Variations in atherosclerosis and remodeling patterns in aorta and carotids.

BACKGROUND: Atherosclerosis is a progressive disease that causes vascular remodeling that can be positive or negative. The evolution of arterial wall thickening and changes in lumen size under current "standard of care" in different arterial beds is unclear. The purpose of this study was to examine arterial remodeling and progression/regression of atherosclerosis in aorta and carotid arteries of individuals at risk for atherosclerosis normalized over a 1-year period. METHODS: In this study, 28 patients underwent at least 2 black-blood in vivo cardiovascular magnetic resonance (CMR) scans of aorta and carotids over a one-year period (Mean 17.8 +/- 7.5 months). Clinical risk profiles for atherosclerosis and medications were documented and patients were followed by their referring physicians under current "standard of care" guidelines. Carotid and aortic wall lumen areas were matched across the time-points from cross-sectional images. RESULTS: The wall area increased by 8.67%, 10.64%, and 13.24% per year (carotid artery, thoracic aorta and abdominal aorta respectively, p < 0.001). The lumen area of the abdominal aorta increased by 4.97% per year (p = 0.002), but the carotid artery and thoracic aorta lumen areas did not change significantly. The use of statin therapy did not change the rate of increase of wall area of carotid artery, thoracic and abdominal aorta, but decreased the rate of change of lumen area of carotid artery (-3.08 +/- 11.34 vs. 0.19 +/- 12.91 p < 0.05). CONCLUSIONS: Results of this study of multiple vascular beds indicated that different vascular locations exhibited varying progression of atherosclerosis and remodeling as monitored by CMR.

Plasma Cell Myeloma Presenting With Amyloid-Laden Crystal-Negative Histiocytosis.

OBJECTIVES: Crystal-storing histiocytosis (CSH) is rare in plasma cell dyscrasias, with only 3 cases reported in the setting of amyloid. No cases of crystal-negative histiocytosis coincident with multiple myeloma and amyloidosis have been reported previously. METHODS: A 58-year-old woman presented with pain due to destructive bone lesions and was found to have plasma cell myeloma (PCM) and marrow amyloid deposition associated with crystal-negative histiocytosis. Differential diagnoses included Langerhans cell histiocytosis, Erdheim-Chester disease, and Rosai Dorfman disease. BRAF mutations were negative, and there was no evidence of paraprotein crystals, arguing against typical CSH. RESULTS: The patient was treated with bortezomib, cyclophosphamide, and dexamethasone, and she subsequently underwent autologous stem cell transplant and ixazomib maintenance. She achieved complete remission with improvement of her symptoms and preserved remission after following up at 60 months. CONCLUSIONS: We describe a case of crystal-negative histiocytosis associated with PCM. CSH is a rare disorder associated with paraprotein-producing conditions in which immunoglobulins aggregate as intracellular crystals in the lysosomes of organ-specific phagocytic macrophages. Light chain tropism in PCM can also lead to the development of amyloid deposition in organs and, in rare cases, is associated with light chain aggregation as intracellular crystals in macrophages.

Cardiovascular magnetic resonance parameters of atherosclerotic plaque burden improve discrimination of prior major adverse cardiovascular events.

AIMS: Patients with prior major cardiovascular or cerebrovascular events (MACE) are more likely to have future recurrent events independent of traditional cardiovascular disease risk factors. The purpose of this study was to determine if patients with traditional risk factors and prior MACE had increased cardiovascular magnetic resonance (CMR) plaque burden measures compared to patients with risk factors but no prior events. METHODS AND RESULTS: Black blood carotid and thoracic aorta images were obtained from 195 patients using a rapid extended coverage turbo spin echo sequence. CMR measures of plaque burden were obtained by tracing lumen and outer vessel wall contours. Patients with prior MACE had significantly higher MR plaque burden (wall thickness, wall area and normalized wall index) in carotids and thoracic aorta compared to those without prior MACE (Wall thickness carotids: 1.03 +/- 0.03 vs. 0.93+/- 0.03, p = 0.001; SD wall thickness carotids: 0.137 +/- 0.0008 vs. 0.102 +/- 0.0004, p < 0.001; wall thickness aorta: 1.63 +/- 0.10 vs. 1.50 +/- 0.04, p = 0.009; SD wall thickness aorta: 0.186 +/- 0.035 vs. 0.139 +/- 0.012, p = 0.009 respectively). Plaque burden (wall thickness) and plaque eccentricity (standard deviation of wall thickness) of carotid arteries were associated with prior MACE after adjustment for age, sex, and traditional risk factors. Area under ROC curve (AUC) for discriminating prior MACE improved by adding plaque eccentricity to models incorporating age, sex, and traditional CVD risk factors as model inputs (AUC = 0.79, p = 0.05). CONCLUSION: A greater plaque burden and plaque eccentricity is prevalent among patients with prior MACE.

