Impact of salt intake on inflammation markers in cardiovascular disease: a retrospective observational case-control study

Background. Salt intake currently poses a serious threat due to the cardiovascular challenge incurred by excessive sodium consumption.

Objectives. The identification of markers associated with high salt intake in hypertensive patients.

Methods. A retrospective observational case-control study surveyed 251 persons, including 194 hypertensive patients with stable salt intake. The intake was assessed in the “Charlton: SaltScreener” questionnaire. General, biochemical blood panels and interleukin levels (IL-1, IL-2, IL-4, IL-6, IL-8, IL-10, IL-18) were evaluated in the outcome of medical examination. Statistical data processing was performed with R using the RStudio software.

Results. The mean patient age in survey was 72.47 ± 9.8 years, women prevailed in the selected cohort (n = 151, 60.1%). All patients were assigned in cohorts by the daily salt intake rate, ≤5 g (n = 12), 6–10 g (n = 144), >10 g salt per day (n = 38). The largest cohort (74.2%) united patients consuming 6–10 g salt per day, whereas only 6.2% patients consumed salt <5 g/day. Final analysis included patients consuming ≥6 g/day and having a C-reactive protein (CRP) level <20 mg/L. The analysis elicited an association between the monocyte count, CRP and salt intake towards the statement that higher salt intake leads to higher monocyte counts at CRP <20 mg/L in blood. Modelling revealed a close monocyte count–salt intake relationship, with a low-to-high intake transition sharply increasing the probability of elevated absolute monocyte count in blood provided the CRP level is <20 mg/L.

Conclusion. The study infers a direct relationship between salt intake >10 g/day and blood monocyte count. However, its significance ceases at CRP rising to ≥20 mg/L.

1. Mozaffarian D., Fahimi S., Singh G.M., Micha R., Khatibzadeh S., Engell R.E., Lim S., Danaei G., Ezzati M., Powles J.; Global Burden of Diseases Nutrition and Chronic Diseases Expert Group. Global sodium consumption and death from cardiovascular causes. N. Engl. J. Med. 2014; 371(7): 624–634. DOI: 10.1056/NEJMoa1304127

2. Suckling R.J., He F.J., Markandu N.D., MacGregor G.A. Dietary salt infl uences postprandial plasma sodium concentration and systolic blood pressure. Kidney Int. 2012; 81(4): 407–411. DOI: 10.1038/ki.2011.369

3. Yamamoto K., Takeda Y., Yamashita S., Sugiura T., Wakamatsu Y., Fukuda M., Ohte N., Dohi Y., Kimura G. Renal dysfunction impairs circadian variation of endothelial function in patients with essential hypertension. J. Am. Soc. Hypertens. 2010; 4(6): 265–271. DOI: 10.1016/j.jash.2010.09.004

4. Kopp C., Linz P., Dahlmann A., Hammon M., Jantsch J., Müller D.N., Schmieder R.E., Cavallaro A., Eckardt K.U., Uder M., Luft F.C., Titze J. 23Na magnetic resonance imaging-determined tissue sodium in healthy subjects and hypertensive patients. Hypertension. 2013; 61(3): 635–640. DOI: 10.1161/HYPERTENSIONAHA.111.00566

5. Intersalt: an international study of electrolyte excretion and blood pressure. Results for 24 hour urinary sodium and potassium excretion. Intersalt Cooperative Research Group. BMJ. 1988; 297(6644): 319–328. DOI: 10.1136/bmj.297.6644.319

6. Nishida C., Uauy R., Kumanyika S., Shetty P. The joint WHO/FAO expert consultation on diet, nutrition and the prevention of chronic diseases: process, product and policy implications. Public. Health. Nutr. 2004; 7(1A): 245–250. DOI: 10.1079/phn2003592

7. Dragunov D.O., Arutyunov G.P., Sokolova A.V. Modern view on the sodium exchange. Clinical Nephrology. 2018; 1: 62–73 (In Russ., English abstract). DOI: 10.18565/nephrology.2018.1.62-73

8. Mills K.T., Chen J., Yang W., Appel L.J., Kusek J.W., Alper A., Delafontaine P., Keane M.G., Mohler E., Ojo A., Rahman M., Ricardo A.C., Soliman E.Z., Steigerwalt S., Townsend R., He J.; Chronic Renal Insuffi ciency Cohort (CRIC) Study Investigators. Sodium Excretion and the Risk of Cardiovascular Disease in Patients With Chronic Kidney Disease. JAMA. 2016; 315(20): 2200–2210. DOI: 10.1001/jama.2016.4447

9. Wang Y.J., Yeh T.L., Shih M.C., Tu Y.K., Chien K.L.. Dietary Sodium Intake and Risk of Cardiovascular Disease: A Systematic Review and Dose-Response Meta-Analysis. Nutrients. 2020; 12(10): 2934. DOI: 10.3390/nu12102934

10. Müller S., Quast T., Schröder A., Hucke S., Klotz L., Jantsch J., Gerzer R., Hemmersbach R., Kolanus W. Salt-dependent chemotaxis of macrophages. PLoS One. 2013; 8(9): e73439. DOI: 10.1371/journal.pone.0073439

