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From the Departments of Medicine, Brigham and Women's Hospital and
Harvard Medical School, Boston, Mass (P.M.R., M.A.P., F.M.S., E.B.); the
Children's Hospital Medical Center, Boston (N.R.); the University of
Texas School of Public Health, Houston (L.A.M.); the Veterans Administration
Medical Center, Tucson, Ariz (S.G.); and the University of Missouri, Columbia
(G.C.F.).
Correspondence to Dr Paul M. Ridker, Division of Cardiovascular Diseases, Brigham and Women's Hospital, 75 Francis St, Boston, MA 02115. E-mail pmridker{at}bics.bwh.harvard.edu
Methods and Results—A nested case-control design was used
to compare C-reactive protein (CRP) and serum amyloid A (SAA) levels in
prerandomization blood samples from 391 participants in the
Cholesterol and Recurrent Events (CARE) trial who
subsequently developed recurrent nonfatal MI or a fatal
coronary event (cases) and from an equal number of age- and
sex-matched participants who remained free of these events during
follow-up (control subjects). Overall, CRP and SAA were higher among
cases than control subjects (for CRP P=0.05; for SAA
P=0.006) such that those with levels in the highest
quintile had a relative risk (RR) of recurrent events 75% higher than
those with levels in the lowest quintile (for CRP RR=1.77,
P=0.02; for SAA RR=1.74, P=0.02). The
study group with the highest risk was that with consistent
evidence of inflammation (elevation of both CRP and SAA) who were
randomly assigned to placebo (RR=2.81, P=0.007); this
risk estimate was greater than the product of the individual risks
associated with inflammation or placebo assignment alone. In stratified
analyses, the association between inflammation and risk was
significant among those randomized to placebo (RR=2.11,
P=0.048) but was attenuated and nonsignificant among
those randomized to pravastatin (RR=1.29,
P=0.5).
Conclusions—Evidence of inflammation after MI is associated with
increased risk of recurrent coronary events. Therapy with
pravastatin may decrease this risk, an observation
consistent with a nonlipid effect of this agent.
To address these issues, we measured 2 serum markers of inflammation,
CRP and SAA, among postmyocardial infarction patients enrolled in the
Cholesterol and Recurrent Events (CARE) trial who were
prospectively followed for incident events of recurrent myocardial
infarction and coronary death.11 As the
CARE trial randomized participants between 40 mg of
pravastatin per day and placebo, we were afforded the
additional unique opportunity to evaluate directly whether any
association between markers of inflammation and risk of recurrent
coronary events might be affected by the use of this
3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase
inhibitor.
Blood samples were collected in the CARE trial during prerandomization
clinic visits designed in part to determine baseline lipid levels for
study eligibility. On average, these visits occurred 8.9 months after
the qualifying acute myocardial infarction. Samples were collected in
EDTA, shipped to a central collection site on cooled gel packs, and
frozen at -80°C for future analyses. Details of the blood
collection and storage procedures used in the CARE trial are outlined
elsewhere.12
For this analysis, prerandomization blood samples were assayed
for CRP and SAA among 391 study participants who subsequently developed
recurrent myocardial infarction or death from coronary heart
disease (cases), and among an equal number of age- and sex-matched
study participants who remained free of these recurrent
coronary events during a follow-up period lasting 5 years
(control subjects). High sensitivity assays for CRP and SAA were
performed according to methods described by the manufacturer (Behring
Diagnostics).13 14 Case and control
blood specimens were assayed in blinded pairs with the position of the
case specimen varied at random within the pairs to reduce the
possibility of systematic bias and decrease interassay variability.
Laboratory investigators were unaware of case or control status.
Means or proportions for baseline risk factors were computed for the
case and control subjects, and the significance of any differences in
means tested with the Student's t test; differences in
proportions were tested with the
Tests for trend were used to assess for any relation of increasing CRP
or SAA values and the risk of recurrent coronary events after
dividing the study sample into quintiles defined by the distribution of
the control values. Risk estimates and confidence intervals were
obtained with the use of conditional logistic regression
analyses. To assess for nonlinear effects, we further evaluated
for evidence of association between CRP or SAA and recurrent
coronary events among patients with baseline levels of each
inflammatory parameter
To examine the influence of pravastatin among those with
and those without serum markers of inflammation, we classified study
patients into 2 groups, those with consistent evidence of
inflammation (defined as having both CRP and SAA greater than or equal
to the respective 90th percentile cut points) and those without
consistent evidence of inflammation (defined as having both CRP
and SAA below the respective 90th percentile cut points). Logistic
regression analyses were then used to evaluate the risks of
recurrent coronary events among those with and those without
inflammation who were randomly assigned either to
pravastatin or placebo. All P values are
2-tailed and confidence intervals calculated at the 95% level.
