Association between familial atrial fibrillation and risk of new-onset atrial fibrillation

Steven A. Lubitz, Xiaoyan Yin, Joao Daniel T. Fontes, Jared W. Magnani, Michiel Rienstra, Manju Pai, Mark L. Villalon, Ramachandran S. Vasan, Michael J. Pencina, Daniel Levy, Martin G. Larson, Patrick T. Ellinor, Emelia J. Benjamin

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Abstract

Context: Although the heritability of atrial fibrillation (AF) is established, the contribution of familial AF to predicting new-onset AF remains unknown. Objective: To determine whether familial occurrence of AF is associated with newonset AF beyond established risk factors. Design, Setting, and Participants: The Framingham Heart Study, a prospective community-based cohort study started in 1948. Original and Offspring Cohort participants were aged at least 30 years, were free of AF at the baseline examination, and had at least 1 parent or sibling enrolled in the study. The 4421 participants in this analysis (mean age, 54 [SD, 13] years; 54% women) were followed up through December 31, 2007. Main OutcomeMeasures: Incremental predictive value of incorporating different features of familial AF (any familial AF, premature familial AF [onset ≤65 years old], number of affected relatives, and youngest age of onset in a relative) into a risk model for new-onset AF. Results: Across 11 971 examinations during the period 1968-2007, 440 participants developed AF. Familial AF occurred among 1185 participants (26.8%) and premature familial AF occurred among 351 participants (7.9%). Atrial fibrillation occurred more frequently among participants with familial AF than without familial AF (unadjusted absolute event rates of 5.8% and 3.1%, respectively). The association was not attenuated by adjustment for AF risk factors (multivariable-adjusted hazard ratio, 1.40; 95% confidence interval [CI], 1.13-1.74) or reported AF-related genetic variants. Among the different features of familial AF examined, premature familial AF was associated with improved discrimination beyond traditional risk factors to the greatest extent (traditional risk factors, C statistic, 0.842 [95% CI, 0.826-0.858]; premature familial AF, C statistic, 0.846 [95% CI, 0.831-0.862]; P=.004). Modest changes in integrated discrimination improvement were observed with premature familial AF (2.1%). Net reclassification improvement (assessed using 8-year risk thresholds of <5%, 5%-10%, and >10%) did not change significantly with premature familial AF (index statistic, 0.011; 95% CI, -0.021 to 0.042; P=.51), although categoryless net reclassification was improved (index statistic, 0.127; 95% CI, 0.064-0.189; P=.009). Conclusions: In this cohort, familial AF was associated with an increased risk of AF that was not attenuated by adjustment for AF risk factors including genetic variants. Assessment of premature familial AF was associated with a very slight increase in predictive accuracy compared with traditional risk factors.

Original languageEnglish (US)
Pages (from-to)2263-2269
Number of pages7
JournalJAMA - Journal of the American Medical Association
Volume304
Issue number20
DOIs
StatePublished - Nov 24 2010
Externally publishedYes

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Atrial Fibrillation
Confidence Intervals

ASJC Scopus subject areas

  • Medicine(all)

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Association between familial atrial fibrillation and risk of new-onset atrial fibrillation. / Lubitz, Steven A.; Yin, Xiaoyan; Fontes, Joao Daniel T.; Magnani, Jared W.; Rienstra, Michiel; Pai, Manju; Villalon, Mark L.; Vasan, Ramachandran S.; Pencina, Michael J.; Levy, Daniel; Larson, Martin G.; Ellinor, Patrick T.; Benjamin, Emelia J.

In: JAMA - Journal of the American Medical Association, Vol. 304, No. 20, 24.11.2010, p. 2263-2269.

