Penn Presbyterian Medical Center

Philadelphia, PA, United States

Penn Presbyterian Medical Center

Philadelphia, PA, United States

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Multicenter study shows AF ablation is safe and just as effective in patients with CHD compared to those with normal hearts PHILADELPHIA--Congenital heart disease (CHD) includes a range of defects that occur in the heart which patients are born with, such as a hole in the heart's wall, a leaky valve or even an inversion in the heart's orientation. CHD was once a severe condition often resulting in early death, but now, more and more CHD patients are living long and healthy lives. Therefore, as this population grows, so does the number of patients who are treated for other complications of their disease, such as early onset atrial fibrillation (AF), a quivering or irregular heartbeat that can lead to blood clots, stroke, heart failure and other complications. AF is often treated with a catheter ablation, a minimally invasive procedure in which the areas of the heart causing the irregularity are cauterized, but until now, there was limited data to support the safety and efficacy of treating CHD patients with an AF ablation. In a new study presented today at the Heart Rhythm Society's 38th Annual Scientific Session in Chicago, researchers from the Perelman School of Medicine at the University of Pennsylvania have found that CHD patients--even with complex defects--can safely undergo ablation for AF, with similar success rates as patients with normal hearts. "Treatment for atrial fibrillation is critical, whether the patient has a normal heart or whether they have complex congenital heart disease," said the study's presenter Jackson J. Liang, DO, a third-year cardiovascular disease fellow in the Perelman School of Medicine at the University of Pennsylvania. "In fact, atrial fibrillation can be especially detrimental in patients with complex congenital heart disease since they may be more reliant on the "atrial kick" provided during sinus rhythm. Unfortunately for some CHD patients, AF ablation may be more challenging due to the presence of complex anatomy, and the optimal ablation strategy for these patients remains to be defined." In this multicenter study, researchers performed a retrospective analysis of 69 CHD patients who underwent AF ablation, by collecting data from Penn, University of Colorado, University of California San Francisco, and Texas Cardiac Arrhythmia Institute at St. David's Medical Center. Researchers looked at those who underwent AF ablation for paroxysmal (intermittent) or persistent AF between 2008 and 2016. They identified the type of CHD, and tracked the ablation strategy - pulmonary vein isolation (PVI), PVI with additional ablation, or non-PV ablation only. "Some physicians may not be aware that catheter ablation can be performed to treat atrial fibrillation in patients with congenital heart disease, and instead they may prescribe anti-arrhythmic medications," said David Frankel, MD, an assistant professor of Cardiovascular Medicine at Penn. "We hope this study will increase awareness of catheter ablation as a viable treatment option for atrial fibrillation in these patients." Of the 69 patients, 34 had paroxysmal AF and 25 had complex CHD. The team defined complete success as freedom from recurrent AF for one year off antiarrhythmic medications, and partial success as freedom from AF recurrences for one year on previously ineffective anti-arrhythmic medications. At one year, researchers concluded that 53 percent of the patients had complete success with an additional 13 percent experiencing partial success. 92 percent of patients underwent a PVI approach, while seven percent had a non-PVI ablation alone. "We also found that 12 patients needed a repeat ablation within the first year, but most notably, there were no major procedural complications identified and only five minor complications, which is on par with rates in non-CHD patients," said Liang. "While PVI should remain the cornerstone of ablation, an individualized approach utilizing pre-procedural imaging to help to define the anatomy is necessary to improve outcomes in patients with CHD." Researchers conclude that AF ablation in this complex population was safe and effective, with similar outcomes to those seen in non-CHD patients, despite anatomical differences. However, they noted that more research is needed to further define the challenges and optimal ablation strategies in CHD patients. Penn Medicine is one of the world's leading academic medical centers, dedicated to the related missions of medical education, biomedical research, and excellence in patient care. Penn Medicine consists of the Raymond and Ruth Perelman School of Medicine at the University of Pennsylvania (founded in 1765 as the nation's first medical school) and the University of Pennsylvania Health System, which together form a $6.7 billion enterprise. The Perelman School of Medicine has been ranked among the top five medical schools in the United States for the past 20 years, according to U.S. News & World Report's survey of research-oriented medical schools. The School is consistently among the nation's top recipients of funding from the National Institutes of Health, with $392 million awarded in the 2016 fiscal year. The University of Pennsylvania Health System's patient care facilities include: The Hospital of the University of Pennsylvania and Penn Presbyterian Medical Center -- which are recognized as one of the nation's top "Honor Roll" hospitals by U.S. News & World Report -- Chester County Hospital; Lancaster General Health; Penn Wissahickon Hospice; and Pennsylvania Hospital -- the nation's first hospital, founded in 1751. Additional affiliated inpatient care facilities and services throughout the Philadelphia region include Good Shepherd Penn Partners, a partnership between Good Shepherd Rehabilitation Network and Penn Medicine. Penn Medicine is committed to improving lives and health through a variety of community-based programs and activities. In fiscal year 2016, Penn Medicine provided $393 million to benefit our community.


