* Combining the old and the recent definitions, FCH is now defined as a common metabolic disorder characterized by: (a) increase in cholesterolemia and/or triglyceridemia in at least two members of the same family, (b) intra-individual and intrafamilial variability of the lipid phenotype, and (c) increased risk of premature coronary heart disease (CHD) (Goldstein et al 1973; Sniderman et al 2002).

* @Gaddi A, Cicero A, Odoo F, Poli A A, Paoletti R, On behalf of the Atherosclerosis and Metabolic Diseases Study Group. Practical guidelines for familial combined hyperlipidemia diagnosis: an up-date. Vascular Health and Risk Management. 2007;3(6):877-886.

Very good question. I follow.

Dear Olena Polyakova

But what are the possible genetic causes or main factors which cause FCHL?

And someone needs to be labeled with FCHL, is there a criteria for that?

Regards

Hi Sikandar,

Unlike Familial hypercholesterolemia, FCHL is a less well defined entity. It is characterised by increased total cholesterol, LDL, TG and Apo B 100 in the background of similar lipid abnormalities in at least 2 first degree family members. Environmental factors also could be contributing. The atherosclerosis risk is variable but usually less compared to FH.Homogygous FH present very early due to atherosclerotic vascular disease. Heterozygous FH present at the same age group when FCHL also presents - usually fourth to sixth decades. FCHL very often require combination of statins and fenofibrate.If LDL do not reach target levels, Ezetimibe and PCSK 9 inhibitors may have to be added. Yield of cascade screening is less compared to FH.

thanks a lot A. George Koshy

But as we have some well-defined criteria for FH as sharing below, do we have one for FCHL, I understand he apparent phenotype of FCHL is so very broad to include not only poorly fasted lipid profilers, to secondary causes and then a lot many genetic alterations like apoE gene polymorphism but still if u ever come across any criteria SPECIFICALLY to label patients with FCHL as we have a scoring system for UK.

The Dutch ONE and the one used in UK for diagnosing FH, I am attaching below for reference.

I need a criteria for FCHL as it seems very prevalent and i could not find one

regards

I am not aware of a diagnostic criteria for FCHL.

I also feel FCHL has no specific criteria, and we have here so many moving within my hospital with this label which i think could be either because of poor fasting related raised triglycerides elevation or some secondary cause for elevating triglycerides.

Anyway A. George Koshy thanks a lot

I guess FCHL should only be labeled with these per-requisites:

1- Sampling to be done in appropriate fasting 8-12 hrs with sampling to be done around 0800 hrs to 0900 hrs and not later than this. I also suggest patient to not have some high fatty feel a day or two prior to that

2- We call it "Familial"so family history must be established

3- We should rule common causes of mixed hyperlipidemia like diabetes mellitus, obesity, certain drugs, kidney disease and may be others

4-Ensuring genetic testing if available like Apo E gene polymorphism and may be others.

If others can add more to it, it will help everybody to have some kind of criteria for diagnosis of FCHL.

Regards

It looks like genetic establishment of FCHL will be needed

Posting from Suviolahti E et al's abstract " The recent linkage and association studies and their replications are beginning to elucidate the genetic variations underlying the susceptibility to FCHL. Three chromosomal regions on 1q21-23, 11p and 16q22-24.1 have been replicated in different study samples, offering targets for gene hunting. In addition, several candidate gene studies have replicated the influence of the lipoprotein lipase (LPL) gene and apolipoprotein A1/C3/A4/A5 (APOA1/C3/A4/A5) gene cluster in FCHL. Recently, the linked region on chromosome 1q21 was successfully fine-mapped and the upstream transcription factor 1 (USF1) gene identified as the underlying gene for FCHL. This finding has now been replicated in independent FCHL samples."

So i guess future way forward to FCHL will and should on establishing the genetic association with:

1- Studying 1q21-23, 11p and 16q22-24.1 chromosomal region.

2- Lipoprotein lipase (LPL) gene mutations/polymorphisms

3-apolipoprotein A1/C3/A4/A5 (APOA1/C3/A4/A5) gene cluster

Reference: Suviolahti E et al. Unraveling the complex genetics of familial combined hyperlipidemia. Ann Med. 2006;38(5):337-51.

So i guess we can guide patients towards a diagnosis. I feel i need to study this area more.

Please add any advise if you have some link or guidance or experience

Regards

Olena Polyakova

That looks like bull's eye. Thanks a lot.

Can you share with me the link to mentioned guidelines?

Thanks a lot

Regards

Sorry i missed that..... got it now

Thanks a lot