Carotid Plaque Characterization, Stenosis, and Intima-Media Thickness According to Age and Gender in a Large Registry Cohort.

Carotid intima-media thickness (CIMT) is a well-established predictor of cardiovascular disease events. Not well described, however, is the prevalence of plaque and stenosis severity and how this varies according to extent of CIMT, age, and gender. We evaluated the extent of carotid plaque and stenosis severity according to CIMT, age, and gender in a large CIMT screening registry. We studied 9,347 women and 12,676 men (n = 22,023) who received carotid ultrasound scans. The presence and severity of both carotid plaque and stenosis was compared according to extent of CIMT (≥1 mm vs <1 mm), age, and gender using the chi-square test of proportions. Among those aged <45 to ≥80 years, the prevalence of CIMT ≥1 mm ranged from 0.13% to 29.3% in women and 0.6% to 40.1% in men, stenosis ≥50% from 0.1% to 14.9% in women and 0.1% to 13.2% in men, and mixed and/or soft plaque from 7.1% to 66.5% in women, and 9.2% to 65.8% in men (all p <0.001 across age groups). Even when CIMT levels were <1 mm, >30% of patients demonstrated mixed or soft plaque potentially prone to rupture. Of those with CIMT ≥1 mm, more than 70% had such mixed or soft plaque and more than 40% demonstrated stenoses of 30% or greater. In conclusion, we describe in a large CIMT registry study a substantial age-related increase in both men and women of increased CIMT, plaque presence, and severity, and stenosis. Even in those with normal CIMT, mixed or soft plaque was common, further demonstrating the value in assessing for plaque when doing carotid ultrasound.

Identification by ultrasound evaluation of the carotid and femoral arteries of high-risk subjects missed by three validated cardiovascular disease risk algorithms.

Atherosclerotic cardiovascular disease (ASCVD) events are the leading cause of death in the United States and globally. Traditional global risk algorithms may miss 50% of patients who experience ASCVD events. Noninvasive ultrasound evaluation of the carotid and femoral arteries can identify subjects at high risk for ASCVD events. We examined the ability of different global risk algorithms to identify subjects with femoral and/or carotid plaques found by ultrasound. The study population consisted of 1,464 asymptomatic adults (39.8% women) aged 23 to 87 years without previous evidence of ASCVD who had ultrasound evaluation of the carotid and femoral arteries. Three ASCVD risk algorithms (10-year Framingham Risk Score [FRS], 30-year FRS, and lifetime risk) were compared for the 939 subjects who met the algorithm age criteria. The frequency of femoral plaque as the only plaque was 18.3% in the total group and 14.8% in the risk algorithm groups (n = 939) without a significant difference between genders in frequency of femoral plaque as the only plaque. Those identified as high risk by the lifetime risk algorithm included the most men and women who had plaques either femoral or carotid (59% and 55%) but had lower specificity because the proportion of subjects who actually had plaques in the high-risk group was lower (50% and 35%) than in those at high risk defined by the FRS algorithms. In conclusion, ultrasound evaluation of the carotid and femoral arteries can identify subjects at risk of ASCVD events missed by traditional risk-predicting algorithms. The large proportion of subjects with femoral plaque only supports the use of including both femoral and carotid arteries in ultrasound evaluation.

Prevalence and distribution of sub-clinical atherosclerosis by screening vascular ultrasound in low and intermediate risk adults: the New York physicians study.

BACKGROUND: Many persons experiencing cardiovascular disease (CVD) events are not at high calculated CVD risk by Framingham risk score. The identification of carotid and femoral plaque has been associated with CVD events. In this study, the prevalence of plaques in adults at low and intermediate risk was examined. METHODS: Asymptomatic patients without CVD (n = 715; 43% women) were screened for carotid and femoral plaque using B-mode ultrasound. RESULTS: Significant predictors of plaque were male gender and age and, among women, dyslipidemia. Overall plaque prevalence was 32.8% among women and 40.5% among men aged 50 to 64 years. Among subjects with plaque in this age group, 56% of women and 31% of men had plaque exclusively in the femoral artery and would have been missed if only carotid ultrasound had been performed. CONCLUSION: Ultrasound screening of the carotid and femoral arteries in a population with low and intermediate Framingham risk scores can identify potentially high risk subjects for whom intensive CVD risk factor modification may be appropriate.

Cross-sectional, prospective study of MRI reproducibility in the assessment of plaque burden of the carotid arteries and aorta.

