| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
(Circulation. 2000;102:1917.)
© 2000 American Heart Association, Inc.
Clinical Investigation and Reports |
Cytomegalovirus Seropositivity and C-Reactive Protein Have Independent and Combined Predictive Value for Mortality in Patients With Angiographically Demonstrated Coronary Artery Disease
From LDS Hospital (J.B.M., B.D.H., J.F.C., T.E.M., T.L.B., R.R.P.) and the University of Utah (J.B.M., J.F.C., J.L.A.), Salt Lake City.
Correspondence to Joseph B. Muhlestein, MD, Division of Cardiology, LDS Hospital, 8th Ave and C St, Salt Lake City, UT 84143. E-mail ldbmuhle{at}ihc.com
Background—The role of inflammation in coronary artery disease (CAD) is being increasingly recognized. Markers of inflammation (eg, C-reactive protein [CRP]) and infection (eg, seropositivity to Chlamydia pneumoniae, cytomegalovirus [CMV], and Helicobacter pylori) have been proposed as risk factors for CAD, but these associations require further evaluation.
Methods and Results—We prospectively tested whether CRP levels
and IgG seropositivity to C pneumoniae, CMV, and
H pylori are predictors of subsequent mortality in 985
consecutive patients with angiographically demonstrated CAD
(stenosis 
70%). Patients were followed for an average of 2.7
years (range 1.5 to 4.0 years). Patients averaged 65 years of age; 77%
were men; and 110 (11.2%) died during follow-up. CRP levels were
significantly elevated in nonsurvivors compared with survivors (mean
CRP 3.1 mg/dL versus 1.5 mg/dL, P=0.003). After
controlling for all known baseline variables, the 2nd and 3rd
tertiles of CRP compared with the 1st produced a Cox hazard ratio (HR)
for mortality of 2.4 (P=0.001). Of the 3 infectious
markers tested, only seropositivity to CMV (HR=1.9,
P<0.05) was predictive of mortality. The majority of
mortality risk associated with elevated CRP or CMV seropositivity
occurred when both risk factors were present (P for
trend <0.0001). Other independent predictors of increased risk of
mortality were age (HR=1.07 per year, P<0.0001), left
ventricular ejection fraction (HR=0.97 per percent,
P<0.0001), and diabetes mellitus (HR=1.7,
P=0.02).
Conclusions—CMV seropositivity and elevated CRP, especially when in combination, are strong, independent predictors of mortality in patients with CAD. This suggests an interesting hypothesis that a chronic, smoldering infection (CMV) might have the capacity to accelerate the atherothrombotic process.
Key Words: coronary disease • risk factors • survival • antibodies • follow-up studies
This article has been cited by other articles:
 |
|
 |
|
  Z. Qian, B. Xuan, T. T. Hong, and D. Yu The Full-Length Protein Encoded by Human Cytomegalovirus Gene UL117 Is Required for the Proper Maturation of Viral Replication Compartments J. Virol., April 1, 2008; 82(7): 3452 - 3465. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. G. H. Betjes, N. H. R. Litjens, and R. Zietse Seropositivity for cytomegalovirus in patients with end-stage renal disease is strongly associated with atherosclerotic disease Nephrol. Dial. Transplant., November 1, 2007; 22(11): 3298 - 3303. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. Hussain, M. Burch, M. J. Fenton, P. M. Whitmore, P. Rees, M. Elliott, and P. Aurora Positive Pretransplantation Cytomegalovirus Serology Is a Risk Factor for Cardiac Allograft Vasculopathy in Children Circulation, April 3, 2007; 115(13): 1798 - 1805. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. S. V. Elkind, W. Tai, K. Coates, M. C. Paik, and R. L. Sacco High-sensitivity C-reactive protein, lipoprotein-associated phospholipase A2, and outcome after ischemic stroke. Arch Intern Med, October 23, 2006; 166(19): 2073 - 2080. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. K. Salem, P. Ranjzad, A. Driessen, C. E. Appleby, A. M. Heagerty, and P. A. Kingston Beta-Adrenoceptor Blockade Markedly Attenuates Transgene Expression From Cytomegalovirus Promoters Within the Cardiovascular System Arterioscler. Thromb. Vasc. Biol., October 1, 2006; 26(10): 2267 - 2274. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Charakida, A. E. Donald, M. Terese, S. Leary, J. P. Halcox, A. Ness, G. D. Smith, J. Golding, P. Friberg, N. J. Klein, et al. Endothelial Dysfunction in Childhood Infection Circulation, April 5, 2005; 111(13): 1660 - 1665. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
I. Volanen, O. T. Raitakari, R. Vainionpaa, M. Arffman, J. Aarnisalo, S. Angle, K. Kallio, and O. Simell Serum Lipid Profiles Poorly Correlate With Chlamydia pneumoniae, Helicobacter pylori, and Cytomegalovirus Seropositivity in Prospectively Followed-Up Healthy Children Arterioscler. Thromb. Vasc. Biol., April 1, 2005; 25(4): 827 - 832. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Leis, M. Marschall, and T. Stamminger Downregulation of the cellular adhesion molecule Thy-1 (CD90) by cytomegalovirus infection of human fibroblasts J. Gen. Virol., July 1, 2004; 85(7): 1995 - 2000. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Weis, T. N. Kledal, K. Y. Lin, S. N. Panchal, S. Z. Gao, H. A. Valantine, E. S. Mocarski, and J. P. Cooke Cytomegalovirus Infection Impairs the Nitric Oxide Synthase Pathway: Role of Asymmetric Dimethylarginine in Transplant Arteriosclerosis Circulation, February 3, 2004; 109(4): 500 - 505. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P. L. Nerheim, J. L. Meier, M. A. Vasef, W.-G. Li, L. Hu, J. B. Rice, D. Gavrila, W. E. Richenbacher, and N. L. Weintraub Enhanced Cytomegalovirus Infection in Atherosclerotic Human Blood Vessels Am. J. Pathol., February 1, 2004; 164(2): 589 - 600. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. Khairy, S. Rinfret, J.-C. Tardif, R. Marchand, S. Shapiro, J. Brophy, and J. Dupuis Absence of Association Between Infectious Agents and Endothelial Function in Healthy Young Men Circulation, April 22, 2003; 107(15): 1966 - 1971. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. J. Angiolillo, G. Liuzzo, S. Pelliccioni, E. De Candia, R. Landolfi, F. Crea, A. Maseri, and L. M. Biasucci Combined role of the Lewis antigenic system, Chlamydia pneumoniae, and C-reactive protein in unstable angina J. Am. Coll. Cardiol., February 19, 2003; 41(4): 546 - 550. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. B. Muhlestein and J. L. Anderson Infectious Serology and Atherosclerosis: How Burdensome Is the Risk? Circulation, January 21, 2003; 107(2): 220 - 222. [Full Text] [PDF]
|
|
|
|
|
|
B. D. Horne, J. B. Muhlestein, J. F. Carlquist, T. L. Bair, T. E. Madsen, N. I. Hart, J. L. Anderson, and for the Intermountain Heart Collaborative (IHC) St Statin Therapy Interacts With Cytomegalovirus Seropositivity and High C-Reactive Protein in Reducing Mortality Among Patients With Angiographically Significant Coronary Disease Circulation, January 21, 2003; 107(2): 258 - 263. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. A. Allen Maycock, J. B. Muhlestein, B. D. Horne, J. F. Carlquist, T. L. Bair, R. R. Pearson, Q. Li, J. L. Anderson, and Intermountain Heart Collaborative Study Statin therapy is associated with reduced mortality across all age groups of individuals with significant coronary disease, including very elderly patients J. Am. Coll. Cardiol., November 20, 2002; 40(10): 1777 - 1785. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. Maisch, B. Kropff, C. Sinzger, and M. Mach Upregulation of CD40 Expression on Endothelial Cells Infected with Human Cytomegalovirus J. Virol., November 13, 2002; 76(24): 12803 - 12812. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. J. LaMonte, J. L. Durstine, F. G. Yanowitz, T. Lim, K. D. DuBose, P. Davis, and B. E. Ainsworth Cardiorespiratory Fitness and C-Reactive Protein Among a Tri-Ethnic Sample of Women Circulation, July 23, 2002; 106(4): 403 - 406. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Prasad, J. Zhu, J. P.J. Halcox, M. A. Waclawiw, S. E. Epstein, and A. A. Quyyumi Predisposition to Atherosclerosis by Infections: Role of Endothelial Dysfunction Circulation, July 9, 2002; 106(2): 184 - 190. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. Stollberger and J. Finsterer Role of Infectious and Immune Factors in Coronary and Cerebrovascular Arteriosclerosis Clin. Vaccine Immunol., March 1, 2002; 9(2): 207 - 215. [Full Text] [PDF]
|
|
|
|
|
|
J. S. Zebrack, J. B. Muhlestein, B. D. Horne, J. L. Anderson, and Intermountain Heart Collaboration Study Group C-reactive protein and angiographic coronary artery disease: independent and additive predictors of risk in subjects with angina J. Am. Coll. Cardiol., February 20, 2002; 39(4): 632 - 637. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G. J. Blake and P. M. Ridker Novel Clinical Markers of Vascular Wall Inflammation Circ. Res., October 26, 2001; 89(9): 763 - 771. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. N. Streblow, S. L. Orloff, and J. A. Nelson Do Pathogens Accelerate Atherosclerosis? J. Nutr., October 1, 2001; 131(10): 2798S - 2804. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. A. Paramo, O. Beloqui, and J. Diez Atherosclerosis: Is it Time for a New Name? Circulation, August 14, 2001; 104 (7): e38 - e38. [Full Text] [PDF]
|
|
|
|
|
|
B. Freedman, J. B. Muhlestein, B. D. Horne, J. F. Carlquist, T. E. Madsen, T. L. Bair, R. R. Pearson, and J. L. Anderson Cytomegalovirus Seropositivity and C-Reactive Protein Have Independent and Combined Predictive Value for Mortality in Patients With Angiographically Demonstrated Coronary Artery Disease Response Circulation, July 31, 2001; 104 (5): e20 - e21. [Full Text] [PDF]
|
|
|
|
|
|
H. J. Rupprecht, S. Blankenberg, C. Bickel, G. Rippin, G. Hafner, W. Prellwitz, W. Schlumberger, and J. Meyer Impact of Viral and Bacterial Infectious Burden on Long-Term Prognosis in Patients With Coronary Artery Disease Circulation, July 3, 2001; 104(1): 25 - 31. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Blankenberg, H. J. Rupprecht, C. Bickel, C. Espinola-Klein, G. Rippin, G. Hafner, M. Ossendorf, K. Steinhagen, and J. Meyer Cytomegalovirus Infection With Interleukin-6 Response Predicts Cardiac Mortality in Patients With Coronary Artery Disease Circulation, June 19, 2001; 103(24): 2915 - 2921. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. W. Chan, D. L. Bhatt, D. P. Chew, M. J. Quinn, D. J. Moliterno, E. J. Topol, and S. G. Ellis Early and Sustained Survival Benefit Associated With Statin Therapy at the Time of Percutaneous Coronary Intervention Circulation, February 12, 2002; 105(6): 691 - 696. [Abstract] [Full Text] [PDF]
|
|