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C P Cannon

Publications and source records attributed to C P Cannon.

At least 19 recordsLinked to original sources
PubMed2006

Influence of genetic variation in the C-reactive protein gene on the inflammatory response during and after acute coronary ischemia.

The aim of this research was to assess whether common genetic variants within the C-reactive protein gene (CRP) are related to the degree of acute rise in plasma C-reactive protein (CRP) levels following an acute coronary syndrome (ACS). While polymorphisms within CRP are associated with basal CRP levels in healthy men and women, less is known about the relationship of such genetic variants and the degree of CRP rise during and after acute ischemia. Plasma CRP is associated with increased rates of recurrent coronary events. We evaluated seven common genetic variants within CRP and assessed their relationship to the degree of rise in CRP levels immediately following an acute coronary syndrome in 1827 European American patients. Variants in the putative promoter region, -757T > C and -286C > T > A, were associated with the highest CRP elevations after ACS. Patients with two copies of the A allele of SNP -286C > T > A had median CRP values of 76.6 mg/L, compared to 11.1 mg/L in patients with no copies of the rare variant (p-value <0.0001), post ACS. The lowest CRP values were found for patients with minor alleles of the exonic 1059G > C and the 3'untranslated region 1846G > A SNPs. For example, patients homozygous for the minor allele of 1059G > C had 71% lower median CRP values than those homozygous for the major allele [3.5 vs 12.0 mg/L, p < 0.0001]. These trends persisted in the chronic stable phase after ischemia had resolved, and after adjustment for infarct size by peak creatinine kinase levels and clinical status by Killip class. Assessment of CRP genetic variants identified patients with higher and lower CRP elevation after acute coronary syndrome.

Acute Disease↗
PubMed2002

The contribution of genetic factors to thrombotic and bleeding outcomes in coronary patients randomised to IIb/IIIa antagonists.

Genetic variants are risk factors for coronary disease, but their role in recurrent events and in response to treatment is less clear. We genotyped genetic variants implicated in primary coronary disease in 924 Caucasians with acute coronary syndromes participating in the OPUS-TIMI16 trial of the GPIIb/IIIa antagonist orbofiban. These were the platelet glycoprotein (GP) receptors GPIIIa, GPIa, GPIbalpha; platelet ligands beta-fibrinogen and von Willebrand Factor (vWF); interleukins (IL) IL-1RN, and IL-6; adhesion proteins E-selectin and P-selectin; and metalloproteinase MMP-9. Cox modelling of all genetic variants demonstrated no significant impact on the composite endpoint (P = 0.88), which included myocardial infarction (MI), death, recurrent ischemia, urgent revascularisation and stroke, but a significant impact on recurrent myocardial infarction alone (chi(2) = 20.4, 10 df, P = 0.04). There was a significant interaction of the polymorphisms with orbofiban treatment influencing bleeding outcomes (P = 0.004). Thus, genetic polymorphisms may be associated with subsequent myocardial infarction, and may also be associated with treatment-associated bleeding among coronary patients.

Alanine↗
PubMed2001

Genetic variation in glycoprotein IIb/IIIa (GPIIb/IIIa) as a determinant of the responses to an oral GPIIb/IIIa antagonist in patients with unstable coronary syndromes.

