Presence, Characteristics, and Volumes of Coronary Plaque Determined by Computed Tomography Angiography in Young Type 2 Diabetes Mellitus.

Prevention and management of coronary artery disease (CAD) is of great concern in patients with diabetes mellitus. Although the impact of coronary atherosclerosis is described well for subjects older than 40 years, the prevalence and types of coronary atherosclerosis in young patients are not well known. The aim of this study was to evaluate the prevalence, extent, severity, and volumes of coronary plaque in type 2 diabetes mellitus (T2DM) population younger than of 40 years. This prospective study enrolled 181 subjects (25-40 year old) undergoing coronary computed tomography angiography, with 86 T2DM and 95 nondiabetic age/gender-matched subjects. Coronary artery calcium (CAC), plaque assessment including total segment stenosis (sum of individual segmental stenosis), total plaque scores (sum of semiquantitative segmental plaque burden), segment involvement scores (number of segments with plaque) were evaluated. In addition, we quantitatively measured plaque volumes in total, fibrous, fibrous fatty, dense calcified, and low-attenuation plaque using novel plaque software. Compared with nondiabetic patients, the prevalence of CAD, calcified, and noncalcified plaques was higher in patients with T2DM (19% vs 58%; p <0.001). In patients with a zero CAC, T2DM had a higher prevalence (46%) of noncalcified plaque (p <0.0001). In multivariate linear regression models after adjusting for traditional cardiovascular risk factors, increased total segmental stenosis, total plaque scores, and segment involvement scores were associated with T2DM. Regarding quantitative plaque assessment, all volumes in noncalcified plaque type were approximately threefold higher in patients with T2DM. In conclusion, young patients with T2DM are susceptible to premature CAD with more calcified and noncalcified plaques. Early prevention program using computed tomography angiography might be helpful in identifying young diabetic patients with subclinical atherosclerosis.

Significance of Epicardial and Intrathoracic Adipose Tissue Volume among Type 1 Diabetes Patients in the DCCT/EDIC: A Pilot Study.

INTRODUCTION: Type 1 diabetes (T1DM) patients are at increased risk of coronary artery disease (CAD). This pilot study sought to evaluate the relationship between epicardial adipose tissue (EAT) and intra-thoracic adipose tissue (IAT) volumes and cardio-metabolic risk factors in T1DM. METHOD: EAT/IAT volumes in 100 patients, underwent non-contrast cardiac computed tomography in the Diabetes Control and Complications Trial /Epidemiology of Diabetes Interventions and Complications (DCCT/EDIC) study were measured by a certified reader. Fat was defined as pixels' density of -30 to -190 Hounsfield Unit. The associations were assessed using-Pearson partial correlation and linear regression models adjusted for gender and age with inverse probability sample weighting. RESULTS: The weighted mean age was 43 years (range 32-57) and 53% were male. Adjusted for gender, Pearson correlation analysis showed a significant correlation between age and EAT/IAT volumes (both p<0.001). After adjusting for gender and age, participants with greater BMI, higher waist to hip ratio (WTH), higher weighted HbA1c, elevated triglyceride level, and a history of albumin excretion rate of equal or greater than 300 mg/d (AER≥300) or end stage renal disease (ESRD) had significantly larger EAT/IAT volumes. CONCLUSION: T1DM patients with greater BMI, WTH ratio, weighted HbA1c level, triglyceride level and AER≥300/ESRD had significantly larger EAT/IAT volumes. Larger sample size studies are recommended to evaluate independency.

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.

BACKGROUND: Data 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. OBJECTIVE: We 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. METHODS: The 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. RESULTS: A 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). CONCLUSION: The Cardiovascular Trial will test the hypothesis that testosterone therapy inhibits coronary plaque progression, as assessed by serial CCTA.

All-cause mortality by age and gender based on coronary artery calcium scores.

