The 9p21.3 Locus

Coronary artery calcium score and polygenic risk score have each separately been proposed as novel markers to identify risk of coronary heart disease (CHD), but no prior studies have directly compared these markers in the same cohorts. To evaluate change in CHD risk prediction when a coronary artery calcium score, a polygenic risk score, or both are added to a traditional risk factor-based model. Two observational population-based studies involving individuals aged 45 years through 79 years of European ancestry and free of clinical CHD at baseline: the Multi-Ethnic Study of Atherosclerosis (MESA) study involved 1991 participants at 6 US centers and the Rotterdam Study (RS) involved 1217 in Rotterdam, the Netherlands. Traditional risk factors were used to calculate CHD risk (eg, pooled cohort equations [PCEs]), computed tomography for the coronary artery calcium score, and genotyped samples for a validated polygenic risk score. Model discrimination, calibration, and net reclassification improvement (at the recommended risk threshold of 7.5%) for prediction of incident CHD events were assessed. The median age was 61 years in MESA and 67 years in RS. Both log (coronary artery calcium+1) and polygenic risk score were significantly associated with 10-year risk of incident CHD (hazards ratio per SD, 2.60; 95% CI, 2.08-3.26 and 1.43; 95% CI, 1.20-1.71, respectively), in MESA. The C statistic for the coronary artery calcium score was 0.76 (95% CI, 0.71-0.79) and for the polygenic risk score, 0.69 (95% CI, 0.63-0.71). The change in the C statistic when each was added to the PCEs was 0.09 (95% CI, 0.06-0.13) for the coronary artery calcium score, 0.02 (95% CI, 0.00-0.04) for the polygenic risk score, and 0.10 (95% CI, 0.07-0.14) for both. Overall categorical net reclassification improvement was significant when the coronary artery calcium score (0.19; 95% CI, 0.06-0.28) but was not significant when the polygenic risk score (0.04; 95% CI, -0.05 to 0.10) was added to the PCEs. Calibration of the PCEs and models with coronary artery calcium and/or polygenic risk scores was adequate (all χ2<20). Subgroup analysis stratified by the median age demonstrated similar findings. Similar findings were observed for 10-year risk in RS and in longer-term follow-up in MESA (median, 16.0 years). In 2 cohorts of middle-aged to older adults from the US and the Netherlands, the coronary artery calcium score had better discrimination than the polygenic risk score for risk prediction of CHD. In addition, the coronary artery calcium score but not the polygenic risk score significantly improved risk discrimination and risk reclassification for CHD when added to traditional risk factors.

Gene function can be described using various measures. We integrated association studies of three types of omics data to provide insights into the pathophysiology of subclinical coronary disease and myocardial infarction (MI). Using multivariable regression models, we associated: (1) single nucleotide polymorphism, (2) DNA methylation, and (3) gene expression with coronary artery calcification (CAC) scores and MI. Among 3106 participants of the Framingham Heart Study, 65 (2.1%) had prevalent MI and 60 (1.9%) had incident MI, median CAC value was 67.8 [IQR 10.8, 274.9], and 1403 (45.2%) had CAC scores > 0 (prevalent CAC). Prevalent CAC was associated with AHRR (linked to smoking) and EXOC3 (affecting platelet function and promoting hemostasis). CAC score was associated with VWA1 (extracellular matrix protein associated with cartilage structure in endomysium). For prevalent MI we identified FYTTD1 (down-regulated in familial hypercholesterolemia) and PINK1 (linked to cardiac tissue homeostasis and ischemia–reperfusion injury). Incident MI was associated with IRX3 (enhancing browning of white adipose tissue) and STXBP3 (controlling trafficking of glucose transporter type 4 to plasma). Using an integrative trans-omics approach, we identified both putatively novel and known candidate genes associated with CAC and MI. Replication of findings is warranted.

Heart Disease and Stroke Statistics—2009 Update

Comparison of coronary calcification among South Asians and Caucasians in the UK

Significance of a Positive Family History for Coronary Heart Disease in Patients With a Zero Coronary Artery Calcium Score (from the Multi-Ethnic Study of Atherosclerosis)

