Int J Angiol 2015; 24(04): 278-282
DOI: 10.1055/s-0035-1555133
Original Article
Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Coronary Artery Disease Severity and Cardiovascular Biomarkers in Patients with Peripheral Artery Disease

Hiroyuki Hikita
1   Cardiovascular Center, Yokosuka Kyosai Hospital, Yokosuka, Kanagawa, Japan
Takatoshi Shigeta
1   Cardiovascular Center, Yokosuka Kyosai Hospital, Yokosuka, Kanagawa, Japan
Shigeki Kimura
1   Cardiovascular Center, Yokosuka Kyosai Hospital, Yokosuka, Kanagawa, Japan
Atsushi Takahashi
1   Cardiovascular Center, Yokosuka Kyosai Hospital, Yokosuka, Kanagawa, Japan
Mitsuaki Isobe
2   Department of Cardiovascular Medicine, Tokyo Medical and Dental University, Tokyo, Japan
› Author Affiliations
Further Information

Publication History

Publication Date:
26 June 2015 (online)


Cardiovascular mortality in peripheral artery disease (PAD) patients is higher in critical limb ischemia (CLI) than in intermittent claudication (IC). We sought to evaluate differential characteristics of coronary artery disease (CAD) severity and prognostic biomarkers for cardiovascular events between CLI and IC patients. Coronary angiography was performed on 242 PAD patients (age 73 ± 8 years) with either CLI or IC. High-sensitivity troponin T (hs-TnT), eicosapentaenoic acid–arachidonic acid ratio (EPA/AA), and lipoprotein(a), as biomarkers for prognostic factors, were measured from blood samples. The study patients were divided into a CLI-group (n = 42) and IC-group (n = 200). The Gensini score as an indicator of coronary angiographic severity was higher in the CLI-group than in the IC-group (39.1 ± 31.2 vs. 8.5 ± 8.3, p < 0.0001). Hs-TnT and lipoprotein(a) values were higher in the CLI-group than in the IC-group (0.152 ± 0.186 ng/mL vs. 0.046 ± 0.091, p < 0.0001, 45.9 ± 23.3 mg/dL vs. 26.2 ± 27.7, p = 0.0002, respectively) and EPA/AA was lower in the CLI-group than in the IC-group (0.22 ± 0.11 vs. 0.38 ± 0.29, p = 0.0049, respectively). Greater CAD severity, higher hs-TnT, and lipoprotein(a), and lower EPA/AA were observed in the CLI-group, which may explain higher cardiovascular events in patients with CLI.

