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Gender difference in the response tovalsartan/amlodipine single-pill
作者:陈慧[1] 
单位:福建省立医院[1]  
文章号:W114543  
2016/8/20 10:34:57    
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643903JRA0010.1177/1470320316643903Journal of the Renin-Angiotensin-Aldosterone SystemWang and Chen 365医学网 转载请注明
research-article2016 365医学网 转载请注明
Abstract 365医学网 转载请注明
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Background: The China STATUS II is a prospective, multicentre, open-label, post-marketing, observational study including Chinese adults (aged ⩾ 18 years) with essential hypertension who were prescribed once-daily valsartan/ amlodipine (Val/Aml 80/5 mg) single-pill combination. In order to examine gender differences in treatment response to Val/Aml, we further analysed data from the China STATUSII study. 365医学网 转载请注明
Methods: A total of 11,312 patients (6456 (57%) men and 4856 (43%) women) received the Val/Aml treatment for 8 365医学网 转载请注明
weeks. After the treatment, we compared the proportion of patients not achieving the target systolic blood pressure (SBP: < 140 mm Hg) or diastolic blood pressure (DBP: < 90 mm Hg) in different age groups (by Fisher exact probability test) and estimated the changes in blood pressure (BP) according to age and gender, using a mixed model. 365医学网 转载请注明
Results: At enrolment, mean SBP was higher in the female versus the male patients (160.0 ± 12.71 versus 159.3 ± 365医学网 转载请注明
12.31 mm Hg; p = 0.003), whereasthe mean DBPwashigher in the male versusthe female patients(96.4 ± 10.65 versus 365医学网 转载请注明
94.5 ± 10.72 mm Hg; p < 0.001). The overall proportion of women not achieving the target BP was less than that of men (57.41%versus 59.59%; p < 0.05) at 4 weeks and (22.22%versus 23.78%; p < 0.05) at 8 weeks after the Val/Aml 365医学网 转载请注明
treatment. Among both men and women, the proportion of patients not achieving the target SBP increased with age; 365医学网 转载请注明
however, the proportion not achieving the target DBPdecreased with age. The mixed-model analysis showed that the 365医学网 转载请注明
changes in SBPwere closely related to gender, indicating that the SBP-lowering effect after Val/Aml treatment might be better in women. In addition, the changes in DBPwere closely related to age. 365医学网 转载请注明
Conclusions: Gender might beafactor for considerationinthedecision-makingprocessofindividualisedantihypertensive 365医学网 转载请注明
therapy, in the future. 365医学网 转载请注明
Keywords 365医学网 转载请注明
Amlodipine, essential hypertension, gender differences, renin angiotensin aldosterone system, single-pill combination, 365医学网 转载请注明
STATUSII, valsartan 365医学网 转载请注明
Date received: 2 September 2015; accepted: 22 December 2015 365医学网 转载请注明
Introduction 365医学网 转载请注明
Essential hypertension is a common risk factor for cardio- 365医学网 转载请注明
vascular diseases (CVDs). Except for lifestyle modifica- tion, drug therapy is the main treatment strategy. A single-pill combination (SPC) of two drugs is recom- 365医学网 转载请注明
mended by several recent international guidelines for 365医学网 转载请注明
hypertension,1,2 including the Chinese guidelines of 20103 365医学网 转载请注明
for the treatment of hypertension in high-risk patients who require marked blood pressure (BP) reductions. The China STATUS II (Survey of hyperTensive pAtienTs blood pressUre control rate in clinic Service) is a prospective, 365医学网 转载请注明
365医学网 转载请注明
multicentre, open-label, post-marketing, observational study; including 11,312 Chinese adults (aged ⩾18 years) 365医学网 转载请注明
