High-sensitivity cardiac troponin I is a biomarker for occult coronary plaque burden and cardiovascular events in patients with rheumatoid arthritis.

Objectives: Patients with RA display greater occult coronary atherosclerosis burden and experience higher cardiovascular morbidity and mortality compared with controls. We here explored whether pro-inflammatory cytokines and high-sensitivity cardiac troponin I (hs-cTnI), a biomarker of myocardial injury, correlated with plaque burden and cardiovascular events (CVEs) in RA. Methods: We evaluated 150 patients with 64-slice coronary CT angiography. Coronary artery calcium, number of segments with plaque (segment involvement score), stenotic severity and plaque burden were assessed. Lesions were described as non-calcified, mixed or fully calcified. Blood levels of hs-cTnI and pro-inflammatory cytokines were assessed during coronary CT angiography. Subjects were followed over 60 (s.d. 26) months for both ischaemic [cardiac death, non-fatal myocardial infarction (MI), stroke, peripheral arterial ischaemia] and non-ischaemic (new-onset heart failure hospitalization) CVEs. Results: Plasma hs-cTnI correlated with all coronary plaque outcomes (P < 0.01). Elevated hs-cTnI (⩾1.5 pg/ml) further associated with significant calcification, extensive atherosclerosis, obstructive plaque and any advanced mixed or calcified plaques after adjustments for cardiac risk factors or Framingham D'Agostino scores (all P < 0.05). Eleven patients suffered a CVE (1.54/100 patient-years), eight ischaemic and three non-ischaemic. Elevated hs-cTnI predicted all CVE risk independent of demographics, cardiac risk factors and prednisone use (P = 0.03). Conversely, low hs-cTnI presaged a lower risk for both extensive atherosclerosis (P < 0.05) and incident CVEs (P = 0.037). Conclusion: Plasma hs-cTnI independently associated with occult coronary plaque burden, composition and long-term incident CVEs in patients with RA. Low hs-cTnI forecasted a lower risk for both extensive atherosclerosis as well as CVEs. hs-cTnI may therefore optimize cardiovascular risk stratification in RA.

Aged Garlic Extract Reduces Low Attenuation Plaque in Coronary Arteries of Patients with Metabolic Syndrome in a Prospective Randomized Double-Blind Study.

BACKGROUND: Although several previous studies have demonstrated that aged garlic extract (AGE) inhibits the progression of coronary artery calcification, its effect on noncalcified plaque (NCP) has been unclear. OBJECTIVE: This study investigated whether AGE reduces coronary plaque volume measured by cardiac computed tomography angiography (CCTA) in patients with metabolic syndrome (MetS). METHODS: Fifty-five patients with MetS (mean ± SD age: 58.7 ± 6.7 y; 71% men) were prospectively assigned to consume 2400 mg AGE/d (27 patients) or placebo (28 patients) orally. Both groups underwent CCTA at baseline and follow-up 354 ± 41 d apart. Coronary plaque volume, including total plaque volume (TPV), dense calcium (DC), NCP, and low-attenuation plaque (LAP), were measured based upon predefined intensity cutoff values. Multivariable linear regression analysis, adjusted for age, gender, number of risk factors, hyperlipidemia medications, history of coronary artery disease, scan interval time, and baseline %TPV, was performed to examine whether AGE affected each plaque change. RESULTS: The %LAP change was significantly reduced in the AGE group compared with the placebo group (-1.5% ± 2.3% compared with 0.2% ± 2.0%, P = 0.0049). In contrast, no difference was observed in %TPV change (0.3% ± 3.3% compared with 1.6% ± 3.0%, P = 0.13), %NCP change (0.2% ± 3.3% compared with 1.4% ± 2.9%, P = 0.14), and %DC change (0.2% ± 1.4%, compared with 0.2% ± 1.7%, P = 0.99). Multivariable linear regression analysis found a beneficial effect of AGE on %LAP regression (ß: -1.61; 95% CI: -2.79, -0.43; P = 0.008). CONCLUSIONS: This study indicates that the %LAP change was significantly greater in the AGE group than in the placebo group. Further studies are needed to evaluate whether AGE has the ability to stabilize vulnerable plaque and decrease adverse cardiovascular events. This trial was registered at clinicaltrials.gov as NCT01534910.

Epicardial and intra-thoracic adipose tissue and cardiovascular calcifications in type 1 diabetes (T1D) in epidemiology of diabetes Interventions and Complications (EDIC): A pilot study.

