11

New Trends in Heart New Trends in Heart DiseaseDisease

Prof Chu-Pak LauProf Chu-Pak LauCardiology DivisionCardiology Division

University of Hong KongUniversity of Hong KongQueen Mary HospitalQueen Mary Hospital

Public Health Conference6 March 2004

22CP03-2004

Global Burden of CVS diseaseGlobal Burden of CVS diseaseBonow RO et al Circ 2002; 106:1602-160Bonow RO et al Circ 2002; 106:1602-16055

CVS death toll :CVS death toll :14.7M in 1990 to 17M 199914.7M in 1990 to 17M 1999

Main burden due to CAD, is the leading cause of Main burden due to CAD, is the leading cause of death worldwide (30%). CVA second leading death worldwide (30%). CVA second leading causecause

WHO : 1 Billion people overweight WHO : 1 Billion people overweight 18M children <5 are overweight18M children <5 are overweight

60% of the world population is physically 60% of the world population is physically inactiveinactive

DM : 150M people, will double in 2025DM : 150M people, will double in 2025 Tobacco consumption still increasingTobacco consumption still increasing

33CP03-2004

Coronary Artery DiseaseCoronary Artery Disease

Heart FailureHeart Failure

Atrial FibrillationAtrial Fibrillation

44CP03-2004

CVS Death per 100,00 population CVS Death per 100,00 population AHA Heart & Stroke Statistics AHA Heart & Stroke Statistics 19991999

0 200 400 600 800

Japan

China (rural)

China (Urban)

Hong Kong

Australia

New Zealand

US

Germany

Scotland

Russia

Argentina

0 100 200 300

Men Women

55CP03-2004

CAD mortality in Asian-PacificCAD mortality in Asian-Pacific(Men /100,000)(Men /100,000)

66CP03-2004

CAD mortality in Asian-PacificCAD mortality in Asian-Pacific(Women /100,000)(Women /100,000)

1010CP03-2004

Sino-MONICA Project.Sino-MONICA Project.Circulation 2001; 103:462-Circulation 2001; 103:462-468(1)468(1)

7 Year project (1987-1993)

•WHO project

•Collaboration with BIHLBD

1111CP03-2004

Sino-MONICA Project.Sino-MONICA Project.Circulation 2001; 103:462-Circulation 2001; 103:462-468(2)468(2)

1.1. Incidence and mortality of CVS disease is low bIncidence and mortality of CVS disease is low but those of CVA were high ut those of CVA were high

2.2. Great disparity in incidenceGreat disparity in incidenceCVS : 108.7/100,000 to 3.3/100,000 for menCVS : 108.7/100,000 to 3.3/100,000 for menCVA : 553.3/100,000 to 33/100,000CVA : 553.3/100,000 to 33/100,000

3.3. Geographical difference :Geographical difference :North > SouthNorth > Southe.g. Beijing 70.3 vs Guangdong 59.7/100,000e.g. Beijing 70.3 vs Guangdong 59.7/100,000

1212CP03-2004

Leading Cause of Death in HK Leading Cause of Death in HK (2000)(2000)

6943

2846

1744

4279

2691

1809

0

1000

2000

3000

4000

5000

6000

7000

8000

Cancer Heart disease CVA

Male Female

1313CP03-2004

Leading Causes of Death in Leading Causes of Death in US and HK (Female) Year US and HK (Female) Year 20002000

145.3

57.8

42.8

26.6

44.351.6

29.5

11.3

0

20

40

60

80

100

120

140

160

CAD CVA Long Cancer Breast Cancer

US HK

Per 100,000

population

1414CP03-2004

Special Features of Heart Special Features of Heart Disease of WomenDisease of Women

1.1. OlderOlder2.2. Delayed presentationDelayed presentation3.3. Higher mortality rateHigher mortality rate4.4. Triple vessel disease and smaller vessel Triple vessel disease and smaller vessel

sizesize5.5. Higher CABG riskHigher CABG risk6.6. Suboptimal response to PTCASuboptimal response to PTCA7.7. Despite a lower CAD risk, HK women Despite a lower CAD risk, HK women

have mortality from strokes comparable have mortality from strokes comparable to the USto the US

1515CP03-2004

Modifiable Risk FactorsModifiable Risk Factors

HypertensionHypertensionHypercholesterolemiaHypercholesterolemiaDiabetes mellitusDiabetes mellitusHomocysteineHomocysteineC-Reactive ProteinC-Reactive ProteinExerciseExerciseObesityObesityCigarette smokingCigarette smoking

