Fibrinogen in relation to degree and composition of coronary plaque on intravascular ultrasound in patients undergoing coronary angiography.

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, 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 [ß (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 [ß (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.

Plasma concentrations of molecular lipid species in relation to coronary plaque characteristics and cardiovascular outcome: Results of the ATHEROREMO-IVUS study.

BACKGROUND AND AIMS: Previous lipidomics analyses have demonstrated that several lipid molecules in plasma are associated with fatal outcome in patients with coronary artery disease (CAD). This study aims to investigate the associations of previously identified high risk lipid molecules in plasma with coronary plaque characteristics derived from intravascular ultrasound virtual histology (IVUS-VH) imaging, with coronary lipid core burden index (LCBI) on near-infrared spectroscopy (NIRS), and with one year cardiovascular outcome in patients with CAD. METHODS: Between 2008 and 2011, IVUS-VH imaging of a non-culprit coronary artery was performed in 581 patients who underwent coronary angiography for acute coronary syndrome (ACS) or stable CAD. NIRS imaging was additionally performed in 191 patients. Plasma concentrations of molecular lipids were measured with mass spectrometry. RESULTS: Several cholesteryl ester, ceramide and lactosylceramide species and ceramide ratios were associated with vulnerable plaque characteristics on IVUS-VH and NIRS imaging and with 1-year major adverse cardiac events (MACE, defined as all-cause mortality, ACS and unplanned coronary revascularization). In particular, ceramide d18:1/16:0 was consistently associated with higher necrotic core fraction on IVUS-VH (p = 0.001), higher LCBI (p = 0.024) on NIRS and higher MACE rate (adjusted HR 1.79 per standard deviation increase in log-transformed lipid concentration, 95%CI 1.24-2.59, p = 0.002). CONCLUSION: Several molecular lipid species, and particularly ceramide(d18:1/16:0), are associated with the fraction of necrotic core tissue and lipid core burden in coronary atherosclerosis, and are predictive for 1-year clinical outcome after coronary angiography. These molecular lipids may improve risk stratification in CAD and may also be interesting therapeutic targets for the treatment of atherosclerotic disease.

Smoking in Relation to Coronary Atherosclerotic Plaque Burden, Volume and Composition on Intravascular Ultrasound.

BACKGROUND: This 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 RESULTS: Between 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. CONCLUSIONS: An 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.

In vivo detection of high-risk coronary plaques by radiofrequency intravascular ultrasound and cardiovascular outcome: results of the ATHEROREMO-IVUS study.

AIMS: Acute coronary syndromes (ACS) are mostly caused by plaque rupture. This study aims to investigate the prognostic value of in vivo detection of high-risk coronary plaques by intravascular ultrasound (IVUS) in patients undergoing coronary angiography. METHODS AND RESULTS: Between November 2008 and January 2011, IVUS of a non-culprit coronary artery was performed in 581 patients who underwent coronary angiography for ACS (n = 318) or stable angina (n = 263). Primary endpoint was major adverse cardiac events (MACEs) defined as mortality, ACS, or unplanned coronary revascularization. Culprit lesion-related events were not counted. Cumulative Kaplan-Meier incidence of 1-year MACE was 7.8%. The presence of IVUS virtual histology-derived thin-cap fibroatheroma (TCFA) lesions (present 10.8% vs. absent 5.6%; adjusted HR: 1.98, 95% CI: 1.09-3.60; P = 0.026) and lesions with a plaque burden of ≥70% (present 16.2% vs. absent 5.5%; adjusted HR: 2.90, 95% CI: 1.60-5.25; P < 0.001) were independently associated with a higher MACE rate. Thin-cap fibroatheroma lesions were also independently associated with the composite of death or ACS only (present 7.5% vs. absent 3.0%; adjusted HR: 2.51, 95% CI: 1.15-5.49; P = 0.021). Thin-cap fibroatheroma lesions with a plaque burden of ≥70% were associated with a higher MACE rate within (P = 0.011) and after (P < 0.001) 6 months of follow-up, while smaller TCFA lesions were only associated with a higher MACE rate after 6 months (P = 0.033). CONCLUSION: In patients undergoing coronary angiography, the presence of IVUS virtual histology-derived TCFA lesions in a non-culprit coronary artery is strongly and independently predictive for the occurrence of MACE within 1 year, particularly of death and ACS. Thin-cap fibroatheroma lesions with a large plaque burden carry higher risk than small TCFA lesions, especially on the short term.

Life-years gained by smoking cessation after percutaneous coronary intervention.