Overall, median plasma concentrations of both CRP and SAA before
randomization were significantly higher among those in whom
coronary events subsequently developed than among those who
remained free of recurrent disease (for CRP P=0.05, for SAA
P=0.006) (Table 2
In analyses evaluating for evidence of association between
increasing levels of CRP or SAA and recurrent coronary events,
statistically significant trends were observed across quintiles of both
parameters (for CRP P-trend=0.044; for SAA
P-trend=0.006). As shown in Table 3
To explore further the apparent nonlinearity of the relation between
CRP and SAA and recurrent coronary events, relative risks were
computed for a series of cut points based on the control distribution
(Tables 4
Log-normalized prerandomization concentrations of CRP and SAA were
highly correlated (r=0.67, P<0.001).
Furthermore, 708 of the 782 study participants (91%) had concordant
evidence regarding the presence (or absence) of low-grade inflammation
in that their plasma levels of both CRP and SAA were
consistently above (or below) the 90th percentile cut points
for each parameter. To investigate for evidence of an
interrelation between inflammation and pravastatin, we
divided these 708 study subjects with concordant CRP and SAA levels
into 4 groups on the basis of the presence or absence of high levels of
both markers and on randomization to either pravastatin or
placebo. As shown in Figure 3
Finally, among the 708 patients who had concordant results for both
inflammatory markers, randomized treatment with pravastatin
reduced the risk of recurrent MI or coronary death by 28%
(P=0.03), a finding similar to that in the CARE study as a
whole (risk reduction=24%, P=0.003).9
Among those with evidence of inflammation, the proportion of recurrent
coronary events prevented by pravastatin was 54%
compared with 25% among those without inflammation, even though
baseline levels of total cholesterol, LDL
cholesterol, HDL cholesterol, and
triglycerides were virtually identical in comparisons of
those with and those without evidence of inflammation (Table 6
The current data describing the predictive value of CRP among patients
with prior myocardial infarction extends recent observations that CRP
predicts risk of coronary disease among apparently healthy
individuals3 4 5 6 as well as those at high risk
because of smoking7 and among patients with
stable and unstable angina.8 9 10 Moreover, the
current data for SAA indicate that a second marker of inflammation is
also predictive of future cardiovascular risk. This
observation suggests that the associations noted are more likely due to
inflammation than to any direct effect of either CRP or SAA. In this
regard, the current findings conflict with data describing no
association between SAA and vascular risk in one recent study of
patients with stable and unstable angina.9
The finding that the effect of inflammation on risk was attenuated and
no longer statistically significant among patients randomly assigned to
pravastatin raises several intriguing issues. For example,
it is possible that the clinical benefits of lipid reduction with
pravastatin in the presence of inflammation are greater
than in its absence. However, as baseline lipid levels were virtually
identical among those with and those without evidence of inflammation
(and among those randomly assigned to pravastatin as
compared with placebo), it seems unlikely that this effect is due to
lipid lowering alone. Thus it is tempting to speculate that nonlipid
effects of pravastatin may be responsible for the current
observations.15 16 With specific regard to the
inflammatory process, experimental studies suggest that
pravastatin inhibits endogenous
cholesterol synthesis in
macrophages,17 a process with the
potential to reduce macrophage activation and foam cell
formation.15 Other hypothesized nonlipid effects
of pravastatin and other HMG-CoA reductase
inhibitors include modulation of immune function in
vitro,15 18 antiproliferative effects on vascular
smooth muscle,19 20 21 and antithrombotic
properties.22 23 24 25 Finally, several studies
demonstrate that endothelial function and
coronary vasomotion improve with the use of HMG-CoA reductase
inhibitors including
pravastatin.26 27 28 29 30
Potential limitations of these data merit consideration. Because
cigarette consumption increases levels of both CRP and SAA, it is
possible that our results reflect confounding by this factor. However,
as demonstrated in the multivariate analyses,
adjustment for smoking had no effect on the point estimates of risk
observed. We further believe it unlikely that our results reflect
ongoing subclinical ischemia, which might have led to
inadvertent elevations of both CRP and SAA. In this regard,
the levels of CRP and SAA described in these data are substantially
below those typically associated with the acute-phase
response.31 32 Furthermore, prior data indicate
that elevations of CRP and SAA associated with acute myocardial
infarction return to baseline within 8 to 10
days.31 33 34 Because blood samples in our study
were obtained a minimum of 3 months after the qualifying myocardial
infarction occurred (mean 8.9 months), inadvertent bias on
this basis seems unlikely.
