Association Between the Prothrombin Time-International Normalized Ratio and Concomitant Use of Antibiotics in Warfarin Users: Focus on Type of Antibiotic and Susceptibility of Bacteroides fragilis to Antibiotics.

BACKGROUND: The difference in type of antibiotics and susceptibility of Bacteroides fragilis to antibiotics may influence warfarin anticoagulation. However, these influences have not been clarified in clinical settings. OBJECTIVES: This study aimed to investigate association the between the prothrombin time-international normalized ratio (PT-INR) and concomitant use of antibiotics in a real-world population of warfarin users. METHODS: This was a single-center cohort study using data from health records and included patients who received ß-lactams (BLs)/fluoroquinolones (FQs) during ongoing warfarin treatment (2011-2015) at Hamamatsu University Hospital in Japan. Antibiotics were categorized into those to which B fragilis is susceptible (BLsus, FQsus) and those to which it is not (BLnon, FQnon) and into those given orally (BLpo, FQpo) or intravenously (BLiv, FQiv). Outcomes were excessive PT-INR and changes in PT-INR, defined as the ratio (INR ratio) and difference (ΔINR) of maximum PT-INR and baseline PT-INR. Excessive PT-INR was graded as INR ratio of >1.5 or >2.5. RESULTS: A total of 1185 warfarin users were included. The proportion of INR ratio >2.5 in FQiv was higher than in BLiv (95% CI: 1.59-46.5). The proportions with an INR ratio of >1.5 in BLsus and FQsus were higher than in BLnon (1.72-14.1) and FQnon (1.05-9.36), respectively. ΔINR values in FQpo, FQiv, and FQsus were higher than those in BLpo, BLiv, and FQnon, respectively. CONCLUSIONS AND RELEVANCE: Concomitant use of FQs, or of antibiotics to which B fragilis is susceptible is associated with higher risk of excessive anticoagulation. These findings would contribute to safe and proper antibiotic treatment in warfarin users.

Characteristics of carotid atherosclerosis in patients with plaque erosion.

Plaque erosion (PE) is a major underlying mechanism of acute coronary syndrome (ACS). Patients with PE may have less systemic atherosclerosis. We aimed to clarify the status of carotid atherosclerosis in patients with PE. A total of 115 consecutive patients with ACS who underwent optical coherence tomography (OCT) imaging of the culprit lesion were enrolled. Patients were classified into PE (n = 26), plaque rupture (n = 56) or calcified plaque (CP, n = 33) based on OCT findings of the culprit lesions. The status of carotid atherosclerosis was assessed by the findings of carotid echography. The mean IMT was the lowest in the PE group (1.5 ± 0.6 mm) among the three groups (p = 0.004) with a significant difference between the PE group and the CP group (2.1 ± 0.6 mm, p < 0.001). The plaque score was the lowest in the PE group (6.6 ± 2.5) among the three groups (p = 0.004) with a significant difference between the PE group and the CP group (9.0 ± 2.7, p < 0.001). Multivariate analyses demonstrated that the PE was independently associated with the presence of lower mean IMT (below median; 1.85 mm) (odds ratio 3.34; 95 % confidence interval 1.07-10.4; p = 0.035) and the lack of heterogenous plaque (odds ratio 2.92; 95 % confidence interval 1.02-8.32; p = 0.037). Patients with PE were associated with less atherosclerosis in the carotid artery than other patients with ACS. These findings may help further clarify the distinct pathophysiology of PE. Carotid atherosclerosis and plaque erosion.

Achilles tendon thickening is associated with higher incidence of adverse cardiovascular event in patients with coronary artery disease.

