MESA EVENTS DATA SET VARIABLE GUIDE

Data Set Name : MESAEventsPreFU6_10142008 SQL Database Table Name : vEventsF6 Contact Information : [email protected]

Variable Description Value Labels idno MESA Participant Identification Number fuptt Time until most recent Follow-up assessment within the ascertainment period prebase Type of pre-baseline event exall Exclusion from all events follow-up due to pre- 0=No, 1=Yes baseline event expvd Exclusion from PVD due to pre-baseline PVD 0=No, 1=Yes mi Myocardial Infarction (MI) 0=No, 1=Yes mitype MI type mitt Time to MI or last follow-up rca Resuscitated Cardiac Arrest 0=No, 1=Yes rcatype Resuscitated Cardiac Arrest type rcatt Time to Resuscitated Cardiac Arrest or last follow-up ang Angina Pectoris 0=No, 1=Yes angtype Angina type angtt Time to Angina or last follow-up ptca Percutaneous Transluminal Coronary Angioplasty 0=No, 1=Yes (PTCA), coronary stent, or coronary atherectomy ptcatype PTCA type ptcatt Time to PTCA or last follow-up cbg Coronary Bypass Graft (CBG) 0=No, 1=Yes cbgtype CBG type cbgtt Time to CBG or last follow-up othrev Other Revascularization 0=No, 1=Yes othrevtt Time to other revascularization or last follow-up chf Congestive Heart Failure (CHF) 0=No, 1=Yes chftype CHF type chftt Time to CHF or last follow-up pvd Peripheral Vascular Disease (PVD) 0=No, 1=Yes pvdtype PVD type pvdtt Time to PVD or last follow-up

Page 1 of 13 Variable Description Value Labels strk Stroke 0=No, 1=Yes strktype Stroke type 1=Subarachnoid Hemorrhage (SAH) 2=Intraparenchymal Hemorrhage (IPH) 3=Other Hemorrhage 4=Brain Infarction 5=Other Stroke Type 6=Unknown Stroke Type strktt Time to stroke or last follow-up tia Transient Ischemic Attack (TIA) 0=No, 1=Yes tiatype TIA type tiatt Time to TIA or last follow-up dth Death 0=No, 1=Yes dthtype Death type 1=Atherosclerotic coronary heart disease 2=Stroke 3=Atherosclerotic disease other than coronary disease, stroke 4=Other cardiovascular disease, not defined above 5=Non-cardiovascular disease 6=Death type unknown- no death certificate 9=Non-cardiovascular disease (Ineligible for Review) dthtext Death Type Text dthtt Time to all-cause death or last follow-up chdh Coronary Heart Disease (CHD), Hard 0=No, 1=Yes chdhtt Time to Hard CHD or last follow-up (days) chda Coronary Heart Disease (CHD), All 0=No, 1=Yes chdatt Time to All CHD or last follow-up (days) cvdh Cardiovascular Disease (CVD), Hard 0=No, 1=Yes cvdhtt Time to Hard CVD or last follow-up (days) cvda Cardiovascular Disease (CVD), All 0=No, 1=Yes cvdatt Time to All CVD or last follow-up (days) revc Coronary Revascularization 0=No, 1=Yes revctt Time to Coronary Revascularization or last follow-up

Page 2 of 13 Summary of MESA Endpoint Methods

For more information on the criteria used, please see Section 4 (“Criteria for Events”) in the MESA Events Manual of Operation, which is available on this web site at http://www.mesa-nhlbi.org/Mesa- Internal/manuals.asp

For this dataset we followed the cohort for incident cardiovascular events from baseline until the participant‟s Follow-Up 6 telephone interview. The average participant surveillance time is 4.6 years. At intervals of 9-12 months, a telephone interviewer contacted each participant to inquire about all interim hospital admissions, cardiovascular outpatient diagnoses and procedures, and deaths. In addition, MESA occasionally identified additional medical encounters through cohort clinic visits, participant call- ins, medical record abstractions or obituaries. In order to verify self-reported diagnoses, we requested copies of all death certificates and medical records for all hospitalizations and selected outpatient cardiovascular diagnoses and procedures. We also obtained next of kin interviews for out of hospital cardiovascular deaths. We were successful in getting hospital records on an estimated 98% of hospitalized cardiovascular events and some information on 96% of outpatient diagnostic encounters.

