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Age and Duration of Follow-up as Modulators of the Risk for Ischemic Heart Disease Associated With High Plasma C-Reactive Protein Levels in Men
Matteo Pirro, MD;
Jean Bergeron, MD;
Gilles R. Dagenais, MD;
Paul-Marie Bernard, MSc;
Bernard Cantin, MD, PhD;
Jean-Pierre Després, PhD;
Benoît Lamarche, PhD
Arch Intern Med. 2001;161:2474-2480.
ABSTRACT
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Background Plasma C-reactive protein (CRP) levels recently have been identified
as an emerging risk factor for ischemic heart disease (IHD). However, whether
plasma CRP levels predict an increased risk for future IHD beyond traditional
risk factors has yet to be evaluated in a large prospective, population-based
study.
Methods The association between elevated plasma CRP levels and the risk for
future IHD was investigated in the prospective, population-based cohort of
2037 IHD-free middle-aged men from the Quebec Cardiovascular Study. During
a 5-year follow-up, 105 first IHD events were recorded. Baseline plasma CRP
levels were measured using a highly sensitive assay.
Results High plasma CRP concentrations (equal to or above vs below the median
level of 1.77 mg/L) were associated with a significant 1.8-fold increase in
IHD risk (95% confidence interval [CI], 1.2-2.7). This association remained
significant after adjustment for lipid risk factors but not when the simultaneous
contribution of nonlipid traditional risk factors was taken into account.
Multivariate analyses indicated that CRP level predicted short-term risk for
IHD (events that occurred  2 years after the baseline evaluation), but
not long-term risk (>2 years). Moreover, high plasma CRP levels predicted
an increased risk for IHD, independent of any other confounder, in younger
(55 years) but not in older (>55 years) individuals.
Conclusion Plasma CRP levels may provide independent information on IHD risk only
in younger middle-aged men and in the case of IHD events that may occur relatively
soon after the baseline evaluation.
INTRODUCTION
ACCUMULATING evidence suggests that inflammation may be etiologically
important in the development of atherosclerosis.1
In this respect, plasma C-reactive protein (CRP), a marker of low to moderate
systemic inflammation, has received much attention in recent years. Results
from cross-sectional and prospective studies2
have indicated that raised plasma CRP levels were associated with an increased
risk for future cardiovascular events among apparently healthy subjects3-4 as well as in individuals with stable
and unstable angina5 or with previous myocardial
infarction.6 Moreover, results from the Physicians'
Health Study disclosed that baseline plasma CRP concentration added to the
predictive value of traditional lipid risk factors in determining risk for
first myocardial infarction.7 Although these
data suggest that adding plasma CRP levels to the list of cardiovascular risk
factors commonly assessed in the clinical practice would improve our ability
to predict future cardiovascular events, critical issues remain to be specifically
addressed. First, our current interpretation of the relationship between plasma
CRP level and the risk for ischemic heart disease (IHD) in middle-aged men
is based almost exclusively on data derived from cross-sectional or prospective
nested case-control studies,8 with only 1 population-based
study9 conducted in a relatively small cohort
of subjects. Second, the ability of plasma CRP levels to predict an increased
risk for IHD has yet to be tested while considering a comprehensive number
of lipid and nonlipid cardiovascular risk factors as confounders. Third, the
CRP prognostic value of IHD risk showed a strong time-to-event dependency
in the elderly,10 whereas it appeared to be
stable during follow-ups of varying lengths in a nested case-control study
in middle-aged men.3 Thus, the chronological
relationship between plasma CRP levels and the risk for future IHD events
remains to be fully elucidated using population-based, prospective data.
The purpose of the present study was to examine the association between
plasma CRP levels and the risk for future IHD when controlling for a significant
set of IHD risk factors in the prospective, population-based Quebec Cardiovascular
Study. Baseline plasma CRP concentrations were measured in the entire cohort
of 2037 middle-aged men initially free of clinical manifestations of IHD,
among whom 105 developed IHD during the 5-year follow-up.