Objective: Coronary artery, aortic valve, and descending aorta calcification (CAC, AVC, DAC) are manifestations of atherosclerosis, and cardiac epicardial adipose tissue (EAT) indicates heart adiposity. This study explored the association between cardiac adipose tissue and cardiovascular calcification in participants with long-standing T1D. Methods: EAT and intra-thoracic adipose tissue (IAT) were measured in 100 T1D subjects with cardiac computed tomography (CT) scans in the EDIC study. Volume analysis software was used to measure fat volumes. Spearman correlations were calculated between CAC, AVC, DAC with EAT, and IAT. Associations were evaluated using multiple linear and logistic regression models. Results: Participants ranged in age from 32 to 57. Mean EAT, and IAT were 38.5 and 50.8 mm3, respectively, and the prevalence of CAC, AVC, and DAC was 43.6 %, 4.7 %, and 26.8 %, respectively. CAC was positively correlated with age (p-value = 0.0001) and EAT (p-value = 0.0149) but not with AVC and DAC; IAT was not associated with calcified lesions. In models adjusted for age and sex, higher levels of EAT and IAT were associated with higher CAC (p-value < 0.0001 for both) and higher AVC (p-values of 0.0111 and 0.0053, respectively), but not with DAC. The associations with CAC remained significant (p-value < 0.0001) after further adjustment for smoking, systolic blood pressure, BMI, and LDL, while the associations with AVC did not remain significant. Conclusion: In participants with T1D, higher EAT and IAT levels are correlated with higher CAC scores. EAT and IAT were not independently correlated with DAC or AVC.

Use of noninvasive imaging in the evaluation of coarctation of aorta.

Coarctation of the aorta is a congenital heart disease, which is often associated with other cardiac and noncardiac anomalies. Early diagnoses, information about associated anomalies, and defining the severity of the disease are critical for appropriate treatment planning. In this regard, several noninvasive imaging modalities, such as echocardiography, cardiac computed tomography (CT), and cardiac magnetic resonance imaging, have been used. Echocardiography, as an available and safe method, should be used as a primary screening test. It is also useful for intraoperative and hemodynamic studies, but cardiac CT is recommended before any corrective procedure or surgery. Cardiac CT angiography showed an excellent spatial resolution and a good capability for finding associated anomalies. After correction of coarctation of the aorta, serial cardiac magnetic resonance imaging is most commonly performed to avoid repeated radiation exposure.

Epicardial Adipose Tissue Volume As a Marker of Subclinical Coronary Atherosclerosis in Rheumatoid Arthritis.

OBJECTIVE: To assess epicardial adipose tissue volume (EATV) and its link to coronary atherosclerosis and plaque morphology in patients with rheumatoid arthritis (RA) and in age- and sex-matched controls. METHODS: Computed tomography angiography was used to evaluate EATV and coronary plaque in 139 RA patients and 139 non-RA controls. All models assessing the effect of EATV on plaque were adjusted for age, sex, hypertension, diabetes, dyslipidemia, smoking status, family history of coronary artery disease, and obesity (body mass index of ≥30 kg/m2 ). Odds ratios (ORs) and 95% confidence intervals (95% CIs) were calculated. RESULTS: Mean ± SD log-transformed EATV was similar in patients with RA (4.69 ± 0.36) and controls (4.70 ± 0.42). EATV was higher in RA patients with atherosclerosis compared to those without atherosclerosis (P = 0.046). In stratified analyses, EATV was associated with the number of segments with plaque in RA patients (rate ratio 1.20 [95% CI 1.01-1.41] per 1-SD increment of log-unit increase in EATV) but not in controls (P for interaction = 0.089). Likewise, EATV (per 1-SD log-unit increase) was related to the presence of multivessel or obstructive disease (OR 1.63 [95% CI 1.04-2.61]), noncalcified plaque (OR 1.78 [95% CI 1.17-2.70]), and vulnerable plaque (OR 1.77 [95% CI 1.03-3.04]) in RA patients but not in controls (P for interaction ≤ 0.048 for each). Among RA patients, EATV was associated with the number of segments with plaque in those with RA for <10 years who did not develop any cardiovascular risk factors and who were not obese (P for interaction ≤ 0.017). CONCLUSION: Despite similar EATVs in RA patients and controls, EATVs were associated with greater plaque burden and presence of plaques with a noncalcified component and vulnerability features only in RA patients. EAT may be more pathogenic in RA and play a role in early-stage atherosclerosis. Its value as a biomarker of subclinical atherosclerosis and cardiovascular risk in RA warrants further studies.

