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Background: GlycA is an inflammatory marker that is raised in patients with cardiometabolic diseases and associated with cardiovascular (CV) events. We sought to determine if GlycA adds independent value to hsCRP for CV risk prediction., Methods: Patients in the Intermountain Heart Collaborative Study who underwent coronary angiography and had plasma GlycA and hsCRP levels were studied (n = 2996). Patients were followed for 7.0 ± 2.8 years. GlycA and hsCRP were moderately correlated (r = 0.46, P < .0001). GlycA and hsCRP concentrations were stratified into high and low categories by their median values. Multivariable cox hazard regression was utilized to determine the associations of GlycA quartiles, as well as high and low categories of GlycA and hsCRP, with major adverse cardiovascular events (MACE) defined as the composite of death, myocardial infarction (MI), heart failure (HF) hospitalization, and stroke., Results: The highest GlycA quartile was associated with future MACE [HR: 1.43; 95% CI: 1.22-1.69; P < .0001]. Patients with high GlycA and high hsCRP had more diabetes, hyperlipidemia, hypertension, HF, renal failure and MI, but not coronary artery disease. High GlycA and hsCRP (H/H) versus low GlycA and hsCRP (L/L) was associated with MACE, death and HF hospitalization, but not MI or stroke. Combined MACE rates were 33.5%, 41.3%, 35.7% and 49.1% for L/L, L/H, H/L and H/H categories of GlycA/hsCRP, respectively (P-trend < .0001). The interaction between GlycA and hsCRP was significant for the outcome of death (P = .03)., Conclusion: In this study, levels of GlycA and hsCRP were independent and additive markers of risk for MACE, death and HF hospitalization., (Copyright © 2018. Published by Elsevier Inc.)

Background: Red cell distribution width (RDW) is associated with morbidity and mortality in coronary artery disease (CAD), but the connection of RDW with chronic inflammation is equivocal., Methods: In 1,489 patients with CAD and 8.4-15.2 years of follow-up all-cause mortality and RDW were studied using Cox regression. RDW and its associations with inflammation, liver function, renal function, and body mass were assessed. A population of 449 normal (No-CAD) patients also was evaluated., Results: RDW predicted all-cause mortality in a step-wise manner (HR=1.37 per quintile; 95% CI=1.29, 1.46; p-trend<0.001). A significant but meaningless correlation between RDW and high-sensitivity C-reactive protein (hsCRP) was identified (r=0.181; p<0.001). With full adjustment, RDW remained significant (p-trend<0.001) and the strongest predictor of mortality among all factors included in the model. RDW also strongly predicted all-cause mortality in the normal control population (HR=1.33 per quintile, CI=1.15, 1.55; p-trend<0.001), but hsCRP did not predict mortality among normal controls., Conclusions: RDW was associated with mortality in patients with CAD and may provide clinically useful prognostication. Although RDW was correlated with hsCRP, they were independent predictors of mortality. RDW has been incorporated into risk prediction tool using data from basic chemistries available at: http://intermountainhealthcare.org/IMRS., (Copyright © 2011 Elsevier B.V. All rights reserved.)

Background: Inflammation has been shown to have a direct role in the initiation, maintenance, and recurrence of atrial fibrillation (AF) although the underlying mechanisms are unknown. Similarly, it is unclear if inflammatory markers are elevated due to the AF alone or the coexisting cardiovascular diseases that increase the risk of AF., Methods: Consecutive patients who underwent angiography for suspicion of coronary artery disease, but without a myocardial infarction, were studied. Serum was analyzed to determine high-sensitivity C-reactive protein (hs-CRP) level. Patients' AF status was determined through ICD-9 codes, review of hospital discharge summaries, clinical evaluations, and electrocardiograms., Results: A total of 2,340 patients were studied (64+/-12 years). Comorbid diseases included 1,438 (61%) coronary artery disease, 1,309 (56%) hypertension, 433 (19%) diabetes, 345 (15%) congestive heart failure, and 43 (2%) a prior stroke. The hs-CRP level was significantly higher in patients with AF (n = 238) compared to those without (14.0 mg/L vs 9.1 mg/L, P < 0.001). Greater CHADS2 score was also significantly associated with higher hs-CRP in a linear fashion (medians [mg/L], 0: 1.99, 1: 2.91, 2: 3.49, 3: 3.89, 4-5: 4.82, P <0.001). The presence of AF was associated with higher hs-CRP level across all scores (medians [mg/L], 0: 2.22 vs 1.98, P = 0.83, 1: 3.85 vs 2.86, P = 0.057, 2: 4.96 vs 3.29, P = 0.021, 3: 6.29 vs 3.17, P = 0.09, 4-5: 4.82 vs 4.50, P = 0.87)., Conclusion: Risks factors associated with AF were associated with higher hs-CRP in an incremental manner. The presence of AF increased hs-CRP across the CHADS2 score strata is supportive of the concept that AF is an inflammatory process and may convey independent risk.

