If you don't remember your password, you can reset it by entering your email address and clicking the Reset Password button. You will then receive an email that contains a secure link for resetting your password
If the address matches a valid account an email will be sent to __email__ with instructions for resetting your password
Asymptomatic coronary artery disease assessed by coronary computed tomography in patients with systemic lupus erythematosus: A systematic review and meta-analysis
Department of Rheumatology, Medicine School, Meritorious Autonomous University of Puebla, Puebla, MexicoSystemic Autoimmune Diseases Research Unit, Specialties Hospital UMAE, Mexican Social Security Institute, Puebla, México
In our systematic review and meta-analysis, we demonstrated that subclinical CAD by CCS is more prevalent in patients with SLE compared to controls.
•
However, the extent of CAC by CCS was not higher in patients with SLE than controls.
•
Moreover, analysis for limited studies showed that CAC measured by CCTA showed non-calcified plaque burden is increased SLE compared to controls.
Abstract
Background
Coronary artery disease (CAD) assessed by coronary computed tomography (CT) in patients with systemic lupus erythematosus (SLE) has been investigated in several studies, but with conflicting results. The aim of this systematic review and meta-analysis of the literature was synthesize the evidence on this topic.
Methods
The relevant literature was identified and evaluated from inception until January 2021 in PubMed, Embase, Web of Science and Cochrane library. Studies reporting coronary artery calcification (CAC), and its prevalence and extent using the coronary calcium score (CCS) were included. Data extracted from eligible studies were used to calculate effect estimates (ESs) and 95% confidence intervals (95%CI) and weighted mean differences (WMD) with 95%CI.
Results
Twenty-four studies were eligible for inclusion. For the CAC prevalence, 11 studies were included (918 SLE patients and 3952 controls) and the pooled prevalence for the random effect was 29.8% (95%CI 25.7–32.9%) for SLE patients and 11.8% (95%CI 16.2-20.4%) in controls (RR 2.22, 95%CI 1.42 to 3.48; p= 0.0005) and no significant increase in the WMD for CCS (MD= 0.32, 95%CI −5.55 to 6.20, p= 0.91) compared with controls in seven studies. Greater organ damage and glucocorticoid use has been associated with a higher CCS. According to two studies, the coronary CT angiography calcified and non-calcified plaque burden were increased in SLE patients compared with controls.
Conclusions
In SLE, asymptomatic CAD by CAC is more prevalent and there is more multivessel disease compared with controls without lupus. However, the extent of CAC was not increased in SLE patients.
Systemic lupus erythematosus (SLE) is a systemic autoimmune disease with female predominance: cardiovascular disease (CVD) is the leading cause of morbidity and mortality. Accelerated atherosclerosis and coronary artery disease (CAD) are major contributors to the pathogenesis of CVD in SLE patients [
]. Previously, it was thought that CAD was a condition affecting exclusively older men; however, patients with SLE (young female-predominant) have an increased risk of CVD compared with the general population [
Traditional risk models, such as the Framingham risk score, do not capture the CV risk in patients with SLE. Therefore, new markers for subclinical CVD are required for stratification of these high-risk patients. The use of imaging has the potential to improve this stratification for future CV events and may determine personalized effective CVD management and medical therapy. Arterial calcium development is closely related to vascular injury, inflammation, and repair. Various factors have been considered as components of the arterial calcification pathophysiological process in patients with autoimmune diseases such as SLE, including traditional cardiovascular risk factors, lipid oxidation, endothelial damage, which can lead to accelerated vascular aging, in which the inflammatory cascade, which might be called "inflammaging", can play an important role [
Coronary artery calcium (CAC) is most commonly evaluated by non-contrast electrocardiographic-gated cardiac electron beam computerized tomography (EBCT) or multidetector computerized tomography (MDCT). The coronary calcium score (CCS) is associated with the plaque burden and provides insight into the level of CV risk [
Coronary risk stratification, discrimination, and reclassification improvement based on quantification of subclinical coronary atherosclerosis: the Heinz Nixdorf Recall study.
]. CAC may also be measured by coronary computed tomography angiography (CCTA), which is a reliable non-invasive method to characterize the coronary artery burden and has been validated against intravascular ultrasound, the gold standard for imaging coronary plaque [
Detection and quantification of coronary atherosclerotic plaque by 64-slice multidetector CT: a systematic head-to-head comparison with intravascular ultrasound.
