 |
|
|
Vol. 161 No. 22, December 10, 2001 |
 |
|
|
|
|
|
|
|
|
|
Review Article |
|
|
|
A Practical Approach to Achieving Recommended Blood Pressure Goals in Diabetic Patients
George L. Bakris, MD
Arch Intern Med. 2001;161:2661-2667.
ABSTRACT
| |
Approximately 11 million Americans have both hypertension and diabetes
mellitus. This double diagnosis places such patients at high risk for renal
damage, especially end-stage renal disease. The sixth report of the Joint
National Committee on Prevention, Detection, Evaluation, and Treatment of
High Blood Pressure recommends a blood pressure goal of less than 130/85 mm
Hg to reduce or slow the onset of renal disease and cardiovascular events
in patients with hypertension and diabetes mellitus. Recent data, however,
now suggest that an even lower diastolic blood pressure goal (ie, <80 mm
Hg) may be necessary. Studies have shown that use of angiotensin-converting
enzyme inhibitors can prevent the progression of microalbuminuria to overt
proteinuria, reduce proteinuria in patients with overt diabetic nephropathy,
slow the deterioration of the glomerular filtration rate, delay progression
to end-stage renal disease, and lower blood pressure. Thus, all diabetic patients
with blood pressure greater than 130/80 mm Hg should begin angiotensin-converting
enzyme inhibitor treatment and be titrated to moderate or high doses until
the blood pressure goal is achieved. However, monotherapy still may not control
blood pressure to the recommended target. Studies have shown that use of multiple
antihypertensive agents is necessary and successful in helping patients reach
their target blood pressure, and this may offer more renoprotection than one
agent used singly. A case study that applies these concepts in outpatient
practice is included.
INTRODUCTION
Hypertension and diabetes mellitus damage not only the cardiovascular
system but also the kidneys. Diabetes mellitus, for instance, contributes
to a reduced filtration rate, which leads to increased glomerular blood flow
and glomerular capillary pressure, which in turn leads to proteinuria and
glomerular damage. Hypertension can be either a cause or a consequence of
chronic renal disease. Uncontrolled elevated blood pressure (BP) is believed
to cause renal damage via ischemia in the renal tubule, provoking a reduction
in renal mass and increased glomerular capillary pressure.1-2
More than 11 million Americans have both diabetes mellitus and hypertension—comorbid
conditions that strongly predispose the individual to renal and cardiovascular
damage.3 In patients with diabetes mellitus,
hypertension can contribute as much as 75% of all diabetes mellitus–related
complications, including nephropathy and end-stage renal disease (ESRD).4
Blood pressure has been shown to directly affect renal function. The
declining rate of renal function in patients with diabetic nephropathy seems
to be a continuous function of arterial pressure of 125/75 mm Hg or less (Figure 1).5
Therefore, individuals with diabetes mellitus and BP values greater than 125/75
mm Hg have a greater likelihood of progressing to ESRD. To that end, intensive
BP control, using lifestyle modification and pharmacotherapy, is important
in managing the diabetic patient with hypertension. The purpose of this article
is to discuss the importance of BP control in patients with diabetes mellitus,
with emphasis on using multidrug therapy in this patient population. To illustrate
this strategy, a patient management case is presented.
|
|
|
|
Figure 1. Rates of decline in glomerular
filtration rate (GFR) vs the systolic blood pressure (SBP) in studies extending
for 3 years or more in patients with type 2 diabetes mellitus nephropathy.
Adapted from Bakris.5
|
|
|
IMPORTANCE OF BP CONTROL VS GLUCOSE CONTROL
Aggressive management of high BP is more important in reducing cardiovascular
events and slowing renal disease progression than is intensive control of
blood glucose levels.5-9
The United Kingdom Prospective Diabetes Study9
was a 9-year, randomized controlled trial that evaluated the effect of tight
BP control and glucose level control in more than 4000 people with type 2
diabetes mellitus. This study9 found that diastolic
BP control (goal, <85 mm Hg) had a greater impact on reducing cardiovascular
events than did tight glucose level control (ie, hemoglobin A1c
goal, <7%) (Figure 2). This reduction
in cardiovascular risk included a decrease in the number of strokes and any
diabetes mellitus–associated end point, including deaths.