Research output: Contribution to journalArticle

Lubitz, SA, Yin, X, Fontes, JDT, Magnani, JW, Rienstra, M, Pai, M, Villalon, ML, Vasan, RS, Pencina, MJ, Levy, D, Larson, MG, Ellinor, PT & Benjamin, EJ 2010, 'Association between familial atrial fibrillation and risk of new-onset atrial fibrillation', JAMA - Journal of the American Medical Association, vol. 304, no. 20, pp. 2263-2269. https://doi.org/10.1001/jama.2010.1690
Lubitz, Steven A. ; Yin, Xiaoyan ; Fontes, Joao Daniel T. ; Magnani, Jared W. ; Rienstra, Michiel ; Pai, Manju ; Villalon, Mark L. ; Vasan, Ramachandran S. ; Pencina, Michael J. ; Levy, Daniel ; Larson, Martin G. ; Ellinor, Patrick T. ; Benjamin, Emelia J. / Association between familial atrial fibrillation and risk of new-onset atrial fibrillation. In: JAMA - Journal of the American Medical Association. 2010 ; Vol. 304, No. 20. pp. 2263-2269.
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abstract = "Context: Although the heritability of atrial fibrillation (AF) is established, the contribution of familial AF to predicting new-onset AF remains unknown. Objective: To determine whether familial occurrence of AF is associated with newonset AF beyond established risk factors. Design, Setting, and Participants: The Framingham Heart Study, a prospective community-based cohort study started in 1948. Original and Offspring Cohort participants were aged at least 30 years, were free of AF at the baseline examination, and had at least 1 parent or sibling enrolled in the study. The 4421 participants in this analysis (mean age, 54 [SD, 13] years; 54{\%} women) were followed up through December 31, 2007. Main OutcomeMeasures: Incremental predictive value of incorporating different features of familial AF (any familial AF, premature familial AF [onset ≤65 years old], number of affected relatives, and youngest age of onset in a relative) into a risk model for new-onset AF. Results: Across 11 971 examinations during the period 1968-2007, 440 participants developed AF. Familial AF occurred among 1185 participants (26.8{\%}) and premature familial AF occurred among 351 participants (7.9{\%}). Atrial fibrillation occurred more frequently among participants with familial AF than without familial AF (unadjusted absolute event rates of 5.8{\%} and 3.1{\%}, respectively). The association was not attenuated by adjustment for AF risk factors (multivariable-adjusted hazard ratio, 1.40; 95{\%} confidence interval [CI], 1.13-1.74) or reported AF-related genetic variants. Among the different features of familial AF examined, premature familial AF was associated with improved discrimination beyond traditional risk factors to the greatest extent (traditional risk factors, C statistic, 0.842 [95{\%} CI, 0.826-0.858]; premature familial AF, C statistic, 0.846 [95{\%} CI, 0.831-0.862]; P=.004). Modest changes in integrated discrimination improvement were observed with premature familial AF (2.1{\%}). Net reclassification improvement (assessed using 8-year risk thresholds of <5{\%}, 5{\%}-10{\%}, and >10{\%}) did not change significantly with premature familial AF (index statistic, 0.011; 95{\%} CI, -0.021 to 0.042; P=.51), although categoryless net reclassification was improved (index statistic, 0.127; 95{\%} CI, 0.064-0.189; P=.009). Conclusions: In this cohort, familial AF was associated with an increased risk of AF that was not attenuated by adjustment for AF risk factors including genetic variants. Assessment of premature familial AF was associated with a very slight increase in predictive accuracy compared with traditional risk factors.",
author = "Lubitz, {Steven A.} and Xiaoyan Yin and Fontes, {Joao Daniel T.} and Magnani, {Jared W.} and Michiel Rienstra and Manju Pai and Villalon, {Mark L.} and Vasan, {Ramachandran S.} and Pencina, {Michael J.} and Daniel Levy and Larson, {Martin G.} and Ellinor, {Patrick T.} and Benjamin, {Emelia J.}",
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T1 - Association between familial atrial fibrillation and risk of new-onset atrial fibrillation

AU - Lubitz, Steven A.

AU - Yin, Xiaoyan

AU - Fontes, Joao Daniel T.

AU - Magnani, Jared W.

AU - Rienstra, Michiel

AU - Pai, Manju

AU - Villalon, Mark L.

AU - Vasan, Ramachandran S.

AU - Pencina, Michael J.

AU - Levy, Daniel

AU - Larson, Martin G.

AU - Ellinor, Patrick T.

AU - Benjamin, Emelia J.

