American Heart Journal
Volume 157, Issue 2 , Pages 334.e1-334.e8 , February 2009

Angiotensin-converting enzyme inhibition and novel cardiovascular risk biomarkers: Results from the Trial of Angiotensin Converting Enzyme Inhibition and Novel Cardiovascular Risk Factors (TRAIN) study

  • Matteo Cesari, MD, PhD

      Affiliations

    • Department of Aging and Geriatric Research, University of Florida-Institute on Aging, Gainesville, FL
    • Corresponding Author InformationReprint requests: Matteo Cesari, MD, PhD, Department of Aging and Geriatric Research, University of Florida-Institute on Aging, 210 East Mowry Road, Gainesville, FL 32611.
  • ,
  • Stephen B. Kritchevsky, PhD

      Affiliations

    • Section on Gerontology and Geriatric Medicine, J. Paul Sticht Center on Aging, Wake Forest University School of Medicine, Winston Salem, NC
  • ,
  • Hal H. Atkinson, MD

      Affiliations

    • Section on Gerontology and Geriatric Medicine, J. Paul Sticht Center on Aging, Wake Forest University School of Medicine, Winston Salem, NC
  • ,
  • Brenda W. Penninx, PhD

      Affiliations

    • Department of Psychiatry / EMGO Institute, VU University Medical Center, Amsterdam, The Netherlands
  • ,
  • Mauro Di Bari, MD, PhD

      Affiliations

    • Department of Critical Care Medicine and Surgery, University of Florence, Florence, Italy
  • ,
  • Russell P. Tracy, PhD

      Affiliations

    • Laboratory for Clinical Biochemistry Research, University of Vermont College of Medicine, Burlington, VT
  • ,
  • Marco Pahor, MD

      Affiliations

    • Department of Aging and Geriatric Research, University of Florida-Institute on Aging, Gainesville, FL

Received 23 May 2008 ,Accepted 23 October 2008.