|
|
|
|
Figure 2. Comparative effects of tight glucose
control vs tight blood pressure control in the United Kingdom Prospective
Diabetes Study.9 Asterisk indicates P<.05 compared with glucose control; DM, diabetes mellitus. Reproduced
with permission from Bakris et al.3
|
|
|
These data demonstrate the link between hypertension and renal damage
and the connection between BP control and renoprotection. The Multiple Risk
Factor Intervention Trial10 identified significant
associations between BP and the rate of renal dysfunction, thereby creating
a presumption for a causal role for hypertension. In that study, a strong,
graded relationship was demonstrated between both systolic and diastolic BP
and ESRD, independent of associations between the disease and age, race, income,
use of hypoglycemic medication, history of myocardial infarction, serum cholesterol
concentration, and cigarette smoking. Compared with men who have optimal BP
(ie, <120/80 mm Hg), the relative risk of ESRD for those with a BP greater
than 210/120 mm Hg was 22.1 (P<.001). In short,
the higher the BP, the higher the risk for renal disease.10
The sixth report of the Joint National Committee on Prevention, Detection,
Evaluation, and Treatment of High Blood Pressure (JNC VI)11
suggests that antihypertensive drug therapy should be initiated, along with
lifestyle modifications and, particularly, weight loss, to reduce BP to less
than 130/85 mm Hg. The JNC VI also states that use of angiotensin-converting
enzyme (ACE) inhibitors, calcium channel blockers (CCBs), and low-dose diuretics
is preferred because of fewer adverse effects on glucose metabolism, lipid
profiles, and renal function.12-13
CONTROLLING PROTEINURIA CAN CURB RENAL DAMAGE
Increased urinary protein or albumin excretion (microalbuminuria) is
a fundamental sign of and an independent predictor for the outcome of renal
and cardiovascular disease. The prevalence of microalbuminuria in hypertensive
individuals without diabetes mellitus can be as low as 7%, depending on age,
race, and ethnicity. The prevalence of microalbuminuria in patients with type
2 diabetes mellitus is estimated to be as high as 40%.14
The Modification of Diet in Renal Disease Study15
found that strict BP control slowed the decline in glomerular filtration rate
(GFR) in a subgroup of patients with proteinuria, an independent risk factor
for the progression of renal disease. Therefore, the presence of proteinuria
may identify patients with renal disease or diabetes mellitus who would benefit
from stricter control of BP (than the current JNC VI recommendations of <130/85
mm Hg). Based on the Modification of Diet in Renal Disease Study, patients
with urinary protein levels of 0.25 to 1.0 g/d should have a target BP of
130/80 mm Hg. For patients with urinary protein levels greater than 1 g/d,
a BP as low as 125/75 mm Hg may be advisable.15
Moderate protein restriction (0.8 g per kilogram of body weight per day) is
recommended in proteinuric patients to assist in reducing the degree of proteinuria,
which in turn reduces the rate of progression of renal disease.14
RENAL BENEFITS OF VARIOUS ANTIHYPERTENSIVE AGENTS
Some antihypertensive agents confer more renoprotection than do others.
The JNC VI11 states that low-dose diuretics
have a favorable impact on type 2 diabetes mellitus. Diuretics are often preferred
in patients with concomitant diabetes mellitus because of fewer adverse effects
on glucose homeostasis and renal function than  -adrenergic blocking
agents, another class that is recommended as first-line therapy in hypertension.11 However, thiazide diuretics are not effective with
advanced renal insufficiency (serum creatinine level  2.5 mg/dL [221
µmol/L]), and loop diuretics are needed (often at relatively large doses).
Combining a loop diuretic with a long-acting thiazide diuretic, such as metolazone
or hydrochlorothiazide (high dose), is effective in patients resistant to
a loop diuretic alone.
Treatment with ACE inhibitors can also benefit the hypertensive patient
with concomitant diabetes mellitus. A meta-analysis16
of 41 studies showed that although all the available antihypertensive drug
classes lowered BP to a greater extent than did placebo, ACE inhibitors lowered
urinary protein excretion more than the other classes. A meta-analysis17 of 100 studies of patients with type 1 and type 2
diabetes mellitus concluded that appropriate lowering of BP by any means slowed
the rate of loss of renal function. However, only ACE inhibitors seemed to
preserve GFR and decrease proteinuria independent of the BP effects.17
The salutary effects of ACE inhibitors may be related to their ability
to dilate efferent arterioles, thereby reducing intraglomerular pressure.
The beneficial effects may also result from restoration of glomerular permselectivity
in proteinuric nephropathies.18-19
This may explain why use of ACE inhibitors delays the progression of renal
disease in normotensive diabetic patients with microalbuminuria.20
Clinically, studies have shown that ACE inhibitors slow the deterioration
in GFR and delay progression to ESRD. In a clinical trial using the drug captopril,21 a 50% risk reduction in the combined end points of
death, dialysis, and transplantation was noted among patients with type 1
diabetes mellitus nephropathy who received an ACE inhibitor compared with
other agents used to lower arterial pressure. Similarly, the Ramipril Efficacy
in Nephropathy study22 showed that in patients
with chronic nephropathies and a urinary protein level of 3 g/d or less, use
of the ACE inhibitor ramipril safely reduced the rate of GFR decline and halved
the combined risk of doubling of the serum creatinine level or ESRD. Furthermore,
the Angiotensin-Converting-Enzyme Inhibition in Progressive Renal Insufficiency
Study23 showed that use of benazepril hydrochloride
significantly improved renal survival compared with use of placebo (P<.001) in patients with various underlying renal diseases.
