Place and Health: Understanding the Relationship Between Genetics, the Environment, and Our Health Behaviors April 5, 2011 Michigan Department of Community.

Place and Health: Understanding the

Relationship Between Genetics, the Environment, and Our Health Behaviors

April 5, 2011

Michigan Department of Community Health Genomics Program

Debra Duquette, MS, [email protected]

Presentation Objectives

• Identify two examples of health issues relevant to Genesee County that are related to genomics– Childhood asthma– Sudden cardiac death of the young

• Appreciate that prevention of health conditions related to genomics requires collaboration between local public health, state public health, communities, universities and genomic experts– State resources

“…no important health problem will be solved by clinical care alone, or research alone, or by public health alone- But rather by all

public and private sectors working together…..”

JS Marks. Managed Care 2005;14:p11Supplement on “The Future of Public Health”

Genomics Integration Requires Partners, Partners, Partners…!

Asthma:An Example of Genomics/Family

History Expanding Reach Of Environmental Project

“The Past Becomes the Future”MDCH Healthy Homes Section

“Unlock your past for a healthier future”MDCH Genomics and Genetic Disorders Section

State of Michigan Healthy Homes University

ProgramMission

StatementMaximize efforts to make homes safer by reducing multiple housing-related hazards that contribute to asthma, unintentional injury and overall quality of life

State of MichiganHealthy Homes University

(HHU) ProgramHHU I 2005-2008 • $989,737 HUD/$600,000

Leveraged Funds• 300 low-moderate income

families residing in Ingham County, MI with child with diagnosed asthma

• Basic and Custom Intervention

HHU II 2008-2011• $875,000 HUD Funds/$560,000

Leveraged Funds• 250 low-moderate income

families with a child diagnosed with asthma residing in Ingham County, MI and certain ZIP codes in Eaton and Clinton counties

• Basic and Custom Intervention• 10 homes in Flint, MI• Pre/post environmental dust

sampling for 50 homes

Genomics Approach of Healthy Homes University

I• Objectives:

– Identify asthma triggers and injury hazards

– Assess knowledge, attitudes and behaviors

– Provide education and intervention products

– Promote behavior change.• The HHU staff complete four visits per

home– Family history of asthma

collected at first visit• All 300 homes receive the Basic

Intervention• Eligible homes receive the additional

Custom Intervention products and services– More family members with

asthma in household, more resources provided

Baseline Questionnaire• Demographics• Family History

– First and second degree relatives ever diagnosed with asthma

– Affected relative(s) who live in household

• Asthma Severity• Medical Visit Frequency• Asthma Medication• Asthma Trigger Knowledge• Home Cleaning Frequency

Family History DataRelative (n=162) Positive Family

History (%)

1+ 1st or 2nd degree relatives 130 (80%)

0 first-degree relatives 56 (34.5%)

1 first-degree relative 56 (34.5%)

2 first degree relatives 34 (21%)

3+ 1st degree relatives 16 (10%)

Father 48 (30%)

Mother 61 (38%)

2+ paternal 2nd degree relatives 16 (10%)

2+ maternal 2nd degree relatives 36 (22%)

Family History and Asthma: Mean number of days with symptoms - past 30 days.

Question0 first degree

relatives

1 first degree relative

2 first degree

relatives

3+ first

degree relativ

es

1+ first degree

relatives

t-test p-value: 0 vs. 1+

How many days did [CHILD] have wheezing first thing in the morning? 3.6 5.8 6.3 14.8 7.4 0.004

How many nights did [CHILD] wake up because of wheezing or tightness in the chest or cough?

4.9 7.3 7.7 11.4 8.1 0.015

How many days did [CHILD] have shortness of breath because of asthma? 6.5 9.0 11.1 13.9 10.4 0.007

How many days did [CHILD] have wheezing or tightness in the chest or cough?

8.2 11.0 11.6 19 12.4 0.006

How many days did [CHILD] have itchy or watery eyes? 5.3 6.2 10.2 11.9 8.4 0.034

Healthy Homes University

Genomics: Outcomes • Applied principles of gene-environment interactions and family

history knowledge in an actual public health project• Promote positive change in family knowledge, attitudes and behaviors

regarding asthma triggers – 70% reduction in hospital visits and 50% decrease in self-reported

symptoms for primary child identified with asthma in home• Show impact of collection of family history of asthma and collection of

number of household members with asthma• Broader impact than one affected child per household• Reaches more than just 300 children/households• Document actual number of children and family members in

household– For first 162 households enrolled, there were 150 relatives who ever

affected with asthma in addition to the primary child with asthma in 93 households that also benefited from program

• Demonstrated genomics value in allocation of limited resources – Families at greatest risk with greatest number of affected receive

greater amounts of resources– Helping largest number of people with limited budget

What to look for in a family history?

