Coronary Artery Plaque Burden Research Articles

Coronary Plaque Characteristics in Patients With Chronic Kidney Failure: Impact on Cardiovascular Events and Mortality.

In patients with coronary artery disease, coronary plaques with high-risk features and low-attenuation plaque burden are independent measures associated with major adverse cardiovascular events (MACEs). Patients with chronic kidney failure may have different coronary artery disease characteristics. The aim was to assess the association of coronary plaque characteristics and coronary artery disease extent with MACE and all-cause mortality in patients with chronic kidney failure. Potential kidney transplant candidates who underwent coronary computed tomography angiography as part of the cardiac screening program before kidney transplantation were included. We evaluated high-risk plaques and diameter stenosis semiqualitatively and quantified coronary artery calcium score and plaque burden (percentage atheroma volume). In 484 patients with chronic kidney failure and few or no symptoms of coronary artery disease (mean age, 53±12 years; 62% men; 32% on dialysis), 56 (12%) patients suffered MACE and 69 (14%) patients died during a median follow-up of 4.9 years. High-risk plaques were present in 39 (70%) patients with MACE. Median calcified plaque burden was 3.7% in patients with MACE versus 0.2% in patients without MACE. The median low-attenuation plaque burden was 0.3% versus 0.03%, respectively. In semiqualitative analyses, the presence of high-risk plaque and a higher coronary artery calcium score were associated with increased risk of MACE (hazard ratio (HR), 2.0 [95% CI, 1.0-3.7]; P=0.040; HR, 1.2 [95% CI, 1.0-1.3]; P=0.014), respectively. Neither were associated with all-cause mortality. In quantified analysis, increasing levels of both calcified and low-attenuation plaque burdens were associated with risk of MACE (HR, 2.6 [95% CI, 1.8-3.7]; P<0.001; HR, 2.6 [95% CI, 1.5-4.5]; P=0.001 [per variable doubling, respectively]) and all-cause mortality (HR, 1.6 [95% CI, 1.2-2.1]; P=0.002; HR, 1.8 [95% CI, 1.1-3.0]; P=0.028, respectively). In patients with chronic kidney failure, calcified and low-attenuation plaque burdens were independently associated with MACE and all-cause mortality, while high-risk plaques and coronary artery calcium score were only associated with MACE. URL: https://www.clinicaltrials.gov; Unique identifier: NCT01344434.

Age- and sex-based heterogeneity in coronary artery plaque presence and burden in familial hypercholesterolemia: A multi-national study

ObjectivesIndividuals with familial hypercholesterolemia (FH) are at an increased risk for coronary artery disease (CAD). While prior research has shown variability in coronary artery calcification (CAC) among those with FH, studies with small sample sizes and single-center recruitment have been limited in their ability to characterize CAC and plaque burden in subgroups based on age and sex. Understanding the spectrum of atherosclerosis may result in personalized risk assessment and tailored allocation of costly add-on, non-statin lipid-lowering therapies. We aimed to characterize the presence and burden of CAC and coronary plaque on computed tomography angiography (CTA) across age- and sex-stratified subgroups of individuals with FH who were without CAD at baseline. MethodsWe pooled 1,011 patients from six cohorts across Brazil, France, the Netherlands, Spain, and Australia. Our main measures of subclinical atherosclerosis included CAC ranges (i.e., 0, 1–100, 101–400, >400) and CTA-derived plaque burden (i.e., no plaque, non-obstructive CAD, obstructive CAD). ResultsNinety-five percent of individuals with FH (mean age: 48 years; 54% female; treated LDL-C: 154 mg/dL) had a molecular diagnosis and 899 (89%) were on statin therapy. Overall, 423 (42%) had CAC=0, 329 (33%) had CAC 1–100, 160 (16%) had CAC 101–400, and 99 (10%) had CAC >400. Compared to males, female patients were more likely to have CAC=0 (48% [n = 262] vs 35% [n = 161]) and no plaque on CTA (39% [n = 215] vs 26% [n = 120]). Among patients with CAC=0, 85 (20%) had non-obstructive CAD. Females also had a lower prevalence of obstructive CAD in CAC 1–100 (8% [n = 15] vs 18% [n = 26]), CAC 101–400 (32% [n = 22] vs 40% [n = 36]), and CAC >400 (52% [n = 16] vs 65% [n = 44]). Female patients aged 50–59 years were less likely to have obstructive CAD in CAC >400 (55% [n = 6] vs 70% [n = 19]). ConclusionIn this large, multi-national study, we found substantial age- and sex-based heterogeneity in CAC and plaque burden in a cohort of predominantly statin-treated individuals with FH, with evidence for a less pronounced increase in atherosclerosis among female patients. Future studies should examine the predictors of resilience to and long-term implications of the differential burden of subclinical coronary atherosclerosis in this higher risk population.

