Published online before print February 2, 2004, doi: 10.1161/01.CIR.0000116763.91992.F1
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(Circulation. 2004;109:837-842.)
© 2004 American Heart Association, Inc.
Clinical Investigation and Reports |
Lipoprotein-Associated Phospholipase A2, High-Sensitivity C-Reactive Protein, and Risk for Incident Coronary Heart Disease in Middle-Aged Men and Women in the Atherosclerosis Risk in Communities (ARIC) Study
From the Section of Atherosclerosis and Lipoprotein Research, Department of Medicine, Baylor College of Medicine, and Center for Cardiovascular Disease Prevention, Methodist DeBakey Heart Center, Houston, Tex (C.M.B., R.C.H.); the Departments of Biostatistics (H.B.) and Epidemiology (G.H.), School of Public Health, the University of North Carolina at Chapel Hill; the Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Johns Hopkins University, Baltimore, Md (J.C., A.R.S.); and the Division of Epidemiology, School of Public Health, University of Minnesota, Minneapolis (A.R.F.).
Correspondence to Christie M. Ballantyne, Baylor College of Medicine, 6565 Fannin, M.S. A-601, Houston, TX 77030. E-mail cmb{at}bcm.tmc.edu
Received August 27, 2003; revision received November 18, 2003; accepted November 20, 2003.
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Abstract |
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Background— Measuring C-reactive protein (CRP) has been recommended to identify patients at high risk for coronary heart disease (CHD) with low LDL cholesterol (LDL-C). Lipoprotein-associated phospholipase A2 (Lp-PLA2) is a proinflammatory enzyme associated primarily with LDL.
Methods and Results— In a prospective, case cohort study in 12 819 apparently healthy middle-aged men and women in the Atherosclerosis Risk in Communities study, the relation between Lp-PLA2, CRP, traditional risk factors, and risk for CHD events over a period of 
6 years was examined in a proportional hazards model, stratified by LDL-C. Lp-PLA2 and CRP levels were higher in the 608 cases than the 740 noncases. Both Lp-PLA2 and CRP were associated with incident CHD after adjustment for age, sex, and race with a hazard ratio of 1.78 for the highest tertile of Lp-PLA2 and 2.53 for the highest category of CRP versus the lowest categories. Lp-PLA2 correlated positively with LDL-C (r=0.36) and negatively with HDL-C (r=-0.33) but not with CRP (r=-0.05). In a model adjusted for traditional risk factors including LDL-C, the association of Lp-PLA2 with CHD was attenuated and not statistically significant. For individuals with LDL-C below the median (130 mg/dL), Lp-PLA2 and CRP were both significantly and independently associated with CHD in fully adjusted models. For individuals with LDL-C <130 mg/dL, those with both Lp-PLA2 and CRP levels in the highest tertile were at the greatest risk for a CHD event.
Conclusions— Lp-PLA2 and CRP may be complementary in identifying individuals at high CHD risk who have low LDL-C.
Key Words: Key Words: • coronary disease • epidemiology • inflammation • risk factors
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Introduction |
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Although screening for elevated LDL cholesterol (LDL-C) remains a major component of national guidelines for the prevention of coronary heart disease (CHD), LDL-C level is insufficient to identify individuals who would develop CHD, because many CHD events occur in individuals without elevated LDL-C,1 indicating the influence of other risk factors. Inflammation plays an important role in both atherogenesis and atherothrombotic events, and several biomarkers of inflammation, including high-sensitivity C-reactive protein (hs-CRP),2 interleukin-6,3 and soluble intercellular adhesion molecule-1,4 have been associated with increased risk for CHD events. hs-CRP measurement has been recommended for some patients to refine risk assessment5 because hs-CRP levels have been shown to provide additional predictive information beyond traditional risk factors such as LDL-C.6 Increased hs-CRP levels may also be useful to identify patients with low LDL-C who are at increased CHD risk and may benefit from statin therapy.7
Lipoprotein-associated phospholipase A2 (Lp-PLA2) is an enzyme that can hydrolyze oxidized phospholipids to generate lysophosphatidylcholine and oxidized fatty acids, which have proinflammatory properties. However, hydrolysis of platelet-activating factor and other phospholipids by Lp-PLA2 could also reduce inflammation,8 and it is not clear whether Lp-PLA2 is proinflammatory or anti-inflammatory in humans. Lp-PLA2 is associated primarily with LDL, and enzyme activity is increased in small, dense LDL.9
In a case–cohort analysis of the West of Scotland Coronary Prevention Study (WOSCOPS), high baseline Lp-PLA2 levels were associated with increased risk for CHD events, even after adjustment for traditional risk factors and hs-CRP.10 In a case–control analysis from the Women’s Health Study, baseline Lp-PLA2 levels were higher in women with subsequent cardiovascular events but were not associated with increased CHD risk after adjustment for traditional risk factors and hs-CRP.11
The purpose of this study was to examine whether levels of Lp-PLA2 and hs-CRP in middle-aged American men and women were associated with increased risk for incident CHD in the Atherosclerosis Risk in Communities (ARIC) study.
