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Lesly A Pearce

Publications and source records attributed to Lesly A Pearce.

12 recordsLinked to original sources
PubMed2005

Avoiding central nervous system bleeding during antithrombotic therapy: recent data and ideas.

BACKGROUND: Approximately 7000 intracerebral hemorrhages (ICHs) annually in the US are caused by use of antithrombotic therapies. We review the incidence, risk factors, and predictors of ICH in patients receiving long-term anticoagulation or antiplatelet therapy. SUMMARY OF REVIEW: ICH rates range from 0.3% to 0.6% per year during oral anticoagulation in recent reports. Major risk factors are advanced patient age, elevated blood pressure, intensity of anticoagulation, and previous cerebral ischemia. Combining antiplatelet agents with anticoagulation and the combined use of aspirin plus clopidogrel appear to increase ICH risk. Modest blood pressure-lowering halves the frequency of ICH during antiplatelet therapy. CONCLUSIONS: ICH is an uncommon, but often fatal, complication of antithrombotic therapy that particularly afflicts patients with previous stroke. Recent data support that keeping international normalized ratio < or =3.0, control of hypertension, and avoiding the combination of aspirin with warfarin reduce its frequency.

Administration, Oral↗
PubMed2004

Multi-biomarker risk stratification of N-terminal pro-B-type natriuretic peptide, high-sensitivity C-reactive protein, and cardiac troponin T and I in end-stage renal disease for all-cause death.

BACKGROUND: In patients with end-stage renal disease (ESRD), the ability of single and multiple biomarker monitoring to predict adverse outcomes has not been well established. This study determined the prognostic value of multiple biomarkers for all-cause death over 2 years in 399 ESRD patients. METHODS: The risk of all-cause death was determined by use of multiple biomarkers based on concentrations for a reference population (normal) and cutoffs based on tertile distributions in the ESRD group. Biomarkers studied included N-terminal pro-B-type natriuretic peptide (NT-proBNP), high-sensitivity C-reactive protein (hsCRP; Dade Behring and Roche assays), and cardiac troponin T (cTnT; Roche) and I (cTnI; Dade Behring and Beckman Coulter assays). Relative risks of death were estimated and survival curves computed. RESULTS: A total of 101 deaths occurred during 594 patient-years of follow-up. Increased NT-proBNP concentrations were not predictive of death on the basis of the normal cutoffs. However, tertile analysis of NT-proBNP was significantly predictive of death and had a ROC area under the curve equivalent to or better than any of the other biomarkers. Biomarkers independently predictive of survival were hsCRP (P <0.001, either assay), cTnT (P <0.05), and cTnI (Dade, P <0.05). Two-year mortality rates were 6% (n = 45) with normal hsCRP, cTnI, and cTnT concentrations; 19% (n = 173) with increased hsCRP or cTnT and normal cTnI; 44% (n = 160) with both hsCRP and cTnT increased and normal cTnI; 61% (n = 21) with increased cTnI (Dade) or 47% (n = 74) with increased cTnI (Beckman) regardless of hsCRP or cTnT concentrations. Defined by the normal cutoffs, increased concentrations of biomarkers were present in various proportions of the 399 patients with ESRD: NT-proBNP, 99%; hsCRP, 46% (both Roche and Dade assays); cTnT, 85%; cTnI, 19% (Beckman assay) and 5% (Dade assay). CONCLUSIONS: Although mechanisms likely vary for causation, increased plasma hsCRP, cTnT, and cTnI above the cutoffs for our reference (normal) population were all independently predictive of subsequent death in ESRD patients. Tertile analysis for NT-proBNP also demonstrated prognostic value.

Adult↗
PubMed2004

Transient ischemic attacks in patients with atrial fibrillation: implications for secondary prevention: the European Atrial Fibrillation Trial and Stroke Prevention in Atrial Fibrillation III trial.