Abstract 18480: Type 2 Diabetic Patients Have Increased Coronary Plaque Burden and Plaque Progression During 10-Year Serial Coronary CT Angiography Follow-Up

Background Individuals diagnosed with type 2 diabetes are at high risk for coronary artery disease, however, data on long-term progression of coronary artery plaque burden is lacking. This study investigated atherosclerotic plaque characteristics and long-term plaque progression in patients with and without type 2 diabetes mellitus (T2DM). Methods: Per-protocol, patients from a coronary CT angiography (CCTA) cohort were invited for repeat CCTA imaging, regardless of symptoms. A total of 299 patients underwent follow-up CCTA imaging with a median scan interval of 10.2 [IQR 8.7-11.2] years. Patients who underwent coronary artery bypass grafting and vessels revascularized by percutaneous coronary intervention were excluded. Scans were analyzed using atherosclerosis imaging-quantitative CCTA (AI-QCT; Cleerly Inc.). The associations between diabetic status, baseline and follow-up plaque burden and characteristics were evaluated using multivariable regression adjusted for clinical risk factors, statin use and scanner settings. Results: In total, 274 patients were included, 43 (15.7%) had T2DM at baseline. The mean age was 57±7 years, 42% were women. At baseline, patients with T2DM had a median percent atheroma volume (PAV) of 6.80 (2.80, 17.70) at baseline; patients without T2DM had a median PAV of 3.20 (0.80, 9.55). Adjusted for clinical risk factors, patients with T2DM had a higher rate of plaque progression (Figure 1). The difference in PAV caused by T2DM was similar to the effect of a 13-year age difference. At baseline patients with T2DM had a higher prevalence of high-risk plaque (OR 2.11; p=0.025). After 10 years of follow-up, patients with T2DM had a higher prevalence of both high-risk plaque (OR 3.49; p&lt;0.001) and low-density plaque (OR 3.74; p&lt;0.001). Conclusion Patients with T2DM had a more than twofold higher coronary plaque burden, increased plaque progression during 10-year follow-up and had an increased prevalence of high-risk and low-density plaque.

Insulin resistance is associated with high-risk coronary artery plaque composition in asymptomatic men between 65 and 75 years and no diabetes: A DANCAVAS cross-sectional sub-study

Background and aimsInsulin resistance (IR) and pre-diabetes are associated with an increased risk of cardiovascular disease (CVD). We aimed to investigate vulnerable plaque composition in relation to IR and pre-diabetes in asymptomatic non-diabetic men. MethodsAll participants underwent a contrast-enhanced coronary computed tomography angiography (CCTA) to evaluate coronary artery plaque burden and plaque composition (necrotic core, dense calcium, fibrotic and fibrous-fatty volume). Homeostasis model assessment of IR (HOMA-IR) was used, and participants were stratified into tertiles. Participants underwent a standard oral glucose tolerance test (OGTT) and were categorized into 2 groups (normal glucose tolerance (NGT) or pre-diabetes). A multivariable linear regression model was used to evaluate the association between vulnerable plaque composition and IR or glycemic group. ResultsFour-hundred-and-fifty non-diabetic men without known CAD were included. The mean age was 70 ± 3 years. Participants in the higher HOMA-IR tertile (H-IR) had higher median necrotic plaque volume compared to the lower HOMA-IR tertile (L-IR) (18.2 vs. 11.0 mm3, p = 0.02). H-IR tertile (β 0.37 [95% CI 0.10–0.65], p = 0.008), pack-years (β 0.07 [95% CI 0.007–0.14], p = 0.03) and total atheroma volume (TAV) (β 0.47 [95% CI 0.36–0.57], p < 0.001) remained associated with necrotic plaque volume in the multivariable linear regression model. ConclusionsIR was associated with necrotic plaque volume in asymptomatic men without diabetes. Thus, even in asymptomatic men without diabetes, IR seems to have an incremental effect on necrotic plaque volume and vulnerable plaque composition.

Association of serum cystatin C level with coronary atherosclerotic plaque burden: a comprehensive analysis of observational studies and genetic study