  • References

  • 1 Criqui MH, Langer RD, Fronek A , et al. Mortality over a period of 10 years in patients with peripheral arterial disease. N Engl J Med 1992; 326 (6) 381-386
  • 2 Norgren L, Hiatt WR, Dormandy JA, Nehler MR, Harris KA, Fowkes FG ; TASC II Working Group. Inter-Society Consensus for the Management of Peripheral Arterial Disease (TASC II). J Vasc Surg 2007; 45 (Suppl S): S5-S67
  • 3 Gensini GG. A more meaningful scoring system for determining the severity of coronary heart disease. Am J Cardiol 1983; 51 (3) 606
  • 4 Eapen DJ, Manocha P, Ghasemzedah N , et al. Soluble urokinase plasminogen activator receptor level is an independent predictor of the presence and severity of coronary artery disease and of future adverse events. J Am Heart Assoc 2014; 3 (5) e001118
  • 5 Saunders JT, Nambi V, de Lemos JA , et al. Cardiac troponin T measured by a highly sensitive assay predicts coronary heart disease, heart failure, and mortality in the Atherosclerosis Risk in Communities Study. Circulation 2011; 123 (13) 1367-1376
  • 6 Linnemann B, Sutter T, Herrmann E , et al. Elevated cardiac troponin T is associated with higher mortality and amputation rates in patients with peripheral arterial disease. J Am Coll Cardiol 2014; 63 (15) 1529-1538
  • 7 Gaubatz JW, Heideman C, Gotto Jr AM, Morrisett JD, Dahlen GH. Human plasma lipoprotein [a]. Structural properties. J Biol Chem 1983; 258 (7) 4582-4589
  • 8 McLean JW, Tomlinson JE, Kuang WJ , et al. cDNA sequence of human apolipoprotein(a) is homologous to plasminogen. Nature 1987; 330 (6144) 132-137
  • 9 Sorensen KE, Celermajer DS, Georgakopoulos D, Hatcher G, Betteridge DJ, Deanfield JE. Impairment of endothelium-dependent dilation is an early event in children with familial hypercholesterolemia and is related to the lipoprotein(a) level. J Clin Invest 1994; 93 (1) 50-55
  • 10 Nielsen LB, Nordestgaard BG, Stender S, Niendorf A, Kjeldsen K. Transfer of lipoprotein(a) and LDL into aortic intima in normal and in cholesterol-fed rabbits. Arterioscler Thromb Vasc Biol 1995; 15 (9) 1492-1502
  • 11 Nielsen LB, Stender S, Jauhiainen M, Nordestgaard BG. Preferential influx and decreased fractional loss of lipoprotein(a) in atherosclerotic compared with nonlesioned rabbit aorta. J Clin Invest 1996; 98 (2) 563-571
  • 12 Nielsen LB, Stender S, Kjeldsen K, Nordestgaard BG. Specific accumulation of lipoprotein(a) in balloon-injured rabbit aorta in vivo. Circ Res 1996; 78 (4) 615-626
  • 13 Nielsen LB, Grønholdt ML, Schroeder TV, Stender S, Nordestgaard BG. In vivo transfer of lipoprotein(a) into human atherosclerotic carotid arterial intima. Arterioscler Thromb Vasc Biol 1997; 17 (5) 905-911
  • 14 Boffa MB, Marcovina SM, Koschinsky ML. Lipoprotein(a) as a risk factor for atherosclerosis and thrombosis: mechanistic insights from animal models. Clin Biochem 2004; 37 (5) 333-343
  • 15 Maher VMG, Brown BG, Marcovina SM, Hillger LA, Zhao XQ, Albers JJ. Effects of lowering elevated LDL cholesterol on the cardiovascular risk of lipoprotein(a). JAMA 1995; 274 (22) 1771-1774
  • 16 Kamstrup PR, Benn M, Tybjaerg-Hansen A, Nordestgaard BG. Extreme lipoprotein(a) levels and risk of myocardial infarction in the general population: the Copenhagen City Heart Study. Circulation 2008; 117 (2) 176-184
  • 17 Kamstrup PR, Tybjaerg-Hansen A, Steffensen R, Nordestgaard BG. Genetically elevated lipoprotein(a) and increased risk of myocardial infarction. JAMA 2009; 301 (22) 2331-2339
  • 18 Lavie CJ, Milani RV, Mehra MR, Ventura HO. Omega-3 polyunsaturated fatty acids and cardiovascular diseases. J Am Coll Cardiol 2009; 54 (7) 585-594
  • 19 Weitz D, Weintraub H, Fisher E, Schwartzbard AZ. Fish oil for the treatment of cardiovascular disease. Cardiol Rev 2010; 18 (5) 258-263
  • 20 Iso H, Kobayashi M, Ishihara J , et al; JPHC Study Group. Intake of fish and n3 fatty acids and risk of coronary heart disease among Japanese: the Japan Public Health Center-Based (JPHC) Study Cohort I. Circulation 2006; 113 (2) 195-202
  • 21 Yokoyama M, Origasa H, Matsuzaki M , et al; Japan EPA lipid intervention study (JELIS) Investigators. Effects of eicosapentaenoic acid on major coronary events in hypercholesterolaemic patients (JELIS): a randomised open-label, blinded endpoint analysis. Lancet 2007; 369 (9567) 1090-1098
  • 22 Kondo T, Ogawa K, Satake T , et al. Plasma-free eicosapentaenoic acid/arachidonic acid ratio: a possible new coronary risk factor. Clin Cardiol 1986; 9 (9) 413-416
  • 23 Kashiyama T, Ueda Y, Nemoto T , et al. Relationship between coronary plaque vulnerability and serum n-3/n-6 polyunsaturated fatty acid ratio. Circ J 2011; 75 (10) 2432-2438
  • 24 Domei T, Yokoi H, Kuramitsu S , et al. Ratio of serum n-3 to n-6 polyunsaturated fatty acids and the incidence of major adverse cardiac events in patients undergoing percutaneous coronary intervention. Circ J 2012; 76 (2) 423-429
  • 25 Rutherford RB, Baker JD, Ernst C , et al. Recommended standards for reports dealing with lower extremity ischemia: revised version. J Vasc Surg 1997; 26 (3) 517-538
  • 26 Austen WG, Edwards JE, Frye RL , et al. A reporting system on patients evaluated for coronary artery disease. Report of the ad hoc committee for grading of coronary artery disease, council on cardiovascular surgery, American Heart Association. Circulation 1975; 51 (4, Suppl): 5-40
  • 27 Langsted A, Kamstrup PR, Nordestgaard BG. Lipoprotein(a): fasting and nonfasting levels, inflammation, and cardiovascular risk. Atherosclerosis 2014; 234 (1) 95-101
  • 28 Cheng SW, Ting AC. Lipoprotein (a) level and mortality in patients with critical lower limb ischaemia. Eur J Vasc Endovasc Surg 2001; 22 (2) 124-129
  • 29 Ninomiya T, Nagata M, Hata J , et al. Association between ratio of serum eicosapentaenoic acid to arachidonic acid and risk of cardiovascular disease: the Hisayama Study. Atherosclerosis 2013; 231 (2) 261-267