Trained personnel abstracted any hospital records suggesting possible cardiovascular events. They recorded symptoms, history and biomarkers; scanned ECGs, echocardiograms, catheterization reports, outpatient records, and other relevant diagnostic and procedure reports; and transmitted these to the coordinating center. The coordinating center collated the abstracted or original endpoint records and sent them to two paired physicians for independent endpoint classification and assignment of incidence dates. Cardiologists or cardiovascular physician epidemiologists reviewed non-neurovascular endpoints; neurologists reviewed all neurovascular endpoints. If the reviewing pair disagreed on the classification, they adjudicated differences. If disagreements persisted, the full review committee made the final classification.

Possible nonfatal endpoints in MESA include CHF, angina, myocardial infarction, resuscitated cardiac arrest, peripheral arterial disease, stroke, and TIA. Fatal cardiovascular endpoint categories generally include fatal CHD, fatal stroke, and other fatal CVD (there are a few subcategories under this). All deaths were identified. Cause of death was assigned for potential CVD deaths through committee review. For other deaths, the underlying cause was obtained through state or city vital statistics departments (or occasionally NDI).

MYOCARDIAL INFARCTION. Reviewers classified MI as definite, probable, or absent, based primarily on combinations of symptoms, ECG, and cardiac biomarker levels. In most cases, definite or probable MI required either abnormal cardiac biomarkers (2 times upper limits of normal) regardless of pain or ECG findings; evolving Q waves regardless of pain or biomarker findings; or a combination of chest pain, and ST-T evolution or new LBBB, and biomarker levels 1-2 times upper limits of normal.

RESUSCITATED CARDIAC ARREST. Reviewers classified resuscitated cardiac arrest when a patient successfully recovered from a full cardiac arrest through cardiopulmonary resuscitation (including cardioversion).

ANGINA was classified, except in the setting of MI, as definite, probable, or absent. Definite or probable angina required symptoms of typical chest pain or atypical symptoms, as asymptomatic coronary artery disease is not a MESA endpoint. Probable angina required, in addition to symptoms, a physician diagnosis of angina and medical treatment for it. Definite angina required one or more additional criteria, including CABG surgery or other revascularization procedure; 70% or greater obstruction on coronary angiography; or evidence of ischemia by stress tests or by resting ECG. We considered coronary revascularization or a physician diagnosis of angina or CHD, in the absence of symptoms, to not be angina.

Page 3 of 13 FATAL CHD was classified as definite, possible, or absent. Definite fatal CHD required a documented MI within the previous 28 days, chest pain within the 72 hours before death, or a history of CHD, and required the absence of a known non-atherosclerotic or non-cardiac cause of death. If the definite fatal CHD criteria were not met, possible fatal CHD could be assigned with an underlying cause of death consistent with fatal CHD and required the absence of a known non-atherosclerotic or non-cardiac cause of death.

CHF. Reviewers classified CHF as definite, probable, or absent. Definite or probable CHF required heart failure symptoms, such as shortness of breath or edema, as asymptomatic disease is not a MESA endpoint. In addition to symptoms, probable CHF required CHF diagnosed by a physician and patient receiving medical treatment for CHF. Definite CHF required one or more other criteria, such as pulmonary edema/congestion by chest X-ray; dilated ventricle or poor LV function by echocardiocardiography or ventriculography; or evidence of left ventricular diastolic dysfunction. We considered participants not meeting any criteria, including just a physician diagnosis of CHF without any other evidence, as having no CHF.

PERIPHERAL ARTERIAL DISEASE was classified as definite, probable and absent and included symptomatic disease such as lower extremity claudication, atherosclerosis of the lower extremity, arterial embolism and/or thrombosis of the lower extremity, and abdominal aortic aneurysm. Probable PAD required only a documented physician diagnosis of a PAD condition with symptoms. Definite PAD required one or more other criteria, such as ultrasound evidence of obstruction; an exercise test positive for claudication; revascularization for PAD; amputation for ischemia; ankle-arm ratio <=0.8; imaging of an aortic aneurysm; or a vascular procedure for abdominal aortic aneurysm.

