Angiotensin-Receptor Blockades (ARBs) Found to Raise Risk of Cancer

Dr. Daniel Simon M.D., Division Chief of Cardiovascular Medicine and Director of HM-Heart and Vascular Institute at UHCMC; Dr. James Fang M.D., Section Chief of Heart Failure and Medical Director of Heart Transplantation at UHCMC; IIke Sipahi M.D., Associate Director of Heart Failure & Transplantation at UHCMC at the Harrington-McLaughlin Heart & Vascular Institute of UHCMC researched the effects of Angiotensin-Receptor Blockers (ARBs) on the risk of cancer.

ARBs are a widely utilized drug class used for treatment of hypertension, heart failure, diabetic nephropathy, and recently, for cardiovascular risk reduction.

Randomized controlled trials of ARBs with a follow-up of at least 1 year, and enrolling at least 100 patients were included in this meta-analysis. Information on new cancer development (first diagnosis) was available for 61,590 patients from five trials. Cancer data on common types of solid organ cancers such as lung and prostate cancer were available for 68,402 patients from five trials, and data on cancer deaths were available for 93,515 patients from eight trials.

The meta-analysis showed that patients randomly assigned to receive ARBs had a significantly increased risk of new cancer occurrence compared with patients in control groups (7.2%vs 6.0%). Specifically, the risk of lung cancer was increased by 25%, which was also statistically significant.

“We have found the risk of new cancers was increased with these medications by 8-11 percent.  Most importantly, risk of lung cancer was increased by 25 percent,” said Dr. Sipahi. Although there was no statistically significant excess in cancer deaths (1.8% with ARBs vs 1.6% with control) the investigators pointed out that the average duration of follow-up of 4 years may be too short to capture cancer deaths.

“In medicine, physicians must balance the benefits and risks of all drug and device therapies.  We recommend that patients discuss the findings of this study with their physicians since ARBs are effective agents in the treatment of high blood pressure and heart failure,” said Dr. Simon.

They conclude that because of the limited data, it is not possible to draw conclusions about the exact risk of cancer associated with each individual ARB on the market, but they stated that their findings need further investigation.

In response to this publication from Case Western Reserve University, the European Medicines Agency (EMA) of the European Union announced that they started an investigation about the possible cancer risk of ARBs.

“This is the first time an association between ARBs and cancer development is suggested,” Dr. Sipahi continued. “While our findings are robust, they need to be replicated in other studies before they can be considered as definitive.”

The US Food and Drug Administration has not made any statement regarding this issue yet.

Correlation Between Methicillin-Resistant Staphylococcus Aureus and Cystic Fibrosis Proven

Led by Dr. Elliott Dasenbrook MD MHS, Associate Director of The Adult Cystic Fibrosis Program, a UHCMC team in the Division of Pulmonary, Critical Care, and Sleep Medicine have published the findings from a major study about cystic fibrosis (CF) survival rates in the June 16 issue of JAMA.

Specifically, the study observed patients with CF who had methicillin-resistant Staphylococcus aureus (MRSA) detected in their respiratory tract.

The team composed a study with 19,833 CF patients across the nation between ages 6 and 45.  Times until death after diagnosis with MRSA were recorded in order to compare survival between CF patients with and without respiratory tract MRSA.

The unadjusted mortality rate was 18.3 deaths (95% confidence interval [CI], 17.5-19.1) per 1000 patient-years in patients without MRSA and 27.7 deaths (95% CI, 25.3-30.4) per 1000 patient-years in those with MRSA.  The team showed that there is a significantly higher rate of death in CF in people that have MRSA.

“Our study findings may prompt many doctors to reconsider how they care for CF patients,” says Dr. Dasenbrook. He adds, “Until now, some CF doctors weren’t aggressively treating patients with MRSA.  Doctors often viewed MRSA to not be as important as other respiratory-tract infections. With our study findings, treatment patterns may changes as the risk of death is 1.3 times greater for CF patients with MRSA.”

cardiovascular medicine publications :: Q2 | 2010

Treatment of Pericardial Disease
Azam S, Hoit BD.
Cardiovasc Ther. 2010 Apr

Kruppel-like factor 4 inhibits epithelial-to-mesenchymal transition through regulation of E-cadherin gene expression
Yori JL, Johnson E, Zhou G, Jain MK, Keri RA.
J Biol Chem. 2010 May