AIMS: Although coronary artery calcium (CAC) has been established as a robust tool for predicting total mortality during intermediate follow-up, less is known about the long-term predictive value of CAC. METHODS AND RESULTS: This study included 13 092 asymptomatic patients without known cardiovascular disease who underwent a clinically indicated CAC scan. CAC was categorized as an Agatson score of 0, 1-99, 100-399, and ≥400. We used multivariable Cox proportional hazards to calculate adjusted hazard ratios (HRs) for mortality stratified by age (younger, intermediate, or older) and gender. The mean age of participants was 58 ± 11 years and 67% were men. During a median follow-up of 11.0 ± 3.2 years, there were 522 deaths (4.0%). Compared with CAC = 0, increasing CAC was associated with higher mortality rate: 1-99 [HR: 1.5, 95% confidence interval (95% CI): 1.1-2.1]; 100-399 (HR: 1.8, 95% CI: 1.3-2.5); ≥400 (HR: 2.6, 95% CI: 1.9-3.6). Relative risk according to CAC category did not differ between genders. The strongest associations between CAC and mortality were observed for young and intermediate age participants. Nonetheless, the mortality rate of the older patients with CAC = 0 was far lower than that of the general US population. CAC was more predictive of long-term (15 years) than intermediate-term (5 years) mortality for men [receiver operator characteristics (ROC): 0.723 vs. 0.702] and women (ROC: 0.69 vs. 0.65). CONCLUSION: CAC is strongly associated with the long-term risk of mortality in young- and middle-aged men and women. In older patients, the long-term risk stratification of CAC is lower, due principally to increased mortality rate in patients with low calcium scores; however, even in the older patients, those with absent or low CAC are at a significantly lower risk of mortality compared with the general population.

CAC score as a possible criterion for administration of angiotensin converting enzyme inhibitors and/or angiotensin receptor blockers: the MultiEthnic Study of Atherosclerosis.

INTRODUCTION: Several trials have demonstrated that angiotensin converting enzyme inhibitors (ACEIs) decrease cardiovascular (CV) mortality rates in patients with heart failure; however, the Prevention of Events with Angiotensin-Converting Enzyme Inhibition (PEACE) and European Trial on Reduction of Cardiac Events with Perindopril in Stable Coronary Artery Disease (EUROPA) trials failed to show significant similar preventive effects in normal ejection fraction patients. We evaluated the baseline coronary artery calcium (CAC) score as a predictor of the effects of ACEIs/angiotensin receptor blockers (ARBs) on outcomes among normal ejection fraction participants. METHODOLOGY: Of 6814 MultiEthnic Study for Atherosclerosis population participants (after exclusion of the patients temporarily using ACEIs and/or ARBs during follow-up), we evaluated 2906 participants who never used ACEIs/ARBs and 368 (8.7%) participants who constantly used them during all baseline and follow-up examinations. In the population studied, 53.9% were men, aged 60.8±10.0 years, who had no apparent clinical CV disease. We compared CV event rates and multivariable-adjusted hazard ratios after stratifying by ACEI/ARB use and stratifying CAC scores by category (0, 1-399, and ≥400). RESULTS: The event rates varied from 1.8 to 41.2/1000 person years among the CAC groups. Among the participants with a 1-399 CAC score, ACEI/ARB users had significantly lower event rates than nonusers (4.9 vs. 8.2, respectively). Hazard ratio in the adjusted model was 3.1 (95% confidence interval 1.14-8.78, P<0.05). There was no significant event rate difference between ACEI/ARB users and nonusers among other CAC groups. CONCLUSION: The use of ACEIs/ARBs was associated with significantly fewer CV events in asymptomatic participants with low to intermediate CAC scores. Thus, better risk stratification in asymptomatic individuals (such as using CAC scores) may assist in proper selection of patients for further CV risk reduction strategies.

The role of carotid intimal thickness testing and risk prediction in the development of coronary atherosclerosis.

Carotid ultrasonography is a safe and available noninvasive diagnostic tool that provides information about the carotid arteries' characteristics and may be used for early detection of coronary artery disease as well as cardiovascular and stroke event risk stratifications. We performed a systematic search of articles discussing carotid ultrasonography in the English literature recorded in PubMed from 2010 to September 2012. Generally, the studies showed that internal carotid artery intima-media thickness is a more powerful variable than common carotid artery intima-media thickness. Moreover, the presence of carotid plaque and plaque volumes are more reliable and accurate estimators of coronary artery disease and risk of a stroke or cardiovascular event than intima-media thickness.

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.

Coronary calcium: new insights, recent data, and clinical role.

