Preclinical Atherosclerosis Research Articles

Impact of age and sex on subclinical coronary atherosclerosis in a healthy asian population

Abstract Funding Acknowledgements Type of funding sources: None. Background and Aims The influence of age and gender on clinical atherosclerotic cardiovascular disease is well reported, but literature remains sparse on whether these extend to the disease in its preclinical stage. We aim to report the prevalence, risk-factors and impact of age and gender on the burden of subclinical coronary atherosclerosis in a healthy Asian population. Methods Healthy subjects aged 30-69 years old, with no history of cardiovascular disease or diabetes were recruited from the general population. Subclinical coronary atherosclerosis was quantified via the Coronary Artery Calcium Score (CACS) with CACS of 0 indicating the absence of calcified plaque, 1 to 10 minimal plaque, 11 to 100 mild plaque, and >100 moderate to severe plaque. Results A total of 663 individuals (mean age 49.4 ± 9.2 years, 44.8% male) were included. The prevalence of any CAC was 29.3% with 9% having CAC > 100. The prevalence was significantly higher in males than females (43.1 vs 18.0%, p < 0.001). These gender differences became increasingly pronounced with increasing age, especially in those with moderate-severe CAC. Multivariable analysis revealed significant associations between increasing age, male, higher blood pressure, increased glucose levels and higher LDL cholesterol levels with the presence of any CAC. LDL cholesterol was more significantly associated with CAC in females compared to males (Pinteraction = 0.022). Conclusions The prevalence of preclinical atherosclerosis increased with age, and was higher in males than females, with gender-specific differences in associated risk factors. These results will better inform individualised future risk management strategies to prevent the development and progression of coronary artery disease within healthy individuals.

Upregulated monocyte expression of PLIN2 is associated with early arterial injury in children with overweight/obesity

Background and aimsPerilipin 2 (PLIN2) regulates intracellular lipid metabolism in macrophages, and thus, plays a role in atherosclerosis. Aim of the study was to evaluate whether PLIN2 dysregulation is involved in the onset of preclinical atherosclerosis in children with overweight/obesity and to explore dysregulation mechanisms. MethodsSixty-three children with overweight/obesity and 21 normal weight children (controls) of the same age and sex were enrolled. Carotid intima media thickness (cIMT) was evaluated; mRNA expression of PLIN2 and proteasome subunits (PSMD3, PSMC4) was determined by Real Time PCR, and protein expression of PLIN2, LAMP2A and Hsc70 by Western blot analysis; fluorimetric assay was used to measure proteasome chymotrypsin like activity. We performed transient LAMP2A downregulation by siRNA and quantified intracellular lipids in monocytes by Nile Red staining and flow cytometry analysis. ResultsPLIN2 protein levels were significantly higher in children with overweight/obesity and correlated with cIMT after adjusting for confounders. Accordingly, monocytes of children with overweight/obesity showed a higher intracellular amount of lipids compared with controls. mRNA expression of the regulatory subunits PSMC4 and PSMD3 and proteasome activity were lower in children with overweight/obesity, while expression of LAMP2A and Hsc70 proteins, which belong to the chaperone-mediated autophagy (CMA) pathway, was not different, suggesting that PLIN2 dysregulation in monocytes was due to an impairment of proteasome efficiency and was not CMA related. ConclusionPLIN2 was overexpressed in monocytes of children with overweight/obesity and could contribute to the onset of arteropathy. Our data suggest that proteasome impairment could contribute to PLIN2 overexpression.

The function of matrix metalloproteinase-9 (MMP-9) and its tissue inhibitor (TIMP-1) in several clinical conditions: Results and analysis of our survey.

The goal of this research was to evaluate the plasma concentration of MMP-9 and its tissue inhibitor (TIMP-1) in different clinical conditions. It included several groups of subjects: 31 overweight subjects; 91 obese adults divided into two subgroups according to the BMI value (BMI 30-35 Kg/m2 and BMI > 35 Kg/m2); 90 subjects with metabolic syndrome (MS) divided into two subgroups (with and without diabetes mellitus); 100 subjects with preclinical carotid atherosclerosis (PCA) divided according to the number of cardiovascular risk factors and to the insulin resistance degree; 48 subjects with obstructive sleep apnoea syndrome (OSAS) divided according to the apnoea/hypopnea index (AHI); 27 subjects with chronic kidney disease (CKD) on conservative management; 31 subjects with CKD on regular haemodialysis treatment. We have found a significant increase of MMP-9 and TIMP-1 in overweight subjects, in obese adult and in MS subjects. In obese adults, the behaviour of these two parameters was not influenced by the degree of obesity, while in the group of MS subjects both these parameters were clearly influenced by the presence of diabetes mellitus. In subjects with PCA, we observed an increase of MMP-9 associated with a significant decrease of TIMP-1; the same trend was found by subdividing the entire group in accordance with the number of cardiovascular risk factors and with the insulin resistance degree. In subjects with OSAS, we noted an increase in MMP-9 and TIMP-1; this increase was more evident in subjects with OSAS having AHI > 30. In individuals with CKD on conservative and haemodialysis treatment we have found, at baseline, a marked increase in MMP-9 and a significant decrease of TIMP-1. In dialyzed subjects, after a standard dialysis session was noted, a significant increase in MMP-9 was associated with a further decrease in TIMP-1.

