Coronary artery calcium and bone mineral density by serial CTA: Does menopausal hormone therapy modify the association?

INTRODUCTION: Both osteoporosis and cardiovascular disease (CVD) increase in women after menopause. Estrogen deficiency is thought to be an underlying mechanism for both these conditions. METHODS: Healthy menopausal women (n = 374, age 42-58 years) underwent cardiac CT scans over four years as participants in the Kronos Early Estrogen Prevention Study (KEEPS), a randomized, controlled trial to Women randomized to either oral conjugated equine estrogens (o-CEE, n = 104), transdermal 17ß-estradiol (t-E2, n = 119) or placebo (n-115). CAC (Agatston units, AU), and BMD (mg/cm3) were measured from thoracic vertebrae at baseline and at the 4 years of the study using validated software. ANOVA and multiple linear regression analyzed the association between incident CAC or progression of CAC and BMD among the treatment groups. RESULTS: At baseline 374 women, 40 participants with CAC >0 had greater decrements in BMD than the 334 participants with CAC = 0 at baseline, The average change in BMD in o-CEE group with CAC was -9.6 ± 13.3 versus -3.1 ± 19.5 in those with zero CAC, p = 0.0018. With t-E2, BMD changed by -11.7 ± 26.2 in those with CAC versus +5.7 ± 26.2 in the zero CAC group, p ≤ 0. 0001. Similarly in the 66 participants that showed progression of CAC >1, had more BMD loss, than those with stable CAC regardless of the treatment. CONCLUSION: Progression of bone loss is reduced among women treated with o-CEE or t-E2. Progression of CAC is associated with greater BMD loss, a relationship that is differentially modified by t-E2 and o-CEE.

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.

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

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

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.

Coronary artery calcium score: pivotal role as a predictor for detecting coronary artery disease in symptomatic patients.

Chest pain and dyspnea are common presentations for symptomatic individuals with suspected coronary artery disease (CAD) in the primary care office and cardiology clinics. However, it is imperative to properly diagnose who should undergo further evaluation for cardiac etiologies of chest pain, with either noninvasive or invasive imaging tests. The purpose of this review is to highlight the role of coronary artery calcium (CAC) score as a screening tool for symptomatic patients to detect CAD. The purpose of CAC scoring is to establish the presence and severity of coronary atherosclerosis that can play a vital role in symptomatic patients. The use of CAC testing in symptomatic patients has traditionally been limited due to fundamental concerns, including the occurrence of coronary calcification relatively late in the atherosclerotic process and high prevalence of CAC in the population. Further issue relates to its low specificity for obstructive CAD, as well as demonstration of significant ethnic variability in plaque composition and calcification patterns. CAC testing gained attention as an inexpensive, rapid, reproducible and a well-tolerated alternative to exclude CAD in symptomatic patients and defer further invasive imaging tests. This article will review the available literature in regard to the use of CAC in symptomatic populations.

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.

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.

Association of high-density lipoprotein levels with baseline coronary plaque volumes by coronary CTA in the EVAPORATE trial.