Background and AimsEpidemiological studies show that high circulating cystatin C is associated with risk of cardiovascular disease (CVD), independent of creatinine-based renal function measurements. However, the relationship between serum cystatin C level and coronary atherosclerotic plaque burden is limited. We aimed to evaluate the relationship between circulating cystatin C and coronary atherosclerotic plaque burden.MethodsThis study was a cross-sectional study based on China community population. Measurements of plaque burden were based on the segment-involvement score (SIS) and segment stenosis score (SSS), which derived from the Coronary Artery Tree Model Depicting Coronary Artery Plaque Scores. Logistic regression model was used to demonstrate the association between cystatin C level and coronary artery plaque burden. Mendelian randomization (MR) analyses were conducted to assess the causal effect of cystatin C level on coronary atherosclerosis risk.ResultsA total of 3,043 objects were included in the present study. The odds risks (OR) of severe plaque burden in the highest serum cystatin C levels (OR: 2.50; Cl:1.59–3.91; P < 0.001) and medium-level cystatin C levels (OR: 1.86; 95% Cl: 1.21–2.88; P = 0.005) were significantly higher after fulled adjusted confounders compared with the lowest levels of serum cystatin C by SSS. The MR analysis showed that genetic predicted cystatin C levels was associated with an increased risk of coronary atherosclerosis (OR, 1.004; 95% CI, 1.002–1.006, P < 0.001) .ConclusionElevated serum cystatin C levels were associated with coronary atherosclerotic plaque burden. Cystatin C levels had a causal effect on an increased risk of coronary atherosclerosis at the genetic level.What is already known on this topic?Coronary artery disease is currently the most common cardiovascular disease and the leading global cause of mortality. Previous studies reported that higher serum cystatin C levels were associated with an increased risk for future cardiovascular events, independent of the normal creatinine levels or estimated glomerular filtration rate (eGFR) values. The presence of high-risk coronary atherosclerotic plaque burden is associated with increased risk of cardiovascular events. However, the association between serum cystatin C and coronary atherosclerotic plaque burden is not very clear.What this study adds?Our study demonstrated that the elevated serum cystatin C levels were associated with coronary atherosclerotic plaque burden. In addition, we found that serum cystatin C levels had a causal effect on an increased risk of coronary atherosclerosis at the genetic level.How this study might affect research, practice or policy?Current research finds that serum cystatin C levels were associated with coronary atherosclerosis. The metabolic pathway of cystatin C could be a target for new therapies against CAD.

Prevalence of atherosclerosis in individuals with prediabetes and diabetes compared to normoglycaemic individuals—a Swedish population-based study

BackgroundPatients with type 2 diabetes have an increased risk of death and cardiovascular events and people with diabetes or prediabetes have been found to have increased atherosclerotic burden in the coronary and carotid arteries. This study will estimate the cross-sectional prevalence of atherosclerosis in the coronary and carotid arteries in individuals with prediabetes and diabetes, compared with normoglycaemic individuals in a large population-based cohort.MethodsThe 30,154 study participants, 50–64 years, were categorized according to their fasting glycaemic status or self-reported data as normoglycaemic, prediabetes, and previously undetected or known diabetes. Prevalence of affected coronary artery segments, severity of stenosis and coronary artery calcium score (CACS) were determined by coronary computed tomography angiography. Total atherosclerotic burden was assessed in the 11 clinically most relevant segments using the Segment Involvement Score and as the presence of any coronary atherosclerosis. The presence of atherosclerotic plaque in the carotid arteries was determined by ultrasound examination.ResultsStudy participants with prediabetes (n = 4804, 16.0%) or diabetes (n = 2282, 7.6%) had greater coronary artery plaque burden, more coronary stenosis and higher CACS than normoglycaemic participants (all, p < 0.01). Among male participants with diabetes 35.3% had CACS ≥ 100 compared to 16.1% among normoglycaemic participants. For women, the corresponding figures were 8.9% vs 6.1%. The prevalence of atherosclerosis in the coronary arteries was higher in participants with previously undetected diabetes than prediabetes, but lower than in patients with known diabetes. The prevalence of any plaque in the carotid arteries was higher in participants with prediabetes or diabetes than in normoglycaemic participants.ConclusionsIn this large population-based cohort of currently asymptomatic people, the atherosclerotic burden in the coronary and carotid arteries increased with increasing degree of dysglycaemia. The finding that the atherosclerotic burden in the coronary arteries in the undetected diabetes category was midway between the prediabetes category and patients with known diabetes may have implications for screening strategies and tailored prevention interventions for people with dysglycaemia in the future.

Lipidomics Profiling and Risk of Coronary Artery Disease in the BioHEART-CT Discovery Cohort

The current coronary artery disease (CAD) risk scores for predicting future cardiovascular events rely on well-recognized traditional cardiovascular risk factors derived from a population level but often fail individuals, with up to 25% of first-time heart attack patients having no risk factors. Non-invasive imaging technology can directly measure coronary artery plaque burden. With an advanced lipidomic measurement methodology, for the first time, we aim to identify lipidomic biomarkers to enable intervention before cardiovascular events. With 994 participants from BioHEART-CT Discovery Cohort, we collected clinical data and performed high-performance liquid chromatography with mass spectrometry to determine concentrations of 683 plasma lipid species. Statin-naive participants were selected based on subclinical CAD (sCAD) categories as the analytical cohort (n = 580), with sCAD+ (n = 243) compared to sCAD− (n = 337). Through a machine learning approach, we built a lipid risk score (LRS) and compared the performance of the existing Framingham Risk Score (FRS) in predicting sCAD+. We obtained individual classifiability scores and determined Body Mass Index (BMI) as the modifying variable. FRS and LRS models achieved similar areas under the receiver operating characteristic curve (AUC) in predicting the validation cohort. LRS enhanced the prediction of sCAD+ in the healthy-weight group (BMI &lt; 25 kg/m2), where FRS performed poorly and identified individuals at risk that FRS missed. Lipid features have strong potential as biomarkers to predict CAD plaque burden and can identify residual risk not captured by traditional risk factors/scores. LRS compliments FRS in prediction and has the most significant benefit in healthy-weight individuals.