Quantification of glycoproteins by nuclear magnetic resonance associated with preclinical carotid atherosclerosis in patients with type 1 diabetes

Background and aimsGlycoproteins play a key role in inflammatory and cardiometabolic processes. Their implication in atherosclerosis in type 1 diabetes (T1D) is unknown. We assessed the relationships between classic inflammatory markers, glycoproteins measured by nuclear magnetic resonance (1H-NMR), and preclinical atherosclerosis in these patients. Methods and resultsWe selected patients with T1D, without cardiovascular disease (CVD), with: age ≥40 years, nephropathy (micro/macroalbuminuria), or ≥10 years of evolution with another risk factor. The presence of plaque (intima-media thickness >1.5 mm) was determined by ultrasonography. Concentrations of high-sensitive C-reactive protein (hsCRP), circulating leukocytes (classical inflammation markers) and 1H-NMR-glycoproteins (GlycA, GlycB, GlycF, and the height/width [H/W] ratios of GlycA and GlycB) were determined. We included 189 patients (58% male, age 47.0 [40.7–55.2] years). Thirty-five percent presented plaques (22%, ≥2 plaques). There was no association between hsCRP or leukocytes and atherosclerosis. However, in age- and sex-adjusted models, GlycA, GlycF, and the H/W ratios of GlycA and GlycB gradually increased with the number of plaques (0, 1, ≥2 plaques) only in patients without statins (p < 0.05), with no association in patients receiving this drug (p for interaction <0.05; in ≥2 plaques). Finally, in models adjusted for other classical and T1D-specific risk factors, GlycA and GlycB H/W ratios remained associated with carotid plaque (OR 1.39 [1.12–1.90] and OR 6.89 [1.85–25.62], respectively). ConclusionIn T1D individuals without lipid-lowering treatment, 1H-NMR-glycoproteins were independently associated with the presence and amount of carotid atherosclerosis, unlike other classical inflammatory markers. Further studies are needed to ascertain their utility as CVD biomarkers.

Time in Range Does Not Associate With Carotid Artery Wall Thickness and Endothelial Function in Type 1 Diabetes.

Patients with Type 1 diabetes (T1D) have an increased risk of developing atherosclerosis and complications as myocardial infarction and peripheral artery disease. The thickening of the carotid wall and the brachial artery dysfunction are early and preclinical manifestations of atherosclerosis. The standard marker of care for assessment of glycemic control, glycated hemoglobin, does not associate with early atherosclerosis. We have hypothesized that the emerging metric of glycemic control, as the time spent in the target range (TIR), might be associated with carotid thickening and endothelial dysfunction. According to the hypothesis, we have designed the present research with the aim to evaluate the association between TIR collected in the short and long term and the measures of arterial morphology and function in patients with T1D. In our study, 70 patients and 35 healthy controls underwent ultrasound vascular study to measure carotid artery intima-media thickness (IMT) and brachial artery endothelial function by the flow-mediated dilation (FMD) technique. TIR was collected by a continuous glucose monitoring system for 2 weeks, 3 months, and 6 months before the vascular study. Patients with T1D showed a significantly higher carotid IMT (mean±SE, 644±19 vs. 568±29 µ; p= 0.04) and a significantly lower FMD (mean±SE, 7.6±0.4 vs. 9.8±0.6%; p=0.01) compared with control subjects. No significant relationship between IMT, FMD, and TIR collected in the short and long term emerged. Young patients with T1D have early vascular abnormalities. The percent of TIR does not correlate with preclinical atherosclerosis. This finding underlines the complexity of the interplay between diabetes and atherosclerosis.

