The Relationship of Mitral Annular Calcification and Aortic Valve Sclerosis to Endothelial Dysfunction.

BACKGROUND: Calcific aortic valve disease (CAVD) and mitral annular calcification (MAC) are associated with various cardiovascular diseases and may influence systemic vascular pathologies. However, their relationship with endothelial dysfunction and carotid intima-media thickness (CIMT) remains poorly elucidated. This research aims to explore the associations between MAC, aortic valve sclerosis (AVS), and markers of vascular dysfunction, specifically CIMT and endothelial function. METHODS: This prospective observational study included 200 patients undergoing routine echocardiographic evaluation at the National Heart Institute between May 2022 and April 2023. Patients were stratified into four groups namely isolated MAC (38 patients), isolated AVS (72 patients), combined MAC and AVS (50 patients), and a control group without MAC or AVS (40 patients). All participants underwent comprehensive cardiovascular evaluation, including transthoracic echocardiography (TTE) and carotid duplex ultrasonography. Endothelial function was determined by measuring reactive hyperemia-induced alterations in brachial artery diameter. RESULTS: The mean age of participants was 60.6±8.4 years, with a predominance of male subjects (64%). No significant differences were noted in baseline demographic and clinical characteristics across the groups. Patients with isolated AVS, isolated MAC, and both conditions demonstrated increased CIMT compared to controls, with significant differences noted in the combined MAC and AVS group compared to controls (p-value=0.031). Endothelial dysfunction was observed in 14.8% of the AVS group and 21.1% in the combined group, but no significant differences existed when compared to controls. The study also revealed that patients with AVS are more likely to exhibit increased CIMT (p-value=0.008). CONCLUSIONS: Both MAC and AVS are connected to increased CIMT, suggesting a link with systemic atherosclerotic processes. Although the existence of endothelial dysfunction was not significantly higher in patients with valvular calcifications, the findings support the need for further research into the cardiovascular implications of CAVD and MAC.

Relationship between carotid intima-media thickness and white matter hyperintensities in non-stroke adults: a systematic review.

Introduction: Literature suggests a common pathophysiological ground between carotid atherosclerosis (CAS) and white matter alterations in the brain. However, the association between carotid intima-media thickness (CIMT) and white matter hyperintensities (WMH) has not been conclusively reported. The current systematic review explores and reports the relationship between CIMT and WMH among asymptomatic/non-stroke adults. Methods: A recent literature search on PubMed, SCOPUS, and Web of Science databases was conducted in compliance with the PRISMA protocol. The pre-defined Population-Intervention-Comparison-Outcome-Study (PICOS) criteria included observational studies investigating the CIMT-WMH association among non-stroke adults undergoing magnetic resonance imaging and carotid ultrasound. Results: Out of 255 potential results, 32 studies were critically assessed for selection, and finally, 10 articles were included, comprising 5,116 patients (females = 60.2%; males = 39.8%) aged between 36-71 years. The included studies earned high quality ratings (6-9) based on the Newcastle-Ottawa-Scale criteria. Qualitative synthesis showed a significantly parallel relationship between increased CIMT and greater WMH burden in 50% of the studies. In addition, significant risk factors related to the CIMT-WMH association included older age, hypertension, depression, migraine, Hispanic ethnicity, and apolipoprotein E (ɛ4) in postmenopausal women. Conclusion: Overall, the cumulative evidence showed a consistent CIMT-WMH association in asymptomatic middle-aged and older non-stroke adults, indicating that CAS may contribute to the progression of pathologically hyperintense white matter in the brain. However, further research is warranted to infer the plausible relationship between CIMT and WMH in the absence of stroke.

Relation between interleukin-13 and annexin-V levels and carotid intima-media thickness in nephrotic syndrome.

Background and aim: The aim of the current study is to assess the relation between carotid intima-media thickness (CIMT) measurements, renal Doppler resistive index (RI) and serum levels of interleukin-13 (IL-13) and annexin-V (An-V) in children with idiopathic nephrotic syndrome (INS). Materials and methods: The present case-control study was conducted on 60 children with INS and 60 age- and sex-matched healthy children. All participants were subjected to evaluation of serum levels of IL-13 and An-V and ultrasound Doppler measurement of CIMT and renal RI. Results: Patients expressed significantly higher An-V (5.9 ± 2.6 vs. 2.1 ± 0.8 ng/mL, p<0.001) and IL-13 (19.2 ± 7.6 vs. 3.4 ± 1.4 ng/L) levels when compared with healthy counterparts. Moreover, it was shown that patients had significantly higher CIMT (0.49 ± 0.06 vs. 0.35 ± 0.03, p<0.001) as compared to controls. No significant differences were noted between the studied groups regarding right or left RIs. Correlation analysis identified significant direct correlation between serum An-V levels and albumin/creatinine ratio (ACR) (r = 0.55), cholesterol (r = 0.48), triglycerides (r = 0.36), IL-13 (r = 0.92) and CIMT (r = 0.53). Similar correlations could be found between serum IL-13 levels and CIMT measurements and the corresponding parameters. Conclusions: The present study suggests an association between higher early atherosclerosis expressed as elevated CIMT measurements in children with INS and elevated serum levels of An-V and IL-13.

