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.

Evaluation of atherosclerosis as a risk factor in COPD patients by measuring the carotid intima-media thickness.

BACKGROUND: This study aimed to evaluate atherosclerosis as comorbidity by measuring the carotid (bulb and common carotid artery) Carotid intima-media thickness in COPD-diagnosed patients and to evaluate the relationship of atherosclerosis with the prevalence of COPD, hypoxemia and hypercapnia. METHODS: This study was conducted out between January 2019-December 2019 consisting of a total of 140 participants (70 COPD-diagnosed patients-70 healthy individuals). The COPD-diagnosed patients have been planned according to the selection and diagnosis criteria as per the GOLD 2019 guide. It is planned to evaluate as per prospective matching case-control study of the carotid thickness, radial gas analysis, spirometric and demographic characteristics of COPD diagnosed patients and healthy individuals. RESULTS: The average Carotid intima-media thickness in COPD patients was 0.8746±0.161 (p<0.05), and the thickness of the carotid bulb was 1.04±0.150 (p<0.05). In the control group, the average CCA intima-media thickness was 0.6650±0.139 (p<0.05), and the thickness of the carotid bulb was 0.8250±0.15(p<0.05) For the carotid thickness that has increased in COPD diagnosed patients a significant relationship is determined between hypoxemia (p<0.05) and hypercapnia(p<0.05). A significant relationship determined between CIMT and severity of COPD (p<0.05) The CIMT was high in COPD patients with hypoxemia and hypercapnia(p<0.05). CONCLUSION: Significant difference was determined between the severity (grades) of COPD (mild, moderate, severe, very severe) in carotid thickness. Also, CIMT was found to be high in patients who is in the early phases of the prevalence of COPD. In COPD-diagnosed patients, it was determined that severity of COPD, hypoxemia, hypercapnia and age were determining factors of atherosclerosis.

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.

New insights on the association of weight loss with the reduction in carotid intima-media thickness among patients with obesity: an updated systematic review and meta-analysis.

OBJECTIVES: Carotid intima-media thickness (CIMT) is a noninvasive marker of atherosclerosis, a typical pathologic process underlying cardiovascular diseases (CVDs). It is essential to explore the relationships between weight loss and the reduction of CIMT. STUDY DESIGN: This was an updated systematic review and meta-analysis. METHODS: A systematic literature search was conducted to collect relevant clinical trials. The pooled results of meta-analyses were assessed by weighted mean difference (WMD) and the corresponding 95 % confidence interval (95% CI). RESULTS: Thirty-three articles involving 2273 participants were collected in this meta-analysis. Among all participants with obesity, the pooled mean of weight loss was -23.26 kg (95% CI: -27.71 to -18.81), and the pooled mean change of CIMT was -0.06 mm (95% CI: -0.08 to -0.04). Compared with Non-surgical interventions, Surgical ones could lead to much higher weight loss (Pbetween groups < 0.001). A more significant CIMT reduction was identified among Surgical intervention patients than among Non-surgical intervention participants (Pbetween groups < 0.001). CONCLUSIONS: Effective interventions, especially Surgical interventions, could reduce the weight of patients with obesity, followed by the decline of CIMT, which might further disturb atherosclerosis progression and lower CVD risk.

The Contribution of Serum Sialic Acid Binding Immunoglobulin-Like Lectin 1(sSIGLEC-1) as an IFN I Signature Biomarker in the Progression of Atherosclerosis in Egyptian Systemic Lupus Erythematosus (SLE) Patients.

