1 Department of Cardiology, Nanfang Hospital, Southern Medical University, Guangzhou,
China;
2 Clinical Medicine Research Center, the Affiliated Hospital at Shunde, Southern Medical
University (the First People's Hospital of Shunde), Foshan, China
��The authors contributed equally.
Corresponding author: Professor Dingli Xu, Department of Cardiology, Nanfang Hospital,
Southern Medical University, 1838 North Guangzhou Avenue, Guangzhou 510515, China.
Tel.: + 86 20 61641493, Fax: + 86 20 61360416, email: dinglixu@fimmu.com
We are so thankful for the commentary by Dr Meier et al. [1] on our recently published
paper on BMC medicine [2]. We believe the commentary is very important in the field
of hypertension, and it is helpful to health professionals and those engaged in the
primary prevention of cardiovascular disease (CVD).
Epidemiological studies have showed that individuals with blood pressure (BP) of 120-139/80-89mmHg
are with a high risk to progress to sustained hypertension. However, arguments against
using the definition of prehypertension include that this term would create anxiety
among the general population, and there is heterogeneity within this category of prehypertension,
because the risk of progressing to hypertension and developing CVD is higher in patients
with BP 130��139/85��89 mmHg range (high range) than in those with BP 120��129/80��84
mmHg (low range) [3]. In contrast to the seventh report of the Joint National Committee
on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (JNC 7),
other international and national hypertension guidelines did not adopt the term of
��prehypertension�� [4, 5]. In our study, we found that prehypertension, even in the
low range, elevates the risk of CVD after adjusting for multiple cardiovascular risk
factors. These findings reaffirms the importance of the definition of ��prehypertension��
rather than being ��normal�� for individuals with systolic BP of 120 to 139 mm Hg
or diastolic BP of 80 to 89 mm Hg. Furthermore, our data also indicated the inhomogeneity
of the prehypertension category, as the risk of CVD was significantly higher in paticipants
with high-range prehypertension than those with low-range prehypertension.
Dr Meier et al have discussed that one endpoint that was not assessed in the included
studies was the impact of prehypertension on the kidneys. This is a very interesting
topic. Actually, we had performed another systematic review and meta-analysis on the
topic of prehypertension and incidence of end-stage renal disease (ESRD). Data from
1, 003,793 participants were derived from six prospective cohort studies. Our results
showed that even low-range prehypertension increased the risk of ESRD compared with
optimal blood pressure (RR 1.44, 95% CI 1.19��1.74), and the risk further increased
with high-range prehypertension (RR 2.02, 95% CI 1.70��2.40). The relative risk was
significantly higher in the high-range than in the low-range prehypertensive populations
(P = 0.01). This paper was just published online [6]. These results further support
the findings of our study on CVD and the definition of ��prehypertension��.
Furthermore, Dr Meier et al have discussed therapeutic implications of our study on
prehypertension. We agree that whether treatment of pre-hypertension can reduces cardiovascular
risk is still with controversies. Considering the great incidence of prehypertension
is up to 30��50% [7] and the robust and significant association between prehypertension
and CVD incidence documented in our study, successful intervention in such a large
population could therefore have a major public health impact. Based on the lack of
prospective, randomized trials examining the effects of anti-hypertensive therapy
on reducing cardiovascular events specifically in prehypertensives, professional societies
do not recommend drug treatment in prehypertension, even in high-range prehypertension
[5]. A recent meta-analysis showed that in patients with clinical history of CVD but
without hypertension, antihypertensive treatment was associated with decreased risk
of stroke, CHF, composite CVD events, and all-cause mortality [8]. However, the recently
published study-the AQUARIUS randomized clinical trial [9], showed that among participants
with pre-hypertension and coronary artery disease, the use of aliskiren compared with
placebo did not result in improvement or slowing of progression of coronary atherosclerosis.
This study should be interpreted with caution that the negative results maybe caused
by the small sample (458 cases) and short follow-up duration (104 weeks), as well
as the dilution effect of broadly use of statins, ��-blockers and anti-platelets medicine.
