1. Hot Topic in Cardiology 2014
HYPERTENSION AND DIABETES:
THE TWO TERRORISTS TOGETHER
Kyaw Soe Win
MBBS, MMedSc (Int Med), MRCPUK, FRCP (Edin), FAsCC, FAPSIC
Sedona Hotel
23rd March 2014

2. The Two Terrorists in Cardiovascular World
The ENORMITY of the problem - compounded

3. How Common is this deadly Duo?
HTN is twice HTN is twice aass ccoommmmoonn iinn DDMM
NNeeww oonnsseett DDMM iiss 22..55 ttiimmeess iinn HHTTNN
2200 ttoo 4400%% ooff IIGGTT ppttss hhaavvee HHTTNN
4400 ttoo 5500%% ooff TTyyppee 22 DDMM hhaavvee HHTTNN
OOnnllyy 11//44 ooff HHTTNN iinn DDMM iiss ccoonnttrroolllleedd
DDMM ++ HHTTNN ––  CCVV RRiisskk 33 ffoolldd
long-term survivors of diabetes tend to have lower BP

4. HTN in DM: Prevalence
Hypertension in Type 1 and 2 Diabetes
Type 1
Develop after several years of
DM
Ultimately affects ~30% of
patients
With macroalbuminaemia-65-
88%
Type 2
Mostly present at diagnosis
Ultimately affects at least 60%
of patients
With macroalbuminaemia->90%

5. Slide 26
PPeerrcceenntt CChhaannccee ooff
CCaarrddiioovvaassccuullaarr EEvveenntt iinn 55 YYeeaarrss
NNoo DDiiaabbeetteess
>>2200%%
1155%%--2200%%
1100%%--1155%%
55%%--1100%%
22..55%%--55%%
<<22..55%%
MMeenn
NNoonnssmmookkeerr SSmmookkeerr
TToottaall CChhooll..::HHDDLL--CChhooll..
WWoommeenn
NNoonnssmmookkeerr SSmmookkeerr
TToottaall CChhooll..::HHDDLL--CChhooll..
44 55 66 77 88 44 55 66 77 88 44 55 66 77 88 44 55 66 77 88
AAggee
7700
AAggee
6600
AAggee
5500
118800//110055
116600//9955
114400//8855
112200//7755
118800//110055
116600//9955
114400//8855
112200//7755
118800//110055
116600//9955
114400//8855
112200//7755

6. Slide 27
PPeerrcceenntt CChhaannccee ooff
CCaarrddiioovvaassccuullaarr EEvveenntt iinn 55 YYeeaarrss
DDiiaabbeetteess
MMeenn
NNoonnssmmookkeerr SSmmookkeerr
TToottaall CChhooll..::HHDDLL--CChhooll..
WWoommeenn
NNoonnssmmookkeerr SSmmookkeerr
TToottaall CChhooll..::HHDDLL--CChhooll..
44 55 66 77 88 44 55 66 77 88 44 55 66 77 88 44 55 66 77 88
AAggee
7700
AAggee
6600
AAggee
5500
118800//110055
116600//9955
114400//8855
112200//7755
118800//110055
116600//9955
114400//8855
112200//7755
118800//110055
116600//9955
114400//8855
112200//7755
>>2200%%
1155%%--2200%%
1100%%--1155%%
55%%--1100%%
22..55%%--55%%
<<22..55%%

7. The EVIDENCE BASE
How and Why
DM + HT is dangerous?

8. Cardiovascular Mortality Risk Doubles
With Each 20/10 mm Hg BP Increment*
Cardiovascular
Mortality
Risk
2x
4x
8x
115/75 135/85 155/95 175/105
SBP/DBP (mm Hg)
8
7
6
5
4
3
2
1
0
SBP = systolic blood pressure; DBP = diastolic blood pressure.
*Individuals aged 40-69 years, starting at blood pressure 115/75 mm Hg
Chobanian AV et al. JAMA. 2003;289:2560-2572.
Lewington S et al. Lancet. 2002;360:1903-1913.

9. Association of SBP and CV Mortality
in Men With Type 2 Diabetes
250
200
150
100
50
0
<120 120-139 140-159 160-179 180-199
SBP (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

10. End Point Hazard Ratios Associated
With Increase in SBP
Hazard
ratio
4.0
3.5
3.0
2.5
2.0
1.5
1.0
0.5
Any end point related to diabetes (P<0.0001)
Death related to diabetes (P<0.0001)
All-cause mortality (P<0.0001)
Adler A et al. BMJ. 2000;321:412–419.
Updated mean SBP (mm Hg)
0
110 120 130 140 150 160 170

11. HOT Study: Risk of Morbidity and Mortality in
Diabetic Hypertensive Patients
Myocardial Infarction
Major CV Events
Stroke
CV Mortality
Total Mortality
90 mmHg
80 mmHg
| | | |
0 1 2 3 4
Lancet 1998; 351: 1755–62

12. Each Perpetuates the Other

13. HTN in DM: PARTNERS IN CRIME
DDiiaabbeetteess HHyyppeerrtteennssiioonn
HTN vs No HTN DM vs No DM
2.4 x ↑ in DM 2.0 x ↑ in HTN
 NEJM 2000; 342:905 Diabetes Care 2005; 28:310

14. HTN in DM: PARTNERS IN CRIME
DDiiaabbeetteess HHyyppeerrtteennssiioonn
 CCaauussee:: HHyyppeerrtteennssiioonn iiss uussuuaallllyy rreennooppaarreenncchhyymmaall iinn oorriiggiinn
ccaauusseedd bbyy OOrr ppooiinnttiinngg ttoo uunnddeerrllyyiinngg ddiiaabbeettiicc nneepphhrrooppaatthhyy
 OOnnsseett:: TTyyppiiccaallllyy bbeeccoommeess mmaanniiffeesstt aabboouutt tthhee ttiimmee tthhaatt
ppaattiieennttss ddeevveelloopp mmiiccrrooaallbbuummiinnuurriiaa..
AAmmeerriiccaann DDiiaabbeettiicc AAssssoocciiaattiioonn.. DDiiaabb CCaarree 22000044
 CCaauussee:: MMaaiinnllyy dduuee iinnssuulliinn rreessiissttaannccee ((aass aa ffaacceett ooff MMSS))
BBuutt mmaayy bbee dduuee ttoo uunnddeerrllyyiinngg DDNN oorr ootthheerr ccaauusseess..
American Diabetic Association. Diab Care 2004
 OOnnsseett:: UUssuuaallllyy pprreecceeddeess tthhee oonnsseett ooff nneepphhrrooppaatthhyy aanndd
eevveenn tthhee oonnsseett ooff ttyyppee 22 ddiiaabbeetteess bbyy yyeeaarrss oorr ddeeccaaddee
 RRiittzz eett aall.. JJ IInntt MMeedd.. 22000011 ;; 224499:: 221155--222233
DM-1
DM-2

