Subclinical Atherosclerosis In Asymptomatic Subjects Research Articles

Association of Homocysteine Levels with Subclinical Coronary Atherosclerosis in Asymptomatic Subjects

This article is available from http://www.labmedonline.org 2016, Laboratory Medicine Online This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited. Background: Progression of atherosclerotic plaques is known to be correlated with elevated circulating homocysteine (Hcy). However, whether the level of Hcy is related with coronary atherosclerosis in the subclinical state is unclear. Therefore, we performed this study to investigate the relationship between blood Hcy levels and subclinical atherosclerosis in asymptomatic self-referred subjects. Methods: We retrospectively enrolled 2,968 self-referred asymptomatic subjects (1,374 men, 1,594 women) who had undergone both coronary CT angiography (CCTA) and coronary artery calcium scoring. The relationships between atherosclerosis, Hcy, and other clinical factors were assessed. Results: Higher levels of Hcy were related with age, male gender, body mass index (BMI), waist circumference, blood pressure, high density lipoprotein (HDL), triglyceride, blood glucose, HbA1c, hsCRP, and coronary artery calcium score (CACS). Coronary plaque was more frequently found in higher Hcy quartile groups (21.3%, 28.8%, 34.4%, and 34.3%, P 50%) was also more frequent in higher Hcy quartile groups (1.8%, 5.4%, 5.0%, and 6.6%, P 400) than the first quartile group. Conclusions: Blood Hcy levels were associated with an increased risk of the presence and extent of subclinical atherosclerosis in asymptomatic subjects.

Subclinical atherosclerosis among Chilean subjects classified as having a low cardiovascular Framingham risk

Framingham risk score (FRS) has limitations and can underestimate risk. Carotid ultrasound to measure intima media thickness or plaques is recommended for cardiovascular risk assessment. To determine the prevalence of subclinical atherosclerosis in asymptomatic subjects classified as low and intermediate risk. Cross-sectional study performed in subjects without cardiovascular disease. Cardiovascular risk was estimated using the Chilean FRS and the General Cardiovascular Disease FRS. Carotid ultrasound was performed in all subjects. We defined subclinical atherosclerosis as the presence of carotid plaque or intima media thickness greater than 75th percentile by gender and age. We studied 203 subjects aged 47.2 ± 9.6 years (54% males). Mean intima media thickness was 0.62 ± 0.1 mm. An abnormal value was detected in 68 subjects (33%) and carotid plaques in 32 subjects (15.7%). Based on Chilean FRS, 96% were considered at low risk, 4% at intermediate, and none at high risk. In the low risk group the prevalence of abnormal intima media thickness and plaques was 40 and 14% respectively. Presence of plaques was more common in women than men (23 and 7% respectively, p < 0.01). According to the General Cardiovascular Disease FRS, 23% were at low, 39% at low intermediate and 28% at high intermediate risk. In the low risk group the prevalence of an abnormal intima media thickness was 34% and no subject had plaques. Carotid plaques were detected in Chilean subjects classified as having a low FRS risk. The underestimation of risk was higher in Chilean women.

Comparison of Coronary Computed Tomographic Angiographic Findings in Asymptomatic Subjects With Versus Without Diabetes Mellitus

