Abstract
Purpose
The long-term implications of premature birth on autonomic nervous system (ANS) function are unclear. Heart rate recovery (HRR) following maximal exercise is a simple tool to evaluate ANS function and is a strong predictor of cardiovascular disease. Our objective was to determine whether HRR is impaired in young adults born preterm (PYA).
Methods
Individuals born between 1989 and 1991 were recruited from the Newborn Lung Project, a prospectively followed cohort of subjects born preterm weighing < 1500 g with an average gestational age of 28 weeks. Age-matched term-born controls were recruited from the local population. HRR was measured for 2 min following maximal exercise testing on an upright cycle ergometer in normoxia and hypoxia, and maximal aerobic capacity (VO2max) was measured.
Results
Preterms had lower VO2max than controls (34.88 ± 5.24 v 46.15 ± 10.21 ml/kg/min, respectively, p < 0.05), and exhibited slower HRR compared to controls after 1 and 2 min of recovery in normoxia (absolute drop of 20 ± 4 v 31 ± 10 and 41 ± 7 v 54 ± 11 beats per minute (bpm), respectively, p < 0.01) and hypoxia (19 ± 5 v 26 ± 8 and 39 ± 7 v 49 ± 13 bpm, respectively, p < 0.05). After adjusting for VO2max, HRR remained slower in preterms at 1 and 2 min of recovery in normoxia (21 ± 2 v 30 ± 2 and 42 ± 3 v 52 ± 3 bpm, respectively, p < 0.05), but not hypoxia (19 ± 3 v 25 ± 2 and 40 ± 4 v 47 ± 3 bpm, respectively, p > 0.05).
Conclusions
Autonomic dysfunction as seen in this study has been associated with increased rates of cardiovascular disease in non-preterm populations, suggesting further study of the mechanisms of autonomic dysfunction after preterm birth.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
Abbreviations
- ANS:
-
Autonomic nervous system
- GPAQ:
-
Global Physical Activity Questionnaire
- HR:
-
Heart rate
- HRmax :
-
Maximal heart rate
- HRR:
-
Heart rate recovery
- MET:
-
Metabolic equivalent
- P max :
-
Maximal power
- T max :
-
Maximal time to exhaustion
- VO2max :
-
Maximal aerobic capacity
- VTVO2 :
-
Oxygen consumption per kg of body weight at ventilatory threshold
References
Amann M, Kayser B (2009) Nervous system function during exercise in hypoxia. High Alt Med Biol 10(2):149–164. https://doi.org/10.1089/ham.2008.1105
Amann M, Pegelow DF, Jacques AJ, Dempsey JA (2007) Inspiratory muscle work in acute hypoxia influences locomotor muscle fatigue and exercise performance of healthy humans. Am J Physiol Regul Integr Comp Physiol 293(5):R2036–R2045. https://doi.org/10.1152/ajpregu.00442.2007
Bates ML, Farrell ET, Eldridge MW (2014) Abnormal ventilatory responses in adults born prematurely. N Engl J Med 370(6):584–585. https://doi.org/10.1056/NEJMc1311092
Bilsel T, Terzi S, Akbulut T, Sayar N, Hobikoglu G, Yesilcimen K (2006) Abnormal heart rate recovery immediately after cardiopulmonary exercise testing in heart failure patients. Int Heart J 47(3):431–440. https://doi.org/10.1536/ihj.47.431
Bull FC, Maslin TS, Armstrong T (2009) Global physical activity questionnaire (GPAQ): nine country reliability and validity study. J Phys Activity Health 6(6):790–804
Centers for Disease Control and Prevention (2015) Preterm Birth. https://www.cdc.gov/reproductivehealth/maternalinfanthealth/pretermbirth.htm. Accessed 21 June 2017
Cleland CL, Hunter RF, Kee F, Cupples ME, Sallis JF, Tully MA (2014) Validity of the global physical activity questionnaire (GPAQ) in assessing levels and change in moderate-vigorous physical activity and sedentary behaviour. BMC Public Health. https://doi.org/10.1186/1471-2458-14-1255
Cohen J (1988) Statistical power analysis for the behavioral sciences, 2nd edn. L. Erlbaum Associates, Hillsdale
Cole CR, Blackstone EH, Pashkow FJ, Snader CE, Lauer MS (1999) Heart-rate recovery immediately after exercise as a predictor of mortality. N Engl J Med 341(18):1351–1357. https://doi.org/10.1056/nejm199910283411804
