Relationship of Oxidized Phospholipids and Biomarkers of Oxidized Low-Density Lipoprotein With Cardiovascular Risk Factors, Inflammatory Biomarkers, and Effect of Statin Therapy in Patients With Acute Coronary Syndromes

Fraley, Alexander E.; Schwartz, Gregory G.; Olsson, Anders; Kinlay, Scott; Szarek, Michael; Rifai, Nader; Libby, Peter; Ganz, Patricia A.; Witztum, Joseph L.; Tsimikas, Sotirios

doi:10.1016/j.jacc.2009.02.041

Cited by 100 publications

(53 citation statements)

References 48 publications

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“…Although it is not possible to ascribe a causal association in this relationship, one may speculate that patients with high baseline IgM, perhaps mediated through genetic or other factors, may be protected through undefi ned mechanisms from developing modifi able cardiovascular risk factors. This is consistent with prior data showing that IgM AA are higher in patients considered at lower cardiovascular risk, such as women, nonsmokers, and younger subjects, and are decreased in men, elderly subjects, diabetics, and patients with elevated LDL-C ( 8,34,36,37 ). Alternatively, it is also possible that some patients consume such preformed antibodies as atherosclerosis develops, which are ultimately cleared leading to lower plasma levels.…”

Section: Discussionsupporting

confidence: 91%

Relationship of IgG and IgM autoantibodies and immune complexes to oxidized LDL with markers of oxidation and inflammation and cardiovascular events: results from the EPIC-Norfolk Study

Ravandi

Boekholdt

Mallat

et al. 2011

Journal of Lipid Research

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118

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Section: Discussionsupporting

confidence: 91%

Relationship of IgG and IgM autoantibodies and immune complexes to oxidized LDL with markers of oxidation and inflammation and cardiovascular events: results from the EPIC-Norfolk Study

Ravandi

Boekholdt

Mallat

et al. 2011

Journal of Lipid Research

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118

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“…An inverse association was also noted with Lp(a) and triglycerides, which has been noted previously. 25 Finally, although the prevalence of diabetes mellitus was not known in this study, there was a clear linear trend of increasing hemoglobin A1c with Lp(a), but no clear association with fasting glucose or insulin. These data tend to go against the several studies showing a higher rate of incident diabetes mellitus with very low Lp(a) (1-4 mg/dL), but the data likely reflect the reality of the complexities of studying patients who are potentially on treatment versus the community cohorts.…”

Section: Downloaded Fromcontrasting

confidence: 55%

Prevalence of Elevated Lp(a) Mass Levels and Patient Thresholds in 532 359 Patients in the United States

