Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Original Article
  • Published:

Silent ischemia is more prevalent among hypertensive patients with microalbuminuria and salt sensitivity

Abstract

Some patients with essential hypertension manifest greater than normal urinary albumin excretion (UAE). Salt-sensitive hypertensives also manifest greater UAE compared to salt-resistant individuals. Although the significance of these associations is not well established, several lines of evidence suggest that microalbuminuria and/or salt sensitivity may be associated with greater prevalence of cardiovascular risks and events. In this study, we have evaluated by ergometric exercise 42 subjects with microalbuminuria and 42 matched individuals with normal UAE. All these subjects also underwent a standardized protocol to determine blood pressure sensitivity to a high salt intake. Patients with microalbuminuria displayed greater levels of ambulatory blood pressure and a greater rise in systolic blood pressure during exercise compared to patients with normal UAE (33.1±1.56 vs 26.4±1.7 mmHg, P<0.001). Seven hypertensive patients with microalbuminuria developed ST segment depression during exercise compared to only one subject with normal UAE. Salt-sensitive patients manifested greater UAE than salt-resistant subjects (58 and 14 mg, 24 h, P<0.001) and greater prevalence of silent ischemia (6 vs 2) than salt-resistant individuals. In conclusion, these studies have shown that hypertensive individuals with microalbuminuria and/or salt sensitivity manifest an increased prevalence of silent ischemia.

This is a preview of subscription content, access via your institution

Access options

Buy this article

Prices may be subject to local taxes which are calculated during checkout

Similar content being viewed by others

References

  1. Gerber LM, Shmukler C, Alderman MH . Differences in urinary albumin excretion rate between normotensive and hypertensive white and non white subjects. Arch Intern Med 1992; 152: 373–377.

    Article  CAS  Google Scholar 

  2. Parving HH, Jensen HE, Mogensen CE, Evrin PE . Increased urinary albumin excretion in benign essential hypertension. Lancet 1974; 1: 231–237.

    Google Scholar 

  3. Pedersen EB, Mogensen CE . Effect of antihypertensive treatment on urinary albumin excretion, glomerular filtration rate and renal plasma flow in patients with essential hypertension. Scand J Clin Lab Invest 1976; 36: 231–237.

    Article  CAS  Google Scholar 

  4. Bigazzi R, Bianchi S, Campese VM, Baldari G . Prevalence of microalbuminuria in a large population of patients with mild to moderate essential hyper-tension. Nephron 1992; 61: 94–97.

    Article  CAS  Google Scholar 

  5. Redon J et al. Factors related to the presence of microalbuminuria in essential hypertension. Am J Hypertens 1994; 7: 801–807.

    Article  CAS  Google Scholar 

  6. Sprangler JG, Bell RA, Summerson JH, Konen JC . Correlates of abnormal urinary albumin excretion rates among primary care patients with essential hypertension. J Am Board Fam Pract 1997; 10: 180–184.

    Google Scholar 

  7. 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  CAS  Google Scholar 

  8. Gosling P, Beevers DG . Urinary albumin excretion and blood pressure in the general population. Clin Sci 1989; 76: 39–42.

    Article  CAS  Google Scholar 

  9. Damsgaard EM, Froland A, Jorgensen OD, Mogensen CE . Microalbuminuria as predictor of increased mortality in elderly people. BMJ 1990; 300: 297–300.

    Article  CAS  Google Scholar 

  10. Watts GF, Morris RW, Khan K, Polak A . Urinary albumin excretion in healthy adult subjects: reference values and some factors affecting their interpretation. Clin Chim Acta 1988; 172: 191–198.

    Article  CAS  Google Scholar 

  11. 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, (editorial comments)

    Article  CAS  Google Scholar 

  12. Redon J et al. Microalbuminuria is correlated with left ventricular hypertrophy in male hypertensive patients. J Hypertens 1991; 9 (Suppl 6) S148–S149.

    CAS  Google Scholar 

  13. Pedrinelli R et al. Microalbuminuria is a marker of left ventricular hypertrophy but not hyperinsulinemia in non diabetic atherosclerotic patients. Arterioscler Thromb 1993; 13: 900–906.

