Adverse events associated with early initiation of Eplerenone in patients hospitalized for acute heart failure.

BACKGROUND: The guidelines recommend the initiation or up-titration of heart failure (HF) treatments following an HF hospitalization; however, concerns about adverse events may limit the use of mineralocorticoid receptor antagonists (MRAs). Patient profiles or disease severity might impact adverse events associated with MRA therapy in acute HF. METHODS: The EARLIER trial included patients with acute HF who were randomized to eplerenone or placebo over 6 months. Adverse events (i.e., worsening renal function [WRF], hyperkalemia, hypotension, and volume depletion/dehydration) were assessed. HF-related outcome included a composite of all-cause mortality, HF re-hospitalization, investigator-reported worsening HF and out-of-hospital diuretic intensification. RESULTS: In 297 patients (mean age: 67 ± 13 years; 73% males), adverse events were observed: 44.4% experienced WRF (>20% drop in estimated glomerular filtration rate[eGFR] and/or investigator-reported WRF), 8.4% had hyperkalemia (potassium >5.5 mmol/L and/or investigator-reported hyperkalemia), 27.9% experienced hypotension (systolic blood pressure[SBP] <90 mmHg and/or investigator-reported hypotension), and 16.8% had investigator-reported volume depletion/dehydration. Eplerenone vs. placebo did not elevate the incidence of these events (all-p-values>0.0 5). Multivariable analyses revealed that, irrespective of treatment allocation, older age (>7 5 years), prevalent diabetes, symptomatic congestion, and microalbuminuria were associated with increased risk of WRF. Baseline eGFR<60 ml/min/1.73m2 and SBP < 90 mmHg predicted hyperkalemia and hypotension, respectively, while older patients were more likely to experience volume depletion/dehydration. However, these patient profiles did not alter the benefit of eplerenone on outcomes (HR [9 5%CI] = 0.53 [0.29 to 0.97], P = 0.04; all-p-for-interaction>0.10). CONCLUSION: Eplerenone did not increase adverse events compared with placebo in acute HF. Importantly, disease severity and comorbidity burden greatly influence adverse events, but not benefit from eplerenone.

Lifelong Heterogeneous Contribution of Cardiovascular Risk Factors to Slow and Fast Progression of Arterial Stiffness.

BACKGROUND: Although some cardiovascular risk factors (CVRFs) are known to be associated with increased arterial stiffness, increased arterial stiffness does not mediate the cardiovascular risk associated with all CVRFs. Here, based on long-term repeated-measurement data, we examined the association of the lifelong status of each CVRF with the rate of progression of arterial stiffness. METHODS: We utilized the data from annual health checkups with the brachial-ankle pulse wave velocity measurements over a 16-year period in middle-aged Japanese occupational cohort. RESULTS: Totally, 29 090 brachial-ankle pulse wave velocity data were obtained during the follow-up of 3763 subjects ranging in age from around 30 to 70 years. Smoking, heavy alcohol intake, hypertension, diabetes, hypertriglyceridemia, and hyperuricemia were independently associated with the fast progression of arterial stiffness. Also, lower values in nondisease range in blood pressure, glycosylated hemoglobin A1c, triglyceride, and uric acid were independently associated with the slow progression of arterial stiffness. For body mass index and low-density lipoprotein cholesterol, no clear associations with the progression of arterial stiffness were observed. CONCLUSIONS: The present prospective study provided more robust epidemiological evidence for the heterogeneity of the significance of contribution of lifelong status of each CVRF to the slow and fast rate of progression of arterial stiffness. These findings suggest the important need to examine, in further studies, the effects of global early interventions to control the levels of the culprit CVRFs, even from middle age, not only to prevent a fast progression of the arterial stiffness but also to maintain a relatively slow progression of arterial stiffness.

Effects of caffeine on fractional flow reserve values measured using intravenous adenosine triphosphate.

