The Long-Term Clinical Outcome of Posttraumatic Stress Disorder With Impaired Coronary Distensibility.

OBJECTIVE: Coronary Distensibility Index (CDI) impairments reflect endothelial-dependent process associated with vulnerable-plaque composition. This study investigated the relation of impaired CDI with posttraumatic stress disorder (PTSD) and their predictive value for major adverse cardiovascular events (MACE). METHODS: This study involved 246 patients (age = 63 [10] years, 12% women) with (n = 50) and without (n = 196) PTSD, who underwent computed tomography angiography to determine coronary artery disease and CDI. Extent of coronary artery disease was defined as normal, nonobstructive (<50% luminal stenosis), and obstructive (>50%). Incidence of MACE, defined as myocardial infarction or cardiovascular death, was documented during a mean follow-up of 50 months. Survival regression was employed to assess the longitudinal association of impaired CDI and PTSD with MACE. RESULTS: A significant inverse correlation between CDI and Clinical Global Impression Severity scale of PTSD symptoms was noted (r = .81, p = .001). CDI was significantly lower in patients with PTSD (3.3 [0.2]) compared with those without PTSD (4.5 [0.3]), a finding that was more robust in women (p < .05). Covariate-adjusted analyses revealed that the relative risk of MACE was higher in patients with PTSD (hazard ratio [HR] = 1.56, 95% CI = 1.34-3.14) and those with impaired CDI (HR = 1.95, 95% CI = 1.27-3.01, per standard deviation lower CDI value). There was also a significant interaction between PTSD and impaired CDI (HR = 3.24, 95% CI = 2.02-5.53). CONCLUSIONS: Impaired CDI is strongly associated with the severity of PTSD symptoms. Both impaired CDI and PTSD were independently associated with an increased risk of MACE during follow-up, and evidence indicated an interaction between these two factors. These findings highlight the important role of CDI in identifying individuals with PTSD at risk for MACE.

18F-NaF PET Demonstrating Unusual Focal Tracer Activity in the Brain.

A 60-year-old man with enlarged prostate, hypertension, and diabetes was referred for F-NaF PET/CT to evaluate possible metastatic lesions. The patient appeared asymptomatic on the day of the study, without any signs indicating stroke. Patient also had no known history of malignancy or cerebrovascular disease. He had mild elevation of the prostate-specific antigen level, and biopsy of his prostate was not performed. Patient had long-standing history of chronic back pain and abdominal pain. The PET bone scan demonstrated a large area of very intense tracer uptake in the brain. A subsequent brain MRI revealed prior stroke in the same area.

Impaired coronary artery distensibility is an endothelium-dependent process and is associated with vulnerable plaque composition.

Coronary endothelial-dependent microvascular dysfunction, an early reversible stage of coronary artery disease (CAD), is associated with poor clinical outcome. The current study investigated whether coronary artery distensibility index (CDI) is associated with: (i) coronary endothelial-dependent microvascular dysfunction and (ii) vulnerable plaque composition among subjects with non-obstructive CAD. Seventy-four subjects with non-obstructive CAD (luminal stenosis <30%) were studied. In 20 subjects with and without coronary endothelial-dependent microvascular dysfunction, coronary flow reserve (CFR) of target segment during intracoronary (IC) infusion of acetylcholine (Ach) and bolus injection of adenosine as well as CDI at rest of corresponding target segment were measured. In 54 subjects, plaque compositions and CDI at rest of 154 non-obstructive coronary segments as well as proximal segment without disease were measured by intravascular ultrasound (IVUS). CDI was defined as: [(Early-diastolic cross-sectional-area (CSA) - End-diastolic CSA of target segment)/(end-diastolic CSA of target segment × coronary-pulse-pressure) × 10(3) ]. There is a direct association between endothelial dysfunction and impaired CDI of a coronary segment both in the given coronary segment and corresponding microvessels in which a strong agreement between CDI and CFR Ach (r(2)  = 0·85, P = 0·0001) was observed. Multivariable regression-analysis showed that CDI was an independent predictor of the vulnerable plaque characteristics. The risk of impaired CDI was 125% higher in segments with necrotic core and 60% higher in segments with fibrofatty components as compared to normal segments (P = 0·001). In conclusions, the current study reveals that impaired CDI is an endothelial-dependent process of both given coronary segment and corresponding microvessels and is associated with vulnerable plaque composition.

