Future biomarkers for detection of ischemia and risk stratification in acute coronary syndrome

BACKGROUND: Evaluation of patients who present to the hospital with a complaint of chest pain or other signs or symptoms suggestive of acute coronary syndrome (ACS) is time-consuming, expensive, and problematic. Recent investigations have indicated that increases in biomarkers upstream from biomarkers of necrosis (cardiac troponins I and T), such as inflammatory cytokines, cellular adhesion molecules, acute-phase reactants, plaque destabilization and rupture biomarkers, biomarkers of ischemia, and biomarkers of myocardial stretch may provide earlier assessment of overall patient risk and aid in identifying patients with higher risk of an adverse event. APPROACH AND CONTENT: The purpose of this review is to provide an overview of the pathophysiology and clinical and analytical characteristics of several biomarkers that may have potential clinical utility to identify ACS patients. These biomarkers (myeloperoxidase, metalloproteinase-9, soluble CD40 ligand, pregnancy-associated plasma protein A, choline, ischemia-modified albumin, unbound free fatty acids, glycogen phosphorylase isoenzyme BB, and placental growth factor) have demonstrated promise and need to be more thoroughly evaluated for commercial development for implementation into routine clinical and laboratory practice. SUMMARY: Specifications that have been addressed for cardiac troponins and natriuretic peptides will need to be addressed with the same scrutiny for the biomarkers discussed in this review. They include validating analytical imprecision and detection limits, calibrator characterization, assay specificity and standardization, pre-analytical issues, and appropriate reference interval studies. Crossing boundaries from research to clinical application will require replication in multiple settings and experimental evidence supporting a pathophysiologic role and, ideally, interventional trials demonstrating that monitoring single or multiple biomarkers improves outcomes.     

Posterior chamber intraocular lenses in a series of 75 autopsy eyes. Part I: Loop location

Over a period of 27 months, November 1983 to February 1986, 75 eyes obtained postmortem with posterior chamber intraocular lenses (IOLs) were examined at the Center for Intraocular Lens Research, University of Utah Health Sciences Center. These IOLs were studied by histopathological techniques to determine the location of the loops. The most common combination, found in 47% of the specimens, was one loop in the lens capsular sac (bag) and one loop in the ciliary sulcus. In 32% of the specimens, both loops were in the capsular sac; in 17%, both loops were in the ciliary sulcus. Compared to results observed in other autopsy studies, in which capsular fixation was documented in less than 3% of cases, these findings reflect a trend toward capsular sac (in-the-bag) implantation of open-looped posterior chamber IOLs.     

B-type natriuretic peptide (BNP) and N-terminal pro-BNP in obese patients without heart failure: relationship to body mass index and gastric bypass surgery

BACKGROUND: Further investigations are warranted to better characterize variables that may confound the clinical interpretation of plasma natriuretic peptide measurements, which are increasingly recognized to have diagnostic and predictive importance. METHODS: Blood samples (EDTA plasma) from patients (n = 206) attending clinics for the medical treatment and follow-up of obesity were analyzed for B-type natriuretic peptide (BNP; Bayer assay) and the N-terminal segment of its prohormone (NT-proBNP; Roche assay). Natriuretic peptide concentration ranges were evaluated in those without diagnosis of congestive heart failure (CHF) or chronic kidney disease (CKD). RESULTS: BNP and NT-proBNP were directly correlated (r = 0.87; P = 0.01), with NT-proBNP concentrations higher relative to BNP. Of obese patients without CHF or CKD, 21.6% (40 of 185) had NT-proBNP concentrations greater than the published assay upper reference limit. Concentrations of both natriuretic peptides were higher in patients currently exposed to beta blockers, patients with the diagnosis of hypertension or type 2 diabetes, and patients with a history of gastric bypass surgery. An inverse relationship between body mass index (BMI) and both BNP and NT-proBNP was evident. According to the National Institutes of Health, National Heart, Lung, and Blood Institute classification, more than 95% of the participants sampled in this study were either obesity class 2 (35 kg/m(2) < BMI < 39.9 kg/m(2)) or class 3 (BMI >or=40 kg/m(2)) CONCLUSIONS: A substantial proportion of obese patients without CHF or CKD have concentrations greater than the upper reference limit for NT-proBNP but not for simultaneously measured BNP. A history of gastric bypass surgery appeared to be a significant predictor of increased natriuretic peptide concentrations when assessed in a population of patients with class 2 or 3 obesity.     

