Risk Markers in the Acute Coronary Syndromes

NCT00521976 | Completed Results

• 1 other identifier: NSD9253
• Study Type: observational
• Target: 871
• Locations: 1 country
• Sites: 1

Brief Summary

The main aim of this trial is to assess the long-term prognostic value of different types of Factor XIIa in an unselected, single center series of 871 chest pain patients admitted to the emergency unit, employing blood samples collected at admission. The second purpose of this study is to assess the incremental prognostic value of B-type natriuretic peptide (BNP) and high-sensitive C-reactive protein (hsCRP). A third purpose of this study is to evaluate the prognostic impact of the Omega-3 Index which is a measure of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) relative to other fatty acids in the erythrocyte membrane.

Conditions

Chest Pain; Coronary Artery Disease; Unstable Angina Pectoris; Myocardial Infarction

Keywords

Risk assessment; Chest pain; Coronary Artery Disease; Acute coronary syndromes; Factor XIIa; B-type natriuretic peptide (BNP); high-sensitive C-reactive protein (hsCRP); Omega-3

Outcome Measures

Primary Outcomes (1)

• Total Mortality.

  24 months.

Secondary Outcomes (1)

• Recurrent Troponin-T (TnT) Positive Events

  24 months.

Study Arms (1)

Chest pain

Men and women admitted with chest pain and suspected acute coronary syndrome (ACS).

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Probability Sample

Study Population

871 men and women admitted with chest pain and potential acute cornary syndrome (ACS) at the Stavanger University Hospital between November 2002 and October 2003.

You may qualify if:

• adults \> 18 years able to give informed consent
• a history of chest pain or other symptoms suggestive of an ACS leading to admission at the emergency unit

You may not qualify if:

• \< 18 years of age
• Unwillingness or incapacity to provide informed consent

Sponsors & Collaborators

• Helse Stavanger HF: lead
• Helse Vest: collaborator
• Axis-Shield, Dundee, UK: collaborator

Study Sites (1)

Stavanger University Hospital

Stavanger, Rogaland, 4068, Norway

Location

Related Publications (37)

• Miller GJ, Esnouf MP, Burgess AI, Cooper JA, Mitchell JP. Risk of coronary heart disease and activation of factor XII in middle-aged men. Arterioscler Thromb Vasc Biol. 1997 Oct;17(10):2103-6. doi: 10.1161/01.atv.17.10.2103.

  PMID: 9351378 BACKGROUND

• Zito F, Drummond F, Bujac SR, Esnouf MP, Morrissey JH, Humphries SE, Miller GJ. Epidemiological and genetic associations of activated factor XII concentration with factor VII activity, fibrinopeptide A concentration, and risk of coronary heart disease in men. Circulation. 2000 Oct 24;102(17):2058-62. doi: 10.1161/01.cir.102.17.2058.

  PMID: 11044420 BACKGROUND

• Cooper JA, Miller GJ, Bauer KA, Morrissey JH, Meade TW, Howarth DJ, Barzegar S, Mitchell JP, Rosenberg RD. Comparison of novel hemostatic factors and conventional risk factors for prediction of coronary heart disease. Circulation. 2000 Dec 5;102(23):2816-22. doi: 10.1161/01.cir.102.23.2816.

  PMID: 11104738 BACKGROUND

• Kohler HP, Carter AM, Stickland MH, Grant PJ. Levels of activated FXII in survivors of myocardial infarction--association with circulating risk factors and extent of coronary artery disease. Thromb Haemost. 1998 Jan;79(1):14-8.

  PMID: 9459314 BACKGROUND

• Pritchard D, Polwart R. In-vivo, activated factor XII exists in multiple forms, but predominantly as a 53 kD Species. J Thromb and Haemost 2005; Suppl.1; ISSN 1740-3340.

  BACKGROUND

• Maeda K, Tsutamoto T, Wada A, Hisanaga T, Kinoshita M. Plasma brain natriuretic peptide as a biochemical marker of high left ventricular end-diastolic pressure in patients with symptomatic left ventricular dysfunction. Am Heart J. 1998 May;135(5 Pt 1):825-32. doi: 10.1016/s0002-8703(98)70041-9.

  PMID: 9588412 BACKGROUND

• Nakagawa O, Ogawa Y, Itoh H, Suga S, Komatsu Y, Kishimoto I, Nishino K, Yoshimasa T, Nakao K. Rapid transcriptional activation and early mRNA turnover of brain natriuretic peptide in cardiocyte hypertrophy. Evidence for brain natriuretic peptide as an "emergency" cardiac hormone against ventricular overload. J Clin Invest. 1995 Sep;96(3):1280-7. doi: 10.1172/JCI118162.

