Negin Nezarat

Testosterone Treatment and Coronary Artery Plaque Volume in Older Men With Low Testosterone

Importance Recent studies have yielded conflicting results as to whether testosterone treatment increases cardiovascular risk. Objective To test the hypothesis that testosterone treatment of older men with low testosterone slows progression of noncalcified coronary artery plaque volume. Design, Setting, and Participants Double-blinded, placebo-controlled trial at 9 academic medical centers in the United States. The participants were 170 of 788 men aged 65 years or older with an average of 2 serum testosterone levels lower than 275 ng/dL (82 men assigned to placebo, 88 to testosterone) and symptoms suggestive of hypogonadism who were enrolled in the Testosterone Trials between June 24, 2010, and June 9, 2014. Intervention Testosterone gel, with the dose adjusted to maintain the testosterone level in the normal range for young men, or placebo gel for 12 months. Main Outcomes and Measures The primary outcome was noncalcified coronary artery plaque volume, as determined by coronary computed tomographic angiography. Secondary outcomes included total coronary artery plaque volume and coronary artery calcium score (range of 0 to >400 Agatston units, with higher values indicating more severe atherosclerosis). Results Of 170 men who were enrolled, 138 (73 receiving testosterone treatment and 65 receiving placebo) completed the study and were available for the primary analysis. Among the 138 men, the mean (SD) age was 71.2 (5.7) years, and 81% were white. At baseline, 70 men (50.7%) had a coronary artery calcification score higher than 300 Agatston units, reflecting severe atherosclerosis. For the primary outcome, testosterone treatment compared with placebo was associated with a significantly greater increase in noncalcified plaque volume from baseline to 12 months (from median values of 204 mm3 to 232 mm3 vs 317 mm3 to 325 mm3, respectively; estimated difference, 41 mm3; 95% CI, 14 to 67 mm3; P = .003). For the secondary outcomes, the median total plaque volume increased from baseline to 12 months from 272 mm3 to 318 mm3 in the testosterone group vs from 499 mm3 to 541 mm3 in the placebo group (estimated difference, 47 mm3; 95% CI, 13 to 80 mm3; P = .006), and the median coronary artery calcification score changed from 255 to 244 Agatston units in the testosterone group vs 494 to 503 Agatston units in the placebo group (estimated difference, −27 Agatston units; 95% CI, −80 to 26 Agatston units). No major adverse cardiovascular events occurred in either group. Conclusions and Relevance Among older men with symptomatic hypogonadism, treatment with testosterone gel for 1 year compared with placebo was associated with a significantly greater increase in coronary artery noncalcified plaque volume, as measured by coronary computed tomographic angiography. Larger studies are needed to understand the clinical implications of this finding. Trial Registration clinicaltrials.gov Identifier: NCT00799617

The Cardiovascular Trial of the Testosterone Trials: rationale, design, and baseline data of a clinical trial using computed tomographic imaging to assess the progression of coronary atherosclerosis.

BackgroundData from prior studies have yielded inconsistent results on the association of serum testosterone levels with the risk for cardiovascular disease. There are no clinical trial data on the effects of testosterone replacement therapy on plaque progression. ObjectiveWe designed a study to investigate the effect of testosterone therapy on coronary artery plaque progression using serial coronary computed tomographic angiography (CCTA). In this paper, we describe the study design, methods, and characteristics of the study population. MethodsThe Cardiovascular Trial of the Testosterone Trials (TTrials; NCT00799617) is a double-blind, placebo-controlled trial of 1 year of testosterone therapy in men 65 years or older with clinical manifestations of androgen deficiency and unequivocally low serum testosterone concentrations (<275 ng/dl). CCTA performed at baseline and after 12 months of therapy will determine the effects of testosterone on the progression of the total volume of noncalcified plaques. All scans are evaluated at a central reading center by an investigator blinded to treatment assignment. ResultsA total of 165 men were enrolled. The average age is 71.1 years, and the average BMI is 30.7. About 9% of men had a history of myocardial infarction, 6% angina, and 10% coronary artery revascularization. A majority reported hypertension and/or high cholesterol; 31.8% reported diabetes. Total noncalcified plaque at baseline showed a slight but nonsignificant trend toward lower plaque volume with higher serum testosterone concentrations (P=0.12). ConclusionThe Cardiovascular Trial will test the hypothesis that testosterone therapy inhibits coronary plaque progression, as assessed by serial CCTA.

