Determinants Of Atherosclerosis Research Articles

Evaluation of cardiovascular risk factors, prevalence and determinants of coronary artery disease in renal transplant patients: a single center experience

Aims: Cardiovascular disease is the leading cause of morbidity and mortality in renal transplant patients. In our study, we aimed to determine the cardiovascular (CV) risk factors, the prevalence and determinants of coronary artery disease (CAD) in patients who underwent kidney transplantation in our center.
 Methods: One hundred sixty nine patients who underwent kidney transplantation in our center were included in the study retrospectively. Demographic and clinical characteristics of the patients, cardiac evaluation findings and further examination results were scanned from the database of our center.
 Results: The mean age of the patients was 42.86±12.97 years and 43.19% were female. The most common etiological factors for the development of end-stage renal disease were hypertension (HT) and diabetes mellitus (DM). Ninety seven patients (57.4%) were undergoing dialysis, 4 of whom were on peritoneal dialysis. Renal transplant was performed from a cadaver in two patients and from a living donor in the other patients. CAD was detected in 29 patients (17.15%). The most prevalent CV risk factors were HT and hyperlipidemia (HL). Multivariate logistic regression analysis revealed that age, DM, HL and dialysis history were independent risk factors for the development of CAD. In the postoperative follow-ups, no death or acute coronary syndrome was observed during the hospitalization period.
 Conclusion: Prevalence of CV risk factors is high in renal transplant candidates. Our findings support the need for a detailed cardiac evaluation and effective management of CV risk factors in patients preparing for kidney transplantation.

Apolipoprotein B is associated with CT-angiographic progression beyond low-density lipoprotein cholesterol and non-high-density lipoprotein cholesterol in patients with coronary artery disease

BackgroundAccumulating evidence indicated that apolipoprotein B (apoB) was the principal lipid determinant of coronary artery disease (CAD). Nevertheless, the connection between apoB and angiographic progression of CAD remained undetermined.MethodsFive hundred and forty-four CAD patients with twice coronary computed tomography angiography experiences were enrolled. The Gensini scoring system was used to assess angiographic progression. Incident angiographic progression was defined as an annual change rate of the Gensini score of > 1 point. The predictive efficacy of baseline apoB levels for angiographic progression was assessed using a receiver operating characteristic (ROC) curve. For comparative purposes, patients were categorized into three groups according to their baseline apoB tertiles. Furthermore, discordance analyses defined by the median were performed to assess the superiority of apoB over lipoprotein cholesterol in predicting angiographic progression of CAD.ResultsAngiographic progression was observed in 184 patients (33.8%) during a follow-up period of 2.2-year. The area under the ROC curve was 0.565 (0.522–0.607, P = 0.013). The incidence of angiographic progression was elevated with increasing apoB tertile after adjusting for confounding factors [odds ratio (OR) for the medium apoB tertile: 1.92, 95% confidence interval (CI): 1.15–3.19, P = 0.012; OR for the high apoB tertile: 2.05, 95%CI:1.17–3.60, P = 0.013]. Additionally, discordance analyses showed that the higher apoB group had a significantly higher risk of CAD progression in the fully adjusted model (all P < 0.05).ConclusionsApoB could be used as an accurate and comprehensive indicator of angiographic progression in patients with CAD.

Overexpression of NgBR inhibits high-fat diet-induced atherosclerosis in ApoE-deficiency mice.