News Article | May 10, 2017
Site: www.eurekalert.org

PHILADELPHIA - Studies have shown that loss of the sense of smell can be among the first warning signs of diseases such as Alzheimer's and Parkinson's. Now a researcher at the Perelman School of Medicine at the University of Pennsylvania wants to shift the search for clues about this process back even further, to find out if there is a common factor responsible for the loss of smell that may also serve as an early warning signal for a number of neurodegenerative diseases. In a review published online in Lancet Neurology, Richard L. Doty, PhD, a professor of Otorhinolaryngology and director of the Smell and Taste Center, cites evidence that the common link could be damage to neurotransmitter and neuromodulator receptors in the forebrain - the front part of the brain. "We need to retrace the steps of the development of these diseases," Doty said. "We know loss of smell is an early sign of their onset, so finding common factors associated with the smell loss could provide clues as to the pre-existing processes that initiate the first stages of a number of neurodegenerative diseases. An understanding of such processes could provide novel approaches to their treatment, including ways to slow down or stop their development before irreversible damage has occurred." Currently, it's is generally believed that the smell loss of various neurodegenerative diseases is caused by disease-specific pathology. In other words, different diseases can bring about the same loss of smell for different reasons. Doty's review - the first of its kind - looked at many neurodegenerative diseases with varying degrees of smell loss and sought to find a common link that may explain such losses. He considered physiological factors as well as environmental factors like air pollution, viruses, and exposure to pesticides. "Ultimately, as each possibility was evaluated, there were cases where these factors didn't show up, which ruled them out as potential universal biomarkers." Doty did find compelling evidence for a neurological solution: Damage to the neurotransmitter and neuromodulator receptors in the forebrain - most notably, a system employing the neurochemical acetylcholine. Neurotransmitters are the chemicals that send signals throughout the brain. Neuromodulators influence the activity of neurons in the brain. The receptors receive the signals, and if they are damaged, it hurts the brain's ability to process smells normally. "The good news is we can assess damage to some of the systems by evaluating their function in living humans using radioactive neurochemicals and brain imaging processes such as positron emission tomography (PET)," Doty said. "Unfortunately, few data are currently available, and the historical data of damage to neurotransmitter/neuromodulator systems, including cell counts from autopsy studies, are limited to just a few diseases. Moreover, quantitative data on a patient's olfactory status is rarely available, especially prior to disease diagnosis." Doty said the lack of early data is a problem across the board in the search for factors that may explain smell loss. "Smell testing isn't part of a standard check-up, and people don't recognize a smell problem themselves until it's already severe," Doty said. "Research now starting in Japan will be testing thousands of people over the course of the next few years that will better define associations between changes in smell and a wide variety of physiological measures in older populations." "If a universal factor does exist, the benefits for patients would be obvious," Doty said. "Damage to the neurotransmitter and neuromodulator receptors shows promise as one possibility, but we need more research in this area to truly answer the question. It could be the key to unlocking better understanding of neurological disease." Editor's Note: Doty receives funding from the Michael J. Fox Foundation for Parkinson's Research. He is a consultant to Acorda Therapeutics, Eisai Co., Ltd., and Johnson & Johnson. He is president of and major shareholder in Sensonics International, which manufactures and distributes smell and taste tests. Penn Medicine is one of the world's leading academic medical centers, dedicated to the related missions of medical education, biomedical research, and excellence in patient care. Penn Medicine consists of the Raymond and Ruth Perelman School of Medicine at the University of Pennsylvania (founded in 1765 as the nation's first medical school) and the University of Pennsylvania Health System, which together form a $6.7 billion enterprise. The Perelman School of Medicine has been ranked among the top five medical schools in the United States for the past 20 years, according to U.S. News & World Report's survey of research-oriented medical schools. The School is consistently among the nation's top recipients of funding from the National Institutes of Health, with $392 million awarded in the 2016 fiscal year. The University of Pennsylvania Health System's patient care facilities include: The Hospital of the University of Pennsylvania and Penn Presbyterian Medical Center -- which are recognized as one of the nation's top "Honor Roll" hospitals by U.S. News & World Report -- Chester County Hospital; Lancaster General Health; Penn Wissahickon Hospice; and Pennsylvania Hospital -- the nation's first hospital, founded in 1751. Additional affiliated inpatient care facilities and services throughout the Philadelphia region include Good Shepherd Penn Partners, a partnership between Good Shepherd Rehabilitation Network and Penn Medicine. Penn Medicine is committed to improving lives and health through a variety of community-based programs and activities. In fiscal year 2016, Penn Medicine provided $393 million to benefit our community.


