Inflammation, Infection, and Future Cardiovascular Risk

Cardiovascular Diseases Clinical Trial

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00005496
• Other study ID #: 5014
• Secondary ID: R01HL058755
• Status: Completed
• Phase: N/A
• First received: May 25, 2000
• Last updated: March 15, 2016
• Start date: September 1998
• Est. completion date: August 2002

Study information

• Verified date: February 2005
• Source: National Heart, Lung, and Blood Institute (NHLBI)
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Federal Government
• Study type: Observational

Clinical Trial Summary

To examine markers of underlying chronic inflammation and infection as potential risk factors for future myocardial infarction (MI), stroke (CVA), and venous thromboembolism (VTE) in plasma samples collected at baseline from healthy participants in the Physicians' Health Study (PHS).

Description:

BACKGROUND:

The PHS is a cohort which included 14,916 men initially free of cardiovascular disease and cancer who provided plasma samples at study entry in 1982. These men were randomly assigned in a factorial design to aspirin or beta-carotene therapy, and have been followed prospectively for the occurrence of vascular disease.

DESIGN NARRATIVE:

Employing a nested case-control design, baseline plasma samples are assayed for four markers of inflammation (interleukin-6, TNF-alpha, soluble ICAM, soluble VCAM) and four markers of chronic infection (antibody titers directed against Chlamydia pneumoniae, Helicobacter pylori, Herpes simplex virus, and cytomegalovirus). Case subjects are those study participants who have subsequently developed MI (N=550), CVA (N=400), or VTE (N=200). Control subjects are selected from those study participants who remained healthy during follow-up and are matched to the cases by age, smoking status, and follow-up time. Data on usual cardiovascular risk factors, lipid parameters, and hemostatic markers of risk are already available in the PHS and will be used to evaluate the results for potential confounding and effect modification. Since the PHS was a randomized trial of low-dose aspirin for its initial 5 years, this cohort also provides the unique opportunity to investigate whether the use of an agent with anti-inflammatory properties modifies the risk of subsequent thrombosis among those with underlying inflammation. Indeed, this intriguing hypothesis has recently been raised regarding data relating another marker of inflammation, C-reactive protein, to future risks of myocardial infarction and stroke.

These analyses will take advantage of an existing blood bank from a well-characterized large cohort with many years of follow-up and high quality end-point verification. Thus, this study could provide an efficient and cost-effective mechanism to evaluate the posited, but unproven roles of inflammation and infection as risk factors for future cardiovascular disease.

The study completion date listed in this record was obtained from the "End Date" entered in the Protocol Registration and Results System (PRS) record.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 0
• Est. completion date: August 2002
• Accepts healthy volunteers: No
• Gender: Male
• Age group: N/A to 100 Years
• Eligibility: No eligibility criteria

Study Design

N/A

Related Conditions & MeSH terms

• Cardiovascular Diseases
• Cerebrovascular Accident
• Chlamydia Infections
• Communicable Diseases
• Coronary Artery Disease
• Coronary Disease
• Cytomegalovirus Infections
• Heart Diseases
• Helicobacter Infections
• Herpesviridae Infections
• Infection
• Inflammation
• Myocardial Infarction
• Stroke
• Thromboembolism
• Venous Thromboembolism

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
National Heart, Lung, and Blood Institute (NHLBI)

References & Publications (24)

Albert MA, Rifai N, Ridker PM. Plasma levels of cystatin-C and mannose binding protein are not associated with risk of developing systemic atherosclerosis. Vasc Med. 2001;6(3):145-9. — View Citation

Blake GJ, Dada N, Fox JC, Manson JE, Ridker PM. A prospective evaluation of lipoprotein-associated phospholipase A(2) levels and the risk of future cardiovascular events in women. J Am Coll Cardiol. 2001 Nov 1;38(5):1302-6. — View Citation

Blake GJ, Otvos JD, Rifai N, Ridker PM. Low-density lipoprotein particle concentration and size as determined by nuclear magnetic resonance spectroscopy as predictors of cardiovascular disease in women. Circulation. 2002 Oct 8;106(15):1930-7. — View Citation

Blake GJ, Ridker PM. High sensitivity C-reactive protein for predicting cardiovascular disease: an inflammatory hypothesis. Eur Heart J. 2001 Mar;22(5):349-52. — View Citation

Blake GJ, Schmitz C, Lindpaintner K, Ridker PM. Mutation in the promoter region of the beta-fibrinogen gene and the risk of future myocardial infarction, stroke and venous thrombosis. Eur Heart J. 2001 Dec;22(24):2262-6. — View Citation

Chae CU, Lee RT, Rifai N, Ridker PM. Blood pressure and inflammation in apparently healthy men. Hypertension. 2001 Sep;38(3):399-403. — View Citation