This study examined the influence of the Pl(A) polymorphism of glycoprotein IIIa (GPIIIa) in determining the response to an oral GPIIb/IIIa antagonist, orbofiban, in patients with unstable coronary syndromes. Genotyping for the Pl(A) polymorphism was performed in 1014 patients recruited into the OPUS-TIMI-16 (orbofiban in patients with unstable coronary syndromes-thrombolysis in myocardial infarction 16) trial, in which patients were randomized to low- or high-dose orbofiban or placebo for 1 year. The primary end point (n = 165) was a composite of death, myocardial infarction (MI), recurrent ischemia requiring rehospitalization, urgent revascularization, and stroke. Overall, orbofiban failed to reduce ischemic events when compared with placebo, but increased the rate of bleeding. In the whole population, Pl(A2) carriers had a significant increase in MI (n = 33) during follow up, with a relative risk (RR) of 2.71 (95% CI, 1.37 to 5.38; P =.004). There was a significant interaction between treatment (placebo and orbofiban) and the Pl(A) polymorphism for bleeding (n = 187; P =.05). Thus, while orbofiban increased bleeding in noncarriers (RR = 1.87, 1.29 to 2.71; P <.001) in a dose-dependent fashion, it did not increase bleeding events in Pl(A2) carriers (RR = 0.87, 0.46 to 1.64). There was no interaction between treatment (placebo and orbofiban) and the Pl(A) polymorphism for the primary end point (P =.10). However, in the patients receiving orbifiban there was a higher risk of a primary event (RR = 1.55, 1.03 to 2.34; P =.04) and MI (RR 4.27, 1.82 to 10.03; P <.001) in Pl(A2) carriers compared with noncarriers. In contrast, there was no evidence that Pl(A2) influenced the rate of recurrent events in placebo-treated patients. In patients presenting with an acute coronary syndrome, the Pl(A) polymorphism of GPIIb/IIIa may explain some of the variance in the response to an oral GPIIb/IIIa antagonist.

Aged↗
PubMed2001

Ability of minor elevations of troponins I and T to predict benefit from an early invasive strategy in patients with unstable angina and non-ST elevation myocardial infarction: results from a randomized trial.

CONTEXT: Cardiac troponins I (cTnI) and T (cTnT) are useful for assessing prognosis in patients with unstable angina and non-ST-segment elevation myocardial infarction (UA/NSTEMI). However, the use of cardiac troponins for predicting benefit of an invasive vs conservative strategy in this patient population is not clear. OBJECTIVE: To prospectively test whether an early invasive strategy provides greater benefit than a conservative strategy in acute coronary syndrome patients with elevated baseline troponin levels. DESIGN: Prospective, randomized trial conducted from December 1997 to June 2000. SETTING: One hundred sixty-nine community and tertiary care hospitals in 9 countries. PARTICIPANTS: A total of 2220 patients with acute coronary syndrome were enrolled. Baseline troponin level data were available for analysis in 1821, and 1780 completed the 6-month follow-up. INTERVENTIONS: Patients were randomly assigned to receive (1) an early invasive strategy of coronary angiography between 4 and 48 hours after randomization and revascularization when feasible based on coronary anatomy (n = 1114) or (2) a conservative strategy of medical treatment and, if stable, predischarge exercise tolerance testing (n = 1106). Conservative strategy patients underwent coronary angiography and revascularization only if they manifested recurrent ischemia at rest or on provocative testing. MAIN OUTCOME MEASURE: Composite end point of death, MI, or rehospitalization for acute coronary syndrome at 6 months. RESULTS: Patients with a cTnI level of 0.1 ng/mL or more (n = 1087) experienced a significant reduction in the primary end point with the invasive vs conservative strategy (15.3% vs 25.0%; odds ratio [OR], 0.54; 95% confidence interval [CI], 0.40-0.73). Patients with cTnI levels of less than 0.1 ng/mL had no detectable benefit from early invasive management (16.0% vs 12.4%; OR, 1.4; 95% CI, 0.89-2.05; P<.001 for interaction). The benefit of invasive vs conservative management through 30 days was evident even among patients with low-level (0.1-0.4 ng/mL) cTnI elevation (4.4% vs 16.5%; OR, 0.24; 95% CI, 0.08-0.69). Directionally similar results were observed with cTnT. CONCLUSION: In patients with clinically documented acute coronary syndrome who are treated with glycoprotein IIb/IIIa inhibitors, even small elevations in cTnI and cTnT identify high-risk patients who derive a large clinical benefit from an early invasive strategy.

Adult↗
PubMed2001

Early coronary intervention following pharmacologic therapy for acute myocardial infarction (the combined TIMI 10B-TIMI 14 experience).

