Development and Validation of a Simple-to-Use Nomogram for Predicting 5-, 10-, and 15-Year Survival in Asymptomatic Adults Undergoing Coronary Artery Calcium Scoring

Ó,Hartaigh, Brí,ain,Gransar, Heidi,Callister, Tracy,Shaw, Leslee J.,Schulman-Marcus, Joshua,Stuijfzand, Wijnand J.,Valenti, Valentina,Cho, Iksung,Szymonifka, Jackie,Lin, Fay Y.,Berman, Dan Elsevier 2018 JACC CARDIOVASCULAR IMAGING Vol.11 No.3

<P><B>Abstract</B></P> <P><B>Objectives</B></P> <P>The purpose of this study was to develop and validate a simple-to-use nomogram for prediction of 5-, 10-, and 15-year survival among asymptomatic adults.</P> <P><B>Background</B></P> <P>Simple-to-use prognostication tools that incorporate robust methods such as coronary artery calcium scoring (CACS) for predicting near-, intermediate- and long-term mortality are warranted.</P> <P><B>Methods</B></P> <P>In a consecutive series of 9,715 persons (mean age: 53.4 ± 10.5 years; 59.3% male) undergoing CACS, we developed a nomogram using Cox proportional hazards regression modeling that included: age, sex, smoking, hypertension, dyslipidemia, diabetes, family history of coronary artery disease, and CACS. We developed a prognostic index (PI) summing the number of risk points corresponding to weighted covariates, which was used to configure the nomogram. Validation of the nomogram was assessed by discrimination and calibration applied to a separate cohort of 7,824 adults who also underwent CACS.</P> <P><B>Results</B></P> <P>A total of 936 and 294 deaths occurred in the derivation and validation sets at a median follow-up of 14.6 years (interquartile range: 13.7 to 15.5 years) and 9.4 years (interquartile range: 6.8 to 11.5 years), respectively. The developed model effectively predicted 5-, 10-, and 15-year probability of survival. The PI displayed high discrimination in the derivation and validation sets (C-index 0.74 and 0.76, respectively), indicating suitable external performance of our nomogram model. The predicted and actual estimates of survival in each dataset according to PI quartiles were similar (though not identical), demonstrating improved model calibration.</P> <P><B>Conclusions</B></P> <P>A simple-to-use nomogram effectively predicts 5-, 10- and 15-year survival for asymptomatic adults undergoing screening for cardiac risk factors. This nomogram may be considered for use in clinical care.</P> <P><B>Graphical abstract</B></P> <P>[DISPLAY OMISSION]</P>

Incremental prognostic value of coronary computed tomography angiography over coronary calcium scoring for major adverse cardiac events in elderly asymptomatic individuals

Han, Donghee,Hartaigh, Brí,ain Ó,Gransar, Heidi,Lee, Ji Hyun,Rizvi, Asim,Baskaran, Lohendran,Schulman-Marcus, Joshua,Dunning, Allison,Achenbach, Stephan,Al-Mallah, Mouaz H,Berman, Daniel S Oxford University Press 2018 European heart journal cardiovascular Imaging Vol.19 No.6

<P><B>Abstract</B></P><P><B>Aims</B></P><P>Coronary computed tomography angiography (CCTA) and coronary artery calcium score (CACS) have prognostic value for coronary artery disease (CAD) events beyond traditional risk assessment. Age is a risk factor with very high weight and little is known regarding the incremental value of CCTA over CAC for predicting cardiac events in older adults.</P><P><B>Methods and results</B></P><P>Of 27 125 individuals undergoing CCTA, a total of 3145 asymptomatic adults were identified. This study sample was categorized according to tertiles of age (cut-off points: 52 and 62 years). CAD severity was classified as 0, 1–49, and ≥50% maximal stenosis in CCTA, and further categorized according to number of vessels ≥50% stenosis. The Framingham 10-year risk score (FRS) and CACS were employed as major covariates. Major adverse cardiovascular events (MACE) were defined as a composite of all-cause death or non-fatal MI. During a median follow-up of 26 months (interquartile range: 18–41 months), 59 (1.9%) MACE occurred. For patients in the top age tertile, CCTA improved discrimination beyond a model included FRS and CACS (C-statistic: 0.75 vs. 0.70, <I>P</I>-value = 0.015). Likewise, the addition of CCTA improved category-free net reclassification (cNRI) of MACE in patients within the highest age tertile (e.g. cNRI = 0.75; proportion of events/non-events reclassified were 50 and 25%, respectively; <I>P</I>-value <0.05, all). CCTA displayed no incremental benefit beyond FRS and CACS for prediction of MACE in the lower age tertiles.</P><P><B>Conclusion</B></P><P>CCTA provides added prognostic value beyond cardiac risk factors and CACS for the prediction of MACE in asymptomatic older adults.</P>