Extra-coronary calcification (aortic valve calcification, mitral annular calcification, aortic valve ring calcification and thoracic aortic calcification) in HIV seropositive and seronegative men: Multicenter AIDS Cohort Study.

INTRODUCTION: Previous studies have demonstrated an association between HIV infection and coronary artery disease (CAD); little is known about potential associations between HIV infection and extra-coronary calcification (ECC). METHODS: We analyzed 621 HIV infected (HIV+) and 384 HIV uninfected (HIV-) men from the Multicenter AIDS Cohort Study who underwent non-contrast computed tomography (CT) from 2010-2013. Agatston scores were calculated for mitral annular calcification (MAC), aortic valve calcification (AVC), aortic valve ring calcification (AVRC), and thoracic aortic calcification (TAC). The associations between HIV infection and the presence of each type of ECC (score > 0) were evaluated by multivariable logistic regression. We also evaluated the association of ECC with inflammatory biomarker levels and coronary plaque morphology. RESULTS: Among HIV+ and HIV- men, the age-standardized prevalences were 15% for TAC (HIV+ 14%/HIV- 16%), 10% for AVC (HIV+ 11%/HIV- 8%), 24% for AVRC (HIV+ 23% HIV- 24%), and 5% for MAC (HIV+ 7%/HIV- 3%). After adjustment, HIV+ men had 3-fold greater odds of MAC compared to HIV- men (OR = 3.2, 95% CI: 1.5-6.7), and almost twice the odds of AVC (1.8, 1.1-2.9). HIV serostatus was not associated with TAC or AVRC. AVRC was associated with higher Il-6 and sCD163 levels. TAC was associated with higher ICAM-1, TNF-α RII, and Il-6 levels. AVC and AVRC calcification were associated with presence of non-calcified plaque in HIV+ but not HIV- men. CONCLUSION: HIV infection is an independent predictor of MAC and AVC. Whether these calcifications predict mortality in HIV+ patients deserves further investigation.

The relationship between coronary artery calcium score and the long-term mortality among patients with minimal or absent coronary artery risk factors.

BACKGROUND: Coronary artery calcium (CAC) is strongly predictive of all-cause mortality in intermediate-risk groups, but this relationship is not well defined in very low-risk individuals. We investigated the relationship between CAC scoring and the long-term all-cause mortality among patients with ≤ 1 cardiovascular disease (CVD) risk factor. METHODS: We analyzed a retrospective cohort of 5584 asymptomatic patients with no known CVD (mean 56.6 ± 11.6 years, 69%men) and ≤ 1 risk factor who were physician referred for a CAC scan. Mortality was ascertained through linkage with the Social Security Death Index. We calculated the prevalence of CAC stratified by age and risk factors. We also examined the association between CAC and mortality using multivariable Cox Proportional hazards models. RESULTS: During a mean follow-up of 10.4 ± 3.1 years, 168 individuals (3.0%) died. Overall, 54.5% of patients had a CAC >0 and 9.8% had CAC ≥ 400. There was a greater risk of mortality with increasing CAC 1-99 (HR 1.9, 95% CI 1.2-3.1), 100-399 (HR 2.1, 95% CI 1.2-3.6) and ≥ 400 (HR 2.8, 95% CI 1.6-4.8) compared to CAC=0 (p<0.0001 for trend). Similar results were observed when the population was stratified by zero or one risk factor. Among patients < 45 years old, there was a 0.7% incidence of mortality compared to 8.1% for individuals ≥ 65 years old. CONCLUSIONS: During long-term follow-up, an increasing CAC was significantly associated with a higher risk of all-cause mortality among patients with a very low CVD risk factor profile. CAC scanning may be a potentially useful tool for risk stratification among low CVD risk individuals who are ≥ 45 years old.

HIV and coronary arterial remodeling from the Multicenter AIDS Cohort Study (MACS).

