High Coronary Artery Calcium Score Research Articles

Marked Discordance Between Coronary Artery Calcium Score and Framingham Risk Score in Middle Eastern and Veteran American Populations

Background: Conventionally, the Framingham Risk Score (FRS) was used as a tool to risk stratify individuals for cardiovascular (CV) events and death. More recently, the coronary artery calcium score (CACS) has been used as a complimentary method for the assessment of CV risk. This study’s objective is to quantify the magnitude of marked discordance (MD) between FRS and CACS. The subjects were from two different ethnic groups, namely, a Middle Eastern population and a veteran American population. Methods: This is a retrospective observational cohort study of 499 consecutive patients who underwent multidetector cardiac computerized tomography (MDCT) at King Fahd Armed Forces Hospital (KFAFH), Jeddah, Saudi Arabia and Veterans Affairs Loma Linda Health Care System (VALLHCS). CACS was measured using the Agatston method. FRS was calculated by chart review. MD was defined as a CACS of 400 with low risk FRS. Patients had CACS between 100 and 400 were excluded from the analysis. Results: A total of 499 patient CT studies were reviewed with 450 meeting study criteria,130 patients from the VALLHCS (63 ± 12, 95% males) and 320 from KFAFH (27% males). MD was found in 308 (68%) of the total number enrolled. In the American population, of the 62 patients with a CACS 400, 20 patients (29%) had a discordantly low FRS. In the Middle Eastern population, of the 290 patients with a CACS 400, only 5 patients (16.7%) had a discordantly low FRS. Conclusion: The majority of MD in the Middle Eastern population had a high FRS with a low CACS. In contradistinction, the American veterans with MD had a high CACS and a low FRS.

Association of Homocysteine Levels with Subclinical Coronary Atherosclerosis in Asymptomatic Subjects

This article is available from http://www.labmedonline.org 2016, Laboratory Medicine Online This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited. Background: Progression of atherosclerotic plaques is known to be correlated with elevated circulating homocysteine (Hcy). However, whether the level of Hcy is related with coronary atherosclerosis in the subclinical state is unclear. Therefore, we performed this study to investigate the relationship between blood Hcy levels and subclinical atherosclerosis in asymptomatic self-referred subjects. Methods: We retrospectively enrolled 2,968 self-referred asymptomatic subjects (1,374 men, 1,594 women) who had undergone both coronary CT angiography (CCTA) and coronary artery calcium scoring. The relationships between atherosclerosis, Hcy, and other clinical factors were assessed. Results: Higher levels of Hcy were related with age, male gender, body mass index (BMI), waist circumference, blood pressure, high density lipoprotein (HDL), triglyceride, blood glucose, HbA1c, hsCRP, and coronary artery calcium score (CACS). Coronary plaque was more frequently found in higher Hcy quartile groups (21.3%, 28.8%, 34.4%, and 34.3%, P 50%) was also more frequent in higher Hcy quartile groups (1.8%, 5.4%, 5.0%, and 6.6%, P 400) than the first quartile group. Conclusions: Blood Hcy levels were associated with an increased risk of the presence and extent of subclinical atherosclerosis in asymptomatic subjects.

Estimation of coronary artery calcium by multislice spiral CT scan in asymptomatic high risk cases above forty (40) years of age

Hypertension, diabetes mellitus, smoking, obesity and family history of coronary artery disease are among known risk factors of coronary artery disease. Computed tomography (CT) quantifies the relative burden of CAC deposits as a marker of atherosclerosis. Methodology: This was a case control study conducted at Indira Gandhi Medical College and Hospital, Nagpur from June 2004 to June 2006, with aim to find out the utility of multislice spiral computed tomographic (CT) scan for detection of coronary artery calcium in asymptomatic coronary high risk cases and attempts has been made to correlate CAC Score with various risk factors and has been compared with CAC Score of controls Results: The maximum numbers of cases were in group of 41-50 years (n=31, 53.4%). The male to female ratio was 1.52:1. Among the risk factors studied, dyslipidemia (65.5%) was most common risk factor. Mean CAC score of all cases was significantly higher than, mean CAC score of all controls (p value= 0.0004). There was a progressive increase in the mean CAC score with increasing age. When all the risk factors were individually compared with controls, all showed higher CAC score and all the differences were statistically highly significant. Conclusion: Coronary artery calcium increases with increasing age and male sex. It also increases with presence of major risk factors for coronary artery disease (CAD). Hence, multislice spiral CT scan, being a non-invasive test can be recommended as a screening test for demonstrating significant atherosclerosis in susceptible subjects even when asymptomatic. Keywords: Coronary artery diseases, Coronary artery calcium, Ct scan risk factors

