<?xml version="1.0" encoding="utf-8"?>
<recommendedContent xmlns="http://api.mspoke.com">
    <recommendedItem id="20100101_19_391"
                     title="Rare Genetic Deletion Linked to Morbid Obesity (CME/CE)"
                     score="0.009"
                     href="http://www.medpagetoday.com/Genetics/GeneralGenetics/tb/18286?impressionId=1265805424945"
                     
      &lt;p&gt;Missing sections of DNA may have a powerful impact on weight for a small segment of the population, researchers said.&lt;/p&gt;
&lt;p&gt;Nearly all teens and adults found to have a particular deletion of roughly 30-genes on chromosome 16p11.2 were obese  --  most morbidly so  --  with a body mass index of at least 40 kg/m&lt;sup&gt;2&lt;/sup&gt;, Philippe Froguel, MD, PhD, of Imperial College London, and colleagues reported in &lt;em&gt;Nature&lt;/em&gt;.&lt;/p&gt;
&lt;p&gt;While the variant appeared to explain only a small proportion of morbid obesity  --  0.7% in the study population  --  it was never present in healthy, normal-weight controls.&lt;/p&gt;
&lt;p&gt;&quot;Although the recent rise in obesity in the developed world is down to an unhealthy environment, with an abundance of unhealthy food and many people taking very little exercise, the difference in the way people respond to this environment is often genetic,&quot; Froguel said in a prepared statement.&lt;/p&gt;
&lt;p&gt;But with further findings like these, it may be possible to identify such individuals through genetic testing, he said.&lt;/p&gt;
&lt;p&gt;If so, &quot;We can then offer them appropriate support and medical interventions, such as the option of weight-loss surgery, to improve their long-term health,&quot; Froguel declared.&lt;/p&gt;
&lt;p&gt;Although researchers speculate that one in 20 cases of obesity may have a genetic cause, the genetic component remains largely elusive.&lt;/p&gt;
&lt;p&gt;Even accounting for such a small fraction of cases, the newly discovered 16p11.2 variant would be the second most frequent known genetic cause of obesity, Froguel&apos;s group said.&lt;/p&gt;
&lt;p&gt;Extensive genome-wide association studies have linked numerous single nucleotide polymorphisms (SNPs) to obesity, but added all together they account for only a small fraction of the known heritable component, the researchers said.&lt;/p&gt;
&lt;p&gt;&quot;The &apos;common disease, common variant&apos; hypothesis is increasingly coming under challenge,&quot; they wrote.&lt;/p&gt;
&lt;p&gt;Their team first identified the genetic deletion in teen and adults with learning difficulties or delayed development.&lt;/p&gt;
&lt;p&gt;Because the 31 individuals who had the nearly identical deletions of at least 593 kilobases at chromosome 16p11.2 in one copy of their DNA all had a BMI of over 30 kg/m&lt;sup&gt;2&lt;/sup&gt;, the researchers decided to dig a little deeper.&lt;/p&gt;
&lt;p&gt;&quot;Cohorts with extreme phenotypes that include obesity may be enriched for rare but very potent risk variants,&quot; making them easier to discover, they wrote.&lt;/p&gt;
&lt;p&gt;So they undertook a case-control study among 312 patients at three centers in Britain and France who presented with congenital malformations, developmental delay, or both, in addition to obesity.&lt;/p&gt;
&lt;p&gt;The same deletions were seen in 2.9% of these individuals.&lt;/p&gt;
&lt;p&gt;The function of the missing genes are not well known, but some have previously been associated with delayed development, autism, and schizophrenia.&lt;/p&gt;
&lt;p&gt;Notably, though, the frequency of deletion of these genes in the obese case-control cohort was &quot;appreciably higher&quot; than the less than 1% seen in the autism and other studies that didn&apos;t include obesity as an inclusion criteria, the researchers said.&lt;/p&gt;
&lt;p&gt;A second independent survey of genetic data at eight cytogenetic centers in France, Switzerland, and Estonia turned up a 0.6% rate among 3,947 people with developmental delay, malformations, or both, but who were not selected for obesity (&lt;em&gt;P&lt;/em&gt;=0.00022 versus the cohort selected for obesity).&lt;/p&gt;
