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Impaired endothelial function portends an increased risk of cardiovascular disease. Vascular oxidative stress and systemic inflammation play a critical role in the pathogenesis and progression of vascular disease. Aged garlic extract (AGE) may improve impaired vascular endothelial function, while decreasing the progression of atherosclerotic plaque. We hypothesized that AGE may improve endothelial function, and in this study, we examined this hypothesis to determine whether this can be achieved over a period of 3 months, measured by the cardio-ankle vascular index (CAVI), by reducing intracellular oxidant stress and stimulating nitric oxide generation in endothelial cells. We conducted a double-blinded placebo controlled, randomized clinical trial to investigate the effects of AGE on CAVI in subjects with type 2 diabetes mellitus. A total of 65 individuals (38 men and 27 women) with a mean age of 58.8±11.1 years were enrolled and randomized to the AGE or placebo group in a double-blind placebo controlled trial. An ANOVA model with treatment as the main effect was used to compare changes in CAVI from baseline to follow-up between groups. The primary objective of this study was reduction in CAVI over a 3-month period. In the AGE group, CAVI was reduced on average by 0.71±1.27 vs. a mean reduction of 0.13±0.94 in the placebo group (P=0.04). On the whole, this study demonstrates that AGE has a positive impact on endothelial function in patients with T2DM and may play a role in the primary prevention of cardiovascular disease.

Objectives: Coronary artery calcium (CAC) has been demonstrated as a non-invasive, low-cost means of assessing atherosclerotic burden and risk of major cardiovascular events in asymptomatic individuals. While it has been previously shown that CAC progression predicts all-cause mortality, we sought to further quantify this association by examining a large cohort of individuals over a follow-up period of between 1 to 22 years. Methods: We studied 3,260 persons aged 30 to 89 years who were referred by their primary care physician for CAC measurement, and had a follow-up scan at least 12 months from initial scan. CAC change was evaluated by absolute change between baseline and follow-up scan. Multivariate analyses using Cox proportional hazards models were used to compute hazard ratios (HRs) and 95% confidence intervals (CIs) for the association between CAC progression and death after adjusting for age, gender, race and other risk factors. Participants were considered at risk from the date of exam 1 to the first occurrence of an event of death or lost to follow-up. The occurrence of death across the follow-up period was verified with the National Death Index. Results: The average time between scans was 4.7±3.2 years with an additional average of 9.1±4.0 years of follow-up time. The average age of the cohort was 58.1 ±10.5 years, 70% being male. A total of 164 deaths occurred. A clinical cut point of CAC progression of 100 units was significantly associated with mortality, hazard ratio 1.51 (95% CI 1.10 -2.13) P=0.017, while adjusting for age, gender, race, diabetes mellitus, hypertension, hyperlipidemia, smoking, baseline CAC and family history. Figure 1. Conclusions: CAC progression of greater than 100 units predicts all-cause mortality. This may add clinical value in encouraging close surveillance and aggressive treatment of individuals within this range.

Introduction and Hypothesis: There is a disproportionately higher incidence of atherosclerotic cardiovascular disease (ASCVD) and associated adverse outcomes in South Asians (SA), compared to other races. SA ancestry has been identified as a risk enhancer in the US cholesterol guidelines. Coronary artery calcium (CAC), a validated marker of sub clinical atherosclerosis offers a robust assessment of CVD risk. We sought to compare the distribution of CAC scores as a marker of CVD risk, across various age groups in SA and other races/ethnicities. Methods: Our analyses included 33,663 individuals (517 SA, 24,060 whites, 1,509 African Americans (AA), 3,759 Hispanics, 3,818 Asians), who underwent CAC scoring at our center. CAC scores were stratified by age, across various races/ethnic sub-groups. Age groups were classified into quartiles as follows: 67 years of age. Differences in median CAC across races/ethnicities were tested with the Kruskal-Wallis Test, by age quartiles as described. Results: Mean (SD) age was 59 (11.6) years and 63% were men in the entire cohort. SA over 67 years of age, had significantly higher median CAC score 354.0, Interquartile Range (IQR) 36 - 1476, compared to other race/ethnicities (Median CAC (IQR): whites, 195, (21-762), Hispanics 167.5, (19-779), Asians 144, (14-642), AA 159 (8.5-676) (P=0.0019). In age groups from 50-67 years of age, median CAC scores were not significantly different between these groups (Figure 1). Conclusions: In older age groups, SA have higher median CAC scores compared to whites and other racial/ethnic groups including AAs, Hispanics and other Asians. The observed differences in atherosclerotic burden provide mechanistic insights to higher CVD risk, in the vulnerable SA groups. Future studies should explore the effects of CAC screening on treatment strategies, such as initiation of statins and prognosis in SA.

