Skip to main content
SpringerLink
Log in

Risk prediction with triglycerides in patients with stable coronary disease on statin treatment

  • Original Paper
  • Published:
Clinical Research in Cardiology Aims and scope Submit manuscript

Abstract

Background

The aim of the prospective Homburg Cream and Sugar study was to analyze the role of fasting and postprandial serum triglycerides (TG) as risk modifiers in patients with coronary artery disease (CAD).

Methods and results

A sequential oral triglyceride and glucose tolerance test was developed to obtain standardized measurements of postprandial TG kinetics and glucose in 514 consecutive patients with stable CAD confirmed by angiography (95% were treated with a statin). Fasting and postprandial TG predicted the primary outcome measure of cardiovascular death and hospitalizations after 48 months follow-up (fasting TG >150 vs. <106 mg/dl: Hazard ratio (HR) 1.79, 95% confidence interval (CI) 1.31–2.45, p = 0.0001; area under the curve >1120 vs. <750 mg/dl/5hr: HR 1.78, 95% CI 1.29–2.45, p = 0.0003). Parameters of the postprandial TG increase did not improve risk prediction compared to fasting TG. The number of cardiovascular deaths and myocardial infarctions was higher in the upper tertile of fasting TG (HR 1.79, 95%–CI 1.04–3.09, p = 0.03). Risk prediction by TG was independent of traditional risk factors, medication, glucose metabolism, LDL- and HDL-cholesterol. Total cholesterol, LDL- and HDL-cholesterol concentrations were not associated with the primary outcome.

Conclusions

Fasting serum triglycerides >150 mg/dl independently predict cardiovascular events in patients with coronary artery disease on guideline-recommended medication. Assessment of postprandial TG does not improve risk prediction compared to fasting TG in these patients.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4

Similar content being viewed by others

References

  1. Hulley SB, Rosenman RH, Bawol RD, Brand RJ (1980) Epidemiology as a guide to clinical decisions. The association between triglyceride and coronary heart disease. N Engl J Med 302:1383–1389

    Article  CAS  PubMed  Google Scholar 

  2. Di Angelantonio E, Sarwar N, Perry P, Kaptoge S, Ray KK, Thompson A et al (2009) Major lipids, apolipoproteins, and risk of vascular disease. JAMA 302:1993–2000

    Article  PubMed  Google Scholar 

  3. Freiberg JJ, Tybjaerg-Hansen A, Jensen JS, Nordestgaard BG (2008) Nonfasting triglycerides and risk of ischemic stroke in the general population. JAMA, J Am Med Assoc 300:2142–2152

    Article  CAS  Google Scholar 

  4. Langsted A, Freiberg JJ, Nordestgaard BG (2008) Fasting and nonfasting lipid levels: influence of normal food intake on lipids, lipoproteins, apolipoproteins, and cardiovascular risk prediction. Circulation 118:2047–2056

    Article  CAS  PubMed  Google Scholar 

  5. Langsted A, Freiberg JJ, Tybjaerg-Hansen A, Schnohr P, Jensen GB, Nordestgaard BG (2011) Nonfasting cholesterol and triglycerides and association with risk of myocardial infarction and total mortality: the Copenhagen City Heart Study with 31 years of follow-up. J Intern Med 270:65–75

    Article  CAS  PubMed  Google Scholar 

  6. Mora S, Rifai N, Buring JE, Ridker PM (2008) Fasting compared with nonfasting lipids and apolipoproteins for predicting incident cardiovascular events. Circulation 118:993–1001

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  7. Sarwar N, Danesh J, Eiriksdottir G, Sigurdsson G, Wareham N, Bingham S et al (2007) Triglycerides and the risk of coronary heart disease: 10,158 incident cases among 262,525 participants in 29 Western prospective studies. Circulation 115:450–458

    Article  CAS  PubMed  Google Scholar 

  8. Jackson KG, Poppitt SD, Minihane AM (2011) Postprandial lipemia and cardiovascular disease risk: Interrelationships between dietary, physiological and genetic determinants. Atherosclerosis

  9. Lopez-Miranda J, Williams C, Lairon D (2007) Dietary, physiological, genetic and pathological influences on postprandial lipid metabolism. Br J Nutr 98:458–473

    Article  CAS  PubMed  Google Scholar 

  10. Friedewald WT, Levy RI, Fredrickson DS (1972) Estimation of the concentration of low-density lipoprotein cholesterol in plasma, without use of the preparative ultracentrifuge. Clin Chem 18:499–502

    CAS  PubMed  Google Scholar 

  11. Chapman MJ, Ginsberg HN, Amarenco P, Andreotti F, Boren J, Catapano AL et al (2011) Triglyceride-rich lipoproteins and high-density lipoprotein cholesterol in patients at high risk of cardiovascular disease: evidence and guidance for management. Eur Heart J 32:1345–1361