BACKGROUND AND PURPOSE: Transient ischemic attacks (TIAs) are infrequent in patients with atrial fibrillation, and little is known about the long-term prognosis and response to antithrombotic therapy. METHODS: This study was a pooled analysis of participants in 2 randomized trials, the European Atrial Fibrillation Trial and the Stroke Prevention in Atrial Fibrillation III Trial, comparing those with prior TIA to those with prior stroke. RESULTS: Among 834 atrial fibrillation patients with prior TIA (n=222), prior ischemic stroke (n=551), or both (n=61), the mean age was 71 years, 64% were men, and 56% had hypertension. The frequency of major vascular risk factors was similar for both types of cerebral ischemia. The annualized rate of ischemic stroke during aspirin therapy was 7% per year (95% confidence interval, 4 to 12) for prior TIA and 11% per year (95% confidence interval, 9 to 15) for prior stroke (P=0.08 for rate difference) and was reduced by 56% (P=0.09) and 63% (P<0.001), respectively, by anticoagulation. CONCLUSIONS: Atrial fibrillation patients with TIA have a lower long-term risk of subsequent stroke than those with prior stroke, but their stroke risk during aspirin therapy is still high. For atrial fibrillation patients with either type of cerebral ischemia, recent or remote, secondary prevention with adjusted-dose warfarin instead of aspirin results in substantial absolute reductions in ischemic stroke.

Aged↗
PubMed2003

Prognostic value of plasma von Willebrand factor and soluble P-selectin as indices of endothelial damage and platelet activation in 994 patients with nonvalvular atrial fibrillation.

BACKGROUND: Abnormal plasma markers of a prothrombotic state have been described in atrial fibrillation (AF), but no such marker has yet been shown to reliably predict future stroke or cardiovascular outcome in AF. We hypothesized that raised plasma levels of von Willebrand factor (vWf, an index of endothelial damage/dysfunction) and/or soluble P-selectin (sP-sel, an index of platelet activation) might predict vascular events in AF. METHODS AND RESULTS: We measured vWf and sP-sel levels by ELISA in 994 participants receiving aspirin in the Stroke Prevention in Atrial Fibrillation III trial, at study entry or after 3 months, and related these indices to the subsequent incidence of stroke and vascular events. Plasma vWf levels were a significant predictor of both stroke (P=0.03) and vascular events (P<0.001), with the greatest risk for those with the highest levels of vWf. After adjustment for other clinical predictors, the relationship between vWf and stroke became nonsignificant, but vWf remained an independent predictor of vascular events (relative risk, 1.2 [95% CI, 1.0-1.4] per 20 IU/dL increase in vWf; P=0.02). No significant relationships were found between sP-sel levels and outcome. CONCLUSIONS: Among patients with AF who received aspirin, raised levels of vWf (endothelial damage/dysfunction) were predictive of stroke and vascular events, but raised sP-sel levels (platelet activation) were not associated with increased cardiovascular risk. Endothelial damage/dysfunction (or vWf itself) may play an important role in the mechanisms behind stroke and cardiovascular outcome among aspirin-treated AF patients and might represent a target for novel therapies or an adjunctive aid to risk stratification in AF.

Aspirin↗
PubMed2003

Lessons from the Stroke Prevention in Atrial Fibrillation trials.

Atrial fibrillation predisposes to left atrial thrombus formation and carries a sixfold increased risk for stroke. Antithrombotic therapies are the mainstay for stroke prevention. The National Institute of Neurological Disorders and Stroke-sponsored Stroke Prevention in Atrial Fibrillation (SPAF) studies assessed the value of warfarin, aspirin, and their combination for preventing stroke in six multicenter trials involving 3950 participants. This review presents the major results and implications, which offer unique perspectives on antithrombotic therapies for stroke prevention in atrial fibrillation. Warfarin and aspirin reduce stroke. Anticoagulation substantially benefits high-risk patients with atrial fibrillation, while many younger patients with atrial fibrillation have a low stroke rate when given aspirin. Pathogenetic and transesophageal echocardiographic correlations shed light on mechanisms by which antithrombotic agents prevent stroke. Warfarin inhibits formation of atrial appendage thrombi and markedly reduces cardioembolic strokes, while aspirin primarily prevents smaller, noncardioembolic strokes. The SPAF III stroke risk stratification scheme has been validated for identifying patients with high versus moderate versus low risk for stroke. Women with atrial fibrillation benefit from anticoagulation significantly more than men do. Many elderly patients with recurrent paroxysmal atrial fibrillation have high rates of stroke. Antithrombotic prophylaxis should be individualized on the basis of the estimated risk for stroke during aspirin therapy and the risk for bleeding during anticoagulation. Overall, nearly one third of patients with atrial fibrillation are low risk and should be treated with aspirin, and about one third are high risk and should receive warfarin if it can be given safely. For patients at moderate risk for stroke, patient preferences and access to reliable anticoagulation monitoring are particularly relevant.

