Risk Of Subclinical Atherosclerosis Research Articles

The association of subclinical atherosclerosis with prediabetes is stronger in people with dyslipidaemia than in those with normoglycaemia: A cross-sectional study in Chinese adults

BackgroundPrediabetes is associated with a high risk of cardiovascular disease (CVD) and often occurs with dyslipidaemia. The present study investigated the association between subclinical atherosclerosis profiles and prediabetes with and without dyslipidaemia. MethodsThis cross-sectional analysis included 4786 participants (1441 subjects with prediabetes and 3345 healthy controls). Prediabetes was defined by fasting plasma glucose (FPG) 5.6–6.9mmol/L or HbA1c 5.7–6.4% without antidiabetic drugs. Different markers of subclinical atherosclerosis were analysed: the carotid intima-media thickness (CIMT), carotid plaques (CP), and brachial-ankle pulse wave velocity (baPWV). ResultsSubclinical atherosclerosis was significantly more prevalent in prediabetic subjects than in normoglycaemic subjects (P<0.001). Only individuals with prediabetes in the dyslipidaemic group had significantly elevated adjusted odds ratios for subclinical atherosclerosis profiles. When stratified by FPG-only, HbA1c-only or both, the three subcategories in combination with dyslipidaemia shared a similarly increased risk of subclinical atherosclerosis compared to normoglycaemia without dyslipidaemia (P<0.05). The risk profile increased directionally from FPG-only to HbA1c-only to both overall. ConclusionOur data suggest that subclinical atherosclerotic changes in the prediabetic state are mainly seen in dyslipidaemic subjects. Thus, strategies to prevent atherogenic changes might focus on persons with prediabetes combined with dyslipidaemia, especially for the prediabetes-both subcategory, because of potential effects on CVD risk.

The role of cystatin-C and fetuin-A in the determination of early atherosclerotic risk in psoriasis patients.

Psoriasis is associated with an increased risk of atherosclerosis. The objective of this study is evaluate the relationship between carotid intima-media thickness (CIMT) serum and cystatin-C, fetuin-A levels in determining the increased risk of subclinical atherosclerosis in psoriasis patients. In this study, age and gender compatible 80 psoriasis patients and 78 healthy individuals were included. For both groups, serum cystatin-C, fetuin-A, high-sensitivity C-reactive protein (hs-CRP), oxidized low-density lipoprotein (ox-LDL), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), triglyceride, total cholesterol, and creatinine levels were recorded and carotid intima-media thickness (CIMT) was measured via B-mode ultrasonography by cardiology department. In binary comparisons between patient and control groups, cystatin-C, fetuin-A, hs-CRP, and CIMT values were higher in psoriasis patients and there was a statistically significant difference (P < .05). In control group, serum HDL-C level was statistically significant higher (P < .05). There was no statistically significant difference in hs-CRP, ox-LDL, LDL-C, triglyceride, total cholesterol, and creatinine levels between the groups (P > .05). Our study supported that psoriasis is a risk factor for development of atherosclerosis and we think that cystatin-C can be used as an important marker in determining subclinical atherosclerosis in patients with psoriasis.

High-sensitivity C-reactive protein as a biomarker in detecting subclinical atherosclerosis in psoriasis.

Psoriasis is known to be associated with increased risk of cardiovascular diseases. High-sensitivity C-reactive protein (hs-CRP) is a marker of inflammation and an independent risk factor for atherosclerosis. We aimed to assess the correlation between hs-CRP and subclinical atherosclerosis in psoriatic patients. In 60 patients with moderate to severe psoriasis and 60 age- and gender matched healthy controls, we evaluated the serum hs-CRP level and mean intima-media thickness of the common carotid artery (MIMT-CCA). Psoriatic patients had higher levels of hs-CRP (median, 2.25 mg/L; IQR, 0.98-3.80; and range, 0.29-11.60) than did those in the control group (median, 1.03 mg/L; IQR, 0.36-2.15; and range, 0.10-3.35). Psoriatic patients also had higher mean MIMT (0.74 ± 0.19 and 0.54 ± 0.12, respectively, and P < .0001) compared with healthy subjects. The serum level of hs-CRP was significantly correlated with MIMT (P < .0001). Our results indicate that psoriatic patients have a higher risk of subclinical atherosclerosis and hs-CRP may be a useful marker for future risk of cardiovascular diseases in these patients. So, not only does anti-inflammatory drugs play a key role in the treatment of psoriasis, but also they may reduce the risk of cardiovascular diseases by decreasing level of inflammatory markers including hs-CRP.