Sex differences in computed tomography angiography-derived coronary plaque burden in relation to invasive fractional flow reserve

BackgroundDistinct sex-related differences exist in coronary artery plaque burden and distribution. We aimed to explore sex differences in quantitative plaque burden by coronary CT angiography (CCTA) in relation to ischemia by invasive fractional flow reserve (FFR). MethodsThis post-hoc analysis of the PACIFIC trial included 581 vessels in 203 patients (mean age 58.1 ​± ​8.7 years, 63.5% male) who underwent CCTA and per-vessel invasive FFR. Quantitative assessment of total, calcified, non-calcified, and low-density non-calcified plaque burden were performed using semiautomated software. Significant ischemia was defined as invasive FFR ≤0.8. ResultsThe per-vessel frequency of ischemia was higher in men than women (33.5% vs. 7.5%, p ​< ​0.001). Women had a smaller burden of all plaque subtypes (all p ​< ​0.01). There was no sex difference on total, calcified, or non-calcified plaque burdens in vessels with ischemia; only low-density non-calcified plaque burden was significantly lower in women (beta: -0.183, p ​= ​0.035). The burdens of all plaque subtypes were independently associated with ischemia in both men and women (For total plaque burden (5% increase): Men, OR: 1.15, 95%CI: 1.06–1.24, p ​= ​0.001; Women, OR: 1.96, 95%CI: 1.11–3.46, p ​= ​0.02). No significant interaction existed between sex and total plaque burden for predicting ischemia (interaction p ​= ​0.108). The addition of quantitative plaque burdens to stenosis severity and adverse plaque characteristics improved the discrimination of ischemia in both men and women. ConclusionsIn symptomatic patients with suspected CAD, women have a lower CCTA-derived burden of all plaque subtypes compared to men. Quantitative plaque burden provides independent and incremental predictive value for ischemia, irrespective of sex.

Coronary Artery Lesion Lipid Content and Plaque Burden in Diabetic and Nondiabetic Patients: PROSPECT II.

Patients with diabetes have increased rates of major adverse cardiac events (MACEs). We hypothesized that this is explained by diabetes-associated differences in coronary plaque morphology and lipid content. In PROSPECT II (Providing Regional Observations to Study Predictors of Events in the Coronary Tree), 898 patients with acute myocardial infarction with or without ST-segment elevation underwent 3-vessel quantitative coronary angiography and coregistered near-infrared spectroscopy and intravascular ultrasound imaging after successful percutaneous coronary intervention. Subsequent MACEs were adjudicated to either treated culprit lesions or untreated nonculprit lesions. This substudy stratified patients by diabetes status and assessed baseline culprit and nonculprit prevalence of high-risk plaque characteristics defined as maximum plaque burden ≥70% and maximum lipid core burden index ≥324.7. Separate covariate-adjusted multivariable models were performed to identify whether diabetes was associated with nonculprit lesion-related MACEs and high-risk plaque characteristics. Diabetes was present in 109 of 898 patients (12.1%). During a median 3.7-year follow-up, MACEs occurred more frequently in patients with versus without diabetes (20.1% versus 13.5% [odds ratio (OR), 1.94 (95% CI, 1.14-3.30)]), primarily attributable to increased risk of myocardial infarction related to culprit lesion restenosis (4.3% versus 1.1% [OR, 3.78 (95% CI, 1.12-12.77)]) and nonculprit lesion-related spontaneous myocardial infarction (9.3% versus 3.8% [OR, 2.74 (95% CI, 1.25-6.04)]). However, baseline prevalence of high-risk plaque characteristics was similar for patients with versus without diabetes concerning culprit (maximum plaque burden ≥70%: 90% versus 93%, P=0.34; maximum lipid core burden index ≥324.7: 66% versus 70%, P=0.49) and nonculprit lesions (maximum plaque burden ≥70%: 23% versus 22%, P=0.37; maximum lipid core burden index ≥324.7: 26% versus 24%, P=0.47). In multivariable models, diabetes was associated with MACEs in nonculprit lesions (adjusted OR, 2.47 [95% CI, 1.21-5.04]) but not with prevalence of high-risk plaque characteristics (adjusted OR, 1.21 [95% CI, 0.86-1.69]). Among patients with recent myocardial infarction, both treated and untreated lesions contributed to the diabetes-associated ≈2-fold increased MACE rate during the 3.7-year follow-up. Diabetes-related plaque characteristics that might underlie this increased risk were not identified by multimodality imaging. URL: https://www. gov; Unique identifier: NCT02171065.

Comparison of Framingham risk score and pooled cohort equations for the prediction of coronary atherosclerosis in patients who meet the target LDL-C level of Korean dyslipidemia guideline.

