Aldosterone-to-renin ratio is related to arterial stiffness when the screening criteria of primary aldosteronism are not met

Eeva Kokko, Pasi I Nevalainen, Manoj Kumar Choudhary, Jenni Koskela, Antti Tikkakoski, Heini Huhtala, Onni Niemelä, Marianna Viukari, Jukka Mustonen, Niina Matikainen, Ilkka Pörsti, Eeva Kokko, Pasi I Nevalainen, Manoj Kumar Choudhary, Jenni Koskela, Antti Tikkakoski, Heini Huhtala, Onni Niemelä, Marianna Viukari, Jukka Mustonen, Niina Matikainen, Ilkka Pörsti

Abstract

Aldosterone-to-renin ratio (ARR) is a screening tool for primary aldosteronism (PA), but the significance of ARR when the PA criteria are not met remains largely unknown. In this cross-sectional study we investigated the association of ARR with haemodynamic variables in 545 normotensive and never-medicated hypertensive subjects (267 men, 278 women, age range 19-72 years) without suspicion of PA. Supine haemodynamic data was recorded using whole-body impedance cardiography and radial tonometric pulse wave analysis. In sex-adjusted quartiles of ARR, determined as serum aldosterone to plasma renin activity ratio, the mean values were 282, 504, 744 and 1467 pmol/µg of angiotensin I/h, respectively. The only difference in haemodynamic variables between the ARR quartiles was higher pulse wave velocity (PWV) in the highest quartile versus other quartiles (p = 0.004), while no differences in blood pressure (BP), heart rate, wave reflections, cardiac output or systemic vascular resistance were observed between the quartiles. In linear regression analysis with stepwise elimination, ARR was an independent explanatory factor for PWV (β = 0.146, p < 0.001, R2 of the model 0.634). In conclusion, ARR was directly and independently associated with large arterial stiffness in individuals without clinical suspicion of PA. Therefore, ARR could serve as a clinical marker of cardiovascular risk.Trial registration: ClinicalTrails.gov: NCT01742702.

Conflict of interest statement

The authors declare no competing interests.

Figures

Figure 1
Figure 1
Radial systolic (a) and diastolic (b) blood pressure calibrated from brachial blood pressure measurements, and aortic systolic (c) and diastolic (d) blood pressure in quartiles (n = 135–137) of aldosterone-to-renin ratio (ARR); analyses were adjusted for sex, age, and estimated glomerular filtration rate; ANOVA-RM, analysis of variance for repeated measurements, results are depicted as mean and standard error of the mean.
Figure 2
Figure 2
Heart rate (a), stroke index (b), cardiac index (c) and systemic vascular resistance index (d) in quartiles (n = 135–137) of aldosterone-to-renin ratio (ARR); analyses were adjusted for sex, age, and estimated glomerular filtration rate; ANOVA-RM, analysis of variance for repeated measurements, mean and standard error of the mean.
Figure 3
Figure 3
Forward wave amplitude (a), augmentation index (b), extracellular water balance (c) and aortic-to-popliteal pulse wave velocity (d) in quartiles (n = 135–137) of aldosterone-to-renin ratio (ARR); analyses were adjusted for sex, age, and estimated glomerular filtration rate; ANOVA-RM, analysis of variance for repeated measurements, mean and standard error of the mean.