Adrenergic receptor binders have been shown in short-term clinical studies
to lower urinary protein levels in patients with renal disease. A 6-month
study24 of valsartan therapy showed a sustained
reduction in BP and urinary protein levels, even in patients with advanced
renal failure. A 12-week study25 using losartan
potassium showed that for comparable BP reductions, a greater reduction in
urinary albumin levels was seen with losartan vs felodipine (a CCB) use in
hypertensive patients with or without type 2 diabetes mellitus. Long-term
studies are needed to confirm whether these antiproteinuric effects of losartan
can be deemed renoprotective.25
BP CONTROL MAY REQUIRE MULTIPLE DRUGS
Although use of an ACE inhibitor is key in antihypertensive therapy
of a diabetic patient, other drugs may also have renal benefits. In fact,
some combinations are more beneficial together than they would be if used
alone. Because not all patients attain BP control with monotherapy, use of
an additional antihypertensive agent may be necessary.
One reason BP is so difficult to control is because only half of all
hypertensive patients respond to monotherapy.26
Hypertension is a multifactorial disease in which many systems interact and
lead to an increase in BP. Therefore, use of 2 or more complementary agents
may improve response rates because more than 1 physiologic pathway is interrupted.
Studies have underscored the need for combination therapy. In the Hypertension
Optimal Treatment Study,7 74% of study participants
needed to take 2 or more antihypertensive agents to lower their diastolic
BP to 80 mm Hg or less. The cardioprotective effect of low-dose combination
therapy exceeded that of higher-dose monotherapy.7
Likewise, in the United Kingdom Prospective Diabetes Study,9
29% of patients in the tight BP control group required treatment with 3 or
more medications to achieve a BP of 144/82 mm Hg and to reduce the complications
and death related to diabetes mellitus. Clinical trials6, 27-30
that have randomized patients to lower levels of BP require an average range
of 2.8 to 4.2 different antihypertensive agents to achieve the desired goal
BP (Figure 3).
|
|
|
|
Figure 3. Recently completed cardiovascular
and renal trials in which patients received 2 or more antihypertensive agents
for intensive blood pressure control.6, 27-29
BP indicates blood pressure. Reproduced with permission from Bakris et al.3
|
|
|
Which drugs work best in a combination that can benefit the kidneys
and the rest of the cardiovascular system? A 3-year comparison31
between captopril and nifedipine-based therapy on the progression of renal
insufficiency showed no difference between the agents on BP reduction or progression
of renal insufficiency in the first 2 years. In the last year, however, 5
times more people went on to receive dialysis in the nifedipine group. In
general, this study31 demonstrated that better
BP control lowered the rate of decline in renal function in both treatment
groups as opposed to any independent renoprotective pathway. Thus, administering
an ACE inhibitor with a CCB can be potentially useful. In another study32 of proteinuria, when an ACE inhibitor was combined
with a long-acting dihydropyridine CCB, amlodipine, the results were more
favorable than when the CCB was used as monotherapy. Benazepril monotherapy
produced, as expected, significantly reduced urinary albumin excretion (UAE).
Yet, combination therapy tended to produce a greater reduction in UAE and
also increased creatinine clearance (P<.02), an
effect not seen with benazepril used alone. At study termination (6 months),
the ACE and CCB therapy showed a greater decrease (-24.6%; P<.02) than did monotherapy (-19.7%; P<.04);
however, BP was also lower in the combination group. This study supports the
results of an earlier study33 that suggest
that the combination of an ACE inhibitor, lisinopril, and a CCB, verapamil,
provides greater reduction in UAE than does use of either agent alone. That
combination resulted in the slowest decline in renal function over time, an
effect that correlated with reductions in albumin excretion. Moreover, this
benefit on proteinuria occurred without additional BP reduction. An additional
study34 demonstrates that the combination of
an ACE inhibitor and a nondihydropyridine CCB reduces proteinuria better than
either agent used alone; this effect occurred independent of its BP-lowering
activity. A recent trial35 compared the effects
of felodipine added to ramipril therapy in hypertensive patients with type
2 diabetes mellitus and impaired renal function. This ACE inhibitor–CCB
combination improved UAE and led to further improvement in BP control and
renal function than did ACE inhibitor monotherapy.35
Additional drugs can also be added to ACE inhibitor therapy to achieve
target BP. For example, very low doses of a diuretic (eg, hydrochlorothiazide,
6.25 mg/d) can potentiate the effect of the other agent without producing
adverse metabolic effects.36 -Adrenergic
blocking agents have additive BP-lowering abilities if the patient's baseline
pulse rate is 84/min or greater.37 At pulse
rates less than 84/min, little effect on BP has been observed when -adrenergic
blocking agents are combined with ACE inhibitors.
A PLAN TO ACHIEVE TARGET BPs
Based on data that evaluated the success of reaching BP goals in an
outpatient setting, BPs greater than 15/10 mm Hg above the target BP require
the use of 2 different antihypertensive agents.38
These data, together with the results of clinical trials, have led to the
development of a treatment algorithm for hypertensive patients with diabetes
mellitus, renal insufficiency, or both (Figure
4).3, 39
|
|
|
|
Figure 4. Clinical approach to managing
hypertension in a diabetic patient. Everyone with diabetes mellitus, renal
insufficiency, or both should be instructed on lifestyle modifications as
per the sixth report of the Joint National Committee on Prevention, Detection,
Evaluation, and Treatment of High Blood Pressure.11
Everyone, however, should initiate therapy if blood pressure (BP) is greater
than 130/85 mm Hg. If BP is less than 15/10 mm Hg above goal (ie, 130/80 mm
Hg), then angiotensin-converting enzyme (ACE) inhibitors can be used alone.