STROKE was classified as present or absent and consisted of rapid onset of a documented focal neurologic deficit lasting 24 hours or until death, or if < 24 hours, there was a clinically relevant lesion on brain imaging. Patients with focal neurologic deficits secondary to brain trauma, tumor, infection, or other non-vascular cause were excluded. Strokes were subclassified on the basis of neuroimaging or other tests into subarachnoid hemorrhage, intraparenchymal hemorrhage, other hemorrhage, brain infarction, or other stroke. Infarcts were also subtyped.

TIA (present/absent) consisted of one or more documented episodes of focal neurologic deficit lasting 30 seconds to 24 hours, and without brain imaging suggesting stroke.

Page 4 of 13 Event Ascertainment Period Event and follow-up time inclusion is based upon the participant‟s completion of the Follow-Up 6 telephone interview. If the participant did not complete Follow-Up 6, a „projected‟ Follow-Up 6 date is used. This calculated date is determined by the adding the average number of days from enrollment to the Follow-Up 6 telephone interview for completed reviews to the enrollment date for those with no completed Follow-Up 6. This criterion was selected to ensure that events ascertainment is completed on the MESA cohort for the time period being reported while maximizing the amount of data which can be released. While it is possible for some events which occurred prior to the participant‟s Follow-Up 6 interview to be identified in the future, the number of such events is expected to be very low and should not have a meaningful effect on results. Nevertheless, latently discovered events will be added to subsequent datasets when they are discovered (future datasets are planned to be cumulative and will include previously released event data).

Deaths A minor exception to the ascertainment period noted above exists for participant deaths. If the participant death date is prior to their projected Follow-Up 6 date, the time to death value equals the time in days from Exam 1 visit until death, even if the General Health Form was collected later (via proxy). Rationale for these criteria was to ensure that death events would be included along with all related events.

Missing Follow-up Time (in days) from Exam 1 until the Follow-up 6 call is calculated for each participant in the cohort (total follow-up time). If no follow-up was completed for an individual participant, then the follow-up time is set to zero. Participants who are lost-to-follow-up are then effectively censored when their status was last known. Participants who miss a follow-up call but who subsequently complete a follow-up call are also appropriately included.

Page 5 of 13 Event Type Variables labeled as indicating an event type contain an indication of the certainty of the reviewers. To be classified as an event, the reviewers must have indicated that the event was either definite or probable.

Time to (First) Event Separate time to (first) event or last follow-up variables are calculated for each type of event. Participants who do not have a particular event type have their total follow-up time recorded as the time to event value. Participants for which one or more instances of an event are recorded have the time from Exam 1 until the first instance of an event (either probable or definite) recorded as the time to event value.

Pre-Baseline Exclusions Only incident event data are provided in MESA events datasets. Therefore, participants were not recruited if they had the following medical diagnosis or procedures:  Physician-diagnosed heart attack  Physician-diagnosed angina  Physician-diagnosed stroke or TIA  Physician-diagnosed heart failure  Physician-diagnosed resuscitated cardiac arrest  Having undergone procedures related to cardiovascular disease (CABG, angioplasty, valve replacement, pacemaker or defibrillator implantation, or any surgery on the heart or arteries).

While MESA participants were intended to be free of baseline cardiovascular disease, surveillance has identified events that occurred prior to baseline. Participants with a pre-baseline exclusionary diagnosis and/or procedures will have all of their events excluded from event datasets and will have all event indicator variables and time to event variables set to missing.

Page 6 of 13 Event Data Set Inclusion/Exclusion Summary

The Follow-up bounding the end of the data set window. For a data set covering Baseline to Follow-up 6, the Cut- Cut-off Follow-up off Follow-up is Follow-up 6.

Last Completed F/U A participant's last actually completed F/U (General Health Form) equal or prior to the Cut-off F/U.

For participants who did not complete the Cut-off Follow-up, the Projected F/U date is the estimated date of their Projected F/U date Cut-off F/U. The Project F/U date is obtained by adding (a) the average time from baseline to the Cut-off F/U for all completed Cut-off F/Us to (b) the baseline visit date of the participant missing a completed Cut-off F/U.

