Marker Of Subclinical Atherosclerosis Research Articles

Serum metabolomic profiles associated with subclinical and clinical cardiovascular phenotypes in people with type 2 diabetes

BackgroundAtherosclerotic cardiovascular diseases (CVD) is the leading cause of death in diabetes, but the full range of biomarkers reflecting atherosclerotic burden and CVD risk in people with diabetes is unknown. Metabolomics may help identify novel biomarkers potentially involved in development of atherosclerosis. We investigated the serum metabolomic profile of subclinical atherosclerosis, measured using ankle brachial index (ABI), in people with type 2 diabetes, compared with the profile for symptomatic CVD in the same population.MethodsThe Edinburgh Type 2 Diabetes Study is a cohort of 1,066 individuals with type 2 diabetes. ABI was measured at baseline, years 4 and 10, with cardiovascular events assessed at baseline and during 10 years of follow-up. A panel of 228 metabolites was measured at baseline using nuclear magnetic resonance spectrometry, and their association with both ABI and prevalent CVD was explored using univariate regression models and least absolute shrinkage and selection operator (LASSO). Metabolites associated with baseline ABI were further explored for association with follow-up ABI and incident CVD.ResultsMean (standard deviation, SD) ABI at baseline was 0.97 (0.18, N = 1025), and prevalence of CVD was 35.0%. During 10-year follow-up, mean (SD) change in ABI was + 0.006 (0.178, n = 436), and 257 CVD events occurred. Lactate, glycerol, creatinine and glycoprotein acetyls levels were associated with baseline ABI in both univariate regression [βs (95% confidence interval, CI) ranged from − 0.025 (− 0.036, − 0.015) to − 0.023 (− 0.034, − 0.013), all p < 0.0002] and LASSO analysis. The associations remained nominally significant after adjustment for major vascular risk factors. In prospective analyses, lactate was nominally associated with ABI measured at years 4 and 10 after adjustment for baseline ABI. The four ABI-associated metabolites were all positively associated with prevalent CVD [odds ratios (ORs) ranged from 1.29 (1.13, 1.47) to 1.49 (1.29, 1.74), all p < 0.0002], and they were also positively associated with incident CVD [ORs (95% CI) ranged from 1.19 (1.02, 1.39) to 1.35 (1.17, 1.56), all p < 0.05].ConclusionsSerum metabolites relating to glycolysis, fluid balance and inflammation were independently associated with both a marker of subclinical atherosclerosis and with symptomatic CVD in people with type 2 diabetes. Additional investigation is warranted to determine their roles as possible etiological and/or predictive biomarkers for atherosclerotic CVD.

Markers of Subclinical Atherosclerosis in Severe Obesity and One Year after Bariatric Surgery.

Background: Aortic valve sclerosis (AVS), mitral valve sclerosis (MVS), remodeling of major arteries, and increased pericardial fat are associated with subclinical atherosclerosis. We assessed these markers of atherosclerosis in severely obese patients before and 1 year after bariatric surgery. Methods: Eighty-seven severely obese patients (43 ± 10 years, preoperative body mass index [BMI] 41.8 ± 5 kg/m2) underwent echocardiography before and 1 year after Roux-en-Y bypass surgery in the FatWest (Bariatric Surgery on the West Coast of Norway) study. We measured the end-diastolic aortic wall thickness (AWT), pericardial fat thickness at the right ventricular free wall, and AVS/MVS based on combined aortic leaflet thickness and hyperechoic valve lesions. Results: Postoperatively, patients experienced a reduction of 12.9 ± 3.9 kg/m2 in BMI, 0.5 ± 1.9 mm in AWT, 2.6 ± 2.3 mm in pericardial fat, and 45%/53% in AVS/MVS (p < 0.05). In multivariate regression analyses with adjustment for clinical and hemodynamic variables, less pericardial fat reduction was associated with male sex and higher 1-year blood pressure and BMI, and less AWT-reduction with higher age and 1-year BMI (p < 0.05). Persistent AVS and MVS were related to higher 1-year BMI and more advanced valve sclerosis preoperatively (p < 0.05). Conclusions: Markers of subclinical atherosclerosis decreases significantly 1 year after bariatric surgery, particularly in younger patients that achieve a BMI < 28 kg/m2.

