ArticlesEffects of statin therapy on coronary artery plaque volume and high-risk plaque morphology in HIV-infected patients with subclinical atherosclerosis: a randomised, double-blind, placebo-controlled trial
Introduction
Coronary artery disease is a major cause of morbidity and mortality for patients living with long-term HIV infection.1, 2, 3, 4 Epidemiological studies fully adjusting for numerous risk factors and investigating validated cardiovascular events show increased risk in patients with HIV compared with that in those without.5 Efficacious cardiovascular risk reduction interventions for HIV-infected patients are urgently needed.
Several studies have shown increased prevalence of subclinical atherosclerosis, including a predominant increase in non-calcified plaque in HIV-infected patients compared with patients without HIV, controlling for traditional coronary artery disease risk factors.6, 7, 8 Additional studies in HIV-infected patients have shown evidence of arterial inflammation9 and increased vulnerable plaque morphology on coronary CT angiography (CCTA).10 Greater volumes of non-calcified plaque and vulnerable plaque morphology on CCTA are associated with future major adverse cardiac events.11
Inhibitors of 3-hydroxy-3-methylglutaryl coenzyme A reductase (statins) reduce the numbers of cardiac events and mortality in the general population. Imaging trials in patients without HIV have also shown that intensive statin therapy can slow progression of coronary atherosclerosis and even result in disease regression.12, 13, 14 Previous studies of statin therapy in HIV-infected patients have shown improvement in lipid concentrations and reduction in markers of inflammation, as well as improvement in endothelial function, but no studies have prospectively investigated the effects of statins on direct measurements of arterial inflammation and coronary atherosclerosis in this population of patients.15, 16, 17, 18 We did a randomised, double-blind, placebo-controlled trial to investigate the effects of a statin on arterial inflammation and coronary atherosclerosis in HIV-infected people without known cardiovascular disease or raised LDL cholesterol concentrations but with subclinical atherosclerosis and arterial inflammation.
We hypothesised that coronary atherosclerosis would progress at a rapid rate in this population of HIV-infected people, despite normal concentrations of baseline LDL-cholesterol, and that treatment with a statin would reduce arterial inflammation, deter the progression of coronary atherosclerosis, and reduce non-calcified plaque volume and vulnerable plaque morphology, resulting in a decrease in high-risk atherosclerotic lesions.
Section snippets
Study design and participants
This study was a single-site, randomised, double-blind, placebo-controlled clinical trial. Study participants were men and women with HIV disease, no history of cardiovascular disease or cardiac symptoms, and evidence of subclinical coronary atherosclerosis, defined by presence of one or more plaques on CCTA but without clinically significant stenosis, defined as greater than 50% left main stenosis or greater than 70% stenosis in any major vessel. Additionally, participants who showed plaque on
Results
The study ran from Nov 13, 2009, to Jan 13, 2014. We screened 81 HIV-infected patients; screening was sequential such that the presence of plaque was first established by CCTA (figure 1). The study took several years to complete because treatment duration was 1 year and recruitment was at a single site. 40 participants were randomly assigned to receive either atorvastatin (n=19) or placebo (n=21). Age, sex, race and ethnicity, body-mass index, and Framingham 10 year risk estimate were similar
Discussion
In this randomised, double-blind, placebo-controlled study of HIV-infected patients with subclinical atherosclerosis, atorvastatin did not seem to reduce arterial inflammation in the aorta, but treatment deterred overall coronary plaque progression and induced coronary plaque regression in HIV-infected patients, largely through effects on non-calcified plaque volume. Atorvastatin reduced coronary non-calcified plaque volume by 19·4% in 1 year in the patients in our study, compared with an
References (51)
- et al.
Increased prevalence of subclinical coronary atherosclerosis detected by coronary computed tomography angiography in HIV-infected men
AIDS
(2010) - et al.
Prognostic implications of nonobstructive coronary plaques in patients with non-ST-segment elevation myocardial infarction: a multidetector computed tomography study
J Am Coll Cardiol
(2011) - et al.
SCCT guidelines for the interpretation and reporting of coronary computed tomographic angiography
J Cardiovasc Comput Tomogr
(2009) - et al.
Natural history of coronary atherosclerosis by multislice computed tomography
JACC Cardiovasc Imaging
(2012) - et al.
Normalization of automatic plaque quantification in cardiac computed tomography (CCT)
Int J Cardiol
(2011) - et al.
Aggregate plaque volume by coronary computed tomography angiography is superior and incremental to luminal narrowing for diagnosis of ischemic lesions of intermediate stenosis severity
J Am Coll Cardiol
(2013) - et al.
Additive value of semiautomated quantification of coronary artery disease using cardiac computed tomographic angiography to predict future acute coronary syndrome
J Am Coll Cardiol
(2013) - et al.
Characterization of noncalcified coronary plaques and identification of culprit lesions in patients with acute coronary syndrome by 64-slice computed tomography
JACC Cardiovasc Imaging
(2009) - et al.
Computed tomographic angiography characteristics of atherosclerotic plaques subsequently resulting in acute coronary syndrome
J Am Coll Cardiol
(2009) - et al.
Noninvasive assessment of plaque morphology and composition in culprit and stable lesions in acute coronary syndrome and stable lesions in stable angina by multidetector computed tomography
J Am Coll Cardiol
(2006)
Multislice computed tomographic characteristics of coronary lesions in acute coronary syndromes
J Am Coll Cardiol
Quantification of coronary artery calcium using ultrafast computed tomography
J Am Coll Cardiol
Assessment of abdominal fat content by computed tomography
Am J Clin Nutr
Simvastatin attenuates plaque inflammation: evaluation by fluorodeoxyglucose positron emission tomography
J Am Coll Cardiol
Computed tomographic angiography characteristics of atherosclerotic plaques subsequently resulting in acute coronary syndrome
J Am Coll Cardiol
Effect of statin treatment on coronary plaque progression—a serial coronary CT angiography study
Atherosclerosis
Serial coronary CT angiography-verified changes in plaque characteristics as an end point: evaluation of effect of statin intervention
JACC Cardiovasc Imaging
Increased acute myocardial infarction rates and cardiovascular risk factors among patients with human immunodeficiency virus disease
J Clin Endocrinol Metab
Ischemic heart disease in HIV-infected and HIV-uninfected individuals: a population-based cohort study
Clin Infect Dis
Survival of persons with and without HIV infection in Denmark, 1995–2005
Ann Intern Med
Mortality in the highly active antiretroviral therapy era: changing causes of death and disease in the HIV outpatient study
J Acquir Immune Defic Syndr
HIV infection and the risk of acute myocardial infarction
JAMA Intern Med
Associations between HIV infection and subclinical coronary atherosclerosis
Ann Intern Med
Noncalcified coronary atherosclerotic plaque and immune activation in HIV-infected women
J Infect Dis
Arterial inflammation in patients with HIV
JAMA
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