Pre-clinical atherosclerosis is found at post-mortem, in the brains of men with HIV

The aim of this study is to ascertain the burden of pre-clinical atherosclerotic changes in the brains of young adult males with HIV and explore the impact of anti-retroviral therapy (ART). The study design is case-control, cross-sectional. Histological sections from HIV-positive post-mortem brain samples, with no associated opportunistic infection, from the MRC Edinburgh brain bank were evaluated. These were age and sex matched with HIV-negative controls. Immunohistochemical stains were performed to evaluate characteristics of atherosclerosis. The pathological changes were graded blinded to the HIV status and a second histopathologist reassessed 15%. Univariable models were used for statistical analyses; p ≤ 0.05 was considered significant. Nineteen HIV-positive post-mortem cases fulfilled our inclusion criteria. Nineteen HIV-negative controls were selected. We assessed mostly small-medium-sized vessels. For inflammation (CD45), 7 (36%) of the HIV+ had moderate/severe changes compared with none for the HIV− group (p < 0.001). Moderate/severe increase in smooth muscle remodeling (SMA) was found in 8 (42%) HIV+ and 0 HIV− brains (p < 0.001). Moderate/severe lipoprotein deposition (LOX-1) was found in 3 (15%) and 0 HIV−brains (p < 0.001). ART was associated with less inflammation [5 (63%) no ART versus 2 (18%) on ART (p = 0.028)] but was not associated with reduced lipid deposition or smooth muscle damage. In HIV infection, there are pre-clinical small- to medium-sized vessel atherosclerotic changes and ART may have limited impact on these changes. This could have implications on the increasing burden of cerebrovascular disease in HIV populations and warrants further investigation.

Predictors and reference equations for augmentation index, an arterial stiffness marker, in healthy children and adolescents

OBJECTIVES:To investigate predictors and propose reference equations for the augmentation index normalized to 75 bpm heart rate (AIx@75) in healthy children and adolescents.METHODS:This was a cross-sectional, observational study involving 134 healthy children and adolescents aged 9 to 19 years old. Participants were categorized into child (n=53) and adolescent (n=81) groups, as well as into male (n=69) and female (n=65) groups. We evaluated AIx@75, vascular and hemodynamic parameters, anthropometric data, physical activity profile, and quality of life (Peds-QL4.0; physical, emotional, social and school domains).RESULTS:The predictors of AIx@75 in the whole sample were age, peripheral diastolic blood pressure (pDBP), mean arterial pressure, pulse pressure amplification (PPA), systolic volume (SV), cardiac index (CI), and pulse wave velocity (PWV; R2=80.47%). In the male group, the predictors of AIx@75 were SV, CI, total vascular resistence (TVR), and PWV (R2=78.56%), while in the female group, they were pDBP, PPA, SV, and PWV (R2=82.45%). In the children, they were pDBP, PPA, SV, and PWV (R2=79.17%), while in the adolescents, they were body mass index, pDBP, PPA, SV, TVR, and PWV (R2=81.57%).CONCLUSION:In the present study, we used a representative sample from Belo Horizonte to establish normality values of AIx@75. We also identified, for the first time, independent predictors of AIx@75 in healthy children and adolescents categorized by sex and age. Determining AIx@75 reference equations may facilitate the early diagnosis of preclinical atherosclerosis and allow an objective measure of the vascular effects of therapeutic interventions aimed at modifying cardiovascular risk factors.

Prediction of coronary atherosclerosis in young patients with coronary artery disease using a non-invasive biomarker

Aim . To develop a combined biomarker for non-invasive diagnostics of the severity of coronary artery (CA) atherosclerosis in patients with coronary artery disease (CAD) and in those without clinical manifestations of atherosclerosis under 50 years of age using structural and functional parameters of large arteries and the lipid profile. Material and methods . A total of 92 patients with CAD and 28 healthy ones were included. Depending on the results of coronary angiography, patients with CAD were divided into 3 groups: without hemodynamically significant stenosis (HSS) (HSS 1&lt;50% , n=30), with HSS of one CA (HSS 1&gt;50% , n=37), with HSS of 2 and more CA (HSS 2&gt;50% , n=25). The subjects underwent a biochemical blood test, carotid duplex ultrasound, volumetric sphygmography. Results . In individuals with HSS1&lt;50%, lipid metabolism disorders were diagnosed in 63,3% (n=19), in HSS 1&gt;50% group — 78,4% (n=29), in HSS2&gt;50% group — 92% of cases (n=23) (p 1-3 &lt;0,05). Carotid intima-media thickness exceeding the threshold level was found in 40% of patients with HSS 1&lt;50% , in 51% of patients with HSS 1&gt;50% and 64% of patients with HSS 2&gt;50% (p 1-3 &lt;0,05). According to the results of volumetric sphygmography, the severity of CA atherosclerosis was associated with a higher pulse wave velocity and L-/CAVI 1 . At the next stage, a complex parameter for predicting coronary atherosclerosis (CA biomarker) was developed, including sex, structural and functional indicators of the arteries (intima-media thickness, в-stiffness index, L-/CAVI 1 ) and biochemical parameters (total cholesterol, triglycerides, low density lipoproteins). In healthy people, the level of CA biomarker was 2,7 (95% CI, 2,3-3,9); in patients with CAD with any degree of CA lesion — 6,4 (95% CI, 5,2-9,6). The CA biomarker threshold of 5 points with a sensitivity of 87,5% and a specificity of 90,5% was determined as the optimal cut-off point; area under the curve — 0,965 (95% CI, 0,943-0,987) (p&lt;0,0001). Conclusion . In patients with CAD, the presence and degree of coronary atherosclerosis are associated with the deterioration of most structural and functional artery parameters. The developed complex CA biomarker is of interest for non-in-vasive screening of preclinical CA atherosclerosis in patients with a low relative risk.