APOL1 Genetic Variants Are Associated with Serum-Oxidized Low-Density Lipoprotein Levels and Subclinical Atherosclerosis in South African CKD Patients

Introduction: Apolipoprotein L1 (APOL1) plays an important role in cholesterol metabolism and attenuation of low-density lipoprotein (LDL) oxidation. While protecting against Trypanosoma brucei rhodesiense infection, APOL1 risk alleles confer greater risk for CKD and cardiovascular disease among patients of African descent. Objectives: We investigated whether APOL1 risk variants are associated with atherosclerosis and oxidized LDL (OxLDL) levels among black South African CKD patients. Methods: A cross-sectional study of 120 adult CKD patients and 40 controls was undertaken. DNA samples of participants were genotyped for APOL1 G1 and G2 variants. High-sensitivity C-reactive protein, serum lipids, and OxLDL levels were measured, and carotid doppler ultrasonography was performed on all participants. Results: APOL1 alleles rs73885319, rs60910145, and rs71785313 had minor allele frequencies of 9.2, 8.8, and 17.5%, respectively, in the patients, and 8.8, 8.8, and 13.8%, respectively, in the controls. Of the 9 patients with 2 APOL1 risk alleles, 77.8% were compound G1/G2 heterozygotes and 22.2% were G2 homozygotes. Carriers of at least 1 APOL1 risk allele had a 3-fold increased risk of subclinical atherosclerosis (odds ratio 3.19; 95% confidence interval: 1.64–6.19; p = 0.01) compared to individuals with no risk alleles. Patients with 1 or 2 APOL1 risk alleles showed a significant increase in OxLDL levels when compared with those without the APOL1 risk allele. Conclusion: These findings suggest an increased risk for atherosclerosis in carriers of a single APOL1 risk variant, and the presence of APOL1 risk variants was associated with increased serum OxLDL levels in black South African CKD patients.

2014-P: Obesity Phenotypes and Subclinical Atherosclerosis among Whites, African Americans, and South Asians: The Genestar and Masala Studies

Background: Whether obesity in the absence of cardiometabolic abnormalities increases the risk of subclinical atherosclerosis remains debatable. Methods: We compared coronary artery calcium (CAC) across obesity phenotypes in 505 Whites and 306 African Americans (AAs) from the Genetic Study of Aspirin Responsiveness (GeneSTAR); and 875 South Asians (SAs) from MASALA (Mediators of Atherosclerosis in South Asians Living in America). Using BMI and the International Harmonized Definition of metabolic syndrome, participants were categorized as Metabolically Healthy Non-Obese (MHNO), Metabolically Healthy Obese (MHO), Metabolically Unhealthy Non-Obese (MUNO), and Metabolically Unhealthy Obese (MUO). Results: The prevalence of any detectable CAC was similar in MHNO versus MHO among all ethnic groups (Whites 35 versus 30%, AAs 30 versus 23%, SAs 29 versus 26%; respectively, all p&amp;gt;0.05). In contrast, the prevalence of CAC was the highest in the MUNO and MUO groups in all ethnic groups. After adjusting for potential confounders; the odds of CAC in MUNO and MUO compared to MHNO were significantly higher in Whites and SAs; but not in AAs. Conclusion: Metabolically unhealthy Whites, AAs, and SAs had higher CAC scores regardless of obesity status suggesting that metabolic health is more closely associated with atherosclerosis than obesity alone especially in Whites and SAs. Disclosure M. Al-Sofiani: Speaker’s Bureau; Self; Novo Nordisk Inc. D. Vaidya: None. A.M. Kanaya: None. L. Yanek: None. M. Mongraw-Chaffin: None. N.R. Kandula: None. L. Becker: None. B.G. Kral: None. D. Becker: None. N.M. Maruthur: Other Relationship; Self; Johns Hopkins HealthCare Solutions. C. Lee: Employee; Self; Eli Lilly and Company. Funding National Institutes of Health (R01HL093009, K24HL112827); National Center for Research Resources (UL1RR024131, M01-RR000052); National Heart, Lung, and Blood Institute (U01HL72518)

Obstetric antiphospholipid syndrome is not associated with an increased risk of subclinical atherosclerosis.