Although previous studies have demonstrated that various "statins" decrease levels of high-sensitivity C-reactive protein (hs-CRP), the dose-response relation for lowering hs-CRP by the clinically important drug simvastatin compared with lipid lowering is unclear. A 16-week, randomized, double-blind study was performed in patients with stable coronary artery disease and high hs-CRP levels (>3 mg/L). Subjects were randomized to placebo, 20 mg of simvastatin, or 80 mg of simvastatin for 12 weeks. Those currently on a statin first underwent a 4-week washout. Of the 107 total patients randomized, 96 completed the trial, and 89 were able to be evaluated for efficacy. Changes in hs-CRP differed across simvastatin and placebo groups (change score +1.6 vs -0.6 mg/L, p = 0.004), but no dose response was observed when comparing 80 with 20 mg/day (-0.6 vs -0.5 mg/L, respectively). A strong dose response was observed for changes in total (p <0.01) and low-density lipoprotein (p <0.001) cholesterol. hs-CRP changes did not correlate with low-density lipoprotein changes. In conclusion, this randomized trial in patients with chronic stable coronary artery disease showed a strong dose response for simvastatin for total and low-density lipoprotein cholesterol lowering but not for hs-CRP.

Although increased cholesterol levels predict mortality in patients with coronary artery disease, it is unclear whether hypercholesterolemia is associated with adverse survival in patients with heart failure. A cohort of subjects derived from the Intermountain Heart Collaborative Study Registry (1993 to 2003) who had ejection fractions < or = 40% or clinical diagnoses of heart failure and long-term follow-up for death were studied (n = 1,646). Total cholesterol (TC) was divided into quartiles: quartile 1, < 141.3 mg/dl; quartile 2, 141.3 to 167.9 mg/dl; quartile 3, 168.0 to 201.0 mg/dl; and quartile 4, > 201.0 mg/dl. Multivariate Cox regression models were used to evaluate the associations of cholesterol, statin therapy, and C-reactive protein to mortality. The mean age was 65.5 years; 65% of the subjects were men and 65% had coronary artery disease. Although 53% were using statins, statin use was not different across TC quartiles. Average time to death was 2.4 years (maximum 10). Mortality for quartile 4 versus quartile 1 was not different (hazard ratio [HR] 1.12, p = 0.52); mortality was reduced for quartile 3 versus quartile 1 (HR 0.66, p = 0.027) and tended to be reduced for quartile 2 versus quartile 1 (HR 0.77, p = 0.14). Subanalysis of patients not using statins (n = 737, death = 20.2%) found no association between TC and survival (for quartile 3 vs quartile 1, HR 0.97, p = 0.89), but for patients using statins (n = 848, death = 16.3%), the effect was even greater for quartile 3 versus quartile 1 (HR 0.40, p = 0.002) than in the overall population. Nonsurvivors had higher levels of C-reactive protein than survivors. In conclusion, elevated TC appears to be associated with improved survival. The effect was stronger in patients receiving statin therapy, but the cause of this differential effect is uncertain.

Background: The prognosis associated with metabolic syndrome and high-sensitivity C-reactive protein (hs-CRP) in patients with stable coronary artery disease has not been well established., Methods: The WIZARD study was to determine the effects of 12 weeks of antibiotic therapy on coronary heart disease events in patients with stable coronary artery disease and known Chlamydia pneumoniae exposure. Baseline metabolic risk factors were available for 3319 patients enrolled from 1997 to 1998. The primary outcome was the first occurrence of death, recurrent myocardial infarction, coronary revascularization procedure, or hospitalization for angina., Results: Of the 3319 subjects, 825 patients experienced the primary outcome during the mean follow-up of 37 months. For the composite outcome, there was an increased hazard ratio (HR) for metabolic syndrome (HR 1.40, 95% CI 1.22-1.61) (unadjusted) and for hs-CRP (HR 1.60, 95% CI 1.38-1.85) (unadjusted). Both the metabolic syndrome and hs-CRP indicated, in a multivariable model including age and sex, an increased HR for the primary outcome (metabolic syndrome: HR 1.33, 95% CI 1.15-1.53; hs-CRP: HR 1.52, 95% CI 1.30-1.76)., Conclusions: Although related, the presence of the metabolic syndrome and increased levels of hs-CRP were associated with increased risk of adverse cardiovascular outcomes.

