Early Signs Of Atherosclerosis Research Articles

T-cell senescence was correlated with early atherosclerosis inpatients with systemic lupus erythematosus.

To investigate the correlation between T-cell senescence with the atherosclerosis markers in patients with systemic lupus erythematosus (SLE). The study participants were 40 female SLE patients aged 18-45 years who met the 2019 EULAR/ACR criteria and 40 healthy individuals. The atherosclerosis markers were investigated using the Doppler ultrasonography examinations to measure the cIMT (carotid intima-media thickness) and flow-mediated dilation (FMD) and serological markers using soluble ICAM-1 and VCAM-1. Flow cytometry of CD4+CD57+, CD8+CD57+, CD4+CD28null, and CD8+CD28null T cells were used to assess the immunosenescence markers. The cIMT (p < .001), sICAM-1 (p < .001), and sVCAM-1 (p < .001) were significantly higher in SLE patients compared with control, while FMD was significantly lower in SLE patients (p < .001). The percentages of all T-cell senescence markers are also significantly higher in SLE patients than in healthy individuals. Positive correlations were shown between cIMT with the CD4+CD57+ (R = .301, p = .005), CD4+CD28null (R = .448, p < .001), and CD8+CD28null (R = .422, p < .001). Conversely, negative correlations were demonstrated between the FMD with CD4+CD57+ (R = -.236, p = .023), CD8+CD57+ (R = -.409, p < .001), CD4+CD28null (R = -.422, p < .001), and CD8+CD28null (R = -.318, p = .003). The soluble markers of sICAM-1 and sVCAM-1 were also positively correlated with the T-cell senescence markers. Early sign of atherosclerosis was demonstrated in patients with SLE in this study. T-cell senescence markers had significant correlations with the atherosclerosis markers, including the cIMT, FMD, and soluble adhesion molecules levels. Understanding the link between immunosenescence and atherosclerosis might help to identify a new method for early detection and treatment of atherosclerosis in SLE.

Association between multiple sleep dimensions in OSA and early sign of atherosclerosis: results from the SSHS

Association between multiple sleep dimensions in OSA and early sign of atherosclerosis: results from the SSHS

Effectiveness of Continuous Positive Airway Pressure in Treating Hypertension in Obstructive Sleep Apnea: A Traditional Review.

Almost one billion individuals worldwide suffer from obstructive sleep apnea (OSA). The most widely used treatment for OSA has been continuous positive airway pressure (CPAP), but its effect on blood pressure (BP) has been challenged. Our review aims to evaluate the effects of treating OSA with CPAP on BP and BP-related morbidities in adult hypertensive patients. Medical subject headings (MeSH) terminology was used to search the PubMed Central, MEDLINE, and PubMed databases for articles on the use of CPAP in OSA patients with hypertension. We selected various forms of academic writing, encompassing complete texts that were published in the English language. The study included a total of 21 papers. OSA is a serious health concern associated with a higher risk of cardiovascular disease, kidney disease, pulmonary hypertension, and aortic stiffness, which is brought on by the periodic hypoxia caused by nocturnal respiratory episodes. For individuals with moderate-to-severe OSA, CPAP therapy has been shown to have a considerable long-term benefit with a median drop of 11 mm Hg, and high adherence results in a decrease in diastolic BP. CPAP therapy directly lowers BP in OSA patients with a body mass index (BMI) of more than 30 kg/m2 and has also demonstrated improvement in early signs of atherosclerosis with lower nocturnal systolic BP levels. OSA patients with resistant hypertension also experienced lower BP after using CPAP for a year. Therefore, our findings suggest that obesity, hypersomnolence, high nocturnal BP, prolonged CPAP usage, and resistant hypertension may all have a major impact on the BP response to CPAP therapy in individuals with severe OSA.