We believe these data support 3 main conclusions. First, plasma
concentrations of CRP and SAA both appear to predict the risk of
recurrent coronary events among stable patients with a history
of prior myocardial infarction. As such, these data suggest that
markers of inflammation may provide a mechanism to stratify
postinfarction patients into relatively high-risk and low-risk groups.
Second, because both CRP and SAA appeared equally predictive of risk
and were highly correlated with each other, these data suggest that the
associations noted are not a direct effect of either of these proteins
but rather are a reflection of underlying systemic
inflammation.35 Finally, these data raise the
possibility that the effect of inflammation on coronary risk
may be attenuated by pravastatin therapy. Thus these data
also raise the intriguing possibility that the efficacy of
pravastatin may result in part from anti-inflammatory as
well as lipid-lowering properties.
Received January 1, 1998;
revision received April 6, 1998;
accepted April 20, 1998.
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© 1998 American Heart Association, Inc.
Clinical Investigation and Reports
Inflammation, Pravastatin, and the Risk of Coronary Events After Myocardial Infarction in Patients With Average Cholesterol Levels
Abstract
Top
Abstract
Introduction
Methods
Results
Discussion
References
Background—We studied whether
inflammation after myocardial infarction (MI) is a risk factor for
recurrent coronary events and whether randomized treatment with
pravastatin reduces that risk.
Key Words: C-reactive protein • serum amyloid A • myocardial infarction • atherosclerosis • cholesterol
Introduction
Top
Abstract
Introduction
Methods
Results
Discussion
References
Although basic
laboratory research indicates that several components of the
inflammatory response are associated with the initiation and
progression of
atherosclerosis,1 2 clinical data
relating inflammation to risks of future coronary events are
sparse. In this regard, recent prospective data demonstrate that
low-grade inflammation as assessed by C-reactive protein (CRP) predicts
risk of first myocardial infarction and other atherosclerotic events
among apparently healthy middle-aged men.3 4 5 In
addition, CRP appears to predict risks of infarction and
coronary death among high-risk
patients6 7 as well as ischemic
complications among those with stable and unstable
angina.8 9 10 However, whether markers of
inflammation such as CRP and serum amyloid A (SAA) predict risk of
recurrent coronary events among stable patients with a prior
history of myocardial infarction has not been evaluated. Furthermore,
although aspirin may modify the effects of inflammation on
coronary risk,3 it is unknown whether
other preventive agents might also have differential effects among
those with and without evidence of inflammation.
Methods
Top
Abstract
Introduction
Methods
Results
Discussion
References
The CARE trial was a randomized, double-blind,
placebo-controlled trial of 40 mg pravastatin per day in
the secondary prevention of cardiovascular disease
among 4159 patients with a prior history of myocardial infarction who
had total cholesterol levels <240 mg/dL and LDL
cholesterol levels between 115 and 175
mg/dL.11 Patients were eligible for inclusion if
they had had an acute myocardial infarction between 3 and 20 months
before randomization, were 21 to 75 years of age, had left
ventricular ejection fraction of not <25%, and no
evidence of congestive heart failure. The primary end point of the CARE
trial was death from coronary heart disease (including fatal
myocardial infarction, either definite or probable; sudden death; death
during a coronary intervention; and death from other
coronary causes) or a symptomatic (unless during
noncardiac surgery) nonfatal myocardial infarction confirmed by serum
creatine kinase measurements. 
2 statistic.
Because the distributions of both CRP and SAA are rightward skewed,
median concentrations were computed for these parameters
and the significance of any differences between cases and control
subjects assessed using the Wilcoxon rank-sum test. Mean
concentrations of both CRP and SAA were also computed after log
transformation that resulted in nearly normal distributions. 
25th, 50th, 75th, 90th, and 95th
percentile cut points as defined by the control values. Adjusted
estimates of risk were obtained with conditional logistic regression
models that accounted for the matching variables of age and sex and
that controlled for smoking status (past, former, current) and for
baseline levels of LDL cholesterol, HDL
cholesterol, and triglycerides.
