C-reactive Protein Tertile Research Articles

Elevated C-Reactive Protein Is a Predictor of the Development of Diabetes in a General Japanese Population

We examined the association between high-sensitivity C-reactive protein (CRP) levels and the development of diabetes in a general Japanese population. A total of 1,759 Japanese subjects, aged 40-79 years and without diabetes (according to American Diabetes Association fasting criteria), were stratified into three groups according to CRP tertiles by sex and followed up prospectively for a mean of 9.0 years. During the follow-up, 131 subjects (67 men and 64 women) developed diabetes. In both sexes, the age-adjusted cumulative incidence of diabetes increased significantly as the tertiles of CRP levels increased. In multivariate analyses, the risk of developing diabetes was significantly higher in the highest CRP tertile than in the lowest after adjustment for a number of confounding factors (odds ratio 2.63 [95% CI 1.23-5.65] for men and 2.25 [1.01-5.01] for women). In stratified analyses, this CRP-diabetes association was stronger in subjects without obesity or other risk factors related to insulin resistance and in nondrinking subjects. Our findings suggest that elevated CRP concentration is a significant predictor of diabetes in the general Japanese population, independent of obesity and insulin resistance.

Inflammation and endothelial dysfunction are associated with retinopathy: the Hoorn Study

The exact pathogenesis of retinopathy in diabetic and non-diabetic individuals is incompletely understood, but may involve chronic low-grade inflammation and dysfunction of the vascular endothelium. The aim of this study was to investigate the association of inflammation and endothelial dysfunction with prevalent retinopathy in individuals with and without type 2 diabetes. As part of a population-based cohort study, 625 individuals aged 50-74 years, stratified according to age, sex and glucose tolerance status, underwent an extensive physical examination. Retinopathy was assessed by an ophthalmological examination, including funduscopy and two-field 45 degrees fundus photography with mydriasis in both eyes. Levels of C-reactive protein (CRP), soluble intercellular adhesion molecule-1 (sICAM-1), von Willebrand factor, and soluble vascular adhesion molecule-1 (sVCAM-1) were assessed, together with the urinary albumin : creatinine ratio, and the results were combined to obtain summarising z scores for inflammation and endothelial dysfunction. The prevalence of retinopathy was positively associated with tertiles of CRP and sICAM-1. When compared with the lowest tertile, the highest tertile of the inflammatory z score was associated with retinopathy in all subjects (odds ratio [OR]=2.2, 95% CI 1.2-4.1, adjusted for age, sex and glucose tolerance status). The highest tertile of the endothelial dysfunction z score was associated with retinopathy among diabetic individuals (OR=4.4, 95% CI 1.2-15.9, adjusted for age and sex) but not in non-diabetic individuals. Additional adjustment for other risk factors, such as systolic and diastolic blood pressure, BMI, total cholesterol and triglycerides, or mutual adjustment of the inflammatory and endothelial dysfunction z scores did not change the results. In this study, inflammatory activity and endothelial dysfunction were associated with retinopathy, which suggests their involvement in the pathogenesis of retinopathy.

Increased circulating C-reactive protein and macrophage-colony stimulating factor are complementary predictors of long-term outcome in patients with chronic coronary artery disease

We investigated, in a 6 year follow-up study, whether circulating levels of C-reactive protein (CRP) and macrophage colony stimulating factor (MCSF) have an independent or complementary prognostic value in patients with chronic coronary artery disease (CAD). MCSF and CRP were measured in 100 patients with chronic CAD. Of 95 (33%) patients, 31 who completed the 6 year follow-up presented adverse events (death, myocardial infarction, and unstable angina). In multivariable analysis (including traditional risk factors and medications), the upper tertiles of MCSF (> or =814 pg/mL) and CRP (> or =2.5 mg/L) levels were independently associated with a 13- and 6-fold increase in risk of events, respectively (P<0.01). Patients with combined high CRP and MCSF had a higher absolute risk of events than patients with elevated MCSF or CRP alone (75 vs. 59 vs. 32%, respectively, P<0.01). The mean event-free time was 39, 64, and 52 months in patients with elevated MCSF, elevated CRP, and their combination, respectively. In patients with chronic CAD, the prognostic value of MCSF is independent and complementary to that of CRP. MCSF is a particularly useful prognostic marker when CRP levels are low, but also provides additional information concerning risk and time-course of events in patients with elevated CRP.

