Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Review Article
  • Published:

Lipid parameters for measuring risk of cardiovascular disease

Nature Reviews Cardiology volume 8, pages 197–206 (2011)Cite this article

Subjects

Abstract

Besides measuring blood pressure and glucose levels, assessing the lipid spectrum is the method most commonly used to identify individuals at high risk of cardiovascular disease (CVD), as well as those who are likely to benefit most from lipid-lowering therapy. Although lowering LDL-cholesterol levels is the primary target of therapy in most clinical guidelines, accumulating evidence indicates that other lipoprotein–lipid measurements could provide a predictive value over and above that of LDL-cholesterol levels. For example, individuals treated with statins who achieve low LDL-cholesterol levels, but have high concentrations of either non-HDL cholesterol or apolipoprotein (apo) B, remain at increased cardiovascular risk. Similarly, individuals with low levels of either HDL cholesterol or apo A-I are also likely to experience cardiovascular events, despite having normal LDL-cholesterol levels. The residual cardiovascular risk, beyond that characterized by LDL-cholesterol levels alone, is exacerbated by physical inactivity and abdominal obesity, which are both increasingly prevalent risk factors for CVD. In this Review, we discuss the measurement of various lipoprotein–lipid parameters for the prediction of CVD risk, and their importance in identifying those patients who are likely to benefit from lipid-lowering therapy. The impact of recent studies on clinical guidelines is also considered.

Key Points

  • Although lowering LDL-cholesterol levels is associated with decreased cardiovascular risk, the majority of clinical events are not prevented with LDL-cholesterol-lowering therapy

  • Obesity, and abdominal obesity in particular, is associated with impairment of the lipoprotein–lipid metabolism independently of LDL-cholesterol levels

  • Lipoprotein–lipid measurements based on cholesterol and apolipoprotein levels, and assessed by nuclear magnetic resonance spectroscopy, could provide an improved estimate of cardiovascular risk in primary and secondary prevention

  • Clinical trials have shown that monitoring levels of apolipoprotein B, or the apolipoprotein B/apolipoprotein A-I ratio, might be the optimal method to assess the efficacy of lipid-lowering therapy

  • Additional risk factors or biomarkers, such as levels of triglycerides, lipoprotein(a), and C-reactive protein, could predict cardiovascular events in the general population, and also in patients receiving lipid-lowering therapy

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Figure 1: Relationship between the incidence of major clinical events and reduction in LDL-cholesterol levels.

Similar content being viewed by others

References

  1. [No authors listed] The epidemiology of cardiovascular diseases. Am. J. Public Health Nations Health 41, 335–336 (1951).

  2. Kannel, W. B., Dawber, T. R., Friedman, G. D., Glennon, W. E. & McNamara, P. M. Risk factors in coronary heart disease: an evaluation of several serum lipids as predictors of coronary heart disease; the Framingham Study. Ann. Intern. Med. 61, 888–899 (1964).

    CAS  PubMed  Google Scholar 

  3. Dawber, T. R. et al. Some factors associated with the development of coronary heart disease: six years' follow-up experience in the Framingham study. Am. J. Public Health Nations Health 49, 1349–1356 (1959).

    CAS  PubMed  PubMed Central  Google Scholar 

  4. Yusuf, S. et al. Effect of potentially modifiable risk factors associated with myocardial infarction in 52 countries (the INTERHEART study): case-control study. Lancet 364, 937–952 (2004).

    Article  PubMed  Google Scholar 

  5. Yeh, R. W. et al. Population trends in the incidence and outcomes of acute myocardial infarction. N. Engl. J. Med. 362, 2155–2165 (2010).

    CAS  PubMed  Google Scholar 

  6. Brown, M. S. & Goldstein, J. L. Receptor-mediated control of cholesterol metabolism. Science 191, 150–154 (1976).

    CAS  PubMed  Google Scholar 

  7. Kuroda, M., Tsujita, Y., Tanzawa, K. & Endo, A. Hypolipidemic effects in monkeys of ML-236B, a competitive inhibitor of 3-hydroxy-3-methylglutaryl coenzyme A reductase. Lipids 14, 585–589 (1979).

