1804 Chin Med J 2012;125(10):1804-1810

Meta analysis
Effect of angiotensin receptor blockers in the prevention of type 2
diabetes and cardiovascular events: a meta-analysis of
randomized trials
SONG Hui-fen, WANG Su and LI Hong-wei

Keywords: angiotensin receptor blockers; hypertension; diabetes mellitus; cardiovascular events

Background As the incidence of type 2 diabetes is rapidly increasing, prevention of the disease should be considered
as a crucial objective in the near future. Several studies have shown angiotensin receptor blockers (ARBs) may
contribute to the prevention of new-onset type 2 diabetes. This study was conducted to determine if ARBs as
monotherapy or combination therapy may experience a decreased incidence of new-onset type 2 diabetes and prevent
cardiovascular events.
Methods Relevant experimental and clinical studies were identified by searching MEDLINE (1969 to May 30, 2011) to
extract a consensus of trial data involving the effect of ARBs on prevention of new-onset type 2 diabetes and
cardiovascular events. Studies were included if they were randomized controlled trials versus placebo/routine therapy. A
random-effects model was utilized. Subgroup and sensitivity analyses were conducted.
Results Eleven trials were identified, including 82 738 patients. ARBs prevented new-onset type 2 diabetes (odds ratio
0.8 (95% CI 0.76, 0.85)). Regardless of indication for use, essential hypertension (seven trials), impaired glucose
tolerance (one trial), cardiocerebrovascular disease (two trials) or heart failure (one trial), reductions in new-onset type 2
diabetes were maintained (0.75 (0.69, 0.82), 0.85 (0.78, 0.92), 0.80 (0.76, 0.85) and 0.80 (0.64, 0.99), respectively). No
statistical heterogeneity was observed for any evaluation. However, ARBs did not significantly reduce the odds of
all-cause mortality, myocardial infarction and heart failure versus control therapy among all of these studies. But ARBs
did reduce the odds of cardiac death and heart failure among the heart failure study versus control therapy.
Conclusion ARBs have significant ability to reduce risk of developing new-onset type 2 diabetes but does not improve
cardiovascular outcomes over the study follow-up periods among all of included studies.
Chin Med J 2012;125(10):1804-1810

T he incidence of type 2 diabetes is increasing

worldwide.1 In China, because of the rapid change
in lifestyle, prevalence of total diabetes and pre-diabetes
have been 9.7% and 15.5%, respectively among Chinese
adults, accounting for 92.4 million adults with diabetes
and 148.2 million adults with pre-diabetes.2 Type 2
diabetes is becoming a major health problem associated
with excess morbidity and mortality and posing an
enormous and escalating economic burden.1 The public
health impact of type 2 diabetes makes it important to
continue efforts toward primary prevention of type 2
diabetes.
Type 2 diabetes which often occurs in association with
hypertension, accelerates the development of
hypertension-induced cardiovascular disease and
hypertension is also a strong predictor of the development
of diabetes.3
Thus, the prevention of diabetes is important in the
management of hypertension. Angiotensin receptor
blockers (ARBs), as a new type of antihypertensive
agents, enhance insulin sensitivity and therefore benefit
patients at high risk of developing type 2 diabetes. ARBs
have been studied versus placebo or active therapy among
many clinical trials in patients with hypertension, high
risk of cardiovascular disease, heart failure and/or
impaired glucose tolerance. In pre-specified or post-hoc
analysis, the impact of ARBs usage on the incidence of
new-onset type 2 diabetes has been evaluated. Some trials
found a benefit of ARBs, while many trials shown ARBs
might contribute to the prevention of new-onset type 2
diabetes, others trials did not found significant difference
between groups in terms of new-onset diabetes.4-14
Moreover, if ARBs could provide cardiovascular events
benefit in patients with hypertension especially combined
with high risk factors is yet uncertain. There is an
increasing need to synthesize all the evidence. This
meta-analysis aims to determine the effect of ARBs in
prevention of type 2 diabetes and cardiovascular events.
DOI: 10.3760/cma.j.issn.0366-6999.2012.10.022
Department of Cardiology, Beijing Friendship Hospital, Capital
Medical University, Beijing 100050, China (Song HF, Wang S and
Li HW)
Correspondence to: LI Hong-wei, Department of Cardiology,
Beijing Friendship Hospital, Capital Medical University, Beijing
100050, China (Tel: 86-10-63139780. Fax: 86-10-63023261.
Email: mcw19656@yahoo.com.cn)
This work was supported by a grant from the National Natural
Science Foundation of China (No. 30971240).
The authors have no conflict of interest to declare.
Chinese Medical Journal 2012;125(10):1804-1810 1805