We investigated the effects of caffeine intake on fractional flow reserve (FFR) values measured using intravenous adenosine triphosphate (ATP) before cardiac catheterization. Caffeine is a competitive antagonist for adenosine receptors; however, it is unclear whether this antagonism affects FFR values. Patients were evenly randomized into 2 groups preceding the FFR study. In the caffeine group (n = 15), participants were given coffee containing 222 mg of caffeine 2 h before the catheterization. In the non-caffeine group (n = 15), participants were instructed not to take any caffeine-containing drinks or foods for at least 12 h before the catheterization. FFR was performed in patients with more than intermediate coronary stenosis using the intravenous infusion of ATP at 140 µg/kg/min (normal dose) and 170 µg/kg/min (high dose), and the intracoronary infusion of papaverine. FFR was followed for 30 s after maximal hyperemia. In the non-caffeine group, the FFR values measured with ATP infusion were not significantly different from those measured with papaverine infusion. However, in the caffeine group, the FFR values were significantly higher after ATP infusion than after papaverine infusion (P = 0.002 and P = 0.007, at normal and high dose ATP vs. papaverine, respectively). FFR values with ATP infusion were significantly increased 30 s after maximal hyperemia (P = 0.001 and P < 0.001 for normal and high dose ATP, respectively). The stability of the FFR values using papaverine showed no significant difference between the 2 groups. Caffeine intake before the FFR study affected FFR values and their stability. These effects could not be reversed by an increased ATP dose.

Platypnea-orthodeoxia Syndrome in a Patient with an Atrial Septal Defect: The Diagnosis and Choice of Treatment.

A 77-year-old woman developed dyspnea over three years which occurred during sitting, standing or walking. Her physical examination, chest X-ray, ECG and cardiac catheterization results were all normal. A marked fall in arterial oxygen saturation was observed on sitting or standing. Transesophageal echocardiography showed an increase of right to left shunt flow on sitting. The patient was diagnosed with platypnea-orthodeoxia syndrome and underwent the surgical closure of an atrial septal defect of 19 mm in diameter. After the surgery, the patient's POS symptoms were completely resolved. She was discharged and followed at the outpatient clinic. Her post-treatment course was uneventful.

Diagnostic Performance of a Cadmium-Zinc-Telluride Single-Photon Emission Computed Tomography System With Low-Dose Technetium-99m as Assessed by Fractional Flow Reserve.

BACKGROUND: Although stress single-photon emission computed tomography (SPECT) using a cadmium-zinc-telluride (CZT) camera facilitates radiation dose reduction, only a few studies have evaluated its diagnostic accuracy in Japanese patients by applying fractional flow reserve (FFR) measurements. METHODS AND RESULTS: We prospectively evaluated 102 consecutive patients with suspected or known coronary artery disease with a low-dose stress/rest protocol ((99m)Tc radiotracer 185/370 MBq) using CZT SPECT. Within 3 months, coronary angiography was performed and a significant stenosis was defined as ≥90% diameter narrowing on visual estimation, or as a lesion of <90% and ≥ 50% stenosis with FFR ≤0.80. To detect individual coronary stenosis, the respective sensitivity, specificity, and accuracy were 86%, 75%, and 82% for left anterior descending artery stenosis, 76%, 81%, and 79% for left circumflex artery stenosis, and 87%, 92%, and 90% for right coronary artery stenosis. When limited to 92 intermediate stenotic lesions in which FFR was measured, stress SPECT showed 77% sensitivity, 91% specificity, and 84% accuracy, whereas the diagnostic value decreased to 52% sensitivity, 68% specificity, and 58% accuracy based only on visual estimation of ≥75% diameter narrowing. CONCLUSIONS: CZT SPECT demonstrated a good diagnostic yield in detecting hemodynamically significant coronary stenoses as assessed by FFR, even when using a low-dose (99m)Tc protocol with an effective dose ≤5 mSv. (Circ J 2016; 80: 1217-1224).

Papaverine-induced polymorphic ventricular tachycardia during coronary flow reserve study of patients with moderate coronary artery disease.

BACKGROUND: Papaverine is useful for evaluating the functional status of a coronary artery, but it may provoke malignant ventricular arrhythmia (VA). The aim of this study was to investigate the incidence, and clinical and ECG characteristics of patients with papaverine-induced VAs. METHODS AND RESULTS: The 182 consecutive patients underwent fractional flow reserve (FFR) measurement of 277 lesions. FFR was determined after intracoronary papaverine administration by standard procedures. The clinical and ECG characteristics were compared between patients with and without ventricular tachycardia (VT: ≥3 successive premature ventricular beats (PVBs), or ventricular fibrillation (VF)). After papaverine administration, the QTc interval, QTUc interval, and T-peak to U-end interval were prolonged significantly. Single PVBs on the T-wave or U-wave type developed in 29 patients (15.9%). Polymorphic VT (torsade de pointes) occurred in 5 patients (2.8%), and of those, VF developed in 3 patients (1.7%). No clinical and baseline ECG parameters were predictors for VT or VF except for sex and administration of papaverine into the left coronary artery. Excessive prolongation of QT (or QTU), T-peak to U-end intervals and giant T-U waves were found immediately prior to the ventricular tachyarrhythmias (VTAs), which were unpredictable from the baseline data. CONCLUSIONS: Intracoronary administration of papaverine induced fatal VTAs, although the incidence is rare. Excessive prolongation of the QT (and QTU) interval appeared prior to VTAs; however, they were unpredictable.