References 

  1. The SOLVD Investigators. Effect of enalapril on survival in patients with reduced left ventricular ejection fractions and congestive heart failure.. N Engl J Med. 1991;325:293–302
  2. The SOLVD Investigators. Effect of enalapril on mortality and the development of heart failure in asymptomatic patients with reduced left ventricular ejection fractions.. N Engl J Med. 1992;327:685–691
  3. UK Prospective Diabetes Study Group. Efficacy of atenolol and captopril in reducing risk of macrovascular and microvascular complications in type 2 diabetes: UKPDS 39.. Br Med J. 1998;317:713–720
  4. Tatti P, Pahor M, Byington RP, et al. Outcome results of the Fosinopril versus Amlodipine Cardiovascular Events randomized Trial in patients with hypertension and NIDDM. Diabetes Care. 1998;21:597–603
  5. Estacio RO, Jeffers BW, Hiatt WR, et al. The effect of nisoldipine as compared with enalapril on cardiovascular events in patients with non–insulin-dependent diabetes and hypertension. N Engl J Med. 1998;338:645–652
  6. Pahor M, Psaty BM, Alderman MH, et al. Therapeutic benefits of ACE inhibitors and other antihypertensive drugs in patients with type 2 diabetes. Diabetes Care. 2000;23:888–892
  7. Hansson L, Lindholm LH, Niskanen L, et al. Effect of angiotensin-converting-enzyme inhibition compared with conventional therapy on cardiovascular morbidity and mortality in hypertension: the Captopril Prevention Project (CAPPP) randomized trial. Lancet. 1999;353:611–616
  8. Yusuf S, Sleight P, Pogue J, et al. Effects of an angiotensin-converting-enzyme inhibitor, ramipril, on cardiovascular events in high-risk patients. The Heart Outcomes Prevention Evaluation Study Investigators. N Engl J Med. 2000;342:145–153
  9. Galkina E, Ley K. Vascular adhesion molecules in atherosclerosis. Arterioscler Thromb Vasc Biol. 2007;27:2292–2301
  10. Koenig W. Haemostatic risk factors for cardiovascular diseases. Eur Heart J. 1998;19(Suppl C):C39–C43
  11. Blake GJ, Ridker PM. Inflammatory bio-markers and cardiovascular risk prediction. J Intern Med. 2002;252:283–294
  12. Pahor M, Franse LV, Deitcher SR, et al. Fosinopril versus Amlodipine Comparative Treatments Study: a randomized trial to assess effects on plasminogen activator inhibitor-1. Circulation. 2002;105:457–461
  13. Paterna S, Di Garbo V, Avellone G, et al. Effects of losartan and delapril on the fibrinolytic system in patients with mild to moderate hypertension. Clin Drug Investig. 2003;23:717–724
  14. Trifiletti A, Barbera N, Scamardi R, et al. Effects of medium-term antihypertensive therapy on haemostatic parameters in patients with essential hypertension. Haemostasis. 1997;27:35–38
  15. Tsikouris JP, Suarez JA, Simoni JS, et al. Exploring the effects of ACE inhibitor tissue penetration on vascular inflammation following acute myocardial infarction. Coron Art Dis. 2004;15:211–217
  16. White M, Lepage S, Lavoie J, et al. Effects of combined candesartan and ACE inhibitors on BNP, markers of inflammation and oxidative stress, and glucose regulation in patients with symptomatic heart failure. J Card Fail. 2007;13:86–94
  17. Gullestad L, Aukrust P, Ueland T, et al. Effect of high- versus low-dose angiotensin converting enzyme inhibition on cytokine levels in chronic heart failure. J Am Coll Cardiol. 1999;34:2061–2067
  18. Sheth T, Parker T, Block A, et al. Comparison of the effects of omapatrilat and lisinopril on circulating neurohormones and cytokines in patients with chronic heart failure. Am J Cardiol. 2002;90:496–500
  19. Hlubocka Z, Umnerova V, Heller S, et al. Circulating intercellular cell adhesion molecule-1, endothelin-1 and von Willebrand factor—markers of endothelial dysfunction in uncomplicated essential hypertension: the effect of treatment with ACE inhibitors. J Hum Hypertens. 2002;16:557–562
  20. Schalkwijk CG, Smulders RA, Lambert J, et al. ACE-inhibition modulates some endothelial functions in healthy subjects and in normotensive type I diabetic patients. Eur J Clin Invest. 2000;30:853–860
  21. Cesari M, Kritchevsky SB, Baumgartner RN, et al. Sarcopenia, obesity and inflammation—results from the TRAIN study. Am J Clin Nutr. 2005;82:428–434
  22. Koh KK, Mincemoyer R, Bui MN, et al. Effects of hormone-replacement therapy on fibrinolysis in postmenopausal women. N Engl J Med. 1997;336:683–690
  23. Cushman M, Costantino JP, Tracy RP, et al. Tamoxifen and cardiac risk factors in healthy women: suggestion of an anti-inflammatory effect. Arterioscler Thromb Vasc Biol. 2001;21:255–261
