Osler Journal Club Cohort Study - PowerPoint Presentation

Slide1

Osler Journal ClubCohort Study8/12/09

Racial Differences in Incident Heart Failure among Young Adults

Bibbins

-Domingo K,

et al.

N

Engl

J Med 360(12):1179-90

Presented by: Cristina

Alewine

,

Raymond Givens, Zoe

Orecki

Faculty Advisor: J. Hunter Young

Slide2

Cohort StudyObservationalGroup of subjects followed over time

Non-randomized

Compares differences in outcomes between groups

Types of cohort studies

Prospective

Retrospective

Nested case-control

Household panel survey

Slide3

Cohort Study Design

Group A

Group B

Slide4

Cohort Study LimitationsExpensiveTime-consuming

Attrition

Biases

Assessment bias due to lack of blinding

Information bias

Bias due to attrition

Analytic biasLack of causal inference: confounding

Slide5

Cohort Study StrengthsCan define incidence and possible causes of a conditionEfficient for rare exposures

Can establish timing of exposure to outcome

Allow study of outcome when randomization to exposure is unethical or impractical

Slide6

Heart Failure Epidemiology5.7 million Americans with HF

670,000 new cases diagnosed each year

U.S. mortality rate related to HF estimated at 20.2 deaths per 100,000

HF prevalence increases with age

Prevalence and etiology differ by ethnicity and gender

HF incidence twice as high among older African-American as among older Caucasian

American Heart Association: Heart Disease and Stroke Statistics

Bibbins

-Domingo K,

et al.

N

Engl

J Med 360(12):1179-90

Slide7

HF Risk FactorsNHANES I

Population attributable risk (%)

Modified from: He J, et al. Arch Intern Med 161:996, 2001

Slide8

HF Prevalence by Age and GenderNHANES III

Percent of population (%)

American Heart Association: Heart Disease and Stroke Statistics

Slide9

HF Prevalence by Ethnicity

From:

Yancy

CW. Heart Failure in African Americans. Am J

Cardiol

2005;96[

suppl

]:3i-12i

Slide10

Heart Failure EpidemiologyLimited data about HF incidence among people younger than 50

Better understanding of HF among young adults needed for improving targeting of screening and treatment

Slide11

Friedman GD, et al. CARDIA: Study design, recruitment, and some characteristics of the examined subjects. J

Clin

Epidemiol

1988;41:1105-16.

Slide12

CARDIACoronary

A

rtery

R

isk

D

evelopment in Young

A

dults

Prospective Cohort- initiated in 1984

“Initiated to investigate life-style and other factors that influence , favorably or unfavorably, the evolution of coronary heart disease risk factors during young adulthood.”

Friedman GD, et al. CARDIA: Study design, recruitment, and some characteristics of the examined subjects. J

Clin

Epidemiol

1988;41:1105-16.

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CARDIA- RecruitmentPopulation Goal:Obtain a representative sample of underlying population of black and white adults aged 18 to 30 years

Stratify to achieve equal numbers by race, gender, age, education

Centers:

Birmingham

Chicago

Minneapolis

Oakland

Friedman GD, et al. CARDIA: Study design, recruitment, and some characteristics of the examined subjects. J

Clin

Epidemiol

1988;41:1105-16.

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CARDIA- EligibilityAge - 18-30 years at initial telephone recruitment interview - initial exam before 31

st

birthday

Race

Residence

Health/Medical

- “free of long-term disease or disability”

- excluded if pregnant or up to 3 months post-partum

Other

- excluded if “unsuitable subjections”

emotional instability, drug effects, or hostility

Friedman GD, et al. CARDIA: Study design, recruitment, and some characteristics of the examined subjects. J

Clin

Epidemiol

1988;41:1105-16.

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CARDIA- DesignBrief Screening Telephone Interview16 Questions-

Verification Demographics

Medical Eligibility

CARDIA Exam

Additional Questionnaires

Sociodemographics

, Medical, Psychosocial

Interviews

A/B Behavior Patterns, Diet

Phlebotomy

Blood Pressure

Pulmonary Function Testing

Anthropometry

Treadmill Test

Friedman GD, et al. CARDIA: Study design, recruitment, and some characteristics of the examined subjects. J

Clin

Epidemiol

1988;41:1105-16.

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CARDIA- ParticipantsFriedman GD, et al. CARDIA: Study design, recruitment, and some characteristics of the examined subjects. J

Clin

Epidemiol

1988;41:1105-16.