15. Progression of DM - Nephropathy

16. Microalbuminuria as a Risk Factor
for Death in Type 2 Diabetes
1.
0
0.
8
0.
6
Survival
0.
4
UAC £15 mg/mL
0.
UAC 16-40 mg/mL
2
UAC 41-200 mg/mL
0.
0
Years after Diagnosis 0 1 2 3 4 5 6 7 8 9 10 11
UAC, urinary albumin concentration.
Adapted from Schmitz A et al. Diabetes Med. 1988;5:126-134.

17. Proteinuria & Risk of CV Mortality, Stroke, &
CHD Events in Type 2 Diabetes
1.0
0.9
0.8
0.
7
0.6
0.5
0
40
30
20
10
0 10 20 30 40 50 60 7080 90 Stroke CHD Events*
A: UPC <150 mg/L B: UPC 150-300 mg/L C: UPC >300 mg/L
CCHHDD,, ccoorroonnaarryy hheeaarrtt ddiisseeaassee;; UUPPCC,, uurriinnaarryy pprrootteeiinn ccoonncceennttrraattiioonn..
** DDeeffiinneedd aass CCHHDD ddeeaatthh oorr nnoonnffaattaall MMII..
AAddaapptteedd ffrroomm MMiieettttiinneenn HH eett aall.. SSttrrookkee.. 11999966;;2277::22003333--22003399..
P<.001 for trends
Incidence (%)
Reduction in Survival due
to CV Mortality Months
A
B
C
P-values:
Overall <.001
A vs B =.013
A vs C <.001
B vs C <.001
0

18. HTN in DM: PARTNERS IN CRIME
DDiiaabbeetteess HHyyppeerrtteennssiioonn
 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.
15
10
5
0
11.6%
9.8%
8.1%
Chlorthalidone Amlodipine Lisinopril
ALLHAT: Incidence of New-Onset Diabetes at 4 Years
JAMA 2002;288:2981-2997
Role of Antihypertensive Drugs

19. HTN in DM: PARTNERS IN CRIME
DDiiaabbeetteess HHyyppeerrtteennssiioonn
Role of Antihypertensive Drugs
 TTaakkiinngg aa tthhiiaazziiddee ddiiuurreettiicc,, AACCEE
iinnhhiibbiittoorr,, oorr CCCCBB ccaarrrryy nnoo
ggrreeaatteerr rriisskk ffoorr tthhee ssuubbsseeqquueenntt
ddeevveellooppmmeenntt ooff DDMM..
 DDMM wwaass 2288 ppeerrcceenntt mmoorree lliikkeellyy
ttoo ddeevveelloopp iinn ssuubbjjeeccttss ttaakkiinngg
BBBB tthhaann iinn tthhoossee ttaakkiinngg nnoo
mmeeddiiccaattiioonn..
 TThhiiss aaddvveerrssee eeffffeecctt ooff BBBB mmuusstt
bbee wweeiigghheedd aaggaaiinnsstt tthhee pprroovveenn
bbeenneeffiittss ooff tthhiiss ddrruugg iinn
rreedduucciinngg tthhee rriisskk ooff
ccaarrddiioovvaassccuullaarr eevveennttss

20. b-Blockers and the risk of
new-onset diabetes mellitus
28% Increased Risk
0.91
1.28
1.0
Prospective study of 12 550 patients w/o DM, aged
45-64, followed for 6 y. Multivariate analysis of
3804 who had HT at baseline.
25% Increased Risk
17.4
13.0
20
15
10
5
0
Atenolol Losartan
LIFE1
New Cases Per 1000
Person-Years (%)
1.5 Ratio
1.0
Hazard .5
Prospective study of 9193 hypertensives, aged 55-80,
followed for 4.8 y. Analysis of 7998 w/o DM at baseline.
1. Lancet 2002;359:995–1003.
2. N Engl J Med 2000;342:905–12.
ARIC2
0
Atenolol RR 1.25 (1.12-1.37)
P<.001
b-blocker RR 1.28 (1.04-1.57)
P<.05
Thiazide
b-blocker
None
1.17
CCB
0.98
ACEI

21. HTN in DM: PARTNERS IN CRIME
The TThhee HIPERFRE HHIIPPEERRFFRREE study, ssttuuddyy,, 2008
22000088
1,724 hypertensive patients, 35 physicians, 14 Primary Care Units
Association between refractory hypertension and cardiometabolic risk

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

23. The Compound Jeopardy !!
2 x 4 x
Reilly MP et al – Circulation 2003; 108: 1546-1551

24. Plasma Glucose as Independent Risk Factor
Andersson, DK et al. Diabetes Care 18: 1534-1543

25. Effect of Hypertension on mortality in DM
Mortality vs systolic blood pressure
70
60
50
40
30
20
10
0
110 120 130 140 150 160
Systolic Blood pressure
(mmHg)
Ten Year Mortality (per 1000)
Non-diabetic
Diabetic

26. Effect of Cholesterol on Mortality in DM
Serum cholesterol vs Mortality
70
60
50
40
30
20
10
0
4 5 6 7
s-Cholesterol (mmol/L)
Ten Year Mortality (per
1000)
Non-diabetic
Diabetic

27. D
E
A
T
H
HTN in DM: PARTNERS IN CRIME
Insulin
Resistance
Hyper-insulinemia
Triglycerides
LDL
HDL
Visceral Fat
Angiotensin II
Sympathetic
Activity
+ Hypertension
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.
Diabetes
CHD
Stroke
MI
HF
ESRD
Metabolic Syndrome Morbid States

