help button home button Endocrine Society JCEM JCEM Call for Nominations for EIC
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Journal of Clinical Endocrinology & Metabolism, doi:10.1210/jc.2006-2428
This Article
Right arrow Abstract Freely available
Right arrow Full Text (PDF)
Right arrow All Versions of this Article:
92/7/2532    most recent
Author Manuscript (PDF)
Right arrow Submit a related Letter to the Editor
Right arrow Purchase Article
Right arrow View Shopping Cart
Right arrow Alert me when this article is cited
Right arrow Alert me when eLetters are posted
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow Request Copyright Permission
Citing Articles
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Dai, D.-F.
Right arrow Articles by Hwang, J.-J.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Dai, D.-F.
Right arrow Articles by Hwang, J.-J.
Related Collections
Right arrow Cardiovascular Endocrinology
Right arrow Metabolism
The Journal of Clinical Endocrinology & Metabolism Vol. 92, No. 7 2532-2537
Copyright © 2007 by The Endocrine Society

The Effects of Metabolic Syndrome Versus Infectious Burden on Inflammation, Severity of Coronary Atherosclerosis, and Major Adverse Cardiovascular Events

Dao-Fu Dai, Jou-Wei Lin, Jia-Horng Kao, Chih-Neng Hsu, Fu-Tien Chiang, Jiunn-Lee Lin, Yi-Hua Chou, Kwan-Lih Hsu, Chuen-Den Tseng, Yung-Zu Tseng and Juey-Jen Hwang

Cardiovascular Division (D.-F.D., C.-N.H., F.-T.C., J.-L.L., Y.-H.C., K.-L.H., C.-D.T., Y.-Z.T., J.-J.H.) and Gastroenterology Division (J.-H.K.), Department of Internal Medicine, and Department of Laboratory Medicine (F.-T.C.), National Taiwan University Hospital, Taipei 100, Taiwan; Graduate Institute of Clinical Medicine (J.-H.K.), College of Medicine, National Taiwan University, Taipei 100, Taiwan; and Cardiovascular Center of National Taiwan University Hospital, Yun-Lin Branch (J.-W.L., J.-J.H.), Dou-Liou City, Yun-Lin 640, Taiwan

Address all correspondence and requests for reprints to: Juey-Jen Hwang, M.D., Ph.D., Cardiovascular Division, Department of Internal Medicine, National Taiwan University Hospital, No. 7, Chung-Shan South Road, Taipei 100, Taiwan. E-mail: jueyhwang{at}ntu.edu.tw.


   Abstract
Top
 Abstract
Introduction
 Patients and Methods
 Results
 Discussion
 References
 
Background: The clinical predictors of inflammation in atherosclerosis remain controversial. The objective of this study was to compare the associations of metabolic factors vs. infectious burden (IB) with inflammation, the severity of coronary atherosclerosis, and major adverse cardiovascular events (MACEs).

Design, Setting, and Patients: Coronary angiography with Gensini score was applied to assess the severity of coronary atherosclerosis in 568 patients with coronary artery disease. Metabolic syndrome (MS) score (0–5) was defined according to the modified criteria of National Cholesterol Education Program Adult Treatment Panel III. IB score (0–7) was defined as the number of seropositivities to several agents.

Results: IB score was not associated with plasma C-reactive protein (CRP) concentration, Gensini score, or the risk of MACE. In contrast, MS score significantly correlated with both plasma CRP concentration and Gensini score (P < 0.001 for both). MS score and plasma CRP concentration were also significantly associated with the risk of MACE (hazard ratios 1.51, P < 0.001; and 1.90, P = 0.002, respectively).

Conclusion: Compared with IB, metabolic abnormalities have a more prominent association with the degree of inflammation, the severity of coronary atherosclerosis, and the risk of MACE in patients with coronary artery disease.