    CAS  PubMed  Google Scholar 

  8. Endo, A., Kuroda, M. & Tanzawa, K. Competitive inhibition of 3-hydroxy-3-methylglutaryl coenzyme A reductase by ML-236A and ML-236B fungal metabolites, having hypocholesterolemic activity. FEBS Lett. 72, 323–326 (1976).

    CAS  PubMed  Google Scholar 

  9. Hunink, M. G. et al. The recent decline in mortality from coronary heart disease, 1980–1990. The effect of secular trends in risk factors and treatment. JAMA 277, 535–542 (1997).

    CAS  PubMed  Google Scholar 

  10. [No authors listed] Randomised trial of cholesterol lowering in 4444 patients with coronary heart disease: the Scandinavian Simvastatin Survival Study (4S). Lancet 344, 1383–1389 (1994).

  11. Downs, J. R. et al. Primary prevention of acute coronary events with lovastatin in men and women with average cholesterol levels: results of AFCAPS/TexCAPS. Air Force/Texas Coronary Atherosclerosis Prevention Study. JAMA 279, 1615–1622 (1998).

    CAS  PubMed  Google Scholar 

  12. Heart Protection Study Collaborative Group. MRC/BHF Heart Protection Study of cholesterol lowering with simvastatin in 20,536 high-risk individuals: a randomised placebo-controlled trial. Lancet 360, 7–22 (2002).

  13. Shepherd, J. et al. Prevention of coronary heart disease with pravastatin in men with hypercholesterolemia. West of Scotland Coronary Prevention Study Group. N. Engl. J. Med. 333, 1301–1307 (1995).

    CAS  PubMed  Google Scholar 

  14. Baigent, C. et al. Efficacy and safety of cholesterol-lowering treatment: prospective meta-analysis of data from 90,056 participants in 14 randomised trials of statins. Lancet 366, 1267–1278 (2005).

    Article  CAS  PubMed  Google Scholar 

  15. McQueen, M. J. et al. Lipids, lipoproteins, and apolipoproteins as risk markers of myocardial infarction in 52 countries (the INTERHEART study): a case-control study. Lancet 372, 224–233 (2008).

    CAS  PubMed  Google Scholar 

  16. Yusuf, S., Reddy, S., Ounpuu, S. & Anand, S. Global burden of cardiovascular diseases: part I: general considerations, the epidemiologic transition, risk factors, and impact of urbanization. Circulation 104, 2746–2753 (2001).

    CAS  PubMed  Google Scholar 

  17. Yusuf, S., Reddy, S., Ounpuu, S. & Anand, S. Global burden of cardiovascular diseases: part II: variations in cardiovascular disease by specific ethnic groups and geographic regions and prevention strategies. Circulation 104, 2855–2864 (2001).

    CAS  PubMed  Google Scholar 

  18. Centers for Disease Control and Prevention. Prevalence of overweight, obesity and extreme obesity among adults: United States, trends 1976–80 through 2005–2006 [online], (2008).

  19. Ogden, C. L. et al. Prevalence of overweight and obesity in the United States, 1999–2004. JAMA 295, 1549–1555 (2006).

    CAS  PubMed  Google Scholar 

  20. Olshansky, S. J. et al. A potential decline in life expectancy in the United States in the 21st century. N. Engl. J. Med. 352, 1138–1145 (2005).

    CAS  PubMed  Google Scholar 

  21. Walls, H. L. et al. Comparing trends in BMI and waist circumference. Obesity (Silver Spring) 19, 216–219 (2011).

    Google Scholar 

  22. Goossens, G. H. The role of adipose tissue dysfunction in the pathogenesis of obesity-related insulin resistance. Physiol. Behav. 94, 206–218 (2008).

