Computed tomographic angiography measures of coronary plaque in clinical trials: opportunities and considerations to accelerate drug translation.

Atherosclerotic coronary artery disease (CAD) is the causal pathological process driving most major adverse cardiovascular events (MACE) worldwide. The complex development of atherosclerosis manifests as intimal plaque which occurs in the presence or absence of traditional risk factors. There are numerous effective medications for modifying CAD but new pharmacologic therapies require increasingly large and expensive cardiovascular outcome trials to assess their potential impact on MACE and to obtain regulatory approval. For many disease areas, nearly a half of drugs are approved by the U.S. Food & Drug Administration based on beneficial effects on surrogate endpoints. For cardiovascular disease, only low-density lipoprotein cholesterol and blood pressure are approved as surrogates for cardiovascular disease. Valid surrogates of CAD are urgently needed to facilitate robust evaluation of novel, beneficial treatments and inspire investment. Fortunately, advances in non-invasive imaging offer new opportunity for accelerating CAD drug development. Coronary computed tomography angiography (CCTA) is the most advanced candidate, with the ability to measure accurately and reproducibly characterize the underlying causal disease itself. Indeed, favourable changes in plaque burden have been shown to be associated with improved outcomes, and CCTA may have a unique role as an effective surrogate endpoint for therapies that are designed to improve CAD outcomes. CCTA also has the potential to de-risk clinical endpoint-based trials both financially and by enrichment of participants at higher likelihood of MACE. Furthermore, total non-calcified, and high-risk plaque volume, and their change over time, provide a causally linked measure of coronary artery disease which is inextricably linked to MACE, and represents a robust surrogate imaging biomarker with potential to be endorsed by regulatory authorities. Global consensus on specific imaging endpoints and protocols for optimal clinical trial design is essential as we work towards a rigorous, sustainable and staged pathway for new CAD therapies.

Coronary artery calcium and cardiovascular disease prediction by scanner type: the multi-ethnic study of atherosclerosis.

AIM: To evaluate the predictive value of coronary artery calcium (CAC) scoring methods across cardiac computed tomography (CT) scanner types. MATERIALS AND METHODS: CAC was measured in participants from the MESA (Multi-Ethnic Study of Atherosclerosis), a prospective cohort study of participants free of baseline cardiovascular disease (CVD), using either EBCT (electron beam CT) or MDCT (multidetector CT). The risks for incident coronary heart disease (CHD) and CVD events were compared for CAC scores per SD using Cox proportional hazards models with multivariable adjustment in 3,362 MESA participants with detectable CAC. RESULTS: Using the Agatston score, the hazard ratio (HR) and 95% confidence interval (CI) for CHD was 1.50 (1.27,1.78) for EBCT and 1.60 (1.37,1.87) for MDCT. Using volume and density scores, the HR for CHD was 2.14 (1.71,2.68) for volume and 0.61 (0.48,0.76) for density on EBCT and 1.73 (1.42,2.11) for volume and 0.88 (0.71,1.10) for density on MDCT. Similar results were seen for CVD risk and in analyses stratified by sex, body mass index (BMI), and age. The volume and density score model demonstrated higher areas under the curve (AUC) for CHD than the Agatston score with EBCT (0.702, 95% CI: 0.666,0.738 versus 0.677, 95% CI: 0.638,0.715, p<0.001) and MDCT (0.669, 95% CI: 0.632,0.705 versus 0.660, 95% CI: 0.622,0.697, p=0.216). CONCLUSION: The CAC volume and density scores provide better risk prediction than the Agatston score for CHD and CVD events, regardless of CT scanner type. CAC density was strongly and inversely associated with CHD risk. Both density and volume score prediction were stronger for EBCT than MDCT.

Testosterone use and shorter electrocardiographic QT interval duration in men living with and without HIV.