Calcium artery calcium (CAC) scoring has become an integral part in the era of preventive cardiology, it has been extensively studied and been validated as a powerful tool for cardiovascular risk assessment in conjunction with other traditional well established scoring systems such as Framingham risk score. In addition, CAC testing has found its way into emergency department algorithms assessing low to intermediate risk patients presenting with chest pain, this strategy was recently adopted by the UK NICE guidelines, confidently ruling out cardiac origin of chest pain. Several studies have demonstrated that risk assessment using CAC was motivational to patients leading to better adherence to their preventive practices as well as to medications. Accordingly, this test has several recommendations for use by national and international guidelines.

Cardiorenal syndrome: pathophysiology and potential targets for clinical management.

Combined dysfunction of the heart and the kidneys, which can be associated with haemodynamic impairment, is classically referred to as cardiorenal syndrome (CRS). Cardiac pump failure with resulting volume retention by the kidneys, once thought to be the major pathophysiologic mechanism of CRS, is now considered to be only a part of a much more complicated phenomenon. Multiple body systems may contribute to the development of this pathologic constellation in an interconnected network of events. These events include heart failure (systolic or diastolic), atherosclerosis and endothelial cell dysfunction, uraemia and kidney failure, neurohormonal dysregulation, anaemia and iron disorders, mineral metabolic derangements including fibroblast growth factor 23, phosphorus and vitamin D disorders, and inflammatory pathways that may lead to malnutrition-inflammation-cachexia complex and protein-energy wasting. Hence, a pathophysiologically and clinically relevant classification of CRS based on the above components would be prudent. With the existing medical knowledge, it is almost impossible to identify where the process has started in any given patient. Rather, the events involved are closely interrelated, so that once the process starts at a particular point, other pathways of the network are potentially activated. Current therapies for CRS as well as ongoing studies are mostly focused on haemodynamic adjustments. The timely targeting of different components of this complex network, which may eventually lead to haemodynamic and vascular compromise and cause refractoriness to conventional treatments, seems necessary. Future studies should focus on interventions targeting these components.

Cardiorenal syndrome and vitamin D receptor activation in chronic kidney disease.

Cardiorenal syndrome (CRS) refers to a constellation of conditions whereby heart and kidney diseases are pathophysiologically connected. For clinical purposes, it would be more appropriate to emphasize the pathophysiological pathways to classify CRS into: (1) hemodynamic, (2) atherosclerotic, (3) uremic, (4) neurohumoral, (5) anemic-hematologic, (6) inflammatory-oxidative, (7) vitamin D receptor (VDR) and/or FGF23-, and (8) multifactorial CRS. In recent years, there have been a preponderance data indicating that vitamin D and VDR play an important role in the combination of renal and cardiac diseases. This review focuses on some important findings about VDR activation and its role in CRS, which exists frequently in chronic kidney disease patients and is a main cause of morbidity and mortality. Pathophysiological pathways related to suboptimal or defective VDR activation may play a role in causing or aggravating CRS. VDR activation using newer agents including vitamin D mimetics (such as paricalcitol and maxacalcitol) are promising agents, which may be related to their selectivity in activating VDR by means of attracting different post-D-complex cofactors. Some, but not all, studies have confirmed the survival advantages of D-mimetics as compared to non-selective VDR activators. Higher doses of D-mimetic per unit of parathyroid hormone (paricalcitol to parathyroid hormone ratio) is associated with greater survival, and the survival advantages of African American dialysis patients could be explained by higher doses of paricalcitol (>10 µg/week). More studies are needed to verify these data and to explore additional avenues for CRS management via modulating VDR pathway.

Clinical features, management and in-hospital outcome of ST elevation myocardial infarction (STEMI) in young adults under 40 years of age.

OBJECTIVES: This study was designed to evaluate the demographic and clinical findings and in-hospital management and outcome in patients with an acute ST-segment elevation myocardial infarction (STEMI). MATERIAL AND METHODS: By review of the Cardiovascular Tehran Heart Center Registry (CVDTHCR), 2028 patients were found to have the acute STEMI. We compared the patients' characteristics in 109 (5.4%) subjects < or = 40 and 1919 subjects > 40-years-old. RESULTS: The young patients had less diabetes, hypertension, dyslipidemia and history of MI or prior revascularization, and were more likely to be male (92.7% vs. 74%), smoker (58.7% vs. 31.7%) and have family history of CVD (50.5% vs. 23.4%). The young patients had higher prevalence of angiographically normal coronary artery (13.7% vs. 0.9%; p<0.001). The young patients were more likely to undergo percutaneous coronary intervention (38.5% vs. 18.6%), whereas coronary artery bypass grafting was more common in the old ones (p<0.001). In-hospital death was markedly different among young and old patients (0.9% and 6.1%, respectively; p<0.01). CONCLUSION: In STEMI population, the risk profile, clinical findings and severity of coronary disease of the young differ substantially from the elderly counterparts. Young patients with STEMI have a favorable outcome compared with that in older patients.

