Prognostic implications of C-reactive protein and troponin following percutaneous coronary intervention.

BACKGROUND: C-reactive protein (CRP), a marker of inflammation, plays a role in the pathophysiology of atherosclerotic events. The relationship between CRP levels and myocardial necrosis assessed by troponin T (TnT) in patients undergoing percutaneous coronary intervention (PCI) has not been established. In addition, the long-term significance of TnT rise following PCI is not clear. OBJECTIVES: To examine the relationship between CRP and the rise in TnT levels, and evaluate the long-term prognostic implications of TnT rise following PCI. METHODS: A total of 1208 patients underwent successful nonemergent PCI. Baseline demographic characteristics, CRP and TnT levels were prospectively collected before and 12 h to 18 h following PCI. Long-term follow-up data over two years were available. RESULTS: Among the patients studied (mean age 62 years), 64% presented with acute coronary syndrome. A PCI procedure was associated with a significant increase in TnT levels (higher than 0.1 microg/L) in 238 patients (20%). Multivariate logistic regression identified presentation with acute coronary syndrome or myocardial infarction, no statin use at the time of the procedure, increased CRP and increasing length of stent as independent predictors of TnT rise following PCI. Periprocedural TnT rise was not associated with adverse events in follow-up examinations (OR 1.09, 95% CI 0.73 to 1.65). CONCLUSIONS: Myocardial necrosis commonly occurred in otherwise successful PCI and was particularly prevalent in the proinflammatory milieu of a recent myocardial infarction. This response was blunted with statin therapy. However, there was no long-term adverse sequelae of these troponin rises following otherwise uncomplicated PCI.

Effects of folinic acid on forearm blood flow in patients with end-stage renal disease.

BACKGROUND: Abnormalities of endothelial function are likely to contribute to the accelerated atherosclerotic risk in subjects with end-stage renal disease (ESRD). While folates can improve endothelial function, their role in ESRD has not been fully studied. The objective was to determine the acute and 12 week-effect of folinic acid on endothelium-dependent vasodilation in subjects with ESRD. METHODS: Forearm blood flow (FBF) was assessed by strain gauge plethysmography at baseline and after 12 weeks in 34 ESRD patients (57 +/- 14 years). Vascular function was assessed with acetylcholine (ACh), and sodium nitroprusside (SNP). Patients were randomized to receive folinic acid (50 mg i.v. once weekly) or a matching placebo. A subset of 25 subjects also received folinic acid (500 microg/min intra-arterially) or placebo to determine the acute effect on ACh and SNP mediated dilation at the time of the baseline vascular study. RESULTS: Folinic acid acutely improved the maximum change in ACh mediated FBF (10.0 +/- 2.4 to 12.8 +/- 2.2 ml/min/100 ml, P = 0.017), but did not change SNP responses. Chronic active therapy did not change ACh or SNP-mediated increases in FBF. Folinic acid resulted in a non-significant decrease in homocysteine (21 +/- 6 vs 28 +/- 18 micromol/l, P = 0.16) and diastolic blood pressure was significantly reduced (P = 0.05). CONCLUSIONS: The present study demonstrated that folinic acid acutely improved endothelium-dependent vasodilatation in patients with ESRD suggesting a direct vascular effect. Chronic treatment with folinic acid did not show benefit in endothelial function, but did lower diastolic blood pressure. Further work is required to determine the optimal regime to protect vascular health in subjects with ESRD.

Rationale and design of the Glitazones and the Endothelium (GATE) study: evaluation of rosiglitazone on endothelial function in patients with diabetes.