28. Perpetuating Circus
CKD
Diabetes
 BP
 Lipids
CAD
ED

29. HTN in DM: Accelerates Vascular Age
 Diabetes promotes both the development and adverse
impact of cardiovascular disease (CVD) risk factors (e.g.
hypertension, dyslipidemia, renal dysfunction) and, as a
consequence, accelerates cardiovascular age.
 Persons with diabetes generally have a cardiovascular
age 10 to 15 years in advance of their chronological age.
 Advanced cardiovascular age substantially increases both
the proximate and lifetime risk for CVD events, resulting
in a reduced life expectancy of approximately 12 years.
2013 Canadian Diabetes Association guidelines

30. HTN in DM: Facts
•Hypertension in diabetes :
– it accelerates macrovascular disease
– it accelerates microvascular disease
Glycemic control only is not enough
VASCULAR PROTECTION IS IMPORTANT

31. Vascular Protection for CAD and CKD in DM
Hypertension
Dyslipidemia
Dysglycemia

32. The EVIDENCE BASE
MANAGEMENT Guide

33. Diabetes Guideline Management
 2 main sets of guidelines utilized in U.S.
 American Diabetes Association (ADA)
 American Association of Clinical Endocrinology (AACE)
(Lots of overlap, Evidence based, well accepted, clinically relevant
and can be easily incorporated into clinical practice)
 Canadian Diabetes Association 2013 Clinical Practice
Guidelines (September 2013)
 ESC Guidelines on diabetes, pre-diabetes, and
cardiovascular diseases developed in collaboration
with the EASD ( August 2013 )

34. Canadian Diabetes Association
2013 Clinical Practice Guidelines
The Essentials
Presentation by Dr. Tessa Laubscher
Clinical Associate Professor, Family Medicine
Saskatoon
Sept 2013
guidelines.diabetes.ca | 1-800-BANTING (226-8464) | diabetes.ca
Copyright © 2013 Canadian Diabetes Association

35. STANDARDS OOFF MMEEDDIICCAALL CCAARREE
IINN DDIIAABBEETTEESS——2200114

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

38. UKPDS Mean Blood Pressures
Baseline
(mm Hg)
Mean BP
over 9 yrs
(mm Hg)
Less tight control 160/94 154/87
Tight control 161/94 144/82
Difference 1/0 10/5
P value n.s. <0.0001
UKPDS, United Kingdom Prospective Diabetes Study.
UKPDS 38. BMJ. 1998;317:703-713.

39. Tight BP Control vs. Tight Glucose Control
Any DM
End Point DM Death
TTiigghhtt GGlluuccoossee CCoonnttrrooll
TTiigghhtt BBPP CCoonnttrrooll
0 - Stroke
-10 -
-20 -
-30 -
-40 -
-50 - **PP << 00..0055
Microvascular
Complica tions
Reduction in Risk (%)
UKPDS. BMJ. 1998:317;703-712.

40. Comparisons of More Intensive Blood Pressure
Lowering Strategies With Less Intensive Strategies

41. Comparisons of More Intensive Blood Pressure
Lowering Strategies With Less Intensive Strategies

42. HOT Study(Diabetic Subgroup): Significant
Benefit From Intensive Treatment in the DBP
25
20
15
10
5
0
Events/1000 pt-years
<90 <85 <80
Target diastolic BP
DM
non-DM
Lancet 1998; 351: 1755–62

43. HTN in DM: Therapy
GGooaall BBlloooodd PPrreessssuurree
Less Than 130/80
 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)

44. BP Targets in DM ( before 2013)
Ideal Blood Pressure
Without proteinuria < 130/80
With proteinuria < 125/75
Goal BP maximum for DM < 130/80
Almost all DM pts require > 1 drug for HTN
Identify the co-morbidity – CAD, CKD, CVD

45. HTN in DM: Therapy
GGooaall BBlloooodd PPrreessssuurree Less Than 130/80
Can We Go to More Lower Target ?
 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
IDNT
JASN 2005;16(7):2170–2179

46. ACCORD trial
 ACCORD trial , >4700 patients were assigned to
intensive- ( achieved mean SBP 119mmHg) or
standard treatment ( mean SBP 134mmHg) over a
mean follow-up of 4.7 years.
 The proportion of patients with serious side-effect-such
as hypotension and declining renal function_
increased from 1.3 to 3.3% with aggressive
treatment.
 Since the risk-benefit ratio tipped towards harm, this
study does not support a reduction of systolic BP
below 130mmHg.

47. HTN in DM: Therapy
GGooaall BBlloooodd PPrreessssuurree Less Than 130/80
Can We Go to More Lower Target ?
20,358 individuals studied, 1549 (7.6%) had CKD
HR of Stroke vs SBP
 Lowest Systolic Blood Pressure Is Associated with Stroke in Stages 3 to
4 Chronic Kidney Disease
J Am Soc Nephrol 18: 960–966, 2007

48. Can We Go to More Lower Target ?
GGooaall BBlloooodd PPrreessssuurree Less Than 130/80
 Bangalore et al. reported a meta-analysis of 13
RCTs with 37 736 patients with DM,IFG or IGT who,
in the intensive group, had a systolic pressure ≤135
mm Hg and, in the standard group, ≤140 mmHg.
 The more intensive control related to a 10%
reduction in all-cause mortality (95% CI 0.83–0.98),
a 17% reduction in stroke but a 20% increase in
serious adverse events. Systolic BP ≤130 mmHg was
related to a greater reduction in stroke but did not
affect other cardiovascular events.

