Accuracy of carotid plaque detection and intima–media thickness measurement with ultrasonography in routine clinical practice

BackgroundCurrent guidelines in cardiovascular disease prevention advocate the use of carotid ultrasound measurements for risk stratification. Carotid abnormalities (plaques or increased intima–media thickness (IMT)) are associated with high risk of coronary and peripheral artery disease. An office-based measurement by clinicians would considerably broaden the clinical applicability of carotid ultrasound. In the present study we have assessed the accuracy of ultrasound detection of carotid plaques and intima–media thickness by trained internists in a routine outpatient setting.Methods and resultsCarotid ultrasound was performed in 112 vascular outpatients by internists, after a six-week training period. The internists' results were independently compared to the reference standard, consisting of carotid ultrasound performed in a specialized vascular laboratory. Sensitivity and specificity were calculated for plaque detection and IMT determination. The mean time required to perform the scans on the outpatient department was 7.3 min (range 4.5 to 16.7 min). A high level of accuracy for detecting plaques (sensitivity 78.5%; specificity 93.6%) was achieved. Identifying abnormal IMT had lower sensitivity but adequate specificity of 46.7% and 87.6%, respectively.ConclusionsIn conclusion, our findings demonstrate that clinicians can be trained well enough in six weeks to accurately and efficiently detect carotid plaques in an outpatient setting. IMT abnormalities were less accurately detected in the office-based approach and may require a specialized vascular laboratory.     

Reduced carotid intima–media thickness in systemic lupus erythematosus patients treated with cyclosporine A

Abstract

Background Patients with systemic lupus erythematosus (SLE) are at risk of atherosclerosis. An increased carotid intima–media thickness (IMT) is considered to be a marker of early atherosclerosis.

Objective To determine influential factors for increased carotid IMT in SLE patients.

Methods We evaluated the impact of conventional risk factors for atherosclerosis on carotid IMT in 427 healthy controls and of clinical factors on carotid IMT in 94 SLE patients. Carotid IMT was measured by using a newly developed computer-automated system. Unconditional logistic regression was used to assess the adjusted odds ratios (ORs) and 95 % confidence intervals (95 % CI).

Results Multivariate-adjusted mean carotid IMT (mm) was significantly reduced in SLE patients (0.51, 95 % CI = 0.36–0.66) compared to healthy controls (0.55, 95 % CI = 0.40–0.70) (P = 0.003). The SLE Disease Activity Index (SLEDAI) was associated with carotid IMT in a dose-dependent manner (P_trend = 0.041). The current use of cyclosporine A (adjusted OR = 0.02, 95 % CI = 0.01–0.40, P = 0.011) and a history of steroid pulse therapy (adjusted OR = 0.01, 95 % CI = 0.01–0.25, P = 0.006) were significantly associated with a decreased risk of increased carotid IMT.

Conclusions Our findings suggest that the current use of cyclosporine A can protect against increased carotid IMT, leading to a decreased risk of arteriosclerosis. Future studies with a larger sample size need to confirm that this association holds longitudinally.     

Depression symptoms and the progression of carotid intima–media thickness: A 5-year follow-up study

Objective

Only a few studies have investigated the changes in carotid intima–media thickness (IMT) over time, and uncertainties remain on the underlying mechanisms linking depression and subclinical atherosclerosis. We carried out a prospective cohort study to evaluate whether depression is associated with changes in carotid IMT in subjects with cardiac risk factors but free from coronary heart disease (CHD), and to what extent the atherogenicity of depression can be explained by inflammatory markers and autonomic nervous system dysfunction.

Methods

During baseline and follow-up visits: all participants were asked to provide blood samples and compile a structured questionnaire; trained physicians assessed depression symptoms using Beck Depression Inventory (BDI); altered cardiac autonomic tone was measured using time-domain components of heart rate variability in 24 h Holter recordings; measurements of carotid IMT were carried out using B-mode ultrasound image acquisition. Logistic and linear regression analyses were used to adjust for potential confounders and explore potential mediators.