Results
Top
Abstract
Introduction
Methods
Results
Discussion
References
Table 1
shows baseline clinical
characteristics of the study participants. By matching, case and
control subjects were similar in age and sex. Other baseline
characteristics of the study participants are similar to those reported
for the CARE trial as a whole.11 At study entry,
83% of patients reported aspirin use.
View this table:
[in a new window]
Table 1. Baseline Clinical Characteristics of 391 Subjects
Who Subsequently Had Recurrent Myocardial Infarction Compared With 391
Age- and Sex-Matched Control Subjects Who Remained Free of Vascular
Disease During Follow-up Period ).
View this table:
[in a new window]
Table 2. Mean, Median, and Range Levels of CRP and SAA at
Baseline Among Case and Control Subjects and Figures 1 and 2,
the associations between CRP or SAA concentration and subsequent risk
in these data were nonlinear. For example, although those with
prerandomization levels of CRP or SAA in the highest quintile had
relative risks (RR) of developing recurrent disease 75% higher than
among those in the lowest quintile (for CRP RR=1.77, P=0.02;
for SAA RR=1.74, P=0.02), there was no statistically
significant evidence of increased risk among those with
prerandomization levels in the first through fourth quintiles for
either parameter.
View this table:
[in a new window]
Table 3. Relative Risks of Recurrent Myocardial Infarction or
Coronary Death From Lowest (Referent) to Highest Quintile of
C-Reactive Protein or Serum Amyloid A Concentration at Study Entry
View larger version (13K):
[in a new window]
Figure 1. Relative risks of recurrent coronary
events among postmyocardial infarction patients according to baseline
plasma concentration of CRP.
View larger version (13K):
[in a new window]
Figure 2. Relative risks of recurrent coronary
events among postmyocardial infarction patients according to baseline
plasma concentration of SAA. and 5). In these analyses, the
relative risks associated with prerandomization CRP concentrations
equal to or greater than the 25th, 50th, 75th, 90th, and 95th
percentiles of the control distribution were 1.2 (P=0.2),
1.2 (P=0.2), 1.3 (P=0.08), 1.6
(P=0.03), and 1.9 (P=0.02). Similarly, the
relative risks associated with prerandomization SAA concentrations
exceeding the 25th, 50th, 75th, 90th, and 95th percentiles of the
control distribution were 1.2 (P=0.2), 1.5
(P=0.01), 1.5 (P=0.02), 1.6 (P=0.03),
and 1.7 (P=0.07). As also shown in Tables 4 and 5,
these risk estimates were not materially altered in analyses
controlling for smoking status or for LDL cholesterol, HDL
cholesterol, or triglycerides. Further
adjustment for other risk factors including diabetes had minimal impact
on these risk estimates.
View this table:
[in a new window]
Table 4. Relative Risks of Recurrent Myocardial Infarction or
Coronary Death Associated With Levels of C-Reactive Protein
(CRP) Above or Below Prespecified Cutoffs Defined by Distribution of
Control Values
View this table:
[in a new window]
Table 5. Relative Risks of Recurrent Myocardial Infarction or
Coronary Death Associated With Levels of Serum Amyloid A (SAA)
Above or Below Prespecified Cut Points Defined by Distribution of
Control Values , a
statistically significant increase in risk of recurrent
coronary events was observed across these 4 study groups
(P-trend=0.005). Specifically, compared with the lowest risk
group (those with both markers of inflammation below the 90th
percentile who were randomly assigned to pravastatin), the
group with the highest risk of recurrent events were those with levels
of both CRP and SAA equal to or greater than the 90th percentile who
were randomly assigned to placebo (RR=2.8, 95% confidence interval
[CI] 1.3 to 6.0, P=0.007). This risk estimate was greater
than the product of the individual risks associated with evidence
of either inflammation (RR=1.3) or placebo assignment (RR=1.3) alone
(Figure 3). Results were similar in analyses based solely on
elevations of CRP or based solely on elevations of SAA. Furthermore, in
analyses stratified by treatment assignment, the association
between concordant serum evidence of inflammation and coronary
risk was statistically significant among those randomized to placebo
(RR=2.11, P=0.048) but was attenuated and no longer
significant among those randomized to pravastatin (RR=1.29,
P=0.5).
View larger version (12K):
[in a new window]
Figure 3. Relative risks of recurrent coronary
events among postmyocardial infarction patients according to presence
(both CRP and SAA levels 90th percentile) or absence (both CRP and
SAA levels < 90th percentile) of evidence of inflammation and by
randomized pravastatin assignment.).
