COVID-19 IgG/IgM antibody testing in Los Angeles County, California.

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.

Effect of body mass index on bone mineral density is age-specific.

BACKGROUND AND AIMS: Obesity and osteoporosis are two important and growing public health problems worldwide. Body mass index (BMI) has been found to be inversely related to the risk of osteoporotic fracture. We aimed to assess the association of BMI with thoracic vertebral bone mineral density (BMD) measured from a quantitative computed tomography (QCT). METHODS AND RESULTS: We retrospectively evaluated the data from 15,758 consecutive patients (5675 females and 10,083 males) between age 20-90 years, who underwent Coronary Artery Calcium (CAC) scoring. Quantitative data analyses of thoracic trabecular BMD (mg/cm3) was performed with a phantom system or phantomless using validated software. The gender-specific subgroup was divided based on age (<45, 45-55, 55-65, >65 yrs in females; <40,40-60,>60 yrs in Males) and weight by BMI (kg/m2) as < 25 (normal or low weight), >25 - <30 (overweight) and >30 (obesity). Analysis of variance (ANOVA) and Scheffe's post hoc procedure tested the association of body weight/BMI on BMD. A significant positive association between the body weight and BMD existed in obese population in elder groups in both genders (p < 0.05). There was no significant difference in BMD in 40-60 years in men and <55 years in women with normal or low weight compared to overweight or obese cohorts. CONCLUSIONS: We concluded that the effect of weight on BMD is age-specific and the BMD should be monitored routinely with a cardiac CT scan in the senile population.

Aged Garlic Extract Reduces Low Attenuation Plaque in Coronary Arteries of Patients with Metabolic Syndrome in a Prospective Randomized Double-Blind Study.

BACKGROUND: Although several previous studies have demonstrated that aged garlic extract (AGE) inhibits the progression of coronary artery calcification, its effect on noncalcified plaque (NCP) has been unclear. OBJECTIVE: This study investigated whether AGE reduces coronary plaque volume measured by cardiac computed tomography angiography (CCTA) in patients with metabolic syndrome (MetS). METHODS: Fifty-five patients with MetS (mean ± SD age: 58.7 ± 6.7 y; 71% men) were prospectively assigned to consume 2400 mg AGE/d (27 patients) or placebo (28 patients) orally. Both groups underwent CCTA at baseline and follow-up 354 ± 41 d apart. Coronary plaque volume, including total plaque volume (TPV), dense calcium (DC), NCP, and low-attenuation plaque (LAP), were measured based upon predefined intensity cutoff values. Multivariable linear regression analysis, adjusted for age, gender, number of risk factors, hyperlipidemia medications, history of coronary artery disease, scan interval time, and baseline %TPV, was performed to examine whether AGE affected each plaque change. RESULTS: The %LAP change was significantly reduced in the AGE group compared with the placebo group (-1.5% ± 2.3% compared with 0.2% ± 2.0%, P = 0.0049). In contrast, no difference was observed in %TPV change (0.3% ± 3.3% compared with 1.6% ± 3.0%, P = 0.13), %NCP change (0.2% ± 3.3% compared with 1.4% ± 2.9%, P = 0.14), and %DC change (0.2% ± 1.4%, compared with 0.2% ± 1.7%, P = 0.99). Multivariable linear regression analysis found a beneficial effect of AGE on %LAP regression (ß: -1.61; 95% CI: -2.79, -0.43; P = 0.008). CONCLUSIONS: This study indicates that the %LAP change was significantly greater in the AGE group than in the placebo group. Further studies are needed to evaluate whether AGE has the ability to stabilize vulnerable plaque and decrease adverse cardiovascular events. This trial was registered at clinicaltrials.gov as NCT01534910.

The impact of carbohydrate restriction-induced elevations in low-density lipoprotein cholesterol on progression of coronary atherosclerosis: the ketogenic diet trial study design.

