Serum 25-hydroxyvitamin-D and nonalcoholic fatty liver disease: Does race/ethnicity matter? Findings from the MESA cohort.

BACKGROUND AND AIMS: Low serum 25-hydroxyvitamin D (25(OH)D) is associated with higher nonalcoholic fatty liver disease (NAFLD) risk in studies of mainly white participants. Significant racial/ethnic differences exist in serum 25(OH)D and NAFLD prevalence questioning extending this association to other racial/ethnic groups. We tested whether the association between serum 25(OH)D and NAFLD vary by race/ethnicity. METHODS AND RESULTS: This was a cross-sectional analysis from the Multi-Ethnic Study of Atherosclerosis (MESA) that included 3484 participants (44% male; 38.4% Whites, 27.8% African-Americans, 23.5% Hispanics, and 10.3% Chinese-Americans) who had serum 25(OH)D and upper abdominal CT images available at baseline. Serum 25(OH)D was measured by high-performance liquid chromatography-tandem mass spectrometry. NAFLD was identified if liver-to-spleen Hounsfield-Unit ratio was <1. Whites had the highest 25(OH)D level and African-Americans had the lowest level (mean ± SD: 29.5 ± 10.4 vs.19.9 ± 9.1, respectively). Six hundred and eleven (17.5%) participants had NAFLD; Hispanics had the highest prevalence (26.2%) followed by Chinese-Americans (19.8%), Whites (15.8%) and African-Americans (11.7%), P < 0.0001. In adjusted model, the association of 25(OH)D with NAFLD differed by race/ethnicity (P < 0.0001). Negative association was only evident in Causations (OR (95% CI):1.23 (1.03, 1.47) per 1 SD lower serum 25(OH)D). For other racial/ethnic groups, BMI, triglycerides, diabetic status and/or smoking, but not serum 25(OH)D, were common independent risk factors for NAFLD. CONCLUSIONS: The negative association between serum 25(OH)D and NAFLD in Whites may not be broadly generalizable to other racial/ethnic groups. Modifiable risk factors including BMI, triglycerides, diabetic status and/or smoking associate with NAFLD risk in non-white racial/ethnic groups beyond 25(OH)D.

Association Between Endogenous Sex Hormones and Liver Fat in a Multiethnic Study of Atherosclerosis.

BACKGROUND & AIMS: Levels of circulating of sex hormones are associated with glucose metabolism and adiposity, but little is known about their association with ectopic fat. We aimed to characterize the association between circulating sex hormones and liver fat. METHODS: We conducted a cross-sectional analysis by using data from the Multiethnic Study of Atherosclerosis to assess the association of the circulating levels of bioavailable testosterone, estradiol, dehydroepiandrosterone, and sex hormone binding globulin (SHBG) with fatty liver. Fatty liver was defined as a reduction of ≤40 Hounsfield units, measured by computed tomography, in 2835 postmenopausal women and 2899 men (45-84 years old; white, black, Hispanic, or Chinese) at 6 centers in the United States. RESULTS: Women in the highest tertile of bioavailable testosterone were significantly more likely to have fatty liver than women in the lowest tertile (odds ratio, 1.77; 95% confidence interval, 1.07-2.92). We found an even greater difference for level of estradiol (odds ratio, 2.49; 95% confidence interval, 1.41-4.39) after adjusting for age, race/ethnicity, waist-to-hip ratio, hypertension, total and high-density lipoprotein cholesterol, smoking, insulin sensitivity, and hormone replacement therapy use. Men in the highest tertile of estradiol level were significantly more likely to have fatty liver than men in the lowest tertile (odds ratio, 2.10; 95% confidence level, 1.29-3.40). Men in the highest tertile of SHBG were less likely to have fatty liver than those in the lowest tertile (odds ratio, 0.46; 95% confidence interval, 0.27-0.77). Other associations between hormone levels and fatty liver were not statistically significant. CONCLUSIONS: On the basis of a cross-sectional study, postmenopausal women with high levels of bioavailable testosterone are at greater risk for fatty liver. In men, higher levels of SHBG are associated with reduced risk for fatty liver. Higher levels of estradiol are associated with fatty liver in both sexes. This pattern is consistent with the sex-specific associations of sex hormones with other cardiometabolic risk factors.

Coronary artery calcium screening: does it perform better than other cardiovascular risk stratification tools?