   Introduction
Top
 Abstract
 Introduction
Patients and Methods
 Results
 Discussion
 References
 
DESPITE EVIDENCE OF the role of inflammation in the pathogenesis of atherosclerosis (1), the factors inciting inflammation are controversial. Epidemiological and experimental studies suggested that bacterial and viral infections were associated with coronary as well as carotid atherosclerosis (2, 3, 4). The commonly reported agents were Chlamydia pneumoniae (2, 3), Helicobacter pylori (5, 6), cytomegalovirus (CMV) (7, 8), herpesvirus (HSV) (9, 10), and hepatitis A, B, and C viruses (11, 12, 13, 14). In contrast, several other studies reported a lack of association between atherosclerosis and C. pneumoniae (15, 16), H. pylori (17, 18), CMV (16, 17), HSV (19), or hepatitis viruses (20, 21, 22). Infectious burden (IB), defined as the number of seropositivity to several infectious agents, was shown to correlate with coronary artery disease (CAD), myocardial infarction (MI) and their long-term prognosis (23, 24), as well as endothelial dysfunction (25), but also with controversial results (26, 27).

Beside infectious agents, factors that may incite vessel inflammation are oxidized low-density lipoprotein cholesterol and the metabolic syndrome (MS), which are associated with proinflammatory condition characterized by elevations of C-reactive protein (CRP) (28). MS is a cluster of abnormalities caused by perturbation of multiple metabolic pathways, leading to hyperinsulinemia, insulin resistance, hyperglycemia, atherogenic dyslipidemia, obesity, and hypertension. MS is known to increase the risk of atherosclerosis and major adverse cardiovascular events (MACEs) (29, 30).

This study was designed to compare the association of IB vs. MS with the degree of inflammation, the angiographic severity of coronary atherosclerosis, and the rate of MACE in a hospital-based cohort of CAD.


   Patients and Methods
Top
 Abstract
 Introduction
 Patients and Methods
Results
 Discussion
 References
 
Study population

This study was approved by the hospital institutional review board; written informed consent was obtained from participants. We recruited 568 consecutive patients, 376 men and 192 women (aged 62.5 ± 12.7 yr), with a clinical diagnosis of CAD undergoing coronary angiography in our medical center. All patients had angina pectoris and at least one of the following: evidence of myocardial ischemia on resting or exercise electrocardiogram, or stress Tl201 myocardial perfusion scans. Exclusion criteria included acute coronary syndrome, malignancy, rheumatological disorders, and acute infection (defined by fever, prominent leukocytosis, and symptoms or signs of acute inflammation), all of which were known to increase plasma CRP concentration in the acute phase. During hospitalization, all participants had a record of personal and medical history, including diabetes, hypertension, smoking habit, hypercholesterolemia (total cholesterol ≥ 5.18 mmol/liter and/or low-density lipoprotein cholesterol ≥ 4.14 mmol/liter) and hypertriglyceridemia (triglyceride ≥ 2.26 mmol/liter).

MS score

MS score was defined as the numbers of metabolic abnormalities according to the National Cholesterol Education Program Adult Treatment Panel III criteria (2001) with slight modification: obesity [body mass index (BMI) ≥ 25 kg/m2, according to the criteria for Asians (31)]; serum triglycerides ≥ 1.7 mmol/liter (150 mg/dl); serum high-density lipoprotein cholesterol less than 1.04 mmol/liter (40 mg/dl) in men or less than 1.29 mmol/liter (50 mg/dl) in women; blood pressure ≥ 130/85 mm Hg or the hypertensive taking regular medication; and fasting plasma glucose ≥ 6.1 mmol/liter (110 mg/dl) or diabetes taking regular hypoglycemic agents.

IB score and plasma CRP concentration

Blood was collected, and plasma was stored in –80 C until analysis. The serum antibody status of seven commonly reported infectious agents was measured by commercial ELISA kits and is summarized as the following: anti-C. pneumoniae IgG (Sero CP; Savyon Diagnostics, Ashdod, Israel); anti-H. pylori IgG (Dade Behring Enzygnost, Marburg, Germany); anti-CMV IgG with a positive cutoff of ≥20 relative U/ml (Euroimmun, Luebeck, Germany); anti-herpes simplex virus 1 and 2 (HSV) IgG with a positive cutoff value of ≥10 binding U/ml (SeroHSV IgG; Savyon Diagnostics); anti-hepatitis A virus (HAV) IgG with a positive serum to normal (S/N) ratio cutoff value of ≤1 (competitive binding between anti-HAV in the sample and human anti-HAV); hepatitis B s antigen with S/N ratio cutoff value ≥ 2; and anti-hepatitis C virus IgG with S/N ratio cutoff ≤ 1 (Hepatitis microparticle ELISA; Abbott Laboratories, Abbott Park, IL). All assays were performed and interpreted according to the manufacturer’s protocol. The intraassay and interassay variations of these assays were 2.2–6.2% and 4.2–8.9%, respectively. These assays had a good reproducibility and were widely used for clinical service in our medical center.

