1. No category

THE PREVALENCE AND CONTROL OF HYPERTENSION AMONG PATIENTS WITH
TYPE 2 DIABETES MELLITUS IN NIGERIA
http://dx.doi.org.10.4314/jcm.v17i2.2
Anakwue RC1,2, Arodiwe EB1, Ofoegbu EN1
1 Department of Medicine, College of Medicine, University of Nigeria, Enugu Campus, Nigeria.
2 Department of Pharmacology & Therapeutics, College of Medicine, UNEC, Nigeria.
Corresponding author: Dr RC Anakwue
Email: [email protected], Phone number : +2348033343044
SUMMARY
Background:
Diabetes Mellitus (DM) is an endocrine disease with profound vascular morbidity and mortality,
and hypertension is known to play a prominent role in this regard. The aim of this study is to
determine the prevalence of hypertension and to assess drug control of hypertension among DM
patients seen in Enugu, Nigeria.
Methods:
The medical records of 420 adult patients with diagnosis of type 2 DM and hypertension, managed
consecutively in the outpatient unit of University of Nigeria Teaching Hospital Enugu were
studied.
Results:
Sixty percent of the diabetic patients had hypertension. Only 12% of these patients had their blood
pressure controlled to ≤ 130mmHg and ≤ 80mmHg. About 12.3% of the patients who had
hypertension were not on anti hypertensive drug treatment. Most of the patients were placed on 1
or 2 drugs. Angiotensin converting enzyme inhibitors were the most frequently prescribed drug.
Conclusion:
This study and similar ones from other parts of Nigeria indicate that the prevalence of hypertension
among Nigerians with type 2 DM is high. Clinicians and patients should be reminded that even
though blood glucose control is important, aggressive blood pressure control in diabetics is top
priority in preventing adverse cardiovascular events which causes the highest mortality in the
average population of type 2 diabetics. Appropriate antihypertensive regimen optimizes
nonpharmacological therapies, reduces adverse effects on glucose control, minimizes the risk of
medication-related side-effects, and provides much needed cardiac and renal protection.
Key words: Hypertension, Prevalence, Diabetes Mellitus, Drug control, Nigerians
11
J. College of Med, Dec 2012;17(2)
Prevalence and Control of Hypertension
Anakwue RC, Arodiwe EB , Ofoegbu EN
INTRODUCTION
Diabetes mellitus (DM) is an endocrine
disease, defined by high blood glucose levels,
but with a prominent vascular component.
The major cause of death in treated diabetic
patients is due to cardiovascular problems
(70%), followed by renal failure (10%), and
infections (6%).1 The underlying vascular
component is so significant that the
complications of diabetes mellitus
are
usually divided according to macrovascular
(coronary artery disease, cerebrovascular
disease, peripheral vascular disease) and
microvascular
events
(retinopathy,
2
nephropathy, neuropathy).
One of the extremely common cardiovascular
risk factors in patients with type 2 diabetes is
hypertension. Hypertension may precede
diabetes mellitus, be diagnosed at same time
as diabetes or may be as a result of diabetic
nephropathy. Whenever it occurs, it is the
greatest contributor to increased morbidity
and mortality in macro-vascular and
microvascular events in type 2 DM.3
Macro-vascular complications are more
common; up to 80% of patients with type 2
diabetes will develop or die of macrovascular disease4-12 and the costs associated
with macro-vascular disease are greater than
those associated with micro-vascular
disease13
However,
while
some
observational evidence suggests that the
level of glycemia is a risk factor for
macrovascular disease,14-18 experimental
studies to date have not clearly shown a
causal relationship between improved
glycemic control and reductions in serious
cardiovascular outcomes.3
Hypertension is one of the highly prevalent
risk factors for macro-vascular events
affecting up to 60% of patients with type 2
DM. Hypertension is known to increase
morbidity and mortality among patients with
diabetes mellitus.
The control of
hypertension is dramatically effective in
reducing risk for cardiovascular events and
12
mortality and does so within a 4- to 6-year
period.19-25
Glucose control is clearly effective only in
reducing microvascular end points, but to
date only intermediate outcomes have been
shown to be reduced. The UKPD study
demonstrated that intensive hypertension
control is more effective than intensive
glycemic control in reducing macro-vascular
and micro-vascular events as well as all cause
mortality.3 The benefits of intensive
hypertension control (diastolic blood
pressure, 87 mm Hg vs. 82 mm Hg)
dramatically outweighed those of intensive
glucose control (mean hemoglobin A1c level,
7.9% vs. 7.0%), with substantially greater (by
two- to fivefold) absolute risk reductions for
all published outcomes.3
It is not just the UKPD but also the
Hypertension Optimal Treatment (HOT )26
Trial, has demonstrated that cardiovascular
mortality and total mortality were reduced by
43% when blood pressure is reduced to
<130/80mmHg in diabetic patients with
hypertension.
