14s. cog9923040745908 000) (Aucmtane Care a Berens Resa ol. 28,No.s Ai 199 Effects of Alcohol Use and Gender on the Dynamics of EKG Time-Series Data Paolo B. DePetrilo, Kenneth V. White, Ming Liu, Daniel Hommer, and David Goldman Hurst analysis of EKG data obtained from « population of aleaholie (x ~ 13) and nonalcoholic (2 = 48) subjects was undertaken. Potential subjects (n= 120) were serened using the Schedule for Affective Disorders and Schizophrenia and Strcrored Clinical Interview for DSMCII instruments, Dat fom sub= jects with «diagnosis of creat akofot dependence were analyzed. Subjects with diagnoses such as mjor depression, bipolar disorder or schizophrenia (Axis T diagnoses), or personality disorders (Axis T diag ses) were excluded from analysis Subjects undergoing testing were free of aleohol and it drugs. ‘Alcoholic subjects had n0 clinical evidence of alcohol withdrawal symptoms atthe ime of testing, EKG data EL i i wore obtained with eyes open oF with eves closed. Approximately 35 min of data were ob ined for each ‘ondton, Alcoholic subjeets had less complex heart rate dyaamics as evidenced by higher values of Hf = (018 + 005 {mean * SEM), compared with healthy comparison subjecs with 17 = 009 = 0.02 © 0014 for the eyes dosed cont ‘comparison subjets with = 0.07 = 002.p ind H = 047 ‘005 (mean = SEM) compared with healthy ‘LOU forthe eyes open contin. A gender effet was een ‘vith female subjects showing evidence of more complex heart rate dynamics than male subjects. ‘Key Words: Alcoholism, EKG, Noslinear Dynamies, Fractal REVIOUS WORK suggests a strong correlation be- tween acute alcohol ingestion and altered heart rate dynamics. All studies are in agreement that acute alcobol ingestion results in a decrease in heart rate variability (ARV), as measured using frequency-domain or time- domain analyses (Newlin et al., 1990; Koskinen et al., 1994; Rossinen ct al., 1997; Sehesterd et al, 1998). Although the effects of acute alcohol ingestion are presumed to be due 10 effects of alcohol on parasympathetic activity, the mecha nism modulating these effects remains obscure. Chronic excessive alcohol consumption is associated with decreases in HRV as measured in the frequency domain (Miralles et al,, 1995; Murata et al, 1994). These changes have been correlated with alterations in parasympathetic and sympa- thetic responses, suggesting a long-lasting perturbation of cardiac autonomic control in alcohol-dependent patients. Heart rate dynamics are usually estimated using param- eters obtained from time-do-main or frequency-domain analyses (Hirsch et a., 1993). Results obtained with these methods are confounded by the changing statistical prop- erties of heartbeat interval time series over time. These signals are difficult to interpret with dispersional measures From the Laboruory of Clinical Suds (P.B.D, ML, Di.) and Labs onaory of Neurogenetics (KV, D.G.), Tramural Research Progra [National Institute on Alcohol Aluse and Alcoholism, National Insiutes of Health, Bethesda, Maryland. Received fr publication August 21, 1998; acceped February 3, 1988 Reprni requests: Palo B. DePetrl, M.D. National Institutes of Health 10'3€103, 10 Center Drive, MSC 1256, Bethesda, MD 20892-1236; Fax: (301/402-0445; Email: php@hetocni gs Copyright © 1999 by the Research Society on Alcohol Alebol Cin Exp Res, Vl 2, No 1989p 75-950 in the time domain, such as the standard deviation, because the resulting parameters are not stable with increasing data length. ‘These measures also do not give any information regarding the internal dynamics of the time series, Frequency-domain measures rely on assumptions of sta- tionarity that are not met with interbeat interval (IBI) data, especially with longer recording times. ‘We used a technique to measure the internal dynamics of an IBI time series that calculates the Hurst exponent (H), "The Hurst exponent is a direct measure of the dynamics of a time series, conceived by Hurst (1951) and formalized by Mandelbrot and Van Ness (1968). The value of H varies with 0 =H <1, Visually inspecting « time series with Hl = 1.0 in Fig, LD, we see an overall relative smoothness to the ‘graph of IBI versus time. As Hf tends towards 0, trends are more rapidly reversed, as shown in Fig. 1A, where there are large variations between adjacent values, which