METHODS Statistical analyses

Selection criteria
Studies were included in this meta-analysis if they were
randomized controlled trials and met all the following
criteria: (1) comparison between ARBs with placebo or
routine treatment; (2) inclusion of individuals with
hypertension or others high risk factors; (3) new-onset
type 2 diabetes and cardiovascular outcomes as primary
endpoint, a pre-specified end-point or as a part of
post-hoc analysis; (4) median or average follow-up of at
least 1 year, recruiting more than 100 patients. Trials
which did not meet the above requirements were
excluded from the meta-analysis.
Search strategy
Experimental and clinical studies of relevance to ARBs
and prevention of type 2 diabetes were identified by a
search of MEDLINE (1969 to May 30, 2011). The search
was limited to English-language articles in humans.
Medical subject Search terms including ARBs, RAS
blockade/antagonist and individual drug names within
these classes were combined with “diabetes,”
“pre-diabetes,” “hypertension,” “high risk,” “coronary
disease,” “cardiovascular outcome,” and “randomized,
controlled, trials’’. Reference lists of identified articles,
including previous meta-analyses and reviews on the
field, were evaluated for additional relevant studies and
information.
Data extraction and quality assessment
Titles and abstracts of the retrieved citations were
screened by one of the authors (Song) and full texts of the
articles thought to be potentially eligible were retrieved.
Two of the authors (Song and Wang) independently
reviewed these for eligibility. Data about characteristics
of the participants, interventions, comparisons, and
outcomes (new-onset type 2 diabetes and cardiovascular
events) were extracted from each study. The
methodological quality of included randomized
controlled trials was assessed using standard criteria
(allocation concealment, intention-to-treat analysis,
blinding and completeness of follow-up). Disagreements
between the two authors were resolved by consensus.
New-onset type 2 diabetes and cardiovascular events was
treated as a dichotomous variable and reported as odds
ratios (ORs) with 95% confidential intervals (CIs). Pooled
ORs were calculated using the DerSimonian and Laird
random-effects model or the Mantel-Haenszel
fixed-effects model, depending on the existence or not of
heterogeneity of treatment effects across studies.
The percentage variability of the pooled ORs attributable
to heterogeneity among studies was quantified using the
I2 statistic test.15 Typically, values above 50% are deemed
to suggest large between-study heterogeneity, Sensitivity
analysis was performed by reanalyzing the data using the
fixed-effects model. Evidence of publication bias was
examined by constructing funnel plots.16
Statistical analyses were performed using Review
Manager (RevMan (Computer program), version 5.1 for
Windows, Copenhagen: The Nordic Cochrane Centre,
The Cochrane Collaboration). A value of P <0.05 was
considered statistically significant.
RESULTS
Study selection
Our search identified 11 randomized controlled trials for
inclusion.4-14 These trials enrolled 82 738 patients, of
whom 41 356 were randomized to ARBs therapy, while
the remainder received active control or placebo.
Baseline characteristics
The baseline characteristics of patients are listed in Table
1. Seven trials were performed in patients with essential
hypertension and one trial concerned patients with heart
failure,6 one trial in patients with impaired glucose
tolerance,9 two trials performed in patients with
cardiocerebrovascular diseases.10,12
Five trials compared ARBs with placebo.6,7,10-12 While
two trials included a diuretic and/or a beta-blocker as
comparator4,8 and two trials used amlodipine as reference
drug,5,13 one trials used nateglinide or placebo as control,9
one study compared candesartan with non-ARBs.14

