Aggressive Lowering of Blood Pressure in type 2 Diabetes Mellitus: The Diastolic Cost

(1)

Aggressive Lowering of Blood Aggressive Lowering of Blood

Pressure in type 2 Diabetes Pressure in type 2 Diabetes

Mellitus Mellitus : :

The Diastolic Cost The Diastolic Cost

Naftali

Naftali SternStern

Institute of Endocrinology, Metabolism and Institute of Endocrinology, Metabolism and Hypertension

Hypertension Tel Aviv -Tel Aviv -SouraskySourasky Medical Center and Medical Center and Sackler

Sackler Faculty of Medicine, Tel avivFaculty of Medicine, Tel aviv -University-University, Tel Aviv, , Tel Aviv, Israel

Israel

(2)

GUIDELINES

GUIDELINES FOR BLOOD PRESSURE FOR BLOOD PRESSURE CONTROL IN DIABETES MELLITUS

CONTROL IN DIABETES MELLITUS

<130/85 mmHg

19931993-- NIH NATIONAL CONSENSUSNIH NATIONAL CONSENSUS

19971997-- JNC 6;JNC 6;

<130/80 mmHg

20002000-- National US consensus National US consensus forumforum Universally accepted

Universally accepted

(3)

Some Blood Pressure Patterns in

Type 2 Diabetes

(4)

Prevalence of

Prevalence of Hypertension inHypertension in Diabetes: Diabetes:

Cross sectional analyss in

Cross sectional analyss in 22272227 patientspatients

(Kabakov et al, JCMS 2006) (Kabakov et al, JCMS 2006)

70.070.0

81.081.0

89.089.0

00 2020 4040 6060 8080 100100

140/90

140/90 130/85130/85 130/80130/80

% Hypertensive% Hypertensive

(5)

Prevalence of Hypertension in Prevalence of Hypertension in

Diabetes

Diabetes as a function of ageas a function of age

(Cross sectional analysis in 2227

(Cross sectional analysis in 2227 patients)patients)

00 2020 4040 6060 80 80 100100

2121-30-30 (N=20) (N=20)

31-31-4040 (N=83) (N=83)

41-41-5050 (N=339) (N=339)

5151--6060 (N=541) (N=541)

6161--7070 (N=758) (N=758)

71-71-8080 (N=400) (N=400)

8181--9090 (N=77) (N=77)

Age (yrs) Age (yrs)

% Hypertensive% Hypertensive

130/80 130/80

130/85 130/85

140/90 140/90

(6)

Prevalence

Prevalence of Systolic & of Systolic & Diastolic HypertensionDiastolic Hypertension vs. vs. Age: Age:

Cross sectional analysis of 2227 subjects

Cross sectional analysis of 2227 subjects (Kabakov et al, JCMS 2006)(Kabakov et al, JCMS 2006)

00 2020 4040 6060 8080 100100

2020 3030 4040 5050 6060 7070 8080 9090

FRACTION (%)FRACTION (%)

SYS_SYS_130130 DIAST_80DIAST_80 DIAST_DIAST_8585

Age (years) Age (years)

(7)

BP features in Diabetic Hypertensive BP features in Diabetic Hypertensive

Subjects:

Subjects: SystSyst EurEur as an exampleas an example

Mean

Mean systolic blood pressure 1.7 mm Hg systolic blood pressure 1.7 mm Hg higher

higher than that in the than that in the nondiabeticnondiabetic patientspatients Mean

Mean diastolic blood pressure 1.1 mm Hg diastolic blood pressure 1.1 mm Hg lower

lower than in than in nondiabeticsnondiabetics =>=>

Mean pulse pressure was 2.8 mm Hg wider in Mean pulse pressure was 2.8 mm Hg wider in the diabetic patients

the diabetic patients

Patients with diabetes:

(8)

Copyright restrictions may apply.

Whelton, P. K. et al. Arch Intern Med 2005;165:1401-1409.