Impact of Fat Distribution and Metabolic Diseases on Cerebral Microcirculation: A Multimodal Study on Type 2 Diabetic and Obese Patients.

Background: Since metabolic diseases and atherosclerotic vascular events are firmly associated, herein we investigate changes in central microcirculation and atherosclerosis-related body fat distribution in patients with type 2 diabetes mellitus and obesity. Methods: Resting brain perfusion single-photon emission computed tomography (SPECT) imaging with Technetium-99m hexamethylpropylene amine oxime ([99mTc]Tc-HMPAO SPECT) was performed, and the breath-holding index (BHI) and carotid intima-media thickness (cIMT) were measured to characterise central microcirculation. Besides CT-based abdominal fat tissue segmentation, C-peptide level, glycaemic and anthropometric parameters were registered to search for correlations with cerebral blood flow and vasoreactivity. Results: Although no significant difference was found between the resting cerebral perfusion of the two patient cohorts, a greater blood flow increase was experienced in the obese after the breath-holding test than in the diabetics (p < 0.05). A significant positive correlation was encountered between resting and provocation-triggered brain perfusion and C-peptide levels (p < 0.005). BMI and cIMT were negatively correlated (rho = -0.27 and -0.23 for maximum and mean cIMT, respectively), while BMI and BHI showed a positive association (rho = 0.31 and rho = 0.29 for maximum and mean BHI, respectively), which could be explained by BMI-dependent changes in fat tissue distribution. cIMT demonstrated a disproportional relationship with increasing age, and higher cIMT values were observed for the men. Conclusions: Overall, C-peptide levels and circulatory parameters seem to be strong applicants to predict brain microvascular alterations and related cognitive decline in such patient populations.

Risk Assessment for Cardiovascular Events using Achilles Tendon Thickness and Softness and Intima-Media Thickness in Familial Hypercholesterolemia.

AIMS: This was a retrospective cohort study that aimed to determine cutoff values for major adverse cardiovascular events (MACEs) in patients with heterozygous FH (HeFH) for Achilles tendon (AT) thickness (ATT) measured by ultrasonography (US-ATT) and radiography (Xp-ATT), AT softness, and intima-media thickness of carotid artery (C-IMT), and to examine the effectiveness of these values as well as AT calcification as indexes in assessing risk for MACEs. METHODS: The subjects were 391 clinically diagnosed HeFH patients. Kaplan-Meier curves were drawn based on the threshold values for the individual indexes calculated from ROC curves, and multivariate analysis was used to examine whether they were predictors of the development of MACEs. RESULTS: The median observation period was 1,239 days (700-1,827 days). Twenty-one subjects (5%) had MACEs during the observation period. The cutoff values for MACEs for US-ATT were 9.9 mm in males and 7.1 mm in females, and those for C-IMT were 1.6 mm in males and 1.5 mm in females. Subjects were classified into two groups according to whether they were above or below the cutoff values and presence of calcification, and we compared MACE rates between them. MACE rates were significantly increased in groups with AT thickening determined by ultrasonography (P＜0.001), AT softening (P＜0.001), presence of calcification in AT (P=0.016) and greater C-IMT (P＜0.001). However, classification according to Xp-ATT revealed no significant difference in MACE rate (P=0.112). CONCLUSIONS: These thresholds and examination for AT calcification will help in risk assessment for patients in Japanese FH practice and encourage stricter and more comprehensive management for patients who exceed the thresholds.

Utility of waist-to-height ratio, waist circumference and body mass index in predicting clustered cardiometabolic risk factors and subclinical vascular phenotypes in children and adolescents: A pooled analysis of individual data from 14 countries.