Fujian Provincial Cardiovascular Disease Institute, Fujian Medical University, Fuzhou, Fujian, China 365医学网 转载请注明
Corresponding author: 365医学网 转载请注明
Hui Chen, Department of Internal Medicine, Fujian Provincial Cardiovascular Disease Institute, 134 East Street, Fuzhou, Fujian 350001, P.R. China. 365医学网 转载请注明
Email: chenhuiwyd@sina.com 365医学网 转载请注明
Creative Commons Non Commercial CC-BY-NC: This article is distributed under the terms of the Creative Commons Attribution-NonCommercial 3.0 License (http://www.creativecommons.org/licenses/by-nc/3.0/) which permits non-commercial use, 365医学网 转载请注明
reproduction and distribution of the work without further permission provided the original work is attributed as specified on the SAGEand 365医学网 转载请注明
Open Access pages (https://us.sagepub.com/en-us/nam/open-access-at-sage). 365医学网 转载请注明
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2 Journal of the Renin-Angiotensin-Aldosterone System 365医学网 转载请注明
with essential hypertension, who were prescribed a once- daily valsartan/amlodipine (Val/Aml, 80/5 mg) SPC. China STATUS II is the first evidence-based, real-world data in Chinese hypertensive patients, which shows the efficacy and safety of the Val/Aml SPC.4 365医学网 转载请注明
It is well known that young adult women have lower BP 365医学网 转载请注明
than age-matched men; but the prevalence of CVDs, including hypertension in women, increases rapidly after the onset of menopause. Recent studies show a few possi- ble causes for gender-related differences in CVDs, such as: The change in female hormonal status and the loss of car- 365医学网 转载请注明
diovascular protection provided by oestrogen.5–7 Although 365医学网 转载请注明
numerous studies report gender-related differences in the regulation of arterial pressure and renal function by the 365医学网 转载请注明
renin-angiotensin system (RAS)8–10 and the response to 365医学网 转载请注明
RAS inhibition,11–13 there is no mention of the selection of antihypertensive drugs based on gender, except in preg- 365医学网 转载请注明
nancy-related situations, in any of the guidelines world- 365医学网 转载请注明
wide. Moreover, insufficient gender-specific data has been provided by clinical trials,14 making it difficult to optimise 365医学网 转载请注明
drug selection for both genders. In order to understand 365医学网 转载请注明
gender differences in BP management, we examined the effect of gender on the efficacy of Val/Aml SPC in the China STATUS II study. 365医学网 转载请注明
Methods 365医学网 转载请注明
Study design and participants 365医学网 转载请注明
The study design for China STATUS II has been reported elsewhere.4 To summarise, China STATUS II was a multi- 365医学网 转载请注明
centre, post-marketing, prospective, observational study, 365医学网 转载请注明
which enrolled 11,312 adult Chinese patients with essen- tial hypertension whose BP was not adequately controlled by monotherapy. 365医学网 转载请注明
All enrolled patients had a mean sitting systolic BP 365医学网 转载请注明
(SBP) ⩾140 mm Hg (⩾130 mm Hg for diabetes or chronic kidney disease (CKD)) and/or a mean sitting diastolic BP (DBP) ⩾90 mm Hg (⩾80 mm Hg for diabetes or CKD), 365医学网 转载请注明
whose BP was inadequately controlled by monotherapy. 365医学网 转载请注明
Before enrolment, all patients provided written informed consent. The study complied with the International 365医学网 转载请注明
Conference on Harmonisation-Good Clinical Practice 365医学网 转载请注明
(ICH-GCP) and applicable local regulations in China, and 365医学网 转载请注明
was approved by the Ethical Review Committee of the First Hospital of Harbin Medical University. All procedures fol- 365医学网 转载请注明
