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Familial Combined Hyperlipidemia

Familial combined hyperlipidemia is an autosomal inherited lipid abnormality and one of the most common genetic dyslipidemias, whose features partly overlap with those of the metabolic syndrome. This condition is characterized by high levels of total cholesterol and triglycerides, decreased high density lipoprotein (HDL) cholesterol concentration, high apoB concentration, and high low density lipoprotein (LDL) levels. Patients are usually asymptomatic during childhood, although biochemical abnormalities are present at a young age, but have significant cardiovascular disease as they grow older.


Familial combined hyperlidemia patients are initially asymptomatic, but need to monitor body weight [1] and waist- to- hip ratio [2] in order to avoid abdominal obesity, that seems to be related to lipid profile modification. These parameters are also in relation with other biochemical abnormalities: decreased leptin and adiponectin [3] and high insulin resistance [4]. Same principles apply to children who come from affected parents, who need to maintain body weight within normal range.

Signs of hepatic suffering may be encountered in the context of fatty liver and non-alcoholic steatohepatitis [5], but they are not specific for familial combined hyperlidemia. Clinical examination is noncontributory in some cases, because xanthoma are almost never present in this disease [6].

Patients may also suffer form arterial hypertension [7], which further increases cardiovascular risk.

Coronary Atherosclerosis
  • atherosclerosis. [ PMID 18303204 ] Body mass index is associated with USF1 haplotype in Korean premenopausal women. [ PMID 18445538 ] Upstream transcription factor 1 (USF1) in risk of type 2 diabetes: association study in 2000 Dutch Caucasians. [ PMID[snpedia.com]
  • Association of coronary atherosclerosis with hyperapobetalipoproteinemia [increased protein but normal cholesterol levels in human plasma low density (beta) lipoproteins]. Proc Natl Acad Sci U S A . 1980; 77 : 604–608.[ahajournals.org]
  • atherosclerosis. remnant hyperlipidemia a form in which the accumulated lipoproteins are normally transient intermediates, chylomicron remnants, and intermediate-density lipoproteins; a generic descriptor for the type III hyperlipoproteinemia phenotype[medical-dictionary.thefreedictionary.com]
  • Effects of fluvastatin on coronary atherosclerosis in patients with mild to moderate cholesterol elevations (Lipoprotein and Coronary Atherosclerosis Study [LCAS]). Am J Cardiol. 1997;80:278–86. 15.[aafp.org]
  • The subfractions were carefully aspirated by means of a Pasteur pipette. The volumes were calculated by weighing after correction for the densities.[atvb.ahajournals.org]
  • […] patients and control subjects recruited into the study gave fully informed written consent and the protocol was approved by the Scientific and Ethical Committee of the Hospital Universitari de Sant Joan. analytical methods A 10-mL venous blood sample was withdrawn[clinchem.aaccjnls.org]


The biochemical profile has several specific traits: reduced HDL level (<40 mg/dL), high LDL level (> 160 mg/dL) and/or high triglyceride (TG) level (> 200 mg/dL). High LDL and TG levels (in association) are usually not found in the general population, only one of them is usually present. These parameters must be evaluated in a recurrent manner, keeping in mind that members of the same family may have different phenotypes [8]. Familial combined hyperlidemia is also characterized by increased apo B levels (> 125 mg/dL), which also constitutes a good prognostic factor [9].

Vascular echography is used to measure carotid artery intima-media thickness, which is increased in patients that already had a cardiovascular or cerebrovascular event. Other echography findings, like increased pulse wave velocity and reduced flow mediated dilation are reliable parameters that assess endothelial dysfunction and arterial stiffness, but are unable to increase event prediction [10]. Ultrasound analysis should not be limited to carotid arteries, it should also be performed on femoral arteries and the aorta. Silent myocardial ischemia should also be taken into consideration and evaluated using stress tests. Echography of the heart and the aorta should be performed every year. Computed-tomography coronary angiography is also an option in uncertain cases. Carotid intima medial thickness should also be assessed in children. They can also benefit from positron emission tomography scans in selected cases because if significant plaque is present, hypolipemic treatment may be initialized by a pediatric cardiologist.

