Repeat revascularization after contemporary percutaneous coronary intervention: an evaluation of staged, target lesion, and other unplanned revascularization procedures during the first year.

BACKGROUND: Although drug-eluting stents and intensive secondary prevention have contributed to improved outcomes after percutaneous coronary intervention (PCI), repeat revascularization remains relatively common in contemporary practice. We used data from the multicenter Evaluation of Drug-Eluting Stents and Ischemic Events registry to evaluate the relative frequency and timing of staged revascularization, target lesion revascularization (TLR), and other nontarget revascularization during the first year after contemporary PCI. METHODS AND RESULTS: Patients with staged revascularization, TLR, and other unplanned procedures (elsewhere in the target vessel or in other coronary arteries) were evaluated in time-dependent models using Kaplan-Meier life-table estimation. Predictors of TLR and unplanned revascularization at nontarget sites were identified using logistic regression. Between July 2004 to June 2007, 10 144 patients undergoing PCI were enrolled at 55 US hospitals, of whom 86% were treated with at least 1 drug-eluting stent. Twelve percent required repeat revascularization within the first year (3% staged; 9% unplanned). More than 75% of staged revascularizations were performed <30 days after index PCI, although there was significant variation in this practice across hospitals (range, 0%-54%). TLR occurred in 4.5% of patients, with higher hazard rates between 2 to 9 months after PCI, whereas the risk of unplanned non-TLR (4.4% cumulative incidence) was constant over time. CONCLUSIONS: Among unselected patients undergoing PCI in the drug-eluting stent era, the incidence of repeat revascularization at 1 year is ≈12%. Among unplanned procedures, only half are performed for TLR. To achieve further improvements in PCI outcomes, future efforts should concentrate as much on identifying ischemia-producing lesions and intensifying secondary prevention therapies as on the prevention of restenosis.

Mode of death after contemporary percutaneous coronary intervention: a report from the Evaluation of Drug Eluting Stents and Ischemic Events registry.

BACKGROUND: When selecting clinical trial end points, some investigators prefer cardiovascular death (CVD) while others believe that all-cause mortality is more relevant. However, the relative contribution of CVD to 1-year mortality after contemporary percutaneous coronary intervention (PCI) is not known. METHODS: We evaluated the mode of death (MOD) in EVENT, a prospective PCI registry at 55 US hospitals. Vital status was assessed at 6 and 12 months as part of the study protocol, and MOD was independently reviewed in blinded fashion. RESULTS: Between 2004 and 2007, EVENT enrolled 10,144 patients of whom 295 (2.9%) died within the first year: 51 (17%) ≤30 days; and 244 (83%) between 31 and 365 days after index PCI. Overall, CVD accounted for 42% of deaths, and no clear cause could be identified in a substantial subgroup (25% of deaths). Among patients who died ≤30 days, the MOD was more likely to be CVD (odds ratio 3.96, 95% CI 2.08-7.55), whereas the incidence of CVD and non-CVD was similar after 30 days. Findings were similar after a series of sensitivity analyses including reassignment of unknown MOD to the CVD category, using multiple imputation modeling, or when evaluating MOD in prespecified subgroups of patients with diabetes, acute coronary syndromes, or left ventricular dysfunction. CONCLUSIONS: Among unselected PCI patients, 1-year mortality is approximately 3%, and CVD is confirmed in <50% of all deaths. Regardless of analytic approach, CVD is the primary contributor to overall mortality during the first 30 days after PCI, whereas rates of CVD and non-CVD are remarkably similar after the first month after PCI.

Prognostic implications of creatine kinase-MB elevation after percutaneous coronary intervention: results from the Evaluation of Drug-Eluting Stents and Ischemic Events (EVENT) registry.

