Donghee Han

Incremental Benefit of Coronary Artery Calcium Score Above Traditional Risk Factors for All-Cause Mortality in Asymptomatic Korean Adults

BACKGROUND Coronary artery calcium score (CACS) is a well-recognized marker for subclinical coronary atherosclerosis, particularly in asymptomatic populations. To date, however, the added prognostic benefit of CACS compared with traditional risk factors in an Asian population remains unknown. This study therefore investigated the benefit of CACS over traditional risk factors for all-cause mortality in a large multicenter registry of asymptomatic Korean adults. METHODSANDRESULTS A total of 34,386 individuals were retrospectively enrolled to participate in a general health examination. The Framingham 10-year risk score (FRS) was calculated according to the traditional risk stratification algorithm and CACS was calculated in log(CACS+1) for continuous data and categorized as 0, 1-100, 101-400 and >400. During a median follow-up of 4.9 years (IQR, 3.0-7.1), there were 303 all-cause deaths (0.9%). Following adjustment, CACS was independently associated with all-cause death (hazard ratio, 1.10; 95% confidence interval (CI): 1.05-1.17; P<0.001). Notably, CACS added further prognostic value above and beyond FRS (likelihood ratio, χ(2)=75.42, P<0.001; continuous net reclassification improvement=0.40, 95% CI: 0.29-0.51, P≤0.001; improving C-statistic from 0.64, 95% CI: 0.61-0.67 to 0.68, 95% CI: 0.64-0.71; ∆C=0.04, 95% CI: 0.01-0.06, P=0.002). CONCLUSIONS In an asymptomatic Korean population, CACS improved prediction of all-cause mortality over and above that of a conventional risk tool.

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

There is some disparity in the morbidity and mortality rates of cardiovascular disease (CVD) according to race, ethnicity, and geographic regions. Although prediction algorithms that evaluate risk of cardiovascular events have been established using traditional risk 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 atherosclerotic plaque burden. Although CAC score is now utilized as a useful tool for early detection of coronary artery disease, prior studies have suggested some variability in the presence and severity of coronary calcification according to race, ethnicity, and/or geographic regions. Among Asian populations, it would appear necessary to reappraise the utility of CAC score and whether it remains superior over and above established clinical risk prediction algorithms. To this end, the Korea initiatives on coronary artery calcification (KOICA) registry has been designed to identify the effectiveness of CAC score for primary prevention of CVD in asymptomatic Korean adults. This review discusses the important role of CAC score for prognostication, while also describing the design and rationale of the KOICA registry.

Relationship Between Endothelial Wall Shear Stress and High‐Risk Atherosclerotic Plaque Characteristics for Identification of Coronary Lesions That Cause Ischemia: A Direct Comparison With Fractional Flow Reserve

Background Wall shear stress (WSS) is an established predictor of coronary atherosclerosis progression. Prior studies have reported that high WSS has been associated with high‐risk atherosclerotic plaque characteristics (APCs). WSS and APCs are quantifiable by coronary computed tomography angiography, but the relationship of coronary lesion ischemia—evaluated by fractional flow reserve—to WSS and APCs has not been examined. Methods and Results WSS measures were obtained from 100 evaluable patients who underwent coronary computed tomography angiography and invasive coronary angiography with fractional flow reserve. Patients were categorized according to tertiles of mean WSS values defined as low, intermediate, and high. Coronary ischemia was defined as fractional flow reserve ≤0.80. Stenosis severity was determined by minimal luminal diameter. APCs were defined as positive remodeling, low attenuation plaque, and spotty calcification. The likelihood of having positive remodeling and low‐attenuation plaque was greater in the high WSS group compared with the low WSS group after adjusting for minimal luminal diameter (odds ratio for positive remodeling: 2.54, 95% CI 1.12–5.77; odds ratio for low‐attenuation plaque: 2.68, 95% CI 1.02–7.06; both P<0.05). No significant relationship was observed between WSS and fractional flow reserve when adjusting for either minimal luminal diameter or APCs. WSS displayed no incremental benefit above stenosis severity and APCs for detecting lesions that caused ischemia (area under the curve for stenosis and APCs: 0.87, 95% CI 0.81–0.93; area under the curve for stenosis, APCs, and WSS: 0.88, 95% CI 0.82–0.93; P=0.30 for difference). Conclusions High WSS is associated with APCs independent of stenosis severity. WSS provided no added value beyond stenosis severity and APCs for detecting lesions with significant ischemia.

Metabolic syndrome predicts long-term mortality in subjects without established diabetes mellitus in asymptomatic Korean population: A propensity score matching analysis from the Korea Initiatives on Coronary Artery Calcification (KOICA) registry