&lt;p&gt;Analysis of those with the missing genes revealed an age-dependent link to weight: All four teens and adults were obese. Children were often obese (four of 15) or overweight (two of 15). Children under 2 years all had normal weight.&lt;/p&gt;
&lt;p&gt;So to see whether the deletion was independent of neurodevelopmental problems, Froguel&apos;s group examined genome-wide association study data from general population cohorts totaling 11,856 individuals along with 2,772 from childhood obesity and adult morbid obesity case-control studies, 931 in an extreme early-onset obesity study, and 141 who had bariatric weight-loss surgery.&lt;/p&gt;
&lt;p&gt;All adult carriers of the deletion were obese with the exception of one who was apparently diabetic. Each of the seven children and adolescents who carried the variant had a BMI in the top 0.1% for their age and gender.&lt;/p&gt;
&lt;p&gt;None had any reported developmental or cognitive problems. Four had reported hyperphagia with excessive hunger and food intake.&lt;/p&gt;
&lt;p&gt;Altogether, the 16p11.2 deletions predicted 29.8-fold elevated risk of obesity (&lt;em&gt;P&lt;/em&gt;=0.00000058) and 43.0-fold elevated risk of morbid obesity (&lt;em&gt;P&lt;/em&gt;=0.000000064) compared with lean or normal weight.&lt;/p&gt;
&lt;p&gt;By extrapolation, the researchers extrapolated that about 0.4% of all morbidly obese cases are attributable to an inherited 16p11.2 deletion, with 0.3% arising from a de novo deletion in the same genetic region.&lt;/p&gt;
&lt;p&gt;&quot;Although they may be heterogeneous in nature, these deletions are highly likely to be the causal variants,&quot; they wrote.&lt;/p&gt;
&lt;div style=&quot;float:left;border-style:solid;border-width:1px;border-color:#8dabbc;font-family:arial;font-size:12px;background-color:#DBE9F2;padding:5px;&quot;&gt;&lt;p&gt;The study was supported by &quot;Le Conseil Regional Nord Pas de Calais/FEDER&quot; along with various governmental and industry supporters for the various component studies.&lt;/p&gt;&lt;p&gt;The researchers reported no financial conflicts of interest.&lt;/p&gt;&lt;/div&gt;&lt;div style=&quot;clear:both;&quot;&gt;&lt;/div&gt;
    </recommendedItem>
    <recommendedItem id="20100101_19_352"
                     title="ICAO: Future Chronic Disease Risk Goes Beyond BMI (CME/CE)"
                     score="0.007"
                     href="http://www.medpagetoday.com/Endocrinology/Diabetes/tb/18233?impressionId=1265805424945"
                     
      When it comes to predicting chronic disease, body mass index doesn&apos;t tell the whole story, according to a population-based study that found elevated risk with obesity and other metabolic risk factors independently.&lt;br&gt;
&lt;br&gt;Metabolically-healthy obese people tended toward being at least twice as likely to develop multiple metabolic risk factors and diabetes as healthy, normal weight individuals over the subsequent 3.5 years of a study led by Sarah Appleton, a postgraduate student at the University of Adelaide, Australia.&lt;br&gt;
&lt;br&gt;However, normal weight individuals with metabolic risk factors  --  a group the researchers called &quot;metabolically obese&quot;  --  were at greater risk, she told attendees at the International Congress on Abdominal Obesity in Hong Kong, a conference sponsored by the International Chair on Cardiometabolic Risk.&lt;br&gt;
&lt;br&gt;Overall, just 4.1% of the 3,743 adults in the population-based, North West Adelaide Health Study were in the normal body mass index range at baseline but had at least two of the following metabolic risk factors:&lt;ul&gt; &lt;li&gt;Triglyceride levels of 1.7 mmol/L or greater&lt;/li&gt; &lt;li&gt;HDL cholesterol under 1.0mmol/L for men or 1.3 mmol/L for women&lt;/li&gt; &lt;li&gt;Blood pressure of 130/85 mm Hg or higher&lt;/li&gt; &lt;li&gt;A fasting plasma glucose of at least 5.6mmol/L or self-reported diabetes&lt;/li&gt; &lt;li&gt;Treatment for any of these disorders &lt;/li&gt; &lt;/ul&gt;
