Management of hypertension in diabetes

Dr Mohamed Al-Ameen
Nephrology& Transplantation Specialist
KAAH&OC

• HTN is the leading cause of morbidity and
mortality worldwide.
• Affecting 20–60% of diabetics.
• HTN is common in Diabetics vs in Non
diabetics 1.5 to 3 times.
Management of Hypertension in Diabetics
HTN in DM:HTN in DM: FactsFacts

• Hypertensive Diabetics vs Hypertensive non diabetics
 Twice the risk of CVD
• 1 in every 4 individuals in US has HTN. ADA 2005
• The greatest reduction in cardiovascular mortality
occurs at achieving a diastolic blood pressure of ~80
mmHg and systolic blood pressure to <130 mmHg

IHD Mortality Rate in each age dacade vs HTNIHD Mortality Rate in each age dacade vs HTN

WHOWHO
FactFact
SheetSheet
WorldWorld KSAKSA
20002000 20302030 20002000 20302030
DMDM 171,000,000171,000,000 366,000,000366,000,000 890,000890,000 2,523,0002,523,000
 USA:
o ~ 60% of Diabetics are HTN.
o14% of Af. Am. have HTN& DM
ADA 2005
1,513,8001,513,800543,000543,000219,600,000219,600,000102,600.000102,600.000
EstimatedEstimated
DM+HTNDM+HTN 1,513,8001,513,800543,000543,000219,600,000219,600,000102,600.000102,600.000
EstimatedEstimated
DM+HTNDM+HTN
 Germany:
o 50% of 1ry care pts have HTN.
o 12% of all pts have HTN& DM.
Lehnert H et al. 2005Lehnert H et al. 2005
133,800,000 801,880NOW
HTN in DM:HTN in DM: PrevalencePrevalence

WHOWHO
FactFact
SheetSheet
WorldWorld KSAKSA
20002000 20302030 20002000 20302030
DMDM 171,000,000171,000,000 366,000,000366,000,000 890,000890,000 2,523,0002,523,000
 USA:
o One in every four has HTN.
o ~ 60% of Diabetics are HTN.
ADA 2005
 Germany:
o 50% of 1ry care pts have HTN.
o 12% of all pts have HTN&DM.
Lehnert H et al. 2005Lehnert H et al. 2005
133,800,000 801,880NOW
Only 25 percent of patients with hypertension
have adequate control of their blood pressure
The Third National Health and Nutrition Evaluation SurveyThe Third National Health and Nutrition Evaluation Survey
(NHANES III)(NHANES III)
• 29% of diabetic individuals with hypertension were unaware29% of diabetic individuals with hypertension were unaware
of the diagnosis.of the diagnosis.
• 43% of diabetic individuals with hypertension were untreated.43% of diabetic individuals with hypertension were untreated.
• 55% of diabetic individuals on treatment had a blood pressure55% of diabetic individuals on treatment had a blood pressure
≥140/90.≥140/90.
• 12% of diabetic individuals on treatment had a blood pressure12% of diabetic individuals on treatment had a blood pressure
<130/85.<130/85.
Am J Prev Med 22:42–48, 2002

NEJM 2000; 342:905 Diabetes Care 2005; 28:310 Am J Kid Dis 2007; 49 (Suppl 2):S74
HypertensiveHypertensivePopulationsPopulations
95%95%-- MacroalbuminuriaMacroalbuminuria
80%80%-- MicroalbuminuriaMicroalbuminuria
50%50%-- AtAt DxDx
•• Type 2 DMType 2 DM
30%30%-- NormoalbuminuriaNormoalbuminuria
60%60%Diabetic U.S. adultsDiabetic U.S. adults
30%30%All U.S. adultsAll U.S. adults
HypertensiveHypertensivePopulationsPopulations
50%50%-- AtAt DxDx
30%30%-- NormoalbuminuriaNormoalbuminuria
60%60%Diabetic U.S. adultsDiabetic U.S. adults
30%30%All U.S. adultsAll U.S. adults
Type 1Type 1
(¼ are Htn)(¼ are Htn)
At Diagnosis: 20-40%At Diagnosis: 20-40%
With Microalbuminuria: 30-50%With Microalbuminuria: 30-50%
With Macroalbuminuria: 65-88%With Macroalbuminuria: 65-88%
Type 2Type 2
(½ are Htn)(½ are Htn)
At Diagnosis: 50%At Diagnosis: 50%
With Microalbuminuria: 80%With Microalbuminuria: 80%
With Macroalbuminuria: >90%With Macroalbuminuria: >90%

DiabetesDiabetes HypertensionHypertension
HTN in DM:HTN in DM: PARTNERS IN CRIMEPARTNERS IN CRIME
HTN vs No HTN DM vs No DM
2.4x ↑ in DM 2.0x ↑ in HTN
NEJM 2000; 342:905 Diabetes Care 2005; 28:310