Table 1. Characteristics of studies included in the meta-analysis

Patients Mean age Male Mean follow-up
Studies Intervention Indication for use
(n) (years) (%) (years)
ALPINE (2003) Candesartan 196 HCTZ 196 392 55.0 48.0 1.0 Primary HTN
CASE-J (2008) Candesartan 2354 Amlodipine 2349 4728 63.8 55.2 3.2 HTN
CHARM (2003) Candesartan 3803 Placebo 3796 7599 66.0 68.4 3.1 HF
HIJ-CREATE (2009) Candesartan 1024 Non-ARB 1025 2049 64.8 80.2 4.2 HTN with CVD
KYOTO HEART (2009) Valsartan 1517 Placebo 1514 3031 66.0 57.0 3.3 HTN with high risk of cardiac events
LIFE (2002) Losartan 4605 Atenolol 4588 9193 66.9 46.0 4.8 essential HTN and LVH
NAVIGATOR (2010) Valsartan 4631 Nateglinide or placebo 4675 9306 63.7 49.4 5.0 IGT with CVD
PROFESS (2008) Telmisartan 10146 Placebo 10186 20332 66.1 64.0 2.5 ischemic storke
SCOPE (2003) Candesartan 2477 Placebo 2460 4937 76.4 35.5 3.7 HTN
TRANSCEND (2008) Telmisartan 2954 Placebo2972 5926 66.9 57.0 4.7 CVD or DM
VALUE (2004) Valsartan 7649 Amlodipine 7596 15245 67.2 57.5 4.2 HTN with high risk of cardiac events
HTN: hypertension; CVD: cardiovascular disease; HF: heart failure; ARBs: angiotensin receptor blockers; HCTZ: hydrochlorothiazide; IGT: Impaired glucose tolerance;
MI: myocardial infarction; DM: diabetes mellitus.
1806 Chin Med J 2012;125(10):1804-1810

3685 new cases (12.7%) in subjects

treated with placebo or other agents
(OR 0.8, 95% CI (0.76, 0.85)).
ARBs were associated with
significant reduction in the risk of
new-onset type 2 diabetes in
patients with primary hypertension
(OR 0.75, (0.69, 0.82)), heart failure
(OR 0.80, (0.64, 0.99)), cardiocere-
brovascular diseases (OR 0.84,
(0.72, 0.97)) or impaired glucose
tolerance (OR 0.85, (0.78, 0.92))
(Figure 1). There was no
heterogeneity and no evidence for
publication bias.

Incidence of cardiovascular events

ARBs were not associated with
significant reduction in the risk of
all-cause death in patients with
essential hypertension (OR 0.95,
(0.87, 1.05)), heart failure (OR 0.92,
(0.82, 1.04)), cardiocerebrovascular
diseases (OR 1.04, (0.95, 1.13)) or
Figure 1. Studies or subgroup analyses evaluating incidence of new-onset type 2 diabetes. impaired glucose tolerance (OR
0.90, (0.77, 1.06)), when compared
with controls (Figure 2). There was
low heterogeneity and no evidence
for publication bias.

Similarly, ARBs were not associated

with significant reduction in the risk
of cardiovascular death in patients
with essential hypertension (OR
0.94, (0.84, 1.04)), cardiocerebro-
vascular diseases (OR 0.93, (0.77,
1.12)) or impaired glucose tolerance
(OR 1.12, (0.87, 1.44)), when
compared with controls. Except
among patients with heart failure,
significant reduction in cardiac
death (OR 0.88 (0.78, 0.98))
occurred (Figure 3). There was no
heterogeneity and no evidence for
publication bias.

