Highlights
- •Adventitial Vp and Ktrans were closely associated with plaque Vp and Ktrans.
- •Rosuvastatin reduced both adventitial and plaque Vp significantly at 3 months.
- •Ktrans showed nonstatistically significant decrease during therapy.
Background
Statin therapy can improve plaque stability. However, the time course of effects of
statin on adventitial angiogenesis and plaque neovascularization has not been studied.
Objective
The objective of the study was to investigate whether statin therapy reduces plaque
neovascularization, associated with adventitial angiogenesis, over 24 months as assessed
by using carotid dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI).
Methods
Forty-three lipid treatment–naïve subjects with asymptomatic carotid atherosclerosis
received rosuvastatin (5–20 mg/d) to lower low-density lipoprotein cholesterol to
<80 mg/dL for 24 months. Carotid DCE-MRI was performed at baseline, 3, 12 and 24 months.
Vascularity (Vp = fractional plasma volume) and vascular permeability (Ktrans = transfer constant) derived from kinetic modeling of DCE-MRI were measured in both
adventitia and plaque.
Results
Adventitia Vp and adventitia Ktrans were significantly correlated with plaque Vp and plaque Ktrans at baseline. Rosuvastatin significantly reduced both adventitial and plaque Vp significantly at 3 months from 0.121 ± 0.064 to 0.085 ± 0.049 (P = .008) and from 0.096 ± 0.052 to 0.067 ± 0.043 (P = .013). Adventitial and plaque Vp continued to decrease by 43% and 34% at 12 months and by 49% and 45% at 24 months.
However, the continued reductions from 3 to 12 months and from 12 to 24 months were
not statistically significant. Adventitial and plaque Ktrans showed similar trends, but nonstatistically significant decreases during the 24 months
of treatment.
Conclusions
Rosuvastatin therapy rapidly and significantly decreased adventitial and plaque neovascularization
at 3 months followed by continued, but nonstatistically significant, decreases at
12 and 24 months.
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 Journal of Clinical LipidologyAlready a print subscriber? Claim online access
Already an online subscriber? Sign in
Register: Create an account
Institutional Access: Sign in to ScienceDirect
References
- Role of lipids and intraplaque hypoxia in the formation of neovascularization in atherosclerosis.Ann Med. 2017; 49: 661-677
- Neovascularization of the atherosclerotic plaque: interplay between atherosclerotic lesion, adventitia-derived microvessels and perivascular fat.Curr Opin Lipidol. 2015; 26: 405-411
- Plaque neovascularization is increased in ruptured atherosclerotic lesions of human aorta: implications for plaque vulnerability.Circulation. 2004; 110: 2032-2038
- Carotid plaque instability and ischemic symptoms are linked to immaturity of microvessels within plaques.J Vasc Surg. 2007; 45: 155-159
- Neovascularization of coronary tunica intima (DIT) is the cause of coronary atherosclerosis. Lipoproteins invade coronary intima via neovascularization from adventitial vasa vasorum, but not from the arterial lumen: a hypothesis.Theor Biol Med Model. 2012; 9: 11
- The Interplay of Lipids, Lipoproteins, and Immunity in Atherosclerosis.Curr Atheroscler Rep. 2018; 20: 12
- Leukocyte behavior in atherosclerosis, myocardial infarction, and heart failure.Science. 2013; 339: 161-166
- A change in inflammatory footprint precedes plaque instability: a systematic evaluation of cellular aspects of the adaptive immune response in human atherosclerosis.J Am Heart Assoc. 2015; 4: e001403
- Immaturity of microvessels in haemorrhagic plaques is associated with proteolytic degradation of angiogenic factors.Cardiovasc Res. 2010; 85: 184-193
- Sustained acceleration in carotid atherosclerotic plaque progression with intraplaque hemorrhage: a long-term time course study.JACC Cardiovasc Imaging. 2012; 5: 798-804
- MR imaging-detected carotid plaque hemorrhage is stable for 2 years and a marker for stenosis progression.AJNR Am J Neuroradiol. 2015; 36: 1171-1175
- Predictors of surface disruption with MR imaging in asymptomatic carotid artery stenosis.AJNR Am J Neuroradiol. 2010; 31: 487-493
