After using the APOB for ‘underdiagnosis’ the recommended diagnostic scoring systems abandon them.

So what’s the big deal? What does it matter if we count 1:250 FH with APOB or 1:500 FH without APOB? That old 1 in 500 “dogma” didn’t include the new information about the recently discovered APOB. Now we know better. Isn’t that progress?  And by calling all of them by the better-known, “FH,” instead of the relatively unknown, “ADH,” can’t we now say, albeit tongue-in-cheek, that we have “twice” the number previously used for “FH” prevalence?  Don’t we perform a service by increasing the decibels of the alarm, “Underdiagnosis!” 

It matters because it doesn’t matter. These very authors tell us so by abandoning the APOB in their next step. After all this effort to re-engineer the name “Familial Hypercholesterolemia” to include the APOB, these APOB are abandoned by the diagnostic procedure recommended by the very same authors … in the very same publications. It all makes sense if … the APOB carriers are used for advertising “underdiagnosis” but are no longer necessary at the point of diagnosis – the point in the medical process where prescriptions are sold. The authors’ concern and sympathy for the APOB is fully depleted in the effort to elicit our concern and sympathy, and there’s none left by the time the authors’ get to recommending the actual diagnostic system.

Any move away from clarity and precision and toward obfuscation and imprecision should be sufficient reason for condemning the equivocation of terms within the scientific record. And the real injuries do not stop with mere publications and linguistic distortion: real people are at the other end of diagnostic procedures.

  • Whatever reason there is for including the APOB in “FH” prevalence refutes excluding them in the recommended diagnostic procedure.
  • Whatever reason there is for excluding the APOB from diagnosis refutes the medical necessity of including them in claims of “underdiagnosis.”

Here is the 2nd Danish report, 2016.

Dutch Lipid Clinic Network criteria, Hyperlipidemia, Familial hypercholesterolemia,  FH prevalence

Without the infrastructure, education, and profit motive for widespread genetic testing, 95% of the APOB will not be counted as “FH” when using the recommended scoring system. Here, 105 out of 111 would have been left out. The APOB are emphasized when it comes to academically determined prevalence, which leverages the advertising message, “underdiagnosis,” but then when it comes to real-world diagnosis, theclinical prejudice of what FH should look-like would have passed these over … undetected. When an insurance policy is restricted to Definite FH, 100% — all APOB – would have been abandoned in a real-world clinical setting.  After the APOB entrance for prevalence they are spun right back out of the real-world clinic as if in a revolving door.


So what does it really matter if we conflate or don’t conflate diseases? What’s the big deal?  This feels like a bait and switch scheme, executed from behind the institution of peer review. Whatever reason authors have for saving the APOB when talking about prevalence is not satisfied by discarding them when selling their drugs.

APOB, Hyperlipidemia, Familial hypercholesterolemia,  FH prevalence


A rational demonstration: It’s all about the money and healthcare is in the way

Everyone is complaining about a so-called “broken” healthcare system. But what they fail to mention is the resilience and strength of wealth-care in America. How does this argument sound? For reason X, the underdiagnosis of APOB demands a diagnostic procedure that abandons these underdiagnosed APOB. What could reason X be?  Why conflate the APOB with the LDLR for “FH” prevalence only to leave them out with the recommended diagnostic procedure? Is this an exercise in futility? Or does it serve some function?

The industry has two simultaneous interests, healthcare and making more money. In a conflict, one of the two will dominate. For these industry-funded publications, which is it? A balanced debate in a scientific discussion or an unbalanced push toward more money?

  • It can be rationally demonstrated that Big Pharma’s predicament is solved by sacrificing healthcare as the primary concern.
  • Step 1, Zig: The prevalence study goes against history to include the APOB as “FH” for reason X.
  • Step 2, Zag: The diagnostic procedure identifies individuals for drug sales, but it goes against the effort of Step 1 and suddenly excludes the APOB for reason Y.
  • Reason X can and cannot equal reason Y, depending upon what is referred to.
  • To remain consistent, reason X cannot equal reason Y if either X or Y refers to the health and welfare of the APOB. Under normal, fully disclosed circumstances …
    • … if the APOB are included in prevalence for their well-being, then their exclusion at the diagnostic stage is against their well-being.
    • … if the APOB are excluded at the diagnostic stage for their well-being, then their inclusion in prevalence cannot have been for their well-being.
  • To remain consistent, reason X can equal reason Y if both refer to making more money, within which Prevalence and Diagnosis are successive steps necessary to a bait-and-switch procedure: the inconsistency is the engine, not the obstacle.

Most of the LDLR are also abandoned.