BACKGROUND: Creatine kinase-MB (CK-MB) elevation after percutaneous coronary intervention (PCI) has been associated with increased risk for mortality. Although most studies have defined periprocedural myocardial infarction (pMI) as an elevation in CK-MB >3× upper limit of normal (ULN), use of different CK-MB assays and variation in site-specific definitions of the ULN may limit the value of such relative thresholds. METHODS AND RESULTS: We used data from the multicenter Evaluation of Drug-Eluting Stents and Ischemic Events (EVENT) registry to examine the impact of variations in site-specific thresholds for CK-MB elevation on the incidence of pMI as well as the relationship between absolute peak levels of CK-MB after PCI and 1-year mortality. The study cohort consisted of 6347 patients who underwent nonemergent PCI and had normal CK-MB at baseline. Across the 59 study centers, the ULN for CK-MB ranged from 2.6 to 10.4 ng/mL (median, 5.0 ng/mL), and there was an inverse relationship between the site-specific ULN and the incidence of pMI (defined as CK-MB elevation >3× ULN). Although any postprocedure elevation of CK-MB was associated with an adverse prognosis, in categorical analyses, only CK-MB ≥50 ng/mL was independently associated with increased 1-year mortality (hazard ratio, 4.71; 95% confidence interval, 2.42 to 9.13; P<0.001). Spline analysis using peak CK-MB as a continuous variable suggested a graded, nonlinear relationship with 1-year mortality, with an inflection point at ≈30 ng/mL. CONCLUSIONS: Among unselected patients undergoing PCI, there is a graded relationship between CK-MB elevation after PCI and 1-year mortality that is particularly strong for large CK-MB elevations (>30 to 50 ng/mL). Future studies that include pMI as a clinical end point should consider using a core laboratory to assess CK-MB (to ensure consistency) and raising the threshold for defining pMI above current levels (to enhance clinical relevance).

Clinical and economic outcomes of liberal versus selective drug-eluting stent use: insights from temporal analysis of the multicenter Evaluation of Drug Eluting Stents and Ischemic Events (EVENT) registry.

BACKGROUND: Although the benefits of drug-eluting stents (DES) for reducing restenosis after percutaneous coronary intervention are well established, the impact of alternative rates of DES use on population-level outcomes is unknown. METHODS AND RESULTS: We used data from the Evaluation of Drug Eluting Stents and Ischemic Events (EVENT) registry to examine the clinical impact and cost-effectiveness of varying DES use rates in routine care. Between 2004 and 2007, 10,144 patients undergoing percutaneous coronary intervention were enrolled in the EVENT registry at 55 US centers. Clinical outcomes and cardiovascular-specific costs were assessed prospectively over 1 year of follow-up. Use of DES decreased from 92 in 2004 to 2006 (liberal use era; n=7587) to 68 in 2007 (selective use era; n=2557; P<0.001). One-year rates of death or myocardial infarction were similar in both eras. Over this time period, the incidence of target lesion revascularization increased from 4.1 to 5.1, an absolute increase of 1.0 (95 confidence interval, 0.1 to 1.9; P=0.03), whereas total cardiovascular costs per patient decreased by $401 (95 confidence interval, 131 to 671; P=0.004). The risk-adjusted incremental cost-effectiveness ratio for the liberal versus selective DES era was $16,000 per target lesion revascularization event avoided, $27,000 per repeat revascularization avoided, and $433 000 per quality-adjusted life-year gained. CONCLUSIONS: In this prospective registry, a temporal reduction in DES use was associated with a small increase in target lesion revascularization and a modest reduction in total cardiovascular costs. These findings suggest that although clinical outcomes are marginally better with unrestricted DES use, this approach represents a relatively inefficient use of healthcare resources relative to several common benchmarks for cost-effective care.

Tissue characterisation of atherosclerotic plaque in the left main: an in vivo intravascular ultrasound radiofrequency data analysis.

AIMS: To characterise plaque phenotypes in the left main stem (LMS) and the proximal left anterior descending (LAD) coronary artery using virtual histology assisted intravascular ultrasound (VH-IVUS). METHODS AND RESULTS: Patients with IVUS pullbacks including no less than the proximal 30 mm of the LAD and through the ostium of the left main were identified from a global IVUS registry. Plaque composition and phenotype frequency in the LMS and five consecutive non-overlapping 6 mm segments in the LAD were studied, resulting in six analysed segments per patient. There were 74 patients (72% male, mean age 65 years). The median LMS length was 5.4 mm (IQR 2.8-8.7 mm). The percent of fibrofatty plaque was greater in the LMS compared to the proximal LAD segments (27.9% [20.0-39.2] vs. 17.3% [12.2-23.1], p<0.001). Dense calcium and necrotic core content was less prevalent in the LMS compared to the LAD segments (2.5% [0.9-4.7] vs. 7.9% [4.1-12.3], p<0.001; and 8.0% [3.7-11.8] vs. 14% [9.2-17.9], p<0.001). The frequency of thin cap fibroatheroma (TCFA) was higher in the LAD compared with LMS (0% vs. 16.9% [4.9-34.5], p<0.001). Within the LAD, TCFA was most frequently observed in the second 6 mm segment, 12 mm from the ostium. CONCLUSIONS: TCFA was present more frequently in the proximal LAD than LMS, supporting the notion that plaque rupture occurs in non-uniform locations throughout the coronary tree and preferentially spares the LMS.

