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Background: Abdominal aortic calcium (AAC) and coronary artery calcium (CAC) independently and similarly predict cardiovascular disease (CVD) events. The standard AAC and CAC score, the Agatston method, upweights for greater calcium density, thereby modeling higher calcium density as a CVD hazard., Methods and Results: Computed tomography scans were used to measure AAC and CAC volume and density in a multiethnic cohort of community-dwelling individuals, and Cox proportional hazard was used to determine their independent association with incident coronary heart disease (CHD, defined as myocardial infarction, resuscitated cardiac arrest, or CHD death), cardiovascular disease (CVD, defined as CHD plus stroke and stroke death), and all-cause mortality. In 997 participants with Agatston AAC and CAC scores >0, the mean age was 66±9 years, and 58% were men. During an average follow-up of 9 years, there were 77 CHD, 118 CVD, and 169 all-cause mortality events. In mutually adjusted models, additionally adjusted for CVD risk factors, an increase in ln(AAC volume) per standard deviation was significantly associated with increased all-cause mortality (hazard ratio=1.20; 95% confidence interval, 1.08-1.33; P<0.01) and an increased ln(CAC volume) per standard deviation was significantly associated with CHD (hazard ratio=1.17; 95% confidence interval, 1.04-1.59; P=0.02) and CVD (hazard ratio=1.20; 95% confidence interval, 1.05-1.36; P<0.01). In contrast, both AAC and CAC density were not significantly associated with CVD events., Conclusions: The Agatston method of upweighting calcium scores for greater density may be inappropriate for CVD risk prediction in both the abdominal aorta and coronary arteries., (© 2016 American Heart Association, Inc.)

Background: Early detection of coronary atherosclerosis using coronary computed tomography angiography (CCTA), in addition to coronary artery calcification (CAC) scoring, may help inform prevention strategies. We used CCTA to determine the prevalence, severity, and characteristics of coronary atherosclerosis and its association with CAC scores in a general population.Methods: We recruited 30 154 randomly invited individuals age 50 to 64 years to SCAPIS (the Swedish Cardiopulmonary Bioimage Study). The study includes individuals without known coronary heart disease (ie, no previous myocardial infarctions or cardiac procedures) and with high-quality results from CCTA and CAC imaging performed using dedicated dual-source CT scanners. Noncontrast images were scored for CAC. CCTA images were visually read and scored for coronary atherosclerosis per segment (defined as no atherosclerosis, 1% to 49% stenosis, or ≥50% stenosis). External validity of prevalence estimates was evaluated using inverse probability for participation weighting and Swedish register data.Results: In total, 25 182 individuals without known coronary heart disease were included (50.6% women). Any CCTA-detected atherosclerosis was found in 42.1%; any significant stenosis (≥50%) in 5.2%; left main, proximal left anterior descending artery, or 3-vessel disease in 1.9%; and any noncalcified plaques in 8.3% of this population. Onset of atherosclerosis was delayed on average by 10 years in women. Atherosclerosis was more prevalent in older individuals and predominantly found in the proximal left anterior descending artery. Prevalence of CCTA-detected atherosclerosis increased with increasing CAC scores. Among those with a CAC score >400, all had atherosclerosis and 45.7% had significant stenosis. In those with 0 CAC, 5.5% had atherosclerosis and 0.4% had significant stenosis. In participants with 0 CAC and intermediate 10-year risk of atherosclerotic cardiovascular disease according to the pooled cohort equation, 9.2% had CCTA-verified atherosclerosis. Prevalence estimates had excellent external validity and changed marginally when adjusted to the age-matched Swedish background population.Conclusions: Using CCTA in a large, random sample of the general population without established disease, we showed that silent coronary atherosclerosis is common in this population. High CAC scores convey a significant probability of substantial stenosis, and 0 CAC does not exclude atherosclerosis, particularly in those at higher baseline risk. [ABSTRACT FROM AUTHOR]