C-reactive protein (CRP) has been associated with atherosclerotic complications, and we hypothesized that CRP levels might also predict death in non-ischemic patients with left ventricular dysfunction. Two hundred and three patients with non-ischemic left ventricular dysfunction undergoing cardiac catheterization were included and were followed for 2.4 +/- 1.4 years to determine the incidence of fatal events. Death occurred in 15% of patients with low CRP (1st and 2nd tertiles) and 30% of patients with high CRP (3rd tertile). After adjustment for 11 covariates, high CRP (p = 0.037, hazard ratio = 2.0) significantly and independently predicted mortality. Even in the absence of coronary artery disease, patients with left ventricular dysfunction are at increased risk of mortality based on their baseline CRP concentrations., (Copyright (c) 2005 S. Karger AG, Basel.)

A medium-sensitivity assay for C-reactive protein (CRP) was compared with a high-sensitivity, enhanced immunoturbidimetric assay in 803 angiographically studied patients. Different absolute CRP values were found by the assays, but there was a high correlation by quartile rank and similar predictive values for death and myocardial infarction. This suggests that the conclusions of previous studies performed using the medium-sensitivity assay are still valid but that cross-study comparisons should use percentile rank.

Background: Coronary artery disease (CAD) and, increasingly, diabetes are recognized as having an inflammatory basis. Membrane toll-like receptors (TLRs) activate signaling pathways that up-regulate inflammation. We evaluated whether the Asp299Gly polymorphism in the TLR4 gene, which impairs inflammatory responses, is associated with reduced vascular inflammation (assessed by C-reactive protein [CRP]) and a decreased risk for CAD and diabetes., Methods: 1894 patients without acute myocardial infarction undergoing coronary angiography were studied. Genotyping was performed by real-time polymerase chain reaction. CAD was defined as >or=70% stenosis. Diabetes was diagnosed by patients' referring physicians. CRP was measured by fluorescence polarization immunoassay. Regression analyses adjusted for traditional cardiac risk factors., Results: Patients averaged 64 +/- 11 years of age, and 69% were male. Asp299Gly genotype frequencies were: AA = 0.911 (n = 1725), AG = 0.086 (n = 164), and GG = 0.003 (n = 5), in keeping with Hardy-Weinberg equilibrium. CRP was lower among G-allele carriers (median = 1.11 mg/dL) than wild-type (AA) subjects (1.23 mg/dL, adjusted P = .044). G-allele carriers also had a lower prevalence of CAD (65% vs. 73%, OR = 0.67, CI = 0.46-0.99, adjusted P = .048) and diabetes (11% vs. 18%, OR = 0.63, CI = 0.42-0.95, adjusted P = .029), which persisted in multivariate logistic regression analyses. 299Gly carriage did not affect clinical outcomes nor interact with statin therapy., Conclusions: The TLR4 299Gly allele was associated with reduced CRP levels and, in parallel, a decreased risk of angiographic CAD and clinical diabetes. These findings suggest that down-regulation of innate immune responsiveness could beneficially modify CAD and diabetes risk and might provide a novel basis for genetic risk stratification and therapeutic targeting.