Coronary artery calcium (CAC) has been advocated as one of the strongest cardiovascular risk prediction markers. It performs better across a wide range of Framingham risk categories (6%-10% and 10%-20% 10-year risk categories) and also helps in reclassifying the risk of these subjects into either higher or lower risk categories based on CAC scores. It also performs better among population subgroups where Framingham risk score does not perform well, especially young subjects, women, family history of premature coronary artery disease and ethnic differences in coronary risk. The absence of CAC is also associated with excellent prognosis, with 10-year event rate of 1%. Studies have also compared with other commonly used markers of cardiovascular disease risk such as Carotid intima-media thickness and highly sensitive C-reactive protein. CAC also performs better compared with carotid intima-media thickness and highly sensitive C-reactive protein in prediction of coronary heart disease and cardiovascular disease events. CAC scans are associated with relatively low radiation exposure (0.9-1.1 mSv) and provide information that can be used not only for risk stratification but also can be used to track the progression of atherosclerosis and the effects of statins.

Intramural coronary arterial course is associated with coronary arterial stenosis and prognosis of major cardiac events.

OBJECTIVE: The clinical significance of an intramural course (or bridging) of the coronary artery remains controversial. We investigated the relationship between intramural coronary arteries (ICAs) and coronary stenosis and prognosis of subjects with ICA. METHODS AND RESULTS: ICA and coronary stenosis were assessed by multidetector computed tomography coronary angiography. ICAs in the left anterior descending artery were studied, which were further classified as superficial (≤2 mm) or deep type (>2 mm). Coronary stenosis was classified as nonstenosis, insignificant stenosis (<50%), and significant stenosis (≥50%). A total of 261 subjects with ICA in left anterior descending artery were identified from 2318 enrolled subjects. Most of the ICAs (66.3%) were superficial. ICA was positively associated with insignificant stenosis, and the odds ratios were 2.055 (95% confidence interval, 1.405-3.007), 3.314 (1.818-6.039), and 1.640 (1.036-2.597) for overall, deep, and superficial ICA (all P<0.05), respectively. In the case of significant stenosis, ICA was negatively associated, and the odds ratios were 0.555 (0.416-0.739) and 0.413 (0.288-0.590) for overall and superficial ICA (both P<0.05), respectively, and 0.985 (0.611-1.588; P>0.05) for deep ICA type. The depth and location of ICA correlated with stenosis. The major cardiac events, including cardiovascular death, myocardial infarction, and revascularization, were recorded during 3-year follow-up. ICA predicted a lower incidence of major cardiac events, especially superficial type; the adjusted hazard ratios were 0.585 (0.375-0.911; P=0.018) and 0.535 (0.300-0.954; P=0.034) for total and superficial type, respectively. CONCLUSIONS: ICA, especially deep type, is positively associated with insignificant stenosis proximal to ICA. Meanwhile, ICA, especially superficial type, is negatively associated with significant stenosis proximal to ICA and predicts a better prognosis not only in normal subjects but also in patients with coronary artery disease.

Non-calcified plaque in asymptomatic patients with zero coronary artery calcium score: A systematic review and meta-analysis.

BACKGROUND: There is growing interest in understanding the coronary atherosclerotic burden in asymptomatic patients with zero coronary artery calcium score (CACS). In this population, we aimed to investigate the prevalence and severity of non-calcified coronary plaques (NCP) as detected by coronary CT angiography (CCTA), and to analyze the associated clinical predictors. METHODS: This was a systematic review with meta-analysis of studies indexed in PubMed/Medline and Web of Science from inception of the database to March 31st, 2023. Using the random-effects model, separate Forest and Galbraith plots were generated for each effect size assessed. Heterogeneity was assessed using the I2 statistics whilst Funnel plots and Egger's test were used to assess for publication bias. RESULTS: From a total of 14 studies comprising 37808 patients, we approximated the pooled summary estimates for the overall prevalence of NCP to be 10% (95%CI: 6%-13%). Similarly, the pooled prevalence of obstructive NCP was estimated at 1.1% (95%CI: 0.7%-1.5%) from a total of 10 studies involving 21531 patients. Hypertension [OR: 1.46 (95%CI:1.31-1.62)] and diabetes mellitus [OR: 1.69 (95%CI: 1.41-1.97)] were significantly associated with developing any NCP, with male gender being the strongest predictor [OR: 3.22 (95%CI: 2.17-4.27)]. CONCLUSION: There is a low burden of NCP among asymptomatic subjects with zero CACS. In a subset of this population who have clinical predictors of NCP, the addition of CCTA has a potential to provide a better insight about occult coronary atherosclerosis, however, a risk-benefit approach must be factored in prior to CCTA use given the low prevalence of NCP.