BACKGROUND: Despite innovations in pharmacotherapy to lower lipoprotein cholesterol and apolipoprotein B, risk factors for atherosclerotic cardiovascular disease (ASCVD), ASCVD persists as the leading global cause of mortality. Elevations in low-density lipoprotein cholesterol (LDL-C) are a well-known risk factor and have been a main target in the treatment of ASCVD. The latest research suggests that ketogenic diets are effective at improving most non-LDL-C/apolipoprotein B cardiometabolic risk factors. However, ketogenic diets can induce large increases in LDL-C to >190 mg/dl in some individuals. Interestingly, these individuals are often otherwise lean and healthy. The influence of increased levels of LDL-C resulting from a carbohydrate-restricted ketogenic diet on the progression of atherosclerosis in otherwise metabolically healthy individuals is poorly understood. This observational study aims to assess and describe the progression of coronary atherosclerosis in this population within 12 months. METHODS: Hundred relatively lean individuals who adopted ketogenic diets and subsequently exhibited hypercholesterolemia with LDL-C to >190 mg/dl, in association with otherwise good metabolic health markers, were enrolled and observed over a period of 12 months. Participants underwent serial coronary computed tomography angiography scans to assess the progression of coronary atherosclerosis in a year. RESULTS: Data analysis shall begin following the conclusion of the trial with results to follow. CONCLUSION: Ketogenic diets have generated debate and raised concerns within the medical community, especially in the subset exhibiting immense elevations in LDL-C, who interestingly are lean and healthy. The relationship between elevated LDL-C and ASCVD progression in this population will provide better insight into the effects of diet-induced hypercholesterolemia.

Serum Thyrotropin Elevation and Coronary Artery Calcification in Hemodialysis Patients.

INTRODUCTION: Hypothyroidism is highly prevalent in end-stage kidney disease patients, and emerging data show that lower circulating thyroid hormone levels lead to downregulation of vascular calcification inhibitors and coronary artery calcification (CAC) in this population. To date, no studies have examined the association of serum thyrotropin (TSH), the most sensitive and specific single biochemical metric of thyroid function, with CAC risk in hemodialysis patients. METHODS: In secondary analyses of patients from the Anti-Inflammatory and Anti-Oxidative Nutrition in Hypoalbuminemic Dialysis Patients trial, we examined serum TSH levels and CAC risk assessed by cardiac computed tomography scans collected within a 90-day period. We evaluated the relationship between serum TSH with CAC Volume (VS) and Agatston score (AS) (defined as >100 mm3 and >100 Houndsfield Units, respectively) using multivariable logistic regression. RESULTS: Among 104 patients who met eligibility criteria, higher TSH levels in the highest tertile were associated with moderately elevated CAC VS and AS in case-mix-adjusted analyses (ref: lowest tertile): adjusted ORs (95% CIs) 4.26 (1.18, 15.40) and 5.53 (1.44, 21.30), respectively. TSH levels >3.0 mIU/L (ref: ≤3.0 mIU/L) were also associated with moderately elevated CAC VS and AS. In secondary analyses, point estimates of incrementally lower direct free thyroxine levels trended toward elevated CAC VS and AS, although associations did not achieve statistical significance. CONCLUSIONS: In hemodialysis patients, higher serum TSH was associated with elevated CAC VS and AS. Further studies are needed to determine if thyroid hormone supplementation can attenuate CAC burden in this population.

Coronary computed tomography angiography evaluation of plaque morphology and its relationship to HDL and total cholesterol to HDL ratio.

BACKGROUND: 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. OBJECTIVE: 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). METHODS: 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 (TAVnorm). Multivariate regression models were used to evaluate the association of HDL-C and TC/HDL ratio with coronary plaque volumes. RESULTS: Of 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. CONCLUSION: 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.

Relationship between genomic risk scores (GRS) and coronary artery calcium (CAC) score: A pilot study.

BACKGROUND: Coronary artery disease (CAD) genomic risk scores (GRS), as FDR202, GRS46K, 1.7M, and MetaGRS, help in assessing cardiovascular related morbidity and mortality. Interventions to adhere to a healthy lifestyle as a means of prevention based on the GRS have a potential to greatly reduce incident CAD event rates. We performed a prospective observational study to see the relationship between GRS and coronary artery calcium (CAC) scoring in individuals who are at risk. METHODS: 104 subjects with mean age 55.1 ± 8.8 years were enrolled and consented and all the participants underwent CAC scoring. 55 (53%) were male. CAC score was measured using the Agatston method. Spearman correlation analysis assessed relationships between GRS scores and CAC scores, in the entire sample and in subjects with CAC score greater than zero. Multivariable linear regression analyzed associations while adjusting potential confounding variables. RESULTS: Mean ± SD CAC score of the study population was 49.0 ± 130. A significant negative correlation was noted between FDR202 Prevalence and total CAC Score in 39 subjects with CAC >0, r = -0.35, p = 0.02. Multivariable analysis shows a significant association between FDR202 prevalence and log adjusted CAC score in subjects with CAC >0 while adjusting age, gender, hypertension and hyperlipidemia (ß = -0.2, SE = 0.1, p = 0.04). No significant correlations were found between GRS46K, 1.7M, and MetaGRS with CAC score. CONCLUSION: Additional research is necessary in a larger population to evaluate the potential role of GRS for the detection of CAD. This allows the individuals to adopt a healthy lifestyle modification to minimize the cardiovascular risk and delays the onset of most diseases of old age to prolong the life.

