MRI is considered
reference standard for the
assessment of left ventricular (LV)
volume and mass measurements.
There are few accepted guidelines
for uniform assessment of cardiac
function with MRI. We sought to
investigate different confounding
factors influencing LV measurement
Material and Methods
In 60 diabetic type-II patients
(group A) we compared intra-/inter-reader variability of MRI for
cardiac function measured twice at
a 3 month interval by one MRI
trained reader and one untrained.
In 20 patients (group B) two different
techniques were compared
for determining the epicardial and
Bland Altman analysis showed
excellent intra-observer measurement
agreement for the trained
reader 1 for EDM (mean=–2.3
(–23.6–19)), EDV (2.9(–9.2–15.0)),
ESV (3.3(–5.8–12.4)) and EF
(1.2(–3.3–5.7)). Untrained reader 2
measurement agreement was considerably
less appropriate for EDM
(mean=–8.2 (–25.8–9.5)), EDV
(7.8(–5.1–20.7)), ESV (5.3(–8.0–18.6)). Only for EF (0.8 (–6.5–8.1))
results were comparable to reader
1. Inter-observer measurement
in the beginning was poor for
EDM (–13.5(–55.6–28.6)) and EDV
(7.3(–61.9–76.6)), whereas agreement
for ESV (2.1(–29.9–34.2))
and EF (–0.9(–11.6–9.9)) was
good. After 3 months, measurement
agreement for EDM (–5.3
(–46.4–35.8)) was considerably
improved, for EDV (0.4(–67.0–66.2)) was excellent, whereas
agreement for ESV (3.1(–34.4–28.1)) and EF (–1.7(–13.0–9.6))
was similar. Using different techniques
for determining the epicardial
and endocardial borders,
only end-diastolic volume was
unchanged whereas all other parameters
were significantly different
using the two methods
(p ≤ 0.03).
inter-reader variability, analyst
experience as well as different
techniques for determining the
boundaries of the left ventricle
significantly affect MRI parameters
for cardiac function. These
results suggest a need for developing
commonly accepted standards
for cardiac MRI evaluation.
Clinical Research in Cardiology 04/2012; 96(10):743-751. · 2.95 Impact Factor
ABSTRACT: Fatty liver disease is a common clinical entity in hepatology practice. This study evaluates the prevalence and reproducibility of computed tomography (CT) measures for diagnosis of fatty liver and compares commonly used CT criteria for the diagnosis of liver fat.
The study includes 6814 asymptomatic participants from a population-based sample. The ratio of liver-to-spleen (L/S) Hounsfield units (HU) <1.0 and liver attenuation <40 HU were used for diagnosing and assessing the severity of liver fat content. Participants with heavy alcohol intake (>7 drinks/week for women and >14 drinks/week for men) were excluded. Final analysis was performed on participants where images of both liver and spleen were available on the scans.
The overall prevalence of fatty liver (4175 subjects included in final analysis) was 17.2% (using L/S ratio <1.0), with 6.3% (with <40 HU cutoff) of the population having moderate to severe steatosis (>30% liver fat content). The prevalence was high in participants with dyslipidemia (70.4%), hypertension (56.8%), and obesity (53%). Diabetic patients had 24.1% prevalence of fatty liver. The prevalence provided by L/S ratio <1.0 (17.2%) was comparable to prevalence provided by <51 HU (17.3%), whereas prevalence obtained by <40 HU (6.3%) cutoff corresponded to L/S ratio of <0.8 (6.5%). The measurements of liver and spleen HU attenuations were highly reproducible (0.96, 0.99 and 0.99, 0.99 for intra- and inter-reader variability, respectively) in a sample of 100 scans.
Fatty liver can be reliably diagnosed using nonenhanced CT scans.
