Highlights
- •This study evaluated the role of oxidized HDL in the development of coronary artery calcification.
- •The decrease in oxidized HDL after statin treatment was associated with attenuation of CAC progression.
- •The findings in this study indicate that oxidized HDL may serve as a target for preventing atherosclerosis.
Abstract
Background and aims
Oxidized high-density lipoprotein (oxHDL) is characterized by reduced anti-inflammatory
properties compared with HDL. However, the role of oxHDL in the pathogenesis of coronary
artery calcification (CAC), a marker of subclinical atherosclerosis, remains unclear.
We prospectively investigated the association between the change in oxHDL and progression
of CAC in a substudy of a multicenter study.
Methods
In the principal study, patients with a CAC score of 1–999 were treated with pitavastatin
with/without eicosapentaenoic acid. Measurement of CAC with multidetector-row computed
tomography and a blood test were performed at baseline and at the 1-year follow-up.
In the principal study, the increase in CAC did not differ among treatment groups.
In this substudy, patients were divided into two groups: CAC progression (change in
Agatston score of >0) and no CAC progression.
Results
In total, 140 patients were analyzed. The oxHDL level significantly decreased from
167 (132–246) at baseline to 122 (103–149) after treatment (median [25th–75th percentile], U/ml) (p < 0.001). The annual change in CAC was significantly positively associated with changes
in oxHDL (r = 0.17, p = 0.04), triglycerides (r = 0.17, p = 0.04), and high-sensitivity C-reactive protein (r = 0.22, p = 0.01) but was not associated with changes in low-density lipoprotein cholesterol or
HDL-cholesterol. Multiple logistic analysis demonstrated that the decrease in oxHDL
per 10 U/ml was independently associated with CAC progression (odds ratio, 0.95; 95%
confidence interval, 0.90–0.99; p = 0.04).
Conclusions
The decrease in oxHDL is associated with the attenuation of CAC progression, suggesting
that oxHDL is a potential target for atherosclerosis prevention.
Graphical abstract
Graphical Abstract
Keywords
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References
- Coronary artery calcification.Glob Heart. 2016; 11: 287-293
- Coronary artery calcium score combined with Framingham score for risk prediction in asymptomatic individuals.J. Am. Med. Assoc. 2004; 291: 210-215
- Progression of CAC score and risk of incident CVD.JACC. Cardiovascular imaging. 2016; 9: 1420-1429
- Effect of intensive and standard pitavastatin treatment with or without eicosapentaenoic acid on progression of coronary artery calcification over 12 Months- prospective multicenter study.Circ. J. : OffC.J. Jpn.Circ. Soc. 2018; 82: 532-540
- ACC/AHA guideline on the treatment of blood cholesterol to reduce atherosclerotic cardiovascular risk in adults.J. Am. Coll. Cardiol. 2013; 2014: 2889-2934
- Niacin in patients with low HDL cholesterol levels receiving intensive statin therapy.N. Engl. J. Med. 2011; 365: 2255-2267
- Effects of dalcetrapib in patients with a recent acute coronary syndrome.N. Engl. J. Med. 2012; 367: 2089-2099
- Effects of torcetrapib in patients at high risk for coronary events.N. Engl. J. Med. 2007; 357: 2109-2122
- HDL and cardiovascular disease: atherogenic and atheroprotective mechanisms.Nat. Rev. Cardiol. 2011; 8: 222-232
- Cholesterol efflux capacity, high-density lipoprotein function, and atherosclerosis.N. Engl. J. Med. 2011; 364: 127-135
- HDL cholesterol efflux capacity and incident cardiovascular events.N. Engl. J. Med. 2014; 371: 2383-2393
- Establishment and evaluation of 2 monoclonal antibodies against oxidized apolipoprotein A-I (apoA-I) and its application to determine blood oxidized apoA-I levels.Clin. Chim. Acta. 2007; 378: 105-111
- Oxidized high-density lipoprotein is associated with protein-energy wasting in maintenance hemodialysis patients.Clin. J. Am. Soc. Nephrol. 2010; 5: 1021-1028
- Oxidized high-density lipoprotein as a risk factor for cardiovascular events in prevalent hemodialysis patients.Atherosclerosis. 2012; 220: 493-501
- Quantification of coronary artery calcium using ultrafast computed tomography.J. Am. Coll. Cardiol. 1990; 15: 827-832
- Serum paraoxonase-1 activity in Helicobacter pylori infected subjects.Atherosclerosis. 2008; 196: 270-274
- Progression of coronary artery calcium predicts all-cause mortality.JACC Cardiovasc Imaging. 2010; 3: 1229-1236
- Progression of coronary artery calcium and occurrence of myocardial infarction in patients with and without diabetes mellitus.Hypertension. 2005; 46: 238-243
- Plaque progression assessed by a novel semi-automated quantitative plaque software on coronary computed tomography angiography between diabetes and non-diabetes patients: a propensity-score matching study.Atherosclerosis. 2016; 255: 73-79
- Paraoxonase, a cardioprotective enzyme: continuing issues.Curr. Opin. Lipidol. 2004; 15: 261-267
- Four paraoxonase gene polymorphisms in 11212 cases of coronary heart disease and 12786 controls: meta-analysis of 43 studies.Lancet. 2004; 363: 689-695
- Paraoxonase-1 and oxidized lipoprotein lipids. The Cardiovascular Risk in Young Finns study.Atherosclerosis. 2015; 241: 502-506
- Purified human paraoxonase-1 interacts with plasma membrane lipid rafts and mediates cholesterol efflux from macrophages.Free Radic. Biol. Med. 2012; 52: 1372-1381
- Oxidized lipoprotein lipids and atherosclerosis.Free Radic. Res. 2017; 51: 439-447
- HDL3-mediated inhibition of thrombin-induced platelet aggregation and fibrinogen binding occurs via decreased production of phosphoinositide-derived second messengers 1,2-diacylglycerol and inositol 1,4,5-tris-phosphate.Arterioscler. Thromb. Vasc. Biol. 1998; 18: 861-869
- High density lipoprotein prevents oxidized low density lipoprotein-induced inhibition of endothelial nitric-oxide synthase localization and activation in caveolae.J. Biol. Chem. 2000; 275: 11278-11283
- The role of oxidized HDL in monocyte/macrophage functions in the pathogenesis of atherosclerosis in Rhesus monkeys.Scand. J. Clin. Lab. Invest. 1999; 59: 215-225
- Differential effects of atorvastatin and pitavastatin on inflammation, insulin resistance, and the carotid intima-media thickness in patients with dyslipidemia.J. Atherosclerosis Thromb. 2015; 22: 1158-1171
- Effect of switch to the highest dose of rosuvastatin versus add-on-statin fenofibrate versus add-on-statin nicotinic acid/laropiprant on oxidative stress markers in patients with mixed dyslipidemia.Cardiovasc Ther. 2014; 32: 139-146
- Add-on therapy of EPA reduces oxidative stress and inhibits the progression of aortic stiffness in patients with coronary artery disease and statin therapy: a randomized controlled study.J. Atherosclerosis Thromb. 2011; 18: 857-866
Article info
Publication history
Published online: January 31, 2019
Accepted:
January 22,
2019
Received in revised form:
January 15,
2019
Received:
July 19,
2018
Identification
Copyright
© 2019 Elsevier B.V. All rights reserved.