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.

Prevalence of normal coronary arteries by coronary computed tomography angiography (CCTA) in patients with type 2 diabetes mellitus from Semaglutide Treatment on Coronary Plaque Progression (STOP) trial.

INTRODUCTION: Coronary artery disease (CAD) is leading cause of morbidity and mortality among type 2 diabetics (T2DM). METHODS: 140 T2DM will be enrolled in randomized, double blind, placebo controlled Semaglutide Treatment On Coronary Plaque Progression (STOP) trial to determine effect of weekly subcutaneous semaglutide on coronary plaque progression. All participants will undergo Coronary Artery Calcium (CAC) Scoring and Coronary Computed Tomography Angiography (CCTA) at our center. A Fisher test, ANOVA and Kruskal Wallis were used. RESULTS: As of May 2020, 87 patients (81%) randomized (mean age 56.4 ± 8.4 yrs. and 62% male) with documented CAD by CCTA. Approximately 20% of screened study population were screen failed due to normal coronaries (n= 14) or HbA1C<7 (n=7). Of interest, 14 persons with diabetes with normal coronaries (no calcification) were significantly more likely to be females (21% vs 62%), have higher glomerular filtration rate (106.5 ± 19.4 vs 89.9 ± 22.6 mL/min/1.73m2; p= 0.006), and younger (53.4 ± 9.0 vs 56.4 ± 8.4 yrs.; p=0.02) than those who were randomized. CONCLUSION: Among T2DM, there is a significant portion who have normal coronary arteries and may have a better prognosis. Excluding these participants from cardiovascular studies may improve power and decrease sample size.

Use of Advanced CT Technology to Evaluate Left Atrial Indices in Patients with a High Heart Rate or with Heart Rate Variability: The Converge Registry.

We intended to assess the ability of current-generation 256-slice coronary CT angiography (CCTA) to measure left atrial volume (LAV), comparing patients with a high heart rate (HiHR) of at least 70 bpm and patients with heart rate variability such as atrial fibrillation (AFib). Methods: Using the prospective Converge Registry of patients undergoing 256-detector CCTA on a Revolution scanner, we enrolled 121 HiHR patients (74 men; mean age, 62.7 ± 12.5 y) and 102 AFib patients (72 men; mean age, 60.5 ± 11.0 y) after obtaining informed consent. Quantitative data analysis of LAV was performed using automated methods, and end-systolic phases were chosen for measurements from CCTA. A Student t test, Wilcoxon rank-sum test, or χ2 test assessed baseline parameters. Univariate and multivariate linear regression analysis was used to assess LAV and LAV index (LAVI) while adjusting potentially confounding variables. Results: Mean LAV was significantly higher in AFib subjects (148.6 ± 57.2 mL) than in HiHR subjects (102.1 ± 36.5 mL) (P < 0.0001). Similarly, mean LAVI was significantly higher in AFib subjects (72.4 ± 28.1 mL/m2) than in HiHR subjects (51.5 ± 19.0 mL/m2) (P < 0.0001). After adjusting for age, body mass index, sex, diabetes, hypertension, hyperlipidemia, and smoking, subjects with AFib had, on average, LAV measures higher by 41.2 ± 6.7 mL and LAVI values higher by 23.1 ± 3.4 mL/m2 (P < 0.0001). Conclusion: Misalignment and motion artifacts in CCTA images affect diagnostic CT performance, especially in patients with elevated heart rates or profound arrhythmia. However, the new-generation Revolution CCTA provides detailed information on left-atrium-complex morphology and function, in addition to coronary anatomy, in HiHR and AFib patients without additional radiation, scanning, or contrast requirements.

Measurement of thoracic bone mineral density with quantitative CT.