Investigating peripheral blood monocyte and T-cell subsets as non-invasive biomarkers for asymptomatic hepatic steatosis: results from the Multi-Ethnic Study of Atherosclerosis.

Background: Circulating immune cells have gained interest as biomarkers of hepatic steatosis. Data on the relationships between immune cell subsets and early-stage steatosis in population-based cohorts are limited. Methods: This study included 1,944 asymptomatic participants of the Multi-Ethnic Study of Atherosclerosis (MESA) with immune cell phenotyping and computed tomography measures of liver fat. Participants with heavy alcohol use were excluded. A liver-to-spleen ratio Hounsfield units (HU) <1.0 and liver attenuation <40 HU were used to diagnose liver fat presence and >30% liver fat content, respectively. Logistic regression estimated cross-sectional associations of immune cell subsets with liver fat parameters adjusted for risk factors. We hypothesized that higher proportions of non-classical monocytes, Th1, Th17, and memory CD4+ T cells, and lower proportions of classical monocytes and naive CD4+ T cells, were associated with liver fat. Exploratory analyses evaluated additional immune cell phenotypes (n = 19). Results: None of the hypothesized cells were associated with presence of liver fat. Higher memory CD4+ T cells were associated with >30% liver fat content, but this was not significant after correction for multiple hypothesis testing (odds ratio (OR): 1.31, 95% confidence interval (CI): 1.03, 1.66). In exploratory analyses unadjusted for multiple testing, higher proportions of CD8+CD57+ T cells were associated with liver fat presence (OR: 1.21, 95% CI: 1.02, 1.44) and >30% liver fat content (OR: 1.34, 95% CI: 1.07, 1.69). Conclusions: Higher circulating memory CD4+ T cells may reflect liver fat severity. CD8+CD57+ cells were associated with liver fat presence and severity, but replication of findings is required.

Measurement of phantomless thoracic bone mineral density on coronary artery calcium CT scans acquired with various CT scanner models.

PURPOSE: To determine the accuracy and precision of thoracic phantomless bone mineral density (BMD) measurements obtained on coronary artery calcium (CAC) computed tomography (CT) scans by using a variety of commercially available CT scanners. MATERIALS AND METHODS: The institutional review board approved this Health Insurance Portability and Accountability Act-compliant study. A total of 4126 asymptomatic subjects (2022 [49%] men, 2104 [51%] women; mean age, 63.7 years ± 11.8 [standard deviation]) underwent CAC CT with the use of a quantitative CT calibration phantom for evaluation of subclinical atherosclerosis. Two hundred eighty subjects also underwent CT of the chest, abdomen, and pelvis (C7 through L5). Mean BMD of three consecutive thoracic vertebrae (in the T7-T10 range) was measured in all 4126 subjects. Individual calibration factors for each phantom insert and a general calibration factor for the spine were determined for each CT scanner model. The study population was then divided into three subgroups: All calibration factors were generated from group 1 (n = 1536) and were applied and tested in group 2 (n = 1587), and effects of various image acquisition parameters were assessed in group 3 (n = 1003). Accuracy (bias) and precision of thoracic phantomless BMD measurements across 14 CT scanner models from five manufacturers were determined. RESULTS: Phantomless BMD values correlated highly with standard phantom-based quantitative CT BMD values (r = 0.987, P < .001). Bias was 3.9% ± 1.4 for phantomless BMD measurements, and the mean coefficient of variation for the general calibration factor was 4.9% ± 2.4. CONCLUSION: Phantomless BMD can be measured accurately on CAC CT scans acquired with a variety of CT scanners without additional radiation exposure.

Use of noninvasive imaging in the evaluation of coarctation of aorta.

