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Effect of angiotensin II receptor blocker and salt supplementation on short-term blood pressure variability in type 2 diabetes

Abstract

High blood pressure variability (BPV) has been associated with increased cardiovascular (CV) risk. The effect of dietary salt and renin–angiotensin–aldosterone system (RAAS) activity on short-term BPV in type 2 diabetes mellitus (T2DM) is not well characterised. We aimed to determine the effect of dietary salt (sodium chloride, NaCl) supplementation on 24-h mean arterial BPV (24hBPV) during angiotensin II receptor blocker (telmisartan) use and to evaluate the effects of age, sex, plasma renin activity (PRA) and serum aldosterone on 24hBPV. In a randomised, double-blind, crossover study, patients with T2DM (n = 28), treated with telmisartan received NaCl (100 mmol/24 h) or placebo capsules during 2 weeks of telmisartan. Following a 6-week washout, the protocol was repeated in reverse. 24hBPV was evaluated as a co-efficient of variation [CV (%) = mean/standard deviation] × 100). Twenty-four hour urinary sodium excretion, ambulatory BP and biochemical tests were performed at each phase. Results were analysed using a linear mixed model to generate predicted values for 24hBPV. Predicted 24hBPV was higher with telmisartan vs baseline (p = 0.01), with a trend towards reduced 24hBPV with salt (p = 0.052). Predicted 24hBPV was lower in females (p = 0.017), increasing age (p = 0.001) and increasing PRA (p = 0.011). In patients with T2DM, predicted 24hBPV increased from baseline with telmisartan, but there was no additional increase in predicted 24hBPV with salt supplementation. This suggests that in the short-term, salt supplementation has no apparent deleterious effects on 24hBPV. Long-term studies are required to evaluate the effect of 24hBPV on CV outcomes in patients with T2DM.

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References

  1. Garcia MJ, McNamara PM, Gordon T, Kannell WB. Morbidity and mortality in diabetics in the framingham population: sixteen year follow-up study. Diabetes. 1974;23:105–11.

    Article  CAS  Google Scholar 

  2. Parati G, Ochoa JE, Salvi P, Lombardi C, Bilo G. Prognostic value of blood pressure variability and average blood pressure levels in patients with hypertension and diabetes. Diabetes Care. 2013;36 Suppl. 2:S312–24.

    Article  Google Scholar 

  3. Rothwell PM, Howard SC, Dolan E, O’Brien E, Dobson JE, Dahlöf B, et al. Prognostic significance of visit-to-visit variability, maximum systolic blood pressure, and episodic hypertension. Lancet. 2010;375:895–905.

    Article  Google Scholar 

  4. Poortvliet RK, Ford I, Lloyd SM, Sattar N, Mooijaart SP, de Craen AJ, et al. Blood pressure variability and cardiovascular risk in the PROspective Study of Pravastatin in the Elderly at Risk (PROSPER). PLoS ONE. 2012;7:e52438.

    Article  CAS  Google Scholar 

  5. Okada H, Fukui M, Tanaka M, Matsumoto S, Mineoka Y, Nakanishi N, et al. Visit-to-visit blood pressure variability is a novel risk factor for the development and progression of diabetic nephropathy in patients with type 2 diabetes. Diabetes Care. 2013;36:1908–12.

    Article  CAS  Google Scholar 

  6. Sohn M-W, Epstein N, Huang ES, Huo Z, Emanuele N, Stukenborg G, et al. Visit-to-visit systolic blood pressure variability and microvascular complications among patients with diabetes. J Diabetes Complicat. 2017;31:195–201.

    Article  Google Scholar 

  7. Stevens SL, Wood S, Koshiaris C, Law K, Glasziou P, Stevens RJ, et al. Blood pressure variability and cardiovascular disease: systematic review and meta-analysis. Br Med J. 2016;354:i4098.

    Article  Google Scholar 

  8. Veerman DP, Imholz BP, Wieling W, Karemaker JM, van Montfrans GA. Effects of aging on blood pressure variability in resting conditions. Hypertension. 1994;24:120–30.