]. CCTA permits volumetric quantification of coronary artery plaque, luminal stenosis, arterial remodelling and plaque subcomponents, which include calcified and non-calcified coronary plaque [
]. The latest American Heart Association and American College of Cardiology (AHA/ACC) guidelines for the primary prevention of atherosclerotic CVD permit the use of CAC scores in intermediate-risk patients, and may consider additional individual risk-enhancing clinical factors such as chronic inflammatory disease like SLE if the risk level is uncertain [
2019 ACC/AHA guideline on the primary prevention of cardiovascular disease: a report of the American college of cardiology/American heart association task force on clinical practice guidelines.
]. Thus, the CAC score could be useful in determining CV risk in patients with SLE.
Several recent studies have investigated the association between SLE and CAC. Therefore, to better characterize the prevalence and magnitude of asymptomatic CAD in patients with SLE, as determined by the CCS measured by computed tomography, we conducted a systematic review and meta-analysis of all published studies.
2. Methods
This systematic review and meta-analysis was conducted and reported according to the Preferred Reporting Items for Systematic Review and Meta-analysis (PRISMA) [
] and was registered in PROSPERO (registration number: CRD42021228710).
2.1 Search strategy and screening
Two authors (CMP and KGB) independently searched published studies indexed in PubMed/MEDLINE, EMBASE, Web of Science, and Cochrane library databases from inception to January 2021 using a search strategy that comprised papers that reported the prevalence and magnitude of CAD measured by CCS in patients with SLE, without language, country of origin or age restrictions. We combined the search term “SLE” in all fields with each of the following keywords: coronary calcification, coronary calcium, computed tomography angiography, and coronary artery atherosclerosis. Supplementary table 1 shows the search strategy. References of selected retrieved articles were also manually reviewed to identify any studies missed during the search strategy.
After all duplicate studies were identified, electronically-detected published papers were screened by title and/or abstracts and by reviewing full-text papers if these were considered relevant for inclusion. Two investigators independently evaluated the full texts of selected records. Discrepancies were resolved by consensus. Agreement between the two investigators was estimated using Cohen's kappa coefficient [
]. If multiple articles from the same cohort were found, only the article with the most complete data was included.
2.2 Eligibility criteria
Randomized and non-randomized controlled studies were considered for inclusion if they reported the prevalence of CAD and CCS in adults or children with SLE compared with controls without SLE. The classification criteria for SLE had to be based on either the American College of Rheumatology (ACR) [
Eligible controlled studies had to provide at least one of the following datasets: absolute numbers of patients with prevalent CAD (CCS >0) and total patient numbers to estimate CAD prevalence and/or mean or median CCS measured as Agatston units with standard deviations (SD) or ranges, in order to estimate the extent of CAD disease, respectively. We excluded all studies that reported insufficient data, case reports, comments, editorials and reviews. Studies involving patients with previous CAD or stroke were excluded as were studies published in languages other than English or Spanish. Abstracts without full-text publication in peer-reviewed journals or studies that lacked relevant data needed to compute the prevalence of either CAD or CCS were excluded.
2.3 Quality assessment
The quality of each study was independently evaluated by two authors (KGB and CMP) using the Newcastle-Ottawa quality assessment scale (NOS), which assessed each study in three areas: 1) selection of the study groups; 2) comparability of the groups; and 3) ascertainment of the exposure or outcome of interest in case-control or cohort studies, respectively [
]. The maximum NOS score is 9 and a score of ≥ 6 was considered indicative of good quality. Discrepant opinions between authors were resolved by consensus.
2.4 Data extraction
Two investigators independently extracted data to minimize reporting errors and disagreements were solved by consensus. Data concerning the author, year of publication, study design and study location were extracted. We also extracted all data on demographic characteristics, key baseline clinical variables and diagnostic method of CAD. Absolute numbers of patients who had CAD (CCS >0) and means with the SD of CCS, measured as Agatston units, were extracted. Additional angiographic data on coronary plaque composition, characterized by CCTA, was extracted whenever available. Values reported as medians with ranges or means with standard errors were imputed to the corresponding means with SDs. The values presented as percentages were recalculated to absolute numbers.