lowed were in accordance with the ethical standards of the 365医学网 转载请注明
responsible committee on human experimentation (institu- tional and national) and with the Declaration of Helsinki of 1975, as revised in 2000 and 2008. 365医学网 转载请注明
The baseline characteristics of the randomised patients 365医学网 转载请注明
are described in the report of the China STATUS II study’s main findings.4 365医学网 转载请注明
Eligible patients from 238 regional centres across 29 365医学网 转载请注明
provinces of China were enrolled from 12 October 2010 to 365医学网 转载请注明
365医学网 转载请注明
20 February 2012. After enrolment, there was no dietary, lifestyle nor medication change in all subjects. The lifestyle 365医学网 转载请注明
questionnaires included questions on education and socio- 365医学网 转载请注明
economic status, occupation, history of previous illness and 365医学网 转载请注明
disorders or surgical operations, lifetime history of con- sumption of tobacco and alcoholic beverages, and physical activity. All patients who had stopped taking other antihy- pertensive drugs received Val/Aml 80/5 mg SPC for 4 weeks, instead of their previous antihypertensive drugs. 365医学网 转载请注明
The initial BP target (< 140/90 mm Hg (or < 130/80 mm Hg 365医学网 转载请注明
for diabetes or CKD)) was unified to < 140/90 mm Hg, for 365医学网 转载请注明
easier management. The treatment was in accordance with the routine clinical outpatient practice in China. The study 365医学网 转载请注明
duration was 8 weeks, with a follow-up every 4 weeks. If a 365医学网 转载请注明
patient did not achieve BP control at the end of 4 weeks of the SPC, an additional antihypertensive agent could be added, according to the physician’s decision. 365医学网 转载请注明
Statistical analysis 365医学网 转载请注明
All statistical analyses were performed using SAS® soft- ware version 9.2 (SAS Institute Inc., Cary, NC, USA), 365医学网 转载请注明
with a 2-sided significance level (p) of < 0.05. Demographic 365医学网 转载请注明
and baseline variables were summarised using descriptive 365医学网 转载请注明
statistics, including the mean, SD, median, minimum and 365医学网 转载请注明
maximum values for numeric variables; and the count 365医学网 转载请注明
number and percentage for the categorical variables. We used the T test, chi-square test and Fisher accurate proba- bility test. 365医学网 转载请注明
We estimated the changes in SBP and DBP at 4 and 8 365医学网 转载请注明
weeks for gender and age as fixed effects, by using SAS PROC MIXED (SAS Institute, Cary, NC, USA).15 For the analysis in Mixed Model 1, we calculated variance compo- 365医学网 转载请注明
nents for the baseline BP, their BMI, smoking, drinking, 365医学网 转载请注明
exercise and education level, using gender and age as fixed effects. The same analysis was then used in Mixed Model 2, adjusting for the baseline BP and statistically significant effects in Model 1. 365医学网 转载请注明
Results 365医学网 转载请注明
Demographic and baseline characteristics 365医学网 转载请注明
The detailed demographic and baseline characteristics of 365医学网 转载请注明
the patients are presented in Table 1. We analysed a total of 11,312 patients (6456 (57%) men and 4856 (43%) women). 365医学网 转载请注明
At enrolment, the men were younger in age (p < 0.001) and 365医学网 转载请注明
had a higher BMI (p < 0.001) than women. Compared with the female patients, we observed a higher educational 365医学网 转载请注明
background, more physical activity, and more smoking 365医学网 转载请注明
and drinking in the male patients (p < 0.05). There were no significant differences in their present cardiovascular risk factors and medical history, and their previous use of anti- 365医学网 转载请注明
hypertensive drug classes, between these men and women 365医学网 转载请注明
