Highlights
- •It remains unclear whether Lp-PLA2 is related to subclinical atherosclerosis, independently from small LDL particles.
- •A cross-sectional study in a population-based random sample of asymptomatic Japanese men.
- •Japanese have a wider Lp-PLA2 distribution than Western people.
- •Lp-PLA2 activity was associated with carotid IMT and plaque but not with CAC score, independently from small LDL particles.
- •V279F genotype was not associated with subclinical atherosclerosis, although variant type had low Lp-PLA2 activity.
Abstract
Objective
Lipoprotein-associated phospholipase A2 (Lp-PLA2) is an enzyme predominantly bound to low-density lipoprotein (LDL). Lp-PLA2 is recognized as playing a key role in inflammatory processes and the development
of atherosclerosis. This study aimed to investigate whether Lp-PLA2 is related to subclinical atherosclerosis, independently from traditional risk factors,
in a general Japanese population by analyses of both the observational study and Mendelian
randomization using V279F polymorphism.
Methods and results
We cross-sectionally examined community-based sample of 929 Japanese men aged 40–79
years, without statin treatment, who were randomly selected from the resident registration.
Multiple regression analyses of Lp-PLA2 activity and concentration were undertaken separately for men aged 40–49 years and
50–79 years, to clarify interactions of age and Lp-PLA2. Lp-PLA2 activity for men aged 50–79 years was significantly and positively related to intima-media
thickness (IMT) (P = 0.013) and plaque index (P = 0.008) independent of traditional risk factors including small LDL particles, but
not to coronary artery calcification (CAC) score. Associations with Lp-PLA2 concentration were qualitatively similar to those of activity. Corresponding relationships
were not observed in men aged 40–49 years. Mendelian randomization analyses based
on V279F genotype did not show any significant associations with subclinical atherosclerosis,
although the homozygote and heterozygote of V279F showed low Lp-PLA2 activity and concentration.
Conclusions
Lp-PLA2 activity in Japanese men aged 50–79 years was associated significantly and positively
with IMT and plaque in the carotid artery but Mendelian randomization did not support
that Lp-PLA2 is a causative factor for subclinical atherosclerosis.
Keywords
To read this article in full you will need to make a payment
Purchase one-time access:
Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online accessOne-time access price info
- For academic or personal research use, select 'Academic and Personal'
- For corporate R&D use, select 'Corporate R&D Professionals'
Subscribe:
Subscribe to AtherosclerosisAlready a print subscriber? Claim online access
Already an online subscriber? Sign in
Register: Create an account
Institutional Access: Sign in to ScienceDirect
References
- Lp-PLA(2) and risk of atherosclerotic vascular disease.Lancet. 2010; 375: 1498-1500
- Association between lipoprotein-associated phospholipase A2 and cardiovascular disease: a systematic review.Mayo Clin. Proc. 2007; 82: 159-165
- Lipoprotein-associated phospholipase A(2) and atherosclerosis.Curr. Opin. Lipidol. 2009; 20: 415-420
- Correlations between plasma platelet-activating factor acetylhydrolase (PAF-AH) activity and PAF-AH genotype, age, and atherosclerosis in a Japanese population.Atherosclerosis. 2000; 150: 209-216
- The Val279Phe variant of the lipoprotein-associated phospholipase A2 gene is associated with catalytic activities and cardiovascular disease in Korean men.J. Clin. Endocrinol. Metab. 2006; 91: 3521-3527
- Associations of PLA2G7 gene polymorphisms with plasma lipoprotein-associated phospholipase A2 activity and coronary heart disease in a Chinese Han population: the Beijing atherosclerosis study.Hum. Genet. 2009; 125: 11-20
- The Ile198Thr and Ala379Val variants of plasmatic PAF-acetylhydrolase impair catalytical activities and are associated with atopy and asthma.Am. J. Hum. Genet. 2000; 66: 1522-1530