Achilles tendon thickening (ATT) is a marker of high risk for coronary artery disease (CAD). However, the association between the presence of ATT and the incidence of cardiovascular events in patients with CAD is unclear. A total of 406 consecutive patients who underwent percutaneous coronary intervention (PCI) and ATT assessment were analyzed. ATT was defined as the Achilles tendon thickness of 9 mm or more on radiography. The incidence of major adverse cardiovascular events (MACE) at 1-year was compared between patients with ATT and those without ATT. MACE included cardiac death, non-fatal myocardial infarction, stroke, target vessel revascularization (TVR), and non-TVR. ATT was found in 67 patients (16.5%). The incidence of cardiac death (3.2 vs. 0.0%, p = 0.001), TVR (12.7 vs. 4.0%, p = 0.005) and MACE (20.6 vs. 9.6%, p = 0.011) was significantly higher in the ATT group than the no ATT group. Patients with ATT had significantly higher incidence of cardiac death (5.6 vs. 0%, p < 0.001) than those without ATT even if they did not meet the diagnostic criteria of familial hypercholesterolemia. A multivariate model demonstrated that ATT was independently associated with the MACE at 1-year (Hazard ratio, 2.09; 95% Confidence Interval, 1.09-4.00, p = 0.026). The presence of ATT was independently associated with 1-year recurrence of cardiovascular events in patients with CAD undergoing PCI. Assessment of ATT might be useful for risk stratification of secondary cardiovascular events.

Novel volumetric analysis for stent expansion after drug-eluting stent implantation: An optical coherence tomography study.

OBJECTIVES: To assess the clinical significance of a novel optical coherence tomography (OCT)-derived volumetric parameter of stent expansion by comparing it with the conventional parameters in real-world practice. BACKGROUND: The clinical significance of novel parameters in real-world practice including longer and smaller stents remains to be elucidated. METHODS: A total of 226 de novo lesion treated with drug-eluting stents in 208 consecutive patients were enrolled. Stent expansion was retrospectively assessed on the final OCT images after stent implantation. The novel parameter was the minimum expansion index (MEI) calculated using a novel algorithm that yields the ideal lumen area in each frame by taking into account vessel tapering. The device-oriented clinical end point (DoCE) included cardiac death, target vessel-related myocardial infarction, ischemia-driven target lesion revascularization. RESULTS: The MEI in the lesions with a DoCE (n = 22) at 2 years and cases without a DoCE (n = 204) was 64.3 ± 12.0% and 78.5 ± 14.6%, respectively (p < .001). In the receiver operating characteristic curve analyses, the areas under the curve for the MEI (0.787; p < .001) were larger than that for %stent expansion (0.718; p = .001) and minimum stent area (0.664; p = .004) in predicting the DoCE. The best cutoff of MEI for predicting the DoCE was 74.0. CONCLUSIONS: The novel MEI was better than the conventional %stent expansion and minimum stent area for predicting DoCE.

Age- and Gender-Related Differences in Coronary Lesion Plaque Composition on Optical Coherence Tomography.

BACKGROUND: The pathophysiology and chronological course of atherosclerosis seems to be different between men and women due to biological differences, and age and gender differences in plaque composition of coronary lesions remain to be elucidated.Methods and Results:A total of 860 consecutive patients with a median age of 69 years (IQR, 60-78 years) who underwent optical coherence tomography (OCT) of culprit lesions was included. The composition of culprit plaque on OCT was compared between female (n=171) and male (n=689) subjects in younger (<70 years old) and elderly (≥70 years old) patients. In elderly patients, the prevalence of thin-cap fibroatheroma (TCFA) was significantly higher in women than in men (30.6 vs. 15.2%, P<0.001). In younger patients, the prevalence of large calcification was significantly higher in women than in men (60.0 vs. 32.8%, P<0.001). The prevalence of other vulnerable plaque characteristics (i.e., macrophages, microchannels, and spotty calcification), was similar between women and men. Elderly women had a significantly higher prevalence of TCFA (OR, 2.13; 95% CI: 1.33-3.44, P=0.002) than other patients. CONCLUSIONS: Women had a higher prevalence of TCFA and of large calcification than men in patients ≥70 and <70 years old, respectively. This may facilitate the understanding of gender differences in the pathogenesis of coronary atherosclerosis, and the tailoring of therapy and of prevention according to age and gender.

Physical exertion as a trigger of acute coronary syndrome caused by plaque erosion.

