Case Study

A CASE OF HYPERTENSION IN DIABETES

This case study aims to

• Help understand the association between hypertension and type 2 diabetes mellitus.
• State the goals for treatment of hypertension in patients with diabetes mellitus
• Discuss the choice of antihypertensives in hypertensive patients with diabetes.
• List the various antihypertensives their mechanisms of action
• Describe the routine primary management for a patient with type 2 diabetes.

History
Mr. G is a 45-year-old gentleman with a history of type 2 diabetes, obesity, and hypertension.
The patient was diagnosed with type 2 diabetes 7 years ago when during an insurance
examination. Mr. G. is 172 cms and has always been over weight, with his weight fluctuating
between 85 and 90 kg.
Initial treatment for his diabetes consisted of a Tab glimepiride 1 mg/day with metformin. His
diabetes has been under fair control with a most recent hemoglobin A1c of 7.4%.
Hypertension was diagnosed about 5 years ago when blood pressure (BP) measured in the
family physician’s clinic was noted to be consistently elevated in the range of 160/90 mmHg
on three occasions. Mr.G. was initially treated with ramipril, starting at 5 mg daily and
increasing to 10 mg daily, yet his BP control has fluctuated.
One year ago, microalbuminuria was detected on an annual urine screen, with 2010 mg/dl of
microalbumin identified on a spot urine sample.
Mr. G. comes for his usual follow-up visit for diabetes. Physical examination reveals an a BP
of 150/90 mmHg and a pulse of 80 bpm

1. What is the relationship between hypertension and diabetes?

Hypertension is more common in diabetics than non-diabetics. Hypertension is a major factor
in development of macro vascular and micro vascular complications in a diabetic patient.
The patient is at a greater risk of developing cardiovascular complications. Isolated systolic
hypertension is more common in diabetics than non diabetics and is a risk factor for macro
vascular disease
Diabetes mellitus is a major risk factor for cardiovascular disease (CVD). Approximately
two-thirds of people with diabetes die from complications of CVD. Patients with diabetes are
prone to a number of cardiovascular risk factors beyond hyperglycemia. These risk factors,
including hypertension, dyslipidemia, and a sedentary lifestyle, are particularly prevalent
among patients with diabetes. To reduce the mortality and morbidity from CVD among
patients with diabetes, aggressive treatment of glycemic control as well as other
cardiovascular risk factors must be initiated.

2. Target BP for patients with diabetes and hypertension is

a) < 130/89 mm Hg
b) < 140/90 mm Hg
c) < 150/100 mm Hg
d) Neither of the above
The correct answer is a < 130/80 mm Hg
Blood pressure should be measured at every routine diabetes visit. Patients found to have
systolic blood pressure ≥130 mmHg or diastolic blood pressure ≥80 mmHg should have
blood pressure confirmed on a separate day. Repeat systolic blood pressure ≥130 mmHg or
diastolic blood pressure ≥80 mmHg confirms a diagnosis of hypertension
The United Kingdom Prospective Diabetes Study (UKPDS), which followed patients with
diabetes for an average of 8.5 years, found that patients with tight BP control (< 150/< 85
mmHg) versus less tight control (< 180/< 105 mmHg) had lower rates of myocardial
infarction (MI), stroke, and peripheral vascular events. In the UKPDS, each 10-mmHg
decrease in mean systolic BP was associated with a 12% reduction in risk for any
complication related to diabetes, a 15% reduction for death related to diabetes, and an 11%
reduction for MI.
The Hypertension Optimal Treatment (HOT) trial has shown that patients assigned to lower
BP targets have improved outcomes. In the HOT trial, patients who achieved a diastolic BP
of < 80 mmHg benefited the most in terms of reduction of cardiovascular events. Other
epidemiological studies have shown that BPs > 120/70 mmHg are associated with increased
cardiovascular morbidity and mortality in people with diabetes. The American Diabetes
Association has recommended a target BP goal of < 130/80 mmHg