Baseline Characteristics of 31512 ALLHAT Baseline Characteristics of 31512 ALLHAT

Participants by Glycemic Status*

Baseline characteristics of 31512 ALLHAT Participants by

Baseline characteristics of 31512 ALLHAT Participants by GlycemicGlycemic Status*Status*

Characteristic Characteristic

Age, mean (SD), y Age, mean (SD), y Women

Women Black Black

Education, mean (SD), y Education, mean (SD), y Cigarette smoker Cigarette smoker Atherosclerotic CVD Atherosclerotic CVD History of MI or stroke History of MI or stroke

History of coronary revascularization History of coronary revascularization Other atherosclerotic CVD

Other atherosclerotic CVD Major ST depression/T

Major ST depression/T--wave inversion#wave inversion#

History of CHD at baseline##

History of HDL

History of HDL--C <35 mg/dlC <35 mg/dl

History of LVH by electrocardiogram or echocardiogram History of LVH by electrocardiogram or echocardiogram Taking

Taking anthihypertensiveanthihypertensivemedicationmedication Aspirin

Aspirin

Estrogen supplements 9women only) Estrogen supplements 9women only) Medication to lower lipid levels Medication to lower lipid levels⁺⁺

Systolic/diastolic blood pressure, mean (SD), mm Hg Systolic/diastolic blood pressure, mean (SD), mm Hg Taking

Taking anthihypertensivesanthihypertensives Not taking

Not taking anthihypertensivesanthihypertensives BMI, mean (SD)

BMI, mean (SD)

DM DM (n=13101) (n=13101) 66.6 (7.4)**

66.6 (7.4)**

6463 (49.3)**

5077 (38.8)**

10.7 (4.0)**

1762 (13.4)**

4693 (35.8)**

2412 (18.4)**

1403 (10.7)**

1969 (15.0)**

865 (6.7)**

2578 (19.8)**

1171 (8.9)**

1656 (15.3)**

12098 (92.3)**

4415 (33.7)**

914 (14/1)**

1682 (13.0)**

146.5 (15.4)/82.9 (10.0)**

145.8 (15.5)/82.6 (9.9)**

155.2 (11.5)/87.3 (9.6)**

31.1 (6.3)**

Glycemic GlycemicStatusStatus

IFGIFG (n=1399) (n=1399) 67.0 (7.5) 67.0 (7.5) 528 (37.7)**

528 (37.7)**

413 (29.5) 413 (29.5) 11.1 (3.9) 11.1 (3.9) 329 (23.5)**

329 (23.5)**

876 (62.8) 876 (62.8) 288 (27.7) 288 (27.7) 215 (15.4) 215 (15.4) 394 (28.2) 394 (28.2) 197 (14.3) 197 (14.3) 426 (30.8) 426 (30.8) 252 (18.0)**

252 (18.0)**

322 (26.3) 322 (26.3) 1247 (89.1) 1247 (89.1) 533 (38.1) 533 (38.1) 82 (15.5)**

82 (15.5)**

215 (15.6) 215 (15.6) 146.5 (15.7)/84.0 (9.8) 146.5 (15.7)/84.0 (9.8) 145.1 (15.5)/84.0 (9.8) 145.1 (15.5)/84.0 (9.8) 158.4 (12.0)/89.8 (9.9) 158.4 (12.0)/89.8 (9.9)

30.5 (6.0)**

NG NG (n=17012) (n=17012) 67.1 (7.9) 67.1 (7.9) 7719 (45.4) 7719 (45.4) 5468 (32.1) 5468 (32.1) 11.2 (4.0) 11.2 (4.0) 4714 (27.7) 4714 (27.7) 10495 (61.7) 10495 (61.7) 4493 (26.4) 4493 (26.4) 2479 (14.6) 2479 (14.6) 4994 (29.4) 4994 (29.4) 2104 (12.5) 2104 (12.5) 2951 (17.3) 2951 (17.3) 2250 (13.2) 2250 (13.2) 4061 (27.1) 4061 (27.1) 15107 (88.8) 15107 (88.8) 6451 (37.9 6451 (37.9 1637 (21.2) 1637 (21.2) 2423 (14.4) 2423 (14.4) 146.0 (15.8)/84.8 (10.0) 146.0 (15.8)/84.8 (10.0) 144.7 (15.6/84.1 (9.9) 144.7 (15.6/84.1 (9.9) 156.4 (12.4)/90.4 (8.9) 156.4 (12.4)/90.4 (8.9)

