Methods

The local ethical committee approved the study protocol, and all study participants provided informed consent. The present prospective study compared the presence of subclinical carotid and coronary artery disease in 67 patients with FH to that in 30 controls with nonanginal chest pain from the outpatient clinics of vascular medicine and cardiology at a university medical center. The CIMT and carotid plaque burden were assessed using B-mode ultrasonography, and coronary artery disease was assessed using computed tomographic coronary angiography (CTCA). Patients were asked to participate in the present study if they were asymptomatic, had no known cardiovascular disease, and had an increased cardiovascular risk profile. The inclusion criteria were FH or the presence of ≥1 other clinical risk factor for atherosclerosis and an inclusion age of 45 to 70 years for women and 40 to 70 years for men. The exclusion criteria for CTCA were renal insufficiency (serum creatinine >120 μmol/L), known contrast allergy, and irregular heart rhythm (atrial fibrillation).

FH was diagnosed according to the criteria by van Aalst-Cohen et al. The criteria can be summarized as the presence of a documented LDL receptor mutation or an LDL cholesterol level >95th percentile for gender and age combined with the presence of typical tendon xanthomas in the patient or a first-degree relative; an LDL cholesterol level >95th percentile for gender and age in a first-degree relative; or proven coronary artery disease in the patient or a first-degree relative aged <60 years.

The control group consisted of 30 patients referred for CTCA for the evaluation of coronary atherosclerosis. The Diamond classification was used to select the patients presenting with chest pain complaints atypical for cardiovascular disease. Patients with chest pain or discomfort were eligible for inclusion if they met ≤1 of the following typical angina characteristics: substernal chest pain or discomfort provoked by exertion or emotional stress and relieved by rest and/or nitroglycerin.

Carotid ultrasonography, including Doppler, was performed with a Philips iU-22 ultrasound system (Philips Medical Systems, Bothell, WA), equipped with an L9-3 transducer. Image acquisition was performed using a standard scanning protocol according to the American Society of Echocardiography consensus statement. In brief, the left and right carotid arteries were both examined with the patient in a supine position with the head supported at a 45° angle and turned to the contralateral side. The left and right common carotid arteries, carotid bifurcation, internal carotid artery, external carotid artery, and vertebral arteries were imaged using B-mode ultrasonography, color Doppler, and pulse-wave Doppler. All anatomic sites were examined from different angles of view, and each site was scanned in the cross-sectional and longitudinal views. Each side was extensively evaluated for the presence of carotid plaque.

The carotid ultrasound studies were reviewed offline by 2 independent observers who were unaware of the clinical data. Discrepancies in their evaluation were resolved by consensus. In accordance with previously published studies, the CIMT was measured in the far wall of the distal 1 cm of the common carotid artery. A semiautomated CIMT measurement was performed using Qlab quantification software (Philips Healthcare, Best, The Netherlands). For each side, the CIMT measurement was performed 3 times on selected still frames on different R peaks of the electrocardiographic signal. The mean value of 3 measurements from the left and right carotid arteries was used in additional statistical analysis. Carotid plaque screening was performed using the standard carotid ultrasound images and color Doppler clips. Atherosclerotic plaque was defined as a focal structure encroaching into the lumen of ≥0.5 mm or ≥50% of the surrounding CIMT or demonstrating a thickness >1.5 mm, as measured from the media–adventitia interface to the intima–lumen interface. The presence of plaque was recorded for each side. Stenosis severity was assessed using the criteria from the Society of Radiologists in Ultrasound. In brief, abnormal CIMT or plaque and a peak systolic velocity <125 cm/s were considered indicative of <50% diameter stenosis; plaque and a peak systolic velocity of 125 to 230 cm/s as 50% to 69% stenosis; and plaque and peak systolic velocity >230 cm/s as ≥70% stenosis. No detectable patent lumen and no flow at spectral, power, and color Doppler were considered indicative of total occlusion. The carotid artery was divided into 4 segments (common carotid, bifurcation, internal carotid, and external carotid). The plaque thickness was measured, and the segments were divided into 4 categories: 0, no plaque; 1, <2.5 mm; 2, 2.5–3.5 mm; and 3, >3.5-mm plaque. Summing the score of all segments gave the carotid plaque score.