Inflammation has been implicated in the pathogenesis of cardiovascular diseases. C-reactive protein (CRP), a marker of systemic inflammation, predicts the risk of coronary events and stroke. Atrial fibrillation (AF) is associated with atrial structural changes that may have an inflammatory basis. We tested the hypothesis that CRP is a risk factor for AF. Subjects were those included in the database registry of the Intermountain Heart Collaborative Study from 1994 to 2001. Patients who had >or=1 electrocardiogram that demonstrated AF formed the disease group (n = 347), and those who had neither electrocardiographic nor clinical evidence for AF comprised the control group (n = 2,449). Logistic regression assessed the quartile (Q) of CRP and 13 other clinical and angiographic predictors of AF. Average age was 63 +/- 12 years, 33% were women, and 61% had advanced coronary artery disease. Patients who had AF were older (by 7 years) and more frequently had a history of heart failure than did controls (41% vs 9%). CRP was higher in patients who had AF than in controls (p <0.001). Q-CRP was a univariable predictor of AF (odds ratio 1.39/Q, 95% confidence interval 1.25 to 1.55, p <0.001). Adjusting for age and heart failure decreased the predictive value of Q-CRP to 1.20/Q (95% confidence 1.07 to 1.34, p = 0.002), whereas further adjustment for 11 other variables had little additional effect (odds ratio 1.19/Q, 95% confidence interval 1.06 to 1.33, p = 0.003). Thus, high levels of CRP independently predicted an increased risk of AF among a large, prospectively studied patient cohort that was assessed angiographically. Increased CRP is a new risk marker for AF propensity, and testing therapies that target inflammation should be considered.

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.

Purpose: To determine whether sex and age affect serum C-reactive protein level and its prognostic value in patients with coronary artery disease., Methods: In a consecutive series of 2254 patients with angiographically defined coronary artery disease, baseline C-reactive protein and predictive value for incident death or nonfatal myocardial infarction by sex and age (<55 and > or =55 years) were compared. C-reactive protein levels were measured by fluorescence polarization immunoassay with use of a medium-sensitivity method. Patients were followed for a mean (+/-SD) of 3.1 +/- 2.2 years. Comparisons used ln-transformed C-reactive protein and linear and time-to-event regression analyses, adjusting for confounders., Results: Overall, women had higher geometric mean C-reactive protein levels than did men (1.47 vs. 1.30 mg/dL, P <0.001), even after adjustment for age, hyperlipidemia, diabetes, prior myocardial infarction, body mass index, and heart failure (P = 0.002). High C-reactive protein levels were associated with increased mortality or myocardial infarction among men (adjusted hazard ratio [HR] = 1.9; 95% confidence interval [CI]: 1.5 to 2.3) but not among women (HR = 1.0; 95% CI: 0.69 to 1.4). Among patients aged <55 years, C-reactive protein level was similarly predictive in men and women (HR = 2.2 vs. 2.7), whereas in patients > or =55 years of age, it remained predictive for men (HR = 1.8; 95% CI: 1.5 to 2.3) but not women (HR = 0.93; 95% CI: 0.63 to 1.4)., Conclusion: We found that the prognostic value of C-reactive protein in coronary artery disease patients varied by sex and age. This sex-age interaction may have important implications for C-reactive protein-based secondary risk assessment and requires further investigation.

Objectives: We sought to determine whether the association of higher C-reactive protein levels (CRP) and more extensive coronary artery disease (CAD) explains the high cardiovascular risk of renal insufficiency (RI)., Background: Renal insufficiency and renal failure (RF) have been associated with increased cardiovascular risk in several studies, and it has been suggested that this association may be due to higher CRP levels and greater extent of CAD. To what extent CRP or severity of CAD explains this risk is uncertain., Methods: A total of 1,484 patients without myocardial infarction (MI) undergoing angiography were entered and followed for 3.0 +/- 1.6 years; RI and RF were defined as estimated glomerular filtration rates (GFR) of 30 to 60 and <30 ml/min; CRP was measured by immunoassay and > or = 1.0 mg/dl defined as elevated. A CAD score was determined by extent and severity of angiographic disease. Multivariate Cox regressions were performed using seven standard risk factors, homocysteine, GFR, CRP, and CAD score., Results: Mean age was 64 years, and 67% were men; CAD was absent in 24%, mild in 11%, and severe (> or =70% stenosis) in 60%; CRP and CAD scores increased with declining renal function (median CRP: 1.2, 1.4, 2.2 mg/dl, p < 0.001 and CAD score: 8.1, 8.7, 9.3, p = 0.008 for no-RI, RI, and RF). During follow-up, 208 patients (15%) died or had nonfatal MI. Unadjusted hazard ratio (HR) for death/MI was 2.3 for RI and 5.1 for RF (p < 0.0001). Adjustment for CRP (HR, 2.2, 4.5), CAD score (HR, 2.1, 5.1), and all other risk factors (HR, 1.7, 4.5) had minimal or modest impact on RI and RF risk; HR increased to 5.4 (p < 0.001) for presence of both elevated CRP and RI/RF., Conclusions: Renal insufficiency, CRP, and angiographic CAD, although correlated, are largely independent predictors of cardiovascular risk, suggesting the importance of both inflammation and as yet undefined RI-related risk factors.