References

    1. Young WF. Diagnosis and treatment of primary aldosteronism: practical clinical perspectives. J. Intern. Med. 2019;285:126–148. doi: 10.1111/joim.12831.
    1. Mulatero P, et al. Guidelines for primary aldosteronism: uptake by primary care physicians in europe. J. Hypertens. 2016;34:2253–2257. doi: 10.1097/HJH.0000000000001088.
    1. Rossi E, Perazzoli F, Negro A, Magnani A. Diagnostic rate of primary aldosteronism in emilia-romagna, Northern Italy, during 16 years (2000–2015) J. Hypertens. 2017;35:1691–1697. doi: 10.1097/HJH.0000000000001384.
    1. Hannemann A, Wallaschofski H. Prevalence of primary aldosteronism in patient’s cohorts and in population-based studies—a review of the current literature. Horm. Metab. Res. 2012;44:157–162. doi: 10.1055/s-0031-1295438.
    1. Funder JW, et al. The management of primary aldosteronism: case detection, diagnosis, and treatment: an Endocrine Society clinical practice guideline. J. Clin. Endocrinol. Metab. 2016;101:1889–1916. doi: 10.1210/jc.2015-4061.
    1. Monticone S, et al. Prevalence and clinical manifestations of primary aldosteronism encountered in primary care practice. J. Am. Coll. Cardiol. 2017;69:1811–1820. doi: 10.1016/j.jacc.2017.01.052.
    1. Brown JM, et al. The unrecognized prevalence of primary aldosteronism: a cross-sectional study. Ann. Intern. Med. 2020;173:10–20. doi: 10.7326/M20-0065.
    1. Milliez P, et al. Evidence for an increased rate of cardiovascular events in patients with primary aldosteronism. J. Am. Coll. Cardiol. 2005;45:1243–1248. doi: 10.1016/j.jacc.2005.01.015.
    1. Monticone S, et al. Cardiovascular events and target organ damage in primary aldosteronism compared with essential hypertension: a systematic review and meta-analysis. Lancet Diabetes Endocrinol. 2018;6:41–50. doi: 10.1016/S2213-8587(17)30319-4.
    1. Marney AM, Brown NJ. Aldosterone and end-organ damage. Clin. Sci. 2007;113:267–278. doi: 10.1042/CS20070123.
    1. Fuller PJ, Young MJ. Mechanisms of mineralocorticoid action. Hypertension. 2005;46:1227–1235. doi: 10.1161/01.HYP.0000193502.77417.17.
    1. Strauch B, et al. Increased arterial wall stiffness in primary aldosteronism in comparison with essential hypertension. Am. J. Hypertens. 2006;19:909–914. doi: 10.1016/j.amjhyper.2006.02.002.
    1. Choudhary MK, et al. Primary aldosteronism: higher volume load, cardiac output and arterial stiffness than in essential hypertension. J. Intern. Med. 2020 doi: 10.1111/joim.13115.
    1. Tomaschitz A, et al. Aldosterone/renin ratio determines peripheral and central blood pressure values over a broad range. J. Am. Coll. Cardiol. 2010;55:2171–2180. doi: 10.1016/j.jacc.2010.01.032.
    1. Newton-Cheh C, et al. Clinical and genetic correlates of aldosterone-to-renin ratio and relations to blood pressure in a community sample. Hypertension. 2007;49:846–856. doi: 10.1161/01.HYP.0000258554.87444.91.
    1. Gaddam KK. Characterization of resistant hypertension: association between resistant hypertension, aldosterone, and persistent intravascular volume expansion. Arch. Intern. Med. 2008;168:1159. doi: 10.1001/archinte.168.11.1159.
    1. Meneton P, et al. High plasma aldosterone and low renin predict blood pressure increase and hypertension in middle-aged caucasian populations. J. Hum. Hypertens. 2008;22:550–558. doi: 10.1038/jhh.2008.27.
    1. Lieb W, et al. Multimarker approach to evaluate correlates of vascular stiffness: the Framingham Heart Study. Circulation. 2009;119:37–43. doi: 10.1161/CIRCULATIONAHA.108.816108.
    1. Kisaka T, et al. Association of elevated plasma aldosterone-to-renin ratio with future cardiovascular events in patients with essential hypertension. J. Hypertens. 2012;30:2322–2330. doi: 10.1097/HJH.0b013e328359862d.
    1. Shapiro Y, Boaz M, Matas Z, Fux A, Shargorodsky M. The association between the renin–angiotensin–aldosterone system and arterial stiffness in young healthy subjects. Clin. Endocrinol. (Oxf.). 2008;68:510–512. doi: 10.1111/j.1365-2265.2008.03176.x.
    1. Tahvanainen A, et al. Analysis of cardiovascular responses to passive head-up tilt using continuous pulse wave analysis and impedance cardiography. Scand. J. Clin. Lab. Invest. 2009;69:128–137. doi: 10.1080/00365510802439098.
    1. Tikkakoski AJ, et al. Hemodynamic alterations in hypertensive patients at rest and during passive head-up tilt. J. Hypertens. 2013;31:906–915. doi: 10.1097/HJH.0b013e32835ed605.
