AtheroSpectrum Reveals Novel Macrophage Foam Cell gene Signatures Associated with Atherosclerotic Cardiovascular Disease Risk

Circulation ◽  
2021 ◽  
Author(s):  
Chuan Li ◽  
Lili Qu ◽  
Alyssa J. Matz ◽  
Patrick A. Murphy ◽  
Yongmei Liu ◽  
...  
Keyword(s):  
Gene Expression ◽  
Risk Factors ◽  
Cardiovascular Disease ◽  
Prediction Model ◽  
Specific Gene ◽  
Ratio Test ◽  
Atherosclerotic Cardiovascular Disease ◽  
Gene Set ◽  
Inflammatory Status ◽  
Ascvd Risk

Background: While several interventions can effectively lower lipid levels in people at risk for atherosclerotic cardiovascular disease (ASCVD), cardiovascular event (CVE) risks remain, suggesting an unmet medical need to identify factors contributing to CVE risk. Monocytes and macrophages play central roles in atherosclerosis, but previous work has yet to provide a detailed view of macrophage populations involved in increased ASCVD risk. Methods: A novel macrophage foaming analytics tool, AtheroSpectrum, was developed using two quantitative indices depicting lipid metabolism and the inflammatory status of macrophages. Next, a machine-learning algorithm was developed to analyze gene expression patterns in the peripheral monocyte transcriptome of Multi-Ethnic Study of Atherosclerosis participants (MESA-set1, n=911). A list of 30 genes was generated and integrated with traditional risk factors to create an ASCVD risk prediction model (CR-30), which was subsequently validated in the remaining MESA-set2 (n=228); performance of CR-30 was also tested in two independent human atherosclerotic tissue transcriptome datasets (GTEx and GSE43292). Results: Using single-cell transcriptomic profiles (GSE97310, GSE116240, GSE97941, FR-FCM-Z23S), AtheroSpectrum detected two distinct programs in plaque macrophages: homeostatic-foaming and inflammatory pathogenic-foaming, the latter was positively associated with severity of atherosclerosis in multiple studies. A pool of 2209 pathogenic foaming genes was extracted and screened to select a subset of 30 genes correlated with CVE in MESA-set1. A CVD risk score model (CR-30) was then developed by incorporating this gene-set with traditional variables sensitive to CVE in MESA-set1 after cross-validation generalizability analysis. The performance of CR-30 was then tested in MESA-set2 (p=2.60×10 −4 , AUC=0.742), and two independent datasets (GTEx, p=7.32×10 −17 , AUC=0.664; GSE43292, p=7.04×10 −2 , AUC=0.633). Model sensitivity tests confirmed the contribution of the 30-gene panel to the prediction model (likelihood ratio test, df=31, p=0.03). Conclusions: Our novel computational program (AtheroSpectrum) identified a specific gene expression profile associated with inflammatory macrophage foam cells. A subset of 30 genes expressed in circulating monocytes jointly contributed to prediction of symptomatic atherosclerotic vascular disease. Incorporating a pathogenic foaming gene-set with known risk factors can significantly strengthen the power to predict ASCVD risk. Our programs may facilitate both mechanistic investigations and development of therapeutic and prognostic strategies for ASCVD risk.

Abstract P181: Atherogenic Lipoproteins and Incident Atherosclerotic Cardiovascular Disease in the Framingham Offspring Study

Circulation ◽  
2020 ◽  
Vol 141 (Suppl_1) ◽  
Author(s):  
Hiroaki Ikezaki ◽  
Elise Lim ◽  
Ching-Ti Liu ◽  
L Adrienne Cupples ◽  
Bela F Asztalos ◽  
...  
Keyword(s):  
Risk Factors ◽  
Cardiovascular Disease ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Lipoprotein Cholesterol ◽  
Atherosclerotic Cardiovascular Disease ◽  
Low Density ◽  
Low Density Lipoprotein Cholesterol ◽  
Significant Information ◽  
Ascvd Risk