    CAS  PubMed  Google Scholar 

  23. Després, J. P. & Lemieux, I. Abdominal obesity and metabolic syndrome. Nature 444, 881–887 (2006).

    PubMed  Google Scholar 

  24. Van Gaal, L. F., Mertens, I. L. & De Block, C. E. Mechanisms linking obesity with cardiovascular disease. Nature 444, 875–880 (2006).

    CAS  PubMed  Google Scholar 

  25. Adiels, M., Olofsson, S. O., Taskinen, M. R. & Boren, J. Overproduction of very low-density lipoproteins is the hallmark of the dyslipidemia in the metabolic syndrome. Arterioscler. Thromb. Vasc. Biol. 28, 1225–1236 (2008).

    CAS  PubMed  Google Scholar 

  26. Charansonney, O. L. & Després, J. P. Disease prevention—should we target obesity or sedentary lifestyle? Nat. Rev. Cardiol. 7, 468–472 (2010).

    PubMed  Google Scholar 

  27. Castelli, W. P. Cholesterol and lipids in the risk of coronary artery disease—the Framingham Heart Study. Can. J. Cardiol. 4 (Suppl. A), 5A–10A (1988).

    PubMed  Google Scholar 

  28. Conroy, R. M. et al. Estimation of ten-year risk of fatal cardiovascular disease in Europe: the SCORE project. Eur. Heart J. 24, 987–1003 (2003).

    CAS  PubMed  Google Scholar 

  29. Wilson, P. W. et al. Prediction of coronary heart disease using risk factor categories. Circulation 97, 1837–1847 (1998).

    CAS  PubMed  Google Scholar 

  30. Robinson, J. G. Are you targeting non-high-density lipoprotein cholesterol? J. Am. Coll. Cardiol. 55, 42–44 (2009).

    PubMed  Google Scholar 

  31. Arsenault, B. J. et al. Beyond low-density lipoprotein cholesterol: respective contributions of non-high-density lipoprotein cholesterol levels, triglycerides, and the total cholesterol/high-density lipoprotein cholesterol ratio to coronary heart disease risk in apparently healthy men and women. J. Am. Coll. Cardiol. 55, 35–41 (2009).

    PubMed  Google Scholar 

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

    CAS  PubMed  Google Scholar 

  33. Sarwar, N. et al. 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 (2007).

    CAS  PubMed  Google Scholar 

  34. Bansal, S. et al. Fasting compared with nonfasting triglycerides and risk of cardiovascular events in women. JAMA 298, 309–316 (2007).

    CAS  PubMed  Google Scholar 

  35. Di Angelantonio, E. et al. Major lipids, apolipoproteins, and risk of vascular disease. JAMA 302, 1993–2000 (2009).

    CAS  PubMed  Google Scholar 

  36. Sarwar, N. et al. Triglyceride-mediated pathways and coronary disease: collaborative analysis of 101 studies. Lancet 375, 1634–1639 (2010).

    CAS  PubMed  Google Scholar 

  37. Lemieux, I. et al. Total cholesterol/HDL cholesterol ratio vs LDL cholesterol/HDL cholesterol ratio as indices of ischemic heart disease risk in men: the Quebec Cardiovascular Study. Arch. Intern. Med. 161, 2685–2692 (2001).

    CAS  PubMed  Google Scholar 

  38. Kannel, W. B., Vasan, R. S., Keyes, M. J., Sullivan, L. M. & Robins, S. J. Usefulness of the triglyceride-high-density lipoprotein versus the cholesterol-high-density lipoprotein ratio for predicting insulin resistance and cardiometabolic risk (from the Framingham Offspring Cohort). Am. J. Cardiol. 101, 497–501 (2008).

    CAS  PubMed  PubMed Central  Google Scholar 

  39. Ingelsson, E. et al. Clinical utility of different lipid measures for prediction of coronary heart disease in men and women. JAMA 298, 776–785 (2007).