Doxorubicin inhibits cholesterol efflux through the miR-33/ABCA1 pathway

Doxorubicin (DOX) is extensively used for the treatment of kinds of cancers, and cardiovascular toxicity is one of the side effects. However, it is unclear whether DOX causes impairment of cardiac function by promoting atherosclerosis. Thus, we investigated the role of DOX in regulating the lipid deposition of macrophages and its molecular mechanism. RAW 264.7 cell line was stimulated with DOX in the presence or absence of low-density lipoprotein (LDL). We found that DOX increased miR-33 and reduced ATP binding cassette transporter A1 (ABCA1) protein. Moreover, cholesterol efflux was suppressed by DOX, which was more efficient under a high-cholesterol condition. After transfecting mimics or inhibitors of miR-33 into cells, ABCA1 protein was respectively decreased and increased, and intracellular lipid accumulation was correspondingly regulated. Overall, DOX suppresses the expression of ABCA1 protein by upregulating miR-33, promoting an intracellular lipid deposition in macrophages, which is a sign of early atherosclerosis. This provides new insights for clinical observation and evaluation of the side effects of DOX.

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

BackgroundThe 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.MethodsGenotyping 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.ResultsStrong 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).ConclusionsEstrogen 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.

IDO activity forecasts obesity in males and premenopausal females in a 10-year follow-up study:The Cardiovascular Risk in Young Finns Study

Background and aimsIndoleamine 2,3-dioxygenase (IDO) is an intracellular enzyme associated with artery wall inflammation. Previous studies have verified correlation between IDO activity and early signs of atherosclerosis especially in females. We aimed to elucidate the relationship between an estimate of IDO activity and atherosclerotic risk factors related to non-alchohol-fatty liver (NAFLD) in a 6- and 10-year follow-up. MethodsEstimates of IDO activity along with complete risk factor data were measured from females (n = 506; age 24–39) and males (n = 421; age 24–39) in 2001. Risk factor measurements were conducted again in 2007 and 2011. Statistical examinations were carried out by Pearson correlation and risk ratio analysis. ResultsIn females, age-adjusted IDO correlated with body mass index (BMI) (p = 0.0008), waist (p = 0.0009), C-reactive protein (CRP) (p = 0.0014) and logarithmically modified triglycerides (p = 0.0488) in 2007. Correlation remained significant with BMI (p = 0.0007) and waist (p = 0.0063) in 2011. In males, age-adjusted IDO correlated with waist (p = 0.0367) and high-density lipoprotein cholesterol (HDL-C) (p = 0.0489) in 2007. Correlation remained significant with HDL-C (p = 0.0348) in 2011. In risk ratio analysis, relationship between IDO and obesity was confirmed in females after 10 years (RR = 1.026, p = 0.0147, 95% CI) and in males after 6 and 10 years (RR = 1.019, p = 0.0091, 95% CI and RR = 1.015, p = 0.0404, 95% CI, respectively) when the data was adjusted for age and BMI. ConclusionsIDO activity correlated with obesity and factors related to NAFLD, namely obesity of visceral type, hypertriglyceridemia and CRP (in females), well-characterized risk factors for diabetes and atherosclerosis in 6- and 10-year follow-up in males and premenopausal females.

Vitamin B12, folate and homocysteine concentrations during pregnancy and early signs of atherosclerosis at school-age