Introduction: Elevated plasma low-density lipoprotein cholesterol (LDL-C), small-dense LDL-C (sdLDL-C), LDL-triglyceride (LDL-TG), triglycerides (TG), remnant-lipoprotein cholesterol (RLP-C), triglyceride-rich lipoprotein-C (TRL-C), very low-density lipoprotein cholesterol (VLDL-C), and lipoprotein(a) [Lp(a)] levels have been associated with increased atherosclerotic cardiovascular disease (ASCVD) risk. However, these parameters have not been included in risk factors for ASCVD in the pooled cohort equation (PCE). Hypothesis: We assessed the hypothesis that these atherogenic lipoprotein parameters add significant information for ASCVD risk prediction in the Framingham Offspring Study. Methods: We evaluated 3,147 subjects without ASCVD at baseline (mean age 58 years) from participants of Framingham Offspring Study cycle 6, 677 (21.5%) of whom developed inclusive ASCVD over 16 years. Biomarkers of risk were assessed in frozen plasma samples. Total cholesterol, TG, HDL-C, direct LDL-C, sdLDL-C, LDL-TG, Lp(a), RLP-C, and TRL-C were measured by standardized automated analysis. Calculated LDL-C, large buoyant low-density lipoprotein cholesterol (lbLDL-C), VLDL-C, and non-HDL-C values were calculated. Data were analyzed using Cox proportional regression analysis and net reclassification improvement (NRI) analysis to identify parameters significantly associated with the incidence of ASCVD after controlling for standard ASCVD risk factor and applying the PCE model. Results: All specialized lipoprotein parameters were significant ASCVD risk factors on univariate analysis, but only direct LDL-C, sdLDL-C, and Lp(a) were significant on multivariate analysis with standard risk factors in the model. Together these parameters significantly improved the model c statistic (0.716 vs 0.732, P < 0.05) and net risk reclassification (mean NRI 0.104, P < 0.01) for ASCVD risk. Using the ASCVD risk pooled cohort equation, sdLDL-C, TG, LDL-TG, LDL-C, RLP-C, and TRL-C individually added significant information, but no other parameter added significant information with sdLDL-C (hazard ratio 1.30 for 75th vs 25th percentile, P < 0.0001) in the model. Conclusions: In multivariate analysis, sdLDL-C, direct LDL-C, and Lp(a) contributed significantly to ASCVD risk, but only sdLDL-C added significant risk information to the PCE model, indicating that sdLDL-C may be the most atherogenic lipoprotein particle.

scholarly journals Cardiovascular Risk Awareness and Calculated 10-Year Risk Among Female Employees at Taibah University 2019

2021 ◽  
Vol 9 ◽  
Author(s):  
Amal M. Qasem Surrati ◽  
Walaa Mohammedsaeed ◽  
Ahlam B. El Shikieri
Keyword(s):  
Risk Factors ◽  
Cardiovascular Disease ◽  
High Risk ◽  
Low Risk ◽  
Abdominal Circumference ◽  
Atherosclerotic Cardiovascular Disease ◽  
Cvd Risk ◽  
Limited Knowledge ◽  
Ascvd Risk ◽  
Risk Estimator

