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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
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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
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 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 Caucasian American Heart Association: Heart Disease and Stroke Statistics Bibbins-Domingo K, et al. N Engl J Med 360(12):1179-90
HF Risk FactorsNHANES I Population attributable risk (%) Modified from: He J, et al. Arch Intern Med 161:996, 2001
HF Prevalence by Age and GenderNHANES III Percent of population (%) 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 ClinEpidemiol 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 ClinEpidemiol 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 ClinEpidemiol 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 ClinEpidemiol 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 ClinEpidemiol 1988;41:1105-16.
CARDIA- Participants Friedman GD, et al. CARDIA: Study design, recruitment, and some characteristics of the examined subjects. J ClinEpidemiol 1988;41:1105-16.
CARDIA- Participants Friedman GD, et al. CARDIA: Study design, recruitment, and some characteristics of the examined subjects. J ClinEpidemiol 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 20 ECHO Friedman GD, et al. CARDIA: Study design, recruitment, and some characteristics of the examined subjects. J ClinEpidemiol 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-9 Bibbins-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 1.1% 0.9% 0.08% 0 % 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 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
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 Bivariate Model Hazard Ratio P value
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 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 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.”
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)