Fractal analysis of heart rate variability and mortality in elderly community-dwelling people - Longitudinal Investigation for the Longevity and Aging in Hokkaido County (LILAC) study

N. Hotta, K. Otsuka, S. Murakami, G. Yamanaka, Y. Kubo, O. Matsuoka, T. Yamanaka, M. Shinagawa, S. Nunoda, Y. Nishimura, K. Shibata, H. Saitoh, M. Nishinaga, M. Ishine, T. Wada, K. Okumiya, K. Matsubayashi, S. Yano, K. Ichihara, G. CornélissenF. Halberg

Research output: Contribution to journalArticlepeer-review

30 Scopus citations


Aim. - Fractal analysis of heart rate (HR) variability (HRV) has been used as a new approach to evaluate the risk of mortality in various patient groups. Aim of this study is to examine the prognostic power of detrended fluctuation analysis (DFA) and traditional time- and frequency-domain analyses of HR dynamics as predictors of mortality among elderly people in a community. Methods. - We examined 298 people older than 75 years (average age: 79.6 years) and 1-h ambulatory ECG was monitored. During the last 10 min, deep respiration (6-s expiration and 4-s inspiration) was repeated six times in a supine position. Time-domain and frequency-domain measures were determined by the maximum entropy method. Scaling exponents of short-term (<11 beats, alpha 1) and longer-term (>11 beats, alpha 2) were determined by the DFA method. Six estimates, obtained from 10-min segments, were averaged to derive mean values for the entire recording span. These average values were denoted Alpha 1 and Alpha 2, estimates obtained during the first 10-min segment Alpha 1 S and Alpha 2 S, and those during the last 10-min segment Alpha 1E and Alpha 2E, respectively. The LILAC study started on July 25, 2000 and ended on November 30, 2004. We used Cox regression analysis to calculate relative risk (RR) and 95% confidence interval (CI) for all-cause mortality. Significance was considered at a value of P < 0.05. Results. - Gender, age and Alpha 2E showed a statistically significant association with all-cause mortality. In univariate analyses, gender was significantly associated with all-cause mortality, being associated with a RR of 3.59 (P = 0.00136). Age also significantly predicted all-cause mortality and a 5-year increase in age was associated with a RR of 1.49 (P = 0.01809). The RR of developing all-cause mortality predicted by a 0.2-unit increase in Alpha 2E was 0.58 (P = 0.00390). Other indices of fractal analysis of HRV did not have predictive value. In multivariate analyses, when both Alpha 2E and gender were used as continuous variables in the same model, Alpha 2E remained significantly associated with the occurrence of all-cause mortality (P = 0.02999). After adjustment for both gender and age, a 0.2-unit increase in Alpha 2E was associated with a RR of 0.61 (95% CI: 0.42-0.90, p = 0.01151). Conclusion. - An intermediate-term fractal-like scaling exponent of RR intervals was a better predictor of death than the traditional measures of HR variability in elderly community-dwelling people. It is noteworthy that the longer-term (alpha 2) rather than the short-term fractal component (alpha 1) showed predictive value for all-cause mortality, which suggests that an increase in the randomness of intermediate-term HR behavior may be a specific marker of neurohumoral and sympathetic activation and therefore may also be associated with an increased risk of mortality.

Original languageEnglish (US)
Pages (from-to)S45-S48
JournalBiomedicine and Pharmacotherapy
Issue numberSUPPL. 1
StatePublished - Oct 2005

Bibliographical note

Funding Information:
This study was supported by Fukuda Foundation for Medical (Grant in 2004 for the study on association between arterial stiffness and cognitive impairment in community-dwelling subjects over 70 years old).


  • All-cause mortality
  • Detrended fluctuation analysis
  • Elderly community-dwelling people
  • Fractal
  • Heart rate variability


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