Coronary CT angiography derived fractional flow reserve: Methodology and evaluation of a point of care algorithm

BackgroundRecently several publications described the diagnostic value of coronary CT angiography (coronary CTA) derived fractional flow reserve (CTA-FFR). For a recently introduced on-site CTA-FFR application, detailed methodology and factors potentially affecting performance have not yet been described. ObjectiveTo provide a methodological background for an on-site CTA-FFR application and evaluate the effect of patient and acquisition characteristics. MethodsThe on-site CTA-FFR application utilized a reduced-order hybrid model applying pressure drop models within stenotic regions. In 116 patients and 203 vessels the diagnostic performance of CTA-FFR was investigated using invasive FFR measurements as a reference. The effect of several potentially relevant factors on CTA-FFR was investigated. Results90 vessels (44%) had a hemodynamically relevant stenosis according to invasive FFR (threshold ≤0.80). The overall vessel-based sensitivity, specificity and accuracy of CTA-FFR were 88% (CI 95%:79–94%), 65% (55–73%) and 75% (69–81%). The specificity was significantly lower in the presence of misalignment artifacts (25%, CI: 6–57%). A non-significant reduction in specificity from 74% (60–85%) to 48% (26–70%) was found for higher coronary artery calcium scores. Left ventricular mass, diabetes mellitus and large vessel size increased the discrepancy between invasive FFR and CTA-FFR values. ConclusionsOn-site calculation of CTA-FFR can identify hemodynamically significant CAD with an overall per-vessel accuracy of 75% in comparison to invasive FFR. The diagnostic performance of CTA-FFR is negatively affected by misalignment artifacts. CTA-FFR is potentially affected by left ventricular mass, diabetes mellitus and vessel size.

Relation between coronary artery calcium score and serum tenascin-C level in patients without known coronary artery disease

Objective Presence of coronary artery disease (CAD) also in subjects without traditional risk factors leads to a search for new risk factors. Tenascin-C (TNC), an extracellular matrix glycoprotein is normally found in very low concentrations in tissues and serum of adults, whereas its expression is enhanced in case of pathological conditions accompanied by inflammation. This study aimed to investigate the relation between coronary artery calcium score (CACS) and serum TNC level.Methods Ninety patients (age range, 18-75 years) presenting with chest pain but without known CAD were divided according to their CACSs as control (CACS = O, n = 30), low CACS (CACS between 0 and 400, n = 30), and high CACS (CACS ≥ 400, n = 30) groups. The patients were questioned about risk factors and underwent laboratory analyses for biochemical parameters including TNC.Results The mean TNC level was significantly higher in the high CACS group as compared to both the low CACS group and the control group [4.7 (0.03-30.7), 28 (0.7-212) and 84 (2-456) ng/mL, respectively; P < 0.01]. A positive correlation was determined between serum TNC level and CACS (r = 0.641, P < 0.001). In the ROC curve analysis, when the cut-off value for TNC was accepted as 8.09 ng/mL, the sensitivity and specificity in detecting patients with CACS > 100 (moderate or significant calcification) were 72% and 82%, respectively.Conclusion A significant relationship was found between CACS and serum TNC level. Thus, measurement of TNC level can be used in determining elevated CACS and thereby the risk for CAD.

Prognostic value of myocardial perfusion imaging and coronary artery calcium measurements in patients with end-stage renal disease.