The results were similar when ARBs

were compared with either placebo
or with active treatment for the
outcome of myocardial infarction,
there were no significant deference
occurred in patients with heart
Figure 2. Effect of ARBs on all-cause death in patients with different baseline diseases. failure (OR 1.07, (0.75, 1.53)),
ARBs: angiotensin receptor blockers. cardiocerebrovascular diseases (OR
0.89, (0.71, 1.13)) or impaired
Incidence of new-onset type 2 diabetes glucose tolerance (OR 0.99, (0.78,
Overall, there were 3111 new cases of type 2 diabetes 1.26)), but in patients with primary hypertension, a
(10.7%) in patients treated with ARBs compared with significantly higher risk of myocardial infarction occurred
Chinese Medical Journal 2012;125(10):1804-1810 1807

For the outcome of heart failure,

among patients with primary
hypertension (OR 0.90, (0.80,
1.02)), heart failure (OR 0.78, (0.70,
0.87)), cardiocerebrovascular diseases
(OR 1.04, (0.87, 1.25)) or impaired
glucose tolerance (OR 0.98, (0.73,
1.31)), respectively (Figure 5).
There was moderate heterogeneity
and no evidence for publication
bias.

DISCUSSION

Our meta-analysis provides

evidence on the ability of ARBs to
reduce the incidence of new-onset
type 2 diabetes, when compared to
placebo in patients with essential
hypertension, impaired glucose
tolerance and/or high cardiovascular
risk. In this meta-analysis, 58 122
patients without diabetes were
evaluated for development of
new-onset type 2 diabetes.
Figure 3. Effect of ARBs on cardiovascular death in patients with different baseline Pharmacological treatment based on
diseases. ARBs: angiotensin receptor blockers. ARBs significantly reduced the
odds of new-onset type 2 diabetes
compared to control groups.

Although we found that ARBs can

help to prevent the incidence of
new-onset type 2 diabetes in
patients with aforementioned
diseases. The mechanisms
underlying the prevention of
new-onset type 2 diabetes by ARBs
are complex and not fully
elucidated. There are several
possible explanations for this effect.