PURPOSE: To create standard thoracic bone mineral density (BMD) values for patients undergoing cardiac computed tomography (CT) by using thoracic quantitative CT and to compare these BMDs (in a subpopulation) with those obtained by using lumbar spine quantitative CT. MATERIALS AND METHODS: The institutional review board approved this HIPAA-compliant study. A total of 9585 asymptomatic subjects (mean age, 56 years; age range, 30-90 years) who underwent coronary artery calcium scanning, including 4131 women, were examined. Patients with vertebral deformities or fractures were excluded. Six hundred forty-four subjects (322 of whom were female) also underwent lumbar quantitative CT. The mean thoracic vertebral BMDs for both sexes were reported separately in a subgroup of subjects aged 30 years and in 29 age-based subgroups in 2-year intervals from ages 30 to 90 years. The formulas used to calculate the female T score (T(f)) and the male T score (T(m)) on the basis of thoracic quantitative CT measurements were as follows: T(f) = (BMD(im) - 222)/36, and T(m) = (BMD(im) - 215)/33, where BMD(im) is the individual mean BMD. Comparisons between thoracic quantitative CT and lumbar quantitative CT measurements, as well as analyses of intraobserver, interobserver, and interscan variability, were performed. RESULTS: The young-subgroup mean BMD was 221.9 mg/mL ± 36.2 (standard deviation) for the female subjects and 215.2 mg/mL ± 33.2 for the male subjects. The mean thoracic BMDs for the female and male subjects were found to be 20.7% higher and 17.0% higher, respectively, than the values measured with lumbar quantitative CT (P < .001 for both comparisons). A significant positive association between the thoracic and lumbar quantitative CT measurements (r > 0.85, P < .001) was found. Intraobserver, interobserver, and interscan variabilities in thoracic quantitative CT measurements were 2.5%, 2.6%, and 2.8%, respectively. CONCLUSION: There was a significant association between the mean thoracic and lumbar BMDs. Therefore, standard derived measurements (young-subgroup BMD ± standard deviation) based on these data can be used with thoracic CT images to estimate the bone mineral status.

Total and individual coronary artery calcium scores as independent predictors of mortality in hemodialysis patients.

Many traditional and nontraditional risk factors contribute to vascular calcification among maintenance hemodialysis (MHD) patients. It is not clear whether coronary artery calcification (CAC) delineates a higher mortality risk independent of known risk factors. We examined 6-year (10/2001-9/2007) survival of 166 MHD patients, aged 53 +/- 13 years, with baseline CAC scores. Patients were grouped into four CAC groups: 0, 1-100, 101-400, and 400+. The 101-400 and 400+ groups were associated with a significantly higher adjusted risk of death than CAC 0 with hazard ratios (HR) 8.5 (95% CI: 1.1-48.1, p = 0.02) and 13.3 (95% CI: 1.3-65.1, p = 0.01), respectively, independent of demographics, comorbidity, lipids and other cardiovascular risks, surrogates of bone disease, nutritional and inflammatory markers and dialysis dose. Total CAC [HR 6.7 (1.1-21.5, p = 0.03)] followed by the presence of CAC in the left main [4.6 (2.2-9.8, p = 0.001)] and left anterior descending artery [4.3 (2.1-14.2, p = 0.001)] were strong independent predictors of mortality even after adjusting for above covariates. Total and vessel-specific CAC predict mortality in MHD patients independent of traditional and nontraditional risk factors.

Prospective randomized trial of venous cardiac computed tomographic angiography for facilitation of cardiac resynchronization therapy.

BACKGROUND: Cardiovascular computed tomographic angiography (CTA) can visualize the coronary veins. We sought to assess the ability of CTA to facilitate resynchronization therapy (CRT) procedures using a prospective randomized single-center pilot study. METHODS: Patients underwent CTA for characterization of cardiomyopathy prior to biventricular implantable cardiac-defibrillator implant. Randomization was performed with operator review of the CTA for coronary venous anatomy prior to CRT in one-half of the cases. Invasive coronary venous angiograms were used in all procedures. Analysis included procedure times and utilization of contrast, fluoroscopy, and guide catheters. RESULTS: Characteristics of the 26 patients enrolled were mean age 55 ± 11 years, male 76.9%, ischemic etiology 35%, ejection fraction 25 ± 3%, class III congestive heart failure 100%, and QRS duration 179 ± 29 ms. Of patients enrolled, 22 had both CTA and procedure initiation. Three patients (two with CTA review and one without CTA review) had aborted procedures due to hemodynamic issues. Analysis of the 22 patients (nine with preprocedure CTA review and 13 without CTA review) demonstrated that preprocedure review of CTA coronary venous anatomy led to significantly decreased procedure times and utilization of contrast, fluoroscopy, and guide catheters. CONCLUSIONS: Preprocedure review of CTA coronary venous anatomy may lead to decreased procedural times and utilization of contrast, fluoroscopy, and guide catheters. These preliminary results will need to be evaluated in larger heart failure populations undergoing CRT.