All computed tomographic scans were performed with a dual-source scanner (Somatom Definition, Siemens Medical Solutions, Forchheim, Germany). For the nonenhanced scan, a prospective electrocardiographically triggered scan protocol was applied. The computed tomographic coronary angiographic scan protocol, contrast protocol, and reconstruction procedure have been described previously. In brief, CTCA was obtained using a retrospective electrocardiographic-gated scan protocol with optimal heart rate-dependent electrocardiographic pulsing to lower the radiation dose. The maximum tube current was 380 mA, and the tube voltage was 120 kV. Just before the scan, all patients received nitroglycerin (0.4 mg/dose) sublingually. An iodinated contrast agent (Ultravist 370 mgI/ml, Schering AG, Berlin, Germany), with a scan time-dependent volume (94 ml, range 80 to 100), was administered for enhancement of the coronary arteries. The calcium score data sets were reconstructed with a slice thickness of 3 mm and an increment of 1.5 mm at 70% of the RR interval. The computed tomographic coronary angiographic data sets were reconstructed using a slice thickness of 0.75 mm and an increment of 0.4 mm at an automatically or manually determined optimal phase of the RR interval. The data sets were sent to a dedicated workstation (MMWP, Siemens Medical Solutions, Forchheim, Germany). Two readers, unaware of the carotid ultrasound and clinical data, analyzed the computed tomographic scans. Discrepancies in their evaluations were resolved by consensus. The coronary calcium score (CCS) was calculated semiautomatically using dedicated software and expressed as the Agatston score per patient. Coronary plaque was defined as a separate structure within the vessel wall that could be clearly distinguished from the contrast-enhanced lumen and the surrounding pericardial tissue. For each segment, using the American Heart Association 16-segment model, the absence or presence of a coronary plaque was determined, as was the severity of the lumen narrowing. Obstructive coronary artery disease was defined as the presence of a >50% diameter stenosis. The coronary plaque burden was assessed using a segment involvement score (summing the number of segments containing plaque >20% lumen stenosis) and a coronary artery disease extent score (summing the segments with plaque weighted for the stenosis severity; 0%, 0; 0% to 20%, 1; 20% to 50%, 2; 50% to 70%, 3, >70%, 4).

The statistical analyses were performed using SPSS, version 17.0 (SPSS, Chicago, Illinois). Continuous variables are presented as the mean ± SD or median and interquartile range. Categorical variables are expressed as numbers and percentages. The percentages were rounded. The Student t test was used to compare continuous variables. The chi-square test was used to compare the categorical variables. The correlation of carotid ultrasound and coronary artery disease was evaluated using Spearman’s rank correlation coefficient. Because of the non-normal distribution, the nonparametric Mann-Whitney U test was used to compare the CIMT and carotid plaque score with the CCS, segment involvement score, and coronary artery disease extent score between the 2 groups. Receiver operating characteristic curves and the area under the curve were used to determine the optimal cutoff values of the carotid plaque sum for the prediction of a CCS >100 or the presence of obstructive coronary artery disease. The optimal cutoff value was that that yielded the greatest sum of sensitivity and specificity. p Values <0.05 were considered statistically significant.

Results

The patient characteristics are listed in Table 1 . The gender distribution and mean age were comparable between the patients with FH and the controls. As expected, the patients with FH had significantly greater total cholesterol and LDL cholesterol levels than the controls, although the patients with FH had received more frequent and more intensive statin treatment.