The persistent positivity of aPLs, either isolated or associated with thrombotic and/or obstetric events (APS), has been associated with the increase of intima-media thickness (IMT) and carotid plaques. Despite the fact that aPLs can promote both thrombotic and obstetric complications, some pathogenic differences have been documented between the two entities. This study aimed to evaluate whether the atherosclerotic risk differs between subjects with obstetric and thrombotic APS. A total of 167 APS women (36 obstetric and 131 thrombotic) were compared with 250 aPLs negative controls. IMT of the common carotid artery (CCA) and of the bulb and the prevalence of carotid plaques were assessed. CCA- and bulb-IMT were significantly higher in women with thrombotic APS, while being similar between the obstetric APS and the controls [CCA-IMT: mean (s.d.) 0.97 (0.49), 0.78 (0.22) and 0.81 (0.12) mm for the thrombotic, obstetric and control groups, respectively, P < 0.001 between thrombotic and controls, P = 0.002 between thrombotic and obstetric; bulb-IMT: mean (s.d.) 1.38 (0.79), 0.96 (0.27) and 0.96 (0.51) mm for the thrombotic, obstetric and control groups, P < 0.001]. Women with thrombotic APS had significantly increased risk of presenting carotid plaques. This risk was significantly lower in obstetric APS. Unlike thrombotic APS, obstetric APS is not associated with an increase of markers of subclinical atherosclerosis. If confirmed on wider populations, these results could suggest different pathogenetic role of aPLs in promoting atherosclerosis in vascular and obstetric APS, and raise questions on the risk-benefit profile of thromboprophylaxis in obstetric APS outside pregnancy periods.

The association between fat mass and subclinical atherosclerosis in healthy schoolchildren

Childhood obesity is associated with increased risk of cardiovascular disease (CVD) later in life. The aims of this study were to investigate the change of atherosclerosis risk factors in three fat mass percentiles and to examine the association between fat mass and atherosclerosis risk factors among a group of schoolchildren. A total of 125 schoolchildren (64 boys) aged 10-15 years were distributed into three groups: (i) the lower fat mass (LFM) group, for participants who reported fat mass ≤50th percentile; (ii) the middle fat mass (MFM) group, for participants who reported fat mass >50th percentile and <75th percentile; and (iii) the higher fat mass (HFM) group for participants who reported≥75th percentiles. Measurements of carotid intima-media thickness (cIMT) using high-resolution B-mode ultrasound, lipemic profile, blood pressure, serum proinflammatory cytokines and soluble adhesion molecules were performed. Significant differences (p≤0.05) were shown between the three groups in total cholesterol (TC), triglycerides (TG), LDL, interlukien-6 (IL-6), and interlukien-1 beta (IL-1β). Using multiple linear regression analysis of fat mass as the dependent variable with the studied subclinical atherosclerosis risk, fat mass was significantly (p≤0.05) associated with the variation expressed in systolic blood pressure (β=0.490), diastolic blood pressure (β=0.470), TC (β=0.399), TG (β=0.306), HDL (β=-0.281), LDL (β=0.446), E-selectin (β=0.314), and cIMT (β=0.257). Higher fat mass is associated with increased risk of atherosclerosis in schoolchildren. Atherosclerosis risk factors including biomarkers of inflammation, endothelial dysfunction, a state of dyslipidemia, increased cIMT, and high blood pressure were associated with fat mass. Studies evaluating the appropriate fat mass cut-off points in children and adolescents are needed.

Transition of metabolic phenotypes and risk of subclinical atherosclerosis according to BMI: a prospective study

The cardiometabolic risk associated with metabolically healthy obesity (MHO) remains the subject of debate. It is unclear whether MHO is a transient condition that affects subclinical atherosclerosis risk. In this study, we aimed to investigate the association of MHO and its transition over time with incident subclinical atherosclerosis. A prospective study was conducted with 6220 Chinese adults who were free of cardiovascular disease (CVD) at baseline. Obesity was defined as BMI ≥25.0kg/m2. Metabolic health was defined as an individual having fewer than two of the National Cholesterol Education Program Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (NCEP ATP III) criteria for components of the metabolic syndrome (excluding waist circumference). Subclinical atherosclerosis was measured by brachial-ankle pulse wave velocity, pulse pressure and albuminuria, separately or combined. Participants were cross-classified by BMI categories and by metabolic health status and its transition during follow-up. Inverse probability weighted logistic regression models were used to estimate ORs and 95% CIs for subclinical atherosclerosis. The MHO phenotype accounted for 16.3% of the total population and 32.8% of the population with obesity at baseline. Baseline MHO was not significantly associated with incident subclinical atherosclerosis. During a follow-up period of 4.4years, 46.8% of individuals with MHO developed a metabolically unhealthy status. Those with transient MHO had an increased risk of composite subclinical atherosclerosis compared with those in the metabolically healthy non-obesity reference group (OR 2.52 [95% CI 1.89, 3.36]). A transition from metabolically unhealthy to healthy status was shown to decrease the outcome risk. The relationship between BMI and subclinical atherosclerosis was partly mediated by BP and plasma glucose. MHO is not a stable condition and transient MHO conferred an increased risk of subclinical atherosclerosis, the early stage of CVD. Hence, individuals may benefit from early behavioural or medical management in order to avoid a deterioration of metabolic status and prevent atherosclerosis and CVD.