49. Rethinking Lower Blood Pressure Goals for
Diabetic Patients with Coronary Artery Disease –
Findings from the INternational VErapamil SR –
Trandolapril STudy (INVEST)
Rhonda M. Cooper-DeHoff, Yan Gong, Eileen M. Handberg,
Anthony A. Bavry, Scott J. Denardo, George L. Bakris and
Carl J. Pepine
on behalf of the INVEST Investigators
University of Florida
Gainesville, FL

50. Methods

51. Results: Outcome Rates
INVEST Follow Up
n=6400
Tight
Control
n=2,255
Usual
Control
n=1,970
Not
Controlled
n=2,175
p value
Outcome # of Events (Event Rate %)
Primary Outcome 286 (12.7) 249 (12.6) 431 (19.8) < 0.0001
Nonfatal MI 29 (1.3) 33 (1.7) 67 (3.1) 0.008
Nonfatal Stroke 22 (1.0) 26 (1.3) 52 (2.4) 0.001
Total MI 108 (4.8) 100 (5.0) 185 (8.5) < 0.0001
Total Stroke 34 (1.5) 33 (1.7) 70 (3.2) 0.0001
All Cause Mortality 248 (11.0) 201 (10.2) 334 (15.4) < 0.0001
Extended Follow Up
n=4370
Tight
Control
n=1,389
Usual
Control
n=1,423
Not
Controlled
n=1,558
p value
Outcome # of Events (Event Rate %)
All Cause Mortality 270 (19.4) 259 (18.2) 370 (23.7) 0.01

52. Results: Outcomes – Tight Control Group
(n=2,255)
Reference

53. Summary

55. Recommendations: Hypertension/Blood Pressure
Control
AADDAA 22001144
Goals
 People with diabetes and hypertension
should be treated to a systolic blood pressure
goal of <140 mmHg
 Lower systolic targets, such as <130 mmHg,
may be appropriate for certain individuals,
such as younger patients, if it can be
achieved without undue treatment burden
 Patients with diabetes should be treated to a
diastolic blood pressure <80 mmHg
ADA. VI. Prevention, Management of Complications. Diabetes Care 2014;37(suppl 1):S36

56. Recommendations: Hypertension/Blood Pressure
Control
AADDAA 22001144
Treatment
 Patients with blood pressure >120/80 mmHg
should be advised on lifestyle changes to
reduce blood pressure
 Patients with confirmed blood pressure
higher than 140/80 mmHg should, in addition
to lifestyle therapy, have prompt initiation
and timely subsequent titration of
pharmacological therapy to achieve blood
pressure goals
ADA. VI. Prevention, Management of Complications. Diabetes Care 2014;37(suppl 1):S36

57. Hypertension / BP control
• Screening and diagnosis
– BP should be measured at every diabetes related visit and at least twice a
year.
– Patients found to have elevated BP should have high BP confirmed on a
separate day.
– Threshold for diagnosing hypertension in person with diabetes is BP ≥130/80
mmHg (may consider SBP up to 140 in elderly).
– Target for treating BP is <130/80.
• Lifestyle therapy for elevated BP
– Weight loss if overweight
– DASH-style diet with reduced sodium and increased potassium intake
– Moderation of alcohol intake
– Increased physical activity
guidelines.diabetes.ca | 1-800-BANTING (226-8464) | diabetes.ca
Copyright © 2013 Canadian Diabetes Association

58. The EVIDENCE BASE FOR
Non- Pharmaco and
Pharmacotherapy

59. IInntteerrvveennttiioonn TTaarrggeett
RReedduuccee ffooooddss wwiitthh
aaddddeedd ssooddiiuumm << 22330000 mmgg //ddaayy
WWeeiigghhtt lloossss BBMMII <<2255 kkgg//mm22
AAllccoohhooll rreessttrriiccttiioonn LLeessss oorr eeqquuaall ttoo 22 ddrriinnkkss//ddaayy
PPhhyyssiiccaall aaccttiivviittyy aatt lleeaasstt 3300 mmiinnuutteess 44 ttiimmeess//wweeeekk
DDiieettaarryy ppaatttteerrnnss DDAASSHH ddiieett
SSmmookkiinngg cceessssaattiioonn SSmmookkee ffrreeee eennvviirroonnmmeenntt
WWaaiisstt CCiirrccuummffeerreennccee
-- EEuurrooppiidd,, SSuubb--SSaahhaarraann
AAffrriiccaann,, MMiiddddllee EEaasstteerrnn
-- SSoouutthh AAssiiaann,, CChhiinneessee
-- JJaappaanneessee
MMeenn WWoommeenn
<<9944 ccmm <<8800 ccmm
<<9900 ccmm <<8800 ccmm
<<8855 ccmm <<9900 ccmm
HTN in DM: Therapy
LLiiffee SSttyyllee MMooddiiffiiccaattiioonnss

60. DASH Diet Plan
Type of Food Servings (1600 K cal)
Grains (whole grains) 6 per day
Vegetables 3 per day
Fruits (not tinned juices) 4 per day
Low fat milk 2 per day
Lean meat, poultry 3 per day
Nuts, seeds (dry roast, soak) 3 per week
Fats and oils 2 per day
Sweets and pastries 0 per day
Salt at table & salted foods None

61. HTN – Lifestyle modifications

62. Hypertension In Diabetes
Does choice of Antihepertensive
Drug matter?
Yes

63. Pathophysiology of hypertension in DM
Type 1 DM
Secondary to
nephropathy
Activation of the
RAAS
Type 2 DM
Hyperinsulinemia
Secondary to insulin
resistance
Activation of the
sympathetic nervous
system

64. Ideal anti HTN drug in DM
 Must decrease blood pressure to £ 140/80
 Must reduce the RAAS activity, improve ED
 Must prevent, improve or arrest proteinuria
 Must prevent and protect from CAD, CKD, CHF
 Must be favourable on glycemic control
 Must improve the dyslipidemia – not worsen it
 Must not worsen peripheral arterial disease
 Must improve ED and not cause impotence
 Must not decrease eGFR and  serum creatinine
 Must not raise uric acid, serum potassium

65. Management Options
Diuretics
NDHP - CCBs
MNT
Exercise
New BB
ACEi, ARB

66. ACEi or ARB – A must for VP
 Antihypertensive, vasoprotective,
anti-thrombotic and anti-inflammatory
 Inevitable in DM more so in DM + HT/CVD
 Reduce CV events, Reduce atherosclerosis
 Reduce renal disease - a strong CV risk factor
 Metabolically ‘friendly’ drugs in DM
 They prevent new onset DM, Nephropathy
 Well-tolerated with few side effects