SUBJECTS AND METHODS
STUDY POPULATION AND FOLLOW-UP
The Quebec Cardiovascular Study cohort has been described in detail
previously.11-12 In 1973, a random
sample of 4637 men (aged 35-64 years) was recruited using the provincial electoral
lists from 7 cities of the Quebec metropolitan area for an evaluation of cardiovascular
risk factors. Subsequent evaluations were performed at regular intervals,
and data collected in 1985 were used as the baseline characteristics for the
present prospective analyses. In 1985, 61.1% (n = 2443) of the living cohort
of men without IHD at the 1973 visit came to the lipid clinic in a fasting
state for their evaluation. Among the 1557 other potential living participants,
10.0% could not be located, 18.8% showed up in a nonfasting state, and 71.4%
refused to participate or underwent evaluation in a nonfasting state at their
home by nurses of the project. Analyses of data collected in 1973 revealed
that the age distribution of the 2443 participating men in 1985 was representative
of the original cohort. During 1990 and 1991, all participants were contacted
by mail and invited to answer a short standardized questionnaire on smoking
habits, medication use, and history of cardiovascular diseases and diabetes
mellitus. Telephone calls were made to participants who did not answer a second
letter or, if unsuccessful, to a close family member. For those patients who
reported cardiovascular diseases or diabetes and for those who died, hospital
charts were reviewed. Mortality and morbidity data were obtained in 98.7%
and 96.1%, respectively, of the participants of the 1973 initial screening.
EVALUATION OF RISK FACTORS
Data on demographic and lifestyle variables, medical history, and medication
were obtained in 1985 through a standardized questionnaire administered to
each participant by trained nurses and reviewed by a physician. Body weight
and height were recorded. Resting blood pressure was measured after 5 minutes
in a sitting position. The mean of 2 blood pressure measures obtained 5 minutes
apart was used in the analyses. Information on personal and family history
of IHD and diabetes, smoking habits, alcohol consumption, and medication use
was also obtained. Diabetes was considered in men who self-reported the disease
or who were treated with hypoglycemic agents. Only 1.1% of men were using
hypolipidemic drugs in 1985, whereas 6.1% and 3.1% of men were using  -blockers
and diuretics, respectively, on a regular basis at the 1985 screening. Family
history of IHD was considered positive if at least 1 parent and/or 1 sibling
had a history of IHD.
DEFINITION OF IHD EVENTS
The diagnosis of a first IHD event included typical angina of effort,
coronary insufficiency, nonfatal myocardial infarction, and coronary death.
All myocardial infarctions met the criteria previously described,11 ie, diagnostic electrocardiographic (ECG) changes
alone or 2 of the following criteria: typical chest pain lasting at least
20 minutes, creatine kinase enzyme level at least twice the upper limit of
the reference range, or characteristic ECG changes. Coronary insufficiency
was considered if a typical retrosternal chest pain lasting at least 15 minutes
was associated with transient ischemic ECG changes but without substantial
elevation in levels of creatine kinase. Diagnoses of myocardial infarction
and coronary insufficiency were all confirmed using hospital medical charts.
All ECGs were read by the same cardiologist (G.R.D.), who was unaware of the
participants' risk profile. The diagnosis of angina of effort, obtained by
a cardiologist of the study (G.R.D.), was based on typical symptoms of retrosternal
squeezing or pressure-type discomfort occurring on exertion and relieved by
rest and/or nitroglycerine. Criteria for the diagnosis of coronary deaths
included confirmation from death certificate or autopsy report describing
the presence of coronary disease, without evidence of noncardiac disease that
could explain death. Myocardial infarction was considered fatal if death occurred
within 4 weeks of the initial event or if it was diagnosed at autopsy. We
confirmed IHD-related deaths from the Provincial Death Registry. Informed
consent was obtained to review relevant hospital files. Autopsies were performed
in about a third of deaths. The total IHD event frequency during the 5-year
follow-up was similar in participants (5.4%) and nonparticipants (6.5%) in
the study.
