C-Reactive Protein and Other Circulating Markers of Inflammation in the Prediction of Coronary Heart Disease
John Danesh, M.B., Ch.B., D.Phil., Jeremy G. Wheeler, M.Sc., Gideon M. Hirschfield, M.R.C.P., Shinichi Eda, Ph.D., Gudny Eiriksdottir, M.Sc., Ann Rumley, Ph.D., Gordon D.O. Lowe, M.D., F.R.C.P., Mark B. Pepys, M.D., Ph.D., and Vilmundur Gudnason, M.D., Ph.D.
Background C-reactive protein is an inflammatory marker believedto be of value in the prediction of coronary events. We reportdata from a large study of C-reactive protein and other circulatinginflammatory markers, as well as updated meta-analyses, to evaluatetheir relevance to the prediction of coronary heart disease.
Methods Measurements were made in samples obtained at base linefrom up to 2459 patients who had a nonfatal myocardial infarctionor died of coronary heart disease during the study and fromup to 3969 controls without a coronary heart disease event inthe Reykjavik prospective study of 18,569 participants. Measurementswere made in paired samples obtained an average of 12 yearsapart from 379 of these participants in order to quantify within-personfluctuations in inflammatory marker levels.
Conclusions C-reactive protein is a relatively moderate predictorof coronary heart disease. Recommendations regarding its usein predicting the likelihood of coronary heart disease may needto be reviewed.
We measured C-reactive protein concentrations in approximately2400 patients with coronary heart disease diagnosed since theirenrollment in the cohort and approximately 4000 controls nestedwithin the Reykjavik Study, a prospective cohort study of about19,000 middle-aged men and women without a history of myocardialinfarction. The number of cases of coronary heart disease inthis cohort was about four times as great as in the largestprevious study4 and should reduce the scope for random errorin our estimates. We also assessed the effect of within-personvariation in the concentrations of inflammatory markers5 inserial blood samples obtained over a period of several yearsin several hundred participants. To compare the predictive valueof the C-reactive protein concentration with that of some otherinflammatory markers studied in coronary heart disease, we alsoanalyzed the erythrocyte sedimentation rate and circulatingconcentrations of von Willebrand factor, each of which can alsofluctuate considerably in acute-phase inflammatory responses.6,7To help put the new data in context, we updated meta-analysesof previous relevant studies of each of these inflammatory markers.
Methods
Patients and Controls
The Reykjavik Study, initiated in 1967 as a prospective studyof cardiovascular disease, has been described in detail previously.8All men born between 1907 and 1934 and all women born between1908 and 1935 who were residents of Reykjavik, Iceland, andits adjacent communities on December 1, 1966, were identifiedin the national population register and then invited to participatein the study during five stages of recruitment between 1967and 1991. A total of 8888 men and 9681 women without a historyof myocardial infarction were enrolled, reflecting a responserate of 72 percent.9
Nurses administered questionnaires, made physical measurements,performed spirometry and electrocardiography, and collectedvenous blood samples after an overnight fast for the measurementof the erythrocyte sedimentation rate and to prepare aliquotsof serum, which were stored at –20°C for subsequentanalysis. All participants have subsequently been monitoredwith respect to death from any cause and the occurrence of majorcardiovascular conditions, with a total loss to follow-up ofonly about 0.6 percent of participants.9
A total of 2459 men and women with available serum samples hadmajor coronary events between the beginning of follow-up andDecember 31, 1995, for a mean (±SD) duration of follow-upof 17.5±8.7 years, as compared with 20.6±8.2 yearsamong controls. Among the men, 1073 deaths from coronary heartdisease and 701 nonfatal myocardial infarctions were recorded(564 confirmed and 137 possible myocardial infarctions), andamong the women, 385 died of coronary heart disease and 300had a nonfatal myocardial infarction (237 confirmed and 63 possiblemyocardial infarctions). Deaths from coronary heart diseasewere ascertained from central registers on the basis of a deathcertificate listing an International Classification of Diseasescode of 410 through 414, and the diagnosis of nonfatal myocardialinfarction was based on the criteria of the Monitoring Trendsand Determinants in Cardiovascular Disease study.
We selected 3969 control subjects from among the participantswho had survived to the end of the study period without havinga myocardial infarction. The controls were frequency-matchedto the patients with respect to the calendar year of recruitment,sex, and age (in five-year increments).10
The National Bioethics Committee and the Data Protection Authorityof Iceland approved the study protocol. All participants providedinformed consent.
Laboratory Methods
Laboratory measurements were made without knowledge of the participants'disease status, and thus samples from patients and controlswere randomly distributed among assay plates. Concentrationsof C-reactive protein were measured by latex-enhanced immunoturbidimetry,with a lower limit of detection of 0.02 mg per liter (RocheDiagnostics).11 The variation in C-reactive protein values withinruns was less than 1 percent, and the between-day variabilitywas 1 percent at a concentration of 14 mg per liter and 3.7percent at a concentration of 3.8 mg per liter. The concentrationof von Willebrand factor was determined by means of a sensitiveenzyme immunoassay. We also determined the concentration ofvon Willebrand factor in paired plasma and serum samples from56 healthy persons from another study and found close agreementbetween plasma and serum values (correlation coefficient, 0.94).7The Wintrobe method was used to measure the erythrocyte sedimentationrate in fresh blood samples obtained at the time of base-linevenesection.6 Other biochemical and hematologic measurementsinvolved the use of standard assays, as previously described.8Measurements were made in pairs of samples obtained from 379participants a mean of about 12 years apart. Data on erythrocytesedimentation rate from the Reykjavik Study have been reportedpreviously.12
Statistical Analysis
Comparisons between patients and controls were made by meansof unmatched stratified logistic regression fitted accordingto the unconditional maximum likelihood (Stata software, version7). To maximize the ability to compare our results with thoseof previous reports, primary analyses of values of C-reactiveprotein, erythrocyte sedimentation rate, and von Willebrandfactor were prespecified to compare extreme thirds of patientsand controls with respect to the distribution of values in thecontrols. Subsidiary analyses involved other cutoff values.Odds ratios were sequentially adjusted for the following variables:age, sex, calendar year of enrollment, smoking status, systolicblood pressure, total cholesterol level, triglyceride level,body-mass index (the weight in kilograms divided by the squareof the height in meters), forced expiratory volume in one second,presence or absence of diabetes, socioeconomic status, and theconcentrations of other markers of inflammation.
To estimate the discriminative value of predictive models, wecalculated the areas under the receiver-operating-characteristiccurve, in order to determine whether the sequential additionof data on inflammatory markers increased the predictive valueof major established coronary risk factors, as described previously.13We performed meta-analyses of studies published before January2003 that included essentially general populations (i.e., cohortsnot selected on the basis of preexisting disease) with morethan a year of follow-up, using search, abstraction, and data-synthesismethods that have been described previously and using nonfatalmyocardial infarction or death from coronary heart disease asend points.6,7,14 We combined the results of the studies byusing inverse variance-weighted averages of logarithmic oddsratios. Heterogeneity was assessed by means of standard 2 tests.Odds ratios are given with 95 percent confidence intervals,and two-sided P values are reported. Since previous studieshave reported on the predictive values of single base-line measurementsof inflammatory markers with respect to coronary heart disease,odds ratios have not been corrected for regression dilutionin the present study, so as to allow direct comparisons withprevious work.5
Results
The mean age at the time of the coronary heart disease eventwas 70.2±9.7 years. There were significant differencesbetween patients and controls with respect to established coronaryrisk factors, such as smoking status, body-mass index, bloodpressure, and serum lipid concentrations (Table 1).
