Friday, May 13, 2016
Is it time to reconsider the cholesterol hypothesis?
This post is purposely controversial. I write it because I believe that mounting evidence suggests that we should encourage “out of the box” thinking about this issue. This post is hypothesis challenging. I may be right or I may be wrong. I hope we get some debate on my speculations.
The latest blow to the cholesterol hypothesis is the New York Times article, “Dashing Hopes, Study Shows a Cholesterol Drug Had No Effect on Heart Health,” which states:
“We had an agent that seemed to do all the right things,” said Dr. Stephen J. Nicholls, the study's principal investigator and the deputy director of the South Australian Health and Medical Research Institute in Adelaide. “It's the most mind-boggling question. How can a drug that lowers something that is associated with benefit not show any benefit?” he said, referring to the 37 percent drop in LDL levels with the drug.
Two other drugs in the same class as evacetrapib, known as CETP inhibitors, have also failed: One, which lowered LDL levels by only 20 percent, had toxic side effects. The other raised HDL levels but did not lower LDL levels at all. Cardiologists thought evacetrapib, a safe and potent drug, would be different.
“All of us would have put money on it,” said Dr. Peter Libby, a Harvard cardiologist. The drug, he said, “was the great hope.”
But previous studies had already foreshadowed these results. Adding ezetimibe to a statin does not improve outcomes. Only statins show significant clinical benefits. Statins help patients after myocardial infarctions regardless of their initial cholesterol levels.
Perhaps we have overstated the cholesterol hypothesis. Some believe that statins achieve clinical benefits because of their pleiotropic effects of stabilizing plaques. Statins have an anti-inflammatory impact on the endothelium (as I understand it) and perhaps that is where the real action is.
Perhaps these cardiologists need to examine their paradigm. I am clearly not an expert in this field, but we have too much data challenging the paradigm. At what point do we continue running expensive studies for a failing hypothesis. These studies recall the 80s when they kept trying to improve myocardial contractility in patients with systolic dysfunction, and drug after drug causes increased mortality.
The cardiologists have made us all obsessed with the LDL and HDL numbers. While they do predict heart disease risk, we really do not have appropriate evidence that changing the numbers changes our risk. Perhaps they should re-examine their obsession.
db is the nickname for Robert M. Centor, MD, FACP. db stands both for Dr. Bob and da boss. He is an academic general internist at the University of Alabama School of Medicine, and is the Regional Associate Dean for the Huntsville Regional Medical Campus of UASOM. He still makes inpatient rounds over 100 days each year. This post originally appeared at his blog, db's Medical Rants.
Contact ACP Internist
Send comments to ACP Internist staff at firstname.lastname@example.org.
- Patient-centered care
- Not just another guideline
- Does appendicitis need surgery?
- Should we track sepsis trends using administrative...
- There's so much more to the whole observation vers...
- Watching as the patient digs herself a hole
- Health care: of United, and citizens
- Capitation? What capitation?
- Extensivists, "big picture-ists," and more
- Joke of the day
Members of the American College of Physicians contribute posts from their own sites to ACP Internistand ACP Hospitalist. Contributors include:
Albert Fuchs, MD, FACP, graduated from the University of California, Los Angeles School of Medicine, where he also did his internal medicine training. Certified by the American Board of Internal Medicine, Dr. Fuchs spent three years as a full-time faculty member at UCLA School of Medicine before opening his private practice in Beverly Hills in 2000.
And Thus, It Begins
Amanda Xi, ACP Medical Student Member, is a first-year medical student at the OUWB School of Medicine, charter class of 2015, in Rochester, Mich., from which she which chronicles her journey through medical training from day 1 of medical school.
Ira S. Nash, MD, FACP, is the senior vice president and executive director of the North Shore-LIJ Medical Group, and a professor of Cardiology and Population Health at Hofstra North Shore-LIJ School of Medicine. He is Board Certified in Internal Medicine and Cardiovascular Diseases and was in the private practice of cardiology before joining the full-time faculty of Massachusetts General Hospital.
Zackary Berger, MD, ACP Member, is a primary care doctor and general internist in the Division of General Internal Medicine at Johns Hopkins. His research interests include doctor-patient communication, bioethics, and systematic reviews.
Controversies in Hospital
Run by three ACP Fellows, this blog ponders vexing issues in infection prevention and control, inside and outside the hospital. Daniel J Diekema, MD, FACP, practices infectious diseases, clinical microbiology, and hospital epidemiology in Iowa City, Iowa, splitting time between seeing patients with infectious diseases, diagnosing infections in the microbiology laboratory, and trying to prevent infections in the hospital. Michael B. Edmond, MD, FACP, is a hospital epidemiologist in Iowa City, IA, with a focus on understanding why infections occur in the hospital and ways to prevent these infections, and sees patients in the inpatient and outpatient settings. Eli N. Perencevich, MD, ACP Member, is an infectious disease physician and epidemiologist in Iowa City, Iowa, who studies methods to halt the spread of resistant bacteria in our hospitals (including novel ways to get everyone to wash their hands).
db's Medical Rants
Robert M. Centor, MD, FACP, contributes short essays contemplating medicine and the health care system.
Suneel Dhand, MD, ACP Member
Suneel Dhand, MD, ACP Member, is a practicing physician in Massachusetts. He has published numerous articles in clinical medicine, covering a wide range of specialty areas including; pulmonology, cardiology, endocrinology, hematology, and infectious disease. He has also authored chapters in the prestigious "5-Minute Clinical Consult" medical textbook. His other clinical interests include quality improvement, hospital safety, hospital utilization, and the use of technology in health care.
