Skip to main content

Advertisement

SpringerLink
Log in

Proteinuria is an independent predictor of rapid progression of mild to moderate aortic stenosis in patients with preserved renal function

  • Original Paper
  • Published:
The International Journal of Cardiovascular Imaging Aims and scope Submit manuscript

Abstract

Although proteinuria is a well-known risk factor for cardiovascular disease, its relationship with the progression of aortic stenosis (AS) has not been established. Our aim was to investigate the relationship between proteinuria (detected by urine dipstick test) and AS progression (assessed by the annualized reduction rate of aortic valve area [AVA]). A total of 460 patients with mild to moderate AS (defined by a peak velocity of 2.0–4.0 m/s) without end-stage renal disease who underwent two echocardiograms at least 3 months apart were included. The progression of AS was significantly faster in patients with proteinuria than those without (108 patients vs. 352 patients; annualized reduction rate of AVA, − 7.7 ± 13.5% vs. − 4.5 ± 11.6%; p = 0.017). The relationship between the presence of proteinuria and the accelerated progression of AS was significant among patients with estimated glomerular filtration rate (eGFR) ≥ 60 mL/min/1.73 m2 (− 11.0 ± 17.5% vs. − 4.2 ± 10.0%; p < 0.001), but not among those with eGFR 15–60 mL/min/1.73 m2 (− 5.8 ± 10.3 vs. − 5.3 ± 14.8%; p = 0.822). When stratified by the presence of diabetes, the association of proteinuria with AS progression was only significant in patients without diabetes (− 8.1 ± 12.0% vs. − 8.1 ± 15.7%; p = 0.018). Multivariable logistic regression analysis identified that the presence of proteinuria was an independent predictor of AS progression. The progression of AS was accelerated in patients with mild to moderate AS and proteinuria, particularly among those with preserved renal function and no diabetes.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3

Similar content being viewed by others

References

  1. Coffey S, Cox B, Williams MJ (2014) The prevalence, incidence, progression, and risks of aortic valve sclerosis: a systematic review and meta-analysis. J Am Coll Cardiol 63(25 Pt A):2852–2861. https://doi.org/10.1016/j.jacc.2014.04.018

    Article  PubMed  Google Scholar 

  2. Murphy ES, Lawson RM, Starr A, Rahimtoola SH (1981) Severe aortic stenosis in patients 60 years of age or older: left ventricular function and 10-year survival after valve replacement. Circulation 64(2 Pt 2):184–188

    Google Scholar 

  3. Rosenhek R, Klaar U, Schemper M, Scholten C, Heger M, Gabriel H, Binder T, Maurer G, Baumgartner H (2004) Mild and moderate aortic stenosis. Natural history and risk stratification by echocardiography. Eur Heart J 25(3):199–205. https://doi.org/10.1016/j.ehj.2003.12.002

    Article  PubMed  Google Scholar 

  4. Stewart BF, Siscovick D, Lind BK, Gardin JM, Gottdiener JS, Smith VE, Kitzman DW, Otto CM (1997) Clinical factors associated with calcific aortic valve disease. Cardiovascular Health Study. J Am Coll Cardiol 29(3):630–634

    Article  CAS  PubMed  Google Scholar 

  5. Palta S, Pai AM, Gill KS, Pai RG (2000) New insights into the progression of aortic stenosis—implications for secondary prevention. Circulation 101(21):2497–2502

    Article  CAS  PubMed  Google Scholar 

  6. Tastet L, Capoulade R, Clavel MA, Larose E, Shen M, Dahou A, Arsenault M, Mathieu P, Bedard E, Dumesnil JG, Tremblay A, Bosse Y, Despres JP, Pibarot P (2017) Systolic hypertension and progression of aortic valve calcification in patients with aortic stenosis: results from the PROGRESSA study. Eur Heart J Cardiovasc Imaging 18(1):70–78. https://doi.org/10.1093/ehjci/jew013

