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Hemodynamic responses to the cold pressor test in individuals with metabolic syndrome: a case-control study in a multiracial sample of adults

Abstract

Previous research shows that exercise pressor and metaboreflex responses are significantly exaggerated in individuals with metabolic syndrome, but it is unclear if these exaggerated responses extend to the cold pressor test (CPT). This study tested the hypothesis that, contrary to previously reported exaggerated responses during exercise, CPT responses would not be significantly exaggerated in individuals with MetS compared to matched controls. Eleven individuals with MetS and eleven control participants matched by age, race, sex, and ethnicity completed a cardiometabolic prescreening and a CPT. Each CPT required participants to immerse their hand in ice water for two minutes while beat-by-beat blood pressure, heart rate (HR), and leg blood flow (LBF) were continuously measured. Leg vascular conductance (LVC) was calculated as LBF divided by mean arterial pressure (MAP). The precent changes in MAP, systolic blood pressure (SBP), diastolic blood pressure (DBP), HR, LBF, and LVC were compared across time (BL vs. Minutes 1 and 2 of CPT) and between groups (MetS vs. Control) using repeated measures analyses of variance. As expected, MAP (f = 32.11, p < 0.001), SBP (f = 23.18, p < 0.001), DBP (f = 40.39, p < 0.001), and HR (f = 31.81, p < 0.001) increased during the CPT, and LBF (f = 4.75, p = 0.014) and LVC (f = 13.88, p < 0.001) decreased. However, no significant main effects of group or group by time interactions were observed (f ≤ 0.391, p ≥ 0.539). These findings indicate that the hemodynamic responses to the CPT are not significantly exaggerated in MetS, and therefore, previous reports of exaggerated exercise pressor and metaboreflex responses in MetS cannot be attributed to generalized sympathetic overexcitability.

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Fig. 1: Blood pressure and heart rate responses to the cold pressor test.
Fig. 2: Blood flow and vascular conductance responses to the cold pressor test.
Fig. 3: Results from two-one sided t-tests (TOST) employing three separate bounds of equivalence.

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Data availability

The raw data used in this study will be made available by authors upon reasonable request without undue delay and within the regulations of the University of Southern Mississippi.

References

  1. Victor RG, Leimbach WN Jr, Seals DR, Wallin BG, Mark AL. Effects of the cold pressor test on muscle sympathetic nerve activity in humans. Hypertension. 1987;9:429–36.

    Article  CAS  PubMed  Google Scholar 

  2. Yamamoto K, Iwase S, Mano T. Responses of muscle sympathetic nerve activity and cardiac output to the cold pressor test. Jpn J Physiol. 1992;42:239–52.

    Article  CAS  PubMed  Google Scholar 

  3. Kasagi F, Akahoshi M, Shimaoka K. Relation between cold pressor test and development of hypertension based on 28-year follow-up. Hypertension. 1995;25:71–76.

    Article  CAS  PubMed  Google Scholar 

  4. Han Y, Du J, Wang J, Liu B, Yan YL, Deng SB, et al. Cold Pressor Test in Primary Hypertension: A Cross-Sectional Study. Front Cardiovasc Med. 2022;9:860322.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Wood DL, Sheps SG, Elveback LR, Schirger A. Cold pressor test as a predictor of hypertension. Hypertension. 1984;6:301–6.

    Article  CAS  PubMed  Google Scholar 

  6. Dutra-Marques AC, Rodrigues S, Cepeda FX, Toschi-Dias E, Rondon E, Carvalho JC, et al. Exaggerated Exercise Blood Pressure as a Marker of Baroreflex Dysfunction in Normotensive Metabolic Syndrome Patients. Front Neurosci. 2021;15:680195.

    Article  PubMed  PubMed Central  Google Scholar 

  7. Stavres J, Aultman RA, Brandner CF, Newsome TQA, Vallecillo-Bustos A, Wise HL et al. Hemodynamic responses to handgrip and metaboreflex activation are exaggerated in individuals with metabolic syndrome independent of resting blood pressure, waist circumference, and fasting blood glucose. Front Physiol. 2023;14:1212775.

  8. Eldridge FL, Millhorn DE, Kiley JP, Waldrop TG. Stimulation by central command of locomotion, respiration and circulation during exercise. Respir Physiol. 1985;59:313–37.

    Article  CAS  PubMed  Google Scholar 

  9. Gandevia SC, Macefield VG, Bigland-Ritchie B, Gorman RB, Burke D. Motoneuronal output and gradation of effort in attempts to contract acutely paralysed leg muscles in man. J Physiol. 1993;471:411–27.