Traumatic brain injury, coronary atherosclerosis and cardiovascular mortality.

BACKGROUND: Traumatic-brain-injury (TBI) is a devastating-condition resulting in cerebral edema and ischemia. This study investigates the association of mild-TBI (mTBI) to sub-clinical atherosclerosis and cardiovascular (CV) mortality. METHODS: Five hundred and forty-three veterans without known coronary artery disease or diagnosed mental disorder, who underwent coronary artery calcium (CAC) scanning for clinical indications, were followed for a median of 4-years. Veterans' medical diagnoses and neuropsychiatric health status (mTBI vs non-mTBI) were evaluated using VA electronic medical records. CAC was defined as 0, 1-100, 101-400 and 400+. RESULTS: CAC was higher in mTBI, compared to without-mTBI (p < 0.05). TBI was more prevalent with the-severity of CAC (p < 0.05). Regression-analyses revealed that mTBI is an independent-predictor of CAC (p < 0.01). The CV mortality rate was 25% in mTBI and 10.5% in without-mTBI (p = 0.0001). Multivariable survival regression analyses revealed a significant-association between mTBI and CAC, with increased-risk of CV mortality (p < 0.05). The hazard-ratio of CV mortality was 5.25 in mTBI & CAC > 0, compared to without-mTBI & CAC = 0 (p < 0.05). The risk of CV-mortality was 2.25 for mTBI & CAC = 1-100, 4.93 for mTBI & CAC = 101-400 and 7.06 for mTBI & CAC ≥ 400, compared to matched CAC-categories without-mTBI (p < 0.05). The area under ROC curve to predict CV mortality was 0.64 for mTBI, 0.69 for mTBI & PTSD, 0.85 for mTBI & CAC > 0 and 0.92 for the combination. The prognostication of mTBI to predict CV mortality is superior to the Framingham risk score. Also the combination of mTBI & PTSD provided incremental prognostic values to predict CV mortality (p < 0.05). CONCLUSIONS: mTBI is associated with the severity of sub-clinical coronary atherosclerosis and independently predicts CV mortality.

Increased epicardial adipose tissue is associated with coronary artery disease and major adverse cardiovascular events.

BACKGROUND: Increased-epicardial-adipose tissue (EAT) is associated with the presence and severity of subclinical-atherosclerosis. This study investigates the long-term clinical-outcome of subjects with and without increased-EAT. METHODS: Two hundred and forty-five subjects, aged 61 ± 9 years and 34% women underwent clinically-indicated computed-tomography-angiography (CTA), and body-surface-area adjusted EAT was measured and were followed prospectively. CTA-diagnosed coronary-artery-disease (CAD) was defined as obstructive (luminal-stenosis ≥ 50%), non-obstructive (luminal-stenosis: 1-49%) and zero-obstruction. Major-adverse-cardiac-event (MACE) was defined as myocardial-infarction or cardiovascular-death. RESULTS: EAT increased significantly from subjects with zero-obstruction-coronaries (93 ± 37 cm(3)/m(2)) to non-obstructive-CAD (132 ± 25 cm(3)/m(2)) to obstructive-CAD (145 ± 35 cm(3)/m(2)) (P = 0.01). During the 48-month follow-up, the event-rate was 8.6% (21). The event free survival-rate decreased significantly from 99% in the lowest-quartile to 86.6% in the highest-quartile of EAT. After adjustment for risk-factors, the hazard ratio of MACE was 1.4, 3.1 and 5.7 in lower mid-, upper mid- and highest-quartiles of EAT as compared to lowest-quartile of EAT (P < 0.05). CONCLUSION: Increased EAT is directly associated with CAD and predicts MACE independent of the age, gender and conventional-risk-factors.

Accurate detection of metabolically active "brown" and "white" adipose tissues with computed tomography.

