Skip to main content
SpringerLink
Log in

Atorvastatin Decreases Triacylglycerol-Associated Risk of Vascular Events in Coronary Heart Disease Patients

  • Original Articla
  • Published:
Lipids

Abstract

High triacylglycerol (TAG) levels may predict vascular risk. The effect of a statin-induced reduction in TAG levels, irrespective of HDL-C increase, on clinical outcome has not yet been addressed by an endpoint study in patients with coronary heart disease (CHD). The GREACE study compared usual with structured care aimed at achieving LDL-C = 100 mg/dL (2.6 mmol/L) by dose titration with atorvastatin. All patients had CHD and were followed for 3 years. This post hoc analysis of GREACE examines the effect of statins on TAG levels and their relation with cardiovascular disease (CVD) events in all patients and in the subgroup of patients with metabolic syndrome (MetS). Baseline TAG levels >150 mg/dL (1.7 mmol/L) were predictive of subsequent CVD events [cardiac mortality, non-fatal myocardial infarction (MI), unstable angina (UA), revascularisation, congestive heart failure (CHF), and stroke] only in statin untreated patients. Stepwise regression analysis showed that with every 20% statin-related TAG reduction there was a decrease in CVD risk by 12% (HR 0.88, 95% CI 0.75–0.95, P = 0.007) in the structured care group vs. the usual care group, by 8% (HR 0.92, 95% CI 0.81–0.97, P = 0.02) in all statin treated patients vs. the untreated ones and by 15% (HR 0.85, 95% CI 0.65–0.94, P = 0.005) in those with MetS treated with a statin vs. those untreated. Using the same analysis but only taking into consideration vascular events (cardiac mortality, non-fatal MI, UA, revascularisation, and stroke) there was a 18% (HR = 0.82, 95% CI 0.57–0.96, P = 0.03) decrease in risk in the MetS (+) patients treated with a statin vs. those not on a statin, and a decrease in risk by 16% (HR = 0.84, 95% CI 0.53–1.07, P = 0.08), when only hard vascular endpoints (cardiac mortality, non-fatal MI, and stroke) were considered. TAG levels are predictive of subsequent CVD events in statin untreated CHD patients. Statin (mainly atorvastatin)-induced decrease in TAG levels was related to a significant reduction in subsequent CVD events. This benefit was more pronounced in CHD MetS (+) 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

Similar content being viewed by others

References

  1. Castelli WP (1986) The triglyceride issue: a view from Framingham. Am Heart J 112:432–437

    Article  PubMed  CAS  Google Scholar 

  2. Assmann G, Schulte H (1992) Role of triglycerides in coronary artery disease: lessons from the Prospective Cardiovascular Munster Study. Am J Cardiol 70:10H–13H

    Article  PubMed  CAS  Google Scholar 

  3. Criqui MH, Heiss G, Cohn R, Cowan LD, Suchindran CM, Bangdiwala S, Kritchevsky S, Jacobs DR Jr, O’Grady HK, Davis CE (1993) Plasma triglyceride level and mortality from coronary heart disease. N Engl J Med 328:1220–1225

    Article  PubMed  CAS  Google Scholar 

  4. Hokanson JE, Austin MA (1996) Plasma triglyceride level is a risk factor for cardiovascular disease independent of high-density lipoprotein cholesterol level: a meta-analysis of population-based prospective studies. J Cardiovasc Risk 3:213–219

    Article  PubMed  CAS  Google Scholar 

  5. Ninomiya JK, L’Italien G, Criqui MH, Whyte JL, Gamst A, Chen RS (2004) Association of the metabolic syndrome with history of myocardial infarction and stroke in the third national health and nutrition examination survey. Circulation 109:42–46

    Article  PubMed  Google Scholar 

  6. Sacks FM, for the Expert Group on HDL Cholesterol (2002) The role of high-density lipoprotein (HDL) cholesterol in the prevention and treatment of coronary heart disease: expert group recommendations. Am J Cardiol 90:139–143