AIMS: The clinical utility of waist-to-height ratio (WHtR) in predicting cardiometabolic risk factors (CMRFs) and subclinical markers of cardiovascular disease remains controversial. We aimed to compare the utility of WHtR with waist circumference (WC) and body mass index (BMI) in identifying children and adolescents (youths) at risk for cardiometabolic outcomes, including clustered CMRFs, high carotid intima-media thickness (cIMT), and arterial stiffness (assessed as high pulse wave velocity, PWV). METHODS: We analyzed data from 34,224 youths (51.0 % boys, aged 6-18 years) with CMRFs, 5004 (49.5 % boys, aged 6-18 years) with cIMT measurement, and 3100 (56.4 % boys, aged 6-17 years) with PWV measurement from 20 pediatric samples across 14 countries. RESULTS: WHtR, WC, and BMI z-scores had similar performance in discriminating youths with ≥3 CMRFs, with the area under the curve (AUC) (95 % confidence interval, CI)) ranging from 0.77 (0.75-0.78) to 0.78 (0.76-0.80) using the modified National Cholesterol Education Program (NCEP) definition, and from 0.77 (0.74-0.79) to 0.77 (0.74-0.80) using the International Diabetes Federation (IDF) definition. Similarly, all three measures showed similar performance in discriminating youths with subclinical vascular outcomes, with AUC (95 % CI) ranging from 0.67 (0.64-0.71) to 0.70 (0.66-0.73) for high cIMT (≥P95 values) and from 0.60 (0.58-0.66) to 0.62 (0.58-0.66) for high PWV (≥P95 values). CONCLUSIONS: Our findings suggest that WHtR, WC, and BMI are equally effective in identifying at-risk youths across diverse pediatric populations worldwide. Given its simplicity and ease of use, WHtR could be a preferable option for quickly screening youths with increased cardiometabolic risk in clinical settings.

Abnormal vascular thickness and stiffness in young adults with type 1 diabetes: new insights from cutting-edge ultrasound modalities.

BACKGROUND: Cardiovascular disease (CVD) remains the leading cause of morbidity and mortality in patients with Type 1 Diabetes (T1D). Early markers of CVD include increased carotid intima-media thickness (CIMT) and pulse wave velocity (PWV), but these existing ultrasound technologies show limited spatial and temporal resolution in young adults. The purpose of this study is to evaluate the utility of high-resolution ultrasound modalities, including high frequency ultrasound CIMT (hfCIMT) and ultrafast ultrasound PWV (ufPWV), in young adults with Type 1 Diabetes. METHODS: This is a prospective single-center observational cohort study including 39 participants with T1D and 25 age and sex matched controls. All participants underwent hfCIMT and ufPWV measurements. hfCIMT and ufPWV measures of T1D were compared with controls and associations with age, sex, BMI, A1c, blood pressure, and lipids were studied. RESULTS: Mean age was 24.1 years old in both groups. T1D had a greater body mass index (27.7 [5.7] vs 23.1 [3.2] kg/m2), LDL Cholesterol, and estimated GFR, and had a mean A1c of 7.4 [1.0] % (57 mmol/mol) and diabetes duration of 16.1 [3.7] years with 56% using insulin pumps. In T1D, hfCIMT was significantly increased as compared to controls (0.435 ± 0.06 mm vs 0.379 ± 0.06 mm respectively, p < 0.01). ufPWV measures were significantly increased in T1D (systolic foot PWV: 5.29 ± 0.23 m/s vs 5.50 ± 0.37 m/s, p < 0.01; dicrotic notch PWV = 7.54 ± 0.46 m/s vs 7.92 ± 0.41 m/s, p < 0.01). Further, there was an impact of A1c-measured glycemia on hfCIMT, but this relationship was not seen with ufPWV. No significant statistical correlations between hfCIMT and ufPWV measures in either T1D or healthy controls were observed. CONCLUSION: Young adults with T1D present with differences in arterial thickness and stiffness when compared with controls. Use of novel high-resolution ultrasound measures describe important relationships between early structural and vascular pathophysiologic changes and are promising tools to evaluate pre-clinical CVD risk in youth with T1D. TRIAL REGISTRATION: ISRCTN91419926.

Distinct gut microbiota signatures associated with progression of atherosclerosis in people living with HIV.

BACKGROUND: The relationship of microbiota composition dynamics and the progression of subclinical atherosclerosis in people with HIV (PWH) remains unknown. METHODS: 96-week, prospective, longitudinal study in virologically-suppressed PWH. Carotid intima-media thickness (cIMT) measurements and stool samples were obtained at baseline, 48-week and 96-week visits. cIMT progression was defined as an increase >10% and/or detection of new carotid plaque. To profile the gut microbiome, amplification and sequencing of 16S ribosomal-RNA (V3-V4 variable regions) were carried out following the Illumina protocol. Sequencing was performed with MiSeq platform. RESULTS: 191, 190 and 167 patients had available fecal samples for microbiome analysis at the baseline, 48- and 96-week visits, respectively. 87 (43%) participants showed atherosclerosis progression, and 54 (26.7%) presented new carotid plaque. No significant differences were observed in adjusted α-diversity indices between groups defined by cIMT progression. Beta-diversity determined through principal coordinate analysis distances showed that the groups exhibited distinct microbial profiles (PERMANOVA p-value = 0.03). Longitudinal analysis with ANCOM-BC2 adjusted for traditional cardiovascular risk factors, MSM and nadir CD4 count revealed that cIMT progression was consistently associated with Agathobacter and Ruminococcus_2, while non-progression was consistently associated with Prevotella_7. CONCLUSION: Progression of atherosclerosis in PWH might be associated with distinctive signatures in the gut microbiota.

