belgium enrolled 13,774 consecutive treated hypertensive patients ( � 18 years old).
The following data were collected using a struc-tured questionnaire on demographic and anthropo-metric data (age, sex, height, weight, duration of hypertension, BP and heart rate), CV risk factors [e.g. body mass index (BMI), waist circumference, smoking status, hypercholesterolemia, diabetes mellitus (DM), and familial history of premature CVD], subclinical organ damage [e.g. left ventricle hypertrophy (LVH), increased carotid wall thicken-ing or plaque, further in the text referred to as IMT: intima media thickness], microalbuminuria (MAU) and slight increase in serum creatinine (115 – 133 μ mol/l for men and 107 – 124 μ mol/l for women), present and past CVD (e.g. cerebrovascular, coro-nary artery, peripheral artery and renal disease), antihypertensive drug treatment and lifestyle modi-fi cations. Whether the treatment was adjusted and the reason were also recorded. Except for the anthropometric and BP measurements, the avail-able information of the fi les was used (data not older than 6 months), as I-inSYST was a non-interventional study in primary care. Patients were questioned about changes in their lifestyles on earlier recommendations from their physician. The accuracy of the information was verifi ed in a ran-dom sample (5%).
BP was measured, as recommended by the guidelines, in the sitting position after 5 min of rest, using a calibrated device with an appropriate cuff. BP was measured at least twice with 1 – 2-min inter-val (16). Different age groups were predefi ned: � 50, 50 – 79 and � 80 years. Overweight and obesity were defi ned respectively as a BMI between 25 – 29.9 and � 30 kg/m ² . Abdominal obesity was defi ned as an abdominal circumference � 102 cm for men and � 88 cm for women. The presence of hypercholes-terolemia was defi ned as a total cholesterol � 6.5 mmol/l or LDL-C � 4.0 mmol/l or HDL-C � 1.0 mmol/l for men and � 1.2 mmol/l for women. The defi nitions of the risk stratifi cation of the 2003 European Society of Hypertension – European Society of Cardiology (ESH/ESC) guidelines were used (16).
The study was approved by a central independent Ethics Committee. A signed informed consent was obtained from all patients.
Hypertension control
Hypertension was defi ned as a mean SBP � 140 mmHg and/or mean DBP � 90 mmHg, or current treatment for hypertension. Overall BP control was defi ned as a SBP � 140 mmHg and a DBP � 90 mmHg. A SBP � 140 mmHg and a DBP � 90 mmHg was considered on-treatment isolated systolic hyper-tension (ISH). An SBP � 140 mmHg and a DBP � 90 mmHg were considered on-treatment isolated diastolic hypertension (IDH).
Statistical analysis
The statistical analysis was performed with SAS statistical software version 8.2 (SAS Institute Inc., Cary, NC, USA). All tests were two-sided using a signifi cance level of 0.05. Continuous variables are described as mean values with their corresponding standard deviation (SD), and dichotomous variables are described as counts and percentages. To evaluate the differences in clinical characteristics between men and women, chi-square tests and Student ’ s t -tests were applied as appropriate. Stepwise multiple logistic regression models were used to assess the relationship between the prevalence of controlled hypertension and clinical variables according to gen-der. Adjustment for age, SBP and DBP, BMI, abdominal obesity, presence of diabetes mellitus, smoking, number of antihypertensive drugs and duration of hypertension (continuous variable) was performed. Odds ratios (OR) and corresponding 95% confi dence intervals (CI) are reported.
Results
Study sample
Table I shows the gender-specifi c demographic char-acteristics of the 11,562 evaluable (patients with missing data were excluded for analysis) patients (ratio men/women: 1.03). Mean age of the 5691 women was signifi cantly higher, because of a higher proportion of � 80-year-old patients and a lower proportion of � 50-year-old patients than in the male subgroup ( p � 0.0001). Mean BMI did not differ, but signifi cantly less women than men presented with weight excess, defi ned as BMI � 25 kg/m 2 (respec-tively 67% compared with 74%, p � 0.0001).