    1. Kangas P, et al. Changes in hemodynamics associated with metabolic syndrome are more pronounced in women than in men. Sci. Rep. 2019;9:18377. doi: 10.1038/s41598-019-54926-0.
    1. Williams B, et al. ESC/ESH guidelines for the management of arterial hypertension. Eur. Heart J. 2018;39:3021–3104. doi: 10.1093/eurheartj/ehy339.
    1. KDIGO 2012 Clinical practice guideline for the evaluation and management of chronic kidney disease. Kidney Int. Suppl. 2013;3:1–150. doi: 10.1038/kisup.2012.73.
    1. Treatment of alcohol abuse. Current Care Guideline by the Finnish Medical Society Duodecim and the Finnish Society of Addiction Medicine. (2015). . Accessed 10 August 2020.
    1. Inker LA, et al. Estimating glomerular filtration rate from serum creatinine and cystatin C. N. Engl. J. Med. 2012;367:20–29. doi: 10.1056/NEJMoa1114248.
    1. Katz A, et al. Quantitative insulin sensitivity check index: a simple, accurate method for assessing insulin sensitivity in humans. J. Clin. Endocrinol. Metab. 2000;85:2402–2410. doi: 10.1210/jcem.85.7.6661.
    1. Muniyappa R, Lee S, Chen H, Quon MJ. Current approaches for assessing insulin sensitivity and resistance in vivo: advantages, limitations, and appropriate usage. Am. J. Physiol.-Endocrinol. Metab. 2008;294:E15–E26. doi: 10.1152/ajpendo.00645.2007.
    1. Matsuda M, DeFronzo RA. Insulin sensitivity indices obtained from oral glucose tolerance testing: comparison with the euglycemic insulin clamp. Diabetes Care. 1999;22:1462–1470. doi: 10.2337/diacare.22.9.1462.
    1. Koskela JK, et al. Association of resting heart rate with cardiovascular function: a cross-sectional study in 522 Finnish subjects. BMC Cardiovasc. Disord. 2013;13:102. doi: 10.1186/1471-2261-13-102.
    1. Chen CH, et al. Estimation of central aortic pressure waveform by mathematical transformation of radial tonometry pressure. Validation of generalized transfer function. Circulation. 1997;95:1827–1836. doi: 10.1161/01.CIR.95.7.1827.
    1. Kaess BM, et al. Aortic stiffness, blood pressure progression, and incident hypertension. JAMA. 2012;308:875–881. doi: 10.1001/2012.jama.10503.
    1. Mitchell GF, et al. Changes in arterial stiffness and wave reflection with advancing age in healthy men and women: the Framingham Heart Study. Hypertension. 2004;43:1239–1245. doi: 10.1161/01.HYP.0000128420.01881.aa.
    1. Kööbi T, Kaukinen S, Ahola T, Turjanmaa VM. Non-invasive measurement of cardiac output: whole-body impedance cardiography in simultaneous comparison with thermodilution and direct oxygen fick methods. Intensive Care Med. 1997;23:1132–1137. doi: 10.1007/s001340050469.
    1. Kööbi T, Kaukinen S, Turjanmaa VM, Uusitalo AJ. Whole-body impedance cardiography in the measurement of cardiac output. Crit. Care Med. 1997;25:779–785. doi: 10.1097/00003246-199705000-00012.
    1. Kööbi T, Kähönen M, Iivainen T, Turjanmaa V. Simultaneous non-invasive assessment of arterial stiffness and haemodynamics—a validation study. Clin. Physiol. Funct. Imaging. 2003;23:31–36. doi: 10.1046/j.1475-097X.2003.00465.x.
    1. DuBois D, DuBois EF. A formula to estimate the approximate surface area if height and weight be known. Arch. Intern. Med. 1916;17:863–871. doi: 10.1001/archinte.1916.00080130010002.
    1. Wilenius M, et al. Central wave reflection is associated with peripheral arterial resistance in addition to arterial stiffness in subjects without antihypertensive medication. BMC Cardiovasc. Disord. 2016;16:131. doi: 10.1186/s12872-016-0303-6.
    1. Laurent S, et al. Expert consensus document on arterial stiffness: methodological issues and clinical applications. Eur. Heart J. 2006;27:2588–2605. doi: 10.1093/eurheartj/ehl254.
    1. Vlachopoulos C, Aznaouridis K, Stefanadis C. Prediction of cardiovascular events and all-cause mortality with arterial stiffness. J. Am. Coll. Cardiol. 2010;55:1318–1327. doi: 10.1016/j.jacc.2009.10.061.
    1. Satoh M, et al. Aldosterone-to-renin ratio as a predictor of stroke under conditions of high sodium intake: the Ohasama study. Am. J. Hypertens. 2012;25:777–783. doi: 10.1038/ajh.2012.33.
    1. Safar ME, London GM. Therapeutic studies and arterial stiffness in hypertension: recommendations of the European Society of Hypertension. J. Hypertens. 2000;18:1227–1535.