(Table 1). 365医学网 转载请注明
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Wang and Chen 3 365医学网 转载请注明
Table 1. Demographic and baseline characteristics of the study patients (n = 11,312).a 365医学网 转载请注明
Men (n = 6456) Women (n = 4856) p-value 365医学网 转载请注明
Mean age (SD) 57.4 (14.27) 59.8 (13.09) < 0.001 365医学网 转载请注明
Patients in each group, n (%) < 0.0001 365医学网 转载请注明
< 55 years old 2913 (45.12%) 1798 (37.03%) 365医学网 转载请注明
55–64 years old 1641 (25.42%) 1351 (27.82%) 365医学网 转载请注明
65–74 years old 1019 (15.78%) 1015 (20.90%) 365医学网 转载请注明
⩾75 years old 883 (13.68%) 692 (14.25%) 365医学网 转载请注明
BMI (kg/m2) 25.0 (2.95) 24.3 (3.34) < 0.001 365医学网 转载请注明
BMI ⩾25 kg/m2, n (%) 3088 (47.9%) 1824 (37.6%) < 0.0001 365医学网 转载请注明
Ethnicity, n (%) 0.3074 365医学网 转载请注明
Han 6262 (96.9%) 4727 (97.3%) 365医学网 转载请注明
Hui 98 (1.51%) 78 (1.60%) 365医学网 转载请注明
Manchu 38 (0.58%) 22 (0.45%) 365医学网 转载请注明
Mongolian 18 (0.27%) 7 (0.14%) 365医学网 转载请注明
other 40 (0.61%) 22 (0.45%) 365医学网 转载请注明
SBP(SD), mm Hg 159.3 (12.31) 160.0 (12.71) 0.003 365医学网 转载请注明
DBP(SD), mm Hg 96.4 (10.65) 94.5 (10.72) < 0.001 365医学网 转载请注明
Heart rate (SD), bpm 75.6 ( 7.74) 75.2 (8.00) 0.003 365医学网 转载请注明
Current smoker, n (%) 2090 (32.3%) 94 (1.93%) < 0.0001 365医学网 转载请注明
Current alcohol drinker, n (%) 1446 (22.3%) 50 (1.02%) < 0.0001 365医学网 转载请注明
College degree or above, n (%) 1615 (25.0%) 630 (12.9%) < 0.0001 365医学网 转载请注明
Appropriate physical activityb, n (%) 4908 (76.0%) 3607 (74.2%) 0.0334 365医学网 转载请注明
Present cardiovascular risk factors or 365医学网 转载请注明
medical history, n (%) 365医学网 转载请注明
Dyslipidemia 1588 (24.5%) 1114 (22.9%) 0.1136 365医学网 转载请注明
Diabetes 1038 (16.0%) 827 (17.0%) 0.3029 365医学网 转载请注明
CHD 957 (14.8%) 796 (16.3%) 0.0726 365医学网 转载请注明
Heart failure 104 (1.61%) 85 (1.75%) 0.6971 365医学网 转载请注明
Kidney disease 206 (3.19%) 149 (3.06%) 0.9317 365医学网 转载请注明
Previous antihypertensive drugclasses, n (%) 0.9889 365医学网 转载请注明
β-Blockers 518 (8.02%) 385 (7.92%) 365医学网 转载请注明
CCBs 3083 (47.7%) 2330 (47.9%) 365医学网 转载请注明
ACEIs 994 (15.3%) 734 (15.1%) 365医学网 转载请注明
Diuretics 181 (2.80%) 140 (2.88%) 365医学网 转载请注明
ARB 1630(25.2%) 1223(25.1%) 365医学网 转载请注明
Others 44 (0.68%) 38 (0.78%) 365医学网 转载请注明
Unknown 6 (0.09%) 6 (0.12%) 365医学网 转载请注明
We used the T test for mean age, mean height, mean weight, BMI, SBP, DBPand heart rate; Chi square test for patients in each group: BMI ⩾25, ethnicity, current smoker, current alcohol drinker, college degree or above, appropriate physical activity, present risk factors of medical history related to cardiovascular disease, and previous anti-hypertensive drugclasses used. 365医学网 转载请注明
ACEI: ACEinhibitor; ARB: angiotensin II receptor blocker; BMI: body mass index; BPM: beats per minute; CCB: calcium channel blocker; 365医学网 转载请注明
DBP:diastolic blood pressure; mm Hg: millimetres of mercury as units of pressure; SBP: systolic blood pressure. 365医学网 转载请注明
aAppropriate physical activity (if the subject participates in any regular physical activities, such as walking, swimming, running, etc.). 365医学网 转载请注明
Blood pressure during follow-up 365医学网 转载请注明
SBP was higher in the female patients versus the male patients (160.0 ± 12.71 versus 159.3 ± 12.31 mm Hg; p = 365医学网 转载请注明
0.003); whereas DBP was higher in male patients versus 365医学网 转载请注明
female patients, at enrolment (96.4 ± 10.65 versus 94.5 ± 365医学网 转载请注明
10.72 mm Hg; p < 0.001). 365医学网 转载请注明
After the treatment, a significantly lower proportion of women did not achieve the target BP, compared with men 365医学网 转载请注明