Concomitant CV risk factors and disease
The prevalence of concomitant CV risk factors, sub-clinical organ damage and established CV and renal disease is shown in Table I. The distribution of the number of the different CV risk factors (Figure 1), subclinical organ damage and established CV and renal disease, was similar in women and men,
Gender and hypertension management 71
Women Men p
n (%) 5691 (49) 5871 (51)Demographic data (mean � SD)
Age (years)Weight (kg)BMI (kg/m ² )SBP (mmHg)DBP (mmHg)PP (mmHg)HR (beats/min)
64.9 � 12.4 61.3 � 12 � 0.000174.3 � 14.4 84.3 � 14.1 � 0.000127.7 � 5.2 27.8 � 4.3 NS151 � 18 150 � 17 � 0.0587 � 11 88 � 11 � 0.00264 � 15 62 � 14 � 0.000174 � 9 73 � 10 � 0.003
Cardiovascular risk factors (%)Smoker, currentDiabetesAbdominal obesityHypercholesterolemiaFamilial history premature CVD
16.1 33.8 � 0.000118.9 17.3 � 0.0236.4 36.1 NS37.8 41.1 � 0.000127.5 29.5 � 0.01
Subclinical organ damage (%)Left ventricle hypertrophyCarotid thickeningSlight increased serum creatinineMicroalbuminuria
13.2 16.1 � 0.00011.4 2.3 � 0.00014.7 4.9 NS4.9 5.2 NS
Established cardiovascular and renal disease (%)Cerebrovascular diseaseCoronary artery diseaseRenal diseasePeripheral artery diseaseAdvanced retinopathy
8.1 6.8 � 0.00511.9 18.3 � 0.00015.1 4.3 � 0.037.2 9.1 � 0.00011.8 1.5 NS
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irrespective the type of uncontrolled (ISH, IDH or combined) hypertension (data not shown), while the mean number of CV risk factors, subclinical and clinical organ damage was signifi cantly lower in women than in men (1.4 � 1.1 vs 1.6 � 1.1, 0.3 � 0.6 vs 0.2 � 0.5 and 0.4 � 0.7 vs 0.3 � 0.6 respec-tively; p � 0.0001).
BP and BP control
Mean SBP at the study visit was slightly but signifi -cantly higher in women than in men, whereas DBP was slightly but signifi cantly lower. As a consequence, pulse pressure was signifi cantly higher in women compared with men (Table I). Only 1239 women (21.8%) and 1243 men (21.2%) had both SBP and DBP at goal (Figure 2). The age-adjusted prevalence of uncontrolled BP, 78% in women and 79% in men, was not different. On-treatment ISH was signifi cantly more prevalent in women than in men (30% vs 27%; p � 0.002) (Figure 2). Both women and men with on-treatment ISH were signifi cantly older (on aver-age 4 years) than patients with controlled or uncon-trolled diastolic/systolic-diastolic hypertension. Target BP was signifi cantly more often present in the oldest age group ( p � 0.009), but without any differ-ence between gender; a BP � 140/ � 90 mmHg was present in 20.5%, 20.8% and 24.0% (ns) in female patients and in 18.3%, 21.1% and 23.9% ( p � 0.05)
in male patients aged respectively � 50, 50 – 79 and � 80 years. Overall BP control was similar in patients with and without diabetes (20.2% and 21.1%, respectively), for both gender (for female and male patients 19.9% and 20.4%, and 21.4% and 20.8%, respectively).
The stepwise multiple logistic regression analysis (Table II) showed that gender was not associated with BP control [OR for male vs female sex, 1.026 (95% CI 0.942 – 1.117)], even when adjusted for age, BP, BMI, diabetes, abdominal obesity, smoking and the number of antihypertensive drugs [OR, 1.103 (95% CI 0.872 – 1.396)].
Use of antihypertensive medications – Lifestyle modifi cations
Women were treated with slightly but signifi cantly more antihypertensive drugs than men (1.7 � 0.9 vs 1.5 � 0.9, p � 0.0001). Both women and men with their BP at goal were treated with 1.7 � 0.8 antihy-pertensive drug classes, whereas women not at goal received 1.6 � 0.9 and men 1.5 � 0.9 antihyperten-sive drugs ( p � 0.0001). Respectively, 46.1% and 49.2% of women and men were treated with antihy-pertensive monotherapy, and 34.7% of women and 32.1% of men received two antihypertensive drug classes. The remainder took three or more different antihypertensive drug classes ( p � 0.0009).