Backgound: The inability to detect premature atherosclerosis significantly hinders implementation of personalized therapy to prevent coronary heart disease. A comprehensive understanding of arterial protein networks and how they change in early atherosclerosis could identify new biomarkers for disease detection and improved therapeutic targets.Methods: Here we describe the human arterial proteome and proteomic features strongly associated with early atherosclerosis based on mass spectrometry analysis of coronary artery and aortic specimens from 100 autopsied young adults (200 arterial specimens). Convex analysis of mixtures, differential dependent network modeling, and bioinformatic analyses defined the composition, network rewiring, and likely regulatory features of the protein networks associated with early atherosclerosis and how they vary across 2 anatomic distributions.Results: The data document significant differences in mitochondrial protein abundance between coronary and aortic samples (coronary>>aortic), and between atherosclerotic and normal tissues (atherosclerotic<Conclusions: The human arterial proteome can be viewed as a complex network whose architectural features vary considerably as a function of anatomic location and the presence or absence of atherosclerosis. The data suggest important reductions in mitochondrial protein abundance in early atherosclerosis and also identify a subset of plasma proteins that are highly predictive of angiographically defined coronary disease. [ABSTRACT FROM AUTHOR]

Background--Impaired vasodilator function is an early manifestation of coronary artery disease and may precede angiographic stenosis. It is unknown whether noninvasive assessment of coronary vasodilator function in patients with suspected or known coronary artery disease carries incremental prognostic significance. Methods and Results--A total of 2783 consecutive patients referred for rest/stress positron emission tomography were followed up for a median of 1.4 years (interquartile range, 0.7-3.2 years). The extent and severity of perfusion abnormalities were quantified by visual evaluation of myocardial perfusion images. Rest and stress myocardial blood flows were calculated with factor analysis and a 2-compartment kinetic model and were used to compute coronary flow reserve (coronary flow reserve equals stress divided by rest myocardial blood flow). The primary end point was cardiac death. Overall 3-year cardiac mortality was 8.0%. The lowest tertile of coronary flow reserve (<1.5) was associated with a 5.6-fold increase in the risk of cardiac death (95% confidence interval, 2.5-12.4; P<0.0001) compared with the highest tertile. Incorporation of coronary flow reserve into cardiac death risk assessment models resulted in an increase in the c index from 0.82 (95% confidence interval, 0.78-0.86) to 0.84 (95% confidence interval, 0.80-0.87; P = 0.02) and in a net reclassification improvement of 0.098 (95% confidence interval, 0.025-0.180). Addition of coronary flow reserve resulted in correct reclassification of 34.8% of intermediate-risk patients (net reclassification improvement=0.487; 95% confidence interval, 0.262-0.731). Corresponding improvements in risk assessment for mortality from any cause were also demonstrated. Conclusion--Noninvasive quantitative assessment of coronary vasodilator function with positron emission tomography is a powerful, independent predictor of cardiac mortality in patients with known or suspected coronary artery disease and provides meaningful incremental risk stratification over clinical and gated myocardial perfusion imaging variables. [ABSTRACT FROM AUTHOR]

