Naser Ahmadi

Mortality Incidence and the Severity of Coronary Atherosclerosis Assessed by Computed Tomography Angiography

OBJECTIVES This study investigated whether cardiac computed tomography angiography (CTA) can predict all-cause mortality in symptomatic patients. BACKGROUND Noninvasive coronary angiography is being increasingly performed by CTA to assess for obstructive coronary artery disease (CAD), and minimal outcome data exist for coronary CTA. We have utilized a cohort of symptomatic patients who underwent electron beam tomography to allow for longer follow-up (up to 12 years) than currently available with newer 64-slice multidetector-row computed tomography studies. METHODS In all, 2,538 consecutive patients who underwent CTA by electron beam tomography (age 59 +/- 14 years, 70% males) without known CAD were studied. Computed tomographic angiography results were categorized as significant CAD (> or =50% luminal narrowing), mild CAD (<50% stenosis), and normal coronary arteries. Multivariable Cox proportional hazards models were developed to predict all-cause mortality. Risk-adjusted models incorporated traditional risk factors for coronary disease and coronary artery calcification (CAC). RESULTS During a mean follow-up of 78 +/- 12 months, the death rate was 3.4% (86 deaths). The CTA-diagnosed CAD was an independent predictor of mortality in a multivariable model adjusted for age, gender, cardiac risk factors, and CAC (p < 0.0001). The addition of CAC to CTA-diagnosed CAD increased the concordance index significantly (0.69 for risk factors, 0.83 for the CTA-diagnosed CAD, and 0.89 for the addition of CAC to CAD, p < 0.0001). Risk-adjusted hazard ratios for CTA-diagnosed CAD were 1.7-, 1.8-, 2.3-, and 2.6-fold for 3-vessel nonobstructive, 1-vessel obstructive, 2-vessel obstructive, and 3-vessel obstructive CAD, respectively (p < 0.0001), when compared with the group who did not have CAD. CONCLUSIONS The primary results of our study reveal that the burden of angiographic disease detected by CTA provides both independent and incremental value in predicting all-cause mortality in symptomatic patients independent of age, gender, conventional risk factors, and CAC.

Atorvastatin and Antioxidants for the Treatment of Nonalcoholic Fatty Liver Disease: The St Francis Heart Study Randomized Clinical Trial

OBJECTIVES:Nonalcoholic fatty liver disease (NAFLD) is defined as the spectrum of benign fatty liver to necroinflammation and fibrosis. Its prevalence has been found to be as high as 39%. It is estimated that up to 15% of those affected will go on to have progressive liver disease. Currently, there is no proven therapy for NAFLD. In this study, we aim to determine whether statin therapy may be an effective treatment for NAFLD and identify independent predictors of NAFLD.METHODS:In all, 1,005 men and women, aged 50–70 years were randomized to receive either a daily combination of atorvastatin 20 mg, vitamin C 1 g, and vitamin E 1,000 IU vs. matching placebo, as part of the St Francis Heart Study randomized clinical trial. Liver to spleen (LS) ratios were calculated on 455 subjects with available computed tomography scans performed at baseline and follow-up to determine NAFLD prevalence. Baseline and final LS ratios were compared within treatment groups, and results were compared between the treatment and placebo groups using univariate and multivariate analyses. Mean duration of follow-up was 3.6 years.RESULTS:There were 80 patients with NAFLD at baseline. We identified baseline triglyceride levels (odds ratio (OR)=1.003, P<0.001) and body mass index (OR=0.10, P<0.001) as independent correlates of NAFLD. Treatment with atorvastatin combined with vitamins E and C significantly reduced the odds of NAFLD at the end of follow-up, 70 vs. 34% (OR=0.29, P<0.001).CONCLUSIONS:In conclusion, atorvastatin 20 mg combined with vitamins C and E is effective in reducing the odds of having hepatic steatosis by 71% in healthy individuals with NAFLD at baseline after 4 years of active therapy.

