osler journal club cohort study 8/12/09
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Osler Journal Club Cohort Study 8/12/09. 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. Cohort Study. Observational - PowerPoint PPT PresentationTRANSCRIPT
OSLER JOURNAL CLUBCOHORT STUDY
8/12/09Racial Differences in Incident Heart
Failure among Young AdultsBibbins-Domingo K, et al. N Engl J Med 360(12):1179-90
Presented by: Cristina Alewine , Raymond Givens, Zoe OreckiFaculty Advisor: J. Hunter Young
Cohort Study Observational Group 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
Cohort Study Design
Defined Population
Exposed
Develop Disease
Do Not Develop Disease
Non-exposed
Develop Disease
Do Not Develop Disease
Group A Group B
Cohort Study Limitations Expensive Time-consuming Attrition Biases
Assessment bias due to lack of blinding Information bias Bias due to attrition Analytic bias
Lack of causal inference: confounding
Cohort Study Strengths Can define incidence and possible causes
of a condition Efficient for rare exposures Can establish timing of exposure to
outcome Allow study of outcome when
randomization to exposure is unethical or impractical
Heart Failure Epidemiology 5.7 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 CaucasianAmerican Heart Association: Heart Disease and Stroke StatisticsBibbins-Domingo K, et al. N Engl J Med 360(12):1179-90
HF Risk FactorsNHANES I
010203040506070 61.6
17.110.1 9.2 8.9 8.9 8 3.1 2.2
Risk Factor
Popu
latio
n at
tribu
tabl
e ris
k (%
)
Modified from: He J, et al. Arch Intern Med 161:996, 2001
HF Prevalence by Age and Gender
NHANES III
20-24 25-34 35-44 45-54 55-64 65-74 75+0123456789
10
0.1 0.10.7
1.8
6.26.8
9.8
0.1 0.10.5
1.3
3.4
6.6
9.7
MenWomen
Perc
ent o
f pop
ulat
ion
(%)
American Heart Association: Heart Disease and Stroke Statistics
HF Prevalence by Ethnicity
From: Yancy CW. Heart Failure in African Americans. Am J Cardiol 2005;96[suppl]:3i-12i
Heart Failure Epidemiology• Limited data about HF incidence
among people younger than 50 Better understanding of HF among young
adults needed for improving targeting of screening and treatment
Friedman GD, et al. CARDIA: Study design, recruitment, and some characteristics of the examined subjects. J Clin Epidemiol 1988;41:1105-16.
CARDIA Coronary Artery Risk
Development in Young Adults
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.
CARDIA- Recruitment Population 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.
CARDIA- Eligibility Age
- 18-30 years at initial telephone recruitment interview - initial exam before 31st 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.
CARDIA- Design Brief Screening Telephone Interview
16 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.
CARDIA- Participants
Friedman GD, et al. CARDIA: Study design, recruitment, and some characteristics of the examined subjects. J Clin Epidemiol 1988;41:1105-16.
CARDIA- Participants
Friedman GD, et al. CARDIA: Study design, recruitment, and some characteristics of the examined subjects. J Clin Epidemiol 1988;41:1105-16.
CARDIA- Time Line
CARDIA 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
20ECHO
Friedman GD, et al. CARDIA: Study design, recruitment, and some characteristics of the examined subjects. J Clin Epidemiol 1988;41:1105-16.
Bibbins-Domingo et al. (2009). Racial Differences in Incident Heart Failure among Young Adults. NEJM. 360:12- 1179-1190.
Study Cohort Retention Retention at Year 20
Telephone 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.
CHF Related- End Points questioned 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-9Bibbins-Domingo et al. (2009). Racial Differences in Incident Heart Failure among Young Adults. NEJM. 360:12- 1179-1190.
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.
Which risk factors are important in determining who develops early heart
failure?
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.
BP, HTN, BMI, DM, HDL and CKD Increased in Participants with Heart
FailureWhite Black participants
Blacks +HF vs.All Participants No HF ***p <0.001, ** <0.01, *<0.05Blacks +HF vs. Blacks No HF ### p <0.001, ## <0.01, 0.05
##
***###***###
***###***###
**#**##
**###
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.
20 yr Risk of Heart Failure Based on Baseline Measurements
Hazard Ratio
P value
Bivariate Model
FHx Early CAD, and Substance Use No
Different In Those With Subsequent HF.
White Black participants
Lower EF and Worse Systolic Fxn Seen in Pts with HF
*#
*#*#
Blacks +HF vs.All Participants No HF ***p <0.001, ** <0.01, *<0.05Blacks +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.
20 yr Risk of Heart Failure Based on Echo Measurements at Year 5
Not statistically significant in Multivariate Model Adjusted for Clinical Measures
Conclusions of the Study Racial disparity in development of early HF Rates 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
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
Chronic Kidney Disease Heart 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
condition and it is classified as ESRD
Missed Cases? Unreported hospitalizations Subclinical 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? Bias
Are the persons on the reviewing committee more likely to diagnose HF in black vs. white patients?
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”
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.”
Any Questions?
HOUSESTAFF JOURNAL CLUB
Evidence of causality Temporal association Strong association Dose-response Consistency/replication Biologic plausibility No alternate explanation (confounding) Cessation of exposure Specific association
Types of Studies Trial: 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
From Journal to Bedside Internal 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
Internal Validity: Sources of error
Bias: 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
Study type: Trials Strength: 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
Study type: Cohort Studies Strengths
Long duration of follow-up Temporal association of exposure with outcome Increased generalizability
Weaknesses: Validity Confounding
Factor 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
Study type: Cross-Sectional Studies
Strengths: Efficient Can address prevalence
Weaknesses: Validity
Confounding Bias
Survivor bias Reverse causality
Cannot address incidence
Study type: Case-Control Studies
Strengths: Efficient
Weaknesses: Validity
Confounding Bias:
Selection bias Recall bias
Cannot address prevalence or incidence
Current Article Bibbins-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
Current Article Internal 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)