IB score was defined as the number of seropositivities against the aforementioned infectious agents. Plasma CRP was quantified by high-sensitivity immunonephelometry (Dade Behring Enzygnost), with the lowest detection limit of 0.16 mg/liter.

The severity of coronary atherosclerosis

To examine the angiographic severity of coronary atherosclerosis, we applied modified Gensini score (32). This score assigned a heavier weight to the more severe luminal narrowings. Weights were also assigned to each segment depending on vessel size and importance. Each arterial segment was weighted by a value from 0.5 (small branches) to 5.0 (left main coronary artery). The stenosis was weighed from two (minimal stenosis) to 64 (total occlusion). The Gensini score was the sum of the products of all segments.

Follow-up and MACEs

All participants were followed up at the outpatient clinic by cardiologists 1 wk after hospital discharge, then every 1–3 months. Participants who did not visit the outpatient clinic (8.4%) were phone interviewed by medical staffs. Long-term follow-up data up to 36 months were available in 94% of the participants. Most of the lost follow-up patients were dwelling in Southern Taiwan, hundreds of miles away from our medical center.

During follow-up, emphasis was put on the symptoms and signs related to MACEs, such as chest pain and new neurological deficit. MACEs included cardiovascular mortality, MI, and stroke. Cardiovascular mortality was defined as sudden cardiac death within 24 h of cardiovascular symptoms’ onset. MI was defined according to the consensus criteria of the European Society of Cardiology and American College of Cardiology. Stroke was defined as acute presentation of focal or global neurological deficits with pathological changes in the corresponding areas by brain computerized tomography or magnetic resonance imaging. All MACEs were verified by medical records or confirmed by physicians in charge.

Statistical analyses

The baseline characteristics of patients were analyzed according to the MS score (from 0–5) and IB score (from 0–7). IB score 0–2 and 6–7 were pooled together because of the small number in each group. Continuous variables were presented as mean ± SD, and categorical variables were reported as percentages. ANOVA was used to compare the mean of continuous variables across different MS and IB scores. Differences between proportions were calculated by the {chi}2 test. Plasma CRP concentration and Gensini score, which were skewed, were presented as median and interquartile range (25%, 75%). The Wilcoxon rank sum test was performed to evaluate the association with a single infectious agent, and a nonparametric test for trend across MS and IB score groups was applied. Logarithmic transformation of both plasma CRP concentration and Gensini score was put into multivariate models to adjust for covariates, and included gender, age, hypercholesterolemia, present smoker, and prior aspirin and statin use. Diabetes and hypertension were excluded to avoid colinearity with MS score. We created three models. Model 1 was created for MS score vs. IB score, predicting plasma CRP concentration. Model 2 was to evaluate the impact of MS score, IB score, and plasma CRP concentration on Gensini score. Model 3 was a Cox regression model to predict MACEs. The Kaplan-Meier curve was created to compare the effect of MS and IB scores on MACE-free survival. IB score was classified into IB scores 0–2, 3–4, and 5–7. A two-tailed P value of <0.05 was considered significant. STATA 8.0 (StataCorp LP, College Station, TX) was used for all statistical calculations.