- A mutation in plasma platelet-activating factor acetylhydrolase (Val279-->Phe) is a genetic risk factor for stroke.Stroke. 1997; 28: 2417-2420
- Platelet-activating factor acetylhydrolase deficiency. A missense mutation near the active site of an anti-inflammatory phospholipase.J. Clin. Invest. 1996; 97: 2784-2791
- 'Mendelian randomization': can genetic epidemiology contribute to understanding environmental determinants of disease?.Int. J. Epidemiol. 2003; 32: 1-22
- Lipoprotein-associated phospholipase A(2) and risk of coronary disease, stroke, and mortality: collaborative analysis of 32 prospective studies.Lancet. 2010; 375: 1536-1544
- Lipoprotein particle profiles by nuclear magnetic resonance compared with standard lipids and apolipoproteins in predicting incident cardiovascular disease in women.Circulation. 2009; 119: 931-939
- Small dense low-density lipoprotein-cholesterol concentrations predict risk for coronary heart disease: the Atherosclerosis Risk in Communities (ARIC) study.Arterioscler. Thromb. Vasc. Biol. 2014; 34: 1069-1077
- Carotid intima-media thickness and plaque in apparently healthy Japanese individuals with an estimated 10-year absolute risk of CAD death according to the Japan Atherosclerosis Society (JAS) guidelines 2012: the Shiga Epidemiological Study of Subclinical Atherosclerosis (SESSA).J. Atheroscler. Thromb. 2013; 20: 755-766
- Lipoprotein particle profiles compared with standard lipids in association with coronary artery calcification in the general Japanese population.Atherosclerosis. 2014; 236: 237-243
- High-density lipoprotein particle concentration and subclinical atherosclerosis of the carotid arteries in Japanese men.Atherosclerosis. 2015; 239: 444-450
- Marine-derived n-3 fatty acids and atherosclerosis in Japanese, Japanese-American, and white men: a cross-sectional study.J. Am. Coll. Cardiol. 2008; 52: 417-424
- Less subclinical atherosclerosis in Japanese men in Japan than in White men in the United States in the post-World War II birth cohort.Am. J. Epidemiol. 2007; 165: 617-624
- Measurement variability in duplex scan assessment of carotid atherosclerosis.Stroke. 1992; 23: 215-220
- Carotid atherosclerosis in premenopausal and postmenopausal women and its association with risk factors measured after menopause.Stroke. 1998; 29: 1116-1121
- Cross-sectional comparison of coronary artery calcium scores between Caucasian men in the United States and Japanese men in Japan: the multi-ethnic study of atherosclerosis and the Shiga epidemiological study of subclinical atherosclerosis.Am. J. Epidemiol. 2014; 180: 590-598
- Quantification of coronary artery calcium using ultrafast computed tomography.J. Am. Coll. Cardiol. 1990; 15: 827-832
- Coronary artery calcification by computed tomography in epidemiologic research and cardiovascular disease prevention.J. Epidemiol. 2012; 22: 188-198
- Comparison of coronary artery calcium scores between electron beam computed tomography and 64-multidetector computed tomographic scanner.J. Comput. Assist. Tomogr. 2009; 33: 175-178
- Improvement in Japanese clinical laboratory measurements of total cholesterol and HDL-cholesterol by the US Cholesterol Reference Method Laboratory Network.J. Atheroscler. Thromb. 2003; 10: 145-153
- Measurement issues related to lipoprotein heterogeneity.Am. J. Cardiol. 2002; 90: 22i-29i
- Lipid-related Markers and cardiovascular disease prediction.JAMA. 2012; 307: 2499-2506
- Darapladib for preventing ischemic events in stable coronary heart disease.N. Engl. J. Med. 2014; 370: 1702-1711
- Effect of darapladib on major coronary events after an acute coronary syndrome: the SOLID-TIMI 52 randomized clinical trial.JAMA. 2014; 312: 1006-1015
Article Info
Publication History
Published online: December 22, 2015
Accepted:
December 19,
2015
Received in revised form:
December 7,
2015
Received:
June 11,
2015
Identification
Copyright
© 2015 Elsevier Ireland Ltd. Published by Elsevier Inc. All rights reserved.
