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BackgroundThis study aimed to evaluate the relationship between cigarette smoking and coronary atherosclerotic burden, volume and composition as determined in-vivo by grayscale and virtual histology (VH) intravascular ultrasound (IVUS).Methods and ResultsBetween 2008 and 2011, (VH-)IVUS of a non-culprit coronary artery was performed in 581 patients undergoing coronary angiography. To account for differences in baseline characteristics, current smokers were matched to never smokers by age, gender and indication for catheterization, resulting in 280 patients available for further analysis. Coronary atherosclerotic plaque volume, burden, composition (fibrous, fibro-fatty, dense calcium and necrotic core) and high-risk lesions (VH-IVUS derived thin-cap fibroatheroma (TCFA), plaque burden ≥70%, minimal luminal area ≤4.0 mm2) were assessed. Cigarette smoking showed a tendency towards higher coronary plaque burden (mean±SD, 38.6±12.5% in current versus 36.4±11.0% in never smokers, p = 0.080; and odds ratio (OR) of current smoking for plaque burden above versus below the median 1.69 (1.04–2.75), p = 0.033). This effect was driven by an association in patients presenting with an acute coronary syndrome (ACS) (current smokers, plaque burden 38.3±12.8% versus never smokers, plaque burden 35.0±11.2%, p = 0.049; OR 1.88 (1.02–3.44), p = 0.042). Fibrous tissue tended to be lower in current smokers (mean±SD, 57.7±10.5% versus 60.4±12.6%, p = 0.050) and fibro-fatty tissue was higher in current smokers (median[IQR], 9.6[6.0–13.7]% versus 8.6[5.8–12.2]%, p = 0.039). However, differences in percentage necrotic core and dense calcium could not be demonstrated. Also, no differences were found with regard to high-risk lesions.ConclusionsAn association between smoking and degree of coronary atherosclerosis was present in patients undergoing coronary angiography who presented with ACS. Although smoking was associated with higher fibro-fatty percentage, no associations could be demonstrated with percentage necrotic core, nor with VH-IVUS derived TCFA lesions. Since the magnitude of the differences in both degree and composition of atherosclerosis was modest, clinical relevance of the findings may be questioned.

Mild-to-moderate kidney dysfunction modifies the relationship between CysC and high-risk coronary lesions. This has not been established before, and offers an explanation for the difference in findings between experimental and epidemiologic studies.

OBJECTIVE: The aim of this study was to provide additional insight into the role of fibrinogen in coronary artery disease by investigating the associations between plasma fibrinogen with both degree and composition of coronary atherosclerosis as determined by virtual histology-intravascular ultrasound. PATIENTS AND METHODS: In 581 patients undergoing coronary angiography for acute coronary syndrome (ACS) or stable angina pectoris, preprocedural blood samples were drawn for fibrinogen, Creactive protein (CRP), interleukin-6, and plasminogen activator inhibitor-1 measurements, and virtual histology-intravascular ultrasound of a nonculprit coronary artery was performed. The degree [plaque volume, plaque burden (PB), and lesions with PB70%] and the composition of coronary atherosclerotic plaque (fibrous, fibrofatty, dense calcium, necrotic core tissue, and thin-cap fibroatheroma lesions) were assessed. RESULTS: Fibrinogen showed a tendency toward a positive association with PB [ (95% CI): 2.55 (-0.52-5.61) increase in PB per ln(g/l) fibrinogen, P=0.09], which was driven significantly by an association in the ACS subgroup [ (95% CI): 4.11 (0.01-8.21) increase in PB per ln(g/l) fibrinogen, P=0.049]. Fibrinogen was also related to the presence of lesions with PB 70% or more in both the full cohort [OR (95% CI): 2.27 (1.17-4.43), P=0.016] and ACS patients [OR (95% CI): 2.92 (1.17-7.29), P=0.022]. All associations were independent of established cardiovascular risk factors, but not CRP. Interleukin-6 and plasminogen activator inhibitor-1 did not provide incremental value to fibrinogen when examining the associations with degree of atherosclerosis. Substantial associations with plaque composition were absent. CONCLUSION: Fibrinogen is associated with degree of coronary atherosclerosis, especially in ACS patients. However, whether this association is independent of CRP might be questioned and needs further investigation. Objective The aim of this study was to provide additional insight into the role of fibrinogen in coronary artery disease by investigating the associations between plasma fibrinogen with both degree and composition of coronary atherosclerosis as determined by virtual histologyintravascular ultrasound. Patients and methodsIn 581 patients undergoing coronary angiography for acute coronary syndrome (ACS) or stable angina pectoris, preprocedural blood samples were drawn for fibrinogen, C-reactive protein (CRP), interleukin-6, and plasminogen activator inhibitor-1 measurements, and virtual histology-intravascular ultrasound of a nonculprit coronary artery was performed. The degree [plaque volume, plaque burden (PB), and lesions with PB ≥ 70%] and the composition of coronary atherosclerotic plaque (fibrous, fibrofatty, dense calcium, necrotic core tissue, and thin-cap fibroatheroma lesions) were assessed.Results Fibrinogen showed a tendency toward a positive association with PB [β (95% CI): 2.55 (− 0.52-5.61) increase in PB per ln(g/l) fibrinogen, P = 0.09], which was driven significantly by an associat...

