Abstract-Inflammatory processes play a pivotal role in the pathogenesis of atherosclerosis and mediate many of the stages of atheroma development from initial leukocyte recruitment to eventual rupture of the unstable atherosclerotic plaque. Elevated plasma levels of several markers of the inflammatory cascade have been shown to predict future risk of plaque rupture. These markers include P-selectin, interleukin-6, tumor necrosis factor-␣, soluble intercellular adhesion molecule-1, and C-reactive protein (CRP). Produced in the liver in response to interleukin-6, CRP has emerged as the most powerful inflammatory marker of future cardiovascular risk. Initially considered an innocent bystander in the atherosclerotic process, recent evidence suggests that CRP may have direct proinflammatory effects. Numerous large-scale, prospective studies have found that elevated baseline levels of CRP are a strong independent predictor of future vascular risk. Furthermore, aspirin and statin therapy appear to be particularly effective among individuals with high CRP levels. The addition of CRP screening to traditional lipid testing has the potential to identify individuals at high risk for future cardiovascular events who may benefit from targeted preventive interventions. Key Words: inflammation Ⅲ risk factors Ⅲ atherosclerosis F rom the initial phases of leukocyte recruitment, to eventual rupture of vulnerable atherosclerotic plaque, inflammatory mediators appear to play a key role in the pathogenesis of atherosclerosis. 1 Early atherosclerotic lesion development involves tethering and adherence of monocytes to, and subsequent transmigration through, the vascular endothelium. Differentiation of monocytes to macrophages and subsequent accumulation of lipid results in foam cell generation and fatty streak formation. Further recruitment of inflammatory cells and proliferation of smooth muscle cells lead to the development of a mature atherosclerotic plaque, with a fibrous cap separating the prothrombotic lipid pool from luminal blood flow. Fibrous cap thinning may lead to plaque rupture and precipitate the onset of an acute ischemic event. 2 Accumulating evidence suggests that inflammatory processes are intimately involved in each of these stages in atherogenesis. Inflammatory Mechanisms in AtherothrombosisThe adherence and subsequent transmigration of leukocytes across the vascular endothelium are mediated by cellular adhesion molecules (CAMs). 3 The selectins are adhesion molecules that mediate the initial rolling of inflammatory cells along endothelial cells and platelets. P-selectin is stored in the ␣ granules of platelets and the Weibel-Palade bodies of endothelial cells 4 and can be rapidly redistributed to the surface of these cells after stimulation by agonists such as thrombin and ADP. E-selectin is synthesized de novo by endothelial cells when activated by interleukin-1 (IL-1) or tumor necrosis factor-␣ (TNF-␣). 5 Available evidence suggests a role for the selectins in the early stages of atherogenesis. P-selectin express...

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Context Although it has been hypothesized that hypertension is in part an inflammatory disorder, clinical data linking inflammation with incident hypertension are scarce.Objective To examine whether C-reactive protein levels, a marker of systemic inflammation, are associated with incident hypertension. Design, Setting, and ParticipantsA prospective cohort study that began in 1992 of 20525 female US health professionals aged 45 years or older who provided baseline blood samples with initially normal levels of blood pressure (BP) (systolic BP Ͻ140 mm Hg and diastolic BP Ͻ90 mm Hg, and no history of hypertension or antihypertensive medications) and then followed up for a median of 7.8 years for the development of incident hypertension. Plasma C-reactive protein levels were measured and baseline coronary risk factors were collected.Main Outcome Measure Incident hypertension, defined as either a new physician diagnosis, the initiation of antihypertensive treatment, or self-reported systolic BP of at least 140 mm Hg or a diastolic BP of at least 90 mm Hg. ResultsDuring follow-up, 5365 women developed incident hypertension. In crude models, the relative risks (RRs) and 95% confidence intervals (CIs) of developing hypertension from the lowest (referent) to the highest levels of baseline C-reactive protein were 1.00, 1.25 (95% CI, 1.14-1.40), 1.51 (95% CI, 1.35-1.68), 1.90 (95% CI, 1.72-2.11), and 2.50 (95% CI, 2.27-2.75) (linear trend PϽ.001). In fully adjusted models for coronary risk factors, the RRs and 95% CIs were 1.00, 1.07 (95% CI, 0.95-1.20), 1.17 (95% CI, 1.04-1.31), 1.30 (95% CI, 1.17-1.45), and 1.52 (95% CI, 1.36-1.69) (linear trend PϽ.001). C-reactive protein was significantly associated with an increased risk of developing hypertension in all prespecified subgroups evaluated, including those with very low levels of baseline BP, as well as those with no traditional coronary risk factors. Similar results were found when treating C-reactive protein as a continuous variable and controlling for baseline BP.Conclusion C-reactive protein levels are associated with future development of hypertension, which suggests that hypertension is in part an inflammatory disorder.