Any confirmed endpoint or death with event date prior to the Cut-off F/U. Unconfirmed participant reports of Endpoints in Data Set endpoints are excluded, although such reports may censor an endpoint's exposure time in some situations (see below for details).

If event endpoint exists prior to Cut-off F/U, then exposure time for the endpoint is Baseline to Event date. Endpoint Exposure Time If no event endpoint exists prior to Cut-off F/U, then exposure time for the endpoint is Baseline to Last completed F/U. See below for details on exposure time censored by unconfirmed participant reports.

If participant never completed any F/U, then exposure time is set to "missing" rather than 0

In the instance of an unconfirmed participant report of an endpoint or major CVD procedure, exposure time for that endpoint/procedure is from baseline to the unconfirmed event date (given no other confirmed occurrence of the Exposure time censored by endpoint/procedure and given the unconfirmed event preceded the last completed F/U). An unconfirmed unconfirmed participant participant report could be either an event pending records collection or an event for which MESA has determined reports that records/confirmation cannot be obtained (e.g., participant/proxy is no longer locatable or fails to authorized records collection).

If death precedes the Cut-off F/U: Baseline to death date

If death follows the Cut-off F/U: Baseline to Cut-off F/U Mortality Exposure Time If morbid event, exam, or other living indication follows last completed F/U: Baseline to indication of living if

indication is prior to Cut-off F/U, or Baseline to Cut-off F/U if indication is after Cut-off F/U.

Page 7 of 13 Examples of Participant Events (fictitious) for Data Set covering Baseline to F/U6

A

Baseline CHF Completed MI Completed Stroke Completed 1/1/2001 F/U5 F/U6 F/U7 12/31/2007

B

Baseline CHF Completed MI discovered upon Projected F/U6 CVD Death 1/1/2001 F/U5 death investigation (actual missing) 12/31/2007

C

Baseline CHF Unconfirmed participant PVD Completed Unconfirmed participant Projected F/U6 1/1/2001 report of Angina F/U5 report of TIA (actual missing) 12/31/2007

Data Set for F/U 1-6 Participant A Participant B Participant C Cut-off Follow-up F/U6 (completed) F/U6 (projected date) F/U6 (projected date) (end of data set window) Last Completed F/U F/U6 F/U5 F/U5 CHF Indicator 1 1 1 CHF: Exposure Time Baseline to CHF event date Baseline to CHF event date Baseline to CHF event date MI Indicator 1 1 0 MI: Exposure Time Baseline to MI Event date Baseline to MI Event date Baseline to Last Completed F/U (F/U5) Stroke Indicator 0 0 0 Stroke: Exposure Time Baseline to Completed F/U6 Baseline to Last Completed F/U (F/U5) Baseline to Last Completed F/U (F/U5) TIA Indicator 0 0 0 TIA: Exposure Time Baseline to Completed F/U6 Baseline to Last Completed F/U (F/U5) Baseline to Last Completed F/U (F/U5) PVD Indicator 0 0 1 PVD: Exposure Time Baseline to F/U6 Baseline to Last Completed F/U (F/U5) Baseline to PVD event date Angina Indicator 0 0 0 Baseline to event date of unconfirmed Angina: Exposure Time Baseline to Completed F/U6 Baseline to Last Completed F/U (F/U5) participant report of Angina CVD Death Indicator 0 0 0 Mortallity Indicator 0 0 0 Baseline to Projected F/U6 Mortality: Exposure Time Baseline to Completed F/U6 Baseline to Last Completed F/U (F/U5) (per knowledge of later death)

Page 8 of 13

Summary: Participants with Endpoints from Completed Reviews

(Average of 4.6 years of surveillance)

Multiple instances of the same endpoint occurring in the same participant are counted only once in the table below. “Definite” and “probable” classifications are combined for each endpoint. The rate of endpoint events is per 10,000 person-years.