   Results
Top
 Abstract
 Introduction
 Patients and Methods
 Results
Discussion
 References
 
The demography of our patients is shown in Table 1Go. No significant difference was noted in terms of gender and smokers across MS and IB scores. Subjects with no metabolic abnormality (MS = 0) or lower IB (<2) were significantly younger than those with higher MS or IB scores. Subjects with higher MS scores also have significantly higher metabolic-related parameters, including fasting glucose, cholesterol, and triglyceride, as well as the proportions of diabetes, hypertension, hypercholesterolemia, and prior aspirin or statin use. The average BMI in the controls (MS score of zero) was only 21 kg/m2 and in subjects with a MS score of five was 27.5 kg/m2, consistent with our obesity criteria (BMI ≥ 25 kg/m2 for Asians) (31). Except for age, the baseline characteristics were not significantly different across all groups of IB score, including the white blood cell count.


View this table:
[in this window]
[in a new window]

  		TABLE 1. Baseline characteristics of the study population stratified by MS and IB scores

 
The prevalence of MS in our patients was 56.5%. High blood pressure was the most common (84%), followed by low high-density lipoprotein cholesterol (50.3%), increased triglycerides (45.9%), obesity (45.5%), and impaired fasting glucose (38.4%). The prevalence of seropositivity of each infectious agent (in percentage) is shown in Table 2Go.


View this table:
[in this window]
[in a new window]

  		TABLE 2. The effects of infectious agents on plasma CRP concentration and Gensini score

 
The effect of individual infectious agent

There was no difference in plasma CRP concentration between infected and noninfected subjects for any of the infectious agents. Table 2Go shows that of all infectious agents, only HAV had a significant correlation with Gensini score (median = 52 in infected vs. four in noninfected; P = 0.01). This correlation became insignificant after adjustment for age.

MS score vs. IB score

The associations of MS score vs. IB score with plasma CRP concentration and Gensini score are shown in Table 1Go. Plasma CRP concentration increased steadily with the increment of MS score (P for trend < 0.01). Likewise, MS score was also significantly associated with Gensini score (P for trend < 0.01). On the contrary, IB score had a significant association with neither plasma CRP concentration (P for trend = 0.26) nor Gensini score (P for trend = 0.08).

Model 1 showed that MS score, but not IB score, independently affected plasma CRP concentration (Table 3Go, model 1). Other independent predictors included age, male, hypercholesterolemia, smoking, and prior use of statins. As shown in model 2, although MS score and plasma CRP concentration were both independent predictors of Gensini score, the former was a better predictor than the latter [ß = 0.34, 95% confidence interval (CI) 0.24–0.44, P < 0.001; and ß = 0.24, 95% CI 0.16–0.32, P < 0.001, respectively). Again, IB score did not significantly affect Gensini score. Among the other independent covariates, male gender and hypercholesterolemia were found to have the highest regression coefficients (ß = 0.76, P = 0.001 and ß = 0.68, P < 0.001, respectively) for Gensini score.


View this table:
[in this window]
[in a new window]

  		TABLE 3. Multivariate models of IB score vs. MS score on plasma CRP concentration, Gensini score, and MACEs

 
MACEs

During follow-up (median 24 months, range 8–36 months), MACEs occurred in 61 patients (10.2%). Cardiovascular mortality developed in 25 patients (4.2%), MI in 40 (6.7%), and stroke in 16 (2.7%). Fig. 1Go depicts MACE-free survival across different MS and IB scores. Subjects with higher MS scores had a significantly higher risk of MACEs (log-rank P < 0.001) (Fig. 1AGo). No significant difference in the rate of MACEs was noted among patients with different IB scores (log-rank P = 0.57) (Fig. 1BGo). In Cox analysis, four factors were independently associated with MACEs: plasma CRP concentration [hazard ratio (HR) 1.51, 95% CI 1.28, 1.77; P < 0.001); MS score (HR 1.43, 95% CI 1.14, 1.80; P = 0.002); male (HR 1.90, 95% CI 1.03, 3.58; P = 0.04); and age (HR 1.04, 95% CI 1.01, 1.07; P = 0.003). IB score did not correlate with the risk of MACEs (Table 3Go, model 3).


Figure 1
View larger version (9K):
[in this window]
[in a new window]

  		FIG. 1. Event-free survival stratified by MS (A) and IB scores (B). MS, MS score ≥ 3; Non-MS, MS score = 0; pre-MS, MS score = 1 or 2.

