25/07/2010   From Vulnerable Plaque to Vulnerable Patient—Part III: Executive Summary of the Screening for Heart Attack Prevention and Education (SHAPE) Task Force Report   Screening for early-stage asymptomatic cancers (eg, cancers of breast and colon) to prevent late-stage malignancies has been widely accepted. However, although atherosclerotic cardiovascular disease (eg, heart attack and stroke) accounts for more death and disability than all cancers combined, there are no national screening guidelines for asymptomatic (subclinical) atherosclerosis, and there is no government- or healthcare-sponsored reimbursement for atherosclerosis screening. Part I and Part II of this consensus statement elaborated on new discoveries in the field of atherosclerosis that led to the concept of the “vulnerable patient.” These landmark discoveries, along with new diagnostic and therapeutic options, have set the stage for the next step: translation of this knowledge into a new practice of preventive cardiology. The identification and treatment of the vulnerable patient are the focuses of this consensus statement. In this report, the Screening for Heart Attack Prevention and Education (SHAPE) Task Force presents a new practice guideline for cardiovascular screening in the asymptomatic at-risk population. In summary, the SHAPE Guideline calls for noninvasive screening of all asymptomatic men 45–75 years of age and asymptomatic women 55–75 years of age (except those defined as very low risk) to detect and treat those with subclinical atherosclerosis. A variety of screening tests are available, and the cost-effectiveness of their use in a comprehensive strategy must be validated. Some of these screening tests, such as measurement of coronary artery calcification by computed tomography scanning and carotid artery intima–media thickness and plaque by ultrasonography, have been available longer than others and are capable of providing direct evidence for the presence and extent of atherosclerosis. Both of these imaging methods provide prognostic information of proven value regarding the future risk of heart attack and stroke. Careful and responsible implementation of these tests as part of a comprehensive risk assessment and reduction approach is warranted and outlined by this report. Other tests for the detection of atherosclerosis and abnormal arterial structure and function, such as magnetic resonance imaging of the great arteries, studies of small and large artery stiffness, and assessment of systemic endothelial dysfunction, are emerging and must be further validated. The screening results (severity of subclinical arterial disease) combined with risk factor assessment are used for risk stratification to identify the vulnerable patient and initiate appropriate therapy. The higher the risk, the more vulnerable an individual is to a near-term adverse event. Because <10% of the population who test positive for atherosclerosis will experience a near-term event, additional risk stratification based on reliable markers of disease activity is needed and is expected to further focus the search for the vulnerable patient in the future. All individuals with asymptomatic atherosclerosis should be counseled and treated to prevent progression to overt clinical disease. The aggressiveness of the treatment should be proportional to the level of risk. Individuals with no evidence of subclinical disease may be reassured of the low risk of a future near-term event, yet encouraged to adhere to a healthy lifestyle and maintain appropriate risk factor levels. Early heart attack care education is urged for all individuals with a positive test for atherosclerosis. The SHAPE Task Force reinforces existing guidelines for the screening and treatment of risk factors in younger populations. Cardiovascular healthcare professionals and policymakers are urged to adopt the SHAPE proposal and its attendant cost-effectiveness as a new strategy to contain the epidemic of atherosclerotic cardiovascular disease and the rising cost of therapies associated with this epidemic From SHAPE Task Force

