Agarwal, Sunil

Background: Multiple studies have shown that atrial fibrillation (AF), a common cardiac arrhythmia, is associated with increased mortality and higher incidence of stroke and heart failure. However, evidence for this association in African Americans is lacking. Methods: We studied 4,063 African Americans and 11,280 whites in the Atherosclerosis Risk in Communities (ARIC) Study, a US community-based cohort study, aged 45-64 (55% women) and free of AF at baseline in 1987-89. Three additional follow-up exams were conducted in 1990-92, 1993-95, and 1996-98. AF was ascertained during follow-up with study visit ECGs and hospital surveillance. Mortality and incidence of stroke and heart failure were ascertained according to study protocols. Using multivariable Cox proportional hazards models with time-dependent covariates, we calculated hazard ratios (HR) and 95% confidence intervals (CI) of mortality, stroke and heart failure in those with new-onset AF compared to those without AF by race. Results: During an average follow-up of 18 years, 332 AF cases were ascertained in African Americans and 1407 in whites. Overall, African Americans showed higher all-cause mortality and cardiovascular disease rates than whites ( Table ). AF was associated with increased mortality and risk of incident stroke and heart failure in whites and African Americans, even after adjustment for baseline and time-dependent potential confounders ( Table ). Associations of AF with all-cause mortality and stroke were of similar magnitude in both racial groups. However, the association between AF and heart failure was stronger in whites than in African Americans (HR 3.6, 95% CI 3.1-4.2 in whites, vs. HR 2.2, 95% CI 1.6-3.0 in African Americans). Conclusion: New-onset AF was associated with an increased risk of all-cause mortality, stroke, and heart failure in whites and African Americans independently of other cardiovascular risk factors. Table. Hazard ratios (95% confidence interval) of all-cause mortality, stroke, and heart failure in those with new-onset atrial fibrillation (AF) versus those without AF by race, ARIC, 1987-2008 Blacks Whites P for interaction No AF (n=3731) AF (n=332) No AF (n=9873) AF (n=1407) Mortality Deaths (n) 1144 188 2042 630 Person-years 69,483 1268 200,878 7493 Mortality rate 1 18.6 126.3 10.1 62.3 Model 1 1 (ref.) 5.80 (4.93-6.82) 1 (ref.) 4.58 (4.17-5.04) 0.27 Model 2 1 (ref.) 3.20 (2.71-3.76) 1 (ref.) 2.87 (2.61-3.17) 0.68 Stroke Events (n) 281 23 347 64 Person-years 51,082 867 147,608 5040 Incidence rate 1 6.0 25.0 2.4 11.5 Model 1 1 (ref.) 2.91 (1.81-4.68) 1 (ref.) 2.52 (1.86-3.43) 0.94 Model 2 1 (ref.) 1.83 (1.13-2.96) 1 (ref.) 1.91 (1.39-2.62) 0.82 Heart failure Events 613 71 992 364 Person-years 62,570 721 187,847 4578 Incidence rate 1 10.7 108.1 5.3 76.1 Model 1 1 (ref.) 3.35 (2.41-4.65) 1 (ref.) 4.75 (4.09-5.51) 0.02 Model 2 1 (ref.) 2.18 (1.56-3.04) 1 (ref.) 3.63 (3.12-4.21) 0.0006 1 Age- and sex-standardized, per 1000 person-years; Model 1 : Cox proportional hazards model adjusted for age, sex, and study center, with AF incidence as a time-dependent covariate; Model 2 : As model 1, but additionally adjusting for baseline education, and time-dependent body mass index, smoking, diabetes, hypertension, stroke, heart failure, and myocardial infarction Funding(This research has received full or partial funding support from the American Heart Association, National Center)