LABORATORY ANALYSES
Fasting lipoprotein-lipid and apolipoprotein levels were measured in
fresh plasma samples in 1985 when participants came to the clinic for evaluation.
Aliquots of fasting plasma frozen at time of collection were subsequently
used for the assessment of baseline plasma CRP concentrations. Aliquots had
been stored at -80°C since the 1985 baseline evaluation. Plasma
cholesterol and triglyceride levels were determined on an autoanalyzer (Technicon
RA-500; Bayer Corporation Inc, Tarrytown, NY) as previously described.13 Plasma high-density lipoprotein (HDL) cholesterol
levels were measured in the supernatant fraction after precipitation of apolipoprotein
B–containing lipoproteins using a combination of heparin and manganese
chloride.14 Low-density lipoprotein (LDL) cholesterol
levels were estimated by means of the equation of Friedewald et al,15 as men with triglyceride levels of greater than 400
mg/dL (>4.5 mmol/L) (n = 52) were excluded from the analyses.12
Plasma apolipoprotein B levels were measured by means of the rocket immunoelectrophoresis
method of Laurell,16 as described previously.13 The interassay coefficients of variation for cholesterol,
HDL cholesterol, triglyceride, and apolipoprotein B levels were all less than
3%. Plasma CRP levels were measured using a commercially available, highly
sensitive CRP assay (Behring Latex-Enhanced on the Behring Nephelometer BN-100;
Behring Diagnostic, Westwood, Mass) and the calibrators provided by the manufacturer
(N Rheumatology Standards SL; Behring Diagnostic). The sensitivity of the
assay ranged from 0.175 to 11 mg/L. The mean interassay coefficient of variation
for plasma CRP levels calculated using 2 separate measures of the same aliquot
in 134 men was less than 1% at low and high plasma CRP concentrations (data
not shown).
STATISTICAL ANALYSES
Baseline characteristics of men in whom IHD developed during the 5-year
follow-up were compared with the characteristics of those who remained free
of clinical manifestations of IHD by the t test or
the  2 statistic. Variables with a skewed distribution were
logarithm-transformed, resulting in near-normal distributions. Geometric means
were calculated and reported where indicated. Correlation analyses were performed
using the Pearson and Spearman coefficients of correlation for parametric
and nonparametric variables, respectively.
We investigated the relationship between plasma CRP levels and the risk
for future IHD events by dichotomizing plasma CRP levels using the median
(1.77 mg/L) of the entire cohort and quartiles of plasma CRP levels. Both
approaches yielded similar results. Thus, only data derived from the dichotomized
CRP levels are presented. The Kaplan-Meier event-free survival probability
(estimated probability of not having IHD during 5-year follow-up) was compared
among men with elevated or low plasma CRP levels ( 1.77 or <1.77 mg/L,
respectively). The log-rank test was used to compare the survival distributions.
Cox proportional hazard models were used to estimate the risk for IHD associated
with low or high plasma CRP concentrations. Relative risks were adjusted for
potential confounding effects of age, smoking habits (smokers vs nonsmokers),
diabetes mellitus (presence or absence), medication use at baseline (yes or
no), systolic blood pressure, body mass index (BMI), and different plasma
lipid variables. The potential confounding effects of age at baseline, smoking,
and duration of follow-up in modulating the relationship between plasma CRP
levels and the risk for future IHD events were investigated by introducing
appropriate interaction terms into the multivariate Cox proportional hazard
models. Statistical analyses were all performed using SAS software (SAS Institute,
Cary, NC).
RESULTS
The baseline characteristics of the 2037 men who participated in the
study are presented in Table 1.
Men with incident IHD were older at baseline (P<.001)
and had a higher systolic blood pressure (P<.001)
and a higher prevalence of type 2 diabetes (P<.001),
compared with men who remained free of clinical manifestations of IHD during
the 5-year follow-up. Plasma concentrations of total cholesterol (P<.001), LDL cholesterol (P<.001), triglycerides
(P<.001), and CRP (P
= .01) were all significantly higher among those with incident IHD compared
with IHD-free individuals. The 105 subjects who subsequently had a first IHD
event during the 5-year follow-up also had reduced HDL cholesterol concentrations
compared with those who did not (P<.001).
