doi: 10.1161/hq0202.104059
© 2002 American Heart Association, Inc.
Atherosclerosis and Lipoproteins |
Diagnosis of Familial Combined Hyperlipidemia Based on Lipid Phenotype Expression in 32 Families
Results of a 5-Year Follow-Up Study
From the Department of Medicine, Division of General Internal Medicine, and the Department of Epidemiology and Biostatistics (J.C.M.H.), University Medical Center Nijmegen, Nijmegen, the Netherlands.
Correspondence to M. Veerkamp, MD, Department of Medicine, Division of General Internal Medicine 541, University Medical Center Nijmegen, PO Box 9101, 6500 HB Nijmegen, Netherlands. E-mail m.veerkamp{at}aig.azn.nl
Familial combined hyperlipidemia (FCH) is characterized by a variable expression of hypercholesterolemia and/or hypertriglyceridemia. We evaluated the variability in lipid phenotype expression over a 5-year period and studied factors affecting the lipid phenotype expression. A total of 32 families (299 subjects) were studied in 1994 and in 1999. Subjects were classified as having FCH when total cholesterol and/or triglyceride levels exceeded the 90th percentile adjusted for age and sex. In 1994, 93 (31%) of the 299 subjects were affected, whereas 206 (69%) of the subjects were unaffected relatives. In 1999, a diagnosis of FCH was consistent in 69 (74%) of the 93 subjects. So, 26% of the FCH subjects in 1994 showed a sporadic normolipidemic pattern (ie, total cholesterol and/or triglycerides <90th percentile) in 1999. Among the 206 unaffected relatives in 1994, 178 (86%) remained unaffected in 1999, and 28 (14%) developed an FCH lipid phenotype. Multiple regression analysis showed that sex (odds ratio 2.03, 95% CI 1.09 to 3.87; P=0.03) and body mass index (odds ratio 1.14, 95% CI 1.05 to 1.24; P<0.01) significantly contributed to the variability in lipid phenotype expression. Thus, a diagnosis of FCH, based on plasma total cholesterol and/or triglyceride levels, is consistent in only 74% of the subjects over a 5-year period. Two other major characteristics of our FCH group, compared with the unaffected relatives, included elevated apolipoprotein B (apoB) levels and the presence of small dense low density lipoprotein (LDL), as reflected by a low value of the parameter K (apoB 1461±305 versus 997±249 mg/L, respectively [P<0.001]; K value -0.22±0.19 versus -0.02±0.19, respectively [P<0.001]). We now report that the apoB concentration and the K value show less variability in time and are more consistently associated with FCH, inasmuch as affected FCH subjects, compared with the unaffected relatives, persistently show a higher apoB level and a lower value of parameter K, reflecting small dense LDL, even when they present a sporadic normolipidemic pattern. In conclusion, our results emphasize the need for reevaluation of the diagnostic criteria for FCH. We demonstrate that apoB and small dense LDL are attractive new candidates for defining FCH. Further studies are indicated to evaluate the role of apoB and small dense LDL as diagnostic criteria for FCH.
Key Words: familial combined hyperlipidemia • follow-up study • diagnosis • apolipoprotein B • small dense LDL
This article has been cited by other articles:
 |
|
 |
|
  F. Wiesbauer, H. Blessberger, D. Azar, G. Goliasch, O. Wagner, L. Gerhold, K. Huber, K. Widhalm, F. Abdolvahab, G. Sodeck, et al. Familial-combined hyperlipidaemia in very young myocardial infarction survivors (<=40 years of age) Eur. Heart J., May 1, 2009; 30(9): 1073 - 1079. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. de Graaf, G. M. van der Vleuten, E. ter Avest, G. M. Dallinga-Thie, and A. F. H. Stalenhoef High Plasma Level of Remnant-Like Particles Cholesterol in Familial Combined Hyperlipidemia J. Clin. Endocrinol. Metab., April 1, 2007; 92(4): 1269 - 1275. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Nohara, M.-a. Kawashiri, T. Claudel, M. Mizuno, M. Tsuchida, M. Takata, S. Katsuda, K. Miwa, A. Inazu, F. Kuipers, et al. High Frequency of a Retinoid X Receptor {gamma} Gene Variant in Familial Combined Hyperlipidemia That Associates With Atherogenic Dyslipidemia Arterioscler Thromb Vasc Biol, April 1, 2007; 27(4): 923 - 928. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M De Michele, A Iannuzzi, A Salvato, P Pauciullo, M Gentile, G Iannuzzo, S Panico, A Pujia, G M Bond, and P Rubba Impaired endothelium-dependent vascular reactivity in patients with familial combined hyperlipidaemia Heart, January 1, 2007; 93(1): 78 - 81. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. S. van Aalst-Cohen, A. C.M. Jansen, M. W.T. Tanck, J. C. Defesche, M. D. Trip, P. J. Lansberg, A. F.H. Stalenhoef, and J. J.P. Kastelein Diagnosing familial hypercholesterolaemia: the relevance of genetic testing Eur. Heart J., September 2, 2006; 27(18): 2240 - 2246. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. C.G.J. Brouwers, N. Kono, M. M.J. van Greevenbroek, C. J.H. van der Kallen, A. J. Lusis, T. W.A. de Bruin, and R. M. Cantor Longitudinal Differences in Familial Combined Hyperlipidemia Quantitative Trait Loci. Arterioscler Thromb Vasc Biol, June 1, 2006; 26(6): e118 - e119. [Full Text] [PDF]
|
|
|
|
 |
|
 G. M. van der Vleuten, L. J. H. van Tits, M. den Heijer, H. Lemmers, A. F. H. Stalenhoef, and J. de Graaf Decreased adiponectin levels in familial combined hyperlipidemia patients contribute to the atherogenic lipid profile J. Lipid Res., November 1, 2005; 46(11): 2398 - 2404. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. M. Crooke, M. J. Graham, K. M. Lemonidis, C. P. Whipple, S. Koo, and R. J. Perera An apolipoprotein B antisense oligonucleotide lowers LDL cholesterol in hyperlipidemic mice without causing hepatic steatosis J. Lipid Res., May 1, 2005; 46(5): 872 - 884. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M.J. Veerkamp, J. de Graaf, and A.F.H. Stalenhoef Role of Insulin Resistance in Familial Combined Hyperlipidemia Arterioscler Thromb Vasc Biol, May 1, 2005; 25(5): 1026 - 1031. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 W. Putt, J. Palmen, V. Nicaud, D.-A. Tregouet, N. Tahri-Daizadeh, D. M. Flavell, S. E. Humphries, P. J. Talmud, and on behalf of the EARSII group Variation in USF1 shows haplotype effects, gene : gene and gene : environment associations with glucose and lipid parameters in the European Atherosclerosis Research Study II Hum. Mol. Genet., August 1, 2004; 13(15): 1587 - 1597. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. J. Veerkamp, J. de Graaf, J. C.M. Hendriks, P. N.M. Demacker, and A. F.H. Stalenhoef Nomogram to Diagnose Familial Combined Hyperlipidemia on the Basis of Results of a 5-Year Follow-Up Study Circulation, June 22, 2004; 109(24): 2980 - 2985. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. C. Carr and J. D. Brunzell Abdominal Obesity and Dyslipidemia in the Metabolic Syndrome: Importance of Type 2 Diabetes and Familial Combined Hyperlipidemia in Coronary Artery Disease Risk J. Clin. Endocrinol. Metab., June 1, 2004; 89(6): 2601 - 2607. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. Verseyden, S. Meijssen, H. van Dijk, H. Jansen, and M. C. Cabezas Effects of atorvastatin on fasting and postprandial complement component 3 response in familial combined hyperlipidemia J. Lipid Res., November 1, 2003; 44(11): 2100 - 2108. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C.J.M. Halkes, H. van Dijk, C. Verseyden, P.P.Th. de Jaegere, H.W.M Plokker, S. Meijssen, D.W. Erkelens, and M. C. Cabezas Gender Differences in Postprandial Ketone Bodies in Normolipidemic Subjects and in Untreated Patients With Familial Combined Hyperlipidemia Arterioscler Thromb Vasc Biol, October 1, 2003; 23(10): 1875 - 1880. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. N. Hopkins, G. Heiss, R. C. Ellison, M. A. Province, J. S. Pankow, J. H. Eckfeldt, and S. C. Hunt 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 Circulation, August 5, 2003; 108(5): 519 - 523. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. F. Ayyobi, S. H. McGladdery, M. J. McNeely, M. A. Austin, A. G. Motulsky, and J. D. Brunzell Small, Dense LDL and Elevated Apolipoprotein B Are the Common Characteristics for the Three Major Lipid Phenotypes of Familial Combined Hyperlipidemia Arterioscler Thromb Vasc Biol, July 1, 2003; 23(7): 1289 - 1294. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. D. Attie, R. M. Krauss, M. P. Gray-Keller, A. Brownlie, M. Miyazaki, J. J. Kastelein, A. J. Lusis, A. F. H. Stalenhoef, J. P. Stoehr, M. R. Hayden, et al. Relationship between stearoyl-CoA desaturase activity and plasma triglycerides in human and mouse hypertriglyceridemia J. Lipid Res., November 1, 2002; 43(11): 1899 - 1907. [Abstract] [Full Text] [PDF]
|
|