Background: Seropositivity to cytomegalovirus (CMV) and elevated C-reactive protein (CRP) may jointly predict increased mortality rates in patients with coronary artery disease (CAD). Therapy with statins reduces lipid levels but may also have other beneficial (eg, antiinflammatory) effects. This study prospectively evaluated the effect of statins on CMV-and CRP-associated death among patients with significant, angiographically defined CAD., Methods and Results: We monitored 2315 patients with angiographically significant CAD (stenosis > or =70%) for an average of 2.4 years (maximum, 5.8 years). Anti-CMV IgG antibody levels and CRP concentrations were measured at baseline, and statin prescription was recorded. As previously reported, mortality rate was higher for CMV seropositivity (+) with high CRP (hazard ratio [HR], 2.0) and lower for statins (HR, 0.50). Compared with CMV(-)/low CRP (mortality rate, 5% with statin versus 4% without statin), the protective effect of statin therapy was markedly greater for CMV(+)/low CRP (mortality rate, 2% versus 7%; HR, 0.44; 95% CI, 0.16 to 1.3), CMV negative (-)/high CRP (mortality rate, 1% versus 8%; HR, 0.16), and CMV(+)/high CRP (mortality rate, 6% versus 17%; HR, 0.42; 95% CI, 0.25 to 0.70). After adjustment, interactions were found for statin therapy with CMV(+)/low CRP (P for interaction=0.065), CMV(-)/high CRP (P for interaction=0.051), and CMV(+)/high CRP (P for interaction=0.024)., Conclusions: The survival benefit of statins interacted with CMV seropositivity and high CRP to significantly reduce mortality rates among patients with CAD. This finding supports the hypothesis that statins have beneficial, "lipid-independent," antiinflammatory effects. The mechanism of statin benefit associated with CMV seropositivity remains to be determined.

Background: Restenosis after percutaneous coronary intervention (PCI) constitutes a serious complication in the treatment of cardiovascular disease, but known risk factors do not fully account for the observed restenosis risk. Preliminary studies of infection or inflammation in restenosis report varied results. We tested whether C-reactive protein (CRP) or pathogen burden (seropositivity to 0, 1, 2, or 3 pathogens, of Chlamydia pneumoniae [Cpn], cytomegalovirus [CMV], or Helicobacter pylori [Hpy]) predict clinical restenosis after percutaneous coronary intervention (PCI)., Methods: Blood samples were collected from 415 patients undergoing PCI, and levels of plasma CRP and antibodies to Cpn, CMV, and Hpy were measured. The patient's medical history, demographics, and procedural data were recorded. Patient end points were determined for as long as 6 months as a means of evaluating the incidence of clinical restenosis and major adverse cardiac events., Results: The average patient age was 62 years, and 80% of patients were male. Fifty-eight patients (14%) experienced clinical restenosis, whereas 17 patients (4%) died or had an acute myocardial infarction. After adjusting for 19 possible predictors, we found the pathogen burden (P-trend =.04, adjusted odds ratio [OR] 1.5 per number of pathogens) and minimum luminal diameter (P =.003, OR 1.8 per mm decrease) to be significant predictors of clinical restenosis. Male sex was a nonsignificant predictor of restenosis (P =.06, OR 2.2), but CRP was not significant after adjustment (P-trend =.10, OR 0.73 per tertile)., Conclusion: Pathogen burden was associated with clinical coronary restenosis, an association that deserves further exploration and evaluation. CRP, a marker of inflammation, was not associated with an increased risk of restenosis.