    Article  CAS  Google Scholar 

  14. Cerasola D et al. Microalbuminuria as a predictor of cardiovascular damage in essential hypertension. J Hypertens 1989; 7 (Suppl 6) S332–S333.

    Article  CAS  Google Scholar 

  15. Agewall S et al. Microalbuminuria in treated hypertensive men at high risk of coronary disease. The Risk Factor Intervention Study Group. J Hypertens 1993; 11: 461–469.

    Article  CAS  Google Scholar 

  16. Horton RC et al. Microalbumin excretion in patients with positive exercise electrocardiogram tests. Eur Heart J 1994; 15: 1353–1355.

    Article  CAS  Google Scholar 

  17. Bigazzi R et al. Increased thickness of the carotid artery in patients with essential hypertension and microalbuminuria. J Hum Hypertens 1995; 9: 827–833.

    CAS  Google Scholar 

  18. Bigazzi R et al. Microalbuminuria in salt-sensitive patients. A marker for renal and cardiovascular risk factors. Hypertension 1994; 23: 195–199.

    Article  CAS  Google Scholar 

  19. Campese VM . Salt sensitivity in hypertension. Renal and cardiovascular implications. Hypertension 1994; 23: 531–550.

    Article  CAS  Google Scholar 

  20. Campese VM . Salt-sensitive hypertension: renal and cardiovascular implications. Nutr Metab Cardiovasc Dis 1999; 9: 143–156.

    CAS  PubMed  Google Scholar 

  21. Cohn PF . Prognosis in exercise-induced silent myocardial ischemia and implications for screening asymptomatic populations. Prog Cardiovasc Dis 1992; 34: 399–412.

    Article  CAS  Google Scholar 

  22. The Sixth Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure Arch Int Med 1997; 157: 2413–2446.

  23. ACP/ACC/AHA Task Force Statement Clinical competence in exercise testing: a statement for Physicians from the ACP/ACC/AHA Task Force on clinical previleges in Cardiology. JACC 1990; 16: 1061–1085.

  24. ESC Working Group Guidelines for cardiac exercise testing. Eur Heart J 1993; 14: 969–988.

  25. AHA Medical/Scientific Statement Special report Exercise standards: a statement for healthcare professional from the American Heart Association. Circulation 1995; 30: 260–315.

  26. Watts GF et al. Assessment of immunochemical methods for determining low concentration of albumin in urine. Clin Chem 1986; 32: 1544–1548.

    CAS  PubMed  Google Scholar 

  27. Friedewald WT, Levy R, Fredrickson DS . Estimation of the concentration of low-density lipoprotein cholesterol in plasma without use of the preparative ultracentrifuge. Clin Chem 1972; 18: 499–502.

    CAS  Google Scholar 

  28. Watts GF et al. Assessment of immunochemical methods for determing low concentrations of albumin in urine. Clin Chem 1986; 32: 1544–1548.

    CAS  PubMed  Google Scholar 

  29. Silver A, Dawnay A, Landon J, Catteli WR . Immono-assays for low concentrations of albumin in urine. Clin Chem 1986; 32: 1303–1306.

    CAS  PubMed  Google Scholar 

  30. Dixon WJ (ed). BMDP Statistical Software, Vol. 1 University of California Press: Berkeley, CA 1990.

    Google Scholar 

  31. Heiberger RM, Becker RA . Design of an S function for robust regression using iteratively reweighted least squares. J Comp Graph Stat 1992; 3: 181–196.

    Google Scholar 

  32. Bianchi S et al. Diurnal variation of blood pressure and microalbuminuria in patients with essential hyper-tension. Am J Hypertens 1994; 7: 23–29.

    Article  CAS  Google Scholar 

  33. Earle KA et al. Microalbuminuria as a marker of silent myocardial ischaemia in IDDM patients. Diabetologia 1996; 39: 854–856.

    CAS  PubMed  Google Scholar 

  34. Rutter MK, McComb JM, Brady S, Marshall SM . Silent myocardial ischemia and microalbuminuria in asymptomatic subjects with non-insulin-dependent diabetes mellitus. Am J Cardiol 1999; 83: 27–31.

    Article  CAS  Google Scholar 

  35. Janand-Delenne B et al. Silent myocardial ischemia in patients with diabetes: who to screen. Diabetes Care 1999; 22: 1396–1400.