Previous studies have shown that smoking cessation after a cardiac event reduces the risk of subsequent mortality in patients. The aim of this study was to describe the effect of smoking cessation in terms of prolonged life-years gained. The study sample comprised 856 patients who underwent percutaneous coronary intervention (PCI; balloon angioplasty) during 1980 to 1985. Patients were followed up for 30 years and smoking status at 1 year could be retrieved in 806 patients. The 27 patients who died within 1 year were excluded from the analysis. The median follow-up was 19.5 years (interquartile range 6.0 to 23.0). Cumulative 30-year survival rate was 29% in the group of patients who quit smoking and 14% in persistent smokers (p = 0.005). After adjustment for baseline characteristics at the time of PCI, smoking cessation remained an independent predictor of lesser mortality (adjusted hazard ratio 0.57, 95% confidence interval 0.46 to 0.71). The estimated life expectancy was 18.5 years in those who quit smoking and 16.4 years in the persistent smokers (p <0.0001). In conclusion, in patients with coronary heart disease who underwent PCI in the late 1980s, smoking cessation resulted in at least 2.1 life-years gained.

Short- and long-term outcomes in octogenarians undergoing percutaneous coronary intervention with stenting.

AIMS: To investigate the incidence of cardiac events in octogenarians who underwent percutaneous coronary intervention (PCI) with stenting, as well as to evaluate the efficacy and safety of drug-eluting stents (DES) in this population. METHODS AND RESULTS: The study included 6,129 consecutive patients who underwent PCI with stenting from 2000 to 2005 in our centre, of whom 291 (4.7%) were octogenarians. After adjusting for confounders, age ≥80 years appeared a significant predictor of high mortality at 30 days (adjusted hazard ratio [aHR] 1.92, 95% CI 1.23-3.01), and four years (aHR 2.25, 95% CI 1.77-2.85). No differences were seen with respect to incident myocardial infarction (MI), but target lesion (63.2 vs. 32.6 per 1,000 person-years at one year and 27.9 vs. 16.6 per 1,000 person-years at four years) and vessel (83.1 vs. 52.9 per 1,000 person-years at one year and 37.7 vs. 25.0 per 1,000 person-years at four years) revascularisation rates were lower in octogenarians. When comparing DES with bare metal stents (BMS) in octogenarians, mortality and MI rates were comparable, but there was a significantly lower incidence of target lesion revascularisation at one- (9.5 vs. 0.6 per 1,000 person-years, aHR 0.07, 95% CI 0.01-0.57) and four-year (3.4 vs. 0.7 per 1,000 person-years, aHR 0.16, 95% CI 0.04-0.59) follow-up in patients who received a DES. CONCLUSIONS: Octogenarians undergoing PCI with stenting have an increased mortality risk, whereas the rates of repeat revascularisation in octogenarians are lower. This study suggests that the benefit of DES in reducing revascularisation rates is extended to elderly patients.

Short- and long-term major adverse cardiac events in patients undergoing percutaneous coronary intervention with stenting for acute myocardial infarction complicated by cardiogenic shock.

OBJECTIVES: To determine the risk of short- and long-term mortality and major adverse cardiac events (MACE) in acute myocardial infarction (AMI) patients complicated by cardiogenic shock (CS) in the contemporary practice of primary percutaneous coronary intervention with stenting. METHODS: Of the 1,755 consecutive AMI patients undergoing percutaneous coronary intervention with stenting enrolled, 103 had CS at admission. Primary endpoints were early mortality (within 30 days after the index event) and late mortality (from day 31 up to 4 years). Secondary endpoints included MACE [all-cause death, myocardial infarction or target vessel revascularization (TVR)], myocardial infarction, TVR and stent thrombosis. RESULTS: Thirty-day mortality was higher among CS patients, and CS was a strong independent predictor of a higher risk of early death (adjusted HR 3.64, 95% CI 2.44-5.44). The late mortality rate was significantly higher in CS patients, and CS was also a predictor of higher risk of death at a 4-year follow-up (adjusted HR 1.95, 95% CI 1.11-3.45). Recurrent AMI, TVR and stent thrombosis rates were similar among patients with and without CS. CONCLUSION: CS complicating AMI is still a severe clinical event, mainly with regard to a significant higher risk of early mortality, but also associated with a worse prognosis in 30-day survivors.

Primary PCI during off-hours is not related to increased mortality.