Clinical symptoms of systemic lupus erythematosus (SLE), such as atherosclerosis and related cardiovascular diseases, are caused by inflammatory cytokines and endothelial cell damage. The serum sialic acid binding immunoglobulin-like lectin 1 (sSIGLEC-1) is thought to be an alternative biomarker of IFN signature and may have a role in the pathogenesis of atherosclerosis. The aim of the study was to measure the levels of sSIGLEC-1 in the serum of SLE patients in comparison to a control group and examine the associations between sSIGLEC-1, SLEDAI, lipid profile, oxidized low density lipoprotein (oxLDL), and carotid intima media thickness (CIMT) to investigate whether sSIGLEC-1 participates in the development of atherosclerosis. sSIGLEC-1 levels were tested in 53 patients and 20 volunteers using ELISA kit. Duplex measurements were performed on all subjects to measure CIMT. SLE patients had significantly higher values of sSIGLEC-1 (P < 0.0001), total cholesterol (P = 0.029), triglycerides (P = 0.001), low density lipoprotein (P = 0.032), oxLDL (P = 0.001), right CIMT (P = 0.0099) and a significantly lower value of high-density lipoprotein (P = 0.04) when compared to controls. sSIGLEC-1 had significant positive correlations with right CIMT (r = 0.5, P < 0.0002) and oxLDL (r = 0.67, P < 0.0001) in all SLE patients. When compared to non-dyslipidemic patients, the dyslipidemic group exhibited significantly higher levels of all previous parameters except HDL and left CIMT. Circulating form of SIGLEC-1 accelerates atherosclerosis and provides a simple way to predict the occurrence of atherosclerosis in SLE patients.

Muscle Oxygenation and Microvascular Reactivity Across Different Stages of CKD: A Near-Infrared Spectroscopy Study.

RATIONALE & OBJECTIVE: Previous studies in chronic kidney disease (CKD) showed that vascular dysfunction in different circulatory beds progressively deteriorates with worsening CKD severity. This study evaluated muscle oxygenation and microvascular reactivity at rest, during an occlusion-reperfusion maneuver, and during exercise in patients with different stages of CKD versus controls. STUDY DESIGN: Observational controlled study. SETTING & PARTICIPANTS: 90 participants (18 per CKD stage 2, 3a, 3b, and 4, as well as 18 controls). PREDICTOR: CKD stage. OUTCOME: The primary outcome was muscle oxygenation at rest. Secondary outcomes were muscle oxygenation during occlusion-reperfusion and exercise, and muscle microvascular reactivity (hyperemic response). ANALYTICAL APPROACH: Continuous measurement of muscle oxygenation [tissue saturation index (TSI)] using near-infrared spectroscopy at rest, during occlusion-reperfusion, and during a 3-minute handgrip exercise (at 35% of maximal voluntary contraction). Aortic pulse wave velocity and carotid intima-media thickness were also recorded. RESULTS: Resting muscle oxygenation did not differ across the study groups (controls: 64.3% ± 2.9%; CKD stage 2: 63.8% ± 4.2%; CKD stage 3a: 64.1% ± 4.1%; CKD stage 3b: 62.3% ± 3.3%; CKD stage 4: 62.7% ± 4.3%; P=0.6). During occlusion, no significant differences among groups were detected in the TSI occlusion magnitude and TSI occlusion slope. However, during reperfusion the maximum TSI value was significantly lower in groups of patients with more advanced CKD stages compared with controls, as was the hyperemic response (controls: 11.2%±3.7%; CKD stage 2: 8.3%±4.6%; CKD stage 3: 7.8%±5.5%; CKD stage 3b: 7.3%±4.4%; CKD stage 4: 7.2%±3.3%; P=0.04). During the handgrip exercise, the average decline in TSI was marginally lower in patients with CKD than controls, but no significant differences were detected across CKD stages. LIMITATIONS: Moderate sample size, cross-sectional evaluation. CONCLUSIONS: Although no differences were observed in muscle oxygenation at rest or during occlusion, the microvascular hyperemic response during reperfusion was significantly impaired in CKD and was most prominent in more advanced CKD stages. This impaired ability of microvasculature to respond to stimuli may be a crucial component of the adverse vascular profile of patients with CKD and may contribute to exercise intolerance. PLAIN-LANGUAGE SUMMARY: Previous studies in chronic kidney disease (CKD) have shown that vascular dysfunction in different circulatory beds progressively deteriorates with CKD severity. This study evaluated muscle oxygenation and microvascular reactivity at rest, during an occlusion-reperfusion maneuver, and during exercise in patients with nondialysis CKD versus controls, as well as across different CKD stages. It showed that the microvascular hyperemic response after an arterial occlusion was significantly impaired in CKD and was worst in patients with more advanced CKD. No significant differences were detected in skeletal muscle oxygenation or muscle oxidative capacity at rest or during the handgrip exercise when comparing patients with CKD with controls or comparing across CKD stages. The impaired ability of microvasculature to respond to stimuli may be a component of the adverse vascular profile of patients with CKD and may contribute to exercise intolerance.