Impact of bariatric surgery on carotid intima-media thickness and arterial stiffness in metabolically healthy obesity: a prospective study.

PURPOSE: Cardiovascular disease is one of the leading causes of mortality in patients with obesity. Metabolically healthy obesity (MHO), in which people do not have metabolic disorders, is a transient state of obesity. However, over the long term, a proportion of individuals with MHO develop metabolic syndrome (MetS). We aimed to investigate the effect of substantial weight loss following bariatric surgery in MHO on carotid intima-media thickness (CIMT) and pulse-wave velocity (PWV), which are independent predictors of subclinical atherosclerosis. METHODS: This prospective study included 38 patients (34 women, four men) undergoing bariatric surgery who had severe obesity but without comorbidities (hypertension, diabetes, and hyperlipidemia), and 28 control individuals who were matched for age and sex. CIMT and PWV of the left common carotid artery were measured. At 12-month follow-up after bariatric surgery, measurements were repeated in the 38 patients with obesity. RESULTS: Mean baseline body mass index (BMI) in the MHO group was 40.55 ± 3.59 kg/m2, which decreased by 33.1% after bariatric surgery. Compared with controls, CIMT and PWV were increased in MHO (543.53 ± 55.29 vs. 407.82 ± 53.09 µm, 6.70 ± 1.22 vs. 5.45 ± 0.74 m/s, respectively; all P < 0.001). At 12 months post-bariatric surgery, CIMT in MHO was lower than baseline (466.79 ± 53.74 vs. 543.53 ± 55.29 µm, P = 0.009), but PWV was not significantly different from baseline (6.27 ± 0.86 vs. 6.70 ± 1.22 m/s, P = 0.132). Multivariate regression showed that BMI was an independent predictor of CIMT (ß = 0.531, P < 0.001). CONCLUSION: Carotid artery structure and function were impaired in MHO, and improved carotid artery structure was associated with weight loss in MHO after bariatric surgery.

Multi-perspective ultrasound evaluation of Carotid Intima-Media thickness in hemodialysis access patients and its possible use to predict clinical outcomes.

BACKGROUND: Hemodialysis (HD) patients present an increased carotid intima-media thickness (CIMT) and calcified plaques, and studies have demonstrated that CIMT is predictor for cardiovascular death in this patient population; hence, the importance of identifying early non-invasive markers of atherosclerosis. We aim to propose a new three-perspective CIMT measuring method in HD population, and to further investigate the possible use and value of this method to predict outcomes. METHODS: A cross-sectional study was conducted, the CIMT was measured with duplex ultrasound during the perioperative access planning. Software provided maximum CIMT in a 10 mm (mm) width of the common carotid artery. CIMT was measured in Right (R) and Left (L) carotid arteries, both in anterior (a), lateral (l), and posterior (p) view. The sum of these values (Ra+Rl+Rp+La+Ll+Lp) was completed and termed as Sixth Carotid Intimal (SCI) score. We stratified either in low (summation <4) or high (>=4) SCI score groups. Demographics, patency rates, complications, and mortality were collected; chi-square test was used for our analysis. RESULTS: A total of 30 patients (mean age 49 years and 56% females) that underwent access creation in the upper arm from 2010 to 2016 were selected and studied. A low SCI score was found 19 patients and 11 had high SCI, no significant difference was observed in demographics, history cardiovascular disease, and clinical outcomes as early thrombosis, and primary, primary-assisted patency at 12 months. Interestingly, during the follow up period of 36 months a significant higher difference in late thrombosis rates occurred (63.6% vs 26.3%, p = .044) and a higher all-cause mortality (54.4% vs 15.7%, p = .025) in patients with SCI score group above 4. CONCLUSIONS: The SCI score method, might offer a screening tool for traditional cardiovascular risk factors in HD patients. In this study, we demonstrate an increased rate in late thrombosis and mortality in those with high SCI. Further research is necessary to better define the role of CIMT in vascular surgical procedures.

Plasma proteome association with coronary heart disease and carotid intima media thickness: results from the KORA F4 study.