Inflammation Markers, Adhesion Molecules, and All-Cause and Cardiovascular Mortality in Patients with ESRD

Inflammation is a major risk factor for mortality and cardiovascular (CV) complications in patients with ESRD. The predictive value of C-reactive protein (CRP) of the main proinflammatory cytokines (IL-1beta, IL-6, IL-18, and TNF-alpha) and of two adhesion molecules (intercellular adhesion molecule-1 and vascular cell adhesion molecule-1) in 217 dialysis patients was compared. Serum IL-6 and CRP added significant prediction power to the multivariate Cox model of all-cause death, and the gain in the prediction power attributable to IL-6 was approximately two times higher than that of CRP. Patients in the third tertiles of serum IL-6 and CRP had a relative risk of all-cause mortality 2.5 and 1.8 times higher than those in the first corresponding tertiles, and there was no statistical difference between these two relative risks. The gain in prediction power associated with TNF-alpha, IL-beta, IL-18, intercellular adhesion molecule-1, and vascular cell adhesion molecule-1 was of small degree (P = NS). Similarly, serum IL-6 added the highest prediction power to the CV death model, and the IL-6 attributable gain was approximately two times higher than that of serum CRP. However, the risk estimate for CV mortality of patients with high serum IL-6 did not differ significantly from that of patients with high serum CRP. IL-6 adds significantly greater predictive power for all-cause and CV death to statistical models based on traditional and nontraditional risk factors in ESRD patients. However, the risk estimate by CRP being reasonably close to that of IL-6, CRP may be a cheap alternative to IL-6 in clinical practice.

Resting energy expenditure of chronic kidney disease patients: Influence of renal function and subclinical inflammation

The resting energy expenditure (REE) of patients with chronic kidney disease (CKD) might be influenced by the degree of renal function and by a subclinical inflammatory condition. The aim of this study is to evaluate the impact of these 2 variables on the REE of patients with CKD. A cross-sectional study was performed on 91 nondialyzed and nondiabetic patients with CKD with no clinical signs of inflammation. Patients were divided into quartiles of creatinine clearance (CrCl) and tertiles of C-reactive protein (CRP) level. REE was measured by means of indirect calorimetry, and the presence of a subclinical inflammatory condition was assessed by means of serum CRP concentration. CrCl interquartile ranges calculated were: quartile 1 (CrCl < or = 18 mL/min [< or =0.30 mL/s]; n = 24); quartile 2 (CrCl, 19 to 29 mL/min [0.31 to 0.48 mL/s]; n = 22); quartile 3 (CrCl, 30 to 42 mL/min [0.49 to 0.70 mL/s]; n = 23), and quartile 4 (CrCl > or = 43 mL/min [> or =0.71 mL/s]; n = 22). Nonadjusted REE and REE adjusted for sex, age, and lean body mass did not differ among the 4 CrCl quartiles. The following ranges were calculated for CRP tertiles: tertile 1 (CRP < or = 0.14 mg/dL; n = 30), tertile 2 (CRP, 0.15 to 0.49 mg/dL; n = 31), and tertile 3 (CRP > or = 0.50 mg/dL; n = 30). The nonadjusted REE in CRP tertile 3 was significantly greater than those in tertiles 1 and 2. REE adjusted for sex, age, and lean body mass was greater in CRP tertile 3 than tertile 1, a difference equivalent to 123.7 kcal/d (P = 0.003; 95% confidence interval, 42.9 to 204.5). A borderline difference was observed between CRP tertiles 3 and 2. When analyzing the entire group, REE did not correlate with either serum creatinine level or CrCl, and a borderline correlation between REE and log of CRP was observed (r = 0.19; P = 0.07). This study suggests that REE is not influenced by degree of renal function, but it may be elevated during a condition of subclinical inflammation.