Effects of NAD+ precursors on blood pressure, C-reactive protein concentration and carotid intima-media thickness: A meta-analysis of randomized controlled trials.

BACKGROUND: There are contradictory effects regarding the effect of NAD+ precursor on blood pressure and inflammation. In order to obtain a better viewpoint from them, this study aimed to comprehensively investigate the effects of NAD+ precursor supplementation on blood pressure, C-reactive protein (CRP) and carotid intima-media thickness (CIMT). METHODS: PubMed/MEDLINE, Web of Science, SCOPUS and Embase databases were searched using standard keywords to identify all controlled trials investigating the effects of NAD+ precursor on blood pressure, CRP and CIMT. Pooled weighted mean difference (WMD) and 95% confidence intervals (95% CI) were achieved by random-effects model analysis for the best estimation of outcomes. RESULTS: Twenty-nine articles (with 8664 participants) were included in this article. Results from meta-analyses of RCTs from random-effects models indicated a significant reduction in systolic (SBP) (weighted mean difference (WMD): -2.54 mmHg, p < .001) and diastolic blood pressure (DBP) (WMD: -2.15 mmHg, p < .001), as well as in CRP (WMD: -.93 mg/L, 95% CI -1.47 to -.40, p < .001) concentrations and CIMT (WMD: -.01 mm, 95% CI -.02 to -.00, p = .005) with the NAD+ precursors supplementation compared with the control group. In addition, a greater effect of supplementation with NAD+ precursors in reducing blood pressure (BP) were observed with the highest dose (≥2 g) and duration of the intervention (>12 weeks), as well as with NA supplementation when compared to NE. CONCLUSIONS: Overall, these findings suggest that NAD+ precursor supplementation might have a beneficial effect on cardiovascular risk factors such as BP, CRP concentration and CIMT.

Long-term complications in patients with childhood-onset nephrotic syndrome.

BACKGROUND: Reports on long-term complications of childhood-onset nephrotic syndrome (NS), such as obesity, osteoporosis, growth failure, and hypertension, are mostly from developed countries not representing South Asian ethnicities. Furthermore, data on cardiovascular health among patients with childhood-onset NS are limited. METHODS: This was an observational study involving patients attending a tertiary care center. Patients aged 15 years and older were examined for long-term complications and remission of NS at their visit in December 2021. Childhood-onset NS meant onset of NS before 10 years of age. Long-term complications included obesity, growth failure, low bone mineral density (BMD) Z score, hypertension, and increased carotid intima-media thickness (cIMT). Long-term remission was defined as no relapse for the last [Formula: see text] 3 consecutive years without immunosuppressive medication to maintain remission. RESULTS: Of 101 patients studied (~ 80% with frequent relapsing (FR)/steroid-dependent (SD) NS), the mean age was 17.6 (± 2.4) years at the time of study. Long-term complications were noted in 89.1% of patients which included one or more of the following: obesity (22.7%), growth failure (31.7%), low BMD Z score (53.5%), hypertension (31.7%), and high cIMT (50.5%). Thirty-nine patients (38.6%) were in long-term remission at the time of the study. Growth failure and low BMD Z scores were less frequent in patients with long-term remission compared to those without long-term remission. CONCLUSIONS: In patients with childhood-onset NS (predominantly FR/SDNS) who were studied at [Formula: see text] 15 years of age, ~ 90% had long-term complications which included high cIMT in 50%. Only ~ 40% were in long-term remission. A higher resolution version of the Graphical abstract is available as Supplementary information.

Comparison of Cardiovascular Disease Risk Factors Between 2 Subclinical Atherosclerosis Measures in Healthy Postmenopausal Women: Carotid Artery Wall Thickness and Echogenicity: Carotid Artery Wall Thickness and Echogenicity.

