Oral Fludrocortisone Test for Salt-Sensitive Screening in Hypertensive Patients: A Randomized Crossover Trial

Andrea Pio-Abreu, Isac de Castro, Giovanio Vieira da Silva, Katia Coelho Ortega, Decio Mion Jr, Andrea Pio-Abreu, Isac de Castro, Giovanio Vieira da Silva, Katia Coelho Ortega, Decio Mion Jr

Abstract

Background: Salt sensitivity is associated with an increased cardiovascular risk, but the gold standard method (diet cycles) requires 24-h urine samples and has poor patient compliance.

Objectives: Test the hypothesis that oral fludrocortisone (0.4 mg per day for 7 days) is a good alternative in identifying salt-sensitive patients.

Methodology: We conducted a randomized crossover study with 30 hypertensive individuals comprising the following steps: (1) washout; (2) phase A (low- and high-sodium diet cycles); (3) washout 2; (4) phase B (fludrocortisone test). Phase A and B steps were performed in a random way. Consistent with the literature, we found that 53.3% were salt-sensitive according to the reference test. Using the ROC curve, the fludrocortisone test defined salt sensitivity by a median blood pressure increase of ≥3 mmHg. A good accuracy of fludrocortisone in detecting salt sensitivity was observed (AUC: 0.732±0.065; p<0.001), with 80% sensitivity and 53% specificity.

Conclusion: The fludrocortisone test is a good option for screening salt sensitivity in hypertensive patients. However, the low specificity prevents this test from being an ideal substitute to the labor-intensive diet cycles exam in the definition of salt sensitivity. This clinical trial is registered with NCT01453959.

Figures

Figure 1
Figure 1
Study randomized crossover design. Na+ = sodium.