There are limited data on the impact of diabetes mellitus (DM) on the risk of subclinical atherosclerosis. Therefore, we sought to investigate the impact of DM on the risk of subclinical atherosclerosis in asymptomatic subjects. We analyzed 2,034 propensity score-matched asymptomatic subjects who underwent coronary computed tomographic angiography (mean age 55.9 ± 8.2years; men 1,725 [84.8%]). Coronary artery calcium score, degree and extent of coronary artery disease (CAD), and clinical outcomes were assessed. High-risk CAD was defined as at least 2-vessel coronary disease with proximal left anterior descending artery involvement, 3-vessel disease, or left main disease. Compared with subjects without DM, those matched with DM had higher coronary artery calcium score (89.9 ± 240.4 vs 62.8 ± 179.5, p= 0.004) and more significant CAD (≥50% diameter stenosis, 15.2% vs 10.2%, p= 0.001), largely in the form of 1-vessel disease (10.8% vs 7.3%, p= 0.007). However, there were no significant differences between matched pairs in significant CAD in the left main or proximal left anterior descending artery (5.3% vs 3.8%, p= 0.138), multivessel disease (4.4% vs 2.9%, p= 0.101), and high-risk CAD (4.3% vs 2.7%, p= 0.058). During the follow-up period (median 21.8, interquartile range 15.2 to 33.4 months), there was no significant difference in the composite of all-cause death, myocardial infarction, acute coronary syndrome, and coronary revascularization between 2 groups (hazard ratio 1.438, 95% confidence interval 0.844 to 2.449, p= 0.181). In asymptomatic subjects, those matched with DM have more subclinical atherosclerosis, mainly confined to non-high-risk CAD, than those matched without DM, and there are no differences in high-risk CAD and clinical outcomes.

Detection of subclinical atherosclerosis in asymptomatic subjects using ultrasound radiofrequency-tracking technology.

ObjectiveAtherosclerosis is a chronic and systemic disease and its developmental process involves the synergism of multiple risk factors such as hypertension, dyslipidemia, diabetes, obesity and smoking. The diagnosis of subclinical atherosclerosis is essential for strategic guidance towards suitable treatments and efficient prevention against acute cardiovascular events. This study employed ultrasound radiofrequency (RF) tracking technology to characterize human carotid arteries in vivo in terms of intima-media thickness (IMT) and artery stiffness, and evaluated the statistical correlation between carotid IMT and stiffness, and the number of risk factors for atherosclerosis.MethodsA total of 160 asymptomatic subjects were enrolled. Ultrasound RF-tracking technology was employed to acquire carotid IMT and stiffness parameters: maximum IMT (MAXIMT), RF Quality IMT (RFQIMT), distensibility coefficient (), compliance coefficient (), index, index and local pulse wave velocity (). The subjects were categorized in four groups in terms of the number of risk factors: ‘zero’, ‘single’, ‘double’, and ‘multiple’, and statistical analyses of carotid IMT and stiffness parameters were performed between these different groups.ResultsThe subjects (n = 145) with MAXIMT smaller than 1.0 mm matched the IMT criteria for non-atherosclerosis and were named as NA-subjects. Spearman’s rho correlation analysis of the whole group and the NA-subjects both showed that MAXIMT correlated positively with RFQIMT, , , and , and negatively with and (p<0.01). The analysis of covariance of NA-subjects showed significant differences between subjects with and without risk factors, and also showed significant differences between the ‘zero’, ‘single’, ‘double’, and ‘multiple’ groups.ConclusionsThe carotid IMT and stiffness parameters obtained by the ultrasound RF-tracking technology were demonstrated to possess significant statistical correlation with the number of risk factors from 160 subjects, and these anatomical and mechanical parameters may potentially be used together with the IMT criteria to support subclinical atherosclerosis diagnosis.

Early Atherosclerosis Detection in Asymptomatic Patients: A Comparison of Carotid Ultrasound, Coronary Artery Calcium Score, and Coronary Computed Tomography Angiography

