Overview of Cardiovascular

Disease in American Indians and Alaskan

Natives Barbara V. Howard, PhD

MedStar Research Institute

Terry Raymer MD, CDE

terry.raymer@mail.ihs.gov

The Rising Tide of CVD

Strong Heart Study

Ak-Chin

Phoenix

Salt River Indian Community

ARIZONA

Gila RiverIndianCommunity

Oklahoma City

AnandarkoLawton

OKLAHOMA

NORTH DAKOTA

SOUTH DAKOTA

Rapid CityPine Ridge

Oglala

Cheyenne RiverEagle Butte

Bismarck

Spirit Lake

Ak-Chin

4549 American Indians ages 45-74 years

Arizona: Pima/Maricopa/Papago in the Gila River, Salt River, and Ak-Chin Indian communities

Oklahoma: Apache, Caddo, Comanche, Delaware, Fort Sill Apache, Kiowa, and Wichita

South/North Dakota: Oglala Sioux and Cheyenne River Sioux (SD) and the Spirit Lake Tribe in the Fort Totten area (ND)

Strong Heart Study 1988-2003• Community Mortality Study

35–74-year-old men and womenDeaths between 1984 and 1994Medical record review of all possible CVD deaths

• Physical Examinations of Cohort1989-91, 1993-5 and 1998-9 ECG, Cardiac and Carotid ECHO, Anthropometry, BP, ABI, PFT, Blood, urine

and DNA samples, Medical and medication history

• LifestyleDiet, Activity, Quality of Life, smoking, alcohol

Strong Heart Study 1988-

2003 • Cohort SurveillanceYearly contactMedical record review for all cause and CVD Mortality and nonfatal CVD

• Family Study120 families of 30 members eachExamination similar to that of cohort10cM genetic map

Hospital AdmissionsPhoenix PHS Indian Hospital, 1957-1966

Myocardial All hospital infarction admissions (n = 61) (N = 24,121)

Tribe No. % %

Pima 28 45.9 36.2Apache 7 11.5 22.0Navajo 1 1.6 10.5Papago 5 8.2 8.4Hopi 7 11.5 6.5Other SW Indians 13 21.3 16.4Total 61 100.0 100.0

Sievers, Ann Intern Med 1967;67:800

CVD and Total Mortality Rates

Arizona vs Strong Heart Study, Men, 1986per 10,000

45-54 65-7455-64

CHD Incidence in American Indians

Compared to ARIC Population

Women Men

ARICSHS

Rate per 1000 person-years

CHD(45-64 years)

CHD includes fatal and nonfatal events plus revascularization

10

20

Prevalence of DiabetesStrong Heart Study, by Gender and Center

Women Men

%

Contribution of Diabetes to CHD

Strong Heart Study

Hazard Ratio 6.3 3.1

Prevalence 60% 50%

PAR* 76% 51%

Women Men

*PAR = Attributable riskDiabetes is the engine driving the increase in CVD

Acute Myocardial Infarction

Among Navajo Men

1976 -1979

1980 -1983

1984 -1986

35 - 4445 - 54

55 - 64>65

0123456

Age in years

Hospitalization rates per 1000

Klain, Coulehan, Arena, & Janett, AJPH, 1988

Acute Myocardial Infarctions

Hopi Tribal Members

Average values 1957-66 from Seivers and average for 1975-78 taken from Sievers and Fisher; p,0.001

1957 1962 1967 1972 1977 1982 1987 1992

Year

0

2

4

6

8

10

12

Num

ber

of M

yoc a

rdia

l In f

a rc t

ion

Actual Data Regression line

per 100,000. Ages 45 to 79. Arch Intern Med 2002;162:1368-1372.C.

The Apache Heart StudyIncidence of Confirmed CAD Cases

0

5

10

15

20

87 -88 89 - 90 91 - 92 93 - 94 95 - 96

Prevalence of Atherosclerotic Plaque in GOCADAN and U.S.

Whites & Blacks

010

2030

4050

6070

8090

100

15-19 20-29 30-39 40-49 50-59 60-69 70-89

GOCADANARIC/CHS

Age (years)15 May 2003

American Indian Mortality Rates

0

50

100

150

HeartDisease

Cancer Accidents Diabetes

AI/AN Mortality US All Races

Trends in Indian Health, 1997; Age-adjusted data

Age-Adjusted Heart Disease Mortality

0

50

100

150

200

250

300

US All Races AI/AN Actual AI/AN Adjusted

Trends in Indian Health, 2000

Strong Heart Study conclusions for CVD in

American Indians CVD rates in American Indians are now

higher than in the general U.S. population The rates are increasing The majority of CVD occurs in people

with diabetes

• Conventional Risk Factors

• New Risk Factors

CVD Risk Factorswhat’s important in

diabetes? Age (!) Gender not significantly different:

diabetes is the “equalizer” LDL cholesterol HDL cholesterol Blood Pressure (systolic) Smoking (!) Non-HDL cholesterol

Distribution of LDL Cholesterol

in American Indians

LDL Cholesterol (mg/dl)

Men Men Women Women

FHS SHS FHS SHS

160-199 Ref Ref Ref Ref

200-239 1.19 1.63 1.23 1.09

240-279 1.66 2.31 1.28 1.55

> = 280 1.93 2.87 1.71 2.57

RR for Total Cholesterol in Framingham vs Strong

Heart Study

Are all LDL levels created equal?

Vs.