BackgroundProspective data on the associations of adiponectin with in-vivo measurements of degree, phenotype and vulnerability of coronary atherosclerosis are currently lacking.ObjectiveTo investigate the association of plasma adiponectin with virtual histology intravascular ultrasound (VH-IVUS)-derived measures of atherosclerosis and with major adverse cardiac events (MACE) in patients with established coronary artery disease.Methods In 2008-2011, VH-IVUS of a non-culprit non-stenotic coronary segment was performed in 581 patients undergoing coronary angiography for acute coronary syndrome (ACS, n = 318) or stable angina pectoris (SAP, n = 263) from the atherosclerosis-intravascular ultrasound (ATHEROREMO-IVUS) study. Blood was sampled prior to coronary angiography. Coronary plaque burden, tissue composition, high-risk lesions, including VH-IVUS-derived thin-cap fibroatheroma (TCFA), were assessed. All-cause mortality, ACS, unplanned coronary revascularization were registered during a 1-year-follow-up. All statistical tests were two-tailed and p-values < 0.05 were considered statistically significant.Results In the full cohort, adiponectin levels were not associated with plaque burden, nor with the various VH-tissue types. In SAP patients, adiponectin levels (median[IQR]: 2.9(1.9-3.9) µg/mL) were positively associated with VH-IVUS derived TCFA lesions, (OR[95%CI]: 1.78[1.06-3.00], p = 0.030), and inversely associated with lesions with minimal luminal area (MLA) ≤ 4.0 mm2 (OR[95%CI]: 0.55[0.32-0.92], p = 0.025). In ACS patients, adiponectin levels (median[IQR]: 2.9 [1.8-4.1] µg/mL)were not associated with plaque burden, nor with tissue components. Positive association of adiponectin with death was present in the full cohort (HR[95%CI]: 2.52[1.02-6.23], p = 0.045) and (borderline) in SAP patients (HR[95%CI]: 8.48[0.92-78.0], p = 0.058). In ACS patients, this association lost statistical significance after multivariable adjustment (HR[95%CI]: 1.87[0.67-5.19], p = 0.23).Conclusion In the full cohort, adiponectin levels were associated with death but not with VH-IVUS atherosclerosis measures. In SAP patients, adiponectin levels were associated with VH-IVUS-derived TCFA lesions. Altogether, substantial role for adiponectin in plaque vulnerability remains unconfirmed.

for the BIOMArCS investigators Growth differentiation factor-15 (GDF-15) has appeared as a promising biomarker with strong predictive abilities in acute coronary syndrome (ACS). However, studies are solely based on single measurements in the acute phase of an ACS event. The way GDF-15 patterns in post-ACS patients behave on the long term is largely unknown. We conducted a nested case-control study within our multicenter, prospective, observational biomarker study (BIOMArCS) of 844 ACS patients. Following an index ACS event, high-frequency blood sampling was performed during 1-year of follow-up. GDF-15 was determined batchwise by electrochemiluminescence immunoassays in 37 cases with a recurrent event during 1-year follow-up, and in 74 event-free controls. Cases and controls had a mean § standard deviation age of 66.9 § 11.3 years and 81% were men. From 30 days onwards, patients showed stable levels, which were on average 333 (95% confidence interval 68 to 647) pg/mL higher in cases than controls (1704 vs 1371 pg/mL; p value 0.013). Additionally, in the post 30-day period, GDF-15 showed low within-individual variability in both cases and controls. In conclusion, post-ACS patients experiencing a recurrent event had stable and systematically higher GDF-15 levels during 30-day to 1-year follow-up than their event-free counterparts with otherwise similar clinical characteristics. Thus, postdischarge blood sampling might be used throughout the course of 1 year to improve prognostication, whereas, in view of the low within-individual variation, the number of repeated sampling moments might be limited.

Background: Population means of conventional cardiovascular biomarkers are known to differ between ethnic groups. In this study we performed detailed comparisons in the temporal pattern of these biomarkers between Caucasian and Chinese diabetic patients with acute coronary syndrome (ACS). Methods: We studied differences in temporal changes of established cardiovascular biomarkers, including high-density lipoprotein (HDL), low-density lipoprotein (LDL), total cholesterol, cardiac Troponin T (TnT), NT-proBNP and C-reactive protein (CRP), in 48 Chinese and 48 clinically matched Caucasian patients with type 2 diabetes mellitus who were admitted for ACS. Blood samples were collected at regular time intervals during 30 days to 1 year after the index ACS. Results: In the >30 day post ACS period, mean serum levels of LDL (2.16 vs. 1.47 mmol/L; p-value <0.001), total cholesterol (4.08 vs. 3.11 mmol/L; p-value <0.001), TnT (11.0 vs. 7.76 ng/L; p-value 0.010) and CRP (2.0 vs. 0.78 mg/L; p-value <0.001) were systematically higher in Caucasian than in Chinese patients. HDL and NT-proBNP levels were similar. Conclusions: Our study showed clinically relevant differences in levels of established cardiovascular biomarkers between Caucasian and Chinese post ACS patients. Further cross-ethnic studies are warranted to determine secondary prevention treatment biomarker targets in specific populations.

RANTES is a promising biomarker that is inversely associated with coronary plaque burden and vulnerability, as well as with death and acute coronary syndrome.