(57.41% versus 59.59%, p < 0.05 at 4 weeks; and 22.22% 365医学网 转载请注明
versus 23.78%, p < 0.05, at 8 weeks). In order to examine 365医学网 转载请注明
365医学网 转载请注明
the effect of age on drug efficacy, both genders were divided into four different age groups: < 55, 55–64, 65–75 and > 75 years. As a result, for all enrolled patients, the proportion of patients not achieving the target SBP increased with age; however, the proportion of patients not achieving the target DBP was the opposite (Figure 1). 365医学网 转载请注明
The next assessment included the changes in SBP and 365医学网 转载请注明
DBP at 4 and 8 weeks after treatment, according to gender and age, by using SAS PROC MIXED. The p values obtained from the Mixed Model were as follows: Changes in SBP at 4 weeks, p < 0.0001 for gender and p = 0.3832 365医学网 转载请注明
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4 Journal of the Renin-Angiotensin-Aldosterone System 365医学网 转载请注明
Figure 1(a). The proportion of patients not achievingthe target SBPof < 140 mm Hgin different age groups of men and women, respectively; at baseline, 4 weeks and 8 weeks after their treatment with the Val/Aml combination therapy. 365医学网 转载请注明
Figure 1(b). The proportion of patients not achievingthe target diastolic blood pressure (DBP) of < 90 mmHgin different age groups of men and women, respectively: at baseline, 4 weeks and 8 weeks after their treatment with the Val/Aml combination therapy. 365医学网 转载请注明
Aml: amlodipine; DBP: diastolic blood pressure; mmHg: millimetres of mercury; SBP: systolic blood pressure; Val: valsartan. 365医学网 转载请注明
for age; changes in SBP at 8 weeks, p = 0.0026 for gender 365医学网 转载请注明
and p = 0.0225 for age; changes in DBP at 4 weeks, p = 365医学网 转载请注明
0.0602 for gender and p = 0.0219 for age; changes in DBP at 8 weeks, p = 0.1035 for gender and p = 0.0057 for age. In the Mixed Model 1 analysis, age and gender were fixed effects and the baseline BP, BMI, smoking, drinking, exer- 365医学网 转载请注明
cise and education level were random effects. There was 365医学网 转载请注明
no significant correlation between the patients’ age, gen- 365医学网 转载请注明
der, BMI, smoking, drinking, exercise and education level. The Mixed Model 2 was adjusted for the baseline BP and statistically significant effects in the Model 1. That mixed model showed that the changes in SBP were closely related to gender. Given that the proportion of the women who did not achieve the target BP was lower as compared with the men in this study, the SBP-lowering effect of the Val/Aml treatment might be better in women. In addition, the changes in DBP were closely related to 365医学网 转载请注明
365医学网 转载请注明
age. These findings were consistent in both Mixed Model 365医学网 转载请注明
1and Mixed Model 2 (Table 2). 365医学网 转载请注明
Discussion 365医学网 转载请注明
One major finding of our study was that a gender differ- ence existed in the treatment response to Val/Aml among Chinese hypertension patients, indicating that this therapy might show better SBP-lowering effects in women. 365医学网 转载请注明
Major gender differences exist in the development and 365医学网 转载请注明
progression of hypertension and CVD. Before menopause, 365医学网 转载请注明
women usually have lower BP and less hypertension and CVD, relative to age-matched men16,17; however, this car- diovascular protection in women is lost after menopause.18 365医学网 转载请注明
Several studies confirm that gender differences exist in 365医学网 转载请注明
terms of the pharmacokinetic and pharmacodynamic char- acteristics of drugs.19–21 Wing et al.22 shows that treatment 365医学网 转载请注明