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Methods |
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Study Population
The ARIC design, objectives, sampling strategies, and examination techniques have been described previously.12 ARIC is a large, biracial cohort study of 15 792 adults 45 to 64 years old. A baseline examination was conducted in 1987 to 1989, with 3 more examinations through 1998.
Participants were followed up for incident CHD, defined by combinations of chest pain, ECG changes, cardiac enzyme levels, and surgical revascularization. Potential CHD events were reviewed by 2 members of the ARIC Morbidity and Mortality Classification Committee, and any differences between reviewers were adjudicated by the committee chairperson.
Study Design
Because plasma samples from the first visit were depleted, Lp-PLA2 and hs-CRP were measured in duplicate in plasma from visit 2 (1990–1992) in individuals who subsequently developed a CHD event (cases) and in a cohort random sample (CRS). Of the 14 560 participants with visit 2 data, 1272 were excluded because of CHD or missing CHD information before visit 2, 376 for transient ischemic attack or stroke, and 93 who belonged to an underrepresented minority group. The potential full cohort consisted of 12 819 individuals who were followed up for the subsequent development of a CHD event, including CHD-related death. Subjects alive and event-free at the end of 1998 or lost to follow-up were censored. We constructed a case–cohort design (n=1652)13 in which cases are compared with a CRS of all participants at the beginning of follow-up. The case–cohort design has the advantages that a single comparison group can be used for multiple disease outcomes (such as incident CHD and stroke), the comparison group is representative of the entire study population, and both absolute risks and relative hazards can be obtained with appropriate statistical analyses.
We selected the CRS by stratification on sex, race (black versus white) and age at baseline (
55 versus <55). After exclusion of 304 subjects with missing information, the final sample size for the analysis was 1348 (608 cases and 740 noncases). The CRS included 785 individuals: 45 cases and all 740 noncases.
Risk Factor Assessment
Information about medical history, cigarette smoking, and alcohol consumption was based on standardized, validated interviewer-administered questionnaires at visit 2. Body mass index (BMI) was derived from measured height and weight. Hypertension was defined as systolic blood pressure 140 mm Hg, diastolic blood pressure 90 mm Hg, or use of antihypertensive medication in the previous 2 weeks. Diabetes was defined as fasting blood glucose 126 mg/dL, nonfasting blood glucose 200 mg/dL, a physician’s diagnosis of diabetes, or use of antidiabetic medication in the previous 2 weeks.
Laboratory Measurements
Plasma lipids were measured in centralized laboratories by standard, validated methods reported previously.14–16 Lp-PLA2 was assessed by a dual monoclonal antibody immunoassay standardized to recombinant Lp-PLA2 (PLAC test, diaDexus, Inc).17 To assess interassay precision for Lp-PLA2 measurement, 2 controls of known concentration (low and high) were measured in 40 separate assays. The interassay coefficient of variation on all 40 plates was 12.7% and 9.6%, respectively. hs-CRP was assessed by the immunoturbidimetric CRP-Latex (II) hs assay from Denka Seiken using a Hitachi 911 analyzer. The assay was performed according to the manufacturer’s protocol and has been validated against the Dade-Behring method.18 For quality control, in addition to the measurement of each sample in duplicate, 6% of samples were measured as blinded replicates on different dates to assess repeatability of measurements of Lp-PLA2, hs-CRP, and other analytes. The reliability coefficient for blinded quality control replicates was 0.76 for the Lp-PLA2 assay (67 blinded replicates) and 0.95 for the hs-CRP assay (70 blinded replicates).
Statistical Analyses
For the primary analysis, all variables were categorized, with cutpoints taken from the National Cholesterol Education Program Adult Treatment Panel III (ATP III) guidelines for cholesterol19 and the Joint National Committee VI guidelines for blood pressure.20 Some categories were combined to maintain sufficient numbers of events per cell. Tertiles of the major study covariate, Lp-PLA2, were used. For hs-CRP, both tertiles and American Heart Association (AHA)/Centers for Disease Control and Prevention (CDC) cutpoints5 were examined. Covariates also were treated as continuous to examine the potential (non)linear trend in ancillary analyses. The primary null hypothesis was that Lp-PLA2 is not predictive of CHD events, over and above a set of traditional risk factors included in the model, with special attention to the interrelationship of Lp-PLA2 with LDL-C and hs-CRP. The association was tested at the 0.05 level using a Wald test for the 2-sided alternative.
Crude and adjusted (for demographic factors: race, sex, age) means or proportions of baseline variables were examined in cases versus noncases using ANCOVA and logistic regression.21 Beyond basic demographic variables, variables for risk factors recommended by ATP III19 for CHD risk assessment were considered as potential confounders: LDL-C, HDL cholesterol (HDL-C), total cholesterol, diabetes, smoking, and hypertension. Weighted Pearson and Spearman’s rank correlation coefficients were computed between variables among subjects in the CRS. In all analyses, weighting schemes based on sampling proportions were used so that the resulting inferences were pertinent to the entire cohort.