Effect of metformin as an add-on therapy on neuregulin-4 levels and vascular-related complications in adolescents with type 1 diabetes: A randomized controlled trial

BackgroundInflammation is closely associated with atherosclerosis and plays a crucial role in the development of cardiovascular disease. Metformin sensitizes body cells to insulin, which may cause a reduction of atherogenic lipid fractions. Low neuregulin-4 (Nrg-4) levels, an adipokine, are linked to obesity, insulin resistance, impaired glucose tolerance and type 2 diabetes. ObjectivesWe assessed the effect of oral supplementation with metformin on glycemic control, neuregulin-4 levels and carotid intima media thickness (CIMT) as a marker for subclinical atherosclerosis in adolescents with type 1 diabetes mellitus (T1DM) and microvascular complications. MethodsThis randomized placebo-controlled trial included 80 type 1 diabetic patients with microvascular complications who were randomly divided to receive either 24 weeks of metformin 500 mg/day or matching placebo. Fasting blood glucose (FBG), HbA1c, C-reactive protein (CRP), urinary albumin creatinine ratio (UACR), lipid profile, Nrg-4 and CIMT were assessed at baseline and study end. ResultsBoth groups were well-matched as regards baseline clinical and laboratory data (p greater than 0.05). After 24-weeks, metformin therapy for the intervention group resulted in a significant decrease of HbA1c, CRP, UACR, total cholesterol and CIMT while Nrg-4 levels were increased compared with baseline levels (p < 0.001) and with placebo group(p < 0.001). Baseline Nrg-4 levels were negatively correlated to FBG, HbA1c, total cholesterol, CRP and CIMT. Metformin was well-tolerated. ConclusionsOral metformin supplementation once daily for 24 weeks as an adjuvant therapy to intensive insulin in pediatric T1DM was safe and effective in improving glycemic control, dyslipidemia and Nrg-4 levels; hence, it decreased inflammation, microvascular complications and subclinical atherosclerosis.

GDF-15 is associated with atherosclerosis in adults with transfusion-dependent beta-thalassemia.

Objectives: To study serum growth differentiation factor‐15 (GDF‐15) serum level in β‐thalassemia patients and its relation to carotid intima‐media thickness.Background: Thalassemia is a common genetic disease resulting in decreased beta‐chains, leading to manifested anemia. It may be subsequently complicated by iron overload, which induces numerous morbidities and even death. Growth differentiation factor‐15 (GDF‐15) is a strong and independent predictor of mortality and disease progression in patients with atherosclerosis alongside with carotid‐intimal media thickness (CIMT).Patients and methods: This monocentric case‐control study was done on 90 subjects in the period from January 2020 to March 2021. Sixty transfusion‐dependent beta‐thalassemia (TDβT) cases (≥18 years) were selected from the thalassemia clinic of Hematology division at Menoufia University hospitals. We included also 30 sex and age matched healthy as the controls. Routine investigations were done beside. Serum GDF‐15 was measured by ELISA. CIMT was measured by Doppler Ultrasonography.Results: CIMT on both sides was statistically significant higher in cases (median of 0.08 cm) than in the controls (median of 0.04). GDF‐15 was also significantly higher in cases (median of 1839.89 pg/dl) than in controls (median of 256.14 pg/dl). So, we found that GDF‐15 is a predictor of and associated with atherosclerosis in thalassemic adults (OR = 39.198, p value 0.008, 95% CI: 2.576–596.5).Conclusion: GDF‐ 15 is increased in TDβT. CIMT (as a marker of subclinical atherosclerosis) is increased in these patients alongside with GDF‐15, is a predictor, and associated with atherosclerosis in thalassemic adults.

Comprehensive Meta-Analysis of Functional and Structural Markers of Subclinical Atherosclerosis in Women with Polycystic Ovary Syndrome.

The relationship between polycystic ovary syndrome (PCOS) and subclinical atherosclerosis remains unclear. We performed a comprehensive systematic review and meta-analysis to evaluate the effect of PCOS on functional and structural markers of subclinical atherosclerosis as measured by carotid intima-media thickness (cIMT), flow-mediated vasodilation (FMD), nitroglycerin-mediated vasodilation (NMD), pulse wave velocity (PWV), and coronary artery calcium (CAC). Standard mean differences (SMDs) or odds ratios (ORs) and corresponding 95% confidence intervals (CIs) were calculated. Ninety-six articles involving 5550 PCOS patients and 5974 controls were included. Compared with controls, PCOS patients showed significantly thicker cIMT (SMD (95% CI) = .587 (.398, .776), P < .001), lower FMD (SMD (95% CI) = -.649 (-.946, -.353), P < .001) and NMD (SMD (95% CI) = -.502 (-.686, -.317), P < .001), as well as higher PWV (SMD (95% CI) = .382 (.019, .746), P = .039), and increased CAC incidence (OR (95% CI) = 2.204 (1.687, 2.879), P < .001). When analyzing subgroups by age and body mass index (BMI), results were still significant (P < .05) except for PWV in the BMI subgroup. There was no significant result on sensitivity analysis, and Begg' test or Egger's test. PCOS contributes to subclinical atherosclerosis, resulting in functional and structural changes in cIMT, FMD and NMD, PWV, and CAC incidence.