  PMID: 7657802 BACKGROUND

• Richards AM, Nicholls MG, Espiner EA, Lainchbury JG, Troughton RW, Elliott J, Frampton C, Turner J, Crozier IG, Yandle TG. B-type natriuretic peptides and ejection fraction for prognosis after myocardial infarction. Circulation. 2003 Jun 10;107(22):2786-92. doi: 10.1161/01.CIR.0000070953.76250.B9. Epub 2003 May 27.

  PMID: 12771003 BACKGROUND

• de Lemos JA, Morrow DA, Bentley JH, Omland T, Sabatine MS, McCabe CH, Hall C, Cannon CP, Braunwald E. The prognostic value of B-type natriuretic peptide in patients with acute coronary syndromes. N Engl J Med. 2001 Oct 4;345(14):1014-21. doi: 10.1056/NEJMoa011053.

  PMID: 11586953 BACKGROUND

• Morrow DA, de Lemos JA, Sabatine MS, Murphy SA, Demopoulos LA, DiBattiste PM, McCabe CH, Gibson CM, Cannon CP, Braunwald E. Evaluation of B-type natriuretic peptide for risk assessment in unstable angina/non-ST-elevation myocardial infarction: B-type natriuretic peptide and prognosis in TACTICS-TIMI 18. J Am Coll Cardiol. 2003 Apr 16;41(8):1264-72. doi: 10.1016/s0735-1097(03)00168-2.

  PMID: 12706919 BACKGROUND

• Omland T, Persson A, Ng L, O'Brien R, Karlsson T, Herlitz J, Hartford M, Caidahl K. N-terminal pro-B-type natriuretic peptide and long-term mortality in acute coronary syndromes. Circulation. 2002 Dec 3;106(23):2913-8. doi: 10.1161/01.cir.0000041661.63285.ae.

  PMID: 12460871 BACKGROUND

• Wang TJ, Larson MG, Levy D, Benjamin EJ, Leip EP, Omland T, Wolf PA, Vasan RS. Plasma natriuretic peptide levels and the risk of cardiovascular events and death. N Engl J Med. 2004 Feb 12;350(7):655-63. doi: 10.1056/NEJMoa031994.

  PMID: 14960742 BACKGROUND

• Ross R. Atherosclerosis--an inflammatory disease. N Engl J Med. 1999 Jan 14;340(2):115-26. doi: 10.1056/NEJM199901143400207. No abstract available.

  PMID: 9887164 BACKGROUND

• Liuzzo G, Biasucci LM, Gallimore JR, Grillo RL, Rebuzzi AG, Pepys MB, Maseri A. The prognostic value of C-reactive protein and serum amyloid a protein in severe unstable angina. N Engl J Med. 1994 Aug 18;331(7):417-24. doi: 10.1056/NEJM199408183310701.

  PMID: 7880233 BACKGROUND

• Berk BC, Weintraub WS, Alexander RW. Elevation of C-reactive protein in "active" coronary artery disease. Am J Cardiol. 1990 Jan 15;65(3):168-72. doi: 10.1016/0002-9149(90)90079-g.

  PMID: 2296885 BACKGROUND

• de Lemos JA. The latest and greatest new biomarkers: which ones should we measure for risk prediction in our practice? Arch Intern Med. 2006 Dec 11-25;166(22):2428-30. doi: 10.1001/archinte.166.22.2428. No abstract available.

  PMID: 17159006 BACKGROUND

• Rothenbacher D, Koenig W, Brenner H. Comparison of N-terminal pro-B-natriuretic peptide, C-reactive protein, and creatinine clearance for prognosis in patients with known coronary heart disease. Arch Intern Med. 2006 Dec 11-25;166(22):2455-60. doi: 10.1001/archinte.166.22.2455.

  PMID: 17159010 BACKGROUND

• Kim H, Yang DH, Park Y, Han J, Lee H, Kang H, Park HS, Cho Y, Chae SC, Jun JE, Park WH. Incremental prognostic value of C-reactive protein and N-terminal proB-type natriuretic peptide in acute coronary syndrome. Circ J. 2006 Nov;70(11):1379-84. doi: 10.1253/circj.70.1379.

  PMID: 17062957 BACKGROUND

• Ndrepepa G, Kastrati A, Braun S, Mehilli J, Niemoller K, von Beckerath N, von Beckerath O, Vogt W, Schomig A. N-terminal probrain natriuretic peptide and C-reactive protein in stable coronary heart disease. Am J Med. 2006 Apr;119(4):355.e1-8. doi: 10.1016/j.amjmed.2005.10.060.