Coronary artery disease (CAD) is highly prevalent in patients with end-stage renal disease (ESRD), owing to clustering of traditional and uremic-specific risk factors. However, in this population asymptomatic course of CAD is common and it has been reported that myocardial perfusion imaging (MPI) with single-photon emission tomography (SPET) has lower sensitivity. In the current study, we assessed the value of MPI gated-SPET and its combination with coronary artery calcium (CAC) score measurements in risk stratification of ESRD patients. MPI gated-SPET was performed with dual-headed SPET camera and CAC score measured by multi-detector computed tomography (MDCT) system.There were tested 77 ESRD individuals. During the follow-up study, cardiac events (CE) defined as cardiac death or nonfatal myocardial infarction (MI) or the necessity for coronary revascularization were recorded. Univariate and stepwise multivariable Cox proportional hazards-models were used to identify the predictors of CE. Eighteen CE were recorded during the follow-up. They were significantly associated with higher summed stress scores on MPI, higher percentage of ischaemic myocardium, higher occurrence of defects in multiple territories and higher CAC score (all with P<0.05). Univariate Cox proportional hazard-models showed that severe perfusion abnormalities as well as CAC score ≥1000 were significantly associated with cardiac events (P<0.0001, P=0.0056). In stepwise Cox proportional hazards-models considering age, gender, history of diabetes mellitus, post-stress left ventricular stunning, the degree of perfusion abnormality and CAC score, only severe perfusion abnormalities and CAC score ≥1000 were independent predictors of CE. There was no CE in patients with normal perfusion, normal function and zero CAC score. This study suggests that combined evaluation of MPI and CAC can predict the outcome in ESRD individuals, while severe perfusion abnormality on gated-SPET and high CAC score ≥1000 are predictors of future cardiac events.

Abstract 16624: Lung Cancer Screening With CT, Coronary Artery Calcification and Cardiovascular Events

Background: The Centers for Medicare &amp; Medicaid Services (CMS) recently approved lung cancer screening with CT. It is unclear whether reporting coronary artery calcium (CAC) on lung screening CT could improve identification of adults at risk for cardiovascular events (CVD) and competing risk from lung cancer. Thus we determined the incidence of hard CVD (myocardial infarction, stroke or coronary/cerebrovascular death), lung cancer (diagnosis or death) and CAC in adults eligible and ineligible for lung cancer screening. Methods: This longitudinal community-based cohort study included Framingham Heart Study Offspring Cohort participant-exams age 55-77 and free of prevalent cardiovascular disease and lung cancer from exams 3 (1984 – 1987) and 7 (1998 – 2001). Participants were divided into screening eligible and ineligible groups by CMS criteria (current or recent (≤15 years) former smokers with ≥30 pack-year history). Multivariate-adjusted cox proportional hazards models assessed the effect of screening eligibility on incident hard CVD and incident lung cancer. In participants who had CAC CT at exam 7, cross-sectional association between screening eligibility, high CAC score &gt;300 and incident CVD was assessed. Raw incidence rates are reported; p values are adjusted for age, sex and traditional risk factors aside from smoking. Results: Of 3085 participant-exams 20% were eligible for lung cancer screening. In mean follow up of 9.9 years, there were 281 incident CVD and 69 lung cancer events. In both groups, incident CVD was more frequent than lung cancer (eligible: 13% vs 7%, p=0.002; ineligible: 8% vs 1%, p&lt;0.001). The screening eligible had more incident CVD (13% vs 8%, p&lt;0.001) and lung cancer (7% vs 1%, p&lt;0.001) than the ineligible. CAC CT was available in 107 screening eligible and 667 ineligible participants; CAC &gt;300 was more common in the screening eligible (33% vs 23%, p=0.007). Conclusion: In a community-based primary prevention cohort, 20% aged 55-77 were eligible for lung cancer screening CT. CMS eligibility criteria identified disease-free persons with substantially more incident hard CVD and CAC; CVD was more common than lung cancer. The results support cardiovascular prevention and reporting of CAC as part of routine lung cancer screening CT.

Abstract 15854: Prognostic Value of Coronary CT Angiography and Coronary Artery Calcium Score Performed Before Revascularization

Introduction: Cardiac events after revascularization are equally attributable to recurrence at site of culprit lesions and development of non-culprit lesions. Because coronary CT angiography (CCTA) performed before revascularization can evaluate all plaque, including non-culprit lesions, and in theory can serve as a predictor of cardiac events after treatment. We evaluated the hypothesis that CCTA and coronary artery calcium score (CACS) performed before revascularization predicts cardiac events after treatment. Methods: Among 2238 consecutive patients without known coronary artery disease who underwent coronary CCTA and CACS, 359 patients underwent revascularization within 30 days after CT; in 337 of 359 (93.9%) follow-up clinical information was available. In addition to known cardiac risk factors, CT findings were evaluated as predictors of cardiac events after revascularization: CACS and the presence of CT-verified high risk plaque (CT-HRP). Improvement of predictive accuracy by including CT findings was evaluated from discrimination (Harrell’s C-statistics) and reclassification (net reclassification indices (NRI)) standpoints. Results: During the follow-up period (median: 673, interquartile range: 47-1529 days), a total of 98 cardiac events occurred. Cox proportional hazard model revealed that age, diabetes, triglyceride, CACS and non-culprit CT-HRP were significant predictors of overall cardiac events. Although not statistically significant, discriminatory power was greater for the model with CACS (C-stat: 63.2%) and the model with both CACS and CT-HRP (65.8%) compared to the model including neither CACS nor CT-HRP (60.7%). Reclassification improved by including CACS into the model when compared to the model without it (NRI=12.7%; category-free NRI=40.7%) and CT-HRP added to CACS further improved the classification (NRI=6.9%; category-free NRI=14.3%). Conclusions: High CACS and the presence of non-culprit CT-HRP performed before revascularization are significant predictors of cardiac events after revascularization.