BACKGROUND: Adipose tissues (AT) are highly metabolically active complex endocrine organs and are classified into white (WAT) and brown AT (BAT) with proinflammatory and anti-inflammatory characteristics. The current study investigated the accuracy of computed tomography (CT) to quantitatively detect BAT and WAT based on Hounsfield unit (HU) threshold compared to standardized uptake values (SUVs) of corresponding AT with the use of positron emission tomography (PET). METHODS: One hundred twenty-four patients who underwent whole-body (18)F-fluorodeoxyglucose ((18)F-FDG) PET/CT were studied. The SUVs and HUs of regions of BAT and WAT were measured and compared in these scans. The receiver operator characteristic (ROC) analysis was used to detect the HU threshold values for the detection of BAT and WAT. RESULTS: The CT HU of BAT, with high (18)F-FDG uptake, was significantly higher compared to WAT (-67.1 ± 8.2 [-10 to -87] versus -93.5 ± 10.1 [-88 to -190], P = .0006). Generalized linear-regression models revealed that mean CT HU of BAT was 26.4 HU higher than that of WAT (P = .001). A strong agreement between CT HU and PET SUV in measuring metabolically active AT (r(2) = 0.81, P = .0001) was observed. The ROC curve showed that the optimal cutoff value of CT HU to detect BAT was HU ≥-87 with sensitivity of 83.3% and specificity of 100%, and the negative CT HU below -87 is highly specific for WAT. CONCLUSION: In our study, CT can accurately and quantitatively detect BAT and WAT based on CT HU threshold, which is -10 to -87 for BAT and -88 to -190 for WAT.

Aged garlic extract with supplement is associated with increase in brown adipose, decrease in white adipose tissue and predict lack of progression in coronary atherosclerosis.

BACKGROUND: Aged garlic extract with supplement (AGE-S) significantly reduces coronary artery calcium (CAC). We evaluated the effects of AGE-S on change in white (wEAT) and brown (bEAT) epicardial adipose tissue, homocysteine and CAC. METHODS: Sixty subjects, randomized to a daily capsule of placebo vs. AGE-S inclusive of aged garlic-extract (250 mg) plus vitamin-B12 (100 µg), folic-acid (300 µg), vitamin-B6 (12.5mg) and L-arginine (100mg) underwent CAC, wEAT and bEAT measurements at baseline and 12 months. The postcuff deflation temperature-rebound index of vascular function was assessed using a reactive-hyperemia procedure. Vascular dysfunction was defined according to the tertiles of temperature-rebound at 1 year of follow-up. CAC progression was defined as an annual-increase in CAC>15%. RESULTS: From baseline to 12 months, there was a strong correlation between increase in wEAT and CAC (r(2)=0.54, p=0.0001). At 1 year, the risks of CAC progression and increased wEAT and homocysteine were significantly lower in AGE-S to placebo (p<0.05). Similarly, bEAT and temperature-rebound were significantly higher in AGE-S as compared to placebo (p<0.05). Strong association between increase in temperature-rebound and bEAT/wEAT ratio (r(2)=0.80, p=0.001) was noted, which was more robust in AGE-S. Maximum beneficial effect of AGE-S was noted with increase in bEAT/wEAT ratio, temperature-rebound, and lack of progression of homocysteine and CAC. CONCLUSIONS: AGE-S is associated with increase in bEAT/wEAT ratio, reduction of homocysteine and lack of progression of CAC. Increases in bEAT/wEAT ratio correlated strongly with increases in vascular function measured by temperature-rebound and predicted a lack of CAC progression and plaque stabilization in response to AGE-S.

Reproducibility and variability of digital thermal monitoring of vascular reactivity.

BACKGROUND: Previous studies demonstrated that digital thermal monitoring (DTM) of vascular reactivity, a new test for vascular function assessment, is well correlated with Framingham Risk Score, coronary calcium score and CT angiography. This study evaluates the variability and reproducibility of DTM measurements. We hypothesized that DTM is reproducible, and its variability falls within the accepted range of clinical diagnostic tests. METHOD: A fully automated DTM device (VENDYS, Endothelix Inc., Houston, TX, USA) was used for repeated measurement of vascular function in 18 healthy volunteers (age 35 ± 4 years, 74% men) after 24 h. All subjects underwent overnight fasting, and the test was preceded by 30-min rest in a supine position inside a dimmed room with temperature 22-24°C. The measurements were obtained during and after a 2-min supra systolic arm-cuff occlusion-induced reactive hyperaemia procedure. As a part of this study, the Doppler ultrasound hyperaemic, low-frequency, blood velocity of radial artery and a fingertip DTM of vascular function were compared simultaneously. Postcuff deflation temperature rebound and area under the curve, DTM indices of vascular function, were studied. RESULTS: Temperature rebound area under the curve correlated closely with Doppler hyperaemic, low-frequency, blood velocity (r = 0·97, P = 0·0001). Day-to-day intra-subject variability was 6·2% for baseline temperature, 8·7% for mean blood pressure and 11·4% for heart rate. The coefficient of repeatability of temperature rebound and area under the curve were 2·4% and 2·8%. CONCLUSION: In a controlled environment, the repeatability of DTM is excellent. DTM can be used as a reproducible and operator-independent test for non-invasive measurement of vascular function.

