Usefulness of carotid intimal medial thickness and Flow-Mediated dilation in a preventive cardiovascular practice

Arterial thickening is a precursor to atherosclerosis. Carotid intima-medial thickness (CIMT), a measure of arterial thickening, is a validated surrogate for prediction of cerebrovascular events. This study investigates CIMT as an early marker of radiation-induced carotid artery damage.

Head and neck cancer patients treated with radiotherapy (RT) (minimum dose of 50 Gy) to one side of the neck (unirradiated side as control) at least 2 years previously were included. CIMT was measured in 4 arterial segments: proximal, mid, distal common carotid artery (CCA), and bifurcation and were compared to corresponding unirradiated segments. CIMT measurements >75th percentile of a reference population were considered abnormal and at increased cerebrovascular risk.

50 patients (34 males) with a median age of 58 years (interquartile range (IQR) 50–62) were included. The mean maximum dose to the irradiated and unirradiated artery was 53 Gy (standard deviation (SD) 13 Gy) and 1.9 Gy (SD 3.7 Gy), respectively. Mean CIMT was significantly greater in irradiated versus unirradiated arteries: proximal CCA (0.76 mm ±0.15 vs 0.68 mm ±0.14 (p < 0.0001), mid CCA (0.74 mm ±0.2 vs 0.68 mm ±0.16 (p = 0.01), distal CCA (0.77 mm ±0.2 vs 0.68 mm ±0.15 (p = 0.004), and bifurcation (0.85 mm ±0.25 vs 0.72 mm ±0.17 (p = 0.001). For all arterial segments, a significantly greater number of CIMT measurements were abnormal on the irradiated side (proximal: p = 0.004, mid: p = 0.05, distal: p = 0.005, bifurcation: p = 0.03). There was no effect of time from RT, age, smoking status, surgery and chemotherapy on CIMT difference (irradiated–unirradiated) in all segments.

CIMT is increased after RT and may be a useful marker of radiation-induced carotid atherosclerosis. There appears to be no additional effect of other atherosclerotic risk factors on CIMT following RT.

Anxiety has been shown to be associated with cardiovascular disease. Atherosclerosis is responsible for the vast majority of cardiovascular events. Recent evidence is accumulating to show that insulin resistance (IR) plays a central role in determining the clinical manifestations of established atherosclerotic lesions. The current preliminary study aimed to investigate the associations between trait anxiety, IR, and atherosclerotic progression in healthy elderly subjects with normal fasting glucose and without metabolic syndrome. Thirty-five healthy elderly subjects (19 males and 16 females, mean age 64.5±4.7 years) were enrolled in this study. Trait anxiety was measured using a questionnaire corresponding to the trait anxiety scale taken from the State and Trait Anxiety Inventory. The homeostasis model assessment (HOMA-R) and plasma leptin-to-adiponectin ratio (L/A ratio), which are convenient IR indexes calculated from fasting blood sampling, were examined. As measurements of atherosclerotic progression, we performed two ultrasound methods, namely brachial artery flow-mediated dilation (FMD), an endothelial function assessment quantitatively reflecting the endothelium-dependent vasodilation responses following hyperemia, and measurement of carotid intima-media thickness (IMT). The severity of trait anxiety was positively associated with HOMA-R and L/A ratio, and negatively associated with the percent change of brachial artery FMD (%FMD). HOMA-R and L/A ratio were positively associated with carotid IMT, and L/A ratio was negatively associated with %FMD. These data showed the associations between trait anxiety, IR indexes and endothelial dysfunction or atherosclerotic progression. This pilot study, with a cross-sectional design, supports the promising role of IR for clarifying the pathophysiological mechanism by which anxiety contributes to an increasing risk of atherosclerosis.

Continuing Medical Education Course for “Use of Carotid Ultrasound to Identify Subclinical Vascular Disease and Evaluate Cardiovascular Disease Risk: A Consensus Statement for the American Society of Echocardiography Carotid Intima-Media Thickness Task Force”

The American Society of Echocardiography is accredited by the Accreditation Council for Continuing Medical Education to provide continuing medical education for physicians.

The American Society of Echocardiography designates this educational activity for a maximum of 1 AMA PRA Category 1 Credits™. Physicians should only claim credit commensurate with the extent of their participation in the activity.

ARDMS and CCI recognize ASE’s certificates and have agreed to honor the credit hours toward their registry requirements for sonographers.

The American Society of Echocardiography is committed to resolving all conflict of interest issues, and its mandate is to retain only those speakers with financial interests that can be reconciled with the goals and educational integrity of the educational program. Disclosure of faculty and commercial support sponsor relationships, if any, have been indicated.