BACKGROUND: The reliability of imaging techniques to assess early atherosclerosis remains unclear. We did a cross-sectional, prospective study to test reproducibility of MRI when imaging arteries, to assess risk of cardiovascular disease and correlations with age and sex. METHODS: Between January 2003 and December 2006 we performed black-blood MRI of both common carotid arteries and the thoracic descending aorta in patients with cardiovascular risk factors who were referred from clinics in New York, NY, USA. Mean wall area, wall thickness, lumen area, total vessel area, and ratio of the mean wall area to the mean total vessel area (WA/TVA) were manually measured. Reproducibility within and between readers was tested on subsets of images from randomly chosen patients. RESULTS: MRI was performed on 300 patients. Intrareader reproducibility, assessed in images from 20 patients, was high for all parameters (intraclass correlation coefficients >0.8), except WA/TVA ratio in the descending aorta. The inter-reader reproducibility, assessed in images from 187 patients, was acceptable (intraclass correlation coefficients >0.7) for the mean wall, lumen, and total vessel areas. Values for all MRI parameters in all vessels increased with increasing age for both sexes (all P <0.0005) but were always significantly higher in men than in women, except for aortic mean wall thickness and WA/TVA ratio in the carotid arteries. Mean wall area values correlated well between the carotid arteries and aorta, reflecting the systemic nature of atherosclerosis. CONCLUSIONS: Our findings support MRI as a reproducible measurement of plaque burden and demonstrate the systemic distribution of atherosclerosis.

Ultrasound detection of increased carotid intima-media thickness and carotid plaque in an office practice setting: does it affect physician behavior or patient motivation?

BACKGROUND: The aim of this multicenter study was to determine if identifying increased carotid intima-media thickness (CIMT) or carotid plaque during office-based ultrasound screening examinations could alter physicians' treatment plans and patients' motivation regarding health-related behaviors. METHODS: Carotid ultrasound studies were performed by a nonsonographer clinician using a handheld system. Changes in physicians' treatment plans and patients' motivation on the basis of scan results were analyzed using multivariate regression. RESULTS: There were 253 subjects (mean age, 58.1 +/- 6.6 years). When increased CIMT or carotid plaque was detected, physicians were more likely to prescribe aspirin and lipid-lowering therapy (P < .001). Subjects were more likely to report increases in plans to take cholesterol-lowering medication (P = .002) and the perceived likelihood of having or developing heart disease (P = .004). CONCLUSIONS: Findings from office-based carotid ultrasound studies can influence physicians' prescriptions of evidence-based interventions. Patients with abnormal ultrasound findings recognize their increased cardiovascular risk and plan to take cholesterol-lowering medication.

Carotid intima-media thickness testing by non-sonographer clinicians: the office practice assessment of carotid atherosclerosis study.

BACKGROUND: The purpose of this study was to determine whether a non-sonographer clinician (NSC) could obtain ultrasound images of the carotid artery, measure carotid intima-media thickness (CIMT), and identify findings indicating increased cardiovascular risk in an office setting. METHODS: Eight NSCs from five sites were trained to use a handheld ultrasound device to screen the carotid arteries for plaques and to measure CIMT. RESULTS: NSCs scanned 150 subjects who provided 900 images, of which 873 (97%) were interpretable. Differences between NSCs and the core laboratory were small (0.002 +/- 0.004 mm) and bioequivalent (P(TOST) < 0.05) with a low coefficient of variation (3.9% +/- 0.5%). There was > or = 90% agreement on the presence of CIMT > or = 75th percentile and > or = 80% agreement on plaque presence. CONCLUSIONS: This is the first multicenter study to show that NSCs can obtain images of the carotid arteries using a handheld ultrasound device, accurately measure CIMT, and identify findings indicating increased cardiovascular risk.

Carotid black blood MRI burden of atherosclerotic disease assessment correlates with ultrasound intima-media thickness.

The aim of this study was to correlate carotid black blood MRI based measurements with those obtained by ultrasound intima-media thickness (IMT). Seventeen patients with intermediate to high Framingham cardiovascular risk score underwent both carotid ultrasound and rapid extended coverage double inversion recovery black blood carotid MRI. Overall, there was good correlation between wall area, wall thickness, and plaque index measured by MRI and the IMT measurements obtained from the ultrasound images (max r2 = 0.72, p < 0.05). Patients with mean IMT > or = 1.2 mm had significantly higher values of wall area, plaque index and wall thickness compared to patients with mean IMT < 1.2 mm. Vessel wall measurements assessed by black-blood MRI may be potentially used clinically to evaluate plaque progression and regression.