For the association between Lp-PLA2 level and incident CHD, the Cox proportional hazards model was used to investigate the independent and joint prognostic effects, accounting for the fact that all incident CHD cases are included but only a stratified random sample of the full cohort. The statistical method and computer software used were developed for case–cohort design within a framework of proportional hazard regression, with an appropriate modification to take into account the stratified nature of the CRS and robust variance estimation.22,23 The results were summarized as hazard ratios (HRs) with 95% CIs.
Tests for various potential interactions and (non)linearity were conducted as a secondary analysis, and subgroup analyses were considered to confirm findings. For the overall association of Lp-PLA2 and outcome, a 
2 test statistic was calculated. All other overall associations were tested similarly. SAS version 8 was used for all statistical analyses, except that SUDAAN version 8.0.0 was used to compute probability values for weighted correlation coefficients.
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Results |
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Of the 608 CHD events, 41.6% were nonfatal myocardial infarctions, 9.5% were silent myocardial infarctions, 39.0% were revascularization procedures, and 9.9% were fatal events, with mean time to event 4.1 years. Baseline characteristics of the study population are shown in Table 1. Compared with noncases, individuals with incident CHD had significantly higher BMI, systolic blood pressure, and levels of total cholesterol, triglycerides, and LDL-C and significantly lower HDL-C levels. Hypertension, diabetes, and current smoking were more prevalent in CHD cases. In addition to these differences in traditional risk factors, the weighted mean levels of both Lp-PLA2 and hs-CRP were higher in cases than noncases, 404 versus 372 µg/L and 4.05 versus 3.04 mg/L, respectively.
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Lp-PLA2 level was positively correlated with LDL-C (r=0.36) and total cholesterol (r=0.23) levels and negatively correlated with HDL-C level (r=-0.33) in both men and women (Table 2). There was a weak positive correlation with triglyceride (r=0.13) and no significant correlation with hs-CRP or BMI. Spearman’s rank correlation gave similar results. Weighted mean Lp-PLA2 was 421 µg/L in men and 339 µg/L in women, 366 µg/L in individuals <55 years old and 384 µg/L in individuals 55 years old, 388 µg/L in whites and 333 µg/L in African Americans, 362 µg/L in diabetics and 376 µg/L in nondiabetics, and 404 µg/L in current smokers and 366 µg/L in nonsmokers.
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Because hs-CRP tertiles in ARIC (<1.01, 1.01 to 2.82, and >2.82 mg/L) were similar to the cutpoints defined in the AHA/CDC guidelines (<1 mg/L, 1 to 3 mg/L, >3 mg/L),5 the AHA/CDC cutpoints were used to facilitate comparison across studies. In a Cox proportional hazards model adjusted for age, sex, and race, high hs-CRP as defined by the AHA/CDC cutpoint of >3.0 mg/L was associated with a significant increase in risk (2.53 HR, 95% CI 1.88 to 3.40) (Table 3). Further adjustment for smoking, hypertension, diabetes, LDL-C, and HDL-C attenuated risk associated with high hs-CRP, but risk remained significantly elevated (1.72 HR, 95% CI 1.24 to 2.39). For individuals with LDL-C <130 mg/dL, approximately the median LDL-C in this population, high hs-CRP was associated with increased CHD risk (1.76 HR, 95% CI 1.02 to 3.03). The use of tertiles for hs-CRP and the addition of BMI to the model did not significantly alter the findings (data not shown).
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Lp-PLA2 levels in the highest tertile (422 µg/L) were associated with increased CHD risk (1.78 HR, 95% CI 1.33 to 2.38) in a model adjusted for age, sex, and race (Table 4). In a Cox proportional hazards model also adjusted for traditional risk factors, including LDL-C and HDL-C, the relative risk associated with the upper tertile of Lp-PLA2 was attenuated and no longer significant. Tests for potential interaction with variables used in the model showed no interaction with race or sex but a significant 3-way interaction of Lp-PLA2 with hs-CRP and LDL-C (P=0.02); therefore, subgroup analysis defined by LDL-C categories (<130 and 130 mg/dL) was performed. No significant Lp-PLA2 associations were seen for individuals with higher LDL-C. However, for individuals with low LDL-C (<130 mg/dL), elevated Lp-PLA2 was associated with a significantly higher risk for incident CHD (1.99 HR, 95% CI 1.17 to 3.38), and even after further adjustment of the model to include hs-CRP, elevated Lp-PLA2 remained associated with increased CHD risk (2.08 HR, 95% CI 1.20 to 3.62) in these individuals. Inclusion of BMI in the model did not alter these findings. To address the impact of the 3-way effect modification, we added the interaction of Lp-PLA2 and hs-CRP in the model, which was restricted to the subgroup with low LDL-C. Results of this model with dichotomized conditions are illustrated in Figure 1; individuals with low LDL-C who were in the highest tertile of both Lp-PLA2 and hs-CRP were at the highest risk for CHD events (2.95 HR, 95% CI 1.47 to 5.94) compared with those in the lower 2 tertiles for both. Individuals with either high Lp-PLA2 (422 µg/L) and low to average hs-CRP (
3 mg/L) or high hs-CRP (>3 mg/L) and low to medium Lp-PLA2 (<422 µg/L) did not have markedly increased risk compared with those with low to medium levels of both (Figure). The addition of BMI and triglycerides did not significantly influence the regression analyses for hs-CRP or Lp-PLA2.