Introduction: Optical coherence tomography (OCT) is thought to be capable of identifying lipid-rich plaque (LRP). However, several histopathological correlative studies have shown that LRP assessment by OCT alone may be indecisive for identifying advanced plaque containing a necrotic core. This study aims to investigate the feasibility of multi-modality OCT-near-infrared autofluorescence (NIRAF) imaging to identify advanced necrotic-core LRP. Methods: We constructed a new fully integrated multi-modality OCT-NIRAF imaging system and catheter that allows simultaneous and co-registered acquisition of OCT and NIRAF data. NIRAF excitation was 635nm and emission was collected between 690-750nm. OCT-NIRAF pullback imaging was performed with excised human cadaver coronary arteries during saline perfusion. Subsequently, H&E sections were obtained and co-registered (longitudinally and azimuthally) with corresponding OCT-NIRAF images, using the known pullback distances, and anatomic landmarks and features such as calcium nodules seen in the OCT and histopathology images. In addition, a bench top confocal microscope was used to obtain images of NIRAF on corresponding unstained, formalin-fixed, paraffin-embedded slides. Results: A total of 187 histopathological sections and corresponding OCT-NIRAF images from 13 cadaver coronary arteries from 5 patients were imaged and analyzed. Several LRP that were identified by histopathology in these arteries showed regions with evidence of necrotic core with hemosiderin granules that had significantly higher catheter-based NIRAF than regions without hemosiderin granules. Confocal NIRAF microscopy also showed that regions of high NIRAF were associated with accumulation of hemosiderin in corresponding histological sections. Conclusions: This study provides suggestive data that an integrated OCT-NIRAF imaging system and catheter may be able to be used to identify advanced LRP that contains a necrotic core with hemosiderin granules. Future investigation of NIRAF from cadaver arteries from additional patients is merited to robustly confirm these findings. [ABSTRACT FROM AUTHOR]

Introduction: Data-driven guidelines for the optimal medical and interventional management of cancer patients according to the primary malignancy are absent. Hypothesis: We aimed to assess whether specific malignancies and their treatments (chemotherapy, radiation) can modify the natural progression of coronary artery disease (CAD) and lesion location. Methods: From April 2008 to February 2018, cancer and non-cancer patients from a high-volume onco-cardiology center and a tertiary cardiology center, respectively, who underwent coronary angiography (CA) for any indication were enrolled. Baseline demographics, current and prior CA findings, and cancer status and treatment were collected. Neural network machine learning supported multivariable regression of CAD (left main [LM], left anterior descending [LAD], right coronary artery [RCA], and left circumflex [LCx]) according to the primary malignancy. Results: We included 480 patients who underwent coronary angiography, of which 240 (50%) had cancer. Mean age was 63.87 ± 11.69 years and 34.79% of patients were women. The main indications for CA were chest pain (30.00%), abnormal stress test (23.96%), and prior coronary artery disease (18.75%), with 35.08% having a prior percutaneous coronary intervention (PCI) and 5.63% having post-PCI referral for CABG. In multivariable regression, patients with lung cancer compared to those without this malignancy had higher odds of significant LAD (OR 5.19, 95%CI 1.13-23.80, p=0.034) and RCA (OR 9.92, 95% CI 1.99-49.32, p=0.005) stenoses, but not of LM or LCx stenoses, even after controlling for age, peripheral artery disease, dyslipidemia, diabetes, platelet number, and triglycerides. Hematological malignancies, breast cancer, and prostate cancer did not have independent associations with any particular vessel. Conclusions: This innovative machine learning and statistical analysis suggests that particular cancer types can impact lesion severity in specific coronary vessels, potentially altering management. [ABSTRACT FROM AUTHOR]