Asterisk indicates that calcium channel blockers (CCBs) (eg, verapamil and
diltiazem) have been shown to reduce cardiovascular mortality rates and progression
of diabetic nephropathy independent of ACE inhibitor use.27, 39
To convert serum creatinine levels to micromoles per liter, multiply milligrams
per deciliter by 88.4. Modified with permission from Bakris et al.3
|
|
|
Diuretic and ACE inhibitor combinations seem to be ideal as initial
therapy based on both drug classes' records of reducing cardiovascular events
and renal disease progression (Figure 4). 3 If the patient's BP is not at goal (ie, 130/80 mm
Hg), then a CCB should be added because these agents have shown additive BP-lowering
abilities with either ACE inhibitors or diuretics. If goal BP is achieved,
then the patient should be converted to a fixed-dose combination product (ie,
an ACE inhibitor and a CCB or an ACE inhibitor and a diuretic). If BP does
not remain at goal and the baseline pulse rate is 83/min or greater, then
an adrenergic blocking agent should be added; otherwise, another subgroup
CCB (other than the one added earlier) should be added. For example, the combination
of a nondihydropyridine and a dihydropyridine CCB has additive, even synergistic,
BP-reducing capabilities.40-41
Thereafter, if BP remains uncontrolled, then a long-acting  -adrenergic
blocking agent should be added at bedtime, and referral to a hypertension
specialist should be considered.3
PATIENT MANAGEMENT CASE
The application of these principles is described in the following patient
management case. The patient is a 57-year-old black woman who recently moved
to the city and has a 5-year history of diabetes mellitus and a 10-year history
of hypertension. She stated that she was feeling well and had no somatic complaints.
She was seen at the office because she needed to establish a relationship
with a physician who would continue managing her diabetes mellitus and hypertension.
Her review of systems was unremarkable. The patient's family history was positive
for cardiovascular disease; her parents both died of myocardial infarction.
Her mother also had diabetes mellitus and hypertension. She was uncertain
whether her father was hypertensive.
Regarding her social history, she works as a receptionist in a business
office and denies smoking cigarettes or drinking alcohol. She is married and
has 3 children. Physical examination showed that she is moderately obese,
170 cm in height, and 89.6 kg (body mass index [calculated as weight in kilograms
divided by the square of height in meters], 31.2; body mass index >25.0 is
considered an indication of obesity). She had a sitting BP of 164/100 mm Hg
with no orthostatic change. Her pulse rate was 88/min and regular.
The patient's current medications included hydrochlorothiazide, 25 mg
once daily; metformin, 500 mg twice daily; and glyburide, 2.5 mg once daily.
When queried why she was not taking an ACE inhibitor, she stated that her
former physician considered ACE inhibitors to be ineffective in black persons.
A head, eyes, ears, nose, and throat examination revealed grade 2 hypertensive
retinopathy but was otherwise unremarkable. Her lungs were clear, and the
remainder of her physical examination was unremarkable other than 1+ pedal
edema. Laboratory analysis findings were unremarkable except for a hemoglobin
A1c level of 8.3%; fasting blood sugar level, 192 mg/dL (10.6 mmol/L);
low-density lipoprotein cholesterol, 153 mg/dL (4.0 mmol/L); high-density
lipoprotein cholesterol, 36 mg/dL (0.93 mmol/L); triglyceride level, 350 mg/dL
(4.0 mmol/L); elevated total cholesterol, 300 mg/dL (7.8 mmol/L); and urinalysis
showing 1+ proteinuria. Her serum creatinine level was 1.4 mg/dL (124 µmol/L).
This patient has several risk factors—age, dyslipidemia, diabetes
mellitus, and family history of cardiovascular disease—that highlight
her need to achieve goal BP and lipid management. First, glucose control should
be improved, with stronger emphasis on dietary restraint and weight loss,
particularly because her body mass index is 31.2. Also, an increase in the
dose of her oral hypoglycemic agent may be beneficial. Second, lipid management
should be obtained with dietary modifications and lipid-lowering therapy.
Concomitantly, the patient's BP management must be changed.
Using the previously recommended scheme for treating elevated BP (Figure 4), the following approach is suggested
for this patient. This patient needs to take an ACE inhibitor to protect her
kidneys because ACE inhibitors have renal benefits in patients with diabetes
mellitus, including impeding the increase in UAE, slowing the transition from
microalbuminuria to overt albuminuria, and delaying the progression of albuminuria
to overt nephropathy in diabetic patients.17, 21, 42
She can continue taking the thiazide diuretic for 2 reasons: (1) her serum
creatinine level is less than 1.8 mg/dL (159 µmol/L) (she would be given
a loop diuretic if it were not) and (2) thiazide diuretics are often preferred
in patients with concomitant diabetes mellitus because of their favorable
adverse event profile and benign effect on glucose homeostasis and renal function.
