<img loading="lazy" decoding="async" class="alignright size-full wp-image-5233" title="iStock_000000481784XSmall" src="https://blog-api.23andme.com/wp-content/uploads/2009/10/iStock_000000481784XSmall.jpg" alt="iStock_000000481784XSmall" width="320" height="236" srcset="https://blogcms.23andme.com/wp-content/uploads/2009/10/iStock_000000481784XSmall.jpg 403w, https://blogcms.23andme.com/wp-content/uploads/2009/10/iStock_000000481784XSmall-300x222.jpg 300w" sizes="auto, (max-width: 320px) 100vw, 320px" />
<a href="http://www.medco.com/medco/corporate/home.jsp" target="_blank" rel="noopener noreferrer">Medco Health Solutions, Inc.</a>, announced this week that it will conduct a clinical trial to assess whether clopidogrel bisulfate (Plavix ®, Bristol-Myers Squibb and Sanofi-aventis) is just as effective as the newer drug prasugrel (Effientâ„¢, Eli Lilly and Company) in people who lack a genetic variation that inhibits their metabolism of clopidogrel. This new research has important implications for both patient safety and health care costs.
Both clopidogrel and prasugrel are anti-platelet medications that reduce the ability of blood to form clots. The drugs are used to reduce the risk of a heart attack and stroke in people who have suffered from a recent cardiovascular event, and in those who have peripheral artery disease, unstable angina or a stent.
Variations in the CYP2C19 gene that prevent clopidogrel from being converted into its active form in the body have been shown to prevent patients from receiving the drug&#8217;s full benefit. People with these gene variations who are taking clopidogrel may be at a higher risk for heart attacks, strokes and death from cardiovascular causes than those whose genetics allow them to metabolize the drug.
(Prasugrel is metabolized through a different biological pathway than clopidogrel, and is not affected by CYP2C19 variants.)
Medco&#8217;s study will assess patients&#8217; rates of nonfatal heart attacks, nonfatal strokes and cardiovascular deaths after six months of treatment with either clopidogrel or prasugrel. Researchers will be looking to see if there is any difference between those patients who are taking clopidogrel, and whose genetics predict that they should be able to metabolize it–and those patients who are taking prasugrel.
&#8220;Plavix is going generic in 2011 and if found to be equally effective as Effient for patients who have a normally functioning version of the CYP2C19 gene, the study provides the evidence that would allow these patients to opt for a lower cost treatment,&#8221; said Medco&#8217;s chief medical officer Dr. Robert Epstein in a press release.
Former U.S. Secretary of Health and Human Services Michael O. Leavitt was quoted in the Medco press release as saying, &#8220;Studies like this are necessary to show how innovation can derive greater value from what we spend on health care.   A simple test can identify a drug&#8217;s ability to work for a particular patient or point them to another one that could provide a better outcome. Personalized medicine is the new frontier in making medication safer and more effective. What we learn from this study, and others like it, will save lives and money.&#8221;
Patients aren’t the only ones who would save if Medco&#8217;s research shows that the soon-to-be generic clopidogrel is an effective choice for them. An Associated Press story notes that generic drugs are more profitable for Medco than higher-priced brand name products.
Comparative effectiveness research has received a lot of attention in the United States health care debate lately.   Some worry that it will result in policies that are not in patients&#8217; best interests.
&#8220;We need to be mindful of the goal of comparative effectiveness research and not lose all that we have gained in understanding how individuals differ and how that could be factored into better diagnostics and preventive strategies,&#8221; said National Institutes of Health (NIH) director Francis Collins, speaking at a recent American Association for the Advancement of Science <a href="https://www.reuters.com/article/healthNews/idUSTRE59P4UD20091026?feedType=RSS&amp;feedName=healthNews&amp;pageNumber=1&amp;virtualBrandChannel=0" target="_blank" rel="noopener noreferrer">forum on personalized medicine</a>.
Collins recommended that genetic factors be included in comparative effectiveness research (as is the case in Medco&#8217;s study), to make sure that treatments that work for specific groups of patients are not &#8220;lost in the wash by considering everybody equivalent.&#8221;
The Genotype-Guided Comparison of Clopidogrel and Prasugrel Outcomes Study (GeCCO) is part of Medco&#8217;s “<a href="http://www.genomeweb.com/dxpgx/medcos-new-idea-pgx-program-generics-dispense-smarter-treatments-and-increase-sa" target="_blank" rel="noopener noreferrer">Genetics for Generics</a>” program and is <a href="http://clinicaltrials.gov/ct2/show/NCT00995514?term=NCT00995514&amp;rank=1" target="_blank" rel="noopener noreferrer">registered with the NIH</a>.
Related Blog Posts: 
<a href="https://blog.23andme.com/articles/more-evidence-that-genetics-can-reduce-the-efficacy-of-anti-clotting-medication-clopidogrel" target="_blank" rel="noopener noreferrer">More Evidence that Genetics Can Reduce the Efficacy of Anti-Clotting Medication Clopidogrel</a> 
<a href="https://blog.23andme.com/2008/12/23/snpwatch-genetic-variants-may-reduce-ability-of-anti-clotting-drug-clopidogrel-to-prevent-a-second-heart-attack/" target="_blank" rel="noopener noreferrer">SNPwatch: Genetic Variants May Reduce Ability of Anti-Clotting Drug Clopidogrel to Prevent a Second Heart Attack</a>