  24. Piepho RW. Overview of the angiotensin-converting-enzyme inhibitors. Am J Health Syst Pharm. 2000;57(Suppl 1):S3–S7
  25. Greenbaum R, Zucchelli P, Caspi A, et al. Comparison of the pharmacokinetics of fosinoprilat with enalaprilat and lisinopril in patients with congestive heart failure and chronic renal insufficiency. Br J Clin Pharmacol. 2000;49:23–31
  26. Hansson L, Forslund T, Hoglund C, et al. Fosinopril versus enalapril in the treatment of hypertension: a double-blind study in 195 patients. J Cardiovasc Pharmacol. 1996;28:1–5
  27. Wagstaff AJ, Davis R, McTavish D. Fosinopril: a reappraisal of its pharmacology and therapeutic efficacy in essential hypertension. Drugs. 1996;51:777–791
  28. Pahor M, Psaty B, Alderman MH, et al. The health outcomes associated with calcium antagonists compared with other first-line antihypertensive therapies: a meta-analysis of randomized controlled trials. Lancet. 2000;356:1949–1954
  29. Neal B, MacMahon S, Chapman N, et al. Effects of ACE inhibitors, calcium antagonists, and other blood-pressure-lowering drugs: results of prospectively designed overviews of randomised trials. Blood Pressure Lowering Treatment Trialists' Collaboration. Lancet. 2000;356:1955–1964
  30. Garg R, Yusuf S. Overview of randomized trials of angiotensin-converting enzyme inhibitors on mortality and morbidity in patients with heart failure. Collaborative Group on ACE Inhibitor Trials. JAMA. 1995;273:1450–1456
  31. Macy EM, Hayes TE, Tracy RP. Variability in the measurement of C-reactive protein in healthy subjects: implications for reference intervals and epidemiological implications. Clin Chem. 1997;43:52–58
  32. Ridker PM, Cushman M, Stampfer MJ, et al. Inflammation, aspirin, and the risk of cardiovascular disease in apparently healthy men. N Engl J Med. 1997;336:973–979
  33. Declerck PJ, Alessi MC, Verstreken M, et al. Measurement of plasminogen activator inhibitor 1 in biological fluids with a murine monoclonal antibody-based enzyme-linked immunosorbent assay. Blood. 1988;71:220–225
  34. Ridker PM, Rifai N, Stampfer MJ, et al. Plasma concentration of interleukin-6 and the risk of future myocardial infarction among apparently healthy men. Circulation. 2000;101:1767–1772
  35. Juhan-Vague I, Pyke SD, Alessi MC, et al. Fibrinolytic factors and the risk of myocardial infarction or sudden death in patients with angina pectoris. ECAT Study Group. European Concerted Action on Thrombosis and Disabilities. Circulation. 1996;94:2057–2063
  36. Held C, Hjemdahl P, Rehnqvist N, et al. Fibrinolytic variables and cardiovascular prognosis in patients with stable angina pectoris treated with verapamil or metoprolol. Results from the Angina Prognosis study in Stockholm. Circulation. 1997;95:2380–2386
  37. Ridker PM, Hennekens CH, Buring JE, et al. C-reactive protein and other markers of inflammation in the prediction of cardiovascular disease in women. N Engl J Med. 2000;342:836–843
  38. Oubina MP, De Las Heras N, Cediel E, et al. Synergistic effect of angiotensin-converting enzyme (ACE) and 3-hydroxy-3-methyl-glutaryl-CoA (HMG-CoA) reductase inhibition on inflammatory markers in atherosclerotic rabbits. Clin Sci (Lond). 2003;105:655–662
  39. Oubina MP, De Las Heras N, Vasquez-Perez S, et al. Valsartan improves fibrinolytic balance in atherosclerotic rabbits. J Hypertens. 2002;20:303–310
  40. Mustonen P, Lepantalo M, Lassila R. Physical exertion induces thrombin formation and fibrin degradation in patients with peripheral atherosclerosis. Arterioscler Thromb Vasc Biol. 1998;18:244–249
  41. van der Bom JG, Bots ML, Haverkate F, et al. Fibrinolytic activity in peripheral atherosclerosis in the elderly. Thromb Haemost. 1999;81:275–280
  42. Fogari R, Zoppi A. Antihypertensive drugs and fibrinolytic function. Am J Hypertens. 2006;19:1293–1299
  43. Cruden NL, Newby DE. Clots, kinins and coronaries. Atherosclerosis. 2005;183:189–198

 Clinical trial registration no. NCT0051389.

 The TRAIN study is National Institutes of Health–funded project (NIH grant R01-HL68901). The TRAIN study was also (partially) supported by the University of Florida Claude D. Pepper Older Americans Independence Center (NIH grant 1P30-AG028740), Wake Forest University Claude D. Pepper Older Americans Independence Center (NIH grant 5P30-AG021332), and the Wake Forest University General Clinical Research Center (NIH grant M01-RR07122).

 Fosinopril was donated by Bristol-Myers Squibb (New York, NY).

PII: S0002-8703(08)00918-6

doi: 10.1016/j.ahj.2008.10.026

American Heart Journal
Volume 157, Issue 2 , Pages 334.e1-334.e8 , February 2009