Comparison of Coronary Artery Calcium and Quantitative Coronary Plaque in Predicting Obstructive Coronary Artery Disease: Subgroup Analysis of the CLARIFY Study.

Background: Agatston coronary artery calcium (CAC) score is a strong predictor of mortality. However, the relationship between CAC and quantitative calcified plaque volume (CPV), which is measured on coronary computed tomography angiography (CCTA), is not well understood. Furthermore, there is limited evidence evaluating the difference between CAC versus CPV and CAC versus total plaque volume (TPV) in predicting obstructive coronary artery disease (CAD). Methods: This study included 147 subjects from the CLARIFY registry, a multicentered study of patients undergoing assessment using CCTA and CAC score as part of acute and stable chest pain evaluation. Automated software service (Cleerly.Inc, Denver, CO, USA) was used to evaluate the degree of vessel stenosis and plaque quantification on CCTA. CAC was measured using the standard Agatston method. Spearman correlation and receiver operating characteristic curve analysis was performed to evaluate the diagnostic ability of CAC, CPV and TPV in detecting obstructive CAD. Results: Results demonstrated a very strong positive correlation between CAC and CPV (r=0.76, p=0.0001) and strong correlation between CAC and TPV (r=0.72, p<0.001) at per-patient level analysis. At per-patient level analysis, the sensitivity of CAC (68%) is lower than CPV (77%) in predicting >50% stenosis, but negative predictive value is comparable. However, the sensitivity of TPV is higher compared with CAC in predicting >50% stenosis, and the negative predictive value of TPV is also higher. Conclusion: CPV and TPV are more sensitive in predicting the severity of obstructive CAD compared with the CAC score. However, the negative predictive value of CAC is comparable to CPV, but is lower than TPV. This study elucidates the relationship between CAC and quantitative plaque types, and especially emphasizes the differences between CAC and CPV which are two distinct plaque measurement techniques that are utilized in predicting obstructive CAD.

Effect of Colchicine on Progression of Known Coronary Atherosclerosis in Patients with STable CoROnary Artery Disease CoMpared to Placebo (EKSTROM) Trial - Rationale and Design.

BACKGROUND: Cardiovascular disease is the major cause of mortality in the United States. Despite lifestyle modification and traditional risk factor control residual inflammatory risk remains an untreated concern. Colchicine is an oral, medication that has been used for gout, mediterranean fever and pericarditis for decades. In recent trials, colchicine has been shown to reduce major adverse cardiovascular events, however the mechanism of benefit remains unclear. The objective of the randomized, double-blind, placebo controlled EKSTROM trial is to evaluate the effects of colchicine 0.5mg/day on atherosclerotic plaque. METHODS: Eighty-four participants will be enrolled after obtaining informed consent and followed for 12 months. Eligible patients will be randomly assigned to colchicine 0.5mg/day or placebo in a 1:1 fashion as add-on to their standard of care. All participants will undergo coronary computed tomography angiography (CCTA) at baseline and at 12 months. RESULTS: As of November 2023, the study is 100% enrolled with an expected end of study by the second quarter of 2024. The primary endpoint is change in low attenuation plaque volume as measured by CCTA. Secondary endpoints include change in volume of different plaque types (including total atheroma volume, noncalcified plaque volume, dense calcified plaque volume, remodeling index), change in inflammatory markers (IL-6, IL-1ß, IL-18, hs-CRP), change in pericoronary adipose tissue attenuation, change in epicardial adipose tissue volume and attenuation and change in brachial flow mediated dilation. CONCLUSION: EKSTROM is the first randomized study to assess the effects of colchicine on plaque progression, pericoronary and epicardial fat. EKSTROM will provide important information on the mechanistic effects of colchicine on the cardiovascular system.

The impact of carbohydrate restriction-induced elevations in low-density lipoprotein cholesterol on progression of coronary atherosclerosis: the ketogenic diet trial study design.