LDLR abandoned, Familial hypercholesterolemia, FH underdiagnosis

The problem is not limited to the FDB-APOB carriers, but “classic” FH-LDLR carriers are also left behind. In the 2nd report, 70% of the 3 most frequent LDLR would not pass the clinical scoring system, assuming the industry succeeds in discouraging widespread genetic testing.  With the FDB APOB and the three most frequent FH LDLR combined, 86% are abandoned when the recommended diagnostic scoring system is considered sufficient.

The Regeneron report employs the same gimmick but was more thorough. It did not limit itself to the three most frequent LDLR. And yet the Regeneron report also recommends clinical scoring systems as if they were sufficient to determine FH.  76% of 215 carriers were below clinical detection. (Emphasis is mine, here and throughout my report)

Regeneron report, FH diagnosis

A diagnosis of FH can be made with a validated set of criteria, such as those established by the Dutch Lipid Clinic Network (DLCN), Simon Broome, or Make Early Diagnosis to Prevent Early Death (MEDPED). These diagnostic tools estimate the likelihood of FH on the basis of clinical features and, in the case of DLCN and Simon Broome criteria, also include identification of functional variants in the LDLR, APOB, or PCSK9 genes.  However genetic testing for these variants is uncommon in clinical practice in the United States.” ~ Regeneron report

It is easy to see here that given the discouragement and unavailability of widespread genetic testing both the APOB and the LDLR are abandoned with the recommended diagnostic procedure: the clinical scoring systems. Once a reader stops and stares at the material long enough, the eyes adjust to the dark: not only is there a reversal of the APOB, but even the original LDLR are also abandoned at the diagnostic stage. How could this happen? What’s missing from the scientific record? If something is missing can these Pharma-funded reports be balanced presentations with responsible recommendations?

FH, LDLR, APOB,  FH prevalence, underdiagnosis

Most mutations are actually milder than previously thought

The Pharma-funded reports are consistently unbalanced: the consequences of most mutations, especially the APOB, are not as severe as Pharma-funded reports claim. This good news for most mutation carriers presents a big problem for industry profits: Do most of the FH mutation carriers even need these risky new drugs?

In the 2nd Danish report, 38% of the LDLR and APOB had scores just like everyone else, deemed “unlikely” to have FH. As for the chance of having a passing score, 86% would not set off clinical alarm bells.

Familial hypercholesterolemia, FH prevalence not as severe

That deserves emphasis:  contrary to the message of the industry, many of these “FH” are not as severe as they are said to be. It may be the best strategy to monitor these mild LDLR and APOB carriers … the majority … to inform them of their risks … to remain vigilant, but not to jump to conclusions too soon. It certainly does appear, and many scientists have said, that environmental factors do play a role. These carriers are not necessarily doomed if they don’t pay for Pharma’s expensive, risky drugs.

“In heterozygotes identified in the general population, a different genetic makeup or environmental factors could counteract the effect of LDLR mutations by reducing synthesis or increasing breakdown rates of LDL, resulting in lower cholesterol levels.”[1]

“For all other patients with FH caused by LDLR defects, environmental or other inherited factors seem to be more important than the type of mutation in determining the phenotype severity.”[2]

“Consequently, the phenotype of FH individuals is highly variable, probably also due to environmental factors and other genetic polymorphisms influencing the clinical outcome of FH.” [3]

The emphasis on the mildness of the mutations for most carriers has been snipped out of the historical record. Just as we see with the issue of genetic testing, once again there is a peripheral mention of a central issue. Somehow, critical premises do not factor into the conclusions, at all.  The fact that mutations are milder illustrates how the linguistic conflation of diseases is largely irrelevant to the actual treatment of mutation carriers.

However, the fact of mildness is also a fatal premise within a complete argument for the recommended diagnostic procedure. Once this premise is retrieved from the historical record, and re-inserted into today’s record, the recommendation cannot survive. In Part 2, I will demonstrate, with Euclidean precision, a swap of “FH” populations.

[1] Note that this passage was published by some of the same authors who are central to my reports and who were later funded by Big Pharma. I refer to this publication as the “Earlier Report.” “Phenotype of Heterozygotes for Low-Density Lipoprotein Receptor Mutations Identified in Different Background Populations;” Anne Tybjærg-Hansen, Henrik Kjærulf Jensen, Marianne Benn, Rolf Steffensen, Gorm Jensen, Børge G. Nordestgaard 2005

[2] “Mechanisms of Disease: genetic causes of familial hypercholesterolemia;” Anne K Soutar and Rossi P Naoumova 2007

[3] “No certain predictors for mutation status in a Danish cohort with familial hypercholesterolemia: A descriptive study” Mads Nybo, Klaus Brusgaard, Annebirthe Bo Hansen; 2007