BP, Cholesterol and Stroke in Eastern Asia Eastern Stroke and Coronary Heart Disease Collaborative Research Group Lancet 1998; 352; 1801-1807

1717CP03-2004

Serum Cholesterol in Urban Serum Cholesterol in Urban Cities of AsiaCities of Asia

209221

179

211192

206 213223

235219

188

211226

189

210194

213 218237

185

0

50

100

150

200

250

Men Women AllMg/dl

1818CP03-2004

Global Prevalence of Global Prevalence of DiabetesDiabetes

19971997 20102010

124 million (2.1%)124 million (2.1%) 221 million221 million

53% in Asia53% in Asia 61% in Asia61% in Asia

(Amas, McCarthy & Zimmet; Diabetic Med, 1997)(Amas, McCarthy & Zimmet; Diabetic Med, 1997)

1919CP03-2004

Prevalence of Diabetes and IGT Prevalence of Diabetes and IGT ChinaChina

2020CP03-2004

ObesityObesity

AdultsAdults ChildrenChildren

6-11 years6-11 yearsAdolescentsAdolescents

12-19 years12-19 years

MaleMale FemalFemalee

MaleMale FemalFemalee

MaleMale FemalFemalee

27.3%27.3% 30.1%30.1% 12.0%12.0% 11.6%11.6% 12.8%12.8% 12.4%12.4%

Prevalence in the US in American white (1999-2000)

Obesity : BMI > 30CDC 1999-2000

2121CP03-2004

Mortality from CAD in HK Mortality from CAD in HK (Dept of Health Annual Report 1997-2001)(Dept of Health Annual Report 1997-2001)

(1)(1)

1854 1785 1904 1842 1818 1891 1825 1898 1898 2025

1558

1188 1396 1229 1421 1426 1408 1440 1434 14061580

1609

0

500

1000

1500

2000

2500

3000

3500

4000

1991 1992 1993 1994 1995 1996 1997 1998 1999 2000 2001

AMI Other CADNo. of Pts

2222CP03-2004

Mortality from CAD in HK Mortality from CAD in HK (<45yrs)(<45yrs)(Dept of Health Annual Report 1997-2001)(Dept of Health Annual Report 1997-2001)

(2)(2)

2.9 2.62

9.95

0.90.89

1.41

0

2

4

6

8

10

12

1999 2000 2001

CAD Other CAD

% of Heath Disease <45 years

%

2424CP03-2004

The Role of Platelets in The Role of Platelets in Inflammation Inflammation and Plaque Stabilityand Plaque Stability

CD40L

Platelet-derived growth factor

Platelet factor 4

RANTES

Thrombospondin

Transforming growth factor-

Nitric Oxide

Libby P. Circulation 2001:103:1718-1720

Inflammatory modulators

Activated platelets

Plaque rupture & thrombosis

2525CP03-2004

Novel Risk Factors as Predictors Novel Risk Factors as Predictors of of Peripheral Arterial DiseasePeripheral Arterial Disease

Relative Risk of Incident Peripheral Arterial Disease(Adjusted for age, smoking, DM, HTN, family history, exercise level, and BMI)

Ridker et al. JAMA 2001;285:2481-2485

0 1.0 2.0 4.0 6.0

Lipoprotein(a)

Homocysteine

VCAM-1

Fibrinogen

LDL-C

ICAM-1

hs-CRP

TC:HDL-C

CRP + TC: HDL-C

2626CP03-2004

AHA/CDC Recommendations AHA/CDC Recommendations for Clinical and Public for Clinical and Public Health PracticeHealth Practice

• Measurement of hs-CRP is an independent marker of risk and, in those judged at intermediate risk by global risk assessment (10%-20% CHD/10 yr) may help direct further evaluation & therapy in primary prevention of CHD. The benefits of such therapy based on this strategy remain uncertain. (Class IIa, Level of Evidence B)

• Measurement of hs-CRP may be used at discretion of the physician as part of global risk assessment in adults without known CVD. The benefits of such therapy based on this strategy remain uncertain. (Class IIb, Level of Evidence C)

Clinical Practice

AHA/CDC Statement. Circulation 2003; 107:499–511

2727

Hong Kong Hong Kong Cardiovascular Risk Factor Cardiovascular Risk Factor Prevalence Study-2 Prevalence Study-2 (CRISPS2)(CRISPS2)