ObjectiveWe investigated the predictive value of clinical factors combined with coronary artery calcium (CAC) score based on a machine learning method for obstructive coronary heart disease (CAD) on coronary computed tomography angiography (CCTA) in individuals with atypical chest pain.MethodsThe study included data from 1,906 individuals undergoing CCTA and CAC scanning because of atypical chest pain and without evidence for the previous CAD. A total of 63 variables including traditional cardiovascular risk factors, CAC score, laboratory results, and imaging parameters were used to build the Random forests (RF) model. Among all the participants, 70% were randomly selected to train the models on which fivefold cross-validation was done and the remaining 30% were regarded as a validation set. The prediction performance of the RF model was compared with two traditional logistic regression (LR) models.ResultsThe incidence of obstructive CAD was 16.4%. The area under the receiver operator characteristic (ROC) for obstructive CAD of the RF model was 0.841 (95% CI 0.820–0.860), the CACS model was 0.746 (95% CI 0.722–0.769), and the clinical model was 0.810 (95% CI 0.788–0.831). The RF model was significantly superior to the other two models (p < 0.05). Furthermore, the calibration curve and Hosmer–Lemeshow test showed that the RF model had good classification performance (p = 0.556). CAC score, age, glucose, homocysteine, and neutrophil were the top five important variables in the RF model.ConclusionRF model was superior to the traditional models in the prediction of obstructive CAD. In clinical practice, the RF model may improve risk stratification and optimize individual management.

Pulse wave analysis and intima-media thickness (IMT) of carotid artery are the non-invasive indicators of subclinical atherosclerosis. Coronary artery calcification (CAC) score measured by multi-detector computed tomography (MDCT) is well known as a predictor of coronary heart disease (CHD). We investigated the association between coronary calcification assessed by MDCT and extracoronary atherosclerosis measured by pulse wave analysis and IMT of carotid artery. Arterial stiffness and carotid IMT were measured consecutively in 133 patients who underwent their first coronary MDCT angiography due to chest pain. Patients were divided into three groups according to the CAC score (group 1, score = 0, n = 62; group 2, 0 < score < 400, n = 58; group 3, score ≥ 400, n = 13). The classification of CAC score was associated with age, prevalence of hypertension and dyslipidemia, systolic blood pressure, pulse pressure, brachial-ankle pulse wave velocity, percentage of brachial mean artery pressure, upstroke time (UT), augmentation index, and carotid IMT. In a multivariate analysis, age (P = .048), hypertension (P = .007), dyslipidemia (P = .24), and mean ankle UT (P = .038) were independent variables for the classification of CAC score. The UT of pulse wave was significantly associated with the CAC score. The increased UT of pulse wave might provide incremental risk prediction in addition to that defined by conventional CHD risk assessment.

Long-term allogeneic hematopoietic cell transplant (allo-HCT) survivors suffer an elevated risk of coronary heart disease (CHD). We conducted a prospective, nonrandomized, cross-sectional study to screen asymptomatic survivors at a single allo-HCT center using cardiac computed tomography (CT) involving coronary CT angiography (CCTA) and the coronary artery calcium (CAC) score. Seventy-nine subjects with a median age of 39 years at allo-HCT and a median follow-up interval of 8 years were evaluated for CHD by Framingham Risk Score (FRS) and cardiac CT. CHD was detected in 33 of 79 (42%) subjects; 91% of lesions were nonobstructive, 19.5% of were noncalcified and 30% had associated valvular calcification. Overall, CAC was significantly superior to FRS in detecting early CHD in allo-HCT survivors [∆C = 0.25; P < 0.0001]. While both FRS and CAC were highly, >95% specific, FRS had a sensitivity, positive and negative predictive values of only 28% (95% CI, 14%–47%), 90% (95% CI, 55%–100%) and 60% (95% CI, 47%–73%), respectively. In contrast, the sensitivity, positive and negative predictive values of CAC were 78% (95% CI, 60%–91%), 96% (95% CI, 80%–100%) and 83% (95% CI, 69%–93%), respectively. Significantly, cardiac CT detected CHD in 23 of the 68 (34%) survivors deemed to have a low Framingham risk. Radiation exposure during cardiac CT was negligible, and there were no adverse events. In conclusion, CAC score with or without CCTA is a safe, feasible and sensitive screening technique for CHD. The FRS greatly underestimates CHD in allo-HCT survivors.

