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Cardiovascular events with increased lipoprotein-associated phospholipase A(2) and low high-density lipoprotein-cholesterol: the Veterans Affairs HDL Intervention Trial.
Arterioscler Thromb Vasc Biol. 2008 Jun; 28(6):1172-8.AT

Abstract

OBJECTIVE

Lipoprotein-associated phospholipase A(2) (Lp-PLA(2)), a proinflammatory enzyme that predominantly circulates with low-density lipoprotein (LDL), has been shown in general populations to predict cardiovascular (CV) events. We sought to determine whether increased Lp-PLA(2) would also predict CV events in the absence of high LDL-cholesterol (LDL-C), in a population with low high-density lipoprotein-cholesterol (HDL-C).

METHODS AND RESULTS

Plasma Lp-PLA(2) activity was measured at baseline and after 6 months on-trial in 1451 men with low HDL-C (mean, 32 mg/dL) and low LDL-C (mean 110 mg/dL), randomized to either placebo or gemfibrozil therapy in the Veterans Affairs HDL Intervention Trial (VA-HIT). Over a quartile range of increasing Lp-PLA(2) there was a significant increase in LDL-C and decrease in HDL-C (P < 0.0001), and an increased percentage of myocardial infarction (MI), stroke, or CHD death (P=0.03 for trend). In Cox models, adjusted for major CV risk factors, a 1-SD increase in Lp-PLA(2) was associated with a significant increase in CV events (hazard ratio [HR] 1.17 95% CI 1.04 to 1.32). Although gemfibrozil reduced Lp-PLA(2) only modestly (6.6%), at higher levels of Lp-PLA(2) gemfibrozil produced a significant reduction in CV events.

CONCLUSIONS

In VA-HIT, a population with low HDL-C and LDL-C, high Lp-PLA(2) independently predicted CV events that were reduced by gemfibrozil.

Authors+Show Affiliations

Framingham Heart Study, 73 Mt Wayte Avenue, Framingham, MA 01702, USA. sjrobins@bu.eduNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

18356553

Citation

Robins, Sander J., et al. "Cardiovascular Events With Increased Lipoprotein-associated Phospholipase A(2) and Low High-density Lipoprotein-cholesterol: the Veterans Affairs HDL Intervention Trial." Arteriosclerosis, Thrombosis, and Vascular Biology, vol. 28, no. 6, 2008, pp. 1172-8.
Robins SJ, Collins D, Nelson JJ, et al. Cardiovascular events with increased lipoprotein-associated phospholipase A(2) and low high-density lipoprotein-cholesterol: the Veterans Affairs HDL Intervention Trial. Arterioscler Thromb Vasc Biol. 2008;28(6):1172-8.
Robins, S. J., Collins, D., Nelson, J. J., Bloomfield, H. E., & Asztalos, B. F. (2008). Cardiovascular events with increased lipoprotein-associated phospholipase A(2) and low high-density lipoprotein-cholesterol: the Veterans Affairs HDL Intervention Trial. Arteriosclerosis, Thrombosis, and Vascular Biology, 28(6), 1172-8. https://doi.org/10.1161/ATVBAHA.107.160739
Robins SJ, et al. Cardiovascular Events With Increased Lipoprotein-associated Phospholipase A(2) and Low High-density Lipoprotein-cholesterol: the Veterans Affairs HDL Intervention Trial. Arterioscler Thromb Vasc Biol. 2008;28(6):1172-8. PubMed PMID: 18356553.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Cardiovascular events with increased lipoprotein-associated phospholipase A(2) and low high-density lipoprotein-cholesterol: the Veterans Affairs HDL Intervention Trial. AU - Robins,Sander J, AU - Collins,Dorothea, AU - Nelson,Jeanenne J, AU - Bloomfield,Hanna E, AU - Asztalos,Bela F, Y1 - 2008/03/20/ PY - 2008/3/22/pubmed PY - 2008/6/11/medline PY - 2008/3/22/entrez SP - 1172 EP - 8 JF - Arteriosclerosis, thrombosis, and vascular biology JO - Arterioscler. Thromb. Vasc. Biol. VL - 28 IS - 6 N2 - OBJECTIVE: Lipoprotein-associated phospholipase A(2) (Lp-PLA(2)), a proinflammatory enzyme that predominantly circulates with low-density lipoprotein (LDL), has been shown in general populations to predict cardiovascular (CV) events. We sought to determine whether increased Lp-PLA(2) would also predict CV events in the absence of high LDL-cholesterol (LDL-C), in a population with low high-density lipoprotein-cholesterol (HDL-C). METHODS AND RESULTS: Plasma Lp-PLA(2) activity was measured at baseline and after 6 months on-trial in 1451 men with low HDL-C (mean, 32 mg/dL) and low LDL-C (mean 110 mg/dL), randomized to either placebo or gemfibrozil therapy in the Veterans Affairs HDL Intervention Trial (VA-HIT). Over a quartile range of increasing Lp-PLA(2) there was a significant increase in LDL-C and decrease in HDL-C (P < 0.0001), and an increased percentage of myocardial infarction (MI), stroke, or CHD death (P=0.03 for trend). In Cox models, adjusted for major CV risk factors, a 1-SD increase in Lp-PLA(2) was associated with a significant increase in CV events (hazard ratio [HR] 1.17 95% CI 1.04 to 1.32). Although gemfibrozil reduced Lp-PLA(2) only modestly (6.6%), at higher levels of Lp-PLA(2) gemfibrozil produced a significant reduction in CV events. CONCLUSIONS: In VA-HIT, a population with low HDL-C and LDL-C, high Lp-PLA(2) independently predicted CV events that were reduced by gemfibrozil. SN - 1524-4636 UR - https://www.unboundmedicine.com/medline/citation/18356553/Cardiovascular_events_with_increased_lipoprotein_associated_phospholipase_A_2__and_low_high_density_lipoprotein_cholesterol:_the_Veterans_Affairs_HDL_Intervention_Trial_ L2 - http://www.ahajournals.org/doi/full/10.1161/ATVBAHA.107.160739?url_ver=Z39.88-2003&amp;rfr_id=ori:rid:crossref.org&amp;rfr_dat=cr_pub=pubmed DB - PRIME DP - Unbound Medicine ER -