Cluster Individuals Based on Phenotype and Determine the Risk for Atrial Fibrillation in the PREVEND and Framingham Heart Study Populations.
BACKGROUND
Risk prediction of atrial fibrillation (AF) is of importance to improve the early diagnosis and treatment of AF. Latent class analysis takes into account the possible existence of classes of individuals each with shared risk factors, and maybe a better method of incorporating the phenotypic heterogeneity underlying AF.


RESULTS
Two prospective community-based cohort studies from Netherlands and United States were used. Prevention of Renal and Vascular End-stage Disease (PREVEND) study, started in 1997, and the Framingham Heart Study (FHS) Offspring cohort started in 1971, both with 10-years follow-up. The main objective was to determine the risk of AF using a latent class analysis, and compare the discrimination and reclassification performance with traditional regression analysis. Mean age in PREVEND was 49±13 years, 49.8% were men. During follow-up, 250(3%) individuals developed AF. We built a latent class model based on 18 risk factors. A model with 7 distinct classes (ranging from 341 to 1517 individuals) gave the optimum tradeoff between a high statistical model-likelihood and a low number of model parameters. All classes had a specific profile. The incidence of AF varied; class 1 0.0%, class 2 0.3%, class 3 7.5%, class 4 0.2%, class 5 1.3%, class 6 4.2%, class 7 21.7% (p<0.001). The discrimination (C-statistic 0.830 vs. 0.842, delta-C -0.013, p = 0.22) and reclassification (IDI -0.028, p<0.001, NRI -0.090, p = 0.049, and category-less-NRI -0.049, p = 0.495) performance of both models was comparable. The results were successfully replicated in a sample of the FHS study (n = 3162; mean age 58±9 years, 46.3% men).


CONCLUSIONS
Latent class analysis to build an AF risk model is feasible. Despite the heterogeneity in number and severity of risk factors between individuals at risk for AF, latent class analysis produces distinguishable groups.
Department of Cardiology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
Michiel
M
Rienstra
Department of Cardiology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
Bastiaan
B
Geelhoed
National Heart Lung and Blood Institute's and Boston University's Framingham Heart Study, Framingham, Massachusetts, United States of America.
Xiaoyan
X
Yin
Department of Cardiology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
Joylene E
JE
Siland
Department of Cardiology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
Rob A
RA
Vermond
Department of Cardiology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
Bart A
BA
Mulder
Department of Cardiology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
Pim
P
Van Der Harst
Department of Cardiology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
Hans L
HL
Hillege
National Heart Lung and Blood Institute's and Boston University's Framingham Heart Study, Framingham, Massachusetts, United States of America.|Section of Cardiovascular Medicine, Department of Medicine, Boston University School of Medicine, Boston, Massachusetts, United States of America.|Section of Preventive Medicine, Department of Medicine, Boston University School of Medicine, Boston, Massachusetts, United States of America.|Department of Epidemiology, Boston University School of Public Health, Boston, Massachusetts, United States of America.
Emelia J
http://orcid.org/0000-0003-4076-2336
EJ
Benjamin
Department of Cardiology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
Isabelle C
IC
Van Gelder
D000328:Adult; D001281:Atrial Fibrillation / Q000453:epidemiology*; D016000:Cluster Analysis; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D015994:Incidence; D008297:Male; D008875:Middle Aged; D009426:Netherlands / Q000453:epidemiology; D010641:Phenotype; D011446:Prospective Studies; D012307:Risk Factors; D014481:United States / Q000453:epidemiology