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Faculty of Pharmacy and Pharmaceutical Sciences, University of Alberta, Edmonton, Alberta, Canada
Division of Endocrinology and Metabolism, Department of Medicine, McMaster University, Hamilton, Ontario, Canada
c
Department of Family Medicine, University of British Columbia, Vancouver, British Columbia, Canada
d
Pine Valley Medical, Toronto, Ontario, Canada
e
Department of Medicine, University of British Columbia, Okanagan Campus, Kelowna, British Columbia, Canada
b
a r t i c l e i n f o
a b s t r a c t
Article history:
Received 29 June 2012
Received in revised form
8 September 2012
Accepted 17 September 2012
Hypertension is a common problem in people with diabetes and several changes have occurred to the joint
Canadian Hypertension Education Program and Canadian Diabetes Association hypertension recommendations over the past 5 years. This article uses a case-based approach to review contemporary issues in
hypertension management in the context of diabetes, including: treatment targets, optimal combination
therapy, choice of diuretic therapy, the role of aldosterone antagonists, role of aliskiren, bedtime dosing of
antihypertensive agents, benets of sodium reduction, impact of lifestyle interventions, vascular risk
reduction with antiplatelet therapy, adherence strategies, the role of home blood pressure monitoring, and
treatment considerations based on ethnocultural background. Particular emphasis is given to linking the
recommendations to practice. Up to 80% of people with diabetes and hypertension will die of cardiovascular
disease, especially stroke. The 2012 Canadian Hypertension Education Program hypertension in diabetes key
messages for knowledge translation are that clinicians should: 1) ensure people with diabetes are screened
for hypertension, 2) assess blood pressure at all appropriate healthcare visits, 3) encourage home monitoring
with approved devices, 4) initiate pharmacotherapy and lifestyle modication concurrently, 5) assess and
manage all other vascular risk factors, and 6) enable sustained lifestyle and medication adherence.
2012 Canadian Diabetes Association
Keywords:
diabetes
hypertension
r s u m
Mots cls:
diabte
hypertension
Lhypertension est un problme frquent chez les personnes ayant le diabte, et de nombreuses modications sont apparues aux recommandations conjointes sur lhypertension du Programme ducatif canadien
sur lhypertension et de lAssociation canadienne du diabte au cours des 5 dernires annes. Cet article
utilise une approche par cas pour passer en revue les problmes contemporains de la prise en charge de
lhypertension dans le contexte du diabte, incluant les objectifs de traitement, le traitement combin
optimal, le choix dun traitement diurtique, le rle des antagonistes de laldostrone, le rle de laliskirne, la
posologie des agents antihypertenseurs au coucher, les bnces de la rduction du sodium, les effets des
interventions sur le mode de vie, la rduction du risque vasculaire par un traitement antiplaquettaire, les
stratgies dobservance, le rle de la surveillance de la pression artrielle domicile et les plans de traitement
fonds sur le milieu ethnoculturel. Une importance particulire est accorde au fait de lier les recommandations la pratique. Jusqu 80 % des personnes ayant le diabte et de lhypertension mourront dune
maladie cardiovasculaire, particulirement dun accident vasculaire crbral. Les messages cls sur lapplication des connaissances du Programme ducatif canadien sur lhypertension au sujet de lhypertension au
cours du diabte sont que les cliniciens doivent : 1) faire en sorte que les personnes ayant le diabte soient
soumises un dpistage de lhypertension; 2) valuer la pression artrielle lors de toutes visites appropries
en soins de sant; 3) encourager la surveillance domicile laide dappareils approuvs; 4) amorcer
simultanment la pharmacothrapie et la modication du mode de vie; 5) valuer et prendre en charge tous
les autres facteurs de risque vasculaires; 6) permettre un mode de vie viable et lobservance mdicamenteuse.
2012 Canadian Diabetes Association
* Address for correspondence: Ally P.H. Prebtani, HHSC, Hamilton General Hospital
Site, McMaster Wing, Room 411, 237 Barton St. E. Hamilton, Ontario L8L 2X2, Canada.
E-mail address: prebtani@hhsc.ca (A.P.H. Prebtani).
1499-2671/$ e see front matter 2012 Canadian Diabetes Association
http://dx.doi.org/10.1016/j.jcjd.2012.09.002
346
Introduction
Diabetes is a major health issue in Canada with w8.7% of the
adult Canadian population having been diagnosed with diabetes in
2008 to 2009 (1). High blood pressure is a very common problem in
people with diabetes with the most recent national data, from the
2007 to 2009 Canadian Health Measures Survey (CHMS), indicating
that 75% of Canadians reporting diabetes also have hypertension.