Abstract 15155: Good Exercise Capacity Alleviates the Effect of High Coronary Atherosclerotic Burden on All-cause Mortality

Introduction: Both exercise capacity and coronary artery calcium score (CACS) have been reported to be important prognostic factors. It has not been well studied whether there is significant interaction between these two factors in influencing clinical outcome. Hypothesis: The effect size of CACS on all-cause mortality is reduced by higher level of exercise tolerance. Methods: From multicenter registry of health screening cohort, 26,286 subjects were included in the final dataset for analysis who underwent both coronary calcium scoring and treadmill exercise test. All-cause mortality data were obtained from national mortality registry. Results: The mean age of study subjects was 54 ± 8 years and proportion of male subjects 81%. Median follow-up duration was 5.5 (interquartile range 3.6 - 7.5) years and 232 (0.9%) deaths occurred. In fully adjusted Cox’s proportional hazard model with interaction term, exercise capacity ≥ 10 METs (hazard ratio (HR) 0.684, 95% CI 0.483 - 0.971) and CACS ≥ 400 (HR 3.328, 95% CI 1.850 - 5.988) were significant predictors of mortality and the HR of CACS ≥ 400 in those with lower exercise capacity is estimated to be about three times of that in those with higher exercise capacity. (HR 3.328 in &lt; 10 METs vs. 1.108 in ≥ 10 METs, p for interaction = 0.024) after adjustment for age, gender, fasting glucose, serum creatinine, serum ALT and serum albumin. Conclusions: In subjects with higher exercise capacity, the effect of very high CACS on all-cause mortality was significantly smaller than in those with lower exercise capacity. Good physical fitness is likely to override, at least partially, the adverse effect of high coronary atherosclerotic burden.

Abstract 16145: Significance of High-sensitivity Cardiac Troponin T Levels Between the Limit of Blank and the Limit of Detection in the General Population: A Meta-analysis

Introduction: A substantial minority of asymptomatic individuals will have very low but measurable levels of cardiac troponin T using a high sensitive assay (hs-cTnT). It is controversial if levels in this range provide physiologic and prognostic information. We hypothesized that hs-cTnT levels between the limit of blank (LOB) (3 ng/L) and limit of detection (LOD) (5 ng/L) are associated with increased incidence of heart failure (HF) and cardiovascular death compared to levels below the LOB (&lt;3 ng/L). Methods: hs-cTnT was measured in subjects without prevalent HF from the Cardiovascular Health Study (CHS), Atherosclerosis Risk in Communities (ARIC) study, and Dallas Heart Study (DHS). Participants were divided into two groups: levels below the LOB (n=7272) and levels between the LOB and LOD (n=3451). Cross sectional and longitudinal associations with demographics, traditional cardiovascular risk factors, and cardiovascular outcomes were made. A fixed-effect meta-analysis was performed using regression coefficients and variance estimates from fully adjusted models from all three cohorts. Results: Participants with hs-cTnT between the LOB and LOD were older, more likely to be male, and had higher prevalence of cardiovascular risk factors and structural abnormalities such as higher coronary artery calcium score and left ventricular mass. A meta-analysis of the three cohorts showed participants with hs-cTnT between the LOB and LOD were at increased risk of new-onset HF (HR=1.18, 95% CI: 1.02, 1.38) and cardiovascular death (HR=1.29, 95% CI: 1.06, 1.57) after adjusting for demographics and traditional risk factors when compared to participants with hs-cTnT below the LOB (Figure). Conclusions: hs-cTnT levels between the LOB and LOD are associated with a higher prevalence of traditional risk factors, cardiac pathology, and worse outcomes compared with levels below the LOB. Therefore, in general population cohorts, hs-cTnT should be reported down to the LOB.