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Medco to Include Genetics in Comparison of Anti-Clotting Drug Effectiveness

<img loading="lazy" decoding="async" class="alignright size-full wp-image-3921" title="istock_000003091114xsmall" src="https://blog-api.23andme.com/wp-content/uploads/2009/06/istock_000003091114xsmall.jpg" alt="istock_000003091114xsmall" width="332" height="220" srcset="https://blogcms.23andme.com/wp-content/uploads/2009/06/istock_000003091114xsmall.jpg 425w, https://blogcms.23andme.com/wp-content/uploads/2009/06/istock_000003091114xsmall-300x199.jpg 300w" sizes="auto, (max-width: 332px) 100vw, 332px" />
Study after study has shown that high blood levels of C-reactive protein (CRP), a marker of inflammation, are associated with increased risk of cardiovascular disease. But what hasn&#8217;t been clear is whether CRP actually causes heart disease, or just indicates the presence of artery-blocking atherosclerosis.
Researchers from Imperial College London set out to answer this question using a genetic approach.   They reasoned that if high CRP levels really do cause heart disease then genetic variants associated with increased CRP should also be associated with increased heart disease risk.   Their results, published today in <a href="http://jama.ama-assn.org/cgi/content/full/302/1/37?home" target="_blank" rel="noopener">Journal of the American Medical Association</a>, indicate that CRP might not be a key player after all.
Using a sample of 28,000 heart disease patients and 10,000 controls, Paul Elliott and colleagues examined several SNPs in the CRP gene. They found a significant association between the SNPs and CRP levels, and between CRP levels and heart disease – but not between the genetic variations and heart disease.
For example, each T at rs1205 lowered CRP by 20%.   Based on previous studies of CRP, this should have translated into 6% lower odds of heart disease. But there was no association of rs1205 with heart disease at all.
The researchers also identified four SNPs in other genes that were associated with CRP levels.   One was associated with heart disease in the expected direction (that is, the version associated with lower CRP was also associated with decreased heart disease risk). But two others had an inverse relationship with heart disease risk.   The final SNP affected CRP levels but had no relationship with heart disease risk either way.
Medical Implications
The JUPITER trial, published in the <a href="http://content.nejm.org/cgi/content/full/NEJMoa0807646" target="_blank" rel="noopener">New England Journal of Medicine</a> in November, showed that middle-aged men and women with low LDL cholesterol (below 130 mg/dL), but high CRP (greater than 2 mg/L) reduced their CRP levels by 37% and cut their risk of heart attack by 54% by taking rosuvastatin (Crestor ®).
These results suggest that CRP should be taken into account when deciding whether to prescribe statins to a patient, a move that would result in millions more Americans taking the drugs.
But the results of this new genetic study suggest that lower CRP doesn&#8217;t necessarily translate into a lower heart disease risk.   These findings support skeptics of the JUPITER trial, who argued that the improvements in cardiovascular disease risk seen with rosuvastatin treatment could have been due solely to their reduction (50%) of the study participants&#8217; already low cholesterol levels.
But the new study doesn&#8217;t necessarily mark end of the road for CRP testing.   In an <a href="http://jama.ama-assn.org/cgi/content/extract/302/1/92" target="_blank" rel="noopener">editorial</a> accompanying the new report in JAMA, Svati Shah and James de Lemos argue that even if CRP does not cause heart disease, it might still be valuable as a marker for identifying people who are at risk but do not exhibit traditional indicators such as high cholesterol.