View this table:
[in a new window]
Table 6. Baseline Lipid Levels Among Study Patients With and
Without Evidence of Inflammation
Discussion
Top
Abstract
Introduction
Methods
Results
Discussion
References
These prospective data indicate that plasma concentration of 2
markers of inflammation, CRP and SAA, predict the risk of recurrent
coronary events among stable patients with a prior history of
myocardial infarction. In these data, the risk of recurrent
coronary events associated with elevations of CRP or SAA was
independent of smoking status and baseline levels of LDL
cholesterol, HDL cholesterol, and
triglycerides. These data also raise the possibility of an
interrelation between serum evidence of inflammation,
pravastatin, and coronary risk. Specifically, the
magnitude of the risk of recurrent coronary events observed
among those with evidence of inflammation who were randomly assigned to
placebo (RR=2.81, P=0.007) was greater than the product
of the observed risks associated with either inflammation alone or
placebo assignment alone. Moreover, while a statistically significant
association was observed between evidence of inflammation and
coronary events among those assigned to placebo, this risk was
attenuated and no longer significant among those assigned to
pravastatin.
Acknowledgments
Dr Paul Ridker is supported by an Established Investigator Award
from the American Heart Association.
Footnotes
Guest editor for this article was Antonio M. Gotto, Jr, MD, Cornell University Medical Center, New York, NY.
References
Top
Abstract
Introduction
Methods
Results
Discussion
References
1.
Ross R. The pathogenesis of
atherosclerosis: a perspective for the 1990s.
Nature. 1993;362:801–809.[Medline]
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F. Schiele, N. Meneveau, M. F. Seronde, R. Chopard, V. Descotes-Genon, J. Dutheil, J.-P. Bassand, and on behalf on the 'Reseau de Cardiologie de Franche C-reactive protein improves risk prediction in patients with acute coronary syndromes Eur. Heart J., July 4, 2009; (2009) ehp273v1. [Abstract] [Full Text] [PDF]
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H. Almroth, N. Hoglund, K. Boman, A. Englund, S. Jensen, B. Kjellman, P. Tornvall, and M. Rosenqvist Atorvastatin and persistent atrial fibrillation following cardioversion: a randomized placebo-controlled multicentre study Eur. Heart J., April 1, 2009; 30(7): 827 - 833. [Abstract] [Full Text] [PDF]
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R. J. Glynn, J. G. MacFadyen, and P. M Ridker Tracking of High-Sensitivity C-Reactive Protein after an Initially Elevated Concentration: The JUPITER Study Clin. Chem., February 1, 2009; 55(2): 305 - 312. [Abstract] [Full Text] [PDF]
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P. M Ridker C-Reactive Protein: Eighty Years from Discovery to Emergence as a Major Risk Marker for Cardiovascular Disease Clin. Chem., February 1, 2009; 55(2): 209 - 215. [Full Text] [PDF]
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M. Tonelli, F. Sacks, M. Arnold, L. Moye, B. Davis, M. Pfeffer, and for the Cholesterol and Recurrent Events (CARE) Tr Relation Between Red Blood Cell Distribution Width and Cardiovascular Event Rate in People With Coronary Disease Circulation, January 15, 2008; 117(2): 163 - 168. [Abstract] [Full Text] [PDF]
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T. Rydgren, O. Vaarala, and S. Sandler Simvastatin Protects against Multiple Low-Dose Streptozotocin-Induced Type 1 Diabetes in CD-1 Mice and Recurrence of Disease in Nonobese Diabetic Mice J. Pharmacol. Exp. Ther., October 1, 2007; 323(1): 180 - 185. [Abstract] [Full Text] [PDF]
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J. Kitayama, F. M. Faraci, S. R. Lentz, and D. D. Heistad Cerebral Vascular Dysfunction During Hypercholesterolemia Stroke, July 1, 2007; 38(7): 2136 - 2141. [Abstract] [Full Text] [PDF]
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P. M. Ridker C-Reactive Protein and the Prediction of Cardiovascular Events Among Those at Intermediate Risk: Moving an Inflammatory Hypothesis Toward Consensus J. Am. Coll. Cardiol., May 29, 2007; 49(21): 2129 - 2138. [Abstract] [Full Text] [PDF]