Variation in Cardiac Vein System is Associated with Coronary Artery Calcium - A Venous-Atherosclerosis Paradox?

The factors that determine the different patterns of venous anatomy are not well understood. This study was designed to evaluate the relationship between variation in the cardiac vein system and the extent of coronary artery calcium score (CACS). We reviewed the results of 64-slice CTs of 226 subjects (age 57.2 ± 11.2; 133M) enrolled in our study. The subjects were divided into 3 groups based on coronary artery calcium: 92 patients. with CACS = 0 AU (Agatston Unit, AU); 56 with CACS = 1-100 AU; and 78 patients with CACS > than 100 AU. The cardiac venous system was reconstructed during the optimal phase of the cardiac cycle in each subject. Subjects with a higher CACS had a better quality of vein images (p < 0.01). The number of visible veins differed between the groups. Eight subjects (8.7%) in the group with CACS = 0 AU, 7 (12.5%) in the group with CACS = 1-100 AU, and 23 (29.5%) in the group with CACS > 100 AU had five or more visible veins (p < 0.001), whereas the proportion of subjects with less than three visible veins was 56 (60.8%), 31 (55.4%) and 30 (38.4%), respectively (p < 0.05). The number of visible veins correlated with CACS (r = 0.28; p < 0.05). In a multivariate regression analysis, which included age, gender, CACS, LV ejection fraction, myocardial volume and heart rate, the CACS was found to be an independent determinant of the number of visible veins (p < 0.05). The results of our study suggested that there is a link between a variation in the cardiac venous system and the extent of atherosclerosis. Coronary artery calcium score (CACS); Computed tomography; Coronary veins.

Subclinical Atherosclerosis and Relationship With Risk Factors of Coronary Artery Disease in a Rural Population

BackgroundAnnually, over 150,000 cardiovascular events occur among individuals <65 years old in the United States, including asymptomatic ones. Coronary artery calcium (CAC), a subclinical marker of coronary artery disease (CAD), enhances risk stratification among asymptomatic individuals. This study assessed the prevalence of CAC in a rural population and determined relationships between traditional risk factors for CAD and CAC scores. MethodsDuring January 2011 to December 2012, asymptomatic individuals from central Appalachia were screened for CAC in the largest tertiary cardiovascular institute. Based on Agatston scale, participants were grouped into 4 CAC scores: zero (CAC = 0), mild (CAC = 1–99), moderate (CAC = 100–399) and severe (CAC ≥ 400). Multinomial logistic regression was used to examine associations between potential risk factors of CAD and CAC score. ResultsOf 1,674 participants, 55.4% had positive CAC score (CAC > 0). Increasing age and being male were positively associated with higher CAC scores. Although there was significant association between mild CAC and hypertension and family history of CAD, moderate CAC was positively associated with smoking status. Except hypercholesterolemia and sedentary lifestyle, severe CAC was significantly associated with major health conditions (obesity, diabetes and hypertension), lifestyle (smoking) and family history of CAD. ConclusionsMore than half of participants in the CAC screening had subclinical CAD (CAC score > 0). The association between CAC score and CAD risk factors suggests that education about subclinical atherosclerosis among asymptomatic individuals in this region with high cardiovascular disease prevalence is needed because CAC improves CAD risk stratification, and the knowledge of CAC enhances medication adherence and motivates individuals towards beneficial behavioral/lifestyle modification.

Using aortic distensibility index to detect coronary stenosis

Objective The aortic distensibility index, as a measure of vascular function, can serve as a marker of coronary artery disease severity. This study explores the feasibility of using the non-invasively measured index as an indicator of severity of coronary stenosis.Methods One hundred patients with normal left ventricular systolic function were prospectively enrolled. They were subjected to assessment of aortic distensibility using computed tomographic angiography and transthoracic echocardiography. Coronary artery disease severity and coronary artery calcium score were assessed.Results The mean age of the whole study cohort was 58 ± 9 years, 63 (63%) being males. A signifi cant inverse correlation was found between aortic distensibility measured using computed tomographic angiography and patients’ age, systolic blood pressure, coronary artery calcium score and severity of coronary artery disease (percent luminal stenosis). However, there was no statistical correlation with the number of diseased coronary arteries. A strong direct correlation was recorded upon comparing aortic distensibility index values obtained using computed tomographic angiography and transthoracic echocardiography (r = 0.325, P= 0.004). Receiver operating characteristic curve analysis revealed that an echocardiography-derived aortic distensibility index value of ≤ 6.65% is associated with signifi cant (≥ 50% luminal stenosis) coronary artery disease with a sensitivity of 83%, specifi city of 93%, positive predictive value of 97% and negative predictive value of 65%.Conclusion Non-invasive assessment of aortic distensibility indices is a feasible procedure to predict signifi cant atherosclerotic coronary artery disease. Lower values are associated with signifi cant obstructive coronary artery disease and high coronary artery calcium score.

