Jab Mein Thaa , Tab Guru Nahin ‚ Aub Guru Hai , Mein Nahin Sab Andhiyara Mit Gaya‚

Jab Mein Thaa, Tab Guru Nahin‚

Aub Guru Hai, Mein Nahin

Sab Andhiyara Mit Gaya‚

Jab Deepak Dekhya Mahin

When "I“, the Ego, was with me, then I couldn’t

realize the almighty within; Now, the Almighty "is"

ever with me and there is no place for this Ego.

All the darkness (illusion) within me is mitigated,

on realizing the light (illumination) within.

SK

www.drsarma.in

Diabetic HypertensionDiabetic Hypertension

The Two TerroristsThe Two Terrorists

THE ENORMITY OF THE

PROBLEM - COMPOUNDED

THE ENORMITY OF THE

PROBLEM - COMPOUNDED

How Common is this Duo?How Common is this Duo?

HTN is twice as common in DMHTN is twice as common in DM

New onset DM is 2.5 times in HTNNew onset DM is 2.5 times in HTN

20 to 40% of IGT pts have HTN20 to 40% of IGT pts have HTN

40 to 50% of Type 2 DM have HTN40 to 50% of Type 2 DM have HTN

Only 1/4 of HTN in DM is controlledOnly 1/4 of HTN in DM is controlled

DM + HTN – CV Risk 3 foldDM + HTN – CV Risk 3 fold

What Causes HTN in DMWhat Causes HTN in DM

• Metabolic Syndrome – Mainly IR, ED,

BG

• Excessive RAAS activity is the main

mechanism

• HTN due to nephropathy in T2DM – GS -

KWL

• Renal scarring - Recurrent pyelonephritis

• Endocrine causes for both HTN & DM– Cushing’s, Conn’s, Pheochromo,

Acromegaly

• Coincidental – DM on existing HTN

• Diabetogenic antihypertensive drugs (D

and B)

• Drugs causing both HTN & DM – OCP, CS

Each Perpetuates the OtherEach Perpetuates the Other

Relative Risk of DM + HTNRelative Risk of DM + HTN

Diabetes + HTN versus Diabetes

• Neuropathy 1.6

• Nephropathy 2.0

• Retinopathy 2.0

• Stroke 4.0

• CHD 3.0

• Mortality 2.0

Difficulties of HTN in DMDifficulties of HTN in DM

• Systolic HTN more common in DM

• S-HTN is a stronger predictor of CVE

• 65% of T2DM have S-HTN

• S-HTN is more difficult to control

• Depression is more in DM – Adherence Rx

• ‘Clinician Inertia’ is a big problem

• Glycemic control only is the focus – No VP

The Compound Jeopardy !!The Compound Jeopardy !!

Insulin Resistance

Obesity Diabetes

MS with HT associated

CAD, CKD, PAD, CVD – All same

2 x 4 x

Reilly MP et al – Circulation 2003; 108: 1546-1551

THE DASAVATARAM AND

THE VISWA ROOPAM

THE DASAVATARAM AND

THE VISWA ROOPAM

IGT, IFGIGT, IFG

IR, InsulinIR,

Insulin

Dyslipidemia

Dyslipidemia

Hypertension

Hypertension

ED, Vessel

ED, Vessel

Visceral obesityVisceral obesity

Pro Inflammatory

Pro Inflammatory

Pro Thrombotic

Pro Thrombotic

IncreaseIncreased d

CV RiskCV Risk

Perpetuating Circus Perpetuating Circus

CKD

Diabetes

BP

Lipids

CAD

ED

The Devastating ConspiracyThe Devastating Conspiracy

RF for Nephropathy in DMRF for Nephropathy in DM

Progression of DM - Nephropathy

Progression of DM - Nephropathy

Nephropathy in DMNephropathy in DM

Years after onset of DM

Outcomes of DM NephropathyOutcomes of DM Nephropathy

Diabetic Nephropathy

THE EVIDENCE BASE

DM + HT IS DANGEROUS

THE EVIDENCE BASE

DM + HT IS DANGEROUS

Data from King H et al. Diabetes Care. 1998;21:1414-1431.

Top 3 Countries for DiabetesTop 3 Countries for Diabetes

0

10

20

30

40

50

60

India China US

Mil

lio

ns

of

Cas

es

1995

2025

CV Mortality Risk Doubles withEach 20/10 mm Hg BP Increment

Lewington S, et al. Lancet. 2002; 60:1903-1913.JNC VII. JAMA. 2003.