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Discussion |
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In the ARIC study, Lp-PLA2 and hs-CRP levels were higher in middle-aged American men and women who subsequently developed CHD events than in those who remained free of CHD.
Two previous studies have examined Lp-PLA2 and hs-CRP levels in cases with incident CHD and controls, and both studies found positive associations of Lp-PLA2 and hs-CRP with CHD risk.10,11 In ARIC, both Lp-PLA2 and hs-CRP were associated with incident CHD after adjustment for age, sex, and race, with 1.78 HR (95% CI 1.33 to 2.38) for the highest Lp-PLA2 tertile (422 µg/L) and 2.53 HR (95% CI 1.88 to 3.40) for hs-CRP >3.0 mg/L. The HRs for high Lp-PLA2 in this study are similar to those reported in WOSCOPS10 and the Women’s Health Study11 in the unadjusted models. Although all 3 studies found that Lp-PLA2 levels were increased in individuals with subsequent CHD events, results varied among the studies when statistical models examined whether Lp-PLA2 level had additional predictivity beyond traditional risk factors. In WOSCOPS, Lp-PLA2 remained a significant predictor after adjustment for traditional risk factors and inflammatory factors, including hs-CRP.10 However, in the Women’s Health Study, the predictivity of Lp-PLA2 was no longer statistically significant after adjustment for cardiovascular risk factors.11 In the ARIC study, the relation between Lp-PLA2 and CHD risk was attenuated after adjustment for traditional risk factors including LDL-C and HDL-C, but further analysis motivated by the significant interactions among Lp-PLA2, hs-CRP, and LDL-C indicated that the association remained significant, independent of other traditional risk factors but modifiable by hs-CRP in individuals with low LDL-C (<130 mg/dL). We did not find any significant, meaningful nonlinearity of Lp-PLA2 using polynomial and spline regression, but complex nonlinearity remains a possibility. Moreover, the significant 3-way interaction (P=0.02 in a model with categorical variables and P=0.001 in a model with continuous variables) needs more statistical investigation in future research in this and other populations. The differing results among these studies may be attributed to the markedly different populations. WOSCOPS enrolled middle-aged hypercholesterolemic men in Scotland, with LDL-C entry criterion within a narrow range of 174 to 232 mg/dL, high prevalence of other risk factors, and 5-year event rate of 7.9% in the placebo group (1.6%/yr).24 In addition, half the patients in WOSCOPS were assigned to pravastatin therapy, which lowered LDL-C by 26% on average. The Women’s Health Study examined middle-aged American women who were mostly professionals and had a lower event rate (1.4% over 6.2 years, or 0.2%/yr),11 enrolled fewer African Americans (2.3%) and fewer diabetic patients (2.6%)25 than ARIC, and included only 123 cases (49 of which were stroke) and 123 controls in the Lp-PLA2 analysis.11 In contrast, participants in ARIC were both men and women, including a substantial number of African Americans, and had a wide range of LDL-C levels, as would be expected in the US population; in this analysis of ARIC, the 10th percentile for LDL-C was 89 mg/dL and the 90th percentile was 179 mg/dL, and the event rate was 6.1% over 7 years, or 0.9%/yr.
For the hs-CRP analysis, the cutpoints defined in the AHA/CDC guidelines (1 and 3 mg/L)5 were used because they were similar to the tertile cutpoints in ARIC (1.01 and 2.82 mg/L). A previous analysis that examined hs-CRP in a different ARIC cohort showed similar risk for the upper 2 quintiles.26 The AHA/CDC guidelines provide for the assessment of hs-CRP in individuals at intermediate CHD risk (10% to 20% 10-year risk) as an adjunct to major risk factors to refine risk assessment and in considering whether to intensify therapy. There is a consensus that individuals with CHD risk >20% need preventive intervention and therefore CRP measurement will not influence therapy. Screening very-low-risk populations is not recommended and not thought to be cost-effective, although some groups have considered intermediate risk to include 6% to 20%.27
The ATP III guidelines recommend that calculated 10-year risk for a CHD event be used to determine which patients should receive lipid-lowering therapy and the target level for LDL-C. Two large placebo-controlled randomized clinical trials of statins in high-risk patients have shown that patients benefited from therapy regardless of baseline LDL-C.28,29 In the current guidelines, for individuals with LDL-C <130 mg/dL, drug therapy is not recommended in primary prevention and is considered optional for individuals with CHD or equivalent (ie, 10-year risk estimate >20%).19 If high-risk patients with LDL-C <130 mg/dL receive significant benefit from lipid-lowering drug therapy, as suggested by recent clinical trials, future guidelines may focus more on novel ways to assess CHD risk in low–LDL-C patients to determine who should be selected. This is an important population for CHD prevention, because approximately one third of all events (204 cases in ARIC) occurred in persons with LDL-C <130 mg/dL.