OBJECTIVES: Testosterone usage (T-use) may alter risk factors for sudden cardiac death in men living with HIV (MLWH). Electrocardiographic QT interval prolongation, which could potentiate ventricular arrhythmias, has previously been associated with HIV infection and, separately, with low testosterone levels. We investigated whether T-use shortens the QT interval duration in MLWH and HIV-uninfected men. METHODS: We utilized data from the Multicenter AIDS Cohort Study, a prospective, longitudinal study of HIV infection among men who have sex with men. Multivariable linear regression analyses were used to evaluate associations between T-use and corrected QT interval (QTc) duration. RESULTS: Testosterone usage was more common in MLWH compared with HIV-uninfected men (19% vs. 9%). In a multivariable regression analysis, T-use was associated with a 5.7 ms shorter QT interval [95% confidence interval (CI): -9.5 to -1.9; P = 0.003). Furthermore, stronger associations were observed for prolonged duration of T-use and recent timing of T-use. CONCLUSIONS: This study is the first known analysis of T-use and QTc interval in MLWH. Overall, our data demonstrate that recent T-use is associated with a shorter QTc interval. Increased T-use duration above a threshold of ≥ 50% of visits in the preceding 5 years was associated with a shorter QTc interval while lesser T-use duration was not.

Subclinical cardiovascular disease in HIV controller and long-term nonprogressor populations.

OBJECTIVES: Elite controllers (ECs), viraemic controllers (VCs), and long-term nonprogressors (LTNPs) control HIV viral replication or maintain CD4 T-cell counts without antiretroviral therapy, but may have increased cardiovascular disease (CVD) risk compared to HIV-uninfected persons. We evaluated subclinical carotid and coronary atherosclerosis and inflammatory biomarker levels among HIV controllers, LTNPs and noncontrollers and HIV-uninfected individuals in the Multicenter AIDS Cohort Study (MACS) and the Women's Interagency HIV Study (WIHS). METHODS: We measured carotid plaque presence and common carotid artery intima-media thickness (IMT) in 1729 women and 1308 men, and the presence of coronary artery calcium and plaque in a subgroup of men. Associations between HIV control category and carotid and coronary plaque prevalences were assessed by multivariable regression analyses adjusting for demographics and CVD risk factors. Serum inflammatory biomarker concentrations [soluble CD163 (sCD163), soluble CD14 (sCD14), galectin-3 (Gal-3), galectin-3 binding protein (Gal-3BP) and interleukin (IL)-6] were measured and associations with HIV control category assessed. RESULTS: We included 135 HIV controllers (30 ECs) and 135 LTNPs in the study. Carotid plaque prevalence and carotid IMT were similar in HIV controllers, LTNPs and HIV-uninfected individuals. HIV controllers and LTNPs had lower prevalences of carotid plaque compared to viraemic HIV-infected individuals. The prevalence of coronary atherosclerosis was similar in HIV controllers/LTNPs compared to HIV-uninfected and viraemic HIV-infected men. Controllers and LTNPs had higher concentrations of sCD163 and sCD14 compared to HIV-uninfected persons. CONCLUSIONS: Subclinical CVD was similar in HIV controllers, LTNPs and HIV-uninfected individuals despite elevated levels of some inflammatory biomarkers. Future studies of HIV controllers and LTNPs are needed to characterize the risk of CVD among HIV-infected persons.

Associations between subcutaneous fat density and systemic inflammation differ by HIV serostatus and are independent of fat quantity.

