Circulating Levels of Secretory- and Lipoprotein-Associated Phospholipase A2 Activities: Relation to Atherosclerotic Plaques and Future All-Cause Mortality

Study Questions:

Are circulating levels of secretory (s)- and lipoprotein-associated (Lp)-PLA2 activity associated with vascular disease?

Methods:

The relationship between circulating levels of PLA2 activity and vascular endpoints was determined in 1,016 subjects, age 70 years, during 7-year follow-up. Carotid artery plaques were measured by ultrasound (n = 954), and arterial stenosis by whole-body magnetic resonance angiography (WBMRA) (n = 302). Another sample of 1,029 post-ST-segment elevation myocardial infarction (STEMI) patients was followed for clinical events for 1 year.

Results:

sPLA2 [odds ratio 1.23 for 1 standard deviation (SD) increase, p = 0.007], but not Lp-PLA2 (p = 0.26), activity was related to carotid atherosclerosis and to the amount of stenosis by WBMRA (p = 0.006) following adjustment for multiple risk factors. sPLA2 [hazard ratio (HR) 1.45 for 1 SD increase, p = 0.001], but not Lp-PLA2 (HR, 0.95; p = 0.55), activity was a significant risk factor for all-cause mortality during 7.0 years follow-up after adjustment for other risk factors. In a sample of 1,029 post-MI patients, sPLA2 (adjusted HR 1.32 for 1 unit increase, p = 0.036), but not Lp-PLA2 (HR, 1.03; p = 0.90), activity predicted death or recurrent MI during 1-year follow-up.

Conclusions:

The authors concluded that sPLA2 activity was related to atherosclerosis and predicted all-cause mortality in a sample of elderly subjects, as well as death or MI in post-MI patients.

Perspective:

Phospholipases are involved in the modification of lipoproteins, possibly rendering them more atherogenic. Secretory and lipoprotein-associated forms of phospholipases have both been implicated in atherosclerosis, although sPLA2 may be particularly atherogenic through its actions on low-density lipoprotein. This study extends previous studies by demonstrating that activity levels of sPLA2 are most strongly associated with vascular disease-related endpoints. Although this does not prove causality, clinical trials with PLA2 inhibitors are underway.

Clinical Topics: Dyslipidemia, Vascular Medicine, Lipid Metabolism

Keywords: Myocardial Infarction, Phospholipases, Atherosclerosis, Plaque, Atherosclerotic, Vascular Diseases, Transcription Factors, Carotid Artery Diseases, Psychomotor Performance, Lipoproteins, LDL, Biological Markers, Troponin I, Cardiology, Cardiovascular Diseases, Carotid Stenosis, 1-Alkyl-2-acetylglycerophosphocholine Esterase


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