Soluble Fms-like tyrosine kinase-1 (sFlt-1) is associated with subclinical and clinical atherosclerotic cardiovascular disease: The Dallas Heart Study

Background and aimsSoluble Fms-like tyrosine kinase-1 (sFlt-1) plays a role in angiogenesis, atherogenesis, and preeclampsia. The relationship of sFlt-1 with markers of subclinical atherosclerosis and future atherosclerotic cardiovascular disease (ASCVD) events in a generally healthy population is unknown. MethodsParticipants in the Dallas Heart Study with sFlt-1 measured were included (n = 3292). Abdominal aortic atherosclerosis was measured by MRI and coronary artery calcium (CAC) by CT. The cohort was also followed for subsequent ASCVD events (CV death, MI, stroke, unstable angina, revascularization). Multivariable linear and logistic regression analyses and Cox regression analyses were performed adjusting for demographics and traditional cardiac risk factors. ResultssFlt-1 levels were higher in older individuals, males, and African Americans, and tracked with most traditional risk factors. sFlt-1 was significantly associated with higher prevalence of aortic plaque [OR 1.33 (95% CI 1.02–1.73)], greater abdominal aortic wall thickness (p<0.01) and aortic plaque area (p<0.02) but no difference in coronary artery calcification. There were 322 ASCVD events over 12 years of follow-up. Higher sFlt-1 levels associated with increased ASCVD events in unadjusted (16.1% vs. 8.9%, p<0.001, quartile 4 vs. quartile 1) and adjusted analyses (HR 1.58 [1.14–2.18], p<0.01, quartile 4 vs. quartile 1). Findings were unchanged when analyzing sFlt-1 as a continuous variable or when excluding those with a history of ASCVD. ConclusionsIn a population-based cohort, sFlt-1 is associated with measures of subclinical aortic atherosclerosis and clinical ASCVD events. Future studies are warranted on the therapeutic potential of targeting sFlt-1 for atherosclerotic disease.

Abstract P152: The Association Between Menopause Age And Carotid Plaque In The Multi-Ethnic Study Of Atherosclerosis (MESA)

Background: The menopause transition is associated with an accelerated rise in cardiovascular disease (CVD) risk among women. Early-onset menopause is associated with incident CVD events. Detection of subclinical atherosclerosis may be an opportunity to institute preventive efforts before the onset of clinical CVD. We assessed whether menopause age was associated with carotid plaque, a marker of subclinical atherosclerosis, in a multiethnic cohort. Methods: We studied post-menopausal women in MESA free of CVD who had age of menopause onset ascertained by questionnaire and carotid plaque measured by B-mode ultrasound at baseline. Menopause age was categorized as &lt;45, 45-&lt;50, 50-&lt;55 (ref) and ≥55 yrs. Multivariable logistic and linear regression models were performed to evaluate the association of menopause age with carotid plaque presence (yes/no) and extent (carotid plaque score (CPS)), respectively. Results: Of the 2,297 women included, 38% were White, 28% Black, 12% Chinese, and 22% Hispanic with a mean age (SD) of 64 (9) yrs. The distribution of menopause age was 22.7% at age &lt;45, 28.8% at age 45-49, 36.1% at age 50-54, 12.5% at age ≥55. Overall, carotid plaque was present in 52%. The association of carotid plaque presence/absence and CPS are shown in the Table . There was no statistically significant association of menopause age with carotid plaque presence. Compared to women with menopause age 50-55, menopause before age 45 was significantly associated with a 9% greater CPS [percent difference 9 (95% CI 2, 17) after adjusting for demographics. This was attenuated and no longer statistically significant after further adjustment for CVD risk factors. Conclusion: In a multiethnic cohort of women, a younger age of onset of menopause was associated with a greater extent of carotid plaque, which appears to be mediated through traditional CVD risk factors. Further studies are needed to evaluate the association between the age of onset of menopause and atherosclerotic risk.