The interruption of the rennin-angiotensinsystem (RAS) is considered to be the
cornerstone of pharmacologic therapy to
reduce macrovascular and microvascular
complications in hypertensive type 2 DM
patients, mediated by antihypertensive, antiinflammatory,
antiproliferative,
and
27
oxidative stress lowering properties.
There is evidence, that ACE inhibitors,
angiotensin-receptor blockers and diuretics, ,
may be superior to ß-blockers and calciumchannel blockers and the latter are probably
best used as second- or third-line treatments
for hypertension in diabetes 28-31
Other antihypertensive drugs may have a role
in achieving desired blood pressure targets in
patients with type 2 diabetes. However, there
is little information on the effectiveness of
these drugs in reducing micro-vascular and
macro-vascular outcomes.
J. College of Med, Dec 2012;17(2)
Prevalence and Control of Hypertension
Previous studies
have noted that the
antihypertensive drug compliance as well as
optimal blood pressure control in diabetic
patients is poor and sub optimal in sub
Saharan countries, including Nigeria.32
There are few reports of hypertension and its
control among DM patients from south
western(Ibadan and Benin city), 32,33central
(Ilorin) 34and north eastern belts of Nigeria,35
but non from the south east. The aim of this
study is to determine the prevalence of
hypertension and to assess anti hypertensive
drug control among DM patients seen in
Enugu, south east, Nigeria.
METHODOLOGY
The medical records of 420 adult patients of
both sexes (253 females, 167 males) aged
between 23 and 81 years with diagnosis of
type 2 DM who were seen consecutively in
the outpatient unit of University of Nigeria
Teaching Hospital Enugu from January 2009
were studied. The first 420 patients that
satisfied the inclusion criteria-adult patients
of both sexes, with diabetes mellitus type 2,
whose blood pressure was > 140/90mmHg or
on antihypertensive drugs, were selected.
The anthropometric data- age, sex, weight,
height, fasting blood sugar, blood pressure of
the patients were documented.
Diagnosis of diabetes mellitus was made
using a fasting blood sugar of 7.0 mmol/liter
(126mg/dl) according to the World Health
Organization guidelines.35
The last clinic blood pressure was recorded,
observing the usual standard by taking
measurements in the sitting position on two
occasions at least 15 minutes apart and the
average recorded. Assessment of BP control
was based on the American Diabetes
Anakwue RC, Arodiwe EB , Ofoegbu EN
Association guidelines36 for optimal BP
control in patients with diabetes. The
Accousson’s mercury sphygmomanometer
was
used.
Hypoglycaemic
and
antihypertensive drugs given in the last visit
were recorded and classified.
RESULTS
Out of 420 DM patients studied, those with a
combination of diabetes and hypertension
were significantly more than those with
diabetes only (p<0.001). There were also
more females than males. The diabetic
hypertensives were also significantly older
than the non diabetic patients ( p<0.001)
(table 1).
Sixty percent of the diabetic patients had
hypertension with systolic and diastolic
blood pressures > 140/90mmHg with mean
systolic and diastolic blood pressures of
152.6mmHg ±22.2 and 96.6mmHg±9.9
respectively. The blood pressure control
pattern is shown in figure 1.
Only 18.3% (46) and 21% (53) of these
patients had their mean systolic and diastolic
blood pressure controlled to ≤ 130mmHg and
≤ 80mmHg respectively. Altogether 12%
(51) DM patients had their blood pressure
controlled
to
below
130/80mmHg.
About12.3% (31) of the patients who had
blood
pressure
of
more
than
135/85mmHg±9.2 were not on anti
hypertensive drug treatment.
Forty percent of all the diabetic patients had
normal blood pressure with mean systolic
and diastolic blood pressures of 123.4mmHg
±3.4and 72.4mmHg ±10.6 respectively.
The frequency of antihypertensive drugs is
shown in table 2. Most patients were on 1 and
2 drugs (63%) and only very few (about 20%)
were on 3 and 4 drugs.