    1. McEniery CM, et al. Normal vascular aging: differential effects on wave reflection and aortic pulse wave velocity: the Anglo-Cardiff Collaborative Trial (ACCT) J. Am. Coll. Cardiol. 2005;46:1753–1760. doi: 10.1016/j.jacc.2005.07.037.
    1. Drayer JI, Weber MA, Laragh JH, Sealey JE. Renin subgroups in essential hypertension. Clin. Exp. Hypertens. A. 1982;4:1817–1834.
    1. Markou A, et al. Evidence of primary aldosteronism in a predominantly female cohort of normotensive individuals: a very high odds ratio for progression into arterial hypertension. J. Clin. Endocrinol. Metab. 2013;98:1409–1416. doi: 10.1210/jc.2012-3353.
    1. Rene B, et al. Continuum of renin-independent aldosteronism in normotension. Hypertension. 2017;69:950–956. doi: 10.1161/HYPERTENSIONAHA.116.08952.
    1. Nanba K, et al. Age-related autonomous aldosteronism. Circulation. 2017;136:347–355. doi: 10.1161/CIRCULATIONAHA.117.028201.
    1. Nishimoto K, et al. Aldosterone-stimulating somatic gene mutations are common in normal adrenal glands. Proc. Natl. Acad. Sci. USA. 2015;112:E4591–E4599. doi: 10.1073/pnas.1505529112.
    1. Mahmud A, Feely J. Aldosterone-to-renin ratio, arterial stiffness, and the response to aldosterone antagonism in essential hypertension. Am. J. Hypertens. 2005;18:50–55. doi: 10.1016/j.amjhyper.2004.08.026.
    1. Liao C-W, et al. Time course and factors predicting arterial stiffness reversal in patients with aldosterone-producing adenoma after adrenalectomy: prospective study of 102 patients. Sci. Rep. 2016;6:20862. doi: 10.1038/srep20862.
    1. de Simone G, et al. Estimate of white-coat effect and arterial stiffness. J. Hypertens. 2007;25:827–831. doi: 10.1097/HJH.0b013e32801d1f62.
    1. Barochiner J, et al. Arterial stiffness in treated hypertensive patients with white-coat hypertension. J. Clin. Hypertens. 2017;19:6–10. doi: 10.1111/jch.12913.
    1. Agarwal R, Weir MR. Treated hypertension and the white coat phenomenon: office readings are inadequate measures of efficacy. J. Am. Soc. Hypertens. 2013;7:236–243. doi: 10.1016/j.jash.2013.02.005.
    1. Widimský J, et al. Impaired insulin action in primary hyperaldosteronism. Physiol. Res. 2000;49:241–244.
    1. Sindelka, G. et al. Insulin action in primary hyperaldosteronism before and after surgical or pharmacological treatment. Exp. Clin. Endocrinol. Diabetes. 108, 21-25 (2000).
    1. Catena C, et al. Insulin sensitivity in patients with primary aldosteronism: a follow-up study. J. Clin. Endocrinol. Metab. 2006;91:3457–3463. doi: 10.1210/jc.2006-0736.
    1. Kidambi S, Kotchen JM, Krishnaswami S, Grim CE, Kotchen TA. Hypertension, insulin resistance, and aldosterone: sex-specific relationships. J. Clin. Hypertens. 2009;11:130–137. doi: 10.1111/j.1751-7176.2009.00084.x.
    1. Huan Y, Deloach S, Keith SW, Goodfriend TL, Falkner B. Aldosterone and aldosterone: renin ratio associations with insulin resistance and blood pressure in African Americans. J. Am. Soc. Hypertens. 2012;6:56–65. doi: 10.1016/j.jash.2011.09.005.
    1. Oinonen L, et al. Plasma total calcium concentration is associated with blood pressure and systemic vascular resistance in normotensive and never-treated hypertensive subjects. Blood Press. 2020;29:137–148. doi: 10.1080/08037051.2019.1696180.
    1. Porsti I, et al. High calcium diet down-regulates kidney angiotensin-converting enzyme in experimental renal failure. Kidney Int. 2004;66:2155–2166. doi: 10.1111/j.1523-1755.2004.66006.x.
    1. Freundlich M, et al. Suppression of renin–angiotensin gene expression in the kidney by paricalcitol. Kidney Int. 2008;74:1394–1402. doi: 10.1038/ki.2008.408.
    1. Pörsti IH. Expanding targets of vitamin D receptor activation: downregulation of several ras components in the kidney. Kidney Int. 2008;74:1371–1373. doi: 10.1038/ki.2008.424.
    1. Roman MJ, et al. Central pressure more strongly relates to vascular disease and outcome than does brachial pressure: the Strong Heart Study. Hypertension. 2007;50:197–203. doi: 10.1161/HYPERTENSIONAHA.107.089078.
    1. Kollias A, Lagou S, Zeniodi ME, Boubouchairopoulou N, Stergiou GS. Association of central versus brachial blood pressure with target-organ damage: systematic review and meta-analysis. Hypertension. 2016;67:183–190. doi: 10.1161/HYPERTENSIONAHA.115.06066.

Source: PubMed

3
订阅