Omentin-1 and vaspin serum levels in patients with pre-clinical carotid atherosclerosis and the effect of statin therapy on them

BackgroundOmentin-1 and vaspin are novel adipokines, and their association with atherosclerosis is still under investigation. The present study aimed to assess the relationship of those adipokines with preclinical, non-significant carotid atherosclerosis and the impact of statin therapy on their levels, suggesting a link between adiposity and atherosclerosis. MethodsEighty-four statin-free subjects with non-significant, preclinical carotid atherosclerosis and elevated LDL- cholesterol levels (>130 mg/dl) were recruited to receive atorvastatin (from 10 to 80 mg per day) (atorvastatin group - AG group). Forty-six age- and gender-matched healthy individuals, without any chronic disease served as controls (control group – CG). Clinical parameters, metabolic profile, serum omentin-1, vaspin concentrations and ultrasound measurements of carotid thickening were obtained at the beginning and after 12 months. ResultsAt baseline, AG showed lower omentin-1 and vaspin serum levels than CG (p ≤ 0.001). Along the entire study population at baseline, omentin-1 levels were independently related to LDL-cholesterol, while vaspin levels were independently associated with hsCRP and the presence of carotid atherosclerosis (p < 0.05). Within AG, 12-months atorvastatin treatment significantly increased omentin-1 (from 202.79 ± 91.41 ng/ml to 262.56 ± 101 ng/ml, p < 0.001) and vaspin concentrations (from 1.29 ± 0.51 ng/ml to 1.70 ± 0.5 ng/ml, p = 0.002). In standard multiple regression analysis, the presence of carotid atherosclerosis related to baseline vaspin levels (β = −0.232, p < 0.001), while the atorvastatin-induced increase of vaspin was independently associated with hsCRP reduction (β = −0.198, p = 0.045). ConclusionLow omentin-1 and vaspin serum levels associated with preclinical, non-significant carotid atherosclerosis. Notably, atorvastatin administration significantly increased both adipokines, but the underlying mechanisms and the clinical impact of those changes requires further investigation.

Chronic non-viral liver pathology in military personnel exposed to military-professional factors

Abstract. The prevalence and structure of chronic non-viral liver disease of military personnel whose service is associated with the influence of various military-professional factors are estimated. It is established that the frequency of chronic diffuse liver diseases of viral etiology in a group of servicemen radio-technical troops was 77,3%, from persons engaged in diving and altitude descents 65,9%, pilots of the aerospace defence forces of Russia 62,8%, in persons without exposure to military occupational factors is 69,5%. The largest number of persons suffering from chronic non-viral liver disease in the group of military radio-technical troops, probably related to low levels of physical activity and higher values of body mass index and waist circumference, but also the influence of microwave radiation, can enhance the damaging effects of lipid peroxidation. The lowest prevalence of non-viral chronic diffuse liver diseases among pilots and aquanauts is probably related to the maximum health requirements imposed on military personnel of these categories. It was found that the level of alcohol consumption and the nature of nutrition in the study groups did not significantly differ. The highest values of body mass index and waist circumference in combination with the lowest level of physical activity were observed in the group of military personnel of the radio engineering troops, which is probably due to the nature of daily military service, which is mainly sedentary. Among the metabolic changes of blood serum, increased total cholesterol levels in groups of divers, pilots and military Radio-technical troops compared with a control. In addition, the level of glucose in Aquanauts, as well as triglycerides in soldiers of the radio engineering troops was higher than in the control group. Ultrasound examination in all groups related to the impact of military occupational factors, recorded an increase in the thickness of the left lobe of the liver, and oblique vertical size and thickness of the right lobe in the group of soldiers of the radio-technical troops compared with a control. In addition, the values of the thickness of the intima-media complex as a marker of preclinical atherosclerosis associated with non-alcoholic and alcoholic-metabolic fatty liver diseases in this category of individuals significantly exceed them in the other groups. The maximum level of liver damage in the group of military personnel of radio engineering troops is confirmed by the highest values of the controlled parameter of attenuation of ultrasound, reflecting the degree of liver steatosis.