SummaryBackground & aimsSuboptimal circulating vitamin B12, folate and homocysteine concentrations during fetal life seem to be associated with cardiometabolic health at school-age. We examined whether fetal exposure to lower circulating vitamin B12 and folate concentrations and higher circulating homocysteine concentrations is also associated with early signs of atherosclerosis at school-age.MethodsThis study among 3826 school-age children and their mothers was embedded in the Generation R Study, a population-based prospective cohort study from early pregnancy onwards. We examined the associations of early-pregnancy and cord blood serum total and active B12 and plasma folate and homocysteine concentrations with common carotid artery intima-media thickness and distensibility in the children aged ten years.ResultsAs compared to normal early-pregnancy serum total B12 concentrations (≥145 pmol/L), low serum total B12 concentrations (<145 pmol/L) were associated with higher carotid intima-media thickness in the children at school-age (difference 0.09 standard deviations score (SDS); 95% confidence interval (CI): 0.01, 0.16). As compared to normal early-pregnancy plasma folate concentrations (≥8 nmol/L), low plasma folate concentrations (<8 nmol/L) were associated with lower carotid disten-sibility in the children at school-age (difference −0.16 SDS; 95% CI: −0.28, −0.04). Early-pregnancy circulating total and active B12, folate and homocysteine concentrations measured continuously were not associated with carotid intima-media thickness or carotid distensibility in the children at school-age. One SDS higher plasma homocysteine concentrations measured in cord blood at birth was associated with a −0.05 SDS (95% CI: −0.09, −0.02) lower carotid distensibility at school-age. Cord blood total and active B12 and folate concentrations were not associated with carotid intima-media thickness or carotid distensibility at school-age.ConclusionsCirculating total B12, folate and homocysteine concentrations during fetal life seem to be associated with markers of subclinical atherosclerosis at school-age. Further studies need to examine the causality and mechanisms underlying these associations.

30. SHOULD WE LOWER THE INTIMA MEDIA THICKNESS CUT OFF TO 0.9 TO START SECONDARY STROKE PREVENTION IN HYPERTENSIVE PATIENTS?

Background: Hypertension is a common risk factor of stroke. Carotid intima media thickening (IMT) is an early sign of atherosclerosis in stroke patient. Objective: This study aimed to found IMT cut off difference in hypertension and non-hypertension stroke patient. Methods: This was a retrospective cross-sectional study using stroke registry in Neurology Outpatient Clinic, RSUPN Dr. Cipto Mangunkusumo, Jakarta, in January–December 2020. Hypertension was measured clinically, whereas IMT was measured using carotid duplex. Subjects were categorized into hypertension and non-hypertension. Patients with diabetes mellitus were excluded. Univariate analysis and Mann-Whitney test were performed to evaluate the differences. Result: Of 108 subjects with the mean age of 56.13 + 10.98 years, 73 (67,6%) subjects were male. The proportion of hypertension was 53.7%. The median of left CIMT in hypertension and non-hypertension group were 0.955 (0.5–1.55) and 0.8 (0.4–1.1) (p &lt; 0.001). The median of right IMT in hypertension and non-hypertension group were 0.9 (0.4–1.6) and 0.8 (0.4–1) (p = 0.038). Discussion: Hypertension may cause sheer stress and inflammation at bilateral endothelium common carotid artery (CCA), which predisposed to atherosclerosis and manifested into IMT. The current guideline recommended IMT threshold value of 1 mm to be associated with greater risk to develop a new vascular event. In this study, we found that median of IMT was 0.9 mm in stroke with hypertension patients, which was lower than currently recommended cut off. Conclusion: IMT 0.9 mm should be considered as a new value to start secondary stroke prevention in hypertension patients.

Prevalence of asymptomatic atherosclerosis of extracranial vessels among hypertensive patients in southern Egypt: An extracranial duplex study.

Objectives:The prevalence of atherosclerosis in extracranial vessels among hypertensive patients in southern Egypt is still unknown. Carotid ultrasound is an accurate method used to identify and follow patients with cerebrovascular disorders. The aim of our study is to detect the prevalence and pattern of extracranial atherosclerosis among those patients.Methods:Our case-control study was performed from January 2017 to January 2018, including 200 subjects, 100 patients recruited consecutively from the Hypertension Clinic in Assiut University hospitals, Egypt, and 100 healthy controls. Detailed history collection and thorough physical examinations were carried out for each patient. All subjects underwent extracranial ultrasound. We omitted patients with history of ischemic stroke and TIAs.Results:The presence of increased intima media thickness was detected in 37 patients (37%). 22 patients (22%) had internal carotid artery (ICA) stenosis, 17 patients (17%) had non-significant stenosis <50%, while five patients (5%) had stenosis 50-69%. 9% had stenosis < 50% in vertebral artery. In addition, age and uncontrolled hypertension have a greater impact on increasing the CCA intima media thickness, which is considered an early sign of atherosclerosis.Conclusions:Uncontrolled hypertension is an important risk factor for atherosclerosis and hence ischemic stroke (IS). The cost of screening is considered low compared to IS management. Greater emphasis should be directed toward regular screening programs in this risky population.