Nesfatin-1 is a recently identified anorexigenic peptide derived from nucleobindin 2, which is mainly secreted from brain and adipose tissue. Although nesfatin-1 was suggested to have anti-inflammatory and anti-apoptotic properties, the association between plasma nesfatin-1 levels and atherosclerotic disease, such as coronary artery disease (CAD), has not been elucidated. We investigated plasma nesfatin-1 levels by ELISA in 302 patients (pts) undergoing elective coronary angiography for suspected CAD. Pts with ACS, heart failure, malignancy or a history of PCI were excluded. The severity of CAD was represented as the numbers of >50% stenotic vessels and segments, and the severity score of stenosis. The degree of coronary stenosis in each segment was scored 0 to 4 points (0, ≤25%; 1, 26-50%; 2, 51-75%; 3, 76-90%; 4, >90% stenosis), and the severity score was defined as the sum of scores of all segments. Results: Of the 302 study pts, CAD was present in 172 (57%), of whom 67 had 1-vessel, 49 had 2-vessel, 56 had 3-vessel disease (3-VD). Compared with 130 pts without CAD, 172 with CAD more often had hypertension, hyperlipidemia and DM (P<0.05). Plasma nesfatin-1 levels were higher in pts with CAD than without CAD (median 0.21 vs. 0.17 ng/mL, P<0.01). A stepwise increase in nesfatin-1 levels was found depending on the number of >50% stenotic coronary vessels: 0.17 in CAD(-), 0.20 in 1-VD, 0.21 in 2-VD and 0.22 ng/mL in 3-VD (P<0.05). High nesfatin-1 level (>0.19 ng/mL) was found in 43% of pts with CAD(-), 55% of 1-VD, 55% of 2-VD and 68% of 3-VD (P<0.05). Nesfatin-1 levels also correlated with the number of stenotic segments and the severity score (r=0.14 and r=0.13, P<0.02), but they did not correlate with body mass index or HbA1c level. In multivariate analysis, nesfatin-1 levels were a significant factor associated with CAD, especially 3-VD, independent of atherosclerotic risk factors. The odds ratios for CAD and 3-VD were 1.71 (95%CI=1.01-2.91) and 1.96 (95%CI=1.02-3.76) for high nesfatin-1 level of >0.19 ng/mL (P<0.05). Conclusions: Plasma nesfatin-1 levels were found to be associated with the presence and severity of CAD independent of atherosclerotic risk factors. High nesfatin-1 levels in CAD pts may be aimed at preventing the progression of coronary atherosclerosis. [ABSTRACT FROM AUTHOR]

Betatrophin, also called angiopoietin-llike protein 8, is a recently identified adipokine, mainly produced in liver and adipose tissue, which is recognized to play a dual role in lipid and glucose metabolism. However, any association between plasma betatrophin levels and atherosclerotic diseases, such as coronary artery disease (CAD) and peripheral artery disease (PAD), has not been elucidated yet. We investigated plasma betatrophin levels by ELISA in 457 patients (pts) undergoing elective coronary angiography who also had ankle-brachial index (ABI) test for PAD screening. Pts with ACS or a history of PCI were excluded. Results: Of the 457 study pts, CAD was present in 241 (53%), of whom 99 had 1-vessel, 71 had 2-vessel, 71 had 3-vessel disease (3-VD). Plasma betatrophin levels were higher in 241 pts with CAD than in 216 without CAD (median 1120 vs. 909 pg/mL, P<0.001). A stepwise increase in betatrophin levels was found depending on the number of >50% stenotic coronary vessels: 909 in CAD(-), 962 in 1-VD, 1097 in 2-VD and 1393 pg/mL in 3-VD (P<0.001). Betatrophin levels also correlated with the numbers of >50% and >25% stenotic coronary segments (r=0.22 and r=0.24, P<0.001). Moreover, betatrophin levels correlated with HbA1c (r=0.18, P<0.001) but not with FPG and triglyceride levels. In multivariate analysis, betatrophin levels were not a factor for CAD but were a significant factor for 3-VD independent of atherosclerotic risk factors. Odds ratio for 3-VD was 1.06 (95%CI=1.01-1.11, P<0.02) for a 100 pg/mL increase in betatrophin levels. Of the 457 pts, PAD (ABI<0.9) was found in 41 (9%). Betatrophin levels were also higher in 41 pts with PAD than in 416 without PAD (median 1354 vs. 981 pg/mL, P<0.001). Notably, pts with PAD more often had CAD (85% vs. 65%), especially 3-VD (46% vs. 13%) (P<0.001). In multivariate analysis, betatrophin levels were a significant factor for PAD independent of atherosclerotic risk factors and CAD. Odds ratio for PAD was 1.08 (95%CI=1.01-1.14, P<0.02) for a 100 pg/mL increase in betatrophin levels. Conclusions: Plasma betatrophin levels were found to be associated with the presence and severity of CAD as well as PAD independent of atherosclerotic risk factors. Betatrophin may play a role in the development of atherosclerotic diseases. [ABSTRACT FROM AUTHOR]

