Metabolic and genetic aspects of familial combined hyperlipidaemia with emphasis on low‐density lipoprotein heterogeneity

Bredie, S.J.H.; Demacker, P.N.M.; Stalenhoef, Anton F. H.

doi:10.1046/j.1365-2362.1997.1850734.x

Cited by 31 publications

(19 citation statements)

References 109 publications

(154 reference statements)

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“…FCH is characterized by increased levels of plasma total cholesterol, triglycerides, and/or apolipoprotein B (apoB). Other phenotypes of FCH are decreased levels of HDL-C and the presence of sdLDL (23)(24)(25). In addition, FCH is associated with obesity and insulin resistance (26).…”

Section: Van Der Vleuten Et Al Decreased Adiponectin Levels In Patiementioning

confidence: 99%

Decreased adiponectin levels in familial combined hyperlipidemia patients contribute to the atherogenic lipid profile

Vleuten

Tits

Heijer

et al. 2005

Journal of Lipid Research

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Familial combined hyperlipidemia (FCH) is characterized by increased levels of total cholesterol, triglycerides, and/or apolipoprotein B. Other features of FCH are obesity and insulin resistance. Adiponectin is a secretory product of the adipose tissue. Low levels of adiponectin are associated with insulin resistance and accelerated atherosclerosis. The aim of this study was to determine whether decreased adiponectin levels are associated with FCH and its phenotypes. The study population comprised 644 subjects, including 158 patients with FCH. Serum adiponectin levels were determined using a commercially available ELISA. For both males and females, the mean adiponectin level ( g/ml) was significantly lower in FCH patients [2.0 (1.8-2.2) and 2.5 (2.3-2.8), respectively] compared with normolipidemic relatives [2.3 (2.2-2.5) and 3.1 (2.8-3.3), respectively] and spouses [2.4 (2.1-2.7) and 3.2 (2.8-3.6), respectively]. These differences remain significant after adjusting for waist circumference and insulin resistance. Low adiponectin level in FCH patients was a superior independent predictor of the atherogenic lipid profile, including high triglyceride levels, low HDL-cholesterol levels, and the amount of small, dense LDL present, compared with both obesity and insulin resistance. Low adiponectin levels may contribute to the atherogenic lipid profile in FCH, independent of insulin resistance and obesity, as measured by waist circumference. This finding implies a role of adipose tissue metabolism in the pathophysiology of FCH.

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Section: Van Der Vleuten Et Al Decreased Adiponectin Levels In Patiementioning

confidence: 99%

Decreased adiponectin levels in familial combined hyperlipidemia patients contribute to the atherogenic lipid profile

Vleuten

Tits

Heijer

et al. 2005

Journal of Lipid Research

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“…Thus, based on lipids, the hallmarks of FCH are variability among subjects and within subjects. Among all of this variability, increased concentrations of apoB (apolipoprotein B) and sdLDL [small-dense LDL (lowdensity lipoprotein)] stand out as the two most consistent abnormalities in subjects with FCH [2][3][4][5][6]. These abnormalities might result from a decreased fractional catabolic rate of apoB-containing particles [7], but the majority of studies show that the increased concentrations of apoB and the presence of sdLDL are rather a consequence of increased secretion of VLDL (very-low-density lipoprotein) particles [8][9][10][11][12][13].…”

Section: Introductionmentioning

confidence: 99%

Effect of aging and obesity on the expression of dyslipidaemia in children from families with familial combined hyperlipidaemia

et al. 2006

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The aim of the present study was to delineate the mechanism(s) responsible for the increased secretion of VLDL (very-low-density lipoprotein) particles in patients with FCH (familial combined hyperlipidaemia). In 194 young adults (<25 years of age) recruited from families with FCH, we investigated how plasma lipids, (apo)lipoproteins and BMI (body mass index) varied with age. Furthermore, we performed a 5-year follow-up study of clinical and biochemical characteristics of a subset of this population (n=85) stratified by apoB (apolipoprotein B) levels (below or above the 75th percentile adjusted for age and gender). Plasma apoB concentration (r=0.45, P<0.0001), triacylglycerol (triglyceride) concentration (r=0.45, P<0.0001), LDL (low-density lipoprotein) subfraction profile (r=-0.46, P<0.0001) and BMI (r=0.51, P<0.0001) were significantly associated with age. Plasma apoB concentration in the hyperapoB group was already elevated at a young age, whereas other characteristics of FCH, as observed in adults, including triacylglycerol levels >1.5 mmol/l and/or small-dense LDL, were observed only sporadically. After the 5-year follow-up, BMI increased in both groups, and this increase was associated with changes in apoB (r=0.27, P<0.05), triacylglycerol (r=0.30, P<0.01), VLDL cholesterol (r=0.22, P<0.05), VLDL triacylglycerol (r=0.25, P<0.05) and high-density lipoprotein cholesterol (r=-0.27, P<0.05). In conclusion, we have found indirect evidence of a primary, presumably genetically determined, increase in plasma apoB concentration occurring early in life of offspring from families with FCH. However, aging-related post-maturation increases in adipose tissue mass also appear to contribute to an aggravation and/or modulation of this genetically determined apoB overproduction.

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“…Despite recent progress, the genetic and metabolic backgrounds of FCH have not been elucidated in detail. [4][5][6][7][8][9] This review discusses the evolution of the diagnostic criteria of FCH including the complex genetics and different metabolic pathways in the pathogenesis of this disorder.…”

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Diagnostic Criteria in Relation to the Pathogenesis of Familial Combined Hyperlipidemia

J¹,

G²,

Af³

2004

Seminars in Vascular Medicine

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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.

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Metabolic and genetic aspects of familial combined hyperlipidaemia with emphasis on low‐density lipoprotein heterogeneity

Cited by 31 publications

References 109 publications

Decreased adiponectin levels in familial combined hyperlipidemia patients contribute to the atherogenic lipid profile

Decreased adiponectin levels in familial combined hyperlipidemia patients contribute to the atherogenic lipid profile

Effect of aging and obesity on the expression of dyslipidaemia in children from families with familial combined hyperlipidaemia

Diagnostic Criteria in Relation to the Pathogenesis of Familial Combined Hyperlipidemia

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