Prevalence and Distribution of Coronary Artery Calcification in Asymptomatic United States and Korean Adults — Cross-Sectional Propensity-Matched Analysis —

Han, Donghee,Hartaigh, Brí,ain ó,Gransar, Heidi,Lee, Ji Hyun,Choi, Su-Yeon,Chun, Eun Ju,Sung, Jidong,Han, Hae-Won,Park, Sung Hak,Callister, Tracy UNKNOWN 2016 CIRCULATION JOURNAL Vol.80 No.11

<P>Background: The incidence of coronary artery disease (CAD) varies depending on ethnicity, but the precise differences remain to be firmly established. This study therefore evaluated the disparity in coronary artery calcification (CAC), as a marker of CAD, in asymptomatic US and Korean adults. Methods and Results: CAC score was compared between asymptomatic Korean (n=15,128) and US (n=7,533) adults. Propensity score matching was performed according to age, gender, hypertension, diabetes, dyslipidemia, and current smoking, which generated 2 cohorts of 5,427 matched pairs. Both cohorts were categorized according to age group: 45-54, 55-64, and 65-74 years. Overall, the prevalence of CAC score >0, >100, and >400 in Korean adults was lower than in US adults (P<0.001, all). According to increasing age groups, the likelihood of CAC was most often lower in Korean adults, especially in Korean women. The odds of having CAC >400 in Korean adults aged 65-74 years was 0.66 (95% CI: 0.48-0.91) overall, 0.78 (95% CI: 0.52-1.19) in men, and 0.50 (95% CI: 0.29-0.86) in women, compared with US counterparts. Conclusions: Korean adults have a lower prevalence and severity of atherosclerotic burden as assessed on CAC, compared with US adults, but the disparity in CAC according to ethnicity may decline with older age.</P>

Assessment of Coronary Artery Calcium Scoring for Statin Treatment Strategy according to ACC/AHA Guidelines in Asymptomatic Korean Adults

한동희,장혁재,Briain O Hartaigh,이지현,Asim Rizvi,박효은,최수연,성지동 연세대학교의과대학 2017 Yonsei medical journal Vol.58 No.1

Purpose: The 2013 American College of Cardiology (ACC)/American Heart Association (AHA) cholesterol management guidelinesadvocate the use of statin treatment for prevention of cardiovascular disease. We aimed to assess the usefulness of coronary artery calcium (CAC) for stratifying potential candidates of statin use among asymptomatic Korean individuals. Materials and Methods: A total of 31375 subjects who underwent CAC scoring as part of a general health examination were enrolledin the current study. Statin eligibility was categorized as statin recommended (SR), considered (SC), and not recommended(SN) according to ACC/AHA guidelines. Cox regression analysis was employed to estimate hazard ratios (HR) with 95% confidentialintervals (CI) after stratifying the subjects according to CAC scores of 0, 1–100, and >100. Number needed to treat (NNT) to prevent one mortality event during study follow up was calculated for each group. Results: Mean age was 54.4±7.5 years, and 76.3% were male. During a 5-year median follow-up (interquartile range; 3–7), there were 251 (0.8%) deaths from all-causes. A CAC >100 was independently associated with mortality across each statin group after adjusting for cardiac risk factors (e.g., SR: HR, 1.60; 95% CI, 1.07–2.38; SC: HR, 2.98; 95% CI, 1.09–8.13, and SN: HR, 3.14; 95% CI, 1.08–9.17). Notably, patients with CAC >100 displayed a lower NNT in comparison to the absence of CAC or CAC 1–100 in SC and SN groups. Conclusion: In Korean asymptomatic individuals, CAC scoring might prove useful for reclassifying patient eligibility for receiving statin therapy based on updated 2013 ACC/AHA guidelines.