A post hoc analysis of the Air Force/Texas Coronary Atherosclerosis Prevention Study (AFCAPS/TexCAPS) suggested that measuring hs-CRP may be useful for targeting statin therapy in primary prevention of acute coronary events.7 AFCAPS/TexCAPS enrolled middle-aged men and women with average LDL-C and low HDL-C levels, and for individuals with LDL-C below the median (149.1 mg/dL), only those with elevated hs-CRP had reduced risk with lovastatin therapy.
The results from ARIC support the rationale that Lp-PLA2 and hs-CRP may be useful to identify patients at increased CHD risk who have low LDL-C (<130 mg/dL) and are not targeted for drug therapy by the current guidelines. ARIC had only a single measurement of Lp-PLA2 and hs-CRP; associations might have been stronger with multiple measurements of these biomarkers. In addition, the risk for Lp-PLA2 may have been underestimated because of a lower reliability coefficient for the Lp-PLA2 manual ELISA than for the hs-CRP automated immunoturbidimetric assay (0.76 versus 0.95). A large prospective randomized trial will test the hypothesis that hs-CRP measurement can identify high-risk patients with LDL-C <130 mg/dL and no clinical evidence of CHD who may benefit from statin therapy.30
Although our results support the use of novel blood tests to identify high-risk patients who may benefit from primary prevention, they are also consistent with a putative causal role for both Lp-PLA2 and hs-CRP in atherogenesis and CHD events. Lp-PLA2 is bound primarily with LDL, with an increased concentration in small, dense LDL.9 Small LDL has enhanced penetration into the vessel wall31 and enhanced susceptibility to oxidation.32 Lp-PLA2 is the enzyme responsible for the hydrolysis of oxidized phospholipids and the generation of lysophosphatidylcholine, which can lead to increased expression of adhesion molecules. Thus, increased Lp-PLA2 in LDL may enhance the atherogenicity of LDL by increasing vascular inflammation. High levels of hs-CRP, which is an acute-phase reactant, may also provoke vascular inflammation,33 and hs-CRP may preferentially bind to oxidized LDL.34 Individuals with low LDL-C but high Lp-PLA2 and hs-CRP may therefore have much greater atherogenicity from LDL than would be expected by the absolute level of LDL-C. Statins lower LDL-C level and LDL particle number, reduce hs-CRP level,7 and reduce Lp-PLA2 activity.35 However, many patients continue to have elevated hs-CRP and Lp-PLA2 even on statin therapy (Chris J. Packard, DSc, personal communication, 2003). Other therapies, such as weight loss and high-dose aspirin, also reduce hs-CRP levels. Fibrates have been shown to reduce Lp-PLA2 activity,36 and a novel agent that inhibits Lp-PLA2 is currently in phase II development.37 Therefore, in addition to potentially identifying high-risk but currently untreated patients who may benefit from therapies such as statins to reduce CHD events, measurement of Lp-PLA2 and hs-CRP may be useful to identify cohorts of patients for clinical trials to determine whether inhibition of Lp-PLA2 or reduction/inhibition of hs-CRP reduces CHD events. In summary, both Lp-PLA2 and hs-CRP may be complementary in identifying middle-aged individuals with high CHD risk but low LDL-C.
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Acknowledgments |
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This research was supported by National Heart, Lung, and Blood Institute contracts N01-HC-55015, N01-HC-55016, N01-HC-55018, N01-HC-55019, N01-HC-55020, N01-HC-55021, and N01-HC-55022 and by an unrestricted research grant from diaDexus, Inc, South San Francisco, Calif. The atherosclerosis laboratory is supported by donations from George and Cynthia Mitchell, Nijad Fares, and Jeffrey Hines. The authors acknowledge the editorial assistance of Kerrie Jara.
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Footnotes |
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Dr Ballantyne is a recipient of research grants and contracts from AstraZeneca, diaDexus, GlaxoSmithKline, Merck, Novartis, Pfizer, Reliant, and Schering-Plough. He has served on the speakers bureaus of and received honoraria from AstraZeneca, Bristol Myers-Squibb, Kos, Merck, Novartis, Pfizer, Reliant, and Schering-Plough. He has served as a consultant to AstraZeneca, Merck, Novartis, Pfizer, Reliant, and Schering-Plough.
Guest Editor for this article was Antonio Gotto, MD, Weill Medical College, New York, NY.
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References |
|---|
|
TopAbstractIntroductionMethodsResultsDiscussionReferences |
|---|
1. Kannel WB. Range of serum cholesterol values in the population developing coronary artery disease. Am J Cardiol. 1995; 76: 69C–77C.[CrossRef][Medline] [Order article via Infotrieve]
2. Ridker PM, Glynn RJ, Hennekens CH. C-reactive protein adds to the predictive value of total and HDL cholesterol in determining risk of first myocardial infarction. Circulation. 1998; 97: 2007–2011.
3. Pradhan AD, Manson JE, Rossouw JE, et al. Inflammatory biomarkers, hormone replacement therapy, and incident coronary heart disease: prospective analysis from the Women’s Health Initiative observational study. JAMA. 2002; 288: 980–987.