Introduction: Heart disease is the leading cause of death amongst active firefighters. Firefighters undergo exercise treadmill test as a part of fitness for duty examinations screening for heart disease. It has been previously shown that coronary artery calcium (CAC) scoring and CT angiography (CTA) together can be used cost effectively in further screening for obstructive coronary artery disease amongst firefighters. A coronary artery calcium score threshold to predict obstructive CAD however is yet to be established. Methods: Firefighters in the County of Los Angeles Fire Department underwent fitness for training tests over a twenty-year period using treadmill ECG tests for cardiac screening. Those with positive tests were referred for further evaluation with coronary calcium scoring (CCS). Individuals with a CCS of > 10 went on to have CTA as prior studies have shown that CCS < 10 is highly unlikely to correlate with obstruction. We used receiver-operating characteristic (ROC) analysis to determine the optimal sensitivity and specificity of a CCS threshold needed to predict which individuals were likely to have a CTA showing greater than 50% stenosis. Results: Annually, about 3000 firefighters undergo fitness for duty testing in Los Angeles County. In our sample population from 1999 to 2019, a total of 1425 firefighters had a positive treadmill test. All 1425 of these firefighters underwent CCS with scores varying from 0 to 1400, the distribution vastly skewed toward 0. A ROC curve analysis indicated that a CCS score of 75 was the optimal cutoff for sensitivity (82%) and specificity (62%), in predicting a stenosis greater than 50% in any segment in the CTA firefighter population. However, given the high stress associated with firefighter duty and the high mortality both on-duty and after-duty, we believe prioritization should be geared toward detection and prevention. For this reason, we chose to maximize sensitivity in our statistical analysis and determined that a CAC score of 10 (sensitivity 95%, specificity 13%) to be the most appropriate threshold. Conclusion: For future testing, a CCS threshold score of 10 can confidently be used to guide further testing for obstructive coronary artery disease with CTA.

Background: Traditionally, osteoporosis and coronary artery disease were considered unrelated. Beyond age, these two conditions appear to share common etiologies that are not yet fully understood. Objective: We sought to evaluate the relationship between thoracic spine bone mineral density (BMD) and severity of coronary artery calcium (CAC) score. Methods: MESA is a cohort study of 6,814 men and women from six U.S. cities between the ages of 45 and 84 years, who were free of clinical CVD. Included participants had thoracic spine BMD and CAC that was assessed by non-contrast chest CT, using methods previously described by Budoff et al 2010. Multivariate regression analysis was performed to examine the association of thoracic spine BMD and CAC score after adjusting for conventional risk factors of atherosclerosis including age, gender, BMI, race/ethnicity, diabetes, hypertension medications, lipid lowering medications, smoking history and family history of CAD. Results: Correlation coefficient, r, was -0.29 (p-1), osteopenia (-2.50 was 36% in normal group, 49% in the osteopenia group and 68% in the osteoporosis group. In adjusted regression models, the odds of CAC were significantly higher in those with osteoporosis (OR: 1.57 95% CI: 1.31,1.88) p Conclusion: The prevalence of CAC was significantly higher in osteoporosis group compared to normal BMD. There is an inverse relationship between BMD and CAC independent of cardiovascular risk factors.

Introduction: Multiple trials demonstrate efficacy of eicosapentaenoic acid (EPA) for lowering cardiovascular risk. Imaging studies suggest this benefit may relate to measurable effects on coronary plaque. Interestingly, EPA mixed with docosahexaenoic acid (DHA) has largely failed to show clinical benefit. The differential effects of EPA and EPA/DHA on coronary plaque burden and characteristics, including prognostically significant features such as lipid volume, remain unclear. Methods: We performed a systematic review of clinical trials that longitudinally measured coronary plaque volume in patients randomized to statin+EPA or statin+EPA/DHA versus statin alone, and performed network meta-analysis to estimate the standardized mean difference (SMD) of these treatments in percent change of total plaque volume and plaque lipid volume. Results: Ten trials comprising 860 patients met inclusion criteria among 535 articles. Four studies used intravascular ultrasound, three used coronary CTA, and three used optical coherence tomography. Among statin, statin+EPA, and statin+EPA/DHA treatments, random effects analysis yielded changes of +1.7% [-2.8%, +6.3%], -11.0% [-20.7%, -1.3%], and -3.4% [-14.5%, +7.8%] in total plaque volume and +3.1% [-1.6%, +7.8%], -19.8% [-27.5%, -12.1%], and -6.4% [-20.3%, +7.5%] in plaque lipid volume. Compared with statin, statin+EPA achieved greater percent reduction in coronary plaque volume (total volume: SMD = 0.92, P = 0.002; lipid volume: SMD = 1.04, P = 0.003) but statin+EPA/DHA showed no difference (total volume: SMD = 0.19, P = 0.58; lipid volume: SMD = 0.42, P = 0.38). Conclusions: In this most up-to-date meta-analysis, EPA as an adjunct to statins is associated with significant reductions in coronary plaque burden, including plaque lipid volume - unlike EPA/DHA combinations. These differential effects on coronary atherosclerosis offer mechanistic insights to observed clinical benefits of statin+EPA therapy.