    Article  CAS  Google Scholar 

  36. Asmar R et al. Prevalence and circadian variations of ST-segment depression and its concomitant blood pressure changes in asymptomatic systemic hyper-tension. Am J of Cardiol 1996; 77: 384–390.

    Article  CAS  Google Scholar 

  37. Go BM et al. Association of systolic blood pressure at time of myocardial ischemia with angina pectoris during exercise testing. Am J Cardiol 1997; 79: 954–956.

    Article  CAS  Google Scholar 

  38. Deedwania PC, Nelson JR . Pathophysiology of silent myocardial ischemia during daily life: hemodynamic evaluation by simultaneous electrocardiographic and blood pressure monitoring. Circulation 1990; 82: 1296–1304.

    Article  CAS  Google Scholar 

  39. Dworkin BR, Filewich RJ, Miller NE, Craigmyle N . Baroreceptor activation reduces reactivity to noxious stimulation: implications for hypertension. Science 1979; 205: 1299–1301.

    Article  CAS  Google Scholar 

  40. Ghione S, Rosa C, Mezzasalma L, Panattoni E . Arterial hypertension is associated with hypoalgesia in humans. Hypertension 1988; 12: 491–497.

    Article  CAS  Google Scholar 

  41. Salonen JT, Salonen R . Ultrasonographically assessed carotid morphology and the risk of coronary heart disease. Arterioscler and Thromb 1991; 11: 1245–1249.

    Article  CAS  Google Scholar 

  42. Yudkin JS, Forrest RD, Jackson CA . Microalbuminuria as predictor of vascular disease in non-diabetic subjects. Islington Diabetes Survey. Lancet 1988; ii: 530–533.

    Article  Google Scholar 

  43. Haffner SM et al. Microalbuminuria. A marker for increased cardiovascular risk factors in nondiabetic subjects?. Arteriosclerosis 1990; 10: 727–731.

    Article  CAS  Google Scholar 

  44. Winocour PH et al. Microalbuminuria and associated risk factors in the community. Atherosclerosis 1992; 93: 71–81.

    Article  CAS  Google Scholar 

  45. Damsgaard EM, Froland A, Jorgensen OD, Mogensen CE . Microalbuminuria as predictor of increased mortality in elderly people. BMJ 1990; 300: 297–300.

    Article  CAS  Google Scholar 

  46. Damsgaard EL, Froland A, Jorgensen OD, Mogensen CE . Prognostic value of urinary albumin excretion rate and other risk factors in elderly diabetic patients and non-diabetic control subjects surviving the first 5 years after assessment. Diabetologia 1993; 36: 1030–1036.

    Article  CAS  Google Scholar 

  47. Bigazzi R, Bianchi S, Baldari D, Campese VM . Microalbuminuria predicts cardiovascular events and renal insufficiency in patients with essential hypertension predicts. J Hypertens 1998; 16: 1325–1333.

    Article  CAS  Google Scholar 

  48. Lydakis C, Lip GYH . Microalbuminuria and cardiovascular risk. QMJ 1998; 91: 381–391.

    Article  CAS  Google Scholar 

  49. Agewall S, Wilkstrand J, Ljungman S, Herlitz H, Fagerberg B . Does microalbuminuria predict cardiovascular events in non diabetic men with treated hypertension? Risk Factors Intervention Study Group. Am J Hypertens 1995; 8: 337–342.

    Article  CAS  Google Scholar 

  50. Palatini P et al. Prevalence and clinical correlates of microalbuminuria in Stage 1 hypertension. Results from the Hypertension and Ambulatory Recording Venetia Study (HARVEST) study. Am J Hypertens 1996; 9: 334–341.

    Article  CAS  Google Scholar 

  51. Taddei S et al. Lack of correlation between microalbuminuria and endothelial function in essential hypertensive patients. J Hypertens 1995; 13: 1003–1008.

    Article  CAS  Google Scholar 

  52. Gosling P . Microalbuminuria and cardiovascular risk: a word of caution. J Hum Hypertens 1998; 12: 211–213.

    Article  CAS  Google Scholar 

  53. Kuusisto J, Mykkanen L, Pyorealea K, Laakso M . Hyperinsulinemic microalbuminuria. A new risk indicator for coronary heart disease. Circulation 1995; 9: 831–837.