Abstract P454: Impact of Air Pollution on Subclinical Atherosclerosis Risk in Middle Aged Women With and Without Polycystic Ovary Syndrome

Objective: To study the association of ambient air pollution and subclinical atherosclerosis (SCA) risk in middle aged women with and without a history polycystic ovary syndrome (PCOS). Background: The harmful impact of air pollution relates to the increased risk in cardiovascular disease (CVD), a leading cause of mortality in the US. Atherosclerosis measured by coronary artery calcification (CAC) is highly correlated with the degree of atherosclerosis. Fine particulate matter (particles ≤ 2.5 μm in aerodynamic diameter [PM 2.5 ]), is known to affect cardiovascular health, but no study has focused on the impact in middle aged women with PCOS, a heterogeneous disorder involving altered ovarian function and often with higher risk of CVD. Methods: We evaluated 310 women (at first visit: age 47.7 ± 6.3 years; BMI 30.1 ± 7.6; 46.4% PCOS) from the Cardiovascular Health and Risk Measurement III study, who had data on SCA measured by CAC Agaston score, PCOS measures and PM 2.5 levels. Logistic regression models were used to estimate the association between PM 2.5 exposures (categorized into quartiles) and CAC (categorized into a binary variable, where CAC Agaston score ≤ 10 as reference group), adjusting for age, BMI, and PCOS status. Subgroup analyses were conducted to test associations between PM 2.5 and CAC among the vulnerable population of women with PCOS. Results: Annual mean PM 2.5 levels were 16.8 ± 1.1 and 16.6 ± 1.3 μg/m 3 , respectively, among women with CAC Agaston score &gt; 10 and ≤ 10 (N=76 vs. 234). In addition, women with PCOS had an annual mean PM 2.5 levels of 16.5 ± 1.3 μg/m 3 , and women without PCOS had an annual mean PM 2.5 levels of 16.8 ± 1.1 μg/m 3 (N=143 for PCOS cases vs. 165 for controls). In adjusted analysis, the odds ratio of CAC risk was 1.32 (95% CI: 0.54, 3.28) for the highest quartile of PM 2.5 vs. the lowest one (Q4: 17.5-18.9 VS. Q1: 12.7-16.0 μg/m 3 ). Within the PCOS group, the likelihood of CAC was 4.78 times higher (95% CI: 1.37, 16.76) in the highest quartile of PM 2.5 levels, compared to the lowest. Conclusions: Women with PCOS appear to be at higher risk for the impact of PM2.5 exposure on SCA, compared to those without PCOS in this middle aged group. Replication of this work in other groups of women with PCOS would be of a high priority.

Systematic Coronary Risk Evaluation estimated risk and prevalent subclinical atherosclerosis in coronary and carotid arteries: A population-based cohort analysis from the Swedish Cardiopulmonary Bioimage Study.

It is not clear if the European Systematic Coronary Risk Evaluation algorithm is useful for identifying prevalent subclinical atherosclerosis in a population of apparently healthy individuals. Our aim was to explore the association between the risk estimates from Systematic Coronary Risk Evaluation and prevalent subclinical atherosclerosis. The design of this study was as a cross-sectional analysis from a population-based study cohort. From the general population, the Swedish Cardiopulmonary Bioimage Study randomly invited individuals aged 50-64 years and enrolled 13,411 participants mean age 57 (standard deviation 4.3) years; 46% males between November 2013-December 2016. Associations between Systematic Coronary Risk Evaluation risk estimates and coronary artery calcification and plaques in the carotid arteries by using imaging data from a computed tomography of the heart and ultrasonography of the carotid arteries were examined. Coronary calcification was present in 39.5% and carotid plaque in 56.0%. In men, coronary artery calcium score >0 ranged from 40.7-65.9% and presence of carotid plaques from 54.5% to 72.8% in the age group 50-54 and 60-65 years, respectively. In women, the corresponding difference was from 17.1-38.9% and from 41.0-58.4%. A doubling of Systematic Coronary Risk Evaluation was associated with an increased probability to have coronary artery calcium score >0 (odds ratio: 2.18 (95% confidence interval 2.07-2.30)) and to have >1 carotid plaques (1.67 (1.61-1.74)). Systematic Coronary Risk Evaluation estimated risk is associated with prevalent subclinical atherosclerosis in two major vascular beds in a general population sample without established cardiovascular disease or diabetes mellitus. Thus, the Systematic Coronary Risk Evaluation risk chart may be of use for estimating the risk of subclinical atherosclerosis.