Relation of subclinical left and right ventricular dysfunctions measured by computed tomography angiography with the severity of coronary artery disease.

OBJECTIVE: Ventricular dysfunction in asymptomatic patients is directly linked to the eventual development of symptomatic congestive heart failure. This study investigates whether subclinical left ventricular (LV) and right ventricular (RV) dysfunctions measured by computed tomography angiography is associated with the severity of coronary artery disease (CAD). METHODS AND RESULTS: We studied 1608 consecutive patients with suspected CAD (age 62 ± 10 years, 64% male), who underwent coronary artery calcium (CAC) scanning and computed tomography angiography. RV and LV volumes at end systole and end diastole were measured, and stroke volume and ejection fraction were calculated using the Simpson method and piecewise smooth subdivision surface (PSSS) method. Analysis by Simpson was performed on short axis and apical four-chamber views. Axial images were used to measure RV and LV volumes by the PSSS method. CAD was defined as normal, nonobstructive, and obstructive (0% stenosis, luminal stenosis 1-49 and 50%+, respectively). There was a strong agreement between PSSS and Simpson method RV ejection fraction (RVEF) and LV ejection fraction (LVEF) measurement. RVEF and LVEF decreased proportionally from CAC 0 to CAC 100+, also from normal-to-diseased coronaries (P=0.001). After adjustment for cardiovascular risk factors, the mean LVEF and RVEF decreased 2.8 and 2.4%, respectively in CAC 100+ compared with CAC 0. Similarly, LVEF and RVEF decreased significantly in nonobstructive CAD (-3.5 and -3.1%, respectively) and obstructive CAD (-5.9 and -4.5%, respectively) compared with normal coronaries, respectively (P<0.05). The relative risk of each 5% decrease in LVEF and RVEF was 1.33 and 1.29 for nonobstructive CAD and 1.54 and 1.33 for obstructive CAD, respectively. CONCLUSION: The presence and severity of coronary atherosclerosis is significantly associated with subclinical RV and LV dysfunctions.

Post-traumatic stress disorder, coronary atherosclerosis, and mortality.

Post-traumatic stress disorder (PTSD) is associated with increased risk of multiple medical problems including myocardial infarction. However, a direct link between PTSD and atherosclerotic coronary artery disease (CAD) has not been made. Coronary artery calcium (CAC) score is an excellent method to detect atherosclerosis. This study investigated the association of PTSD to atherosclerotic CAD and mortality. Six hundred thirty-seven veterans without known CAD (61 ± 9 years of age, 12.2% women) underwent CAC scanning for clinical indications and their psychological health status (PTSD vs non-PTSD) was evaluated. In subjects with PTSD, CAC was more prevalent than in the non-PTSD cohort (76.1% vs 59%, p = 0.001) and their CAC scores were significantly higher in each Framingham risk score category compared to the non-PTSD group. Multivariable generalized linear regression analysis identified PTSD as an independent predictor of presence and extent of atherosclerotic CAD (p <0.01). During a mean follow-up of 42 months, the death rate was higher in the PTSD compared to the non-PTSD group (15, 17.1%, vs 57, 10.4%, p = 0.003). Multivariable survival regression analyses revealed a significant linkage between PTSD and mortality and between CAC and mortality. After adjustment for risk factors, relative risk (RR) of death was 1.48 (95% confidence interval [CI] 1.03 to 2.91, p = 0.01) in subjects with PTSD and CAC score >0 compared to subjects without PTSD and CAC score equal to 0. With a CAC score equal to 0, risk of death was not different between subjects with and without PTSD (RR 1.04, 95% CI 0.67 to 6.82, p = 0.4). Risk of death in each CAC category was higher in subjects with PTSD compared to matched subjects without PTSD (RRs 1.23 for CAC scores 1 to 100, 1.51 for CAC scores 101 to 400, and 1.81 for CAC scores ≥400, p <0.05 for all comparisons). In conclusion, PTSD is associated with presence and severity of coronary atherosclerosis and predicts mortality independent of age, gender, and conventional risk factors.

