scholarly journals Genome-Wide Polygenic Score, Clinical Risk Factors, and Long-Term Trajectories of Coronary Artery Disease

2020 ◽  
Vol 40 (11) ◽  
pp. 2738-2746
Author(s):  
George Hindy ◽  
Krishna G. Aragam ◽  
Kenney Ng ◽  
Mark Chaffin ◽  
Luca A. Lotta ◽  
...  

Objective: To determine the relationship of a genome-wide polygenic score for coronary artery disease (GPS CAD ) with lifetime trajectories of CAD risk, directly compare its predictive capacity to traditional risk factors, and assess its interplay with the Pooled Cohort Equations (PCE) clinical risk estimator. Approach and Results: We studied GPS CAD in 28 556 middle-aged participants of the Malmö Diet and Cancer Study, of whom 4122 (14.4%) developed CAD over a median follow-up of 21.3 years. A pronounced gradient in lifetime risk of CAD was observed—16% for those in the lowest GPS CAD decile to 48% in the highest. We evaluated the discriminative capacity of the GPS CAD —as assessed by change in the C-statistic from a baseline model including age and sex—among 5685 individuals with PCE risk estimates available. The increment for the GPS CAD (+0.045, P <0.001) was higher than for any of 11 traditional risk factors (range +0.007 to +0.032). Minimal correlation was observed between GPS CAD and 10-year risk defined by the PCE ( r =0.03), and addition of GPS CAD improved the C-statistic of the PCE model by 0.026. A significant gradient in lifetime risk was observed for the GPS CAD , even among individuals within a given PCE clinical risk stratum. We replicated key findings—noting strikingly consistent results—in 325 003 participants of the UK Biobank. Conclusions: GPS CAD —a risk estimator available from birth—stratifies individuals into varying trajectories of clinical risk for CAD. Implementation of GPS CAD may enable identification of high-risk individuals early in life, decades in advance of manifest risk factors or disease.

2021 ◽  
Vol 8 ◽  
Author(s):  
Hui Chen ◽  
Zixian Wang ◽  
Min Qin ◽  
Bin Zhang ◽  
Lu Lin ◽  
...  

Background: Coronary stenosis severity determines ischemic symptoms and adverse outcomes. The metabolomic analysis of human fluids can provide an insight into the pathogenesis of complex disease. Thus, this study aims to investigate the metabolomic and lipidomic biomarkers of coronary artery disease (CAD) severity and to develop diagnostic models for distinguishing individuals at an increased risk of atherosclerotic burden and plaque instability.Methods: Widely targeted metabolomic and lipidomic analyses of plasma in 1,435 CAD patients from three independent centers were performed. These patients were classified as stable coronary artery disease (SCAD), unstable angina (UA), and myocardial infarction (MI). Associations between CAD stages and metabolic conditions were assessed by multivariable-adjusted logistic regression. Furthermore, the least absolute shrinkage and selection operator logistic-based classifiers were used to identify biomarkers and to develop prediagnostic models for discriminating the diverse CAD stages.Results: On the basis of weighted correlation network analysis, 10 co-clustering metabolite modules significantly (p &lt; 0.05) changed at different CAD stages and showed apparent correlation with CAD severity indicators. Moreover, cross-comparisons within CAD patients characterized that a total of 72 and 88 metabolites/lipid species significantly associated with UA (vs. SCAD) and MI (vs. UA), respectively. The disturbed pathways included glycerophospholipid metabolism, and cysteine and methionine metabolism. Furthermore, models incorporating metabolic and lipidomic profiles with traditional risk factors were constructed. The combined model that incorporated 11 metabolites/lipid species and four traditional risk factors represented better discrimination of UA and MI (C-statistic = 0.823, 95% CI, 0.783–0.863) compared with the model involving risk factors alone (C-statistic = 0.758, 95% CI, 0.712–0.810). The combined model was successfully used in discriminating UA and MI patients (p &lt; 0.001) in a three-center validation cohort.Conclusion: Differences in metabolic profiles of diverse CAD subtypes provided a new approach for the risk stratification of unstable plaque and the pathogenesis decipherment of CAD progression.


