Diabetes and its Cardiovascular Diabetes and its Cardiovascular ImpactImpact

Dr Rashid IqbalDr Rashid Iqbal

Consultant CardiologistConsultant Cardiologist

Surrey and Sussex Healthcare NHS TurstSurrey and Sussex Healthcare NHS Turst

St Georges Hospitals NHS TrustSt Georges Hospitals NHS Trust

AimsAims

Epidemiology of DM Epidemiology of DM

Coronary Artery Disease in DiabetesCoronary Artery Disease in Diabetes

How to protect Diabetic Heart?How to protect Diabetic Heart?

Diabetes Prevalence WorldwideDiabetes Prevalence Worldwide

In 2000 2.8% (171 million)In 2000 2.8% (171 million)

By 2030 4.4% (366 million)By 2030 4.4% (366 million)

A 36 % increase in 30 yearsA 36 % increase in 30 years

Wild S et al Diabetes Care 2004;27:1047-53

0

1995 2000 2005 2010 2015 2020 2025 2030

100

150

300

350

50

200

250

Diabetes – Prevalence

Year 2000:177 million

Year 2030:370 million.

equivalent to 2/3rd of Europe population

Diabetes and cardiovascular illnessDiabetes and cardiovascular illness Prevalence has increased by 42% in Prevalence has increased by 42% in

developed world and quadrupled in developed world and quadrupled in developing countries developing countries (Amos Diabetic Medicine (Amos Diabetic Medicine 1997;14:s5:S1-S85)1997;14:s5:S1-S85)

One third of individuals born after One third of individuals born after 2000 will be diabetic when adult 2000 will be diabetic when adult (ADA (ADA statement 2003)statement 2003)

DM magnifies risk of cardiovascular DM magnifies risk of cardiovascular mortality and morbidity andmortality and morbidity and

is associated with three fold increase is associated with three fold increase in CV events in CV events (Stein Circulation 1995;91:979-81)(Stein Circulation 1995;91:979-81)

Amos Diabetic Medicine 1997;14:S5:S1-S85

Obesity and type 2 diabetesObesity and type 2 diabetes

0

50

100

<22 23-23.9

25-26.9

29-30.9

>35

Body Mass Index

Age

adj

uste

d R

elat

ive

Ris

k of

D

iabe

tes

MenWomen

Chan et al (1994) and Colditz et al (1995)

Insulin Resistance and the Metabolic Insulin Resistance and the Metabolic SyndromeSyndrome

Insulin ResistanceInsulin Resistance

Resistance to the action of insulin occurring in the Resistance to the action of insulin occurring in the adipocyte, skeletal muscle and the liveradipocyte, skeletal muscle and the liver

Metabolic SyndromeMetabolic Syndrome

Insulin Resistance plus clustering of inflammatory Insulin Resistance plus clustering of inflammatory atherothrombotic cardiovascular riskatherothrombotic cardiovascular risk

Type 2 DiabetesType 2 Diabetes

Metabolic Syndrome plus dysglycaemiaMetabolic Syndrome plus dysglycaemia

Cardiovascular Risk Clustering in Viscerally Obese PatientsCardiovascular Risk Clustering in Viscerally Obese Patients

. Hypertriglyceridemia

. Low HDL-cholesterol. High apolipoprotein B

. Small, dense LDL particles

. Inflammatory profile

. Insulin resistance

. Hyperinsulinemia

. Glucose intolerance. Impaired fibrinolysis. Endothelial dysfunction

Costs - Fact FileCosts - Fact File

Studies have shown that diabetes is a Studies have shown that diabetes is a costly disease costly disease

Type 2 diabetes accounted for between 3% Type 2 diabetes accounted for between 3% and 6% of total healthcare expenditure in and 6% of total healthcare expenditure in eight European countrieseight European countries

Hospital in-patient costs are the largest Hospital in-patient costs are the largest single contributor to direct healthcare costs single contributor to direct healthcare costs

Coronary heart disease and diabetesCoronary heart disease and diabetes

Studied using Studied using

– epidemiology

– post-mortem

– electrocardiography

– Angiography

High prevalence of subclinical atherosclerosisHigh prevalence of subclinical atherosclerosis

CAD more prevalent, more extensive, more diffuse, CAD more prevalent, more extensive, more diffuse, increased calcificationincreased calcification

High prevalence of Lt. Main disease, less collaterals High prevalence of Lt. Main disease, less collaterals

High prevalence of ‘silent ischemia’High prevalence of ‘silent ischemia’

Copyright © 2008 Society for Heart Attack Prevention and Eradication. All Rights Reserved.