Hyperlipidemia (hypercholesterolemia and/or hypertriglyceridemia) is a risk factor for atherosclerosis. Nogo-B receptor (NgBR) plays important roles in hepatic steatosis and cholesterol transport. However, the effect of NgBR overexpression on atherosclerosis remains unknown. Apolipoprotein E deficient (ApoE-/-) mice infected with adeno-associated virus (AAV)-NgBR expression vector were fed a high-fat diet for 12 weeks, followed by determination of atherosclerosis and the involved mechanisms. We determined that high expression of NgBR by AAV injection mainly occurs in the liver and it can substantially inhibit en face and aortic root sinus lesions. NgBR overexpression also reduced levels of inflammatory factors in the aortic root and serum, and levels of cholesterol, triglyceride, and free fatty acids in the liver and serum. Mechanistically, NgBR overexpression increased the expression of scavenger receptor type BI and the genes for bile acid synthesis, and decreased the expression of cholesterol synthesis genes by reducing sterol regulatory element-binding protein 2 maturation in the liver, thereby reducing hypercholesterolemia. In addition, NgBR overexpression activated AMP-activated protein kinase α via the Ca2+ signaling pathway, which inhibited fat synthesis and improved hypertriglyceridemia. Taken together, our study demonstrates that overexpression of NgBR enhanced cholesterol metabolism and inhibited cholesterol/fatty acid synthesis to reduce hyperlipidemia, and reduced vascular inflammation, thereby inhibiting atherosclerosis in ApoE-/- mice. Our study indicates that NgBR might be a potential target for atherosclerosis treatment.

Ubiquitin-Specific Proteases (USPs) and Metabolic Disorders.

Ubiquitination and deubiquitination are reversible processes that modify the characteristics of target proteins, including stability, intracellular localization, and enzymatic activity. Ubiquitin-specific proteases (USPs) constitute the largest deubiquitinating enzyme family. To date, accumulating evidence indicates that several USPs positively and negatively affect metabolic diseases. USP22 in pancreatic β-cells, USP2 in adipose tissue macrophages, USP9X, 20, and 33 in myocytes, USP4, 7, 10, and 18 in hepatocytes, and USP2 in hypothalamus improve hyperglycemia, whereas USP19 in adipocytes, USP21 in myocytes, and USP2, 14, and 20 in hepatocytes promote hyperglycemia. In contrast, USP1, 5, 9X, 14, 15, 22, 36, and 48 modulate the progression of diabetic nephropathy, neuropathy, and/or retinopathy. USP4, 10, and 18 in hepatocytes ameliorates non-alcoholic fatty liver disease (NAFLD), while hepatic USP2, 11, 14, 19, and 20 exacerbate it. The roles of USP7 and 22 in hepatic disorders are controversial. USP9X, 14, 17, and 20 in vascular cells are postulated to be determinants of atherosclerosis. Moreover, mutations in the Usp8 and Usp48 loci in pituitary tumors cause Cushing syndrome. This review summarizes the current knowledge about the modulatory roles of USPs in energy metabolic disorders.

Socioeconomic and Clinical Determinants of Coronary Artery Disease in Symptom-Free Type 2 Diabetes Mellitus Patients

Background: There are global reports of rising cardiovascular burden in persons living with type 2 diabetes mellitus (T2DM) patients. The presence of coronary artery disease (CAD) increases mortality risk in T2DM patients. There are currently no data on the determinants of CAD in Nigerian T2DM patients. Objective: The objective was to determine the determinants of CAD in persons with T2DM. Methods: This was a cross-sectional study involving T2DM patients with and without CAD attending the diabetes clinic of Nnamdi Azikiwe University Teaching Hospital, Nnewi, Nigeria. The diagnosis of CAD was made based on personal information obtained using the Rose angina questionnaire and resting electrocardiogram findings. Medical history and other clinical evaluations were done to identify the socioeconomic and clinical variables in the study participants. Data obtained were analyzed using appropriate statistical software. Results: The study involved 400 asymptomatic T2DM patients with a median age of 60 years and a female-to-male ratio of 1.3:1. Sixty-four (16%) participants had CAD. The male: female ratio in CAD and non-CAD groups was 1.8:1 and 0.7:1 (χ2 = 1.7, P = 0.22). Formal education (χ2 = 4.1, P = 0.02), upper socioeconomic class (χ2 = 5.1, P = 0.02), hypertension (χ2 = 2.2, P = 0.03), dyslipidemia (χ2 = 4.7, P = 0.02), cerebrovascular disease (χ2 = 5.2, P = 0.01), smoking (χ2 = 9.1, P = 0.01), waist circumference (Mann–Whitney U = 358, P = 0.02), carotid intima-media thickness (Mann–Whitney U = 300, P = 0.01), and ankle brachial pressure index (Mann–Whitney U = 315, P = 0.01) were significantly associated with CAD in the study participants. Multivariate logistic regression analysis showed that formal education had the least odds of predicting CAD (odd ratio [OR] =2.1, 95% confidence interval [CI] =1.6–6.2; P = 0.02), while low-density lipoprotein cholesterol had the highest odds of predicting CAD (OR = 5.2, 95% CI = 2.1–9.5, P = 0.01) among the study participants. Conclusions: Early screening for comorbidities and lipid abnormalities in T2DM patients is required, especially in those with formal education and within the high socioeconomic class.