  PMID: 16564781 BACKGROUND

• Harris WS, Sands SA, Windsor SL, Ali HA, Stevens TL, Magalski A, Porter CB, Borkon AM. Omega-3 fatty acids in cardiac biopsies from heart transplantation patients: correlation with erythrocytes and response to supplementation. Circulation. 2004 Sep 21;110(12):1645-9. doi: 10.1161/01.CIR.0000142292.10048.B2. Epub 2004 Sep 7.

  PMID: 15353491 BACKGROUND

• Ponitz V, Pritchard D, Grundt H, Nilsen DW. Specific types of activated Factor XII increase following thrombolytic therapy with tenecteplase. J Thromb Thrombolysis. 2006 Dec;22(3):199-203. doi: 10.1007/s11239-006-9031-6.

  PMID: 17111198 RESULT

• Ponitz V, Pritchard D, Grundt H, Mehus MB, Nilsen DW. Changes of plasma activated Factor XII type A (XIIaA) concentrations following percutaneous coronary intervention (PCI). J Thromb Thrombolysis. 2007 Oct;24(2):131-5. doi: 10.1007/s11239-007-0041-9. Epub 2007 May 11.

  PMID: 17492403 RESULT

• Brugger-Andersen T, Hetland O, Ponitz V, Grundt H, Nilsen DW. The effect of primary percutaneous coronary intervention as compared to tenecteplase on myeloperoxidase, pregnancy-associated plasma protein A, soluble fibrin and D-dimer in acute myocardial infarction. Thromb Res. 2007;119(4):415-21. doi: 10.1016/j.thromres.2006.03.009. Epub 2006 May 2.

  PMID: 16650886 RESULT

• Ponitz V, Brugger-Andersen T, Pritchard D, Grundt H, Staines H, Nilsen DW; RACS Study Group. Activated factor XII type A predicts long-term mortality in patients admitted with chest pain. J Thromb Haemost. 2009 Feb;7(2):277-87. doi: 10.1111/j.1538-7836.2008.03248.x. Epub 2008 Dec 1.

  PMID: 19054318 RESULT

• Brugger-Andersen T, Ponitz V, Staines H, Grundt H, Hetland O, Nilsen DW. The prognostic utility of D-dimer and fibrin monomer at long-term follow-up after hospitalization with coronary chest pain. Blood Coagul Fibrinolysis. 2008 Oct;19(7):701-7. doi: 10.1097/MBC.0b013e32830b1512.

  PMID: 18832914 RESULT

• Brugger-Andersen T, Ponitz V, Staines H, Pritchard D, Grundt H, Nilsen DW. B-type natriuretic peptide is a long-term predictor of all-cause mortality, whereas high-sensitive C-reactive protein predicts recurrent short-term troponin T positive cardiac events in chest pain patients: a prognostic study. BMC Cardiovasc Disord. 2008 Nov 25;8:34. doi: 10.1186/1471-2261-8-34.

  PMID: 19032759 RESULT

• Aarsetoy H, Ponitz V, Nilsen OB, Grundt H, Harris WS, Nilsen DW. Low levels of cellular omega-3 increase the risk of ventricular fibrillation during the acute ischaemic phase of a myocardial infarction. Resuscitation. 2008 Sep;78(3):258-64. doi: 10.1016/j.resuscitation.2008.04.007. Epub 2008 Jun 16.

  PMID: 18556107 RESULT

• Aarsetoey H, Ponitz V, Grundt H, Staines H, Harris WS, Nilsen DW. (n-3) Fatty acid content of red blood cells does not predict risk of future cardiovascular events following an acute coronary syndrome. J Nutr. 2009 Mar;139(3):507-13. doi: 10.3945/jn.108.096446. Epub 2009 Jan 21.

  PMID: 19158216 RESULT

• Naesgaard PA, Ponitz V, Aarsetoey H, Brugger-Andersen T, Grundt H, Harris WS, Staines H, Nilsen DW. Prognostic utility of vitamin D in acute coronary syndrome patients in coastal Norway. Dis Markers. 2015;2015:283178. doi: 10.1155/2015/283178. Epub 2015 Feb 5.

  PMID: 25722531 RESULT

• Mjelva OR, Brugger-Andersen T, Ponitz V, Grundt H, Kontny F, Staines H, Nilsen DW. Long-term prognostic utility of PAPP-A and calprotectin in suspected acute coronary syndrome. Scand Cardiovasc J. 2013 Apr;47(2):88-97. doi: 10.3109/14017431.2013.764571. Epub 2013 Feb 13.