    Article  CAS  Google Scholar 

  9. Thayer JF, Sollers JJ, Friedman BH, Koenig J. Gender differences in the relationship between resting heart rate variability and 24-hour blood pressure variability. Blood Press. 2016;25:58–62.

    Article  Google Scholar 

  10. Webb AJ, Fischer U, Mehta Z, Rothwell PM. Effects of antihypertensive-drug class on interindividual variation in blood pressure and risk of stroke: a systematic review and meta-analysis. Lancet. 2010;375:906–15.

    Article  CAS  Google Scholar 

  11. Chen AX, Jerums G, Baqar S, Lambert E, Somarajah G, Thomas G, et al. Short-term dietary salt supplementation blunts telmisartan induced increases in plasma renin activity in hypertensive patients with type 2 diabetes mellitus. Clin Sci. 2015;129:415–22.

    Article  CAS  Google Scholar 

  12. Ekinci EI, Thomas G, Thomas D, Johnson C, MacIsaac RJ, Houlihan CA, et al. Effects of salt supplementation on the albuminuric response to telmisartan with or without hydrochlorothiazide therapy in hypertensive patients with type 2 diabetes are modulated by habitual dietary salt intake. Diabetes Care. 2009;32:1398–403.

    Article  CAS  Google Scholar 

  13. Ekinci EI, Thomas G, MacIsaac RJ, Johnson C, Houlihan C, Panagiotopoulos S, et al. Salt supplementation blunts the blood pressure response to telmisartan with or without hydrochlorothiazide in hypertensive patients with type 2 diabetes. Diabetologia. 2010;53:1295–303.

    Article  CAS  Google Scholar 

  14. Houlihan CA, Allen TJ, Baxter AL, Panangiotopoulos S, Casley DJ, Cooper ME, et al. A low-sodium diet potentiates the effects of losartan in type 2 diabetes. Diabetes Care. 2002;25:663–71.

    Article  CAS  Google Scholar 

  15. Parati G, Ochoa JE, Lombardi C, Bilo G. Assessment and management of blood-pressure variability. Nat Rev Cardiol. 2013;10:143–55.

    Article  Google Scholar 

  16. Mallinckrod CH, Lane PW, Schnell D, Peng Y, Mancuso JP. Recommendations for the primary analysis of continuous endpoints in longitudinal clinical trials. Drug Inf J. 2008;42:303–19.

    Article  Google Scholar 

  17. Williams R. Using the margins command to estimate and interpret adjusted predictions and marginal effects. Stata J. 2012;12:308.

    Article  Google Scholar 

  18. Burnier M, Brunner H. Angiotensin II receptor antagonists. Lancet. 2000;355:637–45.

    Article  CAS  Google Scholar 

  19. Mancia G. Blood pressure variability: mechanisms and clinical significance. J Cardiovasc Pharmacol. 1990;16:S1–6.

    Article  Google Scholar 

  20. Zhang Y, Agnoletti D, Safar ME, Blacher J. Effect of antihypertensive agents on blood pressure variability. Hypertension. 2011;58:155–60.

    Article  CAS  Google Scholar 

  21. Omboni S, Kario K, Bakris G, Parati G. Effect of antihypertensive treatment on 24-h blood pressure variability: pooled individual data analysis of ambulatory blood pressure monitoring studies based on olmesartan mono or combination treatment. J Hypertens. 2018;36:720–33.

    Article  CAS  Google Scholar 

  22. Ushigome E, Fukui M, Hamaguchi M, Tanaka T, Atsuta H, Mogami S, et al. Factors affecting variability in home blood pressure in patients with type 2 diabetes: post hoc analysis of a cross-sectional multicenter study. J Hum Hypertens. 2014;28:594–9.

    Article  CAS  Google Scholar 

  23. Vogiatzakis N, Tsioufis C, Georgiopoulos G, Thomopoulos C, Dimitriadis K, Kasiakogias A, et al. Effect of renal sympathetic denervation on short-term blood pressure variability in resistant hypertension: a meta-analysis. J Hypertens. 2017;35:1750–7.