Abstract MP68: Association Of Multiparity With Carotid Artery Plaque Prevalence: The Multi-Ethnic Study Of Atherosclerosis (MESA)

Background: Multiparity may be associated with an increased risk of cardiovascular disease (CVD); however, responsible mechanisms are incompletely understood. Carotid artery plaque is a marker of subclinical atherosclerosis and an indicator of CVD risk. We hypothesized that multiparity would be independently associated with greater atherosclerosis, as measured by carotid plaque. Methods: We included women in MESA free of CVD who had data on parity ascertained by questionnaire and carotid plaque measured by B-mode ultrasound at baseline. Parity was categorized as nulliparity (ref), 1-2, 3-4 and ≥5 live births. Multivariable logistic and linear regression were performed to evaluate the association of parity categories with carotid plaque presence (yes/no) and extent [carotid plaque score (CPS)], respectively. Results: Of 2789 women included, 38% were White, 29% Black, 12% Chinese, and 22% Hispanic with a mean (SD) age of 62±10 yrs. Carotid plaque prevalence increased with greater parity ( Figure) . Compared to nulliparity, a history of 1-2 live births, 3-4 live births, and grand multiparity (≥5 live births) were significantly associated with carotid plaque presence after adjustment for demographics ( Table, Model 1 ) . Grand multiparity remained significantly associated with carotid plaque presence after full covariate adjustment [OR 1.42 (95% 1.01-2.01), Model 2]. In addition, a history of 1-2 live births and grand multiparity was associated with a greater CPS compared to nulliparity after adjustment for demographics (Model 1). The association of parity with CPS was attenuated and no longer significantly associated with CPS after further adjustment for lifestyle and CVD risk factors (Model 2). Conclusion: In a multiethnic cohort of US women, grand multiparity was independently associated with carotid plaque presence. Further studies are needed to understand the increased risk and prognostic significance of subclinical atherosclerosis among parous women.

Aortic intima media thickness in children and adolescents with type 1 diabetes: A systematic review.

AimsGreater aortic intima media thickness (aIMT), a marker of subclinical atherosclerosis, can identify individuals at risk of CVD. This systematic review with meta‐analysis compared aIMT in youth with type 1 diabetes and healthy controls.MethodsA systematic search of published literature (to July 2021) was undertaken using electronic databases MEDLINE, EMBASE, Scopus, CINAHL and AMED. Eligible studies reported aIMT in participants aged <20 years with type 1 diabetes and healthy controls. Meta‐analysis was used to combine outcome data, presented as forest plots. Moderator analysis and metaregression were conducted to identify study and participant characteristics associated with aIMT. Publication bias was assessed by funnel plot inspection.ResultsMeta‐analysis of nine studies (n = 1030 with type 1 diabetes and n = 498 healthy control participants) indicated, with high heterogeneity (I2 98%), that youth with type 1 diabetes have higher aIMT compared with healthy controls (mean difference [95% CIs]: 0.11 [0.04, 0.18] mm, P = 0.003). Factors associated with greater aIMT in type 1 diabetes compared to controls included: use of a phased array probe versus linear array probe; longer diabetes duration; higher insulin dose; higher BMI z score and waist circumference; higher LDL cholesterol; higher triglycerides; and higher diastolic blood pressure.ConclusionsType 1 diabetes in youth is associated with higher aIMT compared with healthy control individuals. Longer duration of diabetes and major CVD risk factors were also associated with higher aIMT. Together, these findings provide a strong rationale for targeting modifiable risk factors in CVD prevention. Registered in PROSPERO on 8 August 2019 (CRD42019137559).

Association of arterial stiffness with coronary artery calcium score in the general-population: the Swedish CArdioPulmonary bioImage study.

Coronary artery calcium score (CACS) is a marker of subclinical atherosclerosis. However, there is little data related to the association between arterial stiffness and CACS in the general population. The aim of this study was to explore the association between carotid femoral-pulse wave velocity (c-f PWV), a widely accepted marker of arterial stiffness, and CACS. Participants with complete measurements on c-f PWV, CACS and confounding variables from the Swedish CArdioPulmonary bioImage Study (SCAPIS) cohort were included in the final study population (n = 8725). CACS was divided into three categories (<10, >10 and ≤100, and >100) and multinomial logistic regression was performed to explore the association between these categories of CACS and quartiles of c-f PWV, and for per one standard deviation (SD) increment of c-f PWV. CACS ≤10, >10 and ≤100, and >100 were present in 69.3, 17.8 and 12.9% of the study population, respectively. The odds ratio (OR) for CACS >100 for the fourth quartile (Q4) of c-f PWV vs. Q1 (reference category) was 1.62 (95% confidence interval [CI] 1.25-2.12) after adjustments. One standard deviation increase in c-f PWV was independently associated with a higher odds of having a CACS category >100 (OR: 1.25, 95% CI 1.14-1.36) in the final multivariable model. c-f PWV is positively associated with increased risk of higher CACS, and can be valuable in identifying individuals at risk for sub-clinical atherosclerosis.