Guidelines advise that all adults undergo coronary heart disease (CHD) risk assessment to guide preventive treatment intensity. Although the Framingham Risk Score (FRS) is often recommended for this, it has been suggested that risk assessment may be improved by additional tests such as coronary artery calcium scoring (CACS). To determine whether CACS assessment combined with FRS in asymptomatic adults provides prognostic information superior to either method alone and whether the combined approach can more accurately guide primary preventive strategies in patients with CHD risk factors. Prospective observational population-based study, of 1461 asymptomatic adults with coronary risk factors. Participants with at least 1 coronary risk factor (>45 years) underwent computed tomography (CT) examination, were screened between 1990-1992, were contacted yearly for up to 8.5 years after CT scan, and were assessed for CHD. This analysis included 1312 participants with CACS results; excluded were 269 participants with diabetes and 14 participants with either missing data or had a coronary event before CACS was performed. Nonfatal myocardial infarction (MI) or CHD death. During a median of 7.0 years of follow-up, 84 patients experienced MI or CHD death; 70 patients died of any cause. There were 291 (28%) participants with an FRS of more than 20% and 221 (21%) with a CACS of more than 300. Compared with an FRS of less than 10%, an FRS of more than 20% predicted the risk of MI or CHD death (hazard ratio [HR], 14.3; 95% confidence interval [CI]; 2.0-104; P =.009). Compared with a CACS of zero, a CACS of more than 300 was predictive (HR, 3.9; 95% CI, 2.1-7.3; P<.001). Across categories of FRS, CACS was predictive of risk among patients with an FRS higher than 10% (P<.001) but not with an FRS less than 10%. These data support the hypothesis that high CACS can modify predicted risk obtained from FRS alone, especially among patients in the intermediate-risk category in whom clinical decision making is most uncertain.

Background/AimsHelicobacter pylori causes numerous extragastric manifestations, including coronary heart disease. The coronary artery calcification (CAC) score, measured using computed tomography (CT) has been used as a screening test for coronary atherosclerosis. This study investigated the association between H. pylori seropositivity and CAC scores in a screening population.MethodsPatients who underwent a health checkup between October 2003 and July 2007 and who did not have a history of ischemic heart disease were enrolled in the study. Subjects were screened with a multidetector CT scan to determine the CAC score and for anti-H. pylori antibody immunoglobulin G; traditional risks for coronary heart disease were evaluated using a structured questionnaire, anthropometric measurements, and laboratory tests.ResultsOf the 2,029 subjects enrolled (1,295 males), 1,214 (59.8%) subjects were H. pylori positive and 815 were H. pylori negative. There were no significant differences in the baseline characteristics of the seropositive and seronegative patients. When the CAC presence or absence scores were considered, multivariate analysis revealed that H. pylori seropositivity was statistically associated with the presence of CAC and that this association was stronger in the mild CAC score category.ConclusionsH. pylori seropositive patients are at a higher risk for coronary atherosclerosis regardless of traditional cardiovascular risk factors. This association is particularly applicable for early coronary atherosclerosis.

American Journal of Medical Genetics Part AVolume 131A, Issue 1 p. 109-110 Correspondence In reply to: Proving pathogenicity—when evolution is not enough Fernando Scaglia, Corresponding Author Fernando Scaglia [email protected] Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TexasAssistant Professor of Genetics, Department of Molecular and Human Genetics, Baylor College of Medicine, One Baylor Plaza, Houston, Texas, 77030.Search for more papers by this authorHannes Vogel, Hannes Vogel Department of Pathology, Stanford University, Stanford, CaliforniaSearch for more papers by this authorEdith P. Hawkins, Edith P. Hawkins Department of Pathology, Baylor College of Medicine, Houston, TexasSearch for more papers by this authorGeorgirene D. Vladutiu, Georgirene D. Vladutiu Department of Pediatrics, Division of Genetics, School of Medicine & Biomedical Sciences, State University of New York at Buffalo, Buffalo, New YorkSearch for more papers by this authorMin-Xin Guan, Min-Xin Guan Division and Program in Human Genetics and Center for Hearing and Deafness Research, Cincinnati Children's Hospital Medical Center, Cincinnati, OhioSearch for more papers by this authorLing-Ling Liu, Ling-Ling Liu Institute for Molecular and Human Genetics, Georgetown University Medical Center, Washington, DCSearch for more papers by this authorLee-Jun C. Wong, Lee-Jun C. Wong Institute for Molecular and Human Genetics, Georgetown University Medical Center, Washington, DCSearch for more papers by this author Fernando Scaglia, Corresponding Author Fernando Scaglia [email protected] Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TexasAssistant Professor of Genetics, Department of Molecular and Human Genetics, Baylor College of Medicine, One Baylor Plaza, Houston, Texas, 77030.Search for more papers by this authorHannes Vogel, Hannes Vogel Department of Pathology, Stanford University, Stanford, CaliforniaSearch for more papers by this authorEdith P. Hawkins, Edith P. Hawkins Department of Pathology, Baylor College of Medicine, Houston, TexasSearch for more papers by this authorGeorgirene D. Vladutiu, Georgirene D. Vladutiu Department of Pediatrics, Division of Genetics, School of Medicine & Biomedical Sciences, State University of New York at Buffalo, Buffalo, New YorkSearch for more papers by this authorMin-Xin Guan, Min-Xin Guan Division and Program in Human Genetics and Center for Hearing and Deafness Research, Cincinnati Children's Hospital Medical Center, Cincinnati, OhioSearch for more papers by this authorLing-Ling Liu, Ling-Ling Liu Institute for Molecular and Human Genetics, Georgetown University Medical Center, Washington, DCSearch for more papers by this authorLee-Jun C. Wong, Lee-Jun C. Wong Institute for Molecular and Human Genetics, Georgetown University Medical Center, Washington, DCSearch for more papers by this author First published: 14 September 2004 https://doi.org/10.1002/ajmg.a.30319Read the full textAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinkedInRedditWechat No abstract is available for this article. Volume131A, Issue115 November 2004Pages 109-110 RelatedInformation