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S. Lavi, J. P. McConnell, C. S. Rihal, A. Prasad, V. Mathew, L. O. Lerman, and A. Lerman Local Production of Lipoprotein-Associated Phospholipase A2 and Lysophosphatidylcholine in the Coronary Circulation: Association With Early Coronary Atherosclerosis and Endothelial Dysfunction in Humans Circulation, May 29, 2007; 115(21): 2715 - 2721. [Abstract] [Full Text] [PDF]
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M. S. Sabatine, D. A. Morrow, K. A. Jablonski, M. M. Rice, J. W. Warnica, M. J. Domanski, J. Hsia, B. J. Gersh, N. Rifai, P. M Ridker, et al. Prognostic Significance of the Centers for Disease Control/American Heart Association High-Sensitivity C-Reactive Protein Cut Points for Cardiovascular and Other Outcomes in Patients With Stable Coronary Artery Disease Circulation, March 27, 2007; 115(12): 1528 - 1536. [Abstract] [Full Text] [PDF]
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N. Sattar, H. M. Murray, A. McConnachie, G. J. Blauw, E. L.E.M. Bollen, B. M. Buckley, S. M. Cobbe, I. Ford, A. Gaw, M. Hyland, et al. C-Reactive Protein and Prediction of Coronary Heart Disease and Global Vascular Events in the Prospective Study of Pravastatin in the Elderly at Risk (PROSPER) Circulation, February 27, 2007; 115(8): 981 - 989. [Abstract] [Full Text] [PDF]
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P. Libby and P. M. Ridker Inflammation and Atherothrombosis: From Population Biology and Bench Research to Clinical Practice J. Am. Coll. Cardiol., October 27, 2006; 48(9_Suppl_A): A33 - A46. [Abstract] [Full Text] [PDF]
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D. A. Morrow, J. A. de Lemos, M. S. Sabatine, S. D. Wiviott, M. A. Blazing, A. Shui, N. Rifai, R. M. Califf, and E. Braunwald Clinical Relevance of C-Reactive Protein During Follow-Up of Patients With Acute Coronary Syndromes in the Aggrastat-to-Zocor Trial Circulation, July 25, 2006; 114(4): 281 - 288. [Abstract] [Full Text] [PDF]
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A. Zambon, P. Gervois, P. Pauletto, J.-C. Fruchart, and B. Staels Modulation of Hepatic Inflammatory Risk Markers of Cardiovascular Diseases by PPAR-{alpha} Activators: Clinical and Experimental Evidence Arterioscler Thromb Vasc Biol, May 1, 2006; 26(5): 977 - 986. [Abstract] [Full Text] [PDF]
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S. Tsimikas, J. T. Willerson, and P. M. Ridker C-reactive protein and other emerging blood biomarkers to optimize risk stratification of vulnerable patients. J. Am. Coll. Cardiol., April 18, 2006; 47(8 Suppl): C19 - C31. [Abstract] [Full Text] [PDF]
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C. J. Boos, R. A. Anderson, and G. Y.H. Lip Is atrial fibrillation an inflammatory disorder? Eur. Heart J., January 2, 2006; 27(2): 136 - 149. [Abstract] [Full Text] [PDF]
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N. Christodoulides, P. N. Floriano, S. A. Acosta, K. L. M. Ballard, S. E. Weigum, S. Mohanty, P. Dharshan, D. Romanovicz, and J. T. McDevitt Toward the Development of a Lab-on-a-Chip Dual-Function Leukocyte and C-Reactive Protein Analysis Method for the Assessment of Inflammation and Cardiac Risk Clin. Chem., December 1, 2005; 51(12): 2391 - 2395. [Full Text] [PDF]
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G. S. Ginsburg, M. P. Donahue, and L. K. Newby Prospects for Personalized Cardiovascular Medicine: The Impact of Genomics J. Am. Coll. Cardiol., November 1, 2005; 46(9): 1615 - 1627. [Abstract] [Full Text] [PDF]
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F. Tomai, F. Ribichini, A. S. Ghini, V. Ferrero, G. Ando, C. Vassanelli, F. Romeo, F. Crea, and L. Chiariello Elevated C-reactive protein levels and coronary microvascular dysfunction in patients with coronary artery disease Eur. Heart J., October 2, 2005; 26(20): 2099 - 2105. [Abstract] [Full Text] [PDF]
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T. A. Lakka, H.-M. Lakka, T. Rankinen, A. S. Leon, D.C. Rao, J. S. Skinner, J. H. Wilmore, and C. Bouchard Effect of exercise training on plasma levels of C-reactive protein in healthy adults: the HERITAGE Family Study Eur. Heart J., October 1, 2005; 26(19): 2018 - 2025. [Abstract] [Full Text] [PDF]