Earlier studies have suggested that immediate percutaneous coronary intervention (PCI) following thrombolytic therapy for acute myocardial infarction (AMI) is associated with an increase in adverse events and that routine PCI in this setting has offered no advantage over a conservative strategy. To reassess this issue in a more recent era, we evaluated 1,938 patients from the Thrombolysis in Myocardial Infarction (TIMI) 10B and 14 trials of AMI. Patients in TIMI 10B were randomized to receive tissue plasminogen activator or TNK tissue plasminogen activator, whereas patients in TIMI 14B trial were randomized to receive thrombolytic therapy with or without abciximab. All patients underwent angiography 90 minutes after receiving pharmacologic therapy. Patients who underwent PCI were classified as having undergone a rescue procedure (TIMI 0 or 1 flow at 90 minutes), an adjunctive procedure (TIMI 2 or 3 flow at 90 minutes), or a delayed procedure (performed >150 minutes after symptom onset, median of 2.75 days). Among patients with TIMI 0 or 1 flow, there was a trend for lower 30-day mortality among patients who underwent rescue PCI than among those who did not (6% vs 17%, p = 0.01, adjusted p = 0.28). Patients who underwent adjunctive PCI had similar 30-day mortality and/or reinfarction as those who underwent delayed PCI. In a multivariate model both had lower 30-day mortality and/or reinfarction than patients with "successful thrombolysis" (i.e., TIMI 3 flow at 90 minutes) who did not undergo revascularization (p = 0.02). Thus, early PCI following AMI is associated with excellent outcomes. Randomized trials of an early invasive strategy following thrombolysis are warranted.

Abciximab↗
PubMed2001

The prognostic value of B-type natriuretic peptide in patients with acute coronary syndromes.

BACKGROUND: Brain (B-type) natriuretic peptide is a neurohormone synthesized predominantly in ventricular myocardium. Although the circulating level of this neurohormone has been shown to provide independent prognostic information in patients with transmural myocardial infarction, few data are available for patients with acute coronary syndromes in the absence of ST-segment elevation. METHODS: We measured B-type natriuretic peptide in plasma specimens obtained a mean (+/-SD) of 40+/-20 hours after the onset of ischemic symptoms in 2525 patients from the Orbofiban in Patients with Unstable Coronary Syndromes-Thrombolysis in Myocardial Infarction 16 study. RESULTS: The base-line level of B-type natriuretic peptide was correlated with the risk of death, heart failure, and myocardial infarction at 30 days and 10 months. The unadjusted rate of death increased in a stepwise fashion among patients in increasing quartiles of base-line B-type natriuretic peptide levels (P< 0.001). This association remained significant in subgroups of patients who had myocardial infarction with ST-segment elevation (P=0.02), patients who had myocardial infarction without ST-segment elevation (P<0.001), and patients who had unstable angina (P<0.001). After adjustment for independent predictors of the long-term risk of death, the odds ratios for death at 10 months in the second, third, and fourth quartiles of B-type natriuretic peptide were 3.8 (95 percent confidence interval, 1.1 to 13.3), 4.0 (95 percent confidence interval, 1.2 to 13.7), and 5.8 (95 percent confidence interval, 1.7 to 19.7). The level of B-type natriuretic peptide was also associated with the risk of new or recurrent myocardial infarction (P=0.01) and new or worsening heart failure (P<0.001) at 10 months. CONCLUSIONS: A single measurement of B-type natriuretic peptide, obtained in the first few days after the onset of ischemic symptoms, provides powerful information for use in risk stratification across the spectrum of acute coronary syndromes. This finding suggests that cardiac neurohormonal activation may be a unifying feature among patients at high risk for death after acute coronary syndromes.

Acute Disease↗
PubMed2001

Application of the TIMI risk score for ST-elevation MI in the National Registry of Myocardial Infarction 3.

