A Case of Isolated Superior Mesenteric Artery Dissection Resulting in Recurrent Necrosis of the Small Intestine.

Isolated superior mesenteric artery dissection (ISMAD) is a rare cause of acute abdominal conditions. Most cases of ISMAD have a favorable prognosis, and only a few cases of ISMAD-associated intestinal necrosis have been reported. A 75-year-old male was referred to our department because of abdominal pain and portal venous gas detected on imaging. Computed tomography suggested ileal necrosis, necessitating emergency surgery. Indocyanine green was used for blood flow assessment; however, no fluorescence was observed in the ileum proximal to the Bauhin valve, leading to the decision for ileocecal resection. On postoperative day 6, abdominal pain recurred when meals were resumed. As a surgical intervention for ISMAD, a bypass was created using the left great saphenous vein as a graft between the superior mesenteric artery and the right external iliac artery. This case highlights a rare occurrence where intestinal necrosis recurred due to ISMAD. We propose that in cases of ISMAD with concomitant intestinal necrosis, a more aggressive revascularization strategy for the dissected segment of the superior mesenteric artery may be required.

Development of a micronucleus test using the EpiAirway™ organotypic human airway model.

BACKGROUND: The use of organotypic human tissue models in genotoxicity has increased as an alternative to animal testing. Genotoxicity is generally examined using a battery of in vitro assays such as Ames and micronucleus (MN) tests that cover gene mutations and structural and numerical chromosome aberrations. At the 7th International Workshop on Genotoxicity Testing, working group members agreed that the skin models have reached an advanced stage of maturity, while further efforts in liver and airway models are needed [Pfuhler et al., Mutat. Res. 850-851 (2020) 503135]. Organotypic human airway model is composed of fully differentiated and functional respiratory epithelium. However, because cell proliferation in organotypic airway models is thought to be less active, assessing their MN-inducing potential is an issue, even in the cytokinesis-blocking approach using cytochalasin B (CB) [Wang et al., Environ. Mol. Mutagen. 62 (2021) 306-318]. Here, we developed a MN test using EpiAirway™ in which epidermal growth factor (EGF) was included as a stimulant of cell division. RESULTS: By incubating EpiAirway™ tissue with medium containing various concentrations of CB, we found that the percentage of binucleated cells (%BNCs) almost plateaued at 3 µg/mL CB for 72 h incubation. Additionally, we confirmed that EGF stimulation with CB incubation produced an additional increase in %BNCs with a peak at 5 ng/mL EGF. Transepithelial electrical resistance measurement and tissue histology revealed that CB incubation caused the reduced barrier integrity and cyst formation in EpiAirway™. Adenylate kinase assay confirmed that the cytotoxicity increased with each day of culture in the CB incubation period with EGF stimulation. These results indicated that chemical treatment should be conducted prior to CB incubation. Under these experimental conditions, it was confirmed that the frequency of micronucleated cells was dose-dependently increased by apical applications of two clastogens, mitomycin C and methyl methanesulfonate, and an aneugen, colchicine, at the subcytotoxic concentrations assessed in %BNCs. CONCLUSIONS: Well-studied genotoxicants demonstrated capability in an organotypic human airway model as a MN test system. For further utilization, investigations of aerosol exposure, repeating exposure protocol, and metabolic activation are required.

Indirect cholecystoduodenal fistula via hepatoduodenal ligament secondary to gangrenous cholecystitis: a case report.

BACKGROUND: Cholecystoduodenal fistula is an infrequent complication of gallbladder diseases. In the majority of cases, the fistula is formed by direct communication between the gallbladder and duodenum due to gallstone impaction in the gallbladder neck. We herein report a rare case of indirect cholecystoduodenal fistula via the hepatoduodenal ligament secondary to gangrenous cholecystitis. CASE PRESENTATION: An 80-year-old woman suspected of having emphysematous cholecystitis by a previous doctor was referred to our hospital for urgent surgery. The initial diagnosis based on additional examinations was gangrenous cholecystitis penetrating the hepatoduodenal ligament. Since she did not complain of signs of peritonitis and was taking an anticoagulant medicine, we avoided surgery and selected percutaneous gallbladder drainage (PTGBD) instead. Contrast imaging of the PTGBD tube and upper endoscopy identified the indirect cholecystoduodenal fistula via the hepatoduodenal ligament. Despite repeated attempts at endoscopic fistula closure using clips, the fistula did not close successfully. We therefore performed laparoscopic cholecystectomy and fistula closure. The postoperative clinical course was uneventful, and she left the hospital on postoperative day 15. The resected gallbladder contained small black stones, and a histological examination revealed gangrenous cholecystitis with no malignant signatures. CONCLUSION: We encountered a rare case of indirect cholecystoduodenal fistula via the hepatoduodenal ligament secondary to gangrenous cholecystitis that was successfully treated by laparoscopic cholecystectomy and fistula closure. It is important to recognize the possible formation of indirect cholecystoduodenal fistula in cases of gangrenous cholecystitis penetrating the hepatoduodenal ligament.