This study aims to compare the predicting performance of coronary atherosclerosis between Framingham Risk Score (FRS) and Pooled Cohort Equations (PCE) in moderate to high-risk patients who meet the target low-density lipoprotein cholesterol (LDL-C) level of Korean dyslipidemia guidelines. Among 1207 patients aged 40 to 65 who underwent coronary computed tomography angiography at outpatient for chest discomfort, we included 414 moderate-risk patients (non-diabetes) and 86 high-risk patients (diabetes). They were divided into 3 groups according to FRS and PCE, then compared with coronary artery calcification score (CACS) and plaque burden degree strata. We presented receiver operating characteristic curves for the presence of coronary artery calcification (CAC) and any plaque. In moderate-risk patients, the distribution of CACS and plaque burden degree according to FRS and PCE risk strata showed significant differences between groups and a consistent trend (P < .001). Both FRS and PCE showed good discrimination for the presence of CAC [area under the curve (AUC); 0.711 vs 0.75, P = .02] and any plaque (AUC; 0.72 vs 0.756, P = .025). However, in high-risk patients, there was no significant differences or consistent trend between groups and the AUC values of FRS and PCE were (0.537 vs 0.571, P = .809) for CAC and (0.478 vs 0.65 P = .273) for any plaque showing poor discrimination. In predicting coronary atherosclerosis in moderate to high-risk patients who meet the target LDL-C level of Korean dyslipidemia guidelines, both FRS and PCE can be used in moderate-risk patients but not in high-risk patients.

Coronary Computed Tomography Angiography Evaluation of Plaque Morphology and Its Relationship to HDL and Total Cholesterol to HDL Ratio

<h3>Lead Author's Financial Disclosures</h3> Nothing to disclose. <h3>Study Funding</h3> None. <h3>Background/Synopsis</h3> Traditionally non-high-density lipoprotein (non-HDL) indicators have been utilized to stratify cardiovascular risk. Population studies have demonstrated an inverse relationship between HDL cholesterol levels and cardiovascular risk, however, the mechanism by which HDL exhibits its protective effect on the cardiovascular system remains unclear. <h3>Objective/Purpose</h3> To investigate the relationship between the HDL-C level and the total cholesterol to HDL (TC/HDL) ratio with coronary artery plaque burden as determined by coronary computed tomography angiography (CCTA). <h3>Methods</h3> This is a cross-sectional study evaluating the association of HDL-C and TC/HDL ratio with coronary artery plaque volumes. We identified 190 subjects who had undergone quantitative plaque analysis and had lipoprotein values available at our institution. Plaque was analyzed quantitatively utilizing semi-automated plaque analysis software (QAngio version 2.0.5). The plaque volumes are presented as total atheroma volume normalized (TAVnorm). The HDL-C level and TC/HDL ratio were analyzed as continuous variables and categorized at clinically relevant levels. Multivariate regression models adjusted for cardiovascular risk factors were used to evaluate the association of HDL-C and TC/HDL ratio with coronary plaque volumes. <h3>Results</h3> The mean (SD) age of the 190 subjects was 58.9 (+/-9.8) years, and 63% were male. After adjustment for cardiovascular risk factors, HDL- C (>40mg/dL) is inversely associated with fibrous (p=0.003), fibrous fatty (p=0.009), low attenuation plaque (LAP) (p=0.014), total non- calcified plaque (TNCP)(p=0.003), and total plaque (TP)(p=0.005) volume but not associated with dense calcified plaque (p=0.229). TC/HDL ratio (>4.0) is directly associated with LAP (p=0.024) and not associated with fibrous, fibrofatty, TNCP, dense calcified plaque and TP volume. Notably, when examined as continuous variables, increasing HDL- C level is inversely associated with fibrous plaque, TNCP and TP volume and increasing TC/HDL ratio is directly associated with increasing fibrous plaque, and fibrous fatty plaque, LAP, TNCP and TP volume, independent of other risk factors. <h3>Conclusions</h3> There is a strong association between low HDL-C and increasing TC/HDL ratio with increasing coronary plaque volumes, independent of traditional risk factors of atherosclerosis. The findings of this study suggest mechanistic evidence supporting the protective role of HDL-C in coronary artery disease. Additionally, TC/HDL ratio offers value as a secondary treatment target beyond LDL-C, which is especially beneficial in individuals with prevalent lipid discordance, such as those with diabetes and metabolic syndrome.

Multimodality Imaging Trials Evaluating the Impact of Omega-3 Fatty Acids on Coronary Artery Plaque Characteristics and Burden.

Treatment of established risk factors, especially low-density lipoprotein (LDL) cholesterol, is the cornerstone of preventing atherosclerotic coronary artery disease. Despite reducing LDL cholesterol, there remains a significant risk of cardiovascular disease. Inflammatory and metabolic pathways contribute to recurrence of cardiovascular events, and are often missed in clinical practice. Eicosapentaenoic acid (EPA) may play a crucial role in reducing residual risk of cardiovascular disease. In this review we discuss the clinical applications of omega-3 fatty acids (OM3FAs), their mechanism of action, the difference between pure EPA and docosahexaenoic acid components, and the latest cardiovascular outcome trials and imaging trials evaluating coronary plaque. PubMed and EMBASE were searched to include all the remarkable clinical trials investigating OM3FAs and cardiovascular disease. Beyond statins, additional medications are required to reduce the risk of cardiovascular disease. EPA has shown cardiovascular benefit in addition to statins in large outcome trials. Additionally, multiple serial-imaging studies have demonstrated benefits on plaque progression and stabilization. Due to its pleotropic properties, icosapent ethyl outperforms other OM3FAs in decreasing cardiovascular disease risk in both patients with and without high triglycerides, and is currently recommended as an adjunct to statins. To further strengthen the current evidence, additional research is required to elucidate the inconsistencies between the effects of pure EPA and EPA plus docosahexaenoic acid.