BACKGROUND: Despite innovations in pharmacotherapy to lower lipoprotein cholesterol and apolipoprotein B, risk factors for atherosclerotic cardiovascular disease (ASCVD), ASCVD persists as the leading global cause of mortality. Elevations in low-density lipoprotein cholesterol (LDL-C) are a well-known risk factor and have been a main target in the treatment of ASCVD. The latest research suggests that ketogenic diets are effective at improving most non-LDL-C/apolipoprotein B cardiometabolic risk factors. However, ketogenic diets can induce large increases in LDL-C to >190 mg/dl in some individuals. Interestingly, these individuals are often otherwise lean and healthy. The influence of increased levels of LDL-C resulting from a carbohydrate-restricted ketogenic diet on the progression of atherosclerosis in otherwise metabolically healthy individuals is poorly understood. This observational study aims to assess and describe the progression of coronary atherosclerosis in this population within 12 months. METHODS: Hundred relatively lean individuals who adopted ketogenic diets and subsequently exhibited hypercholesterolemia with LDL-C to >190 mg/dl, in association with otherwise good metabolic health markers, were enrolled and observed over a period of 12 months. Participants underwent serial coronary computed tomography angiography scans to assess the progression of coronary atherosclerosis in a year. RESULTS: Data analysis shall begin following the conclusion of the trial with results to follow. CONCLUSION: Ketogenic diets have generated debate and raised concerns within the medical community, especially in the subset exhibiting immense elevations in LDL-C, who interestingly are lean and healthy. The relationship between elevated LDL-C and ASCVD progression in this population will provide better insight into the effects of diet-induced hypercholesterolemia.

Thoracic versus coronary calcification for atherosclerotic cardiovascular disease events prediction.

This study compared the prognostic value of quantified thoracic artery calcium (TAC) including aortic arch on chest CT and coronary artery calcium (CAC) score on ECG-gated cardiac CT. METHODS: A total of 2412 participants who underwent both chest CT and ECG-gated cardiac CT at the same period were included in the Multi-Ethnic Study of Atherosclerosis Exam 5. All participants were monitored for incident atherosclerotic cardiovascular disease (ASCVD) events. TAC is defined as calcification in the ascending aorta, aortic arch and descending aorta on chest CT. The quantification of TAC was measured using the Agatston method. Time-dependent receiver-operating characteristic (ROC) curves were used to compare the prognostic value of TAC and CAC scores. RESULTS: Participants were 69±9 years of age and 47% were male. The Spearman correlation between TAC and CAC scores was 0.46 (p<0.001). During the median follow-up period of 8.8 years, 234 participants (9.7%) experienced ASCVD events. In multivariable Cox regression analysis, TAC score was independently associated with increased risk of ASCVD events (HR 1.31, 95% CI 1.09 to 1.58) as well as CAC score (HR 1.82, 95% CI 1.53 to 2.17). However, the area under the time-dependent ROC curve for CAC score was greater than that for TAC score in all participants (0.698 and 0.641, p=0.031). This was particularly pronounced in participants with borderline/intermediate and high 10-year ASCVD risk scores. CONCLUSION: Our study demonstrated a significant association between TAC and CAC scores but a superior prognostic value of CAC score for ASCVD events. These findings suggest TAC on chest CT provides supplementary data to estimate ASCVD risk but does not replace CAC on ECG-gated cardiac CT.

Methods and Reproducibility of Liver Fat Measurement Using 3-Dimensional Liver Segmentation From Noncontrast Computed Tomography in EVAPORATE Cohort.

OBJECTIVE: Nonalcoholic fatty liver disease not only shares multiple risk factors with cardiovascular disease but also independently predicts its increased risk and related outcomes. Here, we evaluate reproducibility of 3-dimensional (3D) liver volume segmentation method to identify fatty liver on noncontrast cardiac computed tomography (CT) and compare measures with previously validated 2-dimensional (2D) segmentation CT criteria for the measurement of liver fat. METHODS: The study included 68 participants enrolled in the EVAPORATE trial and underwent serial noncontrast cardiac CT. Liver attenuation < 40 Hounsfield units (HU) was used for diagnosing fatty liver, as done in the MESA study. Two-dimensional and 3D segmentation of the liver were performed by Philips software. Bland-Altman plot analysis was used to assess reproducibility. RESULTS: Interreader reproducibility of 3D liver mean HU measurements was 96% in a sample of 111 scans. Reproducibility of 2D and 3D liver mean HU measurements was 93% in a sample of 111 scans. Reproducibility of change in 2D and 3D liver mean HU was 94% in 68 scans. Kappa, a measure of agreement in which the 2D and 3D measures both identified fatty liver, was excellent at 96.4% in 111 scans. CONCLUSIONS: Fatty liver can be reliably diagnosed and measured serially in a stable and reproducible way by 3D liver segmentation of noncontrast cardiac CT scans. Future studies need to explore the sensitivity and stability of measures for low liver fat content by 3D segmentation, over the current 2D methodology. This measure can serve as an imaging biomarker to understand mechanistic correlations between atherosclerosis, fatty liver, and cardiovascular disease risk.