Angiology ◽  
2021 ◽  
pp. 000331972110280
Author(s):  
Sukru Arslan ◽  
Ahmet Yildiz ◽  
Okay Abaci ◽  
Urfan Jafarov ◽  
Servet Batit ◽  
...  

The data with respect to stable coronary artery disease (SCAD) are mainly confined to main vessel disease. However, there is a lack of information and long-term outcomes regarding isolated side branch disease. This study aimed to evaluate long-term major adverse cardiac and cerebrovascular events (MACCEs) in patients with isolated side branch coronary artery disease (CAD). A total of 437 patients with isolated side branch SCAD were included. After a median follow-up of 38 months, the overall MACCE and all-cause mortality rates were 14.6% and 5.9%, respectively. Among angiographic features, 68.2% of patients had diagonal artery and 82.2% had ostial lesions. In 28.8% of patients, the vessel diameter was ≥2.75 mm. According to the American College of Cardiology lesion classification, 84.2% of patients had either class B or C lesions. Age, ostial lesions, glycated hemoglobin A1c, and neutrophil levels were independent predictors of MACCE. On the other hand, side branch location, vessel diameter, and lesion complexity did not affect outcomes. Clinical risk factors seem to have a greater impact on MACCE rather than lesion morphology. Therefore, the treatment of clinical risk factors is of paramount importance in these patients.


Circulation ◽  
2000 ◽  
Vol 102 (11) ◽  
pp. 1227-1232 ◽  
Author(s):  
Jeffrey L. Anderson ◽  
Joseph B. Muhlestein ◽  
Benjamin D. Horne ◽  
John F. Carlquist ◽  
Tami L. Bair ◽  
...  

2008 ◽  
Vol 9 (1) ◽  
pp. 146
Author(s):  
G. Tacoy ◽  
S. Balcioglu ◽  
S. Akinci ◽  
S.A. Kocaman ◽  
G.E. Yazici ◽  
...  

2014 ◽  
Vol 25 (6) ◽  
pp. 1124-1129 ◽  
Author(s):  
Jalaj Garg ◽  
Parasuram Krishnamoorthy ◽  
Chandrasekar Palaniswamy ◽  
Rajiv Paudel ◽  
Saurav Chatterjee ◽  
...  

AbstractBackground: Accelerated coronary atherosclerosis in patients with Kawasaki disease, in conjunction with coronary artery aneurysm and stenosis that characterise this disease, are potential risk factors for developing coronary artery disease in young adults. We aimed to determine the prevalence and predictors of coronary artery disease in adult patients with Kawasaki disease. Methods: All patients aged 18−55 years of age diagnosed with Kawasaki disease were sampled from Nationwide Inpatient Sample database using International Classification of Diseases 9th revision (ICD 9 code 446.1) from 2009 to 2010. Demographics, prevalence of coronary artery disease, and other traditional risk factors in adult patients with Kawasaki disease were analysed using ICD 9 codes. Results: The prevalence of Kawasaki disease among adults was 0.0005% (n=215) of all in-hospital admissions in United States. The mean age was 27.3 years with women (27.6 years) older than men (27.1 years). Traditional risk factors were hypertension (21%), hyperlipidaemia (15.6%), diabetes (11.5%), tobacco use (8.8%), and obesity (8.8%), with no significant difference between men and women. Coronary artery disease (32.4%), however, was more prevalent in men (44.7%) than in women (12.1%; p=0.03). In multivariate regression analysis, after adjusting for demographics and traditional risk factors, hypertension (OR=13.2, p=0.03) was an independent risk factor of coronary artery disease. Conclusion: There was increased preponderance of coronary artery disease in men with Kawasaki disease. On multivariate analysis, hypertension was found to be the only independent predictor of coronary artery disease in this population after adjusting for other risk factors.


Author(s):  
Roopali Khanna ◽  
Avinash Bansal ◽  
Sudeep Kumar ◽  
Naveen Garg ◽  
Satyendra Tewari ◽  
...  