Cholesterol uptake capacity: A new measure of high-density lipoprotein functionality as a predictor of subsequent revascularization in patients undergoing percutaneous coronary intervention

Background and aimsHigh-density lipoprotein (HDL) functionality is an important determinant of coronary artery disease (CAD) development. We recently developed cholesterol-uptake capacity (CUC), a rapid cell-free assay system that directly evaluates the capacity of HDL to accept additional cholesterol. We aimed to evaluate the association between CUC and revascularization in patients who have undergone percutaneous coronary intervention (PCI). MethodsWe retrospectively reviewed patients who underwent PCI with subsequent revascularization or coronary angiography (CAG) without revascularization. The patients who had frozen blood samples for which CUC were measurable at the index PCI and follow-up were enrolled. ResultsWe finally enrolled 74 patients who underwent subsequent revascularization and 183 patients who underwent follow-up CAG without revascularization. The serum CUC level at the index PCI was significantly lower in the revascularization group than that in the non-revascularization group (84.3 [75.2–98.9] vs. 92.0 [81.6–103.3 A U.]; p = 0.004). Multivariate logistic regression analysis revealed that decreased serum CUC level at the index PCI was independently associated with subsequent revascularization (odds ratio, 0.98; 95% confidence interval, 0.969–1.000). After adjusting for 16 cardiovascular risk factors, the serum CUC level at the index PCI and follow-up and the absolute change in serum CUC level from the index PCI to follow-up were significantly lower in the revascularization group than those in the non-revascularization group. ConclusionsSerum CUC level at index PCI was independently associated with subsequent revascularization after PCI. Continuous assessment of HDL functionality by CUC might help predict subsequent revascularization after PCI.

ERK1/2 inhibition reduces vascular calcification by activating miR-126-3p-DKK1/LRP6 pathway.

Rationale: Vascular microcalcification increases the risk of rupture of vulnerable atherosclerotic lesions. Inhibition of ERK1/2 reduces atherosclerosis in animal models while its role in vascular calcification and the underlying mechanisms remains incompletely understood.Methods: Levels of activated ERK1/2, DKK1, LRP6 and BMP2 in human calcific aortic valves were determined. ApoE deficient mice received ERK1/2 inhibitor (U0126) treatment, followed by determination of atherosclerosis, calcification and miR-126-3p production. C57BL/6J mice were used to determine the effect of U0126 on Vitamin D3 (VD3)-induced medial arterial calcification. HUVECs, HAECs and HASMCs were used to determine the effects of ERK1/2 inhibitor or siRNA on SMC calcification and the involved mechanisms.Results: We observed the calcification in human aortic valves was positively correlated to ERK1/2 activity. At cellular and animal levels, U0126 reduced intimal calcification in atherosclerotic lesions of high-fat diet-fed apoE deficient mice, medial arterial calcification in VD3-treated C57BL/6J mice, and calcification in cultured SMCs and arterial rings. The reduction of calcification was attributed to ERK1/2 inhibition-reduced expression of ALP, BMP2 and RUNX2 by activating DKK1 and LRP6 expression, and consequently inactivating both canonical and non-canonical Wnt signaling pathways in SMCs. Furthermore, we determined ERK1/2 inhibition activated miR-126-3p production by facilitating its maturation through activation of AMPKα-mediated p53 phosphorylation, and the activated miR-126-3p from ECs and SMCs played a key role in anti-vascular calcification actions of ERK1/2 inhibition.Conclusions: Our study demonstrates that activation of miR-126-3p production in ECs/SMCs and interactions between ECs and SMCs play an important role in reduction of vascular calcification by ERK1/2 inhibition.

