HHS Public Access Author manuscript Author Manuscript
Circ Cardiovasc Imaging. Author manuscript; available in PMC 2016 December 01. Published in final edited form as: Circ Cardiovasc Imaging. 2015 December ; 8(12): . doi:10.1161/CIRCIMAGING.115.003786.
Coronary Artery Calcium Progression and Atrial Fibrillation: The Multi-Ethnic Study of Atherosclerosis (MESA) Wesley T. O’Neal, MD, MPH1, Jimmy T. Efird, PhD, MSc2, Waqas T. Qureshi, MD3, Joseph Yeboah, MD3, Alvaro Alonso, MD, PhD4, Susan R. Heckbert, MD, PhD5, Saman Nazarian, MD, PhD6, and Elsayed Z. Soliman, MD, MSc, MS3,7 1Department
of Internal Medicine, Wake Forest School of Medicine, Winston-Salem, NC
Author Manuscript
2Department
of Cardiovascular Sciences, East Carolina Heart Institute, Brody School of Medicine, East Carolina University, Greenville, NC
3Department
of Internal Medicine, Section on Cardiology, Wake Forest School of Medicine, Winston-Salem, NC
4Division
of Epidemiology and Community Health, School of Public Health, University of Minnesota, Minneapolis, MN
5Cardiovascular
Health Research Unit and Department of Epidemiology, University of Washington, Seattle, WA
6Departments
of Medicine and Cardiology, Johns Hopkins University School of Medicine,
Author Manuscript
Baltimore, MD 7Epidemiological
Cardiology Research Center (EPICARE), Department of Epidemiology and Prevention, Wake Forest School of Medicine, Winston-Salem, NC
Abstract Background—Coronary artery calcium (CAC) measured at a single time point has been associated with an increased risk for atrial fibrillation (AF). It is unknown whether CAC progression over time carries a similar risk.
Author Manuscript
Methods and Results—This analysis included 5,612 study participants (mean age: 62 ± 10; 52% women; 39% whites; 27% blacks; 20% Hispanics; 12% Chinese-Americans) from the MultiEthnic Study of Atherosclerosis. Phantom-adjusted Agatston scores for baseline and follow-up measurements were used to compute change in CAC per year (≤0, 1 to 100, 101 to 300, and >300 units/year). AF was ascertained by review of hospital discharge records and from Medicare claims data through December 31, 2010. Cox regression was used to compute hazard ratios (HR) and 95% confidence intervals (CI) for the association between CAC progression and AF. Over a median follow-up of 5.6 years (25th, 75th percentiles=5.1, 6.8), a total of 203 (3.6%) incident AF cases were detected. Any CAC progression (>0/year) was associated with an increased risk for AF Correspondence to: Wesley T. O’Neal, MD, Department of Internal Medicine, Wake Forest School of Medicine, Medical Center Boulevard, Winston Salem, NC 27157, Phone: +1.336.716.2715, Fax: +1.336.716.2273, [email protected]. Disclosures Dr. Nazarian is a consultant and principal investigator for research funding awarded to Johns Hopkins University from Biosence Webster Inc.
O’Neal et al.
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Author Manuscript
(HR=1.55, 95%CI=1.10, 2.19) and the risk increased with higher levels of CAC progression (≤0/ year: HR=1.0 [reference]; 1 to 100/year: HR=1.47, 95%CI=1.03, 2.09; 101 to 300/year: HR=1.92, 95%CI=1.15, 3.20; >300/year: HR=3.23, 95%CI=1.48, 7.05). An interaction was observed by age with the association of CAC progression with AF being stronger for younger (0 units of change per year, intervals (e.g., 1 to 100, 101 to 300, and >300 units/year) that have been described previously from MESA were used to compare with participants who had ≤ 0/year change (e.g., no change or reduction in CAC score).9 Participants with any progression (>0/year change) also were compared with those without progression (≤0/year change).
