Prevalence of Aortic Valve Calcium and the Long-Term Risk of Incident Severe Aortic Stenosis.

BACKGROUND: Aortic valve calcification (AVC) is a principal mechanism underlying aortic stenosis (AS). OBJECTIVES: This study sought to determine the prevalence of AVC and its association with the long-term risk for severe AS. METHODS: Noncontrast cardiac computed tomography was performed among 6,814 participants free of known cardiovascular disease at MESA (Multi-Ethnic Study of Atherosclerosis) visit 1. AVC was quantified using the Agatston method, and normative age-, sex-, and race/ethnicity-specific AVC percentiles were derived. The adjudication of severe AS was performed via chart review of all hospital visits and supplemented with visit 6 echocardiographic data. The association between AVC and long-term incident severe AS was evaluated using multivariable Cox HRs. RESULTS: AVC was present in 913 participants (13.4%). The probability of AVC >0 and AVC scores increased with age and were generally highest among men and White participants. In general, the probability of AVC >0 among women was equivalent to men of the same race/ethnicity who were approximately 10 years younger. Incident adjudicated severe AS occurred in 84 participants over a median follow-up of 16.7 years. Higher AVC scores were exponentially associated with the absolute risk and relative risk of severe AS with adjusted HRs of 12.9 (95% CI: 5.6-29.7), 76.4 (95% CI: 34.3-170.2), and 380.9 (95% CI: 169.7-855.0) for AVC groups 1 to 99, 100 to 299, and ≥300 compared with AVC = 0. CONCLUSIONS: The probability of AVC >0 varied significantly by age, sex, and race/ethnicity. The risk of severe AS was exponentially higher with higher AVC scores, whereas AVC = 0 was associated with an extremely low long-term risk of severe AS. The measurement of AVC provides clinically relevant information to assess an individual's long-term risk for severe AS.

Imaging subclinical coronary atherosclerosis to guide lipid management, are we there yet?

Atherosclerotic cardiovascular disease risk (ASCVD) is an ongoing epidemic, and lipid abnormalities are its primordial cause. Most individuals suffering a first ASCVD event are previously asymptomatic and often do not receive preventative therapies. The cornerstone of primary prevention has been the identification of individuals at risk through risk calculators based on clinical and laboratory traditional risk factors plus risk enhancers. However, it is well accepted that a clinical risk calculator misclassifies a significant proportion of individuals leading to the prescription of a lipid-lowering medication with very little yield or a missed opportunity for lipid-lowering agents with a potentially preventable event. The development of coronary artery calcium scoring (CAC) and CT coronary angiography (CCTA) provide complementary tools to directly visualize coronary plaque and other risk-modifying imaging components that can potentially provide individualized lipid management. Understanding patient selection for CAC or potentially CCTA and the risk implications of the different parameters provided, such as CAC score, coronary stenosis, plaque characteristics and burden, epicardial adipose tissue, and pericoronary adipose tissue, have grown more complex as technologies evolve. These parameters directly affect the shared decision with patients to start or withhold lipid-lowering therapies, to adjust statin intensity or LDL cholesterol goals. Emerging lipid lowering studies with non-invasive imaging as a guide to patient selection and treatment efficacy, plus the evolution of lipid lowering therapies from statins to a diverse armament of newer high-cost agents have pushed these two fields forward with a complex interaction. This review will discuss existing risk estimators, and non-invasive imaging techniques for subclinical coronary atherosclerosis, traditionally studied using CAC and more recently CCTA with qualitative and quantitative measurements. We will also explore the current data, gaps of knowledge and future directions on the use of these techniques in the risk-stratification and guidance of lipid management.

Risk factors based vessel-specific prediction for stages of coronary artery disease using Bayesian quantile regression machine learning method: Results from the PARADIGM registry.