2.5 Statistical analysis
To assess the prevalence of CAD, the number of SLE patients with CCS > 0 and the total number of SLE patients were pooled and compared with similar data for controls without SLE to estimate the risk ratio (RR) for CAD. CCS means with SDs reported in the included studies were pooled to estimate the weighted mean difference between patients with SLE and controls. Due to data heterogeneity, we reported the results of analyses using a random effects model (Mantel-Haenszel method). Forest plots were used to show the final effect model. For overall estimated RR or weighted mean differences, a p-value < 0.05 was considered statistically significant. Heterogeneity between studies was tested using the chi-square method, where a p-value < 0.05 was considered statistically significant. The I2 value indicates the percentage of variation in the pooled study results and an I2 value above 20% was considered statistically significant. A sensitivity analysis was performed to determine the robustness of the results. Publication bias was visually estimated and assessed through funnel plots and confirmed by Egger's regression test. All analyses were performed using the meta-analysis statistical software Review Manager (Version 5.4.1). A narrative synthesis was the alternative option to report findings when meta-analysis was impossible.
3. Results
3.1 Results of literature search
The initial search yielded 691 articles, of which 290 were screened; 217 articles were excluded based on title and abstract review. Seventy-three articles underwent full-length review. Fifty-nine articles were excluded (Supplementary table 2 shows reasons for exclusion). Fourteen articles, which all were cross-sectional, involving 918 SLE patients and 3952 controls were finally included. Agreement between the authors was high (kappa= 0.83) Details of the literature search and excluded studies are shown in Fig. 1. Eleven studies contributed to the meta-analysis of the prevalence of CAD [
Chronic inflammatory disease is an independent risk factor for coronary flow velocity reserve impairment unrelated to the processes of coronary artery calcium deposition.
Chronic inflammatory disease is an independent risk factor for coronary flow velocity reserve impairment unrelated to the processes of coronary artery calcium deposition.
]. Although selection was not restricted by age, all studies identified as candidates for selection were in adults. The diagnosis of SLE was based on fulfilment of the ACR [
]. The demographic and clinic characteristics of the study populations are shown in Table 1 and Table 2. For CCS quantification, two older studies used EBTC scanners [
Chronic inflammatory disease is an independent risk factor for coronary flow velocity reserve impairment unrelated to the processes of coronary artery calcium deposition.
SCCT guidelines for the performance and acquisition of coronary computed tomographic angiography: a report of the society of cardiovascular computed tomography guidelines committee: endorsed by the north American society for cardiovascular imaging (NASCI.).
] in two studies ([29,30]). On assessment of study quality based on the NOS (see Supplementary table 3), only four studies had a high risk of bias, and the remaining studies had a low risk.
Table 1Characteristics of the studies included.
Author and publication year
N (SLE/Controls)
Type of controls
Age SLE/Controls, years
Ethnicity SLE%/Controls %
Type of CT scanner
Asanuma 2003
65/69
Age, sex and race-matched controls
40.3±11.6/42.7±12.6
Caucasian 72/75
EBCT
Kao 2008
105/105
Age and race-matched healthy controls
51.1±9.3/51.6±8.6
Caucasian 96.2/96.2
EBT
Greco 2009
161/161
Age and race- matched healthy women from population study
50.1±10/51.0±9.6
Caucasian 88/90
EBCT
Yiu 2009
50/50
Age and sex-matched controls
45.7±8.8/47.7±4.8
Chinese 100/100
MDCT
Bicakcigil 2011
106/98
Age, sex, BMI, waist/hip-matched controls
41.1±11.9/38.7±6.6
NA
MDCT
Romero-Diaz 2012
139/100
Age and sex-matched controls
31.8±10.1/32.5±9.7
Hispanics 100/100
MDCT
Somers 2012
95/38
Age and sex-matched controls from population study
37.6±9.1/39.3±10.2
White 84.2/89.5
MDCT
Heshmat 2015
30/30
Age and sex-matched control
32.1±5.1/32.3±5.4
Egyptian 100/100
MDCT
Kiani 2015
80/241
Controls from population study
NA
Caucasians 65/41 African American 31/59
MDCT
Kakuta 2016
21/23
NA
60±11/65±10
Japanese 100/100
MDCT
Romero-Diaz 2018
95/100 (only men)
Age-matched controls
34.7±10.1/34.8±9.7
Hispanics 100/100
MDCT
Gartshteyn 20019
76/3042
Age and sex-matched control
40.0±13.0/NA
African America 40/45.2 Caucasians 16/54.8 Hispanics 33/0
MDCT
Purmalek 2019
64/30
Age and gender-matched controls
45±12/37±11
Caucasians 39/53 African American 20/17
MDCT
Stojan 2020
72/100
No matched controls
51.1±1.4/66.3±9.6
Caucasians 70.8/71.3 African American 23.6/5.3
MDCT
EBCT: electron beam computed tomography; MDCT: multi-detector computed tomography; NA: not available.
