Atherosclerosis 231 (2013) 198e204
Contents lists available at ScienceDirect
Atherosclerosis journal homepage: www.elsevier.com/locate/atherosclerosis
Effect of statin treatment on coronary plaque progression e A serial coronary CT angiography study Irfan Zeb a, *, Dong Li b, Khurram Nasir c, d, e, f, Jennifer Malpeso b, Aisha Batool a, Ferdinand Flores b, Christopher Dailing b, Ronald P. Karlsberg g, Matthew Budoff b a
Department of Medicine, Bronx-Lebanon Hospital Center, USA Department of Cardiology, Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center, CA, USA Center for Prevention and Wellness Research, Baptist Health Medical Group, Miami Beach, FL, USA d The Johns Hopkins Ciccarone Center for the Prevention of Heart Disease, Baltimore, MD, USA e Department of Epidemiology, Robert Stempel College of Public Health, Florida International University, Miami, FL, USA f Department of Medicine, Herbert Wertheim College of Medicine, Florida International University, Miami, FL, USA g Cardiovascular Research Foundation of Southern California, Cedars Sinai Heart Institute, Los Angeles, CA, USA b c
a r t i c l e i n f o
a b s t r a c t
Article history: Received 29 May 2013 Received in revised form 31 July 2013 Accepted 19 August 2013 Available online 29 August 2013
Objectives: Statins have been shown to reduce plaque progression using data on intravascular ultrasound, carotid intima-media thickness and coronary artery calcium scans. However, there is little data on effects of statins on plaque progression using Coronary CTA. The objective is to evaluate the effect of statin therapy on plaque progression using serial Coronary CTA (CCTA). Methods: The study included 100 consecutive patients who underwent serial Coronary CTA (mean follow up: 406 92 days) for evaluation of CAD without known prior heart disease or revascularization. We performed volumetric assessment of low attenuation plaque (LAP < 30 Hounsfield units), non-calcified (NCP) and calcified plaque volumes at baseline and follow up scans for vessels >2 mm in diameter. Patients who received statins were compared to those that did not. Results: Total plaque progression was significantly reduced among statin user compared to non-statin users (33.3 mm3 90.5 vs. 31.0 mm3 84.5, p ¼ 0.0006). Statin users had significantly reduced progression of NCP volume (47.7 mm3 71.9 vs. 13.8 mm3 76.6, p < 0.001) and significantly reduced progression of LAP volume (12.2 mm3 19.2 vs. 5.9 mm3 23.1, p < 0.0001). When we compared for remodeling index, no statistical difference was found between the two groups (p ¼ 0.25) and a nonsignificant trend toward calcium progression (29.3 mm3 67.9 vs. 10.0 mm3 53.2, p ¼ 0.133). After adjustment for cardiovascular risk factors, mean plaque volume difference between statin and non-statin users was statistically significant for both LAP and NCP volumes (18.1, 95% CI: 26.4, 9.8 for LAP; 101.7, 95% CI: 162.1, 41.4 for NCP; p < 0.001) respectively. Conclusion: Statin therapy resulted in significantly lower progression of LAP and NCP plaques compared to non-statin users. Ó 2013 Published by Elsevier Ireland Ltd.