TABLE 1 :Characteristics of Patients Studied
No studied
Mean Age(yrs)
All Patients
Diabetes Only
420
59.9± 10.2
176 (42%)
52.6 ±9.5
Diabetic
hypertensive
244(58%)
57.9 ±12.7
P value
0.001
0.001
Prevalence and Control of Hypertension
M/F
Mean Dur(yrs)
Mean BMI(kg/m2)
Mean SBP(mmHg)
Mean DBP(mmHg)
Anakwue RC, Arodiwe EB , Ofoegbu EN
167/253
8.2± 6.2
27.4 ±4.5
137.4 ±11.3
84.4 ±10.6
70/98
8.6 ±8.7
26.7± 5.5
121.5± 4.8
73.4 ±10.4
97/155
9.1 ±5.8
27.9± 4.7
152.6± 22.2
96.6 ±9.9
0.24
0.68
0.022
0.00
0.00
TABLE 2 : Frequency of antihypertensive drug combination in diabetic patients studied
Number of different drug classes
0
1
2
3
4
Number of diabetic patients (%)
31
(12.3)
68
(27)
103
(40.9)
45
(17.8)
5
(2%)
The classes and pattern of antihypertensive
pharmacotherapy are depicted in figure 2.
Angiotensin converting enzyme inhibitors
was the most frequently prescribed drug for
the
hypertensive
diabetics
(64%).
Angiotensin receptor blocker was prescribed
in only 12% of hypertensive diabetics.
Diuretics, calcium channel blockers and
central acting agents were prescribed in 35%,
17% and 8% of hypertensive diabetics
respectively. No beta blockers were given.
Angiotensin converting enzyme inhibitors
and angiotensin receptor blockers were also
prescribed in 15% of diabetics who had
normal blood pressure for renal protective
effects.
The study showed that the average prescribed
dose of Angiotensin converting enzyme
inhibitors (ACEI) and Angiotensin receptor
blockers (ARB) were on the low side of
recommended dose. The percentage of
hypertensive diabetics that achieved the
median recommended doses of ACEI/ARB
were very low, ranging from 12 to 20%.(table
3)
70
60
50
% of Patients on Drugs
40
30
20
FIGURE 1: The pattern of antihpertertensive drugs
prescribed
in
percentages:ACEI-Angiotensin
Converting enzyme inhibitors, ARB-Angiotensin
receptor blockers, CCB-Calcium channel blockers,
DIU-Diuretics, CENTRAL-Central acting drugs.
10
0
ACEI
ARB
CCB
DIU
CENT
Antihypertensive Drug Classes
TABLE 3 : The recommended ACEI/ARB target dose in Hypertensive patients and the prescribed
doses in the study group
ACEI/ARB drugs
Lisinopril
Enalapril
Ramipril
Valsartan
Losartan
Recommended dose range
in mg(median dose in mg)
10-40(25)
5-40(22.5)
5-20(12.5)
80-320(200)
50-100(75)
13
Average Prescribed dose in
mg
8
7
5
160
50
J. College of Med, Dec 2012;17(2)
% of study patients
achieving the median dose
20
15
12
18
16
Prevalence and Control of Hypertension
Anakwue RC, Arodiwe EB , Ofoegbu EN
DISCUSSION
Hypertension is a major cardiovascular disease risk factor and when present in diabetic patients
increases the cardiovascular disease burden substantially. It has been documented that
hypertension in diabetic patients markedly increases the risks of coronary heart disease, stroke,
nephropathy and retinopathy.37,38,39Indeed, when hypertension coexists with diabetes, the risk of
CVD is increased by 75%37,40
Reports of prevalence of hypertension in diabetic patients help to assess the added risks it poses in
management. It also exposes the weaknesses and shows the vigour in implementing already
recommended guidelines.
The prevalence of hypertension among diabetics in this study, done in Enugu, south eastern
Nigeria (60%) is comparable to that obtained in Ibadan, south western Nigeria (57%) 32 and Benin
city (59%)33 ,Ilorin (63%)34 and Sweden (56%), 41but understandably lower than that of United
kingdom(73%)3 and USA (77%)2 were diet, physical inactivity and obesity have combined to place
hypertension and diabetes as competing risk factors of cardiovascular disease in these two
countries. The Swedish and American studies were nationwide surveys. Our study and that from
Ibadan were hospital based and we await a nation-wide survey to provide the true prevalence of
diabetes in Nigeria.
