Serum albumin predicts cardiac adverse events in patients with advanced atherosclerosis – interrelation with traditional cardiovascular risk factors

Summary

Low serum albumin is a powerful predictor of cardiovascular adverse events in healthy subjects and patients with subclinical atherosclerosis. We investigated the association between serum albumin, traditional cardiovascular risk factors, markers of inflammation and cardiovascular outcome in 515 patients with advanced atherosclerosis and severe peripheral artery disease. Cardiovascular risk profile, serum albumin, serum amyloid A (SAA) and fibrinogen were obtained at baseline, and patients were followed for median 21 months (interquartile range 12 to 25) for the occurrence of major adverse cardiac events (MACE: myocardial infarction, percutaneous coronary interventions, coronary artery bypass graft, and death). We observed 135 MACE in 109 patients (21%). Cumulative event-free survival rates at 6, 12, and 24 months were 95%, 91%, and 80%, respectively. Low albumin predicted MACE independently of SAA and fibrinogen. Adjusted hazard ratios for the occurrence of MACE, any death, and the composite of death and MI according to increasing quartiles of albumin were 2.40, 1.14 and 1.09 (p<0.001), 2.94, 1.34 and 1.11 (p=0.003) and 3.63, 1.86 and 1.29 (p<0.001), respectively, as compared to the highest quartile. Considering albumin in conjunction with traditional cardiovascular risk factors (smoking, hyperlipidemia, hypertension and diabetes), we found that low albumin predicted MACE only in patients with a low risk profile (less than 3 risk factors) (p<0.001), whereas low albumin was not associated with MACE in patients with three or more risk factors (p=0.66). We conclude that low serum albumin is associated with cardiovascular outcome of patients with advanced atherosclerosis adding to the prognostic information of other inflammatory markers, and may be particularly useful for risk prediction in patients with few traditional risk factors.

Keywords

Arteriosclerosis - complications - inflammation - albumin

• References

• 1 Newman AB, Shemanski L, Manolio TA. et al. Ankle-arm index as a predictor of cardiovascular disease and mortality in the Cardiovascular Health Study. The Cardiovascular Health Study Group. Arterioscler Thromb Vasc Biol 1999; 19: 538-45.
• 2 Dieter RS, Chu WW, Pacanowski JP. et al. The significance of lower extremity peripheral arterial disease. Clin Cardiol 2002; 25: 3-10.
• 3 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: 836-43.
• 4 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: 973-9.
• 5 Lusis AJ. Atherosclerosis. Nature 2000; 407: 233-41.
• 6 Ross R. Atherosclerosis: an inflammatory disease. N Engl J Med 1999; 340: 115-26.
• 7 Libby P, Ridker P, Maseri A. Inflammation and atherosclerosis. Circulation 2002; 105: 1135-43.
• 8 Glass CK, Witztum JL. Atherosclerosis: the road ahead. Cell 2001; 104: 503-16.
• 9 Gabay C, Kushner I. Acute phase proteins and other systemic responses to inflammation. N Engl J Med 1999; 340: 448-54.
• 10 Danesh J, Whincup P, Walker M. et al. Low grade inflammation and coronary heart disease: prospective study and updated metaanalysis. BMJ 2000; 321: 199-204.
• 11 Danesh J, Collins R, Appleby P. et al. Fibrinogen, C-reactive protein, albumin or white blood cell count: meta-analysis of prospective studies of coronary heart disease. JAMA 1998; 279: 1477-82.
• 12 Kuller LH, Eichner JE, Orchard TJ. et al. The relation between serum albumin levels and risk of coronary heart disease in the Multiple Risk Factors Intervention Trial. Am J Epidemiol 1991; 134: 1266-77.
• 13 Phillips A, Shaper AG, Whincup PH. Association between serum albumin and mortality from cardiovascular disease, cancer, and other causes. Lancet 1989; 02: 1434-6.
• 14 Djoussé L, Rothman KJ, Cupples LA. et al. Serum albumin and risk of myocardial infarction and all-cause mortality in the Framingham Offspring Study. Circulation 2002; 106: 2919.
• 15 Danesh J, Muir J, Wong YK. et al. Risk factors for coronary heart disease and acute-phase proteins. A population-based study. Eur Heart J 1999; 954-9.
• 16 Dormandy JA, Rutherford B. Management of peripheral arterial disease (PAD) TASC Working Group. TransAtlantic Inter-Society Consensus (TASC). J Vasc Surg 2000; 31: S1-S296.
• 17 Alpert JS, Thygesen K, Antman E. et al. Myocardial infarction redefined – a consensus document of The Joint European Society of Cardiology/American College of Cardiology Committee for the redefinition of myocardial infarction. J Am Coll Cardiol 2000; 36: 959-69.
• 18 Goldwasser P, Feldman J. Association of serum albumin and mortality risk. J Clin Epidemiol 1997; 50: 693-703.
• 19 Weijenberg MP, Feskens EJ, Souverijn JH. Serum albumin, coronary heart disease risk, and mortality in an elderly cohort. Epidemiology 1997; 08: 87-92.
• 20 Gillum RF, Makuc DM. Serum albumin, coronary heart disease, and death. Am Heart J 1992; 123: 507-13.
• 21 Corti MC, Guralnik JM, Salive M. et al. Serum albumin level and physical disability as predictors of mortality in older persons. JAMA 1994; 272: 1036-42.
• 22 Darne B, Ducimetiere P, Guize L. Serum albumin and mortality. Lancet 1990; 335: 350-1.
• 23 Reuben DB, Ferrucci L, Wallace R. et al. The prognostic value of serum albumin in healthy older persons with low and high serum interleukin-6 (IL-6) levels. J Am Geriatr Soc 2000; 48: 1404-7.
• 24 Halliwell B. Albumin: an important extracellular antioxidant?. Biochem Pharmacol 1988; 37: 569-71.
• 25 Wayner DD, Burton GW, Ingold KU. et al. Quantitative measurement of the total, peroxyl radical-trapping anti-oxidant capability of human blood plasma by controlled peroxidation: the important contribution made by plasma proteins. FEBS Lett 1985; 187: 33-7.
• 26 Luoma PV, Nayha S, Sikkila K. et al. High serum alpha-tocopherol, albumin, selenium and cholesterol, and low mortality from coronary heart disease in northern Finland. J Intern Med 1995; 237: 49-54.
• 27 Zoellner H, Hofler M, Beckmann R. et al. Serum albumin is a specific inhibitor of apoptosis in human endothelial cells. J Cell Sci 1996; 109: 2571-80.