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Table 1. Baseline Characteristics of the 2037 Study Participants*
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The magnitude of the association between lipid or nonlipid risk factors
and plasma CRP levels was estimated by correlation analyses in the entire
cohort. Similar results were obtained among subjects with incident IHD and
IHD-free subjects, taken separately (results not shown). Plasma CRP concentrations
were weakly but significantly correlated with levels of triglycerides (r = 0.21; P<.001), total cholesterol
(r = 0.06; P = .004), LDL
cholesterol (r = 0.06; P
= .009), BMI (r = 0.22; P<.001),
and HDL cholesterol (r = -0.23; P<.001). Age and systolic blood pressure were also significant correlates
of plasma CRP concentrations (r = 0.17 and r = 0.18, respectively; P<.001).
Higher plasma CRP levels were documented among smokers and diabetic subjects
(P<.001 for both).
Figure 1 depicts the Kaplan-Meier
event-free survival curves according to plasma CRP levels equal to or above
vs below the 50th percentile (1.77 mg/L) of the entire cohort. The log-rank
test of the differences between both curves was significant (P = .004), indicating that men with plasma CRP levels of at least 1.77
mg/L were at greater risk for future IHD events compared with men having plasma
CRP level of less than 1.77 mg/L. More specifically, among the 1016 subjects
with plasma CRP levels of less than 1.77 mg/L, 39 had a first IHD event, whereas
IHD developed in 66 men among the 1021 individuals with plasma CRP concentrations
of at least 1.77 mg/L.
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Figure 1. Kaplan-Meier survival curves according
to plasma concentrations of C-reactive protein equal to or above vs below
the 50th percentile (1.77 mg/L). Estimates of the survival probability were
significantly different between groups (log-rank test, P= .004).
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The association between plasma CRP concentrations and the risk for future
IHD events was investigated before and after adjustment for different lipid
and nonlipid cardiovascular risk factors (Table 2). High plasma CRP concentrations (1.77 mg/L) were associated
with a 1.8-fold increase in the relative risk (RR) for IHD (95% confidence
interval [CI], 1.2-2.7). Individual and simultaneous adjustment for the potential
confounding effects of LDL cholesterol, the ratio of total cholesterol to
HDL cholesterol, and triglyceride levels attenuated to some extent, but not
completely, the increased risk for IHD associated with elevated plasma CRP
levels. Similarly, the association between LDL cholesterol, the ratio of total
cholesterol to HDL cholesterol, and triglyceride levels and the risk for IHD
was not materially weakened after adjustment for plasma CRP levels (results
not shown), suggesting independent influences of these variables on the risk
for future IHD. The association between elevated plasma CRP levels and the
risk for IHD remained significant when we controlled for the individual contributions
of age, smoking status, diabetes, systolic blood pressure, medication use
at baseline, or BMI (results not shown). On the other hand, plasma CRP levels
of at least 1.77 mg/L did not predict an increased risk for IHD when the contribution
of all nonlipid risk factors was simultaneously taken into consideration (model
6; RR, 1.2; 95% CI, 0.8-1.9). We repeated the same analyses after stratifying
the study population according to quartiles of plasma CRP concentrations.
The crude RR for IHD associated with the highest quartile of plasma CRP levels
(3.80 mg/L), using the lowest quartile as reference (<0.85 mg/L), was
2.1 (95% CI, 1.2-3.7). Adjustment for nonlipid traditional cardiovascular
risk factors completely abolished the relationship between high plasma CRP
levels (fourth quartile) and the risk for IHD (RR, 1.0; 95% CI, 0.5-1.8).
Excluding smokers from the analyses yielded results that were comparable to
those obtained in the entire population.