Diabetic patients in Cameroon exhibit a very high prevalence of hypertension (66%) and are about
three times more affected than the general population42. A study conducted in Kenya during the
year 2005 to determine the proportion of specific cardiovascular risk factors in ambulatory patients
with type 2 DM reported that 50% of the patients had HTN 43. The recent EPIDIAM Study
conducted in 525 type 2 individuals in three Moroccan regions reported that 70.4% of the
individuals had HTN 44.In India about 50% of diabetic patients have hypertenson45. In a cohort
study in China the age- and sex-adjusted prevalence of hypertension among diabetic subjects was
twice that of non diabetic subjects (30.6 vs. 16.4%, P < 0.0005). 46
Globally, the frequency of diabetic hypertension in diabetic population is almost twice as
compared to non-diabetic general population.2 Hypertension and diabetes mellitus are really deadly
cardiovascular duets. Generally, hypertension in type 2 diabetic persons clusters with other CVD
risk factors such as microalbuminuria, central obesity, insulin resistance, dyslipidaemia,
hypercoagulation, increased inflammation and left ventricular hypertrophy. 47 This clustering risk
factor in diabetic patients ultimately results in the development of CVD, which is the major cause
of premature mortality in patients with type 2 diabetes. In all there is now considerable evidence
for an increased prevalence of hypertension in diabetic persons. 48
Blood pressure goals in diabetics are lower and thus more difficult to control. Globally, 25% of
hypertensive diabetics achieve control. 39 The control achieved in this study(12%) is comparable to that in Ibadan-Nigeria (12%) 32, Ilorin-Nigeria(11%)34 but lower than that
of United Kingdom (<27%),3Sweden (33.3%)41 and USA (35.5%).3 were there are better care for
patients with cardiovascular risk factors such as hypertension and diabetes mellitus.
The mean systolic and diastolic blood pressure for the hypertensive diabetic patients in our study
was high (153/97mmHg). The poor rate of control of hypertension among hypertensive diabetics
in this study may be due to inadequate optimization of the antihypertensive agents. The same
reason was also adduced for the control in Ibadan and Ilorin studies.
Majority of the antihypertensive prescriptions in this study were 1 or 2 drugs in combination but
studies have recommended 3 drugs as required for optimal control of hypertension in diabetics
16
J. College of Med, Dec 2012;17(2)
Prevalence and Control of Hypertension
Anakwue RC, Arodiwe EB , Ofoegbu EN
particularly in those whose systolic blood pressure is 25-30mmHg above target goal.3 In fact the
United Kingdom Prospective Diabetic study found out that one-third of patients needed three or
more antihypertensive drugs in combination, and two-thirds of treated patients needed two or more
for control of blood pressure.3
It should be emphasized that blood pressure targets in diabetics should be aggressive. For example,
a four point blood pressure difference in the HOT trial (84 to 81mmHg) resulted in a decrease by
50% in cardiovascular events in patients with DM. The study noted that the risk reduction seen
with hypertension control in patients with diabetes is substantially greater than that seen in persons
in the general population who have similar blood pressure levels26
The ACE inhibitors and particularly the ARB are underutilized in this study (64% and 12%
respectively) gave rise to the poor control of hypertension. The Ibadan and Ilorin studies 32,34 had
also recorded ACE inhibitors in only 52% and 44.3% respectively of their prescriptions. The
Ibadan study pointed at the high cost of ACE inhibitors/ARB as possible reason for its low
patronage. It has been recommended that treating people with diabetes and at least one other major
cardiovascular risk factor with an ACE-inhibitor produces a 25-35% lowering of the risk of heart
attack, stroke, overt nephropathy or cardiovascular death. 39
It has been noted that in patients with bilateral renal artery stenosis, ACE inhibitors can cause renal
insufficiency. To help detect the presence of undiagnosed bilateral renal artery stenosis, physicians
should monitor the serum creatinine level at baseline and one week after initiation of ACE inhibitor
therapy.
Diuretics were not used optimally in this study. This finding is in keeping with the Ibadan study.
33
Diuretics are however recommended in the multiple regimen required to control hypertension
inspite of their diabetogenic potential. Diuretics, particularly, hydrochlorothiazides when used in
low doses, have no significant disturbance on glucose metabolism and are useful in blacks in the
control of hypertension.
