INSIDE THIS ISSUE OF JACC
Inside This Issue of JACC
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Clinical Trials
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Proton Pump Inhibitors May Reduce the Efficacy of Clopidogrel.
Clopidogrel is a prodrug that must undergo several transformations before becoming metabolically active; one of the transformations utilizes the isoenzyme CYP2C19, which is also involved in the metabolism of several proton pump inhibitors (PPIs). Gilard and colleagues randomized post-percutaneous coronary intervention (PCI) patients receiving clopidogrel and aspirin to either omeprazole or placebo and assessed the efficacy of clopidogrel by measuring vasodilator-stimulated phosphoprotein phosphorylation. Omeprazole significantly decreased the antiplatelet effect of clopidogrel; subjects receiving omeprazole were twice as likely to be classified as non-responders. This study suggests a significant drug–drug interaction between omeprazole, and potentially other PPIs, and clopidogrel. The authors caution against the routine use of PPIs in post-PCI patients. See page 256. See figure.
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Coronary Heart Disease
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Impaired Fasting Glucose Increases Cardiovascular Risk in Women.
In 1997, the American Diabetes Association introduced the concept of impaired fasting glucose (IFG) for those with a fasting plasma glucose (FPG) level of 110 to 125 mg/dl. An FPG over 125 mg/dl defines diabetes. In 2003, the threshold for IFG was lowered to 100 mg/dl, but there is little known about the cardiovascular risk associated with either definition. Levitzky and colleagues used data collected from the Framingham Offspring Study to compare the two definitions for predicting medium-term (<4 year) cardiovascular risk. Neither IFG definition identified men at increased risk. In women, there was increased risk, especially in those with FPG >110 mg/dl. Women with an FPG of 110 to 125 mg/dl had similar cardiovascular risk as did women with diabetes. These results suggest that FPG >110 mg/dl identifies women at increased cardiovascular risk, whereas the threshold may be higher in men. See page 264.
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Coronary Heart Disease
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Ethanol Negates the Benefits of Ischemic Preconditioning.
Ischemic preconditioning is a phenomenon whereby repeated episodes of ischemia produce less negative effects. Niccoli and colleagues noted that in animal models, ethanol seems to abolish this effect, and so they studied it in humans. Thirty patients undergoing percutaneous coronary intervention underwent 2 episodes of occlusive intracoronary balloon inflations separated by 5 min; one-half of the subjects ingested 149 ml of Gordon’s Gin, approximately 5 oz, 30 min before the study. The control patients had less intracoronary ST-segment elevation during the second balloon inflation, whereas there was increased ischemia in those assigned to ethanol. This study confirms that ethanol negates the benefits of ischemic preconditioning. See page 271. See figure.
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Heart Rhythm Disorders
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Risk Stratification for Syncope.
Syncope accounts for 3% of all emergency department visits and 6% of hospital admissions, yet its prognosis and management varies widely. The STePS (Short-Term Prognosis of Syncope) study followed nearly 700 subjects who presented with syncope. Six percent of subjects experienced severe outcomes in the 10 days after presentation. Risk factors for short-term severe outcomes were an abnormal electrocardiogram, concomitant trauma, absence of symptoms of impending syncope, and male gender. Outcomes after the initial 10 days, but less then 1 year later, occurred in an additional 9% of patients. Risk factors for these events were age >65 years, history of neoplasms, cerebrovascular diseases, structural heart diseases, and ventricular arrhythmias. This study helps to identify patients with syncope who need more aggressive monitoring. See page 276.
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Heart Failure
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Elevated Abdominal Pressure Contributes to Renal Dysfunction During Heart Failure Decompensation.
Patients with decompensated heart failure may have elevated intra-abdominal pressure (IAP), but little is known about the hemodynamic effects of IAP or its effects on renal function. Mullens and colleagues measured IAP using a modified Foley catheter in patients with ejection fraction <30% admitted with decompensated heart failure. All subjects also had pulmonary artery catheters placed and were treated with diuresis and/or vasodilator therapy. Elevated IAP (>8 mm Hg) was directly associated with worse renal function; medical therapy improved both hemodynamic measurements and IAP. However, the reduction in IAP was a better predictor of improved renal function than any hemodynamic measurement. These results suggest that elevated IAP may be a significant component of the cardio-renal syndrome. See page 300. See figure.
Related Articles
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Influence of Omeprazole on the Antiplatelet Action of Clopidogrel Associated With Aspirin: The Randomized, Double-Blind OCLA (Omeprazole CLopidogrel Aspirin) Study
- Martine Gilard, Bertrand Arnaud, Jean-Christophe Cornily, Grégoire Le Gal, Karine Lacut, Geneviève Le Calvez, Jacques Mansourati, Dominique Mottier, Jean-François Abgrall, and Jacques Boschat
J. Am. Coll. Cardiol. 2008 51: 256-260.
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Impact of Impaired Fasting Glucose on Cardiovascular Disease: The Framingham Heart Study
- Yamini S. Levitzky, Michael J. Pencina, Ralph B. D’Agostino, James B. Meigs, Joanne M. Murabito, Ramachandran S. Vasan, and Caroline S. Fox
J. Am. Coll. Cardiol. 2008 51: 264-270.
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Ethanol Abolishes Ischemic Preconditioning in Humans
- Giampaolo Niccoli, Luca Altamura, Alessandro Fabretti, Gaetano A. Lanza, Luigi M. Biasucci, Antonio G. Rebuzzi, Antonio Maria Leone, Italo Porto, Francesco Burzotta, Carlo Trani, and Filippo Crea
J. Am. Coll. Cardiol. 2008 51: 271-275.
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Short- and Long-Term Prognosis of Syncope, Risk Factors, and Role of Hospital Admission: Results From the STePS (Short-Term Prognosis of Syncope) Study
- Giorgio Costantino, Francesca Perego, Franca Dipaola, Marta Borella, Andrea Galli, Giulia Cantoni, Simonetta Dell’Orto, Simonetta Dassi, Nicola Filardo, Pier Giorgio Duca, Nicola Montano, Raffaello Furlan on behalf of the STePS Investigators
J. Am. Coll. Cardiol. 2008 51: 276-283.
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Elevated Intra-Abdominal Pressure in Acute Decompensated Heart Failure: A Potential Contributor to Worsening Renal Function?
- Wilfried Mullens, Zuheir Abrahams, Hadi N. Skouri, Gary S. Francis, David O. Taylor, Randall C. Starling, Emil Paganini, and W.H. Wilson Tang
J. Am. Coll. Cardiol. 2008 51: 300-306.
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Clinical Trials
Coronary Heart Disease