Impaired fasting plasma glucose is a risk indicator of interventricular septum thickening among non-diabetic subjects with obesity

AimsTo evaluate whether progressively higher fasting plasma glucose (FPG) is associated to thickening of the interventricular septum (IVS) among non-diabetic subjects with obesity. MethodologyWe studied 227 consecutive non diabetic patients (155 women and 72 men, age range 18–72 years) with overweight or obesity (BMI ≥ 25 Kg/m2), taking no medication or supplement. Hormonal, metabolic and routine laboratory parameters were collected. Echocardiography and ultrasonography echo-color Doppler of intima-media thickness of the common carotid artery (IMT-CCA) were performed to evaluate intima-media thickness of the common carotid artery (IVST) and early signs of atherosclerosis, respectively, in all enrolled subjects. ResultsOf the 227 subjects, 48.9% had higher IVST values. Age (p 0.04), waist circumference (p 0.01), systolic (p < 0.01) and diastolic blood pressure (p < 0.01), FPG (p < 0.01), insulin (p 0.04), HOMA IR (p = 0.01), uric acid (p < 0.01) serum levels, IMT-CCA (p < 0.01), and left atrial diameter (LAD) (p < 0.01) were significantly higher in subjects with pathological IVST. Logistic regression models demonstrated an independent relation of FPG to IVST, both in semi and fully adjusted models (ORs 1.045 and 1.039, respectively). Moreover, graph presentation of the ORs and 95% CIs by FPG quintiles showed a positive risk trend for pathological IVST. ConclusionsHigher FPG levels represent an independent sensitive predictor of IVS thickening in subjects with obesity, even before overt diabetes. These results emphasize the importance of preventive management of the diabetes risk in obesity.

Body fat percentage and CRP correlates with a composite score of vascular risk markers in healthy, young adults - The Lifestyle, Biomarkers, and Atherosclerosis (LBA) study

BackgroundIdentification of early signs of atherosclerosis in young adults have the potential to guide early interventions to prevent later cardiovascular disease. We therefore analyzed measures of vascular structure and function and biomarkers of cardiovascular risk in a sample of young healthy adults.MethodsPulse-wave velocity (PWV), carotid-intima media thickness (cIMT) and augmentation index (AIX) were measured in 834 healthy non-smokers (ages 18.0–25.9). Emphasis was put on discriminating between individuals having a vascular structure and function associated with a higher or lower risk, and cluster analysis algorithms were employed to assign the subjects into groups based on these vascular measurements. In addition, a vascular status score (VSS) was calculated by summarizing the results according to quintiles of the vascular measurements. The associations between VSS and cardiovascular biomarkers were examined by regression analyses.ResultsThe cluster analyses did not yield sufficiently distinct clustering (groups of individuals that could be categorized unequivocally as having either a vascular structure and function associated with a higher or lower CVD risk). VSS proved a better classificatory variable. The associations between VSS and biomarkers of cardiovascular risk were analyzed by univariable and multivariable regressions. Only body fat percentage and C-reactive protein (CRP) were independently associated with VSS.ConclusionsA VSS calculation, which integrates PWV, cIMT, and AIX measurements is better suited for cardiovascular risk evaluation in young adults than cluster analyses. The independent associations of VSS with body fat percentage and CRP highlight the decisive role of adiposity and systemic inflammation in early atherosclerotic progression and suggests a subordinate role of insulin and lipid metabolism in this age span.