Liu S, Manson JE, Buring JE, Stampfer MJ, Willett WC, Ridker PM. Relation between a diet with a high glycemic load and plasma concentrations of high-sensitivity C-reactive protein in middle-aged women. Am J Clin Nutr. 2002 Mar;75(3):492-8. — View Citation

Pradhan AD, Manson JE, Rifai N, Buring JE, Ridker PM. C-reactive protein, interleukin 6, and risk of developing type 2 diabetes mellitus. JAMA. 2001 Jul 18;286(3):327-34. — View Citation

Pradhan AD, Rifai N, Ridker PM. Soluble intercellular adhesion molecule-1, soluble vascular adhesion molecule-1, and the development of symptomatic peripheral arterial disease in men. Circulation. 2002 Aug 13;106(7):820-5. — View Citation

Redberg RF, Rifai N, Gee L, Ridker PM. Lack of association of C-reactive protein and coronary calcium by electron beam computed tomography in postmenopausal women: implications for coronary artery disease screening. J Am Coll Cardiol. 2000 Jul;36(1):39-43. — View Citation

Ridker PM, Danesh J, Youngman L, Collins R, Stampfer MJ, Peto R, Hennekens CH. A prospective study of Helicobacter pylori seropositivity and the risk for future myocardial infarction among socioeconomically similar U.S. men. Ann Intern Med. 2001 Aug 7;135(3):184-8. — View Citation

Ridker PM, Hennekens CH, Buring JE, Kundsin R, Shih J. Baseline IgG antibody titers to Chlamydia pneumoniae, Helicobacter pylori, herpes simplex virus, and cytomegalovirus and the risk for cardiovascular disease in women. Ann Intern Med. 1999 Oct 19;131(8):573-7. — View Citation

Ridker PM, Hennekens CH, Buring JE, Rifai N. C-reactive protein and other markers of inflammation in the prediction of cardiovascular disease in women. N Engl J Med. 2000 Mar 23;342(12):836-43. — View Citation

Ridker PM, Hennekens CH, Rifai N, Buring JE, Manson JE. Hormone replacement therapy and increased plasma concentration of C-reactive protein. Circulation. 1999 Aug 17;100(7):713-6. — View Citation

Ridker PM, Hennekens CH, Stampfer MJ, Wang F. Prospective study of herpes simplex virus, cytomegalovirus, and the risk of future myocardial infarction and stroke. Circulation. 1998 Dec 22-29;98(25):2796-9. — View Citation

Ridker PM, Rifai N, Clearfield M, Downs JR, Weis SE, Miles JS, Gotto AM Jr; Air Force/Texas Coronary Atherosclerosis Prevention Study Investigators. Measurement of C-reactive protein for the targeting of statin therapy in the primary prevention of acute coronary events. N Engl J Med. 2001 Jun 28;344(26):1959-65. — View Citation

Ridker PM, Rifai N, Stampfer MJ, Hennekens CH. Plasma concentration of interleukin-6 and the risk of future myocardial infarction among apparently healthy men. Circulation. 2000 Apr 18;101(15):1767-72. — View Citation

Rifai N, Tracy RP, Ridker PM. Clinical efficacy of an automated high-sensitivity C-reactive protein assay. Clin Chem. 1999 Dec;45(12):2136-41. — View Citation

Zee RY, Bates D, Ridker PM. A prospective evaluation of the CD14 and CD18 gene polymorphisms and risk of stroke. Stroke. 2002 Apr;33(4):892-5. — View Citation

Zee RY, Bates D, Ridker PM. A prospective evaluation of the heat shock protein 70 gene polymorphisms and the risk of stroke. Thromb Haemost. 2002 Apr;87(4):622-5. — View Citation

Zee RY, Hegener HH, Cook NR, Ridker PM. C-reactive protein gene polymorphisms and the risk of venous thromboembolism: a haplotype-based analysis. J Thromb Haemost. 2004 Aug;2(8):1240-3. — View Citation

Zee RY, Lindpaintner K, Struk B, Hennekens CH, Ridker PM. A prospective evaluation of the CD14 C(-260)T gene polymorphism and the risk of myocardial infarction. Atherosclerosis. 2001 Feb 15;154(3):699-702. — View Citation

Zee RY, Lunze K, Lindpaintner K, Ridker PM. A prospective evaluation of the interleukin-1 receptor antagonist intron 2 gene polymorphism and the risk of myocardial infarction. Thromb Haemost. 2001 Nov;86(5):1141-3. — View Citation

Zee RY, Ridker PM. Polymorphism in the human C-reactive protein (CRP) gene, plasma concentrations of CRP, and the risk of future arterial thrombosis. Atherosclerosis. 2002 May;162(1):217-9. — View Citation

* Note: There are 24 references in all — Click here to view all references