News Article | May 10, 2017
Site: www.eurekalert.org

PHILADELPHIA - Bacteria in the gut microbiome drive the formation of cerebral cavernous malformations (CCMs), clusters of dilated, thin-walled blood vessels in the brain that can cause stroke and seizures, according to new research published this week in Nature by researchers from the Perelman School of Medicine at the University of Pennsylvania. Led by Mark Kahn, MD, a professor of Cardiovascular Medicine, the team's research suggests that altering the microbiome in CCM patients may be an effective therapy for this cerebrovascular disease. CCM disease, which occurs in about one in 100 to 200 people, can present in two forms. One is sporadic, accounting for 80 percent of cases, and is most frequent in older individuals. The remaining 20 percent are familial, inherited cases. In 2016, the Kahn lab discovered the molecular mechanism in endothelial cells that underlies the formation of CCMs. In the current Nature study, the team discovered that this molecular pathway is activated by TLR4, a receptor for the bacterial molecule lipopolysaccharide (LPS). Activation of TLR4 on brain endothelial cells by LPS vastly accelerated CCM formation. Conversely, if TLR4 was removed from endothelial cells genetically, or if the mice were treated with drugs that block TLR4 function, CCM formation is prevented. Since TLR4 primarily responds to LPS from Gram-negative bacteria, Alan Tang, an MD-PhD student in the Kahn lab, proposed that bacteria from the animal's gut microbiome may drive CCM formation. To test this theory, he examined CCM formation in mice that were housed under germ-free conditions (in collaboration with the Children's Hospital of Philadelphia through the PennCHOP Microbiome Program Core Facility) or treated with antibiotics to reduce the number of bacteria living in the gut. In both cases, CCM formation was dramatically reduced, demonstrating a key role for bacteria in the pathology of CCM disease. The team next sought evidence that bacterial LPS-TLR4 signaling might also support CCM formation in human patients. They worked with researchers at the University of New Mexico (UNM) and the University of California, San Francisco (UCSF) who have studied several hundred patients who carry an identical mutation in one CCM gene but display a widely variable disease course. "Some of these patients experience severe stroke by the age of two and others have no symptoms over their lifetime," Kahn said. "What makes the disease outcome so variable?" Working with the team from UNM and UCSF, they discovered that genetic variations that raise the amount of TLR4 that is produced are associated with higher numbers of CCM lesions, suggesting that the key role for LPS-TLR4 signaling identified in mice is also present in humans. These studies identify an unexpected, direct link between the microbiome and a common cerebrovascular disease. "This suggests that treatments designed to block TLR4 signaling or alter the microbiome may be used to treat this disease," Kahn said. These studies were in part supported by the National Institutes of Health (R01HL094326, P01NS092521) and a PennCHOP Microbiome Program Pilot & Feasibility Award Grant. Penn Medicine is one of the world's leading academic medical centers, dedicated to the related missions of medical education, biomedical research, and excellence in patient care. Penn Medicine consists of the Raymond and Ruth Perelman School of Medicine at the University of Pennsylvania (founded in 1765 as the nation's first medical school) and the University of Pennsylvania Health System, which together form a $6.7 billion enterprise. The Perelman School of Medicine has been ranked among the top five medical schools in the United States for the past 20 years, according to U.S. News & World Report's survey of research-oriented medical schools. The School is consistently among the nation's top recipients of funding from the National Institutes of Health, with $392 million awarded in the 2016 fiscal year. The University of Pennsylvania Health System's patient care facilities include: The Hospital of the University of Pennsylvania and Penn Presbyterian Medical Center -- which are recognized as one of the nation's top "Honor Roll" hospitals by U.S. News & World Report -- Chester County Hospital; Lancaster General Health; Penn Wissahickon Hospice; and Pennsylvania Hospital -- the nation's first hospital, founded in 1751. Additional affiliated inpatient care facilities and services throughout the Philadelphia region include Good Shepherd Penn Partners, a partnership between Good Shepherd Rehabilitation Network and Penn Medicine. Penn Medicine is committed to improving lives and health through a variety of community-based programs and activities. In fiscal year 2016, Penn Medicine provided $393 million to benefit our community.