 

   Discussion
Top
 Abstract
 Introduction
 Patients and Methods
 Results
 Discussion
References
 
The clinical predictors of inflammation in atherosclerosis remain controversial. This study compared the associations of two previously proposed factors, IB and metabolic abnormalities, with the degree of inflammation and the angiographic severity of coronary atherosclerosis as well as their effect on MACEs in patients with CAD.

Although many related works have been published, the association between infectious agents with atherosclerosis is still controversial. The most reported pathogens in relation to atherosclerosis included C. pneumoniae (2, 3), H. pylori (5, 6, 7), HSV, and CMV (8, 9, 10). We and others (15, 16) have shown that C. pneumoniae was not associated with CAD, MI, or endothelial dysfunction. The correlations of HSV and CMV with atherosclerosis were also debatable (16, 17, 19). Likewise, the association between HAV infection and the risk of CAD was inconsistent (13, 33). Hepatitis B and C viruses were shown to increase the risk of carotid atherosclerosis measured by carotid duplex (11, 12, 14) but, again, were not observed in recent studies (20, 21, 22). In this study no specific infectious agent was correlated with plasma CRP concentration or the severity of coronary atherosclerosis (Gensini score) after adjustment for covariates.

According to Epstein et al. (34), it is the IB rather than any specific infectious agent that correlates with the extent of atherosclerosis. Because it is impossible to include all infectious agents, we selected seven commonly reported pathogens. Using the summation of infectious seropositivities, as done by previous studies (23, 24), we still failed to show any significant correlation between IB score and plasma CRP concentration or Gensini score. In addition, higher IB score also did not increase the risk of MACEs. Thus, we could not prove the hypothesis that IB was associated with the degree of inflammation leading to atherosclerosis, in consent with studies showing the absence of association between IB and CAD (26) or endothelial dysfunction in healthy young men (27).

On the contrary, we found that the number of metabolic abnormalities (MS score) had significant effects on Gensini score. It also had a significant correlation with plasma CRP concentration, similar to a report by Ridker et al. (28). Multivariate regression model revealed that MS score and plasma CRP concentration were both independent predictors for Gensini score. Indeed, the simple MS score was a better predictor for Gensini score than was CRP (ß = 0.34, 95% CI 0.24–0.44, P < 0.001; and ß = 0.24, 95% CI 0.16–0.32, P < 0.001, respectively). This model also showed that cholesterol level was among the strongest predictors for higher Gensini score. This complies with the study by Solymoss et al. (30), who applied a simplified cumulative coronary stenosis score. We used a more complicated Gensini score that has been demonstrated to be a good prognostic indicator for nonoperative survival in patients with CAD, as reported in CASS (32). The Cox model indicated that higher MS score, but not IB score, was associated with the risk of MACEs. Our results were similar to a study reported in the Third National Health and Nutrition Examination Survey (35), which showed that the MS was independently associated with a self-reported history of MI/stroke.

We are unaware of prior studies that directly compared the associations of IB vs. metabolic abnormalities with the degree of inflammation and the severity of coronary atherosclerosis. Contradictory to previously published positive studies, we failed to show the association between IB and the severity of coronary atherosclerosis or MACEs. Many possible reasons might explain the discrepancy. First, different pathogens may have a different contribution, if any, to atherosclerosis. Because there is no consensus on which pathogens are included in the scheme of IB, different studies have selected different seromarkers and obtained contradictory results. Second, the effect of IB on atherosclerosis may be more prominent in the earlier stage of atherogenesis. Prasad et al. (25) showed that IB was significantly associated with coronary endothelial dysfunction in subjects with normal coronary angiography. However, the study by Khairy et al. (27) did not show any association between infectious agents and endothelial function in healthy young men. Third, the effect of IB on inflammation and the late stage of atherosclerosis, as in patients with CAD, may be minor when compared with metabolic abnormalities, so that its effect is masked by the dominating triggers of MS.

The limitations of our study were 2-fold. First, although the Gensini score is the most comprehensive scoring for the severity of coronary atherosclerosis, this angiography based method might underestimate the early lesions as well as lesions with outward remodeling. Second, the application of both MS and IB scores was based on the assumption that each component had a similar contribution.