    Article  PubMed  CAS  Google Scholar 

  7. The UK HDL-C consensus group (2004) Role of fibrates in reducing coronary risk: a UK consensus. Curr Med Res Opin 20:241–247

    Article  Google Scholar 

  8. Expert Panel on Detection, Evaluation, Treatment of High Blood Cholesterol in Adults (2001) 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 285:2486–2497

    Article  Google Scholar 

  9. Smith SC Jr, Allen J, Blair SN, Bonow RO, Brass LM, Fonarow GC, Grundy SM, Hiratzka L, Jones D, Krumholz HM, Mosca L, Pasternak RC, Pearson T, Pfeffer MA, Taubert KA (2006) AHA/ACC guidelines for secondary prevention of patients with coronary and other atherosclerotic vascular disease: 2006 update: endorsed by the National Heart, Lung and Blood Institute. Circulation 113:2363–2372

    Article  PubMed  Google Scholar 

  10. British Cardiac Society., British Hypertension Society., Diabetes UK., HEART UK., Primary Care Cardiovascular Society., Stroke Association. (2005) JBS 2: Joint British Societies’ guidelines on prevention of cardiovascular disease in clinical practice. Heart 91(Suppl 5):v1–v52

    Google Scholar 

  11. Daskalopoulou SS, Mikhailidis DP (2006) Reaching goal in hypercholesterolaemia: dual inhibition of cholesterol synthesis and absorption with simvastatin plus ezetimibe. Curr Med Res Opin 22:511–528

    Article  PubMed  CAS  Google Scholar 

  12. Athyros VG, Mikhailidis DP, Kakafika AI, Karagiannis A, Hatzitolios A, Tziomalos K, Ganotakis ES, Liberopoulos EN, Elisaf M (2007) Identifying and attaining LDL-C goals: mission accomplished? Next target: new therapeutic options to raise HDL-C levels. Curr Drug Targets 8:483–488

    Article  PubMed  CAS  Google Scholar 

  13. Athyros VG, Papageorgiou AA, Mercouris BR, Athyrou VV, Symeonidis AN, Basayannis EO, Demitriadis DS, Kontopoulos AG (2002) Treatment with atorvastatin to the National Cholesterol Educational Program goals versus usual care in secondary coronary heart disease prevention. The GREek Atorvastatin and coronary-heart-disease evaluation (GREACE) study. Curr Med Res Opin 18:220–228

    Article  PubMed  Google Scholar 

  14. Athyros VG, Mikhailidis DP, Papageorgiou AA, Bouloukos VI, Pehlivanidis AN, Symeonidis AN, Kakafika AI, Daskalopoulou SS, Elisaf M (2005) Effect of statins and aspirin alone and in combination on clinical outcome in dyslipidaemic patients with coronary heart disease. A subgroup analysis of the GREACE study. Platelets 16:65–71

    Article  PubMed  CAS  Google Scholar 

  15. Athyros VG, Mikhailidis DP, Papageorgiou AA, Symeonidis AN, Daskalopoulou SS, Kakafika AI, Pehlivanidis AN, Bouloukos VI, Langer A, GREACE Study Collaborative Group (2004) Relationship between LDL-C and non-HDL-C levels and clinical outcome in the GREek Atorvastatin and coronary-heart-disease evaluation (GREACE) study. Curr Med Ress Opin 20:1385–1392

    Article  CAS  Google Scholar 

  16. Athyros VG, Mikhailidis DP, Papageorgiou AA, Bouloukos VI, Pehlivanidis AN, Symeonidis AN, Elisaf M, GREACE Study Collaborative Group (2004) Effect of statins and ACE inhibitors alone and in combination on clinical outcome in patients with coronary heart disease. J Hum Hypertens 18:781–788

