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.

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.

Pentoxifylline ameliorates subclinical atherosclerosis progression in patients with type 2 diabetes and chronic kidney disease: a randomized pilot trial.

BACKGROUND: Diabetic kidney disease (DKD) is associated with a higher risk of cardiovascular disease (CVD). Pentoxifylline (PTF), a nonselective phosphodiesterase inhibitor with anti-inflammatory, antiproliferative, and antifibrotic actions, has demonstrated renal benefits in both clinical trials and meta-analyses. The present work aimed to study the effects of PTF on the progression of subclinical atherosclerosis (SA) in a population of patients with diabetes and moderate to severe chronic kidney disease (CKD). METHODS: In this open-label, randomized controlled, prospective single-center pilot study the evolution of carotid intima-media thickness (CIMT) and ankle-brachial index (ABI) were determined in 102 patients with type 2 diabetes mellitus and CKD assigned to PTF, aspirin or control groups during 18 months. We also determined the variations in the levels of inflammatory markers and Klotho (KL), a protein involved in maintaining cardiovascular health, and their relationship with the progression of SA. RESULTS: Patients treated with PTF presented a better evolution of CIMT, increased KL mRNA levels in peripheral blood cells (PBCs) and reduced the inflammatory state. The progression of CIMT values was inversely related to variations in KL both in serum and mRNA expression levels in PBCs. Multiple regression analysis demonstrated that PTF treatment and variations in mRNA KL expression in PBCs, together with changes in HDL, were significant determinants for the progression of CIMT (adjusted R2 = 0.24, P < 0.001) independently of traditional risk factors. Moreover, both variables constituted protective factors against a worst progression of CIMT [OR: 0.103 (P = 0.001) and 0.001 (P = 0.005), respectively]. CONCLUSIONS: PTF reduced SA progression assessed by CIMT variation, a beneficial effect related to KL gene expression in PBCs. TRIAL REGISTRATION: The study protocol code is PTF-AA-TR-2009 and the trial was registered on the European Union Drug Regulating Authorities Clinical Trials (EudraCT #2009-016595-77). The validation date was 2010-03-09.

Relationships of serum FGF23 and α-klotho with atherosclerosis in patients with type 2 diabetes mellitus.

BACKGROUND: Compelling evidence suggests that calcium/phosphorus homeostasis-related parameters may be linked to diabetes mellitus and cardiovascular events. However, few studies have investigated the association of fibroblast growth factor 23 (FGF23), α-klotho and FGF23/α-klotho ratio with atherosclerosis in patients with type 2 diabetes mellitus (T2DM). OBJECTIVE: This study was designed to evaluate whether FGF23, α-klotho and FGF23/α-klotho ratio are associated with T2DM and further to explore the relationships between these three factors and atherosclerosis in Chinese patients with T2DM. METHODS: Serum FGF23 and α-klotho levels were measured via an enzyme-linked immunosorbent assay (ELISA) kit, and the carotid intima-media thickness (CIMT) was assessed via high-resolution color Doppler ultrasonography. The associations of serum FGF23, α-klotho and FGF23/α-klotho ratio with atherosclerosis in T2DM patients were evaluated using multivariable logistic regression models. RESULTS: This cross-sectional study involved 403 subjects (207 with T2DM and 196 without T2DM), 41.7% of the patients had atherosclerosis, and 67.2% of the carotid intima were thickened to a thickness greater than 0.9 mm. Compared with those in the lowest tertile, higher tertiles of FGF23 levels and FGF23/α-klotho ratio were positively associated with T2DM after adjusting for covariates, and serum α-klotho concentration was inversely correlated with T2DM (all P values < 0.01). Moreover, elevated serum FGF23 levels and FGF23/α-klotho ratio were positively associated with CIMT and carotid atherosclerosis in T2DM patients (all P values < 0.01). Further spline analysis similarly revealed linear dose‒response relationship (all P values < 0.01). And there was still significant differences in CIMT and carotid atherosclerosis between the highest group of α-klotho and the reference group in T2DM patients (P values = 0.05). CONCLUSIONS: T2DM was positively linearly related to serum FGF23 concentration and FGF23/α-klotho ratio, and negatively correlated with serum α-klotho concentration. Furthermore, both FGF23 and FGF23/α-klotho ratio were positively correlated with CIMT and atherosclerosis in T2DM patients, while α-klotho was inversely correlated with both CIMT and atherosclerosis, although the associations were not completely significant. Prospective exploration and potential mechanisms underlying these associations remain to be further elucidated.