Introduction: Patients with renal impairment are considered a coronary artery disease (CAD) equivalent. Repeated coronary artery calcium (CAC) scoring has been recognized as a robust tool for tracking progression of atherosclerosis. Further, CAC progression is an important marker of future adverse event. However, the evidence for an independent association of renal function with CAC progression remains unclear. Hypothesis: To examine the cross-sectional association between renal function and CAC progression. Methods: From a 6-center, single ethnicity observational registry, a total of 10,033 asymptomatic adults (mean age: 51.1±8.5 years, 84.9% men) without prior history of CAD and stroke underwent 2 examinations, including CAC screening as part of a broader health study with an average of 3.3±1.9 years between baseline scan and follow-up scan. Estimated glomerular filtration rate (eGFR; mL/min/1.73 m2) was ascertained using the modified MDRD formula, and was categorized as: ≥90 (normal), 60-89 (mildly decreased), and <60 (moderate-to-severely decreased) based on current guidelines. CAC progression was calculated as the difference between the square root of baseline and square root of follow-up CAC score ≥2.5. Results: During an 8.7-year follow-up (IQR, 6.4-10.6 years), CAC progression was found in 766 subjects (7.6%). The patients with more impaired renal function were older, likely to be women and higher prevalence of hypertension, diabetes mellitus, and dyslipidemia. Among patients with normal or mildly decreased renal function, no difference of the proportion was found according to the presence or absence of CAC progression. Yet, patients with moderate-to-severely decreased renal function of eGFR <60 had higher prevalence of CAC progression (7.3% vs. 4.5%) (Figure). Notably, multivariate logistic regression model revealed that impaired renal function was associated with the progression of CAC (Odds ratio [OR]: 1.11, 95% confidence interval [CI]: 1.00-1.33 for eGFR 60-89 and OR: 1.80, 95% CI: 1.31-2.42 for eGFR <60). Conclusions: Impaired renal function evoked a strong relationship with a higher risk of the progression of subclinical atherosclerosis as measured by CAC scoring. [ABSTRACT FROM AUTHOR]

Background: Epicardial coronary endothelial dysfunction is associated with development and progression of local coronary atherosclerotic lesion. However, the role of coronary microvascular endothelial function in the development of coronary atherosclerosis is largely unknown. The aim of the present study was to test the hypothesis that coronary microvascular endothelial dysfunction (CMED) is associated with epicardial atherosclerotic coronary artery disease (CAD). Methods and Results: 148 patients with chest pain, referred for the evaluation of coronary vasomotion and found to have angiographically normal coronary arteries or mild CAD (<40% stenosis), underwent invasive coronary endothelial function testing and virtual-histology intravascular ultrasound (VH-IVUS) of the left anterior descending coronary artery. Endothelium-dependent coronary vascular reactivity was evaluated by graded administration of intracoronary acetylcholine. CMED was defined as percent increase in coronary blood flow of ≤50% in response to a maximum dose of acetylcholine. Patients with CMED (n=87), as compared to those with normal microvascular endothelial function (n=61), had higher averaged epicardial plaque necrotic core area [0.07 (0.01-0.34) vs. 0.03 (0.00-0.17) mm2, p=0.016] and higher frequency of imaged arteries containing at least one VH-IVUS-derived thin-cap fibroatheroma (TCFA) [n=22 (25.3%) vs. 5 (8.2%), p=0.008] (Figure). After adjusting for age, gender and CAD risk factors, CMED was an independent predictor of VH-IVUS-derived larger averaged necrotic core area (β=0.176, p=0.033) and TCFA frequency (β=0.180, p=0.028). Conclusions: CMED is an independent predictor of larger necrotic core plaque area and higher TCFA frequency, both of which are characteristics of rupture-prone plaques. [ABSTRACT FROM AUTHOR]