    Article  CAS  Google Scholar 

  24. Mente A, O’Donnell M, Rangarajan S, McQueen M, Dagenais G, Wielgosz A, et al. Urinary sodium excretion, blood pressure, cardiovascular disease, and mortality: a community-level prospective epidemiological cohort study. Lancet. 2018;392:496–506.

    Article  Google Scholar 

  25. Brian MS, Dalpiaz A, Matthews EL, Lennon-Edwards S, Edwards DG, Farquhar WB. Dietary sodium and nocturnal blood pressure dipping in normotensive men and women. J Hum Hypertens. 2017;31:145–50.

    Article  CAS  Google Scholar 

  26. Iuchi H, Sakamoto M, Suzuki H, Kayama Y, Ohashi K, Hayashi T, et al. Effect of one-week salt restriction on blood pressure variability in hypertensive patients with type 2 diabetes. PloS ONE. 2016;11:e0144921.

    Article  Google Scholar 

  27. Grassi G, Dell’Oro R, Seravalle G, Foglia G, Trevano FQ, Mancia G. Short-and long-term neuroadrenergic effects of moderate dietary sodium restriction in essential hypertension. Circulation. 2002;106:1957–61.

    Article  CAS  Google Scholar 

  28. Hall JE. Control of sodium excretion by angiotensin II: intrarenal mechanisms and blood pressure regulation. Am J Physiol. 1986;250:R960–72.

    CAS  PubMed  Google Scholar 

  29. Ozkayar N, Dede F, Akyel F, Yildirim T, Ateş I, Turhan T, et al. Relationship between blood pressure variability and renal activity of the renin–angiotensin system. J Hum Hypertens. 2016;30:297.

    Article  CAS  Google Scholar 

  30. Chau NP, Chanudet X, Larroque P. Inverse relationship between upright plasma renin activity and twenty-four hour blood pressure variability in borderline hypertension. J Hypertens. 1990;8:913–8.

    Article  CAS  Google Scholar 

  31. Campbell DJ, Nussberger J, Stowasser M, Danser AHJ, Morganti A, Frandsen E, et al. Activity assays and immunoassays for plasma renin and prorenin: information provided and precautions necessary for accurate measurement. Clin Chem. 2009;55:867–77.

    Article  CAS  Google Scholar 

  32. Deppe S, Böger RH, Weiss J, Benndorf RA. Telmisartan: a review of its pharmacodynamic and pharmacokinetic properties. Exp Opi Drug Metab Toxicol. 2010;6:863–71.

    Article  CAS  Google Scholar 

  33. Imai Y, Aihara A, Ohkubo T, Nagai K, Tsuji I, Minami N, et al. Factors that affect blood pressure variability. Am J Hypertens. 1997;10:1281–9.

    Article  CAS  Google Scholar 

  34. Migneco A, Ojetti V, Covino M, Mettimano M, Montebelli MR, Leone A, et al. Increased blood pressure variability in menopause. Eur Rev Med Pharm Sci. 2008;12:89.

    CAS  Google Scholar 

  35. Holbrook J, Patterson K, Bodner J, Douglas L, Veillon C, Kelsay J, et al. Sodium and potassium intake and balance in adults consuming self-selected diets. Am J Clin Nutr. 1984;40:786–93.

    Article  CAS  Google Scholar 

  36. di Rienzo M, Grassi G, Pedotti A, Mancia G. Continuous vs intermittent blood pressure measurements in estimating 24-hour average blood pressure. Hypertension. 1983;5:264–9.

    Article  Google Scholar 

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Acknowledgements

The authors would like to acknowledge the support of Department 310 of Endocrinology, Austin Health, University of Melbourne in undertaking this study.

Funding

This work was supported by an NHMRC Postgraduate Research Scholarship (grant number APP466611 to EIE), NHRMC Early Career Fellowship (grant number APP1054312 to EIE) and Heart Foundation Scholarship (grant number 100287 to SB).

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Correspondence to Elif I. Ekinci.

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Chen, A.X., Moran, J.L., Libianto, R. et al. Effect of angiotensin II receptor blocker and salt supplementation on short-term blood pressure variability in type 2 diabetes. J Hum Hypertens 34, 143–150 (2020). https://doi.org/10.1038/s41371-019-0238-3

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