  10. Amann M, Blain GM, Proctor LT, Sebranek JJ, Pegelow DF, Dempsey JA. Group III and IV muscle afferents contribute to ventilatory and cardiovascular response to rhythmic exercise in humans. J Appl Physiol. 2010;109:966–76.

    Article  PubMed  PubMed Central  Google Scholar 

  11. Kaufman MP, Longhurst JC, Rybicki KJ, Wallach JH, Mitchell JH. Effects of static muscular contraction on impulse activity of group III and IV afferents in cats. J Appl Physiol. 1983;55:105–12.

    Article  CAS  PubMed  Google Scholar 

  12. Tschakovsky ME, Hughson RL. Rapid blunting of sympathetic vasoconstriction in the human forearm at the onset of exercise. J Appl Physiol. 2003;94:1785–92.

    Article  CAS  PubMed  Google Scholar 

  13. Kuniyoshi FH, Trombetta IC, Batalha LT, Rondon MU, Laterza MC, Gowdak MM, et al. Abnormal neurovascular control during sympathoexcitation in obesity. Obes Res. 2003;11:1411–9.

    Article  PubMed  Google Scholar 

  14. Park J, Middlekauff HR, Campese VM. Abnormal sympathetic reactivity to the cold pressor test in overweight humans. Am J Hypertens. 2012;25:1236–41.

    PubMed  PubMed Central  Google Scholar 

  15. Lee BS, Kim KA, Kim JK, Nho H. Augmented Hemodynamic Responses in Obese Young Men during Dynamic Exercise: Role of the Muscle Metaboreflex. Int J Environ Res Public Health. 2020;17:7321.

  16. Sayinalp S, Sözen T, Ozdoğan M. Cold pressor test in diabetic autonomic neuropathy. Diabetes Res Clin Pract. 1994;26:21–8.

    Article  CAS  PubMed  Google Scholar 

  17. Holwerda SW, Restaino RM, Manrique C, Lastra G, Fisher JP, Fadel PJ. Augmented pressor and sympathetic responses to skeletal muscle metaboreflex activation in type 2 diabetes patients. Am J Physiol Heart Circ Physiol. 2016;310:H300–9.

    Article  PubMed  Google Scholar 

  18. Grundy SM, Cleeman JI, Daniels SR, Donato KA, Eckel RH, Franklin BA, et al. Diagnosis and Management of the Metabolic Syndrome. Circulation. 2005;112:e285–e290.

    Google Scholar 

  19. Stavres J, Aultman RS, Brandner CF, Newsome TQA, Vallecillo-Bustos A, Graybeal AJ. Fat-free mass is associated with exercise pressor responses, but not cold pressor responses, in humans: influence of maximal voluntary contraction. Front Sports Active Living. 2024;6:1352192.

  20. Faul F, Erdfelder E, Lang AG, Buchner AG. Power 3: a flexible statistical power analysis program for the social, behavioral, and biomedical sciences. Behav Res Methods. 2007;39:175–91.

    Article  PubMed  Google Scholar 

  21. Cohen J. Statistical Power Analysis for the Behavioral Sciences. 2nd edn. New York: Routledge; 1988.

    Google Scholar 

  22. Seals DR, Enoka RM. Sympathetic activation is associated with increases in EMG during fatiguing exercise. J Appl Physiol. 1989;66:88–95.

    Article  CAS  PubMed  Google Scholar 

  23. Coutsos M, Sala-Mercado JA, Ichinose M, Li Z, Dawe EJ, O’Leary DS. Muscle metaboreflex-induced coronary vasoconstriction functionally limits increases in ventricular contractility. J Appl Physiol. 2010;109:271–8.

    Article  PubMed  PubMed Central  Google Scholar 

  24. Kaur J, Machado TM, Alvarez A, Krishnan AC, Hanna HW, Altamimi YH, et al. Muscle metaboreflex activation during dynamic exercise vasoconstricts ischemic active skeletal muscle. Am J Physiol Heart Circ Physiol. 2015;309:H2145–51.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Monahan KD, Feehan RP, Sinoway LI, Gao Z. Contribution of sympathetic activation to coronary vasodilatation during the cold pressor test in healthy men: effect of ageing. J Physiol. 2013;591:2937–47.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. O’Leary DS, Sala-Mercado JA, Hammond RL, Ansorge EJ, Kim JK, Rodriguez J, et al. Muscle metaboreflex-induced increases in cardiac sympathetic activity vasoconstrict the coronary vasculature. J Appl Physiol. 2007;103:190–4.