Sodium bicarbonate plus isotonic saline versus saline for prevention of contrast-induced nephropathy in patients undergoing coronary angiography: a randomized controlled trial.

BACKGROUND: There is controversy about the prophylactic measures proposed for the prevention of contrast-induced nephropathy (CIN). We aim to compare the efficacy of the combination of sodium bicarbonate and isotonic saline and that of isotonic saline alone in preventing CIN. STUDY DESIGN: Randomized double-blind controlled trial. SETTING & PARTICIPANTS: 265 consecutive patients 18 years or older with a serum creatinine level of 1.5 mg/dL or greater undergoing elective coronary angiography from August 2007 to June 2008 in Tehran Heart Center, Tehran, Iran. INTERVENTION: Study participants were randomly assigned to receive either 75 mL of 8.4% sodium bicarbonate added to 1 L of isotonic saline (n = 135) or isotonic saline alone (n = 130) as a bolus of 3 mL/kg for 1 hour before contrast injection, followed by an infusion of 1 mL/kg/h for 6 hours after the procedure. OUTCOMES & MEASUREMENTS: The primary end point was an absolute (>or=0.5 mg/dL) or relative (>or=25%) increase in serum creatinine level 48 hours after the procedure (CIN). RESULTS: There were no significant differences between the bicarbonate and saline groups regarding baseline demographic and biochemical characteristics, including baseline serum creatinine level (1.63 +/- 0.32 [SD] versus 1.66 +/- 0.50 mg/dL), baseline glomerular filtration rate (46.4 +/- 12 versus 45.4 +/- 12 mL/min/1.73 m(2)), and baseline urine pH (5.42 +/- 0.6 versus 5.46 +/- 0.8). Nine patients (7.4%) receiving sodium bicarbonate developed CIN as opposed to 7 patients (5.9%) in the saline group, which was not statistically different (odds ratio, 1.26; 95% confidence interval, 0.45 to 3.50; P = 0.6). LIMITATIONS: The trial did not follow up participants to assess need for dialysis and mortality rate. CONCLUSION: The combination therapy of sodium bicarbonate plus saline does not offer additional benefits over hydration with saline alone in the prevention of CIN.

Relationship between myocardial viability and coronary run-off in jeopardized myocardium.

OBJECTIVE: The aim of this study was to evaluate the relationship between coronary run-off and myocardial viability in jeopardized regions. METHOD: We studied 50 patients (40 male, mean age: 55.63 +/- 10.54 years) with coronary artery stenosis >70% and ejection fraction <40% referred for viability study via dobutamine stress echocardiography. The relationship between coronary run-off and viability was evaluated. Good run-off demonstrates good or moderate and no run-off means poor or no run-off. RESULTS: In the apical region, 33% of the segments with good antegrade run-off were viable and 67% nonviable. Also, 72% of the segments with no run-off were nonviable and 28% viable. In the midportion region, 70% of the segments with good antegrade run-off were viable and 30% nonviable; 50% of the segments with no run-off were nonviable and 50% viable. In the basal region, 85% of the segments with good antegrade run-off were viable and 15% nonviable; 19% of the segments with no run-off were nonviable and 81% viable. The proportion of the nonviable segments increased significantly from the basal to apical regions either with good (p < 0.001) or no run-off (p = 0.004). From 239 viable segments, 58.6% had antegrade, 15.4% retrograde, and 25.5% no run-off. Of 181 nonviable segments, 44% had antegrade, 34% retrograde, and 34.8% no run-off. CONCLUSION: There was more susceptibility to nonviability in the apical regions despite good run-off, while the basal segments showed more viability in spite of having no run-off. The findings may be helpful for selecting patients with coronary artery disease and left ventricular systolic dysfunction that benefit from revascularization.

Giant unruptured noncoronary sinus of Valsalva aneurysm.