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Table 2. Multivariate Analysis of the 5-Year Relative Risk for IHD
in Men With High Plasma CRP Levels*
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Further analyses were conducted to examine the relationship between
plasma CRP levels and the risk for future IHD using "hard" end points only,
ie, acute myocardial infarction and coronary death (n = 61). Results were
virtually identical to those obtained using the more generic IHD end point,
which included cases of angina pectoris, coronary insufficiency, nonfatal
myocardial infarction, and coronary death (results not shown). Indeed, elevated
plasma CRP levels predicted an increased risk for IHD after adjustment for
lipid risk factors but not after controlling simultaneously for several nonlipid
risk factors.
To evaluate whether the duration of follow-up affected the ability of
plasma CRP levels to predict future IHD events independent of lipid and nonlipid
risk factors, participants were stratified according to number of years of
follow-up. Figure 2A shows that
plasma CRP levels of at least 1.77 mg/L predicted an increased risk for future
IHD events within the first 2 years of follow-up, but not beyond 2 years of
follow-up. The baseline plasma CRP concentrations in individuals stratified
according to the number of years of follow-up essentially matched its ability
to predict the risk for IHD during the same period (Figure 2B). Indeed, plasma CRP levels at baseline were higher among
men whose follow-up was less than 2 years compared with men for whom follow-up
exceeded 2 years. Evidently, most men followed up for less than 4 years belonged
to the group of individuals who had a first IHD event during the follow-up.
When we considered only incident IHD cases (n = 105), baseline plasma CRP
levels were significantly higher among men who had their first event within
2 years of the baseline evaluation compared with those in whom the event occurred
more than 2 years into follow-up (geometric mean, 3.0 mg/L vs 1.9 mg/L; P = .03). Multivariate Cox proportional hazard analysis
indicated that there was a significant interaction between duration of follow-up
and plasma CRP levels in determining the risk for future IHD events, with
plasma CRP levels of at least 1.77 mg/L predicting an increased risk for future
IHD events only for a short follow-up (Table 3).
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Figure 2. A, Relative risks for future ischemic
heart disease (IHD) events associated with high baseline plasma concentrations
of C-reactive protein (CRP) (1.77 mg/L) according to the number of years
of follow-up. B, Plasma CRP concentrations (geometric means) in subgroups
of subjects stratified according to length of follow-up. Bars represent SEM.
Asterisk indicates significantly different from follow-up of less than 1 year
(P<.001); dagger, significantly different from
follow-up of 1 to 2 years (P<.001).
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Table 3. Effects of Duration of Follow-up and Age at Baseline on Unadjusted
and Adjusted Relative Risks for IHD*
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Analyses were conducted to further examine the potential confounding
effects of age at baseline on the relationship between plasma CRP levels and
the risk for IHD. Plasma CRP concentrations among younger subjects were lower
than in older middle-aged men (geometric means, 1.5 and 2.1 mg/L, respectively; P<.001). Cox proportional hazard analysis showed that
the multivariate term describing multiplicative interaction between age and
plasma CRP levels was significant (P = .04). Thus,
high plasma CRP levels predicted an increased risk for IHD, independent of
the confounding effects of lipid and nonlipid cardiovascular risk factors,
in younger but not in older individuals (Table 3).
COMMENT
A number of clinically relevant observations can be drawn from this
prospective, population-based study. First, plasma CRP levels of at least
1.77 mg/L were associated with an approximately 2-fold increase in the risk
for future IHD events. Second, this increased risk for IHD associated with
elevated plasma CRP levels remained significant in multivariate analyses only
when considering events that occurred no later than 2 years into follow-up,
but not when considering those that occurred beyond 2 years of follow-up.
Third, elevated plasma CRP levels at baseline predicted an increased risk
for a first IHD event independent of lipid and nonlipid cardiovascular risk
factors in men younger than 55 years, but not in older individuals.
CRP LEVEL VS TRADITIONAL CARDIOVASCULAR RISK FACTORS
Plasma CRP is a nonspecific marker of underlying systemic inflammation.