12

Table 2. Risk of Coronary Heart Disease based on the UKPDS model*

Kirk et al. Coronary Artery Disease 2007,18:595-600

Follow-up point†

White Mexican American Black

5-year10-year15-year20-year

11.0% (9.5-12.4)23.0% (20.4-25.7)35.8% (32.1-39.5)48.7% (44.3-53.0)

9.6% (7.9-11.4)20.0% (16.7-23.3)31.0% (26.4-35.6)42.3% (36.7-47.9)

10.1% (8.1-12.2)21.5% (17.7-25.4)33.6% (28.3 -38.9)45.8% (39.6-52.0)

Values are accompanied by 95% CI (in parentheses) CHD = Coronary Heart Disease, UKPDS = United Kingdom Prospective Diabetes Study.*UKPDS model assuming all participants are white, †All comparisons non-significant (NS)

Mortality in DiabetesMortality in Diabetes

Diabetic patients without previous MI have as high a risk of MI as non-diabetic patients with previous MI

New England Journal of Medicine 1998;339:229–234.

Without previousMI previous MIWith previousMIprevious MI

7-ye

ar i

nci

den

ce o

f M

I (%

)

0

5

10

15

20

25

30

35

40

45

non-diabetic with diabetes

7 year follow-up

Diabetes-CVD Facts

More than 65% of all deaths in people with diabetes are caused by cardiovascular disease.

Heart attacks occur at an earlier age in people with diabetes and often result in premature death.

3

Diabetes-CVD Facts

Up to 60% of adults with diabetes have high blood pressure.

Nearly all adults with diabetes have one or more cholesterol problems, such as:

– high triglycerides

– low HDL (“good”) cholesterol

– high LDL (“bad”) cholesterol

4

The Good News…

By managing the ABCs of diabetes, people with diabetes can reduce their risk for heart disease and stroke.

A stands for A1C

B stands for Blood pressure

C stands for Cholesterol

5

Ask About Your A1C

A1C measures average blood glucose over the last three months.

Get your A1C checked at least twice a year.

A1C Goal = less than 7%

6

Treating Cardiovascular risk factors… Treating Cardiovascular risk factors…

Managing the ABCs of diabetes, people Managing the ABCs of diabetes, people with diabetes can reduce their risk for with diabetes can reduce their risk for heart disease and stroke.heart disease and stroke.

A stands for A1C

B stands for Blood pressure

C stands for Cholesterol

5

HbAHbA1c1c% 7.0% versus 7.9%% 7.0% versus 7.9%

Reduction in risk by:

25% for eye disease and early kidney disease

16% for Heart Attacks

24% for cataract surgery

Reduction in risk by:

25% for eye disease and early kidney disease

16% for Heart Attacks

24% for cataract surgery

Risk Reduction With a Risk Reduction With a 1% Reduction in HbA1% Reduction in HbA1c1c : :

Any lower is therefore better!Any lower is therefore better!

16%16%Heart failureHeart failure

43%43%Amputation / death from leg vessel Amputation / death from leg vessel problemsproblems

37%37%Eye and early kidney diseaseEye and early kidney disease

12%12%StrokeStroke

14%14%Heart AttacksHeart Attacks

21%21%Deaths related to diabetesDeaths related to diabetes

Pharmacotherapy of HypertensionPharmacotherapy of Hypertension

Aim for 125/75-80Aim for 125/75-80

ACE inhibitors and ARBs have a favorable effectACE inhibitors and ARBs have a favorable effect

on renal and cardiovascular systems.on renal and cardiovascular systems.

ß-blockers along with ACE inhibitorsß-blockers along with ACE inhibitors help in help in reducingreducing myocardial infarction and heart failure.myocardial infarction and heart failure.

Calcium channel blockers in combination with ACE Calcium channel blockers in combination with ACE inhibitors, ß-blockers,inhibitors, ß-blockers, and diuretics help in and diuretics help in controlling blood pressure.controlling blood pressure.

Diuretics are recommended when BP control is Diuretics are recommended when BP control is still uncontrolled.still uncontrolled.

Cholesterol lowering reduces Heart Disease Cholesterol lowering reduces Heart Disease in Patients with Diabetes by up to 55% !in Patients with Diabetes by up to 55% !

