Predictive value of coronary calcifications for future cardiac events in asymptomatic individuals

doi:10.1016/j.ahj.2007.08.024

American Heart Journal

Volume 155, Issue 1, January 2008, Pages 154-160

https://doi.org/10.1016/j.ahj.2007.08.024 Get rights and content

Background

Reliable risk stratification is crucial for efficient prevention of coronary artery disease. The following prospective study determined the predictive value of coronary calcifications for future cardiovascular events.

Methods

We included 1726 asymptomatic individuals (1018 men, 708 women, age 57.7 ± 13.3 years) referred for a cardiological examination. Coronary calcifications were determined with the Imatron C 150 XP electron beam computed tomography scanner. For quantification of coronary calcifications, we calculated the Agatston score. Over a mean observation period of 40.3 ± 7.3 months we registered the event rate for cardiac death (CD) and myocardial infarction (MI).

Results

The Agatston score in patients who died of CD (n = 65) or had an MI (n = 114) was significantly higher compared with those without cardiac events (458 ± 228 vs 206 ± 201, P < .01). An Agatston score above the 75th percentile was associated with a significantly higher annualized event rate for MI (3.6% vs 1.6%, P < .05) and for CD (2.2% vs 0.9%) compared with patients with scores below the 75th percentile. No cardiac events were observed in patients where coronary calcifications could be excluded.

Conclusions

By determination of coronary calcifications, patients at risk for future MI and CD could be identified within an asymptomatic population independent of concomitant risk factors. At the same time, future cardiovascular events could be excluded in patients without coronary calcifications.

Section snippets

Study protocol

The research protocol was approved by the local clinical institutional review board and complies with the declaration of Helsinki. We examined 3078 consecutive patients referred to the outpatient department of our hospital by a primary care physician for preventive cardiological examination between 1997 and 1999. All patients underwent clinical examination, ECG, stress ECG, and echocardiography. Of these patients, 1515 patients either showed typical clinical symptoms of CAD or were suspected of

Results

Of the 1813 initially included patients, 1726 individuals (1018 men and 708 women, age 57.7 ± 13.3 years) completed the follow-up. Nineteen patients who did not complete the follow-up died of noncardiac causes. The mean observation time was 40.3 ± 7.3 months. The distribution of cardiovascular risk factors is shown in Table I. The mean number of risk factors per person was 2.7 ± 1.3 in men and 2.5 ± 1.1 in women (range 0-5) (Table I). There was no difference in age, risk factor distribution,

Discussion

The aim of this study was to evaluate the possibility of identifying the patient at risk for future cardiovascular events by determination of coronary calcification. Furthermore, the results were compared with conventional risk stratification using the PROCAM, ATP III, and ESC risk scores.

The study population consisted of solely asymptomatic patients selected from a group of patients referred to our hospital for preventive cardiological examinations. This preselection explains the higher number

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Cited by (128)