Results

A total of 381 subjects completed the 5-year follow-up. The mean carotid IMT significantly increased in all subjects but the amount of increase was significantly larger among subjects with depression symptoms: mean IMT increased by 0.16 ± 0.14 mm; 0.31 ± 0.28 mm and 0.61 ± 0.54 mm among the subjects with no, mild and moderate/severe depression, respectively (all p < 0.01). The association between moderate/severe depression and IMT increase remained highly significant even after controlling for all the variables considered, however when both IL-6 and CRP were included in multivariate models the regression coefficient decreased by 42.3%. Some of the inflammation markers and autonomic nervous system dysfunction were also independently correlated with carotid IMT increase.

Conclusion

Depression symptoms are independently associated with an accelerated progression of carotid IMT in subjects with CHD risk factors, and inflammation may substantially modulate the association between depression and carotid IMT progression.     

Association between levels of serum perfluorooctane sulfate and carotid artery intima–media thickness in adolescents and young adults

Background

Perfluorinated chemicals (PFCs) have been widely used for years in a variety of products worldwide. Although epidemiological findings have shown that PFC levels are positively associated with cholesterol and uric acid levels, it is unknown whether PFCs are associated with atherosclerosis.

Methods

We recruited 664 subjects (12–30 years) from a population-based sample of adolescents and young adults based on a mass urine screening to determine the relationship between serum levels of PFCs and carotid intima–media thickness (CIMT).

Results

The median concentrations and ranges of perfluorooctanoic acid (PFOA), perfluorooctane sulfate (PFOS), perfluorononanoic acid (PFNA), and perfluorodecanoic acid (PFUA) were 3.49 (0.75–52.2) ng/mL, 8.65 (0.11–85.90) ng/mL, 0.38 (0.38–25.4) ng/mL, and 6.59 (1.50–105.7) ng/mL, respectively. After controlling for age, gender, smoking status, systolic blood pressure, body mass index, low-density lipoprotein cholesterol, triglyceride, high-sensitivity C-reactive protein, and homeostasis model assessment of insulin resistance, multiple linear regression analysis revealed that CIMT increased significantly across quartiles of PFOS (0.434 mm, 0.446 mm, 0.458 mm, 0.451 mm; P for trend < 0.001). Subpopulation analysis showed the association between PFOS and CIMT was more evident and significant in females, non-smokers, subjects of age 12–19 years, BMI < 24, and those with APOE genotype of E2 carrier and E3/E3.

Conclusions

Higher serum concentrations of PFOS were associated with an increase of carotid IMT in this cohort of adolescents and young adults. Further studies are warranted to clarify the causal relationship between PFOS and atherosclerosis.     

Increased carotid intima–media thickness associated with high hs-CRP levels is a predictor of unstable coronary artery disease

Abstract

Increased values of carotid intima–media thickness (CIMT) and high-sensitivity C-reactive protein (hs-CRP) are predictors of acute coronary events. We analysed the link between CIMT and hs-CRP in cases with coronary artery disease (CAD). From 1 January to 30 June 2012, we evaluated 43 patients with acute coronary syndrome (group A), 50 patients with stable coronary artery disease (group B) and 50 healthy volunteers (group C). All were analysed for CIMT and hs-CRP levels. CIMT values were higher in groups A and B (0.94 ± 0.21 mm, 0.89 ± 0.19 mm, respectively) and lower in group C (0.64 ± 0.09 mm), and this was statistically significant (p < 0.0001). However the values of hs-CRP were higher in group A (1.87 ± 0.36 mg/l) and lower in groups B and C (1.07 ± 0.28 mg/l, 0.97 ± 0.45 mg/l, respectively) and this was also statistically significant (p < 0.0001).     