28.7 (5.8) 28.7 (5.8) Abbreviations: ALLHAT, Antihypertensive and Lipid

Abbreviations: ALLHAT, Antihypertensive and Lipid--Lowering Treatment to prevent Heart Lowering Treatment to prevent Heart AtackAtackTrial; BMI, body mass index (calculated as weight in kilogramsTrial; BMI, body mass index (calculated as weight in kilograms Divided by the square of height in maters); CHD, coronary heart

Divided by the square of height in maters); CHD, coronary heart disease; CDV, cardiovascular disease; DM, diabetes mellitus; HDLdisease; CDV, cardiovascular disease; DM, diabetes mellitus; HDL--C, highC, high--density lipoprotein density lipoprotein cholesterol; IFG, impaired fasting glucose level; LVH, left vent

cholesterol; IFG, impaired fasting glucose level; LVH, left ventricular ricular hypertrophy;MIhypertrophy;MI, myocardial , myocardial infarcationinfarcation; NG, ; NG, normoglycemicnormoglycemic.. SI conversion factor: to convert HDL

SI conversion factor: to convert HDL--C to C to millimolesmillimolesper liter, per liter, mutiplymutiplyby 0.0259.by 0.0259.

*Unless otherwise indicated, data are expressed as number (perce

*Unless otherwise indicated, data are expressed as number (percentage) of patients. Because of missing or invalid values, some dntage) of patients. Because of missing or invalid values, some denominators varied.enominators varied.

**Denominators were 12957 for DM, 1381 for IFG and 16878 for NG.

#

#Denominators were 12991 for DM, 1376 for IFG and 16902 for NG.Denominators were 12991 for DM, 1376 for IFG and 16902 for NG.

##

##Denominators were 10797 for DM, 1225 for IFG and 14966 for NG. Denominators were 10797 for DM, 1225 for IFG and 14966 for NG.

+

+Denominators were 12927 for DM, 1376 for IFG and 16857 for NG.Denominators were 12927 for DM, 1376 for IFG and 16857 for NG.

Archives of Internal Medicine

(9)

Diastolic Blod pressure is lower in Diastolic Blod pressure is lower in

Diabetes: Baseline BP Characteristics of Diabetes: Baseline BP Characteristics of 31512 ALLHAT Participants by Glycemic 31512 ALLHAT Participants by Glycemic

Status*

156.4 (12.4)/

90.4 (8.9) 90.4 (8.9) 158.4 (12.0)/

158.4 (12.0)/

89.8 (9.9) 89.8 (9.9) 155.2 (11.5)/

155.2 (11.5)/

87.3 (9.6)**

Not taking anthihypertensives Not taking anthihypertensives

144.7 (15.6/

84.1 (9.9) 84.1 (9.9) 145.1 (15.5)/

145.1 (15.5)/

84.0 (9.8) 84.0 (9.8) 145.8 (15.5)/

145.8 (15.5)/

82.6 (9.9)**

Taking anthihypertensives Taking anthihypertensives

146.0 (15.8)/

84.8 (10.0) 84.8 (10.0) 146.5 (15.7)/

146.5 (15.7)/

84.0 (9.8) 84.0 (9.8) 146.5 (15.4)/

146.5 (15.4)/

82.9 (10.0)**

Systolic/

diastolic BP, mean (SD), diastolic BP, mean (SD), mm Hg

mm Hg

NGNG

(n=17012) (n=17012) IFGIFG

(n=1399) (n=1399) DMDM

(n=13101) (n=13101)

(10)

RECENT GUIDELINES FOR BLOOD RECENT GUIDELINES FOR BLOOD PRESSURE CONTROL IN DIABETES PRESSURE CONTROL IN DIABETES

MELLITUS MELLITUS

<130/85 mmHg

19931993-- NIH NATIONAL CONSENSUSNIH NATIONAL CONSENSUS

19971997-- JNC 6;JNC 6;

<130/80 mmHg

20002000-- National US consensus forumNational US consensus forum

(11)

Achieved blood pressure in major Achieved blood pressure in major

studies including diabetic studies including diabetic

hypertensive subjects hypertensive subjects

BP,mmHg

BP,mmHg mean age mean age drug(sdrug(s)) HOT 143/82

HOT 143/82 penedilpenedil IDDNT 141/83

IDDNT 141/83 ++58 58 irbesartanirbesartan RENAAL 140/74

RENAAL 140/74 ++60 60 losartanlosartan UKPDS 144/86

UKPDS 144/86 atenololatenolol ABCD 133/78

ABCD 133/78 ++58 58 enalaprilenalapril SYST-SYST-EUR 162/82 >EUR 162/82 >60 nitendip.60 nitendip.