Severe obstructive sleep apnea increases left atrial volume independently of left ventricular diastolic impairment.

PURPOSE: Severe obstructive sleep apnea (OSA) directly impairs left ventricular (LV) diastolic function. Left atrial volume index (LAVI), an independent predictor of future cardiovascular events, is also related to OSA severity. This study aimed to assess whether OSA is associated with an increase in LAVI independently of LV diastolic function. METHODS: Two hundred six OSA patients (apnea hypopnea index, AHI ≥ 5/h) without cardiac disease, hypertension, and diabetes were enrolled. They underwent overnight fully attended polysomnography and 2-dimensional echocardiography in order to estimate LA volumes and LV diastolic function which was assessed by the ratio of transmitral early diastolic flow velocity to late diastolic flow velocity (E/A), deceleration time, and mitral annular velocity (e') which was derived from tissue Doppler imaging. Patients were divided into two groups based on AHI, namely, group M (5 ≤ AHI < 30/h) and group S (AHI ≥ 30/h). RESULTS: The LAVI value in group S was significantly larger than that in group M (20 ± 5 vs. 23 ± 5 mL/m(2), P < 0.001). E/A in group S was significantly lower than that in group M (P < 0.001), whereas the ratio of E to e' (E/e') in group S was significantly higher than that in group M (P < 0.001). AHI showed a statistically significant correlation with LAVI (P < 0.001). On multivariate linear regression analysis, severe OSA was independently related with LAVI even after adjusting for age, sex, systolic blood pressure, body mass index, and measurements of LV diastolic function (P = 0.04). CONCLUSIONS: Severe OSA itself might directly increase LAVI, independently of LV diastolic function.

Diagnostic performance of a novel cadmium-zinc-telluride gamma camera system assessed using fractional flow reserve.

BACKGROUND: Although the novel cadmium-zinc-telluride (CZT) camera system provides excellent image quality, its diagnostic value using thallium-201 as assessed on coronary angiography (CAG) and fractional flow reserve (FFR) has not been validated. METHODS AND RESULTS: To evaluate the diagnostic accuracy of the CZT ultrafast camera system (Discovery NM 530c), 95 patients underwent stress thallium-201 single-photon emission computed tomography (SPECT) and then CAG within 3 months. Image acquisition was performed in the supine and prone positions after stress for 5 and 3 min, respectively, and in the supine position at rest for 10 min. Significant stenosis was defined as ≥90% diameter narrowing on visual estimation, or a lesion with <90% and ≥50% stenosis and FFR ≤0.75. To detect individual coronary stenosis, the respective sensitivity, specificity, and accuracy were 90%, 64%, and 78% for left anterior descending coronary artery stenosis, 78%, 84%, and 81% for left circumflex stenosis, and 83%, 47%, and 60% for right coronary artery (RCA) stenosis. The combination of prone and supine imaging had a higher specificity for RCA disease than supine imaging alone (65% vs. 47%), with an improvement in accuracy from 60% to 72%. CONCLUSIONS: Using thallium-201 with short acquisition time, combined with prone imaging, CZT SPECT had a high diagnostic yield in detecting significant coronary stenosis as assessed using FFR.

[Cardiovascular magnetic resonance imaging].

Cardiac magnetic resonance imaging (CMR) evolves and is occupying an important status in cardiovascular diagnostic imaging. In particular, in the estimation of the cause of heart failure, or evaluation of severity-of-illness and prognostic presumption, utility is high clinically. In this chapter, about a selection sequence for taking image according to the purpose, description of findings, and its clinical utility are introduced. And the role which this imaging plays will be discussed in the near future.

Arterial stiffness/central hemodynamics, renal function, and development of hypertension over the short term.