OBJECTIVES: Adipose tissue (AT) density measurement may provide information about AT quality among people living with HIV. We assessed AT density and evaluated relationships between AT density and immunometabolic biomarker concentrations in men with HIV. DESIGN: Cross-sectional analysis of men enrolled in the Multicenter AIDS Cohort Study. METHODS: Abdominal visceral adipose tissue (VAT) and subcutaneous adipose tissue (SAT) density (Hounsfield units, HU; less negative = more dense) were quantified from computed tomography (CT) scans. Multivariate linear regression models described relationships between abdominal AT density and circulating biomarker concentrations. RESULTS: HIV+ men had denser SAT (-95 vs -98 HU HIV-, P < 0.001), whereas VAT density was equivalent by HIV serostatus men (382 HIV-, 462 HIV+). Historical thymidine analog nucleoside reverse transcriptase inhibitor (tNRTI) use was associated with denser SAT but not VAT. In adjusted models, a 1 s.d. greater SAT or VAT density was associated with higher levels of adiponectin, leptin, HOMA-IR and triglyceride:HDL cholesterol ratio and lower hs-CRP concentrations in HIV- men. Conversely, in HIV+ men, each s.d. greater SAT density was not associated with metabolic parameter improvements and was significantly (P < 0.05) associated with higher systemic inflammation. Trends toward higher inflammatory biomarker concentrations per 1 s.d. greater VAT density were also observed among HIV+ men. CONCLUSIONS: Among men living with HIV, greater SAT density was associated with greater systemic inflammation independent of SAT area. AT density measurement provides additional insight into AT density beyond measurement of AT quantity alone, and may have implications for metabolic disease risk.

Depression and all-cause mortality risk in HIV-infected and HIV-uninfected US veterans: a cohort study.

OBJECTIVES: The contribution of depression to mortality in adults with and without HIV infection is unclear. We hypothesized that depression increases mortality risk and that this association is stronger among those with HIV infection. METHODS: Veterans Aging Cohort Study (VACS) data were analysed from the first clinic visit on or after 1 April 2003 (baseline) to 30 September 2015. Depression definitions were: (1) major depressive disorder defined using International Classification of Diseases, Ninth Revision (ICD-9) codes; (2) depressive symptoms defined as Patient Health Questionnaire (PHQ)-9 scores ≥ 10. The outcome was all-cause mortality. Covariates were demographics, comorbid conditions and health behaviours. RESULTS: Among 129 140 eligible participants, 30% had HIV infection, 16% had a major depressive disorder diagnosis, and 24% died over a median follow-up time of 11 years. The death rate was 25.3 [95% confidence interval (CI) 25.0-25.6] deaths per 1000 person-years. Major depressive disorder was associated with mortality [hazard ratio (HR) 1.04; 95% CI 1.01, 1.07]. This association was modified by HIV status (interaction P-value = 0.02). In HIV-stratified analyses, depression was significantly associated with mortality among HIV-uninfected veterans but not among those with HIV infection. Among those with PHQ-9 data (n = 7372), 50% had HIV infection, 22% had PHQ-9 scores ≥ 10, and 28% died over a median follow-up time of 12 years. The death rate was 27.3 (95% CI 26.1-28.5) per 1000 person-years. Depressive symptoms were associated with mortality (HR 1.16; 95% CI 1.04, 1.28). This association was modified by HIV status (interaction P-value = 0.05). In HIV-stratified analyses, depressive symptoms were significantly associated with mortality among veterans with HIV infection but not among those without HIV infection. CONCLUSIONS: Depression was associated with all-cause mortality. This association was modified by HIV status and method of depression ascertainment.

The relation of low levels of bone mineral density with coronary artery calcium and mortality.