In conclusion, our findings emphasize that MS has more prominent association than IB with the degree of inflammation, progression of atherosclerosis, and risk of MACEs in patients with CAD, yet could not completely exclude the impact of IB on coronary atherosclerosis.


   Footnotes
 
This work is supported by the Taiwan National Science Council Grant NSC92-2314-B-002-320.

Disclosure Statement: The authors have nothing to disclose.

First Published Online April 10, 2007

Abbreviations: BMI, Body mass index; CAD, coronary artery disease; CI, confidence interval; CMV, cytomegalovirus; CRP, C-reactive protein; HAV, hepatitis A virus; HR, hazard ratio; HSV, herpesvirus; IB, infectious burden; MACE, major adverse cardiovascular event; MI, myocardial infarction; MS, metabolic syndrome; S/N, serum to normal.

Received November 6, 2006.

Accepted April 2, 2007.


   References
Top
 Abstract
 Introduction
 Patients and Methods
 Results
 Discussion
 References
 

  1. Libby P 2002 Inflammation in atherosclerosis. Nature 420:868–874[CrossRef][Medline]
  2. Danesh J, Whincup P, Walker M, Lennon L, Thomson A, Appleby P, Wong Y, Bernardes-Silva M, Ward M 2000 Chlamydia pneumoniae IgG titres and coronary heart disease: prospective study and meta-analysis. BMJ 321:208–213[Abstract/Free Full Text]
  3. LaBiche R, Koziol D, Quinn TC, Gaydos C, Azhar S, Ketron G, Sood S, DeGraba TJ 2001 Presence of Chlamydia pneumoniae in human symptomatic and asymptomatic carotid atherosclerotic plaque. Stroke 32:855–860[Abstract/Free Full Text]
  4. Kiechl S, Egger G, Mayr M, Wiedermann CJ, Bonora E, Oberhollenzer F, Muggeo M, Xu Q, Wick G, Poewe W, Willeit J 2001 Chronic infections and the risk of carotid atherosclerosis: prospective results from a large population study. Circulation 103:1064–1070[Abstract/Free Full Text]
  5. Danesh J, Youngman L, Clark S, Parish S, Peto R, Collins R 1999 Helicobacter pylori infection and early onset myocardial infarction: case-control and sibling pairs study. BMJ 319:1157–1162[Abstract/Free Full Text]
  6. Ameriso SF, Fridman EA, Leiguarda RC, Sevlever GE 2001 Detection of Helicobacter pylori in human carotid atherosclerotic plaques. Stroke 32:385–391[Abstract/Free Full Text]
  7. Mayr M, Kiechl S, Willeit J, Wick G, Xu Q 2000 Infections, immunity, and atherosclerosis: associations of antibodies to Chlamydia pneumoniae, Helicobacter pylori, and cytomegalovirus with immune reactions to heat-shock protein 60 and carotid or femoral atherosclerosis. Circulation 102:833–839[Abstract/Free Full Text]
  8. Shi Y, Tokunaga O 2002 Herpesvirus (HSV-1, EBV and CMV) infections in atherosclerotic compared with non-atherosclerotic aortic tissue. Pathol Int 52:31–39[CrossRef][Medline]
  9. Alber DG, Powell KL, Vallance P, Goodwin DA, Grahame-Clarke C 2000 Herpesvirus infection accelerates atherosclerosis in the apolipoprotein E-deficient mouse. Circulation 102:779–785[Abstract/Free Full Text]
  10. Sorlie PD, Nieto FJ, Adam E, Folsom AR, Shahar E, Massing M 2000 A prospective study of cytomegalovirus, herpes simplex virus 1, and coronary heart disease: the atherosclerosis risk in communities (ARIC) study. Arch Intern Med 160:2027–2032[Abstract/Free Full Text]
  11. Ishizaka N, Ishizaka Y, Takahashi E, Toda EE, Hashimoto H, Ohno M, Nagai R, Yamakado M 2002 Increased prevalence of carotid atherosclerosis in hepatitis B virus carriers. Circulation 105:1028–1030[Abstract/Free Full Text]