News Article | May 25, 2017
Site: www.eurekalert.org

PHILADELPHIA -- There are more than 98,000 people currently awaiting a kidney transplant in the United States. But the organs are in short supply: only about 17,000 patients will receive transplants each year. For sicker patients and those facing the longest wait times -- five to seven years or more on the waiting list -- a new study finds there may be a benefit to accepting a kidney from a deceased diabetic donor. In a study published today in the Clinical Journal of the American Society of Nephrology, researchers from the Perelman School of Medicine at the University of Pennsylvania, have found that the best chance of survival, for older patients, those who live in areas with long waits for transplantation, or those who already have diabetes, may come from accepting a kidney from a deceased donor who had diabetes. "Most often, these organs are considered 'high-risk' as diabetes is a risk factor for kidney disease, and there may be underlying kidney damage that is not detected in initial organ screenings prior to transplantation," said lead author Jordana Cohen, MD, MSCE, an instructor of Medicine in the division of Renal-Electrolyte and Hypertension. "However, there are many patients on the wait list who will die before they receive a kidney transplant. For these patients, based on this study, their best chance of survival and of having a better quality of life may come from accepting this kind of organ." Researchers performed an observational study of 437,619 kidney transplant candidates using data from the Organ Procurement and Transplantation Network database. They identified 8,101 recipients of diabetic donor kidneys and 126,560 recipients of nondiabetic donor kidneys. The team assessed the risk an adverse event after accepting a diabetic donor kidney as compared to remaining on the waitlist or receiving a nondiabetic donor kidney. "Our goal was to evaluate the mortality risk of transplantation with diabetic donor kidneys compared to remaining on the kidney transplant waitlist, and to determine which patients would benefit most from transplantation with these organs," said senior author Deirdre L. Sawinski, MD, assistant medical director of Kidney Pancreas Transplantation, and an assistant professor of medicine in the division of Renal-Electrolyte and Hypertension. "In this analysis, we were able to determine that kidney transplant candidates who are at highest risk of dying on the waitlist, such as the elderly, patients with diabetes themselves, and those at centers with the longest average waiting times, benefit most from transplantation with diabetic donor kidneys, with a nearly 10 percent improvement in long term survival." The team also found that poor quality diabetic donor kidneys, as determined by a donor index that takes into account factors such as donor age and kidney function, provide no survival benefit, and that younger kidney transplant candidates--those under age 40 years old--do not benefit from transplantation with diabetic donor kidneys. While kidneys from diabetic donors may not last as long or work as well as kidneys from non-diabetic donors, the initial survival benefits seem to outweigh these risks. Sawinski added that "patients, who are over the age of 40 or those who already have diabetes, should consider accepting a kidney from a deceased diabetic donor when available, in order to increase their chances of being transplanted sooner, and increasing their survival." Additional Penn authors on this study include Kimberly Forde and Peter Reese. This study was supported in part by the National Institutes of Health (K23-HL133843), (K23-DK103918) and (K23-DK090209). Penn Medicine is one of the world's leading academic medical centers, dedicated to the related missions of medical education, biomedical research, and excellence in patient care. Penn Medicine consists of the Raymond and Ruth Perelman School of Medicine at the University of Pennsylvania (founded in 1765 as the nation's first medical school) and the University of Pennsylvania Health System, which together form a $6.7 billion enterprise. The Perelman School of Medicine has been ranked among the top five medical schools in the United States for the past 20 years, according to U.S. News & World Report's survey of research-oriented medical schools. The School is consistently among the nation's top recipients of funding from the National Institutes of Health, with $392 million awarded in the 2016 fiscal year. The University of Pennsylvania Health System's patient care facilities include: The Hospital of the University of Pennsylvania and Penn Presbyterian Medical Center -- which are recognized as one of the nation's top "Honor Roll" hospitals by U.S. News & World Report -- Chester County Hospital; Lancaster General Health; Penn Wissahickon Hospice; and Pennsylvania Hospital -- the nation's first hospital, founded in 1751. Additional affiliated inpatient care facilities and services throughout the Philadelphia region include Good Shepherd Penn Partners, a partnership between Good Shepherd Rehabilitation Network and Penn Medicine. Penn Medicine is committed to improving lives and health through a variety of community-based programs and activities. In fiscal year 2016, Penn Medicine provided $393 million to benefit our community.