BACKGROUND AND AIMS: Atherosclerosis is the main cause of stroke and coronary heart disease (CHD), both leading mortality causes worldwide. Proteomics, as a high-throughput method, could provide helpful insights into the pathological mechanisms underlying atherosclerosis. In this study, we characterized the associations of plasma protein levels with CHD and with carotid intima-media thickness (CIMT), as a surrogate measure of atherosclerosis. METHODS: The discovery phase included 1000 participants from the KORA F4 study, whose plasma protein levels were quantified using the aptamer-based SOMAscan proteomics platform. We evaluated the associations of plasma protein levels with CHD using logistic regression, and with CIMT using linear regression. For both outcomes we applied two models: an age-sex adjusted model, and a model additionally adjusted for body mass index, smoking status, physical activity, diabetes status, hypertension status, low density lipoprotein, high density lipoprotein, and triglyceride levels (fully-adjusted model). The replication phase included a matched case-control sample from the independent KORA F3 study, using ELISA-based measurements of galectin-4. Pathway analysis was performed with nominally associated proteins (p-value < 0.05) from the fully-adjusted model. RESULTS: In the KORA F4 sample, after Bonferroni correction, we found CHD to be associated with five proteins using the age-sex adjusted model: galectin-4 (LGALS4), renin (REN), cathepsin H (CTSH), and coagulation factors X and Xa (F10). The fully-adjusted model yielded only the positive association of galectin-4 (OR = 1.58, 95% CI = 1.30-1.93), which was successfully replicated in the KORA F3 sample (OR = 1.40, 95% CI = 1.09-1.88). For CIMT, we found four proteins to be associated using the age-sex adjusted model namely: cytoplasmic protein NCK1 (NCK1), insulin-like growth factor-binding protein 2 (IGFBP2), growth hormone receptor (GHR), and GDNF family receptor alpha-1 (GFRA1). After assessing the fully-adjusted model, only NCK1 remained significant (ß = 0.017, p-value = 1.39e-06). Upstream regulators of galectin-4 and NCK1 identified from pathway analysis were predicted to be involved in inflammation pathways. CONCLUSIONS: Our proteome-wide association study identified galectin-4 to be associated with CHD and NCK1 to be associated with CIMT. Inflammatory pathways underlying the identified associations highlight the importance of inflammation in the development and progression of CHD.

Homocysteine, Carotid Intima Media Thickness and NIHSS Score: Clinical Relevance in Indian Stroke Patients.

Background: Stroke is one of the leading causes of mortality and morbidity worldwide accounting for 85% of global deaths from stroke. This study aimed to evaluate the role of homocysteine (HCY) in modulating various stroke parameters and it's with carotid intima-media thickness (IMT). Methods: 78 patients of radiology-confirmed acute ischemic stroke were recruited for this study and National Institutes of Health Stroke Scale (NIHSS) score was evaluated upon admission. Blood samples were tested for serum HCY, fasting blood glucose (FBG) and lipid profile. Ultrasonography of neck ascertained IMT of Common (CCA) and internal carotid artery (ICA). Results: Average age of male and female subjects was 57.88 ± 13.97 & 59.16 ± 13.62 years respectively. 71.93% of stroke patients were hyperhomocysteinemic (HHcyc) and 24.36% were hyperlipidemic. Patients with NIHSS ≥ 5 had higher low-density lipoprotein cholesterol (LDLC) than those with NIHSS < 5. HCY cutoff of ≥ 15 µmol/L had 91.7% sensitivity & 66.7% specificity for predicting. HHcyc state was associated with increased ICA IMT. HHcyc state was best predicted by ICA IMT with which it is positively correlated (P-Value = 0.012). Conclusion: HHcyc state holds a good predictive value for severity of stroke. We also came to a conclusion that ICA IMT measurement may also reduce the need for a homocysteine test as it predicts higher HCY levels; this will reduce the burden on resources. We suggest that evaluating HCY and ICA IMT should be made part of the standard protocol for management of stroke.

Carotid intima media thickness in multiple sclerosis: A CLSA study.

BACKGROUND: People with multiple sclerosis (MS) have an increased incidence of atherosclerotic disease, including ischemic heart disease and stroke, compared to people without MS even after accounting for risk factors such as hypertension, dyslipidemia, diabetes and smoking. We compared carotid intima media thickness (CIMT), a surrogate of atherosclerosis, in people with MS and in two groups of people without MS (rheumatoid arthritis [RA]; all other participants). METHODS: We used data from participants in the Canadian Longitudinal Study on Aging (CLSA) who did not have known vascular disease (ischemic heart disease, stroke, transient ischemic attack, peripheral vascular disease) and who underwent carotid ultrasound for assessment of CIMT. We selected participants with MS, RA and controls who did not have MS or RA. Using age and gender-stratified norms for average CIMT in the CLSA, we identified participants in each cohort with a CIMT ≥75th percentile (subclinical atherosclerosis). We also calculated ten-year level of cardiovascular risk using the Framingham Risk Score (FRS). We tested the association between cohort membership (MS, RA, controls) and atherosclerosis using logistic regression, adjusted for FRS, abdominal obesity, excess alcohol intake, education and elevated symptoms of depression. We adjusted all analyses for the stratified sampling design. RESULTS: We included 78 participants with MS, 364 participants with RA and 13,891 controls. Overall, the average (SE) CIMT was 0.699 (0.002), and this did not differ between cohorts. Logistic regression analyses revealed that cohort membership was not associated with atherosclerosis based on the average CIMT in unadjusted or adjusted models. However, a 1-point higher FRS was associated with 1.032 (95 %CI: 1.021, 1.043) increased odds of atherosclerosis. CONCLUSION: Average CIMT does not differ between people with MS, people with RA and people without these diseases. Subclinical atherosclerosis as defined by a CIMT ≥75 % is not observed in people with MS at an increased rate beyond what FRS would predict. Further evaluation is needed to determine what mechanisms underlie the increased rates of cardiovascular disease and stroke in MS.