Cardiovascular safety of liraglutide assessed in a patient-level pooled analysis of phase 2: 3 liraglutide clinical development studies.

We assessed the cardiovascular safety of liraglutide, a glucagon-like peptide-1 receptor agonist, using existing clinical data. Patient-level results from all completed phase 2 and 3 studies from the liraglutide clinical development programme were pooled to determine rates of major adverse cardiovascular events (MACE): cardiovascular death, myocardial infarction, stroke. MACE were identified by querying the study database using Medical Dictionary for Regulatory Activities (MedDRA) terms combined with serious adverse events recorded by study investigators. Broad, narrow, and custom groups of MedDRA queries were used. Candidate events from each query were independently adjudicated post hoc. In 15 studies (6638 patients; 4257 liraglutide treated), there were 114 patients with MACE identified using the broad MedDRA query. Of these, 44 were classified as serious adverse events and 39 were adjudicated as MACE. The incidence ratio for adjudicated broad/serious MACE associated with liraglutide was 0.73 (95% CI 0.38-1.41) versus all comparator drugs (metformin, glimepiride, rosiglitazone, insulin glargine, placebo), within cardiovascular safety limits defined by the United States Food & Drug Administration for diabetes therapies under current investigation.

Comparison of bleeding complications using arterial closure device versus manual compression by propensity matching in patients undergoing percutaneous coronary intervention.

Arterial closure devices (ACDs) provide immediate hemostasis, improve comfort, and allow early ambulation after percutaneous coronary intervention (PCI). The aim of this study was to evaluate ACD utilization and post-PCI major bleeding in an unselected cohort. Patients receiving ACDs were propensity matched to those with manual compression to evaluate a primary end point of National Cardiovascular Data Registry (NCDR) major bleeding and a secondary end point of major bleeding stratified by previously developed NCDR bleeding risk categories. Bleeding events that required transfusion, prolonged hospital stays, and/or decreases in hemoglobin ≥3.0 g/dl were included. Length of stay, defined as days after PCI until discharge, was also evaluated. Secondary analysis of bleeding and complication rates between ACD types (suture vs collagen plug) was performed. Five thousand four hundred twenty-one patients underwent PCI, and 2,324 patients (43%) were included in the final propensity matching: 1,162 with ACDs and 1,162 manual compression patients. Major bleeding was reduced in ACD patients compared to those with manual compression (2.4% vs 5.2%, p <0.001), and NCDR high-risk patients receiving ACDs had the greatest reduction in major bleeds (3.1% vs 10.3%, p <0.001). Length of stay (1.9 ± 1.9 vs 2.3 ± 5.3 days, p = 0.007) and pseudoaneurysms (0.3% vs 1.1%, p = 0.028) were decreased in ACD patients. Suture-based devices revealed a lower composite event rate than collagen-plug ACDs (1.4% vs 3.4%, p = 0.048). In conclusion, ACD use is associated with reductions in NCDR major bleeding, length of stay, and pseudoaneurysms in PCI patients.

In-hospital outcomes and cost comparison of femoropopliteal reopening strategies.