 Cause:Cause: Hypertension is usuallyHypertension is usually renoparenchymalrenoparenchymal in originin origin
caused by Or pointing to underlying diabetic nephropathycaused by Or pointing to underlying diabetic nephropathy
 Onset:Onset: Typically becomes manifest about the time thatTypically becomes manifest about the time that
patients developpatients develop microalbuminuriamicroalbuminuria..
American Diabetic Association.American Diabetic Association. DiabDiab Care 2004Care 2004
 Cause:Cause: Mainly due insulin resistance (as a facet of MS)Mainly due insulin resistance (as a facet of MS)
But may be due to underlying DN or other causes.But may be due to underlying DN or other causes.
American Diabetic Association. Diab Care 2004
 Onset:Onset: Usually precedes the onset of nephropathy andUsually precedes the onset of nephropathy and
even the onset of type 2 diabetes by years or decadeeven the onset of type 2 diabetes by years or decade
 Ritz et al. J Int Med. 2001 ; 249: 215Ritz et al. J Int Med. 2001 ; 249: 215--223223
DM-2DM-2
DM-1DM-1

Hypertensive patients without diabetes tend to be resistant to insulin
and are hyperinsulinaemic compared with normotensive controls.
Pollare T et al. Metabolism 1990, 39(2):167-174.
About 20% of patients with hypertension will develop type 2 diabetes
in a three year period. Bosch J et al. N Engl J Med 2006, 355(15):1551-1562.
Fasting glucose levels increase in older adults with hypertension
regardless of treatment type. BarzilayJ I et al. Arch Intern Med. 2006;166:2191-
2201
 The RAS itself plays imp. role in the development of
diabetes.
 Over activity of RAS appears to be linked to reduced
insulin and glucose delivery to the peripheral
skeletal muscle and impaired glucose transport and
response to insulin signalling pathways, thus
increasing insulin resistance.
Jandeleit-Dahm KA et al. J Hypertens 2005, 23(3):463-473.
 Activation of a local pancreatic RAS, in particular
within the islets, may represent an independent
mechanism for the progression of islet cell damage
in diabetes.
Ferrannini E et al. Diabetologia 2003, 46(9):1211-1219.

 The risk of diabetes associated
with antihypertensive-drug therapy
appears to be explained by the
presence of hypertension.
 Among the subjects who had
hypertension, the risk among those
not taking medication was similar to
that among those taking one or
more agents.
 Among the subjects who were not
taking any antihypertensive
medication, the risk of diabetes
was much higher among
hypertensive Pts. than in non
hypertensive.
0
5
10
15
Chlorthalidone Amlodipine Lisinopril
11.6%
9.8%
8.1%
ALLHAT: Incidence of New-Onset Diabetes at 4 Years
JAMA 2002;288:2981-2997
Role of Antihypertensive Drugs

 Taking a thiazide diuretic, ACETaking a thiazide diuretic, ACE
inhibitor, or CCB carry noinhibitor, or CCB carry no
greater risk for the subsequentgreater risk for the subsequent
development of DM.development of DM.
 DM was 28 percent more likelyDM was 28 percent more likely
to develop in subjects takingto develop in subjects taking
BB than in those taking noBB than in those taking no
medication.medication.
 This adverse effect of BB mustThis adverse effect of BB must
be weighed against the provenbe weighed against the proven
benefits of this drug inbenefits of this drug in
reducing the risk ofreducing the risk of
cardiovascular eventscardiovascular events
Role of Antihypertensive Drugs

AMERICAN FAMILY PHYSICIAN www.aafp.org/afp VOLUME 66, NUMBER 7 / OCTOBER 1, 2002
Diabetes andDiabetes and
HTNHTN vsvs DiabetesDiabetes
Relative RiskRelative Risk
ofof
ComplicationsComplications
CHDCHD X 3.0X 3.0
StrokeStroke X 4.0X 4.0
RetinopathyRetinopathy X 2.0X 2.0
NephropathyNephropathy X 2.0X 2.0
NeuropathyNeuropathy X 1.6X 1.6
MortalityMortality X 2.0X 2.0
75% die from CVD75% die from CVD
NEJM 2005; 352:341

Association between refractory hypertension and cardiometabolic risk
The HIPERFRE study, 2008
1,724 hypertensive patients, 35 physicians, 14 Primary Care Units
The HIPERFRE study, 2008
1,724 hypertensive patients, 35 physicians, 14 Primary Care Units

D
E
A
T
H
LDL=low-density lipoprotein; HDL=high-density lipoprotein; MI=myocardial infarction; CHD=congestive heart
failiure; HF=heart failure; ESRD=end-stage renal disease
Adapted from Arch Intern Med. 2000; 160:1277-1283.
Insulin
Resistance
Hyper-
insulinemia
Triglycerides
LDL
HDL
Visceral Fat
Angiotensin II
Sympathetic
Activity
+ Hypertension
Diabetes
CHD
Stroke
MI
HF
ESRD
Metabolic Syndrome Morbid States

