INSIDE THIS ISSUE OF JACC
Inside This Issue of JACC
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Interventional Cardiology
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DES Reduce Mortality Compared to BMS, Even When Used "Off-Label".
The indications approved by the Food and Drug Administration for drug-eluting stents (DES), based on the inclusion/exclusion criteria of randomized trials, only include patients with a single de novo native coronary artery lesion <30 mm in length, a left ventricular ejection fraction 
25%, and no myocardial infarction (MI) within 7 days of the procedure. Applegate and colleagues compared outcomes in almost 3,000 patients with either bare-metal stent (BMS) or DES and stratified by whether or not their use should be considered "off-label." At 2 years, the hazard ratio for DES compared to BMS for nonfatal MI or death was 0.77 for all patients. For "off-label" stent procedures this hazard ratio was 0.78, and for all-cause mortality it was 0.72. In this study, the use of DES for "off-label" indications was associated with similar nonfatal MI and death at 2 years than in a comparable group of patients treated with BMS. See page 607. See figure.
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Interventional Cardiology
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SES Superior to BMS for STEMI.
Van der Hoeven and colleagues randomized >300 ST-segment elevation myocardial infarction (STEMI) patients to either sirolimus-eluting stents (SES) or bare-metal stents (BMS), with intravascular ultrasound follow-up at 9 months, and clinical events follow-up 1 year. Late lumen loss and target vessel revascularization were significantly reduced with SES. However, late stent malapposition (LSM), defined as a separation of at least one stent strut from the intimal surface with blood flow behind the strut, developed in 25% of SES patients versus only 5% of BMS patients. Rates of death, myocardial infarction and stent thrombosis were not different. SES implantation in STEMI patients results in improved mid-term clinical and angiographic outcomes compared to treatment with BMS; however, LSM raises concern about the future risk of stent thrombosis. See page 618.
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Coronary Artery Disease
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Large HDL Particles May Increase Cardiac Risk.
Increased plasma high-density lipoprotein cholesterol (HDL-C) is generally associated with decreased cardiac risk, but recent studies evaluating the effect of potent HDL-C increases through torcetrapib did not demonstrate clinical benefit. van der Steeg and colleagues therefore studied the relationship between HDL-C, high-density lipoprotein (HDL) particle size and apolipoprotein A-I (apoA-I) concentrations and cardiac events in two large datasets, with a particular focus on those subjects with very high values of these parameters. When levels of apolipoprotein B and apoA-I were adjusted for, very high values of HDL-C (>70 mg/dl) and HDL particle size (>9.5 nm) were associated with increased risk of coronary artery disease. These results suggest that large HDL particles increase cardiac risk, possibly by serving as cholesterol donors rather than scavengers. See page 634. See figure.
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Preclinical Research
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Early Versus Late Endothelial Progenitor Cells.
The identity, origin, and function of endothelial progenitor cells (EPCs) remains debated. There appear to be two different times when EPCs appear in culture: early EPCs and late-outgrowth endothelial cells (OECs). Early EPCs, which appear in culture after 4 to 7 days, have been used for therapeutic studies. The OECs appear much later in culture, after 14 to 21 days. Sieveking and colleagues developed an assay to functionally characterize the angiogenic properties of these 2 cell types. The OECs formed branched, interconnecting tubules, and responded appropriately to known pro- and antiangiogenic agents. In contrast, early EPCs failed to independently form tubules or incorporate into differentiated EC tubules. Nevertheless, early EPCs augmented tubulogenesis via a paracrine mechanism. These results suggest that early EPCs augment angiogenesis while late OECs directly participate in tubulogenesis. See page 660.
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"Off-Label" Stent Therapy: 2-Year Comparison of Drug-Eluting Versus Bare-Metal Stents
- Robert J. Applegate, Matthew T. Sacrinty, Michael A. Kutcher, Renato M. Santos, Sanjay K. Gandhi, Talal T. Baki, and William C. Little
J. Am. Coll. Cardiol. 2008 51: 607-614.
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Sirolimus-Eluting Stents Versus Bare-Metal Stents in Patients With ST-Segment Elevation Myocardial Infarction: 9-Month Angiographic and Intravascular Ultrasound Results and 12-Month Clinical Outcome: Results From the MISSION! Intervention Study
- Bas L. van der Hoeven, Su-San Liem, J. Wouter Jukema, Navin Suraphakdee, Hein Putter, Jouke Dijkstra, Douwe E. Atsma, Marianne Bootsma, Katja Zeppenfeld, Pranobe V. Oemrawsingh, Ernst E. van der Wall, and Martin J. Schalij
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High-Density Lipoprotein Cholesterol, High-Density Lipoprotein Particle Size, and Apolipoprotein A-I: Significance for Cardiovascular Risk: The IDEAL and EPIC-Norfolk Studies
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J. Am. Coll. Cardiol. 2008 51: 634-642.
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Strikingly Different Angiogenic Properties of Endothelial Progenitor Cell Subpopulations: Insights From a Novel Human Angiogenesis Assay
- Daniel P. Sieveking, Andrew Buckle, David S. Celermajer, and Martin K.C. Ng
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Interventional Cardiology
Interventional Cardiology