SBP/DBP (mm Hg)

0

1

2

3

4

5

6

7

8

115/75 135/85 155/95 175/105

SBP & CV Mortality in T2DMSBP & CV Mortality in T2DM

250

200

150

100

50

0<120 120-139 140-159 160-179 180-199

SBP (mm Hg)

NondiabeticDiabetic

Stamler J et al. Diabetes Care. 1993;16:434-444.

≥200

Metabolic Syndrome and AgeP r

e va l

e nc e

, %

Age in yr

Adapted from: Ford ES, et al. JAMA. 2002;287:356-359.

33% of Indian Adults Have Metabolic Syndrome

0

5

10

15

20

25

30

35

40

45

20-29 30-39 40-49 50-59 60-69 ?70

Men (n=4265)Women (n=4559)

HOT Study – Imp. of DBPHOT Study – Imp. of DBP

0

5

10

15

20

25

Ev

ents

/10

00 p

t-y

ears

<90 <85 <80

Target diastolic BP

DMnon-DM

Lancet 1998; 351: 1755–62

RR .66, 95% Cl .46 - .94

RR .66, 95% Cl .55 - .79

DiabetesNondiabetes

Curb JD, et al. JAMA. 1996;276:1886-1892.

35

15

30

25

20

5

0

10

5-Ye

ar C

umul

ativ

e Ev

ent R

ates

for A

llM

ajor

Car

diov

ascu

lar E

vent

s (%

) Active treatmentActive treatment

PlaceboPlacebo

SHEP – DM and CVE RatesSHEP – DM and CVE Rates

Mortality

CV Endpoints

Stroke

Coronary

Active Better

SHEP SYST-EUR

Rate in Placebo Group*

SHEP SYST-EUR

35.6 45.1

63.0 57.6

28.8 26.6

32.2 21.3

-100% -50% 0 50% Placebo Better

*Number of endpoints / 1000 patient years

-25

-55 -34

-59 -22

-73 -56

-57

Mortality and Morbidity in DM

Myocardial Infarction

Major CV Events

Stroke

CV Mortality

Total Mortality

90 mmHg

80 mmHg

0 1 2 3 4

| | | |

HOT – Diabetic Hypertension

Lancet 1998; 351: 1755–62

Tight Glucose ControlTight Glucose Control

Tight BP ControlTight BP Control

**P < 0.05P < 0.05-50 -

-40 -

-30 -

0 - StrokeAny DM

End Point DM DeathMicrovascular

Complications

Red

uctio

n in

Ris

k (%

)

UKPDS. BMJ. 1998:317;703-712.

-20 -

-10 -

BP v/s Glucose ControlBP v/s Glucose Control

Hypertension & DM MortalityHypertension & DM Mortality

0% 20% 40% 60% 80% 100%

Captopril (UKPDS)

Atenolol

(UKPDS)

Diuretic(SHEP)

Nitrendipine (Syst-Eur)

Nitrendipine (Syst-China))

STENO-2 Study in DM – Event

STENO-2 Study in DM – Event

1. Nephropathy 56%

2. Proliferative retinopathy 55%

3. Cardiovascular events 59%

4. Total Mortality 40%

% in Complications with intensive Rx

NEJM 2003; 358:580

SOLVD: Enalapril – Reductionin New-Onset Diabetes

SOLVD: Enalapril – Reductionin New-Onset Diabetes

0

6

12

18

24

30

36

Placebo Enalapril

P <.0001

Absolute risk reduction in development of diabetes

Absolute risk reduction in development of diabetes

No. of New Diabetes

Cases

Vermes E et al. Circulation. 2003;107:1291-1296.

1 2 3 4 5Time (y)

Vermes E et al. Circulation. 2003;107:1291-1296.

25

50

75

100

0

Enalapril

Placebo

45% risk reduction

P < 0.0001

45% risk reduction

P < 0.0001

Patients With IFG at Baseline (n = 55)

SOLVD: Enalapril – Reductionin New-Onset Diabetes in IFGSOLVD: Enalapril – Reductionin New-Onset Diabetes in IFG

LIFE Study: ResultsLIFE Study: Results

0

5

10

15

20

25

30

Primary Endpoint: CV Death, MI,and Stroke

New Cases of Diabetes

Eve

nts

/100

0 P

atie

nt-

Yea

rs

Atenolol

Losartan

P <.001

P <.05

Dahlöf B et al. Lancet. 2002;359:995-1003.