Early effects of statins in patients with coronary artery disease and high C-reactive protein

Statins improve survival in patients with coronary artery disease, especially those with elevated C-reactive protein (CRP). Although some randomized studies have shown a delay in statin-related survival advantage of up to 2 years, recent studies demonstrated early (<2 months) survival benefit in certain patient groups. We hypothesized that this early benefit relates to baseline CRP concentration. Patients (n = 2,924) with significant, angiographically defined coronary artery disease (>/=70% stenosis in >/=1 coronary artery) were followed for an average of 2.4 years after discharged on a statin prescription. CRP was divided into tertiles (<1.2, 1.2 to 1.7, >1.7 mg/dl), and Kaplan-Meier methods were used to determine timing of statin benefit in both the overall population and a propensity score-matched subgroup. Cox regressions (multivariable and propensity score approaches) were used to predict mortality. Statins were prescribed for 28.4% of patients. In the first CRP tertile, no early statin benefit was observed (adjusted hazard ratio 0.69, 95% confidence interval [CI] 0.30 to 1.6, p = 0.39), and survival curves separated after >2 years. However, in the second and the third tertiles, statin survival curves separated much earlier ( approximately 3 months and 1 week, respectively) and statins predicted improved survival (second tertile: hazard ratio 0.63, 95% CI 0.32 to 1.2, p = 0.17; third tertile: hazard ratio 0.35, 95% CI 0.18 to 0.67, p = 0.002). Propensity score analysis confirmed both statin benefit and early timing. Thus, statin use in patients with high CRP provides not only a larger but also a significantly earlier absolute survival benefit than statin use in patients with lower CRP. This provides further evidence of an anti-inflammatory effect of statins.

C-reactive protein and arterial stiffness in older adults: the Rotterdam Study

Arterial stiffness is one of the characteristics of vascular aging. Increases in pulse pressure, which reflect an increase in the stiffness of the large arteries, are associated with elevated C-reactive protein (CRP) levels. This may suggest a role of inflammation in the development of arterial stiffness. We investigated the relation between measures of arterial stiffness and CRP within the framework of the Rotterdam Study, a population-based cohort study including subjects aged 55 years and older. The carotid-femoral pulse wave velocity and the distensibility coefficient of the carotid artery were used as measures of arterial stiffness. Data on both arterial stiffness and CRP were available for 866 participants. In adjusted models, levels of CRP were linearly associated with pulse wave velocity (regression coefficient 0.088, 95% CI 0.006–0.170). Adjusted mean values of pulse wave velocity were significantly different across tertiles of CRP, being higher in the highest tertile of CRP. However, no significant association between CRP and carotid distensibility was observed.

A prospective study of maternal serum C-reactive protein concentrations and risk of preeclampsia

Background We measured C-reactive protein (CRP), a clinical marker of systemic inflammation, in maternal serum collected at 13 weeks gestation on average, to determine whether elevations precede the clinical manifestation of preeclampsia. Methods Using a prospective, nested, case-control study design we measured CRP concentrations using a competitive immunoassay in 60 women who developed preeclampsia and in 506 women who remained normotensive throughout pregnancy. Logistic regression procedures were used to calculate odds ratio (OR) and 95% CI. Because maternal serum CRP is highly correlated with maternal prepregnancy body mass index (BMI), all analyses were repeated after stratification by maternal prepregnancy overweight status (BMI <25 v ≥25 kg/m 2). Results Overall, the risk of preeclampsia increased across successively higher tertiles of CRP (OR = 1.0, 1.6, and 3.5, with the lowest tertile as the referent group; P < .001 for trend). After adjusting for parity and first-degree family history of chronic hypertension, the OR in the highest tertile was 3.2 (95% CI = 1.5 to 6.7). Further adjustment for BMI greatly attenuated this association (OR = 1.8, 95% CI = 0.8 to 4.1). Elevated CRP concentrations (≥4.9 mg/L) were associated with a 2.5-fold increased risk of preeclampsia (95% CI = 1.1 to 5.5) in lean women. No similar association was observed among overweight women. Conclusions Elevated CRP is highly correlated with prepregnancy adiposity and appears to be an independent predictor of preeclampsia in lean women. Further work is needed to identify modifiable risk factors for systemic inflammation in early pregnancy and to explore further the extent to which CRP and prepregnancy adiposity independently and jointly contribute to preeclampsia risk.