OBJECTIVES: Although carotid artery intima media thickness (CIMT) is a widely used determinant of subclinical atherosclerosis, gray-scale median of the intima-media complex (IM-GSM) of the common carotid artery is a relatively novel measure of echogenicity reflecting composition of the arterial wall. It is important to compare cardiovascular disease (CVD) risk factor correlates across CIMT and IM-GSM to determine whether these measures reflect distinct aspects of atherosclerosis. METHODS: Baseline information from a completed randomized clinical trial of 643 healthy postmenopausal women without clinically apparent CVD was included in this cross-sectional study. The women were on average ± SD 61 ± 7 years old, and predominantly non-Hispanic White. CIMT and IM-GSM were measured by high-resolution B-mode ultrasonogram in the far wall of the right common carotid artery. CVD risk factors including age, race, body mass index (BMI), smoking, weekly hours of physical activity, systolic (SBP) and diastolic blood pressure (DBP), lipids, glucose, and inflammatory markers were measured at baseline. Linear regression models were used to assess associations of CVD risk factors with CIMT and IM-GSM. Multivariable models included groups of risk factors added one at a time with and withoutbasic demographic factors (age, race, BMI, physical activity) with model R2 values compared between CIMT and IM-GSM. RESULTS: In multivariable analysis, age, Black race, BMI, SBP, and DBP were associated with CIMT (all P < .05), whereas age, Hispanic race, BMI, SBP, physical activity, LDL-cholesterol, and leptin were correlates of IM-GSM (all P < .05). Adjusted for age, race, BMI, and physical activity, the R2 value for SBP was greater for CIMT association, whereas R2 values for lipids, glucose, inflammatory markers, and adipokines were greater for IM-GSM associations. CONCLUSIONS: CIMT and IM-GSM assess different attributes of subclinical atherosclerosis. Integrating both measures may provide improved assessment of atherosclerosis in asymptomatic individuals.

Syndecan 1 may slow the progression of subclinical atherosclerosis in patients with ankylosing spondylitis.

BACKGROUND: Subclinical atherosclerosis may be seen at an early age of ankylosing spondylitis (AS). Syndecan 1 (S1) expression is increased in response to proinflammatory cytokine and inflammation. High S1 may reduce carotid atherosclerosis progression. We aimed to investigate the relationship between S1 levels and subclinical atherosclerosis in patients with AS. METHODS: Fifty-eight patients diagnosed with AS and 58 age-, sex-, and body mass index-matched controls were included in the study. S1 level and carotid intima-media thickness (cIMT) were evaluated using appropriate methods. RESULTS: AS patients' cIMT (0.53 ± 0.1 vs 0.45 ± 0.1 mm, p = .008), S1 (6.0 [1.7-149.2] vs 5.5 [1.0-29.8] ng/ml, p = .020), CRP (C-reactive protein) (2.1 [0.1-19.7] vs 1.1 [0.3-9.6] mg/dl, p = .012), fibrinogen (330.2 ± 87.0 vs 278.0 ± 54.5 mg/dl, p < .001) values were significantly higher than the values of the control group. There was a negative correlation between cIMT and CRP (p = .034), age (p < .001), disease duration (p = .005), BASDAI (p = .048) and fibrinogen (p = .009) in AS patients. There was a negative correlation between cIMT and S1 (p = .029). In multivariate analysis, an independent relationship was found between cIMT and age (ß = 0.611, p < .001) and syndecan (ß = -0.196, p = .046). CONCLUSION: S1 level may rise in AS patients to suppress the inverse effects of proinflammatory cytokines and inflammation. A negative relationship between the cIMT values of AS patients and S1 level may reveal that S1 has a protective effect on the development of atherosclerosis in AS patients, independent of disease activity.

The effect of nutrition on stroke risk: A systematic review.

Background: An estimated 33% reduction in cardiovascular events can be achieved when incorporating whole grains, fruits, vegetables, poultry, nuts, and vegetable oils in the diet along with reduced consumption of refined carbohydrates, processed meats, and sugar sweetened beverages. We performed a systematic review to analyze the impact of nutritional intervention on stroke risk, as there is no current consensus concerning dietary recommendation for primary and secondary stroke prevention. Methods: A literature search of the PubMed database from January 2010 to June 2020 was performed using combinations of the following search terms: carotid disease, carotid artery disease, carotid stenosis, carotid intima-media thickness (CIMT), diet, nutrition, micronutrition, embolic stroke, and stroke. We used the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2009 checklist. Results: 28 studies met our inclusion criteria. Multiple studies showed an inverse relationship between consumption of vegetables and fruits and stroke risk. Vitamin B12 or a combination of B Vitamins was the most common supplement studied in stroke prevention. Only one RCT showed the use of B12 (500 micrograms/day) correlated with lower CIMT at follow up in healthy vegetarians. Discussion: The key findings from this systematic review indicate that adopting a diet rich in fruits and vegetables earlier in life may lower stroke risk compared with meats and fat intake. B vitamins also appear to confer some protection against stroke. However, not enough data exists to support the use of multivitamins, calcium, soy products and other supplements for primary or secondary stroke prevention.