Large “Fluffy” LDL Small “Dense” LDL

Less atherogenic More atherogenic

LDL = 130 mg/dL in both examples

Non-HDL Cholesterol:

Non-HDL cholesterol = Total Cholesterol - HDL

A secondary target of therapy when serum triglycerides

are 200 mg/dL (esp. 200–499 mg/dL)““The simple non-HDL cholesterol measurement,which can The simple non-HDL cholesterol measurement,which can be conducted in the be conducted in the nonfasting statenonfasting state and can be determined and can be determined

regardless of triglyceride concentration, may be of particularregardless of triglyceride concentration, may be of particular

clinical utility.” clinical utility.”

Lu et al; Diabetes Care 26:16-21Lu et al; Diabetes Care 26:16-21

Non-HDL Cholesterol as a Predictor of Cardiovascular Disease in Type 2 Diabetes:

The Strong Heart Study*

Non-HDL cholesterol is a better predictor of risk for CVD than LDL & TG in men & women and Total/HDL in women

Conclusion: This study suggests that non-HDL cholesterol index may be particularly useful in predicting CVD risk in patients with diabetes.

*Lu W et al Diabetes Care 2003 26:16-23

Distribution of Systolic Blood Pressure in Diabetic and

Nondiabetic American Indians Diabetic

Nondiabetic

Systolic blood pressure (mmHg)

Systolic blood pressure (mmHg)mm Hg

Diabetic

Systolic Blood Pressure and CVD Relative Risk in Diabetic

American Indians

Adjusted by LDL, HDL, TG, gender, smoking and age

• Conventional Risk Factors

• New Risk Factors

Women Men

1.02.0

4.0

6.0

8.0 Macro-albuminuria

Women Men

1.0 2.0

4.0

6.0

8.0 Micro-albuminuria

Hazard Ratiosfor Albuminuria as Predictor of

CVD

Survival

Miettinen H et al. Stroke. 1996;27:2033-2039.

<150 mg/L >300 mg/L150-300 mg/LUrinary protein

All-cause mortality1

0.6

0.5

0.4

0

0.7

0.8

0.9

Months30 40 50 60 70 80 9020100

A

B

C

CVD mortality

0

Months30 405060 70 80 9020100

A

B

C

A: B: C:

1

0.6

0.5

0.4

0.7

0.8

0.9

Overall <0.001A vs B <0.001A vs C <0.001B vs C <0.001

Overall <0.001A vs B 0.013A vs C <0.001B vs C <0.001

Proteinuria: All-Cause and CVD Mortality in Patients With Type

2 DM

C

0

5

10

15

20

25

30

35

1st Tertile 2nd tertile 3rd Tertile

Tertile of HOMA IR

Pe

rce

nt

(%)

0

5

10

15

20

25

30

Absent Present

ATP III Metabolic Syndrome

Per

cent

(%

)

IR and MS as Predictors of Diabetes

01

23

45

67

89

10

1st Tertile 2nd tertile 3rd Tertile

Tertile of HOMA IR

Per

cen

t (%

)

0

1

2

3

4

5

6

7

8

9

10

Absent Present

ATP III Metabolic Syndrome

Perc

ent (

%)

IR and MS as Predictors of CVD

The metabolic syndrome is not a strong determinant of CVD in American Indians without diabetes as in other populations studied

IR/MS leads to diabetes before it leads to CVD Diabetes + Metabolic Syndrome =

Bad Prevent Diabetes in Metabolic Syndrome =

Good

All in the Family: Metabolic Syndrome, CVD, and Diabetes

so far

Inflammatory Markers?

Markers of Pre-Clinical Disease?

LV Function and CVD Mortality in Diabetes

Time (months)

706050403020100-10

Cumu

lativ

e Su

rviva

l

1.1

1.0

.9

.8

E/A>1.5

No

Yes

Months

50403020100

Cum

ulat

ive S

urviv

al

1.00

.98

.96

.94

.92

.90

EF

<40%

40-54%

>=55%

LVEF Abnormal LV Filling

Multivariate Relative Risk of Mortality in Diabetes*

0.0

0.5

1.0

1.5

2.0

2.5

3.0

3.5

4.0ST DepressionPCA RatioQTc

Rel

ativ

e R

isk

Cardiovascular Mortality All-Cause Mortality

p=0.0009

p=0.006

p=0.082

3.68

p=0.242

p=0.001p=0.002

2.61

1.87

2.36

1.33

2.03

* Adjusted for age, sex, BMI, BP, HDL, LDL, TGs, albuminuria, alcohol use, smoking, prevalent CHD, and center

Application to the Clinical ECG

50 uV of ST depression = 1/2 mm (half

a small box) The QTc is the longest interval from

onset of QRS to the end of the T-wave

“It’s not all epidemiology and bad

news”

Multifactorial Intervention in DM

The Steno-2 trial

0

5

10

15

20

25

30

35

40

45

50

12 24 36 48 60 72 84 96

Months

En

d P

oin

t %

Conventional Intensive

44%

24%

Composite end-point: CV death, MI, CABG, PCI, stroke, amputation from ischemia, surgery for PVD.

P=0.008

47% Risk Reduction

There is a rising tide of CVD in AI/AN Most CVD is in those with diabetes Diabetes care should include attention to

major CVD risk factors – LDL, BP, smoking In addition, albuminuria and ECG

abnormalities can be considered in identifying those with increased risk

Research is focusing on future strategies for therapy and prevention of CVD in diabetes

Summary