Post-traumatic Stress Disorder, Coronary Atherosclerosis, and Mortality

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

Aged garlic extract supplemented with B vitamins, folic acid and l-arginine retards the progression of subclinical atherosclerosis: A randomized clinical trial

OBJECTIVES Previous studies demonstrated that aged garlic extract reduces multiple cardiovascular risk factors. This study was designed to assess whether aged garlic extract therapy with supplements (AGE+S) favorably affects inflammatory and oxidation biomarkers, vascular function and progression of atherosclerosis as compared to placebo. METHODS In this placebo-controlled, double-blind, randomized trial (conducted 2005-2007), 65 intermediate risk patients (age 60+/-9 years, 79% male) were treated with a placebo capsule or a capsule containing aged garlic extract (250 mg) plus Vitamin B12 (100 microg), folic acid (300 microg), Vitamin B6 (12.5 mg) and l-arginine (100 mg) given daily for a 1 year. All patients underwent coronary artery calcium scanning (CAC), temperature rebound (TR) as an index of vascular reactivity using Digital Thermal Monitoring (DTM), and measurement of lipid profile, autoantibodies to malondialdehyde (MDA)-LDL, apoB-immune complexes, oxidized phospholipids (OxPL) on apolipoprotein B-100 (OxPL/apoB), lipoprotein (a) [Lp (a)], C-reactive protein (CRP), homocysteine were measured at baseline and 12 months. CAC progression was defined as an increase in CAC>15% per year and an increase in TR above baseline was considered a favorable response. RESULTS At 1 year, CAC progression was significantly lower and TR significantly higher in the AGE+S compared to the placebo group after adjustment of cardiovascular risk factors (p<0.05). Total cholesterol, LDL-C, homocysteine, IgG and IgM autoantibodies to MDA-LDL and apoB-immune complexes were decreased, whereas HDL, OxPL/apoB, and Lp (a) were significantly increased in AGE+S to placebo. CONCLUSION AGE+S is associated with a favorable improvement in oxidative biomarkers, vascular function, and reduced progression of atherosclerosis.

Association of Serum Alkaline Phosphatase with Coronary Artery Calcification in Maintenance Hemodialysis Patients

BACKGROUND AND OBJECTIVES Recent in vitro studies have shown a link between alkaline phosphatase and vascular calcification in patients with chronic kidney disease (CKD). High serum levels of alkaline phosphatase are associated with increased death risk in epidemiologic studies of maintenance hemodialysis (MHD) patients. We hypothesized that coronary artery calcification is independently associated with increased serum alkaline phosphatase levels in MHD patients. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS We examined the association of coronary artery calcification score (CACS) and alkaline phosphatase in 137 randomly selected MHD patients for whom markers of malnutrition, inflammation, and bone and mineral disorders were also measured. RESULTS Serum alkaline phosphatase was the only measure with significant and robust association with CACS (P < 0.003), whereas either other biochemical markers had no association with CACS or their association was eliminated after controlling for case-mix variables. Serum alkaline phosphatase >120 IU/L was a robust predictor of higher CACS and was particularly associated with the likelihood of CACS >400 (multivariate odds ratio 5.0 95% confidence interval 1.6 to 16.3; P = 0.007). Serum alkaline phosphatase of approximately 85 IU/L seemed to be associated with the lowest likelihood of severe coronary artery calcification, but in the lowest tertile of alkaline phosphatase, the CACS predictability was not statistically significant. CONCLUSIONS An association between serum alkaline phosphatase level and CACS exists in MHD patients. Given the high burden of vascular calcification in patients with CKD, examining potential therapeutic interventions to modulate the alkaline phosphatase pathway may be warranted.

Total and individual coronary artery calcium scores as independent predictors of mortality in hemodialysis patients.