Author Manuscript
Atrial Fibrillation Follow-up phone calls to study participants every 9–12 months were used to identify AF events. Medical records, including discharge diagnoses, were obtained for each hospitalization. Additionally, for participants 65 years or older enrolled in fee-for-service Medicare, Medicare claims data were used to identify AF diagnoses in the inpatient setting. Incident AF was defined by International Classification of Disease Ninth Revision codes 427.31 or 427.32.
Circ Cardiovasc Imaging. Author manuscript; available in PMC 2016 December 01.
O’Neal et al.
Page 4
Statistical analysis
Author Manuscript Author Manuscript
Baseline characteristics were compared by the presence of baseline CAC. Categorical variables were reported as frequency and percentage while continuous variables were recorded as mean ± standard deviation. Statistical significance for categorical variables was tested using the chi-square method and for continuous variables using the student’s t-test procedure. Kaplan-Meier estimates were used to compute cumulative incidence of AF by CAC progression and the differences in estimates were compared using the log-rank procedure.10 Follow-up time was defined as the time between the follow-up CT scan until a diagnosis of AF, death, loss to follow-up, or end of follow-up (December 31, 2010). Cox regression was used to compute hazard ratios (HR) and 95% confidence intervals (CI) for the association between CAC progression and AF. Multivariable models were constructed with incremental adjustment as follows: Model 1 adjusted for age, sex, race/ethnicity, education, income, and baseline CAC; Model 2 adjusted for Model 1 covariates plus systolic blood pressure, body mass index, diabetes, smoking, total cholesterol, HDL cholesterol, antihypertensive medications, lipid-lowering therapies, aspirin, and left ventricular hypertrophy. The proportional-hazards assumption was not violated in our analysis. Additionally, we tested for interactions by age (dichotomized at median age), sex, race/ ethnicity (white vs. non-white), and the presence of baseline CAC (CAC=0 vs. CAC >0). We examined the graphical dose-response relationship between CAC progression and the multivariable HR for AF using a restricted cubic spline model with incorporated knots at the 5th, 50th, and 95th percentiles.11 Sensitivity analyses were conducted with adjustment for study visit 3 covariates, incident coronary heart disease, and incident heart failure. We also performed a secondary analysis to determine if those with reductions in CAC score (
Circ Cardiovasc Imaging. Author manuscript; available in PMC 2016 December 01. Published in final edited form as: Circ Cardiovasc Imaging. 2015 December ; 8(12): . doi:10.1161/CIRCIMAGING.115.003786.
Coronary Artery Calcium Progression and Atrial Fibrillation: The Multi-Ethnic Study of Atherosclerosis (MESA) Wesley T. O’Neal, MD, MPH1, Jimmy T. Efird, PhD, MSc2, Waqas T. Qureshi, MD3, Joseph Yeboah, MD3, Alvaro Alonso, MD, PhD4, Susan R. Heckbert, MD, PhD5, Saman Nazarian, MD, PhD6, and Elsayed Z. Soliman, MD, MSc, MS3,7 1Department
of Internal Medicine, Wake Forest School of Medicine, Winston-Salem, NC
Author Manuscript
2Department
of Cardiovascular Sciences, East Carolina Heart Institute, Brody School of Medicine, East Carolina University, Greenville, NC
3Department
of Internal Medicine, Section on Cardiology, Wake Forest School of Medicine, Winston-Salem, NC
4Division
of Epidemiology and Community Health, School of Public Health, University of Minnesota, Minneapolis, MN
5Cardiovascular
Health Research Unit and Department of Epidemiology, University of Washington, Seattle, WA
6Departments
of Medicine and Cardiology, Johns Hopkins University School of Medicine,
Author Manuscript
Baltimore, MD 7Epidemiological
Cardiology Research Center (EPICARE), Department of Epidemiology and Prevention, Wake Forest School of Medicine, Winston-Salem, NC
Abstract Background—Coronary artery calcium (CAC) measured at a single time point has been associated with an increased risk for atrial fibrillation (AF). It is unknown whether CAC progression over time carries a similar risk.