Risk stratifying individuals with zero, minimal, and mild coronary artery calcium for cardiovascular disease by determining coronary plaque burden.

BACKGROUND AND AIMS: Use of coronary artery calcium (CAC) continues to expand, and several different categories of risk have been developed. Some categorize CAC as <10, 11-100 and â€‹> â€‹100, while others use CAC â€‹= â€‹0,1-10, 11-100 and â€‹> â€‹100 as categories. We sought to evaluate the plaque burden in patients with CAC 0, 1-10 and 11-100 to evaluate the best use of CAC scoring for risk assessment. METHODS: Patients were recruited from existing prospective CCTA trials with CAC scores ≤100 and quantitative coronary plaque analysis (QAngio, Medis). CAC was categorized into three groups: zero (CAC â€‹= â€‹0), minimal (CAC 1-10), and mild (CAC 11-100). Plaque levels (low attenuated, fibrous, fibro-fatty, dense calcified, total non-calcified) were assessed using multivariable linear regression adjusted for cardiovascular risk factors (age, ethnicity, BMI, gender, hypertension, dyslipidemia, diabetes mellitus, past smoking). RESULTS: 378 subjects were included, with an average age of 53.9 â€‹± â€‹10.7 years and 53 â€‹% female. Among them, 51 â€‹% had 0 CAC, 16 â€‹% had minimal CAC (scores 1-10), and 33 â€‹% had mild CAC (scores 11-100). The minimal and mild CAC groups were significantly older, with higher rates of diabetes, hypertension, and hyperlipidemia. Multivariable analysis found no significant difference in low attenuated, fibro-fatty, and dense calcified plaque levels between the minimal and zero CAC groups. However, minimal CAC subjects had significantly higher fibrous, total non-calcified, and total plaque volumes than zero CAC. All plaque types were significantly higher in the mild group when comparing mild CAC to minimal CAC. CONCLUSION: Individuals with minimal calcium scores (1-10) had greater noncalcified coronary plaque (NCAP) and total plaque volume than individuals with a calcium score of zero. The increased presence of NCAP and total plaque volume in the minimal CAC (1-10) is clinically significant and place those patients at higher coronary vascular disease (CVD) risk than individuals with absent CAC (CAC â€‹= â€‹zero). Therefore, the use of CAC â€‹= â€‹0, 1-10 and 11-100 is prudent to better categorize CVD risk.

Evaluation of Image Quality for High Heart Rates for Coronary Computed Tomographic Angiography with Advancement in CT Technology: The CONVERGE Registry.

OBJECTIVE: This study aims to evaluate image quality in patients with heart rates above or equal to 70 beats per minute (bpm), performed on a 16 cm scanner (256-slice General Electric Revolution) in comparison to a CT scanner with only 4 cm of coverage (64 slice Volume CT). BACKGROUND: Recent advancements in image acquisition, such as whole-heart coverage in a single rotation and post-processing methods in coronary computed tomographic angiography (CCTA), include motion-correction algorithms, such as SnapShot Freeze (SSF), which improve temporal resolution and allow for the assessment of coronary artery disease (CAD) with lower motion scores and better image qualities. Studies from the comprehensive evaluation of high temporal- and spatial-resolution cardiac CT using a wide coverage system (CONVERGE) registry (a multicenter registry at four centers) have shown the 16 cm CT scanner having a better image quality in comparison to the 4 cm scanner. However, these studies failed to include patients with undesirable or high heart rates due to well-documented poor image acquisition on prior generations of CCTA scanners. METHODS: A prospective, observational, multicenter cohort study comparing image quality, quantitively and qualitatively, on scans performed on a 16 cm CCTA in comparison to a cohort of images captured on a 4 cm CCTA at four centers. Participants were recruited based on broad inclusion criteria, and each patient in the 16 cm CCTA arm of the study received a CCTA scan using a 256-slice, whole-heart, single-beat scanner. These patients were then matched by age, gender, and heart rate to patients who underwent CCTA scans on a 4 cm CT scanner. Image quality was graded based on the signal-to-noise ratio, contrast-to-noise ratio, and on a Likert scale of 0-4: 0, very poor-4, excellent. RESULTS: 104 patients were evaluated for this study. The mean heart rate was 75 ± 7 in the 4 cm scanner and 75 ± 7 in the 16 cm one (p = 0.426). The signal-to-noise and contrast-to-noise ratios were higher in the 16 cm scanner (p = 0.0001). In addition, more scans were evaluated as having an excellent quality on the 16 cm scanner than on the 4 cm scanner (p < 0.0001) based on a 4-point Likert scale. CONCLUSIONS: The 16 cm scanner has a superior image quality for fast heart rates compared to the 4 cm scanner. This study shows that there is a significantly higher frequency of excellent and good studies showing better contrast-to-noise and signal-to-noise ratios with the 16 cm scanner compared to the 4 cm scanner.