Aims Screening for a high cardiovascular disease (CVD) risk followed by preventive treatment can potentially reduce coronary heart disease (CHD)-related morbidity and mortality. ROBINSCA (Risk Or Benefit IN Screening for CArdiovascular disease) is a population-based randomized controlled screening trial that investigates the effectiveness of CVD screening in asymptomatic participants using the Systematic COronary Risk Evaluation (SCORE) model or Coronary Artery Calcium (CAC) scoring. This study describes the distributions in risk and treatment in the ROBINSCA trial. Methods and results Individuals at expected elevated CVD risk were randomized (1:1:1) into the control arm (n=14,519; usual care); screening arm A (n=14,478; SCORE, 10-year fatal and non-fatal risk); or screening arm B (n=14,450; CAC scoring). Preventive treatment was largely advised according to current Dutch guidelines. Risk and treatment differences between the screening arms were analysed. 12,185 participants (84.2%) in arm A and 12,950 (89.6%) in arm B were screened. 48.7% were women, and median age was 62 (InterQuartile Range 10) years. SCORE screening identified 45.1% at low risk (SCORE&amp;lt;10%), 26.5% at intermediate risk (SCORE 10–20%), and 28.4% at high risk (SCORE≥20%). According to CAC screening, 76.0% were at low risk (Agatston&amp;lt;100), 15.1% at high risk (Agatston 100–399), and 8.9% at very high risk (Agatston≥400). CAC scoring significantly reduced the number of individuals indicated for preventive treatment compared to SCORE (relative reduction women: 37.2%; men: 28.8%). Conclusion We showed that compared to risk stratification based on SCORE, CAC scoring classified significantly fewer men and women at increased risk, and less preventive treatment was indicated. ROBINSCA flowchart Funding Acknowledgement Type of funding source: Public grant(s) – EU funding. Main funding source(s): Advanced Research Grant

Purpose To evaluate whether adding costal cartilage calcification (CCC) to coronary artery calcium (CAC) scores from chest CT improves coronary heart disease (CHD) prediction in patients with chronic kidney disease (CKD). Materials and Methods This study was a secondary analysis of the Multi-Ethnic Study of Atherosclerosis. Participants (April 2010 to January 2012) were stratified into low- and high-risk CKD groups based on Kidney Disease Improving Global Outcomes staging. CAC and CCC were measured from noncontrast CT scans. The primary outcome was incident CHD. Cox proportional hazards regression was performed for each group, with clinical risk factors and CAC (conventional CAC model), and with the addition of CCC (CCC model). Discriminative power was assessed using the area under the receiver operating characteristic curve (AUC). Results A total of 2355 participants (1314 female; median age, 68 years; IQR, 62-76) were included. Median baseline CAC scores were 22 (IQR, 0-183) and 133 (IQR, 20-649), and median CCC scores were 2055 (IQR, 900-4405) and 3187 (IQR, 1370-6516), for low- and high-risk CKD groups, respectively (P < .001 for CAC and P < .05 for CCC). The conventional CAC model showed lower discriminative power for CHD among the high-risk group (AUC, 0.70; 95% CI: 0.56, 0.84) versus the low-risk group (AUC, 0.74; 95% CI: 0.70, 0.78). Adding CCC improved the AUC to 0.75 (95% CI: 0.61, 0.89) in the high-risk group (P = .04), although there was no evidence of improved discrimination in the low-risk group (AUC, 0.74; 95% CI: 0.69, 0.78). Conclusion Clinical and conventional CAC models showed lower discriminative power for predicting CHD in the high-risk CKD group versus the low-risk group. In the high-risk group, adding CCC improved prediction over clinical models. Keywords: CT, Cardiac, Coronary Arteries, Coronary Artery Calcium Score, Costal Cartilage Calcification, Chronic Kidney Disease, Cardiovascular Disease, Coronary Heart Disease ClinicalTrials.gov identifier: NCT00005487 © RSNA, 2025.

Coronary evaluation in patients with stroke: Recognizing the risk

Comparison of coronary artery calcium detected by electron beam tomography in patients with to those without symptomatic coronary heart disease