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.

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.

Sex-Related Differences in Cardiovascular Risk in Adolescents with Overweight or Obesity.

Background: Pediatric obesity is closely associated with cardiometabolic comorbidities, but the role of sex in this relationship is less investigated. We aimed to evaluate sex-related differences on cardiometabolic risk factors and preclinical signs of target organ damage in adolescents with overweight/obesity (OW/OB). Methods: The main cross-sectional study included 988 adolescents (510 boys and 478 girls) with OW/OB aged 10-18 years. In all youths clinical and biochemical variables were evaluated and an abdominal echography was performed. Echocardiographic data for the assessment of left ventricular mass (LVM) and relative wall thickness (RWT) were available in an independent sample of 142 youths (67 boys and 75 girls), while echographic data of carotid intima media thickness (cIMT) were available in 107 youths (59 boys and 48 girls). Results: The three samples did not differ for age, body mass index, and sex distribution. In the main sample, boys showed higher waist-to-height ratio (WHtR) values (p < 0.0001) and fasting glucose levels (p = 0.002) than girls. Lower levels of estimates glomerular filtration rate (eGFR) were found in girls vs boys (p < 0.0001). No sex-related differences for prediabetes and hyperlipidemia were observed. A higher prevalence of WHtR ≥ 0.60 (57.3% vs 49.6%, p = 0.016) and fatty liver disease (FLD) (54.5% vs 38.3%, p < 0.0001) as well as a trend for high prevalence of hypertension (40.4 vs 34.7%, p = 0.06) were observed in boys vs girls. More, a higher prevalence of mild reduced eGFR (MReGFR) ( < 90 mL/min/1.73 m 2 ) was observed in girls vs boys (14.6% vs 9.6 %, p < 0.0001). In the sample with echocardiographic evaluation, boys showed higher levels of LVM (p = 0.046), and RWT (p = 0.003) than girls. Again, in the sample with carotid echography, boys showed higher levels of cIMT as compared to girls (p = 0.011). Conclusions: Adolescent boys with OW/OB showed higher risk of abdominal adiposity, FLD, and increased cardiac and vascular impairment than girls, whereas the latter had a higher risk of MReGFR. Risk stratification by sex for cardiometabolic risk factors or preclinical signs of target organ damage should be considered in youths with OW/OB.

Normal pediatric values of carotid artery intima-media thickness measured by B-mode ultrasound and radiofrequency echo tracking respecting the consensus: a systematic review.

BACKGROUND: Carotid artery intima-media thickness (IMT) is a sub-clinical radiologic marker of atherosclerosis in children. It is associated with adult-onset vascular disease. OBJECTIVE: To determine normal pediatric values of IMT from results observed in the literature. METHODS: Our systematic review was conducted according to PRISMA guidelines. We reviewed 2298 English articles from inception to February 2023. Inclusion criteria included studies evaluating B-mode and radiofrequency (RF)-based IMT measurements based on the American Heart Association, the Association for European Pediatric Cardiology, the Mannheim Consensus, and the American Society of Echocardiography recommendations. A meta-analysis of aggregate data was conducted to obtain the confidence interval (CI) for IMT, using a 95% confidence level. RESULTS: We obtained 88 B-mode-based IMT measurement studies with 6184 children and six radiofrequency echo-tracking-based studies with 766 children. Mean IMT in the pediatric population was 0.43 mm, 95% [CI] 0,42 to 0.44, using the B-mode technique, and 0.41 mm, 95% [CI] 0.36 to 0.45 using the radiofrequency technique. No significant relationship was detected between IMT and age (p value = 0.83). Finally, no significant effect of sex on IMT was found (p value = 0.82 for B-mode and p value = 0.62 for RF). CONCLUSION: Based on the studies selected in this literature review, we were unable to conclude that there was a significant difference between the average IMT of boys and girls. No relationship was demonstrated between age and IMT. IMT is technique-specific, and normal values should be interpreted according to recommendations of recognized consensus to counteract the current heterogeneity in literature. CLINICAL RELEVANCE STATEMENT: Technique and children-specific Intima media thickness measurements help clinicians and scientists to assess the risk of atherosclerosis in children. KEY POINTS: • Intima-media thickness (IMT) does not correlate with age in children without risk factors. • According to current literature, there is no difference in IMT between healthy boys and girls. • There is heterogeneity, even with studies abiding by the official consensus.