PURPOSE: Atherectomy has emerged as an alternative to percutaneous transluminal angioplasty (PTA) for endovascular reopening. Despite increasing use of atherectomy (and higher cost of atherectomy catheters compared with balloon catheters), few studies have compared outcomes and costs with other reopening strategies. METHODS: We performed a retrospective cohort study involving all patients undergoing isolated femoropopliteal PTA (n=69) or atherectomy (n=92) at our institution from 1/2005 to 4/2006. The choice of reopening strategy was left to the treating physician, and no patients with relative contraindications to stent placement (specifically common femoral artery lesions) were included. Device and supply costs were calculated using the hospital resource-based accounting system, and other costs were calculated using the hospital micro-cost accounting system. Professional fees were calculated from the Medicare Fee Schedule. RESULTS: Baseline characteristics were generally well matched. There were no significant differences in complications (vascular complications, urgent repeat reopening, death, myocardial infarction, or stroke) between groups (PTA 8.7% vs. atherectomy 5.4%, P=.53). PTA required more balloons (2.0±0.8 vs. 0.7±1.0, P<.001) and stents (1.5±0.8 vs. 0.2±0.5, P<.001), but fewer atherectomy catheters (0.0±0.0 vs. 1.2±0.4, P<.001). Neither procedural supply costs (PTA $3137±1459 vs. atherectomy $3338±1505, P=.20) nor total costs differed between PTA and atherectomy patients ($10,945±4521 vs. $10,783±3857, P=.42). CONCLUSIONS: Initial outcomes and costs are comparable for femoropopliteal PTA and atherectomy. The choice of reopening strategy should therefore be based on operator experience and anatomic suitability. Further studies are required to determine whether there are differences in long-term outcomes or costs between these approaches.

Predicting restenosis of drug-eluting stents placed in real-world clinical practice: derivation and validation of a risk model from the EVENT registry.

BACKGROUND: Prediction of restenosis after percutaneous coronary intervention (PCI) remains challenging, and existing risk assessment algorithms were developed before the widespread adoption of drug-eluting stents (DES). METHODS AND RESULTS: We used data from the EVENT registry to develop a risk model for predicting target lesion revascularization (TLR) in 8829 unselected patients undergoing DES implantation between 2004 and 2007. Using a split-sample validation technique, predictors of TLR at 1 year were identified from two thirds of the subjects (derivation cohort) using multiple logistic regression. Integer point values were created for each predictor, and the summed risk score (range, 0 to 10) was applied to the remaining sample (validation cohort). At 1 year, TLR occurred in 4.2% of patients, and after excluding stent thrombosis and early mechanical complications, the incidence of late TLR (more likely representing restenosis-related TLR) was 3.6%. Predictors of TLR were age <60, prior PCI, unprotected left main PCI, saphenous vein graft PCI, minimum stent diameter < or =2.5 mm, and total stent length > or =40 mm. Comparison of observed versus predicted rates of TLR according to risk score demonstrated good model fit in the validation set. There was more than a 3-fold difference in TLR rates between the lowest risk category (score=0; TLR rate, 2.2%) and the highest risk category (score > or =5; TLR rate, 7.5%). CONCLUSIONS: The overall incidence of TLR remains low among unselected patients receiving DES in routine clinical practice. A simple risk model incorporating 6 readily available clinical and angiographic variables helps identify individuals at extremely low (<2%) and modestly increased (>7%) risk of TLR after DES implantation.

The impact of bivalirudin on percutaneous coronary intervention-related bleeding.

AIMS: We studied the clinical and economic impact of bivalirudin in clinical practice. METHODS AND RESULTS: Consecutive patients undergoing PCI via the common femoral artery for stable, unstable, or atypical angina, silent ischaemia, or non-ST-elevation myocardial infarction indications during 2007-2008 were prospectively studied. In-hospital bleeding events were systematically assessed and classified as either major or minor. Use of bivalirudin, vascular closure devices, heparin and/or glycoprotein (GP) IIb/IIIa inhibitor was at the operator's discretion. Among 1,364 patients, 503 received bivalirudin and 861 received usual care consisting of either heparin monotherapy (n=687) or heparin+GP IIb/IIIa (n=174). Any post-PCI bleeding occurred in 356 (26.1%) patients, including 32 (2.3%) major and 324 (23.8%) minor events. Compared with usual care, bivalirudin was associated with reduced bleeding before adjustment (any: 17.3% vs. 31.2%, P<0.001; major: 1.2% vs. 3.0%, P=0.03; minor: 16.1% vs. 28.2%, P<0.01) and after propensity-matching (OR 0.46, 95% CI 0.34-0.63, P<0.001). Use of vascular closure devices was associated with an increase in any bleeding (32.2% vs. 17.7%, P<0.001), primarily due to an increase in minor bleeding (30.8% vs. 14.1%, P<0.001) while there was a significant decrease in major bleeding (1.4% vs. 3.7%, P=0.007). Bivalirudin was associated with total hospitalisation costs that were lower than usual care (mean cost savings, $463/patient; 95% CI 1,594 less to 621 more). CONCLUSIONS: In this prospective PCI cohort, bivalirudin was associated with reduced major and minor bleeding without a significant increase in hospital costs compared with other anticoagulation regimens. Closure device use was associated with decreased major but increased minor bleeding.