Background Incidence of coronary artery disease (CAD) increases significantly in postmenopausal women, which is assumed to be an imbalance between serum androgen and estrogen levels. However, studies assessing serum sex hormones and CAD are few and have shown conflicting results. Objective To compare serum sex hormone levels and traditional risk factors among postmenopausal women with angiographically proven CAD and without CAD. Method The study included consecutive postmenopausal women undergoing coronary angiography in our institute from May 2016 to June 2017. The clinical and coronary angiographic data and traditional risk factors were assessed. Fasting serum levels of estradiol (E2), testosterone (T), sex hormone-binding globulin (SHBG), dehydroepiandrosterone sulfate (DHEA-S), and insulin were measured. Results A total of 121 postmenopausal women were included in the study; 69 were CAD and 52 without CAD. Single-vessel disease was most common (55.1%), followed by double-vessel disease (24.6%) and triple-vessel disease (20.3%). Women with CAD had significantly lower estradiol/testosterone (E2/T) ratio (3.7 ± 2.6 vs. 5.4 ± 4.2, p = 0.008) compared with non-CAD group. SHBG, DHEA-S, and insulin levels were similar in CAD and non-CAD groups. The serum level of estradiol predicted the E2/T ratio (r = 0.316, p < 0.001) and positively associated with DHEA (r = 0.181, p = 0.047). Testosterone was negatively associated with E2/T ratio (r = – 0.682, p < 0.001). There was no significant correlation of estrogen, testosterone, or E2/T ratio to lipid profile (total cholesterol, HDL, LDL) in women with CAD. Conclusion E2/T ratio was significantly lowered in postmenopausal women with CAD. E2/T ratio may be a used a predictor of CAD in postmenopausal women


2019 ◽  
Vol 40 (Supplement_1) ◽  
Author(s):  
S E Lee ◽  
G Pontone ◽  
I Gottlieb ◽  
M Hadamitzky ◽  
J A Leipsic ◽  
...  

Abstract Background It is still debatable whether the so-called high-risk plaque (HRP) simply represents a certain phase during the natural history of coronary atherosclerotic plaques or the disease progression would differ according to the presence of HRP. Purpose We determined whether the pattern of non-obstructive lesion progression into obstructive lesions would differ according to the presence of HRP. Methods Patients with non-obstructive coronary artery disease, defined as % diameter stenosis (%DS) ≥50%, were enrolled from a prospective, multinational registry of consecutive patients who underwent serial coronary computed tomography angiography at an inter-scan interval of ≥2 years. HRP was defined as lesions with ≥2 of positive remodelling, spotty calcification, and low-attenuation plaque. The total and compositional percent atheroma volume (PAV) at baseline and annualized PAV change were compared between non-HRP and HRP lesions. Results A total of 1,115 non-obstructive lesions were identified from 327 patients (61.1±8.9 years old, 66.0% male). There were 690 non-HRP and 425 HRP lesions. HRP lesions possessed greater PAV and %DS at baseline compared to non-HRP lesions. However, the annualized total and non-calcified PAV change were greater in non-HRP lesions than in HRP lesions. On multivariate analysis, addition of baseline PAV and %DS to clinical risk factors improved the predictive power of the model (Table). When clinical risk factors, PAV, %DS, and HRP were all adjusted on Model 3, only baseline PAV and %DS independently predicted the development of obstructive lesions (hazard ratio (HR) 1.046 [95% confidence interval (CI): 1.026–1.066] and HR 1.087 [95% CI: 1.055–1.119], respectively, all p<0.001), while HRP did not (p>0.05). Comparison of C-statistics of per-lesion analysis to predict progression to obstructive lesion C-statistics (95% CI) P Model 1: Baseline PAV 0.880 (0.879–0.884) – Model 2: Model 1 + baseline %DS 0.938 (0.937–0.939) vs. Model 1: <0.001 Model 3: Model 2 + HRP 0.935 (0.934–0.937) vs. Model 2: 0.004 Adjusted for age, male sex, hypertension, diabetes mellitus, hyperlipidemia, family history of coronary artery disease, smoking, body mass index, and statin use. Conclusion The pattern of individual coronary atherosclerotic plaque progression differed according to the presence of HRP. Baseline PAV was the most important predictor for lesions developing into obstructive lesions rather than the presence of HRP features at baseline. Acknowledgement/Funding This work was supported by the National Research Foundation of Korea funded by the Ministry of Science and ICT (Grant No. 2012027176).


Sign in / Sign up

Export Citation Format

Share Document