Common Variants in IL-20 Gene are Associated with Subclinical Atherosclerosis, Cardiovascular Risk Factors and IL-20 Levels in the Cohort of the Genetics of Atherosclerotic Disease (GEA) Mexican Study.

Inflammation has been involved in the development of atherosclerosis, type 2 diabetes mellitus, insulin resistance, and obesity. Interleukin 20 is a pro-inflammatory cytokine encoded by a polymorphic gene located in chromosome 1. The aim of the study was to evaluate the association of two IL-20 polymorphisms (rs1400986 and rs1518108) with subclinical atherosclerosis (SA), cardiovascular risk factors and IL-20 levels in a cohort of Mexican individuals. The polymorphisms were determined in 274 individuals with SA and 672 controls. Under different models, rs1400986 (OR = 0.51, Pcodominant1 = 0.0001; OR = 0.36, Pcodominant2 = 0.014; OR = 0.49, Pdominant = 0.0001 and OR = 0.55, Padditive = 0.0001) and rs1518108 (OR = 0.62, Pcodominant2 = 0.048 and OR = 0.79, Padditive = 0.048) were associated with a lower risk of SA. These polymorphisms were associated with cardiovascular risk factors in individuals with SA and controls. Controls with the rs1400986 TT genotype presented high levels of IL-20 (p = 0.031). In individuals with the rs1400986 CC genotype, we observed a negative correlation between IL-20 levels and total abdominal tissue (TAT), visceral abdominal tissue (VAT) and subcutaneous abdominal tissue (SAT). Our results indicate that the IL-20 rs1400986 and rs1518108 polymorphisms were associated with decreased risk of developing SA and with some cardiovascular risk factors in individuals with SA and healthy controls. Negative correlation between BMI and VAT/SAT ratio in individuals with rs1400986 CC genotype and among IL-20 levels and TAT, VAT and SAT was observed.

Carotid doppler ultrasound evaluation in patients with lichen planus

Background: Lichen planus is a chronic inflammatory disease associated with an increased risk of subclinical atherosclerosis and cardiovascular diseases. This study aimed to evaluate patients with lichen planus using carotid Doppler ultrasound parameters.Methods: Forty patients with lichen planus and 40 controls were included in this study. Common carotid artery intima-media thickness (CIMT) and the number of atherosclerotic plaque weremeasured and compared to the control group. Total cholesterol, triglyceride, low-density lipoprotein (LDL) and high-density lipoprotein (HDL) levels were measured. Leptin level (Pg/ml)was measured using the enzyme-linked immunosorbent assay (ELISA) method (Leptin ELISA kit, Orgenium, Finland).Results: Significant difference was found between the groups in terms of CIMT (P=0.005). The median range for blood leptin level, triglyceride, cholesterol, and LDL was higher for lichen planus patients than for controls. We found a significant difference between the severity of LP and CIMT (P=0.035). No statistical difference was found between LP and the number of atherosclerotic plaque.Conclusions: Our study suggested that measurement of the mean intima media wall thickness of the common carotid artery could be beneficial as a valuable method for early diagnosis of atherosclerosis in lichen planus.

P3418The relationship between circulating vitamin d3 and subclinical atherosclerosis in elderly asian: contributor or bystander?