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  12. Miller M, Stone NJ, Ballantyne C, Bittner V, Criqui MH, Ginsberg HN et al (2011) Triglycerides and cardiovascular disease: a scientific statement from the american heart association. Circulation 123:2292–2333

    Article  PubMed  Google Scholar 

  13. Goldberg IJ, Eckel RH, McPherson R (2011) Triglycerides and heart disease: still a hypothesis? Arterioscler Thromb Vasc Biol 31:1716–1725

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  14. Moreton JR (1950) Chylomicronemia, Fat Tolerance, and Atherosclerosis. J Lab Clin Med 35:373–384

    Google Scholar 

  15. Zilversmit DB (1979) Atherogenesis: a postprandial phenomenon. Circulation 60:473–485

    Article  CAS  PubMed  Google Scholar 

  16. Nordestgaard BG, Benn M, Schnohr P, Tybjaerg-Hansen A (2007) Nonfasting triglycerides and risk of myocardial infarction, ischemic heart disease, and death in men and women. JAMA 298:299–308

    Article  CAS  PubMed  Google Scholar 

  17. Lindman AS, Veierod MB, Tverdal A, Pedersen JI, Selmer R (2010) Nonfasting triglycerides and risk of cardiovascular death in men and women from the Norwegian Counties Study. Eur J Epidemiol 25:789–798

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  18. Bansal S, Buring JE, Rifai N, Mora S, Sacks FM, Ridker PM (2007) Fasting compared with nonfasting triglycerides and risk of cardiovascular events in women. JAMA 298:309–316

    Article  CAS  PubMed  Google Scholar 

  19. Boren J, Matikainen N, Adiels M, Taskinen MR (2014) Postprandial hypertriglyceridemia as a coronary risk factor. Clinica Chimica Acta, Intern J Clin Chem 431C:131–142

    Article  Google Scholar 

  20. Brunzell JD (2007) Clinical practice. Hypertriglyceridemia. The New England J Medicine. 357:1009–1017

    Article  CAS  Google Scholar 

  21. Cohn JS (2006) Postprandial lipemia and remnant lipoproteins. Clin Lab Med. 26:773–786

    Article  PubMed  Google Scholar 

  22. Fontbonne A, Eschwege E, Cambien F, Richard JL, Ducimetiere P, Thibult N et al (1989) Hypertriglyceridaemia as a risk factor of coronary heart disease mortality in subjects with impaired glucose tolerance or diabetes. Results from the 11-year follow-up of the Paris Prospective Study. Diabetologia 32:300–304

    Article  CAS  PubMed  Google Scholar 

  23. Ginsberg HN (2000) Insulin resistance and cardiovascular disease. J Clin Invest. 106:453–458

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  24. Ridker PM (2008) Fasting versus nonfasting triglycerides and the prediction of cardiovascular risk: do we need to revisit the oral triglyceride tolerance test? Clin Chem 54:11–13

    Article  CAS  PubMed  Google Scholar 

  25. Lahiri K, Rettig-Ewen V, Böhm M, Laufs U (2007) Perceived psychosocial stress and cardiovascular risk factors in obese and non-obese patients. Clin Res Cardiol: off J Ger Card Soc 96:365–374

    Article  Google Scholar 

  26. Farhan S, Jarai R, Tentzeris I, Kautzky-Willer A, Samaha E, Smetana P et al (2012) Comparison of HbA1c and oral glucose tolerance test for diagnosis of diabetes in patients with coronary artery disease. Clin Res Cardiol: off J Ger Card Soc 101:625–630

    Article  CAS  Google Scholar 

  27. Stone NJ, Robinson J, Lichtenstein AH, Merz CN, Blum CB, Eckel RH, et al. (2013) ACC/AHA guideline on the treatment of blood cholesterol to reduce atherosclerotic cardiovascular risk in adults: a report of the American college of cardiology/American heart association task force on practice guidelines. Circulation

  28. Mora S, Wenger NK, Demicco DA, Breazna A, Boekholdt SM, Arsenault BJ et al (2012) Determinants of residual risk in secondary prevention patients treated with high- versus low-dose statin therapy: the Treating to New Targets (TNT) study. Circulation 125:1979–1987

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  29. Boekholdt SM, Arsenault BJ, Mora S, Pedersen TR, LaRosa JC, Nestel PJ et al (2012) Association of LDL cholesterol, non-HDL cholesterol, and apolipoprotein B levels with risk of cardiovascular events among patients treated with statins: a meta-analysis. JAMA 307:1302–1309