Cardiometabolic outcomes of women exposed to hyperglycaemia first detected in pregnancy at 3-6 years post-partum in an urban South African setting.

BackgroundHyperglycaemia first detected during pregnancy(HFDP) has far-reaching maternal consequences beyond the pregnancy. Our study evaluated the cardiometabolic outcomes in women with prior HFDP versus women without HFDP 3–6 years post-partum in urban South Africa.Design and methodsA prospective cohort study was performed of 103 black African women with prior HFDP and 101 without HFDP, 3–6 years post-partum at Chris Hani Baragwanath Academic Hospital, Soweto. Index pregnancy data was obtained from medical records. Post-partum, participants were re-evaluated for anthropometric measurements, body composition utilizing dual energy X-ray absorptiometry(DXA) and biochemical analysis (two-hour 75gm OGTT fasting insulin, lipids, creatinine levels and glucose levels). Cardiovascular risk was assessed by Framingham risk score(FRS). Carotid intima media thickness(cIMT) was used as a surrogate marker for subclinical atherosclerosis. Factors associated with progression to cardiometabolic outcomes were assessed using multivariable logistic and linear regression models.ResultsForty-six(45.1%) HFDP women progressed to diabetes compared to 5(4.9%) in non HFDP group(p<0.001); only 20(43.4%) were aware of their diabetic status in the whole group. The odds(OR, 95% confidence interval(CI)) of progressing to type 2 diabetes(T2DM) and metabolic syndrome(MetS) after correcting for confounders in the HFDP group was 10.5(95% CI 3.7–29.5) and 6.3(95%CI 2.2–18.1), respectively. All visceral fat indices were found to be significantly higher in the HFDP group after adjusting for baseline body mass index. Ten-year estimated cardiovascular risk(FRS) and mean cIMT was statistically higher in the HFDP group(8.46 IQR 4.9–14.4; 0.48 mm IQR 0.44–0.53 respectively) compared to the non-HFDP group(3.48 IQR 2.1–5.7; 0.46mm IQR 0.42–0.50) respectively and this remained significant for FRS but was attenuated for cIMT after correcting for confounders. HIV did not play a role in progression to any of these outcomes.ConclusionWomen with a history of HFDP have a higher risk of cardiometabolic conditions within 6 years post-partum in an urban sub-Saharan African setting.

Chronic inflammatory diseases, subclinical atherosclerosis, and cardiovascular diseases: Design, objectives, and baseline characteristics of a prospective case-cohort study ‒ ELSA-Brasil

ObjectivesThis analysis describes the protocol of a study with a case-cohort to design to prospectively evaluate the incidence of subclinical atherosclerosis and Cardiovascular Disease (CVD) in Chronic Inflammatory Disease (CID) participants compared to non-diseased ones. MethodsA high-risk group for CID was defined based on data collected in all visits on self-reported medical diagnosis, use of medicines, and levels of high-sensitivity C-Reactive Protein >10 mg/L. The comparison group is the Aleatory Cohort Sample (ACS): a group with 10% of participants selected at baseline who represent the entire cohort. In both groups, specific biomarkers for DIC, markers of subclinical atherosclerosis, and CVD morbimortality will be tested using weighted Cox. ResultsThe high-risk group (n = 2,949; aged 53.6 ± 9.2; 65.5% women) and the ACS (n=1543; 52.2±8.8; 54.1% women) were identified. Beyond being older and mostly women, participants in the high-risk group present low average income (29.1% vs. 24.8%, p < 0.0001), higher BMI (Kg/m2) (28.1 vs. 26.9, p < 0.0001), higher waist circumference (cm) (93.3 vs. 91, p < 0.0001), higher frequencies of hypertension (40.2% vs. 34.5%, p < 0.0001), diabetes (20.7% vs. 17%, p = 0.003) depression (5.8% vs. 3.9%, p = 0.007) and higher levels of GlycA a new inflammatory marker (p < 0.0001) compared to the ACS. ConclusionsThe high-risk group selected mostly women, older, lower-income/education, higher BMI, waist circumference, and of hypertension, diabetes, depression, and higher levels of GlycA when compared to the ACS. The strategy chosen to define the high-risk group seems adequate given that multiple sociodemographic and clinical characteristics are compatible with CID.