The impact of vildagliptin as an add-on therapy on matrix metalloproteinase-14 levels, liver stiffness and subclinical atherosclerosis in adolescents with type 1 diabetes and non-alcoholic steatohepatitis: A randomized controlled trial.

AIM: Many patients with type 1 diabetes mellitus (T1DM) met the histological criteria for non-alcoholic steatohepatitis (NASH), which leads to cardiovascular disease morbidity and mortality. Matrix metalloproteinase-14 (MMP-14) is involved in cardiovascular disease and atherosclerosis. OBJECTIVES: To assess the impact of oral dipeptidyl peptidase-4 inhibitor, vildagliptin, as adjunctive therapy on NASH in adolescents with T1DM and its effect on glycaemic control, MMP-14 levels and carotid intima media thickness (CIMT). METHODS: Sixty adolescents with T1DM and NASH were randomly assigned to receive oral vildagliptin (50 mg once daily) for 6 months or not. Glycated haemoglobin, lipid profile, hepatic steatosis index, triglyceride glucose (TyG) index and MMP-14 levels were assessed. Transient elastography with controlled attenuation parameter (CAP) was performed together with measuring CIMT. RESULTS: By transient elastography, 12 (20%) patients with T1DM with NASH had elevated liver stiffness ≥7 kPa (F2 stage or higher). Baseline MMP-14 was positively correlated to insulin dose (p = 0.016), triglycerides and TyG index, CIMT, liver stiffness and CAP levels among the studied patients (p < 0.001 for all). After 6 months, patients with T1DM on vildagliptin therapy had significantly lower glycated haemoglobin, lipid profile, hepatic steatosis index and TyG index, as well as MMP-14 (p < 0.001). CIMT, liver stiffness and CAP were significantly decreased post-therapy compared with baseline levels and compared with the control group (p < 0.001). Vildagliptin was safe and well-tolerated. CONCLUSIONS: Administration of vildagliptin for adolescents with T1DM and NASH improved glycaemic control, dyslipidaemia and MMP-14 levels and decreased liver stiffness and CIMT; hence, reducing subclinical atherosclerosis and disease progression.

Associations of childhood diet quality scores with arterial stiffness and carotid artery intima-media thickness in adolescence/early adulthood: findings from the ALSPAC cohort.

This study examined the relationship between childhood diet quality and arterial stiffness and thickness during adolescence/early adulthood. Participants were from the Avon Longitudinal Study of Parents and Children (ALSPAC) with dietary data at ages 7, 10 and 13 years and pulse wave velocity (PWV) and carotid intima-media thickness (cIMT) at ages 17 and/or 24 years. Diet quality (DQ) was assessed using five scores: a children's Mediterranean-style diet (C-rMED) Z-score, a children's Dietary Inflammatory Z-score (C-DIS), a DASH diet Z-score, a children's Eatwell Guide (C-EWG) Z-score reflecting UK dietary guidelines and a data-driven obesogenic Z-score. Adjusted regression models examined the associations between DQ scores at 7-13 years and PWV and cIMT at 17 and 24 years. In adjusted models, a high v. low Obesogenic Z-score at 7 and 10 years was associated with higher PWV at 17: ß 0.07 (95 % CI 0.01, 0.13) and ß 0.10 (95 % CI 0.04, 0.16), respectively. A high v. low C-rMED Z-score at 7 years was associated with lower PWV at 17 (ß -0.07; 95 % CI -0.14, -0.01). A high (more anti-inflammatory) vs low C-DIS Z-score at 10 years was associated with a lower PWV at 17 years: ß -0.06 (95 % CI -0.12, -0.01). No other associations were observed. In conclusion, an Obesogenic dietary pattern in childhood (7-10 years) was related to increased arterial stiffness, while Mediterranean-style and anti-inflammatory diets were related to decreased arterial stiffness in adolescence. This highlights the importance of establishing healthy dietary habits early in life to protect against vascular damage.