Micro

Micro--HOPE 140/77 HOPE 140/77 ++65 65 ramiprilramipril

(12)

Recently completed cardiovascular and Recently completed cardiovascular and renal trials in which patients received 2 renal trials in which patients received 2

or more antihypertensive agents for or more antihypertensive agents for

intensive blood pressure control intensive blood pressure control

United Kingdom Prospective Diabetes Study United Kingdom Prospective Diabetes Study⁹⁹ (<85 mm Hg [Diastolic BP])

(<85 mm Hg [Diastolic BP])

Appropriate Blood Pressure in Diabetes Trial Appropriate Blood Pressure in Diabetes Trial (<75 mm Hg [Diastolic BP])

(<75 mm Hg [Diastolic BP])

Modification of Diet in Renal Disease Study1 Modification of Diet in Renal Disease Study1⁴⁴ (<92 mm Hg [Mean arterial Pressure])

(<92 mm Hg [Mean arterial Pressure]) Hypertension Optimal Treatment Study Hypertension Optimal Treatment Study⁷⁷ (<80 mm Hg [Diastolic BP])

(<80 mm Hg [Diastolic BP]) African

African-American Study of kidney Disease-American Study of kidney Disease (<92 mm Hg [mean Arterial pressure]) (<92 mm Hg [mean Arterial pressure])

11 22 33 44

Antihypertensive Agents, No Antihypertensive Agents, No

(13)

Attempted Lowering of Both Systolic and Diastolic Pressure in Clinical Practice

As of 1997 we systematically implemented JNCAs of 1997 we systematically implemented JNC-- VI guidelines (target < 130/85 mm Hg) for the VI guidelines (target < 130/85 mm Hg) for the treatment of hypertension in all type 2 diabetic treatment of hypertension in all type 2 diabetic

hypertensive patients treated for hypertension at a hypertensive patients treated for hypertension at a university

university--affiliated medical center (n=257). affiliated medical center (n=257).

Results of this intervention were reviewed in all Results of this intervention were reviewed in all subjects who had a minimal follow up period of subjects who had a minimal follow up period of 12 months (mean 20 months).

12 months (mean 20 months).

Osher et al, J Clin Hypert 2006

(14)

Principles of Intervention

Individualized tailoring of medications Individualized tailoring of medications based on a) the use of flexible drug

based on a) the use of flexible drug combinations

combinations

Gradual increments in dose or number of Gradual increments in dose or number of medications at 4

medications at 4--12 week intervals 12 week intervals

Use of ACE inhibitors whenever possible Use of ACE inhibitors whenever possible

Use of beta blockers in individuals with Use of beta blockers in individuals with documented previous coronary events documented previous coronary events

(15)

FINAL DIASTOLIC & SYSTOLIC PRESSURES FINAL DIASTOLIC & SYSTOLIC PRESSURES

DISTRIBUTION DISTRIBUTION

>

>=130=130; <85 ; <85 ((NN==150150))

58%58%

<130<130; >; >85 85 ((NN==44)) 22%%

>130>130; >; >85 (85 (NN ==2121)) 8%8%

<85<85//130130 (N(N==8282))

32%32%

(16)

70 70 mmHg mmHg (N(N==9393))

3636%% 71

71--84 84 mmHg mmHg ((NN==8686))

3333%%

FINAL DIASTOLIC PRESSURE GROUPS FINAL DIASTOLIC PRESSURE GROUPS

<70 <70 mmHg mmHg (N(N==5353))

21%21%

>

>==85 85 mmHg mmHg (N(N==2525))

10%10%

(17)

Final diastolic pressure Final diastolic pressure

(by diastolic pressure groups) (by diastolic pressure groups)

90+90+11

7979

70 70

60+60+11

5050 6060 7070 8080 9090 100100

<70 mmHg

<70 mmHg (N=57) (N=57)