Tight Glucose ControlTight Glucose Control
Tight BP ControlTight BP Control
**P < 0.05P < 0.05
-50 -
-40 -
-30 -
0 - Stroke
Any DM
End Point DM Death
Microvascular
Complications
ReductioninRisk(%)
UKPDS. BMJ. 1998:317;703-712.
-20 -
-10 -
Tight BP Control vs. Tight Glucose ControlTight BP Control vs. Tight Glucose Control
HTN in DM:HTN in DM: Effect of BP ControlEffect of BP Control

Tight BP Control vs. Tight Glucose ControlTight BP Control vs. Tight Glucose Control
HTN in DM:HTN in DM: Effect of BP ControlEffect of BP Control
Tight BP Control Tight Glucose Control

1. Measure BP properly.
2. Define Hypertensive Patients.
3. Evaluate hypertensive Patients.
4. Therapy
HTN in DM:HTN in DM: Practical StrategyPractical Strategy

HTN in DM:HTN in DM: 1- Measure BP Properly1- Measure BP Properly
The measurement of BP is likely
the clinical procedure of greatest
importance that is performed in
the sloppiest manner.”
(Norman Kaplan, M.D.)
Lancet 2007; 370:591
Health care professionals should take
particular care to ensure that they are
using accurate techniques to measure
BP in all their patients.”
(International Working Group, 2008)
J Hum Hypertens 2008; 22:63
∆ BP (mm Hg)
if not done
Rest ≥ 5min, quite ↑ 12/6
Seated, back supported ↑ 6/8
Cuff medsternal level ↑ ↓ 2/inch
Correct cuff size ↑ 6-18/3-14
Bladder center over
artery
↑ 3-5/2-3
Deflate 2 mm Hg/ sec ↑ SBP/↓ DBP
Can J Card 2007; 23:529

Joint National CommiteeJoint National Commitee
Caffeine, exercise, and smoking should be avoided for
at least 30 minutes prior to measurement. JNC-7
The patient should be seated for at least 5 minutes, relaxed and not
moving or speaking.
The arm must be supported at the level of the heart. Ensure no tight
clothing constricts the arm.
Place the cuff on neatly with the centre of the bladder over the
brachial artery. The bladder should encircle at least 80% of the arm
(but not more than 100%).
The column of mercury must be vertical, and at the observers eye
level.
Estimate the systolic beforehand:
a) Palpate the brachial artery
b) b) Inflate cuff until pulsation disappears
c) Deflate cuff
d) Estimate systolic pressure
Then inflate to 30 mmHg above the estimated systolic level needed to
occlude the pulse.
Place the stethoscope diaphragm over the brachial artery and deflate
at a rate of 2-3mm/sec until you hear regular tapping sounds.
Measure systolic (first sound) and diastolic (disappearance) to nearest
2mmHg.

Indications of Ambulatory BP monitoringIndications of Ambulatory BP monitoring
JNC-7

High Normal BP and CVD Risk
HTN in DM:HTN in DM: 22-- Define Hypertensive PatientsDefine Hypertensive Patients
Joint National Committee 7 (JNC-7)Joint National Committee 7 (JNC-7)

HTN in DM:HTN in DM: 2-2- Define Hypertensive PatientsDefine Hypertensive Patients
Systolic or Diastolic Hypertension???????Systolic or Diastolic Hypertension???????
250
200
150
100
50
0
<120 120-139 140-159 160-179 180-199
Systolic BP (mm Hg)Systolic BP (mm Hg)
CV
mortality
rate/
10,000
person-yr
Nondiabetic
Diabetic
CV, cardiovascular; SBP, systolic blood pressure.
Stamler J et al. Diabetes Care. 1993;16:434-444.
≥200
CV Mortality Risk Doubles WithCV Mortality Risk Doubles With
Each 20/10 mm Hg BP Increment*Each 20/10 mm Hg BP Increment*
• Stronger predictor of risk than diastolic BP:
– Cardiovascular disease
– Diabetic Nephropathy
• 65% of DM hypertensives have isolated systolic
hypertension.
• Systolic hypertension more difficult to control
Lancet 2002; 360:1903 Hypertension 2003; 42:1206
National Kidney Foundation: Guideline 8. Am J Kidney Dis 43 (Suppl. 1):S142 –S159, 2004.
Sowers JR et al. Hypertension 37:1053 –1059, 2001.