Academic radiology 04/2012; 19(7):811-8. · 2.09 Impact Factor
JAMA The Journal of the American Medical Association 04/2012; 307(14):1489-90. · 30.03 Impact Factor
ABSTRACT: The value of coronary artery calcium (CAC) scoring versus multiple biomarkers in increasing risk prediction for cardiovascular disease (CVD) remains unknown. The study group consisted of 1,286 asymptomatic participants (mean ± SD 59 ± 8 years old) with no known coronary heart disease. Mean follow-up time was 4.1 ± 0.4 years with the primary outcome of combined CVD (cardiac death, myocardial infarction, stroke, and late target vessel revascularization). CAC was calculated by the method of Agatston. Biomarkers measured were C-reactive protein, interleukin-6, myeloperoxidase, B-type natriuretic peptide, and plasminogen activator-1. During follow-up 35 participants developed CVD events including cardiac deaths (6%), myocardial infarction (23%), strokes (17%), and late revascularizations (54%). In Cox proportional-hazards models adjusted for Framingham Risk Score (FRS), presence of log CAC beyond FRS was associated with increased hazards for CVD events (hazard ratio 1.7, 95% confidence interval [CI] 1.4 to 2.0, p <0.001). Multiple biomarkers score was also associated with increased risk beyond FRS (hazard ratio 2.1, p = 0.02) per 1-U increase in score; however, the c-statistic did not increase significantly (0.75, 95% CI 0.68 to 0.84, p = 0.32). The c-statistic increased when log CAC was incorporated into FRS without or with multiple biomarkers score (c-statistic 0.84, p = 0.003 and p = 0.008 respectively). Addition of CAC to risk factors showed significant reclassification (net reclassification improvement 0.35 (95% CI 0.11 to 0.58, p = 0.007; integrated discrimination index 0.076, p = 0.0001), whereas addition of multiple biomarkers score did not show significant reclassification. In conclusion, in this study of asymptomatic subjects without known CVD, addition of CAC but not biomarkers substantially improved risk reclassification for future CVD events beyond traditional risk factors.
The American journal of cardiology 03/2012; 109(10):1449-53. · 3.58 Impact Factor
ABSTRACT: It is unclear whether coronary artery calcium (CAC) is effective for risk stratifying patients with diabetes in whom treatment decisions are uncertain.
Of 44,052 asymptomatic individuals referred for CAC testing, we studied 2,384 individuals with diabetes. Subjects were followed for a mean of 5.6 ± 2.6 years for the end point of all-cause mortality.
There were 162 deaths (6.8%) in the population. CAC was a strong predictor of mortality across age-groups (age <50, 50-59, ≥60), sex, and risk factor burden (0 vs. ≥1 additional risk factor). In individuals without a clear indication for aspirin per current guidelines, CAC stratified risk, identifying patients above and below the 10% risk threshold of presumed aspirin benefit.
CAC can help risk stratify individuals with diabetes and may aid in selection of patients who may benefit from therapies such as low-dose aspirin for primary prevention.
Diabetes care 03/2012; 35(3):624-6. · 8.09 Impact Factor
ABSTRACT: The 2006 Cardiac CT Appropriate Use Criteria (AUC) were recently revised in 2010. In addition to rating an expanded number of indications, the new criteria adjusted the appropriateness of existing indications to reflect changes in clinical practice and new evidence since 2006.
We sought to determine how the appropriateness of cardiac CT examinations performed at a tertiary-care hospital changed under the revised criteria compared with the original AUC.
Data were collected from the medical records and personal interview of 267 consecutive patients referred for cardiac CT in 2008. With the use of the 2010 and 2006 AUCs, two physicians designated each examination's indication as appropriate, inappropriate, uncertain, or "not classified" if examination indication could not be assigned.
With the use the new 2010 AUC, a highly significant change was observed in the classification of examination appropriateness (P < 0.001), with 40% of examinations changing appropriateness level compared with the 2006 AUC. Under the 2010 AUC, there were an increased proportion of both appropriate examinations (59% vs. 45%; P < 0.001) and inappropriate examinations (15% vs. 10%; P < 0.001), and approximately the same proportion with uncertain appropriateness (13% vs. 16%; P = 0.33). Consequently, the proportion of examinations that were not classified was significantly reduced under the 2010 AUC (29% vs. 13%; P < 0.001).
The revision of the AUC for cardiac CT had a significant effect on examination appropriateness. In comparison to the 2006 AUC, the 2010 AUC provided improved clarification of examination appropriateness. This shift was because of the inclusion of many previously unaddressed indications and the designation of more examinations as either appropriate or inappropriate.
Journal of cardiovascular computed tomography 03/2012; 6(2):99-107.