Influence of the Mediterranean diet on carotid intima–media thickness in hypercholesterolaemic children: A 12-month intervention study

Background and aimsThe Mediterranean diet has been recognised as having a protective role on the cardiovascular system due to its low lipid and high antioxidant content. Lipid profile and oxidant status represent two important risk factors related to endothelial dysfunction, even at early stages of cardiovascular diseases. The aim of the study was to evaluate the influence of a 12-month Mediterranean diet on the variation of lipid profile and carotid intima–media thickness (cIMT) in pre-pubertal hypercholesterolaemic children.Methods and resultsWe performed a cross-sectional study comparing lipid profile and cIMT in a group of 68 pre-pubertal children (36 with hypercholesterolaemia and 32 controls). In addition, in the hypercholesterolaemic children a 12-month intervention programme with a Mediterranean diet was started to evaluate the variation of lipid profile and cIMT. At baseline, hypercholesterolaemic children showed a significantly higher cIMT (both right and left carotid artery) compared to controls (both p < 0.05). After 12 months of diet intervention, a significant reduction of total cholesterol, LDL-cholesterol and cIMT was documented (all p < 0.05). Furthermore, at the end of follow-up, delta body mass index-Standard Deviation score and delta LDL-cholesterol were significantly and independently related to the changes of cIMT (both p < 0.05).ConclusionThe Mediterranean diet represents a valid approach in the treatment of hypercholesterolaemia even during childhood.     

Impaired systolic blood dipping and nocturnal hypertension: an independent predictor of carotid intima–media thickness in type 1 diabetic patients

ObjectiveType 1 diabetes in children predicts a broad range of later health problems including an increased risk of cardiovascular morbidity and mortality. This study aimed to evaluate whether nocturnal hypertension and impaired nocturnal dipping affect atherosclerosis in children and adolescents with type 1 diabetes and to investigate the relationship between atherogenic risk factors and carotid intima–media thickness (CIMT).MethodsOne hundred fifty-nine type 1 diabetic patients and 100 healthy controls were included in the study. We investigated metabolic and anthropometric parameters such as body mass index (BMI), waist circumference, fasting glucose and insulin, serum lipids, 24 h ambulatory blood pressure monitoring (ABPM), and CIMT and compared these with those in control subjects (CS).ResultsNo difference was found between type 1 diabetic patients and CS in age, weight, waist/hip ratio, triglyceride, HDL-cholesterol level. However in children with type 1 diabetes, total cholesterol (p = 0.016),and LDL-cholesterol (p = 0.002) levels and CIMT (P < 0.001) were greater than those of controls. It was determined that 10% of type 1 diabetic patients had dyslipidemia.In 23.2% of type 1 diabetic patients, ABPM showed arterial hypertension. CIMT was significantly higher in the hypertensive group than in the nonhypertensive group (P = 0.003).Twenty-three (14.4%) diabetic patients had nocturnal hypertension. CIMT was significantly greater in the nocturnal hypertensive group (p = 0.023).Mean systolic blood pressure (SBP) and diastolic blood pressure (DBP) dipping was significantly different in diabetic patients (P < 0.001).CIMT was correlated positively with Hba1c (r = 0.220, p = 0.037), and negatively with SBP dipping (r = − 0.362, p = 0.020) in the diabetic patients.In stepwise regression analysis, Hba1c and SBP dipping emerged as a significant predictor of CIMT (β = 0.300, p = 0.044, β = 0.398 p = 0.009) contributing to 15.58% of its variability.ConclusionThese results provide additional evidence for the presence of subclinical cardiovascular disease (CVD) and its relation to hypertension in type 1 diabetic patients. They also indicate a significant relation between nocturnal hypertension, SBP dipping and increased arterial stiffness. It is also important to note that our findings reveal significant relationships between HBA1c cardiovascular changes and underline the importance of glucose control to predict CVD.     

Long-term anti-tumour necrosis factor therapy reverses the progression of carotid intima–media thickness in female patients with active rheumatoid arthritis

The objective of the study is to evaluate the effect of TNF inhibition on carotid thickness over a 2-year period. 144 women with RA diagnosed according to ACR criteria, without clinical evidence of cardiac and/or vascular disease were enrolled and compared with 78 matched controls. All patients received methotrexate (15–20 mg weekly) for 3 months. Responders (n = 79) continued to be treated with methotrexate, non-responders (n = 40) moved to methotrexate plus a TNF alpha antagonist. Echosonographic studies of carotids were obtained before and after 2-year follow-up. A significant decrease of ca-IMT was observed in anti-TNF-treated patients (P < 0.001); on the other hand, no significant variation of ca-IMT was observed after 2 years in MTX-treated patients. Our study indicates that anti-TNF blocking agents, but not methotrexate, are capable of reducing IMT of carotid arteries in female RA patients in a 2-year follow-up.     