AIM: Previous studies have shown contradictory outcomes in ST-segment elevation myocardial infarction (STEMI) patients who underwent primary percutaneous coronary intervention (pPCI) during off-hours versus regular 'office' hours. We aimed to evaluate the relationship between pPCI timing (off-hours versus regular hours) and mortality in patients with STEMI undergoing pPCI. METHODS: The study population comprised 4352 consecutive STEMI patients treated with pPCI in a high-volume centre with a 24/7 programme during 2000-2009. Descriptive statistics and multivariable survival analyses were applied to evaluate the relationship between treatment during off-hours (Monday-Friday, 6.00 pm-8.00 am and weekends) versus regular hours and the incidence of all-cause mortality at 30-day and 4-year follow-up. RESULTS: A total of 2760 patients (63.4%) were treated during off-hours and 1592 patients (36.6%) during regular hours. With the exception of smoking, diabetes mellitus, use of glycoprotein IIb/IIIa antagonists and calcium antagonists, no major differences in baseline characteristics were observed between the groups. Mortality at 30-day follow-up was similar in patients treated during off-hours and those treated during regular hours (7.7% vs 7.7%; hazard ratio adjusted for potential confounders 1.03; 95% CI 0.82-1.28). Four-year mortality was similar (17.3% vs 17.3%; adjusted hazard ratio 0.95; 95% CI 0.81-1.11). CONCLUSION: In STEMI patients who present during off-hours in a high-volume centre with 24/7 service, pPCI provides similar survival as patients who were treated during regular hours.

NIRS and IVUS for characterization of atherosclerosis in patients undergoing coronary angiography.

OBJECTIVES: The aim of this study was to compare the findings of near-infrared spectroscopy (NIRS), intravascular ultrasound (IVUS) virtual histology (VH), and grayscale IVUS obtained in matched coronary vessel segments of patients undergoing coronary angiography. BACKGROUND: Intravascular ultrasound VH has been developed to add tissue characterization to the grayscale IVUS assessment of coronary plaques. Near-infrared spectroscopy is a new imaging technique able to identify lipid core-containing coronary plaques (LCP). METHODS: We performed NIRS and IVUS-VH pullbacks in a consecutive series of 31 patients with a common region of interest (ROI) between 2 side branches. For each ROI, we analyzed the chemogram blocks by NIRS, plaque area and plaque burden by grayscale IVUS, and tissue types by IVUS-VH. The chemogram block is a summary metric of a 2-mm vertical slice of the chemogram. The value ranges from 0 to 1 according to the presence of lipids and represents the probability of LCP with a color scale from red (low probability) through orange and tan to yellow (high probability). RESULTS: Plaque area (mm(2)) increases as percentage VH derived-necrotic core (NC) content (4.6 ± 2.7 vs. 7.4 ± 3.5 vs. 8.6 ± 3.4 vs. 7.9 ± 3.3, grouped in percentage NC quartiles, p<0.001) and chemogram block probability color bin thresholds increase (4.9 ± 3.8 red, 7.3 ± 3.6 orange, 8.1 ± 3.4 tan, and 8.7 ± 3.4 yellow, p<0.001). The correlation between the block chemogram detection of lipid core and percentage NC content by VH was weak (r=0.149). Correction for the presence of calcium does not improve this correlation. CONCLUSIONS: Larger plaque area by grayscale IVUS was more often associated with either elevated percentage VH-NC or LCP by NIRS; however, the correlation between the detection of LCP by NIRS and necrotic core by VH is weak.

Force plate analysis before and after dorsal decompression for treatment of degenerative lumbosacral stenosis in dogs.

OBJECTIVE: Using force plate analysis (FPA), determine ground reaction forces in dogs with degenerative lumbosacral stenosis (DLS) and evaluate the effects of lumbosacral decompressive surgery. STUDY DESIGN: Prospective clinical study. ANIMALS: Twelve dogs with DLS. METHODS: DLS was diagnosed by clinical signs, radiography, computed tomography, and/or magnetic resonance imaging. FPA was performed before surgery, and 3 days, 6 weeks, and 6 months after surgery. The mean peak braking (Fy+), peak propulsive (Fy-), and peak vertical (Fz+) forces of 8 consecutive strides were determined. The ratio between the total Fy- of the pelvic limbs and the total Fy- of the thoracic limbs (P/TFy-), reflecting the distribution of Fy-, was analyzed to evaluate any changes in locomotion pattern postoperatively. Ground reaction force data for DLS dogs were compared with data derived from 24 healthy dogs (control). RESULTS: In dogs with DLS, the propulsive forces (Fy-) of the pelvic limbs were significantly smaller than those of controls. P/TFy- was significantly smaller in dogs with DLS than in control dogs, and increased during the follow-up period, reaching normal values 6 months after surgery. CONCLUSIONS: Cauda equina compression in dogs with DLS decreases the propulsive force of the pelvic limbs and surgical treatment restores the propulsive force of the pelvic limbs in a 6-month period. CLINICAL RELEVANCE: In dogs with DLS, FPA is an effective method in evaluating the response to surgical treatment. Normal propulsive force in the pelvic limbs was restored during 6 months after decompressive surgery.