BACKGROUND AND HYPOTHESIS: The recently introduced Bayesian quantile regression (BQR) machine-learning method enables comprehensive analyzing the relationship among complex clinical variables. We analyzed the relationship between multiple cardiovascular (CV) risk factors and different stages of coronary artery disease (CAD) using the BQR model in a vessel-specific manner. METHODS: From the data of 1,463 patients obtained from the PARADIGM (NCT02803411) registry, we analyzed the lumen diameter stenosis (DS) of the three vessels: left anterior descending (LAD), left circumflex (LCx), and right coronary artery (RCA). Two models for predicting DS and DS changes were developed. Baseline CV risk factors, symptoms, and laboratory test results were used as the inputs. The conditional 10%, 25%, 50%, 75%, and 90% quantile functions of the maximum DS and DS change of the three vessels were estimated using the BQR model. RESULTS: The 90th percentiles of the DS of the three vessels and their maximum DS change were 41%-50% and 5.6%-7.3%, respectively. Typical anginal symptoms were associated with the highest quantile (90%) of DS in the LAD; diabetes with higher quantiles (75% and 90%) of DS in the LCx; dyslipidemia with the highest quantile (90%) of DS in the RCA; and shortness of breath showed some association with the LCx and RCA. Interestingly, High-density lipoprotein cholesterol showed a dynamic association along DS change in the per-patient analysis. CONCLUSIONS: This study demonstrates the clinical utility of the BQR model for evaluating the comprehensive relationship between risk factors and baseline-grade CAD and its progression.

Role of Omega-3 Fatty Acids in Cardiovascular Disease: the Debate Continues.

PURPOSE OF REVIEW: The omega-3 fatty acids (n3-FAs), eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), have recently undergone testing for their ability to reduce residual cardiovascular (CV) risk among statin-treated subjects. The outcome trials have yielded highly inconsistent results, perhaps attributable to variations in dosage, formulation, and composition. In particular, CV trials using icosapent ethyl (IPE), a highly purified ethyl ester of EPA, reproducibly reduced CV events and progression of atherosclerosis compared with mixed EPA/DHA treatments. This review summarizes the mechanistic evidence for differences among n3-FAs on the development and manifestations of atherothrombotic disease. RECENT FINDINGS: Large randomized clinical trials with n3-FAs have produced discordant outcomes despite similar patient profiles, doses, and triglyceride (TG)-lowering effects. A large, randomized trial with IPE, a prescription EPA only formulation, showed robust reduction in CV events in statin treated patients in a manner proportional to achieved blood EPA concentrations. Multiple trials using mixed EPA/DHA formulations have not shown such benefits, despite similar TG lowering. These inconsistencies have inspired investigations into mechanistic differences among n3-FAs, as EPA and DHA have distinct membrane interactions, metabolic products, effects on cholesterol efflux, antioxidant properties, and tissue distribution. EPA maintains normal membrane cholesterol distribution, enhances endothelial function, and in combination with statins improves features implicated in plaque stability and reduces lipid content of plaques. Insights into reductions in residual CV risk have emerged from clinical trials using different formulations of n3-FAs. Among high-risk patients on contemporary care, mixed n3-FA formulations showed no reduction in CV events. The distinct benefits of IPE in multiple trials may arise from pleiotropic actions that correlate with on-treatment EPA levels beyond TG-lowering. These effects include altered platelet function, inflammation, cholesterol distribution, and endothelial dysfunction. Elucidating such mechanisms of vascular protection for EPA may lead to new interventions for atherosclerosis, a disease that continues to expand worldwide.

Association Between Omega-3 Fatty Acid Levels and Aortic Valve Calcium (from the Multi-Ethnic Study of Atherosclerosis).

Calcific aortic valve disease, a condition of chronic inflammation, is associated with increased cardiovascular events and all-cause mortality. Omega-3 fatty acids (O3FAs) reduce both acute and chronic inflammation, but their associations with aortic valve calcium (AVC) have not been studied. The Multi-Ethnic Study of Atherosclerosis is a prospective cohort study of 6,814 adults without clinical cardiovascular disease. Plasma fatty acid levels and cardiac computed tomography (CT) scans were performed at baseline, and CT scans were performed at subsequent clinical visits over a median 9-year period. We assessed whether plasma levels of O3FAs and their species correlate with the presence, severity, and progression of AVC measured by CT in Multi-Ethnic Study of Atherosclerosis. The mean age of the 6,510 included participants with baseline fatty acid levels, AVC, and covariate data was 62.1 ± 10.2 years, and 47.1% of the participants were male. Race distribution was 38.6% White, 27.2% Black, 22.1% Hispanic/Latino, and 12.1% Chinese. Among the 6,510 participants, 5,884 had a subsequent CT scan, and 3,304 had a third CT scan with AVC measurements. At baseline, 862 participants (13.2%) had prevalent AVC (Agatston score >0), and were more likely to be of older age, male, of the White race, have a lower education level, and have co-morbidities that are associated with a higher risk for AVC. Plasma tertiles of eicosapentaenoic acid, docosahexaenoic acid, and total O3FA were not associated with prevalent AVC at baseline, incident AVC, or change in AVC. In conclusion, plasma levels of O3FAs in subjects not routinely supplemented with O3FAs are not useful for predicting the presence or development of AVC. Whether high plasma O3FA levels, achievable by high-dose O3FA over-the-counter supplementation or pharmacotherapy, is associated with AVC requires further investigation.