25% decrease in RR

ALLHAT: Incidence of New-Onset Diabetes at 4 Years

ALLHAT: Incidence of New-Onset Diabetes at 4 Years

ALLHAT Officers and Coordinators. JAMA. 2002;288:2981-2997.

0

5

10

15

Chlorthalidone Amlodipine Lisinopril

P .001

P = .04

11.6%

9.8%8.1%

%

THE EVIDENCE BASE

MANAGEMENT GUIDE

THE EVIDENCE BASE

MANAGEMENT GUIDE

Hypertension Dyslipidemia

Dysglycemia

Risk Reduction for CAD and CKD

Risk Reduction for CAD and CKD

Na & K SFA

UFA

CHO GL

Risk Reduction for CAD and CKD

Risk Reduction for CAD and CKD

Mandatory Clinical ActionsMandatory Clinical Actions

HTN – Lifestyle modificationsHTN – Lifestyle modifications

• Regular 30’ of moderately intense exercise

• No tobacco and minimizing alcohol

• Na restriction to < 6 g of Nacl per day

• Avoiding high salt foods – pickles, savouries

• Four adult family – 6 x 30 x 4 = 720 g (500 g)

• Use of K containing foods – fruits, vegetables

• Weight reduction – goal ideal weight

• Reducing coffee consumption

HTN – Lifestyle modificationsHTN – Lifestyle modifications

DASH Diet PlanDASH 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

Benefit of Quitting Smoking in HTN

Benefit of Quitting Smoking in HTN

CAD incidence (%) over 5 years

BP Targets in DMBP Targets in DM

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

ADA Guidelines on Rx. of HTN with DM

ADA Guidelines on Rx. of HTN with DM

Systolic Diastolic

Goal (mmHg) <130 <80

Behavioral therapy alone 130–139 80–89(maximum 3 months) TLC

Behavioral therapy + 140 90pharmacologic treatment

Systolic Diastolic

Goal (mmHg) <130 <80

Behavioral therapy alone 130–139 80–89(maximum 3 months) TLC

Behavioral therapy + 140 90pharmacologic treatment

Arauz-Pacheco C et al. Diabetes Care. 2003;26(suppl):S80–S82.

THE EVIDENCE BASE FOR

MANAGEMENT OPTIONS

THE EVIDENCE BASE FOR

MANAGEMENT OPTIONS

Management OptionsManagement Options

Diuretics

NDHP - CCBs

MNT

ExerciseNew BB

ACEi, ARB

Choice of Drug Rx for HTNChoice of Drug Rx for HTN

Younger than 55 yearsYounger than 55 years Older than 55 yearsOlder than 55 years

ACEi or ARB (A)ACEi or ARB (A) Diuretic (D) or CCB (C)Diuretic (D) or CCB (C)

A + D or CA + D or C

A + D + CA + D + C

A + D + C + new or blocker A + D + C + new or blocker

HTN Rx. Algorithm in DMHTN Rx. Algorithm in DMBP > 130/80 (2 readings) No TOD / MAU

ACE/ARB + TLC 1 M

Goal BP 130/80Yes No

Add LD Diuretic

Add Verapamil

Add new B /

Yes

Yes

No

TLC cont.

>140/90/MAU/TOD

1 Month

Sub Amlodepine

No

No

No

Yes

Yes

1 Month

1 Month

1 Month ?Diabetes Spectrum 2004, Vol. 5, # 3, 103-108

Physiological RAAS EffectsPhysiological RAAS Effects

Renin Angiotensin Aldosterone System

Renin Angiotensin Aldosterone System

The RAAS BlockadeThe RAAS Blockade

Ang I

Ang II

Progressive Diabetic Nephropathy

ACE

Renal Injury and Proteinuria

ACEi

AT2 ReceptorAT2 Receptor

Non-ACEPathways

Aldosterone

MRA

AT1 ReceptorAT1 Receptor+

+

ARB

Adverse Renal and CVEffects of AldosteroneAdverse Renal and CVEffects of Aldosterone