In conclusion, there is a great gap to be covered between epidemiological studies
and randomized controlled studies in prehypertension. Prehypertensive individuals
are at a high risk to progress to sustained hypertension, as well as CVD and renal
damage, so we agree with Dr Meier et al that periodic screening is important. For
therapeutic implications, we believe that lifestyle intervention is the mainstay of
treatment for prehypertension for the general population. However, since the incidence
of CVD increased across the whole range of prehypertension, high-risk subpopulations
with prehypertension are need to be selected for future controlled trials of pharmacological
treatment. Many risk factors, such as elevated C-reactive protein, glucose abnormality,
and dyslipidemia had been reported to be associated with prehypertension and CVD [10-12].
These associated risk factors are indicators for selection of subpopulations, especially
in high-range prehypertension, for future controlled trials of pharmacological treatment.
References:
1. Meier P, Messerli FH, Baumbach A, Lansky AJ: Pre-hypertension: another `pseudodisease��?
BMC Med 2013, 11:211.
2. Huang Y, Wang S, Cai X, Mai W, Hu Y, Tang H, Xu D: Prehypertension and incidence
of cardiovascular disease: a meta-analysis. BMC Med 2013, 11:177.
3. Gupta P, Nagaraju SP, Gupta A, Mandya CK: Prehypertension - time to act. Saudi
J Kidney Dis Transpl 2012, 23(2):223-233.
4. National Clinical Guideline Centre (UK): Hypertension: The Clinical Management
of Primary Hypertension in Adults: Update of Clinical Guidelines 18 and 34 [Internet].
London: Royal College of Physicians (UK); 2011 Aug.
5. Mancia G, Fagard R, Narkiewicz K, Redon J, Zanchetti A, Bohm M, Christiaens T,
Cifkova R, De Backer G, Dominiczak A et al: 2013 ESH/ESC Guidelines for the management
of arterial hypertension: The Task Force for the management of arterial hypertension
of the European Society of Hypertension (ESH) and of the European Society of Cardiology
(ESC). Eur Heart J 2013, 34(28):2159-2219.
6. Huang Y, Cai X, Zhang J, Mai W, Wang S, Hu Y, Ren H, Xu D: Prehypertension and
Incidence of ESRD: A Systematic Review and Meta-analysis. Am J Kidney Dis 2013, http://dx.doi.org/10.1053/j.ajkd.20
13.07.024
7. Elliott WJ, Black HR: Prehypertension. Nat Clin Pract Cardiovasc Med 2007, 4(10):538-548.
8. Thompson AM, Hu T, Eshelbrenner CL, Reynolds K, He J, Bazzano LA: Antihypertensive
treatment and secondary prevention of cardiovascular disease events among persons
without hypertension: a meta-analysis. JAMA 2011, 305(9):913-922.
9. Nicholls SJ, Bakris GL, Kastelein JJ, Menon V, Williams B, Armbrecht J, Brunel
P, Nicolaides M, Hsu A, Hu B et al: Effect of aliskiren on progression of coronary
disease in patients with prehypertension: the AQUARIUS randomized clinical trial.
JAMA 2013, 310(11):1135-1144.
10. Tanaka F, Makita S, Onoda T, Tanno K, Ohsawa M, Itai K, Sakata K, Onodera M, Koeda
Y, Kawarura K et al: Prehypertension subtype with elevated C-reactive protein: risk
of ischemic stroke in a general Japanese population. Am J Hypertens 2010, 23(10):1108-1113.
11. Kokubo Y, Okamura T, Watanabe M, Higashiyama A, Ono Y, Miyamoto Y, Furukawa Y,
Kamide K, Kawanishi K, Okayama A et al: The combined impact of blood pressure category
and glucose abnormality on the incidence of cardiovascular diseases in a Japanese
urban cohort: the Suita Study. Hypertens Res 2010, 33(12):1238-1243.
12. Egan BM, Julius S: Prehypertension: risk stratification and management considerations.
Curr Hypertens Rep 2008, 10(5):359-366.
