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Proteinuria: An underappreciated risk factor in cardiovascular disease

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Abstract

Changes in renal function produced by hypertension appear to be associated with higher cardiovascular morbidity and mortality. Indices of altered renal function (eg, micro-albuminuria, increased serum creatinine concentrations, decrease in estimated creatinine clearance, or overt proteinuria) are independent predictors of cardiovascular morbidity and mortality. The Framingham Heart Study documented the relevance of proteinuria for cardiovascular prognosis in the community. The International Nifedipine GITS study: Intervention as a goal in Hypertension Treatment (INSIGHT) study assessed the role of proteinuria as a very powerful risk factor. Several studies demonstrated that microalbuminuria is a predictor of cardiovascular disease. It has been shown that the presence of microalbuminuria in primary hypertension carries an elevated cardiovascular risk. Furthermore, recent data indicate that even minor derangements of renal function are associated with an increase in cardiovascular risk factors, and promote progression of atherosclerosis. All these parameters should routinely be evaluated in clinical practice, and in the future must be considered in any stratification of cardiovascular risk in hypertensive patients.

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References and Recommended Reading

  1. Rostand SG, Brunzell JD, Cannon RO, et al.: Cardiovascular complications in renal failure. J Am Soc Nephrol 1991, 2:1053–1058.

    PubMed  CAS  Google Scholar 

  2. Ruilope LM, Salvetti A, Jamerson K, et al.: Renal function and intensive lowering of blood pressure in the hypertensive subjects of the Hypertension Optimal Treatment (HOT) Study. J Am Soc Nephrol 2001, 12:218–225. This paper confirms the predictive value of serum creatinine previously demonstrated in the HDFP study.

    PubMed  CAS  Google Scholar 

  3. Brown MJ, Palmer CR, Castaigne A, et al.: Morbidity and mortality in patients randomised to double-blind treatment with a long-acting calcium-channel blocker or diuretic in the International Nifedipine GITS study: Intervention as a goal in Hypertension Treatment (INSIGHT). Lancet 2000, 356:366–372. Proteinuria was found to be a very potent predictor of cardiovascular risk in essential hypertension.

    Article  PubMed  CAS  Google Scholar 

  4. Mann JFE, Gerstein HC, Pogue J, et al.: Renal insufficiency as predictor of cardiovascular outcomes and impact of ramipril: the HOPE randomization trial. Ann Intern Med 2001, 134:629–636. This article reviews the relevance of renal function derangement, in particular of microalbuminuria as a predictor of prognosis, and also as a predictor of the response to ramipril.

    PubMed  CAS  Google Scholar 

  5. Hillege HL, Girbes ARJ, de Kam PJ, et al.: Renal function, neurohumoral activation, and survival in patients with chronic heart failure. Circulation 2000, 102:203–210.

    PubMed  CAS  Google Scholar 

  6. Dries DL, Exner DV, Domanski MJ, et al.: The prognostic implications of renal insufficiency in asymptomatic and symptomatic patients with left ventricular dysfunction. J Am Coll Cardiol 2000, 35:681–689.

    Article  PubMed  CAS  Google Scholar 

  7. Culleton BF, Larson MG, Wilson PWF, et al.: Cardiovascular disease and mortality in a community-based cohort with mild renal insufficiency. Kidney Int 1999, 56:2214–2219.

    Article  PubMed  CAS  Google Scholar 

  8. Levey AS, Bosch JP, Lewis JB, et al.: A more accurate method to estimate glomerular rate from serum creatinine: a new prediction equation. Modification of Diet in Renal Disease Study Group. Ann Intern Med 1999, 130:461–470.

    PubMed  CAS  Google Scholar 

  9. Ruilope LM, Rodicio JL: Clinical relevance of proteinuria and microalbuminuria. Curr Opin Nephrol Hypertens 1993, 2:962–967.

    Article  PubMed  CAS  Google Scholar 

  10. Minram A, Ribstein J, DuCalair G: Is microalbuminuria a marker of early intrarenal vascular dysfunction in essential hypertension? Hypertension 1994, 23:1018–1021.

    Google Scholar 

  11. Lindeman R, Tobin J, Shock NW: Longitudinal studies on the rate of decline in renal function with age. J Am Geriat Soc 1985, 33:278–285.