Perfusion and pulsatile pressure: their relationship with target organ damage in the African-PREDICT study.

BACKGROUND: Hypertension is the leading risk factor for subclinical target-organ damage (TOD) and cardiovascular disease (CVD). Little is known about the relationship between different pressure measures and subclinical TOD, especially in young populations. We compared the strength of associations of subclinical TOD markers with perfusion and pulsatile pressure in young adults. METHODS: A total of 1 187 young adults from the African-PREDICT study were included. Ambulatory mean arterial pressure (MAP) and pulse pressure (PP) was obtained. Markers of subclinical TOD were measured and included left ventricular mass index (LVMi), carotid intimamedia thickness (cIMT), carotidfemoral pulse wave velocity (cfPWV), central retinal arteriolar equivalent (CRAE) and albumin to creatinine ratio (ACR). RESULTS: Measures of sub-clinical TOD (cIMT, cfPWV and CRAE), associated stronger with perfusion pressure (all p < 0.001) than pulsatile pressure in unadjusted models. Stronger associations were found between cfPWV (adjusted R2 = 0.26), CRAE (adjusted R2 = 0.12) and perfusion pressure (all p ≤ 0.001) than pulsatile pressure independent of several non-modifiable and modifiable risk factors. CONCLUSIONS: In young, healthy adults, perfusion pressure is more strongly associated with subclinical TOD markers than pulsatile pressure. These findings contribute to the understanding of the development of early cardiovascular changes and may guide future intervention strategies.

Impact on carotid intima-media thickness after laparoscopic sleeve gastrectomy in patients with morbid obesity.

BACKGROUND: We aimed to investigate the impact of laparoscopic sleeve gastrectomy (LSG) on carotid intima-media thickness (CIMT) & left ventricular dysfunction (LVD) which are the independent predictors of subclinical atherosclerosis. METHODS: To assess the change in CIMT & echocardiographic parameters of left ventricular function & correlate with %EWL 6 months and 12 months after LSG, the mean CIMT of bilateral common carotid arteries were measured at 3 different places & 7 parameters were assessed for left ventricular dysfunction after 6 and 12 months of LSG & correlated with the %EWL. RESULTS: A total of 30 patients (27(90%) women & 3(10%) men) with the mean age of 38 ± 7.84 were prospectively enrolled. BMI was significantly reduced from 42.66 ± 3.79 to 37.93 ± 3.60 kg/m2 at six months to 36 ± 3.34 at 12 months after LSG. CIMT values were significantly decreased at 6 months after surgery from 0.50 ± 0.11 mm to 0.46 ± 0.09 mm (p < 0.01) to 0.39 ± 0.07 (p < 0.05) at 12 months. However, no significant change was observed in the right mean CCA values at 6 months after surgery 0.50 ± 0.11 mm vs 0.47 ± 0.09 mm (p = 0.07) as compared to decrease at 12 months after surgery to 0.40 ± 0.08 (p < 0.05). Left mean CCA values at 6 months changed from 0.50 ± 0.11 to 0.45 ± 0.09 (p < 0.01) and at 12 months after surgery to 0.39 ± 007(p < 0.05). On 2D ECHO, ejection fraction increased at 6 months from 60.80 ± 5.89 to 61.93 ± 4.47 (p < 0.5) to after 12 months at 64.30 ± 4.20 (p < 0.05). Wave deceleration time changed at 6 months from 170 ± 36.80 to 150 ± 28.82 (p < 0.05) to 12 months 139.07 ± 17.98 (p < 0.05). Peak early diastolic mitral annular velocity (e) changed at 6 months from 8.12 ± 1.66 to 7.02 ± 1.76 (p < 0.05) to 12 months 6.33 ± 0.76 (p < 0.05). Inter-ventricular septum thickness (IVSD) changed at 6 months from 0.99 ± 0.14 to 0.91 ± 0.14 (p < 0.05) to 12 months 0.82 ± 0.09 (p < 0.05). Intraventricular relaxation time (IVRT) at 6 months changed from 94.33 ± 21.71 to 84.36 ± 14.85 (p < 0.03) to 12 months after surgery 77.40 ± 10.19 (p < 0.05). Left atrial volume index (LAVI) at 6 months decreased from 38.08 ± 11.23 to 30.93 ± 7.16 (p < 0.01) to 12 months after surgery 25.43 ± 3.65 (p < 0.05). Left ventricular diastolic dysfunction [LVIDD] at 6 months changed from 4.32 ± 0.52 to 4.11 ± 0.52 (p < 0.02) to 3.94 ± 0.26 (p < 0.05) to 3.94 ± 0.26 (p < 0.05) at 12 months after surgery. PwD at 6 and 12 months changed from 1.00 ± 0.19 to 0.87 ± 0.10 (p < 0.01) to 0.82 ± 0.08 (p < 0.05) respectively. LV mass changed in 6 months from 148.37 ± 33.09 to 117 ± 29.90 (p < 0.001) to 12 months at 110.64 ± 20.79 (p < 0.05) and left ventricular mass index [LVMI] changed in 6 months from 70 ± 16.89 to 59.626 ± 15.35 (p < 0.001) reaching a value of 57.53 ± 11.18 (p < 0.05) at 12 months. The mean 10-year risk of death due to CVD calculated was significantly reduced from 5.45 ± 6.6 to 2.8 ± 1.7% at 6 months (p < 0.05). This significant decrease in CVD risk has a positive correlation with the decrease in CIMT over 6 months showing a correlation coefficient of 0.018 with statistically significant analysis (p value < 0.05). CONCLUSION: We observed a significant reduction in CIMT & improvement in 2D ECHO parameters at 6 after LSG although no statistically significant change was observed in mean right CIMT & EF at 6 months.