Keywords: Statins Coronary plaque Coronary CTA
1. Introduction Atherosclerotic coronary artery disease is the leading causes of adverse cardiovascular events. Various preventive therapeutic
Abbreviations: Coronary CTA, coronary computed tomography angiography; CP, calcified plaque; MP, mixed plaque; NCP, non-calcified plaque; LAP, low attenuation plaque; SCCT, Society of Cardiovascular Computed Tomography; CAD, coronary artery disease; CAC, coronary artery calcium. * Corresponding author. Bronx-Lebanon Hospital Center, 1650 Grand Concourse, Bronx, NY 10457, USA. Tel.: þ1 310 972 8978. E-mail address: [email protected] (I. Zeb). 0021-9150/$ e see front matter Ó 2013 Published by Elsevier Ireland Ltd. http://dx.doi.org/10.1016/j.atherosclerosis.2013.08.019
options have been tried to reduce the cardiovascular mortality; among which statins are most secure [1e3]. Statins have been shown in multiple studies to be an effective preventive strategy in reducing cardiovascular mortality and adverse cardiovascular events [2,3]. Invasive coronary angiograms with intravascular ultrasound have demonstrated decreased progression and also regression of plaque volume with the use of statins [4,5]. Further, certain plaque characteristics have been identified that may be characterized as vulnerable plaque features due to their association with acute coronary syndromes. Vulnerable plaques may be characterized as large plaque volumes with necrotic cores and thin fibrous caps [6]. Presence of low attenuation plaque (LAP) and
I. Zeb et al. / Atherosclerosis 231 (2013) 198e204
positive remodeling has consistently been found to represent vulnerable plaque features [7e11]. Both of these features can be readily measured using high resolution CT scans. There is very limited data evaluating the effect of statins on these vulnerable plaque characteristics [12]. Plaque progression can be estimated with the use of intravascular ultrasound, which is limited by the fact that it includes only proximal coronary artery plaque volumes, not be representative of the individual total plaque burden and requires an invasive approach not suitable for the non-ischemic patient who is being treated with statins. Coronary CTA has been established as an alternative to invasive angiography in many circumstances and also affords the unique ability to measure both calcified and non-calcified plaque without the risk of an invasive approach reserved for patients with ischemia [13e20]. There is scarce data on effects of statins in regard to plaque progression using Coronary CTA. In current study, we studied the effects of statins on consecutive patients who underwent Coronary CTA to assess effects of statins on coronary artery plaque burden compared with non-statin users using the SCCT Coronary CTA segment scheme [21]. In addition we studied the effect of statin treatment on high risk plaque features such as LAP and positive remodeling index among statin users compared to non-statin users.
199
Fig. 1. Flow sheet regarding patient selection.
2. Methods 2.1. Study population We performed a retrospective observational study on patients who underwent consecutive Coronary CTA at our outpatient center at Los Angeles Biomedical Research Institute at HarborUCLA Medical Center and the Cardiovascular Medical Group of Southern California, Beverly Hills California. Patient medical records were screened for patients undergoing Coronary CTA between 2006 and 2009. Inclusion criteria was patients having 2 consecutive scans at least 1 year apart, without any prior known CAD and scans with good image quality. We excluded patients if the scans had significant artifacts or poor image quality (significant coronary artery motion, mis-registration artifacts or poor contrast enhancement) or interim coronary revascularization procedures. These patients were being referred by their primary physicians for screening of coronary artery disease and the screening interval was decided by the primary physicians. Initially, 110 participants were screened, 10 patients were excluded (flow sheet 1), and 100 patients were included in the final analysis. Among which 60 patients were taking statins at the time of both baseline and follow up scans (Fig. 1). The use of statins was determined based on the discretion of the primary physicians. Information related to risk factors, dietary and risk factor interventions and statin use was obtained. All participants provided informed