Effect of metformin adjunct therapy on cardiometabolic parameters in Indian adolescents with type 1 diabetes: a randomized controlled trial.

Introduction: Insulin resistance is being increasingly reported in type-1 Diabetes (T1D) and is known to accelerate microvascular complications. The Asian Indian population has a higher risk of double diabetes development compared to Caucasians. Hence, we studied the effect of adding Metformin to standard insulin therapy on glycemic control, insulin sensitivity (IS), cardiometabolic parameters and body composition in Indian adolescents with T1D. Methods: A Randomized controlled trial was conducted spanning 9 months (Registration number:CTRI/2019/11/022126). Inclusion: Age 10-19 years, T1D duration>1year, HbA1c>8% Exclusion: Uncontrolled vascular complications/comorbidities, Metformin intolerance, concomitant drugs affecting insulin sensitivity. Participants were randomized to Metformin/Placebo (n=41 each) groups and age, sex, duration-matched. Assessments were performed at baseline, 3 and 9 months. Results: 82 participants aged 14.7 ± 3years (40 females) were enrolled, with a mean diabetes duration of 5.2 ± 2.3 years. Over 9 months, HbA1c decreased significantly by 0.8 (95% confidence interval: -1.2 to -0.3) from 9.8 ± 1.8% to 9.1 ± 1.7% on Metformin but remained largely unchanged (difference of 0.2, 95% confidence interval: -0.7 to 0.2) i.e. 9.9 ± 1.6% and 9.7 ± 2.2% on placebo. HbA1c improvement correlated negatively with baseline IS (EGDR:r= -0.3;SEARCH:r = -0.24, p<0.05) implying better HbA1c-lowering in those with decreased initial IS. CGM-based glycemic variability (standard deviation) reduced by 6.3 mg/dL (95% confidence interval: -12.9 to 0.2) from 100.2 ± 19.1 mg/dL to 93.7 ± 19.9 mg/dL in those on Metformin (p=0.05) but not placebo (94.0 ± 20.5; 90.0 ± 22.6 mg/dL). Insulin sensitivity: CACTIexa & SEARCH scores demonstrated no change with Metformin but significant worsening on placebo. Significant increase in LDL-C(42%), total cholesterol(133.6 to 151.1 mg/dL), triglyceride (60.0 to 88.0 mg/dL) and carotid intima-media thickness was noted on placebo but not Metformin. Weight, BMI, fat Z-scores increased significantly on placebo but not Metformin. Adverse events (AE) were minor; AE, compliance and safety parameters were similar between the two groups. Conclusion: Metformin as an adjunct to insulin in Asian Indian adolescents with T1D demonstrated beneficial effect on glycemic control, glycemic variability, IS, lipid profile, vascular function, weight and body fat, with a good safety profile when administered for 9 months.

Association between arterial health and cognition in adolescents: The PANIC study.

We investigated the associations of the measures of arterial health with cognition in adolescents and whether physical activity (PA) or sedentary time (ST) confounds these associations. One hundred sixteen adolescents (71 boys) aged 15.9 ± 0.4 participated in the study. PA and ST were assessed using a combined accelerometer/heart rate monitor. Overall cognition was computed from the results of psychomotor function, attention, working memory, and paired-associate learning tests. Pulse wave velocity was measured by impedance cardiography, carotid intima-media thickness, and carotid artery distensibility by carotid ultrasonography. Systolic and diastolic blood pressure (SBP and DBP) were measured using an aneroid sphygmomanometer. SBP was inversely associated with overall cognition (standardized regression coefficient [ß] = -0.216, 95% confidence interval (CI) -0.406 to -0.027, p = 0.025). Pulse wave velocity (ß = -0.199, 95% CI -0.382 to -0.017, p = 0.033) was inversely associated with working memory task accuracy. SBP was directly associated with reaction time in the attention (ß = 0.256, 95% CI 0.069 to 0.443, p = 0.008) and errors in the paired-associate learning tasks (ß = 0.308, 95% CI 0.126 to 0.489, p = 0.001). Blood pressure was inversely associated with overall cognition. PA or ST did not confound the associations. Results suggest that preventing high blood pressure is important for promoting cognition in adolescents.