Less

risk

More

risk

fewer number of relatives affected

greater

older relative’s age at diagnosis

younger

distant biological relatedness

close

What is Sudden Cardiac Death?

• Specific– Witnessed death: victim in his

or her usual state of health without acute symptoms for 6 hours prior to death

– Unwitnessed death: victim last seen in his or her usual state of health without acute symptoms until <24 hours before death

• General– Deaths occurring out-of-

hospital or in the emergency room or as “dead on arrival” with an underlying cause of death reported as a cardiac disease

Zheng ZJ, Croft JB, Giles WH, et al. State-Specific Mortality from Sudden Cardiac Death United States, 1999. MMWR Morb Mortal Wkly Rep. 2002;51(06):123-126.

http://www.mlive.com/news/grand-rapids/index.ssf/2011/03/autopsy_determines_cause_of_de.html

Sudden Cardiac Death of the Young (SCDY)

• Variably defined as < 30, < 35, < 40 years of age

• Especially tragic event; often high-profile, associated with young athletes

• A potentially preventable condition, due to the heritable nature of certain cardiac disorders– More likely to have genetic determinants than similar

conditions in older persons– Immediate family members of SCDY victims may be at

increased risk of sudden death since majority of genetic causes are autosomal dominant

Etiologies of SCDY• Coronary artery disease • Coronary artery abnormalities• Myocardial disorders

– Hypertrophic cardiomyopathy– Arrhythmogenic right

ventricular dysplasia (ARVD)– Dilated cardiomyopathy

• Other structural/functional abnormalities– Primary pulmonary

hypertension– Restrictive cardiomyopathy– Marfan syndrome with aortic

dissection– Aortic valve stenosis

• Primary electrical abnormalities/ion channelopathies– Long QT syndromes

• Romano Ward• Jervell Lange Nielsen• Acquired

– Catecholaminergic Polymorphic Ventricular Tachycardia (CPVT)

– Brugada syndrome– Short QT Syndrome– Wolf-Parkinson White

syndrome– Heart block: congenital or

acquired• Environmental causes

E.g., commotio cordis (‘blow to chest’) cocaine, stimulants, inhalants, gasoline, others

Adapted from Berger et al, Pediatric Clinics of North America (2004). 51:1201-1209

MDCH SCDY Case Definition• Aged 1-39

• Death occurred out of the hospital or in the emergency room

• Michigan resident• Death occurred in Michigan• Underlying cause of death cardiac-related, congenital

cardiac malformations, or ill-defined/unexplained

Cases selected from 220 ICD-10 Codes

Cardiac Related Codes

ICD 10: I00-I51

Examples:

•Cardiomyopathy

•Cardiac arrhythmia

•Atherosclerotic CVD

Congenital Cardiac Malformations

ICD 10: Q20-Q24

Examples:

•Atrial septal defect

•Dextrocardia

Ill-defined/ Unexplained

ICD 10: R96-R99

Examples:

•Instantaneous death

•Death occurring less than 24 hours from onset of symptoms, not otherwise explained

Descriptive Statistics and Mortality Rates

Table 1 Sudden cardiac deaths (SCDs)* of Michigan residents

aged 1 - 39 years, 1999 - 2006 Number Percent

Total 2,336

Sex

Male 1,615 69.1

Female 721 30.9

Race

White 1,505 64.4

Black 778 33.3

Other 53 2.3

Age

1-4 years 64 2.7

5-9 years 37 1.6

10-14 years 48 2.1

15-19 years 100 4.2

20-24 years 156 6.7

25-29 years 260 11.1

30-34 535 22.9

35-39 1,136 48.6

Place of death

Home 983 42.1

Nursing home, extended care 16 6.8

Hospital: emergency room / outpatient 1,112 47.6

Ambulance 33 1.4

Other / unknown 192 8.2

Autopsy

Yes 1,832 78.4

No 503 21.5

Unknown 1 0.0

* Includes decedents who died out of the hospital, or in an emergency department, or were dead on arrival to an emergency department, and had one of the following ICD-10 codes reported as the underlying cause of death on the death certificate: I00-I51 (cardiac causes), Q20-Q24 (congenital cardiac malformations), R96-R99 (ill-defined causes).

