Atherosclerosis In Asymptomatic Subjects Research Articles

Differential Impact of Degree of Hypertension on Subclinical Coronary Atherosclerosis in Asymptomatic Subjects With and Without Diabetes Mellitus

This study sought to evaluate the association between the degree of hypertension and subclinical coronary atherosclerosis in asymptomatic subjects with and without diabetes mellitus (DM). We retrospectively analyzed 7,352 asymptomatic subjects (mean age 52.8±7.8years; 4,689 [63.8%] men) with no history of coronary artery disease who voluntarily underwent coronary computed tomography angiography as part of a general health examination. The classification of hypertension was adapted from the American College of Cardiology and American Heart Association 2017 guideline. Subclinical coronary atherosclerosis was defined as the presence of coronary plaque by coronary computed tomography angiography. In subjects without DM (n=6,598), after the adjustment for cardiovascular risk factors, subclinical coronary atherosclerosis was significantly associated with both stage 1 hypertension (adjusted odds ratio [aOR] 1.356; 95% confidence interval [CI], 1.167 to 1.575; p<0.001) and stage 2 hypertension (aOR, 1.614; 95% CI, 1.329 to 1.961; p<0.001) groups compared with the normal group. In contrast, in subjects with DM (n=754), there was no statistical difference in the aOR of the stage 1 hypertension group for the presence of coronary plaque (aOR, 1.449; 95% CI, 0.982 to 2.136; p=0.061). However, the stage 2 hypertension group had a significant association with subclinical coronary atherosclerosis (aOR, 2.067; 95% CI, 1.287 to 3.322; p=0.003). In subjects without DM, both stages 1 and 2 hypertension were associated with subclinical coronary atherosclerosis. However, in subjects with DM, stage 2 hypertension was only associated with an increased risk of subclinical coronary atherosclerosis.

Serum phosphorus and subclinical coronary atherosclerosis in asymptomatic subjects without kidney dysfunction.

There is limited data on the association between serum phosphorus concentration (SPC) and subclinical coronary atherosclerosis in low-risk asymptomatic subjects without kidney dysfunction. We retrospectively analyzed 1,636 Korean individuals (mean age 52.6±7.6 years; males: 712 (43.5%)) without traditional cardiovascular risk factors (CVRFs) and kidney dysfunction who voluntarily underwent coronary computed tomography angiography (CCTA) as part of a general health examination. Traditional CVRFs were defined as follows: systolic/diastolic blood pressure ≥140/90mmHg, fasting blood glucose ≥126mg/dL, hemoglobin A1c ≥6.5%, total cholesterol ≥240mg/dL, low-density lipoprotein cholesterol ≥160mg/dL, high-density lipoprotein cholesterol <40mg/dL, body mass index ≥25.0kg/m2, currently smoking, and medical history of hypertension, diabetes, and hyperlipidemia. Study participants were stratified into tertiles according to their SPC levels (≤3.2, 3.3-3.6, and ≥3.7mg/dL). 297 (18.2%) study participants had subclinical coronary atherosclerosis, characterized by any coronary plaque on CCTA. In multivariable regression analysis, the risk of subclinical coronary atherosclerosis increased in the second (odds ratio (OR): 1.629; 95% confidence interval (CI): 1.149-2.308; p=0.006) and third (OR: 1.645; 95% CI: 1.093-2.476; p=0.017) SPC tertiles compared to the first SPC tertile. In addition, the risk of calcified plaque increased in the second (OR: 1.605; 95% CI: 1.124-2.292; p=0.009) and third (OR 1.790; 95% CI 1.179-2.716; p=0.006) SPC tertiles. In low-risk asymptomatic Korean individuals without kidney dysfunction, a higher SPC level was an independent predictor of subclinical coronary atherosclerosis.

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.