This rate is 4 times higher among hypertensive individuals with
diabetes than among those without diabetes (74% vs. 17%) (2). This
is consistent with other reports, particularly the 2009 National
Diabetes Surveillance System (NDSS), which reported that 63% of
Canadians with diabetes have hypertension (3). Although the
CHMS and NDSS do not differentiate hypertensive individuals
based on type of diabetes, an estimated 90% to 95% of Canadians
living with diabetes have type 2 diabetes mellitus and therefore the
most commonly encountered scenario in clinical practice is that of
individuals with both type 2 diabetes and hypertension (1).
Between 60% to 80% of people with diabetes die of cardiovascular complications and up to 75% of specic cardiovascular
complications are attributable to hypertension (4,5). Epidemiologic
data has shown that hypertension accounts for up to 75% of stroke
(6), 41% of cardiovascular events (7) and 44% of all deaths among
individuals with diabetes (7). Additionally, hypertension is also
a major causal factor of end stage kidney failure, blindness and
nontraumatic amputation in people with diabetes, where attributable risks are 50%, 35% and 35%, respectively (6). Observational
data from the United Kingdom Prospective Diabetes Study (UKPDS)
has shown that the risks of macrovascular and microvascular
complications in type 2 diabetes are strongly associated with mean
systolic blood pressure, with each 10 mm Hg reduction in blood
pressure reducing the risk of a fatal or nonfatal stroke by 19%, fatal
and nonfatal myocardial infarction by 12% and microvascular
disease by 13% (8).
Randomized controlled trials of blood pressure lowering treatments in people with diabetes have demonstrated major reductions in death, stroke, cardiovascular disease and eye and kidney
disease (9e18). For example, the blood pressure lowering arm of
the Action in Diabetes and Vascular Disease: Preterax and
Diamicron-MR Controlled Evaluation (ADVANCE) trial is one of the
largest individual studies to date that illustrates the benets of
blood pressure lowering in patients with diabetes (12). It showed
that in comparison to a placebo, xed dose combination therapy
with perindopril/indapamide, in addition to usual therapy, reduced
the relative risk of a major macrovascular or microvascular event, at
a median of 5 years, by 9%, the relative risks of cardiovascular death
by 18% and total mortality by 14%. The reduction in blood pressure
in this trial was 5.6/2.2 mm Hg vs. placebo. Lowering blood pressure
is likely the single most effective way to prevent death and
disability in those with diabetes (19).
Most recent data from the CHMS indicates that 89% of adults
with diabetes were aware of having hypertension and 88% were
treated with antihypertensive medication, but only 56% were
treated and controlled to the current Canadian Hypertension
Education Program (CHEP)- and Canadian Diabetes Association
(CDA)-endorsed blood pressure target of <130/80 mm Hg (2). This
rate is much improved compared to historical data from <10%
below 140/90 mm Hg from 1986 to 1992 (2). This number is also
higher than previously available data from the province of Ontario
that indicated that only one-third of patients with diabetes and
hypertension were receiving treatment and had controlled hypertension, and that over 25% with diabetes and hypertension were not
being treated for hypertension at all (20).
Several changes have occurred to the CHEP and CDA hypertension recommendations since the publication of the CDA 2008
Clinical Practice Guidelines for the Prevention and Management of
347
Table 1
Hypertension in diabetes: key messages
Up to 80% of people with diabetes and hypertension will die of CV disease, especially stroke.
1. Ensure people with diabetes are screened for hypertension.
Diagnosis of hypertension in diabetes: BP 130/80 mm Hg, conrmed within 1 month.
2. Assess BP at all appropriate healthcare visits.
Regular monitoring of BP forms the basis for making decisions about treatment and reinforces the importance of maintaining a target BP level.
3. Encourage home monitoring with approved devices.
Home BP readings are more strongly associated with improved CV outcomes than readings taken in a healthcare professionals ofce.
Home readings can be used to: conrm the diagnosis of hypertension, improve BP control, reduce the need for medications in those with white coat effect, identify
those with white coat and masked hypertension, and improve medication adherence.
Home BP readings should be obtained twice in the morning and twice in the evening, for a 7-day period. Discard the readings of the rst day and calculate the
average of the last 6 days.
The target home reading is <130/80 mm Hg.
4. Pharmacotherapy and lifestyle modication should be initiated concurrently.
Aggressive treatment using multiple (3 or more) BP lowering medications is often required to achieve target levels of <130/80 mm Hg for people with diabetes.