Huge unruptured sinus of Valsalva aneurysms is rarely observed. We report a 32-year-old woman presenting with exertional dyspnea in which a giant unruptured noncoronary sinus of Valsalva aneurysm was detected after echocardiography. The aneurysm was surgically repaired and the aortic and mitral valves were replaced.

Correlation between endothelial dysfunction in normal coronary patients with slow flow and aortic ectasia: the first report.

BACKGROUND: Slow coronary flow (SCF) is slow dye progression in the coronary arteries during selective angiography, but there is no such study about greater visceral vessels. Studies have suggested that flow-mediated dilation (FMD) is impaired in SCF. Endothelial function can be assessed by FMD in the brachial artery as ischemia-induced vasodilation. Since inflammation is an underlying pathology in the inflammation of visceral vessels and probably SCF, we studied the correlation of aortic ectasia and SCF by means of FMD. METHODS: Patients with normal coronary arteries and SCF formed the case group, and patients with normal coronary arteries and normal coronary flow formed the control group. We measured the diameter of the patients' brachial artery at rest, after inflation of a sphygmomanometer on the forearm [endothelial-dependent vasodilation (EDV)], and after use of sublingual nitrate (endothelial-independent vasodilation) by sonography. We also measured the diameter of the aorta using sonography before administration of sublingual nitrate. Endothelial dysfunction was defined as EDV significantly less than standard EDV. RESULTS: There were insignificant differences between age, gender, and frequency of cardiac risk factors within the case and control groups, but diabetes mellitus was significantly different between the two groups. The diameter of the aorta was insignificantly different between the case and control groups. The response of the brachial artery to the cuff test and sublingual nitrate were insignificantly different between the case and control groups. Endothelial dysfunction based on cuff test and sublingual nitrate administration was significantly more common in men than women, as the p values for cuff and sublingual nitrate were 0.033 and 0.051, respectively. CONCLUSIONS: It seems that there is no correlation between SCFP and aortic ectasia.

The association between coronary arterial dominancy and extent of coronary artery disease in angiography and paraclinical studies.

The association between coronary arterial dominance patterns and the coronary artery diameter, length, and valvular heart diseases were previously studied. However, its association with coronary artery disease (CAD) is unclear. We investigated to determine whether the extent and localization of CAD differ in right, left, or codominant coronary arterial patterns. Twelve thousand five hundred fifty-eight patients admitted to Tehran Heart Center for coronary angiography were studied retrospectively (2004-2006). The extent and localization of CAD and the dominant artery were determined. There were 62.7% males. The mean age was 57.6 +/- 10.3. 84.2% [95% confidence interval (CI); 83.6-84.8%], 10.9% (95% CI; 10.4-11.4%), and 4.8% (95% CI; 4.4-5.2%) of the patients were right, left, and codominant, respectively; No significant difference considering age, sex, positive family history, hypertension, hyperlipidemia, electrocardiography, exercise treadmill stress test, and perfusion scan were seen in the groups. The right-dominant patients tend to have three-vessel disease (33.1% vs. 27%, P < 0.0001), stenosis of more than 50% in right coronary artery (65.9% vs. 57.9%, P < 0.0001) and left circumflex territories (64% vs. 59.4%, P = 0.01), more than the left-dominant patients. The involvements of the left main coronary artery, left anterior descending artery territory, and posterior descending artery were not significantly different. This study demonstrates a relationship between angiographic CAD severity, and the involved arterial territory and dominancy patterns.

Ostial lesions of left main and right coronary arteries: demographic and angiographic features.

In 258 patients with left main tract disease, the atherosclerotic risk factors were compared between patients with ostial and nonostial lesions of the left main coronary artery. Also, it was done for patients with ostial right coronary artery. Women were more likely to have ostial left main coronary artery and/or ostial right coronary artery. A multivariate logistic regression analysis revealed that the female sex (odds ratio: 2.336) and hypertriglyceridemia (odds ratio: 1.004) were independent risk factors of ostial left main coronary artery lesion. For ostial right coronary artery lesion, the female sex and family history of coronary artery disease were independent predictors. Ostial left main coronary artery and right coronary artery lesions were strongly correlated. The demographic and clinical profiles of ostial stenosis suggest that this group may represent a distinct entity, different from the more common atherosclerotic left main trunk stenosis (LMTD). The female sex and serum triglyceride level can be considered as independent predictors of ostial left main tract disease.