Volume 101, Issue 12, Supplement , Pages S1-S2, 16 June 2008
Introduction
Article Outline
Since the early 1970s, the US incidence of coronary artery disease (CAD) has been decreasing mostly because of a reduction in cigarette smoking and low-density lipoprotein (LDL) cholesterol levels. However, the rate of decrease is slowing because of the aging of the US population and an increasing prevalence of metabolic syndrome driven by the epidemic of obesity.1 LDL cholesterol is less predictive of CAD today than in earlier trials, and although the achievement of established LDL cholesterol treatment targets is improving, there remains significant residual risk for CAD events.2 Almost 50% of patients >50 years of age have metabolic syndrome and, therefore, multiple CAD risk factors. Ideally, all CAD risk factors should be well controlled, and increasing evidence shows an enhanced benefit with the more aggressively each individual risk factor is modified.3 Therefore, clinicians are confronted with 2 important challenges: appropriate identification of patients with moderate or intermediate risk in whom pharmacologic therapy should be initiated, and after initiating therapy, determination of the degree of global risk management necessary to adequately reduce CAD risk.
Dr. Paul Ridker4 has pioneered the use of the inflammatory marker high-sensitivity C-reactive protein (hs-CRP) as a valid biomarker to enhance CAD risk prediction and perhaps, determine the adequacy of risk factor modification. The hs-CRP marker has been shown to be an excellent and consistent predictor of primary CAD events and identifier of patients in statin clinical trials who have events despite adequately controlled LDL cholesterol levels. In addition, therapeutic approaches that lower hs-CRP levels reduce cardiovascular disease (CVD) events, whereas therapies that adversely affect hs-CRP (estrogen and torcetrapib) did not improve outcomes in clinical trials. Therefore, with a few exceptions (ie, rosiglitazone, raloxifene), therapeutic agents that lower hs-CRP also reduce CVD, and patients with lower hs-CRP levels have better outcomes.
The discovery of hs-CRP has provided an important link between inflammation and increased CVD risk. This paradigm shift has led to efforts to identify other inflammatory biomarkers that may add to the risk prediction enhancements of hs-CRP. Another interesting and well-studied biomarker is lipoprotein-associated phospholipase A2 (Lp-PLA2). Lp-PLA2 is directly involved in the pathogenesis of atherosclerotic plaque progression and may not only be a biomarker for risk prediction, but also may represent a novel therapeutic target to reduce the disease process.5
In this supplement to The American Journal of Cardiology, experts in the field of biomarkers, cardiovascular risk, and stroke have provided important reviews of the data on Lp-PLA2. In the first article, Dr. Howard S. Weintraub illuminates the identification of the vulnerable patient with rupture-prone plaque. Next, Drs. Amir Lerman and Joseph P. McConnell discuss the pathophysiology of Lp-PLA2 and its direct causal role in vascular inflammation and plaque rupture. Then, Dr. Jeffrey L. Anderson reviews published studies on Lp-PLA2 as a risk marker in the primary and secondary prevention of coronary and cardiovascular events. In the fourth article, the relation between Lp-PLA2 measurement and stroke risk is explored by Dr. Philip Gorelick. Then, Dr. Marshall Corson et al provide a comprehensive review of the current literature and summarize the key points of the other authors in their articles in this supplement. Finally, recommendations by an expert panel on how Lp-PLA2 testing might be used in conjunction with guideline-endorsed CVD risk assessment in an effort to create more aggressive risk reduction strategies.
Michael H. Davidson, MD
Author Disclosures
The author who contributed to this article has disclosed the following industry relationships.
Michael H. Davidson, MD is a member of the Speakers' Bureau for Abbott Laboratories, AstraZeneca Pharmaceuticals, Daiichi-Sankyo, Inc., diaDexus, Inc., Merck & Co., Inc., Merck/Schering-Plough, Oscient Pharmaceuticals, Pfizer, Inc, and Takeda Pharmaceuticals; is a consultant for Abbott Laboratories, AstraZeneca Pharmaceuticals, Daiichi-Sankyo, Inc., diaDexus, Inc., Merck & Co., Inc., Merck/Schering-Plough, Pfizer, Inc, Roche Pharmaceuticals, sanofi aventis, and Takeda Pharmaceuticals; has received grant/research support from Abbott Laboratories, AstraZeneca Pharmaceuticals, Daiichi-Sankyo, Inc., Merck & Co., Inc., Merck/Schering-Plough, Pfizer, Inc., Roche Pharmaceuticals, and Takeda Pharmaceuticals; is on the advisory board for Abbott Laboratories, Access Health, Atherogenics, AstraZeneca Pharmaceuticals, Daiichi-Sankyo, Inc., Merck & Co., Inc., Merck/Schering-Plough, Oscient Pharmaceuticals, Pfizer, Inc., Roche Pharmaceuticals, and Takeda Pharmaceuticals; is on the Board of Directors for Angiogen and Sonogene; and is Chief Medical Officer of Professional Evaluation, Inc.
References
- . Forty-year coronary mortality trends and changes in major risk factors in the first 10 years of follow-up in the seven countries study. Eur J Epidemiol. 2007;22:747–754
- . Reducing residual risk for patients on statin therapy: the potential role of combination therapy. Am J Cardiol. 2005;96(suppl):3K–13Kdiscussion 34K–35K
- . The metabolic syndrome and total and cardiovascular disease mortality in middle-aged men. JAMA. 2002;288:2709–2716
- . High sensitivity C-reactive protein, inflammation, and cardiovascular risk: from concept to clinical practice to clinical benefit. Am Heart J. 2004;148(1 Suppl):S19–S26
- . Association between lipoprotein-associated phospholipase A2 and cardiovascular disease: a systematic review. Mayo Clin Proc. 2007;82:159–165
Statement of author disclosure: Please see the Author Disclosures section at the end of this article.
PII: S0002-9149(08)00683-8
doi:10.1016/j.amjcard.2008.04.012
© 2008 Elsevier Inc. All rights reserved.
Volume 101, Issue 12, Supplement , Pages S1-S2, 16 June 2008
