Supplementary Online Content

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1 Supplementary Online Content Schnabel RB, Aspelund T, Li G, et al. Validation of an atrial fibrillation risk algorithm in whites and African Americans. Arch Intern Med. 2010;170(21): eappendix. Methods etable 1. Supplementary Table 1: Cox proportional hazards regression coefficients for 5- year incidence of atrial fibrillation in AGES, CHS (whites and AA), and FHS etable 2. Supplementary Table 2: Cox proportional hazards regression coefficients for 10- year incidence of atrial fibrillation in CHS whites and FHS etable 3. Supplementary Table 3: Discrimination and calibration for the atrial fibrillation risk model for 10-year incidence of atrial fibrillation in CHS whites and FHS efigure 1. Supplementary Figure 1: Reasons for exclusions based on person-intervals for the 5-year analysis. efigure 2. Supplementary Figure 2: Spline plots for a) 5-year and b) 10-year incidence of atrial fibrillations by age in the Framingham Heart Study This supplementary material has been provided by the authors to give readers additional information about their work American Medical Association. All rights reserved.

2 Methods Atrial fibrillation (AF) Ascertainment Age, Gene/Environment Susceptibility Reykjavik Study (AGES): The Reykjavik Study comprised a random sample of 30,795 men and women born between 1907 and 1935 who were living in Reykjavik in For current analyses a random sample of the original cohort who were still alive in 2002 was chosen. The clinic visit includes a blood draw, blood pressure measurement, electrocardiography, anthropometry, and measures of different domains of physical and cognitive function. AF or atrial flutter was diagnosed from AGES examination Minnesota coded electrocardiograms, and International Classification of Disease (ICD) and (ICD)-10 I48 codes identified from hospital admission diagnosis from the National Hospital of Iceland database from 1983 through December Baseline 12-lead ECG and ICD codes were used to define prevalent AF. Cardiovascular Health Study (CHS): At the baseline clinic visit, CHS participants had a resting 12-lead electrocardiogram. Participants were contacted on a regular basis every 6 months, with clinic visits alternating with telephone contacts, during up to 15 years follow-up. A resting 12-lead electrocardiogram was available from each annual clinic visit through At each follow-up contact, participants were asked about all hospitalizations since the last contact, and hospital discharge summaries and ICD-9 codes were obtained. In addition, hospital discharge ICD-9 codes for all participants were obtained from the Centers for Medicare and Medicaid Services. The diagnosis of AF was made if atrial fibrillation or flutter was present on a CHS clinic visit electrocardiogram between 1989 and 1999, or when a hospital discharge ICD-9 code for atrial fibrillation or flutter was registered. Prevalent AF was defined as AF on the electrocardiogram during the baseline visit. The date of incident AF was the date of the clinic visit for AF identified on clinic electrocardiogram, or the date of hospital admission for AF identified from hospital discharge diagnosis, whichever date was earlier. Framingham Heart Study (FHS): AF is diagnosed if atrial fibrillation or flutter is present on an electrocardiogram derived from a Framingham Study clinic tracing or hospital or

3 30 outpatient records. 3 Biennial health history update calls collect information on whether the participant had experienced interim rhythm abnormalities or AF. If self-reported AF is present at the main examination or on health history updates, outside records are routinely sought. All incident AF cases undergo a review by Framingham cardiologists. If AF is recorded by history only, agreement between two investigators that the evidence for the presence of AF is compelling is necessary. The categorization of incident vs. prevalent AF is based on the time to event from the baseline examination used for the current analyses. The presence of AF on the day of the baseline examination or earlier leads to the categorization into prevalent AF

4 Results Supplementary Table 1. Cox proportional hazards regression coefficients for 5-year incidence of atrial fibrillation in AGES, CHS (whites and AA), and FHS AGES CHS Whites CHS AA Variable SE P SE P SE P Age, yrs Age Male sex Body mass index, kg/m² Systolic blood pressure, mm Hg Hypertension treatment PR interval, ms < Prevalent heart failure Male sex*age Age*prevalent heart failure FHS SE P Age, yrs Age Male sex Body mass index, kg/m² Systolic blood pressure, mm Hg Hypertension treatment PR interval, ms Prevalent heart failure Male sex*age Age*prevalent heart failure AGES S 0 (5)= (5-year baseline survival), CHS whites S 0 (5)=0.9053, CHS AA S 0 (5)=0.9220, FHS S 0 (5)= Betas and standard errors of the betas are given for one unit increase for continuous variables and for the condition present in dichotomous variables.

5 Supplementary Table 2. Cox proportional hazards regression coefficients for 10-year incidence of atrial fibrillation in CHS whites and FHS CHS FHS Variable SE P SE P Age, yrs Age Male sex Body mass index, kgm² Systolic blood pressure, mm Hg < Treatment for hypertension PR interval, ms Valvular heart disease Prevalent heart failure Male sex*age Age*valvular heart disease Age*prevalent heart failure CHS S 0 (10)=0.9634(10-year baseline survival), FHS S 0 (10)=0.9634, with S 0 (10) being the 10-year baseline survival. Betas are given for one unit increase for continuous variables and for the condition present in dichotomous variables.

6 Supplementary Table 3. Discrimination and calibration for the atrial fibrillation risk model for 10-year incidence of atrial fibrillation in CHS whites and FHS 10-Year Incidence Discrimination Calibration C Confidence interval P FHS 0.78 ( ) CHS whites Best Cox 0.68 ( ) Unadjusted 0.66 ( ) < Adjusted 0.66 ( ) The best Cox model (discrimination and calibration) are the results developed from CHS data involving the risk factors established in the Framingham Study. Unadjusted results are derived from the CHS data using the Framingham risk function without modifications. Adjusted indicates that the Framingham risk model was applied for the Cox models and performed.

7 Supplementary Figure 1. Reasons for exclusion based on person-intervals for the 5-year analysis. Exclusions by Cohort Person intervals before exclusions AGES CHS whites CHS AA FHS N=5,093 N=8,488 N=1,596 N=13,929 Age >95 or age <45 years ,344 Missing covariates Person intervals for analysis N=4,238 N=8,254 N=1,552 N=8,044

8 Supplementary Figure 2. Spline plots for a) 5-year and b) 10-year incidence of atrial fibrillation by age in the Framingham Heart Study a) b)