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.

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.

Relationship between cardio-ankle vascular index and obstructive coronary artery disease.

BACKGROUND: Cardio-ankle vascular index (CAVI) is an inexpensive, noninvasive, office-based method to evaluate arterial stiffness in the aorta and legs, which reflects the degree of coronary atherosclerosis. It has been applied clinically to assess arterial stiffness in patients who were diagnosed with coronary artery disease (CAD), stroke and those at risk. We intend to evaluate relationship between the CAVI and obstructive CAD. METHODS: We enrolled 285 individuals with mean age of 55.8 ± 13.5 years, clinically referred for Coronary Artery Calcium (CAC) scoring and coronary computed tomography angiography (CCTA) at our site. After informed consent, CAVI measurements were done using a vascular screening system, VaSera VS-1500 AU (FUKUDA Denshi) on the same day of CCTA. CAC was measured using the Agatston method. A semiquantitative scale was used by CCTA readers to grade the extent of luminal stenosis as a percentage of the vessel diameter using visual estimations. We evaluated if CAVI was associated with severe stenosis (>50%) or CAC >100, defined as obstructive CAD. RESULTS: The degree of CAC and severe coronary stenosis demonstrated significant correlation with CAVI (r = 0.44, P ≤ 0.0001 and r = 0.43, P ≤ 0.0001). Receiver operating characteristic curve analysis indicated that CAVI measure of 7.8 was an optimal cut-point for sensitivity and specificity in detecting obstructive CAD. Unadjusted logistic regression demonstrated CAVI >7.8, significantly associated with obstructive CAD [odds ratio (OR) = 4.60, 95% confidence interval (CI) (2.0-10.56), P = 0.0003] and CAC score >100 [OR = 6.96, 95% CI (3.68-13.17), P < 0.0001]. CONCLUSION: CAVI reflects coronary atherosclerosis and may be used as a screening tool for early identification of subclinical atherosclerosis in preventive care and optimize management.

Association of flow mediated vasodilation and burden of subclinical atherosclerosis by coronary CTA.

BACKGROUND AND AIMS: Endothelial dysfunction and atherosclerosis are linked by multiple mechanisms. Brachial artery flow-mediated dilation (FMD) rate is used to evaluate endothelial function and has been independently associated with adverse cardiac outcomes. The relationship between brachial artery FMD rate and severity of subclinical atherosclerosis by coronary computed tomography angiography (CCTA) is not understood. We hypothesized that brachial FMD is inversely associated with burden of subclinical atherosclerosis measured by CCTA. METHODS: This is a retrospective study of 100 participants with intermediate cardiac risk and atypical symptoms to examine association between brachial artery FMD rate and surrogate markers of severity of subclinical atherosclerosis on CCTA. Multivariate linear regression analysis was used to understand the relationship between brachial artery FMD rate and markers of plaque burden on CCTA including coronary artery calcium (CAC) score, segment involvement score (SIS; total number of segments with any plaque), segment stenosis score (SSS, sum of maximal stenosis score per segment), and total plaque score (TPS, the sum of all segments plaque burden). RESULTS: 52 participants (42%) were female. Mean age of the cohort was 59.3 ± 10.4 years. After adjusting for traditional risk factors, brachial artery FMD rate was inversely associated with higher CAC, TPS, SIS and SSS (p < 0.05 for all). FMD <4.5 predicted the presence of CAC >0 and ≤ 100 most effectively, with a sensitivity of 62.2% and a specificity of 66.7%, respectively (area under the curve (AUC) of 0.5729, p = 0.0302). FMD <2.7 predicted the presence of CAC >100 most effectively, with a sensitivity of 34% and a specificity of 83% respectively (AUC of 0.6226, p = 0.0095). CONCLUSIONS: Brachial FMD is independently associated with the presence and extent of subclinical atherosclerosis on CCTA. Our findings provide more detailed evidence that mechanistically, FMD, a surrogate marker of systemic endothelial dysfunction is a correlate of atherosclerotic burden, assessed by CCTA and CAC.