67. Vascular Protection
ACE inhibitor Trials

68. Heart Outcomes Prevention
Evaluation Study
A large, simple, randomized trial of
Ramipril and vitamin E in patients at
high risk for cardiovascular events

69. Primary Outcome -
Ramipril vs Placebo
0.2
0.15
0.1
0.05
0
0 500 1000 1500
Days of Follow-up
Kaplan-Meier Rates
Ramipril Placebo
RR=0.78 (0.70-0.86) P=0.000002

70. Prespecified Subgroups –
Ramipril vs Placebo
0.6 0.8 1.0 1.2
RR (95% CI)
CVD+
CVD-Diabetes
+
Diabetes
-
No. Of
Pts.
8160
1137
3578
5719
Placebo Rate
18.7
10.1
19.8
16.5

71. Conclusions:
Ramipril vs Placebo
There is overwhelming evidence that Ramipril prevents:
 CV death, strokes and MI
 Heart Failure, Revascularization
 Development of diabetes
 Diabetic microvascular complications and
Nephropathy
These benefits are consistently observed in a very broad
range of high risk patients and in addition to other
effective therapies
The only adverse event is a 5% excess of cough

72. SSttuuddyy eennddppooiinnttss
PPrriimmaarryy eennddppooiinntt
 CCVV mmoorrttaalliittyy ++ nnoonn ffaattaall MMII ++ ccaarrddiiaacc aarrrreesstt
SSeeccoonnddaarryy eennddppooiinnttss
 TToottaall mmoorrttaalliittyy ++ nnoonn ffaattaall MMII ++ uunnssttaabbllee aannggiinnaa ++
ccaarrddiiaacc aarrrreesstt
 HHeeaarrtt ffaaiilluurree
 RReevvaassccuullaarriissaattiioonn ((PPCCII//CCAABBGG))
 SSttrrookkee

73. RRiisskk ffaaccttoorrss
PPeerriinnddoopprriill
((%%))
PPllaacceebboo
((%%))
HHyyppeerrtteennssiioonn 2277..00 2277..22
DDiiaabbeetteess mmeelllliittuuss 1111..88 1122..88
HHyyppeerrcchhoolleesstteerroollaaeemmiiaa 6633..33 6633..33
CCuurrrreenntt ssmmookkeerr 1155..44 1155..11

74. PPrriimmaarryy eennddppooiinntt
%% CCVV ddeeaatthh,, MMII oorr ccaarrddiiaacc aarrrreesstt
RRRRRR:: 200%%
1144
1122
1100
88
66
44
22
PPllaacceebboo aannnnuuaall eevveenntt rraattee:: 22..44%%
PPllaacceebboo
PPeerriinnddoopprriill
pp == 00..00000033
YYeeaarrss
00
00 11 22 33 44 55

75. Fatal aanndd nnoonn ffaattaall MMII
PPllaacceebboo
PPeerriinnddoopprriill
1100
88
66
44
22
00
RRRRRR:: 2244%%
00 11 22 33 44 55 YYeeaarrss
((%%))
pp << 00..000011

76. HHeeaarrtt FFaaiilluurree
PPllaacceebboo
PPeerriinnddoopprriill
RRRRRR:: 3399%%
pp == 00..000022
00 11 22 33 44 55 YYeeaarrss
((%%)) 22..00
11..55
11..00
00..55
00..00

77. SSuubb--ggrroouuppss aannaallyyssiiss
00..55 11..00 2..00
HHyyppeerrtteennssiioonn
PPeerriinnddoopprriill PPllaacceebboo
RRRRRR ((%%))
bbeetttteerr
bbeetttteerr
NNoo hhyyppeerrtteennssiioonn
DDiiaabbeetteess mmeelllliittuuss
NNoo ddiiaabbeetteess mmeelllliittuuss
SSttrrookkee//TTIIAA
NNoo ssttrrookkee//TTIIAA
1188..66
1199..99
1188..99
1199..00
1155..88
1199..99

78. The Prevention of Events with
Angiotensin Converting
Enzyme Inhibition (PEACE)
Trial
 A double-blind, placebo-controlled, randomized trial
 Sponsored by the National Heart, Lung, and Blood Institute
 Study medication and additional support provided by Abbott
Laboratories/Knoll
Marc Pfeffer, MD, Ph.D

79. Patient Flow
T r a n d o l a p r il
( n = 4 1 5 8 )
Target dose 4 mg/day
L o s t t o f o l l o w - u p
n = 6 6 ( 1 . 6 % )
V i t a l s t a t u s u n k n o w n
n = 2 5 ( 0 . 6 % )
P l a c e b o
( n = 4 1 3 2 )
L o s t t o f o l l o w - u p
n = 6 8 ( 1 . 6 % )
V it a l s t a t u s u n k n o w n
n = 2 0 ( 0 . 5 % )
R a n d o m i z e d
( n = 8 2 9 0 )
Nov 1996 to
June 2000
Median follow-up time = 4.8 years
Followed until
December 31, 2003

80. Baseline Medical History
Characteristic, % Trandolapril Placebo
Documented MI 54 56
CABG or PCI 72 72
Diabetes 18 16
Hypertension 46 45
Stroke or TIA 7 6
Current cigarette use 14 15

81. 1º Outcome and its
Components
Outcome Trandolapri
l n=4158
%
Placebo
n=4132
%
Hazard Ratio
(95% CI)
P-value
CV death, MI,
CABG or PCI
21.9 22.5 0.96 (0.88-1.06) NS
CV death 3.5 3.7 0.95 (0.76-1.19) NS
Non-fatal MI 5.3 5.3 1.00 (0.83-1.20) NS
Revasc 17.8 18.0 0.98 (0.88-1.08) NS

82. Other Outcomes
Outcome Trandolap
ril n=4158
%
Placebo
n=4132
%
Hazard Ratio
(95% CI)
P-value
CHF
hospitalization
2.5 3.2 0.77 (0.60-1.00) 0.048
CHF
hospitalization
or CHF death
2.8 3.7 0.75 (0.59-0.95) 0.018
Stroke 1.7 2.2 0.76 (0.56-1.04) 0.09
New diabetes 9.8 11.5 0.83 (0.72-0.96) 0.014
Death (any
7.2 8.1 0.89 (0.76-1.04) 0.13
cause)