consent for the study. The study was approved by the Institutional Review Board of Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center and was conducted in accordance with the Human Insurance Portability and Accountability Act (HIPAA). Information regarding demographic data, tobacco usage, medical conditions, and current use of statins including medication name and dosage was obtained at the baseline and follow up visits of the study. Information was collected either through patient questionnaire or the medical records systems. Diabetes mellitus was defined as fasting blood glucose 126 mg/dl or use of insulin or oral hypoglycemic medications. Resting blood pressure was measured with participants in the seated position. Hypertension was defined as blood pressure higher than 140/90 or use of antihypertensive medications. Height and weight information
was collected from patients, and body mass index was calculated (in kg/m2). 2.2. Image acquisition parameters All Coronary CTA images were acquired using 64-multi-detector row Lightspeed VCT scanner (General Electric Healthcare, Milwaukie, Wisconsin). The details of the image acquisition were previously published [22]. All patients undergoing Coronary CTA had non-contrast studies as a part of the protocol for calcium score measurement (CAC). Patients received beta blockers to achieve a heart rate
Contents lists available at ScienceDirect
Atherosclerosis journal homepage: www.elsevier.com/locate/atherosclerosis
Effect of statin treatment on coronary plaque progression e A serial coronary CT angiography study Irfan Zeb a, *, Dong Li b, Khurram Nasir c, d, e, f, Jennifer Malpeso b, Aisha Batool a, Ferdinand Flores b, Christopher Dailing b, Ronald P. Karlsberg g, Matthew Budoff b a
Department of Medicine, Bronx-Lebanon Hospital Center, USA Department of Cardiology, Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center, CA, USA Center for Prevention and Wellness Research, Baptist Health Medical Group, Miami Beach, FL, USA d The Johns Hopkins Ciccarone Center for the Prevention of Heart Disease, Baltimore, MD, USA e Department of Epidemiology, Robert Stempel College of Public Health, Florida International University, Miami, FL, USA f Department of Medicine, Herbert Wertheim College of Medicine, Florida International University, Miami, FL, USA g Cardiovascular Research Foundation of Southern California, Cedars Sinai Heart Institute, Los Angeles, CA, USA b c
a r t i c l e i n f o
a b s t r a c t
Article history: Received 29 May 2013 Received in revised form 31 July 2013 Accepted 19 August 2013 Available online 29 August 2013
Objectives: Statins have been shown to reduce plaque progression using data on intravascular ultrasound, carotid intima-media thickness and coronary artery calcium scans. However, there is little data on effects of statins on plaque progression using Coronary CTA. The objective is to evaluate the effect of statin therapy on plaque progression using serial Coronary CTA (CCTA). Methods: The study included 100 consecutive patients who underwent serial Coronary CTA (mean follow up: 406 92 days) for evaluation of CAD without known prior heart disease or revascularization. We performed volumetric assessment of low attenuation plaque (LAP < 30 Hounsfield units), non-calcified (NCP) and calcified plaque volumes at baseline and follow up scans for vessels >2 mm in diameter. Patients who received statins were compared to those that did not. Results: Total plaque progression was significantly reduced among statin user compared to non-statin users (33.3 mm3 90.5 vs. 31.0 mm3 84.5, p ¼ 0.0006). Statin users had significantly reduced progression of NCP volume (47.7 mm3 71.9 vs. 13.8 mm3 76.6, p < 0.001) and significantly reduced progression of LAP volume (12.2 mm3 19.2 vs. 5.9 mm3 23.1, p < 0.0001). When we compared for remodeling index, no statistical difference was found between the two groups (p ¼ 0.25) and a nonsignificant trend toward calcium progression (29.3 mm3 67.9 vs. 10.0 mm3 53.2, p ¼ 0.133). After adjustment for cardiovascular risk factors, mean plaque volume difference between statin and non-statin users was statistically significant for both LAP and NCP volumes (18.1, 95% CI: 26.4, 9.8 for LAP; 101.7, 95% CI: 162.1, 41.4 for NCP; p < 0.001) respectively. Conclusion: Statin therapy resulted in significantly lower progression of LAP and NCP plaques compared to non-statin users. Ó 2013 Published by Elsevier Ireland Ltd.