Age-Adjusted Mortality Rates:

Statewide: 5.5 per 100,000

White Males: 6.4 per 100,000

Black Males: 15.8 per 100,000

White Females: 2.5 per 100,000

Black Females: 8.5 per 100,000

1-9 years: 0.5 per 100,000 (n=101)

10-19 years: 0.9 per 100,000 (n=148)

20-29 years: 3.3 per 100,000 (n=416)

30-39 years: 13.8 per 100,000 (n=1,671)

Michigan’s Rate: 5.5 per 100,000 (up to 326 out-of-hospital SCDY per year)

Highest Rates:

•Clare: 7.8 per 100,000

•Kalkaska: 7.3 per 100,000

•Genesee: 7.0 per 100,000

Highest Number of SCDs:

•Wayne: n=838

•Oakland: n=187

•Macomb: n=156

•Genesee: n=127

Family History of SCDY

Table 3

Family History of Sudden Cardiac Death of the Younga 2007 Michigan Behavioral Risk Factor Survey

% 95% Confidence

Interval

Total 6.3 (5.2 - 7.7)

Age

18 – 24 3.8 (1.6 - 8.7)

25 – 34 8.6 (4.9 - 14.6)

35 – 44 4.2 (2.4 - 7.1)

45 – 54 7.7 (5.4 - 10.9)

55 – 64 5.9 (4.1 - 8.5)

65 – 74 8.5 (5.4 - 13.3)

75 + 5.4 (3.5 - 8.2)

Gender

Male 5.4 (3.9 - 7.4)

Female 7.7 (6.1 - 9.6)

Race/Ethnicity

White non-Hispanic 5.4 (4.3 - 6.8)

Black non-Hispanic 11.2 (7.7 - 16.0)

Other non-Hispanic 9.4 (3.8 - 21.3)

Hispanic --b

Education

Less than high school 10.8 (5.8 - 19.3)

High school graduate 8.8 (6.6 - 11.7)

Some college 4.7 (3.3 - 6.8)

College graduate 4.4 (2.8 - 6.8)

Household Income

< $20,000 7.8 (5.1 - 11.7)

$20,000 - $34,999 8.4 (5.9 - 11.8)

$35,000 - $49,999 8.8 (5.5 - 13.8)

$50,000 - $74,999 4.1 (2.1 - 7.9)

$75,000 + 3.2 (1.9 - 5.2) a Among all respondents (n = 2,856), the proportion who reported having at least one biological family member that had a sudden cardiac death, or sudden unexplained death, between the ages of 1 and 39.

Note: Interviewers were instructed not to include spouses of the respondent, infants less than one year of age, as well as drug-related deaths, traumatic deaths (such as car crashes), suicides, homicides, or individuals who had a long illness. b The denominator in this subgroup is less than 50.

Michigan 2007 Behavioral Risk Factor Survey (MiBRFS)

• 2,856 Michigan adults were asked about SCDY

• 6.3% have a family history of SCDY

26.2% with multiple relatives 35.5% with first degree relative

• Significantly more blacks (11.2%) than whites (5.4%) reported SCDY

BRFS SCDY Family History

Expert Panel Objectives

• Confirm the cause of death or suggest an alternative cause

• Describe the factors that may have contributed to the death

• Identify possible risk to family members

• Suggest recommendations for prevention of future deaths

Journal of Community Health. April 27, 2010.

Michigan Case Study Clinical and Family History

• African American teenage male• Student, basketball player• Symptoms 4 months – “skipped

beats and fluttering” especially while playing basketball; dizzy when rising from chair; tired all the time; legs hurt all the time; he thought these symptoms meant he was out of shape so he would practice harder

• Private health insurance coverage• Family History - mother had

“stroke“ as teen; maternal uncle had heart attack at 40 years old

• Sports physical 4.5 months prior• Never referred to cardiologist or

specialist• Weight 82nd percentile

Day of Death• Playing basketball, collapsed• No CPR prior to EMS, police were needed

to allow EMS access• Locked AED at site, coach had no training

on AED• No pulse/not breathing

Autopsy• Enlarged heart, marked left ventricular

hypertrophy. Diffuse myocyte hypertrophy with myofiber disarray and patchy interstitial scarring

• Hypertrophic cardiomyopathy• Toxicology – negative for alcohol, illicit

drugs• Family members not made aware of

genetic implications

Hypertrophic Cardiomyopathy

Inheritance: Autosomal dominantClinical Findings:• Myocardial hypertrophy (wall

thickness greater or equal to 13 mm) in the absence of hemodynamic stress

• Chest pain, dyspnea, syncope– usually exertional, postural,

postprandial• Decrease in exercise tolerance in

youngScreening: ECG, echocardiogram,

genetic testingTreatment: Physical activity

restrictions, medications, ICD, surgery

http://www.nytimes.com/imagepages/2007/08/01/health/adam/18141Hypertrophiccardiomyopathy.html