Distinct clinical characteristics have been demonstrated in patients with plaque erosion as compared with those with plaque rupture. We reasoned that greater physical activity might influence the onset of plaque erosion. In total, 97 consecutive patients with non ST-segment elevation acute coronary syndrome (ACS) who underwent optical coherence tomography (OCT) imaging of the culprit lesion were enrolled. OCT-determined culprit plaque characteristics were plaque erosion (18.6%), calcified plaque (26.8%), plaque rupture (32.0%) and other (22.7%). The physical activity evaluated by estimated metabolic equivalents (METs) at ACS onset was significantly greater in the plaque erosion group than in the plaque rupture group (3.3 ± 1.7 vs. 2.1 ± 1.0, p = 0.011). The rate of ACS onset outdoors was the highest (61.1%) in the plaque erosion group. The combination of greater physical activity (> 3 METs), outdoor onset and higher body mass index (> 25.1 kg/m2) had a significant odds ratio for the incidence of plaque erosion (odds ratio 15.0, 95% confidence interval 3.81 to 59.0, p < 0.001). Plaque erosion was associated with greater physical activity at the onset. This finding may help to further clarify the pathogenesis of ACS Impact of physical exertion on the incidence of plaque erosion. NSTE-ACS, non ST-segment elevation acute coronary syndrome.

Lipoprotein (a) levels and vulnerable characteristics in nonculprit plaque in patients with acute coronary syndrome.

Background: High plasma levels of Lp(a) are associated with a worse prognosis in patients with coronary artery disease. The aim of the present study is to clarify the association between high lipoprotein a [Lp(a)] levels and vulnerable characteristics of nonculprit plaques in patients with acute coronary syndrome (ACS). Methods: A total of 185 consecutive patients with ACS who underwent optical coherence tomography imaging of nonculprit plaques in the culprit vessels were enrolled. Patients were divided into the high Lp(a) group (≥30 mg/dL; 50 nonculprit plaques in 49 patients) or the low Lp(a) group (<30 mg/dL; 139 nonculprit plaques in 136 patients). Results: The prevalence of thin-cap fibroatheroma (TCFA) was significantly higher in the high Lp(a) group than in the low Lp(a) group (38.0 vs. 21.6%, p = 0.034). Multivariate logistic analysis demonstrated that a high Lp(a) level was independently associated with the prevalence of TCFA (odds ratio, 1.18; 95% confidence interval, 1.01-1.36; p = 0.033). The prevalence of TCFA was significantly higher in the high Lp(a) group than in the low Lp(a) group among patients with plaque erosion (50.0 vs. 9.4%, respectively; p = 0.027), although the difference was not statistically significant between the two groups in patients with plaque rupture. Conclusions: High Lp(a) levels were associated with a high prevalence of TCFA in nonculprit plaques among patients with ACS, particularly in patients with plaque erosion. The present results may partly explain the pathogenesis of worse clinical outcomes in patients with ACS and a high Lp(a) level as shown in clinical studies.

Impact of triglyceride levels on plaque characteristics in patients with coronary artery disease.

BACKGROUND: High triglyceride (TG) levels have been demonstrated to be a risk factor for coronary artery disease. This study aimed to clarify the impact of TG levels on the characteristics of coronary plaques. METHODS: A total of 850 consecutive patients who underwent optical coherence tomography (OCT) imaging of the culprit lesion were included. The morphologies of culprit plaques were compared between the higher TG group (nonfasting TG levels ≥150 mg/dL, n = 337) and the lower TG group (nonfasting TG <150 mg/dL, n = 513). RESULTS: The prevalence of lipid-rich plaques (43% vs. 33%, p = 0.005), thin-cap fibroatheromas (TCFAs) (24% vs. 17%, p = 0.015) and macrophages (40% vs. 31%, p = 0.006) was significantly higher in the higher TG group than in the lower TG group. In addition to a high low-density lipoprotein cholesterol (LDL-C) level (≥140 mg/dL), high TGs (≥150 mg/dL) were identified as an independent factor for the presence of TCFAs (odds ratio 1.465, 95% confidence interval 1.004-2.137, p = 0.048). Among patients with lower LDL-C levels (<100 mg/dL), the prevalence of macrophages (38% vs. 26%, p = 0.007) and layered plaques (48% vs. 38%, p = 0.019) was significantly higher in the higher TG group than in the lower TG group. CONCLUSIONS: Higher TG levels were associated with a higher prevalence of TCFAs in culprit coronary lesions. The prevalence of macrophages and layered plaques was more frequently observed in patients with higher TGs than those with lower TGs among patients with LDL-C < 100 mg/dL.