Cardiovascular diseases (CVD) are the most common cause of death and disability worldwide. Saudi Arabia, one of the middle-income countries has a proportional CVD mortality rate of 37%. Knowledge about CVD and its modifiable risk factors is a vital pre-requisite to change the health attitudes, behaviors, and lifestyle practices of individuals. Therefore, we intended to assess the employee knowledge about risk of CVD, symptoms of heart attacks, and stroke, and to calculate their future 10-years CVD risk. An epidemiological, cross-sectional, community-facility based study was conducted. The women aged ≥40 years who are employees of Taibah University, Al-Madinah Al-Munawarah were recruited. A screening self-administrative questionnaire was distributed to the women to exclude those who are not eligible. In total, 222 women met the inclusion criteria and were invited for the next step for the determination of CVD risk factors by using WHO STEPS questionnaire: It is used for the surveillance of non-communicable disease risk factor, such as CVD. In addition, the anthropometric measurements and biochemical measurements were done. Based on the identified atherosclerotic cardiovascular disease (ASCVD) risk factors and laboratory testing results, risk calculated used the Framingham Study Cardiovascular Disease (10-year) Risk Assessment. Data were analyzed using GraphPad Prism 7 software (GraphPad Software, CA, USA). The result showed the mean age of study sample was 55.6 ± 9.0 years. There was elevated percentage of obesity and rise in abdominal circumference among the women. Hypertension (HTN) was a considerable chronic disease among the participants where more than half of the sample had it, i.e., 53%. According to the ASCVD risk estimator, the study participants were distributed into four groups: 63.1% at low risk, 20.2% at borderline risk, 13.5% at intermediate risk, and 3.2% at high risk. A comparison between these categories based on the CVD 10-year risk estimator indicated that there were significant variations between the low-risk group and the intermediate and high-risk groups (P = 0.02 and P = 0.001, respectively). The multivariate analysis detected factors related to CVD risk for women who have an intermediate or high risk of CVD, such as age, smoking, body mass index (BMI), unhealthy diet, blood pressure (BP) measurements, and family history of CVD (P &lt; 0.05). The present study reports limited knowledge and awareness of CVD was 8.6 that is considered as low knowledge. In conclusion, the present study among the university sample in Madinah reported limited knowledge and awareness of CVD risk. These findings support the need for an educational program to enhance the awareness of risk factors and prevention of CVD.

Abstract MP53: The Impact of the Obesity Epidemic on Atherosclerotic Cardiovascular Disease Risk Scores: The CARDIA Study

Circulation ◽  
2015 ◽  
Vol 131 (suppl_1) ◽  
Author(s):  
Duke Appiah ◽  
Pamela J Schreiner ◽  
Raegan W Durant ◽  
Sharina D Person ◽  
Catarina I Kiefe ◽  
...  
Keyword(s):  
Risk Factors ◽  
Cardiovascular Disease ◽  
Young Adults ◽  
Disease Risk ◽  
Risk Scores ◽  
Atherosclerotic Cardiovascular Disease ◽  
Cvd Risk ◽  
Obesity Epidemic ◽  
Ascvd Risk ◽  
The Impact

Introduction: Cardiovascular disease (CVD) mortality has decreased over recent decades, in part, due to changes in the prevalence of risk factors. However, few studies have explored the impact of the obesity epidemic on CVD risk prediction in young adults. Hypothesis: We assessed the hypothesis that BMI trends are positively associated with changes in 10-year AHA/ACC atherosclerotic cardiovascular disease (ASCVD) risk scores from young adulthood to middle age beyond the effect of other CVD risk factors included in the scores (age, sex, race, lipids, blood pressure, hypertension medication, diabetes, smoking). METHODS: Data were obtained from 2437 black and white men and women aged 18-30 years at baseline (1985-1986) enrolled in the Coronary Artery Risk Development in Young Adults (CARDIA) study with follow-up exams at year 0, 5, 10, 15, 20 and 25 (ages 43-55 years). Repeated-measures regression was used to model the association between ASCVD risk scores and time-varying BMI measures. RESULTS: The average 10-year ASCVD risk increased from 0.6% at baseline (mean age: 25.3) to 3.9% at year 25 (mean age: 50.3) with the change higher for men (blacks: 1.0 to 8.2%, whites: 0.3 to 4.6%) than women (blacks: 0.5 to 3.6%, whites: 1.2 to 1.4%). The overall prevalence of obesity at baseline and year 25 was 10% and 42% respectively. BMI trends were positively associated with 10-year change in ASCVD risk scores (0.12% per 1 kg/m2 increase, p<0.001). BMI adjustment minimally reduced risk scores trends with the greatest change between unadjusted and adjusted risk scores observed among black women (0.1 to 3.0%) (Figures A and B). CONCLUSION: In young adults, BMI trends are associated positively with 10-year changes in ASCVD risk independent of other risk factors. This adds to the evidence that weight control in early adulthood is an important predictor of lower future CVD risk.