3.3 Meta-analysis of the prevalence of CAD and mean CCS
As show in Fig. 2, pooled data from ten studies showed that the risk of CAD (CCS > 0) was significantly higher in patients with SLE compared with controls (274/918 [29.8%] vs. 468/3952 [10.6%]; RR 2.22 [95%CI 1.42-3.48]; p= 0.0005) with substantial heterogeneity (I2= 86%, p < 0.0001) (Fig. 2). Seven studies provided data on the severity of CAD in patients with SLE and controls [
Chronic inflammatory disease is an independent risk factor for coronary flow velocity reserve impairment unrelated to the processes of coronary artery calcium deposition.
] according to data from at least two studies. Some SLE-disease factors were associated with the presence or progression of CAD in at least two studies, including greater organ damage [
] the dense calcified plaque burden was significantly elevated in SLE patients compared with controls and the non-calcified plaque burden was increased in SLE [
] found that low attenuation non-calcified plaque (LANCP) was significantly greater in patients with SLE compared with controls and the LANCP volume was significantly higher in patients aged > 60 years and those with a prednisone dose > 10 mg/day.
3.6 Publication bias
The funnel plots demonstrated symmetrical distributions and Egger's tests confirmed the lack of publication bias for either prevalence or mean differences analysis (p= 0.69 and p= 0.22, respectively) (Supplemental Fig. 1). In the sensitivity analyses, no study significantly modified the effect estimator, either in the prevalence or in the mean differences analysis random model (Supplementary Fig. 2).
4. Discussion
Our results show that SLE patients had an increased prevalence of asymptomatic CAD evaluated by coronary computed tomography. CAD by CT was defined as a CSS >0, the cut-off used in all original articles included in our analysis: higher CCS scores are associated with an elevated CV risk and the absence of coronary calcium is a negative marker that confers a favourable prognosis [
]. On the other hand, the use of the total calcium score as a measure of the extent of atherosclerosis raises the question of whether it accurately correlates with the amount of calcified plaque present pathologically [
Correlation of coronary calcification and angiographically documented stenoses in patients with suspected coronary artery disease: results of 1,764 patients.
10-year coronary heart disease risk prediction using coronary artery calcium and traditional risk factors: derivation in the MESA (Multi-Ethnic Study of Atherosclerosis) with validation in the HNR (Heinz Nixdorf Recall) study and the DHS (Dallas Heart St.
]. Therefore, we decided to evaluate the extent of CAC by the mean CCS. However, we did not find that the burden of disease with a higher mean CCS was increased in SLE patients compared with controls. This is probably due to the few studies, with small sample sizes, evaluating mean differences between SLE patients and controls. Data from limited evidence shows that patients with SLE had more multivessel CAD than controls and that greater organ damage and GCT use might be associated with a higher CCS and progression in CAC, respectively.
The importance of absolute risk assessment in determining the net benefit of preventive therapy through CAC measurement was focused on patients at low/moderate risk of CV events, who received less benefit from therapy [
]. However, large prospective studies have also addressed the prognostic value of CAC for more adverse CV events in subsets considered at high risk, such as patients with diabetes and renal diseases, etc. [
Impact of subclinical atherosclerosis on cardiovascular disease events in individuals with metabolic syndrome and diabetes: the multi-ethnic study of atherosclerosis.
]. Although, there are no specific studies evaluating the prognostic value of CAC deposition in patients with SLE, which affects mainly young individuals, these conditions were shown as high risk in diabetic patients and, more recently, evidence has shown they have a higher risk than diabetes [
]. Beyond the prognostic value, CAC has emerged as an effective investigational tool to complement traditional risk stratification in this high-risk inflammatory disease [
], this the first study to explore the association between SLE and CAD in studies which only included patients without a previous clinical CVD risk assessment. Li et al. found that SLE patients were significantly at risk of developing CAD. A recent systematic review evaluating six autoimmune diseases (AID) found that the quantitative CAC score is higher in patients with AID, including SLE [
]. We included studies using different generations of CT technology, EBCT and MDCT scanners. Although the latter offers a higher spatial resolution and overall improved image quality, both scanners are comparable and have equivalent reproducibility for measuring CCS [
]. Therefore, we believe that the results obtained from the inclusion of both methods in our meta-analysis were not seriously affected by this decision.