Osteoporosis and atherosclerosis are two prevalent major healthcare concerns that frequently coexist. The clinical outcome of 5590 consecutive subjects who underwent coronary artery calcium (CAC) scanning and thoracic bone mineral density (BMD) measurement was assessed. A significant link between low BMD levels and CAC with increased risk of mortality in both genders across ethnicities noted. INTRODUCTION: While a relation of CAC with lower levels of BMD reported previously; it is unclear whether low levels of BMD would be an independent risk factor for CAC and mortality. This study investigated the relation of BMD levels with CAC and mortality in both genders across ethnicities. METHODS: This study consisted of 5590 consecutive at-risk subjects without known coronary artery disease (CAD), age 57 ± 12, and 69% male, who underwent non-enhanced cardiac computed tomography, and were followed for mean of 8 years. The subjects' CAC (Agatston score) and thoracic BMD levels (mg/cm3) were measured. CAC stratified based on the severity to CAC 0, 1-100, 101-400, and 400+. Low-BMD levels defined as BMD levels below median (180 mg/cm3). Physician verified that all-cause mortality was assessment hard-endpoint. Multivariate regression analysis, adjusted for age, gender, and other cardiovascular risk factors, was used to assess the relationship between BMD and CAC. RESULTS: The BMD levels were proportionally lowering with the severity of CAC in both genders, especially in postmenopausal women (p < 0.05). The risk of each standard deviation reduce in BMD levels increased with the severity of CAC, as compared to CAC = 0 across ethnicities (p < 0.05). Low BMD levels were an independent predictor of mortality and event-free survival rate decreased from 99% in those within normal BMD levels to 93% in those with low BMD levels (p = 0.0001). Furthermore, a significant link between low BMD levels and CAC > 0 with increased risk of mortality was noted (p = 0.0001). The relative risk of death was 2.8, 5.9, and 14.3-folds higher in CAC 1-100, 101-400, and 400+ with low BMD levels, compared to CAC = 0 and within normal BMD levels, respectively (p < 0.05). CONCLUSIONS: The lower BMD levels are independently associated with the severity of CAC that predicts mortality.

Potential benefits of eicosapentaenoic acid on atherosclerotic plaques.

Residual cardiovascular (CV) risk remains in some patients despite optimized statin therapy and may necessitate add-on therapy to reduce this risk. Eicosapentaenoic acid (EPA), an omega-3 polyunsaturated fatty acid, lowers plasma triglyceride levels without raising low-density lipoprotein cholesterol levels and has potential beneficial effects on atherosclerotic plaques. Animal studies have shown that EPA reduces levels of pro-inflammatory cytokines and chemokines. In clinical trials utilizing a wide spectrum of plaque imaging modalities, EPA has shown beneficial effects on plaque characteristics. Studies of patients with coronary artery disease receiving statin therapy suggest that EPA may decrease plaque vulnerability and prevent plaque progression. EPA also decreased pentraxin-3 and macrophage accumulation. A large, randomized, Japanese study reported that EPA plus a statin resulted in a 19% relative reduction in major coronary events at 5years versus a statin alone in patients with hypercholesterolemia (P=0.011). Icosapent ethyl, a high-purity prescription form of EPA ethyl ester, has been shown to reduce triglyceride levels and markers of atherosclerotic inflammation. Results of an ongoing CV outcomes study will further define the potential clinical benefits of icosapent ethyl in reducing CV risk in high-risk patients receiving statin therapy.

Gender and age effects on risk factor-based prediction of coronary artery calcium in symptomatic patients: A Euro-CCAD study.

BACKGROUND AND AIMS: The influence of gender and age on risk factor prediction of coronary artery calcification (CAC) in symptomatic patients is unclear. METHODS: From the European Calcific Coronary Artery Disease (EURO-CCAD) cohort, we retrospectively investigated 6309 symptomatic patients, 62% male, from Denmark, France, Germany, Italy, Spain and USA. All of them underwent risk factor assessment and CT scanning for CAC scoring. RESULTS: The prevalence of CAC among females was lower than among males in all age groups. Using multivariate logistic regression, age, dyslipidaemia, hypertension, diabetes and smoking were independently predictive of CAC presence in both genders. In addition to a progressive increase in CAC with age, the most important predictors of CAC presence were dyslipidaemia and diabetes (ß = 0.64 and 0.63, respectively) in males and diabetes (ß = 1.08) followed by smoking (ß = 0.68) in females; these same risk factors were also important in predicting increasing CAC scores. There was no difference in the predictive ability of diabetes, hypertension and dyslipidaemia in either gender for CAC presence in patients aged <50 and 50-70 years. However, in patients aged >70, only dyslipidaemia predicted CAC presence in males and only smoking and diabetes were predictive in females. CONCLUSIONS: In symptomatic patients, there are significant differences in the ability of conventional risk factors to predict CAC presence between genders and between patients aged <70 and ≥70, indicating the important role of age in predicting CAC presence.

Diet and adipose tissue distributions: The Multi-Ethnic Study of Atherosclerosis.