Association of Impaired Fasting Glucose with Cardiovascular Disease in the Absence of Risk Factor

2021 ◽  
Author(s):  
Yingting Zuo ◽  
Xinsheng Han ◽  
Xue Tian ◽  
Shuohua Chen ◽  
Shouling Wu ◽  
...  
Keyword(s):  
Risk Factors ◽  
Cardiovascular Disease ◽  
Impaired Fasting Glucose ◽  
Proportional Hazards ◽  
Fasting Glucose ◽  
Cox Proportional Hazards ◽  
Atherosclerotic Cardiovascular Disease ◽  
Primordial Prevention ◽  
Increased Risk ◽  
Ascvd Risk

Abstract Background The association between impaired fasting glucose (IFG) and cardiovascular disease (CVD) in participants without atherosclerotic cardiovascular disease (ASCVD) risk factors based on current definitions is unclear. The study aimed to examine the association of fasting glucose levels with CVD and its subtypes in persons without ASCVD risk factors. Methods This study included 38,297 participants (men, 62.1%; mean age, 47.9 [12.9] years) who were free of a history of CVD, absent of ASCVD risk factors, and had a fasting plasma glucose (FPG) level between 70 to 125 mg/dl at baseline from Kailuan Study during 2006 to 2007, participants were followed up until new-onset CVD event, death or December 31, 2017. Cox proportional hazards models were performed to evaluate the associations. Results During a median follow-up of 11.0 years (interquartile range, 10.7-11.2 years), we observed 1,217 incident CVD events. Compared with participants with FPG 70 to 99 mg/dl, the multivariable adjusted hazard ratios for CVD among participants with FPG 100 to 109 mg/dl and 110 to 125 mg/dl were 1.18 (95% confidence interval [CI], 1.02-1.38) and 1.27 (95%CI, 1.03-1.55), respectively. Multivariable-adjusted spline regression model showed a J-shaped association between FPG and the risk of CVD. Conclusions We found that among individuals without diabetes or other traditional ASCVD risk factors, there is an increased risk of incident CVD with increasing abnormal FPG levels. These results highlight the importance of primordial prevention for FPG level increases along with other traditional ASCVD risk factors.

Abstract 15661: Discordant LDL-C Estimates and Incident Atherosclerotic Cardiovascular Disease: The Dallas Heart Study

Circulation ◽  
2020 ◽  
Vol 142 (Suppl_3) ◽  
Author(s):  
Nicholas Macpherson ◽  
Nestor Vasquez ◽  
Amit Khera ◽  
Anand Rohatgi ◽  
Seth S Martin ◽  
...  
Keyword(s):  
Risk Factors ◽  
Cardiovascular Disease ◽  
Lipid Lowering ◽  
Atherosclerotic Cardiovascular Disease ◽  
Lipid Lowering Therapy ◽  
The Metabolic Syndrome ◽  
Heart Study ◽  
Lipid Panel ◽  
Ascvd Risk ◽  
Dallas Heart Study

Introduction: The Friedewald equation (F-LDL-C) and the Martin-Hopkins algorithm (MH-LDL-C) estimate direct LDL-C from a standard lipid panel. Discordant LDL-C estimates by the two methods may carry significant clinical implications. We evaluated the clinical variables associated with discordant LDL-C estimates and the association of discordance with risk of incident atherosclerotic cardiovascular disease (ASCVD) in the Dallas Heart Study (DHS), a multi-ethnic, population based prospective cohort. Methods: We estimated F-LDL-C and MH-LDL-C in 2824 DHS participants (42% male; mean age 43.5 years) with TG ≤ 400 mg/dL, who were not on baseline lipid lowering therapy and were free of prior ASCVD. We divided the cohort into quintiles of LDL-C discordance (MH-LDL-C minus F-LDL-C, in mg/dL) and assessed associations with ASCVD risk factors. We evaluated associations between discordance and incident ASCVD by sequentially adjusted Cox regression models, and we generated restricted cubic spline plots of discordance and hazard for ASCVD. Results: There were 228 ASCVD events over a median of 12.3 years. Clinical characteristics across discordance quintiles are shown in the Table . After adjustment for traditional ASCVD risk factors, there was a linear association between higher LDL-C discordance and increased risk of ASCVD events ( Figure ) with the highest hazard in Quintile 5 (HR 1.5, 95% CI 1.1 - 2.0). Conclusions: Discordant LDL-C estimates were largely associated with male sex, White and Hispanic races, and characteristics of the metabolic syndrome. Individuals in the highest quintile of discordant LDL-C estimates, with MH-LDL-C > F-LDL-C, had greater risk for incident ASCVD.

scholarly journals Risk factors for venous thromboembolism and atherosclerotic cardiovascular disease: do they differ in patients with rheumatoid arthritis?