Resusc. Death: Death: Cardiac Coro. Death: Death: Other Other Death: Death: Site Name MI Arrest Angina CHF PVD Revasc. Stroke TIA CHD Stroke Athero CVD Non-CVD Unknown Ppts 25 6 36 28 5 47 19 8 8 2 0 1 4 0 3: Wake Forest Rate 49.182 11.709 71.470 55.147 9.778 93.473 37.220 15.649 15.217 3.804 0.000 1.902 7.608 0.000 Ppts 13 2 33 20 6 26 10 3 3 1 1 2 4 0 4: Columbia Rate 26.306 4.024 67.390 40.563 12.091 52.789 20.193 6.043 5.881 1.960 1.960 3.921 7.841 0.000 Ppts 13 3 25 16 9 29 17 5 6 2 0 1 5 0 5: Johns Hopkins Rate 26.632 6.119 51.589 32.839 18.432 59.865 34.930 10.246 11.991 3.997 0.000 1.998 9.992 0.000 Ppts 20 0 22 19 12 32 17 8 3 2 0 2 3 1 6: Minnesota Rate 41.757 0.000 46.057 39.616 25.021 67.048 35.462 16.640 6.135 4.090 0.000 4.090 6.135 2.045 Ppts 16 1 23 17 7 31 10 0 1 0 0 0 2 0 7: Northwestern Rate 29.757 1.846 43.000 31.627 12.970 58.161 18.531 0.000 1.828 0.000 0.000 0.000 3.655 0.000 Ppts 19 1 29 14 7 24 18 4 4 3 0 3 7 0 8: UCLA Rate 31.285 1.637 48.024 23.030 11.479 39.632 29.661 6.565 6.469 4.852 0.000 4.852 11.321 0.000 Ppts 106 13 168 114 46 189 91 28 25 10 1 9 25 1 Total Rate 34.033 4.147 54.291 36.620 14.720 61.054 29.183 8.952 7.835 3.134 0.313 2.821 7.835 0.313

Page 9 of 13 Summary: Participants with CHD & CVD Combination Endpoints

(Average of 4.6 years of surveillance)

“Definite” and “probable” classifications are combined for each endpoint. The rate of combination endpoint events is per 10,000 person-years.

CHD Hard CHD All CVD Hard CVD All Site Name Ppts Rate Ppts Rate Ppts Rate Ppts Rate 3: Wake Forest 34 66.9 57 113.5 52 102.8 76 152.1

4: Columbia 18 36.4 33 67.2 27 54.9 45 92.0

5: Johns Hopkins 19 38.9 35 72.3 35 72.2 52 108.2

6: Minnesota 22 45.9 37 77.7 39 82.0 55 116.4

7: Northwestern 17 31.6 32 60.0 26 48.6 40 75.4

8: UCLA 22 36.2 38 63.1 37 61.3 56 93.5

Total 132 42.4 232 75.1 216 69.7 324 105.5

The definitions for combination endpoints are included with the posted dataset. All of the components will also be there so that people can create whatever definition they want. The following definitions for combination endpoints have been approved by the MESA Steering Committee:

Combination Criteria (any of the following) MI Hard CHD Resuscitated Cardiac Arrest CHD Death MI Resuscitated Cardiac Arrest All CHD Definite Angina Probable Angina (if followed by Revascularization) CHD Death MI Resuscitated Cardiac Arrest Hard CVD Stroke (not TIA) CHD Death Stroke Death MI Resuscitated Cardiac Arrest Definite Angina Probable Angina (if followed by Revascularization) All CVD Stroke Stroke Death CHD Death Other Atherosclerotic Death Other CVD Death

Page 10 of 13

Summary: Participants with Endpoints from Completed Reviews by Cohort

(Average of 4.6 years of surveillance)

“Definite” and “probable” classifications are combined for each endpoint.

