Familial Combined Hyperlipidemia

– Summary:

It is a mixed dyslipidemia when total cholesterol and triglyceride levels are above 200 and 150 mg/dl, respectively. Once this is done, it is about reaching the causal diagnosis.

Familial combined hyperlipidemia (FCH) is the most common inherited disorder of lipid metabolism associated with mixed hyperlipidemia and premature cardiovascular disease (CVD). It was described by Goldstein in 1973 when studying families of survivors of myocardial infarction.

In this sense, there are many secondary causes that can cause this type of dyslipidemia, such as diabetes, obesity, hypothyroidism, kidney disease, liver disease, consumption of a diet high in carbohydrates, saturated fats, alcohol or various drugs (corticosteroids, beta-blockers , estrogens, etc.)

– Developing:

As part of the differential diagnosis, it is necessary to evaluate the possibility of primary dyslipidemias. Among these, both dysbetalipoproteinemia and familial combined hyperlipidemia present as a mixed lipid disorder.

Some clinical data, such as a history of recurrent pancreatitis, a family history of premature ischemic heart disease, very high cholesterol levels (total cholesterol ≥320 mg/dl and low-density lipoprotein cholesterol ≥190 mg/dl), and the presence of xanthomas, may suggest a primary cause.

It is a dyslipidemia of polygenic origin that is considered the most frequent primary dyslipidemia. It is estimated that its prevalence is between 1% and 3% of the population.

Familial combined hyperlipidemia presents with diverse lipid profiles that can be fluctuating, sometimes isolated hypercholesterolemia or hypertriglyceridemia or mixed dyslipidemia.

As well as the elevation of apolipoprotein B levels (defined as the value above the 90th percentile of the population for sex and age: women ≥ 98 mg/dl and men ≥ 108 mg/dl).

In addition, it is very common for this dyslipidemia to manifest itself together with other metabolic disorders, such as diabetes or obesity, which increases its severity and generates a greater cardiovascular risk.

Patients with familial combined hyperlipidemia have first-degree relatives who have mixed or isolated lipid profiles with abnormalities.
The predominance of particles with apolipoprotein B in this dyslipidemia significantly increases cardiovascular risk, which favors the appearance of premature ischemic heart disease.

In the clinic there is a family history of premature ischemic heart disease, in addition to fluctuating lipid profiles with elevated apolipoprotein B and first-degree relatives with mixed dyslipidemia and isolated hypertriglyceridemia.

This strongly suggests the possibility of familial combined hyperlipidemia. It is not a dyslipidemia secondary to diabetes since it does not meet the criteria for it (there are also no biochemical data of another alteration or use of drugs).

On the other hand, homozygous familial hypercholesterolemia tends to present at younger ages, with higher cholesterol levels, and is associated with the presence of xanthomas.

Finally, the profile of familial hypertriglyceridemia is more related to very high triglycerides (above the 95th percentile of the population for age and sex, which sometimes generates figures greater than 1,000 mg/dl).
It is grouped as high cardiovascular risk due to the various cardiovascular risk factors and primary dyslipidemia.

– Conclusions:

Familial combined hyperlipidemia (HCL) is the most common primary dyslipidemia; however, it often goes undiagnosed and its precise definition is controversial.

HCLF is characterized by fluctuations in serum lipid concentrations and can present as mixed hyperlipidemia, isolated hypercholesterolemia, hypertriglyceridemia, or as a normal serum lipid profile in combination with abnormally elevated levels of apolipoprotein B.

HCLF is a primary lipid disorder involving multiple genes, which can result from the interaction of several contributing variants and mutations along with environmental triggers.

The controversies surrounding the relevance of identifying FCHL as a cause of isolated hypertriglyceridemia and the differential diagnosis of familial hypertriglyceridemia are offset by the description of associations with USF1 and other genetic traits that are unique to FCHL.

Patients have an increased risk of cardiovascular disease and mortality, and have a high frequency of comorbidity with other metabolic diseases, such as type 2 diabetes, nonalcoholic fatty liver disease, hepatic steatosis or fatty liver, and metabolic syndrome .

Treatment usually requires lipid-lowering therapy aimed at lowering cholesterol and triglyceride levels.

s along with cardiovascular risk protection.

Eicosapentaenoic (EPA) and docosahexaenoic (DHA) acids, at doses >2g/day, reduce TG levels by up to 25%; however, the available evidence on its benefit in cardiovascular prevention has not been conclusive.
In hypertension, long-acting drugs should be used, with ACE inhibitors, ARBs or calcium antagonists being recommended due to their neutral effect on the lipid and glycemic profile.

– References:

Rev Invest Clin. 2018;70(5):224-236. doi: 10.24875/RIC.18002575.

Familial Combined Hyperlipidemia: Consensus Document
Familial combined hyperlipidemia: Consensus document
Peter Mata. SEMERGEN.Vol. 40. No. 7. pages 374-380 (October 2014)

Polygenic dyslipemia, familial dyslipemia, familial dyslipemia and triglycerides, familial dyslipemia and treatment, hepatic steatosis and dyslipemia.

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