Abstract Despite the different features of diabetes mellitus (DM) in Asian populations compared with Western populations, the impact of metabolic syndrome (MetS) on long-term mortality according to DM status has not yet been elucidated in the Asian population. After performing 1:1 propensity score matching (PSM) using clinical variables including age, gender, smoking, and individual MetS components between DM and non-DM subjects from the data of the Korea Initiatives on Coronary Artery Calcification registry, mortality was evaluated according to DM and MetS in 14,956 asymptomatic Korean subjects. The mean follow-up duration was 53.1 months (interquartile range: 33–80). The overall prevalence of MetS was 60%. DM subjects had higher mortality compared with non-DM subjects (1.2% vs 0.7%, respectively; P = 0.001); the cumulative mortality by Kaplan–Meier analysis was higher in DM subjects than in non-DM subjects (log-rank P = 0.001). DM increased the risk of mortality in PSM participants (hazard ratio [HR] 1.74; P = 0.001). In non-DM subjects, MetS (HR 2.32) and one of its components, central obesity (HR 1.97), were associated with an increased risk of mortality (both P < 0.05). In contrast, there was no significant difference in the risk of mortality according to MetS or its components in DM subjects. After adjusting for confounding risk factors, it was shown that MetS independently increased the risk of mortality in non-DM subjects. Compared with non-DM subjects, DM subjects have an increased risk of long-term mortality among PSM participants. MetS appears to have an independent impact on mortality in subjects without established DM among the asymptomatic Korean population. Our results may not be applicable to the whole subjects with MetS because the PSM using MetS components was performed between subjects with and without DM which was very high risk for adverse clinical events.

Multimodality Imaging in Coronary Artery Disease: Focus on Computed Tomography

Coronary artery disease (CAD) is the leading cause of mortality worldwide, and various cardiovascular imaging modalities have been 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 evaluation of CAD. In this review, we focus on imaging assessment of CAD based upon CT, which includes coronary artery calcium screening, coronary CT angiography, myocardial CT perfusion, and fractional flow reserve CT. Further, we provide a discussion regarding the potential implications, benefits and limitations, as well as the possible future directions according to each modality.

Novel Approaches for the Use of Cardiac/Coronary Computed Tomography Angiography

Recent developments in the novel imaging technology of cardiac computed tomography (CT) not only permit detailed assessment of cardiac anatomy but also provide insight into cardiovascular physiology. Foremost, coronary CT angiography (CCTA) enables direct noninvasive examination of both coronary artery stenoses and atherosclerotic plaque characteristics. Calculation of computational fluid dynamics by cardiac CT allows the noninvasive estimation of fractional flow reserve, which increases the diagnostic accuracy for detection of hemodynamically significant coronary artery disease. In addition, a combination of myocardial CT perfusion and CCTA can provide simultaneous anatomical and functional assessment of coronary artery disease. Finally, detailed anatomical evaluation of atrial, ventricular, and valvular anatomy provides diagnostic information and guidance for procedural planning, such as for transcatheter aortic valve replacement. The clinical applications of cardiac CT will be extended with the development of these novel modalities.

Associations between elevated resting heart rate and subclinical atherosclerosis in asymptomatic Korean adults undergoing coronary artery calcium scoring

Elevated resting heart rate (RHR) and the presence of coronary artery calcium (CAC) are closely related with inflammatory activity and cardiovascular disease outcomes. To date, however, the relationship between a high RHR and CAC has not been well studied, especially in non-western populations. We therefore aimed to examine the cross-sectional relationship between high RHR and the burden of subclinical atherosclerosis as measured by CAC score in a large sample of Korean adults. A total 26,018 subjects were enrolled and underwent CAC screening as part of a broader general health examination. RHR was categorized into four groups as: <60, 60–69, 70–79, and ≥80 beats per minute. Multivariable logistic regression models were employed to estimate the odds of having a CAC score of either >0, >100, or >400 based on RHR. Mean age of the study population was 53.9 ± 8.2 years, and 79.7 % were male. After adjustment, each 10 beat per minute increment in RHR was associated with greater odds of having a CAC score above 100 (OR 1.13, 95 % CI 1.08–1.18) or 400 (OR 1.22, 95 % CI 1.13–1.31). Likewise, following adjustment, the odds of having a CAC >100 or >400 for those with a RHR ≥80 beats per minute were 1.42 (95 % CI 1.19–1.69) and 1.86 (95 % CI 1.42–2.47), respectively, compared with those who had a RHR <60 beats per minute. In a large cohort of Korean adults, elevations in the RHR, particularly above 80 beats per minute, were found to be independently associated with the presence of subclinical atherosclerosis as measured by CAC scoring.

Role of computed tomography screening for detection of coronary artery disease

Coronary artery disease (CAD) is a leading cause of morbidity and mortality in Western populations, and the prediction and prevention of CAD is an inherent challenge facing current health care societies. Computed tomography (CT) has emerged as a noninvasive imaging tool in the field of cardiovascular disease. Notably, CT scanning for detection of coronary artery calcium (CAC) has proven useful in predicting adverse cardiovascular outcomes as well as early identification of CAD. In asymptomatic persons undergoing screening for CAD, CAC is well established as a surrogate of CAD risk and has demonstrated incremental benefit over and above traditional risk prediction tools. In addition, a zero CAC score has shown to reflect a substantially lower risk of CAD and may therefore be considered an important marker of CAD protection. Irrespective of screening in the asymptomatic population, CAC scanning has also displayed a beneficial role in the symptomatic population, specifically as gatekeeper in guiding further treatment decision making. Further still, the combination of alternative CT screening strategies such as CT screening for lung cancer with CAC scanning may hold particular promise as an effective screening approach by lowering overall health costs as well as limiting radiation exposure.

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

Abstract Aims 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. Methods and results 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, P-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; P-value <0.05, all). CCTA displayed no incremental benefit beyond FRS and CACS for prediction of MACE in the lower age tertiles. Conclusion CCTA provides added prognostic value beyond cardiac risk factors and CACS for the prediction of MACE in asymptomatic older adults.

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)

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 ±12.0 years (54.9% male). During a median follow‐up of 5.3 years (interquartile range, 4.6–5.9 years), 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.