Cole CR, Foody JM, Blackstone EH, Lauer MS (2000) Heart rate recovery after submaximal exercise testing as a predictor of mortality in a cardiovascularly healthy cohort. Ann Intern Med 132(7):552–555
Davrath LR, Akselrod S, Pinhas I, Toledo E, Beck A, Elian D, Scheinowitz M (2006) Evaluation of autonomic function underlying slow postexercise heart rate recovery. Med Sci Sports Exerc 38(12):2095–2101. https://doi.org/10.1249/01.mss.0000235360.24308.c7
de Meautsart CC, Dyson RM, Latter JL, Berry MJ, Clifton VL, Wright IMR (2016) Influence of sympathetic activity in the control of peripheral microvascular tone in preterm infants. Pediatr Res 80(6):793–799. https://doi.org/10.1038/pr.2016.160
Duke JW, Elliott JE, Laurie SS, Beasley KM, Mangum TS, Hawn JA, Gladstone IM, Lovering AT (2014) Pulmonary gas exchange efficiency during exercise breathing normoxic and hypoxic gas in adults born very preterm with low diffusion capacity. J Appl Physiol (1985). https://doi.org/10.1152/japplphysiol.00307.2014
Evrengul H, Tanriverdi H, Kose S, Amasyali B, Kilic A, Celik T, Turhan H (2006) The relationship between heart rate recovery and heart rate variability in coronary artery disease. Ann Noninvasive Electrocardiol 11(2):154–162. https://doi.org/10.1111/j.1542-474X.2006.00097.x
Farrell ET, Bates ML, Pegelow DF, Palta M, Eickhoff JC, O’Brien MJ, Eldridge MW (2015) Pulmonary gas exchange and exercise capacity in adults born preterm. Ann Am Thorac Soc 12(8):1130–1137. https://doi.org/10.1513/AnnalsATS.201410-470OC
Florea VG, Cohn JN (2014) The autonomic nervous system and heart failure. Circ Res 114(11):1815–1826. https://doi.org/10.1161/circresaha.114.302589
Gagnon R, Campbell K, Hunse C, Patrick J (1987) Patterns of human-fetal heart-rate accelerations from 26 weeks to term. Am J Obstet Gynecol 157(3):743–748
Haraldsdottir K, Watson AM, Goss KN, Beshish AG, Pegelow DF, Palta M, Tetri LH, Barton GP, Brix MD, Centanni RM, Eldridge MW (2018) Impaired autonomic function in adolescents born preterm. Physiol Rep 6(6):e13620. https://doi.org/10.14814/phy2.13620
Hargens TA, Guill SG, Zedalis D, Gregg JM, Nickols-Richardson SM, Herbert WG (2008) Attenuated heart rate recovery following exercise testing in overweight young men with untreated obstructive sleep apnea. Sleep 31(1):104–110
Hautala AJ, Rankinen T, Kiviniemi AM, Makikallio TH, Huikuri HV, Bouchard C, Tulppo MP (2006) Heart rate recovery after maximal exercise is associated with acetylcholine receptor M2 (CHRM2) gene polymorphism. Am J Physiol Heart Circ Physiol 291(1):H459–H466. https://doi.org/10.1152/ajpheart.01193.2005
Holm S (1979) A simple sequentially rejective multiple test procedure. Scand J Stat 6(2):65–70
Imai K, Sato H, Hori M, Kusuoka H, Ozaki H, Yokoyama H, Takeda H, Inoue M, Kamada T (1994) Vagally mediated heart-rate recovery after exercise is accelerated in athletes but blunted in patients with chronic heart-failure. J Am Coll Cardiol 24(6):1529–1535
Jae SY, Carnethon MR, Heffernan KS, Choi YH, Lee MK, Park WH, Fernhall B (2008) Slow heart rate recovery after exercise is associated with carotid atherosclerosis. Atherosclerosis 196(1):256–261. https://doi.org/10.1016/j.atherosclerosis.2006.10.023
Johansson S, Norman M, Legnevall L, Dalmaz Y, Lagercrantz H, Vanpee M (2007) Increased catecholamines and heart rate in children with low birth weight: perinatal contributions to sympathoadrenal overactivity. J Intern Med 261(5):480–487. https://doi.org/10.1111/j.1365-2796.2007.01776.x
Joyner MJ, Charkoudian N, Wallin BG (2010) Sympathetic nervous system and blood pressure in humans: individualized patterns of regulation and their implications. Hypertension 56(1):10–16. https://doi.org/10.1161/HYPERTENSIONAHA.109.140186
Kennedy MD, Warburton DE, Boliek CA, Esch BT, Scott JM, Haykowsky MJ (2008) The oxygen delivery response to acute hypoxia during incremental knee extension exercise differs in active and trained males. Dyn Med DM 7:11. https://doi.org/10.1186/1476-5918-7-11