Bernard CheungBernard Cheung

Department of MedicineDepartment of Medicine

University of Hong KongUniversity of Hong Kong

HT prevalence

0

10

20

30

40

50

60

<35 35-44 45-54 55-64 65-74 >74Age groups

Pre

vale

nce

% CRISPS1

CRISPS2

2929CP03-2004

Percentage prevalence of diabetes

AgeAge <35<35 35-35-4444

45-45-5454

55-55-6464

65-65-7474 >74>74

1995-61995-6MaleMale 2.0 2.0 5.8 5.8 7.5 7.5 18.6 18.6 21.7 21.7 ----

FemaleFemale 1.4 1.4 3.2 3.2 10.9 10.9 21.2 21.2 29.3 29.3 ----

2001-22001-2MaleMale 2.8 2.8 9.2 9.2 8.8 8.8 23.0 23.0 34.5 34.5 30.0 30.0

FemaleFemale 3.4 3.4 4.8 4.8 6.0 6.0 29.8 29.8 33.3 33.3 43.5 43.5

3030CP03-2004

WeightWeight

Body weight increased by Body weight increased by 0.54±0.14 kg (p<0.001)0.54±0.14 kg (p<0.001)

There was no significant change There was no significant change in body mass index (BMI)in body mass index (BMI)

Waist circumference increased Waist circumference increased from 78.3±0.3 to 80.5±0.3 cm from 78.3±0.3 to 80.5±0.3 cm (p<0.001)(p<0.001)

3131CP03-2004

Prevalence of overweight and Prevalence of overweight and obesity in the study populationobesity in the study population

BMI

<25 25-30 >30

Female N=540 69.3% 26.1% 4.6%

Male N=506 61.2% 34.5% 4.4%

3232CP03-2004

•BMIBMI25 is associated with 25 is associated with diabetes (OR 3.1 [2.0-4.7]) and diabetes (OR 3.1 [2.0-4.7]) and hypertension (OR 3.5 [2.5-5.0])hypertension (OR 3.5 [2.5-5.0])

Overweight, diabetes and hypertension

3333CP03-2004

ConclusionsConclusions

In the CRIPS2 cohort, hypertension In the CRIPS2 cohort, hypertension (27%), diabetes (15%), (27%), diabetes (15%), hypercholesterolaemia (46%) and hypercholesterolaemia (46%) and overweight (35%) are common overweight (35%) are common

As these risk factors can be modified As these risk factors can be modified by diet and lifestyle, the prevention by diet and lifestyle, the prevention of cardiovascular disease requires a of cardiovascular disease requires a community approach community approach

3434CP03-2004

Coronary Artery DiseaseCoronary Artery Disease Heart FailureHeart Failure

Atrial FibrillationAtrial Fibrillation

3535CP03-2004

Heart Failure : How Big is the Heart Failure : How Big is the Problem Really?Problem Really?

4,790,000 Americans have heart failure4,790,000 Americans have heart failure• Based on extrapolation of NHANES dataBased on extrapolation of NHANES data

550,000 new cases each year550,000 new cases each year• Based on extrapolation of 44-year Framingham dataBased on extrapolation of 44-year Framingham data

HF contributed to 287,200 deaths in 1999HF contributed to 287,200 deaths in 1999• Primary cause in 54,913Primary cause in 54,913

HF deaths have increased by 145% in 20yearsHF deaths have increased by 145% in 20years• Age-adjusted rates have not changedAge-adjusted rates have not changed• Mortality rates may be decliningMortality rates may be declining

Hospital discharges increased from 377,000 to Hospital discharges increased from 377,000 to 962,000 between 1979 and 1999962,000 between 1979 and 1999• Age adjusted rates and length of stay are decliningAge adjusted rates and length of stay are declining

65+

45-64

3838CP03-2004

A New Epidemiology of A New Epidemiology of Ventricular DysfunctionVentricular Dysfunction

The Old Epidemiology of CHF :The Old Epidemiology of CHF :

• Included only symptomatic LV failureIncluded only symptomatic LV failure

• Often excluded persons > 75 years oldOften excluded persons > 75 years old

• Did not characterize ventricular functionDid not characterize ventricular function

The New Epidemiology of Ventricular DysfunctionThe New Epidemiology of Ventricular Dysfunction : :

• Includes assessment of ventricular structure and Includes assessment of ventricular structure and

systolic / diastolic functionsystolic / diastolic function

• No age limitsNo age limits

4040CP03-2004

Community Echo Survey of Systolic Community Echo Survey of Systolic and Diastolic LV Dysfunctionand Diastolic LV DysfunctionRedfield MM et al, JAMA 2003; 289: 194-202Redfield MM et al, JAMA 2003; 289: 194-202

Pts & MethodsPts & Methods1997-2000 : 2042 subjects of Ol1997-2000 : 2042 subjects of Olmsted County were screened wimsted County were screened with echo and Doppler, and followth echo and Doppler, and followed for ~5yrsed for ~5yrs