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Wang and Chen 5 365医学网 转载请注明
Table 2. Changes in SBPand DBPat 4 weeks and 8 weeks, accordingto gender and age, usingSASPROC MIXED analysis using the mixed model, with the age group and gender as fixed factors and the baseline BPat 4 weeks and 8 weeks as acovariate. 365医学网 转载请注明
< 55 years of age 55 years to < 64 365医学网 转载请注明
years 365医学网 转载请注明
365医学网 转载请注明
65 years to < 75 > 75 years p value (age) 365医学网 转载请注明
years 365医学网 转载请注明
n (men and women study 2917/1798 1641/1351 1019/1015 883/692 365医学网 转载请注明
subjects) 365医学网 转载请注明
SBP(mm Hg) 365医学网 转载请注明
Baseline men 158.2 ± 12.40 159.3 ± 11.92 160.6 ± 12.04 161.3 ± 12.67 < 0.0001 365医学网 转载请注明
women 158.4 ± 12.07 160.1 ± 12.54 161.6 ± 13.34 161.6 ± 13.23 365医学网 转载请注明
p value (gender) 0.0041 365医学网 转载请注明
Differences at 4 weeks 365医学网 转载请注明
365医学网 转载请注明
men − 19.1 ± 11.10 − 19.7 ± 10.94 − 20.2 ± 11.07 − 20.4 ± 11.12 0.3832 365医学网 转载请注明
women − 19.6 ± 11.29 − 21.1 ± 12.28 − 21.6 ± 12.54 − 21.6 ± 11.97 0.7305a 365医学网 转载请注明
0.6889b 365医学网 转载请注明
p value (gender) < 0.0001 365医学网 转载请注明
Differences at 8 weeks 365医学网 转载请注明
365医学网 转载请注明
< 0.0001a 365医学网 转载请注明
< 0.0001b 365医学网 转载请注明
men 26.1 ± 11.97 26.9 ± 11.75 −27.3 ± 11.86 − 27.9 ± 12.10 0.0225 365医学网 转载请注明
women 26.6 ± 12.07 27.8 ± 12.64 28.7 ± 13.19 − 28.6 ± 12.51 0.0858a 365医学网 转载请注明
0.0225b 365医学网 转载请注明
p value (gender) 0.0026 365医学网 转载请注明
0.0023a 365医学网 转载请注明
0.0026b 365医学网 转载请注明
DBP(mm Hg) 365医学网 转载请注明
Baseline men 98.6 ± 9.97 96.2 ± 9.78 94.6 ± 10.53 91.4 ± 12.27 < 0.0001 365医学网 转载请注明
women 96.7 ± 9.71 94.6 ± 10.31 93.0 ± 11.29 90.4 ± 11.64 365医学网 转载请注明
p value (gender) < 0.0001 365医学网 转载请注明
Differences at 4 weeks 365医学网 转载请注明
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men 12.0 ± 8.54 10.7 ± 7.66 10.1 ± 8.36 − 8.7 ± 8.13 0.0219 365医学网 转载请注明
women 10.7 ± 8.01 10.8 ± 8.61 9.6 ± 8.60 − 8.6 ± 8.90 0.0206a 365医学网 转载请注明
0.0166b 365医学网 转载请注明
p value (gender) 0.0602 365医学网 转载请注明
Differences at 8 weeks 365医学网 转载请注明
365医学网 转载请注明
0.0206a 365医学网 转载请注明
0.0403b 365医学网 转载请注明
men 17.0 ± 9.37 15.5 ± 8.56 14.4 ± 9.20 − 12.8 ± 9.22 0.0057 365医学网 转载请注明
women 15.7 ± 9.03 14.9 ± 9.40 13.6 ± 9.51 − 12.5 ± 9.87 0.0601a 365医学网 转载请注明
0.0023b 365医学网 转载请注明
p value (gender) 0.1035 365医学网 转载请注明
0.8275a 365医学网 转载请注明
0.0771b 365医学网 转载请注明
aAnalysis usingthe Mixed Model 1, age and gender as afixed effects, adjusted for the baseline of BP, BMI, smoking, drinking, exercise and education 365医学网 转载请注明
level. 365医学网 转载请注明
bAnalysis usingthe Mixed Model 2, adjusted for the baseline BPand statistically significant effects in Model 1. BPchanges at 4 weeks and 8 weeks, 365医学网 转载请注明
after beingadjusted for baseline BPand exercise. 365医学网 转载请注明
BMI: body mass index; BP: blood pressure; DBP: diastolic blood pressure; mm Hg: millimetres of mercury as units of pressure; SBP: systolic blood 365医学网 转载请注明
pressure. 365医学网 转载请注明
with angiotensin-converting enzyme (ACE) inhibitors cor- relates with a better outcome, compared with treatment with diuretics; whereas another study concludes that the 365医学网 转载请注明
response to specific treatment agents appears to differ 365医学网 转载请注明
between men and women.23 These findings also suggested that antihypertensive regimens need to be tailored accord- ing to gender. Some might argue that female patients are always more aware of the need for treatment and show bet- ter compliance; thus, could get a better BP-lowering effect. We also evaluated both the physician and patients’ self- 365医学网 转载请注明