Association of aortic stiffness with abdominal vascular and coronary calcifications in patients with stage 3 and 4 chronic kidney disease
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El aumento de la rigidez arterial central (aórtica) tiene repercusiones hemodinámicas con efectos nocivos cardiovasculares y renales. En la enfermedad renal crónica (ERC) puede existir un aumento de la rigidez aórtica secundaria a múltiples alteraciones metabólicas, entre ellas la calcificación de la pared vascular (CV).
El objetivo de este estudio fue analizar la asociación de la rigidez aórtica y de la hemodinámica central con la presencia de CV en dos territorios: aorta abdominal (CAA) y arterias coronarias (CC).
Se incluyeron 87 pacientes con ERC estadios 3 y 4. Usando tonometría de aplanamiento se estudiaron la hemodinámica central y la rigidez aórtica. Esta se determinó mediante la velocidad de pulso carótida-femoral (Vp_c-f). A partir de la Vp_c-f se calculó el índice de la VP_c-f (iVp_c-f) que considera otras variables que influyen en la Vp_c-f, como edad, presión arterial, sexo y frecuencia cardiaca.
La presencia de CAA se valoró mediante radiografía lateral de columna lumbar calculándose el índice de Kauppila (iKauppila) y las CC mediante tomografía computarizada multidetección por el método de Agatston, calculándose su índice (iAgatston).
Para el estudio de la asociación entre iVp_c-f, iKauppila, iAgatston, presión aórtica central, parámetros clínicos y datos de laboratorio se usaron la regresión múltiple y la regresión logística. La capacidad discriminativa del iVp_c-f para evaluar la presencia de CAA y CC se determinó mediante el área bajo la curva (ABC) de ROC (receiver-operating characteristic).
La Vp_c-f y el iVp_c-f fueron 11,3 ± 2,6 m/s y 10,6 m/s, respectivamente. El iVp_c-f fue mayor cuando la ERC coexistía con diabetes mellitus (DM). Se detectaron CAA y CC en el 77% y el 87%, respectivamente.
La albuminuria (β = 0,13, p = 0,005) y el iKauppila (β = 0,36, p = 0,001) se asociaron de forma independiente con la magnitud del iVp_c-f. A su vez, el iVp_c-f (β = 0,39, p = 0,001), la DM (β = 0,46, p = 0,01) y el tabaquismo (β = 0,53; p = 0,006) se asociaron con la intensidad del iKauppila, pero solo el iVp_c-f predijo la existencia de CAA [(OR: 3,33 (IC 95%: 1,6-6,9; p = 0,001)].
El iKauppila se asoció de forma independiente con el iAgatston (β = 1,53, p = 0,001). La presencia de CAA identificó pacientes con CC con una sensibilidad del 73%, una especificidad del 100%, un valor predictivo positivo del 100% y un valor predictivo negativo del 38%.
El iVp_c-f predecía la presencia de CC [OR: 3,35 (IC 95%:1,04-10,2, p = 0,04)]. En las curvas ROC, usando el iVp_c-f, el ABC para las CAA y CC fue 0,82 (IC 95%: 0,71-0,93, p = 0,001) y 0,81 (IC 95%: 0,67-0,96, p = 0,02), respectivamente.
Cuando la ERC se asocia con DM hay un aumento de la rigidez aórtica determinada por el iVp_c-f. En la ERC estadios 3-4 son muy prevalentes las CAA y CC que, con mucha frecuencia, coexisten. El iVp_c-f se asocia de forma independiente con las CAA y CC, y puede ser útil para identificar pacientes con CV en estos territorios.
Increased central (aortic) arterial stiffness has hemodynamic repercussions that affect the incidence of cardiovascular and renal disease. In chronic kidney disease (CKD) there may be an increase in aortic stiffness secondary to multiple metabolic alterations including calcification of the vascular wall (VC).
The objective of this study was to analyze the association of central aortic pressures and aortic stiffness with the presence of VC in abdominal aorta (AAC) and coronary arteries (CAC).
We included 87 patients with CKD stage 3 and 4. Using applanation tonometry, central aortic pressures and aortic stiffness were studied. We investigated the association of aortic pulse wave velocity (Pv_c-f) and Pv_c-f adjusted for age, blood pressure, sex and heart rate (Pv_c-f index) with AAC obtained on lumbar lateral radiography and CAC assessed by multidetector computed tomography. AAC and CAC were scored according to Kauppila and Agatston methods, respectively. For the study of the association between iPv_c-f index, Kauppila score, Agatston score, central aortic pressures, clinical parameters and laboratory data, multiple and logistic regression were used. We investigated the diagnosis performance of the Pv_c-f index for prediction of VC using receiver-operating characteristic (ROC).
Pv_c-f and Pv_c-f index were 11.3 ± 2.6 m/s and 10.6 m/s, respectively. The Pv_c-f index was higher when CKD coexisted with diabetes mellitus (DM). AAC and CAC were detected in 77% and 87%, respectively.
Albuminuria (β = 0.13, p = 0.005) and Kauppila score (β = 0.36, p = 0.001) were independently associated with Pv_c-f index. In turn, Pv_c-f index (β = 0.39, p = 0.001), DM (β = 0.46, p = 0.01), and smoking (β = 0.53; p = 0.006) were associated with Kauppila score, but only Pv_c-f index predicted AAC [OR: 3.33 (95% CI: 1.6–6.9; p = 0.001)].
The Kauppila score was independently associated with the Agatston score (β = 1.53, p = 0.001). The presence of AAC identified patients with CAC with a sensitivity of 73%, a specificity of 100%, a positive predictive value of 100% and a negative predictive value of 38%.
The Vp_c-f index predicted the presence of CAC [OR: 3.35 (95% CI: 1.04–10.2, p = 0.04)]. In the ROC curves, using the Vp_c-f index, the AUC for AAC and CAC was 0.82 (95% CI: 0.71–0.93, p = 0.001) and 0.81 (95% CI: 0.67–0.96, p = 0.02), respectively.