• Diastolic hypertension predominates
before age 50, either alone or in
combination with SBP elevation.
• Systolic hypertension increases with
age, and above 50 years of age, systolic
hypertension represents the most
common form of hypertension.
• DBP is a more potent cardiovascular
risk factor than SBP until age 50;
thereafter, SBP is more important.
• DBP control rates exceeded 90 percent,
but SBP control rates were
considerably less (60–70 percent)
J Clin Hypertens 2002;4:393-404.
Hypertension 2001;37:12-8.
 Three-fourths of 1ry care physicians failed to initiate therapy if SBP 140-159.Three-fourths of 1ry care physicians failed to initiate therapy if SBP 140-159.
 Most physicians have been taught that the diastolic pressure is more importantMost physicians have been taught that the diastolic pressure is more important
than SBP and thus treat accordingly.than SBP and thus treat accordingly.
 Most primary care physicians did not pursue control to <140 mmHg.Most primary care physicians did not pursue control to <140 mmHg.
J Clin Hypertens. 2000;2:324-30.J Clin Hypertens. 2000;2:324-30.

Normal < 120/<80
Prehypertension 120-139/ 80-89
Stage 1 140-159/ 90-99
Stage 2 ≥ 160/ ≥100
Follow up BP MeasurementsFollow up BP Measurements

• Estimate CV Risk Factors.
• Diagnose Target Organ Damage.
• Exclude Identifiable Causes of HTN.
• Routine Laboratory work up with ECG, lipid
profile and urinary albumin.
HTN in DM:HTN in DM: 3- Evaluate3- Evaluate Hypertensive Pts.Hypertensive Pts.

• HTN*
• Age:
• Older than 55 years for men
• Older than 65 years for women
• DM*
• Abnormal Lipid Profile*:
• Elevated LDL (or total) cholesterol
• Low HDL cholesterol*
• Estimated GFR <60 mL/min
• Family history of premature CVD:
• men <55 years of age
• women <65 years of age
• Microalbuminuria
• Obesity* (BMI >30 kg/m2)
• Physical inactivity
• Tobacco usage, particularly cigarettes
Cardiovascular Risk FactorsCardiovascular Risk Factors
(140-age) x weight x 1.23 x (0.85 if female)(140-age) x weight x 1.23 x (0.85 if female)
S Creatinine (micromol/l)S Creatinine (micromol/l)
(140-age) x Weight (Kg) x (0.85 if female)(140-age) x Weight (Kg) x (0.85 if female)
72 x S Creatinine (mg/dl)72 x S Creatinine (mg/dl)
Normoalbuminuria < 30 mg/day
Microalbuminuria 30 - 300 mg /d
Macroalbuminuria > 300 mg / day
BMI= Weight (Kg) / (Height in meter)2

• Heart
• LVH
• Angina/prior MI
• Prior coronary revascularization
• Heart failure
• Brain
• Stroke or transient ischemic attack
• Dementia
• CKD
• Peripheral arterial disease
• Retinopathy
Target Organ DamageTarget Organ Damage

• ABCD diagnosis of 2ry HTN
A: Accuracy, Apnea, Aldosteronism
B: Bruit, Bad Kidney
C: Catecholamines, Coarctation, Cushing's S.
D: Drugs, Diet
Identifiable Causes of HTNIdentifiable Causes of HTN

1. Blood Pressure Goal
2. Life Style Modification
3. Phamacological Therapy
HTN in DM:HTN in DM: 4- Therapy4- Therapy

• HOT (Hypertension Optimal Treatment).
• ABCD-NT (Appropriate Blood Pressure Control in Diabetes)
• UKPDS (UK Prospective Diabetes Study)
• IDNT (Irbesartan in Diabetic Nephropathy Trial)
• INVEST (International Verapamil-Trandolapril)
• ADA (American Diabetic association)
• ISHIB (International Society of Hypertension in Blacks)
• CHEP (Canadian Hypertension Education Program)
• BHS (British Hypertension Society)
• JNC 7 (Joint National Committee 7)
Goal Blood PressureGoal Blood Pressure
Less Than 130/80

• National Kidney Foundation Hypertension and Diabetes Executive Committees Working
Group. Am J Kidney Dis. 2000;36(3):646-661.
• American Association of Clinical Endocrinologist, 2006
• Target BP 125/75 If Proteinuria > 1gm
Goal Blood PressureGoal Blood Pressure Less Than 130/80
Can We Go to More Lower Target ?
IDNT
JASN 2005;16(7):2170–2179

• Lowest Systolic Blood Pressure Is Associated with Stroke inStages 3 to
4 Chronic Kidney Disease
J Am Soc Nephrol 18: 960–966, 2007
HR of Stroke vs SBP
Can We Go to More Lower Target ?
Goal Blood PressureGoal Blood Pressure Less Than 130/80
20,358 individuals studied, 1549 (7.6%) had CKD