Comparison of Cardio-metabolic Profile in NAFLD Patients with and Without Advanced Fibrosis

Background: Advanced fibrosis is independently associated with cardiovascular organ damage. Metabolic syndrome (MetS) contributes to accelerated atherosclerosis in Non-alcoholic fatty liver disease(NAFLD). Carotid Intima-media thickness(CIMT) is a surrogate marker for subclinical atherosclerosis.

Fibroblast growth factor 23 and carotid intima media thickness in non-diabetic chronic kidney disease patients

ObjectivesTo clarify the relationship between fibroblast growth factor-23 (FGF23) and carotid intima-media thickness (CIMT) in nondiabetic chronic kidney disease (CKD) patients on conservative treatment.BackgroundCIMT is a reliable marker of subclinical atherosclerosis, and it has been associated with increased risk of cardiovascular events among CKD. Vascular calcification in CKD patients was independently correlated with FGF23.Patients and methodsThe study included 75 nondiabetic CKD patients on conservative treatment aged from 20 to 65 years as group 1 and 15 healthy individuals aged from 28 to 61 years, who have no medical history as a control group (group 2). Group 1 was subdivided into two groups: patients with increased CMIT and patients with normal CMIT. The study was conducted from October 2018 to May 2019. The patients were excluded if they have any of the following criteria: acute illness, CKD on dialysis, and patients with diabetes mellitus. The study was a case–control study. All patients and healthy individuals were subjected to the following: full history taking, general demographic data, including age, sex, height, weight, drug history, clinical examination, and laboratory investigations in the form of complete blood count, serum creatinine, and fasting and postprandial blood glucose. Estimated glomerular filtration rate (eGFR) was calculated by the Cockcroft–Gault formula as follows: eGFR=[140 − age (years)]×weight (kg)/serum creatinine (mg/dl)×72 [×0.85 if female], liver function tests (alanine transferase, aspartate transferase, serum albumin level), corrected serum calcium, serum phosphorus, lipid profile, carotid ultrasound, and intact FGF23.ResultsFGF23 levels and CIMT were significantly increasing across all the stages of CKD. The CIMT is significantly increasing in nondiabetic CKD patients with FGF23 levels of above 190 pg/ml. FGF23 levels positively correlated with the levels of creatinine, calcium, phosphrous, eGFR, hemoglobin, and albumin in nondiabetic CKD patients.ConclusionNondiabetic CKD patients had higher levels of FGF23 than controls. Nondiabetic CKD patients with increased CIMT had significantly higher phosphorus, creatinine, and FGF23 levels than those with normal CIMT. CIMT and FGF23 were significantly increased across all the stages of CKD. Increasing FGF23 concentrations across the stages of CKD reflect increasing CIMT and progression in CKD nondiabetic patients on conservative treatment.

Cardiovascular risk factors in childhood obesity

Childhood obesity is a major cardiovascular risk factor (CV). Adverse effects of obesity: 1. Increased insulin resistance; 2. Hypertension; 3. Atherogenic dyslipidemia, increased homocysteine values (Hcy); 4. Abnormal LV geometry: LV, systolic and diastolic dysfunction; 5. Endothelial dysfunction; 6. Increased systemic inflammation (subclinical inflammation from atherosclerosis) and the association of high values of high sensitive CRP: increased risk of CV damage and prothrombotic status; increase in carotid intima-media thickness (c-IMT) – marker of subclinical atherosclerosis; 7. Heart failure; 8. Coronary heart disease; 9. Atrial fibrillation; 10. Obstructive sleep apnea. In obese children: early signs of CV dysfunction, independent of other comorbidities associated with obesity. Study of the usefulness of researching some biochemical parameters for detecting the risk of CV in obesity in school children. Clinical study: patients (pts): 42 obese children (7–16 years); control group: 15 healthy children (similar ages), normal weight, without CVD. Investigation of CV dysfunction: by echocardiography (echo) and some markers for CV risk factors in obese school children. Elevated Hcy values (48% pts), correlated with BMI and hypertension (6 pts), normal values at control: 8.9 ± 1.92 μmol/L vs. 6.1 ± 2.4 μmol/L; dyslipidemia (54% pts); increased values c-IMT (44% pts): 0.71 mm vs. 0.38 mm (control); hs CRP (mg%): pts; 0.61 ± 1.08 vs. 0.05 ± 0.18 (control); echo: HLV (67% pts), diastolic dysfunction of LV (34% pts). Cardiological investigation is necessary in all obese school children to highlight CV dysfunction and CV risk factors, for the early establishment of CV prevention measures.

Relationship between Indices of Vascular Function and Presence of Overt Cardiovascular Disease among Persons with Poorly Controlled Type 2 Diabetes.