    PubMed  CAS  Google Scholar 

  12. Segura J, Campo C, Rodicio JL, Ruilope LM: How relevant and frequent is the presence of mild renal insufficiency in essential hypertension? J Clin Hypertens 2002, in press. This paper contains data on the frequency of renal damage, and in particular of proteinuria in patients followed in an in-hospital hypertension unit.

  13. Samuelsson O: Hypertension in middle-aged man: management, morbidity and prognostic factors during long-term hypertensive care. Acta Med Scand 1985, 702:1–79.

    CAS  Google Scholar 

  14. Ruilope LM, Rodicio JL: Microalbuminuria in clinical practice. Kidney: A Current Survey of World Literature 1995, 4:211–216.

    Google Scholar 

  15. Agrawal B, Berger A, Wolf K, Luft FC: Microalbuminuria screening by reagent strip predicts cardiovascular risk in hypertension. J Hypertens 1996, 14:223–228.

    Article  PubMed  CAS  Google Scholar 

  16. Campese VM, Bianchi S, Bigazzi R: Is microalbuminuria a predictor of cardiovascular and renal disease in patients with essential hypertension? Curr Opin Nephrol Hypertens 2000, 9:143–147.

    Article  PubMed  CAS  Google Scholar 

  17. Ruilope LM, Campo C, Rodriguez-Artalejo F, et al.: Blood pressure and renal function therapeutic implications. J Hypertens 1996, 14:1259–1263.

    Article  PubMed  CAS  Google Scholar 

  18. Holtzman NA, Marteau TM: Will genetics revolutionize medicine? N Eng J Med 2000, 343:141–144.

    Article  CAS  Google Scholar 

  19. Watchell K, Olsen MH, Dahlof B, et al.: Microalbuminuria in hypertensive patients with electrocardiographic left ventricular hypertrophy: the LIFE study. J Hypertens 2002, 20:405–412. An interesting paper describing the relationship of microalbuminuria and the different forms of LVH.

    Article  Google Scholar 

  20. Gerstein HC, Mann JF, Yi Q, et al., for the HOPE Study Investigators: Albuminuria and risk of cardiovascular events, death and heart failure in diabetic and nondiabetic individuals. JAMA 2001, 286:421–426. This article shows that the lower limit of microalbuminuria in relation to risk is not the usual cut-off point of 30 mg/d.

    Article  PubMed  CAS  Google Scholar 

  21. Redon J, Williams B: Microalbuminuria in essential hypertension: redefining the threshold. J Hypertens 2002, 20:353–355. The threshold of microalbuminuria could be lowered to values below 30 mg/d.

    Article  PubMed  CAS  Google Scholar 

  22. Ruilope LM, Lahera V, Rodicio JL, et al.: Are renal hemodynamics a key factor in the development and maintenance of arterial hypertension in humans? Hypertension 1994, 23:3–9.

    PubMed  CAS  Google Scholar 

  23. Folkow B: Kidneys in primary hypertension-Initiators, stabilizers or/and victim-aggravators? Blood Press 1994, 3:212–215.

    PubMed  CAS  Google Scholar 

  24. Perera GA: Hypertensive vascular disease: description and natural history. J Chronic Dis 1995, 1:33–42.

    Article  Google Scholar 

  25. Coresh J, Wei GL, McQuillan G, et al.: Prevalence of high blood pressure and elevated serum creatinine level in the United States. Findings from the Third National Health and Nutrition Examination Survey (1988–1994). Arch Intern Med 2001, 161:1207–1216. The prevalence of mild renal insufficiency in the general population is as high as 3% by serum creatinine levels.

    Article  PubMed  CAS  Google Scholar 

  26. Clase CM, Garg AX, Kiberd BA: Prevalence of low glomerular filtration rate in nondiabetic Americans: third National Health and Nutrition Examination Survey (NHANES III). J Am Soc Nephrol 2000, 13:1338–1349.

    Article  Google Scholar 

  27. National Institute of Diabetes and Digestive and Kidney Diseases: US Renal Data System: Annual Data Report. Bethesda: National Institutes of Health, National Institutes of Diabetes and Digestive and Kidney Diseases; 1989.

    Google Scholar 

  28. Ruilope LM, Alcazar JM, Rodicio JL: Renal consequences of arterial hypertension. J Hypertens 1992, 10(Suppl 7):S85-S90.