Circulating endothelial progenitor cells, endothelial function, carotid intima–media thickness and circulating markers of endothelial dysfunction in people with type 1 diabetes without macrovascular disease or microalbuminuria

Aims/hypothesis  Type 1 diabetes is associated with premature arterial disease. Bone-marrow derived, circulating endothelial progenitor cells (EPCs) are believed to contribute to endothelial repair. The hypothesis tested was that circulating EPCs are reduced in young people with type 1 diabetes without vascular injury and that this is associated with impaired endothelial function and increased carotid intima–media thickness (CIMT). Methods  We compared 74 people with type 1 diabetes with 80 healthy controls. CD34, CD133, vascular endothelial (VE) growth factor receptor-2 (VEGFR-2) and VE-cadherin antibodies were used to quantify EPCs and progenitor cell subtypes using flow-cytometry. Ultrasound assessment of endothelial function by brachial artery flow-mediated dilatation (FMD) and CIMT was made. Circulating endothelial markers, inflammatory markers and plasma plasminogen activator inhibitor-1 (PAI-1) levels were measured. Results  CD34+VE-cadherin+, CD133+VE-cadherin+ and CD133+VEGFR-2+ EPC counts were significantly lower in people with diabetes (46–69%; p = 0.004–0.043). In people with type 1 diabetes, FMD was reduced by 45% (p < 0.001) and CIMT increased by 25% (p < 0.001), these being correlated (r = −0.25, p = 0.033). There was a significant relationship between FMD and CD34+VE-cadherin+ (r = 0.39, p = 0.001), CD133+VEGFR-2+ (r = 0.25, p = 0.037) and CD34+ (r = 0.34, p = 0.003) counts. Circulating high-sensitivity C-reactive protein, PAI-1, interleukin-6 and E-selectin were significantly higher in the diabetes group (p < 0.001 to p = 0.049), the last two of these correlating with FMD (r = −0.27, p = 0.028 and r = −0.24, p = 0.048, respectively). Conclusions/interpretation  These findings suggest that abnormalities of endothelial function in addition to pro-inflammatory and pro-thrombotic states are already common in people with type 1 diabetes before development of clinically evident arterial damage. Low EPC counts confirm risk of macrovascular complications and may account for impaired endothelial function and predict future cardiovascular events. Electronic supplementary material  The online version of this article (doi:) contains supplementary material, which is available to authorised users.     

Increased augmentation of central blood pressure is associated with increases in carotid intima–media thickness in type 2 diabetic patients

Aims/hypothesis Type 2 diabetes is associated with a two- to seven-fold increase in cardiovascular morbidity and mortality. The aim of this study was to determine the relationships between intima–media thickness (IMT), an established marker of atherosclerosis, large artery function and other determinants of cardiovascular risk in type 2 diabetic patients.Methods We studied 228 type 2 diabetic patients (75 women, aged 62±2 years [mean±SEM]). Carotid IMT was bilaterally measured using ultrasound technology. Applanation tonometry and pulse wave analysis were used to measure aortic systolic and diastolic blood pressures, central pressure augmentation (AG) and the augmentation index (AIx), a measure of systemic arterial stiffness. Conventional cardiovascular risk factors (lipids, HbA₁c, smoking and diabetes duration) were also assessed.Results Women had higher AG and AIx (p<0.0001), despite comparable systolic BP and heart rate in women and men. In women, AG (r=0.39, p<0.001), age (r=0.32, p<0.01), brachial systolic BP (r=0.34, p<0.01) and aortic systolic BP (r=0.34, p<0.01) correlated with IMT. In men, age (r=0.41, p<0.001), diabetes duration (r=0.25, p<0.01), AG (r=0.22, p<0.01), aortic systolic BP (r=0.21, p<0.01), brachial systolic BP (r=0.21, p<0.01) and body weight (r=0.16, p<0.05) correlated with IMT. In multiple linear regression analyses, AG and aortic systolic BP, but not brachial systolic BP, were age-independent determinants of IMT in men and women. In all patients, increased AG (adjusted for sex, age and heart rate) correlated with longer duration of diabetes, urinary albumin excretion and IMT.Conclusions/interpretation Measures of central systolic pressure correlate with carotid IMT, independently of age and other risk markers.     