Prognostic implications of coronary artery calcium in the absence of coronary artery luminal narrowing

Cho, Iksung,ó,Hartaigh, Brí,ain,Gransar, Heidi,Valenti, Valentina,Lin, Fay Y.,Achenbach, Stephan,Berman, Daniel S.,Budoff, Matthew J.,Callister, Tracy Q.,Al-Mallah, Mouaz H.,Cademartiri, F Elsevier 2017 Atherosclerosis Vol.262 No.-

<P><B>Abstract</B></P> <P><B>Background and aims</B></P> <P>Coronary artery calcium (CAC) scoring is a predictor of future adverse clinical events, and a surrogate measure of overall coronary artery plaque burden. Coronary computed tomographic angiography (CCTA) is a contrast-enhanced method that allows for visualization of plaque as well as whether that plaque causes luminal narrowing. To date, the prognosis of individuals with CAC but without stenosis has not been reported. We explored the prevalence of CAC>0 and its prognostic utility for future mortality for patients without luminal narrowing by CCTA.</P> <P><B>Methods</B></P> <P>From 17 sites in 9 countries, we identified patients without known coronary artery disease, who underwent CAC scoring and CCTA, and were followed for >3 years. CCTA was graded for % stenosis according to a modified American Heart Association 16-segment model. We calculated hazard ratios (HR) with 95% confidence intervals (95% CI) for incident mortality and compared risk of death for patients as a function of presence or absence of CAC and presence or absence of luminal narrowing by CCTA.</P> <P><B>Results</B></P> <P>Among 6656 patients who underwent CCTA and CAC scoring, 399 patients (6.0%) had no coronary luminal narrowing but CAC>0. During a median follow-up of 5.1 years (IQR: 3.9–5.9 years), 456 deaths occurred. Compared to individuals without luminal narrowing or CAC, individuals without luminal narrowing but CAC>0 were older, more likely to be male and had higher rates of diabetes, hypertension, and dyslipidemia. Individuals without luminal narrowing but CAC experienced a 2-fold increased risk of mortality, with increasing risk of mortality with higher CAC score. Following adjustment, incident death persisted (HR, 1.8; 95% CI, 1.1–2.9, <I>p</I> = 0.02) among patients without luminal narrowing but with CAC>0 compared with patients whose CACS = 0. Individuals without luminal narrowing but CAC ≥100 had mortality risks similar to individuals with non-obstructive CAD (0 < stenosis<50%) by CCTA [HR 2.5 (95% CI 1.3–4.9) and 2.2 (95% CI 1.6–3.0), respectively].</P> <P><B>Conclusions</B></P> <P>Patients without luminal narrowing but with CAC experience greater risk of 5-year mortality. Patients with CAC score ≥100 and no coronary luminal narrowing experience death rates similar to those with non-obstructive CAD.</P> <P><B>Highlights</B></P> <P> <UL> <LI> The prevalence of individuals without coronary stenosis but with evident coronary calcium was identified in this large international coronary CT angiography registry. </LI> <LI> Coronary plaques with positive remodeling reflect a potential mechanism for the presence of coronary calcium without luminal narrowing. </LI> <LI> The current study observed a worsened prognosis among those without luminal narrowing but with coronary artery calcium. </LI> </UL> </P>

Reassessing the Usefulness of Coronary Artery Calcium Score among Varying Racial and Ethnic Groups by Geographic Locations: Relevance of the Korea Initiatives on Coronary Artery Calcification Registry

이지현,Bríain Ó Hartaigh,,한동희,박효은,최수연,성지동,장혁재 한국심초음파학회 2015 Journal of Cardiovascular Imaging (J Cardiovasc Im Vol.23 No.4

There is some disparity in the morbidity and mortality rates of cardiovascular disease (CVD) according to race, ethnicity, and geographicregions. Although prediction algorithms that evaluate risk of cardiovascular events have been established using traditionalrisk factors, they have also demonstrated a number of differences along with race and ethnicity. Of various risk assessment modalities,coronary artery calcium (CAC) score is a sensitive marker of calcific atherosclerosis and correlates well with atheroscleroticplaque burden. Although CAC score is now utilized as a useful tool for early detection of coronary artery disease, prior studieshave suggested some variability in the presence and severity of coronary calcification according to race, ethnicity, and/or geographicregions. Among Asian populations, it would appear necessary to reappraise the utility of CAC score and whether it remainssuperior over and above established clinical risk prediction algorithms. To this end, the Korea initiatives on coronary arterycalcification (KOICA) registry has been designed to identify the effectiveness of CAC score for primary prevention of CVD in asymptomaticKorean adults. This review discusses the important role of CAC score for prognostication, while also describing thedesign and rationale of the KOICA registry.