Coarctation of the aorta is a congenital heart disease, which is often associated with other cardiac and noncardiac anomalies. Early diagnoses, information about associated anomalies, and defining the severity of the disease are critical for appropriate treatment planning. In this regard, several noninvasive imaging modalities, such as echocardiography, cardiac computed tomography (CT), and cardiac magnetic resonance imaging, have been used. Echocardiography, as an available and safe method, should be used as a primary screening test. It is also useful for intraoperative and hemodynamic studies, but cardiac CT is recommended before any corrective procedure or surgery. Cardiac CT angiography showed an excellent spatial resolution and a good capability for finding associated anomalies. After correction of coarctation of the aorta, serial cardiac magnetic resonance imaging is most commonly performed to avoid repeated radiation exposure.

A systematic review and meta-analysis of the prevalence, incidence, and predictors of atrial fibrillation in cardiac sarcoidosis.

BACKGROUND: The occurrence of atrial arrhythmias, in particular, atrial fibrillation (AF) in patients with cardiac sarcoidosis (CS) are of growing interest in the field of infiltrative cardiomyopathies. Via a systematic review with meta-analysis, we sought to synthesize data on the prevalence, incidence, and predictors of atrial arrhythmias as well as outcomes in patients with CS. METHODS: PubMed/Medline, Web of Science, and Scopus were systematically queried from inception until April 26th, 2023. Using the random-effects model, separate plots were generated for each effect size assessed. RESULTS: From a total of 8 studies comprising 978 patients with CS, the pooled summary estimates for the prevalence of AF was 23% (95% CI: 13%-34%). Paroxysmal AF was the most common subtype of AF (83%; 95% CI: 77%-90%), followed by persistent AF (17%; 95% CI: 10%-23%). In 9 studies involving 545 patients with CS, the pooled incidence of AF was estimated at 5%, 13.1%, and 8.9% at <2 years, 2-4 years, and > 4 years of follow-up respectively, with an overall cumulative incidence of 10.6% (95% CI: 4.9%-17.8%) over a 6-year follow-up period. Increased left atrial size and atrial 18F-fluorodeoxyglucose uptake were identified as strong independent predictors for the development of atrial arrhythmias on qualitative synthesis. CONCLUSION: The burden of AF and related arrhythmias in CS patients is considerable. This necessitates close follow-up and predictive risk-stratification tools to guide the initiation of appropriate strategies, including therapeutic interventions for prevention of AF-related embolic phenomenon, especially in those with known clinical predictors.

In-Hospital Outcomes of COVID-19 Associated Myocarditis (from a Nationwide Inpatient Sample Database Study).

The prevalence of COVID-19 infection-related myocarditis, its in-hospital cardiovascular outcomes, and its impact on hospital cost and stay at national level are not well studied in the literature. The Nationwide Inpatient Sample Database from 2020 was queried to identify patients with COVID-19 and myocarditis versus those without myocarditis. Cardiovascular outcomes and resource utilization were studied among cohorts with COVID-19, with and without myocarditis, using descriptive statistics, multivariate regression matching, and propensity score matching using STATA version 17. Of 1,678,995 patients, 3,565 (0.21%) had COVID-19 with myocarditis, and 1,675,355 (99.78%) had COVID-19 without myocarditis. On multivariate regression analysis, we found higher odds of in-hospital mortality (adjusted odds ratio [aOR] 1.59, 95% confidence interval [CI] 1.27 to 1.9) in patients with myocarditis than in those without myocarditis, in addition to higher odds of major adverse cardiovascular and cerebrovascular events (aOR 3.54, 95% CI 2.8 to 4.4), acute kidney injury (aOR 1.29, 95% CI 1.27 to 1.9), heart failure (aOR 2.77, 95% CI 2.3 to 3.4), cardiogenic shock (aOR 10.2, 95% CI 7.9 to 13), myocardial infarction (aOR 5.74, 95% CI 4.5 to 7.3), and use of mechanical circulatory support (aOR 2.81, 95% CI 1.6 to 4.9). The propensity-matched cohort also favored similar outcomes. In conclusion, patients with COVID-19 and myocarditis had worse clinical outcomes, having a higher rate of in-hospital mortality, major adverse cardiovascular and cerebrovascular events with longer length of hospital stay, and higher hospitalization costs. Large prospective trials are necessary to validate these findings with diagnostic measures, including biopsy and cardiac magnetic resonance imaging for the extent of myocardial involvement.

Multimodality assessment of high- vs. low-gradient aortic stenosis using echocardiography and cardiac CT.