Kishi T (2012) Heart failure as an autonomic nervous system dysfunction. J Cardiol 59(2):117–122. https://doi.org/10.1016/j.jjcc.2011.12.006
Kleiger RE, Stein PK, Bigger JT (2005) Heart rate variability: Measurement and clinical utility. Ann Noninvasive Electrocardiol 10(1):88–101. https://doi.org/10.1111/j.1542-474X.2005.10101.x
Kuo HK, Gore JM (2015) Relation of heart rate recovery after exercise to insulin resistance and chronic inflammation in otherwise healthy adolescents and adults: results from the National Health and Nutrition Examination Survey (NHANES) 1999–2004. Clin Res Cardiol 104(9):764–772. https://doi.org/10.1007/s00392-015-0843-2
Lewandowski AJ, Bradlow WM, Augustine D, Davis EF, Francis J, Singhal A, Lucas A, Neubauer S, McCormick K, Leeson P (2013) Right ventricular systolic dysfunction in young adults born preterm. Circulation 128(7):713–720. https://doi.org/10.1161/circulationaha.113.002583
Mathewson KJ, Van Lieshout RJ, Saigal S, Morrison KM, Boyle MH, Schmidt LA (2015) Autonomic functioning in young adults born at extremely low birth weight. Glob Pediatr Health 2:2333794 × 15589560. https://doi.org/10.1177/2333794X15589560
Midgley AW, McNaughton LR, Polman R, Marchant D (2007) Criteria for determination of maximal oxygen uptake—a brief critique and recommendations for future research. Sports Med 37(12):1019–1028. https://doi.org/10.2165/00007256-200737120-00002
Minai OA, Gudavalli R, Mummadi S, Liu XB, McCarthy K, Dweik RA (2012) Heart rate recovery predicts clinical worsening in patients with pulmonary arterial hypertension. Am J Respir Crit Care Med 185(4):400–408. https://doi.org/10.1164/rccm.201105-0848OC
Mitchell JH (1985) Cardiovascular control during exercise-central and reflex neural mechanisms. Am J Cardiol 55(10):D34–D41. https://doi.org/10.1016/0002-9149(85)91053-7
Morshedi-Meibodi A, Larson MG, Levy D, O’Donnell CJ, Vasan RS (2002) Heart rate recovery after treadmill exercise testing and risk of cardiovascular disease events (the Framingham Heart Study). Am J Cardiol 90(8):848–852. https://doi.org/10.1016/s0002-9149(02)02706-6
Norman M (2010) Preterm birth—an emerging risk factor for adult hypertension? Semin Perinatol 34(3):183–187. https://doi.org/10.1053/j.sempen.2010.02.009
Ostojic SM, Markovic G, Calleja-Gonzalez J, Jakovljevic DG, Vucetic V, Stojanovic MD (2010) Ultra short-term heart rate recovery after maximal exercise in continuous versus intermittent endurance athletes. Eur J Appl Physiol 108(5):1055–1059. https://doi.org/10.1007/s00421-009-1313-1
Palta M, Weinstein MR, McGuinness G, Gabbert D, Brady W, Peters ME (1994) A population study. Mortality and morbidity after availability of surfactant therapy. Newborn Lung Project Arch Pediatr Adolesc Med 148(12):1295–1301
Palta M, Sadek M, Barnet JH, Evans M, Weinstein MR, McGuinness G, Peters ME, Gabbert D, Fryback D, Farrell P (1998) Evaluation of criteria for chronic lung disease in surviving very low birth weight infants. Newborn Lung Project J Pediatr 132(1):57–63
Palta M, Sadek-Badawi M, Evans M, Weinstein MR, McGuinnes G (2000) Functional assessment of a multicenter very low-birth-weight cohort at age 5 years. Newborn Lung Project. Arch Pediatr Adolesc Med 154(1):23–30
Palta M, Sadek-Badawi M, Sheehy M, Albanese A, Weinstein M, McGuinness G, Peters ME (2001) Respiratory symptoms at age 8 years in a cohort of very low birth weight children. Am J Epidemiol 154(6):521–529
Patural H, Barthelemy JC, Pichot V, Mazzocchi C, Teyssier G, Damon G, Roche F (2004) Birth prematurity determines prolonged autonomic nervous system immaturity. Clin Auton Res 14(6):391–395. https://doi.org/10.1007/s10286-004-0216-9
Peacock JL, Marston L, Marlow N, Calvert SA, Greenough A (2012) Neonatal and infant outcome in boys and girls born very prematurely. Pediatr Res 71(3):305–310. https://doi.org/10.1038/pr.2011.50
