Abstract
Objectives
To examine the cross-sectional and longitudinal relationships between cardiac autonomic tone and serum CRP and to investigate potential causal links between these measures.
Methods
A population-based sample of 188 home-dwelling, middle-aged and older adults (104 women, mean age 59 years) from Cook County, IL, participated in this prospective cohort study. High-frequency heart rate variability (HF) and pre-ejection period (PEP) served as markers of cardiac parasympathetic and sympathetic tone, respectively. Cardiac autonomic balance (CAB) was defined as the arithmetic difference between normalized values of HF and PEP. Multivariate regression and autoregressive cross-lagged panel analyses were used to investigate cross-sectional and longitudinal relationships, respectively. High-sensitivity enzyme immunoassay measured serum CRP.
Results
After removing three cases with CRP values suggesting acute inflammation, the mean CRP value was 1.43 mg/L (range 0.02–7.96 mg/L, SD = 1.55). In models that adjusted for gender, age, race/ethnicity, education, body mass index, smoking, exercise, systolic blood pressure and health conditions including diabetes and hypertension, HF (B = −0.15, SE = 0.04, P < 0.01) and CAB (B = −0.14, SE = 0.04, P < 0.01) were significantly associated with natural log (ln) CRP. In longitudinal analysis, higher CRP levels in any one year predicted greater increases in HF in the subsequent year.
Interpretation
The inverse relationship between HF and CRP in cross-sectional analysis is consistent with previous studies, while the longitudinal results suggest that cardiac parasympathetic tone may increase over time as a result of higher circulating CRP.
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References
Araujo F, Antelmi I, Pereira AC, Latorre MDRDO, Grupi CJ, Krieger JE, Mansur AJ (2006) Lower heart rate variability is associated with higher serum high-sensitivity C-reactive protein concentration in healthy individuals aged 46 or more. Int J Cardiol 107:333–337
Berntson GG, Bigger JT, Eckberg DL, Grossman P, Kaufman PG, Malik M, Nagaraja HN, Porges SW, Saul JP, Stone PH, van der Molen MW (1997) Heart rate variability: origins, methods, and interpretive caveats. Psychophysiology 34:623–648
Berntson GG, Norman GJ, Hawkley LC, Cacioppo JT (2008) Cardiac autonomic balance versus cardiac regulatory capacity. Psychophysiology 45:643–652
Berntson GG, Norman GJ, Hawkley LC, Cacioppo JT (2008) Spirituality and autonomic cardiac control. Ann Behav Med 35:198–208
Browne MW, Cudeck R (1992) Alternative ways of assessing model fit. Sociological methods and research 21:230–258
Cacioppo JT, Berntson GG, Binkley BF, Quigley KS, Uchino BN, Fieldstone A (1994) Autonomic cardiac control. II. Noninvasive indices and basal responses as revealed by autonomic blockades. Psychophysiology 31:586–598
Curran PJ (2000) A latent curve framework for the study of developmental trajectories in adolescent substance abuse. In: Rose JS, Chassin L, Presson CC, Sherman SJ (eds) Multivariate applications in substance use research: new methods for new questions. Lawrence Erlbaum Associates, Mahwah
Elenkov IJ, Chrousos GP (2002) Stress hormones, proinflammatory and antiinflammatory cytokines, and autoimmunity. Ann N Y Acad Sci 966:290–303
Ellenby MS, McNames J, Lai S, McDonald BA, Krieger D, Sclabassi RJ (2001) Uncoupling and recoupling of autonomic regulation of the heart beat in pediatric septic shock. Shock 16:274–277
Ernst JM, Litvack DA, Lozano DL, Cacioppo JT, Berntson GG (1999) Impedence pneumography: noise as signal in impedence cardiography. Psychophysiology 36:333–338
Eskandari F, Webster JI, Sternberg EM (2003) Neural immune pathways and their connection to inflammatory diseases. Arthritis Res Ther 5:251–265
Godin PJ, Fleisher LA, Eidsath A, Vandivier RW, Preas H, Banks S, Buchman T, Suffredini AF (1996) Experimental human endotoxemia increases cardiac regularity: results from a prospective, randomized, crossover trial. Crit Care Med 24:1117–1124
Hawkley LC, Masi CM, Berry JD, Cacioppo JT (2006) Loneliness is a unique predictor of age-related differences in systolic blood pressure. Psychol Aging 21:152–164