Compromised endothelial function in transgender men taking testosterone

Transgender men (TGM) are persons assigned female gender at birth with a male gender identity and are routinely treated with testosterone. Androgen excess is associated with endothelial dysfunction among cisgender females (CGF) and is an early sign of atherosclerosis and hypertension. To determine the effect of testosterone treatment on endothelial function in TGM. The John B. Pierce Laboratory and Yale School of Medicine. Eleven TGM (age 27±5years; BMI 24.4±3.7kg/m2 ) receiving testosterone (T) and 20 CGF (28±5years; BMI 26.0±5.1kg/m2 ) during the early follicular phase of their menstrual cycle. We evaluated brachial vasodilatory responses following stimuli designed to elicit shear stress using 5-minute occlusion to determine endothelial function (flow-mediated vasodilation, FMD). Total T was greater in the TGM compared to CGF (484.6±122.5 vs 1.5±0.7ng/dL), as was free T (83.9±32.4 vs 1.9±0.8pg/dL). FMD was markedly lower in the TGM (4.5±2.7%) compared to the CGF (8.1±2.9%, P=.002) indicating significantly diminished endothelial function in TGM. We have shown for the first time that in TGM the androgen-dominant hormonal milieu was associated with impaired endothelial function. Endothelial dysfunction precedes clinically detectable atherosclerotic plaque in the coronary arteries, so is an important marker for clinical cardiovascular risk. Therefore, attention to cardiovascular risk factors should be integral to the care of transgender men.

P3462IDO activity forecasts obesity in premenopausal females in 10-year follow-up study: the Cardiovascular Risk in Young Finns Study

Abstract Background Indoleamine 2,3-dioxygenase (IDO) is an intracellular enzyme that has an important immunomodulator function. Human inflammatory response promotes upregulation of IDO level in blood. This may lead to suppression of inflammation in atherosclerotic vessel wall and consequently may slow the progression of the disease. Previous studies have shown that IDO activity correlates with early signs of atherosclerosis especially in females but is not an atherosclerosis-specific marker. Materials and methods IDO levels were measured from females (n=544; age 24–39; weight 40.5–134.4 kg) in 2001 along with several risk factors for atherosclerosis. Follow-up risk factor measurements were performed in 2007 and 2011. Here we aimed to elucidate the relationship between IDO measurements from 2001 and several atherosclerotic risk factors from 2007 and 2011 by analyzing correlations and risk ratios from the Cardiovascular Risk in Young Finns Study patient cohort. Results After age standardization, IDO correlated significantly with BMI (p=0.0008), waist (p=0.0009) and logarithmically modified triglycerides (p=0.0488) and CRP (p=0.0014) in female samples (n=434) from 2007. When female samples (n=384) from 2011 were examined, statistically significant correlations were discovered in BMI and Waist in both unadjusted (p&lt;0.0001 and 0.0003, respectively) and age-adjusted analysis (p=0.0007 and 0.006, respectively). In contrast, only weak correlations were found in male samples. In risk ratio analysis IDO promoted obesity (RR=1.027, p=0.01) in females (n=431) in 10-year follow-up study even after the data was adjusted for age, CRP and BMI. Conclusions It is concluded that IDO activity forecasts obesity – a well-characterized risk factor for diabetes and atherosclerosis – in premenopausal females.

P3416Bilateral carotid intima media thickness (cIMT) and plaque measurements was stronger associated with cardiovascular risk factors than unilateral measurements. Results from the VIPVIZA trial