&lt;p&gt;Although free of cardiovascular disease when they entered the study through a random population sample of the northwest region of Adelaide, after a mean of 3.5 years of follow-up, this group was 2.48 times at risk of incident cardiovascular disease or stroke events (95% CI 1.1 to 5.4).&lt;/p&gt;
&lt;p&gt;Compared with metabolically-healthy, normal weight individuals, those with metabolic risk factors tended to be&lt;strong&gt; &lt;/strong&gt;3.27 times as likely to develop diabetes (&lt;em&gt;P&lt;/em&gt;=0.07).&lt;/p&gt;
&lt;p&gt;Identifying these individuals for prevention efforts may require less emphasis on BMI and increased surveillance of central obesity in primary care, the researchers told the congress.&lt;/p&gt;
&lt;p&gt;&quot;The problem with BMI is it doesn&apos;t tell you where the fat is,&quot; Appleton added in an interview. &quot;Visceral fat is really bad for you.&quot;&lt;/p&gt;
&lt;p&gt;Obese individuals without multiple metabolic risk factors at baseline comprised a larger group (12.1%).&lt;/p&gt;
&lt;p&gt;They were more likely to be middle age, live in a disadvantaged neighborhood, have smoked at some point, and get less exercise than their metabolically similar, but slimmer peers.&lt;/p&gt;
&lt;p&gt;Over the subsequent 3.5 years, they were 2.82 times more likely to develop more than one metabolic risk factor than metabolically-healthy, normal weight individuals (95% CI 2.0 to 4.0).&lt;/p&gt;
&lt;p&gt;The metabolically-normal obese also tended to be 2.36 times more likely to develop diabetes (95% CI 0.8 to 7.1). On the other hand, their risk of cardiovascular disease wasn&apos;t elevated, &quot;which likely related to the younger age of that group,&quot; Appleton told &lt;em&gt;MedPage Today&lt;/em&gt;.&lt;/p&gt;
&lt;p&gt;Notably, abdominal obesity as determined by a waist circumference of 80 cm and over for men or 95 cm and greater for women was 6.1 times more likely among metabolically healthy individuals if their BMI was in the obese versus normal range.&lt;/p&gt;
&lt;p&gt;But those who were in the normal BMI range were 2.2-fold more likely to be overweight or obese according to waist circumference if they had metabolic risk factors, which was statistically significant as well and likely contributed to the health risks they faced over the short-term future, Appleton said.&lt;/p&gt;
&lt;p&gt;Maintenance of metabolic health in the obese population was more likely for younger individuals (OR 2.83 for age 40 or younger, 95% CI 1.1 to 7.6) and those who were at least moderately physically active (OR 2.04, 95% CI 1.01 to 4.1).&lt;/p&gt;
&lt;p&gt;Appleton noted that these findings generally fit with data from the U.S. National Health Assessment Survey and Examination.&lt;/p&gt;
&lt;p&gt;Regardless of whether patients have abdominal obesity, BMI obesity, or other metabolic risk factors, the solution is likely similar  --  improved diet and exercise, she said.&lt;/p&gt;
&lt;div style=&quot;float:left;border-style:solid;border-width:1px;border-color:#8dabbc;font-family:arial;font-size:12px;background-color:#DBE9F2;padding:5px;&quot;&gt;&lt;p&gt;The study was supported by the University of Adelaide and the South Australian Department of Health.&lt;/p&gt;&lt;p&gt;Appleton reported no conflicts of interest.&lt;/p&gt;&lt;/div&gt;&lt;div style=&quot;clear:both;&quot;&gt;&lt;/div&gt;
    </recommendedItem>
    <recommendedItem id="20100101_19_311"
                     title="Long QT Syndrome Diagnosis Aided by Standing ECG (CME/CE)"
                     score="0.002"
                     href="http://www.medpagetoday.com/Cardiology/Arrhythmias/tb/18178?impressionId=1265805424945"
                     
      A brief acceleration of the heart rate when a patient stands up quickly may help diagnose long QT syndrome, researchers found.&lt;br&gt;
&lt;br&gt;The sudden movement provokes a short-lived tachycardia, which allows documentation of the characteristic QT prolongation on the electrocardiogram of affected patients, according to Sami Viskin, MD, of Tel-Aviv Medical Center in Israel, and colleagues.&lt;br&gt;