Our results support the increased risk of CAD observed in extensive epidemiological studies of patients with SLE [
Cardiovascular events prior to or early after diagnosis of systemic lupus erythematosus in the systemic lupus international collaborating clinics cohort.
] and reports of a higher risk of subclinical atherosclerosis in other vascular territories in SLE such as increased carotid intima-media thickness and carotid plaque [
Despite a comprehensive body of supporting evidence, barriers have slowed the adaption of CAC testing in routine care. Cost and radiation exposure are concerns, but several features of the CAC score show its value as an optimal tool for atherosclerotic CVD risk stratification. Firstly, CT is a highly sensitive imaging test for the detection of dense calcium structures, including small calcifications in the coronary walls. Second, detection of CAC is almost pathognomonic for atherosclerotic plaque. Third, non-contrast CT cannot detect non-calcified plaque, and there is a strong correlation with the histopathologic plaque area [
Utility of Coronary Calcium Scoring (CCS) in Connective Tissue Disorders (CTDs) for the evaluation of subclinical coronary atherosclerosis - a systematic review.
Given that measuring the non-calcified burden, a marker for coronary wall thickening, enables early detection of atherosclerosis even before clinically detectable plaque, research efforts in chronic systemic inflammatory disease have focused on semiautomatic quantification of the non-calcified burden to better capture rupture-prone CAD, which prompt more aggressive primary prevention management [
] showed that low-attenuation non-calcified plaque and positive remodelling by CCTA are common in patients with SLE. Recent evidence has shown that coronary plaque features detected on CCTA rather than CAC may enhance the risk prediction of CAC. However, the data on the use of CAC for image-guiding therapy is still more developed than data on plaque features.
Clinically, having a chronic inflammatory disease with an increased risk of mortality, like SLE, is enough of a risk-enhancing condition to warrant early statin therapy for primary prevention of atherosclerotic CVD by the AHA/ACC [
2018 AHA/ACC/AACVPR/AAPA/ABC/ACPM/ADA/AGS/APhA/ASPC/NLA/PCNA guideline on the management of blood cholesterol: executive summary: a report of the American college of cardiology/American heart association task force on clinical practice guidelines.
]. Given chronic inflammatory diseases greatly increase atherosclerotic progression, measurement of CAC by CV CT is currently recommended in individuals with borderline intermediate risk categories [
2019 ACC/AHA guideline on the primary prevention of cardiovascular disease: a report of the American college of cardiology/American heart association task force on clinical practice guidelines.
] found that non-calcified and mixed coronary plaque in women, compared with men, is associated with worse clinical outcomes, an extremely pertinent finding for the treatment of young women with SLE. The integration of CCTA as a marker may capture residual CVD risk in patients with SLE, particularly severe initial disease and/or lupus nephritis, which has recently been associated with greater mortality [
The risk of cardiovascular morbidity and cardiovascular mortality in systemic lupus erythematosus and lupus nephritis: a Danish nationwide population-based cohort study.
]. From a therapeutic perspective, CCTA can be used to assess the impact of treatments on atherosclerosis longitudinally, especially those which may have anti-inflammatory effects on CV events in large studies [
]. Furthermore, the use of biologic disease-modifying drugs in rheumatoid arthritis (RA) has been associated with protective calcification of non-calcified lesions and a lower likelihood of new plaque formation [
]. These findings highlight the contribution of systemic inflammation in CAD and support CCTA-measured coronary findings as endpoints for larger randomized, clinical trials. Moreover, the use of CAC scoring has been associated with significant improvements in the reclassification and discrimination of incident ASVD [
Assessment of coronary artery calcium scoring to guide statin therapy allocation according to risk-enhancing factors: the multi-ethnic study of atherosclerosis.
], supporting the utility of CAC scoring as an adjunct to risk-enhancing factor assessment to more accurately classify individuals with an intermediate risk of ASCVD who might benefit from statin therapy.
The study has some limitations. Firstly, most studies included had a small sample size and statistical heterogeneity, which might be due to differences in the population enrolled and the diagnostic method of CAC. Our results may have been skewed by the inclusion of SLE patients with different medications, such as glucocorticoids, hydroxychloroquine (HCQ) and/or statins (Table 2). The use of statins can reduce the risk of clinical CAD and influences CCS and CCTA findings [
Impact of statin therapy on coronary plaque burden and composition assessed by coronary computed tomographic angiography: a systematic review and meta-analysis.