    Article  PubMed  CAS  Google Scholar 

  17. Athyros VG, Mikhailidis DP, Papageorgiou AA, Symeonidis AN, Pehlivanidis AN, Bouloukos VI, Elisaf M (2004) The effect of statins versus untreated dyslipidemia on renal function in patients with coronary heart disease: a subgroup analysis of the Greek atorvastatin and coronary heart disease evaluation (GREACE) study. J Clin Pathol 57:728–734

    Article  PubMed  CAS  Google Scholar 

  18. Athyros VG, Elisaf M, Papageorgiou AA, Symeonidis AN, Pehlivanidis AN, Bouloukos VI, Milionis HJ, Mikhailidis DP, GREACE Study Collaborative Group (2004) Effect of statins versus untreated dyslipidemia on serum uric acid levels in patients with coronary heart disease: a subgroup analysis of the GREek Atorvastatin and coronary-heart-disease evaluation (GREACE) study. Am J Kidney Dis 43:589–599

    Article  PubMed  CAS  Google Scholar 

  19. Liberopoulos EN, Mikhailidis DP, Athyros VG, Elisaf M (2006) The effect of cholesterol lowering treatment on renal function. Am J Kidney Dis 47:561

    Article  PubMed  Google Scholar 

  20. Grundy SM, Cleeman JI, Daniels SR, Donato KA, Eckel RH, Franklin BA, Gordon DJ, Krauss RM, Savage PJ, Smith SC Jr, Spertus JA, Costa F, American Heart Association, National Heart, Lung, Blood Institute (2005) Diagnosis and management of the metabolic syndrome: an American Heart Association/National Heart, Lung, and Blood Institute Scientific Statement. Circulation 112:2735–2752

    Article  PubMed  Google Scholar 

  21. Hopkins PN, Wu LL, Hunt SC, Brinton EA (2005) Plasma triglycerides and type III hyperlipidemia are independently associated with premature familial coronary artery disease. J Am Coll Cardiol 45:1003–1012

    Article  PubMed  CAS  Google Scholar 

  22. Stein EA, Lane M, Laskarzewski P (1998) Comparison of statins in hypertriglyceridemia. Am J Cardiol 81(4A):66B–69B

    Article  PubMed  CAS  Google Scholar 

  23. Ballantyne CM, Olsson AG, Cook TJ, Mercuri MF, Pedersen TR, Kjekshus J (2001) Influence of low high-density lipoprotein cholesterol and elevated triglyceride on coronary heart disease events and response to simvastatin therapy in 4S. Circulation 104:3046–3051

    Article  PubMed  CAS  Google Scholar 

  24. Pyorala K, Ballantyne CM, Gumbiner B, Lee MW, Shah A, Davies MJ, Mitchel YB, Pedersen TR, Kjekshus J, Scandinavian Simvastatin Survival Study (4S) (2004) Reduction of cardiovascular events by simvastatin in nondiabetic coronary heart disease patients with and without the metabolic syndrome. Subgroup analyses of the Scandinavian Simvastatin Survival Study (4S). Diabetes Care 27:1735–1740

    Article  PubMed  CAS  Google Scholar 

  25. Girman CJ, Rhodes T, Mercuri M, Pyorala K, Kjekshus J, Pedersen TR, Beere PA, Gotto AM, Clearfield M, 4S Group, the AFCAPS/TexCAPS Research Group (2004) The metabolic syndrome and risk of major coronary events in the Scandinavian Simvastatin Survival Study (4S) and the Air Force/Texas coronary atherosclerosis prevention study (AFCAPS/TexCAPS). Am J Cardiol 93:136–141

    Article  PubMed  CAS  Google Scholar 

  26. Manninen V, Tenkanen L, Koskinen P, Huttunen JK, Manttari M, Heinonen OP, Frick MH (1992) Joint effects of serum triglyceride and LDL cholesterol and HDL cholesterol concentrations on coronary heart disease risk in the Helsinki heart study. Implications for treatment. Circulation 85:37–45