The aim of this study was to assess the factors associated with impaired vascular function in patients with poorly controlled type 2 diabetes (DM2) with and without overt cardiovascular disease (CVD). Ninety-five patients with DM2 and poor glycemic control were recruited and divided into two groups: Group 1, with known CVD (n = 38), and Group 2, without CVD (n = 57). Patients in Group 2 were further subdivided into those with short (<5 years, group 2b) and long (>5 years, group 2a) diabetes duration. Subclinical markers of atherosclerosis were assessed. Glycemic control was similar in the two groups (HbA1c: 9.2% (1.5) vs. 9.4% (1.8), p = 0.44). In Group 1, lower FMD (3.13 (2.16)% vs. 4.7 (3.4)%, p < 0.05) and higher cIMT (1.09 (0.3) mm vs. 0.96 (0.2) mm, p < 0.05) was seen compared with Group 2, whereas PWV was similar (12.1 (3.4) vs. 11.3 (3.0) m/s, p = 0.10). Patients in Group 2b had significantly lower PWV and cIMT and higher FMD compared to Group 1 (p < 0.05). Among patients with poorly controlled T2D, more pronounced vascular dysfunction was present in those with overt macrovascular disease. In patients with T2D without known CVD, vascular dysfunction was associated with disease duration. The use of vascular indices for cardiovascular risk stratification in patients with T2D requires further study.

Association of Circulating miR-145-5p and miR-let7c and Atherosclerotic Plaques in Hypertensive Patients

Aim: Hypertension is a strong risk factor for atherosclerosis. Increased carotid intima-media thickness (cIMT) and carotid plaques are considered subclinical markers of atherosclerosis. This study aimed at evaluating the serum expression of miRNAs previously related to adverse vascular remodeling and correlating them with carotid plaques and cIMT in hypertensive patients. Methods: We cross-sectionally evaluated the clinical and carotid characteristics as well as serum expression of miR-145-5p, miR-let7c, miR-92a, miR-30a and miR-451 in 177 hypertensive patients. Carotid plaques and cIMT were evaluated by ultrasound, and the expression of selected miRNAs was evaluated by a quantitative polymerase chain reaction. Results: Among all participants (age = 60.6 ± 10.7 years, 43% males), there were 59% with carotid plaques. We observed an increased expression of miR-145-5p (Fold Change = 2.0, p = 0.035) and miR-let7c (Fold Change = 3.8, p = 0.045) in participants with atherosclerotic plaque when compared to those without plaque. In the logistic regression analysis adjusted for relevant covariates, these miRNAs showed a stronger association with carotid plaques (miR-145-5p: Beta ± SE = 0.050 ± 0.020, p = 0.016 and miR-let7c: Beta ± SE = 0.056 ± 0.019, p = 0.003). Conclusions: Hypertensive patients with carotid plaques have an increased expression of miR-145-5p and miR-let7c, suggesting a potential role of these miRNAs as a biomarker for subclinical atherosclerosis in hypertensive individuals.

Twenty-Five Novel Loci for Carotid Intima-Media Thickness: A Genome-Wide Association Study in >45 000 Individuals and Meta-Analysis of >100 000 Individuals.

Objective:Carotid artery intima-media thickness (cIMT) is a widely accepted marker of subclinical atherosclerosis. Twenty susceptibility loci for cIMT were previously identified and the identification of additional susceptibility loci furthers our knowledge on the genetic architecture underlying atherosclerosis.Approach and Results:We performed 3 genome-wide association studies in 45 185 participants from the UK Biobank study who underwent cIMT measurements and had data on minimum, mean, and maximum thickness. We replicated 15 known loci and identified 20 novel loci associated with cIMT at P<5×10−8. Seven novel loci (ZNF385D, ADAMTS9, EDNRA, HAND2, MYOCD, ITCH/EDEM2/MMP24, and MRTFA) were identified in all 3 phenotypes. An additional new locus (LOXL1) was identified in the meta-analysis of the 3 phenotypes. Sex interaction analysis revealed sex differences in 7 loci including a novel locus (SYNE3) in males. Meta-analysis of UK Biobank data with a previous meta-analysis led to identification of three novel loci (APOB, FIP1L1, and LOXL4). Transcriptome-wide association analyses implicated additional genes ARHGAP42, NDRG4, and KANK2. Gene set analysis showed an enrichment in extracellular organization and the PDGF (platelet-derived growth factor) signaling pathway. We found positive genetic correlations of cIMT with coronary artery disease rg=0.21 (P=1.4×10-7), peripheral artery disease rg=0.45 (P=5.3×10-5), and systolic blood pressure rg=0.30 (P=4.0×10-18). A negative genetic correlation between average of maximum cIMT and high-density lipoprotein was found rg=−0.12 (P=7.0×10-4).Conclusions:Genome-wide association meta-analyses in >100 000 individuals identified 25 novel loci associated with cIMT providing insights into genes and tissue-specific regulatory mechanisms of proatherosclerotic processes. We found evidence for shared biological mechanisms with cardiovascular diseases.