CONTEXT: The Thrombolysis in Myocardial Infarction (TIMI) risk score for ST-elevation myocardial infarction (STEMI) is a simple integer score for bedside risk assessment of patients with STEMI. Developed and validated in multiple clinical trials of fibrinolysis, the risk score has not been validated in a community-based population. OBJECTIVE: To validate the TIMI risk score in a population of STEMI patients reflective of contemporary practice. DESIGN, SETTING, AND PARTICIPANTS: The risk score was evaluated among 84 029 patients with STEMI from the National Registry of Myocardial Infarction 3 (NRMI 3), which collected data on consecutive patients with myocardial infarction (MI) from 1529 US hospitals between April 1998 and June 2000. MAIN OUTCOME MEASURES: Ability of the TIMI risk score to correctly predict risk of death in terms of model discrimination (c statistic) and calibration (agreement of predicted and observed death rates). RESULTS: Patients in NRMI 3 tended to be older, to be more often female, and to have a history of coronary disease more often than those in the derivation set. Forty-eight percent received reperfusion therapy. The TIMI risk score revealed a significant graded increase in mortality with rising score (range, 1.1%-30.0%; P<.001 for trend). The risk score showed strong prognostic capacity overall (c = 0.74 vs 0.78 in derivation set) and among patients receiving acute reperfusion therapy (c = 0.79). Predictive behavior of the risk score was similar between fibrinolytic-treated patients (n = 23 960; c = 0.79) and primary percutaneous coronary intervention patients (n = 15 348; c = 0.80). In contrast, among patients not receiving reperfusion therapy, the risk score underestimated death rates and offered lower discriminatory capacity (c = 0.65). CONCLUSIONS: Sufficiently simple to be practical at the bedside and effective for risk assessment across a spectrum of patients, the TIMI risk score may be useful in triage and treatment of patients with STEMI who are treated with reperfusion therapy.

Aged↗
PubMed2001

The platelet Pl(A2) and angiotensin-converting enzyme (ACE) D allele polymorphisms and the risk of recurrent events after acute myocardial infarction.

Chromosome 17q21-23 harbors genes for platelet glycoprotein IIIa and angiotensin-converting enzyme (ACE), which are polymorphic for alleles Pl(A2) and ACE "D." These alleles have been independently and often associated with ischemic coronary artery disease (CAD). We sought to determine if the Pl(A2) and ACE D polymorphisms were risk factors for recurrent coronary events. In the Cholesterol And Recurrent Events (CARE) trial, 4,159 men and women with documented myocardial infarction (MI) were randomized to receive either placebo or pravastatin, and were followed prospectively for 5 years. Pl(A) and ACE genotypes were determined in 767 patients: 385 cases who had experienced a recurrent primary event (death due to coronary disease or nonfatal MI), and 382 age- and gender-matched controls. In patients receiving placebo, the Pl(A1,A2) genotype conferred a relative risk (RR) of 1.38 (confidence intervals [CI] 1.04 to 1.83; p = 0.028; adjusted RR = 1.32, CI = 0.99 to 1.76; p = 0.058]) for the primary end point. Compared with the placebo group, pravastatin reduced the excess RR of coronary disease death and recurrent MI in the Pl(A1,A2) patient population by 31% (p = 0.06). The ACE D allele appeared to have modestly additive effects on the Pl(A1,A2) risk. Among the Pl(A1,A2) patients, pravastatin had little effect on the risk of recurrent events with the ACE II genotype, but reduced the adjusted RR from 1.42 (placebo) to 0.58 for ACE ID patients, and from 1.56 (placebo) to 0.83 for ACE DD. The Pl(A1,A2) genotype was associated with an excess of recurrent coronary events in patients after MI who did not receive pravastatin, and the ACE D allele added to this risk. These data suggest that it would be important to perform a larger study to address the potential role of these genotypes in therapeutic decision making.

Aged↗
PubMed2001

Early noninvasive detection of failed epicardial reperfusion after fibrinolytic therapy.