Kruppellike Factor 15 Regulates Smooth Muscle Response to Vascular Injury
Lu Y, Haldar S, Croce K, Wang Y, Sakuma M, Morooka T, Wang B, Jeyaraj D, Gray SJ, Simon DI, Jain MK.
Arterioscler Thromb Vasc Biol. 2010 May

Krüppel-like factor 4 regulates pressure-induced cardiac hypertrophy
Liao X, Haldar SM, Lu Y, Jeyaraj D, Paruchuri K, Nahori M, Cui Y, Kaestner KH, Jain MK.
J Mol Cell Cardiol. 2010 Aug

Klf15 deficiency is a molecular link between heart failure and aortic aneurysm formation
Haldar SM, Lu Y, Jeyaraj D, Kawanami D, Cui Y, Eapen SJ, Hao C, Li Y, Doughman YQ, Watanabe M, Shimizu K, Kuivaniemi H, Sadoshima J, Margulies KB, Cappola TP, Jain MK.
Sci Transl Med. 2010 Apr

Fatty acid-binding protein 5 and PPARbeta/delta are critical mediators of epidermal growth factor receptor-induced carcinoma cell growth
Kannan-Thulasiraman P, Seachrist D, Mahabeleshwar G, Jain MK, Noy N.
J Biol Chem. 2010 Jun

Cardiac rehabilitation in heart failure: a brief review and recommendations
Piña IL.
Curr Cardiol Rep. 2010 May

Impact of ICD battery longevity on need for device replacements-insights from a Veterans Affairs database
Ramachandra I.
Pacing Clin Electrophysiol. 2010 Mar

Hypoxia influences the vascular expansion and differentiation of embryonic stem cell cultures through the temporal expression of vascular endothelial growth factor receptors in an ARNT-dependent manner
Han Y, Kuang SZ, Gomer A, Ramirez-Bergeron DL.
Stem Cells. 2010 Apr

The intrinsic complement regulator decay-accelerating factor modulates the biological response to vascular injury
Sakuma M, Morooka T, Wang Y, Shi C, Croce K, Gao H, Strainic M, Medof ME, Simon DI.
Arterioscler Thromb Vasc Biol. 2010 Jun

Angiotensin-receptor blockade and risk of cancer: meta-analysis of randomised controlled trials
Sipahi I, Debanne SM, Rowland DY, Simon DI, Fang JC.
Lancet Oncol. 2010 Jun

Vanoxerine, a new drug for terminating atrial fibrillation and flutter
Matsumoto N, Khrestian CM, Ryu K, Lacerda AE, Brown AM, Waldo AL.
J Cardiovasc Electrophysiol. 2010 Mar

[(Methyl)1-(11)C]-Acetate Metabolism in Hepatocellular Carcinoma
Salem N, Kuang Y, Corn D, Erokwu B, Kolthammer JA, Tian H, Wu C, Wang F, Wang Y, Lee Z.
Mol Imaging Biol. 2010 Apr

In situ fluorescence imaging of myelination
Wang C, Popescu DC, Wu C, Zhu J, Macklin W, Wang Y.
J Histochem Cytochem. 2010 Jul

The Prophetic Protein :: Who is at risk for heart attack?

Tense hours in the emergency room while tests confirm a heart attack may be rolled back to mere minutes, thanks to a telltale protein marker identified by Case Western Reserve University School of Medicine researchers. Better yet, a routine blood test for the nefarious protein could serve as an early warning to people at high risk :: Take steps now, and you may dodge the dangerous attack altogether.

When the proverbial elephant takes a seat on one’s chest, it is a decided hint: That person might be having a heart attack, or myocardial infarction (MI). Every 25 seconds, someone in the United States has one, according to the American Heart Association, but the oft-reported sensation of chest tightening or pain is just that-a clue. Even in the hospital, it can take eight to 12 hours for current tests to conclusively rule a heart attack in or out. Common alternative culprits in chest pain are intense heartburn or a gallstone attack.

Led by top physician-researcher Daniel I. Simon, MD, investigators at the School of Medicine, however, have discovered a marker of heart attack that promises to cuthours off the time for definitive MI diagnosis-to the tune of confirmation within 10 to 15 minutes of arriving at the emergency room. What’s more, a simple blood test for the novel myeloid-related protein-8/14 (MRP-8/14) marker could give long-used cholesterol screening a run for its money as a signal of MI in the making, years ahead of the cardiac attack.