    PubMed  CAS  Google Scholar 

  27. Onat A, Sari I, Yazici M, Can G, Hergenc G, Avci GS (2006) Plasma triglycerides, an independent predictor of cardiovascular disease in men: a prospective study based on a population with prevalent metabolic syndrome. Int J Cardiol 108:89–95

    Article  PubMed  Google Scholar 

  28. Imke C, Rodriguez BL, Grove JS, McNamara JR, Waslien C, Katz AR, Willcox B, Yano K, Curb JD (2005) Are remnant-like particles independent predictors of coronary heart disease incidence? The Honolulu heart study. Arterioscler Thromb Vasc Biol 25:1718–1722

    Article  PubMed  CAS  Google Scholar 

  29. Kolovou GD, Anagnostopoulou KK, Daskalopoulou SS, Mikhailidis DP, Cokkinos DV (2005) Clinical relevance of postprandial lipaemia. Curr Med Chem 12:1931–1945

    Article  PubMed  CAS  Google Scholar 

  30. Athyros VG, Papageorgiou AA, Symeonidis AN, Elisaf M (2003) Non-high density lipoprotein cholesterol and coronary events during long-term statin treatment. Atherosclerosis 168:397–398

    Article  PubMed  CAS  Google Scholar 

  31. Stein DT, Devaraj S, Balis D, Adams-Huet B, Jialal I (2001) Effect of statin therapy on remnant lipoprotein cholesterol levels in patients with combined hyperlipidemia. Arterioscler Thromb Vasc Biol 21:2026–2031

    Article  PubMed  CAS  Google Scholar 

  32. Schaefer EJ, McNamara JR, Tayler T, Daly JA, Gleason JA, Seman LJ, Ferrari A, Rubenstein JJ (2002) Effects of atorvastatin on fasting and postprandial lipoprotein subclasses in coronary disease patients versus control subjects. Am J Cardiol 90:689–696

    Article  PubMed  CAS  Google Scholar 

  33. Schaefer EJ, McNamara JR, Tayler T, Daly JA, Gleason JL, Seman LJ, Ferrari A, Rubenstein JJ (2004) Comparisons of effects of statins (atorvastatin, fluvastatin, lovastatin, pravastatin, and simvastatin) on fasting and postprandial lipoproteins in patients with coronary heart disease versus control subjects. Am J Cardiol 93:31–39

    Article  PubMed  CAS  Google Scholar 

  34. Pontrelli L, Parris W, Adeli K, Cheung RC (2002) Atorvastatin treatment beneficially alters the lipoprotein profile and increases low-density lipoprotein particle diameter in patients with combined dyslipidemia and impaired fasting glucose/type 2 diabetes. Metabolism 51:334–342

    Article  PubMed  CAS  Google Scholar 

  35. Guerin M, Lassel TS, Le Goff W, Farnier M, Chapman MJ (2000) Action of atorvastatin in combined hyperlipidemia: preferential reduction of cholesteryl ester transfer from HDL to VLDL1 particles. Arterioscler Thromb Vasc Biol 20:189–197

    PubMed  CAS  Google Scholar 

  36. Kontopoulos AG, Athyros VG, Papageorgiou AA, Hatzikonstandinou HA, Mayroudi MC, Boudoulas H (1996) Effects of simvastatin and ciprofibrate alone and in combination on lipid profile, plasma fibrinogen and low density lipoprotein particle structure and distribution in patients with familial combined hyperlipidaemia and coronary artery disease. Coron Artery Dis 7:843–850

    Article  PubMed  CAS  Google Scholar 

  37. Gazi IF, Tsimihodimos V, Tselepis AD, Elisaf M, Mikhailidis DP (2007) Clinical importance and therapeutic modulation of small dense low-density lipoprotein particles. Expert Opin Biol Ther 7:53–72

    Article  PubMed  CAS  Google Scholar 

  38. Rubins HB, Robins SJ, Collins D, Fye CL, Anderson JW, Elam MB, Faas FH, Linares E, Schaefer EJ, Schectman G, Wilt TJ, Wittes J (1999) Gemfibrozil for the secondary prevention of coronary heart disease in men with low levels of high-density lipoprotein cholesterol: veterans affairs high-density lipoprotein cholesterol intervention trial study group. N Engl J Med 341:410–418