Bleeding in patients undergoing percutaneous coronary intervention: the development of a clinical risk algorithm from the National Cardiovascular Data Registry.

BACKGROUND: Bleeding in patients undergoing percutaneous coronary intervention (PCI) is associated with increased morbidity, mortality, length of hospitalization, and cost. We identified baseline clinical characteristics associated with bleeding complications after PCI and developed a simplified, clinically useful algorithm to predict patient risk. METHODS AND RESULTS: Data were analyzed from 302 152 PCI procedures performed at 440 US centers participating in the National Cardiovascular Data Registry. As defined by the National Cardiovascular Data Registry, bleeding required transfusion, prolonged hospital stay, and/or a drop in hemoglobin >3.0 g/dL from any location, including percutaneous entry site, retroperitoneal, gastrointestinal, genitourinary, and other/unknown location. Bleeding complications occurred in 2.4% of patients. From the best-fitting model consisting of 15 clinical elements associated with post-PCI bleeding in a random 80% training cohort, we developed a parsimonious risk algorithm. Predictors of bleeding included age, gender, previous heart failure, glomerular filtration rate, peripheral vascular disease, no previous PCI, New York Heart Association/Canadian Cardiovascular Society Functional Classification class IV heart failure, ST-elevation myocardial infarction, non-ST-elevation myocardial infarction, and cardiogenic shock. The parsimonious model was validated in the remaining 20% of the population (c-statistic, 0.72) and in clinically relevant subgroups of patients. This simplified model was used to derive a clinical risk algorithm, with larger numbers corresponding with greater risk. In 3 categories, bleeding rates were greater in patients with higher estimates (or=18, 5.1%). CONCLUSIONS: This report identifies baseline clinical factors associated with bleeding and proposes a clinically useful algorithm to estimate bleeding risk. This model is potentially actionable in altering therapeutic decision making and improving outcomes in patients undergoing PCI.

Diabetes duration is associated with increased thin-cap fibroatheroma detected by intravascular ultrasound with virtual histology.

BACKGROUND: Coronary plaque classified as thin-cap fibroatheroma (TCFA) is believed to be associated with plaque rupture and coronary heart disease-related events. Although an association between duration of diabetes and increased coronary heart disease risk has been demonstrated, the relationship between TCFA and diabetes duration is unknown. METHODS AND RESULTS: Prospective registry of diabetic patients undergoing diagnostic coronary angiography and intravascular ultrasound (IVUS) enrolled in a diabetic gene and biomarker banking registry. Plaque composition in the most diseased 10-mm segment of a single coronary artery was assessed using IVUS virtual histology and was classified by phenotype as IVUS-defined adaptive intimal thickening, pathological intimal thickening, TCFA, fibroatheroma, or fibrocalcific. Patients (n=54) were stratified by duration of diabetes (<10 or > or = 10 years). Patients with diabetes > or = 10 years were older, less likely to have a history of tobacco use, had higher total cholesterol levels, and were more likely to be treated with insulin compared with patients with diabetes <10 years. Longer duration of diabetes was associated with greater plaque burden in the most diseased 10-mm segment (60.4% [53.4% to 66.8%] versus 50.2% [47.7% to 58.4%], P=0.008). The proportion of IVUS-defined TCFA in the > or = 10-year group was greater than the <10-year group (54.4% [11.6% to 77.5%] versus 10.8% [0.0% to 26.1%], P=0.009). This association persisted after adjustment for multiple comparisons, clinical characteristics, and diabetes treatment. CONCLUSIONS: In this cohort, longer duration of diabetes was associated with IVUS-defined TCFA, a plaque phenotype associated with risk of rupture and coronary heart disease events. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT00428961.

Prognostic impact of periprocedural bleeding and myocardial infarction after percutaneous coronary intervention in unselected patients: results from the EVENT (evaluation of drug-eluting stents and ischemic events) registry.