BACKGROUND AND AIMS: Dietary quality affects cardiometabolic risk, yet its pathways of influence on regional adipose tissue depots involved in metabolic and diabetes risk are not well established. We aimed to investigate the relationship between dietary quality and regional adiposity. METHODS AND RESULTS: We investigated 5079 individuals in the Multi-Ethnic Study of Atherosclerosis (MESA) who had food-frequency questionnaires and measurement of pericardial fat and hepatic attenuation at the baseline study visit in MESA, as well as a subgroup with imaging for visceral and subcutaneous fat (N = 1390). A dietary quality score (DietQuality) was constructed to include established food group constituents of a Mediterranean-type diet. Linear models estimated associations of dietary score as well as its constituents with regional adiposity. Baseline mean age was 61 (± 10) years, and approximately half of the participants (47%) were male. Those with a higher DietQuality score were generally older, female, with a lower body mass index, C-reactive protein, and markers of insulin resistance. After adjustment, a higher DietQuality score was associated with lower visceral fat (lowest vs. highest dietary score quartile: 523.6 vs. 460.5 cm(2)/m; P < 0.01 for trend), pericardial fat (47.5 vs. 41.3 cm(3)/m; P < 0.01 for trend), lesser hepatic steatosis (by hepatic attenuation; 58.6 vs. 60.7 Hounsfield units; P < 0.01 for trend), but not subcutaneous fat (P = 0.39). Greater fruits, vegetables, whole grains, seeds/nuts and yogurt intake were associated with decreased adiposity, while red/processed meats were associated with greater regional adiposity. CONCLUSION: A higher quality diet pattern is associated with less regional adiposity, suggesting a potential mechanism of beneficial dietary effects on diabetes, metabolic, and cardiovascular risk.

Abdominal fat radiodensity, quantity and cardiometabolic risk: The Multi-Ethnic Study of Atherosclerosis.

BACKGROUND AND AIMS: Fat radiodensity, as measured by fat attenuation on computed tomography (CT), has emerged as a potential biomarker of "fat quality." We sought to characterize the relationship between fat radiodensity and quantity in subcutaneous, visceral, and intermuscular fat depots, and its role in inflammation, insulin resistance, and metabolic syndrome (MetS). METHODS AND RESULTS: We studied 1511 individuals from the Multi-Ethnic Study of Atherosclerosis who underwent CT for measurement of regional fat distribution and radiodensity, along with biomarker assessments and adjudication of incident metabolic syndrome (MetS). Linear, logistic and Cox regression analyses were used to measure association between fat radiodensity and (1) fat quantity, (2) biomarkers of cardiometabolic dysfunction, and (3) both prevalent and incident MetS. In each fat depot, radiodensity was strongly and inversely associated with quantity (e.g., visceral fat radiodensity vs. quantity: ρ = -0.82, P < 0.01). After adjustment for age, sex and race, lower visceral fat radiodensity was associated with greater C-reactive protein, leptin and insulin, but lower adiponectin (P < 0.01 for all). After full adjustment for cardiovascular disease risk factors, visceral (but not subcutaneous or intermuscular) fat radiodensity was associated with prevalent MetS (OR = 0.96, 95% CI = 0.93-0.99, P = 0.01). Moreover, lower visceral fat radiodensity was associated with incident MetS after the same adjustment (HR = 0.95, 95% CI 0.93-0.98, P < 0.01). However, this association became non-significant after further adjustment for visceral fat quantity. CONCLUSION: Fat radiodensity is strongly correlated with fat quantity and relevant inflammatory biomarkers. Fat radiodensity (especially for visceral fat) may be a complementary, easily assessed marker of cardiometabolic risk.

The coronary calcium score is a more accurate predictor of significant coronary stenosis than conventional risk factors in symptomatic patients: Euro-CCAD study.