News Article | May 26, 2017
Site: www.eurekalert.org

PHILADELPHIA -- Irene Hurford, MD, an assistant professor in the department of Psychiatry, has received a 2017 Exemplary Psychiatrist Award from the National Alliance on Mental Illness (NAMI). Hurford is one of only five recipients of the award nationally, which is presented to "honor the exceptional contributions that ... psychiatrists make to improve the lives of people living with mental health conditions." Her research focuses on measuring cognition in psychosis, treatment outcomes in early-episode psychosis, interventions to improve functioning in early psychosis, and program evaluation. In addition to her faculty role at Penn, Hurford developed and directs the Psychosis Education, Assessment, Care, and Empowerment (PEACE) Program through Horizon House, Inc. PEACE helps people in the early stages of psychosis learn to manage their symptoms and meet their life goals. It works to support the entire person towards recovery from, and resiliency to, psychosis. Hurford's philosophy behind PEACE is to treat psychosis as a barrier, not an insurmountable illness that has to define who people are. She and her team take a hopeful approach. The goal is to keep clients in work or school. Hurford educates and engages family members of clients in the PEACE program by including them in the counseling sessions. By participating, they learn about the illness as well as how to help their family members cope. They also come to realize that their loved ones can truly recover from psychosis and lead lives of their own choosing. Also, Hurford has been the coordinated specialty team trainer for three pilot first-episode psychosis projects throughout Pennsylvania, providing training and guidance based on her experience in establishing PEACE. She is the principal investigator for statewide program evaluation of first episode psychosis programs in Pennsylvania. She received her medical degree from McMaster University in Hamilton, Ontario, Canada and BSc in psychology from the University of Toronto. She completed her residency in psychiatry and post-doctoral training at the David Geffen School of Medicine at the University of California, Los Angeles (UCLA) as well as an advanced fellowship in psychiatry at San Diego VA Medical Center. Her awards include the Brain & Behavior Research Foundation's NARSAD Young Investigator Award and designation as a Top Psychiatrist by the Consumer's Research Council of America. NAMI, the nation's largest grassroots mental health organization, offers education programs to individuals, families, and professionals; advocates for public policy in support of people with mental illness and their families; staffs a national help line; and works to increase public awareness of mental illness. Penn Medicine is one of the world's leading academic medical centers, dedicated to the related missions of medical education, biomedical research, and excellence in patient care. Penn Medicine consists of the Raymond and Ruth Perelman School of Medicine at the University of Pennsylvania (founded in 1765 as the nation's first medical school) and the University of Pennsylvania Health System, which together form a $6.7 billion enterprise. The Perelman School of Medicine has been ranked among the top five medical schools in the United States for the past 20 years, according to U.S. News & World Report's survey of research-oriented medical schools. The School is consistently among the nation's top recipients of funding from the National Institutes of Health, with $392 million awarded in the 2016 fiscal year. The University of Pennsylvania Health System's patient care facilities include: The Hospital of the University of Pennsylvania and Penn Presbyterian Medical Center -- which are recognized as one of the nation's top "Honor Roll" hospitals by U.S. News & World Report -- Chester County Hospital; Lancaster General Health; Penn Wissahickon Hospice; and Pennsylvania Hospital -- the nation's first hospital, founded in 1751. Additional affiliated inpatient care facilities and services throughout the Philadelphia region include Good Shepherd Penn Partners, a partnership between Good Shepherd Rehabilitation Network and Penn Medicine. Penn Medicine is committed to improving lives and health through a variety of community-based programs and activities. In fiscal year 2016, Penn Medicine provided $393 million to benefit our community.