Multimodality Imaging Trials Evaluating the Impact of Omega-3 Fatty Acids on Coronary Artery Plaque Characteristics and Burden

Treatment of established risk factors, especially low-density lipoprotein (LDL) cholesterol, is the cornerstone of preventing atherosclerotic coronary artery disease. Despite reducing LDL cholesterol, there remains a significant risk of cardiovascular disease. Inflammatory and metabolic pathways contribute to recurrence of cardiovascular events, and are often missed in clinical practice. Eicosapentaenoic acid (EPA) may play a crucial role in reducing residual risk of cardiovascular disease. In this review we discuss the clinical applications of omega-3 fatty acids (OM3FAs), their mechanism of action, the difference between pure EPA and docosahexaenoic acid components, and the latest cardiovascular outcome trials and imaging trials evaluating coronary plaque. PubMed and EMBASE were searched to include all the remarkable clinical trials investigating OM3FAs and cardiovascular disease. Beyond statins, additional medications are required to reduce the risk of cardiovascular disease. EPA has shown cardiovascular benefit in addition to statins in large outcome trials. Additionally, multiple serial-imaging studies have demonstrated benefits on plaque progression and stabilization. Due to its pleotropic properties, icosapent ethyl outperforms other OM3FAs in decreasing cardiovascular disease risk in both patients with and without high triglycerides, and is currently recommended as an adjunct to statins. To further strengthen the current evidence, additional research is required to elucidate the inconsistencies between the effects of pure EPA and EPA plus docosahexaenoic acid.

Association of Lipoprotein(a) With Atherosclerotic Plaque Progression

BackgroundLipoprotein(a) [Lp(a)] is associated with increased risk of myocardial infarction, although the mechanism for this observation remains uncertain. ObjectivesThis study aims to investigate whether Lp(a) is associated with adverse plaque progression. MethodsLp(a) was measured in patients with advanced stable coronary artery disease undergoing coronary computed tomography angiography at baseline and 12 months to assess progression of total, calcific, noncalcific, and low-attenuation plaque (necrotic core) in particular. High Lp(a) was defined as Lp(a) ≥ 70 mg/dL. The relationship of Lp(a) with plaque progression was assessed using linear regression analysis, adjusting for body mass index, segment involvement score, and ASSIGN score (a Scottish cardiovascular risk score comprised of age, sex, smoking, blood pressure, total and high-density lipoprotein [HDL]–cholesterol, diabetes, rheumatoid arthritis, and deprivation index). ResultsA total of 191 patients (65.9 ± 8.3 years of age; 152 [80%] male) were included in the analysis, with median Lp(a) values of 100 (range: 82 to 115) mg/dL and 10 (range: 5 to 24) mg/dL in the high and low Lp(a) groups, respectively. At baseline, there was no difference in coronary artery disease severity or plaque burden. Patients with high Lp(a) showed accelerated progression of low-attenuation plaque compared with low Lp(a) patients (26.2 ± 88.4 mm3 vs −0.7 ± 50.1 mm3; P = 0.020). Multivariable linear regression analysis confirmed the relation between Lp(a) and low-attenuation plaque volume progression (β = 10.5% increase for each 50 mg/dL Lp(a), 95% CI: 0.7%-20.3%). There was no difference in total, calcific, and noncalcific plaque volume progression. ConclusionsAmong patients with advanced stable coronary artery disease, Lp(a) is associated with accelerated progression of coronary low-attenuation plaque (necrotic core). This may explain the association between Lp(a) and the high residual risk of myocardial infarction, providing support for Lp(a) as a treatment target in atherosclerosis.

Impact of epicardial adipose tissue accumulation on left ventricular mass and hypertrophy in non-obstructive coronary artery disease