 20/07/2010  New guideline advocates MRI over CT for stroke diagnosis   Erlangen, Germany - After reviewing the relevant literature, a panel of neurologists, neuroradiologists, and radiologists has concluded that diffusion-weighted imaging (DWI) MRI is superior to noncontrast CT scans, the current imaging standard, for diagnosing acute ischemic stroke within 12 hours of symptom onset [1]. But while the research shows that DWI is better than CT, the decision about which imaging test to use in clinical practice will depend on issues such as availability and cost, the panel concludes in the new guideline from the American Academy of Neurology. "The doctors taking care of acute-stroke patients as well as the patients themselves need to be aware that MRI-DWI is a superior diagnostic tool in acute stroke less than 12 hours [from symptom onset]," lead author Dr Peter Schellinger (University of Erlangen, Germany) said in an interview. "Whether this translates into a change in practice remains to be seen. Logistical, financial, and personnel requirements need to be weighed against better diagnosis, which—and this was not within the scope of our assessment—may influence management and ultimately the outcome of the stroke." The panel's recommendations are published in the July 13, 2010 issue of Neurology. For their review, the panel members addressed two questions: first, whether DWI and perfusion-weighted imaging (PWI) are sensitive and specific in the diagnosis of acute ischemic stroke compared with concurrent imaging with other techniques; and second, whether the volume of the DWI or PWI abnormality predicts initial clinical severity, final infarct size, and late clinical outcome. The panel performed a literature search of Medline, Embase, and Biosis up to January 2008. For the first question, the search was restricted to studies with a time window of 12 hours after symptom onset. For the second, the search was restricted to studies related to acute ischemic stroke less than 24 hours after symptom onset. One study, comparing the accuracy of MRI (DWI and gradient echo scans) vs CT in 356 consecutive possible stroke patients, found that in the subset of 221 patients scanned within 12 hours of symptom onset, the majority of blinded readers correctly diagnosed acute ischemic stroke by MRI more often than by CT (94 vs 22, p<0.0001). They added that the sensitivity, specificity, and accuracy of DWI in this study was 77%, 96%, and 86% respectively, compared with 16%, 97%, and 55% for CT. In a second study, of 50 patients with ischemic stroke and four with transient ischemic attacks (TIAs), patients were randomized to receive MRI or CT within six hours of stroke onset. Here again, the sensitivity of infarct detection was significantly better with DWI (91%) than CT (61%), as was the accuracy: DWI was 91%, and CT 61%. The panel concluded from this and the other evidence that DWI is superior to CT for the diagnosis of acute ischemic stroke within 12 hours of symptom onset. For the second question, the panel reviewed eight studies, ultimately concluding that baseline DWI volume probably predicts baseline clinical stroke severity and final lesion volume in anterior-circulation stroke syndromes and is possibly accurate in predicting clinical outcome. As well, the evidence showed that baseline DWI volume possibly does not predict the baseline National Institutes of Health Stroke Scale score in posterior circulation stroke syndromes. As for PWI, the panel concluded that there was insufficient evidence to support or refute the value of PWI in diagnosing acute ischemic stroke but said baseline PWI volume may be considered useful in predicting baseline clinical stroke severity. Prospective, well-designed studies are needed to investigate the diagnostic utility of PWI in acute stroke, according to the panel. When CT is best diagnostic tool Still, there are circumstances under which CT should remain the primary diagnostic tool, said Schellinger—for example, comatose patients, patients with MRI contraindications, and patients who are candidates for intravenous thrombolytic therapy with tPA. Here, a CT-based exclusion of intracranial hemorrhage is enough to make a treatment decision. Of note, a plain CT scan is usually performed faster than a multisequence MRI scan, noted Schellinger. "Loss of time from arrival at the hospital to initiation of thrombolytic therapy is associated with a loss of efficacy and reduction of chance for a good outcome and potentially also with a higher bleeding risk and therefore should be avoided by all means." In situations where CT was performed first—for example, in a candidate for thrombolysis—and diagnostic uncertainty remains, MRI may be performed in addition to CT after initiation of thrombolytic therapy to optimize diagnostic assessment, added Schellinger. A disadvantage of MRI imaging in acute stroke is its relatively high cost. According to Schellinger, superior technologists often cost more, although this study did not address cost implications of using MRI to diagnose stroke. "Our objective was an assessment; how and whether this