Serum parathormone, vitamin D and cardiovascular risk factors and markers: A pilot study.

BACKGROUND AND AIMS: Vitamin D deficiency is a common cause of secondary hyperparathyroidism, particularly in elderly people. The aim of this study was to evaluate the associations of serum vitamin D and parathormone (PTH) concentrations with blood pressure values and hypertension-mediated target organ damage (HMOD), including left ventricular (LV) hypertrophy and carotid plaque (CP). METHODS AND RESULTS: We enrolled consecutive patients admitted to the Hypertension Center of Federico II University Hospital in Naples, Italy. All patients underwent carotid doppler ultrasound and echocardiography, measurement of vitamin D and PTH levels and main clinical and laboratory parameters. A total of 126 patients (mean age 54 years, 68% males) were enrolled. Pearson's correlation analysis indicated that PTH levels directly correlated with age, diabetes, dyslipidemia, hypertension, fasting glucose, and LV mass, and inversely with glomerular filtration rate, LDL cholesterol, and vitamin D. Vitamin D levels correlated inversely with PTH, diabetes and CP. Multivariate regression models indicated that an increased LV mass was associated with the presence of obesity (ß = 0.342; P = 0.001). Maximal intima-media thickness was significantly associated with older age (ß = 0.303; P = 0.033). Combined presence of low vitamin D/high PTH levels were associated with more than 4-fold increased risk of having CP in both univariate (OR = 4.77, p = 0.0001) and multivariate regression analysis (OR = 4.52, p = 0.014). CONCLUSION: In a population at high cardiovascular risk, vitamin D and PTH levels were not directly associated with blood pressure values and HMOD. Secondary hyperparathyroidism due to vitamin D deficiency is associated with carotid atherosclerosis independently of other common cardiovascular risk factors.

Investigation of carotid intima-media thickness in patients with schizophrenia.