Commentary
Prehypertension: Gap between Epidemiological Studies and Randomized Controlled Studies
Yuli Huang (2013-10-02 10:58) Department of Cardiology, Nanfang Hospital, Southern Medical University, Guangzhou, China
Yuli Huang, 1, 2 * Xiaoyan Cai, 2 * and Dingli Xu1
1 Department of Cardiology, Nanfang Hospital, Southern Medical University, Guangzhou, China;
2 Clinical Medicine Research Center, the Affiliated Hospital at Shunde, Southern Medical University (the First People's Hospital of Shunde), Foshan, China
��The authors contributed equally.
Corresponding author: Professor Dingli Xu, Department of Cardiology, Nanfang Hospital, Southern Medical University, 1838 North Guangzhou Avenue, Guangzhou 510515, China. Tel.: + 86 20 61641493, Fax: + 86 20 61360416, email: dinglixu@fimmu.com
We are so thankful for the commentary by Dr Meier et al. [1] on our recently published paper on BMC medicine [2]. We believe the commentary is very important in the field of hypertension, and it is helpful to health professionals and those engaged in the primary prevention of cardiovascular disease (CVD).
Epidemiological studies have showed that individuals with blood pressure (BP) of 120-139/80-89mmHg are with a high risk to progress to sustained hypertension. However, arguments against using the definition of prehypertension include that this term would create anxiety among the general population, and there is heterogeneity within this category of prehypertension, because the risk of progressing to hypertension and developing CVD is higher in patients with BP 130��139/85��89 mmHg range (high range) than in those with BP 120��129/80��84 mmHg (low range) [3]. In contrast to the seventh report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (JNC 7), other international and national hypertension guidelines did not adopt the term of ��prehypertension�� [4, 5]. In our study, we found that prehypertension, even in the low range, elevates the risk of CVD after adjusting for multiple cardiovascular risk factors. These findings reaffirms the importance of the definition of ��prehypertension�� rather than being ��normal�� for individuals with systolic BP of 120 to 139 mm Hg or diastolic BP of 80 to 89 mm Hg. Furthermore, our data also indicated the inhomogeneity of the prehypertension category, as the risk of CVD was significantly higher in paticipants with high-range prehypertension than those with low-range prehypertension.
Dr Meier et al have discussed that one endpoint that was not assessed in the included studies was the impact of prehypertension on the kidneys. This is a very interesting topic. Actually, we had performed another systematic review and meta-analysis on the topic of prehypertension and incidence of end-stage renal disease (ESRD). Data from 1, 003,793 participants were derived from six prospective cohort studies. Our results showed that even low-range prehypertension increased the risk of ESRD compared with optimal blood pressure (RR 1.44, 95% CI 1.19��1.74), and the risk further increased with high-range prehypertension (RR 2.02, 95% CI 1.70��2.40). The relative risk was significantly higher in the high-range than in the low-range prehypertensive populations (P = 0.01). This paper was just published online [6]. These results further support the findings of our study on CVD and the definition of ��prehypertension��.
Furthermore, Dr Meier et al have discussed therapeutic implications of our study on prehypertension. We agree that whether treatment of pre-hypertension can reduces cardiovascular risk is still with controversies. Considering the great incidence of prehypertension is up to 30��50% [7] and the robust and significant association between prehypertension and CVD incidence documented in our study, successful intervention in such a large population could therefore have a major public health impact. Based on the lack of prospective, randomized trials examining the effects of anti-hypertensive therapy on reducing cardiovascular events specifically in prehypertensives, professional societies do not recommend drug treatment in prehypertension, even in high-range prehypertension [5]. A recent meta-analysis showed that in patients with clinical history of CVD but without hypertension, antihypertensive treatment was associated with decreased risk of stroke, CHF, composite CVD events, and all-cause mortality [8]. However, the recently published study-the AQUARIUS randomized clinical trial [9], showed that among participants with pre-hypertension and coronary artery disease, the use of aliskiren compared with placebo did not result in improvement or slowing of progression of coronary atherosclerosis. This study should be interpreted with caution that the negative results maybe caused by the small sample (458 cases) and short follow-up duration (104 weeks), as well as the dilution effect of broadly use of statins, ��-blockers and anti-platelets medicine.
