Advertisement

Vascular risk factors, vascular disease, lipids and lipid targets in patients with familial dysbetalipoproteinemia: A European cross-sectional study

      Highlights

      • Large European study in patients with familial dysbetalipoproteinemia (FD).
      • Most FD patients have non HDL-cholesterol levels above treatment target.
      • Lipid-lowering medication is underused in FD patients.
      • High prevalence of cardiovascular risk factors and -disease in this population.

      Abstract

      Background

      Familial dysbetalipoproteinemia (FD), also known as type III hyperlipoproteinemia, is a genetic dyslipidemia characterized by elevated very low density lipoprotein (VLDL) and chylomicron remnant particles that confers increased risk of cardiovascular disease (CVD). The objective of this study was to evaluate the prevalence of vascular risk factors, CVD, lipid values, treatment and lipid targets in patients with FD across Europe.

      Methods

      This cross-sectional study was performed in 305 patients with FD from seven academic hospitals in four European countries. Information was collected from clinical records.

      Results

      Patients mean (± standard deviation) age was 60.9 ± 14.4 years, 201 (66%) were male, 69 (23%) had diabetes mellitus (DM) and 87 (29%) had a prior history of CVD. Mean body mass index was 28.5 ± 5.0 kg/m2. Lipid-lowering medication was used by 227 (74%) patients (27% usual dose (theoretical low-density lipoprotein cholesterol (LDL-C) reduction ≤40%) and 46% intensive dose (theoretical LDL-C reduction >40%)). Non high-density lipoprotein cholesterol (non-HDL-C) levels below treatment target (<3.3 mmol/L) were present in 123 (40%) patients and 163 patients (53%) had LDL-C levels below target (<2.5 mmol/L). No significant determinants were found for having non-HDL-C levels below target, while a prior history of CVD (OR 1.90, 95%CI 1.05–3.47) and presence of DM (OR 2.00, 95%CI 1.08–3.70) were associated with having LDL-C levels below treatment target.

      Conclusion

      The majority of FD patients had non-HDL-C levels above the treatment target of 3.3 mmol/L. Intensive dose lipid-lowering medication was used by only half of the patients, leaving them at increased cardiovascular risk.

      Keywords

      To read this article in full you will need to make a payment

      Purchase one-time access:

      Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online access
      One-time access price info
      • For academic or personal research use, select 'Academic and Personal'
      • For corporate R&D use, select 'Corporate R&D Professionals'

      Subscribe:

      Subscribe to Atherosclerosis
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect

      References

        • Marais A.D.
        • Solomon G.A.
        • Blom D.J.
        Dysbetalipoproteinaemia: a mixed hyperlipidaemia of remnant lipoproteins due to mutations in apolipoprotein E.
        Crit. Rev. Clin. Lab. Sci. 2014; 51: 46-62
        • Bennet A.M.
        • Di Angelantonio E.
        • Ye Z.
        • Wensley F.
        • Dahlin A.
        • Ahlbom A.
        • et al.
        Association of apolipoprotein E genotypes with lipid levels and coronary risk.
        JAMA. 2007; 298: 1300-1311
        • Mahley R.W.
        • Huang Y.
        • Rall Jr., S.C.
        Pathogenesis of type III hyperlipoproteinemia (dysbetalipoproteinemia). Questions, quandaries, and paradoxes.
        J. Lipid Res. 1999; 40: 1933-1949
        • Nordestgaard B.G.
        • Wootton R.
        • Lewis B.
        Selective retention of VLDL, IDL, and LDL in the arterial intima of genetically hyperlipidemic rabbits in vivo. Molecular size as a determinant of fractional loss from the intima-inner media.
        Arterioscler. Thromb. Vasc. Biol. 1995; 15: 534-542
        • Watts G.F.
        • Ooi E.M.
        • Chan D.C.
        Demystifying the management of hypertriglyceridaemia.
        Nat. Rev. Cardiol. 2013; 10: 648-661
        • Varbo A.
        • Benn M.
        • Tybjaerg-Hansen A.
        • Jorgensen A.B.
        • Frikke-Schmidt R.
        • Nordestgaard B.G.
        Remnant cholesterol as a causal risk factor for ischemic heart disease.
        J. Am. Coll. Cardiol. 2013; 61: 427-436
        • Mahley R.W.
        • Weisgraber K.H.
        • Huang Y.
        Apolipoprotein E: structure determines function, from atherosclerosis to Alzheimer's disease to AIDS.
        J. Lipid Res. 2009; 50: S183-S188
        • Henneman P.
        • van der Sman-de Beer F.
        • Moghaddam P.H.
        • Huijts P.
        • Stalenhoef A.F.
        • Kastelein J.J.
        • et al.
        The expression of type III hyperlipoproteinemia: involvement of lipolysis genes.
        Eur. J. Hum. Genet. 2009; 17: 620-628
        • Koopal C.
        • van der Graaf Y.
        • Asselbergs F.W.
        • Westerink J.
        • Visseren F.L.
        Influence of APOE-2 genotype on the relation between adiposity and plasma lipid levels in patients with vascular disease.
        Int. J. Obes. 2015; 39: 265-269
        • Havekes L.
        • de Wit E.
        • Leuven J.G.
        • Klasen E.
        • Utermann G.
        • Weber W.
        • et al.
        Apolipoprotein E3-Leiden. A new variant of human apolipoprotein E associated with familial type III hyperlipoproteinemia.
        Hum. Genet. 1986; 73: 157-163
        • Wardell M.R.
        • Brennan S.O.
        • Janus E.D.
        • Fraser R.
        • Carrell R.W.
        Apolipoprotein E2-Christchurch (136 Arg–--Ser). New variant of human apolipoprotein E in a patient with type III hyperlipoproteinemia.
        J. Clin. Invest. 1987; 80: 483-490
        • Civeira F.
        • Pocovi M.
        • Cenarro A.
        • Casao E.
        • Vilella E.
        • Joven J.
        • et al.
        Apo E variants in patients with type III hyperlipoproteinemia.
        Atherosclerosis. 1996; 127: 273-282
        • Grundy S.M.
        • Cleeman J.I.
        • Merz C.N.
        • Brewer Jr., H.B.
        • Clark L.T.
        • Hunninghake D.B.
        • et al.
        Implications of recent clinical trials for the national cholesterol education program adult treatment panel III guidelines.
        Circulation. 2004; 110: 227-239
        • Genest J.
        • McPherson R.
        • Frohlich J.
        • Anderson T.
        • Campbell N.
        • Carpentier A.
        • et al.
        Canadian cardiovascular society/Canadian guidelines for the diagnosis and treatment of dyslipidemia and prevention of cardiovascular disease in the adult – 2009 recommendations.
        Can. J. Cardiol. 2009; 25: 567-579
        • Wiersma T.
        • Smulders Y.M.
        • Stehouwer C.D.
        • Konings K.T.
        • Lanphen J.
        Summary of the multidisciplinary guideline on cardiovascular risk management (revision 2011).
        Ned. Tijdschr. Geneeskd. 2012; 156: A5104
        • Reiner Z.
        • Catapano A.L.
        • De Backer G.
        • Graham I.
        • Taskinen M.R.
        • Wiklund O.
        • et al.
        ESC/EAS guidelines for the management of dyslipidaemias: the task force for the management of dyslipidaemias of the European Society of Cardiology (ESC) and the European Atherosclerosis Society (EAS).
        Eur. Heart J. 2011; 32: 1769-1818
        • Robinson J.G.
        • Wang S.
        • Smith B.J.
        • Jacobson T.A.