BACKGROUND: Patients with schizophrenia (SCZ) have a higher risk of cardiovascular diseases than the average population. Early diagnosis of SCZ patients with subclinical atherosclerosis is great importance in reducing cardiovascular morbidity and mortality. The aim of this study was to investigate some clinical risk factors for atherosclerosis in patients with SCZ. METHODS: Fifty-one SCZ patients (20 females, 31 males) and 55 healthy controls (HCs) (25 females, 30 males) were included in the study. Electrocardiography (ECG), lipid parameters, hemogram, and biochemistry values of the participants were taken. Low-density lipoprotein (LDL), high-density lipoprotein (HDL), fasting triglycerides, and total cholesterol were measured. The arrhythmogenic index of plasma (AIP) was analyzed. The recorded right and left carotid intima-media thickness (CIMT) measurements by carotid ultrasonography were scanned. RESULTS: QT interval (p = 0.035), CIMT-left (p = 0.008), CIMT-right (p = 0.002), fasting triglyceride (p = 0.005), AIP (p = 0.005) in the SCZ group compared to HCs (< 0.001) was statistically higher, while HDL (p = 0.003) was statistically lower. Smoking rates, QT interval (p = 0.035), CIMT-left (p = 0.008), and CIMT-right (p = 0.002) were significantly higher in the the SCZ group than in the HCs. According to odds ratios, individuals with SCZ have a 6.3-fold higher smoking rate. According to Pearson correlation analysis, CIMT-left was positively correlated with age and QT interval (r = 0.568, p < 0.001 and r = 0.589, p < 0.001, respectively). CIMT-right value was also positively correlated with age and QT interval (r = 0.533, p < 0.001 and r = 0.555, p < 0.001, respectively). QT interval positively and significantly predicted CIMT-left and CIMT-right (p < 0.001, ß = 0.549 and p = 0.001 and ß = 0.506 accordingly). CONCLUSION: In this study, a close relationship was found between the QT interval and CIMT in SCZ patients. This finding could be valuable for using an easy-to-calculate data such as QT in place of a laborious test such as CIMT.

Mobility-related brain regions linking carotid intima-media thickness to specific gait performances in old age.

BACKGROUND: Gait disturbance is common in older adults with vascular diseases. However, how carotid atherosclerosis affects gait remains poorly understood. The objectives were to investigate the associations between carotid intima-media thickness and specific gait performances and explore the potential role of brain structure in mediating these associations. METHODS: A cross-sectional analysis of data from the Taizhou Imaging Study was conducted, including 707 individuals who underwent both gait and carotid ultrasound examinations. Gait assessments include the Timed-Up-and-Go test, the Tinetti test, and quantitative gait assessment using a wearable device. Quantitative parameters were summarized into independent gait domains with factor analysis. Magnetic resonance images were obtained on a 3.0-Tesla scanner, and the volumes of fifteen brain regions related to motor function (primary motor, sensorimotor), visuospatial attention (inferior posterior parietal lobules, superior posterior parietal lobules), executive control function (dorsolateral prefrontal cortex, anterior cingulate), memory (hippocampus, entorhinal cortex), motor imagery (precuneus, parahippocampus, posterior cingulated cortex), and balance (basal ganglia: pallidum, putamen, caudate, thalamus) were computed using FreeSurfer and the Desikan-Killiany atlas. Mediation analysis was conducted with carotid intima-media thickness as the predictor and mobility-related brain regions as mediators. RESULTS: Carotid intima-media thickness was found to be associated with the Timed-Up-and-Go performance (ß = 0.129, p = 0.010) as well as gait performances related to pace (ß=-0.213, p < 0.001) and symmetry (ß = 0.096, p = 0.045). Besides, gait performances were correlated with mobility-related brain regions responsible for motor, visuospatial attention, executive control, memory, and balance (all FDR < 0.05). Notably, significant regions differed depending on the gait outcomes measured. The primary motor (41.9%), sensorimotor (29.3%), visuospatial attention (inferior posterior parietal lobules, superior posterior parietal lobules) (13.8%), entorhinal cortex (36.4%), and motor imagery (precuneus, parahippocampus, posterior cingulated cortex) (27.3%) mediated the association between increased carotid intima-media thickness and poorer Timed-Up-and-Go performance. For the pace domain, the primary motor (37.5%), sensorimotor (25.8%), visuospatial attention (12.3%), entorhinal cortex (20.7%), motor imagery (24.9%), and balance (basal ganglia: pallidum, putamen, caudate, thalamus) (11.6%) acted as mediators. CONCLUSIONS: Carotid intima-media thickness is associated with gait performances, and mobility-related brain volume mediates these associations. Moreover, the distribution of brain regions regulating mobility varies in the different gait domains. Our study adds value in exploring the underlying mechanisms of gait disturbance in the aging population.