Adverse outcome in aortic sclerosis is associated with coronary artery disease and inflammation

ObjectivesThe present study was designed to evaluate the relationship between the presence of aortic sclerosis, serologic markers of inflammation, and adverse cardiovascular outcomes. BackgroundAortic sclerosis is associated with adverse cardiovascular outcomes. However, the mechanism by which such nonobstructive valve lesions impart excess cardiovascular risk has not been delineated. MethodsIn 425 patients (mean age 68 ± 15 years, 54% men) presenting to the emergency room with chest pain, we studied the relationship among aortic sclerosis, the presence and acuity of coronary artery disease, serologic markers of inflammation, and cardiovascular outcomes. Patients underwent echocardiography and serologic testing including C-reactive protein (CRP). Aortic valves were graded for the degree of sclerosis, and cardiovascular outcomes including cardiac death and nonfatal myocardial infarction (MI) were analyzed over one year. ResultsAortic sclerosis was identified in 203 patients (49%) , whereas 212 (51%) had normal aortic valves. On univariate analysis at one year, patients with aortic sclerosis had a higher incidence of cardiovascular events (16.8% vs. 7.1%, p = 0.002) and worse event-free survival (normal valves = 93%, mild aortic sclerosis = 85%, and moderate to severe aortic sclerosis = 77%, p = 0.002). However, by multivariable analysis aortic sclerosis was not independently associated with adverse cardiovascular outcomes; the only independent predictors of cardiac death or MI at one year were coronary artery disease (hazard ratio [HR] 3.23, p = 0.003), MI at index admission (HR 2.77, p = 0.008), ascending tertiles of CRP (HR 2.2, p = 0.001), congestive heart failure (HR 2.15, p = 0.02) and age (HR 1.03, p = 0.04). ConclusionsThe increased incidence of adverse cardiovascular events in patients with aortic sclerosis is associated with coronary artery disease and inflammation, not a result of the effects of valvular heart disease per se.

Admission C-reactive protein levels and 30-day mortality in patients with acute myocardial infarction

Background Elevated C-reactive protein levels are associated with an increased risk of subsequent cardiovascular events in patients with unstable angina. However, limited information is available concerning the value of C-reactive protein levels in patients with acute myocardial infarction. Methods We prospectively studied 448 consecutive patients (mean [± SD] age, 60 ± 12 years) with acute myocardial infarction. Serum C-reactive protein levels were measured within 12 to 24 hours of symptom onset, and divided into tertiles. Infarct size was determined by echocardiographic examination that was performed on day 2 or 3. Patients were followed for 30 days for mortality and subsequent cardiac events. Results At 30 days, 4 deaths (3%) occurred in patients in the lowest C-reactive protein tertile, 15 (10%) in patients in the middle tertile ( P = 0.02 vs. the lowest tertile), and 33 (22%) in patients in the highest tertile ( P <0.001 vs. the lowest tertile). In a multivariate analysis, C-reactive protein in the upper tertile was associated with 30-day mortality (relative risk = 3.0; 95% confidence interval [CI]: 1.3 to 7.2; P = 0.01) and the development of heart failure (odds ratio = 2.6; 95% CI: 1.5 to 4.6; P = 0.0006). C-reactive protein levels were not associated with the development of postinfarction angina, recurrent myocardial infarction, or the need for revascularization. Conclusion Plasma C-reactive protein level obtained within 12 to 24 hours of symptom onset is an independent marker of 30-day mortality and the development of heart failure in patients with acute myocardial infarction. These findings suggest that C-reactive protein levels may be related to inflammatory processes associated with infarct expansion and postinfarction ventricular remodeling.