Life Style ModificationsLife Style Modifications

InterventionIntervention TargetTarget
Reduce foods withReduce foods with
added sodiumadded sodium
< 2300 mg /day< 2300 mg /day
Weight lossWeight loss BMI <25 kg/mBMI <25 kg/m22
Alcohol restrictionAlcohol restriction Less or equal to 2 drinks/dayLess or equal to 2 drinks/day
Physical activityPhysical activity at least 30 minutes 4 times/weekat least 30 minutes 4 times/week
Dietary patternsDietary patterns DASH dietDASH diet
Smoking cessationSmoking cessation Smoke free environmentSmoke free environment
Waist CircumferenceWaist Circumference
- Europid, Sub-Saharan- Europid, Sub-Saharan
African, Middle EasternAfrican, Middle Eastern
- South Asian, Chinese- South Asian, Chinese
- Japanese- Japanese
Men WomenMen Women
<94 cm <80 cm<94 cm <80 cm
<90 cm <80 cm<90 cm <80 cm
<85 cm <90 cm<85 cm <90 cm

Life Style Modifications:Life Style Modifications: DietaryDietary
Dietary Sodium
Less than 2300mg / day
(Most of the salt in food is hidden and comes from
processed food)
Dietary Potassium
If required, daily dietary intake >80
mmol
Calcium supplementation
No conclusive studies for hypertension
Magnesium supplementation
No conclusive studies for hypertension
• High in fresh fruits
• High in vegetables
• High in low fat dairy
products
•High in dietary and
soluble fibre
•High in plant protein
• Low in saturated fat
and cholesterol
•Low in sodium

• Less than:
– 2,300 mg sodium (Na)
– 100 mmol sodium (Na)
– 5,8 g of salt (NaCl)
– 1 teaspoon of table salt
2,300 mg sodium = 1 level teaspoon of table salt
Life Style Modifications:Life Style Modifications: Daily SodiumDaily Sodium

Exercise should be prescribed as adjunctive to pharmacological
therapy
Should be prescribed to reduce blood pressure
Type cardiorespiratory activity
- Walking, jogging
- Cycling
- Non-competitive swimming
Time - 30-60 minutes
Intensity - Moderate
Frequency - Four to seven days per weekF
I
T
T
Life Style Modifications:Life Style Modifications: Physical ActivityPhysical Activity

Hypertensive and all patients
BMI over 25
- Encourage weight reduction
- Healthy BMI: 18.5-24.9 kg/m2
Waist Circumference Men Women
- Europid, Sub-Saharan African, Middle Eastern <94 cm <80 cm
- South Asian, Chinese <90 cm <80 cm
- Japanese <85 cm <90 cm
For patients prescribed pharmacological therapy: weight loss has
additional antihypertensive effects. Weight loss strategies should
employ a multidisciplinary approach and include dietary education,
increased physical activity and behavioural modification
Life Style Modifications:Life Style Modifications: Weight LossWeight Loss

InterventionIntervention AmountAmount SBP/DBPSBP/DBP
Reduce foods withReduce foods with
added sodiumadded sodium
- 1800 mg sodium- 1800 mg sodium
hypertensivehypertensive -5.1 / -2.7-5.1 / -2.7
Weight lossWeight loss per kg lostper kg lost -1.1 / -0.9-1.1 / -0.9
Alcohol intakeAlcohol intake - 3.6 drinks/day- 3.6 drinks/day -3.9 / -2.4-3.9 / -2.4
Aerobic exerciseAerobic exercise 120-150 min/week120-150 min/week -4.9 / -3.7-4.9 / -3.7
Dietary patternsDietary patterns
DASH dietDASH diet
HypertensiveHypertensive
NormotensiveNormotensive
-11.4 / -5.5-11.4 / -5.5
-3.6 / -1.8-3.6 / -1.8

• Use caution in initiating therapy with 2 drugs where
agressive blood pressure lowering is more likely or more
poorly tolerated (e.g. those with postural hypotension).
• ACE inhibitors and ARBs are contraindicated in
pregnancy and caution is required in prescribing to
women of child bearing potential.
• Diuretic-induced hypokalemia should be avoided
through the use of potassium sparing agent if required.
Important ConsiderationsImportant Considerations

• Monitor creatinine and potassium when combining K sparing
diuretics, ACE inhibitors and/or ARBs.
• If Dihydropyridine CCB Chosen: Not to be used without ACEi
or ARB agents.
• If a diuretic is not used as first or second line therapy, triple
drug therapy should include a diuretic, when not
contraindicated.
• Short-acting dihydropyridine calcium antagonists should not
be used in IHD because of their potential to increase risk of
mortality, particularly in the setting of acute myocardial
infarction

• Beta Blockers
– BBs less appealing as first-line agents for treatment of hypertension in patients
with either type 2 or type 1 diabetes mellitus (grade A).
– BBs, however, have proved effective in the management of the ischemic and
congestive cardiomyopathies that are more common in patients with diabetes
than in those without diabetes.
– Because the major adverse effects of BBs may be mediated by peripheral
vasoconstriction and increasing insulin resistance, the use of the new third-
generation BBs (such as Nebivolol) or drugs that block both a and b receptors
(such as Carvedilol) may prove to be particularly beneficial (grade A).
– These agents cause vasodilatation and an increase in insulin sensitivity.
American Association of Clinical Endocrinologist, 2006
– Beta adrenergic blockers are not recommended for patients age 60+ without
another compelling indication. CHEP 2008