Levels of CRP fluctuate into a wide range of concentrations, depending on
several stimuli.17 Infections, physical trauma,
and other inflammatory conditions clearly represent important sources of this
variability. However, several other features, eg, age,18
diabetes,19 smoking status,20
obesity,21 exercise,22
anti-inflammatory drugs,3 and lipid-lowering
agents,23 influence plasma CRP concentrations
and IHD risk. Thus, any combination of these traditional risk factors could
potentially confound the relationship between plasma CRP levels and IHD risk.
To our knowledge, the Monitoring Trends and Determinations in Cardiovascular
Disease (MONICA) study9 is, to date, the only
prospective, population-based study documenting the relationship between plasma
CRP levels and the risk for future coronary events in a cohort of middle-aged
men. It showed that the risk ratio of IHD events associated with a 1-SD increase
in logarithm-CRP was 1.67 (95% CI, 1.29-2.17) and 1.50 (95% CI, 1.14-1.97),
respectively, before and after adjustment for the combined confounding effect
of age and smoking status. Similarly, we observed that individual adjustment
for age and smoking habits did not materially affect the risk for IHD associated
with high baseline plasma CRP concentrations (not shown). Further analyses
indicated that the increased risk for IHD associated with elevated plasma
CRP concentrations remained significant even after adjustment for these 2
risk factors simultaneously (RR, 1.5; 95% CI, 1.0-2.3; P = .04). On the other hand, the relationship between plasma CRP concentrations
and the risk for future IHD events was substantially attenuated when other
nonlipid risk factors (diabetes, hypertension, and BMI) were considered simultaneously
(RR, 1.2; 95% CI, 0.8-1.9). Thus, results from the present study suggest that
the relationship between plasma CRP levels and the risk for future IHD events
is not independent of the sum of nonlipid risk factors.
These findings are in contrast with those of a previous prospective
nested case-control study in middle-aged men, which suggested that the risk
for IHD associated with elevated plasma CRP levels was not modified by other
risk factors,3 including those that were controlled
for in the present study. In this regard, it should be pointed out that the
study by Koenig et al, Ridker as well as other studies,9-10
did not report the impact that a simultaneous adjustment for a comprehensive
list of lipid and nonlipid cardiovascular risk factors may have had on the
relationship between plasma CRP concentrations and the risk for future IHD
events. Results from our large, prospective, population-based study underline
the impact that a number of relatively weak correlates of CRP (r2<5%) such as age, systolic blood pressure, and smoking
habits may exert on the relationship between plasma CRP levels and the risk
for future IHD events. Indeed, although not confounding singularly, these
risk factors greatly attenuated the association between CRP and the risk for
future IHD events when they were considered simultaneously.
CRP LEVEL VS DURATION OF FOLLOW-UP
Results from the present population-based study also indicated that
the relationship between plasma CRP levels and the risk for future IHD onset
was strong during a short-term follow-up, but virtually absent during a longer
follow-up. Specifically, increased plasma CRP levels were associated with
a 2-fold increase in the risk for IHD during the first 2 years of follow-up,
even after adjustment for a series of lipid and nonlipid cardiovascular risk
factors. On the other hand, the relationship between high baseline plasma
CRP concentrations and incident IHD was no longer apparent beyond 2 years
of follow-up. It has been suggested that increased plasma CRP levels may reflect
the presence of unstable plaques,24 which may
be associated with a subsequent IHD event during a shorter time than stable
plaques or atherosclerosis. This hypothesis is consistent with the fact that
individuals who had IHD within the first 2 years of follow-up were characterized
by higher baseline plasma CRP levels than patients in whom IHD occurred more
than 2 years into the follow-up.
These results provide further insight into our understanding of the
chronological relationship between CRP and the risk for future coronary events,
which essentially remained unresolved to date. Indeed, Ridker et al3 found that the risk for arterial thrombosis associated
with increasing plasma CRP levels was stable during long periods of follow-up.
