title: Frailty and impaired cardiac autonomic control: new insights from principal components aggregation of traditional heart rate variability indices.
abstract: BACKGROUND
  Age-related deterioration in homeostatic regulatory mechanisms leads to decreased complexity in their output. For example, the degradation of cardiac autonomic control results in loss of complexity in the heart rate signal. Frailty is a state of critically impaired homeostasis that results in heightened vulnerability to stressors. We propose a new measure of heart rate variability (HRV) to capture the impairment in cardiac autonomic control associated with frailty.
  
  
  METHODS
  Traditional time and frequency domain indices of HRV were obtained from 2-hour ambulatory electrocardiograms (ECGs) of 276 women (65-101 years old) in the Women's Health and Aging Study-I. Principal components analysis was conducted on the correlation matrix of HRV indices. Frailty was defined using a validated instrument. Regression models were used to evaluate associations of HRV measures with age, frailty, and 5-year mortality.
  
  
  RESULTS
  The first two principal components (PCs), PC1 and PC2, explained 90% of the variance in HRV indices. PC1 is the mean of log-transformed HRV indices. PC2 is a linear combination of log-transformed indices, with positive weights for very low frequency (VLF), low frequency (LF), and standard deviation of N-N intervals (SDNN), and negative weights for high frequency (HF), root-mean-squared differences of successive N-N intervals (RMSSD), and proportion of all N-N intervals that are larger than 50 ms (pNN50). Decreases in SDNN, VLF, LF, and LF/HF were associated with an increased risk of frailty. PC2 was more strongly associated with age (beta = -.23, p < .001) and frailty (beta = -.73, p < 10(-5)) than were the individual HRV indices and LF/HF. PC2 was also the best predictor of 5-year mortality (beta = -.60, p < 10(-6)).
  
  
  CONCLUSIONS
  Cardiac autonomic control, as reflected by HRV, is impaired in frailty. A new measure derived from PC aggregation of traditional HRV indices provides a compact summary of this impairment.
authors.affiliation: The Center on Aging and Health, Johns Hopkins University, Baltimore, Maryland, USA. rvaradhan@jhmi.edu
authors.forename: Ravi
authors.initials: R
authors.lastname: Varadhan
authors.forename: Paulo H M
authors.initials: PH
authors.lastname: Chaves
authors.forename: Lewis A
authors.initials: LA
authors.lastname: Lipsitz
authors.forename: Phyllis K
authors.initials: PK
authors.lastname: Stein
authors.forename: Jing
authors.initials: J
authors.lastname: Tian
authors.forename: B Gwen
authors.initials: BG
authors.lastname: Windham
authors.forename: Ronald D
authors.initials: RD
authors.lastname: Berger
authors.forename: Linda P
authors.initials: LP
authors.lastname: Fried
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000375:Aging / Q000502:physiology*; D001341:Autonomic Nervous System; D001342:Autonomic Nervous System Diseases / Q000175:diagnosis* / Q000401:mortality; D015716:Electrocardiography, Ambulatory; D005260:Female; D016330:Frail Elderly; D006329:Heart Conduction System; D006339:Heart Rate; D006801:Humans; D008297:Male; D011237:Predictive Value of Tests; D012016:Reference Values; D015203:Reproducibility of Results; D012307:Risk Factors; D016019:Survival Analysis