The associations between physical activity and inflammatory markers in high-functioning older persons: MacArthur Studies of Successful Aging.

To determine the relationships between recreational activity, house/yard work activity, work activity, and total physical activity and high levels of two peripheral blood markers of inflammation: interleukin-6 (IL-6) and C-reactive protein (CRP). Cross-sectional study. Three communities (Durham, NC; New Haven, CT; and East Boston, MA). Eight hundred seventy persons aged 70 to 79 who were in the top third of community-dwelling older persons with respect to physical and cognitive functioning. Blood levels of IL-6 and CRP and self-reported recreational activity, house/yard work activity, work activity, and total physical activity. The adjusted odds ratios (AORs) for individuals with high levels of recreational activity to have values in the top tertiles of IL-6 and CRP were 0.65 (95% confidence interval (CI) = 0.48-0.87) and 0.70 (95% CI = 0.51-0.95), respectively. The AORs for those with a high level of house/yard work activity to have values in the top tertile of IL-6 and CRP were 0.90 (95% CI = 0.67-1.20) and 0.70 (95% CI = 0.50-0.96), respectively. High levels of house/yard work and recreational activity were independently associated with lower risk of high CRP. The association between high levels of recreational activity and lower levels of the inflammatory markers IL-6 and CRP suggests a mechanism for its protective effect and supports interventions that increase physical activity in older persons. Such potential benefits of increased physical activity on inflammatory markers will need to be confirmed in clinical trials.

Inflammatory markers and cognition in well-functioning African-American and white elders.

Several lines of evidence suggest that inflammatory mechanisms contribute to AD. To examine whether several markers of inflammation are associated with cognitive decline in African-American and white well-functioning elders. The authors studied 3,031 African-American and white men and women (mean age 74 years) enrolled in the Health, Aging, and Body Composition Study. Serum levels of interleukin-6 (IL-6) and C-reactive protein (CRP) and plasma levels of tumor necrosis factor-alpha (TNFalpha) were measured at baseline; cognition was assessed with the Modified Mini-Mental State Examination (3MS) at baseline and at follow-up. Cognitive decline was defined as a decline of >5 points. In age-adjusted analyses, participants in the highest tertile of IL-6 or CRP performed nearly 2 points lower (worse) on baseline and follow-up 3MS (p < 0.001 for all) and declined by almost 1 point over the >2 years (p = 0.01 for IL-6 and p = 0.04 for CRP) compared with those in the lowest tertile. After multivariate adjustment, 3MS scores among participants in the highest tertile of IL-6 and CRP were similar at baseline but remained significantly lower at follow-up (p < or = 0.05 for both). Those in the highest inflammatory marker tertile were also more likely to have cognitive decline compared with the lowest tertile for IL-6 (26 vs 20%; age-adjusted odds ratio [OR] = 1.34; 95% CI 1.06 to 1.69) and for CRP (24 vs 19%; OR = 1.41; 95% CI 1.10 to 1.79) but not for TNFalpha (23 vs 21%; OR = 1.12; 95% CI 0.88 to 1.43). There was no significant interaction between race and inflammatory marker or between nonsteroidal anti-inflammatory drug use and inflammatory marker on cognition. Serum markers of inflammation, especially IL-6 and CRP, are prospectively associated with cognitive decline in well-functioning elders. These findings support the hypothesis that inflammation contributes to cognitive decline in the elderly.

Systemic inflammation, adipose tissue tumor necrosis factor, and leptin expression.