Abstract Background Vitamin D deficiency had been suggested to be the risk factor of cardiovascular diseases and metabolic disorders. However, current evidence about the association between vitamin D deficiency and atherosclerosis are conflicted and inconclusive. Purpose We tried to investigate the relationship between serum vitamin D concentrations and subclinical atherosclerosis in the elderly Asian population. Methods The I-Lan longitudinal study (ILAS), 1798 community-dwelling adults older than 50 years old were enrolled and divided into two groups according to serum vitamin D level (sufficient, ≥20 ng/mL, and deficient &lt;20 ng/mL). The concentrations of serum vitamin D3 was measured by chemiluminescence immunoassay and demographic data recorded from chart review. The carotid intima-media thickness (cIMT) was measured at bilateral common carotid arteries. Subclinical atherosclerosis was defined as mean cIMT more than 0.81mm, which had been proved to be associated with an increased risk of stroke and coronary events. Results Subjects with vitamin D deficiency (n=604, 33.6%) were younger, composed of more woman, smoker, with a higher incidence of hypertension, dyslipidemia, and metabolic syndrome. Compared with subjects without vitamin D sufficiency, patients with vitamin D deficiency were associated with lower risk of subclinical atherosclerosis (crude OR: 0.63, 95% CI: 0.50–0.81, p&lt;0.001) in the univariate analysis. However, after adjusting gender and age, vitamin D deficiency was no more associated with risk of subclinical atherosclerosis. Risk of vitD3 and cIMT Subclinical Atherosclerosis (cIMT &gt;0.8mm) Odds Ratio 95% Confidence Interval p-value Model 1 Vit D3 normal (≥20) Reference – – Vit D3 deficiency (&lt;20) 0.63 0.50–0.81 &lt;0.001 Model 2 Vit D3 normal (≥20) Reference – – Vit D3 deficiency (&lt;20) 0.81 0.62–1.06 0.127 Model 3 Vit D3 normal (≥20) Reference – – Vit D3 deficiency (&lt;20) 0.93 0.69–1.24 0.599 Model 1: adjust for vit D3 (univariate); Model 2: adjusted for age, vit D3, Gender; Model 3: adjusted multivariate significantly in univariate analysis. Conclusion Vitamin D deficiency was not an independent risk factor for subclinical atherosclerosis in the elderly Asian population. The association observed in the univariate analysis may be confounded by gender difference or comorbidities.

Evaluation of Subclinical Atherosclerosis with Carotid Intima-Media and Epicardial Fat Thickness in Patients with Sarcoidosis.

Since many similar mechanisms may play a role in the pathophysiology of sarcoidosis and atherosclerosis, the risk of subclinical atherosclerosis may be increased in patients with sarcoidosis. The aim of this study was to evaluate known markers of subclinical atherosclerosis, namely epicardial fat thickness (EFT) and carotid intima-media thickness (CIMT) in patients with sarcoidosis. This cross-sectional study included a total of 183 subjects, including 94 patients with sarcoidosis (patient group) and a control group of 89 healthy individuals. Measurements of EFT and CIMT were taken from all subjects and recorded. The groups were compared, and differences were analyzed statistically. EFT was higher in patients than in control subjects (6.42±1.12 mm vs 7.13±1.41 mm, p<0.001). CIMT was higher in patients than in control subjects (0.51±0.02 mm vs 0.52±0.02 mm, p=0.003). EFT and CIMT were found to be higher in patients with sarcoidosis than in healthy people. These results indicate that the risk of subclinical atherosclerosis might be increased in these patients.

Cardiovascular Risk in Fatty Liver Disease: The Liver-Heart Axis-Literature Review.

According to the World Health Organization, cardiovascular disease (CVD) remains the leading cause of death worldwide, accounting for approximately 18 million deaths per year. Nevertheless, the worldwide prevalence of metabolic diseases, such as type 2 diabetes mellitus, obesity, and non-alcoholic fatty liver disease (NAFLD), also known to be common risk factors for CVD, have dramatically increased over the last decades. Chronic alcohol consumption is a major cause of chronic liver diseases (CLD) as well as being a major health care cost expenditure accounting for the spending of tremendous amounts of money annually. NAFLD has become one of the major diseases plaguing the world while standing as the most common cause of liver disease in the Western countries by representing about 75% of all CLD. Currently, the most common cause of death in NAFLD remains to be CVD. Several mechanisms have been suggested to be responsible for associating FLD with CVD through several mechanisms including low-grade systemic inflammation, oxidative stress, adipokines, endoplasmic reticulum stress, lipotoxicity and microbiota dysbiosis which may also be influenced by other factors such as genetic and epigenetic variations. Despite of all this evidence, the exact mechanisms of how FLD can causally contribute to CVD are not fully elucidated and much remains unknown. Moreover, the current literature supports the increasing evidence associating FLD with several cardiovascular (CV) adverse events including coronary artery disease, increased subclinical atherosclerosis risk, structural alterations mainly left ventricular hypertrophy, increased epicardial fat thickness, valvular calcifications including aortic valve sclerosis and mitral annular calcification and functional cardiac modifications mainly diastolic dysfunction in addition to cardiac arrhythmias such as atrial fibrillation and ventricular arrythmias and conduction defects including atrioventricular blocks and bundle branch blocks. Patients with FLD should be evaluated and managed accordingly in order to prevent further complications. Possible management methods include non-pharmacological strategies including life style modifications, pharmacological therapies as well as surgical management. This review aims to summarize the current state of knowledge regarding the pathophysiological mechanisms linking FLD with an increased CV risk, in addition to associated CV adverse events and current management modalities.