Table 1. Base-Line Characteristics of the Patients with Coronary Heart Disease and Controls.
Base-Line Associations and Long-Term Stability of Inflammatory Markers
The partial correlation coefficients (adjusted for age, sex,calendar year of recruitment, and smoking status) for C-reactiveprotein, on the one hand, and the erythrocyte sedimentationrate and von Willebrand factor, on the other, were 0.38 and0.18, respectively (P<0.001 for each comparison), and thepartial correlation coefficient for the erythrocyte sedimentationrate and the von Willebrand factor concentration was 0.17 (P<0.001).A higher C-reactive protein concentration was significantlyassociated with cigarette smoking (P<0.001), an increasedbody-mass index (P<0.001), a low forced expiratory volumein one second (P<0.001), and an increased triglyceride concentration(P<0.001) (data not shown). Higher values for the erythrocytesedimentation rate were significantly associated with olderage (P<0.001), female sex (P<0.001), a low hemoglobinvalue (P<0.001), a low hematocrit (P<0.001), an elevatedserum uric acid concentration (P<0.001), a low forced expiratoryvolume in one second (P<0.001), and smoking (P<0.001).A higher von Willebrand factor concentration was significantlyassociated with older age (P<0.001) and smoking (P<0.001).
Among 379 participants who provided paired blood samples, thewithin-person correlation coefficients for C-reactive protein,erythrocyte sedimentation rate, and von Willebrand factor were0.59 (95 percent confidence interval, 0.52 to 0.66), 0.67 (95percent confidence interval, 0.61 to 0.73), and 0.57 (95 percentconfidence interval, 0.50 to 0.64), respectively. These valueswere similar with respect to long-term consistency to the valuesfor systolic blood pressure (correlation coefficient, 0.66;95 percent confidence interval, 0.60 to 0.72), diastolic bloodpressure (correlation coefficient, 0.53; 95 percent confidenceinterval, 0.46 to 0.60), and total serum cholesterol (correlationcoefficient, 0.60; 95 percent confidence interval, 0.54 to 0.66).
Inflammatory Markers and Incident Coronary Heart Disease
The odds ratio for coronary heart disease was 1.92 (95 percentconfidence interval, 1.68 to 2.18; 2=105, with 1 df) among patientswith values in the top third (cutoff value, 2.0 mg per liter),as compared with the bottom third (cutoff value, 0.78 mg perliter), of base-line C-reactive protein concentrations in thecontrol group. The odds ratio fell to 1.45 (95 percent confidenceinterval, 1.25 to 1.68; 2=28, with 1 df) after adjustment forsmoking status, other established coronary risk factors, andindicators of socioeconomic status (Table 2). Comparisons betweenthe top and bottom thirds of patients and controls with respectto the other markers gave the following adjusted odds ratiosfor coronary heart disease: for erythrocyte sedimentation rate(cutoff value of 10 mm in first hour of measurement for thetop third and 4 mm in first hour for the bottom third), 1.30(95 percent confidence interval, 1.13 to 1.51; 2=13, with 1df), and for von Willebrand factor (cutoff value of 124 IU perdeciliter for the top third and 88 IU per deciliter for thebottom third), 1.11 (95 percent confidence interval, 0.97 to1.27; 2=26, with 1 df) (Table 2 and Figure 1). The calculatedareas under receiver-operating-characteristic curves indicatethat information on the C-reactive protein concentration (andthe other inflammatory markers that were assessed) providedcomparatively little additional predictive value over that providedby assessment of major established risk factors (Figure 1).
Table 2. Relative Odds of Coronary Heart Disease (CHD) among Patients Who Had Levels of Inflammatory Markers in the Top Third of the Distribution of Values for Controls, as Compared with Those Who Had Values in the Bottom Third of This Distribution.
Figure 1. Odds Ratios for Coronary Heart Disease among 2459 Patients with Coronary Heart Disease and 3969 Controls.
Comparisons are between patients and controls with values in the top third and those in the bottom third of the distribution of values for controls, except for comparisons involving smoking status. Squares denote odds ratios, and horizontal lines represent 95 percent confidence intervals. The information plotted in this figure is based on odds ratios listed in the next-to-last column of Table 2. Logistic-regression analysis was used to calculate the areas under the receiver-operating-characteristic (ROC) curve after adjustment for age, sex, and period, with data on major established risk factors and inflammatory markers added to the model in the order of the strength of each variable's association with coronary heart disease.
These findings were not materially changed in analyses restrictedto the 2083 patients without evidence of coronary heart diseaseat base line (Table 2), to the 2206 patients with C-reactiveprotein values who had a confirmed myocardial infarction ordied of coronary heart disease, or to the participants withoutevidence of acute-phase reactions at the base-line examination(i.e., this analysis excluded 132 patients and 152 controlswith a C-reactive protein concentration of more than 10 mg perliter15 or an erythrocyte sedimentation rate of more than 30mm during the first hour). The findings were also unaffectedby changes in the cutoff values (e.g., analyses of quartersor fifths, or according to increases of 1 SD) (Table 2).
Associations between the C-reactive protein concentration andthe risk of coronary heart disease did not vary significantlyaccording to established risk factors, such as smoking or increasedblood lipid concentrations, blood pressure, or body-mass index(data not shown). An exploratory analysis suggested the possibilityof more extreme odds ratios among the 1049 patients who diedof coronary heart disease or had a nonfatal myocardial infarctionwithin 10 years after enrollment (odds ratio, 1.84; 95 percentconfidence interval, 1.49 to 2.28), as compared with the 1357patients who had such an event after the first decade (oddsratio, 1.26; 95 percent confidence interval, 1.05 to 1.51).Such a trend, however, was not observed in the updated meta-analysis,described below, which was based on published data from 22 studies2,4,13,14,16,17,18,19,20,21,22,23,24,25,26,27,28,29,30,31,32,33(Figure 2). Therefore, it requires further examination involvinglarger numbers of participants with individual data. Such analysisis also required for a reliable characterization of the shapeof the association between C-reactive protein and coronary heartdisease.
Figure 2. Twenty-Two Prospective Studies of the Association of C-Reactive Protein Concentrations with the Risk of Coronary Heart Disease (CHD) in Essentially General Populations, Grouped According to Several Study Characteristics.
One of the 11 studies published before 2000 was updated in 200213,16; hence, data on 85 cases from this study contributed to two subtotals, but we did not double-count these cases in estimating the overall odds ratio. Two studies17,18 published in 1999 (comprising a total of 98 cases) were not included in a previous meta-analysis of studies published before March 200014; they have been included in the 11 studies published between 2000 and 2002. Although three studies published after 2000,17,18,19 involving a total of 245 cases of coronary heart disease, reported results for deaths from cardiovascular causes rather than specifically from coronary heart disease, the majority of these deaths were likely to have been due to coronary heart disease. It was not possible to separate results for 77 cases of coronary revascularization from results for nonfatal myocardial infarction and death from coronary heart disease in another study.20 The odds ratios used were those reported in studies that had adjusted for age, sex, smoking status, and other established risk factors for coronary heart disease (such as blood lipid levels, blood pressure, body-mass index, and diabetes status). The "Other" category in "Sample" includes participants selected according to various criteria (e.g., the absence of a history of coronary disease in randomized trials). The Reykjavik Study provided separate estimates for men (732 cases with C-reactive protein values) and women (674 cases with C-reactive protein values). Information on the storage temperature used for samples was unavailable for two studies involving a total of 316 cases.26,31 Odds ratios involve comparisons of patients in the top third versus those in the bottom third of C-reactive protein concentrations. The horizontal lines represent 99 percent confidence intervals.