PY - 2010/11/24

Y1 - 2010/11/24

N2 - Context: Although the heritability of atrial fibrillation (AF) is established, the contribution of familial AF to predicting new-onset AF remains unknown. Objective: To determine whether familial occurrence of AF is associated with newonset AF beyond established risk factors. Design, Setting, and Participants: The Framingham Heart Study, a prospective community-based cohort study started in 1948. Original and Offspring Cohort participants were aged at least 30 years, were free of AF at the baseline examination, and had at least 1 parent or sibling enrolled in the study. The 4421 participants in this analysis (mean age, 54 [SD, 13] years; 54% women) were followed up through December 31, 2007. Main OutcomeMeasures: Incremental predictive value of incorporating different features of familial AF (any familial AF, premature familial AF [onset ≤65 years old], number of affected relatives, and youngest age of onset in a relative) into a risk model for new-onset AF. Results: Across 11 971 examinations during the period 1968-2007, 440 participants developed AF. Familial AF occurred among 1185 participants (26.8%) and premature familial AF occurred among 351 participants (7.9%). Atrial fibrillation occurred more frequently among participants with familial AF than without familial AF (unadjusted absolute event rates of 5.8% and 3.1%, respectively). The association was not attenuated by adjustment for AF risk factors (multivariable-adjusted hazard ratio, 1.40; 95% confidence interval [CI], 1.13-1.74) or reported AF-related genetic variants. Among the different features of familial AF examined, premature familial AF was associated with improved discrimination beyond traditional risk factors to the greatest extent (traditional risk factors, C statistic, 0.842 [95% CI, 0.826-0.858]; premature familial AF, C statistic, 0.846 [95% CI, 0.831-0.862]; P=.004). Modest changes in integrated discrimination improvement were observed with premature familial AF (2.1%). Net reclassification improvement (assessed using 8-year risk thresholds of <5%, 5%-10%, and >10%) did not change significantly with premature familial AF (index statistic, 0.011; 95% CI, -0.021 to 0.042; P=.51), although categoryless net reclassification was improved (index statistic, 0.127; 95% CI, 0.064-0.189; P=.009). Conclusions: In this cohort, familial AF was associated with an increased risk of AF that was not attenuated by adjustment for AF risk factors including genetic variants. Assessment of premature familial AF was associated with a very slight increase in predictive accuracy compared with traditional risk factors.

AB - Context: Although the heritability of atrial fibrillation (AF) is established, the contribution of familial AF to predicting new-onset AF remains unknown. Objective: To determine whether familial occurrence of AF is associated with newonset AF beyond established risk factors. Design, Setting, and Participants: The Framingham Heart Study, a prospective community-based cohort study started in 1948. Original and Offspring Cohort participants were aged at least 30 years, were free of AF at the baseline examination, and had at least 1 parent or sibling enrolled in the study. The 4421 participants in this analysis (mean age, 54 [SD, 13] years; 54% women) were followed up through December 31, 2007. Main OutcomeMeasures: Incremental predictive value of incorporating different features of familial AF (any familial AF, premature familial AF [onset ≤65 years old], number of affected relatives, and youngest age of onset in a relative) into a risk model for new-onset AF. Results: Across 11 971 examinations during the period 1968-2007, 440 participants developed AF. Familial AF occurred among 1185 participants (26.8%) and premature familial AF occurred among 351 participants (7.9%). Atrial fibrillation occurred more frequently among participants with familial AF than without familial AF (unadjusted absolute event rates of 5.8% and 3.1%, respectively). The association was not attenuated by adjustment for AF risk factors (multivariable-adjusted hazard ratio, 1.40; 95% confidence interval [CI], 1.13-1.74) or reported AF-related genetic variants. Among the different features of familial AF examined, premature familial AF was associated with improved discrimination beyond traditional risk factors to the greatest extent (traditional risk factors, C statistic, 0.842 [95% CI, 0.826-0.858]; premature familial AF, C statistic, 0.846 [95% CI, 0.831-0.862]; P=.004). Modest changes in integrated discrimination improvement were observed with premature familial AF (2.1%). Net reclassification improvement (assessed using 8-year risk thresholds of <5%, 5%-10%, and >10%) did not change significantly with premature familial AF (index statistic, 0.011; 95% CI, -0.021 to 0.042; P=.51), although categoryless net reclassification was improved (index statistic, 0.127; 95% CI, 0.064-0.189; P=.009). Conclusions: In this cohort, familial AF was associated with an increased risk of AF that was not attenuated by adjustment for AF risk factors including genetic variants. Assessment of premature familial AF was associated with a very slight increase in predictive accuracy compared with traditional risk factors.

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