Incremental prognostic utility of coronary CT angiography for asymptomatic patients based upon extent and severity of coronary artery calcium: results from the COronary CT Angiography EvaluatioN For Clinical Outcomes InteRnational Multicenter (CONFIRM) S

Cho, Iksung,Chang, Hyuk-Jae,Ó,Hartaigh, Brí,ain,Shin, Sanghoon,Sung, Ji Min,Lin, Fay Y.,Achenbach, Stephan,Heo, Ran,Berman, Daniel S.,Budoff, Matthew J.,Callister, Tracy Q.,Al-Mallah, Moua The European Society of Cardiology 2015 European heart journal Vol.36 No.8

<P><B>Aim</B></P><P>Prior evidence observed no predictive utility of coronary CT angiography (CCTA) over the coronary artery calcium score (CACS) and the Framingham risk score (FRS), among asymptomatic individuals. Whether the prognostic value of CCTA differs for asymptomatic patients, when stratified by CACS severity, remains unknown.</P><P><B>Methods and results</B></P><P>From a 12-centre, 6-country observational registry, 3217 asymptomatic individuals without known coronary artery disease (CAD) underwent CACS and CCTA. Individuals were categorized by CACS as: 0–10, 11–100, 101–400, 401–1000, >1000. For CCTA analysis, the number of obstructive vessels—as defined by the per-patient presence of a ≥50% luminal stenosis—was used to grade the extent and severity of CAD. The incremental prognostic value of CCTA over and above FRS was measured by the likelihood ratio (LR) <I>χ</I><SUP>2</SUP>, <I>C</I>-statistic, and continuous net reclassification improvement (NRI) for prediction, discrimination, and reclassification of all-cause mortality and non-fatal myocardial infarction. During a median follow-up of 24 months (25th–75th percentile, 17–30 months), there were 58 composite end-points. The incremental value of CCTA over FRS was demonstrated in individuals with CACS >100 (LR<I>χ</I><SUP>2</SUP>, 25.34; increment in <I>C</I>-statistic, 0.24; NRI, 0.62, all <I>P</I> < 0.001), but not among those with CACS ≤100 (all <I>P</I> > 0.05). For subgroups with CACS >100, the utility of CCTA for predicting the study end-point was evident among individuals whose CACS ranged from 101 to 400; the observed predictive benefit attenuated with increasing CACS.</P><P><B>Conclusion</B></P><P>Coronary CT angiography provides incremental prognostic utility for prediction of mortality and non-fatal myocardial infarction for asymptomatic individuals with moderately high CACS, but not for lower or higher CACS.</P>

Multimodality Imaging in Coronary Artery Disease: Focus on Computed Tomography

이지현,한동희,Ibrahim Danad,Bríain ó Hartaigh,Fay Y. Lin,James K. Min 한국심초음파학회 2016 Journal of Cardiovascular Imaging (J Cardiovasc Im Vol.24 No.1

Coronary artery disease (CAD) is the leading cause of mortality worldwide, and various cardiovascular imaging modalities havebeen introduced for the purpose of diagnosing and determining the severity of CAD. More recently, advances in computed tomography(CT) technology have contributed to the widespread clinical application of cardiac CT for accurate and noninvasive evaluationof CAD. In this review, we focus on imaging assessment of CAD based upon CT, which includes coronary artery calciumscreening, coronary CT angiography, myocardial CT perfusion, and fractional flow reserve CT. Further, we provide a discussion regardingthe potential implications, benefits and limitations, as well as the possible future directions according to each modality.

Diagnostic Performance of Hybrid Cardiac Imaging Methods for Assessment of Obstructive Coronary Artery Disease Compared With Stand-Alone Coronary Computed Tomography Angiography : A Meta-Analysis

Rizvi, Asim,Han, Donghee,Danad, Ibrahim,Ó,Hartaigh, Brí,ain,Lee, Ji Hyun,Gransar, Heidi,Stuijfzand, Wijnand J.,Roudsari, Hadi Mirhedayati,Park, Mahn Won,Szymonifka, Jackie,Chang, Hyuk-Jae Elsevier 2018 JACC CARDIOVASCULAR IMAGING Vol.11 No.4