Cardiovascular health in the menopause transition: a longitudinal study of up to 3892 women with up to four repeated measures of risk factors.

BACKGROUND: Women experience adverse changes in cardiovascular health in mid-life; whether the menopausal transition influences these remains strongly debated. The aim of this study was to examine associations of reproductive age (time since final menstrual period (FMP)) with change in carotid intima media thickness (CIMT) and cardiovascular risk factors and determine the role of chronological and reproductive age. METHODS: We used data from 1702 women from a pregnancy-based UK cohort who had up to four repeat cardiovascular health measures between mean age 51 (SD = 4.0) and 56 (SD = 3.6) years and experienced a natural menopause. Multilevel models were used to assess the relationship between cardiovascular measures and time since FMP (reproductive age), whilst adjusting for the underlying effects of chronological age and confounders (socioeconomic factors, body mass index, smoking, alcohol, parity, age at menarche). In addition, we looked at the relationship between cardiovascular measures by chronological age according to menopausal stages (pre-menopause, peri-menopause and post-menopause) using information from women who had and had not experienced menopause (N = 3892). RESULTS: There was no strong evidence that reproductive age was associated with CIMT (difference in mean 0.8 µm/year, 95% CI - 0.4, 2.1), whereas there was a strong positive association of chronological age (7.6 µm/year, 95% CI 6.3, 8.9). Consistent with this, we found weaker linear associations of reproductive compared with chronological age for atherosclerotic risk factors, such as with systolic blood pressure (- 0.1 mmHg/year, 95% CI - 0.3, 0.1, and 0.4 mmHg/year, 95% CI 0.2, 0.5, respectively) and non-HDL-cholesterol (0.02 mmol/l/year, 95% CI 0.005, 0.03, and 0.06, 95% CI 0.04, 0.07, respectively). In contrast, associations with fat mass (0.06 kg/m2/year, 95% CI 0.03, 0.10, and 0 kg/m2/year, 95% CI - 0.04, 0.04, respectively) and C-reactive protein (0.01, 95% CI 0.001, 0.02, and 0.01, 95% CI - 0.001, 0.02 natural logged mg/l/year, respectively) were stronger for reproductive compared with chronological age. Both reproductive and chronological age were (weakly) positively associated with glucose (0.002, 95% CI 0.0001, 0.003, and 0.002, 95% CI 0.0001, 0.003 natural logged mmol/l/year, respectively). CONCLUSIONS: Our results suggest that going through the menopausal transition does not further increase women's risk of atherosclerosis (measured by CIMT) beyond effects of ageing. Menopausal transition may, in additional to ageing, modestly increase adiposity and glucose levels and therefore a possible associated diabetes risk.

CRP levels are significantly associated with CRP genotype and estrogen use in The Lifestyle, Biomarker and Atherosclerosis (LBA) study.

BACKGROUND: The C-reactive protein (CRP) is an important biomarker for atherosclerosis and single nucleotide polymorphisms (SNPs) in the CRP locus have been associated with altered CRP levels and associated with risk for cardiovascular disease. However, the association between genetic variations in the CRP gene, estrogen use and CRP levels or early signs of atherosclerosis in young healthy individuals is not fully characterized. We aimed to evaluate the influence of five genetic variants on both plasma CRP levels and carotid intima-media thickness (cIMT) values, including aspects on estrogen containing contraceptive use in females. METHODS: Genotyping was performed with TaqMan real time PCR and compared with high sensitivity CRP serum levels in 780 Swedish young, self-reported healthy individuals. Haplotypes of the SNPs were estimated with the PHASE v 2.1. The cIMT was measured by 12 MHz ultrasound. The contraceptive use was self-reported. RESULTS: Strong associations between CRP and genotype were observed for rs3091244, rs1800947, rs1130864, and rs1205 in women (all p < 0.001). In men, only rs1800947 was associated with CRP (p = 0.029). The independent effect of genotypes on CRP remained significant also after adjustment for established risk factors. Female carriers of the H1/ATGTG haplotype had higher CRP than non-carriers. This was specifically pronounced in the estrogen-using group (p < 0.001), and they had also higher cIMT (p = 0.002) than non-carriers but with a small cIMT difference between the haplotype groups (0.02 mm). In parallel, a significant correlation between CRP and cIMT in the estrogen using group was observed (r = 0.194; p = 0.026). CONCLUSIONS: Estrogen use, genotypes and haplotypes in the CRP locus are significantly associated with CRP levels. Based on an observed interaction effect between sex/estrogen use and the H1/ATGTG haplotype on CRP, and a marginally thicker cIMT in the estrogen using group, our data suggest that both genotypes and estrogen usage could be involved in arterial wall structural differences. The causality between CRP levels and cIMT remains unclear, and the observed difference in cIMT is not clinically relevant in the present state. Future larger and longitudinal studies may shed further light on the role of more long-term estrogen use and early atherosclerosis.