BackgroundDetailed multimodality assessment of subclinical atherosclerosis in asymptomatic subjects referred for risk stratification has not been performed. We analyzed the detection of early atherosclerosis using 3 imaging modalities: coronary artery calcium (CAC) scoring, carotid ultrasound (US), and coronary computed tomography angiography (CCTA). MethodsAsymptomatic subjects free of known vascular disease scheduled to undergo a carotid US for risk stratification were invited to undergo CCTA/CAC. Subjects taking lipid-lowering medication were excluded. All images were assessed by experienced core laboratory personnel. Carotid intima media thickness ≥ 75th percentile for age and sex, CAC > 0, and detection of either carotid or coronary artery plaque were indicators of atherosclerosis. ResultsFifty patients were included with a median age of 53 years. Atherosclerosis was observed in 28%, 78%, and 90% of subjects using CAC, CCTA, and carotid US, respectively. All subjects showed atherosclerosis on at least 1 modality. In 36 patients with a CAC score = 0, 69% and 86% had atherosclerosis on CCTA and carotid US, respectively. ConclusionsIn this detailed analysis, all subjects identified to warrant further risk stratification had subclinical atherosclerosis on at least 1 imaging modality. Concordance between modalities was highly variable, dependent on the specific definition of atherosclerosis used. Carotid US and CCTA detection of plaque were significantly more sensitive than CAC > 0 in this middle-aged population. Considering the prevalence of subclinical disease on carotid US and CCTA, the threshold at which to treat warrants further research.

Abstract 9829: Subclinical Atherosclerosis in Asymptomatic Subjects Referred for Risk Stratification: A Comparison of Carotid Ultrasound, Coronary Artery Calcium Scoring and Coronary Computed Tomography Angiography

Introduction: In subjects free of known vascular disease, current guidelines recommend lipid targets according to global risk of cardiovascular events. In select populations, imaging is recommended for refining clinical risk. The purpose of this study was to compare three imaging modalities coronary artery calcium scoring (CACS), carotid ultrasound (US) and coronary computed tomography angiography (CCTA) in a population referred for risk stratification. Hypothesis: We hypothesized that diverse definitions of early atherosclerosis utilized by differing modalities would affect perceived prevalence of subclinical atherosclerosis and consequently, assessment of risk. We sought to determine the degree of concordance among these definitions. Methods: Subjects free of known vascular disease scheduled to undergo a carotid US for clinical risk stratification were invited to undergo CCTA/CACS. Subjects on lipid lowering therapy &gt; 3 months were excluded. All images were assessed by an experienced core laboratory. Carotid intima media thickness ≥75 th percentile for age and sex, CACS &gt; 0 and detection of either carotid or coronary artery plaque were indicators of atherosclerosis. Results: Fifty patients were included. Median age was 53 years; 54% were men. Atherosclerosis was seen in 28%, 78% and 90% of subjects using CACS, CCTA and carotid US, respectively, with all subjects demonstrating one or more markers or findings on at least one method. In the 36 patients with CACS = 0, 69% and 86% had atherosclerosis on CCTA and carotid US, respectively. Maximal concordance (68%, p = 0.021) between carotid US and CCTA was seen when carotid US showed the presence/absence of any plaque with a maximal thickness of ≥ 1.5 mm. Conclusions: In this detailed analysis, all subjects identified to warrant further risk stratification had findings indicating subclinical atherosclerosis on at least one modality. Concordance between the modalities was highly variable, dependent upon the specific definition used. Carotid US and CCTA detection of plaque were more sensitive than CACS &gt; 0. Given strong evidence for low CV risk in patients with CACS = 0, the threshold of subclinical disease at which to treat using Carotid US or CCTA plaque warrants further consideration and caution.

Increased Leucocyte Count could Predict Coronary Artery Calcification In Patients With Free Of Clinically Apparent Cardiovascular Disease.

Several studies have demonstrated that inflammation plays a major role in the development of atherosclerosis and that the inflammatory process might also be involved in coronary artery calcification (CAC). The main purpose of this study was to investigate the relation between leucocyte count and CAC and to determine whether a higher leucocyte count could indicate subclinical atherosclerosis in patients without overt cardiovascular disease. A total of 284 consecutive patients (156 men, 128 women) without established cardiovascular disease were enrolled. CAC was measured using cardiac computed tomography. Leucocyte count was measured via routine blood examination. Patients with CAC had higher leucocyte counts compared to those without calcification (7.87±1.85 vs. 6.01±1.84; p<0.001). Logistic regression analysis identified the following as independent predictors of CAC: leucocyte count (odds ratio [OR]: 1.7, 95% confidence interval [CI]: 1.3-2.1), smoking (OR: 2.4, 95% CI: 1.2-4.6) and age (OR: 1.2, 95% CI: 1.1-2.3). There was also a significant correlation between CAC and leucocyte count (r=0.57, p<0.001). We demonstrated that leucocytes may play an important role in the evolution of CAC and may be used in the detection of subclinical atherosclerosis in asymptomatic subjects.