AIMS: In this retrospective study we assessed the predictive value of the coronary calcium score for significant (>50%) stenosis relative to conventional risk factors. METHODS AND RESULTS: We investigated 5515 symptomatic patients from Denmark, France, Germany, Italy, Spain and the USA. All had risk factor assessment, computed tomographic coronary angiogram (CTCA) or conventional angiography and a CT scan for coronary artery calcium (CAC) scoring. 1539 (27.9%) patients had significant stenosis, 5.5% of whom had zero CAC. In 5074 patients, multiple binary regression showed the most important predictor of significant stenosis to be male gender (B=1.07) followed by diabetes mellitus (B=0.70) smoking, hypercholesterolaemia, hypertension, family history of CAD and age but not obesity. When the log transformed CAC score was included, it became the most powerful predictor (B=1.25), followed by male gender (B=0.48), diabetes, smoking, family history and age but hypercholesterolaemia and hypertension lost significance. The CAC score is a more accurate predictor of >50% stenosis than risk factors regardless of the means of assessment of stenosis. The sensitivity of risk factors, CAC score and the combination for prediction of >50% stenosis when measured by conventional angiogram was considerably higher than when assessed by CTCA but the specificity was considerably higher when assessed by CTCA. The accuracy of CTCA for predicting >50% stenosis using the CAC score alone was higher (AUC=0.85) than using a combination of the CAC score and risk factors with conventional angiography (AUC=0.81). CONCLUSION: In symptomatic patients, the CAC score is a more accurate predictor of significant coronary stenosis than conventional risk factors.

The metabolic syndrome and diabetes mellitus as predictors of thoracic aortic calcification as detected by non-contrast computed tomography in the Multi-Ethnic Study of Atherosclerosis.

AIMS: The metabolic syndrome (MetS) is a clustering of low levels of HDL cholesterol, hyperglycaemia, high waist circumference, hypertension and elevated triglycerides, and is associated with cardiovascular disease. Calcified atherosclerotic plaque in the thoracic aorta (TAC), measured by non-contrast cardiac computed tomography (CT) scans, is a marker for atherosclerosis and relates to mortality. We sought to evaluate the independent association of MetS and TAC on cardiac CT scans. METHODS: We examined the relation of the MetS, and each of its components, to the prevalence of TAC, measured from 2000 to 2002 in 6778 white, Chinese, African-American and Hispanic participants in the Multi-Ethnic Study of Atherosclerosis (MESA). RESULTS: Adjusting for age, gender, race, smoking, LDL cholesterol and lipid-lowering medications, relative risks and 95% confidence intervals (CI) for a TAC score > 0 were: 1.19 (95% CI 1.11 to 1.28) for participants with MetS, 1.34 (95% CI 1.21 to 1.49) for those with diabetes and MetS, and 1.33 (95% CI 1.11, 1.58) for those with diabetes and no MetS compared with participants who were free of the MetS and diabetes. Associations were found for most of the components of the MetS with TAC. CONCLUSIONS: We conclude that in adults without known heart disease, the MetS, most of its components and diabetes are associated with a higher prevalence of calcified atherosclerotic plaque in the thoracic arteries in a multi-ethnic population of men and women.

HIV infection is associated with an increased prevalence of coronary noncalcified plaque among participants with a coronary artery calcium score of zero: Multicenter AIDS Cohort Study (MACS).

OBJECTIVES: HIV-infected individuals bear increased cardiovascular risk even in the absence of traditional cardiovascular risk factors. In the general population, coronary artery calcium (CAC) scanning is of value for cardiovascular risk stratification, but whether a CAC score of zero implies a low noncalcified coronary plaque burden in HIV-infected persons is unknown. METHODS: We assessed the prevalence of noncalcified coronary plaque and compared noncalcified coronary plaque burden between HIV-infected and HIV-uninfected participants who had CAC scores of zero in the Multicenter AIDS Cohort Study (MACS) using coronary computed tomography (CT) angiography. RESULTS: HIV infection was associated with the presence of noncalcified coronary plaque among these men with CAC scores of zero. In a model adjusted only for age, race, centre, and pre- or post-2001 cohort, the prevalence ratio for the presence of noncalcified plaque was 1.27 (95% confidence interval 1.04-1.56; P = 0.02). After additionally adjusting for cardiovascular risk factors, HIV infection remained associated with the presence of noncalcified coronary plaque (prevalence ratio 1.31; 95% confidence interval 1.07-1.6; P = 0.01). CONCLUSIONS: Among men with CAC scores of zero, HIV infection is associated with an increased prevalence of noncalcified coronary plaque independent of traditional cardiovascular risk factors. This finding suggests that CAC scanning may underestimate plaque burden in HIV-infected men.