• Beta Blockers (cont.)
– Two drug combinations of beta blockers, ACE inhibitors and
ARBs have not been proven to have additive hypotensive
effects.
– Therefore these potential two drug combinations should not be
used unless there is a compelling (non blood pressure lowering)
indication such as ischemic heart disease, post myocardial
infarction, congestive heart failure or chronic kidney disease
with proteinuria.
– It is not recommended to combine a non dihydropyridine CCB
and a beta blocker to reduce the risk of bradycardia or heart
block.

• If Diuretic Chosen: (Preferred if no other
compelling indications):
– Creatinine <1.8 mg/dL  Thiazide Diuretic
– Creatinine ≥1.8 mg/dL  Loop Diuretic
– Max. dose 25mg Hydrochlorothiazide or
equivalent)

AASK MAP <92
Target BP (mm Hg)
No. of antihypertensive agents
1
UKPDS DBP <85
ABCD DBP <75
MDRD MAP <92
HOT DBP <80
Trial 2 3 4
DBP, diastolic blood pressure; MAP, mean arterial pressure; SBP, systolic blood pressure.
Bakris GL et al. Am J Kidney Dis. 2000;36:646-661.
Lewis EJ et al. N Engl J Med. 2001;345:851-860.
Cushman WC et al. J Clin Hypertens. 2002;4:393-404.
IDNT SBP <135/DBP <85
ALLHAT SBP <140/DBP <90
Most Hypertensive Patients Need Multiple DrugsMost Hypertensive Patients Need Multiple Drugs

Compelling IndicationsCompelling Indications

ADA GuidelinesADA Guidelines
SystolicSystolic DiastolicDiastolic
Goal (mmHg)Goal (mmHg) <130<130 <80<80
Behavioral therapy aloneBehavioral therapy alone 130–139130–139 80–8980–89
(maximum 3 months)(maximum 3 months)
then add pharmacologicthen add pharmacologic
treatmenttreatment
Behavioral therapy +Behavioral therapy + ≥≥140140 ≥≥9090
pharmacologic treatmentpharmacologic treatment
Arauz-Pacheco C et al. Diabetes Care. 2003;26(suppl):S80–S82.

Practical ViewPractical View
1.1. Pts. At goal BP < 130 / 80.Pts. At goal BP < 130 / 80.
2.2. Pts. with BP 130-139 / 80-89.Pts. with BP 130-139 / 80-89.
3.3. Pts. With BP ≥ 140 /90.Pts. With BP ≥ 140 /90.
1 32
Without
Compelling
Indications
With
Compelling
Indications
With
Compelling
Indications
Without
Compelling
Indications
With
Compelling
Indications
Without
Compelling
Indications
- LSM
- Recheck each
visit
- LSM
- Recheck each
visit
- Treat CI
-LSM 3 m
-- if high BP
drug Therapy
-LSM
-Drug Th of HTN
-Drug Th of CI
-LSM
-Drug Th of HTN
-LSM
- Drug combined
-Drug of CI

ACE -ve or ARB (Or thiazide if no albuminuria or TOD)
• Consider two-drug therapy if BPe ≥ 150/90 mmHg
≥ 140/90 Or albuminuria Or TOD
≥ 130/80 mmHg on two visits≤ 1 month apart
130–139/80–89 No albuminuria, No TOD
LSM for 3 months
≥ 130/80 mmHg after 1 m
Add thiazide (or BID loop diuretic if cr ≥ 1.8
mg/dl or estimated GFR < ml/min/1.73m2)
Add nonDHP CCB (verapamil or diltiazem)
Substitute DHP CCB for nonDHP CCB
• Add B-blocker
Add DHP CCB
Reassess for causes of resistant hypertension
•Add α blocker, hydralazine, clonidine Consider consultation.
Algorithm for the Treatment of Hypertension in DMAlgorithm for the Treatment of Hypertension in DM

• In Type 2 patients: ACE-i or ARBs as a first line.
• In Type 1 patients: ACE-I is recommended to
reduce protein excretion
• Consider the use of verapamil or diltiazem in
patients with proteinuria unable to tolerate
ACEi or ARBs.
For Pts. With Microalbuminuria or ProteinuriaFor Pts. With Microalbuminuria or Proteinuria