Aged garlic extract reduces low attenuation plaque in coronary arteries of patients with diabetes: A randomized, double-blind, placebo-controlled study.

Several previous studies have demonstrated that aged garlic extract (AGE) inhibits the progression of coronary artery calcification and non-calcified plaque (NCP) in the general population. However, its effects on plaque progression in patients with diabetes have not yet been investigated, at least to the best of our knowledge. This study investigated whether AGE reduces the coronary plaque volume measured by cardiac computed tomography angiography (CCTA) in patients with diabetes mellitus (DM). A total of 80 participants with DM with a median age of 57 years were prospectively assigned to consume 2,400 mg AGE/day (after completion, 37 participants) or placebo (after completion, 29 participants) orally. Both groups underwent CCTA at baseline and follow-up 365 days apart. In total, 66 participants completed the study. Coronary plaque volume, including total plaque (TP), dense calcium (DC), fibrous, fibro-fatty and low-attenuation plaque (LAP) volumes were measured based upon pre-defined intensity cut-off values using semi-automated software (QAngio CT). Changes in various plaque types were normalized to the total coronary artery length. The non-parametric Wilcoxon rank-sum test was performed to examine the differences in plaque formation between the 2 groups. No significant differences were found in the baseline characteristics between the AGE and placebo groups. Compared with the placebo group, the AGE group exhibited a statistically significant regression in normalized LAP [median and standard deviation (SD) -0.2 (18.8) vs. 2.5 (69.3), P=0.0415]. No differences were observed in TP, fibrous, or fibrofatty plaque volumes between the AGE and placebo group. On the whole, this study indicated that the %LAP change in the AGE group was significantly greater than that in the placebo group in patients with diabetes. However, further studies are warranted to evaluate whether AGE has the ability to stabilize vulnerable plaque and decrease adverse cardiovascular events.

Short-term impact of aged garlic extract on endothelial function in diabetes: A randomized, double-blind, placebo-controlled trial.

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.

Non-contrast cardiac CT-based quantitative evaluation of epicardial and intra-thoracic fat in healthy, recently menopausal women: Reproducibility data from the Kronos Early Estrogen Prevention Study.

BACKGROUND: Cardiac fat is emerging as an important parameter for cardiovascular risk stratification. Accurate and reproducible volumetric measurements can facilitate in the serial assessment of cardiac fat by computed tomography (CT). We assessed the intra- and inter-observer variability of cardiac fat volumetric measurements using a semi-automated CT software. METHODS: We used non-contrast coronary calcium CT scans to quantify epicardial and intra-thoracic fat volumes. Two expert readers analyzed baseline and follow up CT scans of 45 subjects by using a semi-automated CT software (QFAT 2.0, Cedars Sinai-Medical Center). Correlation and Bland-Altman analysis was performed for both intra- and inter-observer comparisons for each cardiac fat type. RESULTS: The intra-observer correlation coefficients ranged between 0.86 to 0.99 and 0.87 to 0.99 for epicardial (median fat per reader (cm3) 20.9 to 25.7) and intra-thoracic (median fat per reader (cm3) 27.1 to 31.6) fat volumes respectively, with no significant differences between individual data points (all p > 0.38). The inter-observer correlation coefficient was 0.99 (p < 0.0001 for correlation) for both epicardial and intra-thoracic fat. By Bland-Altman analysis for epicardial fat measurements, mean difference of intra-observer was 0.90 cm3 with 95% confidence intervals (0.22,1.7) and -1.8 cm3 for inter-observer, with 95% CI (-2.9, -0.69). Bland-Altman plots for intra-thoracic fat measurements were similarly impressive for both inter- and intra-observer reads. CONCLUSIONS: Our data showed that measuring epicardial and intra-thoracic fat volumes by CT using a semi-automated software has excellent intra-observer and inter-observer reliability. Cardiac fat volumes can be obtained easily and reproducibly from routine calcium scoring scans and may help in assessing cardiovascular risk. CLINICAL TRIAL REGISTRATION: URL: https://www.clinicaltrials.gov. Unique identifier: NCT00154180; Keywords: Epicardial fat volume; intra-thoracic fat volume; computed tomography; intra-observer; inter-observer.