RMD Open ◽  
2021 ◽  
Vol 7 (2) ◽  
pp. e001618
Author(s):  
Gulsen Ozen ◽  
Sofia Pedro ◽  
Rebecca Schumacher ◽  
Teresa Simon ◽  
Kaleb Michaud
Keyword(s):  
Rheumatoid Arthritis ◽  
Risk Factors ◽  
Cardiovascular Disease ◽  
Venous Thromboembolism ◽  
Disease Risk ◽  
Cardiovascular Disease Risk ◽  
Cox Proportional Hazards ◽  
Hospital Death ◽  
Atherosclerotic Cardiovascular Disease ◽  
Ascvd Risk

ObjectiveVenous thromboembolism (VTE) is an increasing concern in rheumatoid arthritis (RA) with little known about risk factors. We aimed to compare risk factors for unprovoked VTE and atherosclerotic cardiovascular disease (ASCVD) in patients with RA and to assess subsequent ASCVD risk after an unprovoked VTE.MethodsPeople with RA participating in a US-wide longitudinal observational registry from 1998 to 2018 were assessed for incident unprovoked VTE (deep venous thrombosis and pulmonary emboli not associated with cancer, recent surgery, hospitalisation, fracture and pregnancy) and ASCVD (myocardial infarction and stroke) validated from hospital/death records. Risk factors for VTE and ASCVD and the risk of ASCVD after an unprovoked VTE were determined using Cox proportional hazards models.ResultsDuring median (IQR) 4 (1.5–7) years of follow-up in 31 366 patients with RA, 539 unprovoked VTE and 1648 ASCVD events were identified. The adjusted models showed increased VTE and ASCVD risk with older age, male sex, comorbidities, prior fracture, worse disability, higher disease activity and glucocorticoids. Traditional cardiovascular disease risk factors were common in both ASCVD and VTE but only increased ASCVD risk with obesity as the exception (VTE HR (95% CI), 1.46 (1.13–1.87)) and ASCVD, 0.58 (0.50–0.68)). ASCVD risk doubled after an unprovoked VTE (HR (95% CI), 2.05 (1.43–2.95)).ConclusionOur findings suggest that unprovoked VTE is mediated by inflammation of RA and may be considered a spectrum of pan-cardiovascular syndrome.

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

2021 ◽  
Vol 28 (Supplement_1) ◽  
Author(s):  
M Wong ◽  
J Yap ◽  
KK Yeo
Keyword(s):  
Risk Factors ◽  
Cardiovascular Disease ◽  
Coronary Artery ◽  
Coronary Atherosclerosis ◽  
Ldl Cholesterol ◽  
Multivariable Analysis ◽  
Asian Population ◽  
Atherosclerotic Cardiovascular Disease ◽  
Age And Gender ◽  
And Gender

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

scholarly journals Protective effects of a unique combination of nutritionally active ingredients on risk factors and gene expression associated with atherosclerosis in C57BL/6J mice fed a high fat diet

2021 ◽  
Author(s):  
Joe W. E. Moss ◽  
Jessica O Williams ◽  
Wijdan Al-Ahmadi ◽  
Victoria O'Morain ◽  
Yee-Hung Chan ◽  
...  
Keyword(s):  
Gene Expression ◽  
Risk Factors ◽  
Cardiovascular Disease ◽  
High Fat Diet ◽  
Inflammatory Disorder ◽  
Protective Effects ◽  
Unique Combination ◽  
Omega 3 ◽  
High Fat ◽  
Food Ingredients

Atherosclerosis, an inflammatory disorder of the vasculature and the underlying cause of cardiovascular disease, is responsible for one in three global deaths. Consumption of active food ingredients such as omega-3...

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