Short-Term Treatment with Alirocumab, Flow-Dependent Dilatation of the Brachial Artery and Use of Magnetic Resonance Diffusion Tensor Imaging to Evaluate Vascular Structure: An Exploratory Pilot Study

Background: Short-term effects of alirocumab on vascular function have hardly been investigated. Moreover, there is a scarce of reliable non-invasive methods to evaluate atherosclerotic changes of the vasculature. The ALIROCKS trial was performed to address these issues using standard ultrasound-based procedures and a completely novel magnetic resonance-based imaging technique. Methods: A total of 24 patients with an indication for treatment with PCSK9 antibodies were recruited. There were 2 visits to the study site, the first before initiation of treatment with alirocumab and the second after 10 weeks of treatment. The key outcome measures included the change of carotid vessel wall fractional anisotropy, a novel magnetic resonance-based measure of vascular integrity, and the changes of carotid intima-media thickness and flow-dependent dilatation of the brachial artery measured with ultrasound. Results: A total of 19 patients completed the trial, 2 patients stopped treatment, 3 patients did not undergo the second visit due to the COVID pandemic. All of them had atherosclerotic vascular disease. Their mean (standard deviation) LDL-cholesterol concentration was 154 (85) mg/dL at baseline and was reduced by 76 (44) mg/dL in response to alirocumab treatment (p < 0.001, n = 19). P-selectin and vascular endothelial growth factors remained unchanged. Flow-dependent dilatation of the brachial artery (+41%, p = 0.241, n = 18), carotid intima-media thickness (p = 0.914, n = 18), and fractional anisotropy of the carotid artery (p = 0.358, n = 13) also did not significantly change. Conclusion: Despite a nominal amelioration for flow-dependent dilatation, significant effects of short-term treatment with alirocumab on vascular function were not detectable. More work would be needed to evaluate, whether fractional anisotropy may be useful in clinical atherosclerosis research.

Histopathology of aortic media tunica and plasma oxidative stress assessment during testosterone deficiency in male rats

Sexual hormones are determinant players in cardiovascular diseases. The aim of this study was to investigate the effects of testosterone deficiency, induced by castration, on oxidative status and the histopathology of the aor-tic media tunica. The experiments were undertaken on a batch of 30 Wistar males’ rats randomised into 3 groups, 10 control (Con), 10 castrated (Cas) and 10 castrated then supplemented with testosterone (Cas-T). Our results showed that testosterone deficiency induced a significant decrease in myeloperoxidase activity (19,95 ± 1, 79 vs 34,86 ± 1,13, p˂0,0001) this was maintained even after testosterone replacement. Furthermore, testosterone deficiency decreased the antioxidant capacity by reducing GSH in plasma (0,118 ± 0,003 vs 0,15 ± 0,011, p˂0,05). Our results also indicate that testos-terone supplementation leads to a significant increase in ceruloplasmin lev-els (62,37 ± 15,89 vs 148,12 ± 27,77, p ˂0.05). The histomorphometric exami-nation of the aortic tunica media in castrated rats showed a significant de-crease of media thickness (274,7 ± 2,96 vs 317,6 ± 5,19, p ˂0.0001) and VSMC count (108,1 ± 6,47 vs 130 ± 6,147, p ˂ 0.05) associated with damaged and broken elastic lamina. Testosterone supplementation restores the media thickness and the count of VSMC. Our findings demonstrate that testos-terone deficiency leads to a decrease in the count of VSMC and a rupture of elastic lamina. Testosterone altered the plasma oxidative status through ac-tions on GSH, MPO and ceruloplasmin.