Keywords: Statins Coronary plaque Coronary CTA
1. Introduction Atherosclerotic coronary artery disease is the leading causes of adverse cardiovascular events. Various preventive therapeutic
Abbreviations: Coronary CTA, coronary computed tomography angiography; CP, calcified plaque; MP, mixed plaque; NCP, non-calcified plaque; LAP, low attenuation plaque; SCCT, Society of Cardiovascular Computed Tomography; CAD, coronary artery disease; CAC, coronary artery calcium. * Corresponding author. Bronx-Lebanon Hospital Center, 1650 Grand Concourse, Bronx, NY 10457, USA. Tel.: þ1 310 972 8978. E-mail address: [email protected] (I. Zeb). 0021-9150/$ e see front matter Ó 2013 Published by Elsevier Ireland Ltd. http://dx.doi.org/10.1016/j.atherosclerosis.2013.08.019
options have been tried to reduce the cardiovascular mortality; among which statins are most secure [1e3]. Statins have been shown in multiple studies to be an effective preventive strategy in reducing cardiovascular mortality and adverse cardiovascular events [2,3]. Invasive coronary angiograms with intravascular ultrasound have demonstrated decreased progression and also regression of plaque volume with the use of statins [4,5]. Further, certain plaque characteristics have been identified that may be characterized as vulnerable plaque features due to their association with acute coronary syndromes. Vulnerable plaques may be characterized as large plaque volumes with necrotic cores and thin fibrous caps [6]. Presence of low attenuation plaque (LAP) and
I. Zeb et al. / Atherosclerosis 231 (2013) 198e204
positive remodeling has consistently been found to represent vulnerable plaque features [7e11]. Both of these features can be readily measured using high resolution CT scans. There is very limited data evaluating the effect of statins on these vulnerable plaque characteristics [12]. Plaque progression can be estimated with the use of intravascular ultrasound, which is limited by the fact that it includes only proximal coronary artery plaque volumes, not be representative of the individual total plaque burden and requires an invasive approach not suitable for the non-ischemic patient who is being treated with statins. Coronary CTA has been established as an alternative to invasive angiography in many circumstances and also affords the unique ability to measure both calcified and non-calcified plaque without the risk of an invasive approach reserved for patients with ischemia [13e20]. There is scarce data on effects of statins in regard to plaque progression using Coronary CTA. In current study, we studied the effects of statins on consecutive patients who underwent Coronary CTA to assess effects of statins on coronary artery plaque burden compared with non-statin users using the SCCT Coronary CTA segment scheme [21]. In addition we studied the effect of statin treatment on high risk plaque features such as LAP and positive remodeling index among statin users compared to non-statin users.
199
Fig. 1. Flow sheet regarding patient selection.
2. Methods 2.1. Study population We performed a retrospective observational study on patients who underwent consecutive Coronary CTA at our outpatient center at Los Angeles Biomedical Research Institute at HarborUCLA Medical Center and the Cardiovascular Medical Group of Southern California, Beverly Hills California. Patient medical records were screened for patients undergoing Coronary CTA between 2006 and 2009. Inclusion criteria was patients having 2 consecutive scans at least 1 year apart, without any prior known CAD and scans with good image quality. We excluded patients if the scans had significant artifacts or poor image quality (significant coronary artery motion, mis-registration artifacts or poor contrast enhancement) or interim coronary revascularization procedures. These patients were being referred by their primary physicians for screening of coronary artery disease and the screening interval was decided by the primary physicians. Initially, 110 participants were screened, 10 patients were excluded (flow sheet 1), and 100 patients were included in the final analysis. Among which 60 patients were taking statins at the time of both baseline and follow up scans (Fig. 1). The use of statins was determined based on the discretion of the primary physicians. Information related to risk factors, dietary and risk factor interventions and statin use was obtained. All participants provided informed consent for the study. The study was approved by the Institutional Review Board of Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center and was conducted in accordance with the Human Insurance Portability and Accountability Act (HIPAA). Information regarding demographic data, tobacco usage, medical conditions, and current use of statins including medication name and dosage was obtained at the baseline and follow up visits of the study. Information was collected either through patient questionnaire or the medical records systems. Diabetes mellitus was defined as fasting blood glucose 126 mg/dl or use of insulin or oral hypoglycemic medications. Resting blood pressure was measured with participants in the seated position. Hypertension was defined as blood pressure higher than 140/90 or use of antihypertensive medications. Height and weight information
was collected from patients, and body mass index was calculated (in kg/m2). 2.2. Image acquisition parameters All Coronary CTA images were acquired using 64-multi-detector row Lightspeed VCT scanner (General Electric Healthcare, Milwaukie, Wisconsin). The details of the image acquisition were previously published [22]. All patients undergoing Coronary CTA had non-contrast studies as a part of the protocol for calcium score measurement (CAC). Patients received beta blockers to achieve a heart rate