The physician prescribed the following medications: benazepril, 10 mg once
daily; hydrochlorothiazide, 25 mg once daily; metformin, 500 mg 3 times daily;
glyburide, 2.5 mg once daily; and a once-daily statin.
After 4 weeks, the patient returned to the physician's office. Her fasting
blood glucose level had decreased slightly. However, her BP was still elevated
at 155/105 mm Hg. The physician increased her benazepril dose to 20 mg once
daily.
Eight weeks after her initial visit, her BP, at 150/98 mm Hg, remained
far from her goal of 130/80 mm Hg. At this point, the physician opted to include
a long-acting CCB in her antihypertensive regimen because, as discussed, such
a combination may control BP and renal complications better than ACE inhibitor
monotherapy. The physician gave her amlodipine, 5 mg once daily.
Six weeks later, this patient returned to her physician. Her BP was
now 135/88 mm Hg. With her goal in sight, the physician decided to use a fixed
combination of an ACE inhibitor and a CCB (ie, amlodipine and benazepril,
5:20). Fixed-dose combination agents serve the purpose of providing 2 different
antihypertensive agents in a single dosage form, and, thus, compliance is
enhanced.
What if this patient still had not approximated her BP goal? Using Figure 4, the decision would be made according
to her baseline pulse rate: if 83/min or more, an - or- -adrenergic
blocking agent could be added. If her pulse rate was less than 83/min, another
CCB subgroup could be added, such as verapamil or diltiazem.
This case study has several lessons. First, all patients with diabetes
mellitus and hypertension should be taking an ACE inhibitor (except those
with advanced renal failure: serum creatinine level >4.0-5.0 mg/dL [>354-442
µmol/L]) for renoprotection and BP control. Second, physicians should
take their time in achieving BP control. A patient may need to be seen monthly
for 4 to 6 months before actually achieving the desired BP goal. Immediate-
or short-acting CCBs or other types of agents (ie, hydralazine) will not produce
long-standing benefits in these patients. Such agents have never been shown
to reduce cardiovascular mortality rates, and, although they reduce the BP
numbers, they markedly increase sympathetic nerve activity. Finally, hypertension
is a multifactorial disease. Using more than 1 agent can attack BP from different
vantage points. Administering a single agent, and maximizing the dosage, can
expose the patient to adverse events that may result in total noncompliance.
COMMENT
Good BP control is important in protecting the human kidney from damage.
The latest position paper from the American Diabetes Association suggests
that urinalysis be performed annually in adults: if the findings are positive
for protein, a quantitative measure can be helpful in the development of a
treatment plan to decrease proteinuria; if the results are negative for protein,
then a test for the presence of microalbumin is necessary. Such screening
should begin at the time of diagnosis for type 2 diabetes mellitus; for patients
with type 1 diabetes mellitus, screening should begin at puberty and then
at 5 years' disease duration.12 Other important
strategies to protect against severe renal insufficiency include the following:
- Control for blood glucose levels in diabetic patients: intensive
insulin therapy reduced the risk of albuminuria and microalbuminuria by 54%
and 39%, respectively, in clinical trials for patients with type 1 diabetes
mellitus43
- Encourage smoking cessation: cigarette smoking is associated with
the development and progression of microalbuminuria44
- Control for hyperlipidemia: limited data confirm that correction
of lipid abnormalities is important in slowing the progression of renal insufficiency45
- Restrict protein intake to help reduce proteinuria
Elevated systolic and diastolic BP markedly accelerate the progression
of diabetic nephropathy. Aggressive antihypertensive management can greatly
reverse a decline in GFR. Appropriate therapy with antihypertensive medications
can significantly increase the median life expectancy in patients with type
1 diabetes mellitus, with a reduction in mortality from 94% to 45% and a reduction
in the need for dialysis and transplantation from 73% to 31% sixteen years
after the development of overt nephropathy.12
A meta-analysis of clinical studies of nondiabetic renal disease progression
has shown that ACE inhibitors can reduce the presence and degree of renal
failure, thus encouraging use of these agents as soon as urinary protein is
detected.46 They also reduce BP to the recommended
diastolic range of 80 to 90 mm Hg while diminishing UAE. All diabetic patients
with a BP of 130/80 mm Hg or greater should receive either a once-daily ACE
inhibitor or a once-daily angiotensin receptor blocker and be titrated to
moderate or high doses until the BP goal is achieved. Moreover, 2 recent trials
support the concept that angiotensin receptor blockers may be the drugs of
first choice to prevent nephropathy in patients with type 2 diabetes mellitus47-48; thus, they should be considered
first-line agents in this clinical setting.
Adding another drug to ACE inhibitor or angiotensin receptor blocker
therapy may result in more renoprotection than the ACE inhibitor or angiotensin
receptor blocker therapy used alone. More studies are emerging that show such
a trend when ACE inhibitors are administered in conjunction with CCBs. Future
trials should concentrate on whether the effects of such combinations offer
novel pathways that curb renal damage independent of their BP-lowering effects.
In that way, we can determine the proper therapies and dosages that can provide
renoprotection before renal damage is extensive.