Lung function and atherosclerosis: a cross-sectional study of multimorbidity in rural Uganda.

BACKGROUND: Chronic obstructive pulmonary disease (COPD) is a leading cause of global mortality. In high-income settings, the presence of cardiovascular disease among people with COPD increases mortality and complicates longitudinal disease management. An estimated 26 million people are living with COPD in sub-Saharan Africa, where risk factors for co-occurring pulmonary and cardiovascular disease may differ from high-income settings but remain uncharacterized. As non-communicable diseases have become the leading cause of death in sub-Saharan Africa, defining multimorbidity in this setting is critical to inform the required scale-up of existing healthcare infrastructure. METHODS: We measured lung function and carotid intima media thickness (cIMT) among participants in the UGANDAC Study. Study participants were over 40 years old and equally divided into people living with HIV (PLWH) and an age- and sex-similar, HIV-uninfected control population. We fit multivariable linear regression models to characterize the relationship between lung function (forced expiratory volume in one second, FEV1) and pre-clinical atherosclerosis (cIMT), and evaluated for effect modification by age, sex, smoking history, HIV, and socioeconomic status. RESULTS: Of 265 participants, median age was 52 years, 125 (47%) were women, and 140 (53%) were PLWH. Most participants who met criteria for COPD were PLWH (13/17, 76%). Median cIMT was 0.67 mm (IQR: 0.60 to 0.74), which did not differ by HIV serostatus. In models adjusted for age, sex, socioeconomic status, smoking, and HIV, lower FEV1 was associated with increased cIMT (ß = 0.006 per 200 mL FEV1 decrease; 95% CI 0.002 to 0.011, p = 0.01). There was no evidence that age, sex, HIV serostatus, smoking, or socioeconomic status modified the relationship between FEV1 and cIMT. CONCLUSIONS: Impaired lung function was associated with increased cIMT, a measure of pre-clinical atherosclerosis, among adults with and without HIV in rural Uganda. Future work should explore how co-occurring lung and cardiovascular disease might share risk factors and contribute to health outcomes in sub-Saharan Africa.

Proprotein convertase subtilisin/kexin type 9 is associated with atherosclerosis in patients with Behcet's disease.

OBJECTIVES: The incidence of cardiovascular disease is increased in patients with Behcet's disease (BD). Proprotein convertase subtilisin/kexin type 9 (PCSK9) causes the acceleration of atherosclerosis. We aimed to investigate whether there is a relationship between PCSK9 with carotid artery intima-media thickness (cIMT), a marker of subclinical atherosclerosis, and BD disease activity. METHODS: Fifty-eight patients with BD and 58 age-, gender-, and body mass index (BMI)-matched healthy control subjects were included in the study. The disease activity of the patients was estimated. Individuals' cIMT values were measured, and PCSK9 levels were studied. RESULTS: Patients with BD' cIMT (0.51 ± 0.1 vs 0.41 ± 0.1 mm, p < .001) and PCSK9 (623.2 ± 101.7 ± 10.1 vs 528.3 ± 242.7 ng/ml, p = .007), values were significantly higher than the control group. In stepwise regression analysis, there was an independent relationship between cIMT with PCSK9 (ß = 0.179, p < .050). There was no independent relationship between disease activities with PCSK9. Based on the ROC curve analysis, the PCSK9 optimal cutoff value for cIMT was 595.1 ng/ml, sensitivity 66.7%, specificity 64.7% (AUC = 0.672; 95% CI: 0.530-0.815, p = .040). CONCLUSION: There is a strong independent association between subclinical atherosclerosis and PCSK9 in patients with BD. There may be no independent association between PCSK9 and disease activity.