Ectopic cardiovascular fat in middle-aged men: effects of race/ethnicity, overall and central adiposity. The ERA JUMP study.

BACKGROUND/OBJECTIVES: Higher volumes of ectopic cardiovascular fat (ECF) are associated with greater risk of coronary heart disease (CHD). Identifying factors that are associated with ECF volumes may lead to new preventive efforts to reduce risk of CHD. Significant racial/ethnic differences exist for overall and central adiposity measures, which are known to be associated with ECF volumes. Whether racial/ethnic differences also exist for ECF volumes and their associations with these adiposity measures remain unclear. SUBJECTS/METHODS: Body mass index (BMI), computerized tomography-measured ECF volumes (epicardial, pericardial and their summation) and visceral adipose tissue (VAT) were examined in a community-based sample of 1199 middle-aged men (24.2% Caucasians, 7.0% African-Americans, 23.6% Japanese-Americans, 22.0% Japanese, 23.2% Koreans). RESULTS: Significant racial/ethnic differences existed in ECF volumes and their relationships with BMI and VAT. ECF volumes were the highest among Japanese-Americans and the lowest among African-Americans. The associations of BMI and VAT with ECF differed by racial/ethnic groups. Compared with Caucasians, for each 1-unit increase in BMI, African-Americans had lower, whereas Koreans had higher increases in ECF volumes (P-values<0.05 for both). Meanwhile, compared with Caucasians, for each 1-unit increase in log-transformed VAT, African-Americans, Japanese-Americans and Japanese had similar increases, whereas Koreans had a lower increase in ECF volumes (P-value<0.05). CONCLUSIONS: Racial/ethnic groups differed in their propensity to accumulate ECF at increasing level of overall and central adiposity. Future studies should evaluate whether reducing central adiposity or overall weight will decrease ECF volumes more in certain racial/ethnic groups. Evaluating these questions might help in designing race-specific prevention strategy of CHD risk associated with higher ECF.

[Preliminary reports of noninvasive accurate method to measure pulmonary vascular capacity in normal volunteers].

OBJECTIVE: Because the traditional loop of breathing control and regulation effect on blood circulation, there was rare study of pulmonary vein capacity. We need a noninvasive and accurate pulmonary vascular capacity measurement and analysis method. METHODS: Twelve normal volunteers were performed a total lung CT scan, image data analysis processing by computer software, the whole lungs from the apex to the base of lung with 40-50 layers by hand-cut, the connection between adjacent layers automatically by a computer simulation, the full pulmonary vascular (≥ 0.6 mm) were treated by high-accuracy three-dimensional imaging technology after removing the interference, and then calculate the whole lung and pulmonary vascular. RESULTS: The whole lung of the 12 normal volunteers from the apex to the base of lung CT scan image layers was 530 ± 98 (range, 431-841). The total capacity of lung and pulmonary vascular blood was 3705 ± 857 (range, 2398-5383) ml, and the total volume of the pulmonary vascular blood was 125 ± 32 (range, 94-201) ml. The pulmonary vein vascular blood volume was 63 ± 16 (range, 47-100) ml. CONCLUSION: The method of measuring the three-dimensional imaging of pulmonary vascular capacity by analyzing lung CT scan data is available and accurate.

[Normal reference values and predict equations of heart function].