Low serum testosterone level was associated with extensive coronary artery calcification in elderly male patients with stable coronary artery disease

Coronary artery calcification (CAC) is a pandemic condition in elderly patients with coronary artery disease (CAD) and associated with a worse prognosis. Although available data have shown an association between testosterone levels in men and CAD, the association between testosterone and CAC in elderly male patients with CAD remains unknown. A total of 211 consecutive male patients (age ≥ 65 years) who underwent first multidetector computed tomography and following angiography were enrolled from our institution between March 2009 and September 2014. CAD was angiographically documented as significant stenoses (reduction ≥ 50% of the lumen diameter) on any major coronary vessel. The standard Agatston calcium score was calculated. The relationship of serum testosterone level with the CAC score measured by multidetector computed tomography in elderly male patients with stable CAD was evaluated. For data analyses, the CAC score was divided into four categories: ≤ 10, 11-99, 100-399, and ≥ 400, corresponding to minimal, moderate, increased, and extensive calcification. Patients with higher CAC scores had significantly lower testosterone levels than patients with lower CAC scores (P = 0.048). In logistic regression analysis, testosterone level remained an independent predictor of extensive CAC (odds ratio 0.997, 95% confidence interval 0.994-0.999, P = 0.043). Our findings indicate an inverse association between testosterone level and the susceptibility to extensive CAC in elderly men with stable CAD.

The value of coronary artery calcium score in the early diagnosis of coronary artery disease in patients with stable chronic obstructive pulmonary disease.

Objective:Our aim was to assess the value of coronary artery calcium score (CACS) in the early diagnosis of coronary artery disease in Global Initiative for Chronic Obstructive Lung Disease (GOLD) stage II chronic obstructive pulmonary disease (COPD) patients and to identify high-risk patients.Methods:Forty-two patients with GOLD stage II COPD and 31 healthy control subjects were enrolled in the study. This study was designed as a prospective observational cross-sectional study. Pearson’s correlation coefficient was used for comparisons between groups. Criteria for stage II COPD diagnosis were forced expiratory volume in 1 second (FEV1)/forced vital capacity (FVC) of <70% and 50%≤FEV1<80%. Excluded from the study were individuals who had a previous diagnosis of coronary artery disease, GOLD stage I-III-IV COPD, or left ventricular systolic dysfunction.Results:As compared with the control group, CACS values were significantly higher in the patient group (p=0.030 and 0.001, respectively). CACS was significantly higher in male patients with a positive family history, physical inactivity, long duration of disease, and low FEV1 (0.027, 0.008; 0.001 and 0.001; 0.001, respectively). Logistical regression analysis of sex, age, diabetes mellitus, hypertension, cigarette smoking, family history, physical inactivity, and FEV1 values showed that physical inactivity was independently correlated with high CACS [odds ratio (OR): 7; confidence interval (CI): 3–20; p=0.001].Conclusion:The value of CACS is high in stage II COPD patients. Male stage II COPD patients with a disease duration of 10 years, physical inactivity, and/or a positive family history should be monitored for early stage coronary artery disease and coronary events, regardless of risk factors such as diabetes, hypertension, and hyperlipidemia.

Very high coronary artery calcium score with normal myocardial perfusion SPECT imaging is associated with a moderate incidence of severe coronary artery disease.