Pierpont GL, Adabag S, Yannopoulos D (2013) Pathophysiology of exercise heart rate recovery: a comprehensive analysis. Ann Noninvasive Electrocardiol 18(2):107–117. https://doi.org/10.1111/anec.12061
Porges SW, Furman SA (2011) The early development of the autonomic nervous system provides a neural platform for social behaviour: a polyvagal perspective. Infant Child Dev 20(1):106–118. https://doi.org/10.1002/icd.688
Prabhakar NR, Peng YJ (2004) Peripheral chemoreceptors in health and disease. J Appl Physiol 96(1):359–366. https://doi.org/10.1152/japplphysiol.00809.2003
Qiu SH, Cai X, Sun ZL, Li L, Zuegel M, Steinacker JM, Schumann U (2017) Heart rate recovery and risk of cardiovascular events and all-cause mortality: a meta-analysis of prospective cohort studies. J Am Heart Assoc. https://doi.org/10.1161/jaha.117.005505
R Development Core Team (2010) R: a language and environment for statistical computing. R Foundation for Statistical Computing, Vienna
Ramos RP, Arakaki JSO, Barbosa P, Treptow E, Valois FM, Ferreira EVM, Nery LE, Neder JA (2012) Heart rate recovery in pulmonary arterial hypertension: Relationship with exercise capacity and prognosis. Am Heart J 163(4):580–588. https://doi.org/10.1016/j.ahj.2012.01.023
Savin WM, Davidson DM, Haskell WL (1982) Autonomic contribution to heart-rate recovery from exercise in humans. J Appl Physiol 53(6):1572–1575
Thayer JF, Lane RD (2007) The role of vagal function in the risk for cardiovascular disease and mortality. Biol Psychol 74(2):224–242. https://doi.org/10.1016/j.biopsycho.2005.11.013
Watanabe J, Thamilarasan M, Blackstone EH, Thomas JD, Lauer MS (2001) Heart rate recovery immediately after treadmill exercise and left ventricular systolic dysfunction as predictors of mortality—the case of stress echocardiography. Circulation 104(16):1911–1916
Watson AM, Brickson SL, Prawda ER, Sanfilippo JL (2017) Short-term heart rate recovery is related to aerobic fitness in elite intermittent sport athletes. J Strength Conditioning Res 31(4):1055–1061. https://doi.org/10.1519/jsc.0000000000001567
Weinstein MR, Peters ME, Sadek M, Palta M (1994) A new radiographic scoring system for bronchopulmonary dysplasia. Newborn Lung Project Pediatr Pulmonol 18(5):284–289
Yiallourou SR, Witcombe NB, Sands SA, Walker AM, Horne RSC (2013) The development of autonomic cardiovascular control is altered by preterm birth. Early Human Dev 89(3):145–152. https://doi.org/10.1016/j.earlhumdev.2012.09.009
Yiallourou SR, Wallace EM, Whatley C, Odoi A, Hollis S, Weichard AJ, Muthusamy JS, Varma S, Cameron J, Narayan O, Horne RSC (2017) Sleep: a window into autonomic control in children born preterm and growth restricted. Sleep. https://doi.org/10.1093/sleep/zsx048
Funding
National Institutes of Health: NIH-NHLBI R01-HL115061, NIH-NHLBI R01Supplement-HL1150613 (PI Eldridge), T32-HL 07936 (Haraldsdottir).
Author information
Authors and Affiliations
Contributions
KH, AMW, KNG, and MWE conceptualized and designed the study and are the guarantor of the content of the manuscript, including the data and analysis. KH, AMW, KNG, AGB, DFP, LHT, MDB, RMC, and MWE assisted with data collection. KH, AMW, KNG, AGB, MP, LHT, MDB, RMC, and MWE contributed to the analysis and interpretation of data. AMW conducted statistical analysis. KH and AMW prepared figures. KH drafted the initial manuscript. All authors reviewed, revised, and approved the final manuscript as submitted.
Corresponding author
Additional information
Communicated by Massimo Pagani.
Publisher’s Note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Rights and permissions
About this article
Cite this article
Haraldsdottir, K., Watson, A.M., Beshish, A.G. et al. Heart rate recovery after maximal exercise is impaired in healthy young adults born preterm. Eur J Appl Physiol 119, 857–866 (2019). https://doi.org/10.1007/s00421-019-04075-z
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00421-019-04075-z