References

    1. Kotchen T. A., Cowley A. W., Jr., Frohlich E. D. Salt in health and disease - A delicate balance. The New England Journal of Medicine. 2013;368(13):1229–1237. doi: 10.1056/NEJMra1212606.
    1. Weinberger M. H. Salt sensitivity of blood pressure in humans. Hypertension. 1996;27(3):481–490. doi: 10.1161/01.HYP.27.3.481.
    1. Rocchini A. P., Key J., Bondie D., et al. The Effect of Weight Loss on the Sensitivity of Blood Pressure to Sodium in Obese Adolescents. The New England Journal of Medicine. 1989;321(9):580–585. doi: 10.1056/NEJM198908313210905.
    1. GenSalt Collaborative Research Group. GenSalt: rationale, design, methods and baseline characteristics of study participants. Journal of Human Hypertension. 2007;21(8):639–646. doi: 10.1038/sj.jhh.1002207.
    1. Weinberger M. H., Miller J. Z., Luft F. C., Grim C. E., Fineberg N. S. Definitions and characteristics of sodium sensitivity and blood pressure resistance. Hypertension. 1986;8(6):127–II-134.
    1. Elijovich F., Weinberger M. H., Anderson C. A. M., et al. Salt sensitivity of blood pressure : A scientific statement from the American Heart Association. Hypertension. 2016;68(3):e7–e46.
    1. Heimann J. C., Drumond S., Alves A. T. R., Barbato A. J. G., Dichtchekenian V., Marcondes M. Left ventricular hypertrophy is more marked in salt-sensitive than in salt-resistant hypertensive patients. Journal of Cardiovascular Pharmacology. 1991;17(2):S122–S124. doi: 10.1097/00005344-199117002-00028.
    1. Bihorac A., Tezcan H., Özener Ç., Oktay A., Akoglu E. Association between salt sensitivity and target organ damage in essential hypertension. American Journal of Hypertension. 2000;13(8):864–872. doi: 10.1016/S0895-7061(00)00253-3.
    1. Franco V., Oparil S. Salt Sensitivity, a Determinant of Blood Pressure, Cardiovascular Disease and Survival. Journal of the American College of Nutrition. 2006;25:247–255. doi: 10.1080/07315724.2006.10719574.
    1. Sharma A. M., Ruland K., Spies K.-P., Distler A. Salt sensitivity in young normotensive subjects is associated with a hyperinsulinemic response to oral glucose. Journal of Hypertension. 1991;9(4):329–335. doi: 10.1097/00004872-199104000-00004.
    1. Morimoto A., Uzu T., Fujii T., et al. Sodium sensitivity and cardiovascular events in patients with essential hypertension. The Lancet. 1997;350(9093):1734–1737. doi: 10.1016/S0140-6736(97)05189-1.
    1. Luft F. C., Grim C. E., Higgins Jr J. T., Weinberger M. H. Differences in response to sodium administration in normotensive white and blacks subjects. J Lab Clin Med. 1997;90:555–562.
    1. Sharma A. M., Schattenfroh S., Kribben A., Distler A. Reliability of salt-sensitivity testing in normotensive subjects. Klinische Wochenschrift. 1989;67(12):632–634. doi: 10.1007/BF01718145.
    1. World Health Organization. Reducing salt intake in populations: report of a WHO fórum and technical meeting. 2007. .
    1. De La Sierra A., Giner V., Bragulat E., Coca A. Lack of correlation between two methods for the assessment of salt sensitivity in essential hypertension. Journal of Human Hypertension. 2002;16(4):255–260. doi: 10.1038/sj/jhh/1001375. doi: 10.1038/sj.jhh.1001375.
    1. Kurtz T. W., Dicarlo S. E., Pravenec M., Morris R. C. The American Heart Association Scientific Statement on salt sensitivity of blood pressure: Prompting consideration of alternative conceptual frameworks for the pathogenesis of salt sensitivity? Journal of Hypertension. 2017;35(11):2214–2225. doi: 10.1097/HJH.0000000000001458.
    1. Felder R. A., White M. J., Williams S. M., Jose P. A. Diagnostic tools for hypertension and salt sensitivity testing. Current Opinion in Nephrology and Hypertension. 2013;22(1):65–76. doi: 10.1097/MNH.0b013e32835b3693.
    1. Kurtz T. W., DiCarlo S. E., Pravenec M., Morris R. C. An Appraisal of Methods Recently Recommended for Testing Salt Sensitivity of Blood Pressure. Journal of the American Heart Association. 2017;6(4) doi: 10.1161/JAHA.117.005653.
    1. Villa L., Sala G., Ballabio C. B. Clinical and Metabolic Effects of 1-Dehydro-9-Alpha-Fluoro Hydrocortisone Acetate. Annals of the Rheumatic Diseases. 1956;15(3):237–240. doi: 10.1136/ard.15.3.237.
    1. Mion D., Jr., Rea R. F., Anderson E. A., Kahn D., Sinkey C. A., Mark A. L. Effects of fludrocortisone on sympathetic nerve activity in humans. Hypertension. 1994;23(1):123–130. doi: 10.1161/01.HYP.23.1.123.
    1. Mano G. M. P., Souza V. F., Pierin A. M. G., et al. Assessment of the DIXTAL DX-2710 automated oscillometric device for blood pressure measurement with the validation protocols of the British Hypertension society (BHS) and the Association for the Advancement of Medical Instrumentation (AAMI) Arquivos Brasileiros de Cardiologia. 2002;79(6):601–610. doi: 10.1590/S0066-782X2002001500006.
    1. Overlack A., Ruppert M., Kolloch R., et al. Divergent hemodynamic and hormonal responses to varying salt intake in normotensive subjects. Hypertension. 1993;22(3):331–338. doi: 10.1161/01.HYP.22.3.331.
    1. Weir M. R., Hall P. S., Behrens M. T., Flack J. M. Salt and Blood Pressure Responses to Calcium Antagonism in Hypertensive Patients. Hypertension. 1997;30(3):422–427. doi: 10.1161/01.HYP.30.3.422.
    1. Wilson D. K., Sica D. A., Miller S. B. Ambulatory blood pressure nondipping status in salt-sensitive and salt- resistant black adolescents. American Journal of Hypertension. 1999;12(2 I):159–165. doi: 10.1016/S0895-7061(98)00234-9.
    1. Zou K. H., O'Malley A. J., Mauri L. Receiver-operating characteristic analysis for evaluating diagnostic tests and predictive models. Circulation. 2007;115(5):654–657. doi: 10.1161/CIRCULATIONAHA.105.594929.
    1. Galletti F., Strazzullo P. The blood pressure-salt sensitivity paradigm: Pathophysiologically sound yet of no practical value. Nephrology Dialysis Transplantation . 2016;31(9):1386–1391. doi: 10.1093/ndt/gfw295.
    1. Hajian-Tilaki K. The choice of methods in determining the optimal cut-off value for quantitative diagnostic test evaluation. Statistical Methods in Medical Research. 2018;27(8):2374–2383. doi: 10.1177/0962280216680383.
    1. Hajian-Tilaki K. Receiver operating characteristic (ROC) curve analysis for medical diagnostic test evaluation. Caspian Journal of Internal Medicine. 2013;4(2):627–635.
    1. Jones B., Kenward M. G. Design and Analysis of Cross-Over Trials. 1st. London: Chapman & Hall; 1989.

Source: PubMed

Sponsorer och medarbetare

Medicinska tillstånd

Läkemedelsinterventioner

3
Prenumerera