Porcelain heart.

Rheumatic heart disease (RHD) was the leading-cause of death in individual aged 5-20 years a century ago. Developments in diagnosis and treatment, decreased the incidence of RHD and dropped its mortality-rate to less than 10% since the 1960s. Despite the existence of proven preventive strategies in early detection and management of rheumatic fever (RF), RHD remained the most common cause of cardiovascular-mortality and morbidity in patients with RF. Previous studies have showed that Jones criteria may have insufficient support to diagnose patients with RF. Patients with subclinical, ongoing, and unrecognized episodes of RF may present late to medical attention with complication of RF such as indolent carditis. Recent studies revealed the superior role of echocardiography, as compared with clinical screening to diagnose subclinical RHD. While valvular involvement and ventricular dysfunction of RHD can be easily detected with echocardiography and magnetic resonance imaging (MRI), it remains problematic to determine the presence of whether there is myocardial-calcification after rheumatic heart carditis and if yes, how much extent it involves. The current case-report suggests the superior role of computed tomography angiography (CTA), as compared with echocardiography and MRI, to diagnose RHD in individuals without known history of RF. CTA with high spatial-resolution accurately evaluates tissue characterization and simultaneous assessment of the anatomy and function of heart and coronaries, and can precisely differentiate RHD from other cause of porcelain heart. The use of CTA in RHD screening provides the opportunity to initiate secondary antibiotic prophylaxis to prevent the poor outcome of rheumatic heart disease.

Mortality in individuals without known coronary artery disease but with discordance between the Framingham risk score and coronary artery calcium.

A risk-management approach based on the Framingham risk score (FRS), although useful in preventing future coronary artery disease (CAD) events, is unable to identify a considerable portion of patients with CAD who need aggressive medical management. Coronary artery calcium (CAC), an anatomic marker of atherosclerosis, correlates well with presence and extent of CAD. This study investigated mortality risk associated with CAC score and FRS in subjects classified as "low risk" versus "high risk" based on FRS. In total 730 veterans without known CAD (61 ± 10 years old, 12.8% women) underwent measurement of their FRS and CAC. Subjects were classified as "discordant low risk" (DLR) if their FRS was <10% and CAC score was ≥ 100 (n = 108, 14.8%) or "discordant high risk" (DHR) if their FRS was ≥ 20% and CAC score was 0 (n = 104, 14.2%). Survival analysis was used to compare mortality rates associated with FRS and CAC in DLR versus DHR subjects. Mortality rate during the mean 48-month follow-up was 7.3% (n = 53) including 18.5% (n = 20) in the DLR group and 7.7% (n = 8) in the DHR group, respectively. Adjusted relative risks of mortality were 5.46 (95% confidence interval [CI] 2.44 to 12.20, p = 0.0001) in subjects with CAC score ≥ 100 compared to CAC score 0 and 1.35 (95% CI 1.01 to 4.32, p = 0.04) in subjects with FRS ≥ 20% compared to FRS <10%. Adjusted relative risk of mortality was 3.6 (95% CI 1.57 to 8.34, p = 0.003) for DLR compared to DHR. Areas under the receiver operator curve to predict mortality were 0.72 for FRS, 0.82 for CAC score, and 0.92 for the combination. In conclusion, the prognostic value of CAC to predict future mortality is superior to the FRS. Addition of CAC score to FRS significantly improves the identification and prognostication of patients without known CAD.

Mortality incidence of patients with non-obstructive coronary artery disease diagnosed by computed tomography angiography.