Updated Meta-Analysis
Twenty-two prospective studies of C-reactive protein (includingthe present study) have involved a total of 7068 patients, witha weighted mean age at entry of 57 years and a weighted meanfollow-up of 12 years2,4,13,14,16,17,18,19,20,21,22,23,24,25,26,27,28,29,30,31,32,33(Table 3). All studies used high-sensitivity assays, and allbut two19,32 reported adjustment for at least smoking statusand some other established risk factors for coronary heart disease.There was evidence of heterogeneity between these studies (2=46,with 21 df; P=0.001), but with the exception of the date ofpublication (2=15, with 2 df; P<0.001), characteristics suchas sample size (2=4.0, with 1 df; P=0.04), location (2=0.3,with 1 df; P=0.58), sampling method (2=5.2, with 1 df; P=0.02),sex of participants (2=3.4, with 2 df; P=0.18), mean durationof follow-up (2=1.6, with 1 df; P=0.20), and sample storagetemperature (2=0.1, with 1 df; P=0.77) did not account for muchof the overall heterogeneity (Figure 2).
Table 3. Comparison of Characteristics of Prospective Studies of C-Reactive Protein and Coronary Heart Disease (CHD) in Essentially General Populations.
The tendency toward more extreme findings in studies publishedbefore 2000 is consistent with the preferential publicationof positive results in earlier studies. Restriction of analysesto the four studies involving more than 500 patients,4,14,20comprising 4107 cases of coronary heart disease, should limitany such bias, and yielded a combined odds ratio of 1.49 (95percent confidence interval, 1.37 to 1.62; 2=10.6, with 3 df;P=0.01). This value is somewhat smaller than the overall oddsratio of 1.58 (95 percent confidence interval, 1.48 to 1.68)derived from combining all 22 studies.
A previous meta-analysis6 of prospective studies of the effectof the erythrocyte sedimentation rate (based on 1703 cases ofcoronary heart disease) reported an odds ratio for coronaryheart disease of about 1.3 (95 percent confidence interval,1.2 to 1.5), and this estimate is reinforced by the odds ratioof 1.33 (95 percent confidence interval, 1.22 to 1.44) thatwe calculated in our updated meta-analysis (which involved anadditional 2683 cases from a further two studies34). The presentupdated meta-analysis of prospective studies of von Willebrandfactor (which adds 2445 cases of coronary heart disease to theprevious total of 1524 cases) yielded an odds ratio of 1.23(95 percent confidence interval, 1.14 to 1.33), which is probablyweaker than the previous estimate of about 1.5 (95 percent confidenceinterval, 1.1 to 2.0).7
The potential limitations of our study merit careful consideration.The validity of our measurements is demonstrated by the reasonablyhigh decade-to-decade consistency of C-reactive protein valuesrecorded in paired samples from 379 participants (a level ofstability that was at least as high as those recorded in previousstudies with sampling intervals of just one to five years35,36,37,38).Further validation is suggested by the finding of the expectedbase-line associations of C-reactive protein with other inflammatorymarkers and with established coronary risk factors.
The mean values and the distributions of several establishedcoronary risk factors (and the strength of their associationswith the risk of coronary heart disease) in our study were generallysimilar to those reported in other western European populations.8Therefore, although the relative homogeneity of the Reykjavikpopulation should have minimized certain residual biases (suchas that due to differences in socioeconomic status), the presentfindings should have wider relevance. Only total serum cholesterolconcentrations were measured in the present study (rather thanthose of its subfractions, which have opposing effects on therisk of coronary heart disease), thereby underestimating thepredictive ability of lipid concentrations (and potentiallyoverestimating the adjusted predictive value of the C-reactiveprotein concentration).
No information was recorded on the use of aspirin and statins,which, like hormone-replacement treatment, may alter C-reactiveprotein values. However, fewer than 5 percent of the women inthis study reported the use of such hormonal treatment duringrecruitment, and the use of aspirin and of statins was similarlyuncommon in the general middle-aged population of Reykjavikbetween 1967 and 1991. We did not address the separate issuesof the predictive value of inflammatory markers with respectto the risk of cardiac complications among patients recentlyhospitalized for acute coronary syndromes39 or the long-termrisk of coronary heart disease in patients with a history ofcardiovascular disease.14
As suggested by the statement of the Centers for Disease Controland Prevention and the American Heart Association,3 furtherclarification of the predictive value of C-reactive proteinin coronary heart disease in general populations will requirethe pooling of studies on the basis of data for individual participantsfrom each of the available prospective studies. Such a strategywill permit more complete adjustment for other risk factorsand for within-person fluctuations of C-reactive protein levels,more precise quantification of the associations in particularsubgroups (such as age-, sex-, and duration-specific associationsas well as assessments of combinations of inflammatory markers),more reliable characterization of the shape of any dose–responserelation, and more detailed investigation of potential sourcesof heterogeneity.
Supported by program grants from the British Heart Foundation(to Profs. Danesh and Lowe) and the Medical Research Council(to Prof. Pepys) and by the Raymond and Beverly Sackler ResearchAward in the Medical Sciences (to Prof. Danesh). Dr. Hirschfieldwas supported by a Medical Research Council Clinical TrainingFellowship.
We are indebted to Prof. Simon Thompson and Dr. Gary Whitlockfor helpful comments, to Kelsey Juzwishin for epidemiologicsupport, to the laboratory staff of the Icelandic Heart Association,to Drs. M. Thomas and D. Goodier of the Clinical Chemistry Departmentat the Royal Free Hospital, to Fiona Key and Karen Craig atthe University Department of Medicine at the Glasgow Royal Infirmary,and to Roche Diagnostics for donating the C-reactive proteinassay kits.
Source Information
From the Department of Public Health and Primary Care, University of Cambridge, Cambridge, United Kingdom (J.D., J.G.W.); the Centre for Amyloidosis and Acute Phase Proteins, Department of Medicine, Royal Free and University College Medical School, Royal Free Campus, London (G.M.H., M.B.P.); Roche Diagnostics, Tokyo, Japan (S.E.); the Icelandic Heart Association, Kopavogur, Iceland (G.E., V.G.); and the University Department of Medicine, Royal Infirmary, Glasgow, Scotland (A.R., G.D.O.L.).
Address reprint requests to Prof. Danesh at the Department of Public Health and Primary Care, Strangeways Site, Institute of Public Health, University of Cambridge, Cambridge CB1 8RN, United Kingdom.