Omega-3 fatty acids, subclinical atherosclerosis, and cardiovascular events: Implications for primary prevention.

BACKGROUND AND AIMS: High-dose eicosapentaenoic acid (EPA) therapy was beneficial in high-risk patients without clinical cardiovascular disease (CVD). Whether higher plasma levels of EPA and docosahexaenoic acid (DHA) have similar benefits in those without subclinical CVD is unclear. We aim to evaluate the interplay between plasma omega-3 fatty acids and coronary artery calcium (CAC) in relation to CVD events. METHODS: We examined 6568 participants from the Multi-Ethnic Study of Atherosclerosis (MESA) with plasma EPA and DHA levels and CAC measured at baseline. The primary outcome was incident CVD events (myocardial infarction, angina, cardiac arrest, stroke, CVD death). Hazard ratios for the primary outcome were adjusted for potential confounder using Cox regression. RESULTS: Mean ± SD age was 62.1 ± 10.2 years and 52.9% were females. The median follow-up time was 15.6 years. Higher loge(EPA) (adjusted hazard ratio, aHR = 0.83; 95% CI, 0.74-0.94) and loge(DHA) (aHR = 0.79; 95% CI, 0.66-0.96) were independently associated with fewer CVD events. The difference in absolute CVD event rates between lowest vs. highest EPA tertile increased at higher CAC levels. The adjusted HR for highest vs. lowest EPA tertile within CAC = 0 was 1.02 (95% CI, 0.72-1.46), CAC = 1-99 was 0.71 (95% CI, 0.51-0.99), and CAC≥100 was 0.67 (95% CI, 0.52-0.84). A similar association was seen in tertiles of DHA by CAC category. CONCLUSIONS: In an ethnically diverse population free of clinical CVD, higher plasma omega-3 fatty acid levels were associated with fewer long-term CVD events. The absolute decrease in CVD events with higher omega-3 fatty acid levels was more apparent at higher CAC scores.

Current methods to assess mitral annular calcification and its risk factors.

INTRODUCTION: Mitral annulus calcification (MAC) is a chronic, non-inflammatory, degenerative mechanism of the fibrous base of the mitral valve. While MAC was originally thought to be an age-related degenerative process, there is evidence that other mechanisms, such as atherosclerosis and abnormal calcium phosphorus metabolism, also contribute to the development of MAC. AREAS COVERED: This paper summarizes, existing perception of clinically valid definition of MAC and the pathophysiological processes that lead to the development of MAC and the diagnostic implications of this disease entity. EXPERT OPINION: Minimal evidence exists on the natural history and progression of MAC. Characterization of MAC progression and identification of predisposing risk factors can help to validate hypotheses. MAC is most commonly asymptomatic and incidental finding. Echocardiography is the primary imaging modality for identification and characterization of MAC and associated mitral valve (MV) disease. For patients with an indication for MV surgery, computed tomography (CT) is a complementary imaging modality for MAC. MAC is generally recognized by its characteristic density, location, and shape on echocardiography and CT, unusual variants are sometimes confused with other lesions.

Association Between Omega-3 Fatty Acid Levels and Risk for Incident Major Bleeding Events and Atrial Fibrillation: MESA.