Expert Panel Findings Patient-related factors• Education when to seek medical care • Family history and screeningPhysician-related factors• Quality of pre-participation sports physical• Awareness of need to screen family members, and when genetics

or cardiology referral indicated• Education on content of family history screening formSystem-related factors• CPR training for coaches, or CPR training for community and

schools• If AED present on-site, require training and availability• Update Michigan High School Athletic Association pre-participation

sports screening template to include 2007 AHA 12 point screen and 2004/2010 national consensus recommendations

• Mechanism for family contact, including assuring autopsy report reaches primary care provider

• Storage of biologic specimen / DNA

Recommended 12 point screening protocol for young athletes (AHA 2007)

• Personal History– Palpitations– Exertional chest pain/discomfort– Unexplained syncope– Exertional unexplained fatigue– Elevated systemic blood pressure– Heart murmur

• Family History– Assess premature death, disability from heart disease in close relative

younger than 50 years old– Known cardiovascular genetic conditions

• Physical Exam– Assess heart murmur– Femoral pulses– Physical stigmata of Marfan syndrome– Brachial artery blood pressure

Examples of 21 Action Steps to Prevent SCDY

• Pre-participation Sports Screening/Physical and Follow-up– Recommend revisions to MHSAA sports participation form

• Provider Education and Public Awareness of SCDY Risk Factors– Increase public awareness and provider assessment of SDY risk

factors, including family history– Create standardized educational presentations for health care

provider training• Public Awareness of Cardiac Symptoms and CPR/AED Training

– Identify gaps in existing CPR/AED training mandates or professional guidelines for specific groups and settings

• Emergency Response Protocols– Explore policies and investigate availability of AEDs for volunteer

and other non-EMS responders• Medical Examiner Protocols

– Develop protocols to cover DNA banking for SCDY cases; mechanisms for follow-up with families; and standardized coding for negative autopsy findings

MDCH SCDY Website

• Posted by MDCH in August 2010

• Features educational video with MDCH Chief Medical Executive and 2 families

• MDCH SCDY data• 6 Expert Presentations• April Proclamation• Links to national and state

resources

www.michigan.gov/genomics

SCDY internal and external partners

• Academia– Wayne State University, Michigan

State University, University of Michigan• Employers/industry

– AED distributors (Phillips, Aventric, Medtronic), Health plans (Priority Health), Michigan Public Health Institute

• Health care delivery system– Michigan State Medical Society,

American College of Cardiology- Michigan Chapter, American Academy of Pediatrics-Michigan Chapter, William Beaumont Hospital, Detroit Medical Center, Spectrum Health, Henry Ford Hospital, Michigan Osteopathic Association, Michigan Association of Physician Assistants, Michigan Association of Certified Nurse Practioners, Society of Adolescent Medicine- Michigan Chapter, Michigan Association of Family Practice, Michigan College of Emergency Physicians, Michigan Association of Medical Examiners

• Media– Local television news– Detroit Free Press

• Communities– American Heart Association, Michigan

Association of Health, Physical Education, Recreation and Dance, Michigan Fitness Foundation, Michigan High School Athletic Association, Hypertrophic Cardiomyopathy Association, Sudden Arrhythmia Death Syndromes Foundation, Sudden Cardiac Arrest Association, Kayla Foundation, Gillary Foundation, families

• Government– Michigan Department of Community

Health (Cardiovascular Section; Vital Records; Genomics), Centers for Disease Control and Prevention, state legislatures (Senator Scott, Senator Clarke,, Representative Tim Bledsoe), local health departments

MDCH Family History Fact Cards

Developed in 2007 and distributed to public and health care providers

Series of 6 cards covering general family history, asthma, cancer, diabetes, heart disease and osteoporosis

www.michigan.gov/genomics

MDCH Family History and Your Health Newsletters

Developed and distributed since November 2004

Sent via e-mail to all Michigan libraries, clinics, chronic disease partners, and others

Focus on awareness of disease or risk factor month

• Number of hits to newsletters ~400-800/month

www.michigan.gov/genomics

www.hhs.gov/familyhistory

• Does It Run in the Family?

http://www.geneticalliance.org/fhh

• Family Reunion Guide

http://www.nkdep.nih.gov/familyreunion/

• Other websites:

http://www.cdc.gov/genomics/famhistory/index.htm

http://www.nchpeg.org/

National Family History Resources

• My Family Health Portrait

“I thought we were forgotten….I thought no one cared…”

- Mother of 18 year old victim, upon being asked for a next-of-kin interview

This project was supported in part by Cooperative Agreement #U58/CCU522826 from the Centers for Disease Control and Prevention. The contents are solely the

responsibility of the authors and do not necessarily represent the official views of CDC.