References
Ross R. Atherosclerosis -- an inflammatory disease. N Engl J Med 1999;340:115-126. [Free Full Text]
Kuller LH, Tracy RP, Shaten J, Meilahn EN. Relation of C-reactive protein and coronary heart disease in the MRFIT nested case-control study. Am J Epidemiol 1996;144:537-547. [Free Full Text]
Pearson TA, Mensah GA, Alexander RW, et al. Markers of inflammation and cardiovascular disease: application to clinical and public health practice: a statement for healthcare professionals from the Centers for Disease Control and Prevention and the American Heart Association. Circulation 2003;107:499-511. [Free Full Text]
Folsom AR, Aleksic N, Catellier D, Juneja HS, Wu KK. C-reactive protein and incident coronary heart disease in the Atherosclerosis Risk In Communities (ARIC) study. Am Heart J 2002;144:233-238. [CrossRef][Web of Science][Medline]
Clarke R, Shipley M, Lewington S, et al. Underestimation of risk associations due to regression dilution in long-term follow-up of prospective studies. Am J Epidemiol 1999;150:341-353. [Free Full Text]
Danesh J, Collins R, Peto R, Lowe GDO. Haematocrit, viscosity, erythrocyte sedimentation rate: meta-analyses of prospective studies of coronary heart disease. Eur Heart J 2000;21:515-520. [Free Full Text]
Whincup PH, Danesh J, Walker M, et al. von Willebrand factor and coronary heart disease: prospective study and meta-analysis. Eur Heart J 2002;23:1764-1770. [Free Full Text]
Jónsdóttir LS, Sigfússon N, Gudnason V, Sigvaldason H, Thorgeirsson G. Do lipids, blood pressure, diabetes, and smoking confer equal risk of myocardial infarction in women as in men? The Reykjavik Study. J Cardiovasc Risk 2002;9:67-76. [CrossRef][Web of Science][Medline]
Tulinius H, Sigfusson N, Sigvaldason H, Bjarnadottir K, Tryggvadottir L. Risk factors for malignant diseases: a cohort study on a population of 22,946 Icelanders. Cancer Epidemiol Biomarkers Prev 1997;6:863-873. [Abstract]
Rothman KJ. Modern epidemiology. Boston: Little, Brown, 1986:237.
Roberts WL, Moulton L, Law TC, et al. Evaluation of nine automated high-sensitivity C-reactive protein methods: implications for clinical and epidemiological applications. Clin Chem 2001;47:418-425. [Erratum, Clin Chem 2001;47:980.] [Free Full Text]
Andresdottir MB, Sigfusson N, Sigvaldason H, Gudnason V. Erythrocyte sedimentation rate, an independent predictor of coronary heart disease in men and women: the Reykjavik Study. Am J Epidemiol 2003;158:844-851. [Free Full Text]
Ridker PM, Rifai N, Rose L, Buring JE, Cook NR. Comparison of C-reactive protein and low-density lipoprotein cholesterol levels in the prediction of first cardiovascular events. N Engl J Med 2002;347:1557-1565. [Free Full Text]
Danesh J, Whincup P, Walker M, et al. Low-grade inflammation and coronary heart disease: prospective study and updated meta-analyses. BMJ 2000;321:199-204. [Free Full Text]
Shine B, de Beer FC, Pepys MB. Solid phase radioimmunoassays for human C-reactive protein. Clin Chim Acta 1981;117:13-23. [CrossRef][Web of Science][Medline]
Ridker PM, Buring JE, Shih J, Matias M, Hennekens CH. Prospective study of C-reactive protein and the risk of future cardiovascular events among apparently healthy women. Circulation 1998;98:731-733. [Free Full Text]
Harris TB, Ferrucci L, Tracy RP, et al. Associations of elevated interleukin-6 and C-reactive protein levels with mortality in the elderly. Am J Med 1999;106:506-512. [CrossRef][Web of Science][Medline]
Jager A, van Hinsbergh VWM, Kostense PJ, et al. von Willebrand factor, C-reactive protein, and 5-year mortality in diabetic and nondiabetic subjects: the Hoorn Study. Arterioscler Thromb Vasc Biol 1999;19:3071-3078. [Free Full Text]
Strandberg TE, Tilvis RS. C-reactive protein, cardiovascular risk factors, and mortality in a prospective study in the elderly. Arterioscler Thromb Vasc Biol 2000;20:1057-1060. [Free Full Text]
Packard CJ, O'Reilly DSJ, Caslake MJ, et al. Lipoprotein-associated phospholipase A2 as an independent predictor of coronary heart disease. N Engl J Med 2000;343:1148-1155. [Free Full Text]
Agewall S, Wikstrand J, Fagerberg B. Prothrombin fragment 1+2 is a risk factor for myocardial infarction in treated hypertensive men. J Hypertens 1998;16:537-541. [CrossRef][Web of Science][Medline]
Ridker PM, Cushman M, Stampfer MJ, Tracy RP, Hennekens CH. Inflammation, aspirin, and the risk of cardiovascular disease in apparently healthy men. N Engl J Med 1997;336:973-979. [Erratum, N Engl J Med 1997;337:356.] [Free Full Text]
Lowe GDO, Yarnell JWG, Rumley A, Bainton D, Sweetnam PM. C-reactive protein, fibrin D-dimer, and incident ischemic heart disease in the Speedwell study: are inflammation and fibrin turnover linked in pathogenesis? Arterioscler Thromb Vasc Biol 2001;21:603-610. [Free Full Text]
Gram J, Bladbjerg EM, Møller L, Sjøl A, Jespersen J. Tissue-type plasminogen activator and C-reactive protein in acute coronary heart disease: a nested case-control study. J Intern Med 2000;247:205-212. [CrossRef][Web of Science][Medline]
Koenig W, Sund M, Fröhlich M, et al. C-reactive protein, a sensitive marker of inflammation, predicts future risk of coronary heart disease in initially healthy middle-aged men: results from the MONICA (Monitoring Trends and Determinants in Cardiovascular Disease) Augsburg Cohort Study, 1984 to 1992. Circulation 1999;99:237-242. [Free Full Text]
Ridker PM, Rifai N, Clearfield M, et al. Measurement of C-reactive protein for the targeting of statin therapy in the primary prevention of acute coronary events. N Engl J Med 2001;344:1959-1965. [Free Full Text]
Pradhan AD, Manson JE, Rossouw JE, et al. Inflammatory biomarkers, hormone replacement therapy, and incident coronary heart disease: prospective analysis from the Women's Health Initiative observational study. JAMA 2002;288:980-987. [Free Full Text]
Mendall MA, Strachan DP, Butland BK, et al. C-reactive protein: relation to total mortality, cardiovascular mortality and cardiovascular risk factors in men. Eur Heart J 2000;21:1584-1590. [Free Full Text]
Pirro M, Bergeron J, Dagenais GR, et al. 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. Arch Intern Med 2001;161:2474-2480. [Free Full Text]
Lowe GDO, Rumley A, Sweetnam PM, Yarnell JWG. Fibrin D-dimer, C-reactive protein and risk of ischaemic heart disease: the Speedwell study. Blood Coagul Fibrinolysis 1999;10:Suppl 1:S92-S93.