    Article  PubMed  Google Scholar 

  27. Kalfon R, Campbell J, Alvarez-Alvarado S, Figueroa A. Aortic Hemodynamics and Arterial Stiffness Responses to Muscle Metaboreflex Activation With Concurrent Cold Pressor Test. Am J Hypertens. 2015;28:1332–8.

    Article  PubMed  Google Scholar 

  28. Estrada JA, Ducrocq GP, Kaufman MP. The magnitude of the exercise pressor reflex is influenced by the active skeletal muscle mass in the decerebrate rat. Am J Physiol Regul Integr Comp Physiol. 2020;318:R30–r37.

    Article  CAS  PubMed  Google Scholar 

  29. Lee JB, Katerberg C, Bommarito J, Power GA, Millar PJ. Blood Pressure Responses to Post-Exercise Circulatory Occlusion Are Attenuated Following Exercise-Induced Muscle Weakness. Med Sci Sports Exerc. 2023;55:1660–71.

  30. Kawakami R, Tanisawa K, Ito T, Usui C, Miyachi M, Torii S, et al. Fat-Free Mass Index as a Surrogate Marker of Appendicular Skeletal Muscle Mass Index for Low Muscle Mass Screening in Sarcopenia. J Am Med Directors Assoc. 2022;23:1955–1961.e3.

    Article  Google Scholar 

  31. ten Hoor GA, Plasqui G, Schols AMWJ, Kok G. A Benefit of Being Heavier Is Being Strong: a Cross-Sectional Study in Young Adults. Sports Med. 2018;4:12.

    Google Scholar 

  32. Hines EA, Brown GE. The cold pressor test for measuring the reactibility of the blood pressure: Data concerning 571 normal and hypertensive subjects. Am Heart J. 1936;11:1–9.

    Article  Google Scholar 

  33. Carvalho LP, Di Thommazo-Luporini L, Mendes RG, Cabiddu R, Ricci PA, Basso-Vanelli RP, et al. Metabolic syndrome impact on cardiac autonomic modulation and exercise capacity in obese adults. Auton Neurosci. 2018;213:43–50.

    Article  PubMed  Google Scholar 

  34. Endukuru CK, Gaur GS, Yerrabelli D, Sahoo J, Vairappan B. Impaired baroreflex sensitivity and cardiac autonomic functions are associated with cardiovascular disease risk factors among patients with metabolic syndrome in a tertiary care teaching hospital of South-India. Diabetes Metab Syndr. 2020;14:2043–51.

    Article  PubMed  Google Scholar 

  35. Grassi G, Dell’Oro R, Quarti-Trevano F, Scopelliti F, Seravalle G, Paleari F, et al. Neuroadrenergic and reflex abnormalities in patients with metabolic syndrome. Diabetologia. 2005;48:1359–65.

    Article  CAS  PubMed  Google Scholar 

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Acknowledgements

The authors would like to thank Kieron Cox, Diavion Stanfield, Alex Henderson, Havens L. Wise, Brandy Lowe, and Anne Speed for their technical support.

Funding

This study was supported by the Mississippi Center for Clinical and Translational Research, the National Institutes of Health, and the National Institute of General Medical Sciences (U54GM115428), as well as the University of Southern Mississippi (to J. Stavres and A.J. Graybeal).

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Conceived and designed research: JS and AJG; Performed experiments: JS, RA, TN, AVB, CFB, AJG; Analyzed data: JS, RA, TN, AVB, CFB, AJG; Interpreted results of experiments: JS, RA, TN, AVB, CFB, AJG; Prepared figures: JS; Drafted manuscript: JS; Edited and revised manuscript: JS, RA, TN, AVB, CFB, AJG; Approved final version of manuscript: JS, RA, TN, AVB, CFB, AJG.

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Correspondence to Jon Stavres.

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The protocols used in this study were approved by the University of Southern Mississippi internal review board (IRB# 22-1012) and all subjects provided written informed consent.

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Stavres, J., Vallecillo-Bustos, A., Newsome, T.A. et al. Hemodynamic responses to the cold pressor test in individuals with metabolic syndrome: a case-control study in a multiracial sample of adults. J Hum Hypertens 38, 655–662 (2024). https://doi.org/10.1038/s41371-024-00938-x

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