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.

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.

Level of advanced oxidation protein products is associated with subclinical atherosclerosis

Background Oxidative stress is an important factor in the pathomechanism of atherosclerosis. Advanced oxidation protein products (AOPPs) are considered markers of oxidative stress. Thickening of the carotid intima-media layers indicates subclinical atherosclerosis and can be detected by carotid ultrasound. Objective Our aim was to examine the association between carotid intima-media thickness (CIMT) and the level of AOPPs. Methods Carotid duplex scans and measurements of AOPPs were performed on 476 participants of a cardiovascular population study. The presence of conventional cardiovascular risk factors was investigated with a questionnaire, physical examination, and laboratory tests. Results There was a positive correlation between maximum CIMT and the level of AOPPs only in the male population (r = 0.219, p = 0.033). Multivariate analysis has revealed that the association between AOPPs and mean or maximum CIMT was independent of cardiovascular risk factors (OR = 1.458, p = 0.004, and OR = 2.038, p < 0.001). Conclusions Among males, the elevated level of AOPPs as a marker of oxidative stress may signal the existence of early atherosclerotic alterations.

Quality of Beverage Intake and Cardiometabolic and Kidney Outcomes: Insights From the STANISLAS Cohort

Background and Aims: Beverages are an important aspect of diet, and their quality can possibly affect health. The Healthy Beverage Index (HBI) has been developed to take into account these effects. This study aimed to highlight the relationships between health and beverage quality by assessing the association of the HBI and its components with kidney and cardiometabolic (CM) outcomes in an initially healthy population-based familial cohort.Methods: This study included 1,271 participants from the STANISLAS cohort. The HBI, which includes 10 components of habitual beverage consumption, was calculated. Associations of the HBI and its components with estimated glomerular filtration rate (eGFR), albuminuria, hypertriglyceridemic waist (HTG waist), metabolic syndrome (MetS), carotid-femoral pulse wave velocity (cfPWV), carotid intima-media thickness (cIMT), and left ventricular mass (LV mass) were analyzed using multivariable linear or logistic regression models.Results: The median HBI score was 89.7 (78.6–95) out of 100 points. While the overall HBI score was not significantly associated with any of the studied outcomes, individual HBI components were found differently associated with the outcomes. cfPWV and cIMT were lower in participants who did not meet the full-fat milk criteria (p = 0.03 and 0.001, respectively). In men, higher cfPWV was observed for the “low Fat milk” (p = 0.06) and “alcohol” (p = 0.03) non-adherence criteria. Odds of HTG waist were higher with the non-adherence to sugar-sweetened beverages criteria (p &lt; 0.001). eGFR was marginally higher with non-adherence to the coffee/tea criteria (p = 0.047).Conclusions: In this initially healthy population, HBI components were differently associated with kidney and cardiometabolic outcomes, despite a good overall HBI score. Our results highlight specific impacts of different beverage types and suggest that beverages could have an impact on kidney and cardiometabolic health.

Exercise and Carotid Properties in the Young–The KiGGS-2 Study

Background: Carotid intima-media thickness (cIMT) and stiffness (cS) are predictive markers of early vascular aging and atherosclerotic risk. This study assessed, whether exercise has protective effects on carotid structure and function or on vascular risk in the young.Methods: Volume and change of exercise (recreational and organized sports participation) of German adolescents and young adults was assessed within the prospective population-study KiGGS at KiGGS-Wave-1 (2009–2012) and KiGGS-Wave-2 (2014–2017) using standardized self-reporting questionnaires. CIMT and cS were measured by real-time B-mode ultrasound sequences with semi-automated edge-detection and automatic electrocardiogram-gated quality control in 2,893 participants (14–28 years, 49.6% female). A cumulative index for atherosclerotic risk (CV-R) included z-scores of mean arterial pressure, triglycerides, total/HDL-cholesterol-ratio, body mass index, and HbA1c.Results: At KiGGS-Wave-2 cross-sectional CV-R but not cS and cIMT was lower in all exercise-groups compared to “no exercise” (B = −0.73, 95%-CI = −1.26 to 0.19, p = 0.008). Longitudinal volume of exercise was negatively associated with CV-R (B = −0.37, 95%-CI = −0.74 to 0.00, p = 0.048) but not with cS and cIMT. Cross-sectional relative risk of elevated CV-R but not cS and cIMT was lower in all exercise-groups compared to “no exercise” (RR = 0.80, 95%-CI = 0.66 to 0.98, p = 0.033). High exercise volumes were associated with lower relative risk of elevated CV-R (RR = 0.80, 95%-CI = 0.65–0.97, p = 0.021) and cS in tendency but not with cIMT.Conclusions: Increased levels of exercise are associated with a better cardiovascular risk profile in young individuals, but not with cS and cIMT. Our study confirms previous recommendations on exercise in this age group without demonstrating a clear benefit on surrogate markers of vascular health.

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.