When stage 3–4 CKD coexists with DM there is an increase in aortic stiffness determined by the Vp_c-f index. In stage 3–4 CKD, AAC and CAC are very prevalent and both often coexist. The Vp_c-f index is independently associated with AAC and CAC and may be useful in identifying patients with VC in these territories.
Coronary artery calcium (CAC) score for cardiovascular risk stratification in a Thai clinical cohort: A comparison of absolute scores and age-sex-specific percentiles
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Coronary artery calcium (CAC) score provides a quantification of atherosclerotic plaque within the coronary arteries. This study aimed to examine the prevalence and CAC score distribution and to evaluate the association of each CAC score classifications with major adverse cardiovascular events (MACE) in a Thai clinical cohort.
This study was a retrospective observational cohort. We included patients aged above 35 years who underwent CAC score testing. The absolute and age-sex specific percentile classifications were categorized as 0, 1 to 10, 11 to 100, 101 to 400, and >400 and 0, <75^th, 75^th – 90^th, and >90^th, respectively. The endpoint was MACE, including cardiovascular death, myocardial infarction, heart failure hospitalization, coronary artery revascularization procedure, and stroke. Multivariable Cox regression was used to estimate the hazard ratios. The discriminative performance between classifications were compared using Harrell's C-statistics. The agreement was assessed via Cohen's Kappa.
This study included 440 patients, with approximately 70% of Thai patients exhibiting a CAC score. CAC score distributed higher in male than female and increased with age. Both CAC score classification demonstrated the acceptable predictive performance. However, fair agreement was observed between classifications (Cohen's kappa 0.51, 95%CI 0.42–0.59). Within the absolute classification, a higher CAC score was associated with increased hazard ratios for MACE across stratified age-sex-specific percentile levels. In contrast, the hazard ratios for MACE did not consistently rise with higher age-sex-specific percentile CAC score when stratified by absolute CAC score levels.
Both absolute and age-sex-specific percentile CAC score demonstrated acceptable performance in predicting MACE. However, the absolute CAC score classification may be more suitable for risk stratification within the Thai clinical cohort. Our findings offer supportive information that could inform future recommendations for CAC score testing criteria within national clinical practice guidelines.
Incorporating a polygenic risk score-triaged coronary calcium score into cardiovascular disease examinations to identify subclinical coronary artery disease (ESCALATE): Protocol for a prospective, nonrandomized implementation trial
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Identifying and targeting established modifiable risk factors has been a successful strategy for reducing the burden of coronary artery disease (CAD) at the population-level. However, up to 1-in-4 patients who present with ST elevation myocardial infarction do so in the absence of such risk factors. Polygenic risk scores (PRS) have demonstrated an ability to improve risk prediction models independent of traditional risk factors and self-reported family history, but a pathway for implementation has yet to be clearly identified. The aim of this study is to examine the utility of a CAD PRS to identify individuals with subclinical CAD via a novel clinical pathway, triaging low or intermediate absolute risk individuals for noninvasive coronary imaging, and examining the impact on shared treatment decisions and participant experience.
The ESCALATE study is a 12-month, prospective, multicenter implementation study incorporating PRS into otherwise standard primary care CVD risk assessments, to identify patients at increased lifetime CAD risk for noninvasive coronary imaging. One-thousand eligible participants aged 45 to 65 years old will enter the study, which applies PRS to those considered low or moderate 5-year absolute CVD risk and triages those with CAD PRS ≥80% for a coronary calcium scan. The primary outcome will be the identification of subclinical CAD, defined as a coronary artery calcium score (CACS) >0 Agatston units (AU). Multiple secondary outcomes will be assessed, including baseline CACS ≥100 AU or ≥75th age-/sex-matched percentile, the use and intensity of lipid- and blood pressure-lowering therapeutics, cholesterol and blood pressure levels, and health-related quality of life (HRQOL).
This novel trial will generate evidence on the ability of a PRS-triaged CACS to identify subclinical CAD, as well as subsequent differences in traditional risk factor medical management, pharmacotherapy utilization, and participant experience.
Australian New Zealand Clinical Trials Registry, ACTRN12622000436774. Trial was prospectively registered on March 18, 2022. https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=383134
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2022, Practical Cardiology: Principles and Approaches
Computed tomography has established itself as a novel diagnostic technique for cardiovascular disease. The constant improvements in the quality of imaging of the heart by computed tomography has resulted in an increasing number of clinical indications for cardiac computed tomography. Indications have expanded from prevention (where coronary calcium imaging is complemented by advanced analysis of plaque morphology and composition) to the modern interventional treatment of cardiac disease, for example, detailed computed tomographic imaging in transcatheter aortic valve replacement (TAVR).