    Article  PubMed  CAS  Google Scholar 

  39. Keech A, Simes RJ, Barter P, Best J, Scott R, Taskinen MR, Forder P, Pillai A, Davis T, Glasziou P, Drury P, Kesaniemi YA, Sullivan D, Hunt D, Colman P, d’Emden M, Whiting M, Ehnholm C, Laakso M, FIELD study investigators (2005) Effects of long-term fenofibrate therapy on cardiovascular events in 9795 people with type 2 diabetes mellitus (the FIELD study): randomised controlled trial. Lancet 366:1849–1861

    Article  PubMed  CAS  Google Scholar 

  40. Athyros VG, Papageorgiou AA, Athyrou VV, Demitriadis DS, Kontopoulos AG (2002) Atorvastatin and micronized fenofibrate alone and in combination in type 2 diabetes with combined hyperlipidemia. Diabetes Care 25:1198–1202

    Article  PubMed  CAS  Google Scholar 

  41. Tsiara S, Elisaf M, Mikhailidis DP (2003) Early vascular benefits of statin therapy. Curr Med Res Opin 19:540–556

    Article  PubMed  CAS  Google Scholar 

  42. Gami AS, Witt BJ, Howard DE, Erwin PJ, Gami LA, Somers VK, Montori VM (2007) Metabolic syndrome and risk of incident cardiovascular events and death: a systematic review and meta-analysis of longitudinal studies. J Am Coll Cardiol 49:403–414

    Article  PubMed  CAS  Google Scholar 

  43. Grundy SM, Cleeman JI, Merz CN, Brewer HB Jr, Clark LT, Hunninghake DB, Pasternak RC, Smith SC Jr, Stone NJ, National Heart, Lung, Blood Institute; American College of Cardiology Foundation; American Heart Association (2004) Implications of recent clinical trials for the National Cholesterol Education Program Adult Treatment Panel III guidelines. Circulation 110:227–239

    Article  PubMed  Google Scholar 

Download references

Conflict of Interest

This study was conducted independently; no company or institution supported it financially. Some of the authors have attended conferences, given lectures and participated in advisory boards or other trials sponsored by various pharmaceutical companies.

Author information

Authors and Affiliations

  1. Atherosclerosis and Metabolic Syndrome Units, 2nd Propedeutic Department of Internal Medicine, Aristotelian University, Hippocration Hospital, Thessaloniki, Greece

    Vasilios G. Athyros, Anna I. Kakafika, Athanasios A. Papageorgiou, Konstantinos Tziomalos, Athanasios Skaperdas, Efstathios Pagourelias, Athina Pirpasopoulou & Asterios Karagiannis

  2. Department of Clinical Biochemistry (Vascular Prevention Clinics), Royal Free Hospital, Royal Free University College Medical School, Pond Street, London , NW3 2QG, UK

    Dimitri P. Mikhailidis

Authors
  1. Vasilios G. Athyros
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Anna I. Kakafika
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Athanasios A. Papageorgiou
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Konstantinos Tziomalos
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Athanasios Skaperdas
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Efstathios Pagourelias
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Athina Pirpasopoulou
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Asterios Karagiannis
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Dimitri P. Mikhailidis
    View author publications

    You can also search for this author in PubMed Google Scholar

Consortia

The GREACE Study Collaborative Group

Corresponding author

Correspondence to Dimitri P. Mikhailidis.

About this article

Cite this article

Athyros, V.G., Kakafika, A.I., Papageorgiou, A.A. et al. Atorvastatin Decreases Triacylglycerol-Associated Risk of Vascular Events in Coronary Heart Disease Patients. Lipids 42, 999–1009 (2007). https://doi.org/10.1007/s11745-007-3103-z

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11745-007-3103-z

Keywords

Search

Navigation