In conclusion, there is a great gap to be covered between epidemiological studies and randomized controlled studies in prehypertension. Prehypertensive individuals are at a high risk to progress to sustained hypertension, as well as CVD and renal damage, so we agree with Dr Meier et al that periodic screening is important. For therapeutic implications, we believe that lifestyle intervention is the mainstay of treatment for prehypertension for the general population. However, since the incidence of CVD increased across the whole range of prehypertension, high-risk subpopulations with prehypertension are need to be selected for future controlled trials of pharmacological treatment. Many risk factors, such as elevated C-reactive protein, glucose abnormality, and dyslipidemia had been reported to be associated with prehypertension and CVD [10-12]. These associated risk factors are indicators for selection of subpopulations, especially in high-range prehypertension, for future controlled trials of pharmacological treatment.
References:
1. Meier P, Messerli FH, Baumbach A, Lansky AJ: Pre-hypertension: another `pseudodisease��? BMC Med 2013, 11:211.
2. Huang Y, Wang S, Cai X, Mai W, Hu Y, Tang H, Xu D: Prehypertension and incidence of cardiovascular disease: a meta-analysis. BMC Med 2013, 11:177.
3. Gupta P, Nagaraju SP, Gupta A, Mandya CK: Prehypertension - time to act. Saudi J Kidney Dis Transpl 2012, 23(2):223-233.
4. National Clinical Guideline Centre (UK): Hypertension: The Clinical Management of Primary Hypertension in Adults: Update of Clinical Guidelines 18 and 34 [Internet]. London: Royal College of Physicians (UK); 2011 Aug.
5. Mancia G, Fagard R, Narkiewicz K, Redon J, Zanchetti A, Bohm M, Christiaens T, Cifkova R, De Backer G, Dominiczak A et al: 2013 ESH/ESC Guidelines for the management of arterial hypertension: The Task Force for the management of arterial hypertension of the European Society of Hypertension (ESH) and of the European Society of Cardiology (ESC). Eur Heart J 2013, 34(28):2159-2219.
6. Huang Y, Cai X, Zhang J, Mai W, Wang S, Hu Y, Ren H, Xu D: Prehypertension and Incidence of ESRD: A Systematic Review and Meta-analysis. Am J Kidney Dis 2013, http://dx.doi.org/10.1053/j.ajkd.20 13.07.024
7. Elliott WJ, Black HR: Prehypertension. Nat Clin Pract Cardiovasc Med 2007, 4(10):538-548.
8. Thompson AM, Hu T, Eshelbrenner CL, Reynolds K, He J, Bazzano LA: Antihypertensive treatment and secondary prevention of cardiovascular disease events among persons without hypertension: a meta-analysis. JAMA 2011, 305(9):913-922.
9. Nicholls SJ, Bakris GL, Kastelein JJ, Menon V, Williams B, Armbrecht J, Brunel P, Nicolaides M, Hsu A, Hu B et al: Effect of aliskiren on progression of coronary disease in patients with prehypertension: the AQUARIUS randomized clinical trial. JAMA 2013, 310(11):1135-1144.
10. Tanaka F, Makita S, Onoda T, Tanno K, Ohsawa M, Itai K, Sakata K, Onodera M, Koeda Y, Kawarura K et al: Prehypertension subtype with elevated C-reactive protein: risk of ischemic stroke in a general Japanese population. Am J Hypertens 2010, 23(10):1108-1113.
11. Kokubo Y, Okamura T, Watanabe M, Higashiyama A, Ono Y, Miyamoto Y, Furukawa Y, Kamide K, Kawanishi K, Okayama A et al: The combined impact of blood pressure category and glucose abnormality on the incidence of cardiovascular diseases in a Japanese urban cohort: the Suita Study. Hypertens Res 2010, 33(12):1238-1243.
12. Egan BM, Julius S: Prehypertension: risk stratification and management considerations. Curr Hypertens Rep 2008, 10(5):359-366.
Competing interests
None declared
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