PurposeMyocardial perfusion imaging (MPI) has limitations in the presence of balanced multivessel disease (MVD) and left main (LM) coronary artery disease, occasionally resulting in false-normal results despite the high cardiovascular risk associated with this condition. The purpose of this study was to assess the incidence of severe coronary artery disease (CAD) in the presence of a very high Agatston coronary artery calcium (CAC) score (>1,000) in stable symptomatic patients without known CAD but with normal MPI results.MethodsA total of 2,659 prospectively acquired consecutive patients were referred for MPI and evaluation of CAC score by CT. Of this patient population, 8 % (222/2,659) had ischemia without myocardial infarction (MI) on MPIand 11 % (298/2,659) had abnormal MPI (MI and/or ischemia). On presentation 1 % of the patients (26/2,659) were symptomatic, had a CAC score >1,000 and normal MPI results. The definition of normal MPI was strict and included a normal hemodynamic response without ischemic ECG changes and normal imaging, particularly absence of transient ischemic dilation. All of these 26 patients with a CAC score >1,000 and normal MPI findings underwent cardiac catheterization.ResultsOf these 26 patients, 58 % (15/26) had severe disease (≥70 % stenosis) leading to revascularization. Of this group, 47 % (7/15) underwent percutaneous intervention, and 53 % (8/15) underwent coronary artery bypass grafting. All of these 15 patients had either MVD (14/15) or LM coronary artery disease (1/15), and represented 0.6 % (15/2,659) of all referred patients (95 % CI 0.3 – 0.9 %). The majority, 90 % (8/9), had severe CAD with typical chest pain.ConclusionA very high CAC score (>1,000) with normal MPI in a small subset of symptomatically stable patients was associated with a moderate incidence of severe CAD (95 % CI 37 – 77 %). Larger studies and/or a meta-analysis of small studies are needed to more precisely estimate the incidence of CAD in this population. This study also supports the concept that a normal MPI result in patients with severe CAD may be due to balanced MVD.Electronic supplementary materialThe online version of this article (doi:10.1007/s00259-015-3072-z) contains supplementary material, which is available to authorized users.

Low cardiorespiratory fitness and coronary artery calcification: Complementary cardiovascular risk predictors in asymptomatic type 2 diabetics.

Despite its well-established prognostic value, cardiorespiratory fitness (CRF) is not incorporated routinely in risk assessment tools. Whether low CRF provides additional predictive information in asymptomatic type 2 diabetics beyond conventional risk scores and coronary artery calcification (CAC) is unclear. We studied 600 type 2 diabetics aged 55-74 years without known coronary heart disease. CRF was quantified in metabolic equivalents (METs) by maximal treadmill testing and categorized as tertiles of percent predicted METs (ppMETs) achieved. CAC was calculated by non-enhanced computed tomography scans. The individual and joint association of both measures with an outcome event of all-cause mortality, myocardial infarction or stroke, was determined over a mean follow-up period of 80±16 months. There were 72 (12%) events during follow-up. Low CRF was independently associated with event risk after adjustment for traditional risk factors and CAC (HR 2.25, 95% CI 1.41-3.57, p=0.001). CRF (unfit/fit) allowed further outcome discrimination both amongst diabetics with low CAC scores (9.5% versus 2.0% event rate), and amongst diabetics with high CAC scores (23.5% versus 12.4% event rate), p<0.001. The addition of CRF to a model comprising UKPDS and CAC scores improved the area under the curve for event prediction from 0.66 to 0.71, p=0.03, with a positive continuous net reclassification improvement (NRI) of 0.451, p=0.002. CRF, quantified by ppMETs, provided independent prognostic information which was additive to CAC. Low CRF may identify asymptomatic diabetic subjects at higher risk for all-cause mortality, myocardial infarction or stroke, despite low CAC.

9 Micrornas Represent Novel Biological Markers of Coronary Artery Calcification

Introduction Conventional risk stratification fails to identify many individuals presenting with major adverse cardiovascular events (MACE). Coronary artery calcification (CAC) is a powerful independent predictor of MACE however its use is limited by radiation and expense. MicroRNAs are non-coding RNAs that regulate transcription and their differential expression is acknowledged to be a hallmark of a number of diseases. We aim to determine if a peripheral blood-based microRNA profile is predictive of the presence and extent of CAC in humans. Methods Study patients met the following inclusion criteria: attendance for elective cardiac computed tomography; age 18–65 years; no history of coronary artery disease, cardiomyopathy or tachyarrhythmia; normal renal function; no history of diabetes mellitus; no autoimmune disease; no infection; no malignancy. Peripheral venesection was performed and an Agatston score was derived using default software. RNA was extracted using the LeukoLOCK Total RNA Isolation System and stored at –80 o C until Toray’s microarray analysis was undertaken. Results 24 participants were recruited (mean age 54 years; 67% male) and divided into the following categories: [CAC score 0] n = 6; [CAC score 1–10] n = 6; [CAC score 11–100] n = 6; [CAC score > 100] n = 6. Groups were matched according to their baseline characteristics; Table 1. The Student’s t-test was performed between groups. MiR-1181 was significantly down-regulated in all case groups compared to controls: [CAC 1–10] effect size (ES) = 1.76, p = 0.012; [CAC 11–100] ES = 1.74, p = 0.013; [CAC > 100] ES = 3.86, p 100 compared to controls (ES = 3, p Conclusions Human blood-based miRNA-1181 appears to predict the presence and extent of CAC. Likewise miRNAs miR-138-2-3p, miR-6816-3p and miR-8059 are differentially expressed in patients with high CAC scores. We plan to validate these findings using quantitative real-time PCR and to test these results in a prospective cohort. Ultimately miRNAs could act as a biomarker for MACE and identifying their associated molecular pathways may explain the mechanisms underpinning CAC.

