C-reactive protein and coronary events following percutaneous coronary angioplasty

doi:10.1016/S0002-9343(03)00238-9

The American Journal of Medicine

Volume 115, Issue 2, 1 August 2003, Pages 85-90

https://doi.org/10.1016/S0002-9343(03)00238-9 Get rights and content

Abstract

Purpose

We investigated the associations between baseline C-reactive protein levels in patients undergoing percutaneous coronary angioplasty and death, nonfatal myocardial infarction, and repeat revascularization during 14 months of follow-up.

Methods

In a single-center, prospective, cohort study, plasma levels of C-reactive protein were measured in 1458 consecutive patients undergoing elective or urgent coronary angioplasty. Patients were followed at 12 to 14 months for the occurrence of death, nonfatal myocardial infarction, and repeat revascularization.

Results

The incidence of death or myocardial infarction was 6.1% (44/716) in patients with an increased C-reactive protein level (>3 mg/L) and 1.5% (11/742) in patients with a normal level (relative risk [RR] = 4.4; 95% confidence interval [CI]: 2.2 to 8.5; P <0.0001). In a multivariate logistic regression model, an increased C-reactive protein level was an independent predictor of death or nonfatal myocardial infarction (RR = 3.6; 95% CI: 1.8 to 7.2; P =0.0001). The incidence of repeat revascularization was similar in patients with or without an increased C-reactive protein level (23% [168/716] vs. 22% [163/742], P = 0.54). Statin therapy at the time of the procedure was associated with a lower mean (± SD) C-reactive protein level (5.8 ± 9.7 mg/L vs. 7.2 ± 12.1 mg/L, P =0.02), but was not associated with the risk of death, nonfatal myocardial infarction, and repeat revascularization during follow-up.

Conclusion

An increased C-reactive protein level is an independent prognostic indicator for the occurrence of death or nonfatal myocardial infarction following coronary angioplasty, but is not associated with the need for repeat revascularization.

Section snippets

Patients

Consecutive patients undergoing percutaneous transluminal coronary angioplasty at the catheterization laboratory at our institution were eligible. Patients undergoing elective angioplasty for stable angina (including Braunwald class I) and patients presenting with non–ST-elevation acute coronary syndrome (Braunwald class II/III) were included, but patients undergoing primary angioplasty for ST-elevation myocardial infarction were excluded. All patients routinely received 5000 IU of

Results

Patients with an abnormal C-reactive protein level (>3 mg/L) were significantly older, more often women, more often smokers, more likely to have hypertension or diabetes, and more often in Braunwald class II or III than were those with normal levels (Table 1). Patients with abnormal levels were also less often taking statins at the time of the procedure but were more often taking statins at follow-up (37% [264/716] vs. 43% [315/742], P = 0.03). Statin therapy was associated with a lower mean

Discussion

We found that C-reactive protein level was a significant independent predictor of death or nonfatal myocardial infarction following percutaneous coronary intervention. Although increased levels were associated with several patient characteristics, including age, sex, diabetes, smoking, and Braunwald class, which are known to influence C-reactive protein levels, C-reactive protein was still associated with these outcomes after multivariate adjustment.

In contrast with previous reports, we failed

Acknowledgements

We are very grateful to the nursing staff of the catheterization laboratory of the Academic Medical Center of the University of Amsterdam and to all the cardiologists and general practitioners who kindly assisted in the follow-up.