BACKGROUND AND AIMS: Dyslipidemia with elevated triglycerides (TGL) and low high-density lipoprotein cholesterol (HDL-C) predicts residual cardiovascular risk, despite goal LDL-C levels and optimal statin therapy. Coronary plaque characterization by CCTA can provide mechanistic understanding of coronary artery disease and associated prognosis. The role of HDL-C in the pathogenesis of atherosclerosis is not well understood in statin-treated patients with elevated TGL. We sought to examine the association of HDL-C levels with baseline coronary plaque volumes, namely total plaque (TP) and total non-calcified plaque (TNCP) volumes by CCTA in participants enrolled in the EVAPORATE trial. METHODS: We analyzed 80 participants who were enrolled in the trial. Linear regression analysis as a univariate and multivariate model adjusted for significant cardiovascular risk factors was performed to evaluate independent association of HDL-C and baseline coronary plaque volumes. In an exploratory analysis, stratified by sex, we compared the association of serum HDL-C levels with baseline coronary plaque volumes in males and females. RESULTS: Mean (SD) age of participants (n = 80) was 57.1 (8.6) years and 43% were male. Median (Inter Quartile Range/IQR) log-TNCP volume was 83.0 (0.1-7.3) mm3 and median (IQR) log-TP volume was 144.8 (0.1-7.1) mm3. After adjustment for relevant clinical covariates including age, gender, BMI, hypertension, diabetes, past smoking and baseline TGL levels, increasing levels of HDL-C remain independently associated with lower baseline log-TNCP volumes (ß: 0.043 ± 0.021, p = 0.042) and baseline log-TP volumes (ß: 0.046 ± 0.022, p = 0.035) on CCTA. On stratifying by sex in a multivariable regression analysis, HDL-C levels were inversely associated with baseline log-TNCP volumes (ß: 0.066 ± 0.026, p = 0.018) and log-TP volumes (ß: 0.077 ± 0.025, p = 0.004) in females, but not in males (log-TNCP volumes ß: 0.038 ± 0.034, p = 0.282) and log-TP volumes (ß: -0.033 ± 0.036, p = 0.364). CONCLUSIONS: In a cohort of statin treated patients with known atherosclerosis and residually elevated TGL, there was a significant inverse relationship between HDL-C levels and baseline coronary plaque, TP and TNCP volumes on CCTA. Our findings provide more detailed mechanistic evidence regarding the protective role of HDL-C in coronary atherosclerosis in a high-risk cohort. Further investigation to evaluate the interaction of HDL-C levels and coronary plaque volumes on differential CVD risk in statin-treated patients with elevated TGL levels is warranted.

Feasibility of measuring pericoronary fat from precontrast scans: Effect of iodinated contrast on pericoronary fat attenuation.

BACKGROUND: Pericoronary adipose tissue (PCAT) attenuation has been identified as a marker for cardiovascular risk. The effect of contrast enhancement on fat attenuation is unknown. We aim to compare precontrast coronary scans to postcontrast CCTA for quantification of pericoronary fat volume and attenuation. METHODS: Thin slice pre- and post-contrast studies obtained at 120 kVp, heart rate <60, with no plaque or artifact in the right coronary artery (RCA) were selected. Analysis was limited to pixels -30 Hounsfield units (HU) to -190 HU and from 10 mm to 50 mm distal to the RCA origin at a radial distance equal to the vessel diameter. A subgroup with no plaque across all coronaries was also analyzed. RESULTS: Of 119 study pairs, the average RCA diameter was highly correlated at 3.85 mm (postcontrast) and 3.84 mm (precontrast), r = 0.97, p < 0.0001. The mean attenuation of pre- and postcontrast images was also highly correlated at -87.02 ±â€¯7.15 HU and -82.74 ±â€¯6.54 HU, respectively (r = 0.65, p < 0.0001). Pericoronary fat volume in the -190 to -30 HU range was 396 mm³ lower in the post contrast versus pre-contrast, consistent with higher attenuation (less negative) voxels postcontrast (p < 0.0001). Inter- and intra-reader agreement ranged 95-100% and 90% for precontrast and 85-90% for postcontrast studies, respectively. Subgroup analysis revealed precontrast attenuation -85.59 ±â€¯7.53 HU and postcontrast -82.21 ±â€¯7.15 HU were highly correlated r = 0.67, p < 0.0001. CONCLUSION: Pericoronary fat enhances with iodinated contrast, potentially explaining some of its risk-predictive capabilities. Fat attenuation and volume can be reliably measured from precontrast calcium scans, with volume quantification showing particularly strong correlation. Excellent inter- and intra-reader agreement is also demonstrated.

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.

Effect of semaglutide on coronary atherosclerosis progression in patients with type II diabetes: rationale and design of the semaglutide treatment on coronary progression trial.