To explore the links between tumor necrosis factor alpha (TNFalpha) and leptin adipose tissue expression and low-grade systemic inflammation and to determine the relationship between inflammation and the degree of adiposity, the presence of type 2 diabetes, and other cardiovascular risk factors. Ninety-one women (BMI 19 to 65 kg/m(2)) were divided into tertiles of CRP. Insulin resistance was calculated using the HOMA method. Albumin, fibrinogen, C-reactive protein (CRP), interleukin-6, sTNFR1, sTNFR2, and leptin levels were measured in serum and plasma samples. TNFalpha and leptin expression were measured by reverse transcription-polymerase chain reaction in abdominal subcutaneous adipose tissue samples. CRP was positively related to BMI and upper distribution of adiposity. TNFalpha and leptin adipose tissue expression were higher in the upper tertile of CRP. Also, peripheral levels of both soluble TNFRs and leptin were higher in patients with the greatest inflammation degree. Diabetes, dislipidemia, and hypertension were most prevalent in patients in the upper CRP tertile. Inflammatory markers of diabetic women were significantly different from those of nondiabetic women, even after adjusting for differences in body fat. BMI, type 2 diabetes, and adipose TNFalpha mRNA levels were significant predictors of serum CRP levels (r(2) = 0.28, p < 0.001). These results are in agreement with the hypothesis that the synthesis of adipose tissue TNFalpha and leptin could induce the production of interleukin-6, CRP, and other acute-phase reactants, thus contributing to the maintenance of chronic low-grade inflammation state involved in the progression of obesity and its associated comorbidities.

Elevated C-reactive protein levels are associated with myocardial ischemia early in the course of non-ST elevation coronary syndromes

Background High plasma levels of C-reactive protein (CRP) are associated with shortor long-term ischemic complications in patients with unstable coronary artery disease. However, a possible direct relationship of plasma CRP with spontaneous myocardial &hernia early I” the course of non ST elevation acute coronary syndromes (NSTACS) was not thoroughly investigated. MethodsTo evaluate this issue 172 consecutive patients with NSTACS with no elevated plasma cardiac troponin T levels upon admission (cTnT-zO.1 yojdl) who underwent a 24 hour continuous IBlead electrocardiographic (ECG) monitoring were studied. The associatlon of plasma CRP levels upon admission with either the incidence or duration of the recorded myocardial ischemla (ST-segment shifts) was evaluated. Patients divided into three groups according to the tertiles of CRP values upon admission. Results During 3,696 hours of contmuous 12.lead ECG monitoring, 169 ST-segment shifts were recorded in 48 patients with a mean number of 3.5k2.0 shifts per patient and a mean duration of 29.6i23.6 min per episode, corresponding to a total duration of 124.4k143.6 mm per patlent. There was a significant gradual increased risk for either the incidence (p<O.OOl) or the total duration of ST-segment shifts with increasing of CRP tertiles (p=O.Ol). MultivarIate analysis showed that CRP tertiles were independently and positively related to the occurrence of ST-segment shifts. Conclusions High plasma levels of CRP may be associated with a higher incidence of myocardial tschemia early III the tours.? of NSTACS, suggesting a direct relationship of inflammation in this process.

First-trimester C-reactive protein and subsequent gestational diabetes.

Systemic inflammation is associated with the development of type 2 diabetes. We tested the hypothesis that increased inflammation, measured early in pregnancy, is associated with the subsequent development of gestational diabetes mellitus (GDM), a precursor of type 2 diabetes. We conducted a prospective nested case-control study in a pregnancy cohort. First-trimester C-reactive protein (CRP) levels were measured using a high-resolution assay in 43 women who subsequently developed GDM and in a random sample of 94 women who remained euglycemic throughout pregnancy. Median CRP levels were compared using Wilcoxon's rank-sum test. Logistic regression was used to compute unadjusted and multivariable-adjusted odds ratios for developing GDM among CRP tertiles. First-trimester CRP levels were significantly increased among women who subsequently developed GDM compared with control subjects (3.1 vs. 2.1 mg/l, P < 0.01). The risk of developing GDM among women in the highest CRP tertile compared with the lowest tertile was 3.2 (95% CI 1.2-8.8). After adjusting for age, race/ethnicity, smoking, parity, blood pressure, and gestational age at CRP sampling, the risk of developing GDM among women in the highest compared with the lowest tertile was 3.6 (95% CI 1.2-11.4). When BMI was included in the model, however, the association between increased CRP and GDM was attenuated (odds ratio for the highest compared with lowest tertile 1.5 [95% CI 0.4-5.5]). In women who develop GDM, there is evidence of increased inflammation during the first trimester. This association is mediated in part by increased BMI. Larger studies are needed to verify these results.