Assessment of Microvessel Permeability in Murine Atherosclerotic Vein Grafts Using Two-Photon Intravital Microscopy.

Plaque angiogenesis and plaque hemorrhage are major players in the destabilization and rupture of atherosclerotic lesions. As these are dynamic processes, imaging of plaque angiogenesis, especially the integrity or leakiness of angiogenic vessels, can be an extremely useful tool in the studies on atherosclerosis pathophysiology. Visualizing plaque microvessels in 3D would enable us to study the architecture and permeability of adventitial and intimal plaque microvessels in advanced atherosclerotic lesions. We hypothesized that a comparison of the vascular permeability between healthy continuous and fenestrated as well as diseased leaky microvessels, would allow us to evaluate plaque microvessel leakiness. We developed and validated a two photon intravital microscopy (2P-IVM) method to assess the leakiness of plaque microvessels in murine atherosclerosis-prone ApoE3*Leiden vein grafts based on the quantification of fluorescent-dextrans extravasation in real-time. We describe a novel 2P-IVM set up to study vessels in the neck region of living mice. We show that microvessels in vein graft lesions are in their pathological state more permeable in comparison with healthy continuous and fenestrated microvessels. This 2P-IVM method is a promising approach to assess plaque angiogenesis and leakiness. Moreover, this method is an important advancement to validate therapeutic angiogenic interventions in preclinical atherosclerosis models.

Brief Report: Cystatin C-Based Estimation of Glomerular Filtration Rate and Association With Atherosclerosis Imaging Markers in People Living With HIV.

Reduced estimated glomerular filtration rate (eGFR) is associated with increased risk of cardiovascular disease among people living with HIV (PLWH). It is unclear whether eGFR equations incorporating cystatin C (CysC) measurements are more predictive of preclinical cardiovascular disease than those using only creatinine (Cr). The study aimed to determine which of the 3 Chronic Kidney Disease Epidemiology (CKD-EPI) eGFR equations is most associated with carotid intima media thickness (CIMT) and coronary artery calcium (CAC) score. This cross-sectional analysis of pooled data from 3 large cohorts compared the associations between the 3 CKD-EPI eGFR equations (Cr, CysC, and Cr-CysC) with CIMT and CAC score using multivariable regression analysis. eGFR and CIMT were analyzed as continuous variables. CAC scores were analyzed as a binary variable (detectable calcification versus nondetectable) and as a log10 Agatston score in those with detectable CAC. Thousand four hundred eighty-seven participants were included, and of these 910 (562 HIV+ and 348 HIV-) had CIMT measurements and 366 (296 HIV+ and 70 HIV-) had CAC measurements available. In HIV- participants, GFR estimated by any CKD-EPI equation did not significantly correlate with CIMT or CAC scores. When PLWH were analyzed separately including HIV-specific factors, only GFR estimated using Cr-Cys C correlated with CIMT [β= -0.90, 95% CI: (-1.67 to -0.13) μm; P = 0.023]. Similarly, eGFR correlated with Agatston scores only when using cystatin C-based eGFR [β= -8.63, 95% CI: (-16.49 to -0.77) HU; P = 0.034]. Associations between other eGFR formulas and CAC did not reach statistical significance. In PLWH, preclinical atherosclerosis may be more closely correlated with eGFR using formulae that incorporate CysC measurements than Cr alone.

Nuclear magnetic resonance-based metabolomic analysis in the assessment of preclinical atherosclerosis in type 1 diabetes and preeclampsia

AimsEvaluate the role of plasma metabolomics in atherosclerosis according to the presence of type 1 diabetes (T1D) or previous preeclampsia. MethodsWe recruited 105 women without cardiovascular disease and last pregnancy ≥5 years previously, divided according to the presence of T1D or previous preeclampsia. Preclinical atherosclerosis was defined as the presence of carotid plaque (intima-media thickness ≥1.5 mm) assessed by ultrasonography. Metabolomics were evaluated by nuclear magnetic resonance (NMR). Bivariate and multivariate-adjusted differences in NMR-metabolomics were evaluated. ResultsThe participants were 44.9 ± 8.1 years-old; 20% harbored plaques. There were significant differences in lipidic-, energetic- and nitrogen-related metabolites according to the presence of T1D/preeclampsia (p < 0.05). In multivariate-adjusted models (by age, statins, blood pressure and T1D/preeclampsia), only lipidomic-related metabolites were associated with atherosclerosis in the whole sample. However, stronger associations were observed in women with previous preeclampsia (vs. without; per 0.5 mmol/L increments); phosphatidylcholine, OR 4.08 (1.32–27.22); free cholesterol, 5.18 (1.22–21.97); saturated fatty acids, OR 2.99 (1.37–6.48); w-7, OR 2.29 (1.15–4.56); and w-9 fatty acids, OR 1.49 (1.00–2.23). ConclusionsNMR-metabolomics showed a differential pattern according to the presence of T1D/preeclampsia in relation to preclinical atherosclerosis. Since most of these metabolites mirror lifestyle factors, they could help tailor dietetic advice in high-risk women.