Carotid Artery Plaque Progression: Proposal of a New Predictive Score and Role of Carotid Intima-Media Thickness

Background: We aimed to investigate if the carotid intima-media thickness (IMT) at baseline and the HAD2S score, composed of the sum of single risk factors (hypertension, age ≥ 75 years, diabetes, dyslipidemia, smoking), were predictive of plaque progression. Methods: We performed a retrospective analysis on real-life prospectively collected data from patients with any detectable carotid plaque at follow up. The plaque score, calculated at baseline (T0) and at a median follow up of 36.6 months (IQR 39.6–34.3) (T3), was defined as 0: no plaque or stenosis < 30%; 1: stenosis in the range 30–49%; 2: in the range 50–69%; 3: in the range 70–99% and 4: occlusion. Carotid IMT was measured at T0 and T3; HAD2S score was calculated at baseline. Results: We included 340 patients with a mean age of 69.9 (9.1) years and 25.3% subjects had plaque progression. Individuals with progression had a median HAD2S score of 3 (1) while those without progression had 2 (1). Patients with progression had a mean baseline IMT of 0.86 (0.17) while those without progression had 0.77 (0.18) (p < 0.0001). A correlation between progression and baseline IMT was found (p = 0.002). Conclusion: Baseline IMT could be considered a predictor of progression. Patients with progression had an HAD2S score higher than those without evolution.

Assessment of Carotid Artery Intima-Media Thickness and Lipid Profile in Term Neonates Born to Smoking Mothers

Background: It is well-known that cigarette smoke contains chemical substances, including nicotine and carbon monoxide, which can have harmful effects on cardiovascular function. Objectives: This study aimed to investigate and compare lipid levels and carotid artery intima-media thickness (CAIMT) among neonates born to smoking and nonsmoking mothers. Methods: This study was conducted on 40 term neonates (over 37 weeks of gestation) within the age range of 0 - 30 days born to smoking mothers (study group) and 34 term neonates born to nonsmoking mothers (control group). Both groups were assessed prospectively for triglyceride (TG), total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), and CAIMT. Results: There was no difference in the mean age of mothers between control and study groups (29.0 ± 4.5 vs. 29.3 ± 5.7 years; P = 0.31). The CAIMT was observed as similar between the groups (0.35 ± 0.05 vs. 0.36 ± 0.05 mm in control and study groups, respectively; P = 0.665). Although HDL-C levels were significantly lower in the study group (48.5 ± 16.2 vs. 39.1 ± 17.8 mg/dL; P = 0.021), no difference was observed in LDL-C, TC, and TG levels between the two groups. Conclusions: Based on the results, there were no differences in CAIMT and lipid profile other than low HDL levels between term neonates born to smoking mothers and neonates born to nonsmoking mothers. Atherosclerosis is a disease in which numerous factors play a role in the formation beginning in the fetal period and emerging with clinical findings in advanced age; therefore, it is required to perform further studies with longer follow-up and larger sample size to confirm the present study findings.

Environmental tobacco smoke and carotid intima–media thickness in healthy children and adolescents: a systematic review

Thicker carotid intima–media thickness (CIMT) has been a valid predictor for atherosclerosis development. A significant association between environmental tobacco smoke (ETS) and thickening of CIMT has been demonstrated in adults, whereas such association has scarcely been reviewed in paediatric population. The dominate electronic databases, including MEDLINE (Ovid), PubMed, Embase, CINAHL, Web of Science, Scopus, were searched from inception. Reference lists of retrieved articles were further scanned as to avoid any missing literatures. Newcastle-Ottawa scale was used to assess the quality of the included studies. Qualitative synthesis analyses were performed on the selected studies. 331 articles were retrieved, and 4 were finally selected. All four studies investigated the association between postnatal ETS and CIMT in children, and three of them reported a statistically significant positive association. Three studies investigated the association between prenatal maternal ETS and CIMT, and one of the three found a positive association. Two studies explored the association between postnatal maternal ETS and CIMT, one reported a positive association. Two studies used serum cotinine measurement to quantify ETS and demonstrated potential dose-response relationship with CIMT. ETS exposure may play an independent role in the development of cardiovascular risks in healthy children and adolescents. In the consideration of the great burden of respiratory and cardiovascular diseases, there is an urgent need of effective surveillance for paediatric population’s ETS exposure to reduce smoke exposure.

