Impact of statins based on high-risk plaque features on coronary plaque progression in mild stenosis lesions: results from the PARADIGM study.

To investigate the impact of statins on plaque progression according to high-risk coronary atherosclerotic plaque (HRP) features and to identify predictive factors for rapid plaque progression in mild coronary artery disease (CAD) using serial coronary computed tomography angiography (CCTA). We analyzed mild stenosis (25-49%) CAD, totaling 1432 lesions from 613 patients (mean age, 62.2 years, 63.9% male) and who underwent serial CCTA at a ≥2 year inter-scan interval using the Progression of AtheRosclerotic PlAque DetermIned by Computed TomoGraphic Angiography Imaging (NCT02803411) registry. The median inter-scan period was 3.5 ± 1.4 years; plaques were quantitatively assessed for annualized percent atheroma volume (PAV) and compositional plaque volume changes according to HRP features, and the rapid plaque progression was defined by the ≥90th percentile annual PAV. In mild stenotic lesions with ≥2 HRPs, statin therapy showed a 37% reduction in annual PAV (0.97 ± 2.02 vs. 1.55 ± 2.22, P = 0.038) with decreased necrotic core volume and increased dense calcium volume compared to non-statin recipient mild lesions. The key factors for rapid plaque progression were ≥2 HRPs [hazard ratio (HR), 1.89; 95% confidence interval (CI), 1.02-3.49; P = 0.042], current smoking (HR, 1.69; 95% CI 1.09-2.57; P = 0.017), and diabetes (HR, 1.55; 95% CI, 1.07-2.22; P = 0.020). In mild CAD, statin treatment reduced plaque progression, particularly in lesions with a higher number of HRP features, which was also a strong predictor of rapid plaque progression. Therefore, aggressive statin therapy might be needed even in mild CAD with higher HRPs. ClinicalTrials.gov NCT02803411.

Park HB ，Arsanjani R ，Sung JM ，Heo R ，Lee BK ，Lin FY ，Hadamitzky M ，Kim YJ ，Conte E ，Andreini D ，Pontone G ，Budoff MJ ，Gottlieb I ，Chun EJ ，Cademartiri F ，Maffei E ，Marques H ，Gonçalves PA ，Leipsic JA ，Lee SE ，Shin S ，Choi JH ，Virmani R ，Samady H ，Chinnaiyan K ，Stone PH ，Berman DS ，Narula J ，Shaw LJ ，Bax JJ ，Min JK ，Chang HJ ... -  《-》

Effects of Statins on Coronary Atherosclerotic Plaques: The PARADIGM Study.

This study sought to describe the impact of statins on individual coronary atherosclerotic plaques. Although statins reduce the risk of major adverse cardiovascular events, their long-term effects on coronary atherosclerosis remain unclear. We performed a prospective, multinational study consisting of a registry of consecutive patients without history of coronary artery disease who underwent serial coronary computed tomography angiography at an interscan interval of ≥2 years. Atherosclerotic plaques were quantitatively analyzed for percent diameter stenosis (%DS), percent atheroma volume (PAV), plaque composition, and presence of high-risk plaque (HRP), defined by the presence of ≥2 features of low-attenuation plaque, positive arterial remodeling, or spotty calcifications. Among 1,255 patients (60 ± 9 years of age; 57% men), 1,079 coronary artery lesions were evaluated in statin-naive patients (n = 474), and 2,496 coronary artery lesions were evaluated in statin-taking patients (n = 781). Compared with lesions in statin-naive patients, those in statin-taking patients displayed a slower rate of overall PAV progression (1.76 ± 2.40% per year vs. 2.04 ± 2.37% per year, respectively; p = 0.002) but more rapid progression of calcified PAV (1.27 ± 1.54% per year vs. 0.98 ± 1.27% per year, respectively; p < 0.001). Progression of noncalcified PAV and annual incidence of new HRP features were lower in lesions in statin-taking patients (0.49 ± 2.39% per year vs. 1.06 ± 2.42% per year and 0.9% per year vs. 1.6% per year, respectively; all p < 0.001). The rates of progression to >50% DS were not different (1.0% vs. 1.4%, respectively; p > 0.05). Statins were associated with a 21% reduction in annualized total PAV progression above the median and 35% reduction in HRP development. Statins were associated with slower progression of overall coronary atherosclerosis volume, with increased plaque calcification and reduction of high-risk plaque features. Statins did not affect the progression of percentage of stenosis severity of coronary artery lesions but induced phenotypic plaque transformation. (Progression of AtheRosclerotic PlAque DetermIned by Computed TomoGraphic Angiography Imaging [PARADIGM]; NCT02803411).