ABSTRACT: The aims of our study were to (1) examine how data from exercise treadmill testing (ETT) can identify patients who have coronary plaque or stenosis, using CT angiography (CTA) as the reference standard, and (2) identify patient characteristics that may be used in selecting ETT versus CTA.
The Rule Out Myocardial Infarction Using Computer-Assisted Tomography (ROMICAT) trial was an observational cohort study of acute chest pain patients presenting to the emergency department with normal initial troponin and a nonischemic ECG. Univariate and multivariable analyses were performed to assess the relationship of baseline clinical data and ETT parameters with coronary plaque and stenosis on CTA. Of the 220 patients who had ETT (mean age, 51 years; 63% men), 21 (10%) had positive results. A positive ETT had a sensitivity of 30% and specificity of 93% to detect >50% stenosis. The sensitivity increased to 83% after excluding uninterpretable segments and evaluating the ability to detect a >70% stenosis. Predictors of plaque included older age, male sex, diabetes, hypertension, hyperlipidemia, lower functional capacity, and a lower Duke Treadmill Score. Both a positive ETT and a low Duke Treadmill Score were significant univariate and multivariable predictors of stenosis >50% on CTA Whereas the prevalence of stenosis by CTA was greater among patients with more risk factors, coronary stenosis was not present among men <40 years old or women <50 years old or individuals who achieved at least 13 metabolic equivalents on ETT.
Among low- to intermediate-risk patients with acute chest pain, a positive ETT has a limited sensitivity but high specificity for the detection of >50% stenosis by CTA. Although patients with a high number of clinical risk factors are more likely to have obstructive coronary artery disease, those who are young or who would be expected to have a very high exercise capacity are unlikely to have coronary stenosis and therefore may benefit from initial ETT testing instead of CTA.
Circulation Cardiovascular Imaging 02/2012; 5(2):233-42. · 5.94 Impact Factor
ABSTRACT: Much attention has been directed toward lifestyle modifications as effective means of reducing cardiovascular disease risk. In particular, physical activity has been heavily studied because of its well-known effects on metabolic syndrome, insulin sensitivity, cardiovascular disease risk, and all-cause mortality. However, data regarding the effects of exercise on various stages of the atherosclerosis pathway remain conflicting. The investigators review previously published reports for recent observational and interventional trials investigating the effects of physical activity on markers of (or causal factors for) atherosclerotic burden and vascular disease, including serum lipoproteins, systemic inflammation, thrombosis, coronary artery calcium, and carotid intima-media thickness. In conclusion, the data show a correlation between physical activity and triglyceride reduction, apolipoprotein B reduction, high-density lipoprotein increase, change in low-density lipoprotein particle size, increase in tissue plasminogen activator activity, and decrease in coronary artery calcium. Further research is needed to elucidate the effect of physical activity on inflammatory markers and intima-media thickness.
The American journal of cardiology 01/2012; 109(2):288-95. · 3.58 Impact Factor
ABSTRACT: We sought to evaluate the ability of the Diamond and Forrester method (DFM) and the Duke Clinical Score (DCS) to predict obstructive coronary artery disease (CAD) on coronary computed tomographic angiography (CCTA) and the effect of these different risk scores on the appropriateness level using the 2010 Appropriate Use Criteria. Consecutive symptomatic patients who underwent CCTA for evaluation of CAD (n = 114) were classified as having a low, intermediate, or high pretest probability using the DFM and DCS. Using the Appropriate Use Criteria, the indications for CCTA were classified according to the pretest probability and previous testing. The CCTA results were classified as revealing obstructive (≥70% stenosis), nonobstructive (<70%), or no CAD. When the patients' risk was classified using the DFM, 18% were low, 65% intermediate, and 17% high risk. When using the DCS, 53% of patients had a reclassification of their risk, most of whom changed from intermediate to either low or high risk (50% low, 19% intermediate, 35% high risk). The net reclassification improvement for the prediction of obstructive CAD was 51% (p = 0.01). Of the 37 patients who were reclassified as low risk, 36 (97%) lacked obstructive CAD. Appropriateness for CCTA was reclassified for 13% of patients when using the DCS instead of the DFM, and the number of appropriate examinations was significantly fewer (68% vs 55%, p <0.001). In conclusion, reclassification of risk using the DCS instead of the DFM resulted in improved prediction of obstructive CAD on CCTA, especially in low-risk patients. More patients were categorized as having a high pretest probability of CAD, resulting in reclassification of their examination indications as uncertain or inappropriate. These results identify the need for improved pretest risk scores for noninvasive tests such as CCTA and suggest that the method of risk assessment could have important implications for patient selection and quality assurance programs.