The prevalence and characteristics of coronary atherosclerosis in asymptomatic subjects classified as low risk based on traditional risk stratification algorithm: assessment with coronary CT angiography

ObjectiveTo evaluate the prevalence and characteristics of coronary atherosclerosis in asymptomatic subjects classified as low risk by National Cholesterol Education Program (NCEP) guideline using coronary CT angiography (CCTA).DesignAn observational study.SettingA...

Sex- and age-related differences of myocardial perfusion at rest assessed with multidetector computed tomography

BackgroundThe clinical presentation of ischemic heart disease in women differs from men, which could reflect sex-related differences of normal physiology. Cardiac CT angiography provides a noninvasive method to assess both regional and transmural myocardial perfusion in addition to coronary atherosclerosis. ObjectiveThe aim of this study was to evaluate potential sex-related differences of (1) left ventricular (LV) myocardial perfusion measured as LV myocardial attenuation density/LV blood pool attenuation density (MyoAD-ratio) at rest and (2) transmural perfusion ratio (TPR) as a measure of endocardial perfusion relative to epicardial perfusion. MethodsMyocardial perfusion at rest and coronary artery atherosclerosis were evaluated with multidetector CT in 206 asymptomatic women and 203 age-matched men from the Copenhagen General Population Study. ResultsLV myocardial perfusion at rest (LV MyoAD-ratio) was higher in women than in men (9% difference; P = 0.039). In a multivariable analysis, including age, sex, cardiovascular risk factors, Agatston score, and presence of coronary stenosis, global LV MyoAD-ratio remained significantly higher in women than in men (P = 0.045). No effect of cardiovascular risk factors on myocardial perfusion at rest was noted. Myocardial perfusion at rest was correlated to age in men (r = 0.15, P = 0.031) but not in women (r = −0.01, P = 0.83). TPR was slightly lower in women than in men (1.12 vs 1.14; P = 0.0019). ConclusionLV myocardial perfusion at rest is higher in women than men independent of coronary atherosclerosis in asymptomatic subjects with risk factors.

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.

Carotid doppler ultrasonography as a surrogate for coronary CT angiography to exclude subclinical coronary atherosclerosis in asymptomatic patients with a negative coronary calcium score

To evaluate the diagnostic accuracy of carotid Doppler ultrasonography (CDU) to predict the presence of subclinical coronary atherosclerosis in asymptomatic subjects with a zero coronary calcium score. Retrospective study of CDU and coronary CT angiography (CTA) findings in 118 asymptomatic subjects with a zero calcium score. CDU was considered abnormal when carotid intima-media thickness was >75 percentile or was ≥ 1 mm, or in presence of carotid plaque(s). We analyzed the diagnostic accuracy of CDU to predict the presence of non-calcified coronary plaque in comparison with coronary CTA. The sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of abnormal CDU to identify the presence of non-calcified coronary plaque on coronary CTA were 82.4% [(14/17); 95% confidence interval (CI), 56.6%-96.2%], 53.5% [(54/101); 95% CI, 43.3%-63.5%], 23.0% [(14/61); 95% CI, 13.1%-35.6%], and 94.7% [(54/57); 95% CI, 85.4%-98.9%], respectively. Although CDU has a low PPV for identifying the presence of non-calcified plaque on coronary CTA, its NPV is high to exclude subclinical coronary atherosclerosis in asymptomatic subjects with a zero calcium score.

Vascular screening in asymptomatic subjects using non-contrast MRA

Summary Vascular screening including the coronary, carotid, renal arteries and aorta using non-contrast MRA in 300 asymptomatic subjects detected atherosclerosis lesions including the coronary artery in 5% of participants. Background Atherosclerosis is a systemic disease affecting arteries in a whole body and a major cause of death in the world. There are few data, however, on the extent of the diseases associated with atherosclerosis in asymptomatic subjects.

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.