ResultsResultsCHF : 2.2%CHF : 2.2%Systolic Dysfunction : 6%Systolic Dysfunction : 6%EF > 50% : 44% EF > 50% : 44% Diastolic Dysfu : Mild 20.6%Diastolic Dysfu : Mild 20.6%

Mod 6.6%Mod 6.6%Severe 0.7%Severe 0.7%

4141CP03-2004

PharmacotherapyPharmacotherapy

ACEIACEI Angiotensin II blockersAngiotensin II blockers BetablockersBetablockers Aldosterone antagonistAldosterone antagonist Newer agentsNewer agents

4242CP03-2004

Declining Mortality in Heart Declining Mortality in Heart Failure TrialFailure Trial

0

5

10

15

20

V-HeFT IPla

SOLVD Pla SOLVDAce

MERIT BB Val-HeFT0

20

40

RALESAldo

Mild-Mod Severe

4343CP03-2004

Prevalence of Heart Failure with Prevalence of Heart Failure with Preserved EFPreserved EF

51% 43% 78% 53% 46%

0%

20%

40%

60%

80%

Framingham Olmstead CHS CA HMO CA Medicare

EF>50%

N=73

EF>50%

N=137

EF>50%

N=269

EF>45%

N=338

EF>40%

N=782

EF>45%

4545CP03-2004

Main Problems of Electrical Main Problems of Electrical AlterationsAlterations

1.1. PR prolongation PR prolongation (improper LV filling)(improper LV filling)2.2. Interventricular asynchrony Interventricular asynchrony (RV-LV asynchron(RV-LV asynchron

y)y)3.3. Intraventricular asynchrony (regional LV asyncIntraventricular asynchrony (regional LV async

hrony)hrony)Results in :Results in :1.1. Stroke volume Stroke volume2.2. Contractility Contractility3.3. MRMR

4646CP03-2004

Before After

CRT or Reverse Remodelling ?

4747CP03-2004

CRT TrialsCRT Trials

342 345

320 318

386* 384*

365*

352*

250

300

350

400

Control Trial

PATH-CHF

MUSTIC MIRACLE CONTAKCD

71

74 7371

68*69* 69

67

40

50

60

70

80

Control Trial

PATH-CHF

MUSTIC MIRACLE CONTAKCD

22

2524

23

28*

30*30*

26*

10

15

20

25

30

35

Control Trial

PATH-CHF

MUSTIC MIRACLE CONTAKCD

*Significant Improvement

6m HW (m) Echo (LVED in mm) LVEF (%)

4848CP03-2004

COMPANION : Death or HF COMPANION : Death or HF HospitalizationHospitalization(% of composite Endpoints)(% of composite Endpoints)

Bristow MR ACC 2003

4949CP03-2004

Coronary Artery DiseaseCoronary Artery Disease

Heart FailureHeart Failure Atrial FibrillationAtrial Fibrillation

5050CP03-2004

AF : Incidence/resource AF : Incidence/resource implicationimplication

In USA :In USA :

2 million; 160,000 new cases/yr2 million; 160,000 new cases/yr

3-5% population >60yr3-5% population >60yr

1.5 million primary reasons for 1.5 million primary reasons for consultationconsultation

1.4 million hospital discharges1.4 million hospital discharges

130,000 A&E visits130,000 A&E visits

6.6 billion US$ Medicare6.6 billion US$ Medicare

5151CP03-2004

Prevalence of AF in ElderlyPrevalence of AF in ElderlyRyder & Benjamin AJC 1999Ryder & Benjamin AJC 1999

4.8

6.5

5.1

1.3 1.3

0.10

1

2

3

4

5

6

7

USA(70-80)

Netherlands(70-80)

UK(70-80)

Hong Kong(60-94)

Japan(>40)

Himalaya(>15)

CountriesAge (yrs)

(%)

5252CP03-2004

AF and Mortality : Framingham Heart AF and Mortality : Framingham Heart StudyStudyBenjamin et al Circulation 1998; 98:946-952Benjamin et al Circulation 1998; 98:946-952

Methods : 5209 subjects, age 55-94, follow-up for 40yrs. AF documented by biennial ECG

Result :AF increases mortality by 50% in men and 100% women

Conclusion :Maintenance of sinus rhythm may decrease mortality

CHD CVA Total

No AF AF

Men : 1yr Cx(%)

1

2

3

4

5

0

5353CP03-2004

Prevalence of AF in Heart Failure Prevalence of AF in Heart Failure TrialsTrials

Study Study NYHCNYHC Prevalence, Prevalence, %%

SOLVD PreventioSOLVD PreventionnSOLVD TreatmentSOLVD TreatmentV-HeFTV-HeFTCHF-STATCHF-STATDIAMOND-CHFDIAMOND-CHFGESICAGESICACONSENSUSCONSENSUS

II

II-IVII-IV

II-IIIII-III

II-IIIII-III

III-IVIII-IV

III-IVIII-IV

IVIV

4.24.2

10.110.1

14.414.4

15.415.4

25.825.8

28.928.9

49.849.8

5454CP03-2004

5555CP03-2004

AT/AF Affect Survival ?AT/AF Affect Survival ?