Quantitative imaging biomarkers of coronary plaque morphology: insights from EVAPORATE.

Aims: Residual cardiovascular risk persists despite statin therapy. In REDUCE-IT, icosapent ethyl (IPE) reduced total events, but the mechanisms of benefit are not fully understood. EVAPORATE evaluated the effects of IPE on plaque characteristics by coronary computed tomography angiography (CCTA). Given the conclusion that the IPE-treated patients demonstrate that plaque burden decreases has already been published in the primary study analysis, we aimed to demonstrate whether the use of an analytic technique defined and validated in histological terms could extend the primary study in terms of whether such changes could be reliably seen in less time on drug, at the individual (rather than only at the cohort) level, or both, as neither of these were established by the primary study result. Methods and Results: EVAPORATE randomized the patients to IPE 4 g/day or placebo. Plaque morphology, including lipid-rich necrotic core (LRNC), fibrous cap thickness, and intraplaque hemorrhage (IPH), was assessed using the ElucidVivo® (Elucid Bioimaging Inc.) on CCTA. The changes in plaque morphology between the treatment groups were analyzed. A neural network to predict treatment assignment was used to infer patient representation that encodes significant morphological changes. Fifty-five patients completed the 18-month visit in EVAPORATE with interpretable images at each of the three time points. The decrease of LRNC between the patients on IPE vs. placebo at 9 months (reduction of 2 mm3 vs. an increase of 41 mm3, p = 0.008), widening at 18 months (6 mm3 vs. 58 mm3 increase, p = 0.015) were observed. While not statistically significant on a univariable basis, reductions in wall thickness and increases in cap thickness motivated multivariable modeling on an individual patient basis. The per-patient response assessment was possible using a multivariable model of lipid-rich phenotype at the 9-month follow-up, p < 0.01 (sustained at 18 months), generalizing well to a validation cohort. Conclusion: Plaques in the IPE-treated patients acquired more characteristics of stability. Reliable assessment using histologically validated analysis of individual response is possible at 9 months, with sustained stabilization at 18 months, providing a quantitative basis to elucidate drug mechanism and assess individual patient response.

Mitral annular calcification as a predictor of stroke in the multiethnic study of atherosclerosis.

BACKGROUND: Mitral annular calcification (MAC) is associated with an increased risk for cardiovascular morbidity and mortality. This study provides recent data on the association between cardiac computed tomography (CT) derived MAC and 15 years of stroke risk in a racially diverse cohort. METHODS: All multiethnic studies of atherosclerosis participants ( n  = 6814) who completed a cardiac CT at baseline were included in this analysis. MAC score was calculated from cardiac CT using the Agatston and volume score methods. Multivariable Cox proportional hazard regression models were used to compute hazard ratios for the association between MAC and stroke after adjusting for traditional cardiovascular risk factors, inflammatory markers, coronary artery calcium score, atrial fibrillation, and left atrial size. RESULTS: Overall, 9% of participants (644/6814) had MAC at baseline. Over a surveillance period of 15 years, 304 strokes occurred, and 79% were ischemic strokes. After adjusting for age, sex, race/ethnicity, SBP, diabetes, smoking, fibrinogen, IL-6, high-sensitivity C-reactive protein, and coronary artery calcium score, baseline MAC was associated with increased risk for all strokes [hazard ratio 1.68; 95% confidence interval (CI) 1.22-2.30: P  = 0.0013]. When atrial fibrillation/flutter and left atrial size were included in the final multivariable model, MAC remained a predictor of all strokes (hazard ratio 1.93; 95% CI 1.22-3.05: P  < 0.0051) and ischemic stroke (hazard ratio 2.03; 95% CI 1.24-3.31: P  < 0.0046). CONCLUSION: MAC is an independent predictor of long-term stroke risk in a racially diverse population beyond conventional cardiovascular risk factors and atrial fibrillation.