Abstract 11225: Comparison of Coronary Artery Calcium Scores in South Asians and Other Racial-Ethnic Groups

Introduction and Hypothesis: There is a disproportionately higher incidence of atherosclerotic cardiovascular disease (ASCVD) and associated adverse outcomes in South Asians (SA), compared to other races. SA ancestry has been identified as a risk enhancer in the US cholesterol guidelines. Coronary artery calcium (CAC), a validated marker of sub clinical atherosclerosis offers a robust assessment of CVD risk. We sought to compare the distribution of CAC scores as a marker of CVD risk, across various age groups in SA and other races/ethnicities. Methods: Our analyses included 33,663 individuals (517 SA, 24,060 whites, 1,509 African Americans (AA), 3,759 Hispanics, 3,818 Asians), who underwent CAC scoring at our center. CAC scores were stratified by age, across various races/ethnic sub-groups. Age groups were classified into quartiles as follows: &lt;51 years, 51-59 years, 59-67 years and &gt;67 years of age. Differences in median CAC across races/ethnicities were tested with the Kruskal-Wallis Test, by age quartiles as described. Results: Mean (SD) age was 59 (11.6) years and 63% were men in the entire cohort. SA over 67 years of age, had significantly higher median CAC score 354.0, Interquartile Range (IQR) 36 - 1476, compared to other race/ethnicities (Median CAC (IQR): whites, 195, (21-762), Hispanics 167.5, (19-779), Asians 144, (14-642), AA 159 (8.5-676) (P=0.0019). In age groups from 50-67 years of age, median CAC scores were not significantly different between these groups (Figure 1). Conclusions: In older age groups, SA have higher median CAC scores compared to whites and other racial/ethnic groups including AAs, Hispanics and other Asians. The observed differences in atherosclerotic burden provide mechanistic insights to higher CVD risk, in the vulnerable SA groups. Future studies should explore the effects of CAC screening on treatment strategies, such as initiation of statins and prognosis in SA.

Abstract 9867: Associations of Urinary Isoprostane Levels with Prevalence and Progression of Coronary Artery Calcification and Carotid Plaque in the Multi-Ethnic Study of Atherosclerosis (mesa)

Introduction: Urinary isoprostanes reflect oxidative stress, which is implicated in the pathogenesis of atherosclerotic cardiovascular disease (ASCVD). Coronary artery calcium (CAC) &amp; carotid plaque are markers of subclinical atherosclerosis and prognostic of ASCVD risk. We examined if the urinary isoprostane iPF2α-III and its metabolite iPF2α-III-M were associated with CAC &amp; carotid plaque. Hypothesis: Higher urinary isoprostanes are associated with a greater prevalence, incidence, burden, and progression of CAC &amp; carotid plaque. Methods: 1097 MESA participants free of ASCVD had urinary isoprostanes measured at baseline. All participants underwent cardiac CT at baseline; 1083 underwent repeat CT ~10 yrs later. CAC was measured by Agatston scoring. All participants had carotid ultrasound (US) at baseline; 837 underwent repeat carotid US ~10 yrs later. Carotid plaque score (CPS) was defined as the number of carotid segments containing plaque. Isoprostane levels were divided into tertiles. Relative risk regression and linear mixed effect models determined prevalence/incidence and burden/progression respectively of CAC &amp; CPS. Results: Mean age of participants at baseline was 62.2 (8.3) yrs; 49% were women. There was no association of isoprostanes with CAC at baseline. There was a positive, but not statistically significant association, comparing the highest vs lowest tertiles of iPF2α-III-M and CAC progression over 10 yrs (Fig 1a). There was a statistically significant association comparing the highest vs lowest tertiles of isoprostanes with prevalence and burden of carotid plaque at baseline, but not with CPS incidence/progression (Fig 1b). Conclusions: In this multiethnic cohort, urinary isoprostanes were weakly but positively associated with carotid plaque burden and prevalence in cross sectional analysis and also showed a non-significant trend toward CAC progression, suggesting this measure of oxidative stress may be associated with ASCVD.