70 mmHg 70 mmHg

(N=93) (N=93)

P=P=0.0.00010001;; All comparisonsAll comparisons

Diastolic pressureDiastolic pressure

71-71-84 mmHg84 mmHg (N=86) (N=86)

>85 mmHg

>85 mmHg (N=25) (N=25)

(18)

90+90+22 89+89+11

85+85+22

5050 5555 6060 6565 7070 7575 80 80 8585 9090 9595

DialosticDialosticpressurepressure

89+89+11

<70 mmHg

<70 mmHg (N=53) (N=53)

70 mmHg 70 mmHg

(N=93) (N=93)

7070--84 mmHg84 mmHg (N=86) (N=86)

>=85 mmHg

>=85 mmHg (N=25) (N=25)

Initial

Initial diastolic pressure diastolic pressure

(by (by final diastolicfinal diastolic pressure groups)pressure groups)

(19)

Decrease in diastolic pressure Decrease in diastolic pressure

(by final diastolic pressure groups) (by final diastolic pressure groups)

P=0.0001 P=0.0001 P=0.001

P=0.001

**

0+0+33

**

10+10+11

**

19+19+11 25+25+22

00 55 10 10 1515 2020 2525 3030

Decrease in diastolic pressureDecrease in diastolic pressure

**

<70 mmHg

<70 mmHg (N=53) (N=53)

70 mmHg 70 mmHg

(N=93) (N=93)

70-70-84 mmHg84 mmHg (N=86) (N=86)

>=85 mmHg

>=85 mmHg (N=25) (N=25) P=0.0001

P=0.0001

(20)

161 161++55

153+153+22 159+159+33

166+166+44

110110 120120 130130 140 140 150150 160160 170170 180 180

Systolic pressure

<70 mmHg

<70 mmHg (N=53) (N=53)

70 mmHg 70 mmHg

(N=93) (N=93)

70-70-84 mmHg84 mmHg (N=86) (N=86)

>=85 mmHg

>=85 mmHg (N=25) (N=25)

Initial systolic pressure Initial systolic pressure

(by final diastolic pressure groups) (by final diastolic pressure groups)

p<0.04, ANOVA p<0.04, ANOVA

(21)

71-71-84 84 >>84 84

INITIAL PULSE PRESSURE INITIAL PULSE PRESSURE

((By Final Diastolic Blood Pressure Groups)By Final Diastolic Blood Pressure Groups)

((

))

5050 5555 6060 6565 7070 7575 8080 8585 9090

Pulse PressurePulse Pressure

<70

<70 7070 mmHgmmHg

p<0.01, ANOVA p<0.01, ANOVA

(22)

Age Age by final diastolic pressure groupsby final diastolic pressure groups

59.6+59.6+33 61.7+61.7+1.21.2

67.4+67.4+1.11.1 70.3+70.3+1.31.3

4040 5050 6060 7070 8080

AgeAge

<70 mmHg

<70 mmHg (N=53) (N=53)

70 mmHg 70 mmHg

(N=93) (N=93)

70-70-84 mmHg84 mmHg (N=86) (N=86)

>=85 mmHg

>=85 mmHg (N=25) (N=25) p<0.0001, ANOVA

p<0.0001, ANOVA

(23)

Diabetic patients who normalized systolic Diabetic patients who normalized systolic

& diastolic pressure

& diastolic pressure vs.vs. patients who patients who normalized diastolic pressure only normalized diastolic pressure only

. .

**

67.5+67.5+0.80.8 63+63+1.41.4

4040 5050 6060 7070 8080

<<130/130/85 85 ((NN==82)82) <85<85;>;>=130 =130 ((NN==150150))

P<0.01 P<0.01

AGEAGE

(24)

Patients

Patients who normalized who normalized both systolicboth systolic & &

diastolic pressure vs. patients who diastolic pressure vs. patients who

normalized diastolic pressure only normalized diastolic pressure only

**

165+165+22

147+147+33

110 110 120120 130130 140140 150150 160160 170 170 180180

P=0.0001 P=0.0001

Initial systolic pressureInitial systolic pressure

<130/85 (N=82)

<130/85 (N=82) <85;>130 (N=150)<85;>130 (N=150)