    CAS  PubMed  Google Scholar 

  40. Vaisar, T. et al. Shotgun proteomics implicates protease inhibition and complement activation in the antiinflammatory properties of HDL. J. Clin. Invest. 117, 746–756 (2007).

    CAS  PubMed  PubMed Central  Google Scholar 

  41. Ganda, O. P. Refining lipoprotein assessment in diabetes: apolipoprotein B makes sense. Endocr. Pract. 15, 370–376 (2009).

    PubMed  Google Scholar 

  42. Arsenault, B. J. et al. Cholesterol levels in small LDL particles predict the risk of coronary heart disease in the EPIC-Norfolk prospective population study. Eur. Heart J. 28, 2770–2777 (2007).

    CAS  PubMed  Google Scholar 

  43. Lamarche, B. et al. Small, dense low-density lipoprotein particles as a predictor of the risk of ischemic heart disease in men. Prospective results from the Québec Cardiovascular Study. Circulation 95, 69–75 (1997).

    CAS  PubMed  Google Scholar 

  44. Sniderman, A. et al. Association of coronary atherosclerosis with hyperapobetalipoproteinemia [increased protein but normal cholesterol levels in human plasma low density (beta) lipoproteins]. Proc. Natl Acad. Sci. USA 77, 604–608 (1980).

    CAS  PubMed  PubMed Central  Google Scholar 

  45. Pischon, T. et al. Non-high-density lipoprotein cholesterol and apolipoprotein B in the prediction of coronary heart disease in men. Circulation 112, 3375–3383 (2005).

    CAS  PubMed  Google Scholar 

  46. Sniderman, A., Williams, K. & Cobbaert, C. ApoB versus non-HDL-C: what to do when they disagree. Curr. Atheroscler. Rep. 11, 358–363 (2009).

    CAS  PubMed  Google Scholar 

  47. Barter, P. J. et al. Antiinflammatory properties of HDL. Circ. Res. 95, 764–772 (2004).

    CAS  PubMed  Google Scholar 

  48. Avogaro, P., Bon, G. B., Cazzolato, G. & Quinci, G. B. Are apolipoproteins better discriminators than lipids for atherosclerosis? Lancet 1, 901–903 (1979).

    CAS  PubMed  Google Scholar 

  49. Lamarche, B. et al. Apolipoprotein A-I and B levels and the risk of ischemic heart disease during a five-year follow-up of men in the Québec cardiovascular study. Circulation 94, 273–278 (1996).

    CAS  PubMed  Google Scholar 

  50. Walldius, G. et al. High apolipoprotein B, low apolipoprotein A-I, and improvement in the prediction of fatal myocardial infarction (AMORIS study): a prospective study. Lancet 358, 2026–2033 (2001).

    CAS  PubMed  Google Scholar 

  51. Parish, S. et al. The joint effects of apolipoprotein B, apolipoprotein A1, LDL cholesterol, and HDL cholesterol on risk: 3510 cases of acute myocardial infarction and 9805 controls. Eur. Heart J. 30, 2137–2146 (2009).

    CAS  PubMed  PubMed Central  Google Scholar 

  52. Ridker, P. M., Rifai, N., Cook, N. R., Bradwin, G. & Buring, J. E. Non-HDL cholesterol, apolipoproteins A-I and B100, standard lipid measures, lipid ratios, and CRP as risk factors for cardiovascular disease in women. JAMA 294, 326–333 (2005).

    CAS  PubMed  Google Scholar 

  53. Sweetnam, P. M. et al. Apolipoproteins A-I, A-II and B, lipoprotein(a) and the risk of ischaemic heart disease: the Caerphilly study. Eur. J. Clin. Invest. 30, 947–956 (2000).

    CAS  PubMed  Google Scholar 

  54. van der Steeg, W. A. et al. Role of the apolipoprotein B-apolipoprotein A-I ratio in cardiovascular risk assessment: a case-control analysis in EPIC-Norfolk. Ann. Intern. Med. 146, 640–648 (2007).