&lt;br&gt;The response of the QT interval to this tachycardia induced by this simple maneuver was a shortening by 21 ms in normal individuals, on average, compared with an average increase of 4 ms in long QT patients (&lt;em&gt;P&lt;/em&gt;&amp;lt;0.001), Viskin&apos;s group reported online in the &lt;em&gt;Journal of the American College of Cardiology&lt;/em&gt;.&lt;br&gt;
&lt;br&gt;Adding the test to routine ECG evaluation improved diagnostic ability in the study, they concluded.&lt;br&gt;
&lt;br&gt;&quot;This is a very simple maneuver that anyone can do that will help diagnose patients with long QT,&quot; Douglas Zipes, MD, of Indiana University, a past president of the ACC, told &lt;em&gt;MedPage Today&lt;/em&gt;.&lt;p&gt;&lt;/p&gt;
&lt;p&gt;Other diagnostic methods to provoke arrhythmia in diagnostic workup of long QT syndrome include an exercise test on the treadmill or infusion of a drug such as epinephrine, although ultimately a genetic test is often conducted.&lt;/p&gt;
&lt;p&gt;Zipes agreed with the researchers that &quot;you don&apos;t hang everything on this  --  this is simply something that you add to your overall evaluation of the potential long QT patient.&quot;&lt;/p&gt;
&lt;p&gt;But patients with long QT shouldn&apos;t be concerned that standing will bring on arrhythmia, Zipes cautioned. &quot;I don&apos;t think there&apos;s any danger in that,&quot; he said.&lt;/p&gt;
&lt;p&gt;The study included 68 patients with definite or highly probable long QT syndrome (46% with the LQT1 mutation, 41% with the LQT2 mutation, 4% with the LQT3 mutation, and 9% unsuccessfully genotyped). Testing was conducted 26 to 30 hours after the last dosage of beta-blockers for any patients taking them.&lt;/p&gt;
&lt;p&gt;Another 82 similarly-aged, healthy volunteers and asymptomatic relatives of long QT patients without familial mutation were included as controls. None was using medications.&lt;/p&gt;
&lt;p&gt;All had a baseline ECG while lying down for 10 minutes and, while still hooked up for continuous recording, were then asked to get up quickly and stand still for five minutes.&lt;/p&gt;
&lt;p&gt;The researchers found a similar acceleration in heart rate upon standing in the two groups.&lt;/p&gt;
&lt;p&gt;But the response of the QT interval differed during maximal sinus tachycardia for long QT syndrome patients and controls.&lt;/p&gt;
&lt;p&gt;Among controls, 59% had a shortening of at least 20 ms in their QT interval, while 39% had less than a 20 ms change, and only 2% had an increase of at least 20 ms.&lt;/p&gt;
&lt;p&gt;Among long QT cases, just 24% had a drop in QT interval while 34% had an increase (&lt;em&gt;P&lt;/em&gt;&amp;lt;0.001 versus controls). The remainder were unchanged.&lt;/p&gt;
&lt;p&gt;The QTc interval was already different between groups at baseline. But the difference increased during standing &quot;since the QT interval decreased less than the RR interval during standing-induced tachycardia.&quot;&lt;/p&gt;
&lt;p&gt;The QTc interval increased during maximal tachycardia by only 50 ms (13% from baseline) in controls, compared with 89 ms (20% from baseline) in long QT patients (&lt;em&gt;P&lt;/em&gt;&amp;lt;0.001).&lt;/p&gt;
&lt;p&gt;At the point of maximal QT interval stretching, the QTc interval rose by 54 ms in controls, versus 94 ms in affected patients (&lt;em&gt;P&lt;/em&gt;&amp;lt;0.001).&lt;/p&gt;
&lt;p&gt;Even after excluding long QT syndrome patients with &quot;very long&quot; baseline QT intervals or unknown genotype, the differences between controls and cases were statistically significant.&lt;/p&gt;
&lt;p&gt;The effect was particularly apparent in patients with the LQT2 mutation.&lt;/p&gt;
&lt;p&gt;Area under the receiver-operating characteristic curves showed incremental diagnostic value to the test, the researchers said.&lt;/p&gt;
&lt;p&gt;In one analysis, these curves of QT and QTc intervals at maximal heart rate showed significantly better diagnostic accuracy than those at baseline (&lt;em&gt;P&lt;/em&gt;=0.008 and &lt;em&gt;P&lt;/em&gt;=0.026, respectively).&lt;/p&gt;
&lt;p&gt;The authors noted that some individuals in the control group had QT interval stretching in response to standing similar in magnitude to those with long QT syndrome.&lt;/p&gt;