On the other hand, results from the Helsinki Ageing Study in elderly subjects
suggested that increased plasma CRP levels predicted cardiovascular events
less than 1 year after blood collection better than events that occurred after
1 year of follow-up.10 The nested case-control
design of the study by Ridker et al3 and the
limited number of subjects in the Helsinki Ageing Study (N = 455)10 limited our ability to draw firm conclusions as to
the confounding effect of follow-up duration on the relationship between plasma
CRP levels and the risk for IHD. The population-based design of our study,
the size of the study cohort, and the analytical strategy used (time-censoring
design vs case-control approach, which does not take into account the time
of the event in the matching procedure) provided a more valid model for the
analysis of the IHD risk associated with elevated plasma CRP levels in relation
to the duration of follow-up compared with previous nested case-control and
smaller prospective studies. As in previous studies, however, we measured
plasma CRP levels only once. Whether having a more stable CRP concentration
by measuring it more than once would have modified this time-dependent relationship
between elevated plasma CRP levels and IHD onset remains to be clarified.
CRP LEVEL VS AGE AT BASELINE
Among the correlates of plasma CRP concentrations, age was of particular
interest. Indeed, results from our study indicated that elevated plasma CRP
levels predicted an increased IHD risk independent of all other confounding
risk factors in younger but not in older individuals. This observation was
rather unexpected, because older individuals tended to have higher plasma
CRP levels at baseline than did younger subjects in the present study and
in other reports.18, 25 It could
be speculated that a greater number of possible covariates of plasma CRP levels,
including cardiovascular risk factors and possibly other conditions associated
with an increasing inflammatory response with aging,26
could dilute to a greater extent the impact of high plasma CRP levels on IHD
risk in older compared with younger subjects. Thus, although younger men had
lower plasma CRP concentrations than did older men, the increased risk for
IHD associated with increasing plasma CRP levels was independent of the simultaneous
confounding effects of lipid and nonlipid cardiovascular risk factors only
in the younger men. These results in middle-aged men concur with recent observations
by Strandberg and Tilvis,10 who have suggested
that the ability of plasma CRP levels to predict the risk for IHD in the elderly
was diluted in older individuals.
CONCLUSIONS
To the best of our knowledge, the Quebec Cardiovascular Study is the
first large-scale, population-based prospective study of the relationship
between plasma CRP levels, a marker of systemic inflammation, and the risk
for future IHD events in men. Our results have indicated that (1) high plasma
CRP levels were associated with an increased risk for future IHD events, independent
of concomitant variations in plasma lipid levels and of a series of nonlipid
risk factors in short-term (2 years) but not long-term (>2 years) follow-up;
and (2) elevated plasma CRP levels were an independent predictor of future
IHD events in younger but not in older men. These results suggest that measuring
plasma CRP levels in an integrated strategy for primary prevention of IHD
could be useful, but only in specific situations. Particularly, younger middle-aged
men may benefit the most from having their plasma CRP levels measured for
short- to long-term assessment of IHD risk. Future studies will be needed
to validate and confirm these hypotheses.
AUTHOR INFORMATION
Accepted for publication September 29, 2001.
This study was supported in part by operating grant MOP 14475 from the
Canadian Institutes for Health Research (Ottawa, Ontario), and by an unrestricted
Medical School Grant from Merck-Frosst (Kirkland, Quebec). Dr Bergeron is
a clinical scientist supported by the Fonds de la Recherche en Santé
du Québec (Montréal).
Dr Lamarche is the recipient of a Canada Research Chair in Nutrition,
Functional Foods, and Cardiovascular Risk.
Corresponding author and reprints: Benoît Lamarche, PhD, Lipid
Research Center, R-9600, CHUL Research Center, 2705 Laurier Blvd, Ste-Foy,
Québec, Canada G1V 4G2 (e-mail: benoit.lamarche{at}crchul.ulaval.ca).
From the Lipid Research Center, Laval University Hospital Research
Center (Drs Pirro, Bergeron, Cantin, Després, and Lamarche), the Québec
Heart Institute, Laval Hospital (Drs Dagenais, Cantin, and Després),
and the Department of Social and Preventive Medicine, Laval University (Mr
Bernard), Québec City, Québec.
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