Anti-atherogenic effect of Nepitrin-7-O-glucoside: A flavonoid isolated from Nepeta hindostana via acting on PPAR – α receptor

Atherogenic dyslipidemia is a condition and responsible for the induction of major cardiovascular diseases. Traditionally, Nepeta hindostana a medicinal plant commonly used as cardioprotective in Indo-Pak regions has gained importance because of its therapeutic active flavonoid Nepitrin-7-O-glucoside. Flavonoid-glycosides are steroids having the ability to exert specific, decisive action on the cardiac muscle. In the present research work flavonoid, Nepitrin-7-O-glucoside was isolated from methanolic extract via chromatographic techniques. The structure was elucidated and confirmed by different spectral techniques like Mass and 1H NMR spectrometry. Various preclinical atherosclerosis parameters such as lipid levels, SGOT/SGPT, body weight, histology of aorta and heart were estimated and beneficial effect of Nepitrin in high-fat diet (HFD) induced atherosclerosis for six weeks were observed. Outcomes of the preclinical results showed and proved that Nepitrin significantly improved dyslipidemia at an effective dose of 50 mg/kg as compared with HFD control and Simvastatin. Molecular docking showed significant binding affinity towards the target PPAR-α receptor (PDB: 2P54). Further the docked ligands with PDB: 2P54 were exposed to molecular dynamics studies to confirm the dynamic behaviour of PPAR-α receptor. Outcomes of the results of the in-vivo study and molecular dynamics study were in correlation with each-others. Further, it can be concluded that Nepitrin has a potent antiatherogenic agent and act by reducing the lipid levels via acting on PPAR-α receptor and regenerating the damaged cells.

The inverse association between lipoprotein(a) levels and metabolic syndorome and its components on coronary artery disease patients

Abstract Purpose Neele DM (Diabetologia 1999) showed that insulin suppressed apolipoprotein(a) synthesis by primary cultures of cynomolgus monkey hepatocytes. Therefore, there is a possibility that inverse association exists between lipoprotein(a) [Lp(a)] and metabolic syndorome (Mets) with insulin resistance/hyperinsulinemia for coronary atherosclerosis. Sung KC (Nutr Metab Cardiovasc Dis 2013) described the inverse association between Lp(a) levels and Mets and its components on an asian occupational cohort. And high levels of Lp(a) were associated with preclinical atherosclerosis, as evaluated by coronary calcium score with cardiac computed tomography. There is no similar examination on coronary artery disease (CAD) patients. The purpose is to examine similar considerations on CAD patients. Method 610 subjects with angiographically demonstrated CAD were enrolled. The patients who receiving medication for dyslipidemia and Insulin administration were excluded. The blood samples for laboratory tests were collected after an over night fast. Subjects were divided into four groups according to quartiles of Lp(a) levels (mg/dL). Ranges of quartile groups of Lp(a) were Q1: &amp;lt;9.0, Q2: 9.0–&amp;lt;16.0, Q3: 16.0–&amp;lt;30.0, Q4: ≥30.0. Results The inverse association Lp(a) levels and Mets and its component. The comparison of Q1 (bottom quartile) versus Q4 (top quartile) was shown below; the comorbidity rate of Mets 19.5% versus 8.0% (p&amp;lt;0.01), BMI (kg/m2) 23.5 versus 22.7 (p&amp;lt;0.05), trigyceride (mg/dL) 144.0 versus 107.5 (p&amp;lt;0.0001), HDL cholesterol (mg/dL) 46.8 versus 50.7 (p&amp;lt;0.05), the comorbidity rate of hypertension 60.4% versus 50.7% (p=0.084), glucose (mg/dL) 107.1 versus 100.6 (p&amp;lt;0.05), insulin (μU/mL) 8.49 versus 5.85 (p&amp;lt;0.0001), HOMA-R 2.26 versus 1.44 (p&amp;lt;0.0001). The mean number of diseased coronary vessel was higher in the Q4 group (2.07) than in the Q1 group (1.87) (p&amp;lt;0.05). Conclusion There was the inverse association between Lp(a) levels and Mets and its components on CAD patients. The robust association was found between Lp(a) levels and severity of coronary atherosclerosis despite this inverse correlation. Funding Acknowledgement Type of funding source: None

Impact of sarcopenia on glycemic control and atherosclerosis in Japanese patients with type 2 diabetes: Cross-sectional study using outpatient clinical data.