11 22 33 44 55 660000

2020

4040

6060

8080

100100

RiskRisk reductionreduction

55%55%

Diabetic,simvastatin Diabetic,simvastatin

Diabetic, placebo Diabetic, placebo

Years since randomisationYears since randomisation

Pat

ien

ts w

ith

hea

rt d

isea

se (

%)

Pat

ien

ts w

ith

hea

rt d

isea

se (

%)

Multiple aetiology of atherosclerosis generationMultiple aetiology of atherosclerosis generation

increased inflammatory markersincreased inflammatory markers

hyperglycaemia induced endothelial dysfunctionhyperglycaemia induced endothelial dysfunction

increased vascular permeabilityincreased vascular permeability

adventitial inflammation (of vasa vasorum)adventitial inflammation (of vasa vasorum)

impaired fibrinolysisimpaired fibrinolysis

dysfunctional arterial remodellingdysfunctional arterial remodelling

vDiabetic Vascular PathologyVascular Pathology of Diabetics

Exp Clin Endocrinol Diabetes 1998; 106:16-24

plasmacoagulation

Altered responseto arterial injury

Diminishedfibrinolysis

endothelialthromboresistance

Platelet hyperreactivity(diabetic

thrombocytopathy)

plateletaggregation

and adhesion

Plaque Disruption & Thrombosis

Journal of medicine

Atherothrombotic plaque in diabetic Atherothrombotic plaque in diabetic patientspatients

More in numberMore in number

More likely to ruptureMore likely to rupture

More likely to have existing surface thrombusMore likely to have existing surface thrombus

PCI Case

Optimising medical therapy

Metformin : reduced incidence of diabetes by 31% (Knowler NEJM 2002;346:393)

Ramipril : by 34% (HOPE JAMA 2001;286:1882)

Lipid lowering : by 22% (Collins Lancet 2003;361:2005)

Blood pressure control : SBP<140

Antiplatelets Antiplatelets

Aspirin 75mg once dailyAspirin 75mg once daily : :

Diabetes UK advises aspirin treatment in all patients with Diabetes UK advises aspirin treatment in all patients with diabetes over the age of 30 years with any of the following: diabetes over the age of 30 years with any of the following:

previous MI, angina, HT, diabetic eye disease, PVD, early kidney previous MI, angina, HT, diabetic eye disease, PVD, early kidney disease, raised cholesterol, family history of heart disease, disease, raised cholesterol, family history of heart disease, obesity, south Asians smokers, DM duration > 10 years.obesity, south Asians smokers, DM duration > 10 years.

Clopidogrel can be used as an alternative. Clopidogrel can be used as an alternative.

DES in Diabetes DES in Diabetes

Both Sirolimus- and Paclitaxel-eluting stents Both Sirolimus- and Paclitaxel-eluting stents substantially reduce angiographic and clinical substantially reduce angiographic and clinical restenosis compared with BMSrestenosis compared with BMS

DES have not eliminated the excess risk of DES have not eliminated the excess risk of restenosis in diabetics c/w non-diabeticsrestenosis in diabetics c/w non-diabetics

CABG: the “diabetic disadvantage”

Society of Thoracic Surgeons database of

1.37 million patients undergoing cardiac surgery

(1990-2000). Diabetic patients had higher rates of:

30 day mortality and

deep sternal wound infections

stroke

longer hospital stay

two-fold worse 10 year survival (36835 pts)

Brown et al Semin Thorac Cardiovasc Surg 2006;18:281

PCI v CABG( SYNTAX)

No mortality difference at 1 year

Higher incidence of CVA after CABG

More frequent angina after PCI

More frequent angiography and repeat revascularisation after PCI

Reducing risk in patients undergoing PCI – what can we do?

Tight glycaemic control (HbA1c ≤7) pre and post procedure (Corpus et al JACC 2004;43:8)

Thiazolidinediones – may reduce neointimal proliferation and restenosis in T2DM receiving BMS

Antithrhrombotic therapy

Drug eluting stents

ConclusionDiabetic patients are different

1. Epidemiology: increasing prevalence worldwide

2. Pathology: their vasculature is different - plaques more frequent and more prone to rupture .

3. Outcomes: for patients with type 2 diabetes sustaining an acute myocardial infarction is poor particularly if they have documented coronary artery disease.

4. Treatment: Modern therapies have a favourable effect but there remains a residual risk not addressed by these therapies.