PHILADELPHIA--A new strategy - an injectable antibody - for lowering blood lipids and thereby potentially preventing coronary artery disease and other conditions caused by the build-up of fats, cholesterol, and other substances on the artery walls, is supported by findings from two new studies from researchers in the Perelman School of Medicine at the University of Pennsylvania. The new approach targets a protein called ANGPTL3, a regulator of enzymes that clear triglycerides and other fat molecules from the blood. Research in recent years has hinted that inherited mutations in the ANGPTL3 gene that disable its function can decrease triglyceride, LDL cholesterol and HDL cholesterol levels. As reported in a paper published today online in the New England Journal of Medicine, researchers from Penn Medicine, Regeneron Pharmaceuticals, and a group of international collaborators studied ANGPTL3 in both humans and mice. They found that blocking ANGPTL3 activity with an investigative injectable antibody, known as evinacumab, reduced triglycerides by up to 76 percent and lowered LDL cholesterol 23 percent in human study participants, and largely reversed signs of atherosclerosis in a mouse models. Researchers also included a human genetics study of approximately 188,000 people, which found that carriers of mutations that disable ANGPTL3 had nearly 40 percent fewer incidents of coronary artery disease as compared to those with fully functioning ANGPTL3. "In the clinic, I treat many patients with very high triglycerides, but our current medications aren't lowering triglycerides enough in many cases. I'm delighted at the prospect of a new treatment that's a lot more potent, all the more because it lowers LDL at the same time," said study co-author Richard L. Dunbar, MD, assistant professor of Cardiovascular Medicine and member of Penn's Division of Translational Medicine and Human Genetics. "It's very reassuring to see that people with this genetic defect actually seem to be protected from heart disease. I think that really bodes well for a therapeutic that's targeting the ANGPTL3 pathway." In a separate study, published in the March issue of the Journal of the American College of Cardiology (JACC) researchers from Penn Medicine, Harvard Medical School, Washington University in St. Louis, and nine other institutions, who also studied humans and mice, reported on a similar set of findings. Among these was the discovery from another large population sample that carriers of ANGPTL3-inactivating mutations had a 34 percent lower rate of coronary artery disease compared to non-carriers. "We used different lines of evidence to show that ANGPTL3 deficiency is associated with a reduced risk of coronary artery disease," said study co-author Kiran Musunuru, MD, PhD, MPH, an associate professor of Cardiovascular Medicine at Penn. "But ultimately we were able to identify that fact that carriers of this genetic mutation did in fact experience a benefit - with little other health risk." The trial of research on ANGPTL3 as a potential target for atherosclerosis prevention began over a decade ago when scientists reported on two cases of familial hypolipidemia, a rare inherited condition involving abnormally low blood levels of cholesterol and triglycerides. Most cases of familial hypolipidemia are linked to other gene mutations that cause liver and digestive problems, but in members of this American family with the condition, Musunuru found mutations in the gene for ANGPTL3, and no associated health problems. In the NEJM study from Dunbar and colleagues, the antibody had similar effects in an initial clinical trial in 83 people, lowering the blood levels of triglycerides measured after fasting by about 75 percent at the highest dose, and lowering LDL cholesterol by about 30 percent. Statins and other drugs are already widely used to lower LDL cholesterol, but there are fewer options for lowering triglycerides. "For treating high triglyceride levels there's really nothing out there that's quite this potent, so that's where I expect this new approach to have its greatest therapeutic benefit," Dunbar said. Hypertriglyceridemia, a condition in which fasting triglyceride levels are greater than 150 mg/dL, is estimated to affect at least tens of millions of American adults. It is associated with coronary artery disease and other forms of atherosclerosis, and can lead