It was previously reported that event-free survival rates of symptomatic patients with coronary artery disease (CAD) diagnosed by computed tomographic angiography decreased incrementally from normal coronary arteries to obstructive CAD. The aim of this study was to investigate the clinical outcomes of symptomatic patients with nonobstructive CAD with luminal stenoses of 1% to 49% on the basis of coronary plaque morphology in an outpatient setting. Among 3,499 consecutive symptomatic subjects who underwent computed tomographic angiography, 1,102 subjects with nonobstructive CAD (mean age 59 ± 14 years, 69.9% men) were prospectively followed for a mean of 78 ± 12 months. Coronary plaques were defined as noncalcified, mixed, and calcified per patient. Multivariate Cox proportional-hazards models were developed to predict all-cause mortality. The death rate of patients with nonobstructive CAD was 3.1% (34 deaths). The death rate increased incrementally from calcified plaque (1.4%) to mixed plaque (3.3%) to noncalcified plaque (9.6%), as well as from single- to triple-vessel disease (p <0.001). In subjects with mixed or calcified plaques, the death rate increased with the severity of coronary artery calcium from 1 to 9 to ≥ 400. The risk-adjusted hazard ratios of all-cause mortality in patients with nonobstructive CAD were 3.2 (95% confidence interval 1.3 to 8.0, p = 0.001) for mixed plaques and 7.4 (95% confidence interval 2.7 to 20.1, p = 0.0001) for noncalcified plaques compared with calcified plaques. The areas under the receiver-operating characteristic curve to predict all-cause mortality were 0.75 for mixed and 0.86 for noncalcified coronary lesions. In conclusion, this study demonstrates that the presence of noncalcified and mixed coronary plaques provided incremental value in predicting all-cause mortality in symptomatic subjects with nonobstructive CAD independent of age, gender, and conventional risk factors.

Impaired aortic distensibility measured by computed tomography is associated with the severity of coronary artery disease.

Impaired aortic distensibility index (ADI) is associated with cardiovascular risk factors. This study evaluates the relation of ADI measured by computed tomographic angiography (CTA) with the severity of coronary atherosclerosis in subjects with suspected coronary artery disease (CAD). Two hundred and twenty-nine subjects,age 63 ± 9 years, 42% female, underwent coronary artery calcium (CAC) scanning and CTA, and their ADI and Framingham risk score (FRS) were measured. End-systolic and end-diastolic (ED) cross-sectional-area(CSA) of ascending-aorta (AAo) was measured 15-mm above the left-main coronary ostium. ADI was defined as: [(Δlumen-CSA)/(lumen-CSA in ED × systemic-pulse-pressure) × 10(3)]. ADI measured by 2D-trans-thoracic echocardiography (TTE) was compared with CTA-measured ADI in 26 subjects without CAC. CAC was defined as 0, 1-100, 101-400 and 400+. CAD was defined as luminal stenosis 0, 1-49% and 50%+. There was an excellent correlation between CTA- and TTE-measured ADI (r(2)=0.94, P=0.0001). ADI decreased from CAC 0 to CAC 400+; similarly from FRS 1-9% to FRS 20% + (P<0.05). After adjustment for risk factors, the relative risk for each standard deviation decrease in ADI was 1.66 for CAC 1-100, 2.26 for CAC 101-400 and 2.32 for CAC 400+ as compared to CAC 0; similarly, 2.36 for non-obstructive CAD and 2.67 for obstructive CAD as compared to normal coronaries. The area under the ROC-curve to predict significant CAD was 0.68 for FRS, 0.75 for ADI, 0.81 for CAC and 0.86 for the combination (P<0.05). Impaired aortic distensibility strongly correlates with the severity of coronary atherosclerosis. Addition of ADI to CAC and traditional risk factors provides incremental value to predict at-risk individuals.

Increased epicardial, pericardial, and subcutaneous adipose tissue is associated with the presence and severity of coronary artery calcium.