Witherell H, Smith KL, Ley C, et al. Helicobacter pylori infection, C-reactive protein and risk for myocardial infarction: a prospective study. Gastroenterology 1999;116:A355-A355. abstract. [Web of Science]
Roivainen M, Viik-Kajander M, Palosuo T, et al. Infections, inflammation, and the risk of coronary heart disease. Circulation 2000;101:252-257. [Free Full Text]
Tracy RP, Lemaitre RN, Psaty BM, et al. Relationship of C-reactive protein to risk of cardiovascular disease in the elderly: results from the Cardiovascular Health Study and the Rural Health Promotion Project. Arterioscler Thromb Vasc Biol 1997;17:1121-1127. [Free Full Text]
Erikssen G, Liestøl K, Bjørnholt JV, Stormorken H, Thaulow E, Erikssen J. Erythrocyte sedimentation rate: a possible marker of atherosclerosis and a strong predictor of coronary heart disease mortality. Eur Heart J 2000;21:1614-1620. [Free Full Text]
Ridker PM, Rifai N, Pfeffer MA, et al. Inflammation, pravastatin, and the risk of coronary events after myocardial infarction in patients with average cholesterol levels. Circulation 1998;98:839-844. [Free Full Text]
Ockene IS, Matthews CE, Rifai N, Ridker PM, Reed G, Stanek E. Variability and classification accuracy of serial high-sensitivity C-reactive protein measurements in healthy adults. Clin Chem 2001;47:444-450. [Free Full Text]
Kayaba K, Ishikawa S, Gotoh T, et al. Five-year intra-individual variability in C-reactive protein levels in a Japanese population-based study: the Jichi Medical School Cohort Study at Yamato, 1993-1998. Jpn Circ J 2000;64:303-308. [CrossRef][Medline]
Koenig W, Sund M, Fröhlich M, Löwel H, Hutchinson WL, Pepys MB. Refinement of the association of serum C-reactive protein concentration and coronary heart disease risk by correction for within-subject variation over time: the MONICA Augsburg studies, 1984 and 1987. Am J Epidemiol 2003;158:357-364. [Free Full Text]
C-Reactive Protein and Coronary Heart Disease
Glynn R. J., Cook N. R., Libby P., Willerson J. T., Braunwald E., Foody J. M., Gotto A. M., Wenger N., Ridker P. M., Koenig W., Fuster V., Danesh J., Pepys M., Gudnason V.
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351:295-298, Jul 15, 2004.
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302: 37-48
[Abstract][Full Text]
Semb, A. G., Ueland, T., Aukrust, P., Wareham, N. J., Luben, R., Gullestad, L., Kastelein, J. J.P., Khaw, K.-T., Boekholdt, S. M.
(2009). Osteoprotegerin and Soluble Receptor Activator of Nuclear Factor-{kappa}B Ligand and Risk for Coronary Events: A Nested Case-Control Approach in the Prospective EPIC-Norfolk Population Study 1993-2003. Arterioscler. Thromb. Vasc. Bio.
29: 975-980
[Abstract][Full Text]
Sattler, K. J.E., Herrmann, J., Yun, S., Lehmann, N., Wang, Z., Heusch, G., Sack, S., Erbel, R., Levkau, B.
(2009). High high-density lipoprotein-cholesterol reduces risk and extent of percutaneous coronary intervention-related myocardial infarction and improves long-term outcome in patients undergoing elective percutaneous coronary intervention. Eur Heart J
0: ehp183v1-ehp183
[Abstract][Full Text]
Almeida, O. P, Norman, P. E, Allcock, R., Bockxmeer, F. v., Hankey, G. J, Jamrozik, K., Flicker, L.
(2009). Polymorphisms of the CRP gene inhibit inflammatory response and increase susceptibility to depression: The Health in Men Study. Int J Epidemiol
0: dyp199v1-dyp199
[Abstract][Full Text]
Ridker, P. M
(2009). The JUPITER Trial: Results, Controversies, and Implications for Prevention. Circ Cardiovasc Qual Outcomes
2: 279-285
[Full Text]
Elovainio, M., Aalto, A.-M., Kivimaki, M., Pirkola, S., Sundvall, J., Lonnqvist, J., Reunanen, A.
(2009). Depression and C-Reactive Protein: Population-Based Health 2000 Study. Psychosom. Med.
71: 423-430
[Abstract][Full Text]
Woodward, M., Welsh, P., Rumley, A., Tunstall-Pedoe, H., Lowe, G. D.O.
(2009). Do inflammatory biomarkers add to the discrimination of cardiovascular disease after allowing for social deprivation? Results from a 10 year cohort study in Glasgow, Scotland. Eur Heart J
0: ehp115v1-ehp115
[Abstract][Full Text]
Fujita, M., Ueno, K., Hata, A.
(2009). Lower Frequency of Daily Teeth Brushing Is Related to High Prevalence of Cardiovascular Risk Factors. Exp. Biol. Med.
234: 387-394
[Abstract][Full Text]
Lui, M. M.-s., Lam, J. C.-m., Mak, H. K.-F., Xu, A., Ooi, C., Lam, D. C.-l., Mak, J. C.-w., Khong, P. L., Ip, M. S.-M.
(2009). C-Reactive Protein Is Associated With Obstructive Sleep Apnea Independent of Visceral Obesity. Chest
135: 950-956
[Abstract][Full Text]
Kooy, A., de Jager, J., Lehert, P., Bets, D., Wulffele, M. G., Donker, A. J. M., Stehouwer, C. D. A.
(2009). Long-term Effects of Metformin on Metabolism and Microvascular and Macrovascular Disease in Patients With Type 2 Diabetes Mellitus. Arch Intern Med
169: 616-625
[Abstract][Full Text]
Chida, Y., Steptoe, A.
(2009). The association of anger and hostility with future coronary heart disease: a meta-analytic review of prospective evidence.. J Am Coll Cardiol
53: 936-946
[Abstract][Full Text]
Denollet, J., Pedersen, S. S.
(2009). Anger, depression, and anxiety in cardiac patients: the complexity of individual differences in psychological risk.. J Am Coll Cardiol
53: 947-949
[Full Text]
Saczynski, J. S., Sigurdsson, S., Jonsdottir, M. K., Eiriksdottir, G., Jonsson, P. V., Garcia, M. E., Kjartansson, O., Lopez, O., van Buchem, M. A., Gudnason, V., Launer, L. J.
(2009). Cerebral Infarcts and Cognitive Performance: Importance of Location and Number of Infarcts. Stroke
40: 677-682
[Abstract][Full Text]
Kelley, D. S., Siegel, D., Fedor, D. M., Adkins, Y., Mackey, B. E.
(2009). DHA Supplementation Decreases Serum C-Reactive Protein and Other Markers of Inflammation in Hypertriglyceridemic Men. J. Nutr.
139: 495-501
[Abstract][Full Text]
Bo, M., Corsinovi, L., Brescianini, A., Sona, A., Astengo, M., Dumitrache, R., Ferrio, M. F., Pricop, L., Fonte, G.
(2009). High-Sensitivity C-Reactive Protein Is Not Independently Associated With Peripheral Subclinical Atherosclerosis. ANGIOLOGY
60: 12-20
[Abstract]
Polotsky, V. Y., Patil, S. P., Savransky, V., Laffan, A., Fonti, S., Frame, L. A., Steele, K. E., Schweizter, M. A., Clark, J. M., Torbenson, M. S., Schwartz, A. R.
(2009). Obstructive Sleep Apnea, Insulin Resistance, and Steatohepatitis in Severe Obesity. Am. J. Respir. Crit. Care Med.