Objectives: The objective of this study was to determine the prognostic value of C-reactive protein (CRP) independent of coronary angiographic findings., Background: High sensitivity CRP, a marker of inflammation, predicts risk of cardiovascular events. However, it is uncertain whether it remains predictive once angiographic findings are considered., Methods: A total of 2,554 patients with angina but without acute myocardial infarction (MI) were studied angiographically; 1,848 patients had coronary artery disease (CAD) and 706 patients did not. Coronary artery disease was quantified in five ways and combined for a CAD score. C-reactive protein was measured and patients were followed for up to five years for death or MI., Results: C-reactive protein correlated with the extent of CAD, but correlation coefficients were low (0.02 to 0.08). Of angiographic measures, the CAD score best predicted future events (hazard ratio [HR] = 1.8 [1.2 to 2.6], p = 0.004, for CAD score > 4). C-reactive protein > or = 1.0 mg/dl was predictive in both patients without CAD (HR = 2.3 [0.9 to 5.5], p = 0.07) and with CAD (HR = 2.1 [1.5 to 3.1], p = 0.0001). Multivariate adjustment resulted in little change in HR. C-reactive protein retained predictive value within each quintile of CAD score. C-reactive protein and CAD independently and additively contributed to the risk prediction: low CRP and lowest CAD score was associated with lowest risk, and high CRP and highest CAD score was associated with the highest risk, with a 10-fold difference between extremes (2.5% vs. 24%)., Conclusions: C-reactive protein correlates with extent of CAD, but the degree of correlation is low. Severity/extent of CAD and CRP are independent and additive predictors of risk. Therapy should target CRP-associated risk as well as angiographically evident stenosis.

High-sensitivity C-reactive protein (CRP), proposed as a new coronary risk marker, may reflect either an acute phase reaction or the level of chronic inflammation. Thus, CRP may be less predictive of long-term outcomes when measured after acute myocardial infarction (AMI) than after unstable angina pectoris (UAP) or stable angina pectoris (SAP). A total of 1,360 patients with severe coronary artery disease (>/=1 stenosis >/=70%) had CRP levels obtained at angiography. Presenting diagnoses were SAP (n = 599), UAP (n = 442), or AMI (n = 319). During follow-up (mean 2.8 years), death or nonfatal AMI (D/AMI) occurred in 19.5%, 16.1%, and 17.2% (p = NS) with SAP, UAP, and AMI, respectively. Corresponding median CRP levels were 1.31, 1.27, and 2.50 mg/dl (p <0.001). For the overall cohort, increasing age, low ejection fraction, revascularization, and elevated CRP were the strongest of 6 independent predictors for D/AMI. Among those presenting with SAP, CRP levels above the first tertile were associated with an adjusted hazard ratio of 1.8 (95% confidence interval [CI] 1.2 to 2.8, p <0.009) for D/AMI. After UAP, the hazard ratio was 2.7 (95% CI 1.4 to 5.0, p <0.002). However, when measured during hospitalization for AMI, CRP was not predictive of long-term outcome (hazard ratio 1.0 [95 % CI 0.5 to 1.7] p = 0.86). In conclusion, predischarge CRP levels are higher after AMI than after UAP or SAP. However, whereas CRP is strongly predictive of long-term D/AMI for patients presenting with SAP or UAP, it is not predictive shortly after AMI, suggesting that measurements should be delayed until the acute phase reaction is over and levels have returned to baseline.

Objectives: The 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)., Background: Hyperlipidemia 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., Methods: Blood samples were collected from a prospective cohort of 985 patients diagnosed angiographically with severe CAD (stenosis > or =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., Results: Mortality 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)., Conclusions: Lipid 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.

Background: The role of inflammation in coronary artery disease (CAD) is being increasingly recognized. Markers of inflammation (eg, C-reactive protein [CRP]) and infection (eg, seropositivity to Chlamydia pneumoniae, cytomegalovirus [CMV], and Helicobacter pylori) have been proposed as risk factors for CAD, but these associations require further evaluation., Methods and Results: We prospectively tested whether CRP levels and IgG seropositivity to C pneumoniae, CMV, and H pylori are predictors of subsequent mortality in 985 consecutive patients with angiographically demonstrated CAD (stenosis >/=70%). Patients were followed for an average of 2.7 years (range 1.5 to 4.0 years). Patients averaged 65 years of age; 77% were men; and 110 (11.2%) died during follow-up. CRP levels were significantly elevated in nonsurvivors compared with survivors (mean CRP 3.1 mg/dL versus 1.5 mg/dL, P:=0.003). After controlling for all known baseline variables, the 2nd and 3rd tertiles of CRP compared with the 1st produced a Cox hazard ratio (HR) for mortality of 2.4 (P:=0.001). Of the 3 infectious markers tested, only seropositivity to CMV (HR=1.9, P:<0.05) was predictive of mortality. The majority of mortality risk associated with elevated CRP or CMV seropositivity occurred when both risk factors were present (P: for trend <0.0001). Other independent predictors of increased risk of mortality were age (HR=1.07 per year, P:<0.0001), left ventricular ejection fraction (HR=0.97 per percent, P:<0.0001), and diabetes mellitus (HR=1.7, P:=0.02)., Conclusions: CMV seropositivity and elevated CRP, especially when in combination, are strong, independent predictors of mortality in patients with CAD. This suggests an interesting hypothesis that a chronic, smoldering infection (CMV) might have the capacity to accelerate the atherothrombotic process.