RATIONALE AND OBJECTIVES: Epicardial adipose tissue (EAT), pericardial adipose tissue (PAT), and subcutaneous adipose tissue (SAT) are mediators of metabolic risk and may be involved in the pathogenesis of coronary artery disease. The aim of this study was to investigate the association of visceral and subcutaneous fat depots with the presence and severity of coronary artery calcium (CAC) in asymptomatic individuals. MATERIALS AND METHODS: One hundred eleven consecutive subjects underwent CAC assessment, and their Framingham risk scores were measured. EAT, total thoracic adipose tissue, and SAT volumes were measured from slice level 15 mm above to 30 mm below the ostium of the left main coronary artery. PAT was calculated as thoracic adipose tissue - EAT. SAT was defined as the volume of fat depot anterior to the sternum and posterior to the vertebra. CAC was defined as 0, 1 to 100, 101 to 400, or ≥ 400. Relative risk regression analysis was used to assess the association between fat depots and CAC. RESULTS: There were modest correlations between EAT (r = 0.58), PAT (r = 0.47), SAT (r = 0.34), and CAC (P < .01). EAT, PAT, and SAT increased proportionally with the severity of CAC in both genders (P < .05). After adjustment for cardiovascular risk factors and body mass index, the relative risks for each standard deviation increase in EAT, PAT, and SAT were 3.3 (95% confidence interval, 1.9-5.6), 2.7 (95% confidence interval, 1.6-3.9), and 2.6 (95% confidence interval, 1.5-4.4) for CAC ≥ 100 compared to CAC 0, respectively (P < .05). The area under the receiver-operating characteristic curve to predict CAC ≥ 100 was higher in each fat depot compared to Framingham risk score, and addition of fat depots to Framingham risk score provided maximum prognostication value to detect CAC ≥ 100. CONCLUSIONS: Increased EAT, PAT, and SAT are associated with the severity of CAC independent of risk factors.

Coronary distensibility index measured by computed tomography is associated with the severity of coronary artery disease.

BACKGROUND: Atherosclerotic changes within the coronary artery wall can affect vessel distensibility. OBJECTIVE: This study evaluated the relationship between the coronary distensibility index (CDI) and the severity of coronary artery disease (CAD) measured by computed tomographic angiography (CTA). METHODS: One hundred thirteen subjects, age 63 +/- 10 years, 32% women, who underwent coronary artery calcium (CAC) scanning and CTA, were studied. Early diastolic and mid diastolic (MD) cross-section area (CSA) of the left anterior descending (LAD) artery were measured 5 mm distal to the left main bifurcation. CDI was defined as Deltalumen CSA/[lumen CSA in MD x estimated central pulse pressure (eCPP)] x 10(3) {eCPP = 0.77 x peripheral pulse pressure}. LAD diameter measured by CTA and quantitative coronary angiography (QCA) was compared in 19 subjects without CAD. CAD was defined as normal (no stenosis and CAC 0), mild (stenosis or= 70%) on CTA. RESULTS: Excellent correlation was observed between CTA and QCA measured by CDI (r(2) = 0.96, P = 0.0001). CDI decreased from normal coronaries (6.75 +/- 1.43) to arteries with mild (5.78 +/- 1.45), moderate (3.96 +/- 1.06), and severe (3.31 +/- 1.06) disease (P = 0.004). The risk factor adjusted odds ratio of lowest versus 2 upper tertiles of CDI was 1.28 for mild, 8.47 for moderate, and 10.59 for severe CAD compared with the normal cohort. The area under the ROC curve to predict obstructive CAD (stenosis >or= 50%) increased significantly from 0.71 to 0.84 by addition of CDI to CAC (P < 0.05). CONCLUSION: CTA-measured CDI is inversely related to the severity of CAD independent of age, sex, cardiovascular risk factors, and CAC.

Relation of oxidative biomarkers, vascular dysfunction, and progression of coronary artery calcium.

The relation between oxidative stress and coronary artery calcium (CAC) progression is currently not well described. The present study evaluated the relation among the biomarkers of oxidative stress, vascular dysfunction, and CAC. Sixty asymptomatic subjects participated in a randomized trial evaluating the effect of aged garlic extract plus supplement versus placebo and underwent measurement of CAC. The postcuff deflation temperature-rebound index of vascular function was assessed using a reactive hyperemia procedure. The content of oxidized phospholipids (OxPL) on apolipoprotein B-100 (apoB) particles detected by antibody E06 (OxPL/apoB), lipoprotein(a), IgG and IgM autoantibodies to malondialdehyde-low-density lipoprotein and apoB-immune complexes were measured at baseline and after 12 months of treatment. CAC progression was defined as an annual increase in CAC >15%. Vascular dysfunction was defined according to the tertiles of temperature-rebound at 1 year of follow-up. From baseline to 12 months, a strong inverse correlation was noted between an increase in CAC scores and increases in temperature-rebound (r(2) = -0.90), OxPL/apoB (r(2) = -0.85), and lipoprotein(a) (r(2) = -0.81) levels (p <0.0001 for all). The improvement in temperature-rebound correlated positively with the increases in OxPL/apoB (r(2) = 0.81, p = 0.0008) and lipoprotein(a) (r(2) = 0.79, p = 0.0001) but inversely with autoantibodies to malondialdehyde-low-density lipoprotein and apoB-immune complexes. The greatest CAC progression was noted with the lowest tertiles of increases in temperature-rebound, OxPL/apoB and lipoprotein(a) and the highest tertiles of increases in IgG and IgM malondialdehyde-low-density lipoprotein. In conclusion, the present results have documented a strong relation among markers of oxidative stress, vascular dysfunction, and progression of coronary atherosclerosis. Increases in OxPL/apoB and lipoprotein(a) correlated strongly with increases in vascular function and predicted a lack of progression of CAC.

