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"Long-term effects of pravastatin on
plasma concentration of C-reactive protein," by Paul M. Ridker, Nader
Rifai, Marc A. Pfeffer, Frank Sacks, and Eugene Braunwald, for the Cholesterol
and Recurrent Events (CARE) investigators, Circulation, 100(3):230-5,
20 July 1999.
[Authors' affiliations: Brigham & Women's
Hospital, Boston, MA; Harvard Medical School, Boston; Children's Hospital
Medical Center, Boston]
Abstract: "Background.
Elevated plasma concentrations of C-reactive protein (CRP) are associated with
increased cardiovascular risk. We evaluated whether long-term therapy with
pravastatin, an agent that reduces cardiovascular risk, might alter levels of
this inflammatory parameter. Methods and Results. CRP levels were
measured at baseline and at 5 years in 472 randomly selected participants in
the Cholesterol and Recurrent Events (CARE) trial who remained free of
recurrent coronary events during follow-up. Overall, CRP levels at baseline
and at 5 years were highly correlated (r=0.60, P<0.001). However, among
those allocated to placebo, median CRP levels and the mean change in CRP
tended to increase over time (median change, +4.2%; P=0.2 and mean change,
+0.07 mg/dL; P=0.04). By contrast, median CRP levels and the mean change in
CRP decreased over time among those allocated to pravastatin (median change,
-17.4%; P=0.004 and mean change, -0.07mg/dL; P=0.002). Thus, statistically
significant differences were observed at 5 years between the pravastatin and
placebo groups in terms of median CRP levels (difference, -21.6%; P=0.007,
mean CRP levels (difference, -37.8%; P=0.002), and absolute mean change in CRP
(difference, -0.137 mg/dL; P=0.003). These effects persisted in analyses
stratified by age, body mass index, smoking status, blood pressure, and
baseline lipid levels. Attempts to relate the magnitude of change in CRP to
the magnitude of change in lipids in both the pravastatin and placebo groups
did not reveal any obvious relationships. Conclusions. Among survivors
of myocardial infarction on standard therapy plus placebo, CRP levels tended
to increase over 5 years of follow-up. In contrast, randomization to
pravastatin resulted in significant reductions in this inflammatory marker
that were not related to the magnitude of lipid alterations observed. Thus,
these data further support the potential for nonlipid effects of this
agent."
This 1999 report from Circulation was
cited 27 times in current journal articles indexed in the ISI
database during July-August 2001. Matching its achievement during a previous
count (March-April 2001), this report attracted enough citations during
July-August to rank as the most-cited of any paper in medicine published in
the last two years, excluding reviews. Prior to the most recent bimonthly
count, citations to the paper have accrued as follows:
May-June 2001: 15 citations
March-April 2001: 29
January-February 2001: 12
November-December 2000: 10
September-October 2000: 7
July-August 2000: 4
May-June 2000: 6
March-April 2000: 4
January-February 2000: 5
November-December 1999: 1
Total citations to date: 120
SOURCE: Hot
Papers Database (Available from the ISI
Research Services Group in a CD-ROM version containing data on
hundreds of highly cited papers published during the last two years.
User interface permits searching by author, organization, journal,
field, and more. Total citations, as well as citations accrued during
successive bimonthly periods, can be assessed and graphed. Database is
combined with subscription to the ISI newsletter Science
Watch®; updated discs containing the
most recent bimonthly data are mailed with each new issue, six times a
year.)
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