Familial Hypercholesterolaemia; heterozygous survival

When you sit here with an LDL cholesterol which makes a cardiologist's trigger finger itch for a reflex prescription of lovastatin, you get quite interested in the fate of others with high LDL cholesterol levels. I found this familial hypercholesterolaemia paper by accident while looking for a paper on blood insulin levels by some big noise in USA cardiology.

BTW: That hunt was triggered by Michael Eades' post (back on line here) on ITT (intention to treat) analysis and the murkier aspects of statistical techniques. The insulin paper was mind boggling. Their limit of detection for plasma insulin was 2.0microIU/ml. A big chunk of their patient base had insulin levels below this, SO THEY MADE UP A DATASET, based on an assumed distribution. Duh. Wish I could find it! Plus I remember them as obese USA citizens, non of whom were type 1 diabetics or were at the end stage of type 2 diabetes. No healthy person runs a fasting insulin below 2.0microIU/ml. So the assay was probably rubbish anyway!

Anyway, back to heterozygous FH. It's another paper by Sijbrands on the mortality of patients with untreated FH.

Here's the first paragraph of the discussion:

"In the present study, mortality was highest in families which were ascertained through cases with a premature onset of CAD. These families — in particular the male patients in middle age — had high excess mortality. This high excess mortality underscores that our results do not detract from the older finding of increased mortality in families in whom the disorder was clinically recognised. These old studies described a decreased life expectancy in families with familial hypercholesterolaemia that were investigated because the probands — or even multiple family members — had presented themselves with premature cardiovascular disease"


This translates as: In families with FH and premature heart disease there is premature heart disease. Yes, that's what it says.


"Presumably these families — and our families with a premature onset of CAD — were characterised by clustering of risk factors. In the present study, a lot of families were not ascertained by clinical outcome but by routine measurement of cholesterol and they had a life expectancy similar to the Dutch population, suggesting the presence of protecting factors or the absence of additional risk factors"


Translation: In families WITH heterozygous familial hypercholesterolaemia, but WITHOUT premature heart disease, life expectancy is NORMAL (rather, the phrase is "similar to the Dutch population"). There is no premature CVD. There are a lot of these families. I wonder if they are all on statins? If so, why?


"Others also observed normal survival of some familial hypercholesterolaemic patients [3 and 4]. The factors involved in this reduced risk of mortality from the disorder are yet unknown and their identification is needed to enable prediction of longevity"


What I feel is missing from the paper is the inclusion, taken from the normocholesterolaemic Dutch population, of a group of people with normal cholesterol receptor genetics but WITH premature heart disease. There are plenty of families with this predicament. Then do some comparisons with the various FH groups discussed by Sijbrands... That might put FH in to perspective.

Peter