Abstract Background Clinical risk factors of cardiovascular diseases (CVD) are related to atherosclerosis and cIMT and plaque are signs of early atherosclerosis. However, associations between risk factors and ultrasound variables are not fully established and comparison between studies is hampered by different imaging protocols. There is limited data regarding study population characteristics and ultrasound measurements differ regarding arterial bed, projections, and plaque definitions and inclusion Purpose 1/ To describe the distribution of asymptomatic atherosclerosis as assessed by carotid ultrasound in a middle-aged population at low/intermediate risk of CVD. 2/ To investigate the associations between clinical risk factors and a set of ultrasound variables Method Bilateral carotid ultrasound examinations were performed according to a standardized protocol in 3532 healthy VIPVIZA-participants with at least one conventional CVD risk factor. CIMT was measured in the distal far wall of CCA, 240o and 210o left and 150o and 120o right side, based on Meijer arch. For each angle, mean and max IMT was measured in a 10 mm segment. Plaques were identified according to the Mannheim consensus. Socio-economic data was also recorded. Associations between the risk factors and the set of ultrasound variables were quantified by a partial least squares (PLS) regression. A new compound ultrasound variable was computed, PLS UL, bya combining all IMT variables and plaque using the weights of the first PLS component. In a second step, to estimate how much risk factors explained the variability of the ultrasound results, associations between risk factors and both PLS UL and single cIMT variables and plaque were determined using step-wise linear regression modelling Results Mean age was 55.6 and 55.8 years among men and women (52.7% women), 13% were smokers in both sexes, and 50.8% and 39.3%, respectively, had carotid plaque. Mean of mean cIMT was 0.68 mm vs 0.64 mm (p&lt;0.001), and max cIMT was 0.90 mm vs 0.82 mm (p&lt;0.001), respectively. Overall, cIMT was slightly higher in the left compared to the right carotid. All ultrasound variables had similar univariate associations with clinical risk factors, positive associations for all risk factors except physical activity, fruit and vegetable consumption, education and HDL-cholesterol. The strongest association between risk factors and ultrasound variables was found with PLS UL (R2=23%), compared to single cIMT variables (R2=14–18%) and plaque (R2=15%). The pattern was similar in both sexes with most risk factors shared between the sexes. The association with factors and PLS UL was stronger among 40-year olds (R2=22%) than among 50- and 60-year olds (R=12%) Conclusion A combination of ultrasound variables are stronger associated to CVD risk factors than plaque or a single CIMT measurement. The pattern is similar in men and women. These findings are relevant for development of a consensus for cIMT measurements Acknowledgement/Funding Västerbotten County Council, the Swedish Research Council, the Heart and Lung Foundation, the Swedish Society of Medicin, Carl Bennet Ltd, Sweden

Compromised endothelial function in transgender men taking testosterone

Approximately 0.6% or 1.4 million people identify as transgender or having a current gender identity that differs from the sex assigned at birth. Transgender men (TGM) are persons assigned female at birth with a male gender identity. In TGM, testosterone therapy may be associated with increased blood pressure (BP), lipids, triglycerides, LDL cholesterol and decreased HDL‐cholesterol. Androgen excess is a major driver of endothelial dysfunction among cisgender females (CGF), and endothelial dysfunction is an early sign of atherosclerosis and hypertension. We therefore examined endothelial function in TGM receiving testosterone. We hypothesized that endothelial function in TGM would be attenuated compared to CGF of similar age and BMI. We compared 4 TGM (age 26 ± 5 y; BMI 26.3 ± 3.2 kg/m2) receiving testosterone (T) to 8 CGF (25 ± 4 y; BMI 25.7 ± 6.8 kg/m2) during the early follicular phase of their menstrual cycle. We evaluated brachial vasodilatory responses following stimuli designed to elicit shear stress using 5‐min occlusion to determine endothelial function (flow mediated vasodilation, FMD). As expected, total T was increased in the TGM compared to CGF (457.4 ± 119.8 vs. 1.9 ± 1.1 ng/dL), as was free T (72. ± 7.5 vs. 1.5 ± 0.9 pg/dL). Blood lipids, including LDL (98.6 ± 38.5 mg/dL), HDL (51.5 ± 11.1 mg/dL) and triglycerides (79.0 ± 31.9 mg/dL) as well as HbA1c (4.9 ± 0.1%) were within normal ranges in the TGM. Systolic BP (SBP) was elevated in 2/4 TGM and 3/8 CGF; MAP was similar between groups (90 ± 21 and 90 ± 10 mm Hg). However, FMD was attenuated in the TGM (3.7 ± 3.5 %) compared to the CGF (9.2 ± 1.2 %, P=0.001) indicating markedly diminished endothelial function in TGM receiving androgen treatment. Further, endothelial dysfunction was independent of other risk factors associated with cardiovascular disease including hyperlipidemia, diabetes and hypertension. In transgender men, the androgen‐dominant hormonal milieu appears to impair endothelial function. Endothelial dysfunction precedes clinically detectable atherosclerotic plaques in the coronary arteries and is an important marker for cardiovascular risk. Therefore, attention to cardiovascular risk factors should be integral to the care of transgender men.Support or Funding InformationR01 HL135089This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

Effect of uric acid serum levels on carotid arterial stiffness and intima-media thickness: A high resolution Echo-Tracking Study.