Asociación de marcadores inflamatorios y aterosclerosis subclínica en relación con la edad en sujetos sin enfermedad cardiovascular

We assessed whether an independent association between inflammatory markers and age-related subclinical atherosclerosis could be found in subjects free from cardiovascular disease.Metabolic parameters, inflammatory and endothelial markers, such as high-sensitivity C-reactive protein, interleukin-6, fibrinogen and von Willebrand factor, as well as the carotid intima-media thickness were assessed in 890 asymptomatic subjects (mean age: 55 years; range: 20-80 years; 80% men) with cardiovascular risk factors.Subjects in the upper quartile (age 61-80 years) showed a significant increase of traditional risk factors, particularly arterial pressure and glucose levels (p < 0.01) as compared with lower quartiles. We also found a significant increase in the levels on inflammatory and endothelial markers (p < 0.001) and intima-media thickness (p < 0.001) in older adults. In the multivarate analysis, after adjustment for cardiovascular risk factors, intima-media thickness was independently associated with inflammation and endothelial dysfunction in older adults (p < 0.01).Besides age, systemic inflammation and vascular damage are associated with subclinical atherosclerosis in asymptomatic subjects. The age-related inflammatory profile may predispose to cardiovascular complications.

Increased subcutaneous fat accumulation has a protective role against subclinical atherosclerosis in asymptomatic subjects undergoing general health screening

Purpose To evaluate the clinical role of subcutaneous fat accumulation in subclinical arteriosclerosis, using computed tomography (CT), we measured the subcutaneous fat area (SFA), the visceral fat area (VFA) and the VFA/SFA ratio and compared these with the calcium score of the whole aorta (CSWA) in asymptomatic subjects who were undergoing general health screening. Methods 122 consecutive asymptomatic subjects (40 female, mean age 56.2 ± 8.4 years) were analyzed. Whole-body low-dose CT scan (mAs = 50, slice thickness = 5 mm) was performed. The SFA and VFA were measured at the umbilical level. Calcification of whole aorta was defined as an area with > 90HU and 1 mm 2, and CSWA was calculated using the modified Agatston method. Results Mean ± SD of SFA, VFA and log CSWA were 158 ± 67.1 cm 2, 94.0 ± 44.8 cm 2, and 7.93 ± 1.08, respectively. SFA was significantly and inversely correlated with log CSWA ( r = − 0.219, P = 0.015) but VFA was not ( r = 0.105, P = 0.250) and as a result, the VFA/SFA ratio was significantly and positively correlated with log CSWA ( r = 0.221, P = 0.015). Subsequently, all predictor variables were used in a stepwise multiple regression model with log CSWA as dependent variable, and age, SFA and fasting plasma glucose significantly influenced log CSWA ( P < 0.001) by the multiple regression formula Y = 0.046X1*** − 0.005X2** + 0.015X3* + 4.426, (*** P < 0.001, ** P < 0.01, and * P < 0.05) where Y = log CSWA, X1 = age, X2 = SFA, and X3 = fasting plasma glucose). Conclusions SFA was significantly and inversely associated with log CSWA, in an independent fashion. These results suggest that subcutaneous fat accumulation might have a protective role against atherosclerosis in asymptomatic subjects.

Monocyte cyclooxygenase-2 overactivity: a new marker of subclinical atherosclerosis in asymptomatic subjects with cardiovascular risk factors?