Carotid Intima-Media Thickness in Patients with Subclinical Hypothyroidism: A Prospective Controlled Study

Purpose: The association between subclinical hypothyroidism (SCH) and cardiovascular risk, particularly with a TSH <10 µIU/ml, remains controversial. The objective of our study was to assess the association between SCH and cardiovascular risk through carotid intima-media thickness, and alternatively, to evaluate its change after treatment with levothyroxine. Methods: A total of 54 individuals were included in the study: 18 with SCH; 18 with overt hypothyroidism (OH); and 18 healthy controls (HC). The carotid intima-media thickness was measured in each group. In SCH, follow-up was performed at three and six months after the start of levothyroxine treatment. Results: The mean age of the total population at baseline was 35.8 years. The median TSH in SCH was 6.15 µIU/ml. The carotid intima-media thickness (mean and standard deviation) was greater in SCH in comparison to the HC group: right common carotid artery (RCCA), 0.486 ± 0.106 mm and 0.413 ± 0.075 mm in SCH and HC, respectively, p=0.01 and left common carotid artery (LCCA), 0.511 ± 0.144 mm and 0.427 mm ± 0.090 in SCH and HC, respectively, p=0.03). In patients with SCH, there was a decrease in the carotid intima-media thickness after treatment with levothyroxine (RCCA and LCCA, p <0.05 at three and six months). Conclusions: There was an association between increased carotid intima-media thickness in patients with SCH in comparison with HC, even with a TSH <10 µIU/ml. The increase was reversed with levothyroxine therapy. The association of this increased thickness with important cardiovascular outcomes remains uncertain and should be evaluated in future studies.

Association between Carotid Intima-Media Thickness and the Use of Biological or Small Molecule Therapies in Patients with Rheumatoid Arthritis

Objective: The objective of this study was to assess the association of carotid intima-media thickness (CIMT), and also the presence of atheromatous plaque, with biological and targeted synthetic disease-modifying antirheumatic drugs, in an established cohort of patients with rheumatoid arthritis (RA). Patients and Methods: We conducted a cross-sectional observational study based on a cohort of patients with RA and a registry of healthy controls, in whom the CIMT and presence of atheromatous plaque were assessed by ultrasound. Data were collected on disease activity, lab results and treatments. Descriptive and bivariate analyses were performed and two multivariate linear regression models (with CIMT as the dependent variable) were constructed to identify variables independently associated with CIMT in our sample of patients with RA. Results: A total of 176 individuals (146 patients with RA and 30 controls) were included. A higher percentage of patients than controls had atheromatous plaque (33.8% vs. 12.5%, p = 0.036), but no differences were found in terms of CIMT (0.64 vs. 0.61, p = 0.444). Compared to values in patients on other therapies, the CIMT was smaller among patients on tumour necrosis factor alpha (TNFα) inhibitors (mean [SD]: 0.58 [0.10] vs. 0.65 [0.19]; p = 0.013) and among those on Janus kinase inhibitors (mean [SD]: 0.52 [0.02] vs. 0.64 [0.18]; p < 0.001), while no differences were found as a function of the use of the other therapies considered. The multivariate linear regression analysis to identify factors associated with CIMT in our patients, adjusting for traditional cardiovascular risk factors such as hypertension, high levels of low-density lipoproteins, diabetes mellitus and smoking, showed that male sex, older age and having a greater cumulative erythrocyte sedimentation rate were independently associated with a larger CIMT, while patients on TNFα inhibitors had a CIMT 0.075 mm smaller than those on other treatments. Conclusions: The use of TNFα inhibitors may protect against subclinical atherosclerosis in patients with RA, patients on this biologic having smaller CIMTs than patients on other disease-modifying antirheumatic drugs. Nonetheless, these results should be confirmed in prospective studies with larger sample sizes.