give it a very irregular look. When H = 0.5, as seen in Fig. 1C, the magnitude of the sequential points of the time series are independent and therefore uncorrelated. The time series can be considered a random walk. Thus, H values ap- proaching 0.5 from either extreme (0 or 1) are symptomatic of a breakdown in the long-range correlations of the heart TBI signal, Inasmuch as these long-term correlations are associated with cardiac health (Peng et al. 1995), Hurst analysis of heart TBIs can provide a measure of cardiac signal dynamics in relationship to disease states such as alcoholism. Furthermore, because the measure H is not significantly altered by changes in data length, statistical moments, oF means of the signal, it allows comparisons of 78DEPETRILO ET AL, f 000 sod 3] z wos Z Spe pment et cnt re eet roe a1 EF jraesrgresonts the na i iltacords é - (ms) and the x-axis represents the beat num & H=0.50 Oe Te tne anon AD were yrthenzad E Eotmwisrmnecwcmeeete f Soieitemestoaprmats ‘ce pon anteater Ee reac nc to Suisptamamrtne bo CO 100 abe te dored using Hurt ana a z we : ye i ota Meal Aa io, wore & fe ere i beat winter cardiac signal compleaity measures between different stud- ‘A time-domain measure such as standard deviation, a classic descriptor of variance in data, does not always cor- relate with HRV. This is because the relationship between ‘each IBI is lost. This is best seen in Fig, 1, All four time series represented in Figs. 1A to ID were generated, as ‘outlined in “Methods,” to have the same mean and stan- dard deviation as an IBI time series obtained from a healthy human subject (mean + SD 1287 ms + 63) as shown in Fig. IE, The time series from the healthy subject hhad an associated H value of 0.16 + 0.05. By visual inspee- tion, the “roughness” of this time series best matches the synthesized IBI series from Fig. 1B, with H = 0.16, It can also easily be seen that beat-to-beat variability is highest as H approaches 0. ‘The term HIRV will be used as a descriptor of beat-to- beat variability, in accordance with curtent usage. For TBI time series, H isa measure of both HRV, as well as cardiae signal complexity, where cardiac signal complexity in creases with the magnitude of the long-term correlations of the time series. Increases or decreases in H correspond to decreases or increases in HRV, respectively, as ong as 0 = H_= 05. In this and other laboratories, human subject IBT time series are found to have Hurst exponents between 0.00 and 0.48 (Yamamoto et al, 1995). Since cardiac IBI time series have an associated H < 0.5, iis correct to state that, for these time series, lower values of H are associated with both increased signal complexity and increased HRV. ‘The current methodology allows a better representation of the internal dynamics of the system than can be obtained from simple dispersional measures, such as mean and stan- dard deviation, Inasmuch as a spectral transform of the IBI data is not required before analysis, short lengths of TBI data with differing statistical characteristics can be com- pared. ‘We used this technique to determine H using IBI time- series data obtained from human subjects stratified based (on gender and the presence or absence of alcohol depen- dence. Because decreases in HRV are associated with higher values of H (Yamamoto et al, 1995), we surmised that a higher H value would characterize EKG data from alcoholic subjects, compared with controls, METHODS Subject ‘This study was approved by the Institutional Review Board at the [National Insitute on Alcohol Abuse and Alcoholism, and was conducted ‘vith writen consent from the subjects, Potential subjects were evaluated ‘sing the Schedule for Affective Disorders and Schizophrenia and the Structured Clinical Interview for DSM-HL-R (Spitzer et al, 1990), Sub jects were instructed not to consume any prescription or nonprescription frog for 24 hr before the star of testing. Urine toxicology testing was performed, and blood alotot concentrations were estimated wsing 3 breathalyzer. Subjects who were positive for drugs of abuse oF aleohol were excluded ‘A total of 120 volunteer subjects were evaluated, sampled from the surrounding community. Two groups of subjects were abstracted rom this ‘Study population. Subjects with a primary diagnosis of alcohol depen-