is taken as a means to change ER practice and stroke care practice remains to be seen." Lack of availability Another perceived disadvantage of MRI is its lack of ready availability. "Many of the major stroke services in the US have implemented MRI as an emergency imaging tool," but not all, Schellinger said. "It is a question of dedication and also a question of whether stroke patients should be treated in stroke centers or not." Until now, noncontrast CT has been the diagnostic standard for acute stroke. "There was nothing else available, and it was clear pretty early that the most important differential diagnosis of acute ischemic stroke—for example, intracranial hemorrhage—can be detected by CT with a close to 100% sensitivity," explained Schellinger. "By deduction, it is assumed that a clear stroke syndrome that is not caused by hemorrhage likely is caused by ischemic stroke even if the CT does not show it." Best identification of early strokes Approached for a comment, Dr Gary Abrams (University of California, San Francisco), said the new guideline is "very timely and important," as therapeutic interventions for acute ischemic stroke continue to advance. The paper validates what most clinicians already know, that DWI is the most effective and sensitive way to diagnose an acute stroke and is superior to CT, said Abrams. "As we move forward in the future, this may be the way that we need to go in terms of best identification of early strokes and identifying the group that's most amenable to treatment." As well, the guideline begins to address the issue of PWI, added Abrams. "This is much less widespread in terms of availability and clinical impact, but it's important, and as the authors suggest, the combination of DWI and PWI may turn out to be the most effective way to understand what's going on in terms of diagnosis and prognosis in acute stroke." Source 1.Schellinger PD, Bryan RN, Caplan LR, et al. Evidence-based guideline: The role of diffusion and perfusion MRI for the diagnosis of acute ischemic stroke: Report of the Therapeutics and Technology Assessment Subcommittee of the American Academy of Neurology. Neurology 2010; 75:177-185. The Heart.org July 15, 2010

 19/07/2010   Healthy weight, rather than fitness, most important for preventing high blood pressure   Dallas, TX - Individuals who have a healthy body weight are more likely than those who are physically fit to have lower blood pressure, according to the results of a new study [1]. In a comparison of fitness vs fatness, body mass index (BMI) was more important than cardiorespiratory fitness for predicting systolic blood pressure, report researchers. "Our findings suggest that achieving normal-weight status should be the primary goal for hypertension prevention, and only modest levels of cardiorespiratory fitness are needed to obtain optimal blood pressure among individuals who are normal weight," write Dr Jennifer Chen (University of Texas Southwestern Medical Center, Dallas) and colleagues in the July issue of the American Heart Journal. The results are from the Cooper Center Longitudinal Study, an analysis of 35 061 patients presenting to a clinic for a comprehensive medical examination between 1990 and present. The purpose of the study was to analyze the relative importance of BMI and cardiorespiratory fitness on systolic blood pressure. Studies have shown that exercise and cardiorespiratory fitness are associated with lower hypertension risk, including reductions in systolic blood pressure of 3 or 4 mm Hg with exercise training. "A key unanswered question is whether hypertension prevention should be focused on weight control by any acceptable intervention, or whether cardiorespiratory fitness, independent of BMI, is a more important first target for prevention of hypertension," explain the researchers. In this cohort, consisting mainly of white men (average age, 46 years), normal-weight individuals had a mean systolic blood pressure 12 mm Hg lower than obese individuals (115 vs 127 mm Hg, p<0.001). In contrast, individuals with high levels of fitness, those in the highest quartile, had a 6 mm Hg lower systolic blood pressure than those least fit (119 vs 125 mm Hg, p<0.001). When assessing BMI and cardiorespiratory fitness concurrently, there was a significant increase in systolic blood pressure by BMI quartile for every level of fitness, including those with low and high levels of fitness. However, level of fitness was associated with blood pressure only in individuals with the lowest and highest BMI, not in women with BMIs of 21 to 27 kg/m2 or men with BMIs of 25 to 