OBJECTIVE: For heart functional parameters, we commonly used normal range. The reference values and predict formulas of heart functional parameters and their relationships with individual characteristics are still lack. METHODS: Left ventricular (LV) volumes (end-diastolic volume and end-systolic volume), stroke volume (SV), ejection fraction (EF) and cardiac output (CO) were measured by cardiac CT angiography (CAT) in 1 200 healthy Caucasian volunteers, men 807 and women 393, and age 20-90yr. The results are analyzed by high-accuracy three-dimensional imaging technology, and then measured the dynamic changes of the volumes of each atriam and ventricule during their contractions and relaxations. The gender, age, height and weight were analyzed by multiple linear regression to predict LV functional parameters. RESULTS: Except the LVEF was lower in man than in women (P < 0.001), all other LV functional parameters of EDV, ESV, SV, FE and CO were higher in man (P < 0.001). Multiple linear regression indicated that age, gender, height and weight are all independent factors of EDV, ESV and SV (P < 0.001). CO could be significantly predicted by age, gender and weight (P < 0.001), but not height (P > 0.05). The predict equation for CO (L x min(-1)) = 6.963+0.446 (Male) -0.037 x age (yr) +0.013 x weight (kg). CONCLUSION: Age, gender, height and weight are predictors of heart functions. The reference values and predict equations are important for noninvasive and accurate evaluation of cardiovascular disease and individualized treatment.

[The correlation of the stroke volume with pulmonary venous volume and left atrial volume].

OBJECTIVE: The same person's pulmonary venous blood volume, left atrial volume and stroke volume were measured by lung CT scans and cardiac CT angiography (CTA). Then their relationships were analyzed in order to investigate the mechanism of breathing control. METHODS: As we described before, full pulmonary vascular (-0.6mm) volume was accurately calculated by three-dimensional imaging technology from lung CT scan; left atrial volume and stroke volume of left ventricle were calculated from the CTA data. Then the relationships among them were analyzed for estimation of the lung-artery time. RESULTS: The total volume of lung and pulmonary vascular blood was 3486 ± 783 (2156-4418) ml, and the pulmonary vascular blood volume was 141 ± 20 (105-163) ml. The estimated pulmonary venous volume was 71 ± 10 (52-81) ml. Left atrial volume at the end diastolic was 97 ± 39 (53-165) ml, Stroke volume of left ventricle was 86 ± 16 (60-106) ml. Pulmonary venous volume and the left atrial volume were double of stroke volume(1.7-2.4). CONCLUSION: The estimated lung-artery time was three heart beat.

Lessons learned from the design and implementation of myocardial infarction adjudication tailored for HIV clinical cohorts.

We developed, implemented, and evaluated a myocardial infarction (MI) adjudication protocol for cohort research of human immunodeficiency virus. Potential events were identified through the centralized Centers for AIDS Research Network of Integrated Clinical Systems data repository using MI diagnoses and/or cardiac enzyme laboratory results (1995-2012). Sites assembled de-identified packets, including physician notes and results from electrocardiograms, procedures, and laboratory tests. Information pertaining to the specific antiretroviral medications used was redacted for blinded review. Two experts reviewed each packet, and a third review was conducted if discrepancies occurred. Reviewers categorized probable/definite MIs as primary or secondary and identified secondary causes of MIs. The positive predictive value and sensitivity for each identification/ascertainment method were calculated. Of the 1,119 potential events that were adjudicated, 294 (26%) were definite/probable MIs. Almost as many secondary (48%) as primary (52%) MIs occurred, often as the result of sepsis or cocaine use. Of the patients with adjudicated definite/probable MIs, 78% had elevated troponin concentrations (positive predictive value = 57%, 95% confidence interval: 52, 62); however, only 44% had clinical diagnoses of MI (positive predictive value = 45%, 95% confidence interval: 39, 51). We found that central adjudication is crucial and that clinical diagnoses alone are insufficient for ascertainment of MI. Over half of the events ultimately determined to be MIs were not identified by clinical diagnoses. Adjudication protocols used in traditional cardiovascular disease cohorts facilitate cross-cohort comparisons but do not address issues such as identifying secondary MIs that may be common in persons with human immunodeficiency virus.