Table I. Demographic characteristics, cardiovascular risk factors, subclinical organ damage and established cardiovascular and renal disease by gender.
n, number of observations; SD, standard deviation; BMI, body mass index; SBP, Systolic blood pressure; DBP, diastolic blood pressure; PP, pulse pressure; HR, heart rate; CVD, cardiovascular disease; NS, not signifi cant.
72 P. Van der Niepen & D. Verbeelen
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Beta-blockers were the most frequently prescribed antihypertensive agents both in men and in women, followed by diuretics, calcium-channel blockers (CCB), angiotensin-converting enzyme inhibitors
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(ACEI) and angiotensin II receptor antagonists (ARB) (Figure 3). This distribution was present in all age groups, except in the oldest one, in which diuretics became the most frequently prescribed
Figure 1. Distribution of the number of cardiovascular risk factors by gender.
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Figure 2. Distribution of blood pressure (a) in men; (b) in women. Systolic and diastolic blood pressure (BP) of the 11,562 treated hypertensive patients. Lines represent higher limit of the target BP range. Percentages in margin indicate the proportion of individuals falling above and below the limit. Percentages in the graph indicate the proportion of individuals in a given quadrant.
Gender and hypertension management 73
Women Men
Parameter (present vs absent) OR (95% CI) p -value OR (95% CI) p -value
Age a 1.001 (0.996 – 1.006) – 1.008 (1.003 – 1.013) � 0.002BMI (kg/m 2 ) a 0.959 (0.947 – 0.971) � 0.0001 0.955 (0.941 – 0.969) � 0.0001Smoking 0.940 (0.796 – 1.110) – 0.750 (0.658 – 0.854) � 0.0001Hypercholesterolemia 0.854 (0.752 – 0.968) � 0.02 0.841 (0.744 – 0.951) � 0.006FH premature CVD 0.773 (0.671 – 0.889) 0.0003 0.956 (0.839 – 1.091) –Abdominal obesity 0.673 (0.590 – 0.767) � 0.0001 0.604 (0.529 – 0.689) � 0.0001Diabetes Mellitus 0.910 (0.778 – 1.065) – 0.978 (0.834 – 1.145) –Left ventricle hypertrophy 0.706 (0.585 – 0.857) 0.0004 0.888 (0.752 – 1.049) –Carotid thickening 0.987 (0.585 – 1.665) – 1.020 (0.688 – 1.514) –Slight increased serum creatinine 0.884 (0.658 – 1.188) – 0.851 (0.638 – 1.137) –Microalbuminuria 0.790 (0.585 – 1.067) – 0.950 (0.723 – 1.248) –Cerebrovascular disease 1.014 (0.813 – 1.265) – 1.329 (1.064 – 1.660) � 0.02Cardiac disease 1.290 (1.080 – 1.540) � 0.005 1.577 (1.366 – 1.821) � 0.0001Renal disease 0.928 (0.703 – 1.227) – 1.043 (0.781 – 1.394) –Peripheral artery disease 0.633 (0.486 – 0.825) 0.0007 1.012 (0.823 – 1.244) –Retinopathy 1.293 (0.844 – 1.981) – 1.211 (0.762 – 1.924) –Number of antiHTN drugs a 1.108 (1.035 – 1.186) � 0.004 1.156 (1.081 – 1.236) � 0.0001Duration of hypertension a 1.004 (0.993 – 1.015) – 1.029 (1.017 – 1.040) � 0.0001
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drugs in both gender (53% in women and 39% in men, p � 0.0001). Beta-blockers (46% and 44%, ns), and ARBs (21% and 20%, ns) were equally pre-scribed in women and men, whereas diuretics were signifi cantly more (45% and 36.5%, p � 0.0001) and CCB (27% and 29%, p � 0.003) and ACEI (20.5% and 22.5%, p � 0.02) signifi cantly less frequently used in women than in men.