        Meta-analysis of the relationship between non-high-density lipoprotein cholesterol reduction and coronary heart disease risk.
        J. Am. Coll. Cardiol. 2009; 53: 316-322
        • van de Woestijne A.P.
        • van der Graaf Y.
        • Liem A.H.
        • Cramer M.J.
        • Westerink J.
        • Visseren F.L.
        Low high-density lipoprotein cholesterol is not a risk factor for recurrent vascular events in patients with vascular disease on intensive lipid-lowering medication.
        J. Am. Coll. Cardiol. 2013; 62: 1834-1841
        • Johnson D.W.
        • Jones G.R.
        • Mathew T.H.
        • Ludlow M.J.
        • Chadban S.J.
        • Usherwood T.
        • et al.
        Chronic kidney disease and measurement of albuminuria or proteinuria: a position statement.
        Med. J. Aust. 2012; 197: 224-225
        • Friedewald W.T.
        • Levy R.I.
        • Fredrickson D.S.
        Estimation of the concentration of low-density lipoprotein cholesterol in plasma, without use of the preparative ultracentrifuge.
        Clin. Chem. 1972; 18: 499-502
        • Jorgensen A.B.
        • Frikke-Schmidt R.
        • West A.S.
        • Grande P.
        • Nordestgaard B.G.
        • Tybjaerg-Hansen A.
        Genetically elevated non-fasting triglycerides and calculated remnant cholesterol as causal risk factors for myocardial infarction.
        Eur. Heart J. 1826-33; 2013: 34
        • Grundy S.M.
        • Cleeman J.I.
        • Daniels S.R.
        • Donato K.A.
        • Eckel R.H.
        • Franklin B.A.
        • et al.
        Diagnosis and management of the metabolic syndrome: an American heart Association/National heart, lung, and blood Institute scientific statement.
        Circulation. 2005; 112: 2735-2752
        • Expert Panel on Detection E, 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: 2486-2497
        • Donders A.R.
        • van der Heijden G.J.
        • Stijnen T.
        • Moons K.G.
        Review: a gentle introduction to imputation of missing values.
        J. Clin. Epidemiol. 2006; 59: 1087-1091
        • Hopkins P.N.
        • Wu L.L.
        • Hunt S.C.
        • Brinton E.A.
        Plasma triglycerides and type III hyperlipidemia are independently associated with premature familial coronary artery disease.
        J. Am. Coll. Cardiol. 2005; 45: 1003-1012
        • de Beer F.
        • Stalenhoef A.F.
        • Hoogerbrugge N.
        • Kastelein J.J.
        • Gevers Leuven J.A.
        • van Duijn C.M.
        • et al.
        Expression of type III hyperlipoproteinemia in apolipoprotein E2 (Arg158--> Cys) homozygotes is associated with hyperinsulinemia.
        Arterioscler. Thromb. Vasc. Biol. 2002; 22: 294-299
        • Selvin E.
        • Erlinger T.P.
        Prevalence of and risk factors for peripheral arterial disease in the United States: results from the National Health and Nutrition Examination survey, 1999–2000.
        Circulation. 2004; 110: 738-743
        • Scarborough P.
        • Morgan R.D.
        • Webster P.
        • Rayner M.
        Differences in coronary heart disease, stroke and cancer mortality rates between England, Wales, Scotland and Northern Ireland: the role of diet and nutrition.
        BMJ Open. 2011; 1: e000263
        • Smelt A.H.
        From gene to disease; apolipoprotein E2 and familial dysbetalipoproteinemia.
        Ned. Tijdschr. Geneeskd. 2003; 147: 157-159
        • Blom D.J.B.P.
        • Jones S.
        • Marais A.D.
        Dysbetalipoproteinemia – clinical and pathophysiological features.
        South Afr. Med. J. 2002; 92: 892-897
        • Schaefer J.R.
        Unraveling hyperlipidemia type III (dysbetalipoproteinemia), slowly.
        Eur. J. Hum. Genet. 2009; 17: 541-542
        • Retterstol K.
        • Hennig C.B.
        • Iversen P.O.
        Improved plasma lipids and body weight in overweight/obese patients with type III hyperlipoproteinemia after 4 weeks on a low glycemic diet.
        Clin. Nutr. 2009; 28: 213-215
        • Civeira F.
        • Cenarro A.
        • Ferrando J.
        • Puzo J.
        • Garcia-Otin A.L.
        • Mozas P.
        • et al.
        Comparison of the hypolipidemic effect of gemfibrozil versus simvastatin in patients with type III hyperlipoproteinemia.
        Am. Heart J. 1999; 138: 156-162
        • Illingworth D.R.
        • O'Malley J.P.
        The hypolipidemic effects of lovastatin and clofibrate alone and in combination in patients with type III hyperlipoproteinemia.
        Metabolism. 1990; 39: 403-409
        • Guyton J.R.
        Treatment of type III hyperlipoproteinemia.
        Am. Heart J. 1999; 138: 17-18
        • Neyman J.
        Statistics; servant of all sciences.
        Science. 1955; 122: 401-406