Anticoagulants↗
PubMed2003

The histopathologic spectrum of cryofibrinogenemia in four anatomic sites. Skin, lung, muscle, and kidney.

Although the histologic characteristics of cryofibrinogenemia have been described in skin lesions, the literature is largely devoid of descriptions of this disorder in other organs. This series is the first to document the histopathologic manifestations of intrapulmonary, intramuscular, and renal cryofibrinogenemia. We describe the histopathologic manifestations of cryofibrinogenemia in 10 cases with manifestations in 4 organ systems: skin in 7 cases, skeletal muscle in 2, lung in 2, and kidney in 1. Irrespective of anatomic site, all lesions showed an occlusive thrombotic diathesis comprising eosinophilic refractile deposits within vessel lumina with extension into the intima, with or without an accompanying characteristic granulomatous vasculitic component. Ultrastructural examination of the renal deposits showed fibrillary material within glomerular capillary lumina with unique morphologic features not previously described. Analysis of plasma from several cases revealed a cold-precipitable protein, which in most cases included a monoclonal paraprotein. The laboratory and histologic distinctions between cryofibrinogenemia and cryoglobulinemia are addressed. We provide guidelines for the proper handling of patient specimens in the workup of cryofibrinogenemia.

Adult↗
PubMed2003

Aspirin dosage and thromboxane synthesis in patients with vascular disease.

STUDY OBJECTIVE: To determine whether urinary 11-dehydrothromboxane B2 (d-TXB2) is a marker of aspirin resistance and define the relationship between aspirin dosage and concentrations of this thromboxane metabolite. DESIGN: Randomized, crossover study. SETTING: Two outpatient clinical centers. PATIENTS: Forty-eight patients (mean age 70 yrs) with vascular disease (52% clinical coronary artery disease, 29% cerebrovascular disease, 46% atrial fibrillation). INTERVENTION: Levels of serum thromboxane B2 and d-TXB2 were measured after patients were treated initially with aspirin 325 mg/day for 4 weeks, then again after random assignment to receive aspirin 81, 325, or 1300 mg/day for 4 weeks, and then again after resumption of 325 mg/day for 4 weeks. MEASUREMENTS AND MAIN RESULTS: During treatment with aspirin 325 mg/day, the mean +/- SD serum thromboxane B2 level was 0.9 +/- 1.2 ng/ml and median (interquartile range) was 0.4 (0.2-0.9) ng/ml. Mean urinary d-TXB2 was 16 +/- 7.9 ng/mmol creatinine, with a median of 15 (9.9-23) ng/mmol creatinine with aspirin 325 mg/day. After 4 weeks of aspirin 81 mg/day, levels of serum thromboxane B2 (p<0.01) and urinary d-TXB2 (p=0.04) were both significantly higher compared with aspirin 325 mg/day; for urinary d-TXB2, the median increase was 3.0 ng/mmol creatinine. After 4 weeks of treatment with aspirin 1300 mg/day, levels of serum thromboxane B2 (p<0.01) and urinary d-TXB2 (p<0.01) were both significantly lower compared with aspirin 325 mg/day; the median decrease in urinary d-TXB2 was 4.4 ng/mmol creatinine. CONCLUSION: Different aspirin dosages significantly affect serum and urinary markers of thromboxane synthesis.

Aged↗
PubMed2002

Predictive value of cardiac troponin I and T for subsequent death in end-stage renal disease.