Slide17

CARDIA- ParticipantsFriedman GD, et al. CARDIA: Study design, recruitment, and some characteristics of the examined subjects. J

Clin

Epidemiol

1988;41:1105-16.

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CARDIA- Time LineCARDIA Examination at Baseline and 2, 5, 7, 10, 15, and 20 years

Transthoracic

Echo at 5 years

Hospitalizations

Deaths at 6 month intervals

0

2

5

7

10

15

20

ECHO

Friedman GD, et al. CARDIA: Study design, recruitment, and some characteristics of the examined subjects. J

Clin

Epidemiol

1988;41:1105-16.

Slide19

Bibbins-Domingo et al. (2009). Racial Differences in Incident Heart Failure among Young Adults. NEJM. 360:12- 1179-1190.

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Study Cohort RetentionRetention at Year 20Telephone Interview 87.5%

Examination 71.8%

Noted- Black Men most likely to be lost to follow-up.

However statistics not supplied by authors.

Bibbins

-Domingo et al. (2009). Racial Differences in Incident Heart Failure among Young Adults. NEJM. 360:12- 1179-1190.

Slide21

CHF Related- End Pointsquestioned about overnight hospitalizations

records requested in cases of suspected

cv

events

classified as heart failure if

physician diagnosis

medical treatment (diuretic and digitalis or after-load reducing agent)

deaths reported at 6 month intervals

records requested after getting consent from next of kin

Classified as heart failure if appropriate ICD-9

Bibbins

-Domingo et al. (2009). Racial Differences in Incident Heart Failure among Young Adults. NEJM. 360:12- 1179-1190.

Slide22

Heart Failure Incidence by Race and Gender

0.9%

1.1%

0 %

0.08%

Bibbins

-Domingo et al. (2009). Racial Differences in Incident Heart Failure among Young Adults. NEJM. 360:12- 1179-1190.

Slide23

Which risk factors are important in determining who develops early heart failure?

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20 yr Risk of Heart Failure Based on Demographic Measures

Bibbins

-Domingo et al. (2009). Racial Differences in Incident Heart Failure among Young Adults. NEJM. 360:12- 1179-1190.

Slide25

BP, HTN, BMI, DM, HDL and CKD Increased in Participants with Heart Failure

White

Black participants

Blacks +HF

vs.All

Participants No HF ***p <0.001, ** <0.01, *<0.05

Blacks +HF vs. Blacks No HF ### p <0.001, ## <0.01, 0.05

##

***###

***###

***###

***###

**#

**##

**###

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Prevalence of HTN in Participants with HF

Bibbins

-Domingo et al. (2009). Racial Differences in Incident Heart Failure among Young Adults. NEJM. 360:12- 1179-1190.

Slide27

20 yr Risk of Heart Failure Based on Baseline Measurements

Hazard Ratio

P value

Bivariate

Model

Slide28

FHx Early CAD, and Substance Use No Different In Those With Subsequent HF.

White

Black participants

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Lower EF and Worse Systolic Fxn Seen in Pts with HF

*#

*#

*#

Blacks +HF

vs.All

Participants No HF ***p <0.001, ** <0.01, *<0.05

Blacks +HF vs. Blacks No HF ### p <0.001, ## <0.01, 0.05

White

Black participants

Bibbins

-Domingo et al. (2009). Racial Differences in Incident Heart Failure among Young Adults. NEJM. 360:12- 1179-1190.

Slide30

20 yr Risk of Heart Failure Based on Echo Measurements at Year 5

Not statistically significant in Multivariate Model Adjusted for Clinical Measures

Slide31

Conclusions of the StudyRacial disparity in development of early HFRates of HF in white pts confirmed earlier studies

Risk factors for heart failure in black pts:

Elevated blood pressure

Obesity

Chronic kidney disease

Systolic dysfunction in early adulthood

Need aggressive screening and intervention in young patients at risk

Need studies to determine best ways to intervene

Slide32

VALIDITY:Should we believe the results?