BACKGROUND: Aortic valve area (AVA) using CT-LVOT area (AVACT-LVOT) <1.2 â€‹cm2 has been shown comparable to echocardiography AVA of <1.0 â€‹cm2 for severe aortic stenosis (AS). Current study evaluates how AS diagnosis will be affected when we substitute CT-LVOT with echo derived LVOT. METHODS: We retrospectively studied 367 patients who underwent cardiac CTA and echocardiogram for assessment of high- and low-gradient AS (HG-AS and LG-AS). AVACT-LVOT was derived from CT-LVOT area and echo doppler data. Three AVACT-LVOT categories were created (<1.0, 1.0-1.2 and â€‹> â€‹1.2 â€‹cm2). Outcomes were defined as composite of all-cause mortality and/or valve intervention. RESULTS: Median echocardiographic profiles were consistent with severe AS across three AVACT-LVOT categories for HG-AS. HG-AS patients with AVACT-LVOT >1.2 â€‹cm2 had larger median CT-LVOT area (5.06 â€‹cm2) and AVC (2917AU). Among LG-AS with AVACT-LVOT â€‹≤1.2 cm2, 57% met echo criteria for low-flow LG-AS and 63% met criteria for severe AS using aortic valve calcium (AVC). Additionally, 45% with AVACT-LVOT >1.2 â€‹cm2 had larger median CT-LVOT area (5.43 â€‹cm2) and AVC (2389AU). Patients with AVACT-LVOT >1.2 â€‹cm2 and high AVC had large body surface area and were mostly characterized as severe with indexed AVA and AVC. Stroke volume index using CT-LVOT reclassified 70% of low-flow, LG-AS as normal flow, LG-AS. Composite outcomes were higher among patients with AVACT-LVOT ≤1.2 â€‹cm2 (p â€‹< â€‹0.01), however, with no superior net reclassification improvement compared to AVAecho <1.0 â€‹cm2. CONCLUSION: AVACT-LVOT ≤1.2 â€‹cm2 is a reasonable CT criterion for severe AS. Large LVOT with elevated AVC identified a severe AS phenotype despite an AVACT-LVOT >1.2 â€‹cm2, best characterized by indexed AVA and AVC.

Predictors of non-calcified plaque presence and future adverse cardiovascular events in symptomatic rural Appalachian patients with a zero coronary artery calcium score.

BACKGROUND: Coronary artery calcium (CAC) scoring is a proven predictor for future adverse cardiovascular events (CVE) in asymptomatic individuals. Data is emerging regarding the usefulness of non-calcified plaque (NCP) assessment on cardiac computed tomography (CCT) angiography in symptomatic patients with a zero CAC score for further risk assessment. METHODS: A retrospective review from January 2019 to January 2022 of 696 symptomatic patients with no known CAD and a zero CAC score identified 181 patients with NCP and 515 patients without NCP by a visual assessment on CCT angiography. The primary endpoint was to identify predictors for NCP presence and adverse CVEs (death, myocardial infarction, or cerebrovascular accident) within two years. RESULTS: Based on logistic regression, age (OR 1.039, 95% CI [1.020-1.058], p â€‹< â€‹0.001), diabetes mellitus (OR 2.192, 95% CI [1.307-3.676], p â€‹< â€‹0.003), tobacco use (OR 1.748, 95% CI [1.157-2.643], p â€‹< â€‹0.008), low-density lipoprotein cholesterol level (OR 1.009, 95% CI [1.003-1.015], p â€‹< â€‹0.002), and hypertension (OR 1.613, 95% CI [1.024-2.540], p â€‹< â€‹0.039) were found to be predictors of NCP presence. NCP patients had a higher pretest probability for CAD using the Morise risk score (p â€‹< â€‹0.001∗), with NCP detection increasing as pretest probability increased from low to high (OR 55.79, 95% CI [24.26-128.26], p â€‹< â€‹0.001∗). 457 patients (66%) reached a full two-year period after CCT angiography completion, with NCP patients noted to have shorter follow-up times and higher rates of elective coronary angiography, intervention, and CVEs. The presence of NCP (aOR 2.178, 95% CI [1.025-4.627], p â€‹< â€‹0.043) was identified as an independent predictor for future adverse CVEs when adjusted for diabetes mellitus, age, and hypertension. CONCLUSION: NCP was identified at high rates (26%) in our symptomatic Appalachian population with no known CAD and a zero CAC score. NCP was identified as an independent predictor of future adverse CVEs within two years.