Background-Nuclear magnetic resonance (NMR) offers an alternative, spectroscopic means of quantifying LDL and of measuring LDL particle size. Methods and Results-We conducted a prospective nested case-control study among healthy middle-aged women to assess LDL particle size (NMR) and concentration (NMR) as risk factors for future myocardial infarction, stroke, or death of coronary heart disease. Median baseline levels of LDL particle concentration (NMR) were higher (1597 vs 1404 nmol/L; Pϭ0.0001) and LDL particle size (NMR) was lower (21.5 vs 21.8 nm; Pϭ0.046) among women who subsequently had cardiovascular events (nϭ130) than among those who did not (nϭ130). Of these 2 factors, LDL particle concentration (NMR) was the stronger predictor (relative risk for the highest compared with the lowest quartileϭ4.17, 95% CI 1. 96 -8.87). This compared with a relative risk of 3.11 (95% CI 1.55-6.26) for the ratio of total cholesterol to HDL cholesterol and a relative risk of 5.91 (95% CI 2.65-13.15) for C-reactive protein.The areas under the receiver operating characteristic curves for LDL particle concentration (NMR), total cholesterol to HDL cholesterol ratio, and C-reactive protein were 0.64, 0.64, and 0.66, respectively. LDL particle concentration (NMR) correlated with several traditionally assessed lipid and nonlipid risk factors, and thus adjustment for these tended to attenuate the magnitude of association between LDL particle concentration (NMR) and risk. Conclusions-In this cohort, LDL particle concentration measured by NMR spectroscopy was a predictor of future cardiovascular risk. However, the magnitude of predictive value of LDL particle concentration (NMR) was not substantively different from that of the total cholesterol to HDL cholesterol ratio and was less than that of C-reactive protein.

Markers of myocyte necrosis such as cardiac troponin or creatine kinase-myocardial band are invaluable tools for risk stratification among patients presenting with acute coronary syndromes (ACS). Nonetheless, many patients without any evidence of myocyte necrosis may be at high risk for recurrent ischemic events. In consideration of the important role that inflammatory processes play in determining plaque stability, recent work has focused on whether plasma markers of inflammation may help improve risk stratification. Of these markers, C-reactive protein (CRP) has been the most widely studied, and there is now robust evidence that CRP is a strong predictor of cardiovascular risk among apparently healthy individuals, patients undergoing elective revascularization procedures, and patients presenting with ACS. Moreover, even among patients with troponin-negative ACS, elevated levels of CRP are predictive of future risk. Other, more upstream markers of the inflammatory cascade, such as interleukin (IL)-6, have also been found to be predictive of recurrent vascular instability. A recent report from the second FRagmin during InStability in Coronary artery disease trial investigators suggests that elevated levels of an inflammatory marker such as IL-6 may indicate which patients may benefit most from an early invasive strategy. Other inflammatory markers currently under investigation include lipoprotein-associated phospholipase A(2), myeloperoxidase, and pregnancy-associated plasma protein A. Of all these novel markers, CRP appears to meet most of the criteria required for potential clinical application. Furthermore, the benefits of lifestyle modification and drug therapy with aspirin or statins may be most marked among those with elevated CRP levels.

Background-Accumulating data suggest a link between blood pressure and vascular inflammation. Methods and Results-We examined the relationship between blood pressure, C-reactive protein (CRP), and incident first cardiovascular events among 15 215 women followed prospectively over a median of 8.1 years. In cross-sectional analyses at baseline, median levels of CRP for women with blood pressure Ͻ120/75, 120 to 129/75 to 84, 130 to 139/85 to 89, 140 to 159/90 to 94, and Ն160/95 mm Hg were 0.96, 1.42, 2.20, 2.82, and 3.34 mg/L, respectively (P for trend Ͻ0.0001). Increasing categories of blood pressure were significant predictors of CRP levels at baseline. In prospective analyses, both elevated CRP levels (Ն3 mg/L) and increasing categories of blood pressure were independent determinants of future cardiovascular events, and CRP had incremental prognostic value at all levels of blood pressure. The adjusted hazard ratio for women with blood pressure Ն160/95 mm Hg and CRP levels Ն3 mg/L was 8.31 (95% CI, 4.44 to 15.55, PϽ0.0001) compared with those with blood pressure Ͻ120/75 and CRP levels Ͻ3 mg/L. After participants had been divided into 4 groups on the basis of CRP levels (Ͻ3 or Ն3 mg/L) and blood pressure levels (Ͻ130/85 or Ն130/85), the risk factor-adjusted hazard ratios were as follows: low CRP/low blood pressure, 1.0; high CRP/low blood pressure,

Cardiac device infection is a rare complication, with significant morbidity and mortality. Complete hardware removal with appropriate duration of antimicrobial therapy results in the best outcomes for patients.

In contrast to prior data among hyperlipidemic men, the current data suggest that Lp-PLA(2) is not a strong predictor of future cardiovascular risk among unselected women.