179: 228-234
[Abstract][Full Text]
Shah, T., Casas, J. P, Cooper, J. A, Tzoulaki, I., Sofat, R., McCormack, V., Smeeth, L., Deanfield, J. E, Lowe, G. D, Rumley, A., Fowkes, F G. R, Humphries, S. E, Hingorani, A. D
(2009). Critical appraisal of CRP measurement for the prediction of coronary heart disease events: new data and systematic review of 31 prospective cohorts. Int J Epidemiol
38: 217-231
[Abstract][Full Text]
Stott, D. J, Welsh, P., Rumley, A., Robertson, M., Ford, I., Sattar, N., Westendorp, R. G J, Jukema, J W., Cobbe, S. M, Lowe, G. D O
(2009). Adipocytokines and risk of stroke in older people: a nested case-control study. Int J Epidemiol
38: 253-261
[Abstract][Full Text]
Mora, S., Musunuru, K., Blumenthal, R. S.
(2009). The Clinical Utility of High-Sensitivity C-Reactive Protein in Cardiovascular Disease and the Potential Implication of JUPITER on Current Practice Guidelines. Clin. Chem.
55: 219-228
[Abstract][Full Text]
Glynn, R. J., MacFadyen, J. G., Ridker, P. M
(2009). Tracking of High-Sensitivity C-Reactive Protein after an Initially Elevated Concentration: The JUPITER Study. Clin. Chem.
55: 305-312
[Abstract][Full Text]
Ridker, P. M
(2009). C-Reactive Protein: Eighty Years from Discovery to Emergence as a Major Risk Marker for Cardiovascular Disease. Clin. Chem.
55: 209-215
[Full Text]
Hingorani, A. D., Shah, T., Casas, J. P., Humphries, S. E., Talmud, P. J.
(2009). C-Reactive Protein and Coronary Heart Disease: Predictive Test or Therapeutic Target?. Clin. Chem.
55: 239-255
[Abstract][Full Text]
Schumacher, W., Cockcroft, J., Timpson, N. J., McEniery, C. M., Gallacher, J., Rumley, A., Lowe, G., Smith, G. D., Wilkinson, I. B., Ben-Shlomo, Y.
(2009). Association Between C-Reactive Protein Genotype, Circulating Levels, and Aortic Pulse Wave Velocity. Hypertension
53: 150-157
[Abstract][Full Text]
de Ruijter, W., Westendorp, R. G J, Assendelft, W. J J, den Elzen, W. P J, de Craen, A. J M, le Cessie, S., Gussekloo, J.
(2009). Use of Framingham risk score and new biomarkers to predict cardiovascular mortality in older people: population based observational cohort study. BMJ
338: a3083-a3083
[Abstract][Full Text]
Grammer, T. B., Marz, W., Renner, W., Bohm, B. O., Hoffmann, M. M.
(2009). C-reactive protein genotypes associated with circulating C-reactive protein but not with angiographic coronary artery disease: the LURIC study. Eur Heart J
30: 170-182
[Abstract][Full Text]
SHISHEHBOR, M. H., HAZEN, S. L.
(2009). JUPITER to Earth: A statin helps people with normal LDL-C and high hs-CRP, but what does it mean?. Cleveland Clinic Journal of Medicine
76: 37-44
[Abstract][Full Text]
Sathiyapriya, V., Nandeesha, H., Selvaraj, N., Bobby, Z., Agrawal, A., Pavithran, P.
(2009). Association Between Protein-Bound Sialic Acid and High-Sensitivity C-Reactive Protein in Essential Hypertension: A Possible Indication of Underlying Cardiovascular Risk. ANGIOLOGY
59: 721-726
[Abstract]
Saczynski, J. S., Jonsdottir, M. K., Garcia, M. E., Jonsson, P. V., Peila, R., Eiriksdottir, G., Olafsdottir, E., Harris, T. B., Gudnason, V., Launer, L. J.
(2008). Cognitive Impairment: An Increasingly Important Complication of Type 2 Diabetes: The Age, Gene/Environment Susceptibility-Reykjavik Study. Am J Epidemiol
168: 1132-1139
[Abstract][Full Text]
Zacho, J., Tybjaerg-Hansen, A., Jensen, J. S., Grande, P., Sillesen, H., Nordestgaard, B. G.
(2008). Genetically Elevated C-Reactive Protein and Ischemic Vascular Disease. NEJM
359: 1897-1908
[Abstract][Full Text]
Schunkert, H., Samani, N. J.
(2008). Elevated C-Reactive Protein in Atherosclerosis -- Chicken or Egg?. NEJM
359: 1953-1955
[Full Text]
Rosenzweig, J. L., Ferrannini, E., Grundy, S. M., Haffner, S. M., Heine, R. J., Horton, E. S., Kawamori, R.
(2008). Primary Prevention of Cardiovascular Disease and Type 2 Diabetes in Patients at Metabolic Risk: An Endocrine Society Clinical Practice Guideline. J. Clin. Endocrinol. Metab.
93: 3671-3689
[Abstract][Full Text]
Welsh, P., Whincup, P.H., Papacosta, O., Wannamethee, S.G., Lennon, L., Thomson, A., Rumley, A., Lowe, G.D.O.
(2008). Serum matrix metalloproteinase-9 and coronary heart disease: a prospective study in middle-aged men. QJM
101: 785-791
[Abstract][Full Text]
Surtees, P. G., Wainwright, N. W. J., Boekholdt, S. M., Luben, R. N., Wareham, N. J., Khaw, K.-T.
(2008). Major Depression, C-Reactive Protein, and Incident Ischemic Heart Disease in Healthy Men and Women. Psychosom. Med.
70: 850-855
[Abstract][Full Text]
Barcelo-Coblijn, G., Murphy, E. J, Othman, R., Moghadasian, M. H, Kashour, T., Friel, J. K
(2008). Flaxseed oil and fish-oil capsule consumption alters human red blood cell n-3 fatty acid composition: a multiple-dosing trial comparing 2 sources of n-3 fatty acid. Am. J. Clin. Nutr.
88: 801-809
[Abstract][Full Text]
Maingrette, F., Li, L., Renier, G.
(2008). C-reactive protein enhances macrophage lipoprotein lipase expression. J. Lipid Res.
49: 1926-1935
[Abstract][Full Text]
Escobar-Morreale, H. F, Botella-Carretero, J. I, Martinez-Garcia, M. A., Luque-Ramirez, M., Alvarez-Blasco, F., Millan, J. L S.
(2008). Serum osteoprotegerin concentrations are decreased in women with the polycystic ovary syndrome. Eur J Endocrinol
159: 225-232
[Abstract][Full Text]
Bonaca, M. P., Morrow, D. A.
(2008). Defining a Role for Novel Biomarkers in Acute Coronary Syndromes. Clin. Chem.
54: 1424-1431
[Abstract][Full Text]
Ho, K. J., Owens, C. D., Longo, T., Sui, X. X., Ifantides, C., Conte, M. S.
(2008). C-reactive protein and vein graft disease: evidence for a direct effect on smooth muscle cell phenotype via modulation of PDGF receptor-{beta}. Am. J. Physiol. Heart Circ. Physiol.
295: H1132-H1140
[Abstract][Full Text]
Agewall, S.
(2008). Acute and stable coronary heart disease: different risk factors. Eur Heart J
29: 1927-1929
[Full Text]
Saczynski, J. S., Jonsdottir, M. K., Sigurdsson, S., Eiriksdottir, G., Jonsson, P. V., Garcia, M. E., Kjartansson, O., van Buchem, M. A., Gudnason, V., Launer, L. J.
(2008). White Matter Lesions and Cognitive Performance: The Role of Cognitively Complex Leisure Activity. Journals of Gerontology Series A: Biological Sciences and Medical Sciences
63: 848-854
[Abstract][Full Text]
Genoud, M., Wietlisbach, V., Feihl, F., Mermod, A., Morin, D., Darioli, R., Nicod, P., Mooser, V., Waeber, B., Hayoz, D., Waeber, G.