FMTVDM-Finally Opens the Doorway from Qualitative to Quantitative Measurement and Treatment of Heart Disease

Diagnostic determination of coronary artery disease has primarily relied upon qualitative image interpretation and tests of minimal measureable value. The introduction of the first measureable test dates back to the late 1890s following its presentation by Willem Einthoven at a Dutch Medical Association Conference in 1893-the electrocardiogram.

Impact of active smoking on the immature platelet fraction and its relationship with the extent of coronary artery disease.

Smoking represents a major cardiovascular risk factor, due to the induction of oxidative stress and low-grade, continuous, inflammation that contribute to promote atherothrombosis. However, the mechanisms leading to increased platelet aggregability associated with smoking are only partially defined. A potential role has been hypothesized for immature platelets, a younger and potentially more reactive fraction, previously associated with the main determinants of coronary artery disease (CAD). Therefore, the aim of our study was to define the impact of smoking on the immature platelet fraction (IPF) and its relationship with prevalence and extent of coronary artery disease. We enrolled a cohort of consecutive patients undergoing coronary angiography in a single centre. Significant CAD was defined as at least 1 vessel stenosis >50%, while severe CAD was defined as left main and/or three-vessel disease. IPF was measured at admission by routine blood cell count (Sysmex XE-2100). We included in our study 2553 patients who were divided according to smoking status (active smokers: 512; nonactive smokers: 2041). Smokers were younger, more frequent males, with lower rate of diabetes mellitus, previous PCI and previous CABG (P<.001, respectively) and were in treatment less often with ARB, BB, nitrates, statins, ASA, clopidogrel, CCB and diuretics (P<.001, respectively) as compared to nonactive smokers. Higher percentage of smokers was observed in patients with higher IPF values, and at multivariate analysis, active smoking resulted as an independent predictor of higher IPF (adjusted OR [95% CI]=1.59[1.03-2.45], P=.035). Among smokers, higher IPF was associated with lower ejection fraction (P=.034), percentage of acute coronary syndrome (P=.002) and platelet count (P<.001) compared to ones with lower IPF. However, the IPF (according to quartiles values) was not associated with the prevalence and extent of CAD (82.5%, 80.4%, 86.1% and 80.9%, from 1st to 4th quartile, respectively, adjusted OR[95% CI]=0.98[0.79-1.23], P=.89) and severe CAD (31%, 31.1%, 39.1% and 35.2%, from 1st to 4th quartile, respectively, adjusted OR[95% CI]=1.03[0.86-1.23], P=.76). The present study shows an independent association between active smoking and the levels of immature platelet fraction in patients undergoing coronary angiography. However, among active smokers, IPF did not result as an independent predictor of CAD or severe CAD.