Background Randomized trials of pharmacologic strength omega-3 fatty acid (n3-FA)-based therapies suggest a dose-dependent cardiovascular benefit. Whether blood n3-FA levels also mediate safety signals observed in these trials, such as increased bleeding and atrial fibrillation (AF), remains uncertain. We hypothesized that higher baseline n3-FA levels would be associated with incident bleeding and AF events in MESA (Multi-Ethnic Study of Atherosclerosis), which included a population free of clinical cardiovascular disease at baseline. Methods and Results We examined the association between baseline plasma n3-FA levels (expressed as percent mass of total fatty acid) with incident bleeding and AF in MESA, an ongoing prospective cohort study. Bleeding events were identified from review of hospitalization International Classification of Diseases, Ninth Revision (ICD-9), and International Classification of Diseases, Tenth Revision (ICD-10), codes, and AF from participant report, discharge diagnoses, Medicare claims data, and study ECGs performed at MESA visit 5. Separate multivariable Cox proportional hazard modeling was used to estimate hazard ratios of the association of continuous n3-FA (log eicosapentaenoic acid [EPA], log docosahexaenoic acid [DHA], log [EPA+DHA]) and incident hospitalized bleeding events and AF. Among 6546 participants, the mean age was 62.1 years and 53% were women. For incident bleeding, consistent statistically significant associations with lower rates were seen with increasing levels of EPA and EPA+DHA in unadjusted and adjusted models including medications that modulate bleeding risk (aspirin, NSAIDS, corticosteroids, and proton pump inhibitors). For incident AF, a significant association with lower rates was seen with increasing levels of DHA, but not for EPA or EPA+DHA. Conclusions In MESA, higher plasma levels of n3-FA (EPA and EPA+DHA, but not DHA) were associated with significantly fewer hospitalized bleeding events, and higher DHA levels (but not EPA or EPA+DHA) with fewer incident AF events.

Effects of chronic kidney disease and declining renal function on coronary atherosclerotic plaque progression: a PARADIGM substudy.

AIMS: To investigate the change in atherosclerotic plaque volume in patients with chronic kidney disease (CKD) and declining renal function, using coronary computed tomography angiography (CCTA). METHODS AND RESULTS: In total, 891 participants with analysable serial CCTA and available glomerular filtration rate (GFR, derived using Cockcroft-Gault formulae) at baseline (CCTA 1) and follow-up (CCTA 2) were included. CKD was defined as GFR <60 mL/min/1.73 m2. Declining renal function was defined as ≥10% drop in GFR from the baseline. Quantitative assessment of plaque volume and composition were performed on both scans. There were 203 participants with CKD and 688 without CKD. CKD was associated with higher baseline total plaque volume, but similar plaque progression, measured by crude (57.5 ± 3.4 vs. 65.9 ± 7.7 mm3/year, P = 0.28) or annualized (17.3 ± 1.0 vs. 19.9 ± 2.0 mm3/year, P = 0.25) change in total plaque volume. There were 709 participants with stable GFR and 182 with declining GFR. Declining renal function was independently associated with plaque progression, with higher crude (54.1 ± 3.2 vs. 80.2 ± 9.0 mm3/year, P < 0.01) or annualized (16.4 ± 0.9 vs. 23.9 ± 2.6 mm3/year, P < 0.01) increase in total plaque volume. In CKD, plaque progression was driven by calcified plaques whereas in patients with declining renal function, it was driven by non-calcified plaques. CONCLUSION: Decline in renal function was associated with more rapid plaque progression, whereas the presence of CKD was not.

New carotid plaque, but not the progression of intima-media thickness, predicts the progression of high-risk coronary plaque.

BACKGROUND: Carotid intima-media thickness (CIMT) is regarded as a controversial risk marker for cardiovascular disease (CVD). We aimed to evaluate the role of CIMT and carotid plaque progression as predictors for the progression of coronary plaque and compositions. METHODS: In the Garlic 4 study, asymptomatic patients with intermediate CVD risk (Framingham risk score 6-20%) were recruited for a serial carotid ultrasound, and coronary artery calcium score (CAC)/coronary computed tomography angiography (CCTA) studies for subclinical atherosclerosis at a baseline and 1 year. The association between progression of quantitatively measured coronary plaque compositions and the progression of CIMT/carotid plaque was analyzed. A P value <0.05 is considered as statistically significant. RESULTS: Forty-seven consecutive patients were included. The mean age was 58.5 ± 6.6 years, and 69.1 % were male. New carotid plaque appeared in 34.0 % (n = 16) of participants, and 55.3 % (n = 26) of subjects had coronary plaque progression. In multilinear regression analysis, adjusted by age, gender, and statin use, the development of new carotid plaque was significantly associated with an increase in noncalcified coronary plaque [ß (SE) 2.0 (0.9); P = 0.025] and necrotic core plaque (1.7 (0.6); P = 0.009). In contrast, CIMT progression was not associated with the progression of coronary plaque, or coronary artery calcium (CAC) (P = NS). CONCLUSION: Compared to CIMT, carotid plaque is a better indicator of coronary plaque progression. The appearance of a new carotid plaque is associated with significant progression of necrotic core and noncalcified plaque, which are high-risk coronary plaque components.