Impact of prehypertension on carotid artery intima–media thickening: Actual or masked?

BackgroundRecent studies have reported that prehypertension is associated with increased values of common carotid artery intima–media thickness (CCA-IMT). The aim of this study was to assess the impact of daytime ambulatory blood pressure (BP) levels on the association of prehypertension with CCA intima–media thickening in prehypertensive subjects.MethodsA total of 807 subjects with office systolic BP < 140 and diastolic BP < 90 mmHg, underwent 24 h ambulatory BP (ABP) monitoring and carotid artery ultrasonographic measurements. The study population was divided into 3 groups according to office and daytime ABP levels: (1) normotensives: subjects with office BP < 120/80 mmHg and daytime ambulatory BP values within the normal range, (2) actual prehypertensives: individuals with office SBP (120–139 mmHg) and/or DBP (80–89 mmHg) and daytime ambulatory BP values within the normal range and (3) prehypertensives with masked hypertension (MH): patients with office SBP (120–139 mmHg) and/or DBP (80–89 mmHg) and elevated daytime ambulatory BP values.ResultsPrehypertensive patients with MH had higher (p < 0.01) CCA-IMT values (0.712 mm; 95%CI: 0.698–0.725) than actual prehypertensives (0.649 mm; 95%CI: 0.641–0.656) and normotensives (0.655 mm; 95%CI: 0.641–0.670) even after adjustment for baseline characteristics. Normotensives and actual prehypertensives did not differ significantly regarding CCA-IMT values (p > 0.05). After adjusting for potential confounders, (including demographic characteristics, vascular risk factors, and office BP) prehypertension with MH was independently (p < 0.01) associated with a 0.06 mm increment in CCA-IMT (95%CI: 0.03–0.09).ConclusionsPatients with office BP levels in the prehypertensive range, who also have elevated daytime ABP levels, had higher CCA-IMT values than patients with prehypertension with normal daytime ABP values and normotensive individuals.     

A comparative study of arterial stiffness, flow-mediated vasodilation of the brachial artery, and the thickness of the carotid artery intima–media in patients with systemic autoimmune diseases

Patients with autoimmune diseases may have increased vascular risk leading to higher mortality rates. Novel imaging techniques are necessary for the early assessment and management of these patients. In this study, we compared augmentation index (AIx) and pulse wave velocity (PWV), indicators of arterial stiffness, to brachial arterial flow-mediated vasodilation (FMD) and common carotid artery intima–media thickness (ccIMT), standard indicators of endothelial dysfunction and atherosclerosis, respectively. We wished to assess the vascular status of autoimmune patients by using a novel, cheap, and reproducible technique, the arteriograph. Altogether, 101 patients with systemic autoimmune diseases including primary antiphospholipid syndrome, systemic sclerosis, rheumatoid arthritis, and polymyositis, all having various types of vasculopathies, as well as 36 healthy individuals were investigated. Arterial stiffness was assessed by a TensioClinic arteriograph, a recently validated technique. Brachial arterial FMD and ccIMT were determined using high-resolution ultrasonography. Autoimmune patients exerted impaired FMD (3.7 ± 3.8%), increased ccIMT (0.7 ± 0.2 mm), AIx (1.2 ± 32.2%), and PWV (9.7 ± 2.4 m/s) in comparison to control subjects (FMD = 8.4 ± 4.0%; ccIMT = 0.6 ± 0.1 mm; Aix = −41.1 ± 22.5%; PWV = 8.0 ± 1.5 m/s; p < 0.05). We found a significant negative correlation of FMD with AIx (R = −0.64; p < 0.0001) and PWV (R = −0.37; p = 0.00014). There were significant positive correlations between ccIMT and AIx (R = 0.34; p = 0.0009), ccIMT and PWV (R = 0.44; p < 0.0001), as well as AIx and PWV (R = 0.47; p < 0.0001). AIx, PWV, and ccIMT positively correlated and FMD negatively correlated with the age of the autoimmune patients. Arterial stiffness indicated by increased AIx and PWV may be strongly associated with endothelial dysfunction and overt atherosclerosis in patients with autoimmune diseases. Assessment of arterial stiffness, FMD, and ccIMT are reproducible and reliable noninvasive techniques for the complex assessment of vascular abnormalities in patients at high risk.     