Genetic Study Casts Doubt On Inflammatory Marker As Cause of Heart Disease

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A common genetic variation may influence how well a person recovers from heart surgery, a study published online yesterday in the <a href="https://dx.doi.org/10.1681/ASN.2008080915" target="_blank" rel="noopener noreferrer">Journal of the American Society of Nephrology</a> suggests.
Coronary artery bypass surgery, which involves using blood vessels from elsewhere in the body to reroute blood around clogged arteries feeding the heart, increases the risk of low blood pressure and shock.   Norepinephrine can be used to bring blood pressure back up to acceptable levels, but a variation in the gene for an enzyme critical to the metabolism of this drug, COMT, may make some people less responsive.
Researchers studied 260 people who had had bypass surgery and found that those who carried an A at both copies of went into shock more often compared to those with other genotypes (69% vs. 57% in AG people and 46.6% in GG people). The A version of produces a less efficient version of the COMT enzyme.
Prolonged shock, lasting more than 48 hours, was also more frequent in people with two As (25% vs. 13% for AG and 6.8% for GG). Because the body responds to shock by restricting blood flow to the kidneys, people with two As at also had greater frequency of acute kidney injury.
The median hospital stay after bypass surgery was longer for people with two As at : nine days vs. eight days for AG and seven days for GG.
More research on the effects of the COMT variation investigated in this study and variations in other genes that could also affect recovery after bypass surgery will be needed.   But if confirmed, the researchers suggest that their findings could help tailor drug regimens and lead to better outcomes.
“If confirmed in larger trials, preoperative COMT genotyping together with known clinical risk factors could aid in preoperative risk stratification to anticipate occurrence of circulatory and renal dysfunction, and prolonged recovery.   Patients thus identified may benefit from an individualized treatment…” the authors conclude.

