Attach #3

Appendix 6. ARIC OSMB 2008 Meeting Minutes
MINUTES
Observational Study Monitoring Board
Atherosclerosis Risk in Communities
Meeting, 12/03/2008
PARTICIPANTS:

OSMB Members Present: Morton Hawkins (Chair); Karen Kaplan, Jose Ordovas,
Veronique Roger, Jerome Rotter
OSMB Members Absent: Robert Goldberg, Jeremiah Stamler, Marvin Ziskin

Investigators: Alvaro Alonso, Christie Ballantyne, Eric Boerwinkle, Diane Catellier, Josef
Coresh, Jing-fei Dong, Aaron Folsom, Gerardo Heiss, Ron Hoogeveen, Thomas Mosley,
Jennifer Nettleton, Richey Sharrett

Data Coordinating Center Staff: Lloyd Chambless (PI); Wayne Rosamond
NHLBI Staff: Cashell Jaquish, Executive Secretary; Kristi Cooper, Michael Lauer, Hanyu Ni,
Jean Olson, Mona Pandey, Phyliss Sholinsky, Paul Sorlie, Elizabeth Zoller
INTRODUCTION (closed session)
Dr. Hawkins called the meeting to order at 8:00 am and introduced the new Board member (Dr.
Ordovas). Dr. Jaquish reminded Board members of the importance of completing COI forms in
a timely manner and confirmed that the Board members had no new conflict of interest issues to
report subsequent to their annual filing. The minutes from the November 28, 2007 meeting
were discussed and approved.
Dr. Ni from the Project Office reported that heart failure (HF) surveillance has been streamlined;
however it is about 1 year behind schedule due to complicated case reviews. The GWAS
genotyping is completed and data will be shared through dbGAP. Investigators are discussing
follow up of findings with sequencing. Dr. Ni commented on the study’s productivity and the
NHLBI sponsored Working Group on Future Research Opportunities in the ARIC study, as well
as ancillary studies. The proposed ARIC Neurocognitive ancillary study has been submitted to
the NIH and should be reviewed in February 2009. The Project Office is satisfied with the
progress of the study and accomplishments of the investigators.
The Board found the responses to recommendations from 2007 to be satisfactory. They also
supported future participation of ARIC in the NHLBI Cohort Studies Workshop.
OPEN SESSION
Progress and Overview (Dr. Folsom)
The investigators have been very successful in their annual follow up and surveillance.
Approximately 93% of living participants are still in contact with the study. Dr. Folsom
summarized events at each field center and overall. Abstraction and classification activities
were summarized.
Publication rates remain high with 59 in the last year and 635 total. Dr. Folsom then highlighted
many recent, important publications in the areas of surveillance, HF and genomics. ARIC

currently has >80 funded ancillary studies, not all currently active. Rationale for a new exam in
the ARIC cohort was presented.
Coordinating Center Report (Drs. Chambless, Heiss and Rosamond)
Dr. Chambless gave an overview of quality control (QC) procedures including abstraction QC
and laboratory QC. Dr. Chambless reported on the training and certification for morbidity and
mortality classification and site visits. The percent disagreement for HF classification increased
in 2006; the Coordinating Center is investigating this further. Out of hospital deaths were
summarized by field center.
Dr. Heiss reported on annual follow up, now in year 22-23. The refusal rate is about 1% per
year and the mortality rate about 2% per year. An additional 2% are living but direct contact is
not possible. Some items have been added to follow-up questionnaires for ancillary studies.
Proxies have been identified for older participants. Many of those who refused commented that
they would participate when and if a new exam is instituted. HF has been self reported in follow
up with a confirmation from the participant’s physician. Approximately 70-80% of physicians
responded and about 60% of those responses confirmed HF diagnosis.
Dr. Rosamond reported on surveillance efforts. Although the goal is no more than a 2-year lag
in surveillance, they are currently a bit behind. An overview of the HF surveillance protocol was
presented. Efforts are being made to differentiate between decompensated HF, chronic stable
HF and unlikely HF. Agreement between 4 algorithms and reviewers was presented. The fact
that reviewers have access to additional information may contribute to increased disagreement
with the algorithm results. In an effort to streamline the process: (1) only one review will be
performed if all algorithms are positive and reviewer finds decompensated HF, otherwise will
adjudicate, (2) one review for all algorithms classified negative or other and (3) double review
for all cohort events with differences adjudicated.
ARIC Genetics Research (Dr. Boerwinkle)
There are 3 major genetic activities occurring: 1) Contract genotyping and analysis (focus on G
x E), 2) GWAS discovery and consortia, and 3) Medical resequencing. Dr. Boerwinkle
emphasized the need for large sample sizes and consortia for GWAS. He highlighted some
interesting findings linking the umodulin gene to CKD; this finding was consistent across age,
sex, diabetic and hypertensive status. Medical resequencing has been progressing. The
investigators have sequenced diabetes candidate genes and are working on HDL (124 genes to
be sequenced in 2009). They are finding a tremendous amount of variation. Dr. Boerwinkle
predicted genome wide sequencing in 2011-12. The major difficulty is analysis and
interpretation of large amounts of data with greater than anticipated genetic variation.
ARIC Laboratory Report (Drs. Ballantyne & Dong)
New blood analytes were reviewed. Several are being measured on 793 PAD samples.
Additional measures related to CKD, diabetes, as well as sex hormone markers, oxysterols,
troponin, BNP and GDF-15 are underway. Dr. Dong outlined a pathways approach to analyzing
these markers. The status of the lipid sample inventory was reviewed. Inventory of Exam 3
samples is underway.
Working Group on Future Research Opportunities in the ARIC study (Dr. Ni)
Dr. Ni gave an overview of the recommendations from the NHLBI Working Group convened in
July 2008 on future research opportunities in ARIC. The current contract ends in 2012. The