In this chapter, we discuss the role of coronary computed tomography in acute chest pain, chronic stable angina, and the most important trials in this field. In addition, in this chapter, we learn more about the physiologic role of coronary computed tomography in coronary artery disease such as computed tomography fractional flow reserve (CT-FFR).
Coronary artery calcium scoring at lower tube voltages – Dose determination and scoring mechanism
2021, European Journal of Radiology
Population dose has been a concern with coronary artery calcium scoring CT since it is performed in adults with borderline risk. Lower tube voltage acquisitions are appealing but there are no agreed schemes for reduced dose determination. Moreover, conventional scoring cannot be used without changing the multiple Agatston thresholds.
By applying consistent calcium contrast-to-noise ratio to two anthropomorphic heart phantoms (medium and large) with 3-cm hydroxyapatite (HA) inserts, scanned using a dual-source CT, the relationship was derived between the volume CT dose index (CTDI_vol) at lower tube voltages and the baseline CTDI_vol at 120 kVp. The baseline CTDI_vol was obtained using the noise thresholds from the images acquired at 120 kVp. To preserve the conventional Agatston thresholds, down-scaling with the found factors was applied to images acquired at lower voltages with a dynamic heart module and 1.2−5 mm inserts (50–400 mg/cc) on the coronary tracks. Scores were evaluated on the scaled images by six readers.
The CTDI_vol at lower voltages was related to the baseline CTDI_vol following a power form of the voltage (index 1.246), regardless of the phantom size. The baseline CTDI_vol was 1.5 and 4.5 mGy, for the medium and large phantoms, respectively. Correspondingly, the reduced CTDI_vol at 100−70 kVp were 1.28−0.76 mGy, and 3.57−2.32 mGy. The downscaling factors were 0.88−0.63. The calcium scores at lower voltages were found within 12 % of the ground-truths.
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Thoracic radiotherapy as a risk factor for heart ischemia in subjects treated with chest irradiation and chemotherapy and without classic cardiovascular RISK factors
2020, Radiotherapy and Oncology
Radiation Induced Heart Disease (RIHD) represents a late effect of chest irradiation, contributing in increasing mortality rate in oncological patients by affecting pericardium, myocardium, valvs and coronaries. Currently, regarding the risk of Coronary Artery Disease (CAD), a cardiological screening involving exercise stress electrocardiography after 5–10 years from radiotherapy is advised. We sought to determine the rate of ischemia at exercise stress electrocardiography in a population of patients without cardiovascular risk factors who sustained radiotherapy, using a cohort of patients presenting with at least one cardiovascular risk factor as control group.
A population of 115 patients who sustained chest irradiation (and associated chemotherapy), presenting without classic cardiovascular risk factors or typical symptoms suggesting CAD, was evaluated with exercise stress electrocardiography. 135 patients with at least one risk factor for cardiovascular disease candidate to stress testing for primary prevention or for atypical symptoms served as control group.
The cohort of irradiated patients without classical cardiovascular risk factors is younger (48.7 ± 10.1 vs 60.5 ± 10.8 years, p < 0.001) and presents a lower percentage of males when compared with the control group. In this latter group 25.9% of subjects has diabetes, 62.9% dyslipidaemia, 67.4% hypertension and 19.2% actively smoke. Despite this important differences regarding classic cardiovascular risk factors, no significant differences were found in the number of positive exercise stress electrocardiography (10.4 vs 5.9%, p = ns).
Chest irradiation represents a strong cardiovascular risk factor. In fact, prevalence of positive ECG-stress test is not different (nor higher and nor lower) in irradiated subjects without cardiovascular risk and not irradiated patients with classic cardiovascular risk.

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Clinical InvestigationImaging and Diagnostic TestingPredictive value of coronary calcifications for future cardiac events in asymptomatic individuals

Background

Methods

Results

Conclusions

Section snippets

Study protocol

Results

Discussion

J Am Coll Cardiol

J Am Coll Cardiol

J Am Coll Cardiol

Am J Cardiol

J Am Coll Cardiol

J Am Coll Cardiol

Ann Epidemiol

Am J Cardiol

Heart disease and stroke statistics—2004 update

Primary prevention of acute coronary events with lovastatin in men and women with average cholesterol levels: results of AFCAPS/TexCAPS. Air Force/Texas Coronary Atherosclerosis Prevention Study

JAMA

Myocardial infarction and coronary deaths in the world health MONICA project. Registration procedures, event rates, and case fatality rates in 38 populations in 21 countries in four continents

Circulation

Cholesterol and mortality: 30 years of follow-up from the Framingham study

JAMA

Clinical Investigation
Imaging and Diagnostic Testing
Predictive value of coronary calcifications for future cardiac events in asymptomatic individuals