Rationale and design of a randomized trial of apixaban vs warfarin to evaluate atherosclerotic calcification and vulnerable plaque progression

Vitamin K antagonists (VKAs) are known to increase vascular calcification, suggesting increased cardiovascular disease events. Apixaban is an oral direct factor Xa inhibitor superior to warfarin at preventing stroke or systemic embolism and may stabilize coronary atherosclerosis. The potential benefits of avoiding VKA therapy and the favorable effects of factor Xa inhibitors could contribute to cardiovascular disease event reduction. We hypothesized that apixaban inhibits vascular calcification and coronary atherosclerosis progression compared with warfarin in patients with atrial fibrillation (AF). This study is a single‐center, prospective, randomized, open‐label study. From May 2014 to December 2015, 66 patients with nonvalvular AF who experienced VKA therapy were enrolled. Patients were randomized into either warfarin or apixaban cohorts and followed for 52 weeks. The primary objective is to compare the rate of change in coronary artery calcification (CAC) from baseline to follow‐up in apixaban vs warfarin cohorts. The key secondary objective is to compare the rate of incident plaques and quantitative changes in plaque types between patients randomized to either warfarin or apixaban cohorts using serial coronary computed tomography angiography. Expert readers will blindly assess CAC and coronary artery plaques. It is thought that this trial will result in significant differences in CAC and coronary artery plaque progression between the VKA and apixaban. The results are anticipated to provide a novel insight into treatment selection for AF patients. The study is registered at http://www.clinicaltrials.gov (NCT 02090075).

Role of Coronary Calcium for Risk Stratification and Prognostication

Opinion statementA multitude of studies now support the understanding that an increased coronary artery calcium (CAC) score represents advanced atherosclerosis and high risk for cardiovascular disease (CVD) and, as such, should be treated with conventional therapies for those considered high risk. Data is now available to guide treatment with aspirin, statins, and lifestyle management. The new ACC/AHA 2013 guidelines support intensifying statin therapy when the CAC is ≥75th percentile for age, sex, and ethnicity/race or when the calcium score is ≥300 Agatston units. This allows for aggressive management of those at the highest risk, matching intensity of therapy with intensity of risk. Most importantly, the asymptomatic person rarely needs to undergo evaluation for obstructive disease, even when CAC scores are high, as revascularization with percutaneous coronary interventions does not improve outcomes in asymptomatic persons with preserved left ventricular function. Treatment should be relegated to improvement in lifestyle, diet, exercise, aspirin, statins, and blood pressure control.

Diagnostic accuracy of Visipaque enhanced coronary computed tomographic angiography: a prospective multicenter trial

Background Although several studies have shown promise for noninvasive angiography by coronary computed tomographic angiography (CCTA), few prospective multicenter trials have been conducted. This study evaluated the diagnostic accuracy of Visipaque enhanced CCTA to detect obstructive coronary stenosis compared with quantitative coronary angiography (QCA). Patients and methods Three sites prospectively enrolled 77 patients (58.1% men, 54 years) with chest pain referred for invasive coronary angiography (ICA). Patients underwent CCTA (Lightspeed VCT/Visipaque 320) before ICA. CCTAs were graded on a 15-segment American Heart Association model by a CCTA core lab with blinded readers for the presence of obstructive stenosis (>50% or >70%); ICAs were independently graded for %stenosis by QCA, considered the reference standard. The efficacy of CCTA was assessed including all vessel segments for per-patient and per-vessel analyses. Results A total of 46 more than 50% stenoses in 27 (35%) patients, and 31 more than 70% stenoses in 20 (26%) patients, were identified by QCA. Per-patient and per-vessel efficacy of CCTA compared with QCA yielded sensitivities of 85% and specificities of 90 and 95%, respectively. Conclusion This study shows the high accuracy of CCTA to reliably detect more than 50% and more than 70% stenoses in low-probability to intermediate-probability chest pain patients being referred for ICA. The high negative predictive values observed (92–100%) indicate that CCTA is also an effective noninvasive alternative to exclude obstructive coronary stenosis.

The relationship between cardio-ankle vascular index and subclinical atherosclerosis evaluated by cardiac computed tomographic angiography

The cardio‐ankle vascular index (CAVI) is a new noninvasive index to evaluate arterial stiffness. We investigated whether CAVI can predict severity, extent, and burden of coronary artery disease by comparing results with cardiac computed tomographic angiography (CCTA).