It has been shown that the

antidiabetic effects of ARBs may be
due to vasodilatory actions that
increase skeletal muscle blood flow,
which are associated with increased
insulin sensitivity. This has been
supported by several studies in
patients and animals.17-19 Secondly,
the increased adiponectin levels
associated with ARBs therapy are
accompanied by reduced insulin
levels and improved insulin
sensitivity. Adiponectin is an
Figure 4. Effect of ARBs on myocardial infarction in patients with different baseline adipose-derived factor that
diseases. ARBs: angiotensin receptor blockers. augments and mimics metabolic
actions of insulin by increasing fatty
(OR 1.11, (1.00, 1.24)) (Figure 4). There was low acid oxidation and insulin-mediated glucose disposal in
heterogeneity and no evidence for publication bias. skeletal muscle as well as decreasing hepatic glucose
1808
Figure 5. Effect of ARBs on heart failure in patients with different baseline diseases.
ARBs: angiotensin receptor blockers.
output.20 Thirdly, there may be direct effects of ARBs to
augment insulin-stimulated glucose uptake and promote
differentiation of adipocytes.21 Moreover, new-onset
diabetes could also be prevented through direct effects on
the pancreas by drugs that block the RAS. Animal studies
have found that RAS blockade is associated with
protection of the pancreatic islets from glucotoxicity and
restoration of beta-cell mass.22 In addition, some ARBs
have been reported to activate peroxisome
proliferator-activated receptor receptor-γ activity, which
are contributing to improve insulin sensitivity.23 Finally,
ARBs therapy may reduce insulin resistance by other
mechanisms, such as inhibited NAD(P)H oxidase, the
consequent reduction in oxidative stress that also
contribute to nitric oxide bioavailability which might also
contribute to improve glucose homeostasis. These
mechanisms are not mutually exclusive and it is possible
that several may combine to provide the beneficial effects
on metabolic function.
Since type 2 diabetes increase the risk of cardiovascular
events, it could be assumed that reducing the incidence of
new-onset type 2 diabetes would result in fewer events.
However, our findings demonstrated that among ARBs
trials evaluating new-onset type 2 diabetes, there were no
significant differences in all-cause mortality,
cardiovascular end points versus control therapy.
Effects of ARBs among involved trials in primary or
cardiovascular outcomes are controversial. In the
Chin Med J 2012;125(10):1804-1810
KYOTO HEART study,7 the median
follow-up period was 3.27 years. In
both groups, blood pressure at
baseline was 157/88 and 133/76
mmHg at the end of study.
Compared with non-ARBs arm,
valsartan add-on arm had fewer
primary endpoints. Valsartan add-on
treatment to improve blood pressure
control prevented more
cardiovascular events than
conventional non-ARBs treatment
in high-risk hypertensive patients in
Japan. Moreover, these benefits
cannot be entirely explained by a
difference in blood pressure control.
In the LIFE study,8 despite similar
falls in blood pressure, losartan
appeared to be more effective in
reducing the primary endpoint, as
well as reducing death from
cardiovascular disease and all cause
mortality. However, the VALUE
study13 demonstrated no difference
in the cardiac outcomes between
valsartan or amlodipine treatment
despite better blood pressure control
in the amlodipine group. Although
there was a 23% lower incidence of
new-onset type 2 diabetes in patients treated with
valsartan compared to patients treated with amlodipine.
The recently published HIJ-CREATE study14 aimed to
test whether candesartan can reduce the incidence of
cardiovascular events compared with non-ARBs-based
standard pharmacotherapy in coronary artery disease
patients with hypertension. During a median follow-up of
4.2 years, candesartan showed no significant differences
in major adverse cardiovascular event (MACE) compared
with the non-ARBs treatment group. In the PRoFESS and
TRANSCEND study,10,12 therapy with telmisartan did not
significantly lower the rate of major cardiovascular
events.
There are several possible reasons that ARBs did not
improve cardiovascular outcomes. We limited our
meta-analysis to studies that also evaluated new-onset
type 2 diabetes. When evaluating the totality of data in
heart failure, ARBs provide clear mortality benefit in