    Article  PubMed  Google Scholar 

  7. London GM, Pannier B, Marchais SJ, Guerin AP (2000) Calcification of the aortic valve in the dialyzed patient. J Am Soc Nephrol 11(4):778–783

    CAS  PubMed  Google Scholar 

  8. Leskinen Y, Paana T, Saha H, Groundstroem K, Lehtimaki T, Kilpinen S, Huhtala H, Airaksinen J (2009) Valvular calcification and its relationship to atherosclerosis in chronic kidney disease. J Heart Valve Dis 18(4):429–438

    PubMed  Google Scholar 

  9. Miettinen H, Haffner SM, Lehto S, Ronnemaa T, Pyorala K, Laakso M (1996) Proteinuria predicts stroke and other atherosclerotic vascular disease events in nondiabetic and non-insulin-dependent diabetic subjects. Stroke 27(11):2033–2039

    Article  CAS  PubMed  Google Scholar 

  10. Nishimura RA, Otto CM, Bonow RO, Carabello BA, Erwin JP 3rd, Guyton RA, O’Gara PT, Ruiz CE, Skubas NJ, Sorajja P, Sundt TM 3rd, Thomas JD, Anderson JL, Halperin JL, Albert NM, Bozkurt B, Brindis RG, Creager MA, Curtis LH, DeMets D, Guyton RA, Hochman JS, Kovacs RJ, Ohman EM, Pressler SJ, Sellke FW, Shen WK, Stevenson WG, Yancy CW, American College of C, American College of Cardiology/American Heart A, American Heart A (2014) 2014 AHA/ACC guideline for the management of patients with valvular heart disease: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines. J Thorac Cardiovasc Surg 148(1):e1–e132. https://doi.org/10.1016/j.jtcvs.2014.05.014

    Article  PubMed  Google Scholar 

  11. Lim D, Lee DY, Cho SH, Kim OZ, Cho SW, An SK, Kim HW, Moon KH, Lee MH, Kim B (2014) Diagnostic accuracy of urine dipstick for proteinuria in older outpatients. Kidney Res Clin Pract 33(4):199–203. https://doi.org/10.1016/j.krcp.2014.10.003

    Article  PubMed  PubMed Central  Google Scholar 

  12. Kristal B, Shasha SM, Labin L, Cohen A (1988) Estimation of quantitative proteinuria by using the protein-creatinine ratio in random urine samples. Am J Nephrol 8(3):198–203

    Article  CAS  PubMed  Google Scholar 

  13. Levey AS, Stevens LA, Schmid CH, Zhang YL, Castro AF 3rd, Feldman HI, Kusek JW, Eggers P, Van Lente F, Greene T, Coresh J, Ckd EPI (2009) A new equation to estimate glomerular filtration rate. Ann Intern Med 150(9):604–612

    Article  PubMed  PubMed Central  Google Scholar 

  14. Inker LA, Astor BC, Fox CH, Isakova T, Lash JP, Peralta CA, Kurella Tamura M, Feldman HI (2014) KDOQI US commentary on the 2012 KDIGO clinical practice guideline for the evaluation and management of CKD. Am J Kidney Dis 63(5):713–735. https://doi.org/10.1053/j.ajkd.2014.01.416

    Article  PubMed  Google Scholar 

  15. Chiu YW, Adler SG, Budoff MJ, Takasu J, Ashai J, Mehrotra R (2010) Coronary artery calcification and mortality in diabetic patients with proteinuria. Kidney Int 77(12):1107–1114. https://doi.org/10.1038/ki.2010.70

    Article  CAS  PubMed  Google Scholar 

  16. DeFilippis AP, Kramer HJ, Katz R, Wong ND, Bertoni AG, Carr J, Budoff MJ, Blumenthal RS, Nasir K (2010) Association between coronary artery calcification progression and microalbuminuria the MESA study. Jacc-Cardiovasc Imag 3(6):595–604. https://doi.org/10.1016/j.jcmg.2010.01.008