Prognostic Value Of Normal Myocardial Perfusion Imaging In Asymptomatic Diabetic Patients With Moderate And High Calcium Scores

Abstract The purpose of this study was to evaluate the intermediate prognostic value of normal myocardial perfusion imaging (MPI) in asymptomatic diabetic patients with intermediate and high coronary artery calcium (CAC) scores. Methods: A total of 115 asymptomatic diabetic patients with no known coronary artery disease (CAD) underwent MPI after multi-slice computed tomography CAC assessment for the detection of suspected CAD. The study included 75 patients with normal MPI results. A 17-segment model for myocardial perfusion and function analysis was used. Patients were divided into three groups: I gr-20 patients with a diabetes duration between 1-5 years; II gr-24 patients with a diabetes duration 5-10 years; and III gr-31 patients with a diabetes duration &gt;10 years. End points (cardiac death, non-fatal myocardial infarction, heart failure, new angina, revascularization) were assessed at 6, 12 and 24 months. All patients had normal resting left ventricular function and normal myocardial perfusion scans. Forty patients had moderate coronary artery calcification with an average CAC of 290+/−95. Thirty-five patients had severe coronary calcification with an average CAC of 568+/−67. A correlation was found between diabetes duration and CAC severity (r-0,62 for diabetes duration over 10 years). Three cardiac events were identified at 24--month follow-up (new angina with percutaneous coronary intervention-PCI). Hard events (cardiac death, nonfatal myocardial infarction) were observed at a rate of 0% in group I, 4.2% in group II and 6.4% in group III. The overall event rate at 24--month follow-up was 4.0%. MPI and CAC are valuable techniques for the preclinical assessment of CAD in asymptomatic diabetic patients. This could guide decision-making to result in optimal treatment and prognosis. Even diabetic patients with normal MPI are at increased intermediate risk for CV events.

Coronary artery calcification, epicardial fat burden, and cardiovascular events in chronic obstructive pulmonary disease.

RationalePatients with chronic obstructive pulmonary disease (COPD) suffer from significantly more cardiovascular comorbidity and mortality than would be anticipated from conventional risk factors. The aim of this study was to determine whether COPD patients have a higher coronary artery calcium score (CACS) and epicardial fat burden, compared to control subjects, and their association with cardiovascular events.MethodsFrom a registry of 1906 patients 81 patients with clinically diagnosed COPD were one-to-one matched to 81 non-COPD control subjects with a smoking history, according to their age, sex, and the number of classic cardiovascular risk factors (arterial hypertension, diabetes mellitus, dyslipidemia, family history of premature coronary artery disease). CACS, epicardial fat, and subsequent major adverse cardiovascular events (MACE) during follow-up were compared between groups.ResultsPatients with COPD (Global Initiative for Chronic Obstructive Lung Disease-classification I: 5%, II: 23%, III: 16% and IV: 56%) showed no difference in CACS (median difference 68 Agatston Units [95% confidence interval -176.5 to 192.5], p=0.899) or epicardial fat volume (mean difference -0.5 cm3 [95% confidence interval -20.9 to 21.9], p=0.961) compared with controls. After a median follow-up of 42.6 months a higher incidence of MACE was observed in COPD patients (RR=2.80, p=0.016) compared with controls. Cox proportional hazard regression identified cardiac ischemias and CACS as independent predictors for MACE.ConclusionCOPD patients experienced a higher MACE incidence compared to controls despite no baseline differences in coronary calcification and epicardial fat burden. Other mechanisms such as undersupply of medication seem to account for an excess cardiovascular comorbidity in COPD patients.