OBJECTIVES: We examined the following: whether the estimated glomerular filtration rate calculated from the serum cystatin C levels (eGFRcys) and the brachial-ankle pulse wave velocity (baPWV) might be independent predictors of the development of hypertension over the short term, without any interaction; whether the baPWV may be directly associated with the development of hypertension without the mediation of the arterial stiffness-related acceleration of renal functional decline; whether the second peak of the radial pressure waveform (SP2) might also be a significant independent predictor of the development of hypertension. METHODS: In 1229 middle-aged normotensive Japanese men with preserved renal function, the baPWV, SP2 and eGFRcys were measured at the baseline and at the end of the 3-year study period. RESULTS: Hypertension was detected at the end of the 3-year study period in 127 men. The logistic regression analysis with adjustments demonstrated significant independent odds ratios of the baPWV and eGFRcys for the presence of hypertension at the end of the 3-year study period, without any interaction. When entered simultaneously in this model, the SP2 also showed a significant odds ratio. General linear model analysis revealed that none of the baPWV or SP2 measured at the baseline was related to the renal function assessed at the end of the 3-year study period. CONCLUSIONS: The mechanisms underlying the association between arterial stiffness/central hemodynamics and the short-term development of hypertension appear to differ from those underlying the association between kidney function and the short-term development of hypertension.

Relationship between flow-mediated vasodilation and cardiovascular risk factors in a large community-based study.

OBJECTIVE: To determine the relationships between flow-mediated vasodilation (FMD) and cardiovascular risk factors, and to evaluate confounding factors for measurement of FMD in a large general population in Japan. METHODS: This was a cross-sectional study. A total of 5314 Japanese adults recruited from people who underwent health screening from 1 April 2010 to 31 August 2012 at 3 general hospitals in Japan. Patients' risk factors (age, Body Mass Index, blood pressure, cholesterol parameters, glucose level and HbA1c level) and prevalence of cardiovascular disease (coronary heart disease and cerebrovascular disease) were investigated. RESULTS: Univariate regression analysis revealed that FMD correlated with age (r=-0.27, p<0.001), Body Mass Index (r=-0.14, p<0.001), systolic blood pressure (r=-0.18, p<0.001), diastolic blood pressure (r=-0.13, p<0.001), total cholesterol (r=-0.07, p<0.001), triglycerides (r=-0.10, p<0.001), high-density lipoprotein cholesterol (r=0.06, p<0.001), low-density lipoprotein cholesterol (r=-0.04, p=0.01), glucose level (r=-0.14, p<0.001), HbA1c (r=-0.14, p<0.001), and baseline brachial artery diameter (r=-0.43, p<0.001) as well as Framingham Risk score (r=-0.29, p<0.001). Multivariate analysis revealed that age (t value=-9.17, p<0.001), sex (t value=9.29, p<0.001), Body Mass Index (t value=4.27, p<0.001), systolic blood pressure (t value=-2.86, p=0.004), diabetes mellitus (t value=-4.19, p<0.001), smoking (t value=-2.56, p=0.01), and baseline brachial artery diameter (t value=-29.4, p<0.001) were independent predictors of FMD. CONCLUSIONS: FMD may be a marker of the grade of atherosclerosis and may be used as a surrogate marker of cardiovascular outcomes. Age, sex, Body Mass Index, systolic blood pressure, diabetes mellitus, smoking and, particularly, baseline brachial artery diameter are potential confounding factors in the measurement of FMD.

Relationship of SYNTAX score to myocardial ischemia as assessed on myocardial perfusion imaging.

BACKGROUND: Although the Synergy between Percutaneous Coronary Intervention with Taxus and Cardiac Surgery (SYNTAX) score is used to characterize coronary anatomy based on 9 anatomic criteria such as lesion location and complexity, the relationship between SYNTAX score and myocardial ischemia has yet to be elucidated. METHODS AND RESULTS: A total of 158 consecutive patients with suspected or known coronary artery disease (CAD), who underwent both (99m)Tc-sestamibi single-photon emission computed tomography (SPECT) and coronary angiography, were evaluated. Stress SPECT was assessed using a 17-segment model, and the percentage of the myocardial defect scores (DS) was calculated. In 37 patients with intermediate-high SYNTAX scores (>22), the number of men and the prevalence of multi-vessel CAD were significantly higher, and the % stress and ischemic DS were significantly greater than in 121 patients with low SYNTAX scores (≤22). Coronary risk factors, however, were similar between the 2 groups. The % stress and ischemic DS significantly correlated with SYNTAX score. In patients with a low SYNTAX score, % stress and ischemic DS also significantly correlated with the SYNTAX score, whereas no such correlation was observed in the intermediate-high SYNTAX score group. CONCLUSIONS: SYNTAX score correlated well with myocardial ischemia as assessed on stress SPECT in general. The higher the SYNTAX score, however, the less clear was the correlation with the extent of myocardial ischemia.

Correlation between Helicobacter pylori infection and low-dose aspirin use on damage of the upper gastrointestinal tract.