Hu L, Bentler PM (1999) Cutoff criteria for fit indexes in covariance structure analysis: conventional criteria versus new alternatives. Struct Equation Model 6:1–55
MacCallum R, Browne MW, Sugawara HM (1996) Power analysis and determination of sample size for covariance structure modeling. Psychol Methods 1:130–149
Masi CM, Hawkley LC, Rickett EM, Cacioppo JT (2007) Respiratory sinus arrhythmia and diseases of aging: obesity, diabetes mellitus, and hypertension. Biol Psych 74:212–223
McDade T, Stallings J, Angold A, Costello E, Burleson MH, Cacioppo JT, Glaser R, Worthman C (2000) Epstein–Barr virus antibodies in whole blood spots: a minimally invasive method for assessing an aspect of cell mediated immunity. Psychosom Med 62:560–567
McDade TW, Burhop J, Dohnal J (2004) High sensitivity immunoassay for C-reactive protein in dried blood spots. Clin Chem 50:652–654
McDade TW, Hawkley LC, Cacioppo JT (2006) Psychological and behavioral predictors of inflammation in middle-aged and older adults: The Chicago Health, Aging, and Social Relations Study. Psychosom Med 68:376–381
McDade TW, Williams S, Snodgrass JJ (2007) What a drop can do: dried blood spots as a minimally invasive method for integrating biomarkers into population-based research. Demography 44:899–925
McPhillips JB, Pellettera KM, Barrett-Connor E, Wingard DL, Criqui MH (1989) Exercise patterns in a population of older adults. Am J Prev Med 5:65–72
Nolan RP, Reid GJ, Seidelin PH, Lau HK (2007) C-reactive protein modulates vagal heart rate control in patients with coronary artery disease. Clin Sci 112:449–456
Pearson TA, Mensah GA, Alexander RW, Anderson JL, Cannon RO, Criqui M, Fadl YY, Fortmann SP, Hong Y, Myers GL, Fifai N, Smith SC, Taubert K, Tracy RP, Vinicor F (2003) Markers of inflammation and cardiovascular disease: application to clinical and public health practice: a statement for healthcare professionals from the Centers for Disease Control and Prevention and the American Heart Association. Circulation 107:499–511
Sajadieh A, Nielsen OW, Rasmussen V, Hein HO, Abedini S, Hansen JF (2004) Increased heart rate and reduced heart-rate variability are associated with subclinical inflammation in middle-aged and elderly subjects with no apparent heart disease. Eur Heart J 25:363–370
Sherwood A, Allen MT, Fahrenberg J, Kelsey RM, Lovallo WR, Van Doornen LJ (1990) Methodological guidelines for impedence cardiography. Psychophysiology 27:1–23
Sloan RP, McCreath H, Tracey KJ, Sidney S, Liu K, Seeman T (2007) RR interval variability is inversely related to inflammatory markers: the CARDIA Study. Mol Med 13:178–184
Stein PK, Barzilay JI, Chaves PHM, Traber J, Domitrovich PP, Heckbert SR, Gottdiener JS (2008) Higher levels of inflammation factors and greater insulin resistance are independently associated with higher heart rate and lower heart rate variability in normoglycemic older individuals: The Cardiovascular Health Study. J Am Geriatr Soc 56:315–321
Tracey KJ (2007) Physiology and immunology of the cholinergic antiinflammatory pathway. J Clin Invest 117:289–296
Wang H, Liao H, Ochani M, Justiniani M, Lin X, Yang L, Al-Abed Y, Wang H, Metz C, Miller EJ, Tracey KJ, Ulloa L (2004) Cholinergic agonists inhibit HMGB1 release and improve survival in experimental sepsis. Nat Med 10:1216–1221
Zhang X, Shu XO, Signorello LB, Hargreaves MK, Cai Q, Linton MF, Fazio S, Zheng W, Blot WJ (2008) Correlates of high serum C-reactive protein levels in a socioeconomically disadvantaged population. Dis Markers 24:351–359
Acknowledgments
This research was supported by a National Institute on Aging Career Development Award 5K08AG027200-02 (P·I. C.M. Masi) and a National Institute on Aging Program Project Grant RO1 AG034052-01 (PI: J.T. Cacioppo).
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Singh, P., Hawkley, L.C., McDade, T.W. et al. Autonomic tone and C-reactive protein: a prospective population-based study. Clin Auton Res 19, 367–374 (2009). https://doi.org/10.1007/s10286-009-0019-0
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DOI: https://doi.org/10.1007/s10286-009-0019-0