Working Group recommended consideration of a new exam in the renewal to focus on HF and
healthy aging. The meeting report will be sent to the OSMB.
Scientific Presentations
Dr. Ballantyne: Use of 9p21 in deciding lipid therapy
Dr. Coresh: Serum 13C to 12C ratio as a biomarker of sweet intake
Dr. Alonso: Atrial Fibrillation
Dr. Rosamond: Obesity and HF
Dr. Hoogeveen: Carotid MRI, MMP, RANTES and 9p21
CLOSED SESSION
The Board members agreed that overall, the study investigators are doing an outstanding job
and agreed that the study should continue. They also complimented the study’s sustained high
productivity in both quality and quantity of publications. The Board also commended NHLBI for
considering a new exam in ARIC in response to the Working Group and OSMB
recommendations.
Recommendations:
1) The Board commended the overall study. The CC is doing a great job with retention and
performing complex analyses. ARIC is leading the field in genetic epidemiology. The
publication record and productivity of ARIC is outstanding and there has been a
concerted effort to incorporate new investigators.
2) The Board recommends ARIC participation in future NHLBI sponsored Cohort Studies
Workshops.
3) The Board requests information regarding processes for prioritization for use of limited
samples and resources, particularly with respect to large “-omics” projects.
4) The Board recommends considering more in depth “-omic” phenotypes, such as
metabolomics and deep phenotyping (transcriptomics, proteomics, high resolution
imaging, cell based phenotypes, etc.) in future ARIC research proposals.
5) The Board recommends interaction between NHLBI and ARIC investigators in
evaluating importance and feasibility of possible exam components in the

eventuality of a new clinical exam.
6) The Board recommends that the ARIC investigators consider incorporating additional
measures, such as BNP and LV ejection fraction, in the criteria for review and
adjudication of heart failure. Incorporation of such measures may help to streamline the
process and reduce reviewer work load.
NEXT MEETING
The next ARIC OSMB meeting was scheduled for Wednesday, December 2, 2009.
SIGNATURES

_____ APPROVAL

_____ DISAPPROVAL

_______________________
Deputy Director, NHLBI

Date

ARIC OSMB meeting minutes is attached. Here are the recommendations:
CLOSED SESSION
The Board members agreed that overall, the study investigators are doing an outstanding job and
agreed that the study should continue. They also complimented the study’s sustained high
productivity in both quality and quantity of publications. The Board also commended NHLBI for
considering a new exam in ARIC in response to the Working Group and OSMB
recommendations.
Recommendations:

1) The Board commended the overall study. The CC is doing a great job with
retention and performing complex analyses. ARIC is leading the field in genetic
epidemiology. The publication record and productivity of ARIC is outstanding
and there has been a concerted effort to incorporate new investigators.
2) The Board recommends ARIC participation in future NHLBI sponsored Cohort
Studies Workshops.
3) The Board requests information regarding processes for prioritization for use of
limited samples and resources, particularly with respect to large “-omics”
projects.
4) The Board recommends considering more in depth “-omic” phenotypes, such as
metabolomics and deep phenotyping (transcriptomics, proteomics, high
resolution imaging, cell based phenotypes, etc.) in future ARIC research
proposals.
5) The Board recommends interaction between NHLBI and ARIC investigators in
evaluating importance and feasibility of possible exam components in the eventuality of
a new clinical exam.

6) The Board recommends that the ARIC investigators consider incorporating
additional measures, such as BNP and LV ejection fraction, in the criteria for
review and adjudication of heart failure. Incorporation of such measures may
help to streamline the process and reduce reviewer work load.

NEXT MEETING
The next ARIC OSMB meeting was scheduled for Wednesday, December 2, 2009.