    CAS  Google Scholar 

  29. Shulman NB, Ford CE, Hall WD, et al.: Prognostic value of serum creatinine and effect of treatment of hypertension on renal function. Results from the Hypertension Detection and Follow-up Program. Hypertension 1989, 13(Suppl I):I–80-I–93.

    Google Scholar 

  30. Fried LP, Kronmal RA, Newman AB, et al.: Risk factors for 5-year mortality in older adults: The Cardiovascular Health Study. JAMA 1998, 279:585–592.

    Article  PubMed  CAS  Google Scholar 

  31. Cockroft DW, Gault MH: Prediction of creatinine clearance from serum creatinine. Nephron 1976, 16:13.

    Google Scholar 

  32. Joint National Committee on Detection, Evaluation and Treatment of High Blood Pressure: The Sixth report of the Joint National Committee on Detection, Evaluation and Treatment of High Blood Pressure (JNV-VI). Arch Intern Med 1997, 157:2413–2446.

    Article  Google Scholar 

  33. Brod J, Bahlman J, Cachoven M, Pretschner PD: Development of hypertension in renal disease. Clin Sci 1983, 64:141–152.

    PubMed  CAS  Google Scholar 

  34. Hall JE: Pathophysiology of obesity hypertension. Curr Hypertens Rep 2000, 2:139–147. A nice review that fits with the aim of this review because obesity is related in a specific manner to proteinuria and renal damage.

    PubMed  CAS  Google Scholar 

  35. Remuzzi G: Cigarette smoking and renal function impairment. Am J Kidney Dis 1999, 33:807–813.

    PubMed  CAS  Google Scholar 

  36. Toto RD, Mitchell HC, Smith RD, et al.: "Strict" blood pressure control and progression of renal disease in hypertensive nephrosclerosis. Kidney Int 1995, 48:851–859.

    PubMed  CAS  Google Scholar 

  37. Peterson JC, Adler S, Burkart JM, et al.: The Modification of Diet in Renal Disease Study. Ann Intern Med 1995, 123:754–762.

    PubMed  CAS  Google Scholar 

  38. Lewis EJ, Hunsicker LG, Bain RP, et al.: The effect of angiotensin-converting-enzyme inhibition on diabetic nephropathy. N Engl J Med 1993, 329:1456–1462.

    Article  PubMed  CAS  Google Scholar 

  39. Maschio G, Alberti D, Janin G, et al.: Effect of the angiotensinconverting-enzyme inhibitor benazepril on the progression of chronic renal insufficiency. N Eng J Med 1996, 334:939–945.

    Article  CAS  Google Scholar 

  40. Ruilope LM, Alcazar JM, Hernandez E, et al.: Long-term influences of antihypertensive therapy on microalbuminuria in essential hypertension. Kidney Int 1994, 45(Suppl 45): S171-S173.

    CAS  Google Scholar 

  41. Sihm I, Shroeder AP, Aalkjaer C, et al.: Regression of media-tolumen ratio of human subcutaneous arteries and left ventricular hypertrophy during treatment with an angiotensinconverting enzyme inhibitor based regimen in hypertensive patients. Am J Cardiol 1995, 76:38E-40E.

    PubMed  CAS  Google Scholar 

  42. Schiffrin EL, Deng LY: Comparison of the effects of angiotensin I-converting enzyme inhibition and beta-blockade for 2 years on function of small arteries from hypertensive patients. Hypertension 1995, 25:699–703.

    PubMed  CAS  Google Scholar 

  43. Segura J, Campo C, Rodicio JL, Ruilope LM: ACE inhibitors and appearance of renal events in hypertensive nephrosclerosis. Hypertension 2001, 38:645–649. This paper shows that ACE inhibitors are positive for renal protection even in the absence of proteinuria.

    PubMed  CAS  Google Scholar 

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Authors and Affiliations

  1. Hospital 12 de Octubre, Unidad de Hipertensión Arterial, Avenida Córdoba s/n, 28041, Madrid, Spain

    Julián Segura MD, Carlos Campo MD & Luis M. Ruilope MD

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  1. Julián Segura MD
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  2. Carlos Campo MD
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  3. Luis M. Ruilope MD
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Segura, J., Campo, C. & Ruilope, L.M. Proteinuria: An underappreciated risk factor in cardiovascular disease. Curr Cardiol Rep 4, 458–462 (2002). https://doi.org/10.1007/s11886-002-0106-5

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