ACE-I + ARBs: Limited UtilityACE-I + ARBs: Limited Utility
• Theoretically attractive: more complete RAAS blockade
• Limited BP ↓ and ↓ CVD events vs ACE-I at max dose
– ONTARGET RCT: 25,620 with CVD ± Stroke ± DM
– Ramipril vs Telmisartan vs R⊕T
• Minimal BP ↓: 2.4/1.4 mm Hg
• No ↓ CVD events
• More side effects
• ↓ Albuminuria 30-40% vs monoRx with ACE-I or ARB
– ? Effects on ESRD?
– NKF, 2007: consider if albumin/cr > 500 mg/g on monoRx
NEJM 2008; 358:1547 Am J Kid Dis 2007; 49(Suppl 2):S74

• • Increased HTN control
• • Reduced hypokalemia
• • Cardioprotective
• • Available as a generic medication
• • Increased adherence
ACE-I + HCTZ: Excellent 1ACE-I + HCTZ: Excellent 1stst
line agentline agent

• Consider continuing the ACE-I:
• 38-55% Likelihood the cough will resolve.
• Consider changing the time of administration or lowering the dose
• Consider antitussives or lozenges while waiting for symptom to resolve.
• Consider switching to a 2nd
ACE-I:
• Effective for 1 in 10 patients
• Consider using a different drug class:
• Diuretic, beta-blocker or calcium channel blocker
• If an ACE-I is indicated because of comorbid conditions (e.g. DM,HF, CKD)
an ARB (i.e. LOSARTAN) can be used as an alternative
ACE-I CoughACE-I Cough

 ACE-I or ARBs may cause
Hyperkalemia:
1. Avoid other medications that cause
hyperkalemia (K suppl, NSAIDs, Cox2
inhibitors, K sparing diuretics).
2. Evaluate causes of hyperkalemia.
3. Treat hyperkalemia with diuretics.
4. Continuo ACE-I or ARBs if K < 5.5 mmol/l.
 Monitor GFR
1. If GFR >30% within 4 weeks, evaluate.
2. Continuo ACE-I or ARBs if GFR < 30%
from baseline over 4 months.
ACE-I or ARBs and HyperkalemiaACE-I or ARBs and Hyperkalemia

Resistant HypertensionResistant Hypertension

ClassClass Drug (Trade Name)Drug (Trade Name) Usual Dose Range in MG/Usual Dose Range in MG/
DAYDAY
Thiazide diureticsThiazide diuretics Chlorothiazed (Diuril)Chlorothiazed (Diuril)
Chlorthalidone (generic)Chlorthalidone (generic)
Hydroclorothiazide (Microzide,Hydroclorothiazide (Microzide,
Hydro DIURIL)Hydro DIURIL)
Polythiazide (Renese)Polythiazide (Renese)
Indapamide (Lozol)Indapamide (Lozol)
Metalozol (Mykrox)Metalozol (Mykrox)
Metalazone (zaroxolyn)Metalazone (zaroxolyn)
125-500125-500
12.5-2512.5-25
12.5-5012.5-50
2-42-4
1.25-2.51.25-2.5
0.5-1.00.5-1.0
2.5-52.5-5
Loop diureticsLoop diuretics Bumetanide (bumex)Bumetanide (bumex)
Furosemide (Lasix)Furosemide (Lasix)
Torsemide (Demadex)Torsemide (Demadex)
0.5-20.5-2
20-8020-80
2.5-102.5-10
Potassium-sparingPotassium-sparing
diureticsdiuretics
Amiloride (Midamor)Amiloride (Midamor)
Triamtrene (Dyrenium)Triamtrene (Dyrenium)
5-105-10
50-10050-100
Aldosterone receptorAldosterone receptor
blockersblockers
Eplernone ( Inspra)Eplernone ( Inspra)
Spironolactone (Aldactone)Spironolactone (Aldactone)
50-10050-100
25-5025-50
Anti Hypertensive Drugs

ACE InhibitorsACE Inhibitors Benazepril (Lotensin) captoprilBenazepril (Lotensin) captopril
(capoten)(capoten)
Enalapril (vasotec)Enalapril (vasotec)
Fosinopril (monopril)Fosinopril (monopril)
Lisinopril (prinivil, zestril)Lisinopril (prinivil, zestril)
Moexipril (Univasc)Moexipril (Univasc)
Perindopril (Accupril)Perindopril (Accupril)
Quinapril (Accupril)Quinapril (Accupril)
Ramipril (Altace)Ramipril (Altace)
Trandolapril(Mavik)Trandolapril(Mavik)
10-4010-40
25-10025-100
2.5-402.5-40
10-4010-40
10-4010-40
7.5-307.5-30
4-84-8
10-4010-40
2.5-202.5-20
1-41-4
Angiotensin IIAngiotensin II
AntagonistsAntagonists
Candesartan (Atacand)Candesartan (Atacand)
Eprosartan (Teveltan)Eprosartan (Teveltan)
Irbesartan (Avapro)Irbesartan (Avapro)
Losartan (Cozaar)Losartan (Cozaar)
Olmesartan (Benicar)Olmesartan (Benicar)
Telmisartan (Micardis)Telmisartan (Micardis)
Valsartan (Diovan)Valsartan (Diovan)
8-328-32
400-800400-800
150-300150-300
25-10025-100
20-4020-40
20-8020-80
80-32080-320