(2008). Surrogate Markers for Atherosclerosis in Overweight Subjects With Atherogenic Dyslipidemia: The GEMS Project. ANGIOLOGY
59: 484-492
[Abstract]
Hogh, A. L., Joensen, J., Lindholt, J. S., Jacobsen, M. R., Ostergaard, L.
(2008). C-Reactive Protein Predicts Future Arterial and Cardiovascular Events in Patients With Symptomatic Peripheral Arterial Disease. VASC ENDOVASCULAR SURG
42: 341-347
[Abstract]
Mauger, J.-F., Levesque, J., Paradis, M.-E., Bergeron, N., Tchernof, A., Couture, P., Lamarche, B.
(2008). Intravascular Kinetics of C-Reactive Protein and Their Relationships with Features of the Metabolic Syndrome. J. Clin. Endocrinol. Metab.
93: 3158-3164
[Abstract][Full Text]
Rodriguez-Moran, M, Guerrero-Romero, F
(2008). Serum magnesium and C-reactive protein levels. Arch. Dis. Child.
93: 676-680
[Abstract][Full Text]
Fujita, T.
(2008). Association between Protein Levels and Mortality in Patients with Peripheral Arterial Disease. ANN INTERN MED
149: 64-64
[Full Text]
Arima, H., Kubo, M., Yonemoto, K., Doi, Y., Ninomiya, T., Tanizaki, Y., Hata, J., Matsumura, K., Iida, M., Kiyohara, Y.
(2008). High-Sensitivity C-Reactive Protein and Coronary Heart Disease in a General Population of Japanese: The Hisayama Study. Arterioscler. Thromb. Vasc. Bio.
28: 1385-1391
[Abstract][Full Text]
Povsic, T. J., Goldschmidt-Clermont, P. J.
(2008). Review: Endothelial progenitor cells: markers of vascular reparative capacity. Ther Adv Cardiovasc Dis
2: 199-213
[Abstract]
Baum, M K, Rafie, C, Sales, S, Lai, S, Duan, R, Jayaweera, D T, Page, J B, Campa, A
(2008). C-reactive protein: a poor marker of cardiovascular disease risk in HIV+ populations with a high prevalence of elevated serum transaminases. Int J STD AIDS
19: 410-413
[Abstract][Full Text]
Kelley-Hedgepeth, A., Lloyd-Jones, D. M., Colvin, A., Matthews, K. A., Johnston, J., Sowers, M. R., Sternfeld, B., Pasternak, R. C., Chae, C. U., for the SWAN Investigators,
(2008). Ethnic Differences in C-Reactive Protein Concentrations. Clin. Chem.
54: 1027-1037
[Abstract][Full Text]
Tabassum, F., Kumari, M., Rumley, A., Lowe, G., Power, C., Strachan, D. P.
(2008). Effects of Socioeconomic Position on Inflammatory and Hemostatic Markers: A Life-Course Analysis in the 1958 British Birth Cohort. Am J Epidemiol
167: 1332-1341
[Abstract][Full Text]
von Eynatten, M., Hamann, A., Twardella, D., Nawroth, P. P., Brenner, H., Rothenbacher, D.
(2008). Atherogenic dyslipidaemia but not total- and high-molecular weight adiponectin are associated with the prognostic outcome in patients with coronary heart disease. Eur Heart J
29: 1307-1315
[Abstract][Full Text]
Levinson, S. S.
(2008). New cardiovascular risk determinants do exist and are clinically useful. Eur Heart J
29: 1335-1335
[Full Text]
Debing, E., Peeters, E., Demanet, C., De Waele, M., Van den Brande, P.
(2008). Markers of Inflammation in Patients With Symptomatic and Asymptomatic Carotid Artery Stenosis: A Case-Control Study. VASC ENDOVASCULAR SURG
42: 122-127
[Abstract]
Thomas, N-E, Baker, J S, Graham, M R, Cooper, S-M, Davies, B
(2008). C-reactive protein in schoolchildren and its relation to adiposity, physical activity, aerobic fitness and habitual diet. Br. J. Sports. Med.
42: 357-360
[Abstract][Full Text]
Anuurad, E., Rubin, J., Chiem, A., Tracy, R. P., Pearson, T. A., Berglund, L.
(2008). High Levels of Inflammatory Biomarkers Are Associated with Increased Allele-Specific Apolipoprotein(a) Levels in African-Americans. J. Clin. Endocrinol. Metab.
93: 1482-1488
[Abstract][Full Text]
Gimeno, D, Ferrie, J E, Elovainio, M, Pulkki-Raback, L, Keltikangas-Jarvinen, L, Eklund, C, Hurme, M, Lehtimaki, T, Marniemi, J, Viikari, J S A, Raitakari, O T, Kivimaki, M
(2008). When do social inequalities in C-reactive protein start? A life course perspective from conception to adulthood in the Cardiovascular Risk in Young Finns Study. Int J Epidemiol
37: 290-298
[Abstract][Full Text]
Nation, D. A., Gonzales, J. A., Mendez, A. J., Zaias, J., Szeto, A., Brooks, L. G., Paredes, J., D'Angola, A., Schneiderman, N., McCabe, P. M.
(2008). The Effect of Social Environment on Markers of Vascular Oxidative Stress and Inflammation in the Watanabe Heritable Hyperlipidemic Rabbit. Psychosom. Med.
70: 269-275
[Abstract][Full Text]
Bennet, A., Di Angelantonio, E., Erqou, S., Eiriksdottir, G., Sigurdsson, G., Woodward, M., Rumley, A., Lowe, G. D. O., Danesh, J., Gudnason, V.
(2008). Lipoprotein(a) Levels and Risk of Future Coronary Heart Disease: Large-Scale Prospective Data. Arch Intern Med
168: 598-608
[Abstract][Full Text]
Spiel, A. O., Gilbert, J. C., Jilma, B.
(2008). Von Willebrand Factor in Cardiovascular Disease: Focus on Acute Coronary Syndromes. Circulation
117: 1449-1459
[Abstract][Full Text]
Clarke, R., Emberson, J. R., Breeze, E., Casas, J. P., Parish, S., Hingorani, A. D., Fletcher, A., Collins, R., Smeeth, L.
(2008). Biomarkers of inflammation predict both vascular and non-vascular mortality in older men. Eur Heart J
29: 800-809
[Abstract][Full Text]
Conen, D, Everett, B M, Glynn, R J, Ridker, P M
(2008). Effect of valsartan compared with valsartan/hydrochlorothiazide on plasma levels of cellular adhesion molecules: the Val-MARC trial. Heart
94: e13-e13
[Abstract][Full Text]
Dandona, P.
(2008). Effects of Antidiabetic and Antihyperlipidemic Agents on C-Reactive Protein. Mayo Clin Proc.
83: 333-342
[Abstract][Full Text]
Smulders, Y. M., Thijs, A., Twisk, J. W.
(2008). New cardiovascular risk determinants do exist and are clinically useful. Eur Heart J
29: 436-440
[Abstract][Full Text]
Lee, S-S., Singh, S., Magder, L., Petri, M.
(2008). Predictors of high sensitivity C-reactive protein levels in patients with systemic lupus erythematosus. Lupus
17: 114-123
[Abstract]
McGuire, D. K., Inzucchi, S. E.
