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Research Article | Open Access

Lipoprotein(a) is associated with coronary atheroma progression: analysis from a serial coronary computed tomography angiography study

Xi WANG1,2, Dong-Kai SHAN2, Guan-Hua DOU3, Yi-Pu DING4, Jing JING2, He-Bin CHE5, Jun-Jie YANG2(), Yun-Dai CHEN2()
Medical School of Chinese PLA, Beijing, China
Department of Cardiology, the Sixth Medical Centre, Chinese PLA General Hospital, Beijing, China
Department of Cardiology, the Second Medical Centre, Chinese PLA General Hospital, Beijing, China
School of Medicine, Nankai University, Tianjin, China
Medical Big Data Research Centre, Chinese PLA General Hospital, Beijing, China
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Abstract

BACKGROUND

Lipoprotein(a) [Lp(a)] has been closely related to coronary atherosclerosis and might affect perivascular inflammation due to its proinflammatory properties. However, there are limited data about Lp(a) and related perivascular inflammation on coronary atheroma progression. Therefore, this study aimed to investigate the associations between Lp(a) and the perivascular fat attenuation index (FAI) with coronary atheroma progression detected by coronary computed tomography angiography (CCTA).

METHODS

Patients who underwent serial CCTA examinations without a history of revascularization and with available data for Lp(a) within one month before or after baseline and follow-up CCTA imaging scans were considered to be included. CCTA quantitative analyses were performed to obtain the total plaque volume (TPV) and the perivascular FAI. Coronary plaque progression (PP) was defined as a ≥ 10% increase in the change of the TPV at the patient level or the presence of new-onset coronary atheroma lesions. The associations between Lp(a) or the perivascular FAI with PP were examined by multivariate logistic regression.

RESULTS

A total of 116 patients were ultimately enrolled in the present study with a mean CCTA interscan interval of 30.80 ± 13.50 months. Among the 116 patients (mean age: 53.49 ± 10.21 years, males: 83.6%), 32 patients presented PP during the follow-up interval. Lp(a) levels were significantly higher among PP patients than those among non-PP patients at both baseline [15.80 (9.09−33.60) mg/dL vs. 10.50 (4.75−19.71) mg/dL, P = 0.029] and follow-up [20.60 (10.45−34.55) mg/dL vs. 8.77 (5.00−18.78) mg/dL, P = 0.004]. However, there were no differences in the perivascular FAI between PP group and non-PP group at either baseline or follow-up. Multivariate logistic regression analysis showed that elevated baseline Lp(a) level (OR = 1.031, 95% CI: 1.005−1.058, P = 0.019) was an independent risk factor for PP after adjustment for other conventional variables.

CONCLUSIONS

Lp(a) was independently associated with coronary atheroma progression beyond low-density lipoprotein cholesterol and other conventional risk factors. Further studies are warranted to identify the inflammation effect exhibited as the perivascular FAI on coronary atheroma progression.

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Journal of Geriatric Cardiology
Volume 18 Issue 12,
December 2021
Pages 996-1007
DOI: 10.11909/j.issn.1671-5411.2021.12.001
Cite this article:
WANG X, SHAN D-K, DOU G-H, et al. Lipoprotein(a) is associated with coronary atheroma progression: analysis from a serial coronary computed tomography angiography study. Journal of Geriatric Cardiology, 2021, 18(12): 996-1007. https://doi.org/10.11909/j.issn.1671-5411.2021.12.001
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Agreement of coronary computed tomography angiography plaque quantification and the perivascular FAI analyses within intraobserver and interobserver.

VariablesLesion levelPatient level
ICC95% CIICC95% CI
ICC values were classified as excellent (> 0.90), good (0.75−0.90), moderate (0.50−0.75) and poor (< 0.50), respectively. The ICC of intraobserver was executed in 70 lesions of 35 patients, while the ICC of interobserver was executed in 75 lesions of 30 patients. CI: confidence interval; FAI: fat attenuation index; ICC: intraclass correlation coefficient; TPV: total plaque volume.
Intraobserver
　TPV 0.967 0.947−0.979 0.949 0.885−0.976
　FAI − − 0.994 0.987−0.997
Interobserver
　TPV 0.949 0.920−0.967 0.937 0.873−0.970
　FAI − − 0.992 0.982−0.996

Baseline demographics and clinical characteristics.

