Background review of 2nd report’s total prevalence: FH + FDB

FH LDLR and FDB APOB combined

Let’s review how the 2nd report[1] derived FH prevalence (FH+FDB). 55 probands were found among the Top4 mutations. In total, 142 probands were found in the whole spectrum. (This means that there were 87 probands found within the spectrum that were not in the Top4. I call these the “Ex-Top4” probands.)  Thus, the 55 Top4 probands are 38.7% of all probands found.[2] (55÷142=.387). 

Prevalence claimed in the second Danish Report

In the general population, it was too expensive and time consuming to test everyone for all known mutations and so only these four most frequent mutations were targeted. This is the reason why we are carrying the ratio of Top4-to-total probands in the spectrum over to the Top4 hits in the general population. We want to use this ratio to factor the Ex-Top4 into the Copenhagen study’s molecular results, giving us “FH” prevalence  (“FH” = FH+FDB).

In this parallel set of numbers, a total of 174 Top4 mutation carriers were found in the Copenhagen study.  How many hits would we have if we had included the Ex-Top4 mutation carriers as targets? We divide 174 by the .387 to factor in the remainder of the mutation carriers in the population and arrive at total of 449.6, which we will round up in the authors’ favor to 450. Dividing the population of 98,098 by 450 we arrive at 1:217.9956. We must round down against the rules to get the 217 found in the report. (There is another red flag here; see footnote [3].)

Mapping the method used to calculate FH prevalence in the Second Danish Report
Table of traditional FH and the new, blended version

The traditional number for HeFH prevalence is 1:500.  So how is it that these new prevalence numbers are so different?

First, 111 of the 174 mutation carriers found were FDB.  Only 63 were FH. So FDB was conflated with FH. That’s a linguistic event, not a recognition of new patients.[4]

When the authors separate the FH and FDB numbers, what do we find?

[1] Review of report relationships: The Authoritative report depends entirely upon the 1st report and its corrigendum.  The 2nd report shares 60,000 of its population with the 1st report. The 2nd report declares that its results are comparable to those of the 1st report.

[2] Red Flag: Compared to the 2nd report’s use of Tybjærg-Hansen’s results, Brusgaard’s much larger spectrum list determined a different set of four most frequent mutations for Denmark. And even when considering the same Top4 mutations used for the 2nd report, his data suggests a 50% proportion to the rest of the spectrum, not 38.7%. That would lower the prevalence results. See Brusgaard, et al, and Supplement to the 2nd report.

[3] Red Flag: Although the title to the report uses 98,098, the actual constituents of the population were not rounded and they totaled exactly 98,000. Elsewhere, 99,098 is used. And the math supporting some of these numbers simply does not add up.  For details and screenshots, see this page.

[4] See this page.