The American journal of cardiology 01/2012; 109(7):998-1004. · 3.58 Impact Factor
JACC. Cardiovascular imaging 01/2012; 5(1):111-8. · 14.29 Impact Factor
ABSTRACT: OPINION STATEMENT: Subclinical coronary artery disease (CAD) is widespread and under-diagnosed. Preventive efforts are required to reduce the burden of this disease and its complications. Imaging of coronary artery calcium (CAC) with cardiac computed tomography is highly specific for the diagnosis of subclinical CAD and can also facilitate treatment decisions in preventive cardiology. Indeed, CAC testing has been recommended by the American Heart Association for asymptomatic patients at intermediate risk for future cardiac events (as defined by clinical risk factors) to refine existing risk estimates. However, the optimal follow-up of those patients who have already undergone CAC testing remains unclear, particularly with regards to repeat CAC testing. The existing literature points to two major considerations for the use of CAC progression in the management of subclinical CAD. On one hand, CAC progression has been used as a surrogate marker to test the efficacy of cardiac preventive medications in halting or regressing CAD. To date, study results have been mostly disappointing and CAC progression appears resistant to medications such as statins. On the other hand, however, CAC progression has potential as a clinical indicator of underlying CAD activity. This may facilitate optimization or up-titration of preventive medications by using CAC progression as a marker of subclinical disease activity. We believe that the data, thus far, argues against the use of a CAC progression as a clinical surrogate marker of preventive therapy efficacy. Further studies with non-statin medications and with concomitant outcome data are needed. However, CAC progression has potential for monitoring subclinical CAD in some patients and may facilitate treatment decisions. In this review we will provide recommendations for repeat CAC testing and discuss when repeat CAC testing may be helpful to assess coronary artery disease progression.
Current Treatment Options in Cardiovascular Medicine 11/2011; 14(1):69-80.
ABSTRACT: The purpose of this study was to compare the association of the Framingham risk score (FRS) and Reynolds risk score (RRS) with subclinical atherosclerosis, assessed by incidence and progression of coronary artery calcium (CAC).
The comparative effectiveness of competing risk algorithms for identifying subclinical atherosclerosis is unknown.
MESA (Multi-Ethnic Study of Atherosclerosis) is a prospective cohort study of 6,814 participants free of baseline cardiovascular disease. All participants underwent risk factor assessment, as well as baseline and follow-up CAC testing. We assessed the performance of the FRS and RRS to predict CAC incidence and progression using relative risk and robust linear regression.
The study population included 5,140 individuals (mean age 61 ± 10 years, 47% males, mean follow-up: 3.1 ± 1.3 years). Among 53% of subjects (n = 2,729) with no baseline CAC, 18% (n = 510) developed incident CAC. Both the FRS and RRS were significantly predictive of incident CAC (relative risk: 1.40 [95% confidence interval (CI): 1.29 to 1.52] and 1.41 [95% CI: 1.30 to 1.54] per 5% increase in risk, respectively) and CAC progression (mean CAC score change: 6.92 [95% CI: 5.31 to 8.54] and 6.82 [95% CI: 5.51 to 8.14] per 5% increase). Discordance in risk category classification (<10% or >10% per 10-year coronary heart disease risk) occurred in 13.7%, with only the RRS consistently adding predictive value for incidence and progression of CAC. These subclinical atherosclerosis findings are supported by a coronary heart disease events analysis over a mean follow-up of 5.6 ± 0.7 years.
Both the RRS and FRS predict onset and progression of subclinical atherosclerosis. However, the RRS may provide additional predictive information when discordance between the scoring systems exists.