Global DNA methylation mediates the association between serum perfluorooctane sulfonate and carotid intima-media thickness in young and middle-aged Taiwanese populations.

PURPOSE: Perfluoroalkyl and polyfluoroalkyl substances (PFAS) are a group of synthetic chemicals used in the manufacture of many everyday products. Previous reports have shown PFAS exposure may contribute to cardiovascular diseases (CVD). Recent studies have also identified a critical role for DNA methylation, a model of epigenetic regulation, in the pathogenesis of CVD. Additionally, PFAS has been shown to affect DNA methylation. Our previous study reported the positive association between serum perfluorooctane sulfonate (PFOS) levels and mean carotid intima-media thickness (CIMT), a biomarker of arteriosclerosis, in a cohort composed of adolescent and young adult Taiwanese. However, the contribution of DNA methylation in the mechanism of PFOS-induced arteriosclerosis has never been explored in previous literature. APPROACH AND RESULTS: In this cross-sectional study, we included 1425 young and middle-aged Taiwanese individuals (12-63 years) to investigate the correlation between serum PFOS levels, 5mdC/dG (a global DNA methylation marker) and the mean CIMT. We showed that the positive association between serum PFOS levels, 5mdC/dG, and mean CIMT. The regression coefficients of mean CIMT with a one-unit increase in ln-PFOS concentration were higher when the levels of 5mdC/dG were above the 50th percentile in the multiple regression analysis. In the structural equation model (SEM), the results showed that serum PFOS levels were directly correlated with mean CIMT and indirectly correlated with CIMT through 5mdC/dG. CONCLUSIONS: Our results showed that PFOS exposure has direct associations on arteriosclerosis and indirect direct associations on arteriosclerosis through DNA methylation. The results suggest that DNA methylation might regulate the relationship between PFOS and arteriosclerosis in the study subjects. Additional works are required to understand the causal inference between PFOS, DNA methylation, and arteriosclerosis.

Interaction of network and rehabilitation therapy parameters in defining recovery after stroke in a Bilateral Neural Network.

BACKGROUND: Restoring movement after hemiparesis caused by stroke is an ongoing challenge in the field of rehabilitation. With several therapies in use, there is no definitive prescription that optimally maps parameters of rehabilitation with patient condition. Recovery gets further complicated once patients enter chronic phase. In this paper, we propose a rehabilitation framework based on computational modeling, capable of mapping patient characteristics to parameters of rehabilitation therapy. METHOD: To build such a system, we used a simple convolutional neural network capable of performing bilateral reaching movements in 3D space using stereovision. The network was designed to have bilateral symmetry to reflect the bilaterality of the cerebral hemispheres with the two halves joined by cross-connections. This network was then modified according to 3 chosen patient characteristics-lesion size, stage of recovery (acute or chronic) and structural integrity of cross-connections (analogous to Corpus Callosum). Similarly, 3 parameters were used to define rehabilitation paradigms-movement complexity (Exploratory vs Stereotypic), hand selection mode (move only affected arm, CIMT vs move both arms, BMT), and extent of plasticity (local vs global). For each stroke condition, performance under each setting of the rehabilitation parameters was measured and results were analyzed to find the corresponding optimal rehabilitation protocol. RESULTS: Upon analysis, we found that regardless of patient characteristics network showed better recovery when high complexity movements were used and no significant difference was found between the two hand selection modes. Contrary to these two parameters, optimal extent of plasticity was influenced by patient characteristics. For acute stroke, global plasticity is preferred only for larger lesions. However, for chronic, plasticity varies with structural integrity of cross-connections. Under high integrity, chronic prefers global plasticity regardless of lesion size, but with low integrity local plasticity is preferred. CONCLUSION: Clinically translating the results obtained, optimal recovery may be observed when paretic arm explores the available workspace irrespective of the hand selection mode adopted. However, the extent of plasticity to be used depends on characteristics of the patient mainly stage of stroke and structural integrity. By using systems as developed in this study and modifying rehabilitation paradigms accordingly it is expected post-stroke recovery can be maximized.

Comparison of SAME verses CIMT on upper-limb functions in chronic stroke: A pilot randomized control trial.