Associations between retinol-binding protein 4 and cardiometabolic risk factors and subclinical atherosclerosis in recently postmenopausal women: cross-sectional analyses from the KEEPS study.

BACKGROUND: The published literature regarding the relationships between retinol-binding protein 4 (RBP4) and cardiometabolic risk factors and subclinical atherosclerosis is conflicting, likely due, in part, to limitations of frequently used RBP4 assays. Prior large studies have not utilized the gold-standard western blot analysis of RBP4 levels. METHODS: Full-length serum RBP4 levels were measured by western blot in 709 postmenopausal women screened for the Kronos Early Estrogen Prevention Study. Cross-sectional analyses related RBP4 levels to cardiometabolic risk factors, carotid artery intima-media thickness (CIMT), and coronary artery calcification (CAC). RESULTS: The mean age of women was 52.9 (± 2.6) years, and the median RBP4 level was 49.0 (interquartile range 36.9-61.5) µg/mL. Higher RBP4 levels were weakly associated with higher triglycerides (age, race, and smoking-adjusted partial Spearman correlation coefficient = 0.10; P = 0.01), but were unrelated to blood pressure, cholesterol, C-reactive protein, glucose, insulin, and CIMT levels (all partial Spearman correlation coefficients ≤0.06, P > 0.05). Results suggested a curvilinear association between RBP4 levels and CAC, with women in the bottom and upper quartiles of RBP4 having higher odds of CAC (odds ratio [95% confidence interval] 2.10 [1.07-4.09], 2.00 [1.02-3.92], 1.64 [0.82-3.27] for the 1st, 3rd, and 4th RBP4 quartiles vs. the 2nd quartile). However, a squared RBP4 term in regression modeling was non-significant (P = 0.10). CONCLUSIONS: In these healthy, recently postmenopausal women, higher RBP4 levels were weakly associated with elevations in triglycerides and with CAC, but not with other risk factors or CIMT. These data using the gold standard of RBP4 methodology only weakly support the possibility that perturbations in RBP4 homeostasis may be an additional risk factor for subclinical coronary atherosclerosis. TRIAL REGISTRATION: ClinicalTrials.gov number NCT00154180.

Burden and predictors of statin use in primary and secondary prevention of atherosclerotic vascular disease in the US: from the National Health and Nutrition Examination Survey 2017-2020.

AIMS: To assess the current state of statin use, factors associated with non-use, and estimate the burden of potentially preventable atherosclerotic cardiovascular diseases (ASCVD) events. METHODS AND RESULTS: Using nationally representative data from the 2017 to 2020 National Health and Nutrition Examination Survey, statin use was assessed in primary prevention groups: high ASCVD risk ≥ 20%, LDL-cholesterol (LDL-C) ≥ 190 mg/dL, diabetes aged 40-75 years, intermediate ASCVD risk (7.5 to <20%) with ≥1 ASCVD risk enhancer and secondary prevention group: established ASCVD. Atherosclerotic cardiovascular disease risk was estimated using pooled cohort equations. We estimated 70 million eligible individuals (2.3 million with LDL-C ≥ 190 mg/dL; 9.4 million with ASCVD ≥ 20%; 15 million with diabetes and age 40-75years; 20 million with intermediate ASCVD risk and ≥1 risk enhancers; and 24.6 million with established ASCVD), about 30 million were on statin therapy. The proportion of individuals not on statin therapy was highest in the isolated LDL-C ≥ 190 mg/dL group (92.8%) and those with intermediate ASCVD risk plus enhancers (74.6%) followed by 59.4% with high ASCVD risk, 54.8% with diabetes, and 41.5% of those with established ASCVD groups. Increasing age and those with health insurance were more likely to be on statin therapy in both the primary and secondary prevention categories. Individuals without a routine place of care were less likely to be on statin therapy. A total of 385 000 (high-intensity statin) and 647 000 (moderate-intensity statin) ASCVD events could be prevented if all statin-eligible individuals were treated (and adherent) for primary prevention over a 10-year period. CONCLUSION: Statin use for primary and secondary prevention of ASCVD remains suboptimal. Bridging the therapeutic gap can prevent ∼1 million ASCVD events over the subsequent 10 years for the primary prevention group. Social determinants of health such as access to care and healthcare coverage were associated with less statin treatment. Novel interventions to improve statin prescription and adherence are needed.