4. Hwang S-J, Ballantyne CM, Sharrett AR, et al. Circulating adhesion molecules VCAM-1, ICAM-1, and E-selectin in carotid atherosclerosis and incident coronary heart disease cases: the Atherosclerosis Risk in Communities (ARIC) study. Circulation. 1997; 96: 4219–4225.
5. Pearson TA, Mensah GA, Alexander RW, et al. Markers of inflammation and cardiovascular disease: application to clinical and public health practice. Circulation. 2003; 107: 499–511.
6. Ridker PM, Rifai N, Rose L, et al. Comparison of C-reactive protein and low-density lipoprotein cholesterol levels in the prediction of first cardiovascular events. N Engl J Med. 2002; 347: 1557–1565.
7. Ridker PM, Rifai N, Clearfield M, et al. Measurement of C-reactive protein for the targeting of statin therapy in the primary prevention of acute coronary events. N Engl J Med. 2001; 344: 1959–1965.
8. Tjoelker LW, Stafforini DM. Platelet-activating factor acetylhydrolases in health and disease. Biochim Biophys Acta. 2000; 1488: 102–123.[Medline] [Order article via Infotrieve]
9. Karabina SA, Liapikos TA, Grekas G, et al. Distribution of PAF-acetylhydrolase activity in human plasma low-density lipoprotein subfractions. Biochim Biophys Acta. 1994; 1213: 34–38.[Medline] [Order article via Infotrieve]
10. Packard CJ, O’Reilly DS, Caslake MJ, et al. Lipoprotein-associated phospholipase A2 as an independent predictor of coronary heart disease. N Engl J Med. 2000; 343: 1148–1155.
11. Blake GJ, Dada N, Fox JC, et al. A prospective evaluation of lipoprotein-associated phospholipase A2 levels and the risk of future cardiovascular events in women. J Am Coll Cardiol. 2001; 38: 1302–1306.
12. The ARIC Investigators. The Atherosclerosis Risk in Communities (ARIC) Study: design and objectives. Am J Epidemiol. 1989; 129: 687–702.
13. Prentice RL. A case-cohort design for epidemiologic cohort studies and disease prevention trials. Biometrika. 1986; 73: 1–11.
14. Brown SA, Hutchinson R, Morrisett J, et al. Plasma lipid, lipoprotein cholesterol, and apolipoprotein distributions in selected US communities: the Atherosclerosis Risk in Communities (ARIC) study. Arterioscler Thromb. 1993; 13: 1139–1158.
15. Chambless LE, McMahon R, Wu KK, et al. Short-term intraindividual variability in hemostatic factors: the ARIC study. Ann Epidemiol. 1992; 2: 723–733.[Medline] [Order article via Infotrieve]
16. Folsom AR, Wu KK, Shahar E, et al. Association of hemostatic variables with prevalent cardiovascular disease and asymptomatic carotid artery atherosclerosis. Arterioscler Thromb. 1993; 13: 1829–1836.
17. Dada N, Kim NW, Wolfert RL. Lp-PLA2: an emerging biomarker of coronary heart disease. Expert Rev Mol Diagn. 2002; 2: 17–22.[CrossRef][Medline] [Order article via Infotrieve]
18. Roberts WL, Moulton L, Law TC, et al. Evaluation of nine automated high-sensitivity C-reactive protein methods: implications for clinical and epidemiological applications, part 2. Clin Chem. 2001; 47: 418–425.
19. 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. 2001; 285: 2486–2497.
20. Joint National Committee on Detection, Evaluation, and Treatment of High Blood Pressure. The sixth report of the Joint National Committee on Detection, Evaluation, and Treatment of High Blood Pressure. Arch Intern Med. 1997; 157: 2413–2446.
21. Zhao DY. Logistic regression adjustment of proportions and its macro procedure. In: Proceedings of the Twenty-Second Annual SAS Users Group International Conference. Cary, NC: SAS Publishing, 1998: 1045–1050.
22. Barlow WE. Robust variance estimation for the case-cohort design. Biometrics. 1994; 50: 1064–1072.[CrossRef][Medline] [Order article via Infotrieve]
23. Barlow WE, Ichikawa L, Rosner D, et al. Analysis of case-cohort designs. J Clin Epidemiol. 1999; 52: 1165–1172.[CrossRef][Medline] [Order article via Infotrieve]
24. Shepherd J, Cobbe SM, Ford I, et al. Prevention of coronary heart disease with pravastatin in men with hypercholesterolemia. N Engl J Med. 1995; 333: 1301–1307.
25. Rexrode KM, Lee IM, Cook NR, et al. Baseline characteristics of participants in the Women’s Health Study. J Womens Health Gend Based Med. 2000; 9: 19–27.[CrossRef][Medline] [Order article via Infotrieve]
26. Folsom AR, Aleksic N, Catellier D, et al. C-reactive protein and incident coronary heart disease in the Atherosclerosis Risk in Communities (ARIC) study. Am Heart J. 2002; 144: 233–238.[CrossRef][Medline] [Order article via Infotrieve]
27. Greenland P, Smith SC Jr, Grundy SM. Improving coronary heart disease risk assessment in asymptomatic people: role of traditional risk factors and noninvasive cardiovascular tests. Circulation. 2001; 104: 1863–1867.