Background Diabetes Mellitus (DM) is a major risk factor for coronary artery disease (CAD) and associated poor outcomes. There is a higher incidence of major adverse cardiac events in patients with DM than those without DM. Coronary plaque characteristics measured by CCTA are correlated with adverse cardiovascular (CV) outcomes. Purpose We sought to evaluate coronary plaque characteristics as well as rates of progression of coronary plaque burden as measured by serial CCTA in patients with DM and those without DM. Methods The study population included a total of 403 participants (mean age 61.4±11.4 years, 53% men; median scan interval 1.5 years) who were prospectively enrolled in serial CCTA trials. We identified 212 participants with DM and 191 participants without DM, who had undergone serial CCTA. Coronary Plaque volumes were measured and characterized as low attenuation plaque (LAP), total non-calcified plaque (TNCP) and total plaque (TP) using semi-automated plaque analysis software (Qangio medis). Multivariate linear regression was used to examine the effect of DM on coronary plaque progression. Results Patients with DM had greater rates of progression of normalized TP volume (median change in annualized plaque (IQR): 39.1 (9.9–114.4) in DM vs 23.5 (4.1–63.8) mm3 in non-DM, p=0.001), TNCP volume (21.6 (3.3–60.8) in DM vs 8.7 (0.1–35.6) mm3 in non-DM, p=0.003) and LAP volumes (0.7 (−0.6 to 7.8) in DM vs 0.1 (−0.4 to 1.9) mm3 in non-DM, p=0.04). After adjusting for relevant risk factors and baseline plaque, the annualized rates of progression were higher in patients with DM by 28% for TP (p=0.004), 27% for TNCP (p=0.011), 23% for fibrous plaque (p=0.026) and by 42% LAP (p=0.050), compared to those without DM. Conclusion Patients with DM have significantly higher rates of coronary plaque progression, including vulnerable LAP, than those without DM. Our findings reveal differences in rates, burden and characteristics of coronary plaque progression in patients with DM vs those without DM. These results provide mechanistic understanding of natural history of coronary atherosclerosis in this vulnerable population, that could explain the increased risk of CV events among patients with DM. Coronary atherosclerotic phenotyping by CCTA could serve as a potential surrogate measure for risk stratification and evaluation in clinical trials to examine therapeutic strategies in this vulnerable population. Funding Acknowledgement Type of funding sources: None.

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.

While population studies have demonstrated that high density lipoprotein cholesterol (HDL-C) and the ratio of total cholesterol to HDL (TC/HDL) improve cardiovascular risk prediction, the mechanism by which these parameters protect the cardiovascular system remains uncertain.To investigate the relationship between the HDL-C level and the total cholesterol to HDL (TC/HDL) ratio with the morphology of coronary artery plaque as determined by coronary computed tomography angiography (CCTA).This is a cross-sectional study involving 190 subjects with stable coronary artery disease. Semi-automated plaque analysis software was utilized to quantify plaque and plaque volumes are presented as total atheroma volume normalized (TAVOf the 190 subjects the average (SD) age was 58.9 (9.8) years, with 63% being male. After adjustment for cardiovascular risk factors, HDL- C (40 mg/dl) is inversely associated with fibrous (p = 0.003), fibrous fatty (p = 0.007), low attenuation plaque (LAP) (p = 0.007), total non-calcified plaque (TNCP) (p = 0.002) and total plaque (TP)(p = 0.004) volume. Furthermore, the TC/HDL ratio (4.0) is associated with fibrous (p = 0.047) and total non-calcified plaque (p = 0.039), but not with fibrofatty, LAP, dense calcified plaque, or TP volume.There is a strong association between low HDL-C levels and increasing TC/HDL ratio with certain types of coronary plaque characteristics, independent of traditional risk factors. The findings of this study suggest mechanistic evidence supporting the protective role of HDL-C and the TC/HDL ratio's clinical relevance in coronary artery disease management.

Evidence suggests that asymptomatic and mild SARS-CoV-2 infections comprise > 95% of all cases. Developing a test that indicates past infection and possible immunity against the virus is important. We administered 244 antibody tests to three groups of high-risk population. The test consisted of an IgG component and an IgM component. The overall IgM/IgG positivity for patients with none, mild, moderate, and severe symptoms were 21.1%, 21.8%, 14.2%, and 26.9%, respectively. Those with moderate or severe symptoms were no more or less likely to have positive antibody tests than those with no or mild symptoms.