Association of Vitamin D Level and Subclinical Coronary Artery Disease

Background: The role of vitamin D level in subclinical atherosclerosis remains controversial. We aimed to investigate the relationship between vitamin D level and coronary artery calcium score (CACS). Patients methods: We investigated 303 consecutive patients referred to an outpatient clinic for CACS. The 25-hydroxy vitamin D [25(OH) D] levels were checked within three months of CACS evaluation. Vitamin D levels of <30 and <20 ng/mL were used as thresholds of vitamin D insufficiency and deficiency, respectively. The correlation between CACS and vitamin D was assessed. Unadjusted and covariate-adjusted logistic regression analyses were used to predict positive CACS. Results: The mean age in this study is 61.8 ± 11.8 years (39.9% female). The majority of patients enrolled were Caucasian (87.4%). Median (interquartile range) serum 25(OH) D concentration was 30.0 (23.0, 39.0) ng/ml. Vitamin D was insufficient ( 0) was prevalent in 206 (68%) participants. In the unadjusted model, the 25 (OH) D levels were not associated with the prevalence of CACS among all cases or among patients with positive CACS. Logistic regression models, after controlling for risk factors, did not change the results. In addition, among the 206 participants with prevalent CACS, 25 (OH) D levels were not associated with CACS severity. Conclusions: Our single centre retrospective study in a population with low prevalence of vitamin D deficiency failed to find a significant relation between 25(OH) D level and CACS even when adjusted for risk factors.

Correlation of Arterial Stiffness With Left Atrial Volume Index and Left Ventricular Mass Index in Young Adults: Evaluation by Coronary Computed Tomography Angiography

BACKGROUND Increased arterial stiffness is reportedly associated with cardiac remodelling, including the left atrium and left ventricle, in middle-aged and older adults. However, little is known about this association in young adults. METHODS In total, 73 patients (44 (60%) men) aged 25 to 45 years with suspected coronary artery disease were included in the analysis. The left atrial volume index (LAVI), left ventricular volume index (LVVI), and left ventricular mass index (LVMI) were measured using coronary computed tomography angiography (CCTA). Arterial stiffness was assessed with the cardio-ankle vascular index (CAVI). An abnormally high CAVI was defined as that above the age- and sex-specific cut-off points of the CAVI. RESULTS Compared with patients with a normal CAVI, those with an abnormally high CAVI were older and had a greater prevalence of diabetes mellitus, higher diastolic blood pressure, greater coronary artery calcification score, and a greater LAVI (33.5±10.3 vs. 43.0±10.3mL/m2, p <0.01). In contrast, there were no significant differences in the LVVI or LVMI between the subgroups with a normal CAVI and an abnormally high CAVI. Multivariate linear regression analysis showed that the LAVI was significantly associated with an abnormally high CAVI (standardised regression coefficient=0.283, p=0.03). CONCLUSIONS The present study demonstrated that increased arterial stiffness is associated with the LAVI, which reflects the early stages of cardiac remodelling, independent of various comorbidity factors in young adults with suspected coronary artery disease.

Ischemic stroke/transient ischemic attack events and carotid artery disease in the absence of or with minimal coronary artery calcification: Results from the Multi-Ethnic Study of Atherosclerosis

BACKGROUND AND AIMS The association between minimally elevated coronary artery calcification (CAC) and cerebrovascular disease is not well known. We assessed whether individuals with minimal CAC (Agatston scores of 1-10) have higher ischemic stroke or transient ischemic attack (TIA) frequencies compared with those with no CAC. We also investigated the relative prevalence of carotid atherosclerosis in these two groups. METHODS A total of 3924 participants from the Multi-Ethnic Study of Atherosclerosis (MESA) without previous cardiovascular events, including stroke, and with baseline CAC scores of 0-10 were followed for the occurrence of incident ischemic stroke/TIA. We used carotid ultrasound to detect carotid artery plaques and to measure the intima-media thickness (IMT). RESULTS During a median follow-up of 13.2 years, 130 participants developed incident ischemic stroke/TIA. There was no significant difference in the ischemic stroke/TIA incidence between those with minimal CAC and no CAC (3.7 versus 2.7 per 1000 person-years). In participants with minimal CAC, we observed a significant association of the condition with an internal carotid artery (ICA) that had a greater-than-average IMT (ICA-IMT; β = 0.071, p = 0.001) and a higher odds ratio (OR) for carotid artery plaques (OR 1.46; with a 95% confidence interval [CI] of 1.18-1.80; p < 0.001). CONCLUSIONS A CAC score of 0-10 is associated with a low rate of ischemic stroke/TIA, and thus a minimal CAC score is not a valuable predictive marker for ischemic stroke/TIA. A minimal CAC score may, however, provide an early and asymptomatic sign of carotid artery disease.

IMPACT OF CARDIAC TROPONIN I ON THE PRESENCE OF THE CORONARY ARTERY PLAQUE IN RHEUMATOID ARTHRITIS PATIENTS

Introduction: The presence of accelerated coronary artery disease in rheumatoid arthritis (RA) was previously reported. The goal of this study was to investigate if using high sensitivity cardiac troponin I (hs-cTnI) identifies patients at higher coronary atherosclerosis risk. Method: A total of