This study examined the association among sarcopenia and various surrogate markers of atherosclerosis in Japanese patients with type 2 diabetes (T2D). Patients with T2D who visited the outpatient clinic comprised the study's participants. Handgrip strength (Grip), usual gait speed (GS) and skeletal muscle index, in addition to glycated hemoglobin, ankle-brachial index (ABI) and intima-media thickening (IMT), were measured in 1030 patients for the diagnosis of sarcopenia. From these results were obtained three categorical data (without sarcopenia [NS], sarcopenia with two factors [Sw2], sarcopenia with three factors [Sw3]), and continuous data for atherosclerosis. Glycated hemoglobin was significantly high among patients in the Sw3 category, as well as among all patients with sarcopenia, compared with those in the NS group, after adjustment was made for age, gender, duration of diabetes, and medications for hypertension and dyslipidemia. ABI was significantly low among the Sw2 and Sw3 patients, as well as among all patients with sarcopenia, but mean and maximum IMT were not when compared with the NS category of patients after the adjustment described above. However, skeletal muscle index, Grip and GS were positively associated with ABI after the adjustment. Grip and GS were negatively associated with maximum IMT after the adjustment. These results imply that measurements to diagnose sarcopenia could play an important role for early detection of preclinical atherosclerosis, specifically peripheral artery disease, among Japanese patients with T2D. Geriatr Gerontol Int 2020; 20: 1196-1201.

Premature Vascular Aging with Features of Plaque Vulnerability in an Atheroprone Mouse Model of Hutchinson-Gilford Progeria Syndrome with Ldlr Deficiency.

Hutchinson–Gilford progeria syndrome (HGPS) is among the most devastating of the laminopathies, rare genetic diseases caused by mutations in genes encoding nuclear lamina proteins. HGPS patients age prematurely and die in adolescence, typically of atherosclerosis-associated complications. The mechanisms of HGPS-related atherosclerosis are not fully understood due to the scarcity of patient-derived samples and the availability of only one atheroprone mouse model of the disease. Here, we generated a new atherosusceptible model of HGPS by crossing progeroid LmnaG609G/G609G mice, which carry a disease-causing mutation in the Lmna gene, with Ldlr−/− mice, a commonly used preclinical atherosclerosis model. Ldlr−/−LmnaG609G/G609G mice aged prematurely and had reduced body weight and survival. Compared with control mice, Ldlr−/−LmnaG609G/G609G mouse aortas showed a higher atherosclerosis burden and structural abnormalities typical of HGPS patients, including vascular smooth muscle cell depletion in the media, adventitial thickening, and elastin structure alterations. Atheromas of Ldlr−/−LmnaG609G/G609G mice had features of unstable plaques, including the presence of erythrocytes and iron deposits and reduced smooth muscle cell and collagen content. Ldlr−/−LmnaG609G/G609G mice faithfully recapitulate vascular features found in patients and thus provide a new tool for studying the mechanisms of HGPS-related atherosclerosis and for testing therapies.

Preclinical atherosclerosis in adolescents with psychotic or bipolar disorders investigated with carotid high-frequency ultrasound.

ObjectiveEarly‐onset psychosis (EOP) and bipolar disorder (EOBP) (at <18 years of age), are associated with an increased future risk of cardiovascular disease (CVD) and premature death. Yet it is unknown whether the arteries show visible signs of atherosclerosis in EOP and EOBP. This study investigated whether having EOP or EOBP was associated with detectable signs of preclinical atherosclerosis.MethodBy using 22 MHz high‐frequency ultrasound, different layers of the arterial wall of the left common carotid artery (LCCA) were assessed in 77 individuals with EOP (n = 25), EOBP (n = 22), and in age‐matched healthy controls (n = 30). Conventional CVD confounders were included in the analyses.ResultsAdolescents with EOP and EOBP, compared to controls, had a significantly thicker LCCA intima thickness (0.132 vs. 0.095 mm, p < .001) and intima/media ratio (0.24 vs. 0.17 p < .001). There was a nonsignificant intima difference between EOP and EOBP. Conventional CVD risk factors did not explain the association between EOP/EOBP and intima thickness. In the group of EOP/EOBP, there was a significant correlation between the dose of current antipsychotic medication and intima thickness; however, the correlation was attenuated to a nonsignificant level when adjusted for global function.ConclusionsAdolescents with EOP or EOBP had an increased LCCA intima thickness, interpreted as a sign of preclinical atherosclerosis. Global function of the disorders was the strongest determinant of intima thickness. The findings, if replicated, might have implications for long‐term treatment of EOP and EOBP in order to reduce a future risk of CVD.