Elevated serum thyrotropin levels and endothelial dysfunction in a prospective hemodialysis cohort.

INTRODUCTION: Thyroid dysfunction is a highly prevalent yet under-recognized complication in hemodialysis patients. In the general population, hypothyroidism has been associated with endothelial dysfunction due to impaired vasodilator synthesis and activity. Little is known about the association of serum thyrotropin (TSH), the most sensitive and specific single biochemical metric of thyroid function, with endothelial function in hemodialysis patients. METHODS: In a secondary analysis of 99 patients from the Anti-inflammatory and anti-oxidative nutrition in hypoalbuminemic dialysis patients (AIONID) trial, we examined measurements of serum TSH and endothelial function ascertained by fingertip digital thermal monitoring (DTM), a novel method used to measure micro-vascular reactivity, collected within a 90-day period. DTM was used to measure changes in fingertip temperature during and after an ischemic stimulus (blood pressure cuff occlusion) as an indicator of changes in blood flow, and two DTM indices were assessed, namely adjusted (a) Temperature Rebound (TR), defined as the maximum temperature rebound post-cuff deflation, and adjusted (b) Area Under the Temperature Curve (TMP-AUC), defined as area under the curve between the maximum and minimum temperatures. We examined the relationship between serum TSH with impaired TR (separately) and TMP-AUC (both defined as less than the median level of observed values) using multivariable logistic regression. FINDINGS: In unadjusted and case-mix analyses, higher serum TSH levels (defined as the three highest quartiles) were associated with lower (worse) TR (ref: lowest TSH quartile): ORs (95% CI) 2.64 (1.01-6.88) and 2.85 (1.08-7.57), respectively. In unadjusted and case-mix analyses, higher TSH levels were associated with lower (worse) TMP-AUC: ORs (95% CI) 2.64 (1.01-6.88) and 2.79 (1.06-7.38), respectively. DISCUSSION: In HD patients, higher serum TSH levels were associated with worse micro-vascular reactivity measured by DTM. Further studies are needed to determine if thyroid hormone supplementation improves endothelial function in hemodialysis patients with lower levels of thyroid function.

Cardiac Computed Tomography Angiography for Device-Related Thrombus Assessment After WATCHMAN FLX™ Occluder Device Implantation: A Single-Center Retrospective Observational Study.

BACKGROUND/PURPOSE: Device-related thrombosis (DRT) is one of the greatest challenges of transcatheter left atrial appendage device occlusion. Due to the invasive nature of transesophageal echocardiography (TEE), cardiac computed tomography angiography (CCTA) is being increasingly utilized in several centers for assessing adequate left atrial appendage closure and monitoring for DRT. There is a paucity of data regarding the standardized definition of DRT on CCTA for the WATCHMAN FLX™ device. METHODS/MATERIALS: A retrospective review was conducted on 43 patients receiving WATCHMAN FLX™ device implantation with CCTA performed at the first follow-up at our institution. A comparative review of DRT predictors was performed on 10 patients who had both CCTA and TEE at the time of follow-up. RESULTS: Hypoattenuated thickening (HAT) was a common finding on CCTA and was noted to be present in 95.35% of the patients. The combination of a large device size, peridevice gap >4 mm, and HAT located on the device gutter and 1 shoulder were characteristics present on CCTA observed in 2 patients with confirmed DRT on TEE. CONCLUSION: CCTA is a noninvasive imaging modality for DRT monitoring, with guidelines still in development. We report potential predictors of DRT on CCTA. Additional studies are needed to further determine standardized parameters for DRT detection on CCTA and the significance of HAT with multimodality correlation.

MESA: the NIH-sponsored study that validates atherosclerosis imaging for primary prevention.

Coronary artery calcium (CAC) score correlates strongly with the burden of atherosclerotic plaques in the coronary arteries. It is the strongest predictor of future coronary events in asymptomatic individuals, being stronger than all traditional risk factors combined. It is also a better predictor of future events than carotid intima-media thickness (CIMT) measurement for the prediction of coronary artery disease but slightly weaker than CIMT for the prediction of cerebrovascular events such as stroke. These findings have been validated by the Multi-Ethnic Study of Atherosclerosis (MESA), a prospective epidemiologic study sponsored by the National Institutes of Health (NIH) investigating the prevalence, correlates, and progression of atherosclerosis in an asymptomatic, ethnically diverse population. That is why the US national guidelines have recently elevated their recommendation levels to Class IIa for use of CAC and CIMT in risk stratification of the asymptomatic intermediate-risk population.