Genetic studies reveal a locus on chromosome 1 (1q21-q23) that is linked both to familial combined hyperlidemia and type 2 diabetes [11]. Apo AV gene may also be linked to disease transmission [12], as well as the gene encoding upstream transcription factor 1 [13]. However, gene expression depends on environmental factors, making the diagnosis even more difficult [14].

  • A 60-yr-old woman was admitted for evaluation of hyponatremia. Administration of hydrocortisone normalized the level of serum Na. A pituitary hormone-stimulating test and brain computed tomography revealed panhypopituitarism with an empty sella.[ncbi.nlm.nih.gov]
Liver Biopsy
  • Finally, gene expression studies in liver biopsies and liver cell culture experiments have gained further insight in the role of upstream stimulatory factor 1, one of the most replicated genes in FCHL, in its pathogenesis.On the basis of these observations[ncbi.nlm.nih.gov]


  • RESULTS: Before treatment, TG were similar between the -493T allele carriers and non-carriers.[ncbi.nlm.nih.gov]


  • To achieve this, lifestyle changes, medications such as statins, and/or treatment of associated conditions may be used The prognosis is favorable if Familial Combined Hyperlipidemia is diagnosed early and treated promptly.[dovemed.com]
  • Outlook (Prognosis) How well you do depends on: How early the condition is diagnosed When you start treatment How well you follow your treatment plan Without treatment, heart attack or stroke may cause early death.[stlukes-stl.com]
  • Other cholesterol-lowering medicines include: Bile acid-sequestering resins Ezetimibe Fibrates (such as gemfibrozil and fenofibrate) Nicotinic acid Expectations (prognosis) How well you do depends on how early the condition is diagnosed, when treatment[kentuckyonehealth.org]


  • BACKGROUND: Familial combined hyperlipidemia (FCH) is the most common genetic lipid disorder with an undefined genetic etiology. Apolipoprotein A5 gene (APOA5) variants were previously shown to contribute to FCH.[ncbi.nlm.nih.gov]
  • (Etiology) Familial Combined Hyperlipidemia is passed down through the families. It is the most common genetic disorder causing abnormal lipid levels in blood.[dovemed.com]


  • See other definitions of FCHL Samples in periodicals archive: Their topics include how much evidence is enough, epidemiological aspects of lipid and lipoprotein levels in relation to cardiovascular diseases, whether raising HDL protects against atherosclerosis[acronymfinder.com]
  • Statistical Analysis for Genetic Epidemiology, Release 2.2. 1994 Computer program package available from the Department of Epidemiology and Biostatistics, Case Western Reserve University, Cleveland, Ohio. This program is supported by a U.S.[diabetes.diabetesjournals.org]
  • Statistical analysis for genetic epidemiology, Version 4.0 Beta 6, 2000. Case Western Reserve University, Cleveland, 2000 22 S.A.G.E. Statistical analysis for genetic epidemiology, Version 3.1 Beta 6, 1997.[nature.com]
  • Thirdly, controversy exists regarding the closeness of the relationship between retinoids and lipids: On one hand, hypertriglyceridemia has been reported to develop as a result of the therapeutic use of retinoids ( 26 ); on the other hand, epidemiological[clinchem.aaccjnls.org]
Sex distribution
Age distribution