BACKGROUND: Cardiovascular morbidity and mortality are a major burden in patients with type 2 diabetic mellitus. In a landmark study, semaglutide (an injectable glucagon like peptide-1 receptor agonist) has been shown to significantly reduce cardiovascular events, however, the mechanism of benefit is still unknown. The primary hypothesis of our current study is to assess the effect of semaglutide to reduce progression of noncalcified coronary atherosclerotic plaque volume as measured by serial coronary CTA as compared to placebo in persons with diabetes over 1 year. METHODS: One hundred forty patients will be enrolled after signing informed consent and followed up for 12 months and with a phone call 30 days after medical discontinuation. All the participants will undergo coronary artery calcium scoring and coronary computed tomography angiography at our center at baseline and 12 months. Eligible participants will be randomly assigned to semaglutide 2 mg/1.5 ml (1.34 mg/ml) prefilled pen for subcutaneous (SC) injection or placebo 1.5 ml, pen-injector for SC injection in a 1:1 fashion as add-on to their standard of care. RESULTS: As of July 2019, the study was approximately 30% enrolled with an estimated enrollment completion by first quarter of 2020 and end of study by first quarter 2021. Thirty patients were enrolled as of 23 July 2019. Preliminary data of demographics and clinical characteristics were summarized. CONCLUSION: Our current study will provide important imaging-derived data that may add relevance to the clinically derived outcomes from liraglutide effect and action in diabetes: evaluation of cardiovascular outcome results and semaglutide and cardiovascular outcomes in patients with type 2 diabetic mellitus 6 trials.

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.

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.

Aged garlic extract reduces left ventricular myocardial mass in patients with diabetes: A prospective randomized controlled double-blind study.

Increased left ventricular myocardial mass (LVM) is a well known prognostic marker of poor cardiac outcomes. Decreases in LVM have been shown to decrease the cardiovascular risk. Aged garlic extract (AGE) has been shown to have an overall favorable effect on cardiac health; however, to the best of our knowledge, no study to date has specifically examined its effects on left ventricular mass. This study investigated whether AGE can affect LVM measured by cardiac computed tomography angiography (CCTA) in patients with diabetes mellitus (DM). This is a double-blind, placebo controlled randomized trial. In total, 65 participants with DM with a mean age of 58 years were prospectively assigned to consume 2,400 mg AGE/day or the placebo orally. Both groups underwent CCTA at baseline and follow-up at 1 year apart. LVM was measured using automated software. The baseline characteristics did not differ between the AGE and placebo groups. There was a trend towards a significant reduction in LVM at follow-up as compared to baseline in the AGE group (119.30±34.77 vs. 121.0±34.70, P=0.059). No change was observed in LVM in the placebo group at 1-year follow-up as compared to baseline (124.6±37.33 vs. 124.6±35.13, P=0.9). On the whole, this study indicated that AGE may decrease or stabilize LVM. Further studies however, with a larger sample size and longer follow-up times are required to evaluate the effects of AGE on hypertension and LVM.

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.

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.

Biomarkers and Noncalcified Coronary Artery Plaque Progression in Older Men Treated With Testosterone.

OBJECTIVE: Recent results from the Cardiovascular Trial of the Testosterone Trials showed that testosterone treatment of older men with low testosterone was associated with greater progression of noncalcified plaque (NCP). We evaluated the effect of anthropometric measures and cardiovascular biomarkers on plaque progression in individuals in the Testosterone Trial. METHODS: The Cardiovascular part of the trial included 170 men aged 65 years or older with low testosterone. Participants received testosterone gel or placebo gel for 12 months. The primary outcome was change in NCP volume from baseline to 12 months, as determined by coronary computed tomography angiography (CCTA). We assayed several markers of cardiovascular risk and analyzed each marker individually in a model as predictive variables and change in NCP as the dependent variable. RESULTS: Of 170 enrollees, 138 (73 testosterone, 65 placebo) completed the study and were available for the primary analysis. Of 10 markers evaluated, none showed a significant association with the change in NCP volume, but a significant interaction between treatment assignment and waist-hip ratio (WHR) (P = 0.0014) indicated that this variable impacted the testosterone effect on NCP volume. The statistical model indicated that for every 0.1 change in the WHR, the testosterone-induced 12-month change in NCP volume increased by 26.96 mm3 (95% confidence interval, 7.72-46.20). CONCLUSION: Among older men with low testosterone treated for 1 year, greater WHR was associated with greater NCP progression, as measured by CCTA. Other biomarkers and anthropometric measures did not show statistically significant association with plaque progression.