1. Physicians, physicians’ assistants, and nurses with an interest in cardiac and vascular imaging, preventive cardiology, and cardiovascular disease risk assessment. 2. Ultrasonographers with interest in vascular imaging and cardiovascular disease risk assessment.

Upon completing this activity, participants will be able to: 1. Describe the rationale for using carotid ultrasound to identify subclinical vascular disease and to evaluate cardiovascular disease risk. 2. Explain the application of carotid ultrasound to cardiovascular disease risk assessment. 3. Describe the scanning technique for identifying subclinical vascular disease using carotid ultrasound. 4. Explain the key components of interpreting carotid ultrasound studies for cardiovascular disease risk assessment.

James H. Stein, MD, FASE:

Research grants: Siemens Medical Solutions, Sonosite

Intellectual property: listed as the inventor of Patent #US 6,730,0235 “Ultrasonic Apparatus and Method for Providing Quantitative Indication of Risk of Coronary Heart Disease.” It has been assigned to the Wisconsin Alumni Research Foundation.

Emile R. Mohler III, MD:

Speakers bureau for Merck, BMS-Sanofi and AstraZeneca; Research grant support from BMS-Sanofi, Pfizer and GSK.

Christopher M. Rembold, MD:

Advisory Board for Sonosite.

Estimated Time to Complete This Activity: 1 hour

While recent reports suggest that both flow-mediated vasodilation (FMD) in the brachial artery (BA), endothelium-dependent vasodilatation, and intima media thickness (IMT) in the carotid artery correlate with the extent of coronary artery disease (CAD), it is not clear which modality is a better predictor for CAD severity and whether either of these modalities are superior to conventional ST-segment depression in exercise stress electrocardiogram (ECG). Thus, the goal of the present study was to compare the predictive value of FMD and IMT for CAD severity and to evaluate the diagnostic accuracy.

A total of 103 consecutive patients (62 ± 9 years, 79 men) with clinically suspected CAD underwent FMD and nitroglycerin-induced dilation (NTG-D) in the BA as well as measurement of carotid artery IMT by using high-resolution ultrasound, and exercise treadmill testing. Coronary stenosis index (CSI) was calculated from coronary angiography.

Seventy-three patients had significant CAD, and 30 patients showed no CAD (NL). FMD was significantly lower and IMT was significantly higher in patients with CAD compared with NL patients (FMD, 3.7 ± 3.0% vs. 7.5 ± 2.9%; IMT, 1.1 ± 0.2 mm vs. 0.7 ± 0.1 mm). FMD and IMT correlated to CSI to a similar degree (r = − 0.67, r = 0.69, respectively), and there was a significant correlation between FMD and IMT. In contrast, NTG-D did not correlate with CSI or IMT. Further, the diagnostic accuracy of FMD and IMT was comparable or even better than that obtained with conventional ST-segment depression during exercise in this cohort.

FMD in BA and IMT could represent a surrogate diagnostic method for assessment of CAD severity.

A longitudinal observational study investigated whether the measurement, in clinical practice, of carotid maximum intima-media thickness (Max-IMT) could be combined with the Framingham risk score (FRS) to improve the predictability of cardiovascular events in dyslipidemic patients who are at low or intermediate risk.

Max-IMT was measured by ultrasound in 1969 patients attending a lipid clinic. The “best threshold values” (BTVs) above which we considered the Max-IMT to be abnormally high were calculated for our dyslipdemic population for each 10-year age interval in men and women. Two hundred and forty-two patients (age 54 ± 10 years; 43.8% women) with an FRS <20%, i.e. at low or intermediate risk, were monitored for more than 5 years. Twenty-four of these patients suffered a cardiovascular event within 5.1 ± 2.3 years. Both FRS and Max-IMT proved to be independent outcome predictors (p < 0.04, both), with a hazard ratio (HR) of 6.7 (95% CI 1.43, 31.04; p = 0.015) in patients in whom FRS was 10–20% and Max-IMT was above the BTV (60th percentile of Max-IMT distribution for men or 80th for women). In Kaplan–Meier analysis, the Max-IMT significantly improved the predictive value of the FRS (χ² = 8.13, p = 0.04). Patients with FRS 10–20% (currently considered intermediate-risk) and also elevated Max-IMT values came into the same high-risk category as patients with FRS 20–30%.

The combination of FRS with Max-IMT measurement can be used in routine clinical practice to greatly enhance the predictability of cardiovascular events in the large number of patients who fall into the intermediate-risk category, which currently does not call for aggressive preventive measures.