CONCLUSIONS
The goal BP in a patient with diabetes mellitus is less than 130/80
mm Hg. Lower BP levels (ie, <125/75 mm Hg) are recommended in patients
with diabetes mellitus who have urinary protein levels greater than 1 g/d.
All patients with diabetes mellitus or renal insufficiency should be taking
an ACE inhibitor as part of their antihypertensive regimen, unless specifically
contraindicated. An alternative to ACE inhibitor therapy may be angiotensin
receptor blockade; however, data from clinical trials are not yet available
to offer such a recommendation. The addition of either a diuretic or a CCB
should be second-line therapy in these patients to help achieve the BP goal.
Also, clinicians should understand that, in most cases, 2 or even 3 different
antihypertensive medications will be needed to help achieve these goals and
that failure to do so will minimize the benefit of antihypertensive treatment
on renal or cardiovascular event reduction.
AUTHOR INFORMATION
Accepted for publication April 9, 2001.
Corresponding author and reprints: George L. Bakris, MD, Departments
of Preventive Medicine and Internal Medicine, Rush Presbyterian-St Luke's-Medical
Center, Rush University Hypertension Center, 1700 W Van Buren, Suite 470,
Chicago, IL 60612 (e-mail: gbakris{at}rush.edu).
From the Department of Preventive Medicine/Hypertension, Clinical Research
Section, Rush-Presbyterian-St Luke's Medical Center, Chicago, Ill.
REFERENCES
| |
1. Rennke HG, Anderson S, Brenner BM. The progression of renal disease: structural and functional correlations. In: Tisher CC, Brenner BM, eds. Renal Pathology:
With Clinical and Functional Correlations. Philadelphia, Pa: Lippincott
Williams & Wilkins; 1994:116-139.
2. Brown TE, Carter BL. Hypertension and endstage renal disease. Ann Pharmacother. 1994;28:359-366.
ABSTRACT
3. Bakris GL, Williams M, Dworkin L, et al for the National Kidney Foundation Hypertension and Diabetes Executive
Committees Working Group. Preserving renal function in adults with hypertension and diabetes:
a consensus approach. Am J Kidney Dis. 2000;36:646-661.
ISI
| PUBMED
4. Bild D, Teutsch SM. The control of hypertension in persons with diabetes: a public health
approach. Public Health Rep. 1987;102:522-529.
ISI
| PUBMED
5. Bakris GL. Progression of diabetic nephropathy: a focus on arterial pressure level
and methods of reduction. Diabetes Res Clin Pract. 1998;39:S35-S42.
6. Estacio RO, Jeffers BW, Hiatt WR, Biggerstaff SL, Gifford N, Schrier RW. The effect of nisoldipine as compared with enalapril on cardiovascular
outcomes in patients with non–insulin-dependent diabetes and hypertension. N Engl J Med. 1998;338:645-652.
FREE FULL TEXT
7. Hansson L, Zanchetti A, Carruthers G, et al for the Hypertension Optimal Treatment (HOT) Study Group. Effects of intensive blood-pressure lowering and low-dose aspirin in
patients with hypertension: principal results of the HOT randomised trial. Lancet. 1998;351:1755-1762.
FULL TEXT
|
ISI
| PUBMED
8. Tuomilehto J, Rastenyte D, Birkenhager WH, et al for the Systolic Hypertension in Europe Trial Investigators. Effects of calcium-channel blockade in older patients with diabetes
and systolic hypertension. N Engl J Med. 1999;340:677-684.
FREE FULL TEXT
9. United Kingdom Prospective Diabetes Study (UKPDS) Group. Tight blood pressure control and risk of macrovascular and microvascular
complications in type 2 diabetes: UKPDS 38. BMJ. 1998;317:703-713.
FREE FULL TEXT
10. Klag MJ, Whelton PK, Randall B, et al. Blood pressure and end-stage renal disease in men. N Engl J Med. 1996;334:13-18.
FREE FULL TEXT
11. The sixth report of the Joint National Committee on Prevention, Detection,
Evaluation, and Treatment of High Blood Pressure. Arch Intern Med. 1997;157:2413-2446.
FREE FULL TEXT
12. American Diabetes Association. Diabetic nephropathy. Diabetes Care. 1999;22(suppl 1):S66-S69.
13. National High Blood Pressure Education Program Working Group. National High Blood Pressure Education Program Working Group report
on hypertension in diabetes. Hypertension. 1994;23:145-158.
FREE FULL TEXT
14. Keane WF, Eknoyan G. Proteinuria, albuminuria, risk, assessment, detection, elimination
(PARADE): a position paper of the National Kidney Foundation. Am J Kidney Dis. 1999;33:1004-1010.
ISI
| PUBMED
15. Peterson JC, Adler S, Burkart JM, et al. Blood pressure control, proteinuria, and the progression of renal disease:
the Modification of Diet in Renal Disease Study. Ann Intern Med. 1995;123:754-762.
FREE FULL TEXT
16. Gansevoort RT, Sluiter WJ, Hemmelder MH, de Zeeuw D, de Jong PE. Antiproteinuric effect of blood-pressure–lowering agents: a meta-analysis
of comparative trials. Nephrol Dial Transplant. 1995;10:1963-1974.