Subclinical and clinical atherosclerosis in rheumatoid arthritis: results from the 3-year, multicentre, prospective, observational GIRRCS (Gruppo Italiano di Ricerca in Reumatologia Clinica e Sperimentale) study

BackgroundRheumatoid arthritis (RA) is associated with an increased risk of morbidity and mortality, when compared with general population, largely due to enhanced atherosclerotic disease. In this work, we aimed at assessing both occurrence and predictive factors of subclinical and clinical atherosclerosis in RA.MethodsFrom January 1, 2015, to December 31, 2015, consecutive participants with RA, admitted to Italian Rheumatology Units, were assessed in the GIRRCS (Gruppo Italiano di Ricerca in Reumatologia Clinica e Sperimentale) cohort. After that, those participants were followed up in a 3-year, prospective, observational study, assessing the occurrence of subclinical and clinical atherosclerosis and possible predictive factors. McNemar test was employed to assess the changes in subclinical and clinical atherosclerosis, and regression analyses exploited the ORs for the occurrence of those comorbidities.ResultsWe analysed 841 participants, mostly female (82.2%) and with median age of 60 years (range 21–90). The remission was achieved and maintained by 41.8% of participants during the follow-up. We observed an increased rate of subclinical atherosclerosis at the end of follow-up (139 vs 203 participants, p < 0.0001), particularly in participants with a disease duration less than 5 years at baseline (70 participants vs 133 participants, p < 0.0001). Type 2 diabetes (T2D) (OR 4.50, 95%CI 1.74–11.62, p = 0.002), high blood pressure (OR 2.03, 95%CI 1.04–4.14, p = 0.042), ACPA (OR 2.36, 95%CI 1.19–4.69, p = 0.014) and mean values of CRP during the follow-up (OR 1.07, 95%CI 1.03–1.14, p = 0.040) were significantly associated with higher risk of subclinical atherosclerosis. We observed an increased rate of clinical atherosclerosis at the end of follow-up (48 vs 76 participants, p < 0.0001). T2D (OR 6.21, 95%CI 2.19–17.71, p = 0.001) was associated with a significant risk of clinical atherosclerosis. The achievement and the maintenance of remission reduced the risk of subclinical (OR 0.25, 95%CI 0.11–0.56, p = 0.001) and clinical atherosclerosis (OR 0.20, 95%CI 0.09–0.95, p = 0.041).ConclusionsWe reported an increased prevalence and incidence of both subclinical and clinical atherosclerosis in 3-year prospectively followed participants, mainly in the subset with a duration of disease less than 5 years. The achievement and the maintenance of remission are associated with a reduction of the risk of subclinical and clinical atherosclerosis. Among “traditional” cardiovascular risk factors, participants with T2D showed a higher risk of clinical and subclinical atherosclerosis.

Genetic Predisposition to Type 2 Diabetes and Risk of Subclinical Atherosclerosis and Cardiovascular Diseases Among 160,000 Chinese Adults.

In observational studies, type 2 diabetes is associated with two- to fourfold higher risk of cardiovascular diseases (CVD). Using data from the China Kadoorie Biobank (CKB), we examined associations of genetically predicted type 2 diabetes with CVD among ∼160,000 participants to assess whether these relationships are causal. A type 2 diabetes genetic risk score (comprising 48 established risk variants) was associated with the presence of carotid plaque (odds ratio 1.17 [95% CI 1.05, 1.29] per 1 unit higher log-odds of type 2 diabetes; n = 6,819) and elevated risk of ischemic stroke (IS) (1.08 [1.02, 1.14]; n = 17,097), nonlacunar IS (1.09 [1.03, 1.16]; n = 13,924), and major coronary event (1.12 [1.02, 1.23]; n = 5,081). There was no significant association with lacunar IS (1.03 [0.91, 1.16], n = 3,173) or intracerebral hemorrhage (ICH) (1.01 [0.94, 1.10], n = 6,973), although effect estimates were imprecise. These associations were consistent with observational associations of type 2 diabetes with CVD in CKB (P for heterogeneity >0.3) and with the associations of type 2 diabetes with IS, ICH, and coronary heart disease in two-sample Mendelian randomization analyses based on summary statistics from European population genome-wide association studies (P for heterogeneity >0.2). In conclusion, among Chinese adults, genetic predisposition to type 2 diabetes was associated with atherosclerotic CVD, consistent with a causal association.

