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Usefulness of Lipoprotein-Associated Phospholipase A2 Activity and C-Reactive Protein in Identifying High-Risk Smokers for Atherosclerotic Cardiovascular Disease (from the Atherosclerosis Risk in Communities Study).

ABSTRACT: Despite the causal role of cigarette smoking in atherosclerotic cardiovascular disease (ASCVD), the underlying mechanisms are not fully understood. We evaluated the joint relation between smoking and inflammatory markers with ASCVD risk. We tested cross-sectional associations of self-reported smoking status (never, former, current) and intensity (packs/day) with lipoprotein-associated phospholipase A2 (Lp-PLA2) activity and high-sensitivity C-reactive protein (hsCRP) in 10,506 Atherosclerosis Risk in Communities participants at Visit 4 (1996 to 1998). Using Cox hazard models adjusted for demographic and traditional ASCVD risk factors, we examined the associations of smoking status and intensity with incident adjudicated ASCVD events (n?=?1,745 cases) over an average of 17 years, stratified by Lp-PLA2 and hsCRP categories. Greater packs/day smoked was linearly associated with higher levels of both Lp-PLA2 and hsCRP among current smokers. Compared with never smokers, the hazard ratio for incident ASCVD in current smokers was 2.04 (95% CI 1.76 to 2.35). Among current smokers, the risk for ASCVD per 1 pack/day greater was 1.39 (1.10 to 1.76). Both Lp-PLA2 activity ?253?nmol/min/ml and hsCRP >3?mg/L identified current smokers at the highest risk for incident ASCVD, with similar hazard ratios. hsCRP risk-stratified current smokers better based on intensity. Among current smokers, hsCRP improved ASCVD prediction beyond traditional risk factors better than Lp-PLA2 (C-statistic 0.675 for hsCRP vs 0.668 for Lp-PLA2, p?=?0.001). In this large cohort with long follow-up, we found a dose-response relation between smoking intensity with Lp-PLA2 activity, hsCRP, and ASCVD events. Although both Lp-PLA2 activity and hsCRP categories identified high risk among current smokers, hsCRP may better stratify risk of future ASCVD.

SUBMITTER: Tibuakuu M

PROVIDER: S-EPMC5927844 | biostudies-literature | 2018 May

REPOSITORIES: biostudies-literature

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Publications

Usefulness of Lipoprotein-Associated Phospholipase A2 Activity and C-Reactive Protein in Identifying High-Risk Smokers for Atherosclerotic Cardiovascular Disease (from the Atherosclerosis Risk in Communities Study).

Tibuakuu Martin M Kianoush Sina S DeFilippis Andrew P AP McEvoy John W JW Zhao Di D Guallar Eliseo E Ballantyne Christie M CM Hoogeveen Ron C RC Blaha Michael J MJ Michos Erin D ED

The American journal of cardiology 20180206 9

Despite the causal role of cigarette smoking in atherosclerotic cardiovascular disease (ASCVD), the underlying mechanisms are not fully understood. We evaluated the joint relation between smoking and inflammatory markers with ASCVD risk. We tested cross-sectional associations of self-reported smoking status (never, former, current) and intensity (packs/day) with lipoprotein-associated phospholipase A2 (Lp-PLA2) activity and high-sensitivity C-reactive protein (hsCRP) in 10, ...[more]

PMID: 29525060

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Project description:Lipoprotein-associated phospholipase A(2) (Lp-PLA(2)), also known as platelet-activating factor acetylhydrolase (PAF-AH), is a unique member of the phospholipase A(2) superfamily. This enzyme is characterized by its ability to specifically hydrolyze PAF as well as glycerophospholipids containing short, truncated, and/or oxidized fatty acyl groups at the sn-2 position of the glycerol backbone. In humans, Lp-PLA(2) circulates in active form as a complex with low- and high-density lipoproteins. Clinical studies have reported that plasma Lp-PLA(2) activity and mass are strongly associated with atherogenic lipids and vascular risk. These observations led to the hypothesis that Lp-PLA(2) activity and/or mass levels could be used as biomarkers of cardiovascular disease and that inhibition of the activity could offer an attractive therapeutic strategy. Darapladib, a compound that inhibits Lp-PLA(2) activity, is anti-atherogenic in mice and other animals, and it decreases atherosclerotic plaque expansion in humans. However, disagreement continues to exist regarding the validity of Lp-PLA(2) as an independent marker of atherosclerosis and a scientifically justified target for intervention. Circulating Lp-PLA(2) mass and activity are associated with vascular risk, but the strength of the association is reduced after adjustment for basal concentrations of the lipoprotein carriers with which the enzyme associates. Genetic studies in humans harboring an inactivating mutation at this locus indicate that loss of Lp-PLA(2) function is a risk factor for inflammatory and vascular conditions in Japanese cohorts. Consistently, overexpression of Lp-PLA(2) has anti-inflammatory and anti-atherogenic properties in animal models. This thematic review critically discusses results from laboratory and animal studies, analyzes genetic evidence, reviews clinical work demonstrating associations between Lp-PLA(2) and vascular disease, and summarizes results from animal and human clinical trials in which administration of darapladib was tested as a strategy for the management of atherosclerosis.

Dataset Information

Usefulness of Lipoprotein-Associated Phospholipase A2 Activity and C-Reactive Protein in Identifying High-Risk Smokers for Atherosclerotic Cardiovascular Disease (from the Atherosclerosis Risk in Communities Study).

Publications

Usefulness of Lipoprotein-Associated Phospholipase A<sub>2</sub> Activity and C-Reactive Protein in Identifying High-Risk Smokers for Atherosclerotic Cardiovascular Disease (from the Atherosclerosis Risk in Communities Study).

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