When Does a Calcium Score Equate to Secondary Prevention?: Insights From the Multinational CONFIRM Registry.

BACKGROUND: Elevated coronary artery calcium (CAC) scores in subjects without prior atherosclerotic cardiovascular disease (ASCVD) have been shown to be associated with increased cardiovascular risk. OBJECTIVES: The authors sought to determine at what level individuals with elevated CAC scores who have not had an ASCVD event should be treated as aggressively for cardiovascular risk factors as patients who have already survived an ASCVD event. METHODS: The authors performed a cohort study comparing event rates of patients with established ASVCD to event rates in persons with no history of ASCVD and known calcium scores to ascertain at what level elevated CAC scores equate to risk associated with existing ASCVD. In the multinational CONFIRM (Coronary CT Angiography Evaluation for Clinical Outcomes: An International Multicenter) registry, the authors compared ASCVD event rates in persons without a history of myocardial infarction (MI) or revascularization (as categorized on CAC scores) to event rates in those with established ASCVD. They identified 4,511 individuals without known coronary artery disease (CAC) who were compared to 438 individuals with established ASCVD. CAC was categorized as 0, 1 to 100, 101 to 300, and >300. Cumulative major adverse cardiovascular events (MACE), MACE plus late revascularization, MI, and all-cause mortality incidence was assessed using the Kaplan-Meier method for persons with no ASCVD history by CAC level and persons with established ASCVD. Cox proportional hazards regression analysis was used to calculate HRs with 95% CIs, which were adjusted for traditional cardiovascular risk factors. RESULTS: The mean age was 57.6 ± 12.4 years (56% male). In total, 442 of 4,949 (9%) patients experienced MACEs over a median follow-up of 4 years (IQR: 1.7-5.7 years). Incident MACEs increased with higher CAC scores, with the highest rates observed with CAC score >300 and in those with prior ASCVD. All-cause mortality, MACEs, MACE + late revascularization, and MI event rates were not statistically significantly different in those with CAC >300 compared with established ASCVD (all P > 0.05). Persons with a CAC score <300 had substantially lower event rates. CONCLUSIONS: Patients with CAC scores >300 are at an equivalent risk of MACE and its components as those treated for established ASCVD. This observation, that those with CAC >300 have event rates comparable to those with established ASCVD, supplies important background for further study related to secondary prevention treatment targets in subjects without prior ASCVD with elevated CAC. Understanding the CAC scores that are associated with ASCVD risk equivalent to stable secondary prevention populations may be important for guiding the intensity of preventive approaches more broadly.

Benefit of icosapent ethyl on coronary physiology assessed by computed tomography angiography fractional flow reserve: EVAPORATE-FFRCT.

AIMS: Icosapent ethyl (IPE) significantly reduced ischaemic events in statin-treated patients with atherosclerosis or diabetes and elevated triglycerides in REDUCE-IT, including large reductions in myocardial infarction and elective, urgent, and emergent coronary revascularization. However, the mechanisms driving this clinical benefit are not fully known. The EVAPORATE trial demonstrated that IPE significantly reduced plaque burden. No study to date has assessed the impact of IPE on coronary physiology. Fractional flow reserve (FFR) derived from coronary computed tomography angiography (CTA) data sets (FFRCT) applies computational fluid dynamics to calculate FFR values in epicardial coronary arteries. Our objective was to assess the impact of IPE on coronary physiology assessed by FFRCT using imaging data from EVAPORATE. METHODS AND RESULTS: A total of 47 patients and of 507 coronary lesions at baseline, 9 months, and 18 months with coronary CTA and FFRCT were studied in a blinded core lab. The pre-specified primary endpoint was the FFRCT value in the distal coronary segment from baseline to follow-up in the most diseased vessel per patient using IPE compared with placebo. The pre-specified secondary endpoint was the change in translesional FFRCT (ΔFFRCT) across the most severe (minimum 30% diameter stenosis) coronary lesion per vessel. Baseline FFRCT was similar for IPE compared with placebo (0.83 ± 0.08 vs. 0.84 ± 0.08, P = 0.55). There was significant improvement in the primary endpoint, as IPE improved mean distal segment FFRCT at 9- and 18-month follow-up compared with placebo (0.01 ± 0.05 vs. -0.05 ± 0.09, P = 0.02, and -0.01 ± 0.09 vs. -0.09 ± 0.12, P = 0.03, respectively). ΔFFRCT in 140 coronary lesions was improved, although not statistically significant, with IPE compared with placebo (-0.06 ± 0.08 vs. -0.09 ± 0.1, P = 0.054). CONCLUSION: Icosapent ethyl demonstrated significant benefits in coronary physiology compared with placebo. This early and sustained improvement in FFRCT at 9- and 18-month follow-up provides mechanistic insight into the clinical benefit observed in the REDUCE-IT trial. Furthermore, this is the first assessment of FFRCT to determine drug effect.