Journal of the American College of Cardiology 11/2011; 58(20):2076-83. · 14.16 Impact Factor
Radiology 11/2011; 261(2):663-4; author reply 664. · 5.73 Impact Factor
Atherosclerosis 09/2011; 219(2):395-6. · 3.79 Impact Factor
ABSTRACT: The JUPITER trial showed that some patients with LDL-cholesterol concentrations less than 3·37 mmol/L (<130 mg/dL) and high-sensitivity C-reactive protein (hsCRP) concentrations of 2 mg/L or more benefit from treatment with rosuvastatin, although absolute rates of cardiovascular events were low. In a population eligible for JUPITER, we established whether coronary artery calcium (CAC) might further stratify risk; additionally we compared hsCRP with CAC for risk prediction across the range of low and high hsCRP values.
950 participants from the Multi-Ethnic Study of Atheroslcerosis (MESA) met all criteria for JUPITER entry. We compared coronary heart disease and cardiovascular disease event rates and multivariable-adjusted hazard ratios after stratifying by burden of CAC (scores of 0, 1-100, or >100). We calculated 5-year number needed to treat (NNT) by applying the benefit recorded in JUPITER to the event rates within each CAC strata.
Median follow-up was 5·8 years (IQR 5·7-5·9). 444 (47%) patients in the MESA JUPITER population had CAC scores of 0 and, in this group, rates of coronary heart disease events were 0·8 per 1000 person-years. 74% of all coronary events were in the 239 (25%) of participants with CAC scores of more than 100 (20·2 per 1000 person-years). For coronary heart disease, the predicted 5-year NNT was 549 for CAC score 0, 94 for scores 1-100, and 24 for scores greater than 100. For cardiovascular disease, the NNT was 124, 54, and 19. In the total study population, presence of CAC was associated with a hazard ratio of 4·29 (95% CI 1·99-9·25) for coronary heart disease, and of 2·57 (1·48-4·48) for cardiovascular disease. hsCRP was not associated with either disease after multivariable adjustment.
CAC seems to further stratify risk in patients eligible for JUPITER, and could be used to target subgroups of patients who are expected to derive the most, and the least, absolute benefit from statin treatment. Focusing of treatment on the subset of individuals with measurable atherosclerosis could allow for more appropriate allocation of resources.
National Institutes of Health-National Heart, Lung, and Blood Institute.
The Lancet 08/2011; 378(9792):684-92. · 38.28 Impact Factor
ABSTRACT: While metabolic syndrome (MetS) and diabetes confer greater cardiovascular disease (CVD) risk, recent evidence suggests that individuals with these conditions have a wide range of risk. We evaluated whether screening for coronary artery calcium (CAC) and carotid intimal-medial thickness (CIMT) can improve CVD risk stratification over traditional risk factors (RFs) in people with MetS and diabetes.
We assessed CAC and CIMT in 6,603 people aged 45-84 years in the Multi-Ethnic Study of Atherosclerosis (MESA). Cox regression examined the association of CAC and CIMT with coronary heart disease (CHD) and CVD over 6.4 years in MetS and diabetes.
Of the subjects, 1,686 (25%) had MetS but no diabetes and 881 (13%) had diabetes. Annual CHD event rates were 1.0% among MetS and 1.5% for diabetes. Ethnicity and RF-adjusted hazard ratios for CHD for CAC 1-99 to ≥400 vs. 0 in subjects with neither MetS nor diabetes ranged from 2.6 to 9.5; in those with MetS, they ranged from 3.9 to 11.9; and in those with diabetes, they ranged from 2.9 to 6.2 (all P < 0.05 to P < 0.001). Findings were similar for CVD. CAC increased the C-statistic for events (P < 0.001) over RFs and CIMT in each group while CIMT added negligibly to prediction over RFs.
Individuals with MetS or diabetes have low risks for CHD when CAC or CIMT is not increased. Prediction of CHD and CVD events is improved by CAC more than by CIMT. Screening for CAC or CIMT can stratify risk in people with MetS and diabetes and support the latest recommendations regarding CAC screening in those with diabetes.
Diabetes care 08/2011; 34(10):2285-90. · 8.09 Impact Factor
ABSTRACT: Our aim was to identify risk factors for coronary heart disease (CHD) events among asymptomatic persons with low (≤ 130 mg/dl) low-density lipoprotein cholesterol (LDL-C).
Even among persons with low LDL-C, some will still experience CHD events and may benefit from more aggressive pharmacologic and lifestyle therapies.