11. Padberg J.S., Wiesinger A., di Marco G.S., Reuter S., Grabner A., Kentrup D., Lukasz A., Oberleithner H., Pavenstädt H., Brand M., Kümpers P. Damage of the endothelial glycocalyx in chronic kidney disease. Atherosclerosis. 2014; 234(2): 335–343. DOI: 10.1016/j.atherosclerosis.2014.03.016

12. Rakova N., Jüttner K., Dahlmann A., Schröder A., Linz P., Kopp C., Rauh M., Goller U., Beck L., Agureev A., Vassilieva G., Lenkova L., Johannes B., Wabel P., Moissl U., Vienken J., Gerzer R., Eckardt K.U., Müller D.N., Kirsch K., Morukov B., Luft F.C., Titze J. Long-term space fl ight simulation reveals infradian rhythmicity in human Na(+) balance. Cell Metab. 2013; 17(1): 125–131. DOI: 10.1016/j.cmet.2012.11.013

13. Kawasaki T., Itoh K., Uezono K., Sasaki H. A simple method for estimating 24 h urinary sodium and potassium excretion from second morning voiding urine specimen in adults. Clin. Exp. Pharmacol. Physiol. 1993; 20(1): 7–14. DOI: 10.1111/j.1440-1681.1993.tb01496.x

14. Tanaka T., Okamura T., Miura K., Kadowaki T., Ueshima H., Nakagawa H., Hashimoto T. A simple method to estimate populational 24-h urinary sodium and potassium excretion using a casual urine specimen. J. Hum. Hypertens. 2002; 16(2): 97–103. DOI: 10.1038/sj.jhh.1001307

15. Yi B., Titze J., Rykova M., Feuerecker M., Vassilieva G., Nichiporuk I., Schelling G., Morukov B., Choukèr A. Effects of dietary salt levels on monocytic cells and immune responses in healthy human subjects: a longitudinal study. Transl. Res. 2015; 166(1): 103–110. DOI: 10.1016/j.trsl.2014.11.007

16. Titze J. A different view on sodium balance. Curr. Opin. Nephrol. Hypertens. 2015; 24(1): 14–20. DOI: 10.1097/MNH.0000000000000085

17. Schatz V., Neubert P., Schröder A., Binger K., Gebhard M., Müller D.N., Luft F.C., Titze J., Jantsch J. Elementary immunology: Na+ as a regulator of immunity. Pediatr. Nephrol. 2017; 32(2): 201–210. DOI: 10.1007/s00467-016-3349-x

18. Laffer C.L., Scott R.C. 3rd, Titze J.M., Luft F.C., Elijovich F. Hemodynamics and Salt-and-Water Balance Link Sodium Storage and Vascular Dysfunction in Salt-Sensitive Subjects. Hypertension. 2016; 68(1): 195–203. DOI: 10.1161/HYPERTENSIONAHA.116.07289

19. Bogdan C. Macrophages as host, effector and immunoregulatory cells in leishmaniasis: Impact of tissue micro-environment and metabolism. Cytokine X. 2020; 2(4): 100041. DOI: 10.1016/j.cytox.2020.100041

20. Charlton K.E., Steyn K., Levitt N.S., Jonathan D., Zulu J.V., Nel J.H. Development and validation of a short questionnaire to assess sodium intake. Public. Health. Nutr. 2008; 11(1): 83–94. DOI: 10.1017/S1368980007000146

21. Dragunov D.O., Sokolova A.V., Arutyunov G.P., Mitrokhin V.M., Kamkin A.G., Latyshev T.V. Correlationsof IL-18 and IL-6 with sodium consumption in patients with arterial hypertension and diabetes mellitus. Kardiologiia. 2017; 57(1S): 355–359 (In Russ., English abstract). DOI: 10.18087/cardio.2389

22. Asaria P., Chisholm D., Mathers C., Ezzati M., Beaglehole R. Chronic disease prevention: health effects and fi nancial costs of strategies to reduce salt intake and control tobacco use. Lancet. 2007; 370(9604): 2044–2053. DOI: 10.1016/S0140-6736(07)61698-5

23. Zhou X., Zhang L., Ji W.J., Yuan F., Guo Z.Z., Pang B., Luo T., Liu X., Zhang W.C., Jiang T.M., Zhang Z., Li Y.M. Variation in dietary salt intake induces coordinated dynamics of monocyte subsets and monocyte- platelet aggregates in humans: implications in end organ infl ammation. PLoS One. 2013; 8(4): e60332. DOI: 10.1371/journal.pone.0060332

24. Wenstedt E.F., Verberk S.G., Kroon J., Neele A.E., Baardman J., Claessen N., Pasaoglu Ö.T., Rademaker E., Schrooten E.M., Wouda R.D., de Winther M.P., Aten J., Vogt L., Van den Bossche J. Salt increases monocyte CCR2 expression and infl ammatory responses in humans. JCI Insight. 2019; 4(21): e130508. DOI: 10.1172/jci.insight.130508

25. Schierke F., Wyrwoll M.J., Wisdorf M., Niedzielski L., Maase M., Ruck T., Meuth S.G., Kusche-Vihrog K. Nanomechanics of the endothelial glycocalyx contribute to Na+-induced vascular infl ammation. Sci. Rep. 2017; 7: 46476. DOI: 10.1038/srep46476