Deep neural survival networks for cardiovascular risk prediction: The Multi-Ethnic Study of Atherosclerosis (MESA).

BACKGROUND: There is growing interest in utilizing machine learning techniques for routine atherosclerotic cardiovascular disease (ASCVD) risk prediction. We investigated whether novel deep learning survival models can augment ASCVD risk prediction over existing statistical and machine learning approaches. METHODS: 6814 participants from the Multi-Ethnic Study of Atherosclerosis (MESA) were followed over 16 years to assess incidence of all-cause mortality (mortality) or a composite of major adverse events (MAE). Features were evaluated within the categories of traditional risk factors, inflammatory biomarkers, and imaging markers. Data was split into an internal training/testing (four centers) and external validation (two centers). Both machine learning (COXPH, RSF, and lSVM) and deep learning (nMTLR and DeepSurv) models were evaluated. RESULTS: In comparison to the COXPH model, DeepSurv significantly improved ASCVD risk prediction for MAE (AUC: 0.82 vs. 0.80, P ≤ 0.001) and mortality (AUC: 0.87 vs. 0.84, P ≤ 0.001) with traditional risk factors alone. Implementing non-categorical NRI, we noted a >40% increase in correct reclassification compared to the COXPH model for both MAE and mortality (P ≤ 0.05). Assessing the relative risk of participants, DeepSurv was the only learning algorithm to develop a significantly improved risk score criteria, which outcompeted COXPH for both MAE (4.22 vs. 3.61, P = 0.043) and mortality (6.81 vs. 5.52, P = 0.044). The addition of inflammatory or imaging biomarkers to traditional risk factors showed minimal/no significant improvement in model prediction. CONCLUSION: DeepSurv can leverage simple office-based clinical features alone to accurately predict ASCVD risk and cardiovascular outcomes, without the need for additional features, such as inflammatory and imaging biomarkers.

Association of inflammatory markers and lipoprotein particle subclasses with progression of coronary artery calcium: The multi-ethnic study of atherosclerosis.

BACKGROUND AND AIMS: Atherosclerosis is a complex phenomenon manifesting several features typical of chronic inflammation and disorders of lipid metabolism. We assessed association of nuclear magnetic resonance (NMR) lipid variables and inflammatory markers with incident coronary artery calcium (CAC) and CAC progression among participants with baseline CAC ≥0. METHODS: MESA is a longitudinal cohort study of 6,814 participants (aged 45-85). 3,115 had CAC = 0 and 2,896 had CAC>0 at baseline. Repeat CAC measurements were obtained (mean duration of follow up, 6.5 years). RESULTS: IL-6 (log pg/mL) and fibrinogen (50 mg/dL) were associated with a higher relative risk (RR) of incident CAC (HU) (RR = 1.09, p=0.010 & RR 1.05, p=0.004, respectively). Small LDL (100 nmol/L) (RR = 1.03, p<0.001) and log large VLDL (log nmol/L) (RR = 1.06, p=0.001) were associated with higher risks, whereas large HDL (µmol/L) was associated with an inverse risk of incident CAC (RR = 0.97, p< 0.001) in a model adjusted for follow up time, age, gender and race. Among participants with baseline CAC>0, progression of CAC was positively associated with hsCRP (log mg/L) (ß = 1.99), IL-6 (log pg/mL) (ß = 2.9), fibrinogen (50 mg/dL) (ß = 1.0), large VLDL (log nmol/L) (ß = 2.2), and small LDL (100 nmol/L) (ß = 0.36) (all p values < 0.05) in a model adjusted for scanner type, age, gender and race. Relationships with inflammatory markers and NMR lipoprotein particles lost significance after adjustment for traditional risk factors and statin use. Traditional risk factors were strongly associated with both CAC incidence and progression with the exception of cholesterol parameters not associated with CAC progression in adjusted model. CONCLUSIONS: Inflammatory markers and lipoprotein particles were associated with CAC incidence and progression in minimally adjusted models, but not after adjustment for traditional risk factors.