Integrated backscatter analysis of carotid intima–media complex in patients with systemic lupus erythematosus

A number of studies based on conventional ultrasound scanning (CUS) gave contrasting results about the occurrence of early atherosclerosis in patients with systemic lupus erythematosus (SLE), while no study on early arterial sclerosis in the same patients are available. Recently, information on early arterial sclerosis can be provided by the integrated backscatter (IBS) analysis which reflects the collagen and calcium content within the vascular wall. In order to evaluate if atherosis and/or sclerosis of carotid arteries are early features of SLE, we performed carotid CUS and IBS analysis in 16 SLE patients (15 females; aged 37 ± 10 years), free from clinically evident cardiovascular diseases and cardiovascular risk factors, with the only exception of five patients who had arterial hypertension. The same investigations were performed in 16 sex- and age-matched healthy control subjects. No statistically significant difference was observed either in carotid corrected IBS values or in carotid intima–media thickness (IMT) values between SLE patients and control subjects (−17.9 ± 2.5 dB vs −19.0 ± 1.7 dB, p = 0.14; 0.66 ± 0.08 mm vs 0.62 ± 0.13 mm, p = 0.35, respectively). The little sub-group of hypertensive SLE patients exhibited a significantly higher carotid corrected IBS mean value compared to control subjects (−16.4 ± 3.1 dB vs −19.0 ± 1.7 dB, p = 0.026), while it did not significantly differ in carotid IMT value from control group (0.67 ± 0.09 mm vs 0.62 ± 0.13 mm, respectively; p = 0.86). These findings show that neither atherosis nor sclerosis of carotid arteries are early features of SLE patients free from cardiovascular risk factors. Further studies are needed to clearly demonstrate that early carotid sclerosis affects hypertensive SLE patients.     

Evaluation of endothelial dysfunction in patients with familial Mediterranean fever: the relationship between the levels of asymmetric dimethylarginine and endocan with carotid intima–media thickness and endothelium-dependent vasodilation

It has been suggested that there is an ongoing subclinical inflammation in familial Mediterranean fever (FMF) patients also in attack-free periods as well. Due to this ongoing inflammation, endothelial dysfunction (ED) may develop. Previously, ED has been suggested to increase the risk of the atherosclerosis and cardiovascular disease (CVD). Endocan is recognized as a specific molecule of the endothelium and has been shown to increase in some cases associated with inflammation. However, there is not sufficient data whether those with FMF could develop ED in the early period of life. In this study, we aimed to investigate ED and its relation with endocan in young FMF patients. A total of 57 male patients diagnosed with FMF according to the Tel Hashomer criteria and a total of 33 healthy males with similar characteristics to the patient group were included in this research. Complete blood count, erythrocyte sedimentation rate (ESR), fibrinogen, serum glucose, serum LDL cholesterol (LDL-C) and triglyceride (TG), asymmetric dimethylarginine (ADMA), and endocan levels were tested from fasting blood samples. Moreover, carotid intima–media thickness (CIMT) and flow-mediated dilatation (FMD) were measured. The endocan levels of the FMF patients during an attack-free period were significantly higher than those of the control group (p < 0.001). On the other hand, FMD measurements were significantly lower among FMF patients (p < 0.001). ADMA levels were higher in the patient group; however, this difference was similar (p > 0.05). CIMT values were similar among FMF patients and healthy controls (p > 0.05). These results have suggested that ED may develop in the patients with FMF who have no additional CVD risk, even during young adulthood, and endocan may be a favorable biomarker at demonstration of ED than ADMA among FMF patients.