OBJECTIVES: Our aim was to examine the prognostic importance of hemorrhagic and ischemic complications after percutaneous coronary intervention (PCI) in unselected patients. BACKGROUND: In randomized trials of PCI, major bleeding and periprocedural myocardial infarction (pMI) have been associated with increased mortality. Whether similar associations exist among un-selected PCI patients is unknown. METHODS: We used data from the EVENT (Evaluation of Drug Eluting Stents and Ischemic Events) registry-a multicenter registry of unselected patients undergoing PCI-to examine the association between both in-hospital bleeding and pMI and 1-year mortality. Cardiac enzyme levels were assessed in all patients, and pMI was defined as a peak creatine kinase-MB value >or=3x the upper limit of normal. Post-PCI bleeding was classified by Thrombolysis In Myocardial Infarction criteria. RESULTS: After excluding patients with elevated pre-PCI creatine kinase-MB values and ST-segment elevation myocardial infarction at presentation (n = 1,626), a total of 5,961 patients were available for evaluation. Rates of post-PCI bleeding and pMI were 3.0% and 7.1%, respectively; 1-year all-cause mortality was 2.8%. After multivariable adjustment, both post-PCI bleeding (adjusted hazard ratio [HR]: 3.83, 95% confidence interval: 2.48 to 5.90, p < 0.001) and pMI (adjusted HR: 1.84, 95% confidence interval: 1.17 to 2.89, p = 0.009) were independently associated with 1-year mortality. Time period-specific analyses demonstrated that the adjusted HR for bleeding was similar for 30-day mortality and mortality between 1 month and 1 year, while the adjusted HR for pMI was greater for 30-day mortality as compared with mortality between 1 month and 1 year. CONCLUSIONS: Among unselected PCI patients, both post-PCI bleeding and pMI are independently associated with increased 1-year mortality. Continued efforts to reduce these complications after PCI are warranted.

Drug-eluting stents and the use of percutaneous coronary intervention among patients with class I indications for coronary artery bypass surgery undergoing index revascularization: analysis from the NCDR (National Cardiovascular Data Registry).

OBJECTIVES: Our purpose was to evaluate percutaneous coronary intervention (PCI) attempt rates in patients with class I indications for coronary artery bypass graft (CABG) surgery after the introduction of drug-eluting stents (DES). BACKGROUND: In patients with severe, multivessel coronary disease, CABG has historically been recommended over PCI. Practice guidelines for CABG were last updated before the emergence of data on DES efficacy. METHODS: We analyzed 265,028 procedures from the NCDR (National Cardiovascular Data Registry) meeting American College of Cardiology/American Heart Association class I indications for surgical revascularization. Temporal trends in PCI attempt rates were analyzed during 3 consecutive time periods: pre-DES (before April 1, 2003), DES diffusion (April 1, 2003 to December 31, 2004), and DES (January 1, 2005 to September 30, 2006). RESULTS: The attempted rate of PCI in patients with class I indications for CABG increased over the 3 time periods (pre-DES: 29.4%, DES diffusion: 33.4%, and DES era: 34.7%, p < 0.001). In a hierarchical multivariable logistic model adjusting for patient and PCI site characteristics, PCI attempts were more likely in the DES compared with pre-DES era (odds ratio: 1.44, 95% confidence interval: 1.40 to 1.48) and the DES diffusion era (odds ratio: 1.20, 95% confidence interval: 1.17 to 1.23). PCI attempt rates increased in all 3 time periods, although the average rate of increase during the DES era was 0.6% per quarter compared with 0.3% per quarter for both the DES diffusion and the pre-DES eras (p = 0.03). CONCLUSIONS: DES use in clinical practice was associated with a significant overall increase in PCI to treat patients with class I indications for CABG. Long-term follow-up of this cohort of patients is warranted.

ST-Segment elevation acute myocardial infarction due to severe hypotension and proximal left subclavian artery stenosis in a prior coronary artery bypass graft patient.

Proximal subclavian artery stenosis may result in cardiac ischemia in coronary artery bypass graft patients with internal mammary grafts. We report a case of acute anterior myocardial infarction in such a patient who developed severe systemic hypotension. Symptoms and electrocardiographic changes resolved after proximal left subclavian artery stenting. Subclavian angiography should be considered in all prior coronary artery bypass graft patients with internal mammary grafts undergoing coronary angiography.