•Glomerulosclerosis•Interstitial Fibrosis•Proteinuria•Renal Failure

•LVH•Cardiac Fibrosis•LV Dysfunction•Heart Failure

•Endothelial

Dysfunction•Inflammation•Oxidative Stress

Aldosterone

MRA – EplerenoneBrand name: Eplirestat

ACEi or ARB – A must for VPACEi 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

ACE inhibitor or ARBACE inhibitor or ARB

• Renal impairment – These improve

e-GFR, microalbuminuria or proteinuria

• LV dysfunction (along with new blocker)

• Previous MI (along with new blocker)

• Contraindicated in pregnancy

• Relative contraindications

- Bilateral renal artery stenosis

- Severe renal impairment (Cr > 3.0)

- Monitor renal function

- Angioedema, ACEi cough

Vascular Protection in DMVascular Protection in DM

1. Atorvastatin (Lipid management)2. ASA (Acetyl Salicylic Acid) – (enteric

coated)3. ACE inhibitors or ARBs4. A1c control (Glycemic control)5. Blood pressure goal (<130/80)6. Control of Nephropathy, Proteinuria

(MAU)7. Cigarette smoking cessation8. Weight and waist management9. Physical Activity – at least 2 km/d x 5 d

AASK MAP <92

Target BP (mm Hg)

# of Antihypertensive Agents Needed to Achieve Target BP

No. of antihypertensive agents1

UKPDS DBP <85

ABCD DBP <75

MDRD MAP <92

HOT DBP <80

Trial 2 3 4

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

Chobanian AV et al. JAMA. 2003;289:2560–2572.

CHF

Post-MI

CAD Risk

Diabetes Mellitus

Nephropathy

Stroke Prevention

BB

ACEI

ARB

CCB

AADiuretic

JNC 7 – Antihypertensive Agents

JNC 7 – Antihypertensive Agents

Based on Favorable Outcome Data From Clinical Trials

Based on Favorable Outcome Data From Clinical Trials

Other Effects of HTN DrugsOther Effects of HTN Drugs

DM + Co-morbidityDM + Co-morbidity

DM + Co-morbidityDM + Co-morbidity Primary DrugPrimary Drug Add on Drug Rx.Add on Drug Rx.

DM alone

DM + HT

LVH

DM + MAU/AU

DM + CAD/MI

DM + CHF

ACEi low dose

ACEi or ARB

ARB, (ACEi)

ACEi (ARB)

ACEi or ARB

BP & ACR

watch

D + C + New

B

Indap + Carve

Carve / New B

D + AA + B

-Blockers and their Effects -Blockers and their Effects

Name of B Receptor ISA Comment

Acebutolol 1 Yes Not Good

Penbutolol 1, 2 Yes Bad

Pindolol 1, 2 Yes Bad

Propranolol 1, 2 No No Good

Nadolol 1, 2 No No Good

Timolol 1, 2 No No Good

Atenolol 1 No OK

Metoprolol 1 No Very Good

Nebivolol 1 No Excellent

Bisoprolol 1 No Excellent

Labetalol , 1, 2 No Emergency

Carvedilol , 1, 2 No CHF, IHD

Advantages of CarvedilolAdvantages of Carvedilol

GEMINI trial and OPTIMIZE-HF Study

Ideal anti HTN drug in DMIdeal anti HTN drug in DM

• Must decrease blood pressure to 130/80• 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

What should We take home ?

What should We take home ?

‘Clinician Inertia’ for HTN in DM must be overcome

HTN in DM is serious; So manage aggressively

TLC, Lipid control, Glycemic targets – VP is a must

HTN Rx. delays or arrests CVD, CKD, PAD, CVD

ACEi or ARBs are the main stay of Rx - RAAS

Postural hypotension, DAN are important in Rx

MAU/ACR must for all DM – Predict CAD, CKD

Typically 2 or more drugs are needed for HTN Rx.

New B, Carvedilol, CCBs are add-on drugs

Amaedhya poornam, krimi raasi

samkulam,

Swaabhava gandham, asaucham,

adhruvam |

Sareeram, mootra pureesha bhaajanam

Ramanti moodha, viramanti pandithaa |

Full of filth, ridden with all bacteria and worms,

Naturally stinking, unclean to the core & perishable,

This body of ours, is drenched in excreta & secreta,

Only the fools engross in it, but the wise shun it. VC by ASA