83. Onset of New Diabetes1
The PEACE trial investigators. Angiotensin-Converting-Enzyme Inhibition in Stable Coronary Artery Disease (the PEACE trial). N Engl J Med
2004;351:2-58-68
†The analysis included 3432 patients in the trandolapril group and 3472 patients in the placebo group and excluded
patients with diabetes at baseline.
Patients (%)
Placebo
(absolute incidence 399/3472)
Trandolapril
(absolute incidence 336/3432)
p=0.01
9.8%
11.5% 12
10
8
6
4
2
0
Risk
Reduction
17%

84. CHF as a primary cause of
hospitalization or death1
Risk
Reduction
25%
p=0.02
3.7%
Placebo
(absolute incidence 1529/4132)
2.8%
Trandolapril
(absolute incidence 115/4158)
Patients (%)
4.0
3.5
3.0
2.5
2.0
1.5
1.0
0.5
0.0
The PEACE trial investigators. Angiotensin-Converting-Enzyme Inhibition in Stable Coronary Artery Disease (the PEACE trial). N Engl J Med 2004;351:2-58-68

85. Role of AACCEE iinnhhiibbiittoorrss iinn VVaassccuullaarr HHeeaalltthh MMaannaaggeemmeenntt && PPrreevveennttiioonn

86. IDNT & RENAAL: Study
Design
IIDDNNTT†† RREENNAAAALL‡‡
PPaattiieennttss:: 11,,771155 HHTTNN ppaattiieennttss wwiitthh ttyyppee 2 11,,551133 HHTTNN ppaattiieennttss wwiitthh
ddiiaabbeetteess && nneepphhrrooppaatthhyy ttyyppee 2 ddiiaabbeetteess &&
SeCr, serum creatinine; EESSRRDD,, eenndd--ssttaaggee rreennaall ddiisseeaassee..
†† LLeewwiiss EEJJ eett aall.. NN EEnnggll JJ MMeedd.. 22000011;;334455::885511--886600..
‡‡ BBrreennnneerr BBMM eett aall.. NN EEnnggll JJ MMeedd.. 22000011;;334455::886611--886699..
nneepphhrrooppaatthhyy
TTrreeaattmmeenntt aarrmmss:: iirrbbeessaarrttaann,, aammllooddiippiinnee,, lloossaarrttaann,, ppllaacceebboo
ppllaacceebboo
TTaarrggeett BBPP:: 113355//8855 mmmm HHgg 114400//9900 mmmm HHgg
AAddjjuunnccttiivvee tthheerraappyy:: PPeerrmmiitttteedd eexxcceepptt AARRBBss,, PPeerrmmiitttteedd iinncclluuddiinngg
AACCEE iinnhhiibbiittoorrss,, oorr CCCCBBss CCCCBBss,, eexxcceepptt AARRBBss oorr
AACCEE iinnhhiibbiittoorrss
PPrriimmaarryy oouuttccoommee:: CCoommppoossiittee ooff ddoouubblliinngg ooff CCoommppoossiittee ooff ddoouubblliinngg ooff
SSeeCCrr,, EESSRRDD,, oorr ddeeaatthh SSeeCCrr,, EESSRRDD,, oorr ddeeaatthh
SSeeccoonnddaarryy oouuttccoommeess:: CCVV eevveennttss CCVV eevveennttss

87. IDNT and RENAAL Trial Results
Comparison of Major Endpoints
RENAAL IDNT
Losartan
vs control
RRR (%)
Irbesartan
vs control
Irbesartan vs
amlodipine
Amlodipin
e vs
control
Doubling of Creat, 16 (P=0.02) 20 (P=0.02) 23 (P=0.006)- 4 (P=0.69)
ESRD, or death
Doubling of Creat 25 (P=0.006) 33 (P=0.003) 37 (P<0.001)- 6 (P=0.60)
ESRD 28 (P=0.002) 23 (P=0.07) 23 (P=0.07) 0 (P=0.99)
Death -2 (P=0.88) 8 (P=0.57) -4 (P=0.8) 12 (P=0.4)
CV Morbidity 10 (P=0.26) 9 (P=0.4) -3 (P=0.79) 12(P=0.29)
& Mortality
Lewis EJ et al. N Engl J Med 2001;345:851-860.
Brenner B et al. N Engl J Med 2001;345:861-869.

88. HTN in DM: Therapy
Most Hypertensive Patients Need Multiple Drugs
Trial Target BP (mm Hg)
2 3 4
AASK MAP <92
No. of antihypertensive agents
1
UKPDS DBP <85
ABCD DBP <75
MDRD MAP <92
HOT DBP <80
IDNT SBP <135/DBP <85
ALLHAT SBP <140/DBP <90
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.

89. Other Effects of HTN Drugs

90. •Largest study in Type 2 diabetes patients
•The first study to evaluate everyday, real life diabetic
patients over a broad range of BP: normotensive and
hypertensive
•Very well treated patient with a lower rate of
cardiovascular events compared to previous studies

91. How to differentiate AADDVVAANNCCEE ::
PPaattiieennttss pprrooffiillee
 ADVANCE is different
• From UKPDS: diabetic hypertensive patients with SBP at
study end > 145 mm Hg and HbA1C= 8.3
• From Micro HOPE: higher risk profile, CAD, diabetes
• From HOT and other hypertension studies: no BP target
• From LIFE-diabetes: a subgroup with hypertension+LVH
• From diabetes studies with ARBS in nephropathy: renal
endpoints

92. Main
results
Blood
pressure

93. Blood pprreessssuurree rreedduuccttiioonn
Δ 5.6 mmHg (95% CI 5.2-6.0); p<0.001
Δ 2.2 mmHg (95% CI 2.0-2.4); p<0.001
Systolic
Diastolic
Placebo
Perindopril-Indapamide
Mean Blood Pressure (mmHg)
165
155
145
135
125
115
105
95
85
75
65
R 6 12 18 24 30 36 42 48 54 60
Follow-up (Months)
Average BP
during follow-up
140.3 mmHg
134.7 mmHg
77.0 mmHg
74.8 mmHg