3. The antihypertensive agents recommended for patients with diabetes are

a) ACE inhibitors
b) ARBS
c) Both of the above
d) Neither of the above
The correct answer is c- both ACEIs and ARBs
ƒ Patients with a systolic blood pressure of 130–139 mmHg or a diastolic blood
pressure of 80–89 mmHg may be given lifestyle therapy alone for a maximum of 3
months and then, if targets are not achieved, treated with addition of pharmacological
agents
ƒ Patients with more severe hypertension (systolic blood pressure ≥140 or diastolic
blood pressure ≥90 mmHg) at diagnosis or follow-up should receive pharmacologic
therapy in addition to lifestyle therapy
ƒ Pharmacologic therapy for patients with diabetes and hypertension should be with a
regimen that includes either an ACE inhibitor or an angiotensin receptor blocker
(ARB). If one class is not tolerated, the other should be substituted. If needed to
achieve blood pressure targets, a thiazide diuretic should be added to those with an
estimated glomerular filtration rate (GFR) (see below) ≥30 ml/min per 1.73 m2 and a
loop diuretic for those with an estimated GFR <30 ml/min per 1.73 m2
ƒ Multiple drug therapy (two or more agents at maximal doses) is generally required to
achieve blood pressure targets
ƒ If ACE inhibitors, ARBs, or diuretics are used, kidney function and serum potassium
levels should be closely monitored
ƒ In pregnant patients with diabetes and chronic hypertension, blood pressure target
goals of 110–129/65–79 mmHg are suggested in the interest of long-term maternal
health and minimizing impaired fetal growth. ACE inhibitors and ARBs are
contraindicated during pregnancy
The UKPDS showed no significant differences in outcomes for treatment for
hypertension using an ACE inhibitor or a β-blocker. In addition, both ACE inhibitors and
angiotensin II receptor blockers (ARBs) have been shown to slow the development and
progression of diabetic nephropathy.
In the Heart Outcomes Prevention Evaluation (HOPE) trial, ACE inhibitors were found to
have a favorable effect in reducing cardiovascular morbidity and mortality, whereas
recent trials have shown a renal protective benefit from both ACE inhibitors and ARBs.
 ACE inhibitors and β-blockers seem to be better than dihydropyridine calcium-channel
blockers to reduce MI and heart failure. However, trials using dihydropyridine calcium-
channel blockers in combination with ACE inhibitors and β-blockers do not appear to
show any increased morbidity or mortality in CVD, as has been implicated in the past for
dihydropyridine calcium-channel blockers alone.
The Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial
(ALLHAT) in high-risk hypertensive patients, including those with diabetes,
demonstrated that chlorthalidone, a thiazide-type diuretic, was superior to an ACE
inhibitor, lisinopril, in preventing one or more forms of CVD.

4. What are the various antihypertensives used in diabetics

________________________________________________________________________
Drug, daily dosage Recommended in Avoid in Side effects
Calcium channel Asthmatics, patients Heart blocks Flushing,
blockers with concomitant (verapamil and headaches, ankle
Nifedipine 15-60mg angina (except diltiazem oedema, gum
Amlodipine 5-10mg nifedipine), PVD, hyperplasia
Felodipine 5-20 mg
Nitrendipine 5-40mg
ACE inhibitors CHF, LVH Renal artery Cough,
Captopril 25-150mg, stenosis, angioneurotic
Enalapril 2.5-15 mg, pregnancy, use oedema
Lisinopril 5 –30 mg, with caution in
Ramipril 1.25-10 mg patients with CRF,
Perindopril 4-8 mg and with diuretics
ARBs CHF, LVH Renal artery
Losartan K 25-100 stenosis,
mg/day pregnancy, use
Valsartan 80-160 with caution in
mg/day patients with CRF,
Olmesartan 20-40 and with diuretics
mg/day
Telmisartan 20-80
mg/day
Alpha blockers Asthmatics, PVD, Severe aortic Headache, dry
Prazosin 1-5 mg prostatic symptoms, stenosis mouth, first dose
Terazosin1-20 mg impotence, syncope
hyperlipidemias

Case contd.
Hydrochlorthiazide 12.5 mg/day was added o the treatment regimen,
The blood pressure dropped to 130 m/84 mm of Hg over aperiod of 2 weeks

Take home messages.

 1. Hypertension is a risk factor for cardiovascular complications of diabetes.
2. Clinical trials demonstrate that drug therapy versus placebo will reduce cardiovascular
events when treating patients with hypertension and diabetes.
3. A target BP goal of < 130/80 mmHg is recommended.
4. Pharmacological therapy needs to be individualized to fit patients' needs.
5. ACE inhibitors, ARBs, diuretics, and β-blockers have all been documented to be
effective pharmacological treatment.
6. Combinations of drugs are often necessary to achieve target levels of BP control.
7. ACE inhibitors and ARBs are agents best suited to retard progression of nephropathy.

References
1) ALLHAT Officers and Coordinators for the ALLHAT Collaborative Research Group:
Major outcomes in high-risk hypertensive patients randomized to angiotensin-
converting enzyme inhibitor or calcium channel-blocker vs. diuretic: the
Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial.
JAMA288 : 2981-2997,2002
2) American Diabetes Association: Hypertension management in adults with diabetes
(Position Statement). Diabetes Care 27 (Suppl. 1):S65 -S67, 2004
3) Hansson L, Zanchetti A, Carruthers SG, Dahlof B, Elmfeldt D, Julius S, Menard J,
Rahn KH, Wedel H, Westerling S: Effects of intensive blood pressure lowering and
low dose aspirin in patients with hypertension: principal results of the Hypertension
Optimal Treatment (HOT) randomized trial. Lancet 351:1755 -1762, 1998
4) U.K. Prospective Diabetes Study Group: Efficacy of atenolol and captopril in
reducing risk of macrovascular and microvascular complications in type 2 diabetes
(UKPDS 39). BMJ 317:713 -720, 1998