Vascular function measured by fingertip thermal reactivity is impaired in patients with metabolic syndrome and diabetes mellitus.

Digital thermal monitoring (DTM) of vascular function has already been shown to correlate well with coronary artery calcium (CAC) score and coronary artery disease. To determine its utility in the metabolic syndrome (MS) and diabetes mellitus (DM), 233 asymptomatic patients with DM/MS but without coronary artery disease underwent DTM during and after 5 minutes of supra-systolic arm cuff inflation, as well as CAC. Post-cuff deflation adjusted temperature rebound (aTR) was lower in MS and DM compared with the normal group. The odds ratio of lowest vs upper 2 tertiles of aTR was 2.3 for MS and 3.5 for DM compared with the normal group, independent of age, sex, and risk factors. The area under the receiver operating characteristic curve to predict CAC > or =100 was 0.69 for metabolic status (DM/MS), 0.79 for aTR, and 0.87 for both. This study demonstrates that vascular dysfunction measured by DTM is associated with DM/MS and could potentially be used to detect asymptomatic individuals with increased subclinical atherosclerosis.

Low fingertip temperature rebound measured by digital thermal monitoring strongly correlates with the presence and extent of coronary artery disease diagnosed by 64-slice multi-detector computed tomography.

Previous studies showed strong correlations between low fingertip temperature rebound measured by digital thermal monitoring (DTM) during a 5 min arm-cuff induced reactive hyperemia and both the Framingham Risk Score (FRS), and coronary artery calcification (CAC) in asymptomatic populations. This study evaluates the correlation between DTM and coronary artery disease (CAD) measured by CT angiography (CTA) in symptomatic patients. It also investigates the correlation between CTA and a new index of neurovascular reactivity measured by DTM. 129 patients, age 63 +/- 9 years, 68% male, underwent DTM, CAC and CTA. Adjusted DTM indices in the occluded arm were calculated: temperature rebound: aTR and area under the temperature curve aTMP-AUC. DTM neurovascular reactivity (NVR) index was measured based on increased fingertip temperature in the non-occluded arm. Obstructive CAD was defined as >or=50% luminal stenosis, and normal as no stenosis and CAC = 0. Baseline fingertip temperature was not different across the groups. However, all DTM indices of vascular and neurovascular reactivity significantly decreased from normal to non-obstructive to obstructive CAD [(aTR 1.77 +/- 1.18 to 1.24 +/- 1.14 to 0.94 +/- 0.92) (P = 0.009), (aTMP-AUC: 355.6 +/- 242.4 to 277.4 +/- 182.4 to 184.4 +/- 171.2) (P = 0.001), (NVR: 161.5 +/- 147.4 to 77.6 +/- 88.2 to 48.8 +/- 63.8) (P = 0.015)]. After adjusting for risk factors, the odds ratio for obstructive CAD compared to normal in the lowest versus two upper tertiles of FRS, aTR, aTMP-AUC, and NVR were 2.41 (1.02-5.93), P = 0.05, 8.67 (2.6-9.4), P = 0.001, 11.62 (5.1-28.7), P = 0.001, and 3.58 (1.09-11.69), P = 0.01, respectively. DTM indices and FRS combined resulted in a ROC curve area of 0.88 for the prediction of obstructive CAD. In patients suspected of CAD, low fingertip temperature rebound measured by DTM significantly predicted CTA-diagnosed obstructive disease.