Familial combined hyperlipidemia
Lipoprotein Disorders Microchapters |
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]
Synonyms and keywords: Type IIB hyperlipoproteinemia
Overview
Based on old and recent definitions, Familial combined hyperlipidemia is a common metabolic disorder charaterized by following:-
- An increased cholesterol and/or triglycerides in at least to members of the same family.
- An intra-individual and intrafamilial variability of the lipid phenotype
- An increased risk of premature coronary heart disease.
The high VLDL levels are due to overproduction of substrates, including triglycerides, acetyl-CoA, and an increase in B-100 synthesis.
Historical perspective
- In 1967, Fredrickson using paper electrophosresis , classified lipoprotein disorder.[1]
- In 1973, Familial combined hyperlipidemia (FCHL) for the first time in medical literature was described by Goldstein.
Classification
- There is no established classification for familial combined hyperlipidemia.
Pathophysiology
Pathogenesis
The exact pathogenesis of Familial combined hyperlipidemia remains unknown. Several theories have been postulated about the development of a familial combined hyperlipidemia. The underlying mechanisms of the disease involves the following:-
VLDL abnormalities
LDL abnormalities
HDLs abnormalities
Causes
The cause of familial combined hyperlipidemia remains genetic.
Differential diagnosis
Epidemiology and Demographics
Epidemiology
Familial combined hyperlipidemia is a a very common genetic hyperlipidemia . The prevalence is estimated to be 0.5-2% in general population annually. Familial combined hyperlipidemia is commonly seen in patients with coronary disease( 10%) , patients less than 60 years of age who have survived an acute infarct (11.3%) and upto 40% in all myocardial infarction survivors. [2][3] More than 3.5 million people in EU and 2.7 million in the US suffer from familial combined hyperlipidemia.[2]
Demographics
Geographical distribution can not be estimated so far as most of the studies conducted on familial combined hyperlipidemia consist of Caucasian population living the United States and Europe.[4]
Age
Familial combined hyperlipidemia is commonly seen in all ages in myocardial infarction survivors.[3] Dr. Iwata in 2003 explained that many patients with familial combined hyperlipidemia present during their childhood.[5]
Gender
Familial combined hyperlipidemia affects men and women equally.
Screening
Natural History, Complications, and Prognosis
Natural History
If left untreated, familial combined hyperlipidemia leads to increased carotid artery initima-media thickness and an increased risk of cardiovascular disease.[6]
Complications
Complications that can develop in patients with familial combined hyperlipidemia include[7][8][9]
- Coronary heart disease
- Coronary vasuclar disease
Prognosis
The presence of hypertriglyceridemia along with hypercholesterolemia is a poor prognostic factor. The coronary flow reserve in young patients is decreased in the presence of this combination.[10]
Diagnosis
History and symptoms
Symptoms of
Physical examination
- Signs of Type
Laboratory findings
Molecular Genetic Testing
Treatment
Pregnancy Management
Investigative Therapies
Gene Therapy
Prevention
Secondary prevention
Prevention of complications
References
- ↑ Culliton BJ (1987). "Fredrickson's bitter end at Hughes". Science. 236 (4807): 1417–8. PMID 3296193.
- ↑ 2.0 2.1 Gaddi A, Galetti C, Pauciullo P, Arca M (1999). "Familial combined hyperlipoproteinemia: experts panel position on diagnostic criteria for clinical practice. Committee of experts of the Atherosclerosis and Dysmetabolic Disorders Study Group". Nutr Metab Cardiovasc Dis. 9 (6): 304–11. PMID 10765523.
- ↑ 3.0 3.1 de Bruin TW, Mailly F, van Barlingen HH, Fisher R, Castro Cabezas M, Talmud P; et al. (1996). "Lipoprotein lipase gene mutations D9N and N291S in four pedigrees with familial combined hyperlipidaemia". Eur J Clin Invest. 26 (8): 631–9. PMID 8872057.
- ↑ Gaddi A, Cicero AF, Odoo FO, Poli AA, Paoletti R, Atherosclerosis and Metabolic Diseases Study Group (2007). "Practical guidelines for familial combined hyperlipidemia diagnosis: an up-date". Vasc Health Risk Manag. 3 (6): 877–86. PMC 2350131. PMID 18200807.
- ↑ Iwata F, Okada T, Kuromori Y, Hara M, Harada K (2003). "Screening for familial combined hyperlipidemia in children using lipid phenotypes". J Atheroscler Thromb. 10 (5): 299–303. PMID 14718747.
- ↑ Keulen ET, Kruijshoop M, Schaper NC, Hoeks AP, de Bruin TW (2002). "Increased intima-media thickness in familial combined hyperlipidemia associated with apolipoprotein B." Arterioscler Thromb Vasc Biol. 22 (2): 283–8. PMID 11834529.
- ↑ Goldstein JL, Schrott HG, Hazzard WR, Bierman EL, Motulsky AG (1973). "Hyperlipidemia in coronary heart disease. II. Genetic analysis of lipid levels in 176 families and delineation of a new inherited disorder, combined hyperlipidemia". J Clin Invest. 52 (7): 1544–68. doi:10.1172/JCI107332. PMC 302426. PMID 4718953.
- ↑ Sniderman AD, Castro Cabezas M, Ribalta J, Carmena R, de Bruin TW, de Graaf J; et al. (2002). "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. 32 (2): 71–3. PMID 11895451.
- ↑ Ayyobi AF, Brunzell JD (2003). "Lipoprotein distribution in the metabolic syndrome, type 2 diabetes mellitus, and familial combined hyperlipidemia". Am J Cardiol. 92 (4A): 27J–33J. PMID 12957324.
- ↑ Pitkänen OP, Nuutila P, Raitakari OT, Porkka K, Iida H, Nuotio I; et al. (1999). "Coronary flow reserve in young men with familial combined hyperlipidemia". Circulation. 99 (13): 1678–84. PMID 10190876.
Template:WikiDoc Sources rance of LDL. Prevalence in the population is 10%.