Circulating monocytes mirror the imbalance in TF and TFPI expression in carotid atherosclerotic plaques with lipid-rich and calcified morphology

BackgroundThrombogenicity of atherosclerotic plaque largely depends on plaque morphology and their content of tissue factor (TF) and tissue factor pathway inhibitor (TFPI). The relationship between morphological composition of plaque (lipid-rich or calcified) and expression of TF and TFPI in circulating blood monocytes and within the plaques is not characterized. ObjectiveTo investigate whether lipid-rich (echolucent) or calcified (echogenic) morphology of carotid atherosclerotic plaques is associated with differences in TF and TFPI expression in circulating blood monocytes and within carotid atherosclerotic plaques. MethodsWe studied levels of monocyte TF and TFPI mRNA and protein expression and association with traditional risk factors for atherosclerosis in asymptomatic subjects with echolucent (n=20) or echogenic (n=20) carotid plaques, or controls without carotid atherosclerosis (n=20) determined by ultrasonography. Sections of calcified or lipid-rich carotid plaques obtained from symptomatic patients were assessed for TF and TFPI antigen expression. ResultsTF and TFPI surface presentation, surface TF/TFPI ratio, and TF activity were higher in monocytes obtained from subjects with echolucent than with echogenic plaques or controls without carotid atherosclerosis. Multiple regression analyses revealed inverse association between serum apoA1 and monocyte surface TF antigen expression (p=0.007), and positive association between serum apoB and monocyte surface TFPI expression (p=0.028). Sections from lipid-rich carotid plaques contained 2.5-fold more TF and 1.5-fold more TFPI antigens relative to calcified lesions, also yielding a higher TF/TFPI ratio. ConclusionsOur findings indicate that circulating monocytes of asymptomatic individuals with echolucent lipid-rich carotid atherosclerosis express an imbalance between TF and TFPI expression cohering with changes found within advanced carotid atherosclerotic plaques obtained from symptomatic patients.

The relationship between oxidized lipoprotein(a) and carotid atherosclerosis in asymptomatic subjects: A comparison with native lipoprotein(a)

BackgroundOxidized lipoprotein(a) (oxLp(a)) can be a more potent marker of atherogenesis than native Lp(a), although Lp(a) is considered to be a risk factor for atherosclerotic diseases. Limited clinical data are available regarding the significance of oxLp(a) in atherosclerotic manifestations. This study aimed to investigate the association between the serum oxLp(a) and carotid artery intima-media thickness (CIMT), in comparison to the serum Lp(a) levels, among asymptomatic subjects.MethodsThe atheroscrerosis-related variables including Lp(a) and oxLp(a) were measured in 136 cardiovascular disease-free subjects (61 males and 75 females, mean age of 64 years). The serum oxLp(a) level was quantified using a sandwich ELISA system. The CIMT level was ultrasonographically measured on bilateral carotid arteries.ResultsThe median level of Lp(a) was 120 μmol/L, oxLp(a) was 0.06 nmol/L, and CIMT was 0.7 mm, respectively. A simple correlation test showed that the CIMT was significantly and positively correlated with age, systolic blood pressure and oxLp(a) (r = 0.208, P < 0.05). A multiple linear regression analysis revealed that oxLp(a) continued to show a significant and positive correlation with the CIMT (β = 0.202, P = 0.01). Although the similar analyses were conducted for Lp(a), it showed only a weak correlation with the CIMT (r = 0.011, β = 0.041, both P < 0.05).ConclusionsThese results suggest that oxLp(a) may be more closely associated with accelerated carotid atherosclerosis, in comparison to Lp(a), in this population. This finding can be important for obtaining a better understanding of the different atherogenic roles played by oxLp(a) in comparison to Lp(a).

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.