94. AAllll--ccaauussee mmoorrttaalliittyy
Placebo
Perindopril-Indapamide
Follow-up (months)
10
0
0 6 12 18 24 30 36 42 48 54 60
Cumulative incidence (%)
Relative risk reduction
14%: 95% CI 2-25%
p=0.025
5

95. DDeeaatthhss
CCaarrddiioovvaassccuullaarr
6 12 18 24 30 36 42 48 54 60
Follow-up (months)
Placebo
Perindopril-indapamide
NNoonn--ccaarrddiioovvaassccuullaarr
6 12 18 24 30 36 42 48 54 60
Follow-up (months)
Placebo
Perindopril-indapamide
Relative risk reduction
18%; p=0.027
Relative risk reduction
8%; p=0.41
5% 5%
Cumulative incidence (%)

96. Combined pprriimmaarryy oouuttccoommeess
MMaajjoorr mmaaccrroo oorr mmiiccrroovvaassccuullaarr
eevveenntt
20
10
0
Placebo
Perindopril-Indapamide
Relative risk reduction
9%: 95% CI: 0 to 17%
0 6 12 18 24 30 36 42 48 54 60
Follow-up (months)
p=0.041
Cumulative incidence (%)

97. PPrriimmaarryy oouuttccoommeess
MMaajjoorr mmaaccrroo oorr mmiiccrroovvaassccuullaarr
Number of events
Per-Ind Placebo
(n=5,569) (n=5,571)
Relative risk
reduction (95% CI)
Favours
Per-Ind
Favours
Placebo
Combined macro+micro 861 938 9% (0 to 17)
Macrovascular 480 520 8% (-4 to 19)
Microvascular 439 477 9% (-4 to 20)
0.5 1.0 2.0
Hazard ratio
*
*2P=0.04
eevveenntt

98. CCoorroonnaarryy eevveennttss
All coronary heart disease 468 535 14% (2 to 24)
Major coronary heart disease† 265 294 11% (-6 to 24)
Other coronary heart disease‡ 283 324 14% (-1 to 27)
*2P=0.02
0.5 1.0 2.0
†Non-fatal MI or death from coronary heart disease
‡Unstable angina requiring hospitalization, coronary revascularization or silent MI
*
Number of events
Per-Ind Placebo
(n=5,569) (n=5,571)
Relative risk
reduction (95% CI)
Favours
Per-Ind
Favours
Placebo
Hazard ratio

99. Cerebrovascular eevveennttss
Number of events
Per-Ind Placebo
(n=5,569) (n=5,571)
All cerebrovascular disease 286 303 6% (-10 to 20)
Major cerebrovascular disease† 215 218 2% (-18 to 19)
Other cerebrovascular disease‡ 79 99 21% (-6 to 41)
2.0
*
*2P=0.40
0.5 1.0
†Non-fatal stroke or death from Cerebrovascular disease
‡Transient ischaemic attack or subarachnoid haemorrhage
Relative risk
reduction (95% CI)
Favours
Per-Ind
Favours
Placebo
Hazard ratio

100. RReennaall eevveennttss
Total renal events 1243 1500 21% (15 to 27)*
New or worsening nephropathy 181 216 18% (-1 to 32)
New microalbuminuria 1094 1317 21% (14 to 27)
2.0
0.5 1.0
Hazard ratio
*2P=<0.01
Number of events
Per-Ind Placebo
(n=5,569)(n=5,571)
Relative risk
reduction (95% CI)
Favours
Per-Ind
Favours
Placebo

101. SSuummmmaarryy
 Routine treatment of type 2 diabetic patients
with
Perindopril-indapamide resulted in:
• 14% reduction in total mortality
• 18% reduction in cardiovascular death
• 9% reduction in major vascular events
• 14% reduction in total coronary events
• 21% reduction in total renal events
Benefits appeared to be similar in all major subgroups.
Treatment was very well tolerated, with few side effects
and adherence similar to that with placebo.

102. HTN in DM: Therapy
WWhhiicchh ccoommbbiinnaattiioonn ??
ACE-I + Thiazide like Diuretics: Excellent 1st line agent
 • Increased HTN control
 • Reduced hypokalemia
 • Cardioprotective
 • Increased adherence
ADVANCE trial

103. HTN in DM: Therapy
WWhhiicchh ccoommbbiinnaattiioonn ??
ACCOMPLISH trial
 The Avoiding Cardiovascular Events through Combination
Therapy in Patients Living with Systolic Hypertension
(ACCOMPLISH) trial indicated that the calcium channel
antagonist amlodipine is superior to hydrochlorothiazide in
combination treatment with an ACE-I.
 In 6946 patients with DM, the number of primary events
was 307 in the group treated with amlodipine and 383 in
the group treated with hydrochlorothiazide as the add-on
to benazepril (P = 0.003), despite a similar reduction of
blood pressure in both groups.

104. ACCOMPLISH trial

105. Cardiovascular mmoorrttaalliittyy
PPeerriinnddoopprriill 44--88mmgg

106. Total ccoorroonnaarryy eenndd ppooiinntt
PPeerriinnddoopprriill 44--88mmgg

107. Fatal and nnoonn ffaattaall ssttrrookkeess
PPeerriinnddoopprriill 44--88mmgg

108. New oonnsseett ooff ddiiaabbeetteess
PPeerriinnddoopprriill 44--88mmgg

109. SBP aanndd DDBBPP oovveerr ttiimmee
PPeerriinnddoopprriill 44--88mmgg

110. HTN in DM: Therapy
AACCEE--II ++ AARRBBss:: LLiimmiitteedd UUttiilliittyy
ONTARGET trial
 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 Å 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

111. HTN in DM: Therapy
WWhhiicchh ccoommbbiinnaattiioonn ??
ALTITUDE trial
 In the Aliskiren Trial in Type 2 Diabetes Using
Cardio-Renal Endpoints (ALTITUDE) trial, the
addition of aliskiren to RAAS blockade in patients
with T2DM at high risk for cardiovascular and renal
events did not result in a decrease in
cardiovascular events and may even have been
harmful.