The MESA (Multi-Ethnic Study of Atherosclerosis) is a prospective cohort of 6,814 participants free of clinical cardiovascular disease. Of 5,627 participants who were not receiving any baseline lipid-lowering therapies, 3,714 (66%) had LDL-C ≤ 130 mg/dl and were included in the present study. Unadjusted and adjusted hazard ratios were calculated to assess the association of traditional risk factors and biomarkers with CHD events. To determine if subclinical atherosclerosis markers provided additional information beyond traditional risk factors, coronary artery calcium (CAC) and carotid intima media thickness were each separately added to the multivariable model.
During a median follow-up of 5.4 years, 120 (3.2%) CHD events were observed. In unadjusted analysis, age, male sex, hypertension, diabetes mellitus, low high-density lipoprotein cholesterol (HDL-C), high triglycerides, and subclinical atherosclerosis markers (CAC >0; carotid intima media thickness ≥1 mm) predicted CHD events. Independent predictors of CHD events included age, male sex, hypertension, diabetes, and low HDL-C. After accounting for all traditional risk factors, the predictive value of CAC was attenuated but remained highly significant. The relationship of all independent clinical predictors remained robust even after accounting for elevated CAC.
Among persons with low LDL-C, older age, male sex, hypertension, diabetes, and low HDL-C are associated with adverse CHD events. Even after accounting for all such variables, the presence of CAC provided incremental prognostic value. These results may serve as a basis for deciding which patients with low LDL-C may be considered for more aggressive therapies.
Journal of the American College of Cardiology 07/2011; 58(4):364-74. · 14.16 Impact Factor
ABSTRACT: We hypothesized that insulin resistance, measured by the homeostasis model assessment of insulin resistance (HOMA), is independently associated with prevalent and incident extra-coronary calcification (ECC).
We studied calcium scores of the aortic valve calcification (AVC), mitral valve calcification (MVC), thoracic aorta calcification (TAC) and aortic valve root calcification (AVR) in 6104 MESA participants not on diabetes medication who had baseline cardiac CT scans; 5312 had follow-up scans (mean 2.4 years). Relative-risk regression modeled prevalent and incident ECC adjusted for baseline demographics (model 1), and additionally for CVD risk factors (model 2).
In model 1, prevalence and incidence risk-ratios for the highest versus lowest quartile of HOMA were 20-30% higher in all ECC locations (p-value for trend ≤0.05 for all but incident-AVC). In model 2, all associations were attenuated, primarily by adjustment for metabolic syndrome components.
HOMA has a positive and graded association with ECC, but not independently of cardiovascular risk factors-particularly metabolic syndrome components.
Atherosclerosis 07/2011; 218(2):507-10. · 3.79 Impact Factor
ABSTRACT: Elevated resting heart rate has been independently associated with cardiovascular and all-cause mortality. The pathophysiological mechanisms by which this increased risk occurs are unclear. We hypothesized that elevated resting heart rate will be associated with increased development of atherosclerosis, as assessed by the incidence and progression of coronary artery calcium (CAC).
The Multi-Ethnic Study of Atherosclerosis is a prospective cohort study of participants free of clinical cardiovascular disease at entry. Among persons without CAC at baseline, the association between increasing clinical categories of heart rate (<60, 61-70, 71-80, >80bpm) and CAC incidence was assessed by relative risk regression after adjusting for covariates. Among those with detectable CAC at baseline, progression of CAC was assessed using multivariable robust linear regression.
Our study population consisted of 6004 individuals (62±10 years, 48% males). Among 3079 individuals with no detectable CAC at baseline, 20% (n=620) developed CAC. After adjusting for CVD risk factors, participants with a baseline resting heart rate >80bpm had an increased risk of incident CAC as compared to those with a resting heart rate <60 (relative risk=1.65, 95% CI=1.02, 2.66). Among persons with CAC present at baseline, participants with a baseline resting heart rate >80bpm had greater CAC score progression than those with a resting heart rate <60 (β=17.10; 95% CI=4.29, 29.85).
Elevated resting heart rate, a well-described predictor of cardiovascular mortality with unclear mechanism, is associated with increased incidence and progression of coronary atherosclerosis among individuals free of CVD at baseline.
Atherosclerosis 06/2011; 220(1):194-200. · 3.79 Impact Factor
Journal of the American College of Cardiology 06/2011; 57(24):2456-7; author reply 2457. · 14.16 Impact Factor