Advertisement

Normalization of daytime triglyceridemia by simvastatin in fasting normotriglyceridemic patients with premature coronary sclerosis

      Abstract

      Postprandial hyperlipidemia is associated with premature coronary sclerosis in fasting normolipidemic subjects. Self-determined daytime capillary triglyceride (cTG) profiles were compared between 26 fasting normotriglyceridemic patients with premature coronary artery disease (CAD) and 26 controls matched for gender, age and BMI. Daytime triglyceridemia was calculated as total area under the cTG-curve (cTG-AUC). Total and LDL cholesterol were not different between CAD patients (5.4±0.8 mmol/l and 3.6±0.7 mmol/l, respectively) and controls (5.0±0.9 mmol/l and 3.3±0.8 mmol/l, respectively). Patients with CAD were characterized by a 44% higher cTG-AUC than matched controls (P<0.01). Using logistic regression analysis, cTG-AUC was the strongest predictor of the presence of CAD (P<0.001). Adding apo AI to the model improved the predictive power from 71 to 77%. Sixteen patients were studied after increasing doses of simvastatin up to 80 mg/day. Although the target for LDL cholesterol was reached by simvastatin 20 mg/day, significant effects on cTG-AUC were found only by higher doses of simvastatin. Simvastatin 40 mg/day decreased cTG-AUC by 28% (P<0.05 versus baseline), reaching comparable values as in controls, without further improvement with simvastatin 80 mg/day (26% reduction versus baseline; P<0.05). Daytime triglyceridemia is linked to premature coronary sclerosis in fasting normotriglyceridemic patients. A higher dose of simvastatin was needed to normalize daytime triglyceridemia than was required to “normalize” LDL cholesterol.

      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

        • Austin M.A.
        • Hokanson J.E.
        • Edwards K.L.
        Hypertriglyceridemia as a cardiovascular risk factor.
        Am. J. Cardiol. 1998; 81: 7B-12B
        • Karpe F.
        • Steiner G.
        • Uffelman K.
        • Olivecrona T.
        • Hamsten A.
        Postprandial lipoproteins and progression of coronary atherosclerosis.
        Atherosclerosis. 1994; 106: 83-97
        • Patsch J.R.
        • Miesenbock G.
        • Hopferwieser T.
        • Muhlberger V.
        • Knapp E.
        • Dunn J.K.
        Relation of triglyceride metabolism and coronary artery disease. Studies in the postprandial state.
        Arterioscler. Thromb. 1992; 12: 1336-1345
        • Weintraub M.S.
        • Grosskopf I.
        • Rassin T.
        • Miller H.
        • Charach G.
        • Rotmensch H.H.
        Clearance of chylomicron remnants in normolipidaemic patients with coronary artery disease: case control study over three years.
        Br. Med. J. 1996; 312: 936-939
        • Proctor S.D.
        • Vine D.F.
        • Mamo J.C.
        Arterial retention of apolipoprotein B(48)- and B(100)-containing lipoproteins in atherogenesis.
        Curr. Opin. Lipidol. 2002; 13: 461-470
        • Castro Cabezas M.
        • Halkes C.J.M.
        • Meijssen S.
        • van Oostrom A.J.H.H.M.
        • Erkelens D.W.
        Diurnal triglyceride profiles: a novel approach to study triglyceride changes.
        Atherosclerosis. 2001; 155: 219-228
        • Delawi D.
        • Meijssen S.
        • Castro Cabezas M.
        Intra-individual variations of fasting plasma lipids, apolipoproteins and postprandial lipemia in familial combined hyperlipidemia compared to controls.
        Clin. Chim. Acta. 2003; 328: 139-145
        • Halkes C.J.M.
        • Castro Cabezas M.
        • van Wijk J.P.H.
        • Erkelens D.W.
        Gender differences in diurnal triglyceridemia in lean and overweight subjects.
        Int. J. Obes. Relat. Metab. Disord. 2001; 25: 1767-1774
        • van Oostrom A.J.H.H.M.
        • Castro Cabezas M.
        • Ribalta J.
        • Masana L.
        • Twickler T.B.
        • Remijnse T.A.
        Diurnal triglyceride profiles in healthy normolipidemic male subjects are associated to insulin sensitivity.
        Eur. J. Clin. Invest. 2000; 30: 964-971
        • van Wijk J.P.H.
        • Castro Cabezas M.
        • Halkes C.J.M.
        • Erkelens D.W.
        Effects of different nutrient intakes on daytime triacylglycerolemia in healthy, normolipemic, free-living men.
        Am. J. Clin. Nutr. 2001; 74: 171-178
        • Luley C.
        • Ronquist G.
        • Reuter W.
        • Paal V.
        • Gottschling H.D.
        • Westphal S.
        Point-of-care testing of triglycerides: evaluation of the Accutrend triglycerides system.
        Clin. Chem. 2000; 46: 287-291
        • Moses R.G.
        • Calvert D.
        • Storlien L.H.
        Evaluation of the Accutrend GCT with respect to triglyceride monitoring.
        Diabetes Care. 1996; 19: 1305-1306
      1. MRC/BHF Heart Protection Study of cholesterol lowering with simvastatin in 20,536 high-risk individuals: a randomised placebo-controlled trial. Lancet 2002;360:7–22.