High serum uric acid and low-grade inflammation are associated with smaller LDL and HDL particles

Elevated serum uric acid (UA) is associated with higher risk for cardiovascular disease (CVD). Smaller, denser low density lipoprotein (LDL) and high-density lipoprotein (HDL) particles are the potential risk factors for CVD, while the role and diagnostic value of inflammatory markers are firmly established. This current cross-sectional study investigates interrelationships between UA, high sensitivity C-reactive protein (hsCRP) and fibrinogen concentrations with LDL and HDL sizes in healthy middle-aged subjects. The outcomes-of-interest were smaller, denser LDL and HDL particles (LDL size ≤25.5nm and HDL size ≤8.8nm). Serum UA, hsCRP and plasma fibrinogen concentrations were measured by standard laboratory methods in a sample of 194 healthy volunteers (112 men and 82 women). LDL and HDL particle sizes were determined by gradient gel electrophoresis. The subjects in the highest UA tertile had significantly smaller LDL and HDL particle sizes (P<0.05 and P<0.01, respectively) and higher concentrations of fibrinogen and hsCRP (P<0.05 and P<0.01, respectively). Elevated UA (≥318μmol/L) was a significant predictor of smaller, denser LDL and HDL particles (OR=3.09; P<0.01; n=19 and OR=4.40; P<0.001; n=23, respectively). The observed relationship with smaller HDL size persisted after adjustment for conventional cardiovascular risk factors. UA strongly correlated with both markers of inflammation. In addition, the higher hsCRP level correlated with smaller LDL size (P<0.05), while fibrinogen concentration was inversely related to HDL size (P<0.05). Multiple regression analysis revealed that HDL size and inflammatory markers remained independent determinants of UA concentration. In conclusion, higher serum UA and low-grade inflammation are closely linked to alterations in lipoprotein metabolism which may represent an early sign of atherosclerosis in asymptomatic subjects.

Value of Electrocardiographic and Ankle–Brachial Index Abnormalities for Prediction of Coronary Atherosclerosis in Asymptomatic Subjects With Type 2 Diabetes Mellitus

Type 2 diabetes mellitus (DM) is associated with increased cardiovascular risk, in part due to accelerated subclinical atherosclerosis. Electrocardiographic (ECG) and ankle-brachial index (ABI) abnormalities are used to screen for cardiovascular risk in the clinic. However, their capacity to identify patients with type 2 DM with nonobstructive subclinical atherosclerosis is unknown. Associations of ECG and ABI abnormalities with coronary artery calcium (CAC), a measure of coronary atherosclerosis, were examined using multivariable ordinal regression modeling in 589 asymptomatic patients with type 2 DM. Sensitivity, specificity, and positive and negative predictive values were determined. CAC was prevalent (44% CAC>00; 32% CAC>5th percentile score) despite normal electrocardiograms (64%) and ABIs (97%) in most subjects. Neither ECG nor ABI changes predicted CAC after adjusting for age, gender, and race. ECG abnormalities were neither sensitive nor specific for detection of CAC>100, >400, or>75th percentile (sensitivities 0.43, 0.45, and 0.34; specificities 0.69, 0.66, and 0.63, respectively). ABI abnormalities were not sensitive (0.03, 0.04, and 0.03) but had high specificity (0.98, 0.98, and 0.98). In subjects with normal electrocardiograms and ABIs, extensive CAC was remarkably prevalent (CAC>00 in 24%). In conclusion, ECG and ABI abnormalities failed to detect patients with subclinical coronary atherosclerosis and therefore may be of limited value in identifying many asymptomatic patients with type 2 DM at increased risk of cardiovascular disease.

Independent association of von Willebrand factor with surrogate markers of atherosclerosis in middle‐aged asymptomatic subjects

Von Willebrand factor (VWF) is considered a reliable marker of endothelial damage. Plasma levels of VWF were measured in 857 middle-aged subjects (80.4% men) free of clinically overt atherosclerotic disease, in relation to cardiovascular risk factors, carotid intima-media thickness (IMT) and microalbuminuria, two established surrogate markers of atherosclerosis. There was linear trend for the increase of VWF, carotid IMT (p < 0.001) and microalbuminuria (p = 0.018). The association between VEF and both markers remained statistically significant after adjusting for cardiovascular risk factors and inflammatory markers (p < 0.01). In conclusion, VWF was independently associated with both structural and functional surrogates of atherosclerosis in asymptomatic subjects, thus representing a systemic biomarker of subclinical atherosclerosis.