    Article  Google Scholar 

  17. Park HE, Heo NJ, Kim M, Choi SY (2013) Significance of microalbuminuria in relation to subclinical coronary atherosclerosis in asymptomatic nonhypertensive, nondiabetic subjects. J Korean Med Sci 28(3):409–414. https://doi.org/10.3346/jkms.2013.28.3.409

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Dinneen SF, Gerstein HC (1997) The association of microalbuminuria and mortality in non-insulin-dependent diabetes mellitus. A systematic overview of the literature. Arch Intern Med 157(13):1413–1418

    Article  CAS  PubMed  Google Scholar 

  19. van der Toll A, Van Biesen W, De Groote G, Verbeke P, Vermeiren F, Eeckhaut K, Vanholder R (2013) Microalbuminuria is more consistent in the presence of cardiovascular risk factors. J Nephrol 26(3):580–585. https://doi.org/10.5301/jn.5000194

    Article  CAS  Google Scholar 

  20. Jensen JS, Borch-Johnsen K, Jensen G, Feldt-Rasmussen B (1995) Microalbuminuria reflects a generalized transvascular albumin leakiness in clinically healthy subjects. Clin Sci 88(6):629–633

    Article  CAS  Google Scholar 

  21. Deckert T, Feldt-Rasmussen B, Borch-Johnsen K, Jensen T, Kofoed-Enevoldsen A (1989) Albuminuria reflects widespread vascular damage. Diabetologia 32(4):219–226

    Article  CAS  PubMed  Google Scholar 

  22. Freeman RV, Otto CM (2005) Spectrum of calcific aortic valve disease: pathogenesis, disease progression, and treatment strategies. Circulation 111(24):3316–3326. https://doi.org/10.1161/CIRCULATIONAHA.104.486738

    Article  PubMed  Google Scholar 

  23. Olsson M, Thyberg J, Nilsson J (1999) Presence of oxidized low density lipoprotein in nonrheumatic stenotic aortic valves. Arterioscler Thromb Vasc Biol 19(5):1218–1222

    Article  CAS  PubMed  Google Scholar 

  24. Ohara T, Hashimoto Y, Matsumura A, Suzuki M, Isobe M (2005) Accelerated progression and morbidity in patients with aortic stenosis on chronic dialysis. Circ J 69(12):1535–1539

    Article  PubMed  Google Scholar 

  25. Kearney LG, Ord M, Buxton BF, Matalanis G, Patel SK, Burrell LM, Srivastava PM (2013) Progression of aortic stenosis in elderly patients over long-term follow up. Int J Cardiol 167(4):1226–1231. https://doi.org/10.1016/j.ijcard.2012.03.139

    Article  CAS  PubMed  Google Scholar 

  26. Coresh J, Selvin E, Stevens LA, Manzi J, Kusek JW, Eggers P, Van Lente F, Levey AS (2007) Prevalence of chronic kidney disease in the United States. JAMA 298(17):2038–2047. https://doi.org/10.1001/jama.298.17.2038

    Article  CAS  PubMed  Google Scholar 

  27. O’Brien KD, Shavelle DM, Caulfield MT, McDonald TO, Olin-Lewis K, Otto CM, Probstfield JL (2002) Association of angiotensin-converting enzyme with low-density lipoprotein in aortic valvular lesions and in human plasma. Circulation 106(17):2224–2230

    Article  PubMed  Google Scholar 

  28. Cote N, Couture C, Pibarot P, Despres JP, Mathieu P (2011) Angiotensin receptor blockers are associated with a lower remodelling score of stenotic aortic valves. Eur J Clin Invest 41(11):1172–1179. https://doi.org/10.1111/j.1365-2362.2011.02522.x