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Many studies have reported hsCRP levels to predict cardiovascular events among patients with CAD [6–8,17–28] as well as apparently healthy individuals [3–5]. However, as shown in Table 3, most of studies reporting the prognostic values of hsCRP in patients with CAD included a mixture of patients with unstable angina and those with stable angina [6–8,17–22]. Since patients with unstable angina are known to have higher hsCRP levels than those with stable angina [6,29], the reported cut-off points of hsCRP for high-risk of cardiovascular events seem to be high in a mixture of patients with unstable and stable angina.
High-sensitivity C-reactive protein (hsCRP) levels can predict cardiovascular events among apparently healthy individuals and patients with coronary artery disease (CAD). However, hsCRP levels vary among ethnic populations. We previously reported hsCRP levels in Japanese to be much lower than in Western populations. We investigated the prognostic value of hsCRP levels in Japanese patients with stable CAD. The hsCRP levels were measured in 373 Japanese patients who underwent elective coronary angiography and thereafter decided to receive only medical treatment. Patients were followed up for 2.9 ± 1.5 years for major cardiovascular events (death, myocardial infarction, unstable angina, stroke, aortic disease, peripheral arterial disease, or heart failure). The median hsCRP level was 0.70 mg/l. During the follow-up, cardiovascular events occurred in 53 (14%) of the 373 patients. Compared with 320 patients without events, 53 with events had higher hsCRP levels (median 1.06 vs. 0.67 mg/l, P < 0.05). To clarify the association between hsCRP levels and cardiovascular events, the 373 study patients were divided into tertiles according to hsCRP levels: lower (<0.4 mg/l), middle (0.4-1.2 mg/l), and higher (>1.2 mg/l). The Kaplan–Meier analysis demonstrated a significant difference in the event-free survival rate between higher vs. middle or lower tertiles (P < 0.05). In multivariate Cox regression analysis, the hsCRP level of >1.0 mg/l was an independent predictor for cardiovascular events (hazard ratio, 2.0; 95%CI, 1.1–3.4; P < 0.05). Thus, in Japanese patients with stable CAD who received only medical treatment, higher hsCRP levels, even >1.0 mg/l, were found to be associated with a significantly increased risk for further cardiovascular events.
Preprocedural high-sensitivity C-reactive protein predicts death or myocardial infarction but not target vessel revascularization or stent thrombosis after percutaneous coronary intervention
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Several studies have shown that hs-CRP elevation is associated with cardiovascular events in the healthy general population [2,3] as well as in patients with CAD [4–7]. However, the prognostic value of preprocedural hs-CRP levels in patients undergoing coronary stent implantation remains debated, especially regarding restenosis and thereby target vessel revascularization (TVR) [8–13]. Furthermore, whether hs-CRP levels may help to predict stent thrombosis (ST) is unknown.
High-sensitivity C-reactive protein (hs-CRP) elevation is associated with poor clinical outcome in patients with coronary artery disease (CAD). However, the prognostic value of preprocedural hs-CRP elevation before coronary stent implantation remains debated especially regarding restenosis and target vessel revascularization (TVR). Furthermore, whether hs-CRP elevation may predict stent thrombosis (ST) is unknown.
We included 560 consecutive patients, who underwent coronary stent implantation in our institution. Blood samples for hs-CRP determination were obtained immediately before the procedure. During a median follow-up of 12.5 months, cardiovascular events including death, myocardial infarction (MI), TVR, and ST were systematically included.
Median hs-CRP was 3.10 [25–75th percentile: 1.36-8.63] mg/l. There were 27 (4.8%) deaths, 17 (3.1%) nonfatal MI, 58 (10.5%) TVR, and 12 (2.1%) ST. The composite criteria death–MI occurred in 44 (7.9%) patients. Independent predictors of the composite death–MI were hs-CRP level [hazard ratio (HR)=1.33 (95% CI: 1.05-1.70); P=.021], diabetes (P=.003), and multivessel CAD (P=.011). The composite death–MI occurred in 31 (13.3%) of the 233 patients with hs-CRP >4.63 mg/l vs. 13 (4.0%) of the 327 patients with hs-CRP <4.63 mg/L (P<.001). By contrast, hs-CRP predicted neither TVR [HR=0.88 (0.73-1.08); P=.23] nor ST [HR=1.15 (0.77-1.71); P=.49].
High hs-CRP levels before coronary stent implantation are associated with risk of death or MI, but are not related to TVR or ST. These data suggest that preprocedural hs-CRP is more a predictor of global cardiovascular risk than a predictor of stent-related complications.
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Patients with stenosis of the left main coronary artery present difficult challenges. The risks associated with this lesion have been known since the early days of angiography when patients were found to have increased mortality during follow-up. This information led to the general guidelines that surgical revascularization should be considered the treatment of choice in patients with significant left main coronary artery stenosis.
Current advances in invasive cardiology have brought important information to the field. Intravascular ultrasound is now used routinely to evaluate angiographically indeterminate lesions with criteria now set forward as to what constitutes an indication for revascularization. Stents have even further dramatically changed the landscape. There are substantial issues, however, that need to addressed. These include the following: (1) the effect of specific lesion location on outcome—it is known that patients with distal bifurcation left main disease have worse outcome; (2) the potential for subacute thrombosis of the left main coronary artery; (3) the impact of left ventricular function and patient comorbidities irrespective of the degree and location of left main coronary artery stenosis; and (4) the risk–benefit ratio of stenting versus coronary artery bypass graft surgery.