(25)

88+88+11 88+88+11

5050 6060 7070 8080 9090 100100

NS NS

Initial diastolic pressureInitial diastolic pressuremmHgmmHg

Diabetic patients who normalized Diabetic patients who normalized

systolic & diastolic pressure vs. patients systolic & diastolic pressure vs. patients

who normalized diastolic pressure only who normalized diastolic pressure only

<130/85 (N=82)

<130/85 (N=82) <85;>130 (N=150)<85;>130 (N=150)

(26)

**

30+30+0.60.6

27.2+27.2+0.80.8

2020 2525 3030 3535

P<0.01 P<0.01

BMI

Diabetic patients who normalized systolic Diabetic patients who normalized systolic

& diastolic pressure vs. patients who

& diastolic pressure vs. patients who normalized diastolic pressure only normalized diastolic pressure only

<130/85

<130/85 <85;>130<85;>130

(27)

0.670.67

**

1.471.47

00 0.0.55 11 1.1.55 22

P<0.005 P<0.005

NormalizedNormalizedFemaleFemaleMaleMaleRatioRatio

Fraction of female gender among diabetic

Fraction of female gender among diabetic patients patients who normalized systolic & diastolic pressure vs.

who normalized systolic & diastolic pressure vs.

patients who normalized diastolic pressure only patients who normalized diastolic pressure only

<130/85 (N=82)

<130/85 (N=82) <85;>130 (N=150)<85;>130 (N=150) F/M=

F/M=

(28)

Prevalence of Ischemic Heart Disease in Prevalence of Ischemic Heart Disease in

Diabetic

Diabetic Hypertensive Patients by Final Hypertensive Patients by Final Diastolic Pressure (groups)

Diastolic Pressure (groups)

**

52.8%

33.3%

25.6%

25.6% 24.0%24.0%

00 1010 2020 3030 4040 5050 6060

Prevalence of IHD (%)Prevalence of IHD (%)

P<0.01 P<0.01

<70 mmHg

<70 mmHg (N=53) (N=53)

70 mmHg 70 mmHg

(N=93) (N=93)

7070--84 mmHg84 mmHg (N=86) (N=86)

>=85 mmHg

>=85 mmHg (N=25) (N=25)

(29)

Use of Nitrates in Diabetic Hypertensive Use of Nitrates in Diabetic Hypertensive Patients

Patients by Final Diastolic Pressure (groups) by Final Diastolic Pressure (groups)

**

34.7%

17.5%

17.5% 16.7%16.7%

10.5%

00 1010 2020 3030 4040 5050

Use of Nitrates (%)Use of Nitrates (%)

P<0.05 P<0.05

<70 mmHg

<70 mmHg 70 mmHg70 mmHg 7070--84 mmHg84 mmHg >=85 mmHg>=85 mmHg

(30)

Excessive diastolic lowering

Excessive diastolic lowering –– an an inevitable outcome of aggressive BP inevitable outcome of aggressive BP

lowering in type 2 diabetes!

1) older age 1) older age

2) high initial systolic pressure and pulse 2) high initial systolic pressure and pulse

pressure pressure

3) female gender 3) female gender

4) presence of known coronary disease 4) presence of known coronary disease

associated particularly with associated particularly with

(31)

In the treatment of hypertension in type 2 diabetes, can we avoid the

diastolic cost?

(32)

In the treatment of hypertension in type 2 diabetes, can we entirely

avoid the diastolic cost?

No BP Control No BP Control (<130/80mmHg) (<130/80mmHg)

No problem No problem (in BP control)(in BP control)

No wayNo way

(33)

““Isolated Systolic hypertensionIsolated Systolic hypertension”” in the in the SystSyst--EurEur Diabetic Population is defined Diabetic Population is defined

as <95 mmHg as <95 mmHg

Diastolic Pressure, mmHgDiastolic Pressure, mmHg

00 1010 2020 30 30 4040 5050 6060 7070 8080 90 90 100100

Initial Initial DP+2SD DP+2SD Initial Initial DP+SD DP+SD Initial DP Initial DP Initial Initial DPDP-SD-SD Initial Initial DP

DP-2SD-2SD

≥≥60 y/o60 y/o

SP: 160 to 219 mmHg SP: 160 to 219 mmHg (seated)