Lower levels of low-density lipoprotein cholesterol are associated with a lower prevalence of thin-cap fibroatheroma in statin-treated patients with coronary artery disease.

BACKGROUND: Reducing low-density lipoprotein cholesterol (LDL-C) levels with statins slows the progression of atherosclerotic plaques and reduces cardiovascular events. The 2019 European Society of Cardiology/European Atherosclerosis Society guidelines recommend absolute LDL-C treatment targets of <100 mg/dL, <70 mg/dL and <55 mg/dL according to coexisting patient risk factors. OBJECTIVE: To clarify the difference in the plaque characteristics of coronary lesions associated with these LDL-C levels in statin-treated patients. METHODS: A total of 685 consecutive statin-treated patients with coronary artery disease (CAD) who underwent optical coherence tomography (OCT) imaging of culprit lesions were enrolled. The characteristics of culprit plaques evaluated by OCT were compared among the high LDL-C group (≥100 mg/dL, n=247), the moderate LDL-C group (70-100 mg/dL, n=289), the low LDL-C group (55-70 mg/dL, n=106) and the very low LDL-C group (<55 mg/dL, n=43). RESULTS: A significant trend toward a lower prevalence of thin-cap fibroatheroma (TCFA) associated with the LDL-C groups was observed (23.1, 18.3, 9.4 and 11.6%, respectively, in each group; p=0.002). A trend toward a lower prevalence of TCFAs associated with the LDL-C groups was also observed among patients with lower hemoglobin A1c (<6.2%; p=0.003). LDL-C <70 mg/dL (the low/very low group) was independently associated with the lack of TCFAs (odds ratio, 0.50; 95% confidence interval, 0.27-0.87, p=0.014). CONCLUSIONS: Lower LDL-C levels were associated with a lower prevalence of TCFAs in culprit plaques among statin-treated patients with CAD.

Endothelial glycocalyx and severity and vulnerability of coronary plaque in patients with coronary artery disease.

BACKGROUND AND AIMS: Endothelial glycocalyx covers the endothelium and maintains vascular integrity. However, its association with the severity and vulnerability of coronary artery disease (CAD) remains to be elucidated. METHODS: A total of 259 consecutive patients with stable CAD requiring percutaneous coronary intervention (PCI) were prospectively enrolled. Patients were classified into 2 groups according to the median value of serum syndecan-1, which is a core component of the endothelial glycocalyx (lower syndecan-1 group [syndecan-1 <99.0 ng/mL], n = 130; higher syndecan-1 group [syndecan-1 ≥99.0 ng/mL], n = 129). Severity of CAD and focal plaque vulnerability in culprit lesion were evaluated using angiography and optical coherence tomography. RESULTS: There was no significant difference in clinical characteristics between the lower syndecan-1 group and the higher syndecan-1 group other than the prevalence of family history of CAD (19 vs. 32%, p = 0.022), prior PCI history (45 vs. 60%, p = 0.015) and estimated glomerular filtration rate (57.8 ± 17.2 vs. 50.9 ± 25.6 ml/min/1.73 m2, p = 0.011). Although disease severity on angiogram was comparable between the 2 groups, the prevalence of lipid-rich plaque (40 vs. 19%, p = 0.004) and thin-cap fibroatheroma (20 vs. 6%, p = 0.006) was significantly higher in the lower syndecan-1 group than the higher syndecan-1 group. Lower syndecan-1 level was independently associated with higher prevalence of lipid-rich plaque (odds ratio 3.626, 95% confidence interval 1.535-8.566, p = 0.003). CONCLUSIONS: Lower syndecan-1 level was associated with higher prevalence of vulnerable plaque in patients with CAD. This finding suggests the association between impaired endothelial glycocalyx and the development of vulnerable plaque.

Incidence, factors, and clinical significance of cholesterol crystals in coronary plaque: An optical coherence tomography study.