28. 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. 2002; 360: 7–22.[CrossRef][Medline] [Order article via Infotrieve]
29. Sever PS, Dahlöf B, Poulter NR, et al. Prevention of coronary and stroke events with atorvastatin in hypertensive patients who have average or lower-than-average cholesterol concentrations, in the Anglo-Scandinavian Cardiac Outcomes Trial—Lipid Lowering Arm (ASCOT-LLA): a multicentre randomised controlled trial. Lancet. 2003; 361: 1149–1158.[CrossRef][Medline] [Order article via Infotrieve]
30. Ridker PM. Rosuvastatin in the primary prevention of cardiovascular disease among patients with low levels of low-density lipoprotein cholesterol and elevated high-sensitivity C-reactive protein: rationale and design of the JUPITER trial. Circulation. 2003; 108: 2292–2297.
31. Anber V, Griffin BA, McConnell M, et al. Influence of plasma lipid and LDL-subfraction profile on the interaction between low density lipoprotein with human arterial wall proteoglycans. Atherosclerosis. 1996; 124: 261–271.[CrossRef][Medline] [Order article via Infotrieve]
32. de Graaf J, Hak-Lemmers HL, Hectors MP, et al. Enhanced susceptibility to in vitro oxidation of the dense low density lipoprotein subfraction in healthy subjects. Arterioscler Thromb. 1991; 11: 298–306.
33. Pasceri V, Willerson JT, Yeh ET. Direct proinflammatory effect of C-reactive protein on human endothelial cells. Circulation. 2000; 102: 2165–2168.
34. Chang MK, Binder CJ, Torzewski M, et al. C-reactive protein binds to both oxidized LDL and apoptotic cells through recognition of a common ligand: phosphorylcholine of oxidized phospholipids. Proc Natl Acad Sci U S A. 2002; 99: 13043–13048.
35. Tsimihodimos V, Karabina SA, Tambaki AP, et al. Atorvastatin preferentially reduces LDL-associated platelet-activating factor acetylhydrolase activity in dyslipidemias of type IIA and type IIB. Arterioscler Thromb Vasc Biol. 2002; 22: 306–311.
36. Tsimihodimos V, Kakafika A, Tambaki AP, et al. Fenofibrate induces HDL-associated PAF-AH but attenuates enzyme activity associated with apoB-containing lipoproteins. J Lipid Res. 2003; 44: 927–934.
37. Blackie JA, Bloomer JC, Brown MJ, et al. The discovery of SB-435495: a potent, orally active inhibitor of lipoprotein-associated phospholipase A2 for evaluation in man. Bioorg Med Chem Lett. 2002; 12: 2603–2606.[CrossRef][Medline] [Order article via Infotrieve]
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|
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|
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|
|
|
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|
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|
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|
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|
|
|
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|
|
|
|
|
|
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|
|
|
|
|
|
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|
|
|
|
|
|
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|
|
|
|
|
|
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|
|
|
|
 |
|
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|
|
|
|
|
|
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|
|
|
|
 |
|
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|
|
|
|
|
|
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|
|
|
|
|
|
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|
|
|
|
|
|
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|
|
|
|
|
|
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|
|
|
|
|
|
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|
|
|
 |
|
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|
|
|
|
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|
|
|
|
|
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|
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|
|
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|
|
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|
|
|
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|
|
|
|
|
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|
|
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|
|
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 G. S. Aldea Invited commentary Ann. Thorac. Surg., June 1, 2005; 79(6): 2038 - 2039. [Full Text] [PDF]
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K. Sudhir Lipoprotein-Associated Phospholipase A2, a Novel Inflammatory Biomarker and Independent Risk Predictor for Cardiovascular Disease J. Clin. Endocrinol. Metab., May 1, 2005; 90(5): 3100 - 3105. [Abstract] [Full Text] [PDF]
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A. Zalewski and C. Macphee Role of Lipoprotein-Associated Phospholipase A2 in Atherosclerosis: Biology, Epidemiology, and Possible Therapeutic Target Arterioscler Thromb Vasc Biol, May 1, 2005; 25(5): 923 - 931. [Abstract] [Full Text] [PDF]
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S. M. Boekholdt, T. T. Keller, N. J. Wareham, R. Luben, S. A. Bingham, N. E. Day, M. S. Sandhu, J. W. Jukema, J. J.P. Kastelein, C. E. Hack, et al. Serum Levels of Type II Secretory Phospholipase A2 and the Risk of Future Coronary Artery Disease in Apparently Healthy Men and Women: The EPIC-Norfolk Prospective Population Study Arterioscler Thromb Vasc Biol, April 1, 2005; 25(4): 839 - 846. [Abstract] [Full Text] [PDF]