        • Vaughan C.J.
        • Gotto Jr., A.M.
        • Basson C.T.
        The evolving role of statins in the management of atherosclerosis.
        J. Am. Coll. Cardiol. 2000; 35: 1-10
      2. Influence of pravastatin and plasma lipids on clinical events in the West of Scotland Coronary Prevention Study (WOSCOPS). Circulation 1998;97:1440–5.

        • Karpe F.
        Postprandial lipemia—effect of lipid-lowering drugs.
        Atheroscler. Suppl. 2002; 3: 41-46
      3. 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) final report. Circulation 2002;106:3143–421.

        • Hulthe J.
        • Bokemark L.
        • Wikstrand J.
        • Fagerberg B.
        The metabolic syndrome, LDL particle size and atherosclerosis. The Atherosclerosis and Insulin Resistance (AIR) Study.
        Arterioscler. Thromb. Vasc. Biol. 2000; 20: 2140-2147
        • Genest J.
        • Sniderman A.
        • Cianflone K.
        • Teng B.
        • Wacholder S.
        • Marcel Y.
        Hyperapobetalipoproteinemia. Plasma lipoprotein responses to oral fat load.
        Arteriosclerosis. 1986; 6: 297-304
        • Karpe F.
        • Bard J.M.
        • Steiner G.
        • Carlson L.A.
        • Fruchart J.C.
        • Hamsten A.
        HDLs and alimentary lipemia. Studies in men with previous myocardial infarction at a young age.
        Arterioscler. Thromb. 1993; 13: 11-22
        • Gaenzer H.
        • Sturm W.
        • Neumayr G.
        • Kirchmair R.
        • Ebenbichler C.
        • Ritsch A.
        Pronounced postprandial lipemia impairs endothelium-dependent dilation of the brachial artery in men.
        Cardiovasc. Res. 2001; 52: 509-516
        • Masana L.
        • Ribalta J.
        • Salazar J.
        • Fernández-Ballart J.
        • Joven J.
        • Castro Cabezas M.
        The apolipoprotein AV gene and diurnal triglyceridemia in normolipidemic subjects.
        Clin. Chem. Lab. Med. 2003; 41: 517-521
        • Genest Jr., J.
        • McNamara J.R.
        • Ordovas J.M.
        • Jenner J.L.
        • Silberman S.R.
        • Anderson K.M.
        Lipoprotein cholesterol, apolipoprotein A-I and B and lipoprotein (a) abnormalities in men with premature coronary artery disease.
        J. Am. Coll. Cardiol. 1992; 19: 792-802
        • Braunwald E.
        Shattuck lecture–cardiovascular medicine at the turn of the millennium: triumphs, concerns, and opportunities.
        N. Engl. J. Med. 1997; 337: 1360-1369
        • van Wijk J.P.H.
        • Halkes C.J.M.
        • Erkelens D.W.
        • Castro Cabezas M.
        Fasting and daytime triglycerides in obesity with and without type 2 diabetes.
        Metabolism. 2003; 52: 1043-1049
        • Després J.P.
        • Lemieux S.
        • Lamarche B.
        • Prud’homme D.
        • Moorjani S.
        • Brun L.D.
        The insulin resistance-dyslipidemic syndrome: contribution of visceral obesity and therapeutic implications.
        Int. J. Obes. Relat. Metab. Disord. 1995; 19: S76-S86
        • Brunzell J.D.
        • Hazzard W.R.
        • Porte Jr., D.
        • Bierman E.L.
        Evidence for a common, saturable, triglyceride removal mechanism for chylomicrons and very low density lipoproteins in man.
        J. Clin. Invest. 1973; 52: 1578-1585
        • Lakka H.M.
        • Laaksonen D.E.
        • Lakka T.A.
        • Niskanen L.K.
        • Kumpusalo E.
        • Tuomilehto J.
        The metabolic syndrome and total and cardiovascular disease mortality in middle-aged men.
        JAMA. 2002; 288: 2709-2716
        • Goris A.H.
        • Westerterp-Plantenga M.S.
        • Westerterp K.R.
        Undereating and underrecording of habitual food intake in obese men: selective underreporting of fat intake.
        Am. J. Clin. Nutr. 2000; 71: 130-134