Cyclooxygenase-2 (COX-2)-mediated prostaglandin production by activated macrophages is associated with inflammation and atherosclerosis. We investigated the relationship between COX-2-mediated prostaglandin-E2 (PGE2) release, cardiovascular risk factors, and carotid atherosclerosis in apparently healthy subjects. PGE2 release by lipopolysaccharide-stimulated blood monocytes was measured by ELISA in 291 subjects (76.5% men, mean age 58) who underwent global vascular risk assessment and carotid ultrasonography. COX-2 expression (real-time RT-PCR) was analysed in a subgroup of 100 subjects (76% men, mean age 59). Inducible PGE2 production was associated with smoking and diabetes (P<0.05), but not with arterial hypertension, dyslipidaemia, or obesity. Subjects in the highest tertile of PGE2 (>8.1 ng/mL) had significantly higher mean carotid intima-media thickness (IMT) than those in the lowest tertile (P<0.01). No significant differences among tertiles were observed in the levels of inflammatory markers (C-reactive protein, fibrinogen, and von Willebrand factor). The association between PGE2 and carotid IMT remained statistically significant (P=0.012) after adjustment for a number of cardiovascular and inflammatory risk factors. A correlation between COX-2 expression and PGE2 production was observed (P<0.005). COX-2-mediated PGE2 overproduction by stimulated monocytes might provide a new marker of subclinical atherosclerosis in asymptomatic subjects exposed to cardiovascular risk factors.

Reduced myocardial flow reserve relates to increased carotid intima-media thickness in healthy young men

Increased carotid artery wall thickness and lipoprotein oxidation are key early events in atherosclerosis. To test the hypothesis that reduced myocardial flow reserve is a marker of subclinical atherosclerosis, we examined the relationships between flow reserve and carotid artery intima-media thickness (IMT) in young men free from coronary heart disease. Basal and dipyridamole stimulated coronary blood flow was measured using positron emission tomography (PET) in 55 healthy men aged 36±4 years. Myocardial flow reserve was calculated as the ratio of stimulated flow to basal flow. The mean carotid artery IMT was measured using high-resolution ultrasound. Oxidised LDL was measured as baseline LDL diene conjugation. Myocardial flow reserve decreased across the quartiles of increasing IMT ( P=0.006), and was 5.2±1.9 in the lowest quartile for IMT and 3.7±1.2 in the highest ( P=0.04, I vs. IV quartile). In univariate analysis, oxidised LDL correlated inversely with flow reserve ( r=−0.35, P=0.01) and directly with IMT ( r=0.51, P<0.001). The association between flow reserve and IMT remained significant ( P≤0.01) in multivariate regression model including age, blood pressure, left ventricular mass, ox-LDL, total cholesterol, HDL-cholesterol and triglycerides as covariates. These data support the concept that reduced myocardial flow reserve reflects subclinical atherosclerosis in asymptomatic subjects, and suggest that increased lipoprotein oxidation is directly related to early structural and functional atherosclerotic vascular changes.

Early detection of subclinical atherosclerosis in asymptomatic subjects at high risk for cardiovascular disease.

Subclinical atherosclerosis can be non-invasively detected via calcifications, thickening and stiffening of arteries. Coronary calcifications seen with ultrafast computed tomography are frequent in hypertension or hypercholesterolemia and synonymous of coronary atherosis but not of coronary stenosis. Wall thickening detectable by extracoronary ultrasonography may be characterized by an intimamedia thickening shown in hypertension or by a focalized plaque whose the presence in the aortic or femoral level seem influenced by systolic pressure. Extracoronary wall thickening may be an aid in the diagnosis of coronary atherosclerosis, a predictor of coronary event, and a therapeutic target. Wall stiffening, which reflects sclerosis, is detected by pulse wave velocity. Its increase in hypertension may be an indicator of atherosclerosis and can be reversed by certain antihypertensive agents. Clinical care of at risk individuals might profit from subclinical atherosclerosis which adds objectivity and sensitivity in the individualization of risk and the decision to treat.