    Article  CAS  PubMed  Google Scholar 

  29. O’Brien KD, Probstfield JL, Caulfield MT, Nasir K, Takasu J, Shavelle DM, Wu AH, Zhao XQ, Budoff MJ (2005) Angiotensin-converting enzyme inhibitors and change in aortic valve calcium. Arch Intern Med 165(8):858–862. https://doi.org/10.1001/archinte.165.8.858

    Article  PubMed  Google Scholar 

  30. Ardehali R, Leeper NJ, Wilson AM, Heidenreich PA (2012) The effect of angiotensin-converting enzyme inhibitors and statins on the progression of aortic sclerosis and mortality. J Heart Valve Dis 21(3):337–343

    PubMed  PubMed Central  Google Scholar 

  31. Rosenhek R, Rader F, Loho N, Gabriel H, Heger M, Klaar U, Schemper M, Binder T, Maurer G, Baumgartner H (2004) Statins but not angiotensin-converting enzyme inhibitors delay progression of aortic stenosis. Circulation 110(10):1291–1295. https://doi.org/10.1161/01.CIR.0000140723.15274.53

    Article  CAS  PubMed  Google Scholar 

  32. Jimenez-Candil J, Bermejo J, Yotti R, Cortina C, Moreno M, Cantalapiedra JL, Garcia-Fernandez MA (2005) Effects of angiotensin converting enzyme inhibitors in hypertensive patients with aortic valve stenosis: a drug withdrawal study. Heart 91(10):1311–1318. https://doi.org/10.1136/hrt.2004.047233

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  33. Rossebo AB, Pedersen TR, Boman K, Brudi P, Chambers JB, Egstrup K, Gerdts E, Gohlke-Barwolf C, Holme I, Kesaniemi YA, Malbecq W, Nienaber CA, Ray S, Skjaerpe T, Wachtell K, Willenheimer R, Investigators S (2008) Intensive lipid lowering with simvastatin and ezetimibe in aortic stenosis. N Engl J Med 359(13):1343–1356. https://doi.org/10.1056/NEJMoa0804602

    Article  PubMed  Google Scholar 

  34. Chan KL, Teo K, Dumesnil JG, Ni A, Tam J, Investigators A (2010) Effect of Lipid lowering with rosuvastatin on progression of aortic stenosis: results of the aortic stenosis progression observation: measuring effects of rosuvastatin (ASTRONOMER) trial. Circulation 121(2):306–314. https://doi.org/10.1161/CIRCULATIONAHA.109.900027

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Republic of Korea

    You-Jung Choi, Jun-Bean Park, Seung-Pyo Lee, Hyung-Kwan Kim, Yong-Jin Kim & Dae-Won Sohn

  2. Cardiovascular Center, Seoul National University Hospital, Seoul, Republic of Korea

    Jun-Bean Park, Seung-Pyo Lee, Hyung-Kwan Kim, Yong-Jin Kim & Dae-Won Sohn

  3. Division of Cardiology, Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam-si, Gyeonggi-do, Republic of Korea

    In-Chang Hwang

  4. Division of Cardiology, Department of Internal Medicine, Office of Medical Education, Seoul National University College of Medicine, Seoul National University Hospital, 101 Daehak-ro, Jongno-gu, Seoul, 110-744, Republic of Korea

    Jun-Bean Park

Authors
  1. You-Jung Choi
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Jun-Bean Park
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. In-Chang Hwang
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Seung-Pyo Lee
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Hyung-Kwan Kim
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Yong-Jin Kim
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Dae-Won Sohn
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Jun-Bean Park.

Ethics declarations

Conflict of interest

The authors declare that they have no competing interests.

Electronic supplementary material

Below is the link to the electronic supplementary material.

Supplementary material 1 (DOCX 28 KB)

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Choi, YJ., Park, JB., Hwang, IC. et al. Proteinuria is an independent predictor of rapid progression of mild to moderate aortic stenosis in patients with preserved renal function. Int J Cardiovasc Imaging 35, 481–489 (2019). https://doi.org/10.1007/s10554-018-1473-3

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10554-018-1473-3

Keywords

Search

Navigation