  • To conduct focused studies of lipoprotein physiology and pathophysiology in genetically characterized patients with the objectives of understanding disease mechanisms, developing better treatments, and identifying and preventing early vascular disease[clinicaltrials.gov]
  • This finding implies a role of adipose tissue metabolism in the pathophysiology of FCH.[ncbi.nlm.nih.gov]
  • To study the pathophysiological basis and genetics of FCHL, we previously reported recruitment of 18 large families.[nyu.pure.elsevier.com]
  • Abstract Familial combined hyperlipidemia (FCHL) and familial hypertriglyceridemia (FHTG) are two common genetic forms of hyperlipidemia that differ in their clinical consequences and pathophysiology but are as yet poorly understood.[link.springer.com]
  • Pathophysiology of hypertriglyceridemia. Biochim Biophys Acta . 2012 May. 1821(5):826-32. [Medline] .[emedicine.medscape.com]


  • This novel mutation, which prevents the synthesis of Apo A-I, was also found in four family members, including three siblings and the daughter of the proband.[ncbi.nlm.nih.gov]
  • Prevention & Expectations What can be done to prevent the condition? An inherited condition cannot be prevented once a person is born. Genetic counseling may be helpful to couples with a family history of the disease.[medicineonline.com]
  • Author affiliations Royal Victoria Hospital, McGill Unit for the Prevention of Cardiovascular Disease, McGill University, Montréal, Québec, Canada Gotto Jr.[karger.com]



  1. Koprovicova J, Kollar J, Petrasova D. Nutrition, body weight and deterioration of familial combined hyperlipidemia. Coll Antropol. 2006;30:777–782.
  2. van der Kallen CJ, Voors-Pette C, de Bruin TW. Abdominal obesity and expression of familial combined hyperlipidemia. Obes Res. 2004;12:2054–2061.
  3. van der Vleuten GM, Veerkamp MJ, van Tits LJ, et al. Elevated leptin levels in subjects with familial combined hyperlipidemia are associated with the increased risk for CVD. Atherosclerosis. 2005;183:355–360.
  4. Veerkamp MJ, de Graaf J, Stalenhoef AF. Role of insulin resistance in familial combined hyperlipidemia. Arterioscler Thromb Vasc Biol. 2005;25:1026–1031.
  5. Sveger T, Nordborg K. Apolipoprotein B as a marker of familial hyperlipoproteinemia. J Atheroscler Thromb. 2004;11:286–292.
  6. Mancuso G, La Regina G, Bagnoli M, et al. “Normolipemic” tendinous and tuberous xanthomatosis. Dermatology. 1996;193:27–32.
  7. Ascaso JF, Merchante A, Lorente RI, et al. A study of insulin resistance, using the minimal model, in non-diabetic Familial combined hyperlipidemic patients. Metabolism. 1998;47:508-513.
  8. Ylitalo K, Syvanne M, Salonen R, et al. Carotid artery intima-media thickness in Finnish families with familial combined hyperlipidemia. Atherosclerosis. 2002;162:171–178.
  9. de Graaf J, van der Vleuten G, Stalenhoef AF. Diagnostic criteria in relation to the pathogenesis of familial combined hyperlipidemia. Semin Vasc Med. 2004;4:229–240.
  10. Ter Avest E, Holewijn S, van Tits LJ, et al. Endothelial function in familial combined hyperlipidaemia. Eur J Clin Invest. 2007;37:381–389.
  11. Allayee H, Krass KL, Pajukanta P, et al. Locus for elevated apolipoprotein B levels on Chromosome 1p31 in families with familial combined hyperlipidemia. Circ Res. 2002;90:926–931.
  12. Eichenbaum-Voline S, Olivier M, Jones EL, et al. Linkage and association between distinct variants of the APOA1/C3/A4/A5 gene cluster and familial combined hyperlipidemia. Arterioscler Thromb Vasc Biol. 2004;24:167–174.
  13. Pajukanta P, Lilja HE, Singheimer JS, et al. Familial Combined hyperlipidemia is associated with upstream transcription factor 1 (USF 1) Nat Gen. 2004;36:371–376.
  14. Stalenhoef AF. Interaction between genes and environment in inherited lipid disorders determines clinical presentation. Cardiovasc Drugs Ther. 2002;16:271–272.

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Last updated: 2019-07-11 20:04