    Article  CAS  PubMed  Google Scholar 

  30. Mora S, Glynn RJ, Boekholdt SM, Nordestgaard BG, Kastelein JJ, Ridker PM (2012) On-treatment non-high-density lipoprotein cholesterol, apolipoprotein B, triglycerides, and lipid ratios in relation to residual vascular risk after treatment with potent statin therapy: JUPITER (justification for the use of statins in prevention: an intervention trial evaluating rosuvastatin). J Am Coll Cardiol 59:1521–1528

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  31. Gitt AK, Junger C, Smolka W, Bestehorn K (2010) Prevalence and overlap of different lipid abnormalities in statin-treated patients at high cardiovascular risk in clinical practice in Germany. Clin Res Cardiol: off J Ger Card Soc 99:723–733

    Article  Google Scholar 

  32. Fihn SD, Gardin JM, Abrams J, Berra K, Blankenship JC, Dallas AP et al (2012) 2012 ACCF/AHA/ACP/AATS/PCNA/SCAI/STS Guideline for the diagnosis and management of patients with stable ischemic heart disease: a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines, and the American College of Physicians, American Association for Thoracic Surgery, Preventive Cardiovascular Nurses Association, Society for Cardiovascular Angiography and Interventions, and Society of Thoracic Surgeons. J Am Coll Cardiol 60:e44–e164

    Article  PubMed  Google Scholar 

  33. Montalescot G, Sechtem U, Achenbach S, Andreotti F, Arden C et al (2013) 2013 ESC guidelines on the management of stable coronary artery disease: the Task Force on the management of stable coronary artery disease of the European Society of Cardiology. Eur Heart J 34:2949–3003

    Article  PubMed  Google Scholar 

  34. National Cholesterol Education Program Expert Panel on Detection (2002) E, Treatment of High Blood Cholesterol in A. 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 106:3143–3421

    Google Scholar 

  35. Alberti KG, Eckel RH, Grundy SM, Zimmet PZ, Cleeman JI, Donato KA et al (2009) Harmonizing the metabolic syndrome: a joint interim statement of the International Diabetes Federation Task Force on Epidemiology and Prevention; National Heart, Lung, and Blood Institute; American Heart Association; World Heart Federation; International Atherosclerosis Society; and International Association for the Study of Obesity. Circulation 120:1640–1645

    Article  CAS  PubMed  Google Scholar 

  36. World Health Organization (2000) Obesity: preventing and managing the global epidemic. Report of a WHO consultation. World Health Orga Tech Rep ser 894:1–253 I-xii

    Google Scholar 

  37. American Diabetes Association (2011) Executive summary: standards of medical care in diabetes–2011. Diabetes Care 34(Suppl 1):S4–S10

    Google Scholar 

  38. Ewen S, Rettig-Ewen V, Mahfoud F, Böhm M, Laufs U (2014) Drug adherence in patients taking oral anticoagulation therapy. Clin Res Cardiol: off J Ger Card Soc 103:173–182

    Article  CAS  Google Scholar 

  39. Thygesen K, Alpert JS, White HD, Joint ESCAAHAWHFTFftRoMI, Jaffe AS, Apple FS et al (2007) Universal definition of myocardial infarction. Circulation 116:2634–2653

    Article  PubMed  Google Scholar 

  40. Anderson JL, Adams CD, Antman EM, Bridges CR, Califf RM, Casey DE Jr et al (2013) 2012 ACCF/AHA focused update incorporated into the ACCF/AHA 2007 guidelines for the management of patients with unstable angina/non-ST-elevation myocardial infarction: a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines. J Am Coll Cardiol 61:e179–e347

    Article  PubMed  Google Scholar 

  41. Wang H, Eckel RH (2009) Lipoprotein lipase: from gene to obesity. Am J Physiol Endocrinol Metab. 297:E271–E288

    Article  CAS  PubMed  Google Scholar 

  42. Pavlic M, Xiao C, Szeto L, Patterson BW, Lewis GF (2010) Insulin acutely inhibits intestinal lipoprotein secretion in humans in part by suppressing plasma free fatty acids. Diabetes 59:580–587

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  43. Mihas C, Kolovou GD, Mikhailidis DP, Kovar J, Lairon D, Nordestgaard BG et al (2011) Diagnostic value of postprandial triglyceride testing in healthy subjects: a meta-analysis. Curr Vasc Pharmacol 9:271–280

    Article  CAS  PubMed  Google Scholar 

  44. Kolovou GD, Mikhailidis DP, Kovar J, Lairon D, Nordestgaard BG, Ooi TC et al (2011) Assessment and clinical relevance of non-fasting and postprandial triglycerides: an expert panel statement. Curr Vasc Pharmacol 9:258–270

    Article  CAS  PubMed  Google Scholar 

  45. Werner N, Kosiol S, Schiegl T, Ahlers P, Walenta K, Link A et al (2005) Circulating endothelial progenitor cells and cardiovascular outcomes. N Engl J Med 353:999–1007