  12. Ishizaka Y, Ishizaka N, Takahashi E, Unuma T, Tooda E, Hashimoto H, Nagai R, Yamakado M 2003 Association between hepatitis C virus core protein and carotid atherosclerosis. Circ J 67:26–30[CrossRef][Medline]
  13. Zhu J, Quyyumi AA, Norman JE, Costello R, Csako G, Epstein SE 2000 The possible role of hepatitis A virus in the pathogenesis of atherosclerosis. J Infect Dis 182:1583–1587[CrossRef][Medline]
  14. Volzke H, Schwahn C, Wolff B, Mentel R, Robinson DM, Kleine V, Felix SB, John U 2004 Hepatitis B and C virus infection and the risk of atherosclerosis in a general population. Atherosclerosis 174:99–103[CrossRef][Medline]
  15. Tsai CT, Kao JH, Hsu KL, Chiang FT, Tseng CD, Liau CS, Tseng YZ, Hwang JJ 2001 Relation of Chlamydia pneumoniae infection in Taiwan to angiographically demonstrated coronary artery disease and to the presence of acute myocardial infarction or unstable angina pectoris. Am J Cardiol 88:960–963[CrossRef][Medline]
  16. Oshima T, Ozono R, Yano Y, Oishi Y, Teragawa H, Higashi Y, Yoshizumi M, Kambe M 2005 Association of Helicobacter pylori infection with systemic inflammation and endothelial dysfunction in healthy male subjects. J Am Coll Cardiol 45:1219–1222[Abstract/Free Full Text]
  17. Videm V, Wiseth R, Gunnes S, Madsen HO, Garred P 2007 Multiple inflammatory markers in patients with significant coronary artery disease. Int J Cardiol 118:81–87[CrossRef][Medline]
  18. Kaklikkaya I, Kaklikkaya N, Buruk K, Pulathan Z, Koramaz I, Aydin F, Tosun I, Osman Kilic A, Ozcan F 2006 Investigation of Chlamydia pneumoniae DNA, chlamydial lipopolisaccharide antigens, and Helicobacter pylori DNA in atherosclerotic plaques of patients with aortoiliac occlusive disease. Cardiovasc Pathol 15:105–109[CrossRef][Medline]
  19. Schlitt A, Blankenberg S, Weise K, Gartner BC, Mehrer T, Peetz D, Meyer J, Darius H, Rupprecht HJ 2005 Herpesvirus DNA (Epstein-Barr virus, herpes simplex virus, cytomegalovirus) in circulating monocytes of patients with coronary artery disease. Acta Cardiol 60:605–610[CrossRef][Medline]
  20. Yang KC, Chen MF, Su TC, Jeng JS, Hwang BS, Lin LY, Liau CS, Lee YT, Hepatitis B virus seropositivity is not associated with increased risk of carotid atherosclerosis in Taiwanese. Atherosclerosis, in press
  21. Tong DY, Wang XH, Xu CF, Yang YZ, Xiong SD 2005 Hepatitis B virus infection and coronary atherosclerosis: results from a population with relatively high prevalence of hepatitis B virus. World J Gastroenterol 11:1292–1296[Medline]
  22. Arcari CM, Nelson KE, Netski DM, Nieto FJ, Gaydos CA 2006 No association between hepatitis C virus seropositivity and acute myocardial infarction. Clin Infect Dis 43:e53–e56
  23. Espinola-Klein C, Rupprecht HJ, Blankenberg S, Bickel C, Kopp H, Rippin G, Victor A, Hafner G, Schlumberger W, Meyer J 2002 Impact of infectious burden on extent and long-term prognosis of atherosclerosis. Circulation 105:15–21[Abstract/Free Full Text]
  24. Rupprecht HJ, Blankenberg S, Bickel C, Rippin G, Hafner G, Prellwitz W, Schlumberger W, Meyer J 2001 Impact of viral and bacterial infectious burden on long-term prognosis in patients with coronary artery disease. Circulation 104:25–31[Abstract/Free Full Text]
  25. Prasad A, Zhu J, Halcox JP, Waclawiw MA, Epstein SE, Quyyumi AA 2002 Predisposition to atherosclerosis by infections: role of endothelial dysfunction. Circulation 106:184–190[Abstract/Free Full Text]