Objective: To investigate the association between low forced expiratory volume in 1 second (FEV 1 ) and incident atrial fibrillation (AF) in a population-based cohort. Background: Impaired FEV 1 , a complex measure indicating genetic, developmental, obstructive and restrictive airway disease, musculoskeletal function, and motivation, has been inconsistently associated with an increased risk of cardiovascular disease mortality. Also, extant reports do not provide separate estimates for African Americans, who surprisingly have lower AF incidence than Caucasians. Methods: We examined 15,282 middle-aged African Americans (26%) and Caucasians, men (45%) and women from four U.S. communities enrolled in the Atherosclerosis Risk in Communities (ARIC) cohort study. Lung volumes by standardized spirometry and information on covariates were collected on these participants at the baseline visit (1987-1989). Prevalent AF cases were excluded by 12-lead ECG at baseline. Incident AF was defined as the first event identified from the following: ICD codes for AF from hospital discharge records or death certificates, or ECGs performed during three triennial follow-up visits. Results: Over an average follow-up of 17.5 years, a total of 1,733 (11%) participants developed new-onset AF. The rate of incident AF increased monotonically and inversely by tertiles of FEV 1 in each of the 4 gender-race strata. The unadjusted average incidence rates of AF per 100 person years of follow up by tertiles of FEV 1 (from lowest to highest tertile) were 13.6, 8.3, and 5.7 for white men; 8.7, 4.5, and 3.4 for white women; 8.2, 5.5, and 3.8 for black men; 6.9, 4.1, and 2.4 for black women. After multivariable adjustment for traditional cardiovascular disease risk factors and height, hazard ratios (95% CI) of AF comparing the lowest with the highest tertile of FEV 1 were 1.44 (1.16,1.78) among white men, 1.45 (1.12, 1.87) among white women, 1.81 (1.09, 3.02) among black men, and 1.84(1.20, 2.82) among black women. The trend estimate for per 1 Standard-Deviation lower FEV 1 for the corresponding race and gender groups were 1.21 (1.12, 1.32), 1.38 (1.25, 1.54), 1.45 (1.18, 1.76), and 1.35 (1.12, 1.63), respectively. The above associations were observed across all smoking status categories (current, former, and never). The association between low lung function and incidence of AF was similarly unchanged after exclusion of participants with heart failure (n = 689) or CHD (n = 558) at baseline. The hazard of AF was about 50% higher among those with FEV1/FVC ratio below 0.7. Conclusions: In this large population-based cohort study with a long term follow-up, reduced FEV 1 is strongly associated with a higher AF risk, independent of race, gender, smoking, and several other CVD risk factors. These findings suggest the need for research on mechanisms underlying the observed association to seek broader opportunities for prevention of AF.

Background— Reduced low forced expiratory volume in 1 second (FEV 1 ) is reportedly associated with an increased risk of atrial fibrillation (AF). Extant reports do not provide separate estimates for never smokers or for blacks, who incongruously have lower AF incidence than whites. Methods and Results— We examined 15 004 middle-aged blacks and whites enrolled in the Atherosclerosis Risk in Communities (ARIC) cohort study. Standardized spirometry data were collected at the baseline examination. Incident AF was identified from the first among the following: International Classification of Diseases codes for AF on hospital discharge records or death certificates or 12-lead ECGs performed during 3 triennial follow-up visits. Over an average follow-up of 17.5 years, a total of 1691 participants (11%) developed new-onset AF. The rate of incident AF was inversely associated with FEV 1 in each of the 4 race and sex groups. After multivariable adjustment for traditional cardiovascular disease risk factors and height, hazard ratios of AF comparing the lowest with the highest quartile of FEV 1 were 1.37 (95% confidence interval, 1.02–1.83) for white women, 1.49 (95% confidence interval, 1.16–1.91) for white men, 1.63 (95% confidence interval, 1.00–2.66) for black women, and 2.36 (95% confidence interval, 1.30–4.29) for black men. The above associations were observed across all smoking status categories. Moderate/severe airflow obstruction (FEV 1 /forced vital capacity <0.70 and FEV 1 < 80% of predicted value) was also associated with higher AF incidence. Conclusions— In this large population-based study with a long-term follow-up, reduced FEV 1 and obstructive respiratory disease were associated with a higher AF incidence after adjustment for measured confounders.

Background Tools for the prediction of atrial fibrillation ( AF ) may identify high‐risk individuals more likely to benefit from preventive interventions and serve as a benchmark to test novel putative risk factors. Methods and Results Individual‐level data from 3 large cohorts in the U nited S tates (Atherosclerosis Risk in Communities [ ARIC ] study, the Cardiovascular Health Study [ CHS ], and the Framingham Heart Study [ FHS ]), including 18 556 men and women aged 46 to 94 years (19% A frican A mericans, 81% whites) were pooled to derive predictive models for AF using clinical variables. Validation of the derived models was performed in 7672 participants from the Age, Gene and Environment—Reykjavik study ( AGES ) and the Rotterdam Study ( RS ). The analysis included 1186 incident AF cases in the derivation cohorts and 585 in the validation cohorts. A simple 5‐year predictive model including the variables age, race, height, weight, systolic and diastolic blood pressure, current smoking, use of antihypertensive medication, diabetes, and history of myocardial infarction and heart failure had good discrimination (C‐statistic, 0.765; 95% CI , 0.748 to 0.781). Addition of variables from the electrocardiogram did not improve the overall model discrimination (C‐statistic, 0.767; 95% CI , 0.750 to 0.783; categorical net reclassification improvement, −0.0032; 95% CI , −0.0178 to 0.0113). In the validation cohorts, discrimination was acceptable ( AGES C‐statistic, 0.664; 95% CI , 0.632 to 0.697 and RS C‐statistic, 0.705; 95% CI , 0.664 to 0.747) and calibration was adequate. Conclusion A risk model including variables readily available in primary care settings adequately predicted AF in diverse populations from the U nited S tates and E urope.