(seated)

DP: <95 mm Hg (seated) DP: <95 mm Hg (seated)

SP SP ≥≥ 140 mm Hg 140 mm Hg (standing)

(standing)

(34)

Intensive Blood Pressure Control Intensive Blood Pressure Control

Reduces the Risk of Reduces the Risk of

Cardiovascular Events in Patients Cardiovascular Events in Patients

With Peripheral Arterial Disease With Peripheral Arterial Disease

and Type 2 Diabetes and Type 2 Diabetes

Mehler

Mehler PM et al, Circulation.PM et al, Circulation. 2003;107:753 2003;107:753

(35)

Mean age

Mean age-- 59y59y

Mild systolic hypertension (135

Mild systolic hypertension (135--136 mmHg)136 mmHg) Mild diastolic hypertension (84.4mmHg)

Mild diastolic hypertension (84.4mmHg) Low prevalence of known cardiovascular Low prevalence of known cardiovascular

disease (10

disease (10--11%)11%)

Intensive treatment with no apparent Intensive treatment with no apparent

diastolic cost (ABCD trial) diastolic cost (ABCD trial)

(36)

The Appropriate Blood

The Appropriate Blood--Pressure Pressure Control in Diabetes (ABCD)

Control in Diabetes (ABCD)

Mehler

Mehler et al, Circulation. 2003;107:753et al, Circulation. 2003;107:753

A prospective interventional study of patients with type 2 diabe

A prospective interventional study of patients with type 2 diabetes. tes.

“Normotensive“Normotensive”” patients (DP 80-patients (DP 80-89mmHg)89mmHg) were randomized to were randomized to placebo or (moderate blood pressure control) intensive treatment placebo or (moderate blood pressure control) intensive treatment with

with enalaprilenalapril or nisoldipineor nisoldipine ..

Moderate BP subjects had a mean blood pressure of

Moderate BP subjects had a mean blood pressure of 137±137±0.7/810.7/81±±0.3 0.3 mm Hg over the last 4 years of treatment.

mm Hg over the last 4 years of treatment.

Intensive treatment with

Intensive treatment with enalaprilenalapril or or nisoldipinenisoldipine had a mean 4had a mean 4--year year blood pressure of

blood pressure of 128±128±0.8/750.8/75±±0.30.3 mm Hg (mm Hg (PP<0.0001 compared with <0.0001 compared with moderate control).

moderate control).

PAD, which is defined as an ankle

PAD, which is defined as an ankle--brachial index <0.90 at the brachial index <0.90 at the baseline visit, was diagnosed in 53 patients.

baseline visit, was diagnosed in 53 patients.

In patients with PAD, there were 3 cardiovascular events (13.6%) In patients with PAD, there were 3 cardiovascular events (13.6%) on on intensive treatment Vs. 12 events (38.7%) on moderate treatment intensive treatment Vs. 12 events (38.7%) on moderate treatment ((PP=0.046).. =0.046)..

(37)

LIFELIFE

ALLHAT ALLHAT

ASCOT

ASCOT-- BPLABPLA

Recent Evidence for Diastolic Cost Recent Evidence for Diastolic Cost

in Large Clinical Trials in Large Clinical Trials

(38)

Cardiovascular morbidity and mortality Cardiovascular morbidity and mortality in patients with diabetes in the

in patients with diabetes in the LosartanLosartan Intervention For Endpoint

Intervention For Endpoint reductionreduction in in hypertension study (LIFE)

hypertension study (LIFE)

0 10 20 30 40 50 60 70 80

Mean DP Mean DP Mean DP

Mean DP--1SD1SD Mean DP

Mean DP--2SD2SD

(39)

Diabetic ALLHAT Patients: Attained Diabetic ALLHAT Patients: Attained

Diastolic Blood Pressure, Year 5 Diastolic Blood Pressure, Year 5

Arch Intern Med. 2005 ;165:1401-9.

00 1010 2020 3030 40 40 5050 6060 7070 8080

Chlorth

Chlorth.. Amlodip.Amlodip. LisinoprilLisinopril

DPDP

DP-DP-1SD1SD DP-DP-2SD2SD

Diastolic pressure, mmHg