Here is a breakdown of the category “Autosomal Dominant” [hypercholesterolemia] as presented by Daniel J. Rader, et al, in 2003.
If we combine the three separate diseases and call the result, “ADH,” then we simply complete the necessary math and find a prevalence of 1:294, which we can round to 1:300. This is not an exercise limited to a specialist of epidemiology. An elementary school student can do it. No study in the field is necessary — just as no trip to the supermarket is required when tallying up items on a shopping receipt.
That was 2003. However, in 2005 Aegerion Pharmaceuticals will submit a filing with the SEC for a sale of securities. Aegerion will focus on patients with the very rare form of familial hypercholesterolemia, those who inherited the gene defect from both parents (“homozygotes”). In 2006, Dr. Rader receives 265,041 shares of Aegerion stock, for under $400. In 2007 he is listed as a member on Aegerion Pharmaceutical’s “Scientific Advisory Board.” (Later, from August 2013 to December 31, 2016, Dr. Rader will receive $228,000 from pharmaceutical companies – including Aegerion, Regeneron, and Sanofi, among others. Collection of this data starts in 2013, so we don’t know what payments he may have received earlier.)
In 2011, Dr. Daniel Rader will join Dr. Anne Goldberg and others in a coordinated series of FH reports published in the Journal of Clinical Lipidology. The reports received funding from Aegerion and other pharmaceutical companies. The lead report is explicit. It admits that “in the past” FH solely referred to the LDLR mutation but tells the reader that it is going to combine the APOB and PCSK9 under the same name, “FH.” The “broader definition” effectively erases the names “FDB” and “FH3” from the scientific record.
While in 1973, Nobel Prize winner Joseph Goldstein put the prevalence of FH between 1:500 and 1:1,000, in this 2011-series of reports the prevalence range will be 1:300 to 1:500. There is no cited, external, contemporary source for 1:300. Even in other reports in this 2011 series, some citations appear to be sources for the new number, but all eventually end with the Nobel Prize winners’ 1:500.
A prevalence of 1:300 in this 2011 report is simply the passive math necessary when combining known sets into a single newly created set. Where the label “FH” was once a set beside other sets – FDB and FH3 – now the new label “FH” has consumed the other sets. By inserting the underlying mutations, APOB and PCSK9, into the FH set, the names, “FDB” and “FH3” remain unmentioned in this context. As I will show, this is an initial move toward the eventual extinction of these other names.
Because the Sunshine act is not yet effective in 2011, we don’t know what payments may have looked like before August 2013, but the authors’ conflicts of interests were inordinately large in 2011. Thirteen out of fifteen of the authors had financial ties to Merck, for example.
Here are the 2011 authors, with my commentary. In the illustration, I’ve called out payments received by most of the authors post-2013, more than $3.3 million. These payments include but are not necessarily restricted to FH related activities. Albeit in the future, a majority of the authors will be willing to accept significant payments from pharmaceutical companies.
The prestige of being a published author is an incentive. One is also declared an “expert” among one’s peers. But there is also money. We don’t know specifically what they may or may not have received in 2011. But if we add in the disclosure of pharma funding found in the 2011 reports, it is not unwarranted to speculate that financial incentives might have influenced this publication. Dr. Rader is also present. He was an Aegerion shareholder. Here he is in the years leading up to the redefinition of FH.
Another person of interest is Dr. Seth Baum. (Item 1 in the illustration below) His online curriculum vitae tells us that he was a peer reviewer for this same Journal of Clinical Lipidology in 2011. He specializes in FH issues, and the 2011 “supplemental series” published by the journal focused on FH issues. Aegerion provided funding for this 2011 publication. We don’t know if or how much Dr. Baum received from Aegerion during 2011. We do know however that he was a speaker, consultant, and scientific advisor for Aegerion. (2) We also know that out of 7,000 doctors who received payment from Aegerion from late 2013 to the end of 2016, Dr. Baum was the highest paid. (3) Although circumstantial, these spokes radiate from the same hub: we also know that Marc Beer was Aegerion’s CEO during the relevant time period. CEO Beer is associated with the SEC, DOJ, FBI, and FDA investigations. (4) Although we don’t know if Dr. Goldberg and Dr. Baum knew each other, or worked together, during 2011, we do know that in 2015 they appeared together in a photo, which serves as promotional material for the FH Foundation, a charity on which Dr. Baum serves as Secretary Treasurer. Of course, the FH Foundation receives money from pharmaceutical companies. Aegerion was listed as a donor in the past. However, they are no longer listed on the FH Foundation website. Presumably, they ceased donations after the federal investigation began. (Part of the investigation included/includes Aegerion’s association with a charitable organization.)