Approximately 59% of both women and men reported to follow a salt-restricting diet, and 36% of them had decreased fat intake following previous recommendations of their physician. Signifi cantly more men than women had stopped smoking (35% vs 15%, p � 0.0001), had lost weight (46% vs 44%, p � 0.02), had decreased alcohol consumption (31% vs 10%, p � 0.0001) and had increased physical
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activity (48% vs 42%, p � 0.0001), whereas signifi -cantly more women than men had increased daily intake of fruit and vegetables (29% vs 26%, p � 0.0001).
Treatment adaptation
In both women and men, antihypertensive treatment remained unchanged in 39.2% of the cases. The main reason for not intensifying treatment despite not achieving BP target was the perception of the physicians that BP was controlled (142 � 9/83 � 7 mmHg) (24%) or almost at target (147 � 9/85 � 8 mmHg) (8%). No difference according to gender was observed. Both female and male patients who did not have their treatment changed received slightly
MenWomen
∗∗∗∗∗
ARBACEICB
Figure 3. Antihypertensive drug classes in men and women. ∗ p � 0.0001, ∗∗ p � 0.003, ∗∗∗ p � 0.02. BB, beta-blockers; Diur, diuretics; CCB, calcium-channel blockers; ACEI, angiotensin-converting enzyme inhibitors; ARB, angiotensin II receptor antagonists.Table II. Factors related to blood pressure control according to gender .
a Continuous variable; OR, odds ratio; CI, confi dence interval; BMI, body mass index; FH, family history; CVD, cardiovascular disease; antiHTN, antihypertensive; –, not signifi cant.
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but signifi cantly more antihypertensive drug classes than those who did have their treatment changed (1.8 � 0.9 vs 1.6 � 0.8 for women and 1.7 � 0.9 vs 1.5 � 0.8 for men, p � 0.0001). Patients who remained on the same antihypertensive treatment were slightly but signifi cantly younger (on average 2 years) and less obese (BMI 0.5 – 0.7 kg/m 2 lower; p � 0.0001) than patients who had their treatment adjusted, irrespective of gender.
Discussion
In the present sub-analysis of the I-inSyst survey, no gender difference in overall BP control ( � 140/ � 90 mmHg) among treated hypertensive patients was observed. Our results are in line with those fi nd by others showing no gender difference in BP control (17 – 23), but are in contrast with other reports showing that women with hypertension are more (24 – 29) or less likely than men to meet BP control (1,17,30 – 37).
In line with the results of other surveys, women had a lower mean DBP than men and a higher SBP, which is a stronger predictor of CV and renal disease than DBP (18,19,30,37 – 39). Sex-specifi c hemody-namic characteristics and the infl uence of sex hor-mones have been suggested to account for some of the differences between women and men, increasing e.g. the incidence of ISH and augmenting pulse pres-sure in elderly women (40 – 43). The latter may explain why CVDs have become the major cause of death in women after menopause.
Although the majority of our patients had uncon-trolled BP, half of them, more women than men, were treated with antihypertensive monotherapy. Despite being well established that the majority of the hyper-tensive population need combination therapy to achieve goal BP, 44% of English patients on treatment for hypertension were, at the same time of our survey, also on only one agent (11,44). The type of antihyper-tensive drug class varied signifi cantly according to gender. Diuretics, in monotherapy as well as in com-bination therapy, were signifi cantly more frequently prescribed in women than in men, whereas CCB and ACEI were signifi cantly less used. This fi nding is in line with previous data (1,18,30,34,36,37,45 – 47) and may partly be explained as a consequence of daily practicing following local authorities ’ guidelines, pro-moting diuretics as the fi rst-line drug. On the other hand, the different prescription pattern of antihyper-tensive drugs may in part refl ect the coexistence of other conditions that are considered “ compelling indi-cations ” (11), e.g. more women than men suffer from chronic oedema of the legs of venous origin, which is a relative contra-indication for using CCBs. While the Blood Pressure Lowering Treatment Trialists ’ Coop-eration has found that all classical BP lowering regi-mens provide broadly similar protection against major
CV events in both men and women (48), ACEI have been reported to be less effective and induce more side-effects in women than in men (38,39). When ACEI and ARB were considered one class, i.e. agents that block the renin – angiotensin – aldosterone system, they became, like in other countries, the most fre-quently prescribed drug class (21).