Abstract MP71: Ten Year Predicted Cardiovascular Disease Risk in Young Women With Adverse Pregnancy Outcomes

Introduction: Cardiovascular disease (CVD) is the leading cause of death among women. In stark contrast to mortality declines in other groups, CVD deaths to young women are increasing. CVD prediction in this group is imprecise, and how adverse pregnancy outcomes (APO) may unmask risk during the reproductive years is unknown. Hypothesis: Women with APO will have higher 10-year predicted CVD risk within 7 years following a first pregnancy compared to women with no APO. Study design: We enrolled 10,038 women at 8 sites in their first pregnancy and followed 4,500 through a CVD visit 2-7 years later. Presented here are results for the first 2,705 with lab results and no hypertension or diabetes before pregnancy. The Atherosclerotic CVD (ASCVD), American Health Association Healthy Heart, Pathobiological Determinants of Atherosclerosis in Youth (PDAY), and Reynolds risk scores were compared in women with preterm birth (PTB), preeclampsia/gestational hypertension (PE/GH), gestational diabetes (GDM), small for gestational age (SGA), and no adverse outcomes (no APO, referent). Results: As expected, 10-year predicted CVD risk was very low in women at a median age of 30, although differences at the tail of the distribution were detected based on APO history. Women with no APO had the lowest CVD risk. Women with PTB, PE/GH, GDM, or SGA had higher 10-year CVD risk as predicted by the ASCVD score compared to women with no APO (p&lt;0.05 for PTB and PE/GH). Six to 10% of women with these APOs had ASCVD scores greater than 5%. The PDAY score that predicts risk of coronary artery calcification in young adults was also higher in women with PE/GH or GDM than in those with no APO. Risk factors perturbed after delivery in women with APOs were blood pressure, BMI, waist circumference, HDL-cholesterol, triglycerides, glucose, and HbA1c. Conclusion: While risk scores customized for women of reproductive age are needed, those with a first pregnancy complicated by PTB, PE/GH or GDM have modest but detectable predicted 10-year CVD risk as soon as 2-7 years after delivery.

Precision Medicine for Assessing Coronary Artery Disease Risk in Asymptomatic Women with Familial Hypercholesterolaemia

Background: The determinants of coronary artery disease in women with familial hypercholesterolaemia (FH) have not been adequately investigated. The concept of cholesterol life-years suggests that those with a mutation may have higher coronary atherosclerotic plaque burden. Coronary computed tomography angiography (CCTA) reliably reflects this burden of disease.

Classical determinants of coronary artery disease as predictors of complexity of coronary lesions, assessed with the SYNTAX score.

BackgroundWe need new biomarkers that can predict cardiovascular disease to improve both diagnosis and therapeutic strategies. The CIRCULATING CELLS study was designed to study the role of several cellular mediators of atherosclerosis as biomarkers of coronary artery disease (CAD). An objective and reproducible method for the quantification of CAD extension is required to establish relationships with these potential biomarkers. We sought to analyse the correlation of the SYNTAX score with known CAD risk factors to test it as a valid marker of CAD extension.Methods and resultsA subgroup of 279 patients (67.4% males) were included in our analysis. Main exclusion criteria were a history of previous percutaneous coronary intervention or surgical revascularisation that prevent an accurate assessment of the SS. Diabetes mellitus, smoking, renal insufficiency, body mass index and a history of CAD and myocardial infarction were all positively and strongly associated with a higher SYNTAX score after adjustment for the non-modifiable biological factors (age and sex). In the multivariate model, age and male sex, along with smoking and renal insufficiency, remain statistical significantly associated with the SYNTAX score.ConclusionIn a selected cohort of revascularisation-naive patients with CAD undergoing coronary angiography, non-modifiable cardiovascular risk factors such as advanced age, male sex, as well as smoking and renal failure were independently associated with CAD complexity assessed by the SYNTAX score. The SYNTAX score may be a valid marker of CAD extension to establish relationships with potential novel biomarkers of coronary atherosclerosis.