Cohort Endpoint MESA MRI MESA 1000 Candidate Gene (n=6809) (n=5004) (n=999) (n=2847) MI 106 69 19 47 Angina 168 119 18 65 CHF 114 76 17 49 PVD 46 31 8 24 Resuscitated Cardiac Arrest 13 7 2 5 PTCA 131 92 17 51 CABG 69 45 8 24 Other Revascularization 31 23 5 16 Stroke 91 58 9 31 TIA 28 16 2 9 CHD 25 18 6 13 Stroke 10 5 0 3 Other Athero 1 0 0 0 Death Other CVD 9 6 1 5 Non-CVD 25 17 2 8 Unknown 1 1 0 0 Non-Cardiovascular (Ineligible) 154 107 27 82 Hard CHD 132 86 23 60 All CHD 232 161 32 97 Composite Hard CVD 216 137 31 88 Endpoints All CVD 324 218 41 129 Any Revascularization 189 131 23 69

Page 11 of 13

Exposure time censored by unconfirmed participant reports

In the instance of an unconfirmed participant report of an endpoint or major CVD procedure, exposure time for that endpoint/procedure is from baseline to the unconfirmed event date (given no other confirmed occurrence of the endpoint/procedure and given the unconfirmed event preceded the last completed F/U). An unconfirmed participant report could be either an event pending records collection or an event for which MESA has determined that records/confirmation cannot be obtained (e.g., participant/proxy is no longer locatable or fails to authorized records collection).

# of participants with unconfirmed participant-reported events for which exposure time was censored Type of unconfirmed participant report reports pending reports for which records records cannot Total collection be obtained

Angina 2 3 5 CHF 2 2 4 MI 1 4 5 PVD 1 8 9 Stroke 4 2 6 TIA 3 9 12 CABG 1 1 2 PTCA 1 2 3 Death (unknown cause) 9 0 9

Revasc. 2 3 5 CHD-All 2 7 9 Composite CHD-Hard Endpoints 1 4 5 CVD-All 5 11 16 CVD-Hard 4 8 12

Some participants with more than one unconfirmed participant report may have more than one report of the same type. For these participants, the endpoint exposure time is censored at the date of the earliest event.

Numbers can be summed across by type but not down by participant or report, since a single participant or report can involve more than one type.

In addition to the reports identified above, there are also seven unconfirmed reports for which the type of morbid event is unknown. For these reports, no endpoint exposure time is censored.

Page 12 of 13 Event Forms of Interest

Follow-Up General Health Forms

Follow-Up 1 : http://www.mesa-nhlbi.org/mesa/PublicDocs/020101- 021231/MESAEventsForms/f1_general_health.pdf

Follow-Up 2 : http://www.mesa-nhlbi.org/PublicDocs/020101- 021231/MESAExam2Forms/general_health.pdf

Follow-Up 3 : http://www.mesa-nhlbi.org/PublicDocs/2004/FollowUp3/Follow- up%203%20General%20Health%20(English%2003-06-2004).pdf

Follow-Up 4 : http://www.mesa-nhlbi.org/PublicDocs/2004/FollowUp4/Follow- up%204%20General%20Health%20(English%2004-02-2004).pdf

Follow-Up 5 : http://www.mesa-nhlbi.org/PublicDocs/2004/FollowUp5/F5- General%20Health%20(English%208-31-2004).pdf

Follow-Up 6 : http://www.mesa-nhlbi.org/PublicDocs/FollowUp6/F6-General_Health.pdf

Events Forms

Cardiac-PVD Hospital http://www.mesa-nhlbi.org/PublicDocs/2004/Events/Cardiac- Abstraction : PVD%20Hospital%20Abstraction%20(English%2003-05-04).pdf

Eligibility : http://www.mesa-nhlbi.org/PublicDocs/2005/Events/Eligibility_(English_9-06- 2005).pdf

Final Notification : http://www.mesa- nhlbi.org/PublicDocs/2004/Events/Final_Notification_(English_03-04-2005).pdf

Initial Notification : http://www.mesa- nhlbi.org/PublicDocs/2004/Events/Initial%20Notification%20(English%203-20- 04).pdf

Stroke-TIA http://www.mesa-nhlbi.org/PublicDocs/2004/Events/Stroke- Hospitalization TIA_Hospital_Abstraction_(English_8-5-2004).pdf Abstraction :

Adjudication Forms

Cardiac Review : http://www.mesa- nhlbi.org/PublicDocs/2006/MESA_Cardiac_Review.pdf

Cerebrovascular Review : http://www.mesa- nhlbi.org/PublicDocs/2006/MESA_Stroke_Review.pdf

Mortality Review : http://www.mesa- nhlbi.org/PublicDocs/2006/MESA_Mortality_Review.pdf

Page 13 of 13