  PMID: 23406538 RESULT

• Nilsen DWT, Aarsetoey H, Poenitz V, Brugger-Andersen T, Harris WS, Staines H, Grundt H. Dihomo-gamma-linolenic acid (DGLA) is inversely related to risk for cardiac death and cardiovascular events during 2 years follow-up after admission for an acute coronary syndrome. Prostaglandins Leukot Essent Fatty Acids. 2025 Jul;205:102684. doi: 10.1016/j.plefa.2025.102684. Epub 2025 Apr 10.

  PMID: 40245567 DERIVED

• Andersen T, Ueland T, Aukrust P, Nilsen DWT, Grundt H, Staines H, Ponitz V, Kontny F. Procollagen type 1 N-terminal propeptide is associated with adverse outcome in acute chest pain of suspected coronary origin. Front Cardiovasc Med. 2023 Sep 4;10:1191055. doi: 10.3389/fcvm.2023.1191055. eCollection 2023.

  PMID: 37731526 DERIVED

• Andersen T, Ueland T, Aukrust P, Nilsen DW, Grundt H, Staines H, Kontny F. Podocan and Adverse Clinical Outcome in Patients Admitted With Suspected Acute Coronary Syndromes. Front Cardiovasc Med. 2022 May 20;9:867944. doi: 10.3389/fcvm.2022.867944. eCollection 2022.

  PMID: 35669474 DERIVED

• Aarsetoy R, Ueland T, Aukrust P, Michelsen AE, Leon de la Fuente R, Grundt H, Staines H, Nygaard O, Nilsen DWT. Complement component 7 is associated with total- and cardiac death in chest-pain patients with suspected acute coronary syndrome. BMC Cardiovasc Disord. 2021 Oct 14;21(1):496. doi: 10.1186/s12872-021-02306-w.

  PMID: 34649504 DERIVED

• Aarsetoy R, Ueland T, Aukrust P, Michelsen AE, de la Fuente RL, Ponitz V, Brugger-Andersen T, Grundt H, Staines H, Nilsen DWT. Angiopoietin-2 and angiopoietin-like 4 protein provide prognostic information in patients with suspected acute coronary syndrome. J Intern Med. 2021 Oct;290(4):894-909. doi: 10.1111/joim.13339. Epub 2021 Jul 8.

  PMID: 34237166 DERIVED

• Ponitz V, Brugger-Andersen T, Pritchard D, Grundt H, Staines H, Nilsen DW; RACS study group. Activated factor XII type A and B-type natriuretic peptide are complementary and incremental predictors of mortality in patients following admission with acute coronary syndrome. Blood Coagul Fibrinolysis. 2009 Dec;20(8):652-60. doi: 10.1097/MBC.0b013e32832fa814.

  PMID: 19809305 DERIVED

• Brugger-Andersen T, Ponitz V, Kontny F, Staines H, Grundt H, Sagara M, Nilsen DW. The long pentraxin 3 (PTX3): a novel prognostic inflammatory marker for mortality in acute chest pain. Thromb Haemost. 2009 Sep;102(3):555-63. doi: 10.1160/TH09-02-0137.

  PMID: 19718477 DERIVED

Biospecimen

Retention: SAMPLES WITHOUT DNA

Serum, Citrated plasma, EDTA-plasma and packed red blood cells are kept in suitable aliquots at -80 degrees Celcius.

MeSH Terms

Conditions

Chest Pain; Coronary Artery Disease; Angina, Unstable; Myocardial Infarction; Acute Coronary Syndrome

Condition Hierarchy (Ancestors)

Pain; Neurologic Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Coronary Disease; Myocardial Ischemia; Heart Diseases; Cardiovascular Diseases; Arteriosclerosis; Arterial Occlusive Diseases; Vascular Diseases; Angina Pectoris; Infarction; Ischemia; Pathologic Processes; Necrosis

Results Point of Contact

• Title: Dennis W.T. Nilsen MD PhD FESC FAHA
• Organization: Stavanger University Hospital

nide@sus.no

+4705151

Study Officials

• Dennis WT Nilsen, MD PhD FESC

  Stavanger University Hospital, Dept. of Cardiology

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: LTE60
• Restrictive Agreement: Yes

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER GOV
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 27, 2007
• First Posted: August 28, 2007
• Study Start: November 1, 2002
• Primary Completion: December 1, 2005
• Study Completion: December 1, 2005
• Last Updated: September 29, 2021
• Results First Posted: August 11, 2009

Record last verified: 2015-05

Locations

NO (1)