“Though we gain great insight into patients’ potential risk for cardiovascular disease using conventional biomarkers, we are limited in identifying some people at risk,” says Douglas Vaughan, MD, professor of cardiology at Northwestern University’s Feinberg School of Medicine and chair of its Department of Medicine. “An additional marker measured in people’s blood could valuably refine our ability to take care of patients with coronary artery disease.”

To hone in on the up-and-coming predictive protein MRP- 8/14, researchers applied an unprecedented scientific approach that scoured entire human genomes for cardiac warning signs. “We were on the hunt. We wanted to know what genes turn on or off in heart attack patients,” explains Dr. Simon, the Herman K. Hellerstein Professor of Cardiovascular Research at the School of Medicine and director of University Hospitals Harrington-McLaughlin Heart & Vascular Institute. Dr. Simon and his team of researchers identified MRP-8/14 as their best-bet marker for heart attack for use in emergency settings and as a potential companion to routine cholesterol screening in the doctor’s office.

Dr. Simon’s account is a tale of finding a little molecule with big potential-a project born in a lab in New England that has grown on a campus in Cleveland.

Read the full story at Medicus.

Director of Institute for Transformative Molecular Medicine, Inaugural Robert S. and Sylvia K. Reitman Family Foundation Distinguished Chair in Cardiovascular Innovation

Pamela B. Davis, M.D., Ph.D., dean of the Case Western Reserve University School of Medicine, announced the appointment of Jonathan S. Stamler, M.D., as the director of the Institute for Transformative Molecular Medicine and the first to hold the Robert S. and Sylvia K. Reitman Family Foundation Distinguished Chair in Cardiovascular Innovation at the Case Western Reserve University Cardiovascular Center and University Hospitals Harrington-McLaughlin Heart & Vascular Institute.

The newly established chair was made possible by a $1.5 million gift from the Reitman Family Foundation and was slated to be held by a preeminent physician scientist dedicated to advancing cardiovascular medicine through compassionate patient care, clinical research, and training of fellows and residents.

As director of the Institute for Transformative Molecular Medicine, primarily based in the Department of Medicine, Stamler will be charged with developing the Institute, with purview across Case Western Reserve University and University Hospitals. His efforts will catalyze scientific discoveries in molecular medicine, formulate new therapies that benefit humankind, and inspire the next generation of physician scientists.

His research specifically has led to elucidating the fundamental role of nitric oxide in control of complex physiological responses through S-nitrosylation, a protein modification that he discovered. His work has helped to transform the simple notion of cellular redox state into the concept of a dynamic and precisely regulated mechanism for control of protein function, analogous to phosphorylation, but operating through covalent modifications at cysteine thiols. The ramifications of his work extend to all major classes of proteins and accumulating evidence suggests that protein S-nitrosylation is aberrant in many diseases.

Stamler completed his undergraduate studies at Brandeis University, earned his medical degree from Mount Sinai School of Medicine, and completed his medical residency and fellowship training in both cardiology and pulmonary medicine at Harvard Medical School and the Brigham and Women’s Hospital. He joined the faculty of Harvard Medical School as Assistant Professor of Medicine in October 1993. In December of 1993, Stamler joined the faculty of Duke University, where he is currently the George Barth Geller Professor of Research in Cardiovascular Disease and Professor of Medicine and Biochemistry.

Cardiologists discover cancer risks in group of blood pressure medications

University Hospitals Case Medical Center cardiologists have uncovered new research showing an increased risk of cancer with a group of blood pressure medications known as angiotensin-receptor blockers (ARBs).

This class of drugs is used by millions of patients not only for high blood pressure but also for heart failure, cardiovascular risk reduction and diabetic kidney disease.

University Hospitals Harrington-McLaughlin Heart & Vascular Institute’s Drs. Ilke Sipahi, Daniel I. Simon and James C. Fang recently completed a meta-analysis of over 60,000 patients randomly assigned to take either an ARB or a control medication. Their findings are published online today at The Lancet Oncology.

The researchers found that patients randomized to ARBs has “significantly increased risk of new cancer” compared to control patients.

“We have found the risk of new cancers was increased with these medications by 8-11 percent,” said Dr. Ilke Sipahi, associate director of heart failure and transplantation and assistant professor at Case Western Reserve University School of Medicine. “Most importantly, risk of lung cancer was increased by 25 percent.”