OBJECTIVE: Positive remodeling (PR), a coronary artery characteristic associated with risk for myocardial infarction (MI), may be more prevalent in HIV-infected (HIV+) people. We evaluated the prevalence of PR using coronary CT angiography (CCTA) in HIV+ and HIV-uninfected (HIV-) men. METHODS: Men enrolled in the Multicenter AIDS Cohort Study underwent CCTA if they were 40-70 years, had normal kidney function and no history of coronary revascularization. Multivariable logistic regression models were used to estimate the odds ratio (OR) of PR by HIV serostatus, adjusting for demographics and coronary artery disease (CAD) risk factors. Analysis of PR among atherosclerotic segments further adjusted for plaque type and stenosis. RESULTS: The prevalence of PR was 8.4% versus 12.1% (p = 0.10) for HIV- and HIV + men, respectively. After demographic adjustment, HIV + men had twice the odds of PR [OR 2.01(95% CI 1.20-3.38)], which persisted after CAD risk factor adjustment [1.76(1.00-3.10)]. Higher systolic blood pressure, total cholesterol, diabetes medication use, older age, segment number with plaque present, mixed and non-calcified plaque, and stenosis>50%, were associated with increased odds of PR, while higher HDL cholesterol, higher nadir CD4 count, and black race were associated with lower PR odds. Among atherosclerotic segments, the association between HIV infection and PR persisted, but was not statistically significantly. CONCLUSION: HIV+ men have more positively remodeled arterial segments, which may be due to more coronary segments with atherosclerosis or HIV-related immunosuppression. Further studies are needed to evaluate whether PR contributes to higher rates of MI in HIV+ individuals.

Epicardial fat is associated with duration of antiretroviral therapy and coronary atherosclerosis.

OBJECTIVE: Cytokines released by epicardial fat are implicated in the pathogenesis of atherosclerosis. HIV infection and antiretroviral therapy have been associated with changes in body fat distribution and coronary artery disease. We sought to determine whether HIV infection is associated with greater epicardial fat and whether epicardial fat is associated with subclinical coronary atherosclerosis. DESIGN: We studied 579 HIV-infected and 353 HIV-uninfected men aged 40-70 years with noncontrast computed tomography to measure epicardial adipose tissue (EAT) volume and coronary artery calcium (CAC). Total plaque score (TPS) and plaque subtypes (noncalcified, calcified, and mixed) were measured by coronary computed tomography angiography in 706 men. METHODS: We evaluated the association between EAT and HIV serostatus, and the association of EAT with subclinical atherosclerosis, adjusting for age, race, and serostatus and with additional cardiovascular risk factors and tested for modifying effects of HIV serostatus. RESULTS: HIV-infected men had greater EAT than HIV-uninfected men (P=0.001). EAT was positively associated with duration of antiretroviral therapy (P=0.02), specifically azidothymidine (P<0.05). EAT was associated with presence of any coronary artery plaque (P=0.006) and noncalcified plaque (P=0.001), adjusting for age, race, serostatus, and cardiovascular risk factors. Among men with CAC, EAT was associated with CAC extent (P=0.006). HIV serostatus did not modify associations between EAT and either CAC extent or presence of plaque. CONCLUSION: Greater epicardial fat volume in HIV-infected men and its association with coronary plaque and antiretroviral therapy duration suggest potential mechanisms that might lead to increased risk for cardiovascular disease in HIV.

Relation of nonalcoholic fatty liver disease to the metabolic syndrome: the Multi-Ethnic Study of Atherosclerosis.

BACKGROUND: An overlap exists between risk factors for metabolic syndrome (MetS) and nonalcoholic fatty liver disease (NAFLD). OBJECTIVES: We studied the association of MetS and its components with NAFLD in a multi-ethnic population. METHODS: Cross-sectional study was designed, including 6814 participants from the Multi-Ethnic Study of Atherosclerosis. Liver fat content was measured with cardiac CT scans by using liver-to-spleen ratio of <1.0 and liver attenuation < 40 HU. Participants with heavy alcohol intake (>14 drinks/week for men and >7 drinks/week for women), self-reported history of cirrhosis, and missing information were excluded. A total of 4140 participants met the criteria for inclusion in the study. RESULTS: The odds ratios (ORs) for presence of NAFLD were highest for persons with diabetes (OR, 4.16; 95% CI, 3.24-5.33), followed by presence of MetS (OR, 3.97; 95% CI, 3.26-4.83). Among components of MetS central obesity was associated with higher odds for presence (OR, 3.41; 95% CI, 2.77-4.20) and severity (OR, 5.58; 95% CI, 3.86-8.06) of NAFLD . The ORs for moderate-to-severe NAFLD were higher for presence of MetS (OR, 5.92; 95% CI, 4.29-8.19)] by using <40 HU as the cutoff. However, odds of NAFLD increased significantly for combination of MetS components: 9.49 (95% CI, 5.67-15.90) and 24.05 (95% CI, 12.73-45.45) for presence of 3 and 5 MetS components, respectively. CONCLUSION: Components of MetS are associated with increased odds for presence and severity of NAFLD and increased risk with increasing number of MetS components in a multi-ethnic population of middle-to-old age persons.