First line therapies include in alphabetic order ACE inhibitors, ARB, dihydropyridine CCBs and thiazide or thiazide-like diuretics.
5. Assess and manage all other vascular risk factors.
A comprehensive approach is needed to address the following risk factors: smoking, dyslipidemia, glycemic control, obesity, unhealthy eating and physical
inactivity.
A reduction in these risk factors can cut an individuals vascular risk by more than half.
6. Enable sustained lifestyle modication and medication adherence.
At every visit, people should be asked how they are managing their BP.
Recommended lifestyle changes, especially limiting sodium intake and medication adherence, should be reviewed at each visit.
ACE, angiotensin-converting enzyme; ARB, angiotensin receptor blockers; BP, blood pressure; CCB, calcium channel blocker; CV, cardiovascular.
Table 2
Treatment of hypertension in association with diabetes mellitus: CHEP 2012 (22)
1. Persons with diabetes should be treated to attain SBPs of <130 mm Hg
(Grade C) and DBPs of <80 mm Hg (Grade A). These target BP levels
are the same as the BP treatment thresholds.
Combination therapy using 2 rst-line agents may also be considered as
initial treatment of hypertension (Grade B) if SBP is 20 mm Hg above target
or if DBP is 10 mm Hg above target. However, caution should be exercised
in patients in whom a substantial fall in BP is more likely or poorly
tolerated (e.g. elderly patients and patients with autonomic neuropathy).
2. For persons with CV or kidney disease, including microalbuminuria or
with CV risk factors in addition to diabetes and hypertension, an
ACE inhibitor or an ARB is recommended as initial therapy (Grade A).
3. For persons with diabetes and hypertension not included in the above
recommendation, appropriate choices include (in alphabetical order):
ACE inhibitors (Grade A), ARB (Grade B), dihydropyridine CCBs (Grade A)
and thiazide/thiazide-like diuretics (Grade A).
4. If target BPs are not achieved with standard-dose monotherapy,
additional antihypertensive therapy should be used. For persons in
whom combination therapy with an ACE inhibitor is being considered,
a dihydropyridine CCB is preferable to hydrochlorothiazide (Grade A).
ACE, angiotensin-converting enzyme; ARB, angiotensin receptor blockers; BP, blood
pressure; CCB, calcium channel blocker; CV, cardiovascular; DBP, diastolic blood
pressure; SBP, systolic blood pressure.
348
to treat [NNT] 9) and all cause mortality modestly reduced (1.1% vs.
2.6% ARR: 1.5% NNT: 67) in the bedtime dosing group. These overall
results were consistent in the diabetes subgroup as well as those
with chronic kidney disease (50,51). In addition to the ADAs strong
recommendation, Portaluppi and Smolensky (52) have called for
urgent reconsideration of a number of commonly accepted
concepts currently applied in practice such as the normotensive
nondipper, aiming for constant blood pressure lowering over the
24-hour dosing interval, and reliance on occasional blood pressure
assessments without regard for blood pressure levels at other times
of the day and night. On the ip side, others have expressed a desire
for more conrmatory research before full-scale implementation of
this studys ndings into practice. This desire is driven by the studys
limitations including poorly described randomization, single center,
open label design, lack of a robust validated algorithm for antihypertensive medication titration, and the large relative risk reduction
for major cardiovascular events (71%) that seems out of line with, for
example, the Heart Outcome Prevention Evaluation (HOPE) trial
that also found a reduction in bedtime blood pressure but showed
a 22% relative risk reduction in cardiovascular events (53).
349
Targeted change
Sodium reduction
Weight loss
Alcohol reduction
Exercise
Dietary patterns
5.1/2.7
1.1/0.9
3.9/2.4
4.9/3.7
11.4/5.5
350
351
Lifestyle interventions
There are several opportunities for lifestyle intervention and the
patients values should be taken into consideration when prioritize
the treatment plan:
Healthy eating and sodium reduction: the target for sodium
intake in this patient of <1300 mg daily should be pursued via
improved awareness and strategies to minimize the most
common sources of sodium in the diet (e.g. restaurant meals,
processed foods, bread products).
Smoking cessation: Mr. J should receive brief advice recommending smoking cessation as even a few cigars contribute to
his risk.
Alcohol consumption: his alcohol consumption should be
further investigated and he should receive advice about low
risk alcohol consumption if he is exceeding 2 drinks per day.
Physical activity and reducing body weight: an increase in
physical activity tailored toward his interests, lifestyle and
concomitant knee osteoarthritis should be discussed. He
should participate in creation of a personalized activity plan
and be aware that his target is a BMI of <25 kg/m2.
352
353
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