compliance assessments, and found that there were 365医学网 转载请注明
365医学网 转载请注明
no significant differences between the male and female genders (p = 0.7517 and p = 0.0702, respectively). Also, given that the longitudinal BP response was appropriate in both men and women and that the study length was short, we did not consider male patients lacking compliance in our study. Although the cause for these gender-related dif- 365医学网 转载请注明
ferences in response to therapy is not certain, these gender 365医学网 转载请注明
differences are associated with sexual dimorphism in the physiological mechanisms that regulate arterial pressure, 365医学网 转载请注明
which can impact the male and female patients’ responses 365医学网 转载请注明
to different therapeutic approaches.24 365医学网 转载请注明
Downloaded from jra.sagepub.com at UNIV OF PENNSYLVANIA on August 5, 2016 365医学网 转载请注明
6 Journal of the Renin-Angiotensin-Aldosterone System 365医学网 转载请注明
Notably, gender-related differences also exist in the RAS, due to differential modulation by sex hormones.25,26 In 365医学网 转载请注明
our study, most patients were aged > 55 years (6601/11,312 365医学网 转载请注明
(58%)); and of these, 46% (3058/6601) of them were women. Given that the mean post-menopausal age is 56 365医学网 转载请注明
years in China,27 quite a few women in our study were in the 365医学网 转载请注明
post-menopausal period. Oestrogen regulates all compo- nents of the RAS, increasing the synthesis of angiotensino- gen, while decreasing the synthesis and activity of renin and ACE. Oestrogen decreases the expression of the angiotensin 365医学网 转载请注明
Type 1 receptor (AT1R) in target tissue, but increases the 365医学网 转载请注明
expression of Type 2 receptor AT2R.28,29 Studies in animal models show that oestrogen and RAS blockade may act syn- 365医学网 转载请注明
ergistically to downregulate the AT1R.30,31 Since valsartan is an angiotensin II receptor blocker (ARB), the Val/Aml com- 365医学网 转载请注明
bination therapy might inhibit RAS activation and provide a 365医学网 转载请注明
better antihypertensive effect for post-menopausal women. A small study among 51 post-menopausal hypertensive women showed that the BP-lowering effect of the ARB 365医学网 转载请注明
irbesartan is augmented by co-administration with 17-estra- 365医学网 转载请注明
diol, suggesting there are potentiating effects of the two dif- ferent antihypertensive mechanisms.32 Of course, further 365医学网 转载请注明
study into the mechanisms of the gender differences in 365医学网 转载请注明
hypertension treatment is needed. 365医学网 转载请注明
Another finding of our study was that for all of the enrolled patients, the proportion of patients not achieving 365医学网 转载请注明
the target SBP (⩽140 mm Hg) increased with age; how- 365医学网 转载请注明
ever, the proportion of patients not achieving the target DBP (⩽90 mm Hg) was the opposite. 365医学网 转载请注明
Elevated BP is an important cardiovascular risk factor. 365医学网 转载请注明
Although the target DBP and SBP are defined by guidelines, 365医学网 转载请注明
DBP has historically taken precedence in hypertension man- agement; however, there is strong evidence that SBP is superior to DBP as a predictor of cardiovascular events, par- ticularly in the elderly.33 Stamler et al.34 found that SBP has 365医学网 转载请注明
a stronger association with cardiovascular risk, as compared 365医学网 转载请注明
with DBP, in middle-aged and elderly individuals. Moreover, the superior predictive ability of SBP was also confirmed in 365医学网 转载请注明
a meta-analysis of 61 prospective observational studies that 365医学网 转载请注明
recorded BP and cause-specific mortality.35 With an increas- ing proportion of aging population, the prevalence of hyper- 365医学网 转载请注明