Assessing radiation-induced carotid artery injury using ultrasound in patients with head and neck cancer.

BACKGROUND AND PURPOSE: Radiotherapy (RT) can damage neck vessels in patients with head and neck cancer (HNC). This study investigated the early effects of RT on carotid artery, including the internal media thickness (IMT) and carotid plaques of the common carotid artery (CCA). MATERIALS AND METHODS: This study included 69 patients with HNC who underwent RT at the First Hospital of Jilin University from March 2017 to September 2022, and 69 healthy participants as controls. Color Doppler ultrasound (CDUS) of the carotid artery was used to measure the CCA IMT and plaques. RESULTS: Left CCA IMT increased from 0.60 mm (0.60, 0.70) before RT to 0.70 mm (0.60, 1.20) after RT (P < 0.0001). Right CCA IMT changed from 0.60 mm (0.60, 0.71) before RT to 0.60 mm (0.60, 1.10) after RT (P = 0.0002). CCA IMT was 0.60 mm (0.60, 0.70) and 0.80 mm (0.60, 1.20) in the ≤40 Gy and >40 Gy groups (P = 0.0004). The CCA plaques number increased significantly after RT on both the left and right sides (Pleft < 0.0001; Pright <0.0001). The CCA plaques volume increased from 0 mm3 (0, 11.35) and 0 mm3 (0, 8.55) before RT to 8.8 mm3 (0, 21.5) and 5.8 mm3 (0, 16.1) on the left and right sides. Correlation analysis revealed a correlation between CCA IMT and age (r = 0.283, P = 0.001), smoking status (r = 0.179, P = 0.020), and radiation dose (r = 0.188, P = 0.028). CONCLUSION: RT significantly increased CCA IMT, and the growth was related to the radiation dose. The number and volume of the CCA plaques also increased after RT.

Phthalate exposure and subclinical carotid atherosclerosis: A systematic review and meta-analysis.

Phthalates may be associated with an increased risk of cardiometabolic diseases by interfering with glucose and lipid metabolism and by promoting adipogenesis. This study aimed to perform a systematic review and meta-analysis of the association between phthalate exposure and subclinical carotid atherosclerosis, using surrogate markers such as carotid intima-media thickness (IMT) and carotid plaques. The literature search was performed using four databases (Web of Science, Medline, PubMed, and Scopus), and this systematic review includes all available observational studies until July 6th, 2023. The Joanna Briggs Institute critical appraisal tool was used to assess the risk of bias. Meta-analyses were performed, and random effects models were used. Six high-quality cross-sectional studies and 2570 participants aged 12 to 70 were included. Six phthalate metabolites showed significant associations with subclinical carotid atherosclerosis. Exposure to MBzP, ΣDEHP, and MnBP was associated with increased carotid IMT. Exposure to MEP was associated with a higher prevalence of carotid plaques, and MiBP was associated with a lower prevalence. Mixed results were observed for MMP in older adults. The meta-analyses showed a high degree of heterogeneity, and the results are based on single studies. This study accurately describes the evidence of this association to date, suggesting that phthalates are associated with increased carotid IMT and a higher prevalence of carotid plaques. Further research is needed to elucidate this association, as phthalates are still used in the manufacture of everyday products, humans continue to be exposed to them, and atherosclerosis is a public health concern.

Phenotypic and genetic effect of carotid intima-media thickness on the risk of stroke.