Thiazide diuretics have been shown to benefit patients with diabetes and systolic hypertension and
lower dosages of thiazides (e.g., hydrochlorothiazide 12.5 mg per day) are generally well tolerated
and not associated with adverse metabolic effects. 4 Thiazide diuretics are not as effective in
patients with renal insufficiency; in such patients, loop diuretics are preferred. In general, diuretics
are effective, affordable and available for the treatment of hypertension in diabetes mellitus.
Calcium channel blockers were prescribed in 17% of the diabetic hypertensive patients studied.
Non-dihydropyridine calcium channel blockers were not prescribed in this study and in other
studies in Nigeria.
Both the non DHP (diltiazem and verapamil) and the DHP CCBs (amlodipine, felodipine, and
others) reduce CVD events in people with diabetes and hypertension. 49,50
NonDHP CCBs significantly reduce albuminuria and may slow the progression of proteinuric
renal disease.51 In contrast, DHP CCBs inconsistently reduce albuminuria and are less effective
than ACE inhibitors or ARBs in slowing the progression of diabetic nephropathy. 51However, DHP
CCBs effectively lower blood pressure and can be safely combined with an ACE inhibitor or ARB
to slow the progression of diabetic nephropathy. 51 B-blockers were not prescribed in this study
unlike in the Ibadan study were it was used in 7% of the patients. 33
17
J. College of Med, Dec 2012;17(2)
Prevalence and Control of Hypertension
Anakwue RC, Arodiwe EB , Ofoegbu EN
Beta blockers worsen hyperglycemia and block adrenergic symptoms. This may produce
dangerous hypoglycemia without giving the patient enough time to react by taking food to increase
the blood glucose level. It is however useful in post myocardial infarction patients and as an
antiarrhythmic agent.
The effectiveness of beta blockers was demonstrated in the UK Prospective Diabetes Study Group,
where atenolol was comparable with captopril in reduction of CVD outcomes52,53. Although these
agents have been associated with adverse effects on glucose and lipid profiles and implicated in
new onset diabetes in obese patients, 4 they are not absolute contraindication for use in diabetic
patients. In fact, carvedilol, which has both alpha and beta receptor blocking properties, has been
shown to induce vasodilatation and improve insulin sensitivity52.
Blood pressure lowering with carvedilol or metoprolol reduces microalbuminuria by 43 and 30%,
respectively, when added to ACE inhibitors or ARBs. 47 However, carvedilol is nearly 50% more
effective than metoprolol for preventing progression from normoalbuminuria to
microalbuminuria.54
Central acting drugs were used in only 8% of diabetic hypertensive studied. This drug was not
used in any of the centers in Nigeria. This group of drugs are prescribed because they are cheap
and affordable.
Our study noted that thirteen percent of the diabetic patients who were hypertensive were not
placed on antihypertensives. The reason for this is not clear except that the patients had mild
hypertension (135/85mmHg±9.2) and may have been erroneously classified as non hypertensive.
These patients are under the threat of renal impairment and other end organ damage.
Our study also showed inertia in the attainment of target doses for the ACEI and ARB was only
12-20% of median doses of ACEI and ARB. It is not clear if the distraction of treating diabetes
mellitus and the adverse effects of these drugs contributed to the below target dose prescription of
these drugs.
CONCLUSION
It is clear from this study that blood pressure control in hypertensive diabetic patients is
unsatisfactory even in a tertiary hospital in Nigeria. The study found out that inspite of high
prevalence of high blood pressure, hypertension was managed less intensively in patients with
diabetes. Findings of other tertiary health institutions in Nigeria and other parts of Africa run
parallel to that of our study. This is inspite of the consensus that blood pressure control in diabetic
patients has dramatic effects in reducing cardiovascular morbidity and mortality. Clinicians and
patients should be reminded that even though blood glucose control is important, aggressive blood
pressure control in diabetics is top priority in preventing adverse cardiovascular events which
causes the highest mortality in the average population of type 2 diabetics. 30
Apart from issues on pharmacotherapy, poor control of hypertension in diabetic patients may be
traced to non pharmacological factors which include inadequate recognition of the role of
therapeutic life style changes, poverty and proper health education. These non drug measures are
obviously not the focus of this study but they can not escape being mentioned here. Availability
of generic drugs and health insurance scheme may help to place antihypertensive drugs at the reach
of the patients.
18
J. College of Med, Dec 2012;17(2)
Prevalence and Control of Hypertension
Anakwue RC, Arodiwe EB , Ofoegbu EN
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