BACKGROUND AND AIM: Low-dose aspirin (LDA), and Helicobacter pylori (HP) infection are considered the two primary causes of peptic ulceration. The interaction between HP infection and non-steroidal anti-inflammatory drugs is, however, a matter of considerable discussion and controversy. In this study, we investigated possible synergistic or negative interactions between HP infection and LDA in gastric mucosal lesions, according to lesion site. METHODS: The subjects were 120 patients attending the Cardiology Outpatients Department (average age, 67.1 ± 8.9 years; male : female ratio 2.9:1). Endoscopic findings were graded using the Modified Lanza score. Lesions were scored for the antral, body and fundal regions. Ulcers were defined as mucosal defects ≥ 5 mm in size. RESULTS: There were 55 HP-positive and 65 HP-negative subjects, and 91 subjects on LDA therapy. The gastric antral Lanza scores were HP(-) LDA(-): 0.2 ± 1.6, HP(-) LDA(+): 1.8 ± 1.5, HP(+) LDA(-): 0.3 ± 0.7, and HP(+) LDA(+): 0.5 ± 1.0. The gastric body and fundal Lanza scores were 0.0 ± 0.0, 0.8 ± 0.9, 0.4 ± 1.1, and 1.0 ± 1.5, respectively, and 0.1 ± 0.3, 0.5 ± 0.9, 0.1 ± 0.3, and 0.1 ± 0.3, respectively. Variance analysis of the correlation between HP infection and LDA by regional Lanza scores identified both HP infection and LDA use as factors that significantly influence the antral Lanza score. However, LDA was an aggressive factor, and HP infection a protective factor. In the gastric body, LDA was a non-significant, and HP infection a significant, aggressive factor. In the gastric fundus, neither HP infection nor LDA was a significant factor (LDA was an aggressive factor, and HP infection a protective factor). CONCLUSIONS: LDA had aggressive effects in all gastric lesions; on the other hand, HP infection had protective effects in the antrum and fundus in the stomach, and aggressive effects in the body in the stomach.

Postischemic myocardial stunning is superior to transient ischemic dilation for detecting multivessel coronary artery disease.

BACKGROUND: Although poststress myocardial stunning is regarded as a marker for severe coronary artery disease (CAD), no study has yet compared the diagnostic value of poststress stunning with transient ischemic dilation (TID) of the left ventricle (LV) for detecting multivessel CAD. METHODS AND RESULTS: A total of 271 patients with suspected or known CAD underwent adenosine triphosphate (ATP) loading and at-rest gated single-photon emission computed tomography. We assessed myocardial perfusion with a 20-segment model, and analyzed the changes in LV volumetric analysis induced by ATP and an automatically derived TID ratio. In 147 patients with multivessel CAD, the prevalence of multi-territorial ischemia was higher, and the post-ATP increase in end-systolic volume (ESV) and TID ratio were greater, than in the 124 with insignificant or single-vessel CAD (P<0.0001, for all cases). The receiver-operating characteristic curves analysis revealed cutoff values for ESV of 5 ml and a TID ratio of 1.11. Multivariate logistic regression analysis revealed that the combination of a poststress increase in ESV of ≥5 ml and multi-territorial ischemia best identified multivessel CAD, with a sensitivity of 78% and a specificity of 84%, whereas the TID ratio was not shown to be an independent predictor. CONCLUSIONS: Post-ATP stress myocardial stunning is superior to the TID ratio for detecting multivessel CAD.

Gastric mucosal damage evaluated by transnasal endoscopy and QOL assessments in ischemic heart disease patients receiving low-dose aspirin.

OBJECTIVE: Transnasal endoscopy was conducted to examine gastric mucosal damage in Japanese patients with ischemic heart disease who were receiving low-dose aspirin for preventing the onset or recurrence of cardiovascular disease. PATIENTS AND METHODS: An endoscopist assessed gastric mucosal damage. Furthermore, the MOS 36-Item Short-Form Health Survey (SF-36(®)) and the Gastrointestinal Symptom-Rating Scale (GSRS) were used to assess the outcomes of their quality of life (QOL) and the possible presence of gastric cancer and H. pylori infection. RESULTS: Seventy-five patients were studied; and 24 (32.0%) and 16 (21.3%) of them concurrently received antithrombotic drugs other than aspirin and antiulcer drugs, respectively. Regarding gastric mucosal damage, 15 (20.0%) and 8 (10.7%) of the patients were endoscopically diagnosed with ulcer and hemorrhagic gastritis, respectively. Furthermore, 5 patients (6.7%) were found to have esophageal or gastric cancer. The positivity rate of Helicobacter pylori (H. pylori) was 45.3%. Patients receiving low-dose aspirin showed a decreased QOL. Consequently, no significant differences were found among the groups. Regarding endoscopic findings, no differences were found in the scores of both SF-36(®) and GSRS with respect to the presence or absence of gastric ulcer, hemorrhagic gastritis, and H. pylori infection. CONCLUSION: Transnasal endoscopy was possible to perform during the oral intake of low-dose aspirin without causing any hemorrhagic complications. Many patients with gastric mucosal lesions showed no subjective symptom, and patients receiving aspirin were strongly recommended to undergo regular transnasal endoscopy, regardless of the presence or absence of symptoms.