Serum uric acid (UA) has been shown to be a predictor of cardiovascular (CV) morbidity and mortality, and it may play a role in the pathogenesis of CV disease affecting vascular structure and function. However, there is limited evidence of its specific association with carotid artery stiffness and structure. The aim of our study was to evaluate whether UA is associated with early signs of atherosclerosis, namely local carotid arterial stiffness and intima-media thickening. We evaluated 698 consecutive asymptomatic patients, referred to the Cardiovascular Department for risk factors evaluation and treatment. All patients underwent carotid artery ultrasonography with measurement of common carotid intima-media thickness (IMT) and echo-tracking carotid artery stiffness index Beta. Patients with hyperuricemia (defined as serum uric acid ≥7 mg/dL in men and ≥6 mg/dL in women) had higher IMT (0.97±0.22 vs 0.91±0.18, p<0.001) and stiffness index Beta (8.3±3.2 vs 7.5±2.7, p=0.005). UA levels correlated with both IMT (r=0.225; p<0.001) and stiffness index Beta (r=0.154; p<0.001); the correlations were statistically significant in males and females. In a multivariate model which included age, arterial pressure, serum glucose and LDL-cholesterol, serum UA emerged as an independent explanatory variable of IMT and stiffness index Beta. Carotid IMT and local arterial stiffness are related to UA independently of established CV risk factors; UA may play a role in the early development of atherosclerosis.

Platelet number is negatively and independently associated with carotid intima-media thickness in apparently healthy overweight/obese subjects

Background and AimA significant change of platelet number may be a risk factor for atherosclerotic cardiovascular disease. The aim of this study was to investigate the association between platelet number and early signs of atherosclerosis, evaluated by carotid intima-media thickness (c-IMT), in a apparently healthy population mainly represented by obese subjects. Methods and ResultsAs many as 961 subjects, 686 women and 275 men, aged between 18 and 74 years, were enrolled in the study. Of these, 54 individuals (5.6% of all subjects) were normal weight, 259 individuals (27.0% of all subjects) were overweight, and 648 individuals (67.4% of all subjects) were obese. Waist circumference (WC) and blood glucose, insulin, total cholesterol, high and low density lipoprotein cholesterol, triglycerides and platelet count were also detected in all subjects, who underwent carotid echo color doppler ultrasound to measure c-IMT.c-IMT was significantly and positively associated to age (r = 0.204, P < 0.0001), fasting glucose (r = 0.073, P < 0.0240), total cholesterol (r = 0.096, P = 0.0031), and systolic and diastolic blood pressure (r = 0.140, P < 0.0001 and r = 0.119, P < 0.0003 respectively); c-IMT was significantly and negatively correlated with platelet count (r = −0.165, P < 0.0001). Only age (P < 0.0001) and systolic blood pressure (P = 0.0393), positively, and platelet number (P < 0.0001), negatively, were significantly and independently associated to c-IMT in a final multiple regression analysis. ConclusionLower platelet number represented an independent determinant of c-IMT in a population, mainly represented by obese patients. These results suggest that a decrease of platelet number may well be an early defensive mechanism in subjects developing the thickening of carotid artery.