Effect of icosapent ethyl on progression of coronary atherosclerosis in patients with elevated triglycerides on statin therapy: a prospective, placebo-controlled randomized trial (EVAPORATE): interim results.

AIMS: Though statin therapy is known to slow coronary atherosclerosis progression and reduce cardiovascular (CV) events, significant CV risk still remains. In the REDUCE-IT study, icosapent ethyl (IPE) added to statin therapy reduced initial CV events by 25% and total CV events by 30%, but its effects on coronary atherosclerosis progression have not yet been fully investigated. Therefore, this study is to determine whether IPE 4 g/day will result in a greater change from baseline in plaque volume measured by serial multidetector computed tomography than placebo in statin-treated patients. METHODS AND RESULTS: EVAPORATE is a randomized, double-blind, placebo-controlled trial. Patients had to have coronary atherosclerosis by coronary computed tomographic angiography (CCTA) (≥1 angiographic stenoses with ≥20% narrowing), on stable statin therapy with low-density lipoprotein cholesterol levels 40-115 mg/dL, and persistently high triglyceride levels (135-499 mg/dL). Patients underwent an interim scan at 9 months and were followed for an additional 9 months with CCTA at 0, 9, and 18 months. Here, we present the protocol-specified interim efficacy results. A total of 80 patients were enrolled, with 67 completing the 9-month visit and having interpretable CCTA at baseline and at 9 months (age = 57 ± 6 years, male = 36, 63%). At the 9-month interim analysis, there was no significant change in low attenuation plaque (LAP) between active and placebo groups (74% vs. 94%, P = 0.469). However, there was slowing of total non-calcified plaque (sum of LAP, fibrofatty, and fibrous plaque) (35% vs. 43%, P = 0.010), total plaque (non-calcified + calcified plaque) (15% vs. 26%, P = 0.0004), fibrous plaque (17% vs. 40%, P = 0.011), and calcified plaque (-1% vs. 9%, P = 0.001), after adjustment by baseline plaque, age, sex, diabetes, baseline triglyceride levels, and statin use. CONCLUSION: EVAPORATE is the first study using CCTA to evaluate the effects of IPE as an adjunct to statin therapy on atherosclerotic plaque characteristics in a high-risk CV population with persistently high triglyceride levels. It provides important mechanistic data in regards to the reduction in CV events in the REDUCE-IT clinical trial. CLINICALTRIALS. GOVIDENTIFIER: NCT029226027.

Effect of a plant-based bioequivalent inorganic nitrate (NO3-) complex with vitamins, antioxidants and phytophenol rich food extracts in hypertensive individuals - A randomized, double-blind, placebo-controlled study.

BACKGROUND: This study assessed efficacy of plant based bioequivalent nitrate complex, consist of vitamins, natural antioxidants and phytophenol rich food extracts to elevate nitric oxide (NO) bioavailability as determined by saliva conversion of nitrate (NO3-) to nitrite (NO2-) a required step to produce NO, in relationship to lowering blood pressure (BP) in both men and women. METHODS: 67 individuals (26 men; mean age of 59.3 ± 9.0 yrs) with mean baseline systolic and diastolic BP >120 and 80 mmHg respectively were randomized to receive daily dosing of 314 mM NO3- or NO3- free (placebo) tablets in double-blinded study for 12 weeks (wks). Inorganic NO3- tablets consist of NO3- rich beetroot extract, thiamine nitrate, and potassium nitrate in the presence of ascorbic acid, to facilitate NO bioavailability. RESULTS: The primary endpoint of the study was reduction in BP at 12 wks by improving endothelial function. At study conclusion, mean ± SD reduction in systolic BP (SBP) in the inorganic NO3- group was 12.5 ± 13.3 mmHg (p = 0.0007), as compared to 6.19 ± 11.39 mmHg (p = 0.004) in the placebo group, for a placebo-corrected reduction of -6.31 mmHg (95% CI 10.89-2.31, p = 0.04). NO3- also reduced diastolic BP by 4.7 ± 10.3 mmHg (p = 0.01), while no significant reduction in placebo group (1.98 ± 9.38 mmHg, p = 0.24) was noted. Endothelial function improved at 12 weeks by 0.8 ± 3.1 (p = 0.03) in active group when compared to 0.1 ± 1.8 (p = 0.82) in placebo group. CONCLUSION: Endothelial function improved robustly reducing both systolic and diastolic BP in hypertensive individuals with daily supplementation of dietary NO3-. CLINICALTRIALS. GOV ID: NCT03909789.