- Plaque hemorrhage is a marker of thromboembolic activity in patients with symptomatic carotid disease.Radiology. 2011; 258: 538-545
- Intraplaque hemorrhage and the plaque surface in carotid atherosclerosis: the plaque at risk study (PARISK).AJNR Am J Neuroradiol. 2015; 36: 2127-2133
- Carotid atherosclerotic plaque characteristics on magnetic resonance imaging relate with history of stroke and coronary heart disease.Stroke. 2016; 47: 1542-1547
- Moderate carotid artery stenosis: MR imaging-depicted intraplaque hemorrhage predicts risk of cerebrovascular ischemic events in asymptomatic men.Radiology. 2009; 252: 502-508
- Meta-analysis and systematic review of the predictive value of carotid plaque hemorrhage on cerebrovascular events by magnetic resonance imaging.J Am Coll Cardiol. 2013; 62: 1081-1091
- Carotid plaque MRI and stroke risk: a systematic review and meta-analysis.Stroke. 2013; 44: 3071-3077
- Composition of carotid atherosclerotic plaque is associated with cardiovascular outcome: a prognostic study.Circulation. 2010; 121: 1941-1950
- Quantitative magnetic resonance imaging analysis of neovasculature volume in carotid atherosclerotic plaque.Circulation. 2003; 107: 851-856
- Inflammation in carotid atherosclerotic plaque: a dynamic contrast-enhanced MR imaging study.Radiology. 2006; 241: 459-468
- Vasa vasorum and plaque progression, and responses to atorvastatin in a rabbit model of atherosclerosis: contrast-enhanced ultrasound imaging and intravascular ultrasound study.Heart. 2013; 99: 48-54
- Pravastatin has cholesterol-lowering independent effects on the artery wall of atherosclerotic monkeys.J Am Coll Cardiol. 1998; 31: 684-691
- Simvastatin preserves the structure of coronary adventitial vasa vasorum in experimental hypercholesterolemia independent of lipid lowering.Circulation. 2002; 105: 415-418
- Carotid artery atherosclerosis: effect of intensive lipid therapy on the vasa vasorum--evaluation by using dynamic contrast-enhanced MR imaging.Radiology. 2011; 260: 224-231
- Longer duration of statin therapy is associated with decreased carotid plaque vascularity bymagnetic resonance imaging.Atherosclerosis. 2016; 245: 74-81
- Contrast-enhanced ultrasound imaging of carotid plaque neovascularization is useful for identifying high-risk patients with coronary artery disease.Circ J. 2013; 77: 1499-1507
- Early decrease in carotid plaque lipid content as assessed by magnetic resonance imaging during treatment of rosuvastatin.BMC Cardiovasc Disord. 2014; 14: 83
- MR imaging of adventitial vasa vasorum in carotid atherosclerosis.Magn Reson Med. 2008; 59: 507-514
- Scan-rescan reproducibility of quantitative assessment of inflammatory carotid atherosclerotic plaque using dynamic contrast-enhanced 3T CMR in a multi-center study.J Cardiovasc Magn Reson. 2014; 16: 51
- Thin-walled microvessels in human coronary atherosclerotic plaques show incomplete endothelial junctions relevance of compromised structural integrity for intraplaque microvascular leakage.J Am Coll Cardiol. 2009; 53: 1517-1527
- Erythrocytes enhance lymphocyte rolling and arrest in vivo.Microvasc Res. 2000; 59: 316-322
- Vascular cell adhesion molecule-1 is expressed in human coronary atherosclerotic plaques. Implications for the mode of progression of advanced coronary atherosclerosis.J Clin Invest. 1993; 92: 945-951
- Adventitial perfusion and intraplaque hemorrhage: a dynamic contrast-enhanced MRI study in the carotid artery.Stroke. 2013; 44: 1031-1036
- Vasa vasorum enhancement on computerized tomographic angiography correlates with symptomatic patients with 50% to 70% carotid artery stenosis.Stroke. 2013; 44: 3344-3349
- Intraplaque neovascularization and hemorrhage: markers for cardiovascular risk stratification and therapeutic monitoring.J Cardiovasc Med (Hagerstown). 2012; 13: 635-639
- CD163+ macrophages promote angiogenesis and vascular permeability accompanied by inflammation in atherosclerosis.J Clin Invest. 2018; 128: 1106-1124
Article info
Publication history
Published online: August 03, 2019
Accepted:
July 30,
2019
Received:
January 5,
2019
Identification
Copyright
© 2019 Published by Elsevier Inc. on behalf of National Lipid Association.