Coronary artery calcium progression and all-cause mortality.

BACKGROUND: Coronary artery calcium (CAC) has been demonstrated as a noninvasive, low-cost means of assessing atherosclerotic burden and risk of major cardiovascular events. While it has been previously shown that CAC progression predicts all-cause mortality, we sought to quantify this association by examining a large cohort over a follow-up period of 1-22 years. METHODS: We studied 3260 persons aged 30-89 years referred by their primary physician for CAC measurement, with a follow-up scan at least 12 months from the initial scan. Receiver operator characteristic (ROC) curves assessed a level of annualized CAC progression that predicted all-cause mortality. Multivariate analyses using Cox proportional hazards models were used to compute hazard ratios and 95% confidence intervals (CIs) for the association between annualized CAC progression and death after adjusting for relevant cardiovascular risk factors. RESULTS: The average time between scans was 4.7 ±â€…3.2 years with an additional average of 9.1 ±â€…4.0 years of follow-up time. The average age of the cohort was 58.1 ±â€…10.5 years, 70% being male, and 164 deaths occurred. Annualized CAC progression of 20 units optimized sensitivity (58%) and specificity (82%) in ROC curve analysis. Annualized CAC progression of 20 units was significantly associated with mortality while adjusting for age, sex, race, diabetes, hypertension, hyperlipidemia, smoking, baseline CAC level, family history, and time between scans, hazard ratio 1.84 (95% CI, 1.28-2.64) P = 0.001. CONCLUSION: Annualized CAC progression of greater than 20 units per year significantly predicts all-cause mortality. This may add clinical value in encouraging close surveillance and aggressive treatment of individuals within this range.

Association between coronary artery calcium and thoracic spine bone mineral density: Multiethnic Study of Atherosclerosis (MESA).

BACKGROUND AND AIMS: Previously, osteoporosis and coronary artery disease were considered unrelated. However, beyond age, these two conditions appear to share common etiologies that are not yet fully understood. We examined the relationship between thoracic spine bone mineral density (BMD) and severity of coronary artery calcium (CAC) score. METHODS AND RESULTS: MESA is a prospective cohort study of 6814 men and women between the ages of 45 and 84 years, without clinical cardiovascular disease. This study included participants who underwent non-contrast chest CT scans to determine CAC score and thoracic spine BMD. The thoracic spine BMD was categorized into osteoporosis (defined as T score: ≤ -2.5), osteopenia (T-score between: -2.5 and -1) and normal BMD (T-score ≥ -1). There were 3392 subjects who had CAC >0 at baseline. The prevalence of CAC >0 was 36% in normal BMD group, 49% in the osteopenia and 68% in osteoporosis group. After adjusting for risk factors of atherosclerosis, in multivariate regression models we found a significant association between CAC and osteoporosis (OR: 1.40, 95% CI 1.16-1.69, p value < 0.0004). Furthermore, we stratified our results by gender and found a statistically significant association in both men and women. CONCLUSION: Results from this cross-sectional analysis of a large population based ethnically diverse cohort indicate a significant inverse relationship between thoracic BMD and CAC in both genders independent of other cardiovascular risk factors. Future studies need to explore the underlying pathophysiological mechanisms relating BMD and coronary artery calcification.