Lee SE ，Chang HJ ，Sung JM ，Park HB ，Heo R ，Rizvi A ，Lin FY ，Kumar A ，Hadamitzky M ，Kim YJ ，Conte E ，Andreini D ，Pontone G ，Budoff MJ ，Gottlieb I ，Lee BK ，Chun EJ ，Cademartiri F ，Maffei E ，Marques H ，Leipsic JA ，Shin S ，Choi JH ，Chinnaiyan K ，Raff G ，Virmani R ，Samady H ，Stone PH ，Berman DS ，Narula J ，Shaw LJ ，Bax JJ ，Min JK ... -  《-》

Differences in Progression to Obstructive Lesions per High-Risk Plaque Features and Plaque Volumes With CCTA.

This study explored whether the pattern of nonobstructive lesion progression into obstructive lesions would differ according to the presence of high-risk plaque (HRP). It is still debatable whether HRP simply represents a certain phase during the natural history of coronary atherosclerotic plaques or if disease progression would differ according to the presence of HRP. Patients with nonobstructive coronary artery disease, defined as percent diameter stenosis (%DS) <50%, were enrolled from a prospective, multinational registry of consecutive patients who underwent serial coronary computed tomography angiography at an interscan interval of ≥2 years. HRP was defined as lesions with ≥2 features of positive remodeling, spotty calcification, or low-attenuation plaque. Quantitative total and compositional percent atheroma volume (PAV) at baseline and annualized PAV change were compared between non-HRP and HRP lesions. A total of 3,049 nonobstructive lesions were identified from 1,297 patients (mean age 60.3 ± 9.3 years; 56.8% men). There were 2,624 non-HRP and 425 HRP lesions. HRP lesions had a greater total PAV and all noncalcified components of PAV and %DS at baseline compared with non-HRP lesions. However, the annualized total PAV changes were greater in non-HRP lesions than in HRP lesions. On multivariate analysis adjusted for clinical risk factors, drug use, change in lipid level, total PAV, %DS, and HRP, only the baseline total PAV and %DS independently predicted the development of obstructive lesions (hazard ratio [HR]: 1.04; 95% confidence interval [CI]: 1.02 to 1.07, and HR: 1.07; 95% CI: 1.04 to 1.10, respectively, all p < 0.05), whereas the presence of HRP did not (p > 0.05). The pattern of individual coronary atherosclerotic plaque progression differed according to the presence of HRP. Baseline PAV, not the presence of HRP features, was the most important predictor of lesions developing into obstructive lesions. (Progression of Atherosclerotic Plaque Determined By Computed Tomographic Angiography Imaging [PARADIGM]; NCT02803411).

Lee SE ，Sung JM ，Andreini D ，Al-Mallah MH ，Budoff MJ ，Cademartiri F ，Chinnaiyan K ，Choi JH ，Chun EJ ，Conte E ，Gottlieb I ，Hadamitzky M ，Kim YJ ，Lee BK ，Leipsic JA ，Maffei E ，Marques H ，de Araújo Gonçalves P ，Pontone G ，Raff GL ，Shin S ，Stone PH ，Samady H ，Virmani R ，Narula J ，Berman DS ，Shaw LJ ，Bax JJ ，Lin FY ，Min JK ，Chang HJ ... -  《-》

Clinical and Coronary Plaque Predictors of Atherosclerotic Nonresponse to Statin Therapy.