Plasma Sphingolipids and Subclinical Atherosclerosis – Novel Associations Uncovered by a Large-scale Lipidomic Analysis (P18-129-19)

ObjectivesSphingolipids (SP) are a diverse class of heterogenous lipids that includes ceramides, sphingomyelins, and glycosphingolipids. Many SPs have diverse roles in cell functions including cell growth, inflammation and angiogenesis, and previous studies suggest that SPs may also be involved in the pathogenesis of cardiovascular diseases. We aimed to identify plasma SPs and subsequently evaluate associations between plasma SPs and subclinical atherosclerosis in a subset of the Multiethnic Cohort of Singapore with the goal of uncovering novel biomarkers predictive of heart disease. MethodsWe conducted a lipidomics evaluation of 103 molecularly-distinct SPs in the plasma of 559 Singaporeans aged 50 years and above using electrospray ionization mass spectrometry coupled with liquid chromatography. All participants did not have a history of diabetes, heart disease, stroke or cancer at baseline, and completed a detailed health screening that evaluated risk factors for cardiovascular disease including computed tomography scans of the abdomen and coronary arteries. Multivariable logistic regression models were used to estimate odds ratios (ORs) and 95% confidence intervals (CIs) for associations between SPs and subclinical atherosclerosis (defined as coronary artery calcium score ≥ 100). ResultsCeramides (Cer), particularly those with a d16:1 or d18:1 backbone, were directly associated with higher risk of subclinical atherosclerosis whereas a small number of monohexosylceramides (MHCer), dihexosylceramides (DHCer) and sphingomyelins (SM) with a d18:2 sphingoid backbone were inversely associated. However most associations were attenuated after adjusting for conventional cardiovascular risk factors, including blood lipid (low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, triglycerides) concentrations and glycemic markers, suggesting that the associations may be mediated by these risk factors. ConclusionsHigh-throughput lipidomics may uncover novel sphingolipids predictive of heart disease. Characterization of these lipid species could provide insights into disease etiology. Funding SourcesThis work was supported by the National University Health System and the National Research Foundation Investigatorship grant. Supporting Tables, Images and/or Graphs▪▪

MRE11A Polymorphisms Are Associated With Subclinical Atherosclerosis and Cardiovascular Risk Factors. A Case-Control Study of the GEA Mexican Project.

DNA damage and subsequent repair pathways have been involved in the initiation and progression of atherosclerosis. Meiotic recombination 11 homolog A (MRE11A) gene polymorphisms have been associated with the presence of myocardial infarction. We analyzed five MRE11A gene polymorphisms in 386 individuals with subclinical atherosclerosis and 1093 healthy controls. Under different models, the rs13447720 (Odds ratio = 0.646, Padditive = 0.009; Odds ratio = 0.636, Pdominant = 0.012; Odds ratio = 0.664, Pover–dominant = 0.025; Odds ratio = 0.655, Pcodominant1 = 0.021) and rs499952 (Odds ratio = 0.807, Padditive = 0.032; Odds ratio = 0.643, Pcodominant2 = 0.034) polymorphisms were associated with a lower risk of subclinical atherosclerosis. On the other hand, the rs2155209 polymorphism was associated with a reduced risk of having a coronary artery calcification score ≥ 100 Agatston units. The rs13447720, rs499952, and rs2155209 polymorphisms, as well as the haplotypes that included the five studied polymorphisms were associated with some clinical and metabolic parameters in both subclinical atherosclerosis and healthy individuals. Our results suggest that the rs13447720 and rs499952 polymorphisms are associated with a decreased risk of developing subclinical atherosclerosis, whereas the rs2155209 is associated with a lower subclinical atherosclerosis severity (coronary artery calcification < 100 Agatston units). MRE11A polymorphisms and haplotypes were associated with clinical and metabolic parameters.

Profiling of risk of subclinical atherosclerosis: possible interplay of genetic and environmental factors as the update of conventional approach

Profiling of risk of subclinical atherosclerosis: possible interplay of genetic and environmental factors as the update of conventional approach