The present study also emphasized a signifi cant difference in clinical profi le following gender. In line with the fi ndings of Banegas et al. (18), but in con-trast with those of Ong et al. (19), treated hyperten-sive women in Belgium tended, despite their older age, to have less CV risk factors than men, with the exception of diabetes. The higher prevalence of dia-betes in these women might be a consequence of the greater use of the combination diuretic-beta blocker. Indeed more incident patients with diabetes have been diagnosed in clinical trials with diuretics and/or beta-blockers (49). The higher prevalence of dia-betes in women may have important consequences, as patients with diabetes have a higher risk of all-cause and CVD mortality than those without diabe-tes (50). The high prevalence of weight excess and abdominal obesity in the studied patients is alarm-ing, as both are well known risk factors for hyperten-sion and for excess CV morbidity and mortality (14). Moreover, in the Epic-Norfolk study, women with high central obesity were 20% more likely to develop coronary heart disease compared with their male counterparts (51).
Different clinical factors in women than in men were associated with BP control. Age and duration of hypertension were positively associated with BP con-trol in men, but not in women. At least at older age, aging has been reported to be a risk factor for uncon-trolled BP, especially in women (1,33,34,52). In con-trast with the results of Ong et al. (19), but in line with the results of Banegas et al. (18), smoking was associ-ated with less BP control in men only. Gender differ-ences in BP values associated with smoking have also been observed in epidemiological surveys, and may be explained in part by differential confounding effects of BMI and alcohol intake (53). The presence of LVH and peripheral artery disease was associated with less BP control in women, while a history of cerebrovas-cular disease in men and of coronary artery disease in both women and men was associated with more BP control. Although the presence of subclinical organ damage and established CVD are likely to be the con-sequence rather than the cause of differences in BP control, their presence may infl uence physicians ’ deci-sion making and consequently BP control. The num-ber of antihypertensive drugs was associated with better BP control in both genders, emphasizing the need for combination therapy.
In spite of poor BP control, the physicians did not intensify treatment in 39% of cases, irrespective of gender, and mainly because they were satisfi ed with a near-normal BP. Therapeutic inertia is indeed
Gender and hypertension management 75
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a recognized barrier to effective care (54). A compa-rable prevalence rate of therapeutic inertia was recently reported by Gil-Guill é n et al. (55), and no gender difference in initiation of new therapy for patients with uncontrolled hypertension was also found by Keyhani et al. (34).
The limitations of the present study are those inherent to observational studies involving volun-tary participating physicians. However, we believe that this does not affect the main objective of this sub-analysis, i.e. the evaluation of BP control according to gender. Unfortunately, we do not have data on contraceptive pill use, menopausal state and the use of hormonal substitution therapy, because the survey was not intended to record these. The strength of this survey is that it includes a large number of unselected and consecutively enrolled patients across all ages and both sexes from a large number of general physicians throughout Belgium, providing a realistic estimate of BP control, and treatment of the hypertensive population in general practice.
In conclusion, the present study showed that there was no difference in overall BP control between treated hypertensive women and men. However, BP control was associated with different clinical characteristics according to gender. An increased knowledge of the gender-specifi c risk for uncontrolled BP and hence for CVD should lead to improved management of hyper-tension. This is of utmost importance, since elderly women represent a growing subset of the population with a higher prevalence of hypertension and a high risk of hypertension-related CVD. As almost half of the women were treated with monotherapy, there is room for improvement using more combinations of well-tolerated antihypertensive drugs. Furthermore, successful treatment of hypertension also implies adherence of physicians to the guidelines targeting for optimal SBP and DBP control, while patients should comply with antihypertensive treatment and adhere to lifestyle modifi cations.
Acknowledgement
The survey was supported by Bristol-Myers Squibb and Sanofi -Aventis. The authors gratefully acknowl-edge the dedicated collaboration of the many general physicians and Mrs Nadia Fenners for the secretarial assistance.
Declaration of interest: No confl ict of interest.
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