112. β -Blockers and their Effects
ββ11
β1
β2
ββ11

113. b-Blockers and the risk of
new-onset diabetes mellitus
28% Increased Risk
0.91
1.28
1.0
Prospective study of 12 550 patients w/o DM, aged
45-64, followed for 6 y. Multivariate analysis of
3804 who had HT at baseline.
25% Increased Risk
17.4
13.0
20
15
10
5
0
Atenolol Losartan
LIFE1
New Cases Per 1000
Person-Years (%)
1.5 Ratio
1.0
Hazard .5
Prospective study of 9193 hypertensives, aged 55-80,
followed for 4.8 y. Analysis of 7998 w/o DM at baseline.
1. Lancet 2002;359:995–1003.
2. N Engl J Med 2000;342:905–12.
ARIC2
0
Atenolol RR 1.25 (1.12-1.37)
P<.001
b-blocker RR 1.28 (1.04-1.57)
P<.05
Thiazide
b-blocker
None
1.17
CCB
0.98
ACEI

114. Name of β B Receptor ISA Comment
Acebutolol β 1 Yes Not Good
Penbutolol β 1, β 2 Yes Bad
Pindolol β 1, β 2 Yes Bad
Propranolol β 1, β 2 No No Good
Nadolol β 1, β 2 No No Good
Timolol β 1, β 2 No No Good
Atenolol β 1 No OK
Metoprolol β 1 No Very Good
Nebivolol β 1 No Excellent
Bisoprolol β 1 No Excellent
Labetalol a, β 1, β 2 No Emergency

115. Advantages of Carvedilol
 Neutral on glycemic control
 Improves insulin resistance, metabolic
syndrome and lipid neutral
 Add on to RAAS blockade in DM
 Improves MAU/ ACR and ED
 First β blockade approved for CHF
GEMINI trial and OPTIMIZE-HF Study

116. RReeccoommmmeennddaattiioonnss::
HHyyppeerrtteennssiioonn//BBlloooodd PPrreessssuurree CCoonnttrrooll
Treatment (3)
• Pharmacological therapy for patients with
diabetes and hypertension C
– A regimen that includes either an ACE inhibitor
or angiotensin II receptor blocker; if one class
is not tolerated, substitute the other
• Multiple drug therapy (two or more agents
at maximal doses) generally required to
achieve blood pressure targets B
• Administer one or more antihypertensive
medications at bedtime A
ADA. VI. Prevention, Management of Complications. Diabetes Care 2014;37(suppl 1):S36

117. Who Should Receive ACEi or ARB Therapy?
• Clinical Macrovascular disease [grade A, level A] or
• ≥55 years of age [grade A, level A for those with additional CVD risk
factors or end organ damage; grade D, consensus for all others] or
• Microvascular disease [grade D, consensus]
At doses that have shown vascular protection
[perindopril 8 mg daily (EUROPA), ramipril 10 mg daily
(HOPE), telmisartan 80 mg daily (ONTARGET)]
Among women with childbearing potential, ACEi or ARB should
only be used in the presence of proper preconception
counseling & reliable contraception. Stop ACEi or ARB either
prior to conception or immediately upon detection of pregnancy
guidelines.diabetes.ca | 1-800-BANTING (226-8464) | diabetes.ca
Copyright © 2013 Canadian Diabetes Association
2013
EUROPA Investigators, Lancet 2003;362(9386):782-788.
HOPE study investigators. Lancet. 2000;355:253-59.
ONTARGET study investigators. NEJM. 2008:358:1547-59

119. HTN Rx. Algorithm in DM
BP > 140/80 (2 readings) No TOD / MAU
ACE/ARB + TLC 1 M
TLC cont.
Yes Goal BP £140/80 No
Add thiazide like Diuretic
Add Amlodipine
Verapamil/ Diltizem
Yes
Yes
No
>140/90/MAU/TOD
1 Month
Add new bB /aB
No
No
No
Yes
Yes
1 Month
1 Month
1 Month ?

120. Drug therapy in
Hypertension with Diabetes
1st potion ACEIs
Monotherapy
OR 2nd option ARBs
+
Combination
 Thiazide like diuretic (low dose→Indapamide)
Long acting calcium channel blockers (amlodipine)
B blocker (cardioselective-e.g. Carvedilol, metoprolol)

121. Take home Message
 HTN in DM is serious; So manage aggressively ( new Target
<140/80mmHg)
 TLC, Lipid control, Glycemic targets – VP is a must
 drugs that act on the RAA axis are recommended for first-line
use
 ACE inhibitor should be considered first, but ARB should be
substituted if ACE inhibitor not tolerated
 MAU/ACR must for all DM – Predict CAD, CKD
 Typically 2 or more drugs are needed for HTN Rx.
 use a diuretic, and in a dosage, which has been shown
effective in clinical endpoint trials
 New b B, Carvedilol, CCBs are add-on drugs

122. Vascular Protection in DM
1. Atorvastatin (Lipid management)
2. ASA (Acetyl Salicylic Acid) – (enteric coated)
3. ACE inhibitors or ARBs for BP goal (140/80 as
well as Control of Nephropathy, Proteinuria
(MAU)
4. A1c control 7%(Glycemic control)
5. Cigarette smoking cessation
6. Weight and waist management
7. Physical Activity – at least 2 km/d x 5 d

123. Thank you

124. Highest Percentage Reduction of the Risk of Diabetic Complications
in People with Type 2 Diabetes shown in Recent Studies
Strategy Complication
Reduction of
Complication
Lipid control · Coronary heart disease mortality
· Major coronary heart disease event
· Any atherosclerotic event
· Cerebrovascular disease event
↓36%¹
↓55%¹
↓37%¹
↓62%¹
Blood Pressure
Control
· Cardiovascular disease
· Heart failure
· Stroke
· Diabetes-related deaths
↓51%²
↓56%³
↓44%³
↓32%³
Blood Glucose Control · Heart Attack ↓37%³
1 The 4S Study
2 Hypertension Optimal Treatment (HOT) Randomised Trial
3 UKPDS