Inflammation, Hemostatic Markers, and Antithrombotic Agents in Relation to Long-Term Risk of New Cardiovascular Events in First-Ever Ischemic Stroke Patients

The measurement of markers of inflammation or thrombosis has been proposed as a method to improve the prediction of risk in patients with vascular disease. We evaluated the usefulness of these markers as predictors of cardiovascular events in ischemic stroke patients. We analyzed levels of C-reactive protein (CRP), fibrinogen, and D-dimer within the first 24 hours after stroke onset in 473 first-ever ischemic stroke patients and determined the cumulative survival curves free of cardiovascular events in relation to the level of each of these markers according to the Kaplan-Meier method. We adjusted for possible confounding variables using a multivariate Cox proportional-hazards model. Patients in the highest tertiles of D-dimer, fibrinogen, and CRP were associated with an excess risk of new cardiovascular events of 36% (P=0.0134), 63% (P<0.0001), and 72% (P<0.0001), respectively, compared with patients in the lowest tertile. The patients in the highest tertile of CRP had 4 times the risk (hazard ratio, 4.04; P<0.0001) of a new cardiovascular event. Smoking, age, sex, and body mass index did not modify risk, and risk was independent of other confounding variables and of D-dimer and fibrinogen levels. The use of ticlopidine was associated with a significant risk reduction among patients with lower (86%, P=0.0159) and middle (69%, P<0.0001) levels of CRP, whereas a nonsignificant excess risk (27%, P=0.3896) was evident among those with the highest levels. Elevated levels of CRP, more than of D-dimer and fibrinogen, are related to the risk of new cardiovascular events after ischemic stroke. The efficacy of antiplatelet therapy in secondary prevention appears to be directly related to level of inflammatory and thrombotic markers.

C-reactive protein and multiple complex coronary artery plaques in patients with primary unstable angina

The aim of this study was to investigate the possible association of plasma C-reactive protein (CRP) levels with the presence of angiographically multiple complex lesions (CLs) in patients with primary unstable angina (PUA). For the purpose of this study, 228 consecutive patients with PUA who underwent in-hospital catheterization were evaluated. Plasma CRP levels were measured upon patients’ admission. Coronary plaques were classified as CL or non-CL according to Ambrose's criteria. There were 100 (43.9%) patients with no or one CL (⩽1) and 128 (56.1%) patients with multiple CLs (⩾2). Tertiles of plasma CRP levels upon admission were significantly associated with the number of CLs on angiographic studies. In particular there was a significant gradual increase in either the number of CLs, or the presence of apparently thrombus-containing CLs with increasing of CRP tertiles. By multivariate analysis CRP was independently associated with the presence of either multiple CLs (R.R.=1.8, 95%CI=1.5–2.2, P<0.001), or angiographically apparent thrombus-containing CLs (R.R.=1.4, 95%CI=1.2–1.7, P=0.03). High plasma levels of CRP may reflect a multifocal activation of the coronary tree in patients with PUA. This finding suggests a generalized inflammatory reaction throughout the coronary tree in these patients.

HRT effects on inflammatory markers: is chronic inflammation a contra-indication for HRT?