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The effects of short term (3 weeks) testosterone treatment on serum inflammatory markers in men undergoing coronary artery stenting
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Inflammation markers can predict restenosis after successful intracoronary stenting. There is evidence that testosterone suppresses the expression of the inflammatory cytokines. We hypothesized that testosterone therapy after coronary stenting can reduce the inflammation markers.
We selected 41 men with coronary artery disease who underwent successful stent implantation for a > 70% diameter stenosis of a major coronary artery. Patients, who had stable angina and positive exercise test results, were recruited after diagnostic coronary angiography. Twenty-five men were treated with 3 doses of i.m. testosterone administration once a week for 3 weeks following diagnostic angiography. Sixteen patients were recruited as a control group and they received standard therapy. First venous blood samples were obtained after angiography. Stents were implanted 3 weeks after diagnostic angiography. Second venous blood samples were taken 24 h after the coronary stenting.
Baseline biochemical or hematological parameters were similar between the control and treatment groups. After coronary stenting, free testosterone, total testosterone, and sex hormone binding globulin were significantly elevated in the testosterone group (P < 0.0001, P < 0.0001 and P = 0.02; respectively). After coronary stent implantation, there was a significant increase in IL-6 and CRP levels in the control group only (P = 0.02 and P = 0.038), while TNF-α levels were increased significantly in both groups (P = 0.016 and P = 0.014; respectively). Statistical analysis revealed that testosterone treatment prior to stent implantation attenuated IL-6 and hs-CRP levels significantly (P = 0.042 and P = 0.043; respectively).
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Citation Excerpt :
Similarly, during acute coronary ischemia, levels of hs-CRP are predictive of high vascular risk even if troponin levels are non-detectable, suggesting that inflammation is associated with plaque vulnerability even in the absence of detectable myocardial necrosis (14–16). The ability of hs-CRP to predict vascular risk has also been consistently demonstrated among patients undergoing elective angioplasty as well as surgical coronary revascularization (17,18), and the clinical combination of hs-CRP, troponin, and brain natriuretic peptide has been advocated as a generalized means to risk stratification (19). Despite these data, the most relevant use of hs-CRP remains in the setting of primary prevention.
Several emerging plasma biomarkers may ultimately prove useful in risk stratification and prognosis of cardiovascular disease. The clinical utility of these biomarkers will depend on their ability to provide a reflection of the underlying atherosclerotic burden or activity; the ability to provide reliable, accurate, and cost-effective information; and the ability to predict future events. High-sensitivity C-reactive protein (hs-CRP) fulfills many, if not all, of these criteria, and blood levels of hs-CRP are now commonly used in clinical practice to improve vascular risk prediction in primary and secondary prevention across all levels of low-density lipoprotein-cholesterol (LDL-C), all levels of the Framingham Risk Score, and all levels of metabolic syndrome. High-sensitivity C-reactive protein may also have clinical relevance as an adjunct to LDL-C for both the targeting and monitoring of statin therapy. Accumulating evidence suggests that several other selected emerging biomarkers may also potentially prove useful in the diagnosis and prognosis of cardiovascular disease. Specifically, data are accumulating on the potential clinical utility of lipoprotein-associated lipoprotein-associated phospholipase A₂, myeloperoxidase, oxidized LDL, lipoprotein (a), isoprostanes, and small, dense LDL. This review focuses on hs-CRP and these emerging plasma biomarkers, and their potential diagnostic and prognostic utility in cardiovascular disease. Plasma biomarkers that reflect the clinical potential of atherothrombotic disease may allow more precise risk stratification and prognostication in high-risk populations, and perhaps earlier diagnosis and intervention in patients at risk for or with occult cardiovascular disease.

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Clinical studyC-reactive protein and coronary events following percutaneous coronary angioplasty

Abstract

Purpose

Methods

Results

Conclusion

Section snippets

Patients

Results

Discussion

Acknowledgements

Blood

Am J Cardiol

Am J Cardiol

J Am Coll Cardiol

Immunol Today

J Am Coll Cardiol

Am J Cardiol

Am J Cardiol

J Am Coll Cardiol

J Am Coll Cardiol

Am J Cardiol

J Am Coll Cardiol

Am Heart J

Molecular cloning and expression of hybridoma growth factor in Escherichia coli

J Immunol

Production of C-reactive protein and risk of coronary events in stable and unstable angina

Lancet

Relation of C-reactive protein and coronary heart disease in the MRFIT nested case-control study. Multiple Risk Factor Intervention Trial

Am J Epidemiol

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

Plasma homocysteine predicts mortality independently of traditional risk factors and C-reactive protein in patients with angiographically defined coronary artery disease

Circulation

Clinical study
C-reactive protein and coronary events following percutaneous coronary angioplasty