Juliet K. Mavromatis, MD, FACP, provides a conversation about health topics for patients and health professionals.
Dr. Mintz' Blog
Matthew Mintz, MD, FACP, has practiced internal medicine for more than a decade and is an Associate Professor of Medicine at an academic medical center on the East Coast. His time is split between teaching medical students and residents, and caring for patients.
Toni Brayer, MD, FACP, blogs about the rapid changes in science, medicine, health and healing in the 21st century.
Vineet Arora, MD, FACP, is Associate Program Director for the Internal Medicine Residency and Assistant Dean of Scholarship & Discovery at the Pritzker School of Medicine for the University of Chicago. Her education and research focus is on resident duty hours, patient handoffs, medical professionalism, and quality of hospital care. She is also an academic hospitalist.
John H. Schumann, MD, FACP, provides transparency on the workings of medical practice and the complexities of hospital care, illuminates the emotional and cognitive aspects of caregiving and decision-making from the perspective of an active primary care physician, and offers behind-the-scenes portraits of hospital sanctums and the people who inhabit them.
Ryan Madanick, MD, ACP Member, is a gastroenterologist at the University of North Carolina School of Medicine, and the Program Director for the GI & Hepatology Fellowship Program. He specializes in diseases of the esophagus, with a strong interest in the diagnosis and treatment of patients who have difficult-to-manage esophageal problems such as refractory GERD, heartburn, and chest pain.
Mike Aref, MD, PhD, FACP, is an academic hospitalist with an interest in basic and clinical science and education, with interests in noninvasive monitoring and diagnostic testing using novel bedside imaging modalities, diagnostic reasoning, medical informatics, new medical education modalities, pre-code/code management, palliative care, patient-physician communication, quality improvement, and quantitative biomedical imaging.
William Hersh, MD, FACP, Professor and Chair, Department of Medical Informatics & Clinical Epidemiology, Oregon Health & Science University, posts his thoughts on various topics related to biomedical and health informatics.
David Katz, MD
David L. Katz, MD, MPH, FACP, is an internationally renowned authority on nutrition, weight management, and the prevention of chronic disease, and an internationally recognized leader in integrative medicine and patient-centered care.
Richard Just, MD, ACP Member, has 36 years in clinical practice of hematology and medical oncology. His blog is a joint publication with Gregg Masters, MPH.
Kevin Pho, MD, ACP Member, offers one of the Web's definitive sites for influential health commentary.
Michael Kirsch, MD, FACP, addresses the joys and challenges of medical practice, including controversies in the doctor-patient relationship, medical ethics and measuring medical quality. When he's not writing, he's performing colonoscopies.
Elaine Schattner, MD, FACP, shares her ideas on education, ethics in medicine, health care news and culture. Her views on medicine are informed by her past experiences in caring for patients, as a researcher in cancer immunology, and as a patient who's had breast cancer.
Mired in MedEd
Alexander M. Djuricich, MD, FACP, is the Associate Dean for Continuing Medical Education (CME), and a Program Director in Medicine-Pediatrics at the Indiana University School of Medicine in Indianapolis, where he blogs about medical education.
Rob Lamberts, MD, ACP Member, a med-peds and general practice internist, returns with "volume 2" of his personal musings about medicine, life, armadillos and Sasquatch at More Musings (of a Distractible Kind).
David M. Sack, MD, FACP, practices general gastroenterology at a small community hospital in Connecticut. His blog is a series of musings on medicine, medical care, the health care system and medical ethics, in no particular order.
Reflections of a Grady
Kimberly Manning, MD, FACP, reflects on the personal side of being a doctor in a community hospital in Atlanta.
The Blog of Paul Sufka
Paul Sufka, MD, ACP Member, is a board certified rheumatologist in St. Paul, Minn. He was a chief resident in internal medicine with the University of Minnesota and then completed his fellowship training in rheumatology in June 2011 at the University of Minnesota Department of Rheumatology. His interests include the use of technology in medicine.
Technology in (Medical)
Neil Mehta, MBBS, MS, FACP, is interested in use of technology in education, social media and networking, practice management and evidence-based medicine tools, personal information and knowledge management.
Peter A. Lipson,
Peter A. Lipson, MD, ACP Member, is a practicing internist and teaching physician in Southeast Michigan. The blog, which has been around in various forms since 2007, offers musings on the intersection of science, medicine, and culture.
Why is American Health Care So Expensive?
Janice Boughton, MD, FACP, practiced internal medicine for 20 years before adopting a career in hospital and primary care medicine as a locum tenens physician. She lives in Idaho when not traveling.
World's Best Site
Daniel Ginsberg, MD, FACP, is an internal medicine physician who has avidly applied computers to medicine since 1986, when he first wrote medically oriented computer programs. He is in practice in Tacoma, Washington.
Other blogs of note:
American Journal of
Also known as the Green Journal, the American Journal of Medicine publishes original clinical articles of interest to physicians in internal medicine and its subspecialities, both in academia and community-based practice.
A collaborative medical blog started by Neil Shapiro, MD, ACP Member, associate program director at New York University Medical Center's internal medicine residency program. Faculty, residents and students contribute case studies, mystery quizzes, news, commentary and more.
Michael Benjamin, MD, ACP member, doesn't accept industry money so he can create an independent, clinician-reviewed space on the Internet for physicians to report and comment on the medical news of the day.
The Public Library of Science's open access materials include a blog.
One of the most popular anonymous blogs written by an emergency room physician.