Available noninvasive techniques for identifying patients with failed epicardial reperfusion after fibrinolytic therapy are limited by poor accuracy. It is unknown whether combining multiple noninvasive predictors would improve diagnostic accuracy and facilitate identification of candidates for rescue percutaneous coronary intervention. In the Thrombolysis In Myocardial Infarction (TIMI) 14 trial, we evaluated the ability of ST-segment resolution (n = 606), chest pain resolution (n = 859), and the ratio of 60-minute/baseline serum myoglobin (n = 308) to identify patients with angiographic evidence of failed reperfusion 90 minutes after fibrinolysis. Three criteria were prospectively defined: <50% ST resolution at 90 minutes, presence of chest pain at the time of angiography, and myoglobin ratio <4. Patients who met any individual criterion were more likely to have less than TIMI 3 flow and an occluded infarct-related artery (TIMI 0/1 flow) than those who did not meet the criterion (p <0.005 for each). When the 3 criteria were used together (n = 169), patients who satisfied 0 (n = 29), 1 (n = 68), 2 (n = 51), or 3 (n = 21) of the criteria had a 17%, 24%, 35%, and 76% probability of failing to achieve TIMI 3 flow (p <0.0001 for trend), a 0%, 6%, 18%, and 57% probability of an occluded infarct-related artery (p <0.0001 for trend), and a 0%, 1.5%, 2.0%, and 9.5% rate of 30-day mortality (p = 0.05 for trend), respectively. Use of the criteria in combination increased positive predictive values without decreasing negative predictive values. In conclusion, ST-segment resolution, chest pain resolution, and early washout of serum myoglobin can be used in combination to aid in the early noninvasive identification of candidates for rescue percutaneous coronary intervention.

Aged↗
PubMed2001

Comparison of early invasive and conservative strategies in patients with unstable coronary syndromes treated with the glycoprotein IIb/IIIa inhibitor tirofiban.

BACKGROUND: There is continued debate as to whether a routine, early invasive strategy is superior to a conservative strategy for the management of unstable angina and myocardial infarction without ST-segment elevation. METHODS: We enrolled 2220 patients with unstable angina and myocardial infarction without ST-segment elevation who had electrocardiographic evidence of changes in the ST segment or T wave, elevated levels of cardiac markers, a history of coronary artery disease, or all three findings. All patients were treated with aspirin, heparin, and the glycoprotein IIb/IIIa inhibitor tirofiban. They were randomly assigned to an early invasive strategy, which included routine catheterization within 4 to 48 hours and revascularization as appropriate, or to a more conservative (selectively invasive) strategy, in which catheterization was performed only if the patient had objective evidence of recurrent ischemia or an abnormal stress test. The primary end point was a composite of death, nonfatal myocardial infarction, and rehospitalization for an acute coronary syndrome at six months. RESULTS: At six months, the rate of the primary end point was 15.9 percent with use of the early invasive strategy and 19.4 percent with use of the conservative strategy (odds ratio, 0.78; 95 percent confidence interval, 0.62 to 0.97; P=0.025). The rate of death or nonfatal myocardial infarction at six months was similarly reduced (7.3 percent vs. 9.5 percent; odds ratio, 0.74; 95 percent confidence interval, 0.54 to 1.00; P<0.05). CONCLUSIONS: In patients with unstable angina and myocardial infarction without ST-segment elevation who were treated with the glycoprotein IIb/IIIa inhibitor tirofiban, the use of an early invasive strategy significantly reduced the incidence of major cardiac events. These data support a policy involving broader use of the early inhibition of glycoprotein IIb/IIIa in combination with an early invasive strategy in such patients.

Aged↗
PubMed2001

Combination therapy with abciximab reduces angiographically evident thrombus in acute myocardial infarction: a TIMI 14 substudy.