  26. Rothenbacher D, Brenner H, Hoffmeister A, Mertens T, Persson K, Koenig W 2003 Relationship between infectious burden, systemic inflammatory response, and risk of stable coronary artery disease: role of confounding and reference group. Atherosclerosis 170:339–345[CrossRef][Medline]
  27. Khairy P, Rinfret S, Tardif JC, Marchand R, Shapiro S, Brophy J, Dupuis J 2003 Absence of association between infectious agents and endothelial function in healthy young men. Circulation 107:1966–1971[Abstract/Free Full Text]
  28. Ridker PM, Buring JE, Cook NR, Rifai N 2003 C-reactive protein, the metabolic syndrome, and risk of incident cardiovascular events: an 8-year follow-up of 14 719 initially healthy American women. Circulation 107:391–397[Abstract/Free Full Text]
  29. Girman CJ, Rhodes T, Mercuri M, Pyorala K, Kjekshus J, Pedersen TR, Beere PA, Gotto AM, Clearfield M 2004 The metabolic syndrome and risk of major coronary events in the Scandinavian Simvastatin Survival Study (4S) and the Air Force/Texas Coronary Atherosclerosis Prevention Study (AFCAPS/TexCAPS). Am J Cardiol 93:136–141[CrossRef][Medline]
  30. Solymoss BC, Bourassa MG, Campeau L, Sniderman A, Marcil M, Lesperance J, Levesque S, Varga S 2004 Effect of increasing metabolic syndrome score on atherosclerotic risk profile and coronary artery disease angiographic severity. Am J Cardiol 93:159–164[CrossRef][Medline]
  31. Anuurad E, Shiwaku K, Nogi A, Kitajima K, Enkhmaa B, Shimono K, Yamane Y 2003 The new BMI criteria for asians by the regional office for the western pacific region of WHO are suitable for screening of overweight to prevent metabolic syndrome in elder Japanese workers. J Occup Health 45:335–343[CrossRef][Medline]
  32. Ringqvist I, Fisher LD, Mock M, Davis KB, Wedel H, Chaitman BR, Passamani E, Russell Jr RO, Alderman EL, Kouchoukas NT, Kaiser GC, Ryan TJ, Killip T, Fray D 1983 Prognostic value of angiographic indices of coronary artery disease from the Coronary Artery Surgery Study (CASS). J Clin Invest 71:1854–1866[Medline]
  33. Auer J, Leitinger M, Berent R, Prammer W, Weber T, Lassnig E, Eber B 2003 Hepatitis A IgG seropositivity and coronary atherosclerosis assessed by angiography. Int J Cardiol 90:175–179[CrossRef][Medline]
  34. Epstein SE, Zhou YF, Zhu J 1999 Infection and atherosclerosis: emerging mechanistic paradigms. Circulation 100:e20–e28
  35. Ninomiya JK, L’Italien G, Criqui MH, Whyte JL, Gamst A, Chen RS 2004 Association of the metabolic syndrome with history of myocardial infarction and stroke in the third national health and nutrition examination survey. Circulation 109:42–46[Abstract/Free Full Text]




This Article
Right arrow Abstract Freely available
Right arrow Full Text (PDF)
Right arrow All Versions of this Article:
92/7/2532    most recent
Author Manuscript (PDF)
Right arrow Submit a related Letter to the Editor
Right arrow Purchase Article
Right arrow View Shopping Cart
Right arrow Alert me when this article is cited
Right arrow Alert me when eLetters are posted
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow Request Copyright Permission
Citing Articles
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Dai, D.-F.
Right arrow Articles by Hwang, J.-J.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Dai, D.-F.
Right arrow Articles by Hwang, J.-J.
Related Collections
Right arrow Cardiovascular Endocrinology
Right arrow Metabolism

HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Endocrinology Endocrine Reviews J. Clin. End. & Metab.
Molecular Endocrinology Recent Prog. Horm. Res. All Endocrine Journals