patients with heart failure.24 Our findings in heart failure
trial were also consistent with it. In addition, the benefit
of ARBs has also been smaller in recent studies when
compared with observed historically, possibly because of
greater use of other effective therapies.9,10,13,25,26 These
factors may have diluted any potential benefit of ARBs.
Furthermore, clinical studies failed to demonstrate any
efficacy. This may be accountable by the relatively short
follow-up period, although long term trials might show
that drugs to ARBs are more beneficial to cardiovascular
prevention in hypertensive patients.27 Finally, lifestyle
Chinese Medical Journal 2012;125(10):1804-1810
modification improves cardiovascular risk factors and
may also reduce the rate of cardiovascular events in the
long term.28,29
Study limitations
It has to be appreciated that there are some limitations of
our analysis with respect to new-onset type 2 diabetes and
cardiovascular outcomes. First, it should be noted that
these are post-hoc analyses of these trials and none of the
studies was primarily designed to address the issue of
new-onset type 2 diabetes. Second, the variety of methods
for the definition of type 2 diabetes between studies.
Thirdly, meta-analyses have intrinsic methodological
limitations related to combining trials with different
designs, treatment strategies, and patient populations. For
example, the present analysis combined trials in patients
with and without heart failure. Moreover we limited our
meta-analysis to studies that evaluated both new-onset
type 2 diabetes and cardiovascular complication. A
number of studies which only evaluated cardiovascular
outcomes were excluded, that might have affected the
result of ARBs on cardiovascular complications.
This meta-analysis found that ARBs have significant
ability to reduce the incidence of new-onset type 2
diabetes among patients with essential hypertension,
cardiocerebrovascular disease, impaired glucose tolerance
and heart failure.
Although reduce of new-onset type 2 diabetes does not
seem to impact the occurrence of cardiovascular
outcomes in the short term. Data supporting the
cardiovascular benefits of ARBs continue to accumulate
and the potential for their ability to modulate the risk of
incident type 2 diabetes remains an important focus of
investigation. Further research efforts are warranted to
identify which patients would most benefit from ARBs
intervention and determine whether these medications
also help to achieving cardiovascular outcomes benefits.
REFERENCES
1. American Diabetes Association. Economic costs of diabetes
in the U.S. In 2007. Diabetes Care 2008; 31: 596-615.
2. Yang W, Lu J, Weng J, Jia W, Ji L, Xiao J, et al. Prevalence of
diabetes among men and women in China. N Engl J Med
2010; 362: 1090-1101.
3. Sowers JR, Epstein M, Frohlich ED. Diabetes, hypertension,
and cardiovascular disease: an update. Hypertension 2001;
37: 1053-1059.
4. Lindholm LH, Persson M, Alaupovic P, Carlberg B, Svensson
A, Samuelsson O. Metabolic outcome during 1 year in newly
detected hypertensives: results of the Antihypertensive
Treatment and Lipid Profile in a North of Sweden Efficacy
Evaluation (ALPINE study). J Hypertens 2003; 21:
1563-1574.
5. Ogihara T, Nakao K, Fukui T, Fukiyama K, Ueshima K, Oba
K, et al. Effects of candesartan compared with amlodipine in
hypertensive patients with high cardiovascular risks:
1809
candesartan antihypertensive survival evaluation in Japan
trial. Hypertension 2008; 51: 393-398.
6. Pfeffer MA, Swedberg K, Granger CB, Held P, McMurray JJ,
Michelson EL, et al. Effects of candesartan on mortality and
morbidity in patients with chronic heart failure: the
CHARM-Overall programme. Lancet 2003; 362: 759-766.
7. Sawada T, Yamada H, Dahlof B, Matsubara H. Effects of
valsartan on morbidity and mortality in uncontrolled
hypertensive patients with high cardiovascular risks: KYOTO
HEART Study. Eur Heart J 2009; 30: 2461-2469.
8. Dahlof B, Devereux RB, Kjeldsen SE, Julius S, Beevers G, de
Faire U, et al. Cardiovascular morbidity and mortality in the
Losartan Intervention For Endpoint reduction in hypertension
study (LIFE): a randomised trial against atenolol. Lancet
2002; 359: 995-1003.
9. McMurray JJ, Holman RR, Haffner SM, Bethel MA,
Holzhauer B, Hua TA, et al. Effect of valsartan on the
incidence of diabetes and cardiovascular events. N Engl J
Med 2010; 362: 1477-1490.
10. Yusuf S, Diener HC, Sacco RL, Cotton D, Ounpuu S, Lawton