&lt;p&gt;While these &quot;outliers&quot; might represent false positives with the standing test, the investigators suggested further research to examine whether they might have repolarization reserve abnormalities.&lt;/p&gt;
&lt;p&gt;&quot;Accurate diagnosis of the long QT syndrome is crucial because this is a potentially lethal disorder for which effective therapy exists,&quot; Viskin&apos;s group wrote.&lt;/p&gt;
&lt;p&gt;They cautioned that baseline T-wave morphology and QT interval may have unblinded the investigator in some cases, leading to the possibility of biased measurements.&lt;/p&gt;
&lt;p&gt;They also warned against overinterpreting the standing test results in isolation.&lt;/p&gt;
&lt;p&gt;Another technical issue to be aware of is that movement may create an artifact in the ECG, so making sure patients stand very still after rising would be important, Zipes added.&lt;/p&gt;
&lt;div style=&quot;float:left;border-style:solid;border-width:1px;border-color:#8dabbc;font-family:arial;font-size:12px;background-color:#DBE9F2;padding:5px;&quot;&gt;&lt;p&gt;The study was supported by a grant from by the Netherlands Heart Foundation. The researchers provided no information on conflicts of interest.&lt;/p&gt;&lt;p&gt;Zipes reported no relevant conflicts of interest.&lt;/p&gt;&lt;/div&gt;&lt;div style=&quot;clear:both;&quot;&gt;&lt;/div&gt;
    </recommendedItem>
    <recommendedItem id="20100101_19_207"
                     title="ISET: Women Fare Better in Small Leg Vessel Procedures (CME/CE)"
                     score="-0.005"
                     href="http://www.medpagetoday.com/Cardiology/PeripheralArteryDisease/tb/18051?impressionId=1265805424945"
                     
      &lt;p&gt;HOLLYWOOD, Fla.  --  Contrary to expectations, women who undergo last-ditch, minimally-invasive procedures to open small blood vessels in the leg  --  and forestall amputation  --  generally have better outcomes than men, researchers reported here.&lt;/p&gt;
&lt;p&gt;Overall, 87.5% of women who underwent the infragenicular endoscopic angioplasty avoided amputation for at least two years, compared with 82.9% of the men who were similarly treated (&lt;em&gt;P&lt;/em&gt;=0.041), according to Tejas Shah, MD, of Mount Sinai Medical Center in New York City.&lt;/p&gt;
&lt;p&gt;&quot;This study is the first to compare the outcomes of men and women being treated for blocked lower-leg arteries with endovascular therapy,&quot; Shah said at the International Symposium on Endovascular Therapy (ISET). &quot;The results suggest endovascular therapy should be strongly considered in women with blocked arteries below the knee.&quot;&lt;/p&gt;
&lt;p&gt;In many endovascular procedures, women tend to do worse then men, generally because they tend to have smaller blood vessels. But in this study, involving the smallest leg blood vessels, the opposite occurred. &quot;We really don&apos;t have any good reason why there should be this gender difference,&quot; Shah said.&lt;/p&gt;
&lt;p&gt;&quot;What made this difference significant,&quot; Shah told &lt;em&gt;MedPage Today&lt;/em&gt;, &quot;was that the women in the study, overall, were at significantly greater risk of amputation than the male patients.&quot; He said that about 22.3% of men underwent treatment for claudication, compared with 12.3% of the women, but 77.7% of men were being treated for limb-threatening conditions compared with 87.7% of women.&lt;/p&gt;
&lt;p&gt;The retrospective study involved review of angioplasties, stenting, and atherectomies performed on 152 men and 125 women at Mount Sinai between July 1999 and November 2009.&lt;/p&gt;
&lt;p&gt;When adjusted for comorbidities, women treated for tibial lesions with concurrent proximal disease had higher 24-month primary patency rates compared with men.&lt;/p&gt;
&lt;p&gt;Some 46% of treated leg arteries in women remained open, compared with 30% (&lt;em&gt;P&lt;/em&gt;=0.016) in men. Shah said that a subanalysis of isolated tibial lesions indicated that 50% of women achieved 24-month primary patency rates, compared with 28.8% of men (&lt;em&gt;P&lt;/em&gt; =0.002).&lt;/p&gt;