However, the research did not establish any link between ARBs and other types of cancer such breast cancer.

“This is the first time an association between ARBs and cancer development is suggested,” Dr. Sipahi continued. “While our findings are robust, they need to be replicated in other studies before they can be considered as definitive.”

Before this study, there were no major safety concerns with ARBs except for their use in pregnancy and in patients with chronic kidney or blockages of kidney arteries. Interestingly, previous animal studies with ARBs have been negative for cancer development.

“In medicine, physicians must balance the benefits and risks of all drug and device therapies,” said Dr. Daniel Simon, director of the Harrington-McLaughlin Heart & Vascular Institute at University Hospitals Case Medical Center and professor at Case Western Reserve University School of Medicine. “We recommend that patients discuss the findings of this study with their physicians since ARBs are effective agents in the treatment of high blood pressure and heart failure. Meta-analyses are a powerful tool to look at low frequency safety signals, but require confirmation with other approaches, such as large national health and managed care registries.”

UH received Top Health System Award

University Hospitals named one of the Top 10 Health Systems in U.S.

For the second consecutive year, University Hospitals (UH) has been named one of the top 10 health systems in the United States based on clinical performance by Thomson Reuters, a leading business and professional information organization.

UH and the other top 10 systems outperformed their peers by a wide margin. They provided better care, followed standards of care more closely, saved more lives, had fewer patient complications, and made fewer patient safety errors.

The list was compiled in a study conducted by researchers from the Thomson Reuters 100 Top Hospitals®. They analyzed the quality and efficiency of 255 health systems based on eight metrics that gauge clinical quality and efficiency: mortality, medical complications, patient safety, average length of stay, 30-day mortality rate, 30-day readmission rate, adherence to clinical standards of care (evidence-based core measures published by the Centers for Medicare and Medicaid Services), and HCAHPS patient survey score (part of a national initiative sponsored by the U.S. Department of Health and Human Services to measure the quality of care in hospitals).

Thomson Reuters rankings are available at www.thomsonreuters.com.

First multi-PI combined training program between CWRU and Cleveland Clinic headed by Fabio Cominelli

Beginning in July, the first multiple-principal investigator combined training program between Case Western Reserve University and Cleveland Clinic will be initiated by Fabio Cominelli MD, PhD, the Hermann Menges, Jr. Chair in Internal Medicine at the School of Medicine, and Claudio Fiocchi MD¸ Clifford and Jane Anthony Chair for Digestive Disease Research and Education, Lerner Research Institute at Cleveland Clinic.

The National Institute of Diabetes, Digestive and Kidney Diseases provided the new joint effort with a five-year grant worth nearly $1M. The funding supports post-doctoral fellows in obtaining digestive disease science training for a period of three years; for physicians this will be in conjunction with their clinical training in gastroenterology.

This training program is unique in that it follows the city-based program model of the Clinical and Translational Science Collaborative (CTSC). Trainees will come to Cleveland with the option to train either at the Lerner Research Institute or the School of Medicine, and they will have the ability to choose among 20 mentors whose laboratories are supported by more than $20 million per year in National Institutes of Health funding.

Ohio Senate grants letter of commendation to School of Medicine

The members of the Senate of the 128^th General Assembly of Ohio paid tribute the School of Medicine in an official letter of commendation for being ranked as the 20th best medical school in research in the nation, as ranked by U.S. News & World Report.

The letter praised our institution, “known for its dedication to medical research, and the world of its highly qualified and committed staff has earned the university an exceptional reputation.”

Signed by Senator Bill Harris, President of the Ohio Senate, and Senator Shirley A. Smith, Assistant Minority Leader, the acknowledgement applauds the School’s innumerable contributions to the study of medicine.

Congratulations Class of 2010

On May 16, Case Western Reserve University School of Medicine had the privilege of graduating 157 of its best scholars into the world as physicians.

The well-rounded Class of 2010 has attained intellectual mastery of the Western Reserve  curriculum and matched to some of the finest residency programs in the nation. These new physicians are well-prepared to practice medicine.

It is the hope of the Department of Medicine that they fulfill their dreams while continuing the rich, long-standing Case Western Reserve tradition of medical excellence.

Congratulations and many thanks to the professors, instructors and staff that helped guide the students through their journey and shape their experience here in Medicine.