Varvel

McConnell

Tsimikas

2016

ATVB

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157

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Objective-Elevated lipoprotein(a) [Lp(a)] is a causal, independent risk factor for cardiovascular disease and aortic stenosis.We aimed to define the prevalence and patient thresholds of elevated Lp(a) levels in the United States. Approach and Results-We analyzed Lp(a) levels in 532 359 subjects from 2 data sets: (1) in 531 144 subjects from a referral laboratory and (2) in 915 patients from a tertiary referral center. Lp(a) mass levels were measured by immunoturbidometric assays in both centers and expressed as mg/dL. At the referral laboratory, the median age (interquartile range) of the subjects was 57.0 (46-67) years, and 51.9% were female. Lp(a) levels were skewed rightward as expected. The mean±SD levels were 34.0±40.0 mg/dL, and median (interquartile range) levels were 17 (7-47) mg/dL, with range 0 to 907 mg/dL. Lp(a) levels at 75%, 80%, 90%, 95%, 99%, and 99.9% percentiles were >47, >60, >90, >116, >180, and >245 mg/dL, respectively. At the referral laboratory, Lp(a) levels >30 and >50 mg/dL were present in 35.0% and 24.0% of subjects, respectively, and at the tertiary referral center, 39.5% and 29.2%, respectively. Females had higher mean (SD) (37. Results Data From the Referral LaboratoryRelationship of Lp(a) to Lipid, Lipoprotein, and High Sensitivity C-Reactive Protein Levels Over the 5-year period, a total of 531 144 Lp(a) measurements, with accompanying information on lipid parameters and high sensitivity C-reactive protein (hsCRP), from individual patients in the referral laboratory were available. The median age of all the subjects was 57.0 (46-67), 51.9% were female, and the mean body mass index was 29.7±6.7. Tables 1 and 2 display the relationship of Lp(a) mass, in quintiles and as Lp(a) <30 mg/dL versus >30 mg/dL and <50 mg/dL versus >50 mg/dL, to mean levels of LDL cholesterol (LDL-C), estimated LDL-C corrected for Lp(a) cholesterol, total cholesterol, high-density lipoprotein cholesterol, triglycerides, apoB-100, and non-high-density lipoprotein cholesterol. The mean±SD Lp(a) levels were 34.0±40.0 mg/dL and median (interquartile range) levels were 17 (7-47) mg/dL, with range 0 to 907 mg/ dL. Lp(a) levels at 75%, 80%, 90%, 95%, 99%, and 99.9% percentiles were >47, >60, >90, >116, >180, and >245 mg/dL, respectively. Females had higher mean (SD) (37. Lp(a) levels >30 and >50 mg/dL were present in 35.0% and 24.0% of subjects, respectively. Evaluating Lp(a) in quintiles, LDL-C linearly increased from 99.1 to 108.6 mg/dL. In contrast, removing the Lp(a) cholesterol component of Lp(a) showed that the corrected LDL-C was actually decreasing from 98.1 to 78.5 mg/dL with increasing Lp(a) mass. Total cholesterol, high-density lipoprotein cholesterol, apoAI, and non-high-density lipoprotein cholesterol were all increasing with increasing Lp(a), but triglycerides decreased across quintiles. hsCRP was also increasing linearly with Lp(a) quintiles or Lp(a) cutoffs of >30 and >50 mg/dL (Tables 1 and 2). Frequency Distribution of Lp(a), LDL-C, and ApoBAs expected, Lp(a) mass levels were skewed rightward (...

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“…Although the mechanistic underpinnings of these changes cannot be determined from these studies, in composite they suggest that increases in plasma OxPL/apoB in response to therapeutic measures, perhaps including diet, may refl ect a benefi cial response within the artery wall leading to reduced OxPL content. In support of improved vascular health, a recent analysis from the MIRACL trial showed that individuals with the largest increases in OxPL/apoB were those who were felt to benefi t the most from statins, such as younger patients with fewest risk factors ( 44 ). Clinical studies are underway to evaluate whether increases in OxPL/apoB in response to statins predict improved clinical outcomes.…”

Section: Downloaded Frommentioning

confidence: 99%

Changes in lipoprotein(a), oxidized phospholipids, and LDL subclasses with a low-fat high-carbohydrate diet

Faghihnia¹,

Tsimikas

Miller

et al. 2010

Journal of Lipid Research

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Relationship of Oxidized Phospholipids and Biomarkers of Oxidized Low-Density Lipoprotein With Cardiovascular Risk Factors, Inflammatory Biomarkers, and Effect of Statin Therapy in Patients With Acute Coronary Syndromes

Cited by 100 publications

References 48 publications

Relationship of IgG and IgM autoantibodies and immune complexes to oxidized LDL with markers of oxidation and inflammation and cardiovascular events: results from the EPIC-Norfolk Study

Relationship of IgG and IgM autoantibodies and immune complexes to oxidized LDL with markers of oxidation and inflammation and cardiovascular events: results from the EPIC-Norfolk Study

Prevalence of Elevated Lp(a) Mass Levels and Patient Thresholds in 532 359 Patients in the United States

Changes in lipoprotein(a), oxidized phospholipids, and LDL subclasses with a low-fat high-carbohydrate diet

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