(2008). New Drugs for the Treatment of Diabetes Mellitus: Part I: Thiazolidinediones and Their Evolving Cardiovascular Implications. Circulation
117: 440-449
[Full Text]
Brevetti, G., Schiano, V., Laurenzano, E., Giugliano, G., Petretta, M., Scopacasa, F., Chiariello, M.
(2008). Myeloperoxidase, but not C-reactive protein, predicts cardiovascular risk in peripheral arterial disease. Eur Heart J
29: 224-230
[Abstract][Full Text]
Packard, R. R. S., Libby, P.
(2008). Inflammation in Atherosclerosis: From Vascular Biology to Biomarker Discovery and Risk Prediction. Clin. Chem.
54: 24-38
[Abstract][Full Text]
Williams, E. S., Shah, S. J., Ali, S., Na, B. Y., Schiller, N. B., Whooley, M. A.
(2008). C-reactive protein, diastolic dysfunction, and risk of heart failure in patients with coronary disease: Heart and Soul Study. Eur J Heart Fail
10: 63-69
[Abstract][Full Text]
Stern, S.
(2008). Are We Getting Nearer to Screening for Atherosclerosis?. Circulation
117: 122-126
[Full Text]
O'Neil, C. E., Nicklas, T. A.
(2007). State of the Art Reviews: Relationship Between Diet/ Physical Activity and Health. AMERICAN JOURNAL OF LIFESTYLE MEDICINE
1: 457-481
[Abstract]
Vaughan, T. B., Ovalle, F., Moreland, E.
(2007). Vascular disease in paediatric type 2 diabetes: the state of the art. Diabetes and Vascular Disease Research
4: 297-304
[Abstract]
Novaro, G. M., Katz, R., Aviles, R. J., Gottdiener, J. S., Cushman, M., Psaty, B. M., Otto, C. M., Griffin, B. P.
(2007). Clinical Factors, But Not C-Reactive Protein, Predict Progression of Calcific Aortic-Valve Disease: The Cardiovascular Health Study. J Am Coll Cardiol
50: 1992-1998
[Abstract][Full Text]
Nylaende, M., Kroese, A.J., Morken, B., Stranden, E., Sandbaek, G., Lindahl, A.K., Arnesen, H., Seljeflot, I.
(2007). Beneficial effects of 1-year optimal medical treatment with and without additional PTA on inflammatory markers of atherosclerosis in patients with PAD. Results from the Oslo Balloon Angioplasty versus Conservative Treatment (OBACT) study. Vasc Med
12: 275-283
[Abstract]
Haugen, S., Casserly, I. P., Regensteiner, J. G., Hiatt, W. R.
(2007). Risk assessment in the patient with established peripheral arterial disease. Vasc Med
12: 343-350
[Abstract]
Authors/Task Force Members, , Graham, I., Atar, D., Borch-Johnsen, K., Boysen, G., Burell, G., Cifkova, R., Dallongeville, J., De Backer, G., Ebrahim, S., Gjelsvik, B., Herrmann-Lingen, C., Hoes, A., Humphries, S., Knapton, M., Perk, J., Priori, S. G., Pyorala, K., Reiner, Z., Ruilope, L., Sans-Menendez, S., Scholte op Reimer, W., Weissberg, P., Wood, D., Yarnell, J., Zamorano, J. L., Other experts who contributed to parts of the guid, , Walma, E., Fitzgerald, T., Cooney, M. T., Dudina, A., European Society of Cardiology (ESC) Committee for, , Vahanian, A., Camm, J., De Caterina, R., Dean, V., Dickstein, K., Funck-Brentano, C., Filippatos, G., Hellemans, I., Kristensen, S. D., McGregor, K., Sechtem, U., Silber, S., Tendera, M., Widimsky, P., Zamorano, J. L., Document reviewers:, , Hellemans, I., Altiner, A., Bonora, E., Durrington, P. N., Fagard, R., Giampaoli, S., Hemingway, H., Hakansson, J., Kjeldsen, S. E., Larsen, M. L., Mancia, G., Manolis, A. J., Orth-Gomer, K., Pedersen, T., Rayner, M., Ryden, L., Sammut, M., Schneiderman, N., Stalenhoef, A. F., Tokgozoglu, L., Wiklund, O., Zampelas, A.
(2007). European guidelines on cardiovascular disease prevention in clinical practice: executive summary: Fourth Joint Task Force of the European Society of Cardiology and Other Societies on Cardiovascular Disease Prevention in Clinical Practice (Constituted by representatives of nine societies and by invited experts). Eur Heart J
28: 2375-2414
[Full Text]
Punjabi, N. M., Beamer, B. A., Jain, A., Spencer, M. E., Fedarko, N.
(2007). Elevated Levels of Neopterin in Sleep-Disordered Breathing. Chest
132: 1124-1130
[Abstract][Full Text]
Kivimaki, M., Lawlor, D. A., Smith, G. D., Eklund, C., Hurme, M., Lehtimaki, T., Viikari, J. S. A., Raitakari, O. T.
(2007). Variants in the CRP Gene as a Measure of Lifelong Differences in Average C-Reactive Protein Levels: The Cardiovascular Risk in Young Finns Study, 1980 2001. Am J Epidemiol
166: 760-764
[Abstract][Full Text]
Hage, F. G., Szalai, A. J.
(2007). C-Reactive Protein Gene Polymorphisms, C-Reactive Protein Blood Levels, and Cardiovascular Disease Risk. J Am Coll Cardiol
50: 1115-1122
[Abstract][Full Text]
Wilson, A. M., Kimura, E., Harada, R. K., Nair, N., Narasimhan, B., Meng, X.-Y., Zhang, F., Beck, K. R., Olin, J. W., Fung, E. T., Cooke, J. P.
(2007). {beta}2-Microglobulin as a Biomarker in Peripheral Arterial Disease: Proteomic Profiling and Clinical Studies. Circulation
116: 1396-1403
[Abstract][Full Text]
Kalantar-Zadeh, K.
(2007). Inflammatory Marker Mania in Chronic Kidney Disease: Pentraxins at the Crossroad of Universal Soldiers of Inflammation. CJASN
2: 872-875
[Full Text]
Conen, D., Ridker, P. M, Buring, J. E, Glynn, R. J
(2007). Risk of cardiovascular events among women with high normal blood pressure or blood pressure progression: prospective cohort study. BMJ
335: 432-432
[Abstract][Full Text]
Asghar, M., George, L., Lokhandwala, M. F.
(2007). Exercise decreases oxidative stress and inflammation and restores renal dopamine D1 receptor function in old rats. Am. J. Physiol. Renal Physiol.
293: F914-F919
[Abstract][Full Text]
Panoulas, V. F., Milionis, H. J., Douglas, K. M. J., Nightingale, P., Kita, M. D., Klocke, R., Elisaf, M. S., Kitas, G. D.
(2007). Association of serum uric acid with cardiovascular disease in rheumatoid arthritis. Rheumatology (Oxford)
46: 1466-1470
[Abstract][Full Text]
2 tests. Odds ratios are given with 95 percent confidence intervals, and two-sided P values are reported. Since previous studies have reported on the predictive values of single base-line measurements of inflammatory markers with respect to coronary heart disease, odds ratios have not been corrected for regression dilution in the present study, so as to allow direct comparisons with previous work.5 
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