Mechanistic insights into cardiovascular protection for omega-3 fatty acids and their bioactive lipid metabolites.

Patients with well-controlled low-density lipoprotein cholesterol levels, but persistent high triglycerides, remain at increased risk for cardiovascular events as evidenced by multiple genetic and epidemiologic studies, as well as recent clinical outcome trials. While many trials of low-dose ω3-polyunsaturated fatty acids (ω3-PUFAs), eicosapentaenoic acid (EPA), and docosahexaenoic acid (DHA) have shown mixed results to reduce cardiovascular events, recent trials with high-dose ω3-PUFAs have reignited interest in ω3-PUFAs, particularly EPA, in cardiovascular disease (CVD). REDUCE-IT demonstrated that high-dose EPA (4 g/day icosapent-ethyl) reduced a composite of clinical events by 25% in statin-treated patients with established CVD or diabetes and other cardiovascular risk factors. Outcome trials in similar statin-treated patients using DHA-containing high-dose ω3 formulations have not yet shown the benefits of EPA alone. However, there are data to show that high-dose ω3-PUFAs in patients with acute myocardial infarction had reduced left ventricular remodelling, non-infarct myocardial fibrosis, and systemic inflammation. ω3-polyunsaturated fatty acids, along with their metabolites, such as oxylipins and other lipid mediators, have complex effects on the cardiovascular system. Together they target free fatty acid receptors and peroxisome proliferator-activated receptors in various tissues to modulate inflammation and lipid metabolism. Here, we review these multifactorial mechanisms of ω3-PUFAs in view of recent clinical findings. These findings indicate physico-chemical and biological diversity among ω3-PUFAs that influence tissue distributions as well as disparate effects on membrane organization, rates of lipid oxidation, as well as various receptor-mediated signal transduction pathways and effects on gene expression.

Per-lesion versus per-patient analysis of coronary artery disease in predicting the development of obstructive lesions: the Progression of AtheRosclerotic PlAque DetermIned by Computed TmoGraphic Angiography Imaging (PARADIGM) study.

To determine whether the assessment of individual plaques is superior in predicting the progression to obstructive coronary artery disease (CAD) on serial coronary computed tomography angiography (CCTA) than per-patient assessment. From a multinational registry of 2252 patients who underwent serial CCTA at a ≥ 2-year inter-scan interval, patients with only non-obstructive lesions at baseline were enrolled. CCTA was quantitatively analyzed at both the per-patient and per-lesion level. Models predicting the development of an obstructive lesion at follow up using either the per-patient or per-lesion level CCTA measures were constructed and compared. From 1297 patients (mean age 60 ± 9 years, 43% men) enrolled, a total of 3218 non-obstructive lesions were identified at baseline. At follow-up (inter-scan interval: 3.8 ± 1.6 years), 76 lesions (2.4%, 60 patients) became obstructive, defined as > 50% diameter stenosis. The C-statistics of Model 1, adjusted only by clinical risk factors, was 0.684. The addition of per-patient level total plaque volume (PV) and the presence of high-risk plaque (HRP) features to Model 1 improved the C-statistics to 0.825 [95% confidence interval (CI) 0.823-0.827]. When per-lesion level PV and the presence of HRP were added to Model 1, the predictive value of the model improved the C-statistics to 0.895 [95% CI 0.893-0.897]. The model utilizing per-lesion level CCTA measures was superior to the model utilizing per-patient level CCTA measures in predicting the development of an obstructive lesion (p < 0.001). Lesion-level analysis of coronary atherosclerotic plaques with CCTA yielded better predictive power for the development of obstructive CAD than the simple quantification of total coronary atherosclerotic burden at a per-patient level.Clinical Trial Registration: ClinicalTrials.gov NCT0280341.