Severe obstructive sleep apnea increases cystatin C in clinically latent renal dysfunction.

BACKGROUND: Obstructive sleep apnea (OSA) increases the risk of cardiovascular disease (CVD) and has been reported to be associated with chronic kidney disease (CKD). Recent studies have demonstrated that cystatin C is a prognostic biomarker of the risk of death and CVD even in patients without established CKD. METHODS: In a cross-sectional study, we enrolled 267 consecutive OSA patients without CKD who had an apnea-hypopnea index (AHI) ≥ 5 events per hour in overnight polysomnography. CKD was defined as an estimated glomerular filtration rate (eGFR) < 60 mL/min/1.73 m(2) according to the modification of diet in renal disease (MDRD) equation (modified for Japanese). Serum cystatin C levels were measured in all patients. RESULTS: Cystatin C was significantly correlated with age (r = 0.37), body mass index (BMI) (r = 0.12), AHI (r = 0.17), C-reactive protein (CRP) (r = 0.12), and Brachial-ankle pulse wave velocity (r = 0.18). Logistic regression analysis demonstrated that severe OSA defined by an AHI ≥ 30 events per hour was an independent variable for the highest quartiles of serum cystatin C levels (≥0.88 mg/L) (OR: 2.04, 95% CI: 1.04-4.01, P = 0.04) even after adjustment for age, BMI ≥ 25, hypertension, and diabetes mellitus. CONCLUSIONS: This study indicates that severe OSA independently increases serum cystatin C levels in patients without CKD. Cystatin C is considered to be a biomarker that reflects both clinically latent renal dysfunction and cardiovascular risk that are influenced by OSA.

[Vascular calcification and serum markers].

Recently, the multidetector computed tomography (CT) is available to measure quantitative analysis of coronary vascular calcification (coronary calcification score [CACscore]). Vascular calcification is recognized not only in the end stage of atherosclerosis but also in the early stage of atherosclerosis. Recent data suggested that bone- related factors are closely related to coronary artery disease and vascular calcification. In this review, we discuss for regulatory mechanisms of vascular calcification.

Impact of upper gastrointestinal lesions in patients on low-dose aspirin therapy: preliminary study.

BACKGROUND AND AIMS: We investigated the incidence of upper gastrointestinal lesions in the esophagus, stomach and duodenum in patients on low-dose aspirin (LDA) therapy. METHODS: The subjects were 101 consecutive outpatients who had been on LDA therapy (average age 67.2 +/- 8.3 years; male : female ratio 3.8:1). All subjects underwent endoscopy without ceasing their antiplatelet or anticoagulant therapy. We investigated the rates of endoscopic peptic ulcer, reflux esophagitis (RE) and malignant lesion. RESULTS: RE was detected in eight subjects and esophageal ulcer in one subject. The severity of RE, according to the Los Angeles classification, was grade A in one subject, B in four, C in two and D in one. All nine subjects (8.9%) with RE and esophageal ulcer were negative for Helicobacter pylori infection. Gastric ulcer was detected in 12 subjects (six H. pylori positive, six negative) and duodenal ulcer in four (one H. pylori positive, three negative). The incidence of gastroduodenal ulcer was 15.8% (16/101). The incidence of esophageal and gastric cancers was high at 5.9% (6/101). Subjects were surveyed using the gastrointestinal symptom rating scale, with no differences in scores for acid reflux, abdominal pain or indigestion according to the presence or absence of RE, gastric ulceration or duodenal ulceration. CONCLUSION: Upper gastrointestinal mucosal injuries and neoplasm were found in not only the stomach, but also the esophagus and duodenum in LDA taking subjects. These results emphasize the importance of endoscopic surveillance in patients on LDA therapy.