BACKGROUND AND AIMS: Intraplaque cholesterol crystal (CC) is recognized as a component of vulnerable plaques. However, the clinical characteristics of patients with CC and the impact of CC on clinical events remain unknown. METHODS: A total of 340 consecutive patients who underwent optical coherence tomography (OCT) imaging of culprit lesions were included in the study. CC was defined as a thin linear structure with high reflectivity and low signal attenuation on OCT images. The incidence of major adverse cardiovascular events (MACE) at 1-year was compared between patients with CC (CC group) and those without CC (non-CC group). MACE included cardiac death, non-fatal myocardial infarction, target vessel revascularization (TVR), and non-TVR (NTVR). RESULTS: CC was observed in 29% (n = 98) of the patients. There was no significant difference in baseline clinical characteristics between the CC and non-CC groups, other than in eicosapentaenoic acid (EPA)/arachidonic acid (AA) ratio (0.39 ±â€¯0.29 vs. 0.47 ±â€¯0.33, p = 0.047) and hemoglobin A1c (HbA1c) levels (6.51 ±â€¯0.97 vs. 6.25 ±â€¯0.87%, p = 0.016). The incidence of MACE and NTVR at 1-year was significantly higher in the CC group than in the non-CC group (15.3 vs. 7.9%, P = 0.038; 8.1 vs. 2.5%, p = 0.017). The presence of CC was significantly associated with a higher rate of 1-year MACE (odds ratio 4.78, confidential interval 2.02-10.10, p < 0.001). CONCLUSIONS: Patients with CC in the culprit lesion had higher HbA1c and lower EPA/AA than patients without CC. The 1-year clinical outcomes in patients with CC in the culprit lesion were worse than in those without CC.

Lipoprotein (a) level is associated with plaque vulnerability in patients with coronary artery disease: An optical coherence tomography study.

BACKGROUND: High lipoprotein (a) [Lp(a)] levels are an independent factor for worse prognosis in patients with coronary artery disease (CAD). However, the association between serum Lp(a) level and coronary plaque vulnerability remains to be determined. METHODS: A total of 255 consecutive patients with CAD who underwent optical coherence tomography imaging of culprit lesions were included. Patients were divided into 2 groups according to their Lp(a) levels (the higher Lp(a) group [≥25 mg/dL], n = 87; or the lower Lp(a) group [<25 mg/dL], n = 168). RESULTS: The prevalence of thin-cap fibroatheroma (TCFA) was significantly higher in the higher Lp(a) group than in the lower Lp(a) group (23% [n = 20] vs. 11% [n = 19], p = 0.014). Although the prevalence of TCFA was comparable between the 2 groups among patients with a lower LDL cholesterol (LDL-C) level (<100 mg/dL), TCFA was significantly more prevalent in the higher Lp(a) group than in the lower Lp(a) group (39% [14/36] vs. 10% [5/50], p = 0.001) among patients with a higher LDL-C level (≥100 mg/dL). CONCLUSIONS: A higher Lp(a) level was associated with a higher frequency of TCFA, particularly in patients with a higher LDL-C level.

Detection of mixed clarithromycin-resistant and -susceptible Helicobacter pylori using nested PCR and direct sequencing of DNA extracted from faeces.

The major cause of chemotherapy failure in patients with chronic gastritis and peptic ulcers caused by Helicobacter pylori is clarithromycin (CAM) resistance due to a mutation in the 23S rRNA gene. This study describes a non-invasive and accurate method for the detection of mixed CAM-resistant and -susceptible H. pylori by sequencing of the H. pylori 23S rRNA gene. Faeces were crushed with beads and the 23S rRNA gene was amplified using a nested PCR on the extracted DNA. Mutation analysis of this gene using this method showed that 20.4 % of patients carried mixed CAM-susceptible (wild type) and -resistant (A2142G or A2143G mutant) H. pylori. Furthermore, it was found that 66.6 % of patients who had been treated unsuccessfully carried one of these mutations in the 23S rRNA gene (including the mixed type), whilst standard culture detected CAM-resistant isolates in only 22.2 % of patients with unsuccessful treatment. These data suggest that, for successful therapy, the diagnosis method described here would more accurately detect CAM-resistant H. pylori, including mixed infections.