Statins reduce the incidence of major cardiovascular events, but residual risk remains. The study examined the determinants of atherosclerotic statin nonresponse. This study aimed to investigate factors associated with statin nonresponse-defined atherosclerosis progression in patients treated with statins. The multicenter PARADIGM (Progression of AtheRosclerotic PlAque DetermIned by Computed TomoGraphic Angiography Imaging) registry included patients who underwent serial coronary computed tomography angiography ≥2 years apart, with whole-heart coronary tree quantification of vessel, lumen, and plaque, and matching of baseline and follow-up coronary segments and lesions. Patients with statin use at baseline and follow-up coronary computed tomography angiography were included. Atherosclerotic statin nonresponse was defined as an absolute increase in percent atheroma volume (PAV) of 1.0% or more per year. Furthermore, a secondary endpoint was defined by the additional requirement of progression of low-attenuation plaque or fibro-fatty plaque. The authors included 649 patients (age 62.0 ± 9.0 years, 63.5% male) on statin therapy and 205 (31.5%) experienced atherosclerotic statin nonresponse. Age, diabetes, hypertension, and all atherosclerotic plaque features measured at baseline scan (high-risk plaque [HRP] features, calcified and noncalcified PAV, and lumen volume) were significantly different between patients with and without atherosclerotic statin nonresponse, whereas only diabetes, number of HRP features, and noncalcified and calcified PAV were independently associated with atherosclerotic statin nonresponse (odds ratio [OR]: 1.41 [95% CI: 0.95-2.11], OR: 1.15 [95% CI: 1.09-1.21], OR: 1.06 [95% CI: 1.02-1.10], OR: 1.07 [95% CI: 1.03-1.12], respectively). For the secondary endpoint (N = 125, 19.2%), only noncalcified PAV and number of HRP features were the independent determinants (OR: 1.08 [95% CI: 1.03-1.13] and OR: 1.21 [95% CI: 1.06-1.21], respectively). In patients treated with statins, baseline plaque characterization by plaque burden and HRP is associated with atherosclerotic statin nonresponse. Patients with the highest plaque burden including HRP were at highest risk for plaque progression, despite statin therapy. These patients may need additional therapies for further risk reduction.

van Rosendael SE ，van den Hoogen IJ ，Lin FY ，Andreini D ，Al-Mallah MH ，Budoff MJ ，Cademartiri F ，Chinnaiyan K ，Choi JH ，Conte E ，Marques H ，de Araújo Gonçalves P ，Gottlieb I ，Hadamitzky M ，Leipsic JA ，Maffei E ，Pontone G ，Raff GL ，Shin S ，Kim YJ ，Lee BK ，Chun EJ ，Sung JM ，Lee SE ，Virmani R ，Samady H ，Stone PH ，Min JK ，Narula J ，Shaw LJ ，Chang HJ ，van Rosendael AR ，Bax JJ ... -  《-》

Differential association between the progression of coronary artery calcium score and coronary plaque volume progression according to statins: the Progression of AtheRosclerotic PlAque DetermIned by Computed TomoGraphic Angiography Imaging (PARADIGM) stud

Coronary artery calcium score (CACS) is a strong predictor of major adverse cardiac events (MACE). Conversely, statins, which markedly reduce MACE risk, increase CACS. We explored whether CACS progression represents compositional plaque volume (PV) progression differently according to statin use. From a prospective multinational registry of consecutive patients (n = 2252) who underwent serial coronary computed tomography angiography (CCTA) at a ≥ 2-year interval, 654 patients (61 ± 10 years, 56% men, inter-scan interval 3.9 ± 1.5 years) with information regarding the use of statins and having a serial CACS were included. Patients were divided into non-statin (n = 246) and statin-taking (n = 408) groups. Coronary PVs (total, calcified, and non-calcified; sum of fibrous, fibro-fatty, and lipid-rich) were quantitatively analysed, and CACS was measured from both CCTAs. Multivariate linear regression models were constructed for both statin-taking and non-statin group to assess the association between compositional PV change and change in CACS. In multivariate linear regression analysis, in the non-statin group, CACS increase was positively associated with both non-calcified (β = 0.369, P = 0.004) and calcified PV increase (β = 1.579, P < 0.001). However, in the statin-taking group, CACS increase was positively associated with calcified PV change (β = 0.756, P < 0.001) but was negatively associated with non-calcified PV change (β = -0.194, P = 0.026). In the non-statin group, CACS progression indicates the progression of both non-calcified and calcified PV progression. However, under the effect of statins, CACS progression indicates only calcified PV progression, but not non-calcified PV progression. Thus, the result of serial CACS should be differently interpreted according to the use of statins.

Lee SE ，Sung JM ，Andreini D ，Budoff MJ ，Cademartiri F ，Chinnaiyan K ，Choi JH ，Chun EJ ，Conte E ，Gottlieb I ，Hadamitzky M ，Kim YJ ，Kumar A ，Lee BK ，Leipsic JA ，Maffei E ，Marques H ，Pontone G ，Raff G ，Shin S ，Stone PH ，Samady H ，Virmani R ，Narula J ，Berman DS ，Shaw LJ ，Bax JJ ，Lin FY ，Min JK ，Chang HJ ... -  《-》