The vascular endothelium has emerged as a critical determinant of cardiovascular health and disease, and improving endothelial function is an important target for therapy. Accumulating evidence suggests that insulin resistance in patients with diabetes and the metabolic syndrome may impair endothelial function, uncovering a proinflammatory, proatherosclerotic vascular phenotype. The rationale and design of the Glitazones and the Endothelium (GATE) study is presented. The GATE study is a randomized, double-blind study for the evaluation of the effects of rosiglitazone versus placebo on endothelial function when used as an add-on therapy in patients with diabetes currently treated with oral therapy. It is hypothesized that the peroxisome proliferator-activated receptor-gamma agonist rosiglitazone will improve endothelium-dependent vasodilation, and that this effect will be related to improvements in insulin sensitivity, with concomitant reductions in whole-body insulin resistance. Furthermore, the beneficial effects of rosiglitazone will be additive to those of existing oral therapies that may modulate endothelial function. Because endothelial dysfunction plays a pivotal role in the development and progression of atherosclerosis, the GATE study may provide the rationale and impetus for the aggressive treatment of insulin-resistant patients with glitazone therapy.

Coronary flow velocity reserve does not correlate with TIMI frame count in patients undergoing non-emergency percutaneous coronary intervention.

OBJECTIVES: The purpose of this research was to compare the Thrombolysis In Myocardial Infarction (TIMI) frame count (CTFC) with coronary flow velocity reserve (CFVR) in patients undergoing percutaneous coronary intervention (PCI). BACKGROUND: The relationship between CTFC and CFVR has not been adequately assessed in patients with coronary artery disease. METHODS: We studied 62 patients who underwent successful non-emergent PCI. All patients had Doppler evaluation of CFVR, CTFC, and quantitative coronary angiography. In an additional 17 patients, a frame count reserve was calculated as baseline CTFC/CTFC at peak hyperemia, induced by intracoronary adenosine after PCI. RESULTS: The CTFC decreased from 27 +/- 13 to 18 +/- 8, and CFVR increased from 1.5 +/- 0.4 to 2.6 +/- 0.7 (both p < 0.0001). The pre-PCI CTFC and the CFVR were closely related to minimal lumen diameter (p < 0.0001). After PCI, there was no correlation between CFVR and CTFC. In addition, no relationship was observed between CFVR and the frame count reserve. CONCLUSIONS: There was no significant correlation between CFVR and CTFC in patients undergoing coronary intervention. The relative utility of these measures in predicting outcomes in this setting requires further evaluation, but CTFC (or frame count reserve) does not appear to be an adequate surrogate measure of Doppler-derived CFVR.

Abciximab attenuates coronary microvascular endothelial dysfunction after coronary stenting.

BACKGROUND: Platelet glycoprotein IIb/IIIa receptor blockade with abciximab decreases ischemic events after percutaneous coronary intervention (PCI); however, the mechanism of this benefit has not been fully elucidated. The present study was designed to assess endothelium-dependent vasomotion after coronary stenting and to determine if abciximab alters this response. METHODS AND RESULTS: The study group consisted of 48 patients (59+/-10 years of age) with discrete coronary stenoses who underwent stenting alone (n=28) or stenting plus abciximab (n=20). A control group consisted of 31 additional patients who had vasomotor testing on a non-PCI vessel. Coronary blood flow (CBF) was measured (0.014-inch Doppler wire) 30 minutes after uncomplicated PCI and in response to the intracoronary infusion of acetylcholine (Ach) (10(-7), 10(-6) mol/L Ach) and adenosine (24 microg). Ach-mediated increase in CBF was impaired after stent insertion when compared with the control group (41+/-52% versus 70+/-48%; P<0.05). The stenting plus abciximab group demonstrated a superior CBF response to Ach compared with the stenting alone group (83+/-93% versus 41+/-52%; P<0.05), with no difference between groups in the peak flow or percent change in flow to adenosine. By multivariate analysis, concomitant administration of abciximab was strongly predictive of the change in CBF to Ach (P<0.005). CONCLUSIONS: Abciximab preserves the CBF response to Ach after coronary stenting. The preservation of microvascular endothelial function may help explain the beneficial clinical effect of this agent in patients undergoing PCI.