Abstract Introduction Increased left ventricular mass index (LVMi) and left ventricular hypertrophy (LVH) by echocardiography are common in obesity and important cardiovascular risk predictors associated with myocardial ischemia in non-obstructive coronary artery disease (CAD). Accumulation of epicardial adipose tissue (EAT) suggest a possible direct impact on LVMi and LVH. Purpose To explore the association between EAT volume, LVMi and LVH in patients with chest pain and non-obstructive CAD. Methods We included 129 patients with chest pain and non-obstructive CAD (&amp;lt;50% stenosis) by coronary computed tomography (CT) angiography. EAT volume was quantified using a semiautomatic analysis software on non-contrast cardiac CT images. Patients were grouped according to EAT volume, where high EAT volume was adjudicated when EAT volume was in the highest tertile (≥125 ml). Left ventricular mass was assessed by echocardiography, calculated by the Devereux formula and indexed for height in the allometric power of 2.7 (LVMi). LVH was defined as LVMi &amp;gt;46.7 g/m2.7 in women and &amp;gt;49.2 g/m2.7 in men. Coronary artery plaque burden was assessed as calcium score and segment involvement score on coronary CT angiography. Results High EAT volume was more common in men with higher BMI, waist circumference, serum triglycerides and higher prevalence of hypertension and obesity (all p&amp;lt;0.05). Age, coronary calcium score and coronary artery segment involvement score did not differ between groups. Patients with high EAT volume had higher LVMi compared to those with low EAT volume (42.5 g/m2.7 vs. 36.1 g/m2.7, p=0.003), while there was no difference in EAT volume among patients with or without LVH. In univariable logistic regression analysis, high EAT volume was associated with higher LVMi (OR 1.05 [95% CI 1.01–1.10] per g/m2.7, p=0.015). After adjusting for hypertension and obesity in a multivariable model, higher LVMi remained significantly associated with high EAT volume (Model 1, Table 1), but the association was attenuated after adjusting for sex (Model 2, Table 1). Conclusion High EAT volume was associated with increased LVMi in patients with non-obstructive CAD, independent of hypertension and obesity, while there was no association with LVH. This suggest that direct infiltration of adipose tissue in the myocardium may contribute to the development of increased LVMi. Funding Acknowledgement Type of funding sources: Public Institution(s). Main funding source(s): Western Norwegian Regional Health Authorities Table 1

Total coronary atherosclerotic plaque burden is associated with myocardial ischemia in non-obstructive coronary artery disease.

AimWhether the total coronary atherosclerotic plaque burden is independently associated with myocardial ischemia in non-obstructive coronary artery disease (CAD) is not well established. We aimed to test the association of total plaque burden quantified by coronary computed tomography angiography (CCTA) with myocardial ischemia in patients with chronic coronary syndrome and non-obstructive CAD.MethodsWe included 125 patients (age 62 ± 9 years, 58% women) with chronic coronary syndrome and non-obstructive CAD (stenosis < 50%) by CCTA, who were grouped according to presence or absence of myocardial ischemia by myocardial contrast stress echocardiography. Total plaque burden was quantified by CCTA as the total plaque volume in the main coronary arteries, and positive remodelling was defined as remodelling index > 1.10.ResultsPatients with myocardial ischemia (n = 66) had higher total plaque burden (847 ± 245 mm3 vs. 758 ± 251 mm3, p = 0.049) and higher left ventricular (LV) mass index (42.1 ± 9.9 g/m2.7 vs. 37.3 ± 8.0 g/m2.7, p = 0.004), while age, sex, prevalence of hypertension, diabetes, calcium score and positive remodelling did not differ between the groups (all p > 0.05). In multivariable regression analysis, total plaque burden remained associated with presence of myocardial ischemia (OR 1.02, 95% CI 1.00–1.04, p = 0.045) independent of age, sex, hypertension, diabetes, LV mass index, coronary calcium score and positive remodelling.ConclusionTotal coronary artery plaque burden by CCTA was independently associated with myocardial ischemia in patients with non-obstructive CAD. Whether plaque quantification is useful for clinical management of patients with non-obstructive CAD should be tested in prospective studies.ClinicalTrials.gov: Identifier NCT01853527.

Diabetic microvascular complications are associated with reduced global longitudinal strain independent of atherosclerotic coronary artery disease in asymptomatic patients with diabetes mellitus: a cross-sectional study

BackgroundReduced left ventricular function, assessed by global longitudinal strain (GLS), is sometimes observed in asymptomatic patients with diabetes mellitus (DM) and is often present in patients with diabetes-related microvascular complications. Our aim was to assess the association between microvascular complications, coronary artery plaque burden (PB) and GLS in asymptomatic patients with DM and non-obstructive coronary artery disease (CAD).MethodsThis cross-sectional study included patients with DM without any history, symptoms or objective evidence of obstructive CAD. All patients were identified in the outpatient Clinic of Endocrinology at Odense University Hospital Svendborg. An echocardiography and a coronary computed tomography angiography were performed to assess GLS and the degree of CAD, respectively. A coronary artery stenosis < 50% was considered non-obstructive. A linear regression model was used to evaluate the impact of potential confounders on GLS with adjustment of body mass index (BMI), mean arterial pressure (MAP), microvascular complications, type of diabetes, tissue Doppler average early diastolic mitral annulus velocity (e’) and PB.ResultsTwo hundred and twenty-two patients were included, of whom 172 (77%) had type 2 DM and 50 (23%) had type 1 diabetes. One hundred and eleven (50%) patients had microvascular complications. GLS decreased as the burden of microvascular complications increased (P-trend = 0.01): no microvascular complications, GLS (− 16.4 ± 2.5%), 1 microvascular complication (− 16.0 ± 2.5%) and 2–3 microvascular complications (− 14.9 ± 2.8%). The reduction in GLS remained significant after multivariable adjustment (β 0.50 [95% CI 0.11–0.88], p = 0.01). BMI (β 0.12 [95% CI 0.05–0.19]) and MAP (β 0.05 [95% CI 0.01–0.08]) were associated with reduced GLS. In addition, an increased number of microvascular complications was associated with increased PB (β 2.97 [95% CI 0.42–5.51], p = 0.02) in a univariable linear regression model, whereas there was no significant association between PB and GLS.ConclusionsThe burden of microvascular complications was associated with reduced GLS independent of other cardiovascular risk factors in asymptomatic patients with DM and non-obstructive CAD. In addition, the burden of microvascular complications was associated with increasing PB, whereas PB was not associated with GLS.