YES

ISSUES

Large study size

Big Association

Long observation

Standardization

Specific risk factors associated

Result makes sense given prior studies

Differential drop-out

Reliance on self-report

Misdiagnosis

Confounded by Chronic Kidney Disease

Missed cases

The missing risk factors:

LDL

Cocaine

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Chronic Kidney DiseaseHeart failure or kidney failure?Hospitalizations (N= 23)

n= 9 kidney dysfunction as a co-existing condition

and 3 of these are ESRD

Deaths (n= 5)

n= 1 kidney dysfunction as a co-

exisiting

conditionand it is classified as ESRD

Slide34

Missed Cases?Unreported hospitalizationsSubclinical cases

Diagnosis based on review of hospital admissions

Excludes diagnoses in clinic

Why not review med lists for drugs like

lasix

or digitalis that would suggest failure?

BiasAre the persons on the reviewing committee more likely to diagnose HF in black vs. white patients?

Slide35

GENERALIZABILITY:Can results apply to everybody?

YES

Some issues

Multiple study centers

Men and women

Black and white subjects

Varied socio-economics

Varied educational background

Does not give info on HF cases by location

Non-black minority groups excluded

Excludes “unsuitable subjects”

Slide36

What does this mean in clinic?

“Our data suggest that the number of young, black patients with hypertension that would need to be treated to prevent one case of heart failure before 50 years of age could be as low as 21.”

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Any Questions?

Slide38

Housestaff Journal Club

Slide39

Evidence of causalityTemporal associationStrong association

Dose-response

Consistency/replication

Biologic plausibility

No alternate explanation (confounding)

Cessation of exposure

Specific association

Slide40

Types of StudiesTrial: Cohort assembled and exposure assigned, usually by randomization

Cohort study

: Cohort assembled and followed over time. Exposures are measured.

Case-control study

: Subjects selected based on presence or absence of disease

Cross-sectional study

: Exposures and outcomes measured at one point in time

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From Journal to BedsideInternal validity

: Is the association real and causal?

External validity (generalizability)

: Do the findings apply to other populations (your patient)?

Statistical significance

: It’s unlikely the results occurred by chance

Clinical Significance:

Findings are compeling enough to influence your practice

Slide42

Internal Validity: Sources of errorBias

: Association not real due to systematic error

Selection bias

Information bias

Chance

: Association not real due to random error

Small sample size

Subgroup analyses

Confounding

: Real association; wrong inference

Grey hair associated with heart disease

Slide43

Study type: TrialsStrength: validity

Trials provide the stongest evidence of causation

Key: the exposure is assigned, usually through randomization

Weaknesses

May not be generalizable

Volunteers

Clinically homogeneous

Ideal setting (extraneous factors controlled)

Expensive

Short duration

Bias: Minimize by blinding participants & staff

Slide44

Study type: Cohort StudiesStrengths

Long duration of follow-up

Temporal association of exposure with outcome

Increased generalizability

Weaknesses

: Validity

ConfoundingFactor related to exposure and outcome

Exposure is often a choice (diet, exercise, drug)

Bias

Assessment of outcome or exposure can be unduly influenced by factors unrelated to disease process

Slide45

Study type: Cross-Sectional StudiesStrengths:

Efficient

Can address prevalence

Weaknesses:

Validity

Confounding

BiasSurvivor bias

Reverse causality

Cannot address incidence

Slide46

Study type: Case-Control StudiesStrengths:

Efficient

Weaknesses:

Validity

Confounding

Bias:

Selection biasRecall bias

Cannot address prevalence or incidence

Slide47

Current ArticleBibbins-Domingo et al. NEJM 2009; 360:1179-90

Study question:

Association of ethnicity with heart failure in young adults

Results:

Young African Americans have greater risk of heart failure than young Americans of European descent

Internal validity:

Is the association real? Yes, but with following caveats

Differential drop outs: probably underestimated incidence in AA men

Authors could have assessed effect using baseline characteristics

Diagnostic bias: Ethnicity may have influenced probability of naming a clinical scenario as heart failure

Differential access to care: European-Americans may have been diagnosed in clinic more often

Subclinical heart failure was not assessed and may account for a substantial portion of heart

falure cases underestimating incidence

Slide48

Current ArticleInternal validity:

(continued)

Is the association confounded?

Renal disease: High prevalence in African Americans and could both lead to and mimic heart failure (volume overload)

External Validity:

Those more likely to be loss to follow-up were excluded

Statistical significance:

No question here. Just lack of power to further explore predictors

Clinical significance:

Not sure these findings were not unexpected. Incidence is still low complared to renal disease. Another reason to be aggressive with blood pressure control (although this is extrapolating from the data)