Abstract P112: Genes in Genome-wide Association Study-identified Loci and Risk of Atherosclerosis in Adolescents and Young Adults

Background: Genome-wide association studies (GWASs) have identified multiple genomic loci associated with atherosclerotic diseases. However, specific genes underlying the observed associations are largely unknown. Objectives: We aimed to examine the associations between genes that harbor variants in high LD with index variants in GWAS-identified loci and pathologically determined atherosclerosis in major arteries from the Pathobiological Determinants of Atherosclerosis in Youth (PDAY) study. Methods and Results: Data for 1,938 single nucleotide polymorphisms (SNPs) from 28 genes were retrieved from whole exome sequence data. Atherosclerosis was confirmed by postmortem examination of major arteries from 1,005 young persons (aged 15-34 years) who died from non-cardiovascular causes. Logistic regression was used to evaluate associations between common SNPs and atherosclerosis controlling for age and sex. Gene-based analysis was conducted using Sequence Kernel Association Test (SKAT) method to test the combined effect of rare and common variants on atherosclerosis controlling for age and gender. All analyses were performed separately in blacks and whites. Statistical significance was determined by false positive discovery rate (FDR) method. In gene-based analyses, BUD13 ( P =1.11х10 -2 ) and COL4A1 ( P =3.58х10 -2 ) were associated with atherosclerosis among young blacks; none of the 28 genes was associated with atherosclerosis in whites. In single marker analysis of common SNPs, LRP1 missense variant rs7397167 ( P =8.50х10 -3 ), COL4A1 variant rs16975492 ( P =4.60х10 -3 ), STK32B variant rs168985 ( P =4.00х10 -3 ), and SMARCA4 variant rs8104480 ( P =1.20х10 -3 ) were associated with atherosclerosis in blacks; MIA3 variant rs17465637 ( P =8.00х10 -3 ), DUS4L missense variant rs6957510 ( P =6.4х10 -3 ), BOLL variant rs771018 ( P =6.2х10 -3 ), BUD3 missense variant rs11820589 ( P =2.1х10 -3 ), and COL4A1 variant rs1133219 ( P =1.8х10 -3 ) were associated with atherosclerosis in whites. Conclusion: Genes in GWAS-identified loci may play a role in the development of atherosclerosis at a young age.

Waist circumference compared with other obesity parameters as a determinant of coronary artery disease in essential hypertension: from statistics to clinical practice.

Waist circumference compared with other obesity parameters as a determinant of coronary artery disease in essential hypertension: from statistics to clinical practice

Waist circumference compared with other obesity parameters as determinants of coronary artery disease in essential hypertension: statistical issues to avoid misinterpretation.

Waist circumference compared with other obesity parameters as determinants of coronary artery disease in essential hypertension: statistical issues to avoid misinterpretation

Waist circumference compared with other obesity parameters as determinants of coronary artery disease in essential hypertension: a 6-year follow-up study.

This study aimed to assess the predictive role of body mass index (BMI), waist circumference (WC) and the waist-to-hip ratio (WHR) for the incidence of coronary artery disease (CAD) in a cohort of essential hypertensive patients. We followed up 2266 essential hypertensive individuals (mean age, 57.8 years; males, 1083; office blood pressure (BP), 143/89 mm Hg) who were free of cardiovascular disease for a mean period of 6 years. All subjects had at least one annual visit and, at baseline, underwent blood sampling and a complete echocardiographic study to determine the left ventricular (LV) mass index. CAD was defined as a history of myocardial infarction or significant coronary artery stenosis that was revealed by angiography or a coronary revascularization procedure. The incidence of CAD throughout the follow-up period was 2.33%. Hypertensive individuals who developed CAD (n=53) had a greater baseline WC (101.1±11.7 vs. 96.4±12 cm, P=0.005), WHR (0.94±0.07 vs. 0.89±0.08 cm, P<0.0001) and LV mass index (117±26.8 vs. 103.3±27 g m(-)(2), P<0.0001) compared with those without CAD at follow-up (n=2213), whereas no difference was observed compared with the baseline office BP and BMI values (P=NS for all). Using a multivariate Cox regression model, WC (hazard ratio (HR) 1.037, P=0.002) and LV mass index (HR 1.010, P=0.044) were found to be independent predictors of CAD. In essential hypertensive patients, WC could predict the future development of CAD, whereas BMI and WHR showed no independent prognostic value. These findings suggest that WC constitutes an easy clinical tool to assess risk in hypertension among individuals with obesity.