Author Manuscript
Methods and Results—This analysis included 5,612 study participants (mean age: 62 ± 10; 52% women; 39% whites; 27% blacks; 20% Hispanics; 12% Chinese-Americans) from the MultiEthnic Study of Atherosclerosis. Phantom-adjusted Agatston scores for baseline and follow-up measurements were used to compute change in CAC per year (≤0, 1 to 100, 101 to 300, and >300 units/year). AF was ascertained by review of hospital discharge records and from Medicare claims data through December 31, 2010. Cox regression was used to compute hazard ratios (HR) and 95% confidence intervals (CI) for the association between CAC progression and AF. Over a median follow-up of 5.6 years (25th, 75th percentiles=5.1, 6.8), a total of 203 (3.6%) incident AF cases were detected. Any CAC progression (>0/year) was associated with an increased risk for AF Correspondence to: Wesley T. O’Neal, MD, Department of Internal Medicine, Wake Forest School of Medicine, Medical Center Boulevard, Winston Salem, NC 27157, Phone: +1.336.716.2715, Fax: +1.336.716.2273, [email protected]. Disclosures Dr. Nazarian is a consultant and principal investigator for research funding awarded to Johns Hopkins University from Biosence Webster Inc.
O’Neal et al.
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Author Manuscript
(HR=1.55, 95%CI=1.10, 2.19) and the risk increased with higher levels of CAC progression (≤0/ year: HR=1.0 [reference]; 1 to 100/year: HR=1.47, 95%CI=1.03, 2.09; 101 to 300/year: HR=1.92, 95%CI=1.15, 3.20; >300/year: HR=3.23, 95%CI=1.48, 7.05). An interaction was observed by age with the association of CAC progression with AF being stronger for younger (0 units of change per year, intervals (e.g., 1 to 100, 101 to 300, and >300 units/year) that have been described previously from MESA were used to compare with participants who had ≤ 0/year change (e.g., no change or reduction in CAC score).9 Participants with any progression (>0/year change) also were compared with those without progression (≤0/year change).
Author Manuscript
Atrial Fibrillation Follow-up phone calls to study participants every 9–12 months were used to identify AF events. Medical records, including discharge diagnoses, were obtained for each hospitalization. Additionally, for participants 65 years or older enrolled in fee-for-service Medicare, Medicare claims data were used to identify AF diagnoses in the inpatient setting. Incident AF was defined by International Classification of Disease Ninth Revision codes 427.31 or 427.32.
Circ Cardiovasc Imaging. Author manuscript; available in PMC 2016 December 01.
O’Neal et al.
Page 4
Statistical analysis
Author Manuscript Author Manuscript
Baseline characteristics were compared by the presence of baseline CAC. Categorical variables were reported as frequency and percentage while continuous variables were recorded as mean ± standard deviation. Statistical significance for categorical variables was tested using the chi-square method and for continuous variables using the student’s t-test procedure. Kaplan-Meier estimates were used to compute cumulative incidence of AF by CAC progression and the differences in estimates were compared using the log-rank procedure.10 Follow-up time was defined as the time between the follow-up CT scan until a diagnosis of AF, death, loss to follow-up, or end of follow-up (December 31, 2010). Cox regression was used to compute hazard ratios (HR) and 95% confidence intervals (CI) for the association between CAC progression and AF. Multivariable models were constructed with incremental adjustment as follows: Model 1 adjusted for age, sex, race/ethnicity, education, income, and baseline CAC; Model 2 adjusted for Model 1 covariates plus systolic blood pressure, body mass index, diabetes, smoking, total cholesterol, HDL cholesterol, antihypertensive medications, lipid-lowering therapies, aspirin, and left ventricular hypertrophy. The proportional-hazards assumption was not violated in our analysis. Additionally, we tested for interactions by age (dichotomized at median age), sex, race/ ethnicity (white vs. non-white), and the presence of baseline CAC (CAC=0 vs. CAC >0). We examined the graphical dose-response relationship between CAC progression and the multivariable HR for AF using a restricted cubic spline model with incorporated knots at the 5th, 50th, and 95th percentiles.11 Sensitivity analyses were conducted with adjustment for study visit 3 covariates, incident coronary heart disease, and incident heart failure. We also performed a secondary analysis to determine if those with reductions in CAC score (