FREE FULL TEXT
17. Kasiske BL, Kalil RSN, Ma JZ, Liao M, Keane WF. Effect of antihypertensive therapy on the kidney in patients with diabetes:
a meta-regression analysis. Ann Intern Med. 1993;118:129-138.
FREE FULL TEXT
18. Morelli E, Loon N, Meyer T, Peters W, Myers BD. Effects of converting-enzyme inhibition on barrier function in diabetic
glomerulopathy. Diabetes. 1990;39:76-82.
ABSTRACT
19. Remuzzi A, Perticucci E, Ruggenenti P, Mosconi L, Limonta M, Remuzzi G. Angiotensin converting enzyme inhibition improves glomerular size-selectivity
in IgA nephropathy. Kidney Int. 1991;39:1267-1273.
ISI
| PUBMED
20. Ravid M, Lang R, Rachmani R, Lishner M. Long-term renoprotective effect of angiotensin-converting enzyme inhibition
in non–insulin-dependent diabetes mellitus: a 7-year follow-up study. Arch Intern Med. 1996;156:286-289.
FREE FULL TEXT
21. Lewis EJ, Hunsicker LG, Bain RP, Rohde RD for The Collaborative Study Group. The effect of angiotensin-converting enzyme inhibition on diabetic
nephropathy. N Engl J Med. 1993;329:1456-1462.
FREE FULL TEXT
22. The GISEN Group. Randomised placebo-controlled trial of effect of ramipril on decline
in glomerular filtration rate and risk of terminal renal failure in proteinuric,
non-diabetic nephropathy. Lancet. 1997;349:1857-1863.
FULL TEXT
|
ISI
| PUBMED
23. Maschio G, Alberti D, Janin G, et al for the Angiotensin-Converting-Enzyme Inhibition in Progressive Renal
Insufficiency Study Group. Effect of the angiotensin-converting-enzyme inhibitor benazepril on
the progression of chronic renal insufficiency. N Engl J Med. 1996;334:939-945.
FREE FULL TEXT
24. Plum J, Bunten B, Nemeth R, Grabensee B. Effects of the angiotensin II antagonist valsartan on blood pressure,
proteinuria, and renal hemodynamics in patients with chronic renal failure
and hypertension. J Am Soc Nephrol. 1998;9:2223-2234.
ABSTRACT
25. Chan JC, Critchley JA, Tomlinson B, Chan TY, Cockram CS. Antihypertensive and anti-albuminuric effects of losartan potassium
and felodipine in Chinese elderly hypertensive patients with or without non–insulin-dependent
diabetes mellitus. Am J Nephrol. 1997;17:72-80.
ISI
| PUBMED
26. Materson BJ, Reda DJ, Cushman WC, et al for the Department of Veterans Affairs Cooperative Study Group on Antihypertensive
Agents. Single-drug therapy for hypertension in men: a comparison of six antihypertensive
drugs with placebo. N Engl J Med. 1993;328:914-921.
FREE FULL TEXT
27. Bakris GL, Mangrum A, Copley JB, Vicknair N, Sadler R. Effect of calcium channel or beta-blockade on the progression of diabetic
nephropathy in African Americans. Hypertension. 1997;29:744-750.
FREE FULL TEXT
28. Davis BR, Cutler JA, Gordon DJ, et al for the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart
Attack Trial (ALLHAT) Research Group. Rationale and design for the ALLHAT. Am J Hypertens. 1996;9:342-360.
FULL TEXT
|
ISI
| PUBMED
29. Hannedouche T, Landais P, Goldfarb, et al. Randomised controlled trial of enalapril and beta blockers in non-diabetic
chronic renal failure. BMJ. 1994;309:833-837.
FREE FULL TEXT
30. Oparil S, Calhoun DA. Managing the patient with hard-to-control hypertension. Am Fam Physician. 1998;57:1007-1014.
ISI
| PUBMED
31. Zucchelli P, Zuccala A, Borghi M, et al. Long-term comparison between captopril and nifedipine in the progression
of renal insufficiency. Kidney Int. 1992;42:452-458.
ISI
| PUBMED
32. Fogari R, Zoppi A, Mugellini A, Lusardi P, Destro M, Corradi L. Effect of benazepril plus amlodipine vs benazepril alone on urinary
albumin excretion in hypertensive patients with type II diabetes and microalbuminuria. Clin Drug Invest. 1997;13(suppl 1):50-55.
33. Bakris GL, Barnhill BW, Sadler R. Treatment of arterial hypertension in diabetic humans: importance of
therapeutic selection. Kidney Int. 1992;41:912-919.
ISI
| PUBMED
34. Bakris GL, Weir MR, DeQuattro V, McMahon FG. Effects of an ACE inhibitor/calcium antagonist combination on proteinuria
in diabetic nephropathy. Kidney Int. 1998;54:1283-1289.
FULL TEXT
|
ISI
| PUBMED
35. Corradi L, Zoopi L, Lusardi P, et al. Effects of felodipine addition to ramipril on albuminuria in diabetic
hypertensive patients with impaired renal function [abstract]. Am J Hypertens. 1998;11:112A.