The associations of epicardial adipose tissue with coronary atherosclerosis

Background and Aims: Epicardial adipose tissue (EAT) is presumed to play an important role in development of coronary artery disease (CAD). The purpose of our study was to examine influence of EAT volume measured by cardiac CT on coronary artery plaque burden and the presence of CAD.

Abstract 16464: Coronary Artery Calcium Score and Incidence of Clinically Significant Carotid Stenosis

Introduction: Coronary artery calcium (CAC) has been found to be associated with coronary artery plaque burden and is a major predictor of coronary heart disease (CHD) events. The data on its role in predicting carotid artery stenosis (CAS) is limited. Methods: Participants age ≥ 18 years with heart screen done from Nov 2008- Feb 2019 were selected and were assessed for documented diagnosis of carotid artery stenosis after their heart screen. Only the most recent heart screen per person and earliest documented CAS was considered. The chi-squared test and Welch’s 2-sample t-test was used to test for significant association between CAS and the nominal variables and mean calcium score respectively. Results: A total of 35,084 patient were screened for CAC score and 1439 (4.1%), were recorded to have a diagnosis of carotid artery stenosis. 53.5% being females and mean age of 63.69±9.31 years. The mean time between heart screen and documented diagnosis of CAS was 1529.4 ± 1211.0 days. The presence of CAS was significantly higher in patients ≥ 60 years (8.5%) as compared to those age &lt;60 years (2%). There was a significant difference in mean CAC score between those with CAS as compared to non- carotid stenosis group (324.2, vs 107.27, p&lt;.0001). In patient with elevated CAC ≥ 100, 9.98% had diagnosis of CAS, as compared to 2.82% in patients with CAC &lt;100, however among patients with diagnosis of CAS 46.6% had elevated CAC ≥ 100. Conclusions: The presence of carotid artery stenosis (CAS) was significantly associated with elevated coronary artery calcium score (≥100) and was significantly higher in patients with age ≥ 60 years, which in correct clinical context is helpful in suspecting CAS.

Myocardial energetic efficiency is depressed in ischemia with non-obstructive coronary arteries

Abstract Background Ischemia with non-obstructive coronary arteries (INOCA) is incompletely understood. Depressed myocardial energetic efficiency index (MEEi), the ratio between external work and myocardial oxygen consumption, has been shown in heart failure. However, MEEi in INOCA has not been explored. Purpose To test whether MEEi is associated with INOCA. Methods We included 125 patients (56% women, age 62±9 years) with exercise-induced chest pain and non-obstructive coronary arteries (stenosis &amp;lt;50%) by coronary computed tomography angiography (CCTA). Stroke volume (SV) and left ventricular (LV) mass were assessed by echocardiography. MEEi was calculated as (systolic blood pressure (SBP) x SV) / (SBP x heart rate) and normalized for LV mass. LV hypertrophy was defined as LV mass index &amp;gt;46.7 g/m2.7 in women and &amp;gt;49.2 g/m2.7 in men. Myocardial ischemia was detected by myocardial contrast stress echocardiography. Coronary artery plaque burden was measured as plaque volume by CCTA. Results In univariable regression analysis, stress-induced ischemia, male sex, diabetes, hypertension, LV hypertrophy, lower LV ejection fraction and higher SBP were associated with MEEi (all p&amp;lt;0.05). There were no associations with age, obesity or coronary artery plaque burden. MEEi was lower in patients with stress-induced ischemia (n=66) compared to patients without ischemia (0.47±0.16 vs. 0.54±0.21 ml/sec x g–1, p=0.026). In multivariable linear regression analysis, MEEi remained associated with stress-induced myocardial ischemia after adjustment for cardiovascular risk factors, SBP, LV hypertrophy, LV ejection fraction and coronary artery plaque burden (R2 0.26, p&amp;lt;0.001, Table). Conclusion MEEi is depressed in patients with INOCA. Our results suggest that myocardial ischemia negatively influences MEEi in patients with non-obstructive coronary arteries. Funding Acknowledgement Type of funding source: Public Institution(s). Main funding source(s): Western Norway Regional Health Authority, University of Bergen