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M. Cushman Leukocyte Count in Vascular Risk Prediction Arch Intern Med, March 14, 2005; 165(5): 487 - 488. [Full Text] [PDF]
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|
 A. Chait, C. Y. Han, J. F. Oram, and J. W. Heinecke Thematic review series: The Immune System and Atherogenesis. Lipoprotein-associated inflammatory proteins: markers or mediators of cardiovascular disease? J. Lipid Res., March 1, 2005; 46(3): 389 - 403. [Abstract] [Full Text] [PDF]
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K. Winkler, B. R. Winkelmann, H. Scharnagl, M. M. Hoffmann, A. B. Grawitz, M. Nauck, B. O. Bohm, and W. Marz Platelet-Activating Factor Acetylhydrolase Activity Indicates Angiographic Coronary Artery Disease Independently of Systemic Inflammation and Other Risk Factors: The Ludwigshafen Risk and Cardiovascular Health Study Circulation, March 1, 2005; 111(8): 980 - 987. [Abstract] [Full Text] [PDF]
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H.-H. S. Oei, I. M. van der Meer, A. Hofman, P. J. Koudstaal, T. Stijnen, M. M.B. Breteler, and J. C.M. Witteman Lipoprotein-Associated Phospholipase A2 Activity Is Associated With Risk of Coronary Heart Disease and Ischemic Stroke: The Rotterdam Study Circulation, February 8, 2005; 111(5): 570 - 575. [Abstract] [Full Text] [PDF]
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I. J. Kullo and C. M. Ballantyne Conditional Risk Factors for Atherosclerosis Mayo Clin. Proc., February 1, 2005; 80(2): 219 - 230. [Abstract] [PDF]
|
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P. M Ridker, C. P. Cannon, D. Morrow, N. Rifai, L. M. Rose, C. H. McCabe, M. A. Pfeffer, E. Braunwald, and the Pravastatin or Atorvastatin Evaluation and Inf C-Reactive Protein Levels and Outcomes after Statin Therapy N. Engl. J. Med., January 6, 2005; 352(1): 20 - 28. [Abstract] [Full Text] [PDF]
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C. H. Macphee and J. J. Nelson An evolving story of lipoprotein-associated phospholipase A2 in atherosclerosis and cardiovascular risk prediction Eur. Heart J., January 2, 2005; 26(2): 107 - 109. [Full Text] [PDF]
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|
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E. S. Brilakis, J. P. McConnell, R. J. Lennon, A. A. Elesber, J. G. Meyer, and P. B. Berger Association of lipoprotein-associated phospholipase A2 levels with coronary artery disease risk factors, angiographic coronary artery disease, and major adverse events at follow-up Eur. Heart J., January 2, 2005; 26(2): 137 - 144. [Abstract] [Full Text] [PDF]
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|
 J. T. Wu and L. L. Wu Association of Soluble Markers with Various Stages and Major Events of Atherosclerosis Ann. Clin. Lab. Sci., January 1, 2005; 35(3): 240 - 250. [Abstract] [Full Text] [PDF]
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C. Iribarren, M. D. Gross, J. A. Darbinian, D. R. Jacobs Jr, S. Sidney, and C. M. Loria Association of Lipoprotein-Associated Phospholipase A2 Mass and Activity With Calcified Coronary Plaque in Young Adults: The CARDIA Study Arterioscler Thromb Vasc Biol, January 1, 2005; 25(1): 216 - 221. [Abstract] [Full Text] [PDF]
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J. K. Pai, T. Pischon, J. Ma, J. E. Manson, S. E. Hankinson, K. Joshipura, G. C. Curhan, N. Rifai, C. C. Cannuscio, M. J. Stampfer, et al. Inflammatory Markers and the Risk of Coronary Heart Disease in Men and Women N. Engl. J. Med., December 16, 2004; 351(25): 2599 - 2610. [Abstract] [Full Text] [PDF]
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W. Koenig, N. Khuseyinova, H. Lowel, G. Trischler, and C. Meisinger Lipoprotein-Associated Phospholipase A2 Adds to Risk Prediction of Incident Coronary Events by C-Reactive Protein in Apparently Healthy Middle-Aged Men From the General Population: Results From the 14-Year Follow-Up of a Large Cohort From Southern Germany Circulation, October 5, 2004; 110(14): 1903 - 1908. [Abstract] [Full Text] [PDF]
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R. J. Glynn, N. R. Cook, P. Libby, J. T. Willerson, E. Braunwald, J. M. Foody, A. M. Gotto, N. Wenger, P. M. Ridker, W. Koenig, et al. C-Reactive Protein and Coronary Heart Disease N. Engl. J. Med., July 15, 2004; 351(3): 295 - 298. [Full Text] [PDF]
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P. M Ridker, N. J. Brown, D. E. Vaughan, D. G. Harrison, and J. L. Mehta Established and Emerging Plasma Biomarkers in the Prediction of First Atherothrombotic Events Circulation, June 29, 2004; 109(25_suppl_1): IV-6 - IV-19. [Full Text] [PDF]
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P. M Ridker, P. W.F. Wilson, and S. M. Grundy Should C-Reactive Protein Be Added to Metabolic Syndrome and to Assessment of Global Cardiovascular Risk? Circulation, June 15, 2004; 109(23): 2818 - 2825. [Abstract] [Full Text] [PDF]
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R. SoRelle Cardiovascular News Circulation, February 24, 2004; 109 (7): e9012 - e9012. [Full Text]
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