Beta-BlockersBeta-Blockers Atenolol (Tenormin)Atenolol (Tenormin)
Betaxolol (Kerlone)Betaxolol (Kerlone)
Bisoprolol (zebeta)Bisoprolol (zebeta)
Metoprolol (lopressor)Metoprolol (lopressor)
Metoprolol extended releaseMetoprolol extended release
(Toprol XL)(Toprol XL)
Nadolol (Corgard)Nadolol (Corgard)
Propranolol (Inderal)Propranolol (Inderal)
Propranolol long-actingPropranolol long-acting
(Inderal LA)(Inderal LA)
Timolol (Blocadren)Timolol (Blocadren)
25-10025-100
5-205-20
2.5-102.5-10
50-10050-100
50-10050-100
40-12040-120
40-16040-160
60-18060-180
20-4020-40
Beta-Blockers withBeta-Blockers with
intrinsic sypathomimeticintrinsic sypathomimetic
activityactivity
Acebutolol (Sectral)Acebutolol (Sectral)
Penbutolol (Levatol)Penbutolol (Levatol)
Pindolol (generic)Pindolol (generic)
200-800200-800
10-4010-40
10-4010-40
Combined Alpha– andCombined Alpha– and
beta-blockersbeta-blockers
Carvedilol (Coreg)Carvedilol (Coreg)
Labetalol (Normodyne)Labetalol (Normodyne)
12.5-5012.5-50
200-800200-800

Calcium channelCalcium channel
blockers- nonblockers- non
DihydropyridinesDihydropyridines
Diltiazem extended releaseDiltiazem extended release
(cardizem CD, Dilacor XR, Tiazac) Diltiazem(cardizem CD, Dilacor XR, Tiazac) Diltiazem
extended release (Cardizem LA)extended release (Cardizem LA)
Verapamil immediate release (calan, isoptin)Verapamil immediate release (calan, isoptin)
Verapamil long acting (calan SR,Verapamil long acting (calan SR,
Isoptin SR)Isoptin SR)
Verapamil – Coer (Covera HS, Verelan PM)Verapamil – Coer (Covera HS, Verelan PM)
180-420180-420
120-540120-540
80-32080-320
120-360120-360
120-360120-360
Calcium ChannelCalcium Channel
Blockers -Blockers -
DihydropyridinesDihydropyridines
Amlodipine ( Norvasc )Amlodipine ( Norvasc )
Felodipine (plendil)Felodipine (plendil)
Isradipine (Dynaciric CR)Isradipine (Dynaciric CR)
Nicardipine sustained release (Cardene SR)Nicardipine sustained release (Cardene SR)
Nifedipine long-acting (Adalat CC, procardiaNifedipine long-acting (Adalat CC, procardia
XL)XL)
Nisoldipine (Sular)Nisoldipine (Sular)
2.5-102.5-10
2.5-202.5-20
2.5-102.5-10
60-12060-120
30-6030-60
10-4010-40

Alpha- BlockersAlpha- Blockers Doxazosin ( Cardura)Doxazosin ( Cardura)
Prazosin (minipress)Prazosin (minipress)
Terazosin (Hytrin)Terazosin (Hytrin)
1-161-16
2-202-20
1-201-20
Central alpha-agonistsCentral alpha-agonists
and other centrallyand other centrally
acting drugsacting drugs
Clonidine (Catapres)Clonidine (Catapres)
Clonidine patch (catapres-TTS)Clonidine patch (catapres-TTS)
Methyldopa (Aldomet)Methyldopa (Aldomet)
Resrpine (generic)Resrpine (generic)
Guanfacine (generic)Guanfacine (generic)
0.1-0.80.1-0.8
0.1-0.30.1-0.3
250-1000250-1000
0.05-0.250.05-0.25
0.5-20.5-2
Direct VasodilatorsDirect Vasodilators Hydralazine (Apresoline)Hydralazine (Apresoline)
Minoxidil (Loniten)Minoxidil (Loniten)
25-10025-100
2.5-802.5-80

Angiotensin II
⇑ AVP
⇑ Aldosterone
Vaso-
constriction
Mesangial
Contraction
Efferent
Constriction
CNS
Dypsogenia
Na
+
Retention
Increased
Norepinephrine
Release
Myocardial
Hypertrophy
Vessel
Hypertrophy
Deleterious Effects of Angiotensin IIDeleterious Effects of Angiotensin II

JNC-7

American Journal of Kidney Diseases, February 2007
NKF. American Journal of Kidney Diseases, February 2007

Management of hypertension in diabetes

Management of hypertension in diabetes

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