While carotid intima-media thickness (cIMT) as a noninvasive surrogate measure of atherosclerosis is widely considered a risk factor for stroke, the intrinsic link underlying cIMT and stroke has not been fully understood. We aimed to evaluate the clinical value of cIMT in stroke through the investigation of phenotypic and genetic relationships between cIMT and stroke. We evaluated phenotypic associations using observational data from UK Biobank (N = 21,526). We then investigated genetic relationships leveraging genomic data conducted in predominantly European ancestry for cIMT (N = 45,185) and any stroke (AS, Ncase/Ncontrol=40,585/406,111). Observational analyses suggested an increased hazard of stroke per one standard deviation increase in cIMT (cIMTmax-AS: hazard ratio (HR) = 1.39, 95%CI = 1.09-1.79; cIMTmean-AS: HR = 1.39, 95%CI = 1.09-1.78; cIMTmin-AS: HR = 1.32, 95%CI = 1.04-1.68). A positive global genetic correlation was observed (cIMTmax-AS: [Formula: see text]=0.23, P=9.44 × 10-5; cIMTmean-AS: [Formula: see text]=0.21, P=3.00 × 10-4; cIMTmin-AS: [Formula: see text]=0.16, P=6.30 × 10-3). This was further substantiated by five shared independent loci and 15 shared expression-trait associations. Mendelian randomization analyses suggested no causal effect of cIMT on stroke (cIMTmax-AS: odds ratio (OR)=1.12, 95%CI=0.97-1.28; cIMTmean-AS: OR=1.09, 95%CI=0.93-1.26; cIMTmin-AS: OR=1.03, 95%CI = 0.90-1.17). A putative association was observed for genetically predicted stroke on cIMT (AS-cIMTmax: beta=0.07, 95%CI = 0.01-0.13; AS-cIMTmean: beta=0.08, 95%CI = 0.01-0.15; AS-cIMTmin: beta = 0.08, 95%CI = 0.01-0.16) in the reverse direction MR, which attenuated to non-significant in sensitivity analysis. Our work does not find evidence supporting causal associations between cIMT and stroke. The pronounced cIMT-stroke association is intrinsic, and mostly attributed to shared genetic components. The clinical value of cIMT as a surrogate marker for stroke risk in the general population is likely limited.

Decoding Cardiovascular Health: Carotid Intima-Media Thickness and Its Association With Coronary Artery Disease in the Indian Population.

Background Coronary artery disease, as well as other cardiovascular diseases, poses a significant health burden globally. Understanding the relationship between clinical variables and coronary artery disease is crucial for effective management. This study explores the link between carotid intima-media thickness and different risk factors in the Indian population. Aims and objectives The primary objective of this study is to investigate the correlation between coronary artery disease and carotid intima-media thickness in a cohort of Indian individuals. Secondary objectives include analyzing the impact of demographic factors, lifestyle choices, and biomarkers on coronary artery disease risk. Methodology This study adopts an analytic, prospective case-control design spanning 18 months from July 2022 to December 2023. The research is conducted in a hospital setting, utilizing data from patients undergoing coronary angiography. The case group comprises 42 patients diagnosed with coronary artery disease, while the control group consists of 18 age-matched individuals without coronary artery disease. Demographic details, lifestyle factors, and biomarker levels are assessed. Statistical analyses involve Fisher's exact tests, chi-square tests, ANOVA, and independent sample t-tests. Primary outcome measures include the association between carotid intima-media thickness and coronary artery disease, as well as the impact of demographic and lifestyle factors on coronary artery disease risk. Secondary outcome measures involve the predictive capability of carotid intima-media thickness through receiver operating characteristic (ROC) curve analysis. Results Significant findings include a notable association between gender and coronary artery disease, with a statistically significant relationship observed for smoking, alcohol consumption, and hypertension. Biomarkers such as high-sensitivity C-reactive protein (hs-CRP) and carotid intima-media thickness exhibit highly significant differences in coronary artery disease patients compared to controls. Conclusions This study underscores the importance of carotid intima-media thickness as a potential predictor for coronary artery disease in the Indian population. Gender, lifestyle choices, and certain biomarkers significantly influence coronary artery disease risk. These findings contribute to a nuanced understanding of coronary artery disease etiology and risk stratification. This study sheds light on the intricate interplay of clinical factors influencing coronary artery disease in the Indian population, paving the way for enhanced risk assessment and preventative strategies.

ABO Blood Groups, RhD Factor and Their Association with Subclinical Atherosclerosis Assessed by Carotid Ultrasonography.

Background: The ABO blood group system has previously been associated with cardiovascular disease (CVD), where non-O blood group individuals have shown an increased risk. Studies assessing early atherosclerotic disease while also including RhD are few. We aimed to determine whether the ABO and RhD blood groups are associated with subclinical atherosclerosis in a healthy population. Methods: We included 3532 participants from the VIPVIZA trial with available carotid ultrasonography results to assess subclinical disease. Information about blood groups was obtained from the SCANDAT-3 database, where 85% of VIPVIZA participants were registered. Results: RhD- individuals aged 40 years showed increased carotid intima-media thickness (B 1.09 CI 95% 1.03; 1.14) compared to RhD+ individuals. For ABO, there were no differences in ultrasonography results when assessing the whole study population. However, 60-year-old individuals with heredity for CVD and a non-O blood group had decreased odds for carotid plaques (OR 0.54 CI 95% 0.33; 0.88). Conclusions: RhD blood group is associated with subclinical atherosclerosis in younger individuals, indicating a role as a mediator in the atherosclerotic process. In addition, a non-O blood group was associated with decreased subclinical atherosclerosis in individuals aged 60 and with heredity (corresponding to the group with the highest atherosclerotic burden).