Paradoxical association between atrial fibrillation/flutter and high cholesterol over age 75 years: The Kuakini Honolulu Heart Program and Honolulu-Asia Aging Study

J Electrocardiol. 2021 Mar-Apr:65:37-44. doi: 10.1016/j.jelectrocard.2020.12.008. Epub 2020 Dec 23.


Introduction: Several studies have indicated high cholesterol is paradoxically associated with low prevalence of atrial fibrillation/flutter (AF). However, the etiology is uncertain. One potential explanation might be the confounding effect of age exemplifying prevalence-incidence (Neyman's) bias. However, this bias has not often been discussed in depth in the literature. Therefore, we conducted a cross-sectional analysis to test the hypothesis that there is a paradoxical association between lipid profile and AF prevalence.

Methods: This is a cross-sectional study design, using data from the Kuakini Honolulu Heart Program. Participants were 3741 Japanese-American men between 71 and 93 years old living in Hawaii. Serum total cholesterol (TC) level was measured and categorized into quartiles. AF was diagnosed by 12‑lead Electrocardiogram. We categorized age into quartiles (71-74, 75-77, 78-80 and 81+ years).

Results: We observed opposite associations between AF and TC among different age groups. For participants age ≥75, higher TC levels were paradoxically associated with lower prevalence of AF after multivariable adjustment, i.e. the odds ratios of AF comparing the highest TC quartile with the lowest TC quartile for age 75-77, 78-80 and 81+ years were 0.17 (95% confidence interval [CI], 0.06-0.52), 0.28 (95% CI, 0.07-1.09) and 0.14 (95% CI, 0.03-0.62), respectively. Conversely, for those who were 71-74 years old, the odds ratio of AF was 2.09 (95% CI, 0.76-5.75) between the highest and the lowest TC quartiles.

Conclusions: There is a paradoxical association of TC with AF in Japanese-American men age ≥75, but not <75 years. The paradox might be explained by Neyman's bias.

Keywords: Atrial fibrillation; Atrial flutter; Cholesterol; Dyslipidemia paradox; Lipid profile.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Aged, 80 and over
  • Aging
  • Asia
  • Atrial Fibrillation* / epidemiology
  • Cholesterol
  • Cross-Sectional Studies
  • Electrocardiography
  • Humans
  • Male
  • Risk Factors


  • Cholesterol