Associations between thrombophilic risk factors and determinants of atherosclerosis and inflammation in patients with non-arteritic anterior ischaemic optic neuropathy.

Non-arteritic anterior ischaemic optic neuropathy (NAION) is caused by ischaemia of the optic nerve head. The pathophysiology of NAION is unclear, and no proven effective treatment exists. We analyzed thrombophilic risk factors and determinants of atherosclerosis and inflammation in 109 consecutive patients and 109 age- and sex-matched volunteers using a case-control design. High levels of fibrinogen (>384 mg/dl; OR 3.2, p = 0.003), factors VIII:C (>183%; OR 2.6, p = 0.02), IX (>153%; OR 2.6, p = 0.026), XI (>142%; OR 3.4, p = 0.006), von Willebrand factor (activity >205%; OR 3.1, p = 0.005; antigen >194%; OR 3.5, p = 0.002), and triglycerides (>228 mg/dl; OR 2.8, p = 0.026), higher platelet counts (>294,000/μl; OR 2.5, p = 0.04), low levels of HDL cholesterol (<40 mg/dl; OR 2.7, p = 0.032), and an accelerated erythrocyte sedimentation rate (>20 mm/h; OR 4.4, p = 0.003) were associated with NAION. Our findings support the contention of a complex pathogenesis of NAION resulting from the coincidence of proatherogenic, prothrombotic and proinflammatory processes. The alterations described could be causative, side effects, or just coincidental findings.

Determinants of atherosclerosis in an Egyptian cohort of systemic sclerosis: Relation to disease activity and severity

BackgroundSystemic sclerosis (SSc) is a rare multi-system autoimmune disease characterized by vascular abnormalities with an increased prevalence of macrovascular disease. Aim of the workTo evaluate macro-vascular disease (atherosclerosis) in SSc patients and determine its relation to the disease activity and severity. Patients and methodsTwenty-five SSc patients and 20 matched controls were included. The modified Rodnan skin score (mRss) and disease severity by Medsger’s severity score were assessed. Carotid intima-media thickness (IMT) and flow mediated vasodilatation (FMD) of the brachial artery were measured. Traditional vascular risk factors were assessed by thorough history taking and laboratory investigations. ResultsThe age of the patients ranged from 15 to 60years and they were 22 females and 3 males. 15 had limited and 10 diffuse cutaneous SSc. All SSc patients had an increased IMT (1.24±0.29mm) which was normal in the control subjects (0.77±0.09mm) (p<0.0001). SSc patients had significantly lower HDL, thickened IMT and lower FMD than controls (p=0.005, p<0.0001 and p<0.0001 respectively). The younger age of disease onset was significantly associated with more FMD impairment (r=−0.4, p=0.04) and Medsger’s severity score (r=0.5, p=0.009). The mRss and Medsger’s severity score significantly correlated with the IMT (r=0.84, p=0.01 and r=0.56, p=0.003 respectively). A significant negative correlation was found between FMD and IMT (r=−0.77, p<0.0001). Medsger’s severity score significantly correlated with FMD (r=−0.44, p=0.02). ConclusionSSc is associated with an increased risk of atherosclerosis when compared to age and sex-matched controls. Determinants of this include; younger age of disease onset and more sever disease and low levels of HDL.