34%34%

43%

21.8%

48%

30%

23%

32%

3.2%

29%

0

10

20

30

40

50

60AF No AF

MiddleKauff1 Framingham2 SOLVD3 DIG4 VA-CHF5

1. Middlekauff HR et al Circulation 1991; 84:40-482. Benjamin EJ et al Circulation 1998; 98:946-9523. Dries DL et al JACC 1998; 32 : 695-7034. Mathew J et al Chest 2000; 118: 914-9225. Carlson PE et al Circulation 1993; 87 (supple) : VI 102-110

Mortality (%)

5656CP03-2004

Emergence of New Emergence of New Epidemics of CVS DiseaseEpidemics of CVS Disease

Two new epidemics of Two new epidemics of

cardiovascular disease are emerging cardiovascular disease are emerging

: heart failure and atrial fibrillation: heart failure and atrial fibrillation

E. Braunwald

5757CP03-2004

Therapeutic Strategies in AFTherapeutic Strategies in AF

Necessary for all therapyMinimal S/ESymptomatic benefit EF? ET

Maintain SR

Theoretically soundAfter restoring SR EF ET atrial function? stroke

vsRate Control

5858CP03-2004

AFFIRM Study : AFFIRM Study : N N Engl J Med Dec 2002; 347 : 1825Engl J Med Dec 2002; 347 : 1825

5959CP03-2004

Strategies for AF Management Strategies for AF Management in CHFin CHF

• DrugDrug• Ablate & paceAblate & pace• Pulmonary vein ablationPulmonary vein ablation• Atrial defibrillatorsAtrial defibrillators• Main cause of AF is HTMain cause of AF is HT

6060CP03-2004

Global Approach to Reduce Global Approach to Reduce CVS/CVA CVS/CVA DeathDeath

International cooperationInternational cooperation Research and EducationResearch and Education Targeted primary prevention Targeted primary prevention

strategiesstrategies

e.g. tobacco use, hypertension e.g. tobacco use, hypertension control, affordable clinical algorithmcontrol, affordable clinical algorithm

Advocacy e.g. World Heart DayAdvocacy e.g. World Heart Day Availability of cost-effective medsAvailability of cost-effective meds

6161CP03-2004

6363CP03-2004

The Hong Kong AMI Registry 1995-The Hong Kong AMI Registry 1995-1996 Woo KS et al for the HK-AMI 1996 Woo KS et al for the HK-AMI Task ForceTask Force

Background :Background :A territory wide survey of all cases of A territory wide survey of all cases of AMI admitted into hospital. Initiated by AMI admitted into hospital. Initiated by the HK College of Cardiologythe HK College of Cardiology

Subject and Methods :Subject and Methods :A total of 3334 AMI (diagnosis by A total of 3334 AMI (diagnosis by symptom, ECG and enzyme) were symptom, ECG and enzyme) were prospectively entered into a centralized prospectively entered into a centralized data base, and uniformity and accuracy data base, and uniformity and accuracy of data were audited by a research of data were audited by a research coordinator. In-hospital mortality coordinator. In-hospital mortality complication were examined 96.2% were complication were examined 96.2% were ethnically Chineseethnically Chinese

6464CP03-2004

Demographics of AMI in HK Demographics of AMI in HK (95-96)(95-96)

32.7%

67.3%

0

10

20

30

40

50

60

70

Male64.8 yrs

Female72.9 yrs

SexAge

14.8%

31.9%31.3%

14.8%

32.7%

1.4%

0

10

20

30

40

Sex Age(%)

6565CP03-2004

AMI Incidence & Mortality in US AMI Incidence & Mortality in US (1975-1995)(1975-1995)Goldberg RJ Et al Circulation 1999; 33: Goldberg RJ Et al Circulation 1999; 33: 1533-15391533-1539

23.822.4

0

5

10

15

20

25

30

75-78 81-84 86-88 90-91 93-95

0

50

100

150

200

250

300Mortality Incidence

HK

HK

Mortality (%) Incidence /100,000