VariablesOverall (n = 116)PP (n = 32)Non-PP (n = 84)P−value
Data are presented as means ± SD or n (%). ACEI: angiotensin converting enzyme inhibitors; ARB: angiotensin receptor blockers; ASCVD: atherosclerotic cardiovascular disease; CAD-RADS: Coronary Artery Disease-Reporting and Data System; CCB: calcium channel blockers; CCTA: coronary computed tomography angiography; PP: plaque progression.
Male 97 (83.6%) 28 (87.5%) 69 (82.1%) 0.584
Age, yrs 53.49 ± 10.21 53.03 ± 9.63 53.67 ± 10.47 0.766
Body mass index, kg/m2 26.46 ± 2.95 27.58 ± 3.21 26.03 ± 2.75 < 0.05
Hypertension 72 (62.1%) 20 (62.5%) 52 (61.9%) 0.953
Diabetes mellitus 37 (31.9%) 14 (43.8%) 23 (27.4%) 0.091
Dyslipidaemias 45 (38.8%) 20 (62.5%) 51 (60.7%) 0.860
Current smoking 35 (30.2%) 9 (28.1%) 26 (31.0%) 0.767
CCTA interscan interval, months 30.80 ± 13.50 33.93 ± 15.37 29.60 ± 12.62 0.123
ASCVD risk stratification 0.942
　Very high risk 26 (22.4%) 7 (21.9%) 19 (22.6%)
　High risk 30 (25.9%) 9 (28.1%) 21 (25.0%)
　Low and moderate risk 60 (51.7%) 16 (50.0%) 44 (52.4%)
CAD-RADS grade 0.154
　0 (0%) 26 (22.4%) 4 (12.5%) 22 (26.2%)
　1 (1%−24%) 27 (23.3%) 9 (28.1%) 18 (21.4%)
　2 (25%−49%) 44 (37.9%) 14 (43.8%) 30 (35.7%)
　3 (50%−69%) 11 (9.5%) 1 (3.1%) 10 (11.9%)
　4 (70%−99%) 8 (6.9%) 4 (12.5%) 4 (4.8%)
Medication
　Aspirin 23 (19.8%) 5 (15.6%) 18 (21.4%) 0.483
　Statin 30 (25.9%) 7 (21.9%) 23 (27.4%) 0.545
　Ezetimibe 1 (0.9%) 0 1 (1.2%) 1.000
　Beta-blockers 20 (17.2%) 4 (12.5%) 16 (19.0%) 0.583
　ACEI or ARB 27 (23.3%) 6 (18.8%) 21 (25.0%) 0.476
　CCB 29 (25.0%) 4 (12.5%) 25 (29.8%) 0.060

Laboratory examination profiles at baseline and follow-up.

VariablesPP (n = 32)Non-PP (n = 84)P−value
Data are presented as means ± SD. *Presented as median (interquartile range). #Presented as P < 0.05 (baseline vs. follow-up). PP: plaque progression.
Fasting blood glucose, mmol/L
　Baseline 6.63 ± 2.56 5.78 ± 1.40 < 0.05
　Follow-up 6.31 ± 1.90 5.82 ± 1.47 0.146
Total cholesterol, mmol/L
　Baseline 4.74 ± 1.31 4.54 ± 1.03 0.389
　Follow-up 4.31 ± 0.95 4.09 ± 0.99# 0.285
Triglyceride, mmol/L
　Baseline 1.95 ± 1.18 1.92 ± 1.28 0.887
　Follow-up 2.01 ± 1.31 2.01 ± 1.82 0.979
Low-density lipoprotein cholesterol, mmol/L
　Baseline 2.96 ± 0.99 2.81 ± 0.89 0.433
　Follow-up 2.73 ± 0.87 2.41 ± 0.82# 0.068
High-density lipoprotein cholesterol, mmol/L
　Baseline 1.15 ± 0.35 1.16 ± 0.25 0.827
　Follow-up 1.11 ± 0.32 1.13 ± 0.29 0.691
Non-high-density lipoprotein cholesterol, mmol/L
　Baseline 3.58 ± 1.14 3.37 ± 0.95 0.313
　Follow-up 3.20 ± 0.87 2.96 ± 0.98# 0.223
Lipoprotein(a), mg/dL
　Baseline 15.80 (9.09−33.60)* 10.50 (4.75−19.71)* < 0.05
　Follow-up 20.60 (10.45−34.55)* 8.77 (5.00−18.78)* < 0.05

Univariate and multivariate logistic analyses of CCTA derived parameters and clinical characteristics predicting coronary plaque progression.

VariablesUnivariate analysisMultivariate analysis
OR95% CIP−valueOR95% CIP−value
CCTA: coronary computed tomography angiography; CI: confidence interval; OR: odds ratio.
Male 1.522 0.464−4.988 0.488
Age, yrs 0.994 0.954−1.035 0.764
Body mass index, kg/m2 1.199 1.035−1.389 < 0.05 1.212 1.026−1.433 < 0.05
Hypertension 1.026 0.443−2.376 0.953
Diabetes mellitus 2.063 0.884−4.813 0.094 1.463 0.456−4.697 0.522
Dyslipidaemias 0.927 0.401−2.146 0.860
CCTA interscan interval 1.024 0.994−1.055 0.125
Statin use 1.314 0.208−8.319 0.772
Calcium channel blockers use 2.841 0.638−12.654 0.171
Fasting blood glucose, mmol/L
　Baseline 1.271 1.011−1.597 < 0.05 1.150 0.862−1.535 0.343
　Follow-up 1.192 0.937−1.515 0.152
Low-density lipoprotein cholesterol, mmol/L
　Baseline 1.200 0.763−1.885 0.430
　Follow-up 1.569 0.962−2.560 0.071 1.553 0.882−2.733 0.127
Lipoprotein(a), mg/dL
　Baseline 1.027 1.004−1.051 < 0.05 1.031 1.005−1.058 < 0.05
Fat attenuation index, HU
　Baseline 0.967 0.918−1.018 0.201
　Follow-up 0.973 0.924−1.024 0.291
Total plaque volume, mm3
　Baseline 1.000 0.999−1.001 0.800