¿Son la velocidad de la onda del pulso y la rigidez arterial marcadores para evaluar la ateroesclerosis preclínica en pacientes con hipertensión resistente?

Introducción: La velocidad de la onda de pulso y la rigidez arterial se considera estándar de oro para evaluar daño a órganos diana que haya surgido subclinicamente. La disfunción endotelial es directamente proporcional al desarrollo de la aterosclerosis preclínica. Estos marcadores sustitutos mencionados anteriormente son relativamente más altos en pacientes con hipertensión no controlada o resistente. El objetivo fue evaluar si la rigidez arterial y la velocidad de la onda del pulso también son marcadores sustitutos del desarrollo de la aterosclerosis preclínica en pacientes con hipertensión resistente.&#x0D; Métodos y materiales: Se incluyeron en el estudio un total de 160 pacientes con hipertensión resistente de Croacia e India. La presión arterial central y otros valores clínicos se evaluaron utilizando un dispositivo no invasivo.&#x0D; Resultados: Las estadísticas del grupo se hicieron con perspectiva de género, los valores de la presión arterial sistólica (PA-S), la presión arterial diastólica (PA-D), la presión arterial media (PAM), la presión central sistólica (PC-S) ,la presión central diastólica ( PC-D), la presión de pulso central (cPP) y la velocidad de la onda de pulso (VOP) han sido descritas. Los valores de PA-S en hombres / mujeres fueron 147.26 ±22.12/ 144.10 ± 21.29; los valores de PA-D en hombres/mujeres fueron 94.98 ± 13.36 / 88.57 ± 12.25 respectivamente.&#x0D; Conclusiones: con los resultados obtenidos se puede concluir que la rigidez arterial es un marcador independiente que es directamente proporcional a la disfunción endotelial y al desarrollo de aterosclerosis preclínica.

The level of N-terminal pro-brain natriuretic peptide depending on vascular wall condition and bone mass in postmenopausal women

Aim. To assess the relationship of serum N-terminal pro-brain natriuretic peptide (NT-proBNP) levels with vascular wall condition and bone mineral density (BMD) in postmenopausal women.Material and methods. The cross-sectional study included 107 outpatients aged 45-82 years who signed informed consent. The inclusion criterion was a menopause during ≥1 year. The level of serum NT-proBNP was determined by electrochemiluminescence. BMD was assessed by dual energy x-ray absorptiometry. Intima-media thickness (IMT), the presence and number of atherosclerotic plaques were evaluated using carotid duplex scanning. Pulse wave velocity (PWV) and augmentation index were estimated by applanation tonometry. To assess 10-year cardiovascular risk, the SCORE high-risk charts were used. Using the Russian model of FRAX® score, 10-year fracture risk was assessed.Results. NT-proBNP level in women with postmenopause &gt;10 years was significantly higher than in those with postmenopause &lt;5 years — 98,7 vs 56,3 pg/ml (p&lt;0,001), but there was no independent relationship according to the regression analysis. According to multivariate regression analysis adjusted for age, menopause duration, systolic blood pressure, hypercholesterolemia, smoking, elevated C-reactive protein and interleukin-6 levels, there were independent relationship between the following parameters: NT-proBNP and IMT (β=2,38, p&lt;0,03), NT-proBNP and PWV (β=1,76, p&lt;0,001). NT-proBNP level in patients with osteoporosis was significantly higher than in women with normal bone mass (p&lt;0,01). A negative correlation was observed between NT-proBNP and BMD of the proximal femur (r=-0,26, p&lt;0,05), while the relationship between BMD of the lumbar vertebrae (L1-L4) and NT-proBNP did not reach significance. In multivariate regression analysis, this relationship has not been confirmed. A positive correlation was obtained between cardiovascular risk (SCORE) and NT-proBNP levels (r=0,28, p&lt;0,001). NT-proBNP levels did not differ in women with a high and low 10-year risk of both major osteoporotic fractures and femoral fractures.Conclusion. An independent relationship of NT-proBNP with vascular stiffness and preclinical atherosclerosis was demonstrated: IMT and PWV. This indicates the participation of NT-proBNP in the atherosclerosis development. The association of elevated NT-proBNP levels with osteoporosis is significant, but not independent, and is apparently related to other factors.