<P><B>Abstract</B></P> <P><B>Objectives</B></P> <P>The current meta-analysis aimed to evaluate the diagnostic performance of hybrid cardiac imaging techniques compared with stand-alone coronary computed tomography angiography (CTA) for assessment of obstructive coronary artery disease (CAD).</P> <P><B>Background</B></P> <P>The usefulness of coronary CTA for detecting obstructive CAD remains suboptimal at present. Myocardial perfusion imaging encompasses positron emission tomography, single-photon emission computed tomography, and cardiac magnetic resonance, which permit the identification of myocardial perfusion defects to detect significant CAD. A hybrid approach comprising myocardial perfusion imaging and coronary CTA may improve diagnostic performance for detecting obstructive CAD.</P> <P><B>Methods</B></P> <P>PubMed and Web of Knowledge were searched for relevant publications between January 1, 2000 and December 31, 2015. Studies using coronary CTA and hybrid imaging for diagnosis of obstructive CAD (a luminal diameter reduction of >50% or >70% by invasive coronary angiography) were included. In total, 12 articles comprising 951 patients and 1,973 vessels were identified, and a meta-analysis was performed to determine pooled sensitivity, specificity, and summary receiver-operating characteristic curves.</P> <P><B>Results</B></P> <P>On a per-patient basis, the pooled sensitivity of hybrid imaging was comparable to that of coronary CTA (91% vs. 90%; p = 0.28). However, specificity was higher for hybrid imaging versus coronary CTA (93% vs. 66%; p < 0.001). On a per-vessel basis, sensitivity for hybrid imaging against coronary CTA was comparable (84% vs. 89%; p = 0.29). Notably, hybrid imaging yielded a specificity of 95% versus 83% for coronary CTA (p < 0.001). Summary receiver-operating characteristic curves displayed improved discrimination for hybrid imaging beyond coronary CTA alone, on a per-vessel basis (area under the curve: 0.97 vs. 0.93; p = 0.047), although not on a per-patient level (area under the curve: 0.97 vs. 0.93; p = 0.132).</P> <P><B>Conclusions</B></P> <P>Hybrid cardiac imaging demonstrated improved diagnostic specificity for detection of obstructive CAD compared with stand-alone coronary CTA, yet improvement in overall diagnostic performance was relatively limited.</P> <P><B>Graphical abstract</B></P> <P>[DISPLAY OMISSION]</P>

Influence of symptom typicality for predicting MACE in patients without obstructive coronary artery disease: From the CONFIRM Registry (Coronary Computed Tomography Angiography Evaluation for Clinical Outcomes: An International Multicenter Registry)

Lee, Ji Hyun,Han, Donghee,Hartaigh, Brí,ain ó,Gransar, Heidi,Lu, Yao,Rizvi, Asim,Park, Mahn Won,Roudsari, Hadi Mirhedayati,Stuijfzand, Wijnand J.,Berman, Daniel S.,Callister, Tracy Q.,DeLa Wiley (John WileySons) 2018 Clinical cardiology Vol.41 No.5

<P>Our objective was to assess the prognostic value of symptom typicality in patients without obstructive coronary artery disease (CAD), determined by coronary computed tomographic angiography (CCTA). We identified 4215 patients without prior history of CAD and without obstructive CAD (<50% CCTA stenosis). CAD severity was categorized as nonobstructive (1%-49%) and none (0%). Based upon the Diamond-Forrester criteria for angina pectoris, symptom typicality was classified as asymptomatic, nonanginal, atypical, and typical. Multivariable Cox proportional hazards models were used to assess the risk of major adverse cardiac events (MACE), comprising all-cause mortality, myocardial infarction, unstable angina, and late revascularization, according to symptom typicality. Mean patient age was 57.0 +/- 12.0years (54.9% male). During a median follow-up of 5.3years (interquartile range, 4.6-5.9years), MACE were reported in 312 (7.4%) patients. Among patients with nonobstructive CAD, there was an association between symptom typicality and MACE (P for interaction=0.05), driven by increased risk of MACE among those with typical angina and nonobstructive CAD (hazard ratio: 1.62, 95% confidence interval: 1.06-2.48, P=0.03). No consistent relationship was found between symptom typicality and MACE among patients without any CAD (hazard ratio: 0.73, 95% confidence interval: 0.34-1.57, P=0.08). In the CONFIRM registry, patients who presented with concomitant typical angina and nonobstructive CAD had a higher rate of MACE than did asymptomatic patients with nonobstructive CAD. However, the presence of typical angina did not appear to portend worse prognosis in patients with no CAD.</P>