OBJECTIVE: To compare the effects of Same Arm Movement Therapy versus Constraint Induced Movement Therapy in improving upper-limb functions in patients of chronic stroke. METHODS: The pilot, assessor-blind, randomised control trial was conducted from February to September 2020 at the Spine and Physiotherapy Rehab Centre, Riphah Rehabilitation Centre, Lahore, Pakistan, and comprised patients of either gender aged 30-60 years having any type of stroke for a minimum 3 months. They were randomised into group A which received same arm movement therapy for 8 weeks of mental rehearsal of upper limb movements during 45min supervised sessions three times a week and structured independent sessions twice a week, and group B which received constrain induced movement therapy for eight weeks of daily intensive training of the affected extremity for two hours per day, five days per week for eight weeks in association with restriction of the non-affected extremity for 10 hours a day. Measurements were taken at baseline and post-intervention. Data was analysed using SPSS 21. RESULTS: Of the 22 patients, 5(22.7%) were male and 17(77.3%) were female. The average age in group A was 54.91±5.89 years compared to 53.18±6.61 years in group B. All 22(100%) patients had ischaemic stroke. Intragroup comparisons showed significant progress in both groups (p<0.05), but intergroup comparisons showed non-significant differences (p>0.05). CONCLUSIONS: Both the study interventions had similar effect on upper limb functions among chronic stroke patients. RCT: Iranian Registry of Clinical Trials: RCT20200620047848N1 https://www.irct.ir/trial/49054.

Constraint Induced Movement Therapy in Infants and Toddlers with Hemiplegic Cerebral Palsy: A Scoping Review.

Cerebral Palsy (CP) is the leading cause of motor disability in childhood. Recent studies have investigated the effectiveness of constraint induced movement therapy (CIMT) as an early intervention for infants and toddlers with hemiplegic CP. This scoping review aims to identify current evidence for CIMT protocols for children 3 months to 5 years 11 months as well as clinical applications for practice and gaps in research. Selected databases and additional studies were searched and reviewed with 10 studies were selected for review. Results show CIMT for infants and toddlers is a feasible and effective treatment consisting of caregiver coaching, treatment in the child's typical environment, and just right activities. Future research is needed to determine the effects of different dosages in early CIMT, and the long term developmental effects throughout childhood.

Imaging-guided evaluation of subclinical atherosclerosis to enhance cardiovascular risk prediction in asymptomatic low-to-intermediate risk individuals: A systematic review.

Carotid intima-media thickness (cIMT), plaque quantification and coronary artery calcium (CAC) scoring have been suggested to improve risk prediction of cardiovascular disease (CVD), particularly for asymptomatic individuals classified as low-to-intermediate risk. We aimed to compare the predictive value of cIMT, carotid plaque identification, and CAC scoring for identifying sub-clinical atherosclerosis and assessing future risk of CVD in asymptomatic, low-to-intermediate risk individuals. We conducted a comprehensive search of Ovid (Embase and Medline), Cochrane Central Register of Controlled Trials (CENTRAL) and Medline complete (EBSCO health). A total of 30 papers were selected and data were extracted. Comparisons were made according to the cIMT measurement (mean, maximum), carotid plaque evaluation (presence or area), and CAC scoring. CVD event rates, hazard ratios (HR), net reclassification index (NRI), and c-statistic of the markers were compared. There were 27 studies that reported cIMT, 24 reported carotid plaque, and 6 reported CAC scoring. Inclusion of CAC scores yielded the highest HR ranging from 1.45 (95% CI, 1.11-1.88, p = 0.006) to 3.95 (95% CI, 2.97-5.27, p < 0.001), followed by maximum cIMT (HR 1.08; 95% CI, 1.06-1.11, p < 0.001 to 2.58; 95% CI, 1.83-3.62, p < 0.001) and carotid plaque presence (HR 1.21; 95% CI, 0.5-1.2, p = 0.39 to 2.43; 95% CI, 1.7-3.47, p < 0.001). The c-statistic enhanced predictive value by a minimum increase of 0.7. Finally, the NRI ranked higher with CAC (≥11.2%), followed by carotid plaque (≥2%) and cIMT (3%). CAC scoring was superior compared to carotid plaque and cIMT measurements in asymptomatic individuals classified as being at low-to-intermediate risk.