Diagnostic and prognostic role of serum interleukin-6 and carotid ultrasonography to detect subclinical atherosclerosis in patients with RA and ANCA-associated vasculitis.

ANCA-associated vasculitis (AAV) can affect multiple organs with severe life-threatening manifestations. Disease monitoring is difficult due to a lack of defined biomarkers. We aimed to assess the diagnostic role of serum interleukin-6 and vascular ultrasonography in AAV and subclinical atherosclerosis. The study included 20 AAV patients and two control groups of 34 patients with rheumatoid arthritis (RA) and 35 healthy controls. The levels of Il-6, carotid intima-media thickness test (CIMT), atherosclerotic plaque, and degree of stenosis were investigated. A GRACE-risk score was calculated for AAV and RA patients. The AAV patients had elevated levels of IL-6 (115 ± 23.96) compared to the RA patients (91.25 ± 42.63) and the healthy controls (15.65 ± 3.30), p < 0.001. IL-6 showed a diagnostic accuracy of 73% in distinguishing AAV from RA patients (AUC = 0.730; 95% CI 0.591 to 0834). In the AAV group, CIMT was 1.09, above the upper reference value of 0.90, p < 0.001. The AAV patients had a higher median GRACE risk score, and 60% of them had a high risk of cardiovascular events as compared to 35% of the RA patients. Sonography of extracranial vessels and serum levels of IL-6 can be used in daily clinical practice to diagnose and monitor patients with AAV.

Aortic arterial stiffness associates with carotid intima-media thickness and carotid plaques in younger middle-aged healthy people.

PURPOSE: Aortic stiffness, assessed as estimated aortic pulse wave velocity (aPWV), and carotid intima-media thickness (cIMT) are markers of vascular age, and carotid plaques are a marker of early atherosclerosis. In this cross-sectional study we aimed to investigate the association between aPWV, cIMT and plaques across different age groups and in women and men, in a middle-aged healthy population. MATERIALS AND METHODS: Participants in the 6.5-year follow-up of the VIPVIZA trial who were aged 47, 57 and 67 underwent an oscillometric measurement which estimates aPWV between 2020 and 2023. Carotid ultrasound examinations were also performed. Linear and ordinal regression models were used to investigate how aPWV associates with cIMT and with carotid plaques, for the overall study group and stratified for age groups and sex. RESULTS: A total of 1046 subjects were included in the analyses. Linear associations between aPWV and cIMT (ß = 0.018, 95% CI: 0.006-0.030, p = 0.003), and between aPWV and plaques (OR: 1.19, 95% CI: 1.03-1.38, p = 0.018), were seen in the 57-year-olds. In the 47-year-olds a significant association was seen between aPWV and plaques (OR: 2.98 95% CI: 1.44-6.14, p = 0.003). No significant associations were seen in the 67-year-olds. For women, a significant association between aPWV and cIMT (ß = 0.011, 95% CI: 0.004-0.017, p = 0.002) was shown. CONCLUSION: Estimated aPWV was positively associated with increasing cIMT and the presence of carotid plaques in younger middle-aged individuals, and with cIMT in women, suggesting that measurement of estimated aPWV may improve cardiovascular risk assessment in younger middle-aged individuals and women.Clinical Trial Registration date 8 May 2013: URL: www.clinicaltrials.gov. Unique identifier: NCT01849575.

What is the context? Vascular ageing is a process where the arteries become stiff, leading to impaired function and organ damage. Stiff arteries increase the risk of cardiovascular disease. Aortic pulse wave velocity is a measurement of arterial stiffness and a marker of vascular age. Carotid intima-media thickness and carotid plaque presence are other markers of vascular age and early atherosclerosis. There are limited data on the association between aortic pulse wave velocity, carotid intima-media thickness and carotid plaques.What is new? We measured estimated aortic pulse wave velocity using an oscillometric device and performed carotid ultrasound examinations for assessment of carotid intima-media thickness and carotid plaques in healthy middle-aged individuals across three different age groups. The association between aortic pulse wave velocity, carotid intima-media thickness and carotid plaques was examined in the different age groups and in women and men separately.What is the impact? Estimated aortic pulse wave velocity was associated with carotid intima-media thickness and carotid plaques in younger middle-aged individuals and with carotid intima-media thickness in women. Suggesting that for these groups ­ healthy younger middle-aged people, and especially women ­ measurement of estimated aortic pulse wave velocity could improve evaluation of cardiovascular risk.