WA, et al. Telmisartan to prevent recurrent stroke and
cardiovascular events. N Engl J Med 2008; 359: 1225-1237.
11. Lithell H, Hansson L, Skoog I, Elmfeldt D, Hofman A,
Olofsson B, et al. The Study on Cognition and Prognosis in
the Elderly (SCOPE): principal results of a randomized
double-blind intervention trial. J Hypertens 2003; 21:
875-886.
12. Yusuf S, Teo K, Anderson C, Pogue J, Dyal L, Copland I, et
al. Effects of the angiotensin-receptor blocker telmisartan on
cardiovascular events in high-risk patients intolerant to
angiotensin-converting enzyme inhibitors: a randomised
controlled trial. Lancet 2008; 372: 1174-1183.
13. Julius S, Kjeldsen SE, Weber M, Brunner HR, Ekman S,
Hansson L, et al. Outcomes in hypertensive patients at high
cardiovascular risk treated with regimens based on valsartan
or amlodipine: the VALUE randomised trial. Lancet 2004;
363: 2022-2031.
14. Kasanuki H, Hagiwara N, Hosoda S, Sumiyoshi T, Honda T,
Haze K, et al. Angiotensin II receptor blocker-based vs.
non-angiotensin II receptor blocker-based therapy in patients
with angiographically documented coronary artery disease
and hypertension: the Heart Institute of Japan Candesartan
Randomized Trial for Evaluation in Coronary Artery Disease
(HIJ-CREATE). Eur Heart J 2009; 30: 1203-1212.
15. Higgins JP, Thompson SG. Quantifying heterogeneity in a
meta-analysis. Stat Med 2002; 21: 1539-1558.
16. Egger M, Davey Smith G, Schneider M, Minder C. Bias in
meta-analysis detected by a simple, graphical test. BMJ 1997;
315: 629-634.
17. Higashiura K, Ura N, Takada T, Li Y, Torii T, Togashi N, et
al. The effects of an angiotensin-converting enzyme inhibitor
and an angiotensin II receptor antagonist on insulin resistance
in fructose-fed rats. Am J Hypertens 2000; 13: 290-297.
18. Higashiura K, Ura N, Miyazaki Y, Shimamoto K. Effect of an
angiotensin II receptor antagonist, candesartan, on insulin
resistance and pressor mechanisms in essential hypertension.
J Hum Hypertens 1999; 13 Suppl 1: S71-S74.
19. Anan F, Takahashi N, Ooie T, Hara M, Yoshimatsu H,
Saikawa T. Candesartan, an angiotensin II receptor blocker,
1810
improves left ventricular hypertrophy and insulin resistance.
Metabolism 2004; 53: 777-781.
20. Heilbronn LK, Smith SR, Ravussin E. The insulin-sensitizing
role of the fat derived hormone adiponectin. Curr Pharm Des
2003; 9: 1411-1418.
21. Sharma AM, Janke J, Gorzelniak K, Engeli S, Luft FC.
Angiotensin blockade prevents type 2 diabetes by formation
of fat cells. Hypertension 2002; 40: 609-611.
22. Jandeleit-Dahm KA, Tikellis C, Reid CM, Johnston CI,
Cooper ME. Why blockade of the renin-angiotensin system
reduces the incidence of new-onset diabetes. J Hypertens
2005; 23: 463-473.
23. Kobayashi N, Ohno T, Yoshida K, Fukushima H, Mamada Y,
Nomura M, et al. Cardioprotective mechanism of telmisartan
via PPAR-gamma-eNOS pathway in dahl salt-sensitive
hypertensive rats. Am J Hypertens 2008; 21: 576-581.
24. White CM. Angiotensin-converting-enzyme inhibition in
heart failure or after myocardial infarction. Am J Health Syst
Pharm 2000; 57 Suppl 1: S18-S25.
25. Haenni A, Andersson PE, Lind L, Berne C, Lithell H.
Electrolyte changes and metabolic effects of
lisinopril/bendrofluazide treatment. Results from a
randomized, double-blind study with parallel groups. Am J
Chin Med J 2012;125(10):1804-1810
Hypertens 1994; 7: 615-622.
26. Lee VC, Rhew DC, Dylan M, Badamgarav E, Braunstein
GD, Weingarten SR. Meta-analysis: angiotensin-receptor
blockers in chronic heart failure and high-risk acute
myocardial infarction. Ann Intern Med 2004; 141: 693-704.
27. Granger CB, Ertl G, Kuch J, Maggioni AP, McMurray J,
Rouleau JL, et al. Randomized trial of candesartan cilexetil in
the treatment of patients with congestive heart failure and a
history of intolerance to angiotensin-converting enzyme
inhibitors. Am Heart J 2000; 139: 609-617.
28. Li G, Zhang P, Wang J, Gregg EW, Yang W, Gong Q, et al.
The long-term effect of lifestyle interventions to prevent
diabetes in the China Da Qing Diabetes Prevention Study: a
20-year follow-up study. Lancet 2008; 371: 1783-1789.
29. Ilanne-Parikka P, Eriksson JG, Lindstrom J, Peltonen M,
Aunola S, Hamalainen H, et al. Effect of lifestyle intervention
on the occurrence of metabolic syndrome and its components
in the Finnish Diabetes Prevention Study. Diabetes Care
2008; 31: 805-807.
(Received December 16, 2011)
Edited by GUO Li-shao