&lt;p&gt;On the downside, women experienced higher rates of blood clots forming at the access site of the treatment (9% versus 0.6%, &lt;em&gt;P&lt;/em&gt;&amp;lt;.0001). Clotting, typically treated with blood thinners, may require a longer stay in the hospital (&lt;em&gt;P&lt;/em&gt;&amp;lt;0.0001).&lt;/p&gt;
&lt;p&gt;&quot;In both men and women it is hard to keep these smaller leg blood vessels open,&quot; said Constantino Pe&amp;#241;a, MD, medical director of vascular imaging at Baptist Cardiac &amp;amp; Vascular Institute, Miami.&lt;/p&gt;
&lt;p&gt;&quot;It might be possible that women do better because of their hormone status. But we need to do prospective clinical trials to see if we can determine what factor is involved in making the procedure work better for women.&quot;&lt;/p&gt;
&lt;div style=&quot;float:left;border-style:solid;border-width:1px;border-color:#8dabbc;font-family:arial;font-size:12px;background-color:#DBE9F2;padding:5px;&quot;&gt;&lt;p&gt;Shah listed no relevant disclosures.  Pe&amp;#241;a reported financial relationships with Bard and Medtronic.&lt;/p&gt;&lt;/div&gt;&lt;div style=&quot;clear:both;&quot;&gt;&lt;/div&gt;
    </recommendedItem>
    <recommendedItem id="20090101_19_963"
                     title="ACC: Genetic Variability in Clopidogrel Response Not Always Overcome by Dosing"
                     score="-0.006"
                     href="http://www.medpagetoday.com/MeetingCoverage/ACC/tb/13486?impressionId=1265805424945"
                     
       ORLANDO, March 29 -- Patients with a genetic variant associated with responsiveness to clopidogrel (Plavix) have double the risk of cardiovascular events even with extreme doses of the drug, according to two studies. 
              &lt;p&gt; 
              &lt;p&gt;Patients on clopidogrel and aspirin who carried the cytochrome P450 2C19*2 polymorphism had a 21% event rate compared with a 10% rate among noncarriers (&lt;em&gt;P&lt;/em&gt;=0.02), Paul A. Gurbel, M.D., of the University of Maryland in Baltimore, reported at the American College of Cardiology meeting.
              &lt;p&gt; 
              &lt;p&gt;A second small study of the same polymorphism, also reported here, found that some carriers remained nonresponsive to the 300-mg loading dose of clopidogrel.
              &lt;p&gt; 
              &lt;p&gt;The variable response to antiplatelet agents has long been recognized, commented Ralph G. Brindis, M.D., M.P.H., of the University of California San Francisco and Kaiser Permanente in Oakland, Calif.
              &lt;p&gt; 
              &lt;p&gt;&quot;Both these studies point out the possibility that we should have more personalized direct care,&quot; said Dr. Brindis, vice president of the ACC and moderator of a press conference where the results were reported.
              &lt;p&gt; 
              &lt;p&gt;Dr. Gurbel agreed that &quot;the day is rapidly approaching&quot; when physicians could prospectively estimate patient response to antiplatelet therapy and chose among agents &quot;rather than blindly administering clopidogrel as we do now.&quot;
              &lt;p&gt; 
              &lt;p&gt;But that day is still beyond the immediate horizon -- in clinical trials rather than at the point of care, he noted.
              &lt;p&gt; 
              &lt;p&gt;Among the many gene variants studied as a possible barometer of outcome, the CYP2C19*2 polymorphism has consistently been linked to high platelet reactivity.
              &lt;p&gt; 
              &lt;p&gt;So, Dr. Gurbel and colleagues looked at the link between carriers of this gene, platelet reactivity, and cardiovascular outcomes during the year after discharge for nonemergent coronary artery stenting.
              &lt;p&gt; 
              &lt;p&gt;The 227 adult participants from two prior genotyping studies included in the analysis received 325 mg of aspirin and 75 mg of clopidogrel each day.
              &lt;p&gt; 
              &lt;p&gt;Among them, 64 patients carried one copy of the risk allele and three carried two copies for a total frequency of 30% with the polymorphism. 