Many traditional and nontraditional risk factors contribute to vascular calcification among maintenance hemodialysis (MHD) patients. It is not clear whether coronary artery calcification (CAC) delineates a higher mortality risk independent of known risk factors. We examined 6-year (10/2001–9/2007) survival of 166 MHD patients, aged 53 ± 13 years, with baseline CAC scores. Patients were grouped into four CAC groups: 0, 1–100, 101–400, and 400+. The 101–400 and 400+ groups were associated with a significantly higher adjusted risk of death than CAC 0 with hazard ratios (HR) 8.5 (95% CI: 1.1–48.1, p = 0.02) and 13.3 (95% CI: 1.3–65.1, p = 0.01), respectively, independent of demographics, comorbidity, lipids and other cardiovascular risks, surrogates of bone disease, nutritional and inflammatory markers and dialysis dose. Total CAC [HR 6.7 (1.1–21.5, p = 0.03)] followed by the presence of CAC in the left main [4.6 (2.2–9.8, p = 0.001)] and left anterior descending artery [4.3 (2.1–14.2, p = 0.001)] were strong independent predictors of mortality even after adjusting for above covariates. Total and vessel-specific CAC predict mortality in MHD patients independent of traditional and nontraditional risk factors.

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

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

Prognostic significance of zero coronary calcium scores on cardiac computed tomography

BACKGROUND Most unexpected cardiovascular events occur in persons at intermediate risk of coronary artery disease (10%-20% 10-year risk). Coronary artery calcium (CAC) has been shown to be highly specific for atherosclerosis, occurring only in the intima of the coronary arteries. Evidence shows that elevated coronary calcium scores (CCSs) are predictive of future cardiovascular events, both independently of and incrementally to conventional cardiovascular risk factors. Several studies reported event rates of zero for those persons without CAC by cardiac computed tomography (CT). OBJECTIVES We sought to evaluate the event rates in persons with negative calcium scores from the reported literature to establish whether these patients may be considered at low risk for hard cardiovascular events (myocardial infarction and death). METHODS English-language studies from January 1, 1975, through February 1, 2007, were retrieved using MEDLINE and Current Contents databases, bibliographies, and expert consultation. RESULTS Summary data show that in a total follow-up of 35,765 asymptomatic persons, 16,106 (45%) had scores of zero. Pooled sensitivity for CAC to detect a cardiovascular event was 98.1% [95% confidence interval (CI), 95.1%-99.9%], and negative predictive value was 99.9% (95% CI, 98.9%-100%). There were 48 hard events in this population, with an annual event rate of 0.027%. CONCLUSION These large observational cohorts show that the absence of CAC by cardiac CT is associated with a low adverse event risk and therefore could be used as a tool to counsel patients about their risk of such events.

Effects of Sevelamer and Calcium-Based Phosphate Binders on Lipid and Inflammatory Markers in Hemodialysis Patients

Introduction: Cardiovascular disease accounts for almost half of all deaths in individuals with chronic kidney disease stage 5 despite advances in both dialysis treatment and cardiology. A combination of lipid-lowering and anti-inflammatory effects along with avoidance of hypercalcemia should be taken into account when choosing phosphorus binders for maintenance hemodialysis (MHD) patients. Methods: We examined the association of sevelamer versus calcium-based phosphorus binders with lipid profile, inflammatory markers including C-reactive protein (CRP), and mineral metabolism in MHD patients who participated in the Nutritional and Inflammatory Evaluation of Dialysis Patients (NIED) study from October 2001 to July 2005. Results: Of the 787 MHD patients in the NIED study, 697 were on either sevelamer, a calcium-based binder, or both and eligible for this study. We compared the groups based on taking sevelamer monotherapy (n = 283) or calcium binder monotherapy (n = 266) for serum phosphate control. There were no differences between the groups on dialysis vintage. There were significant differences in age, serum calcium and phosphorus levels, as well as intact parathyroid hormone levels. Using a logistic regression models, the sevelamer group had a higher odds of serum CRP <10 mg/l [odds ratio (OR): 1.06, 95% CI: 1.02–1.11] and LDL cholesterol <70 mg/dl (OR: 1.33, 95% CI: 1.19–1.47) when compared to the calcium binder group independent of age, vintage, body mass index, statin use or other variables. Conclusion: The improvements in multiple surrogate markers of inflammation and lipids in the NIED study make sevelamer a promising therapy for treatment in MHD patients with high risk of cardiovascular disease and mortality.

Increased Epicardial, Pericardial, and Subcutaneous Adipose Tissue Is Associated with the Presence and Severity of Coronary Artery Calcium

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