    Article  Google Scholar 

  54. Ferrannini E et al. Insulin resistance in essential hypertension. N Engl J Med 1987; 317: 350–357.

    Article  CAS  Google Scholar 

  55. DeFronzo RA et al. The effect of insulin on renal handling of sodium, potassium, calcium, and phosphate in man. J Clin Invest 1975; 55: 845–855.

    Article  CAS  Google Scholar 

  56. Lansberg L, Young JB . Insulin-mediated glucose metabolism in the relationship between dietary intake and sympathetic nervous system activity. Int J Obes 1985; 9: 63–68.

    Google Scholar 

  57. Rocchini AP et al. The effect of weight loss on the sensitivity of blood pressure to sodium in obese adolescents. N Engl J Med 1989; 321: 580–585.

    Article  CAS  Google Scholar 

  58. Sharma AM, Schorr U, Distler A . Insulin resistance in young salt-sensitive normotensive subjects. Hypertension 1993; 21: 273–279.

    Article  CAS  Google Scholar 

  59. Galletti F et al. NaCl sensitivity of essential hyper-tensive patients is related to insulin resistance. J Hypertens 1997; 15: 1485–1491.

    Article  CAS  Google Scholar 

  60. Zavaroni I et al. Association between salt sensitivity and insulin concentrations in patients with hypertension. Am J Hypertens 1995; 8: 855–858.

    Article  CAS  Google Scholar 

  61. Bianchi S et al. Elevated serum insulin levels in patients with essential hypertension and micro-albuminuria. Hypertension 1994; 23, (Part 1) 681–687.

    Article  CAS  Google Scholar 

  62. Bianchi S et al. Insulin resistance in microalbuminuric hypertension: sites and mechanisms. Hypertension 1995; 26: 789–795.

    Article  CAS  Google Scholar 

  63. Bigazzi R, Bianchi S, Baldari G, Campese VM . Clustering of cardiovascular risk factors in salt-sensitive patients with essential hypertension: role of insulin. Am J Hyperten 1996; 9: 24–32.

    Article  CAS  Google Scholar 

  64. Zavaroni I et al. Risk factors for coronary artery disease in healthy persons with hyperinsulinemia and normal glucose tolerance. N Eng J Med 1989; 320: 702–706.

    Article  CAS  Google Scholar 

  65. Pyorala K et al. Macrovascular complications in relation to hyperinsulineamia in non insulin dependent diabetes mellitus. Diabetes Metab 1987; 13: 345–349.

    CAS  Google Scholar 

  66. Fuller JH et al. Coronary heart disease risk and impaired glucose tolerance. The Whitehall study. Lancet 1980; 1: 1373–1376.

    Article  CAS  Google Scholar 

  67. Welbon TA, Wearne K . Coronary heart disease incidence and cardiovascular mortality in Busselton with reference to glucose and insulin concentrations. Diabetes Care 1979; 2: 154–160.

    Article  Google Scholar 

  68. Modan M et al. A link between hypertension, obesity and glucose intolerance. J Clin Invest 1985; 75: 809–817.

    Article  CAS  Google Scholar 

  69. Eschwege E et al. Coronary heart disease mortality in relation with diabetes, blood glucose and plasma insulin levels. The Paris Prospective Study, ten years later. Horm Metab Res 1985; 15: 41–46.

    CAS  Google Scholar 

  70. Ducimetiere P et al. Relationship of plasma insulin levels to the incidence of myocardial infarction and coronary heart disease mortality in a middle-aged population. Diabetologia 1980; 19: 205–210.

    Article  CAS  Google Scholar 

  71. Stern MP, Haffner SM . Body fat distribution and hyper-insulinemia as risk factors for diabetes and cardio-vascular disease. Arteriosclerosis 1986; 6: 123–130.

    Article  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to V M Campese.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Bianchi, S., Bigazzi, R., Amoroso, A. et al. Silent ischemia is more prevalent among hypertensive patients with microalbuminuria and salt sensitivity. J Hum Hypertens 17, 13–20 (2003). https://doi.org/10.1038/sj.jhh.1001498

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/sj.jhh.1001498

Keywords

This article is cited by

Search

Quick links