Pharmacovigilance study of the association between dipeptidyl peptidase-4 inhibitors and angioedema using the FDA Adverse Event Reporting System (FAERS).

Dipeptidyl peptidase-4 (DPP-4) plays a minor role in degrading vasoactive peptides that cause angioedema when angiotensin-converting enzyme (ACE) is present and fully functional. This study investigated the association between DPP-4 inhibitors (DPP-4Is) and angioedema, including cases where the concomitant use of ACE inhibitors (ACEIs) was absent. We obtained data from the US Food and Drug Administration Adverse Event Reporting System and performed a disproportionality analysis, using the reporting odds ratio (ROR) and information component (IC) for signal detection in patients aged ≥ 40 years, stratified by age group and sex. No signal was detected for DPP-4Is when the entire dataset was analyzed. However, a signal was detected for the entire female subset group, the three stratified female groups aged ≥ 60 years, and males in their 40 s. After excluding the data of concomitant ACEI users, most ROR and IC values were lower and significant only for females in their 60 s and males aged ≥ 80 years. Regarding individual DPP-4Is signals, those detected for saxagliptin and sitagliptin in some age groups disappeared after excluding the data of ACEI users. Notably, linagliptin was the only DPP-4I where signals were detected in most female groups, regardless of age and without concomitant ACEI use. Our findings suggest that some DPP-4Is were associated with a higher reporting of angioedema as per age and sex, even in the absence of concomitant ACEI use.

Five-year blood pressure trajectories of survivors of the tsunami following the Great East Japan Earthquake in Iwate.

Whether tsunami survivors who suffered substantial damage experienced increases in blood pressure (BP) immediately after the disaster and in the medium to long term is unclear. We divided tsunami survivors into groups, those who relocated (substantial damage) and those who did not (little damage) and compared the BP trajectories between the groups over the first 5 years after the disaster. Of the 42,831 residents, 3914 were assessed from 2010 to 2015. Subgroup analysis was performed among the 2037 subjects with no information on antihypertensive medications between 2010 and 2015 (no antihypertensive medication group). The BP trajectories in the relocation and no relocation groups were compared using linear mixed models. The multivariate-adjusted mean systolic BP (SBP) values for all subjects significantly decreased after the disaster in both the group who relocated (2010: 130.6 mmHg, 2015: 124.8 mmHg) and the group who did not relocate (2010: 130.7 mmHg, 2015: 126.7 mmHg). The interaction between relocation and time points on SBP was significant (P = 0.017). In the no antihypertensive medication group, the SBP values in the subgroup who relocated were significantly lower in the second, third, and fifth years after the disaster than those in the subgroup who did not relocate. It was concluded that the SBP values of survivors of the tsunami caused by Great East Japan Earthquake decreased in the medium to long term after the disaster, and the group who relocated had a larger decrease in SBP than the group who did not relocate.

A microfluidic device for isolating intact chromosomes from single mammalian cells and probing their folding stability by controlling solution conditions.

Chromatin folding shows spatio-temporal fluctuations in living undifferentiated cells, but fixed spatial heterogeneity in differentiated cells. However, little is known about variation in folding stability along the chromatin fibres during differentiation. In addition, effective methods to investigate folding stability at the single cell level are lacking. In the present study, we developed a microfluidic device that enables non-destructive isolation of chromosomes from single mammalian cells as well as real-time microscopic monitoring of the partial unfolding and stretching of individual chromosomes with increasing salt concentrations under a gentle flow. Using this device, we compared the folding stability of chromosomes between non-differentiated and differentiated cells and found that the salt concentration which induces the chromosome unfolding was lower (≤500 mM NaCl) for chromosomes derived from undifferentiated cells, suggesting that the chromatin folding stability of these cells is lower than that of differentiated cells. In addition, individual unfolded chromosomes, i.e., chromatin fibres, were stretched to 150-800 µm non-destructively under 750 mM NaCl and showed distributions of highly/less folded regions along the fibres. Thus, our technique can provide insights into the aspects of chromatin folding that influence the epigenetic control of cell differentiation.

Nucleosomes of polyploid trophoblast giant cells mostly consist of histone variants and form a loose chromatin structure.