tension and related cardiovascular morbidity in Asian 365医学网 转载请注明
patients continues to rise, placing a substantial and escalat- ing social and economic burden on this region.36 The preva- 365医学网 转载请注明
lence of hypertension in the Chinese population is 39% 365医学网 转载请注明
overall, 59.4% in those aged > 60 years and 72.8% in those 365医学网 转载请注明
aged > 75 years.37 The age-specific prevalence of hyperten- sion increased with age, throughout the age range. In our 365医学网 转载请注明
study, the mean age of the male patients was 57.4 ± 14.27 365医学网 转载请注明
years and that of female patients was 59.8 ± 13.09 years. 365医学网 转载请注明
The proportion of patients who did not achieve the target 365医学网 转载请注明
SBP increased with age. An elevated SBP increases the risk of CVD, mortality and renal function decline, and that risk may increase at lower SBP levels in the Asian than in the 365医学网 转载请注明
Western population. Hence, reducing SBP should be the 365医学网 转载请注明
365医学网 转载请注明
primary goal in the management of hypertension, particu- larly as the patients age.38 365医学网 转载请注明
There were several limitations in our study. First, the 365医学网 转载请注明
focus was only on short-term BP lowering. The long-term clinical outcomes might be more important in elucidating 365医学网 转载请注明
gender differences and cardiovascular events. Besides, 686 365医学网 转载请注明
(6.06%) of the subjects of this study had to take additional 365医学网 转载请注明
antihypertensive agents to control their BP. The most used combined antihypertensive agents were metoprolol (1.67%) 365医学网 转载请注明
and hydrochlorothiazide (1.45%). Because the majority 365医学网 转载请注明
(10,626 out of 11,312 (93.94%)) of the subjects in this study received only Val/Aml SPC for BP control, we con- sider that the potential impact of additional antihyperten- 365医学网 转载请注明
sive treatment on the BP outcome is limited. We will avoid 365医学网 转载请注明
this kind of possible bias in future studies. Moreover, we did not control or monitor the patients’ sodium or protein 365医学网 转载请注明
intake, although that could be extremely difficult to imple- 365医学网 转载请注明
ment in such a large-scale observational study. 365医学网 转载请注明
Conclusions 365医学网 转载请注明
For all the patients enrolled in our study, the proportion of patients not achieving the target SBP increased with age; however, the proportion not achieving the target DBP was the opposite. Although the mechanisms responsible for gender differences in the treatment response to Val/Aml among Chinese patients were not addressed, our findings indicated that women might have a better SBP-lowering effect with such therapy. Gender might be a factor for con- sideration in the decision-making process of individual- ised antihypertensive therapy, in the future. 365医学网 转载请注明
Acknowledgements 365医学网 转载请注明
The contributors to the investigation of ‘Gender difference in response to valsartan/amlodipine single-pill combination in essential hypertension’ using China STATUS II data are grate- fully acknowledged. 365医学网 转载请注明
Declaration of conflicting interests 365医学网 转载请注明
The author(s) d no potential conflicts of interest with respect to the research, authorship, and/or publication of this article. 365医学网 转载请注明
Funding 365医学网 转载请注明
The author(s) received no financial support for the research, authorship, and/or publication of this article. 365医学网 转载请注明
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作者简介
陈慧
单位:福建省立医院
简介: 从医35年,福建省立医院.省心血管病研究所内科二级主任医师、高血压研究室主任、福建医科大学省立临
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