Combined hyperlipidemia (CH) is a common, familial lipid disorder that causes a deranged lipid profile in affected individuals, and there is often a family history of cardiovascular disease or high cholesterol. CH has variable phenotypes, which are thought to be a result of genetic heterogeneity. The prevalence of CH is about 6% in the general population and over double that value among patients with familial coronary heart disease [1]. The suggested disease process is that there is a surplus production of low density lipoprotein (LDL) and very low density lipoprotein (VLDL) by the liver, which contain apolipoprotein B100 (apoB100) [2]. A grading system is in place, by which CH can be categorized into several subtypes depending on the prominent feature of a particular phenotype [3].

It is a very common condition in those with a preexisting cardiovascular disease, such as patients with a history of myocardial infarction. Although patients with CH may be diagnosed in the second or third decade of life, dyslipidemia may be present from birth but may remain asymptomatic in early life. Symptoms usually present later in life, and the prognosis is linked to the age of diagnosis and treatment initiation.

Patients present with signs of vascular compromise, such as angina, chronic ulcers, and intermittent claudication. Complications of CH mostly involve the cardiovascular system and comprise of conditions such as stroke. Furthermore, as it is a metabolic disorder, it is often associated with other metabolic diseases, such as nonalcoholic steatohepatitis (NASH), and glucose intolerance [4] [5]. Individuals with CH may also have metabolic syndrome as comorbidity. They also have a higher prevalence of obesity, diabetes, and coronary artery disease, compared to the general population.

• Hunting

  Coon H, Myers RH, Borecki IB, Arnett DK, Hunt SC, Province MA; et al. (2000). "Replication of linkage of familial combined hyperlipidemia to chromosome 1q with additional heterogeneous effect of apolipoprotein A-I/C-III/A-IV locus. [wikidoc.org]

  Hopkins PN, Heiss G, Ellison RC, Province MA, Pankow JS, Eckfeldt JH, Hunt SC: Coronary artery disease risk in familial combined hyperlipidemia and familial hypertriglyceridemia: a case-control comparison from the National Heart, Lung, and Blood Institute [lipidworld.biomedcentral.com]

  Eckfeldt, J.H. and Hunt, S.C. ( 2003 ) Coronary artery disease risk in familial combined hyperlipidemia and familial hypertriglyceridemia: a case–control comparison from the National Heart, Lung, and Blood Institute Family Heart Study. [academic.oup.com]

  Crossref Medline Google Scholar 3 Hopkins PN, Heiss G, Ellison RC, Province MA, Pankow JS, Eckfeldt JH, Hunt SC. [atvb.ahajournals.org]

• Intermittent Claudication

  Patients present with signs of vascular compromise, such as angina, chronic ulcers, and intermittent claudication. Complications of CH mostly involve the cardiovascular system and comprise of conditions such as stroke. [symptoma.com]

• Gangrene

  […] thickness and an increased risk of cardiovascular disease.[23] Complications Complications that can develop in patients with familial combined hyperlipidemia include:[24][25][26][27] Atherosclerosis Coronary artery disease Peripheral artery disease Gangrene [wikidoc.org]

• Short Arm

  arm of chromosome 19. 56 Nishina PM...Krauss RM 1731344 1992 28 Familial combined hyperlipidaemia linked to the apolipoprotein AI-CII-AIV gene cluster on chromosome 11q23-q24. 56 Wojciechowski AP...Shepherd J 1670899 1991 29 Hypertriglyceridemia as a [malacards.org]

• Withdrawn

  […] 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 [academic.oup.com]

The diagnosis of combined hyperlipidemia is made by evaluation of the lipid profile, that is, serum triglyceride and cholesterol levels. Typically, there are elevated levels of triglycerides, LDL, VLDL, and apoB100. There may also be a decrease in HDL (high density lipoprotein) cholesterol [6]. Genetic testing may be done.

The parameters that best describe CH are not well defined, as different criteria yield different diagnoses [7] [8]. The proposed diagnostic criteria are: hyperlipidemia observed in several consecutive tests in the patient, as well as in a relative [9].

Diagnosis is made even more challenging by the relatively normal lipid levels exhibited by a number of patients; these are correlated to certain factors, such as body weight, and may remain low until the associated factors change [10]. Waist to hip ratio can be a useful tool in diagnosing CH. Other conditions to test for include diabetes and coronary artery disease. The identification of CH in children is complicated, as there is no correlation between lipid levels measured before the age of 12, and the development of CH in adult life.

1. Wiesbauer F, Blessberger H, Azar D, et al. Familial-combined hyperlipidaemia in very young myocardial infarction survivors (< or =40 years of age). Eur Heart J. 2009;30(9):1073-1079.
2. Venkatesan S, Cullen P, Pacy P, Halliday D, Scott J. Stable isotopes show a direct relation between VLDL apoB overproduction and serum triglyceride levels and indicate a metabolically and biochemically coherent basis for familial combined hyperlipidemia. Arterioscler Thromb. 1993;13(7):1110-1118.
3. Pihlajamäki J1, Karjalainen L, Karhapää P, Vauhkonen I, Laakso M. Impaired free fatty acid suppression during hyperinsulinemia is a characteristic finding in familial combined hyperlipidemia, but insulin resistance is observed only in hypertriglyceridemic patients. Arterioscler Thromb Vasc Biol. 2000;20(1):164-170.
4. Sniderman AD, Castro Cabezas M, Ribalta J, et al. A proposal to redefine familial combined hyperlipidaemia -- third workshop on FCHL held in Barcelona from 3 to 5 May 2001, during the scientific sessions of the European Society for Clinical Investigation. Eur J Clin Invest. 2002;32(2):71-73.
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8. del Rincon Jarero JP, Aguilar-Salinas CA, Guillén-Pineda LE, Gómez-Pérez FJ, Rull JA. Lack of agreement between the plasma lipid-based criteria and apoprotein B for the diagnosis of familial combined hyperlipidemia in members of familial combined hyperlipidemia kindreds. Metabolism. 2002;51(2):218-224.
9. Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults. Executive Summary of The Third Report of The National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, And Treatment of High Blood Cholesterol In Adults (Adult Treatment Panel III). JAMA. 2001;285(19):2486-2497.
10. Koprovicová J, Kollár J, Petrásová D. Nutrition, body weight and deterioration of familial combined hyperlipidemia. Coll Antropol. 2006;30(4):777-782.