The impact of dapagliflozin on glucose excursions related to early proatherogenic derangement in the aortic wall

IntroductionCardiovascular risk in the course of diabetes depends greatly on glycemic variability which is even more significant than chronic hyperglycemia. Optimal management of diabetes involves a multidisciplinary approach focused in particular on decreasing the risk of atherosclerosis. Therefore, our purpose was to evaluate the impact of dapagliflozin on glucose excursions and related proatherogenic changes in the aortic wall. Methods and materialsAnimal model of type 2 diabetes rich-fat/STZ rats was used. Wistar rats were randomized into 3 groups: dapagliflozin-treated with glucose excursions, placebo-treated with glucose excursions and placebo-treated with stable diabetes. Dapagliflozin was administered once a day, 1 mg/kg, for 8 consecutive weeks. Glucose levels were measured twice a week at fasting and postprandially. The samples of aortas were taken for histopathological and immunochemistry examinations at the end of the experiment. The derangement in the aortic wall and the distribution of CD68+ cells in the aorta were considered early signs of atherosclerosis. ResultsDapagliflozin reduced glucose excursion to the level characteristic for stable, well-controlled diabetes. It was related to a significant decrease in histopathological changes which were observed in the placebo-treated rats with glucose variability. Dapagliflozin significantly reduced also the accumulation of CD68+ macrophages in the aortic adventitia. ConclusionDapagliflozin provides not only mere beneficial regulation of metabolic status with the depletion of glucose variability, but is also helpful in the prevention of early atherosclerosis related to the course of diabetes type 2.

Obstructive sleep apnea during rapid eye movement sleep is associated with early signs of atherosclerosis in women.

Although obstructive sleep apnea (OSA) is associated with overall cardiovascular disease and mortality, the association with atherosclerotic cardiovascular disease is less clear, especially in women. Recently, it has been suggested that OSA during rapid eye movement (REM) sleep, associated with long apneas and deep desaturations, could have severe cardiometabolic consequences. The aim of this study was to investigate whether OSA during REM sleep is associated with early signs of atherosclerosis in a population-based sample of women. In the community-based "Sleep and Health in Women" (SHE) cohort study, 400 women underwent polysomnography, anthropometric measurements, blood sampling, blood pressure measurement, and answered questionnaires. Ten years later, 201 of the original participants, free of known atherosclerotic disease at baseline and without continuous positive airway pressure treatment for OSA, underwent a high-frequency ultrasound of the common carotid artery to assess the individual thickness of the layers of the artery wall. Severe OSA during REM sleep (REM apnea-hypopnea index [AHI] ≥ 30) was associated with a thicker intima. This association was still significant after adjustment for age, body mass index, alcohol, and smoking, as well as for further adjustment for systolic blood pressure, low-density lipoprotein, C-reactive protein, and diabetes (β-coefficient, 0.008; p-value, 0.022). The association between a REM AHI of ≥30 and intima thickness was also seen in women with no or mild OSA and normal non-REM AHI. In this study of a community-based sample of women, severe OSA during REM sleep was independently associated with early signs of atherosclerosis.

Peripheral Biomarker for Vascular Disorders.

Atherosclerosis is the underlying cause of most myocardial infarction (MI) and ischaemic stroke episodes. An early sign of atherosclerosis is hypertrophy of the arterial wall. It is known that increased intima media thickness (IMT) is a non-invasive marker of arterial wall alteration, which can easily be assessed in the carotid arteries by high-resolution B-mode ultrasound. Similarly, the other key element of MI and ischaemic strokes is the N-methyl-D-aspartate (NMDA) receptor which is an ionotropic glutamate receptor that mediates the vast majority of excitatory neurotransmission in the brain. NMDA activation requires the binding of both glutamate and a coagonist like D-serine to its glycine site. A special enzyme, serine racemase (SR), is required for the conversion of L-serine into D-serine, and alterations in SR activities lead to a variety of physiological and pathological conditions ranging from synaptic plasticity to ischemia, MI, and stroke. The amount of D-serine available for the activation of glutamatergic signalling is largely determined by SR and we have developed ways to estimate its levels in human blood samples and correlate it with the IMT. This research based short communication describes our pilot study, which clearly suggests that there is a direct relationship between the SR, D-serine, and IMT. In this article, we will discuss whether the activity of SR can determine the future consequences resulting from vascular pathologies such as MI and stroke.