              &lt;p&gt; 
              &lt;p&gt;Cardiovascular event-free survival at one year was 2.42 times less likely for patients who were positive for the genetic variant (&lt;em&gt;P&lt;/em&gt;=0.02).
              &lt;p&gt; 
              &lt;p&gt;Notably, platelet aggregation before antiplatelet therapy was no different among those with one, two, or no copies of CYP2C19*2 (&lt;em&gt;P&lt;/em&gt;=0.58). 
              &lt;p&gt; 
              &lt;p&gt;Nor were event rates correlated with pretreatment platelet reactivity (&lt;em&gt;P&lt;/em&gt;=0.86).
              &lt;p&gt; 
              &lt;p&gt;But on treatment, the picture changed to reflect rising residual platelet aggregation with a higher copy number (&lt;em&gt;P&lt;/em&gt;=0.02) and greater reactivity among those with subsequent cardiovascular events (&lt;em&gt;P&lt;/em&gt;=0.004).
              &lt;p&gt; 
              &lt;p&gt;&quot;This common variant encodes a defective enzyme that likely fails to adequately convert clopidogrel to its active metabolite, leading to lesser inhibition of platelet function and diminished cardiovascular protection,&quot; Dr. Gurbel concluded.
              &lt;p&gt; 
              &lt;p&gt;Larger prospective studies are needed to confirm the findings and to determine whether such testing would be clinically useful, he cautioned.
              &lt;p&gt; 
              &lt;p&gt;The second study, presented by Jean-Philippe Collet, M.D., of INSERM in Paris, attempted to find an effective antiplatelet strategy for patients with the genetic variant.
              &lt;p&gt; 
              &lt;p&gt;Among 33 patients with poor response to clopidogrel in their study who survived a first incidence of stent thrombosis or recurrent MI, seven still had a poor response to a 150 mg dose, double the dose indicated on the label. 
              &lt;p&gt; 
              &lt;p&gt;Six of those patients were carriers of CYP2C19*2. They were all poor responders to 150 mg and showed a 30% increase in residual platelet aggregation compared with noncarriers. 
              &lt;p&gt; 
              &lt;p&gt;At 225 mg -- three times the label dose -- along with aspirin, 60% of the six polymorphism carriers remained poor responders according to the functional assay. 
              &lt;p&gt; 
              &lt;p&gt;At the 300 mg loading dose of clopidogrel, two patients had intolerable side effects (back pain and gastrointestinal discomfort) but two were still resistant.
              &lt;p&gt; 
              &lt;p&gt;The six patients resistant to the 225 mg dose were considered for the investigational antiplatelet agent prasugrel, which was recently approved in Europe. All four patients who went on the drug had a good response. Two were not eligible because of age or history of stroke.
              &lt;p&gt; 
              &lt;p&gt;&quot;When you are dealing with these very high risk patients . . . you have to deal with new strategies to prevent recurrent events,&quot; Dr. Collet concluded. 
              &lt;p&gt; 
              &lt;p&gt;One option is the time-consuming strategy of increasing clopidogrel dose, but using a new drug unaffected by the genetic variant is a more attractive and effective strategy, he said. 
              &lt;p&gt; 
              &lt;p&gt; 
              &lt;p&gt;&lt;table cellspacing=&quot;0&quot; hspace=&quot;1&quot; style=&quot;border-style:solid; border-width:1px; border-color:#8dabbc; font-family:arial; font-size:12px; background-color:#DBE9F2; padding:5px 5px 5px 5px;&quot;&gt;
&lt;tr&gt;&lt;td&gt; Dr. Gurbel reported research grants as well as consulting relationships or honoraria from Schering Plough, Astra Zeneca, sanofi-aventis, Bayer, Portola, Daiichi Sankyo, Lilly, and Pozen.
              &lt;p&gt; 
              &lt;p&gt;Dr. Brindis reported no conflicts of interest.
              &lt;p&gt; 
              &lt;p&gt;Dr. Collet&apos;s study was sponsored by DRCD-APHP and a public grant from the Ministry of Health. The group provided no information on individual conflicts of interest.&lt;/td&gt;&lt;/tr&gt;&lt;/table&gt;
    </recommendedItem>
</recommendedContent>