BACKGROUND: This study determined the prevalence of increased cardiac troponin I (cTnI) and T (cTnT) in end-stage renal disease (ESRD) patients and whether an increased troponin was predictive of death. METHODS AND RESULTS: Serum was obtained from 733 ESRD patients and measured for cTnI and cTnT. Relative risks were estimated using Cox proportional hazards regressions univariately and adjusted for age, time on dialysis, and coronary artery disease. Kaplan-Meier curves compared time to event data between groups. Greater percentages of patients had an increased cTnT versus cTnI at each cutoff, as follows: 99th percentile, 82% versus 6%; 10% coefficient of variation, 53% versus 1.0%; and receiver operator characteristic, 20% versus 0.4%. Increased versus normal cTnT was predictive of increased mortality using all cutoffs and only above the 99th percentile for cTnI. Two-year cumulative mortality rates increased (P<0.001) with changes in cTnT from normal (<0.01 microg/L, 8.4%) to small (> or =0.01 to <0.04 microg/L, 26%), moderate (> or =0.04 to <0.1 microg/L, 39%), and large (> or =0.1 microg/L, 47%) increases. Two-year mortalities were 30% for cTnI <0.1 microg/L and 52% if > or =0.1 microg/L. Univariate and adjusted relative risks of death associated with elevated (>99th percentile) cTnT were 5.0 (CI, 2.5 to 10; P<0.001) and 3.9 (CI, 1.9 to7.9; P<0.001) and cTnI were 2.0 (CI, 1.3 to 3.3; P=0.008) and 2.1 (CI, 1.3 to 3.3; P=0.007). Age, coronary artery disease, and time on dialysis were also independent predictors of mortality. CONCLUSIONS: Increases in cTnT and cTnI in ESRD patients show a 2- to 5-fold increase in mortality, with a greater number of patients having an increased cTnT.

Adolescent↗
PubMed2002

Plasma von Willebrand factor and soluble p-selectin as indices of endothelial damage and platelet activation in 1321 patients with nonvalvular atrial fibrillation: relationship to stroke risk factors.

BACKGROUND: Epidemiological studies have identified clinical and echocardiographic factors associated with increased stroke risk in atrial fibrillation (AF), but mechanisms linking these factors to stroke in AF are incompletely understood. We hypothesized that stroke risk factors may be associated with increased endothelial damage/dysfunction and platelet activation among patients with AF. METHODS AND RESULTS: We measured plasma levels of von Willebrand factor (vWF, a marker of endothelial damage/dysfunction) and soluble P-selectin (sP-sel, a marker of platelet activation) by ELISA in 1321 participants in the Stroke Prevention in Atrial Fibrillation (SPAF) III study and related these indices to the presence of stroke risk factors and cardiovascular disease. Age (P<0.001), prior cerebral ischemia (P<0.01), recent heart failure (P<0.001), diabetes (P<0.001), and body mass index (P<0.001) were independently associated with increased vWF (r(2) adjusted=9%). Independent associates of increased sP-sel were diabetes (P=0.01), peripheral vascular disease (P<0.001), and current smoking (P=0.01), whereas prior cerebral ischemia (P=0.002) and female sex (P<0.001) were associated with reduced sP-sel (r(2) adjusted=4%). Using prospectively validated stroke risk stratification criteria, we observed a significant stepwise increase in vWF from low- to moderate- to high-risk groups (r(2) adjusted=3%, P<0.001), whereas sP-sel remained constant (P= 0.24). CONCLUSIONS: Four recognized risk factors for stroke in AF (advancing age, prior cerebral ischemia, recent heart failure, and diabetes) were independently associated with raised plasma vWF (or endothelial damage/dysfunction), whereas only 1 (diabetes) was associated with increased sP-sel (platelet activation). Further longitudinal studies are now needed to confirm relationships between endothelial damage/dysfunction, platelet activation, and stroke in AF.

Aged↗
PubMed2002

Atrial fibrillation, stroke, and acute antithrombotic therapy: analysis of randomized clinical trials.

BACKGROUND: Strokes in patients with atrial fibrillation (AF) are typically larger, are associated with higher early mortality, and occur in older patients versus strokes in patients with sinus rhythm. Until recently, the value of antithrombotic therapies for acute stroke management has been based on empiric evidence. SUMMARY OF REVIEW: We present a critical review of 3 randomized clinical trials testing aspirin, heparin/heparinoid, or both involving 5029 patients with AF and acute stroke. Early recurrent ischemic stroke occurred in about 5% of patients during the 2 to 4 weeks after initial stroke. Data conflict about whether early use of heparin/heparinoid reduced early recurrent ischemic stroke but are consistent regarding its lack of overall benefit on long-term functional outcome. Modest benefits for reduction of early recurrent stroke and functional outcome were associated with aspirin use, based largely on subgroup analysis from a single, large, unblinded trial. CONCLUSIONS: No benefit of heparin has been demonstrated for acute stroke patients with AF; whether selected subgroups would respond differently remains to be proven. Aspirin followed by early initiation of warfarin for long-term secondary prevention is reasonable antithrombotic management.

Acute Disease↗