Oestrogens have been reported to have effects on inflammatory markers in healthy individuals and patients. Published data on increases in the acute phase marker CRP (C-reactive protein) and decreases in soluble vascular adhesion molecules are summarised here. The original data on the effects of a 6-week treatment with 17-β-oestradiol in post-menopausal type II diabetic women are given for CRP and haemostatic factors. The largest increase in CRP is observed in the highest pre-treatment tertile of CRP. This group is also characterised by high levels of haemostatic risk predictors. It is concluded that some pro- and anti-inflammatory effects of oestrogens appear to exist and that the net effect may be different depending upon location or tissue and individual make-up. It is suggested that women with high levels of habitual CRP may represent a group with chronic inflammation with an unfavourable condition and reaction to oestrogen, thus representing a sub-group with a contra-indication for HRT.

Preprocedural C-reactive protein levels and cardiovascular events after coronary stent implantation

OBJECTIVESThis study assessed the predictive value of preprocedural C-reactive protein (CRP) levels on six-month clinical and angiographic outcome in patients undergoing coronary stent implantation.BACKGROUNDRecent data indicate that low-grade inflammation as detected by elevated CRP serum levels predicts the risk of recurrent coronary events.METHODSWe prospectively investigated the predictive value of preprocedural CRP-levels on restenosis and six-month clinical outcome in 276 patients after coronary stent implantation. The primary combined end point was death due to cardiac causes, myocardial infarction related to the target vessel and repeat intervention of the stented vessel.RESULTSGrouping patients into tertiles according to preprocedural CRP-levels revealed that, despite identical angiographic and clinical characteristics at baseline and after stent implantation, a primary end point event occurred in 24 (26%) patients of the lowest tertile, in 42 (45.6%) of the middle tertile and in 38 (41.3%) of the highest CRP tertile, p = 0.01. On multivariate analysis, tertiles of CRP levels were independently associated with a higher risk of adverse coronary events (relative risk = 2.0 [1.1 to 3.5], tertile I vs. II and III, p = 0.01) in addition to the minimal lumen diameter after stent (p = 0.04). In addition, restenosis rates were significantly higher in the two upper tertiles compared with CRP levels in the lowest tertile (45.5% vs. 38.3% vs. 18.5%, respectively, p = 0.002).CONCLUSIONSLow-grade inflammation as evidenced by elevated preprocedural serum CRP-levels is an independent predictor of adverse outcome after coronary stent implantation, suggesting that a systemically detectable inflammatory activity is associated with proliferative responses within successfully implanted stents.

Statin therapy, lipid levels, C-reactive protein and the survival of patients with angiographically severe coronary artery disease

OBJECTIVESThe joint predictive value of lipid and C-reactive protein (CRP) levels, as well as a possible interaction between statin therapy and CRP, were evaluated for survival after angiographic diagnosis of coronary artery disease (CAD).BACKGROUNDHyperlipidemia increases risk of CAD and myocardial infarction. For first myocardial infarction, the combination of lipid and CRP levels may be prognostically more powerful. Although lipid levels are often measured at angiography to guide therapy, their prognostic value is unclear.METHODSBlood samples were collected from a prospective cohort of 985 patients diagnosed angiographically with severe CAD (stenosis ≥ 70%) and tested for total cholesterol (TC), low-density lipoprotein (LDL), high-density lipoprotein (HDL), and CRP levels. Key risk factors, including initiation of statin therapy, were recorded, and subjects were followed for an average of 3.0 years (range: 1.8 to 4.3 years) to assess survival.RESULTSMortality was confirmed for 109 subjects (11%). In multiple variable Cox regression, levels of TC, LDL, HDL and the TC:HDL ratio did not predict survival, but statin therapy was protective (adjusted hazard ratio [HR] = 0.49, p = 0.04). C-reactive protein levels, age, left ventricular ejection fraction and diabetes were also independently predictive. Statins primarily benefited subjects with elevated CRP by eliminating the increased mortality across increasing CRP tertiles (statins: HR = 0.97 per tertile, p-trend = 0.94; no statins: HR = 1.8 per tertile, p-trend < 0.0001).CONCLUSIONSLipid levels drawn at angiography were not predictive of survival in this population, but initiation of statin therapy was associated with improved survival regardless of the lipid levels. The benefit of statin therapy occurred primarily in patients with elevated CRP.