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.

Redefining the exact roles and importance of carotid intima-media thickness and carotid plaque thickness in predicting cardiovascular events.

OBJECTIVE: The survey aimed to evaluate the precise roles and importance of carotid plaque thickness and carotid intima-media thickness measured in plaque-free areas (PF CC-IMTmean) in future cardiovascular risk prediction. MATERIAL AND METHODS: 188 respondents between the age of 46 and 87 divided into two groups (I group - 94 respondents without plaques with CIMT measurement and II Group 94 respondents with carotid plaques; 118 men and 70 women; mean age ± SD, 61.80 ± 5.49) were prospectively examined by the carotid ultrasound Doppler (carotid measurements included plaque thickness PT - nonstenotic plaques (carotid stenosis <50%) and stenotic culprit plaques (carotid stenosis ≥50%), mean CIMT and maximum CIMT). Subjects were followed for 36 months from the inclusion in the study (regular control examinations). Data were recorded on new cases of mortality (CV mortality) and adverse CV events (myocardial infarction - -MI, surgical or endovascular revascularization - coronary or stroke). RESULTS: In this study, CIMT values vary between 0.62 and 1.43 mm (mean CIMT = 1.21 ± 0.2 mm) while 52 subjects had nonstenotic plaques (14 respondents plaque ulceration, 22 type 2 diabetes mellitus, 38 arterial hypertension) and 38 subjects had stenotic culprit plaques (17 respondents plaque ulceration, 20 type 2 diabetes mellitus, 31 arterial hypertension). After 36 months of follow-up, 76 vascular events were noted (MI, transient ischaemic attack - TIA, stroke and cardiovascular angioplasty or surgery) in this period. CONCLUSION: Respondents with carotid plaques had higher cardiovascular events occurrence (p < .01, high statistical difference). Carotid plaques as a parameter have higher predictive vascular event value importance than CIMT. Of note, stenotic plaques, the presence of ulceration on the free surface of the plaque, type 2 diabetes mellitus and hypertension were connected with the highest events occurrence.

Association between apical periodontitis and secondary outcomes of atherosclerotic cardiovascular disease: A case-control study.

AIM: To evaluate the association between apical periodontitis (AP) and atherosclerotic cardiovascular disease (ASCDV). METHODOLOGY: A total of 65 periodontally and systemically healthy patients (age ≥ 40 years) were included in the study. Periapical status was assessed through dental examination and periapical radiographs; 33 subjects had AP (AP+), while 32 acted as control (AP-). Moreover, data regarding their periapical index (PAI) score and the Decayed, Missing, and Filled Teeth (DMFT) index were recorded. All subjects underwent echo-colour Doppler assessment of carotid intima-media thickness (CIMT), carotid plaques, degree of stenosis using the North American Symptomatic Carotid Surgery Trial (NASCET) method, maximum diameter of the abdominal aorta (maximum AA) and common iliac arteries (CIA) diameters. Furthermore, peripheral blood flow was also measured using the ankle-brachial index (ABI). Simple and multiple regression analyses were performed. RESULTS: Among AP+ patients, 57.58% disclosed at least one sign of subclinical carotid atherosclerosis. Multiple regression analysis identified AP as a significant risk indicator for carotid plaques [OR = 4.87 (1.27, 18.98; p = .021)] and marked carotid intima-media thickenings (OR = 14.58 [1.22, 176.15], p = .035). A significant association was established between AP and other cardiovascular (CV) variables (CIMT, NASCET, and maximum AA). On the contrary, a higher PAI score does not correlate to increased odds of carotid alterations, and the presence of AP did not prove any significant change in CIA and ABI. No significant correlation was established between DMFT and other variables. CONCLUSIONS: Results from the current study highlight that the presence of AP may be regarded as a risk indicator for ASCVD, with AP being associated with 5-fold increased odds of having carotid plaques and 15-fold increased odds of having marked carotid intima-media thickenings. Further studies should be conducted in order to verify whether AP treatment could be beneficial for ASCVD signs.