A combined effect of Cavacurcumin, Eicosapentaenoic acid (Omega-3s), Astaxanthin and Gamma -linoleic acid (Omega-6) (CEAG) in healthy volunteers- a randomized, double-blind, placebo-controlled study.

BACKGROUND: Inflammation plays a key role and is one of the early steps in the pathogenesis of endothelial function, thereby increasing the risk of hypertension (HTN), coronary artery disease (CAD), stroke and several other risk factors of cardiovascular disease (CVD). We assessed the efficacy for improving cardiovascular health (blood pressure, inflammation and endothelial reactivity) over a 4-week intervention period in healthy individuals. METHODS: We performed a randomized, double-blinded, placebo-controlled, randomized clinical trial to investigate Curcumin, Eicosapentaenoic acid (EPA), Astaxanthin and Gamma -linoleic acid (GLA) (CEAG) supplements with 80 individuals (30 men and 50 women). The mean age of participants was 48.8 ± 16.0 years. Participants were enrolled and randomized to active or placebo and followed for 4 weeks. Paired and Independent T-tests were used to analyze the mean differences between and within groups. RESULTS: The primary endpoints of the study were the effect on inflammatory markers (IL-6, CRP), endothelial function and blood pressure at 4 weeks. There was a significant reduction in mean SBP at 4 weeks in the CEAG group compared to placebo [mean ± SD 4.7 ± 6.8 (p = 0.002)]. Relative to placebo, active group showed a significant decrease in High sensitivity C Reactive Protein (hsCRP) (-0.49 ± 1.9 vs + 0.51 ± 2.5, p = 0.059) and blunted increase in IL-6 (+0.2 vs + 0.4 in placebo, p = 0.60). CONCLUSION: Inflammatory markers were reduced or blunted by CEAG, with a robust increase in both EPA levels and the fatty acid index. Furthermore, systolic BP was reduced over 4 weeks with concurrent improvement in endothelial function. CLINICALTRIALS. GOV ID: NCT03906825.

Implications of serial coronary computed tomography angiography in the evaluation of coronary plaque progression.

PURPOSE OF REVIEW: The purpose is to review the use of coronary computed tomography (CT) angiography to assess coronary plaque burden/progression and to discuss about recent clinical trials that have utilized this imaging modality to study the effect of new pharmacotherapies on plaque burden/progression. RECENT FINDINGS: There are numerous clinical trials that have utilized coronary CT angiography to demonstrate the potential benefits of statins, apixaban, rivaroxaban, aged garlic extract, biologic agents, and omega-3 fatty acids to reduce coronary plaque progression. Coronary CT angiography can identify high-risk plaques and can also quantify total plaque burden, both of which are independent risk factors to predict major adverse cardiac events. SUMMARY: Coronary heart disease remains one of the leading cause of mortality in the world. Utilizing coronary CT angiography, it is possible to identify rupture-prone plaques and also to quantify the total plaque burden. New pharmacotherapies that have the potential to reduce plaque progression have been used in clinical trials and these trials have utilized coronary CT angiography to track coronary atheroma progression. In future, we will see frequent utilization of coronary CT angiography to track coronary atheroma.

Age- and gender-adjusted percentiles for number of calcified plaques in coronary artery calcium scanning.

BACKGROUND: Age- and gender-adjusted percentiles of coronary artery calcium (CAC) score are commonly reported to compare a patient's coronary atherosclerosis burden to that of others of the same age and gender. The number of calcified plaques (numCP) detected on CAC scanning, a measure of plaque diffusivity, is associated with increased cardiovascular risk and, in the intermediate CAC range, adds to the CAC score in predicting mortality. This study aims to develop adjusted percentiles for numCP to provide a better context for understanding CAC scan findings. METHODS AND RESULTS: Using nonparametric modeling techniques, the distribution of numCP was analyzed in 70,320 consecutive, asymptomatic patients without prior clinically-diagnosed cardiovascular disease who were part of the Coronary Artery Calcium Consortium and supplemented by additional patients referred for clinical CAC scanning in a single center between 1998 and 2016. Nomograms for age-adjusted numCP percentiles for each gender were generated using quantile regression. The prevalence and average number of calcified coronary plaque were found to be higher in men than women. Distribution of numCP in women was found to closely mirror that of men approximately a decade younger. NumCP increased consistently across age groups in both men and women for each quantile category. CONCLUSIONS: A nomogram for age and gender-adjusted percentiles for the numCP on CAC scans has been developed in a large population of asymptomatic patients studied across multiple centers. This numCP nomogram may provide an additional tool for refining physician recommendations regarding treatment and expressing to patients how their CAC findings relate to others of similar age and gender. The numCP percentiles may also provide a meaningful way to evaluate and report the rate of progression of CAC on serial studies.