Evaluation of coronary artery calcium screening strategies focused on risk categories: the Dallas Heart Study.

BACKGROUND: A strategy using coronary artery calcium (CAC) screening to refine coronary heart disease risk assessment in moderately high risk (MHR) subjects (10-year risk 10%-20%) has been suggested. The potential impact of this strategy is unknown. METHODS: Coronary artery calcium screening strategies focused on MHR subjects were modeled in 2,610 subjects aged 30 to 65 years undergoing Framingham risk scoring and CAC assessment in the Dallas Heart Study. The proportions of subjects eligible for imaging and reclassified from MHR to high risk (HR) (10-year risk >20%) based upon CAC scores were determined. RESULTS: Only 1.0% of women and 15.4% of men were at MHR by Framingham risk scoring and thus eligible for imaging, and <0.1% and 1.1% respectively, changed from MHR to HR using a CAC threshold > or = 400. Coronary artery calcium imaging targeting MHR subjects was also relatively inefficient (>100 women, 14.3 men scanned per subject reclassified). Restricting to an older age range (45-65 years) or expanding the MHR group to 6% to 20% risk had virtually no impact on risk assessment in women. In a secondary analysis, a proposed imaging strategy targeting promotion of subjects from lower risk to MHR was more efficient and had greater yield than current recommendations targeting promotion from MHR to HR. CONCLUSIONS: Coronary artery calcium screening strategies focused on MHR subjects will have a negligible impact on risk assessment in women and a modest impact in men. Further studies are needed to optimize the use of CAC screening as an adjunct to coronary heart disease risk assessment, especially for women and those at seemingly lower risk.

Association between circulating soluble receptor for advanced glycation end products and atherosclerosis: observations from the Dallas Heart Study.

OBJECTIVE: To determine the association between circulating soluble receptor for advanced glycation end products (sRAGE) and coronary atherosclerosis. RESEARCH DESIGN AND METHODS: Using data from the Dallas Heart Study, a probability-based population sample, the association between plasma levels of sRAGE and coronary artery calcium (CAC) was assessed among 2,571 subjects with complete imaging and sRAGE data. RESULTS: An inverse graded association was observed between sRAGE quartiles and CAC, with CAC prevalence of 28.5% in quartile 1 compared with 15.7% in quartile 4 (P < 0.0001). After multivariable adjustment, the associations between sRAGE levels in the first and second quartiles (versus fourth quartile) and CAC remained statistically significant (adjusted odds ratio 1.71 [95% CI 1.2-2.4] and 1.5 [1.0-2.1], respectively). CONCLUSIONS: sRAGE is a novel biomarker that is inversely associated with coronary atherosclerosis. The role of sRAGE in the pathobiology of atherosclerosis and its potential prognostic and therapeutic implications warrant further investigation.

Receptor for advanced glycation end-products (RAGE) and soluble RAGE (sRAGE): cardiovascular implications.

Disorders of glucose metabolism are associated with increased risk for cardiovascular disease (CVD) complications, including coronary, peripheral and cerebral arterial disease, that account for the majority of morbidity and mortality among patients with diabetes mellitus (DM). These associations between glucose and CVD risk extend continuously well below the glycaemic thresholds established for the diagnosis of diabetes, including significantly increased risk associated with impaired fasting glucose, impaired glucose tolerance, and even high normal glucose concentrations. While these epidemiological observations have established a clear association between cardiovascular disease and dysglycaemia and suggest a direct causal link, the mechanisms by which hyperglycaemia may contribute to the development, progression and instability of atherosclerosis remain unclear. A number of recent advances in the realm of vascular biology have identified several novel, plausible pathways that might link hyperglycaemia with atherosclerosis, individually or in aggregate. Key among them are the interaction between advanced glycation end-products (AGEs) and the receptor for AGEs (RAGE), which exists as a trans-membrane signalling receptor and as a circulating form, soluble RAGE (sRAGE). The purpose of this review is to provide an overview of the present understanding of RAGE and sRAGE, their plausible role linking perturbed glucose metabolism with the development, progression and instability of atherosclerosis, and the potential therapeutic implications of modulation of this biological system.