BACKGROUND: Use of abciximab in combination with administration of thrombolytics has been shown to improve epicardial and microvascular coronary blood flow in acute myocardial infarction (AMI). As a potential mechanism, we hypothesized that combination therapy would reduce angiographically evident thrombus (AET) and would increase lumen diameter compared with thrombolytic monotherapy. METHODS AND RESULTS: Patients who received combination therapy in TIMI 14 (low-dose thrombolytic plus abciximab, n=732) were compared with patients who received thrombolytic monotherapy without abciximab in the TIMI 4, 10A, 10B, and 14 trials (n=1662). Thrombus burden was assessed 90 minutes after treatment, and quantitative angiography was performed in an angiographic core laboratory by investigators blinded to treatment assignment. The frequency of AET was reduced in patients who received abciximab combination therapy compared with thrombolytic monotherapy (26.6% versus 35.4%, P<0.001). Similar findings were observed when the analysis was restricted to patients with patent arteries (14.7% versus 20.8%, P=0.001). Residual percent diameter stenosis at 90 minutes was also improved in the abciximab therapy group both in patent arteries (64.6+/-16.6 versus 68.3+/-14.8, P<0.001) and between patent and occluded arteries (69.3+/-19.5 versus 73.8+/-17.9, P<0.001). The absence of AET was associated with an increased frequency of >70% ST-segment resolution by 90 minutes (37.2%, 110/296 versus 18.9%, 54/286, P<0.001). CONCLUSIONS: Compared with thrombolytic monotherapy, combination therapy with abciximab reduces AET, which in turn is associated with reduced residual stenosis and improved ST-segment resolution in AMI. These data provide a pathophysiological link between platelet inhibition, reduced thrombus, and improvements in both epicardial and microvascular perfusion in AMI.

Abciximab↗
PubMed2001

New approaches to diagnosis and management of unstable angina and non-ST-segment elevation myocardial infarction.

Recently, it has been demonstrated in multiple clinical research studies that non-Q-wave myocardial infarction shares many of the features of unstable angina pectoris and that both diseases initially are managed similarly. Important new antiplatelet drugs (glycoprotein IIb-IIIa inhibitors) and antithrombin agents (low-molecular-weight heparin) are currently recommended for patients with unstable angina pectoris/non-ST-segment elevation MI who are at high or intermediate risk on the basis of symptoms, electrocardiographic findings, and the presence or absence of serum markers (eg, troponin I, troponin T, and creatine kinase-MB). This review provides important information concerning the results of clinical studies of glycoprotein IIb-IIIa inhibitors (tirofiban hydrochloride and eptifibatide) when used with unfractionated heparin in patients with this syndrome or with low-molecular weight heparin (enoxaparin sodium) in similar patients. The Thrombolysis in Myocardial Infarction IIIB, Veterans Affairs Non-Q-Wave Infarction Studies in Hospital, and Fast Revascularization During Instability in Coronary Artery Disease II studies evaluating a conservative, ischemia-guided approach vs an early aggressive approach to such patients are presented, with a practical algorithm for treating such patients.

Algorithms↗
PubMed2001

Association of white blood cell count with increased mortality in acute myocardial infarction and unstable angina pectoris. OPUS-TIMI 16 Investigators.

We observed in a study of 7,651 patients with acute coronary syndromes that a white blood cell (WBC) count of > 10,000 was associated with increased 30-day and 10-month mortality (6.2% vs 3.2% to 3.6% for WBC count < 10,000; p < 0.000). With its simplicity and widespread availability, WBC count could serve as a simple, inexpensive, new tool for risk stratification in acute coronary syndromes.

Aged↗
PubMed2001

Can we replace the 90-minute thrombolysis in myocardial infarction (TIMI) flow grades with those at 60 minutes as a primary end point in thrombolytic trials? TIMI Study Group.

The establishment of patency (Thrombolysis In Myocardial Infarction [TIMI] grade 2 or 3 flow) and/or TIMI grade 3 flow at 60 minutes after thrombolytic administration is both a univariate and multivariate predictor of in-hospital and 30-day mortality, and the odds ratios for mortality are nearly identical for TIMI grade 3 flow at 60 and 90 minutes. Thus, the 60-minute angiographic end point appears to be a valid alternative to that at 90 minutes and may permit earlier decisions regarding post-thrombolytic intervention.

Coronary Angiography↗