30 kg/m2 (BMI quartiles 2 and 3). The researchers point out that obesity might be such an important determinant of hypertension that the benefits of other lifestyle factors are not obtained until individuals get down to a healthy weight. They also note that the beneficial effects of exercise on blood pressure are modest in obese subjects because of the "competing effects of obesity on vascular and metabolic pathways," including the effects on arterial compliance, sympathetic activity, insulin sensitivity, vascular resistance, and release of endothelium-derived nitric oxide. Source 1. Chen J, Das S, Barlow CE, et al. Fitness, fatness, and systolic blood pressure: Data from the Cooper Center Longitudinal Study. Am Heart J 2010;160:166-170. The Heart.org July 19, 2010

 18/07/2010   Genotyping platelet funcion testing   New meta-analysis: CYP2C19*2 carriers at higher risks of events on clopidogrel Paris, France - A new meta-analysis has shown that carriers of the CYP2C19 loss-of-function gene variant do appear to have an excess risk of cardiovascular events and mortality on clopidogrel [1]. The meta-analysis also looked at the effect of proton-pump-inhibitor (PPI) use in clopidogrel-treated patients and found that the impact of these drugs was significantly influenced by baseline cardiovascular risk and was associated with an increased risk of events only in high-risk patients. The analysis, published in the July 6, 2010 issue of the Journal of the American College of Cardiology, was conducted by a team led by Dr Jean-Sebastien Hulot (Hôpital Pitié-Salpêtrière, Paris, France). Senior author Dr Gilles Montalescot (Hôpital Pitié-Salpêtrière) told heartwire that "we found that CYP2C19*2 carriage is associated with a higher risk of cardiovascular events, of stent thrombosis, and of death in clopidogrel-treated patients. It is thus becoming increasingly more difficult to ignore the potential of genetic testing." He added that the availability of a rapid and inexpensive genetic test is of the utmost importance. "CYP2C19 genotyping is currently available through a number of laboratories, but you usually have to wait several days to get the result. A quasi-immediate test will be required in the near future if we want to integrate such information in a viable therapeutic algorithm. A rapid and low-cost test that provides the genetic profile as fast as we get a troponin level will allow genotype-guided antiplatelet therapy." In the paper, the authors explain that clopidogrel is converted into its active metabolite by the CYP2C19 enzyme, but approximately 30% of the white population has one copy of the CYP2C19*2 allele, which is associated with reduced activity of this enzyme. Its activity can also be reduced by some PPIs. They note that exactly what effect genotype and PPI use has on patients taking clopidogrel is not known and that the many studies conducted have shown large variability in the results. They therefore decided to conduct a meta-analysis of studies looking at this issue. They identified 10 studies involving 11 959 patients that address the effect of the loss-of-function P450 2C19 gene on clinical events in patients taking clopidogrel, and 13 studies involving 48 674 patients on the use of PPIs. Genotype analysis In the genotype meta-analysis, they found that the 28% of patients who were carriers of the CYP2C19*2 allele had an increased risk for major adverse cardiovascular events (MACE), stent thrombosis, and death, compared with noncarriers. Patients who were homozygous for the CYP2C19*2 loss-of-function gene had a higher risk of events than those who were heterozygous. Montalescot told heartwire that "regarding the occurrence of MACE, there is a significantly higher risk in CYP2C19*2 homozygotes and a trend for a higher risk in CYP2C19*2 heterozygotes. Because these data were available in less than half of the included studies, it is likely that the power to detect a significant impact in CYP2C19*2 heterozygotes was insufficient. In line with this assumption, the risk in CYP2C19*2 carriers (homozygotes + heterozygotes) was significantly higher when assessed on the overall data from the 10 studies. However, we have to keep in mind that CYP2C19*2 heterozygotes contribute a very large proportion of this estimate. Also, our data show that the risk of stent thrombosis is significantly higher in both CYP2C19*2 homozygotes and heterozygotes." He added that it was "crucial" to ascertain a gene-dose effect because CYP2C19*2 heterozygotes represent 20% to 25% of the general population. "Whereas the data argue for a complete resistance profile in