The results of carotid ultrasonography, CCS, and CTCA are summarized in Table 2 . No complications occurred during carotid ultrasonography, and all studies were included in the analysis. The patients with FH and the controls had a comparable CIMT, prevalence of carotid plaque, and median carotid plaque score. CTCA failed because of contrast extravasation in 1 control patient; hence, the analyses concerning the coronary plaque burden included 29 controls. The patients with FH had a significantly greater median CCS than that of the controls (62 vs 5, p = 0.015). Additionally, the patients with FH were less likely to have a CCS of 0 (21% vs 47%, p = 0.010). The prevalence of obstructive coronary artery disease was comparable in the patients with FH and the controls ( Table 2 ). The presence of obstructive 1-, 2-, or 3-vessel coronary artery disease did not differ between the patients with FH and the controls (p = 0.965). The coronary plaque burden, as assessed by the median segment involvement score and median coronary artery disease extent score, was comparable in the patients with FH and controls (3, interquartile range 0 to 8, vs 1, interquartile range 0 to 5. p = 0.192; and 10, interquartile range 2 to 16, vs 6, interquartile range 0 to 16, p = 0.099, respectively). In the 67 patients with FH, the CIMT did not correlate with the CCS, segment involvement score, coronary artery disease extent score, or obstructive coronary artery disease (r = 0.18, r = 0.15, r = 0.17, r = 0.05, respectively, p = NS for all). A statistically significant correlation was found between the carotid plaque score and coronary artery disease, as expressed by the CCS, segment involvement score, coronary artery disease extent score, and >50% coronary stenosis (r = 0.54, r = 0.55, r = 0.54, r = 0.28, respectively, p <0.05 for all).

Table 2

Noninvasive imaging results

Variable	FH (n = 67)	Control (n = 30)	p Value
Carotid ultrasound
Median carotid intima-media thickness (mm)	0.64 (0.59–0.73)	0.66 (0.60–0.78)	0.490
Any carotid plaque	62 (93%)	25 (83%)	0.361
Unilateral carotid plaque	19 (28%)	10 (33%)	0.621
Bilateral carotid plaque	43 (64%)	15 (50%)	0.277
Carotid stenosis ≥70%	0 (0%)	0 (0%)	1.000
Median carotid plaque score	3 (1–5)	2 (1–4)	0.216
Computed tomographic coronary angiography
Median coronary calcium score	62 (1–352)	5 (0–219)	0.015
Coronary calcium score 0	14 (21%)	14 (47%)	0.010
Coronary calcium score 1–100	23 (34%)	8 (27%)	0.455
Coronary calcium score 101–400	15 (22%)	6 (20%)	0.792
Coronary calcium score >400	15 (22%)	2 (7%)	0.060
Any obstructive coronary disease	18 (27%)	8 (30%)	0.667
Single vessel disease >50%	11 (17%)	5 (19%)	0.921
2-Vessel disease >50%	5 (8%)	3 (12%)	0.639
3-Vessel disease >50%	2 (3%)	1 (4%)	0.905
Segment involvement score	3 (0–6)	1 (0–4)	0.099
Coronary artery disease extent score	10 (2–16)	6 (0–16)	0.192

Only gold members can continue reading. Log In or Register to continue

Share this:

• Click to share on Twitter (Opens in new window)
• Click to share on Facebook (Opens in new window)

Related

Related posts:

1. Evaluation of Serial Changes in Tissue Characteristics During Statin-Induced Plaque Regression Using Virtual Histology-Intravascular Ultrasound Studies
2. Meta-Analysis Comparing Efficacy and Safety of First Generation Drug-Eluting Stents to Bare-Metal Stents in Patients With Diabetes Mellitus Undergoing Primary Percutaneous Coronary Intervention
3. Two-Year Outcomes for Patients With Severe Symptomatic Aortic Stenosis Treated With Transcatheter Aortic Valve Implantation
4. Reply

Stay updated, free articles. Join our Telegram channel

Join