The impact of antimalarial agents on traditional and non-traditional subclinical atherosclerosis biomarkers in systemic lupus erythematosus: a systematic review and meta-analysis.
]. However, most studies included had no data on statins or antimalarials. Secondly, the absence of adjustment for traditional and non-traditional CAD risk factors, such as depression, and physical inactivity, and anti-phospholipid antibodies, among others, which are more prevalent in patients with SLE [
], may lead to an overestimate of the effects of the disease. Third, most studies included were cross-sectional and, therefore, the prognostic value of CAD assessment by coronary computed tomography remains unclear. Finally, although our search strategy did not restrict by age, all studies retrieved from the search were in adults. Therefore, our results cannot be generalizable to all patients with SLE. Efforts should be made to identify novel biomarkers, such as CAC, that would assist physicians in quantifying the atherosclerotic burden and follow the trajectory.
5. Conclusions
This systematic review and meta-analysis found that, in patients with SLE, subclinical CAD by CCS and CCTA is more prevalent compared with controls. Studies should focus on the longitudinal analysis of CAD assessed by CT and its relationship with injury markers, lipid function and immune cells, to understand inflammatory atherosclerosis and the effects of anti-inflammatory therapies.
Funding
The authors have not declared a specific grant for this study from any funding agency in the public, commercial or not-for-profit sectors.
Conflict of interest
The authors have no ethical conflicts to declare.
Acknowledgment
The abstract of this work was published as a poster at the 2021 American College of Rheumatology meeting. We thank David Buss and Ms. Fernanda Solis for technical assistance.
Coronary risk stratification, discrimination, and reclassification improvement based on quantification of subclinical coronary atherosclerosis: the Heinz Nixdorf Recall study.
Detection and quantification of coronary atherosclerotic plaque by 64-slice multidetector CT: a systematic head-to-head comparison with intravascular ultrasound.
2019 ACC/AHA guideline on the primary prevention of cardiovascular disease: a report of the American college of cardiology/American heart association task force on clinical practice guidelines.
Chronic inflammatory disease is an independent risk factor for coronary flow velocity reserve impairment unrelated to the processes of coronary artery calcium deposition.
SCCT guidelines for the performance and acquisition of coronary computed tomographic angiography: a report of the society of cardiovascular computed tomography guidelines committee: endorsed by the north American society for cardiovascular imaging (NASCI.).
Correlation of coronary calcification and angiographically documented stenoses in patients with suspected coronary artery disease: results of 1,764 patients.
10-year coronary heart disease risk prediction using coronary artery calcium and traditional risk factors: derivation in the MESA (Multi-Ethnic Study of Atherosclerosis) with validation in the HNR (Heinz Nixdorf Recall) study and the DHS (Dallas Heart St.
Impact of subclinical atherosclerosis on cardiovascular disease events in individuals with metabolic syndrome and diabetes: the multi-ethnic study of atherosclerosis.
Cardiovascular events prior to or early after diagnosis of systemic lupus erythematosus in the systemic lupus international collaborating clinics cohort.
Utility of Coronary Calcium Scoring (CCS) in Connective Tissue Disorders (CTDs) for the evaluation of subclinical coronary atherosclerosis - a systematic review.
2018 AHA/ACC/AACVPR/AAPA/ABC/ACPM/ADA/AGS/APhA/ASPC/NLA/PCNA guideline on the management of blood cholesterol: executive summary: a report of the American college of cardiology/American heart association task force on clinical practice guidelines.
The risk of cardiovascular morbidity and cardiovascular mortality in systemic lupus erythematosus and lupus nephritis: a Danish nationwide population-based cohort study.
Assessment of coronary artery calcium scoring to guide statin therapy allocation according to risk-enhancing factors: the multi-ethnic study of atherosclerosis.
Impact of statin therapy on coronary plaque burden and composition assessed by coronary computed tomographic angiography: a systematic review and meta-analysis.
The impact of antimalarial agents on traditional and non-traditional subclinical atherosclerosis biomarkers in systemic lupus erythematosus: a systematic review and meta-analysis.
00137-6&id=gr1.jpg){kind=link}
00137-6&id=gr2.jpg){kind=link}
00137-6&id=gr3.jpg){kind=link}