Now let’s uncover a few more facts. In 2013 Dr. Baum was clearly promoting peer reviewed claims of FH prevalence to investors, and Wall Street analysts were clearly drawing conclusions from the scientific claims. Then in 2014, after the 2013 and 2014 EAS papers had conflated separate diseases through citation kiting, Dr. Baum explains the need for a “language strategy.” Let’s set up the time line and drop these two facts in.
Below are actual quotations from Dr. Baum’s piece. (https://doi.org/10.1016/j.jacl.2014.09.005. It is also available at: http://fpim.org/articles/heart-health/the-doctors-dilemma-challenges-in-the-diagnosis-and-care-of-homozygous-familial-hypercholesterolemia/.)
- Evolution of a definition
- “HoFH is an infrequent inherited disorder usually caused by mutations in both LDL receptor alleles, which results in very high elevated plasma LDL cholesterol concentrations and very early morbidity and mortality due to accelerated atherosclerotic cardiovascular disease (ASCVD), usually before the patient turns 30 years old. In patients with HoFH, the main cause of mortality and morbidity is the aortic stenosis rather than involvement of the coronary arteries.” This was an original definition for HoFH written by the “fathers” of the disorder. This, as well as the original molecular definition, has itself mutated over the years. FH now includes autosomal dominant mutations in at least two other genes, PCSK9 and apoB 100. To further confuse the issue, molecularly defined HoFH now includes both double heterozygotes and compound heterozygotes and may also rarely involve more than two mutations. ….
- For this reason, the newer and less genetically precise terms have appropriately become embedded in our definition of HoFH. This expanded HoFH definition enables doctors to broaden their detection and care of such patients, an extraordinarily high-risk population in need of early and aggressive treatment. ….
- Over the past few years, it has become apparent that the current definition of HoFH (expanded from its original Goldstein and Brown view) is likely inadequate. We now have evidence that the prevalence of HoFH may be one in 160,000, whereas HeFH occurs somewhere between 1 in 200 and 1 in 300. ….
- Reeducation is in order; teaching medical practitioners to have FH as a fixture on their differential diagnostic list of LDL disorders is crucial. ….
- The doctor’s dilemma resolved with a common language strategy: a pragmatic approach to managing clinically severe FH” ….
- We proffer the following clinically grounded approach that may simplify and enhance the care of adult patients with clinically severe FH, regardless of its genetic bases.
 Gathered through the “Physician Payments Sunshine Act.,” For the particular database I accessed, see https://www.propublica.org/article/about-the-dollars-for-docs-data.
 doi:10.1016/j.jacl.2011.04.003, doi:10.1016/j.jacl.2011.03.452, doi:10.1016/j.jacl.2011.03.451, doi:10.1016/j.jacl.2011.03.453, doi:10.1016/j.jacl.2011.04.001, doi:10.1016/j.jacl.2011.04.002,
 Familial Hypercholesterolemia: Screening, diagnosis and management of pediatric and adult patients, Goldberg, et al, 2011, doi:10.1016/j.jacl.2011.04.003
 I refer to the use of empty citations as “citation kiting.” This manipulation occurs in other, widely cited FH publications. Although the act of kiting is conspicuously simple, the consequences require elaborate presentations. In a brief presentation, some of these “fact-ectomies” will appear to be mere typos. But that is not the case: the equivocation engineered by fact-ectomy alters patient identification instructions. In prevalence this inflates the value of Wall Street traded stocks; in medicine it swaps out the genuine patients, and swaps in patients suffering from other diseases.
 See previous page.