    PubMed  Google Scholar 

  55. Otvos, J. D., Jeyarajah, E. J. & Bennett, D. W. Quantification of plasma lipoproteins by proton nuclear magnetic resonance spectroscopy. Clin. Chem. 37, 377–386 (1991).

    CAS  PubMed  Google Scholar 

  56. Jeyarajah, E. J., Cromwell, W. C. & Otvos, J. D. Lipoprotein particle analysis by nuclear magnetic resonance spectroscopy. Clin. Lab. Med. 26, 847–870 (2006).

    PubMed  Google Scholar 

  57. El Harchaoui, K. et al. Value of low-density lipoprotein particle number and size as predictors of coronary artery disease in apparently healthy men and women: the EPIC-Norfolk Prospective Population Study. J. Am. Coll. Cardiol. 49, 547–553 (2007).

    CAS  PubMed  Google Scholar 

  58. Mora, S. et al. LDL particle subclasses, LDL particle size, and carotid atherosclerosis in the Multi-Ethnic Study of Atherosclerosis (MESA). Atherosclerosis 192, 211–217 (2007).

    CAS  PubMed  Google Scholar 

  59. Mora, S. et al. Lipoprotein particle profiles by nuclear magnetic resonance compared with standard lipids and apolipoproteins in predicting incident cardiovascular disease in women. Circulation 119, 931–939 (2009).

    CAS  PubMed  PubMed Central  Google Scholar 

  60. El Harchaoui, K. et al. High-density lipoprotein particle size and concentration and coronary risk. Ann. Intern. Med. 150, 84–93 (2009).

    PubMed  Google Scholar 

  61. Arsenault, B. J. et al. Lipid assessment, metabolic syndrome and coronary heart disease risk. Eur. J. Clin. Invest. 40, 1081–1093 (2010).

    CAS  PubMed  Google Scholar 

  62. Arsenault, B. J. et al. HDL particle size and the risk of coronary heart disease in apparently healthy men and women: the EPIC-Norfolk prospective population study. Atherosclerosis 206, 276–281 (2009).

    CAS  PubMed  Google Scholar 

  63. Arsenault, B. J. et al. Comparison between gradient gel electrophoresis and nuclear magnetic resonance spectroscopy in estimating coronary heart disease risk associated with LDL and HDL particle size. Clin. Chem. 56, 789–798 (2010).

    CAS  PubMed  Google Scholar 

  64. Farnier, M., Perevozskaya, I., Taggart, W. V., Kush, D. & Mitchel, Y. B. VAP II analysis of lipoprotein subclasses in mixed hyperlipidemic patients on treatment with ezetimibe/simvastatin and fenofibrate. J. Lipid Res. 49, 2641–2647 (2008).

    CAS  PubMed  Google Scholar 

  65. Miller, M., Dobs, A., Yuan, Z., Battisti, W. P. & Palmisano, J. The effect of simvastatin on triglyceride-rich lipoproteins in patients with type 2 diabetic dyslipidemia: a SILHOUETTE trial sub-study. Curr. Med. Res. Opin. 22, 343–350 (2006).

    CAS  PubMed  Google Scholar 

  66. Kulkarni, K. R., Garber, D. W., Marcovina, S. M. & Segrest, J. P. Quantification of cholesterol in all lipoprotein classes by the VAP-II method. J. Lipid Res. 35, 159–168 (1994).

    CAS  PubMed  Google Scholar 

  67. Erqou, S. et al. Lipoprotein(a) concentration and the risk of coronary heart disease, stroke, and nonvascular mortality. JAMA 302, 412–423 (2009).

    CAS  PubMed  Google Scholar 

  68. Erqou, S. et al. Apolipoprotein(a) isoforms and the risk of vascular disease: systematic review of 40 studies involving 58,000 participants. J. Am. Coll. Cardiol. 55, 2160–2167 (2010).