CYP2C19*2 homozygotes, CYP2C19*2 heterozygotes display a more intermediate response to clopidogrel, but this is still significantly worse than the one observed in wild-type patients." PPI data The PPI data showed that 42% of clopidogrel patients were taking a PPI and that the use of such a drug was associated with an increased risk of MACE and of mortality. However, the impact of PPI use was significantly influenced by the baseline cardiovascular risk and was significant only in high-risk patients. In patients with an annual rate of MACE below 10%, the odds ratio for an event associated with a PPI was 1.01; in patients with an annual rate of MACE higher than 10%, the odds ratio associated with PPI use was 1.49. Montalescot said: "We were unable to find any significant interaction in low-risk patients, so there is no obvious reason to restrain PPI use in these patients. However, in a high-risk patient, PPI use will have a higher thrombotic risk than in a similar high-risk patient not taking a PPI." He explained that when thinking about prescribing a PPI, consideration needs to be given to whether patients have risk factors for thrombosis or bleeding. Whereas some risks factors are common to both (eg, age), others are specific for one or the other. For example, both a previous episode of stent thrombosis and a previous MI are strong predictors of further ischemic events, whereas a history of bleeding or GI ulcer is a major predictor of bleeding, he added. Sources 1. Hulot JS, Collet JP, Silvain J, et al. Cardiovascular risk in clopidogrel-treated patients according to cytochrome P450 2C19*2 loss-of-function allele or proton pump inhibitor co-administration. A systematic meta-analysis. J Am Coll Cardiol 2010; 56:134-143. 2. Damani SB, Topol EJ. The case for routine genotyping in dual-antiplatelet therapy. J Am Coll Cardiol 2010; 56:109-111. 3. Gurbel PA, Tantry US, Shuldiner AR, Kereiakes DJ. Genotyping: One piece of the puzzle to personalize antiplatelet therapy. J Am Coll Cardiol 2010; 56:112-116. THE HEART.ORG JULY 5, 2010

 06/07/2010   Flavanols Improve Endothelial Function and Mobilize Endothelial Progenitor Cells   Dietary flavanols can improve endothelial dysfunction, but the mechanism is not understood. Heiss and colleagues hypothesized that the mechanism would involve circulating angiogenic cells (CACs), also termed endothelial progenitor cells, which are critical for vascular repair and maintenance of endothelial function. In a randomized, cross-over trial, 16 subjects with stable coronary artery disease received a high-flavanol supplement (HiFl) or nutrient-matched low-flavanol supplement (LoFl). Endothelium-dependent vasomotor function, as measured by flow-mediated vasodilation, improved by 47% in the HiFl period compared with LoFl. Following HiFl, the number of CD34/KDR-CACs increased 2.2-fold. Sustained improvements in endothelial dysfunction by regular dietary intake of flavanols are associated with mobilization of functional CACs JOURNAL of the AMERICAN COLLEGE of CARDIOLOGY, VOLUME 56, NO.3 JULY, 13, 2010

 30/06/2010   Cardiovascular disease (CVD)in women  Cardiovascular disease (CVD) -- including coronary heart disease, heart failure, and stroke -- is the leading cause of death for women. Unfortunately, only 1 in 5 physicians are aware that more women than men die of CVD each year. These gaps in knowledge ultimately translate into gaps in care and disparities in outcomes which are more pronounced in African American women. The underrepresentation of women and minorities in clinical trials and the lack of race-specific and sex-specific reporting of findings compound the problem. (TheHeart.org)

 30/06/2010   Screening Asymptomatic Subjects for Subclinical Atherosclerosis   Unheralded vaso-occlusive cardiovascular events (myocardial infarction, sudden death, and stroke) are commo ifestations of atherothrombotic vascular disease, and accurate identification of individuals at risk of such even highly desirable. Risk factor assessment and management have been the cornerstones of preventive strategie are constrained by less than desirable accuracy and less than optimal compliance, respectively. In selected po tions, noninvasive imaging using carotid ultrasound and/or coronary calcium score can incrementally refine ris sessment and may allow for improved adherence and better matching of preventive interventions to the magn of risk. Further refinements in the future may also be possible with novel biomarkers and measures of plaque phenotype. (J Am Coll Cardiol 2010;56:98–105) © 2010 by the American College of Cardiology Foundation