Coronary plaque progression is greater in systemic lupus erythematosus than rheumatoid arthritis.

BACKGROUND: Systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA) are associated with a high incidence of cardiovascular disease. Coronary atherosclerosis, particularly total plaque and noncalcified plaque on coronary computed tomography angiography (CCTA) has been correlated with cardiovascular events. We compared baseline coronary plaque burden and progression by serial CCTA in SLE and RA patients. METHODS: We prospectively evaluated 44 patients who underwent serial CCTA examinations to quantify coronary plaque progression, 22 SLE patients, and 22 age- and sex-matched RA patients. Semiautomated plaque software was used for quantitative plaque assessment. Linear regression examined the effect of SLE diagnosis (versus RA) on annualized change in natural log-transformed total normalized atheroma volume (ln-TAV norm ) for low-attenuation, fibrofatty, fibrous, total noncalcified, densely calcified, and total plaque. RESULTS: No quantitative differences for any plaque types were observed at baseline between SLE and RA patients ( P = 0.330-0.990). After adjustment for baseline plaque and cardiovascular risk factors, the increase in ln-TAV norm was higher in SLE than RA patients for fibrous [Exp-ß: 0.202 (0.398), P = 0.0003], total noncalcified [Exp-ß: 0.179 (0.393), P = 0.0001], and total plaque volume [Exp-ß: 0.154 (0.501), P = 0.0007], but not for low-attenuation, fibrofatty, or densely calcified plaque ( P = 0.103-0.489). Patients with SLE had 80% more fibrous, 82% more noncalcified, and 85% more total plaque increase than those with RA. CONCLUSION: Coronary plaque volume was similar in RA and SLE at baseline. Progression was greater in SLE, which may explain the greater cardiovascular risk in this disease. Further research to evaluate screening and management strategies for cardiovascular disease in these high-risk patients is warranted.

The effect of icosapent ethyl on left atrial and left ventricular morphology.

Atrial fibrillation (AF) is a common arrhythmia associated with poor outcomes. N-3 fatty acids have been shown to provide significant cardiovascular risk reduction, but they may exacerbate the risk of AF. The pathway by which N-3 fatty acids may be arrhythmogenic is unknown. One possible mechanism involves cardiac chamber morphology alteration. The purpose of this study was to investigate the effect of icosapent ethyl (IPE) on left atrial (LA) size and left ventricular (LV) mass. This study used coronary computed tomographic angiography images gathered from the Effect of Icosapent Ethyl on Progression of Coronary Atherosclerosis (EVAPORATE) trial. EVAPORATE was a randomised, double-blind, placebo-controlled study finding a significant reduction in coronary atherosclerosis progression in patients with residually elevated triglycerides despite statin therapy on 4 g IPE daily versus 4 g placebo daily. Computed tomography images were used to measure LA size and LV mass at 0 and 18 months. Of 80 enrolled patients, 68 were included in the final analysis. Baseline demographics and risk factors were similar between IPE and placebo cohorts. LA anterior- posterior diameter measured on axial (p=0.51) and sagittal (p=0.52) orientations were not different over time. Also, there was no difference between groups in the change in LA volume (p=0.84). Change in LV mass was similar between groups (p=0.13). In conclusion, this study did not detect differences in LA size or LV mass over 18 months between patients on 4 g daily IPE versus placebo.

Physical Activity, Muscle Oxidative Capacity, and Coronary Artery Calcium in Smokers with and without COPD.