Impact of Non-obstructive left main disease on the progression of coronary artery disease: A PARADIGM substudy.

BACKGROUND: The aim of the study is examine the impact of non-obstructive (<50%stenosis) left main (LM) disease on the natural history of coronary artery disease using serial coronary computed tomography angiography (CTA). METHODS: CTAs from the PARADIGM (Progression of atherosclerotic plaque determined by computed tomographic angiography imaging) study, a prospective multinational registry of patients who underwent serial CTA at a ≥2 year interval were analyzed. Those without evidence of CAD on their baseline scan were excluded, as were those with obstructive left main disease. Coronary artery vessels and their branches underwent quantification of: plaque volume and composition; diameter stenosis; presence of high-risk plaque. RESULTS: Of 944 (62 ±â€¯9 years, 60% male) who had evidence of CAD at baseline, 444 (47%) had LM disease. Those with LM disease had a higher baseline plaque volume (194.8 ±â€¯221mm3 versus 72.9 ±â€¯84.3mm3, p < 0.001) and a higher prevalence of high-risk plaque (17.5% versus 13%, p < 0.001) than those without LM disease. On multivariable general linear model, patients with LM disease had greater annual rates of progression of total (26.5 ±â€¯31.4mm3/yr versus 14.9 ±â€¯20.1mm3/yr, p < 0.001) and calcified plaque volume (17 ±â€¯24mm3/yr versus 7 ±â€¯11mm3/yr, p < 0.001), with no difference in fibrous, fibrofatty or necrotic core plaque components. CONCLUSION: The presence of non-obstructive LM disease is associated with greater rates of plaque progression and a higher prevalence of high-risk plaque throughout the entire coronary artery tree compared to CAD without LM involvement. Our data suggests that non-obstructive LM disease may be a marker for an aggressive phenotype of CAD that may benefit from more intensive treatment strategies.

Randomized trial evaluating the effect of aged garlic extract with supplements versus placebo on adipose tissue surrogates for coronary atherosclerosis progression.

AIMS: Increased epicardial adipose tissue (EAT), pericardial adipose tissue (PAT), periaortic adipose tissue (PaAT), and subcutaneous adipose tissue (SAT) are mediators of metabolic risk, and are associated with the severity of coronary artery calcium (CAC). Aged garlic extract (AGE) has been shown to reduce the progression of coronary atherosclerosis. This study evaluates the effect of AGE with supplements (AGE+S) on EAT, PAT, SAT, and PaAT. METHODS: Sixty asymptomatic participants participated in a randomized trial evaluating the effect of AGE+S versus placebo on coronary atherosclerosis progression, and underwent CAC at baseline and after 12 months of treatment. EAT, PAT, PaAT, and SAT volumes were measured on CAC scans. PAT was calculated as: intrathoracic adipose tissue-EAT. SAT was defined as the volume of fat depot anterior to the sternum and posterior to the vertebra. PaAT was defined as fat depot around the descending aorta. RESULTS: At 1 year, the increase in EAT, PAT, PaAT, and SAT was significantly lower in the AGE+S as compared with the placebo group (P<0.05). The odds ratios of increase in EAT, PAT, PaAT, and SAT were 0.63 [95% confidence interval (CI): 0.43-0.90], 0.72 (95% CI: 0.45-0.93), 0.81 (95% CI: 0.65-0.98), and 0.87 (CI: 0.52-0.98), respectively, compared with the placebo group, which even remained significant (all P<0.05) after adjustment for cardiovascular risk factors and statin therapy and BMI. CONCLUSION: This study shows that AGE+S is associated with favorable effects on reducing the progression rate of adipose tissue volumes.