    CAS  PubMed  Google Scholar 

  69. Clarke, R. et al. Genetic variants associated with Lp(a) lipoprotein level and coronary disease. N. Engl. J. Med. 361, 2518–2528 (2009).

    CAS  PubMed  Google Scholar 

  70. Kamstrup, P. R., Tybjaerg-Hansen, A., Steffensen, R. & Nordestgaard, B. G. Genetically elevated lipoprotein(a) and increased risk of myocardial infarction. JAMA 301, 2331–2339 (2009).

    CAS  PubMed  Google Scholar 

  71. Nordestgaard, B. G. et al. Lipoprotein(a) as a cardiovascular risk factor: current status. Eur. Heart J. 31, 2844–2853 (2010).

    CAS  PubMed  PubMed Central  Google Scholar 

  72. Hurt-Camejo, E., Camejo, G., Peilot, H., Oorni, K. & Kovanen, P. Phospholipase A2 in vascular disease. Circ. Res. 89, 298–304 (2001).

    CAS  PubMed  Google Scholar 

  73. Thompson, A. et al. Lipoprotein-associated phospholipase A2 and risk of coronary disease, stroke, and mortality: collaborative analysis of 32 prospective studies. Lancet 375, 1536–1544 (2010).

    CAS  PubMed  Google Scholar 

  74. ClinicalTrials.gov. The stabilization of atherosclerotic plaque by initiation of darapladib therapy trial [online], (2011).

  75. ClinicalTrials.gov. VISTA-16 trial: evaluation of safety and efficacy of short-term A-002 treatment in subjects with acute coronary syndrome [online], (2011).

  76. Libby, P. Inflammation in atherosclerosis. Nature 420, 868–874 (2002).

    CAS  PubMed  Google Scholar 

  77. Duewell, P. et al. NLRP3 inflammasomes are required for atherogenesis and activated by cholesterol crystals. Nature 464, 1357–1361 (2010).

    CAS  PubMed  PubMed Central  Google Scholar 

  78. Boekholdt, S. M. & Kastelein, J. J. C-reactive protein and cardiovascular risk: more fuel to the fire. Lancet 375, 95–96 (2010).

    PubMed  Google Scholar 

  79. Cartier, A. et al. Age-related differences in inflammatory markers in men: contribution of visceral adiposity. Metabolism 58, 1452–1458 (2009).

    CAS  PubMed  Google Scholar 

  80. Rana, J. S. et al. Inflammatory biomarkers, physical activity, waist circumference, and risk of future coronary heart disease in healthy men and women. Eur. Heart J. doi:10.1093/eurheartj/ehp010.

    PubMed  Google Scholar 

  81. Fontana, L., Eagon, J. C., Trujillo, M. E., Scherer, P. E. & Klein, S. Visceral fat adipokine secretion is associated with systemic inflammation in obese humans. Diabetes 56, 1010–1013 (2007).

    CAS  PubMed  Google Scholar 

  82. Kaptoge, S. et al. C-reactive protein concentration and risk of coronary heart disease, stroke, and mortality: an individual participant meta-analysis. Lancet 375, 132–140 (2010).

    PubMed  Google Scholar 

  83. Elliott, P. et al. Genetic loci associated with C-reactive protein levels and risk of coronary heart disease. JAMA 302, 37–48 (2009).

    CAS  PubMed  PubMed Central  Google Scholar 

  84. Lawlor, D. A. et al. The association of C-reactive protein and CRP genotype with coronary heart disease: findings from five studies with 4,610 cases amongst 18,637 participants. PLoS ONE 3, e3011 (2008).

    PubMed  PubMed Central  Google Scholar 

  85. Zacho, J. et al. Genetically elevated C-reactive protein and ischemic vascular disease. N. Engl. J. Med. 359, 1897–1908 (2008).