Clinical, angiographic, and intravascular ultrasound characteristics of early saphenous vein graft failure

OBJECTIVES: We sought to examine saphenous vein graft (SVG) lesions that fail within the first year after operation. BACKGROUND: Saphenous vein grafts remain patent for approximately 10 years; however, up to 15% to 20% of SVGs become occluded within the first year. METHODS: We studied 100 patients who underwent percutaneous coronary intervention (PCI) for early (<1 year post-implantation) SVG failure lesions and compared them with a diabetes- and hypercholesterolemia-matched cohort of late SVG failures (>1 year). Coronary angiography and intravascular ultrasound images were analyzed. RESULTS: The majority of patients in both groups were males who presented with unstable angina; 36% were diabetic. Graft ages were 6.0 +/- 2.9 months and 105.4 +/- 50.8 months, respectively. The early SVG failure lesion location was more often ostial or proximal (62% vs. 42%, respectively). Early SVG failures were angiographically smaller than late failures (reference: 2.47 +/- 0.86 mm vs. 3.26 +/- 0.83 mm, p < 0.001) but had similar lesion lengths. Intravascular ultrasound showed that early failure lesions had smaller proximal and distal reference lumen areas (7.3 +/- 6.8 mm2 vs. 10.6 +/- 3.8 mm2, p = 0.026) and greater reference plaque burden than late failures (52.3% vs. 36.1%, p < 0.001). After PCI, 20.6% of early and 30.6% of late failure lesions had creatine kinase-myocardial band (CK-MB) greater than twice normal. CONCLUSIONS: Early SVG failure is mostly proximal or ostial, lesions appear focal, and early SVGs appear smaller than late SVGs. Intravascular ultrasound shows significant reference segment plaque burden, suggesting more severe, diffuse SVG disease.     

Cardiac troponin assays: analytical issues and clinical reference range cutpoints

A recently published consensus document from the European Society of Cardiology and American College of Cardiology emphasized the unique role cardiac troponin monitoring plays in redefining acute myocardial infarction. The cardiology community has now established criteria to define both the reference cutpoints and acceptable imprecision for troponin assays, which complement previous recommendations by the laboratory community. This article will review the analytical issues confronting laboratories, clinicians, and industry regarding troponin assay standardization, assay imprecision, and how clinical decision cutpoints should be established and implemented for clinical practice.     

Preprocedure hyperglycemia is more strongly associated with restenosis in diabetic patients after percutaneous coronary intervention than is hemoglobin A1C.

BACKGROUND: Although more frequent in diabetic patients, restenosis after percutaneous coronary intervention (PCI) is less common in those with good glycemic control. High circulating insulin levels may also be associated with more frequent restenosis. METHODS: Fasting blood samples were obtained from 162 diabetic patients immediately prior to the PCI and analyzed for glucose, hemoglobin A1C, and insulin. Nine-month follow-up information was obtained in 145 (89.5%) patients. Target vessel revascularization (TVR) was the surrogate for restenosis. RESULTS: Patients were divided into quartiles with regard to their blood levels. Insulin, calculated insulin resistance, and hemoglobin A1C were not associated with increased TVR rates. Glucose level was significantly associated (P=.02). Patients in the two lower quartiles (glucose < or = 128 mg/dl) had a 9-month TVR rate of 12.7% while those in the two higher quartiles (>128 mg/dl) had a rate of 33.8% (P=.005). Level of glucose was independent of hemoglobin A1C. In patients whose A1C level was < or = 7%, the TVR rate was greater in those with a glucose level >128 mg/dl (39.1% vs. 10.6%, P=.009). Similarly, in patients with a hemoglobin A1C level >7%, the TVR rate was lower in patients with a glucose level < or = 128 mg/dl, but this difference did not reach statistical significance (16.6% vs. 31.3%, P=.3). CONCLUSIONS: Hemoglobin A1C, insulin, and insulin resistance at the time of the PCI are not associated with restenosis. Periprocedural hyperglycemia may promote restenosis in diabetics.     

Clinical outcomes following stent implantation in internal mammary artery grafts.

We evaluated our experience with percutaneous coronary intervention (PCI) of internal mammary artery (IMA) grafts. From the institution's database we identified 288 patients with 311 IMA lesions. Of these, 82 (26.4%) had stents placed during PCI. Angiographic success was 92%. Mortality at 1 month was 1.7%, myocardial infarction (MI) 15.7%, and target lesion revascularization (TLR) 0.4%. Cumulative 1-year event rates were mortality 6.4%, MI 20.4%, and TLR 8.0%. TLR rates were significantly higher in the stented lesions than lesions treated with angioplasty alone (19.2% vs. 4.9%; P = 0.004). The higher TLR rate in stented lesions was most apparent at the anastomotic site (25.0% vs. 4.2%; P = 0.006). Percutaneous revascularization of IMA grafts can be performed safely with high procedural success and excellent short- and long-term results. Stenting, particularly at the anastomotic site, was associated with significantly greater rates of TLR than angioplasty alone.