Background: Plasma homocysteine (tHCY) has been associated with coronary artery disease (CAD). We tested whether tHCY also increases secondary risk, after initial CAD diagnosis, and whether it is independent of traditional risk factors, C-reactive protein (CRP), and methylenetetrahydrofolate reductase (MTHFR) genotype., Methods and Results: Blood samples were collected from 1412 patients with severe angiographically defined CAD (stenosis >/=70%). Plasma tHCY was measured by fluorescence polarization immunoassay. The study cohort was evaluated for survival after a mean of 3.0+/-1.0 years of follow-up (minimum 1.5 years, maximum 5.0 years). The average age of the patients was 65+/-11 years, 77% were males, and 166 died during follow-up. Mortality was greater in patients with tHCY in tertile 3 than in tertiles 1 and 2 (mortality 15.7% versus 9.6%, P:=0.001 [log-rank test], hazard ratio [HR] 1.63). The relative hazard increased 16% for each 5-micromol/L increase in tHCY (P:<0.001). In multivariate Cox regression analysis, controlling for univariate clinical and laboratory predictors, elevated tHCY remained predictive of mortality (HR 1.64, P:=0.009), together with age (HR 1. 72 per 10-year increment, P:<0.0001), ejection fraction (HR 0.84 per 10% increment, P:=0.0001), diabetes (HR 1.98, P:=0.001), CRP (HR 1. 42 per tertile, P:=0.004), and hyperlipidemia. Homozygosity for the MTHFR variant was weakly predictive of tHCY levels but not mortality., Conclusions: In patients with angiographically defined CAD, tHCY is a significant predictor of mortality, independent of traditional risk factors, CRP, and MTHFR genotype. These findings increase interest in tHCY as a secondary risk marker and in secondary prevention trials (ie, with folate/B vitamins) to determine whether reduction in tHCY will reduce risk.

Objectives: We sought to test whether C-reactive protein (CRP) and seropositivity to any of three infectious agents are associated with angiographic coronary artery disease (CAD) and clinical myocardial infarction (MI)., Background: CRP, an inflammatory marker, is reported to predict risk of MI. The stimulus for CRP is unknown but might include infection. Chlamydia pneumoniae, cytomegalovirus and Helicobacter pylori have been linked to risk of MI or CAD., Methods: Blood samples were collected from 363 patients undergoing coronary arteriography and tested for CRP and IgG titers to the infectious agents., Results: CRP was higher in patients with CAD (1.32 mg/dl [SE 0.22, n = 80] vs. 0.58 mg/dl [SE 0.11 mg/dl, n = 109], p = 0.004) and in those with MI (2.05 mg/dl [SE 0.36, n = 47] vs. 0.54 mg/dl [SE 0.08, n = 133], p = 0.0002) than in respective control subjects. Seropositivity for each agent was present in a high proportion of patients with CAD (58% to 77%) or MI (54% to 75%) as well as in control subjects (no CAD: 46% to 74%; no MI: 50% to 77%). However, subjects seropositive to both C. pneumoniae and H. pylori had an increased prevalence of CAD (odds ratio [OR] 2.6, p = 0.02) and MI (OR 2.0, p = 0.15) and tended to have higher CRP levels (1.07 mg/dl [SE 0.16]) than those seronegative to both infectious agents (0.53 mg/dl [SE 0.10], p = 0.06)., Conclusions: CRP is elevated in patients with CAD (more than twofold) and in those with MI (fourfold). Infectious serology is highly prevalent in both patients and control subjects. Seropositivity to both C. pneumoniae and H. pylori (but not one agent alone) may predict increased risk and may be associated with higher CRP levels. Infectious serology may be less predictive than previously suggested, but the cause of inflammation in CAD and MI deserves further study.