to potentially fatal inflammation of the pancreas. In principle, the strategy of targeting ANGPTL3 could have an even broader use in treating atherosclerosis in the general population. The researchers found that in a mouse model of atherosclerosis, treatment with evinacumab reduced the area of atherosclerotic lesions by 39 percent. The population study findings, including those from the JACC study, suggest that even the partial inactivation of ANGPTL3--carriers typically have one mutant copy of the gene and one working copy--may be powerfully protective against coronary artery disease, which has long been one of the leading causes of death in developed countries. In the JACC study, for example, carriers of inactivating ANGPTL3 mutations had only a 17 percent reduction in triglycerides on average. But that modest reduction was associated with a 34 percent reduction in coronary artery disease risk. Moreover, Musunuru and his colleagues found that the people in their sample with the lowest blood levels of ANGPTL3 had a 35 percent lower rate of heart attacks compared to those with the highest ANGPTL3 levels. Dunbar noted that the population study findings probably have lain to rest a lingering concern about targeting ANGPTL3, namely its effect in lowering not just LDL and triglycerides but also the so-called "good cholesterol," known as HDL cholesterol. "If lowering HDL were a major concern, then I don't think we would have seen the evidence of overall benefit that we did in this study," he said. The two studies together suggest that single copies of inactivating ANGPTL3 mutations are found in roughly one of every 250 people of European descent, whereas people with mutations in both copies of the gene--as in the family studied by Musunuru and colleagues--are much rarer. According to Dunbar, the next logical step would be to take evinacumab into larger clinical trials to study its safety, effectiveness, and optimal dosing. "The effect of even a single dose lasts for several months, and it's plausible that with multiple doses we would see an even deeper and more sustained effect," he said. Additional Penn authors on the NEJM study include Scott Damrauer, MD, Aeron Small, and Daniel J. Rader MD, and the Journal of the American College of Cardiology study include Xiao Wang, PhD, Daniel J. Rader, MD, and Danish Saleheen, MBBS, PhD. Funding sources for the studies detailed in this press release included grants from the National Heart, Lung, and Blood Institute (NHLBI) (R01HL131961), (K08HL114642), (R01HL118744), (R01HL127564) and (R21HL120781) and Regeneron Pharmaceuticals. Editor's Note: Dunbar has received grant support from and consulted for Regeneron Pharmaceuticals, Inc. Penn Medicine is one of the world's leading academic medical centers, dedicated to the related missions of medical education, biomedical research, and excellence in patient care. Penn Medicine consists of the Raymond and Ruth Perelman School of Medicine at the University of Pennsylvania (founded in 1765 as the nation's first medical school) and the University of Pennsylvania Health System, which together form a $6.7 billion enterprise. The Perelman School of Medicine has been ranked among the top five medical schools in the United States for the past 20 years, according to U.S. News & World Report's survey of research-oriented medical schools. The School is consistently among the nation's top recipients of funding from the National Institutes of Health, with $392 million awarded in the 2016 fiscal year. The University of Pennsylvania Health System's patient care facilities include: The Hospital of the University of Pennsylvania and Penn Presbyterian Medical Center -- which are recognized as one of the nation's top "Honor Roll" hospitals by U.S. News & World Report -- Chester County Hospital; Lancaster General Health; Penn Wissahickon Hospice; and Pennsylvania Hospital -- the nation's first hospital, founded in 1751. Additional affiliated inpatient care facilities and services throughout the Philadelphia region include Good Shepherd Penn Partners, a partnership between Good Shepherd Rehabilitation Network and Penn Medicine. Penn Medicine is committed to improving lives and health through a variety of community-based programs and activities. In fiscal year 2016, Penn Medicine provided $393 million to benefit our community.

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