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M. Di Napoli, M. Schwaninger, R. Cappelli, E. Ceccarelli, G. Di Gianfilippo, C. Donati, H. C.A. Emsley, S. Forconi, S. J. Hopkins, L. Masotti, et al. Evaluation of C-Reactive Protein Measurement for Assessing the Risk and Prognosis in Ischemic Stroke: A Statement for Health Care Professionals From the CRP Pooling Project Members Stroke, June 1, 2005; 36(6): 1316 - 1329. [Abstract] [Full Text] [PDF]
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P. M. Ridker, D. A. Morrow, L. M. Rose, N. Rifai, C. P. Cannon, and E. Braunwald Relative Efficacy of Atorvastatin 80 mg and Pravastatin 40 mg in Achieving the Dual Goals of Low-Density Lipoprotein Cholesterol <70 mg/dl and C-Reactive Protein <2 mg/l: An Analysis of the PROVE-IT TIMI-22 Trial J. Am. Coll. Cardiol., May 17, 2005; 45(10): 1644 - 1648. [Abstract] [Full Text] [PDF]
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B. J. Nicklas, T. You, and M. Pahor Behavioural treatments for chronic systemic inflammation: effects of dietary weight loss and exercise training Can. Med. Assoc. J., April 26, 2005; 172(9): 1199 - 1209. [Abstract] [Full Text] [PDF]
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R. A.H. Stewart, H. D. White, A. C. Kirby, S. R. Heritier, R. J. Simes, P. J. Nestel, M. J. West, D. M. Colquhoun, A. M. Tonkin, and for the Long-Term Intervention With Pravastatin in White Blood Cell Count Predicts Reduction in Coronary Heart Disease Mortality With Pravastatin Circulation, April 12, 2005; 111(14): 1756 - 1762. [Abstract] [Full Text] [PDF]
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K. D. O'Brien, B. J. Brehm, R. J. Seeley, J. Bean, M. H. Wener, S. Daniels, and D. A. D'Alessio Diet-Induced Weight Loss Is Associated with Decreases in Plasma Serum Amyloid A and C-Reactive Protein Independent of Dietary Macronutrient Composition in Obese Subjects J. Clin. Endocrinol. Metab., April 1, 2005; 90(4): 2244 - 2249. [Abstract] [Full Text] [PDF]
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A. Chait, C. Y. Han, J. F. Oram, and J. W. Heinecke Thematic review series: The Immune System and Atherogenesis. Lipoprotein-associated inflammatory proteins: markers or mediators of cardiovascular disease? J. Lipid Res., March 1, 2005; 46(3): 389 - 403. [Abstract] [Full Text] [PDF]
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G. Davi, M. Neri, A. Falco, D. Festi, T. Taraborelli, G. Ciabattoni, S. Basili, F. Cuccurullo, and C. Patrono Helicobacter Pylori Infection Causes Persistent Platelet Activation In Vivo Through Enhanced Lipid Peroxidation Arterioscler Thromb Vasc Biol, January 1, 2005; 25(1): 246 - 251. [Abstract] [Full Text] [PDF]
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L. M. Biasucci CDC/AHA Workshop on Markers of Inflammation and Cardiovascular Disease: Application to Clinical and Public Health Practice: Clinical Use of Inflammatory Markers in Patients With Cardiovascular Diseases: A Background Paper Circulation, December 21, 2004; 110(25): e560 - e567. [Abstract] [Full Text] [PDF]
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P. Amarenco, J. Labreuche, P. Lavallee, and P.-J. Touboul Statins in Stroke Prevention and Carotid Atherosclerosis: Systematic Review and Up-to-Date Meta-Analysis Stroke, December 1, 2004; 35(12): 2902 - 2909. [Abstract] [Full Text] [PDF]
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M. Madjid, I. Awan, J. T. Willerson, and S. W. Casscells Leukocyte count and coronary heart disease: Implications for risk assessment J. Am. Coll. Cardiol., November 16, 2004; 44(10): 1945 - 1956. [Abstract] [Full Text] [PDF]
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K. Becker and M. Chopp Role of Statins in the Treatment and Prevention of Stroke: Introduction Stroke, November 1, 2004; 35(11_suppl_1): 2706 - 2707. [Full Text] [PDF]
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K. Esposito, D. Giugliano, F. Nappo, R. Marfella, and for the Campanian Postprandial Hyperglycemia Study Regression of Carotid Atherosclerosis by Control of Postprandial Hyperglycemia in Type 2 Diabetes Mellitus Circulation, July 13, 2004; 110(2): 214 - 219. [Abstract] [Full Text] [PDF]