    CAS  PubMed  Google Scholar 

  86. Ridker, P. M., Paynter, N. P., Rifai, N., Gaziano, J. M. & Cook, N. R. C-reactive protein and parental history improve global cardiovascular risk prediction: the Reynolds Risk Score for men. Circulation 118, 2243–2251 (2008).

    CAS  PubMed  PubMed Central  Google Scholar 

  87. Ridker, P. M., Buring, J. E., Rifai, N. & Cook, N. R. Development and validation of improved algorithms for the assessment of global cardiovascular risk in women: the Reynolds Risk Score. JAMA 297, 611–619 (2007).

    CAS  PubMed  Google Scholar 

  88. Sattar, N. et al. C-reactive protein and prediction of coronary heart disease and global vascular events in the Prospective Study of Pravastatin in the Elderly at Risk (PROSPER). Circulation 115, 981–989 (2007).

    CAS  PubMed  Google Scholar 

  89. Wilson, P. W. et al. C-reactive protein and risk of cardiovascular disease in men and women from the Framingham Heart Study. Arch. Intern. Med. 165, 2473–2478 (2005).

    CAS  PubMed  Google Scholar 

  90. Koenig, W., Lowel, H., Baumert, J. & Meisinger, C. C-reactive protein modulates risk prediction based on the Framingham Score: implications for future risk assessment: results from a large cohort study in southern Germany. Circulation 109, 1349–1353 (2004).

    PubMed  Google Scholar 

  91. Ridker, P. M. et al. Rosuvastatin to prevent vascular events in men and women with elevated C-reactive protein. N. Engl. J. Med. 359, 2195–2207 (2008).

    CAS  PubMed  Google Scholar 

  92. Gotto, A. M. Jr et al. Relation between baseline and on-treatment lipid parameters and first acute major coronary events in the Air Force/Texas Coronary Atherosclerosis Prevention Study (AFCAPS/TexCAPS). Circulation 101, 477–484 (2000).

    CAS  PubMed  Google Scholar 

  93. Pedersen, T. R. et al. Lipoprotein changes and reduction in the incidence of major coronary heart disease events in the Scandinavian Simvastatin Survival Study (4S). Circulation 97, 1453–1460 (1998).

    CAS  PubMed  Google Scholar 

  94. Ballantyne, C. M. et al. 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 (2001).

    CAS  PubMed  Google Scholar 

  95. Simes, R. J. et al. Relationship between lipid levels and clinical outcomes in the Long-term Intervention with Pravastatin in Ischemic Disease (LIPID) Trial: to what extent is the reduction in coronary events with pravastatin explained by on-study lipid levels? Circulation 105, 1162–1169 (2002).

    CAS  PubMed  Google Scholar 

  96. Kastelein, J. J. et al. Lipids, apolipoproteins, and their ratios in relation to cardiovascular events with statin treatment. Circulation 117, 3002–3009 (2008).

    CAS  PubMed  Google Scholar 

  97. Charlton-Menys, V. et al. Apolipoproteins, cardiovascular risk and statin response in type 2 diabetes: the Collaborative Atorvastatin Diabetes Study (CARDS). Diabetologia 52, 218–225 (2009).

    CAS  PubMed  Google Scholar 

  98. Ray, K. K. et al. Prognostic utility of apoB/AI, total cholesterol/HDL, non-HDL cholesterol, or hs-CRP as predictors of clinical risk in patients receiving statin therapy after acute coronary syndromes: results from PROVE IT-TIMI 22. Arterioscler. Thromb. Vasc. Biol. 29, 424–430 (2009).

    CAS  PubMed  Google Scholar 

  99. Ridker, P. M. et al. Reduction in C-reactive protein and LDL cholesterol and cardiovascular event rates after initiation of rosuvastatin: a prospective study of the JUPITER trial. Lancet 373, 1175–1182 (2009).