Genetic Variation May Influence Heart Surgery Recovery

<img loading="lazy" decoding="async" class="alignright size-full wp-image-3161" title="qt" src="https://blog-api.23andme.com/wp-content/uploads/2009/03/qt.png" alt="" width="322" height="317" srcset="https://blogcms.23andme.com/wp-content/uploads/2009/03/qt.png 608w, https://blogcms.23andme.com/wp-content/uploads/2009/03/qt-300x296.png 300w" sizes="auto, (max-width: 322px) 100vw, 322px" />
Each beat of your heart is the result of a highly coordinated electrical system.   An impulse that starts in a few tiny cells spreads throughout the whole organ, causing cardiac cells to contract, pumping your blood in the never-ending circuit that courses through your body.
The “QT interval”, a measurement made from electrocardiogram recordings of the heart’s electrical activity, reflects the amount of time it takes for cells to reset after a contraction.   If this interval is abnormally long or short, it can scramble the electrical system of the heart, causing an erratic beat and limiting the heart’s ability to supply the body with enough newly oxygenated blood.   This can lead to fainting and, in some cases, sudden cardiac death.
Several genetic mutations that cause long and short QT intervals are known to run in families.   But these mutations don’t account for all cases of sudden cardiac death, nor do they explain the normal variation in QT interval seen in the population.   To learn more about the genetics of heartbeat regulation, two independent research teams (<a href="https://dx.doi.org/10.1038/ng.364" target="_blank" rel="noopener noreferrer">QTGEN</a> and <a href="https://dx.doi.org/10.1038/ng.362" target="_blank" rel="noopener noreferrer">QTSCD</a>) looked for genetic variants associated with natural variation in QT interval in more than 28,000 people.   The results, published online yesterday in the journal Nature Genetics, identify a total of 14 SNPs that can now be used as the basis of future research aimed at understanding susceptibility to QT interval-related irregular heart beat and sudden cardiac death.
“The reason people die from this cardiovascular disorder is because we know nothing about the antecedents,” said Aravinda Chakravarti, QTSCD study senior investigator, in a statement.   “It’s like a truck barreling down a slope: there’s no way to stop it.   The only way out is to understand the science of this in a deep, meaningful way.   If we know, we can begin to intervene.”
More than half of the variants identified by the researchers are located in genes already known to be involved in heart cell regulation, some of which are also mutated in familial syndromes characterized by long QT intervals.   But five of the SNPs are in genes not previously recognized as players in the electrical activity of the heart.   These findings open up new avenues for cardiovascular research.
According to the authors of one study (QTGEN), the variants found in these studies together explain more of the variation in QT interval seen in the population than any other factor except for heart rate.   But they warn that more research is still needed to determine whether the variants actually contribute to the risk for sudden cardiac death in addition to lengthening QT intervals.

Researchers Identify Genetic Variants Linked To Heart Rhythm And Possibly Sudden Cardiac Death

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Genome-wide association studies, the research projects that connect SNPs to different traits and conditions (and fuel much of the 23andMe Health and Traits feature), focus on fairly common genetic variations that generally have small effects on risk.
But critics of this type of research charge that studying common variation is of little value because it misses important information hiding in the genome in the form of rare mutations with large effects.
The results of a new genome-wide association study in the Old Order Amish of Lancaster, PA, may have bridged some of the gap between these two camps. In current issue of <a href="http://www.sciencemag.org/cgi/content/abstract/322/5908/1702" target="_blank" rel="noopener">Science</a>, researchers looking for SNPs associated with elevated triglycerides, a risk factor for heart disease, report finding a rare mutation in the Amish that could have important implications for preventing the condition in everyone.

About 5% of the isolated Amish community was found to carry one copy of a mutation that completely prevents a protein called apoC-III, encoded by the APOC3 gene, from being produced. ApoC-III prevents the breakdown of triglycerides in the bloodstream.
Mutation carriers had about 50% of the normal levels of apoC-III in their blood along with lower triglyceride levels, less “bad” LDL cholesterol and more “good” HDL cholesterol.
Carriers of the mutation were also much less likely to have coronary artery calcification (CAC), a measure of atherosclerosis. The mutation reduced the odds of having detectable CAC by 65%.
There is already a class of lipid-lowering drugs called fibrates that indirectly decrease the amount of protein made by APOC3. Other cholesterol drugs such as statins and niacin have also been associated with decreases in apoC-III levels. But the authors of the current study suggest that their discovery could mean that therapies aimed at directly reducing apoC-III levels will be useful in fighting heart disease.
Although 5% of the Amish carried the APOC3 mutation, it is thought to be rare or even entirely absent in the general population. Researchers believe the mutation was first introduced into the Amish community by a person who was born in the mid-1700’s.
The Amish are often used in genetic studies because they are an isolated and homogenous community with good genealogical records that date back to the time when they first migrated to North America.

Heart Disease — Page 3

Medco to Include Genetics in Comparison of Anti-Clotting Drug Effectiveness

Genetic Study Casts Doubt On Inflammatory Marker As Cause of Heart Disease

Genetic Variation May Influence Heart Surgery Recovery

Researchers Identify Genetic Variants Linked To Heart Rhythm And Possibly Sudden Cardiac Death

Genetic Associations For Heart Disease Prevention

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