Introduction: Severe chronic obstructive pulmonary disease (COPD) is partly characterized by diminished skeletal muscle oxidative capacity and concurrent dyslipidemia. It is unknown whether such metabolic derangements increase the risk of cardiovascular disease. This study explored associations among physical activity (PA), muscle oxidative capacity, and coronary artery calcium (CAC) in COPDGene participants. Methods: Data from current and former smokers with COPD (n = 75) and normal spirometry (n = 70) were retrospectively analyzed. Physical activity was measured for seven days using triaxial accelerometry (steps/day and vector magnitude units [VMU]) along with the aggregate of self-reported PA amount and PA difficulty using the PROactive D-PPAC instrument. Muscle oxidative capacity (k) was assessed via near-infrared spectroscopy, and CAC was assessed via chest computerized tomography. Results: Relative to controls, COPD patients exhibited higher CAC (median [IQR], 31 [0-431] vs 264 [40-799] HU; p = 0.003), lower k (mean ± SD = 1.66 ± 0.48 vs 1.25 ± 0.37 min-1; p < 0.001), and lower D-PPAC total score (65.2 ± 9.9 vs 58.8 ± 13.2; p = 0.003). Multivariate analysis-adjusting for age, sex, race, diabetes, disease severity, hyperlipidemia, smoking status, and hypertension-revealed a significant negative association between CAC and D-PPAC total score (ß, -0.05; p = 0.013), driven primarily by D-PPAC difficulty score (ß, -0.03; p = 0.026). A 1 unit increase in D-PPAC total score was associated with a 5% lower CAC (p = 0.013). There was no association between CAC and either k, steps/day, VMU, or D-PPAC amount. Conclusion: Patients with COPD and concomitantly elevated CAC exhibit greater perceptions of difficulty when performing daily activities. This may have implications for exercise adherence and risk of overall physical decline.

Obstructive coronary artery disease in symptomatic diabetics with zero coronary calcium score: are we missing something?

BACKGROUND: Prevalence and severity of coronary artery disease (CAD) in symptomatic patients with zero coronary artery calcium score (CACS) are unclear, particularly in regard to the diabetic population, which represents, per se, a subgroup at increased cardiovascular risk. The aim of this study was to investigate the prevalence and severity of CAD by coronary computed tomography angiography (CCTA) in a symptomatic diabetic cohort with zero CACS. METHODS: All consecutive symptomatic diabetics referred for CAD suspicion were included in this study. All subjects underwent a noncontrast coronary artery calcium scan followed by CCTA. CACS was quantified using the Agatston method. CAD was defined as a total plaque score (TPS) greater than zero. Obstructive and severe obstructive CAD were defined respectively as luminal stenosis >50% and >70% in at least one coronary segment. RESULTS: We identified 1722 symptomatic diabetics (mean age 62.5 ± 12.9 years, 62% men). One hundred and eleven subjects had zero CACS and TPS >0 (mean age was 49.5 ± 14.8, 58% women, 56% Hispanics). Sixty-five patients (58.5%) had one-vessel disease, followed by 30 (27%) with two-vessel disease and 14 (12.6%) with ≥ three-vessel disease. Obstructive CAD was found in 11 subjects and, among these, three were categorized as severe obstructive CAD. CONCLUSION: In symptomatic diabetic patients with zero CACS, CAD, including obstructive disease, can still occur and is predominant in middle-aged adults, women and Hispanics. In symptomatic diabetics CCTA is a critical step for accurate risk stratification even when CACS would have placed some of these individuals in a lower-risk category.

Coronary artery calcium and bone mineral density by serial CTA: Does menopausal hormone therapy modify the association?

INTRODUCTION: Both osteoporosis and cardiovascular disease (CVD) increase in women after menopause. Estrogen deficiency is thought to be an underlying mechanism for both these conditions. METHODS: Healthy menopausal women (n = 374, age 42-58 years) underwent cardiac CT scans over four years as participants in the Kronos Early Estrogen Prevention Study (KEEPS), a randomized, controlled trial to Women randomized to either oral conjugated equine estrogens (o-CEE, n = 104), transdermal 17ß-estradiol (t-E2, n = 119) or placebo (n-115). CAC (Agatston units, AU), and BMD (mg/cm3) were measured from thoracic vertebrae at baseline and at the 4 years of the study using validated software. ANOVA and multiple linear regression analyzed the association between incident CAC or progression of CAC and BMD among the treatment groups. RESULTS: At baseline 374 women, 40 participants with CAC >0 had greater decrements in BMD than the 334 participants with CAC = 0 at baseline, The average change in BMD in o-CEE group with CAC was -9.6 ± 13.3 versus -3.1 ± 19.5 in those with zero CAC, p = 0.0018. With t-E2, BMD changed by -11.7 ± 26.2 in those with CAC versus +5.7 ± 26.2 in the zero CAC group, p ≤ 0. 0001. Similarly in the 66 participants that showed progression of CAC >1, had more BMD loss, than those with stable CAC regardless of the treatment. CONCLUSION: Progression of bone loss is reduced among women treated with o-CEE or t-E2. Progression of CAC is associated with greater BMD loss, a relationship that is differentially modified by t-E2 and o-CEE.