Abstract 18300: Association Between a Genetic Risk Score for Clinical CAD and Early Stage Lesions in the Coronary and Aorta Provides Insights Into the Pathophysiology of Atherosclerosis

Autopsy studies suggest that the fatty streak is the earliest identifiable lesion of atherosclerosis. However, not all fatty streaks progress to more advanced lesions of atherosclerosis. Furthermore, the correlation between the extent of fatty streaks in younger persons and the extent of more advanced lesions in older persons as well as the community rates of CAD is substantially lower for the aorta compared to the coronaries. These observations suggest that the pathophysiologic processes leading to the formation of fatty streaks and raised atherosclerotic lesions may differ between the two vascular beds. To test this hypothesis, we analyzed genetic data from 564 white participants of the Pathobiological Determinants of Atherosclerosis in Youth study between the age of 15 and 34 at the time of accidental death. We ranked subjects by the percent surface area of involvement of fatty streaks and raised lesions in their right coronary artery, thoracic aorta, and abdominal aorta, respectively, on post-mortem examination. We then defined cases within each lesion type and artery location as subjects with a sex specific ranking that was in the top quartile. We found a genetic risk score (GRS) composed of high-risk alleles at 32 loci for clinical CAD operating independent of traditional risk factors to be robustly associated with the probability of being a case for both fatty streaks and raised atherosclerotic lesions in the right coronary artery (Table). In contrast, the same GRS exhibited no association with case status for fatty streaks in the aorta and only a weak trend for association with case status for raised lesions in the aorta. Our findings support the notion that not all fatty streaks are equivalent in their predisposition to atherosclerosis and suggest that some atherosclerosis susceptibility loci uncovered through GWAS studies of clinical CAD may only be active in the coronary tree.

High visceral fat with low subcutaneous fat accumulation as a determinant of atherosclerosis in patients with type 2 diabetes.

BackgroundAbdominal visceral obesity has been reported to be associated with cardiovascular risks than body mass index, waist circumference, and abdominal subcutaneous fat. On the other hand, there is evidence that subcutaneous fat has a beneficial role against cardio-metabolic risks such as diabetes or dyslipidemia. However, little is known regarding the association between high visceral fat with low subcutaneous fat accumulation and the risk for atherosclerosis.MethodsThis study was designed to elucidate whether high visceral fat with low subcutaneous fat accumulation enhances the risk for atherosclerosis in patients with type 2 diabetes. This is a cross-sectional study of 148 patients with type 2 diabetes (mean age 65 ± 12 years; 44.5 % female). Visceral fat area (VFA, cm2) and subcutaneous fat area (SFA, cm2) were assessed by abdominal computed tomography. Carotid intima media thickness (CIMT, mm) measured by ultrasonography was used for the assessment of atherosclerosis. Patients were divided into four groups: SFA < 100 cm2 and VFA < 100 cm2 [S(−)V(−)], SFA ≥ 100 cm2 and VFA < 100 cm2 [S(+)V(−)], SFA < 100 cm2 and VFA ≥ 100 cm2 [S(−)V(+)], and SFA ≥ 100 cm2 and VFA ≥ 100 cm2 [S(+)V(+)]. Linear regression analysis with a stepwise procedure was used for the statistical analyses.ResultsAmong the patients examined, 16.3 % were S(−)V(+). Mean (95 % confidence interval) of CIMT adjusting for age and gender were 0.80 (0.69–0.91), 0.86 (0.72–1.01), 1.28 (1.11–1.44) and 0.83 (0.77–0.88) in patients with S(−)V(−), S(+)V(−), S(−)V(+) and S(+)V(+), respectively (p < 0.001). The S(−)V(+) patients exhibited significantly older than S(−)V(−) patients and those with S(+)V(+) and had a highest VFA-SFA ratio (V/S ratio) among the four groups. S(−)V(+) patients were male predominant (100 % male), and S(+)V(−) patients showed female predominance (82 % female). In multivariate linear regression analysis (Adjusted R2 = 0.549), S(−)V(+) was significantly associated with CIMT (Standardized β 0.423, p < 0.001). Notably, S(+)V(+) was inversely associated with CIMT in the multivariate model.ConclusionsThis study provides evidence that high visceral fat with low subcutaneous fat accumulation is an important determinant of carotid atherosclerosis and high subcutaneous fat could be protective against atherosclerosis in patients with type 2 diabetes.