    Article  CAS  PubMed  Google Scholar 

  46. Miller M, Cannon CP, Murphy SA, Qin J, Ray KK, Braunwald E (2008) Impact of triglyceride levels beyond low-density lipoprotein cholesterol after acute coronary syndrome in the PROVE IT-TIMI 22 trial. J Am Coll Cardiol 51:724–730

    Article  CAS  PubMed  Google Scholar 

  47. Tentolouris N, Eleftheriadou I, Katsilambros N (2009) The effects of medications used for the management of dyslipidemia on postprandial lipemia. Curr Med Chem 16:203–217

    Article  CAS  PubMed  Google Scholar 

  48. Laufs U, Weintraub WS, Packard CJ (2013) Beyond statins: what to expect from add-on lipid regulating therapy? Eur Heart J 34:2660–2665

    Article  PubMed  Google Scholar 

  49. Sacks FM, Carey VJ, Fruchart JC (2010) Combination lipid therapy in type 2 diabetes. N Engl J Med 363:692–694 author reply 4–5

    Article  CAS  PubMed  Google Scholar 

  50. Werner C, Hoffmann MM, Winkler K, Böhm M, Laufs U (2014) Risk prediction with proprotein convertase subtilisin/kexin type 9 (PCSK9) in patients with stable coronary disease on statin treatment. Vasc Pharm pii:S1537–1891(14)00057–3

  51. Ceriello A, Taboga C, Tonutti L, Quagliaro L, Piconi L, Bais B et al (2002) Evidence for an independent and cumulative effect of postprandial hypertriglyceridemia and hyperglycemia on endothelial dysfunction and oxidative stress generation: effects of short- and long-term simvastatin treatment. Circulation 106:1211–1218

    Article  PubMed  Google Scholar 

  52. Gibson T, Fuller JH, Grainger SL, Jarrett RJ, Keen H (1974) Intralipid triglyceride and oral glucose tolerance. Diabetologia 10:97–100

    Article  CAS  PubMed  Google Scholar 

  53. Wuesten O, Balz CH, Bretzel RG, Kloer HU, Hardt PD (2005) Effects of oral fat load on insulin output and glucose tolerance in healthy control subjects and obese patients without diabetes. Diabetes Care 28:360–365

    Article  PubMed  Google Scholar 

  54. Lewis GF, O’Meara NM, Soltys PA, Blackman JD, Iverius PH, Pugh WL et al (1991) Fasting hypertriglyceridemia in noninsulin-dependent diabetes mellitus is an important predictor of postprandial lipid and lipoprotein abnormalities. J Clin Endocrinol Metab 72:934–944

    Article  CAS  PubMed  Google Scholar 

  55. Sarwar N, Sandhu MS, Ricketts SL, Butterworth AS, Di Angelantonio E, Boekholdt SM et al (2010) Triglyceride-mediated pathways and coronary disease: collaborative analysis of 101 studies. Lancet 375:1634–1639

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgments

We thank Anja Zickwolf and Angelika Knoll for their valuable assistance. This work was supported by the Deutsche Stiftung für Herzforschung (F41/08) and the Universität des Saarlandes (HOMFOR).

Conflict of interest

The authors declare that they have no conflict of interest.

Ethical standards

All human studies have been approved by the local ethics committee (Number 170/07) and have therefore been performed in accordance with the ethical standards laid down in the 1964 Declaration of Helsinki and its later amendments. All patients gave their written informed consent prior to their inclusion in the study.

Author information

Authors and Affiliations

  1. Klinik für Innere Medizin III (Kardiologie, Angiologie und Internistische Intensivmedizin), Universitätsklinikum des Saarlandes, 66421, Homburg/Saar, Germany

    Christian Werner, Anja Filmer, Marco Fritsch, Stephanie Groenewold, Michael Böhm & Ulrich Laufs

  2. Institut für Medizinische Biometrie, Epidemiologie und Medizinische Informatik, Universitätsklinikum des Saarlandes, Homburg/Saar, Germany

    Stefan Gräber

Authors
  1. Christian Werner
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Anja Filmer
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Marco Fritsch
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Stephanie Groenewold
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Stefan Gräber
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Michael Böhm
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Ulrich Laufs
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Christian Werner.

Electronic supplementary material

Below is the link to the electronic supplementary material.

Supplementary material 1 (PPT 220 kb)

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Werner, C., Filmer, A., Fritsch, M. et al. Risk prediction with triglycerides in patients with stable coronary disease on statin treatment. Clin Res Cardiol 103, 984–997 (2014). https://doi.org/10.1007/s00392-014-0740-0

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00392-014-0740-0

Keywords

Search

Navigation