    CAS  PubMed  Google Scholar 

  100. Deedwania, P. et al. Reduction of low-density lipoprotein cholesterol in patients with coronary heart disease and metabolic syndrome: analysis of the Treating to New Targets study. Lancet 368, 919–928 (2006).

    CAS  PubMed  Google Scholar 

  101. Taskinen, M. R. et al. Ability of traditional lipid ratios and apolipoprotein ratios to predict cardiovascular risk in people with type 2 diabetes. Diabetologia 53, 1846–1855 (2010).

    CAS  PubMed  Google Scholar 

  102. Otvos, J. D. et al. Low-density lipoprotein and high-density lipoprotein particle subclasses predict coronary events and are favorably changed by gemfibrozil therapy in the Veterans Affairs High-Density Lipoprotein Intervention Trial. Circulation 113, 1556–1563 (2006).

    CAS  PubMed  Google Scholar 

  103. Expert Panel on Detection, Evaluation, 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 285, 2486–2497 (2001).

  104. Grundy, S. M. et al. Implications of recent clinical trials for the National Cholesterol Education Program Adult Treatment Panel III guidelines. Circulation 110, 227–239 (2004).

    PubMed  Google Scholar 

  105. Barter, P. et al. HDL cholesterol, very low levels of LDL cholesterol, and cardiovascular events. N. Engl. J. Med. 357, 1301–1310 (2007).

    CAS  PubMed  Google Scholar 

  106. Miller, M. et al. 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 (2008).

    CAS  PubMed  Google Scholar 

  107. Sniderman, A. Targets for LDL-lowering therapy. Curr. Opin. Lipidol. 20, 282–287 (2009).

    CAS  PubMed  Google Scholar 

  108. National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III). 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 (2002).

  109. Brunzell, J. D. et al. Lipoprotein management in patients with cardiometabolic risk: consensus conference report from the American Diabetes Association and the American College of Cardiology Foundation. J. Am. Coll. Cardiol. 51, 1512–1524 (2008).

    PubMed  Google Scholar 

  110. Contois, J. H. et al. Apolipoprotein B and cardiovascular disease risk: position statement from the AACC Lipoproteins and Vascular Diseases Division Working Group on Best Practices. Clin. Chem. 55, 407–419 (2009).

    CAS  PubMed  Google Scholar 

  111. Genest, J. et al. 2009 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. 25, 567–579 (2009).

    CAS  PubMed  PubMed Central  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Vascular Medicine, Academic Medical Center, University of Amsterdam, Meibergdreef 9, 1105 AZ, Amsterdam, The Netherlands

    Benoit J. Arsenault & John J. P. Kastelein

  2. Department of Cardiology, Academic Medical Center, University of Amsterdam, Meibergdreef 9, 1105 AZ, Amsterdam, The Netherlands

    S. Matthijs Boekholdt

Authors
  1. Benoit J. Arsenault
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. S. Matthijs Boekholdt
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. John J. P. Kastelein
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

B. J. Arsenault and S. M. Boekholdt researched data to include in the manuscript. B. J. Arsenault wrote the article, and S. M. Boekholdt and J. J. P. Kastelein reviewed and edited the manuscript before submission. B. J. Arsenault and S. M. Boekholdt revised the manuscript in response to the peer-reviewers' comments.

Corresponding author

Correspondence to John J. P. Kastelein.

Ethics declarations

Competing interests

The authors declare no competing financial interests.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Arsenault, B., Boekholdt, S. & Kastelein, J. Lipid parameters for measuring risk of cardiovascular disease. Nat Rev Cardiol 8, 197–206 (2011). https://doi.org/10.1038/nrcardio.2010.223

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/nrcardio.2010.223

This article is cited by

Search

Advanced search

Quick links

Nature Briefing: Translational Research

Sign up for the Nature Briefing: Translational Research newsletter — top stories in biotechnology, drug discovery and pharma.

Get what matters in translational research, free to your inbox weekly. Sign up for Nature Briefing: Translational Research