36. Frishman WH, Bryzinski BS, Coulson LR, et al. A multifactorial trial design to assess combination therapy in hypertension:
treatment with bisoprolol and hydrochlorothiazide. Arch Intern Med. 1994;154:1461-1468.
FREE FULL TEXT
37. Belz GG, Breithaupt K, Erb K, Kleinbloesem CH, Wolf GK. Influence of the angiotensin converting enzyme inhibitor cilazapril,
the beta-blocker propranolol and their combination on haemodynamics in hypertension. J Hypertens. 1989;7:817-824.
FULL TEXT
|
ISI
| PUBMED
38. Hilleman D. Cost effectiveness of combination therapy. Am J Manag Care. 1999;5(suppl):S449-S455.
39. Effect of verapamil on mortality and major events after acute myocardial
infarction (the Danish Verapamil Infarction Trial II—DAVIT II). Am J Cardiol. 1990;66:779-785.
FULL TEXT
|
ISI
| PUBMED
40. Saseen JJ, Carter BL, Brown TE, Elliott WJ, Black HR. Comparison of nifedipine alone and with diltiazem or verapamil in hypertension. Hypertension. 1996;28:109-114.
FREE FULL TEXT
41. Kaesemeyer WH, Carr AA, Bottini PB, Prisant LM. Verapamil and nifedipine in combination for the treatment of hypertension. J Clin Pharmacol. 1994;34:48-51.
ABSTRACT
42. Viberti G, Mogensen CE, Groop LC, Pauls JF for the European Microalbuminuria Captopril Study Group. Effect of captopril on progression to clinical proteinuria in patients
with insulin-dependent diabetes mellitus and microalbuminuria. JAMA. 1994;271:275-279.
FREE FULL TEXT
43. The Diabetes Control and Complications Trial Research Group. The effect of intensive treatment of diabetes in the development and
progression of long-term complications in insulin-dependent diabetes mellitus. N Engl J Med. 1993;329:977-986.
FREE FULL TEXT
44. Bennett PH, Haffner S, Kasiske BL, et al. Screening and management of microalbuminuria in patients with diabetes
mellitus: recommendations to the Scientific Advisory Board of the National
Kidney Foundation from an ad hoc committee of the Council on Diabetes Mellitus
of the National Kidney Foundation. Am J Kidney Dis. 1995;25:107-112.
ISI
| PUBMED
45. Scanferla F, Landini S, Fracasso A, et al. Risk factors for the progression of diabetic nephropathy: role of hyperlipidaemia
and its correction. Acta Diabetol. 1992;29:268-272.
46. Jafar TH, Schmid CH, Landa M, et al. Angiotensin-converting enzyme inhibitors and progression of nondiabetic
renal disease: a meta-analysis of patient-level data. Ann Intern Med. 2001;135:73-87.
FREE FULL TEXT
47. Lewis EJ, Humsicker LG, Clarke WR, et al for the Collaborative Study Group. Renoprotective effect of the angiotensin receptor antagonist irbesartan
in patients with nephropathy due to type 2 diabetes. N Engl J Med. 2001;345:851-860.
FREE FULL TEXT
48. Brenner BM, Cooper ME, DeZeeuw D, et al for the RENAAL Study Investigators. Effects of losartan on renal and cardiovascular outcomes in patients
with type 2 diabetes and nephropathy. N Engl J Med. 2001;345:861-869.
FREE FULL TEXT
 CiteULike  Connotea  Del.icio.us  Digg  Reddit  Technorati  Twitter
What's this?
THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES
|
Resistant Hypertension: Diagnosis, Evaluation, and Treatment: A Scientific Statement From the American Heart Association Professional Education Committee of the Council for High Blood Pressure Research
Calhoun et al.
Circulation 2008;117:e510-e526.
ABSTRACT
| FULL TEXT
Resistant Hypertension: Diagnosis, Evaluation, and Treatment: A Scientific Statement From the American Heart Association Professional Education Committee of the Council for High Blood Pressure Research
Calhoun et al.
Hypertension 2008;51:1403-1419.
ABSTRACT
| FULL TEXT
Diabetes Management Issues for Patients With Chronic Kidney Disease
Cavanaugh
Clin. Diabetes 2007;25:90-97.
ABSTRACT
| FULL TEXT
Relationship Between Low-Normal Blood Pressure and Kidney Disease in Type 1 Diabetes
Shankar et al.
Hypertension 2007;49:48-54.
ABSTRACT
| FULL TEXT
Diabetic Nephropathy: Diagnosis, Prevention, and Treatment
Gross et al.
Diabetes Care 2005;28:164-176.
ABSTRACT
| FULL TEXT
Blood Pressure Control and Nephroprotection in Diabetes
Abbott et al.
J Clin Pharmacol 2004;44:431-438.
ABSTRACT
| FULL TEXT
Effects of Blood Pressure Level on Progression of Diabetic Nephropathy: Results From the RENAAL Study
Bakris et al.
Arch Intern Med 2003;163:1555-1565.
ABSTRACT
| FULL TEXT
|
|
|
