Diagnostic Criteria in Relation to the Pathogenesis of Familial Combined Hyperlipidemia

Jacqueline de Graaf; Gerly van der Vleuten; Anton F. H. Stalenhoef

doi:10.1055/s-2004-861490

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Semin Vasc Med 2004; 4(3): 229-240
DOI: 10.1055/s-2004-861490

Diagnostic Criteria in Relation to the Pathogenesis of Familial Combined Hyperlipidemia

Jacqueline de Graaf¹ , Gerly van der Vleuten¹ , Anton F. H. Stalenhoef¹

¹Department of Medicine, Division of General Internal Medicine, University Medical Center Nijmegen, Nijmegen, The Netherlands

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Publication Date:
03 January 2005 (online)

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ABSTRACT

Familial combined hyperlipidemia (FCH) is the most common inherited hyperlipidemia in humans, affecting 1 to 3% of the adult population and up to 20% of patients with premature myocardial infarction. FCH is traditionally diagnosed by total plasma cholesterol and/or triglyceride levels above the 90th percentile adjusted for age and gender; however, the diagnosis of FCH based on these diagnostic criteria is inconsistent in 26% of the subjects over a five-year period, emphasizing the need for re-evaluation of the diagnostic criteria for FCH. Recently, a nomogram was developed based on absolute apolipoprotein B levels in combination with triglyceride and total cholesterol levels adjusted for both age and gender to simply and accurately diagnose FCH. When percentiles of triglyceride and total cholesterol adjusted for age and gender are not available in a population, the definition of FCH can be established based on hypertriglyceridemia (> 1.5 mmol/l) and hyperapoB (> 1200 mg/l).

Standardized and simple diagnostic criteria are necessary to further delineate the pathogenesis of FCH. Several metabolic pathways have been suggested to be important in causing the FCH phenotype including hepatic VLDL overproduction either with or without impaired clearance of triglyceride-rich lipoproteins from plasma. The presence of insulin resistance and obesity in FCH patients further contribute to the expression of the lipidphenotype. A disturbed adipose tissue metabolism that results in an increased plasma free fatty acid pool may be the culprit in the pathogenesis of FCH.

KEYWORDS

Apolipoproteins - diagnosis - follow-up studies - hyperlipoproteinemia

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Dr.
J. de Graaf

Department of Medicine, Division of General Internal Medicine 541, University Medical Center Nijmegen

P.O. Box 9101, 6500 HB Nijmegen, The Netherlands

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