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S. Fichtlscherer, S. Breuer, C. Heeschen, S. Dimmeler, and A. M. Zeiher Interleukin-10 serum levels and systemic endothelial vasoreactivity in patients with coronary artery disease J. Am. Coll. Cardiol., July 7, 2004; 44(1): 44 - 49. [Abstract] [Full Text] [PDF]
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D.D. Waters and K.K. Khush Management of the acute coronary syndrome patient Eur. Heart J. Suppl., July 1, 2004; 6(suppl_C): C49 - C57. [Abstract] [Full Text] [PDF]
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P. M Ridker, N. J. Brown, D. E. Vaughan, D. G. Harrison, and J. L. Mehta Established and Emerging Plasma Biomarkers in the Prediction of First Atherothrombotic Events Circulation, June 29, 2004; 109(25_suppl_1): IV-6 - IV-19. [Full Text] [PDF]
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R. Paoletti, A. M. Gotto Jr, and D. P. Hajjar Inflammation in Atherosclerosis and Implications for Therapy Circulation, June 15, 2004; 109(23_suppl_1): III-20 - III-26. [Abstract] [Full Text]
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J. Davignon Beneficial Cardiovascular Pleiotropic Effects of Statins Circulation, June 15, 2004; 109(23_suppl_1): III-39 - III-43. [Abstract] [Full Text]
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P. Amarenco and A. M. Tonkin Statins for Stroke Prevention: Disappointment and Hope Circulation, June 15, 2004; 109(23_suppl_1): III-44 - III-49. [Abstract] [Full Text] [PDF]
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J. A. Schaar, E. Regar, F. Mastik, E. P. McFadden, F. Saia, C. Disco, C. L. de Korte, P. J. de Feyter, A. F.W. van der Steen, and P. W. Serruys Incidence of High-Strain Patterns in Human Coronary Arteries: Assessment With Three-Dimensional Intravascular Palpography and Correlation With Clinical Presentation Circulation, June 8, 2004; 109(22): 2716 - 2719. [Abstract] [Full Text] [PDF]
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A. Segev, S. Kassam, C. E Buller, H. K Lau, J. D Sparkes, P. W Connelly, P. H Seidelin, M. K Natarajan, E. A Cohen, and B. H Strauss Pre-procedural plasma levels of C-reactive protein and interleukin-6 do not predict late coronary angiographic restenosis after elective stenting Eur. Heart J., June 2, 2004; 25(12): 1029 - 1035. [Abstract] [Full Text] [PDF]
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 R. Kleemann, L. Verschuren, B.-J. de Rooij, J. Lindeman, M. M. de Maat, A. J. Szalai, H. M. G. Princen, and T. Kooistra Evidence for anti-inflammatory activity of statins and PPAR{alpha} activators in human C-reactive protein transgenic mice in vivo and in cultured human hepatocytes in vitro Blood, June 1, 2004; 103(11): 4188 - 4194. [Abstract] [Full Text] [PDF]
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J. T. Willerson and P. M. Ridker Inflammation as a Cardiovascular Risk Factor Circulation, June 1, 2004; 109(21_suppl_1): II-2 - II-10. [Abstract] [Full Text] [PDF]
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J. P.J. Halcox and J. E. Deanfield Beyond the Laboratory: Clinical Implications for Statin Pleiotropy Circulation, June 1, 2004; 109(21_suppl_1): II-42 - II-48. [Abstract] [Full Text] [PDF]
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D. G. Hackam and S. L. Shumak C-reactive protein for the prediction of cardiovascular risk: Ready for prime-time? Can. Med. Assoc. J., May 11, 2004; 170(10): 1563 - 1565. [Full Text] [PDF]
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B Boland and G Goderis Statins in patients at high risk of cardiovascular disease presenting with peripheral artery disease Eur. Heart J., May 1, 2004; 25(9): 712 - 713. [Full Text] [PDF]
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 F. R. DANESH and Y. S. KANWAR Modulatory effects of HMG-CoA reductase inhibitors in diabetic microangiopathy FASEB J, May 1, 2004; 18(7): 805 - 815. [Abstract] [Full Text] [PDF]
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Yasmin, C. M. McEniery, S. Wallace, I. S. Mackenzie, J. R. Cockcroft, and I. B. Wilkinson C-Reactive Protein Is Associated With Arterial Stiffness in Apparently Healthy Individuals Arterioscler Thromb Vasc Biol, May 1, 2004; 24(5): 969 - 974. [Abstract] [Full Text]
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