Trophoblast giant cells (TGCs) are one of the cell types that form the placenta and play multiple essential roles in maintaining pregnancy in rodents. TGCs have large, polyploid nuclei resulting from endoreduplication. While previous studies have shown distinct gene expression profiles of TGCs, their chromatin structure remains largely unknown. An appropriate combination of canonical and non-canonical histones, also known as histone variants, allows each cell to exert its cell type-specific functions. Here, we aimed to reveal the dynamics of histone usage and chromatin structure during the differentiation of trophoblast stem cells (TSCs) into TGCs. Although the expression of most genes encoding canonical histones was downregulated, the expression of a few genes encoding histone variants such as H2AX, H2AZ, and H3.3 was maintained at a relatively high level in TGCs. Both the micrococcal nuclease digestion assay and nucleosome stability assay using a microfluidic device indicated that chromatin became increasingly loose as TSCs differentiated. Combinatorial experiments involving H3.3-knockdown and -overexpression demonstrated that variant H3.3 resulted in the formation of loose nucleosomes in TGCs. In conclusion, our study revealed that TGCs possessed loose nucleosomes owing to alterations in their histone composition during differentiation.

Ability of B-Type Natriuretic Peptide Testing to Predict Cardioembolic Stroke in the General Population　- Comparisons With C-Reactive Protein and Urinary Albumin.

BACKGROUND: The ability of cardiovascular biomarkers to predict the incidence of stroke subtypes remains ill-defined in the general population.Methods and Results:The blood levels of B-type natriuretic peptide (BNP) and high-sensitivity C-reactive protein (hs-CRP) and urinary albumin corrected by urinary creatinine (UACR) were determined in a general population (n=13,575). The ability to predict the incidence of ischemic stroke subtypes (lacunar, atherothrombotic, cardioembolic) for each biomarker was assessed based on the area under the receiver-operating characteristic curve (AUC-ROC) and using Cox proportional hazard modeling. The predictive abilities of UACR and hs-CRP for any subtype of ischemic event were found to be suboptimal. However, the ability of BNP to predict the incidence of cardioembolic stroke was excellent (AUC-ROC=0.81). When BNP was added to established stroke risk factors, the ability to predict cardioembolic stroke in terms of the AUC-ROC significantly improved (4-year follow-up, P=0.018; 8-year follow-up, P=0.009). Furthermore, when BNP was added to the JPHC score, the ability to predict cardioembolic stroke was significantly improved (net reclassification improvement=0.968, P<0.0001: integrated discrimination improvement=0.039, P<0.05). CONCLUSIONS: In the general population, plasma BNP was an excellent biomarker for predicting the incidence of cardioembolic stroke when used alone or in combination with established stroke risk factors.

Comparison of the Effects of Carperitide and Tolvaptan on Patients with Left Ventricular Dysfunction: A Two-Center Retrospective Study.

In patients with left ventricular (LV) dysfunction, diuretics can reduce blood pressure and lead to electrolyte abnormalities. The aim of this study was to compare the effects of tolvaptan (T group) and carperitide (C group) in these patients. Sixty-one consecutive patients admitted to the Iwate Prefectural Kuji Hospital or the Emergency Center of the Iwate Medical University between July 2011 and April 2015 were included in this study. These patients had acute heart failure (HF) and were initially treated with furosemide. Patients were excluded from the study if they received combined carperitide and tolvaptan, if they received tolvaptan or cardiotonic drugs prior to the study period, if their LV ejection fraction was ≥40%, and if they had renal dysfunction (serum creatinine > 2.0 mg/dL). There were no differences in the change in serum electrolytes in both groups, and none of the patients in the T group received supplementary dobutamine therapy. Oxygen administration was stopped successfully after a significantly shorter treatment period in the T group. These findings suggest that patients treated with tolvaptan did not require dobutamine as frequently as those treated with carperitide and indicated that tolvaptan may improve respiratory function more rapidly in patients with LV dysfunction.

Temporal Trends in the Incidence and Clinical Features of Acute Myocardial Infarction in a Japanese Rural Area From 2006 to 2014.

BACKGROUND: Recent temporal trends in the incidence and clinical features of acute myocardial infarction (MI) in the Japanese population are not well known.Methods and Results:This study used comprehensive registration for first-ever MI during the 9-year period from 2006 to 2014 in a rural area of northeastern Japan. The study period was divided into three 3-year terms (T1, 2006-2008; T2, 2009-2011; T3, 2012-2014). During the study period, a total of 814 patients with MI were registered. Although the age-adjusted incidence rate (100,000 person-years) in the middle-aged group (<70 years) was relatively stable, the rate for the elderly group (≥70 years) in T3 was significantly lower than that in T1 in both men (368 vs. 279; P<0.01) and women (204 vs. 108; P<0.01). In the general population of the study area, the rate of prescribed anticholesterol drugs was significantly increased during the study period, especially in the elderly population (P<0.01). From a clinical perspective, although the performance rate of primary percutaneous coronary intervention significantly increased with a shortened duration of hospital stay, the in-hospital mortality rate, especially in the elderly, did not significantly decrease during the study period. CONCLUSIONS: The present study is the first to demonstrate a decreased age-adjusted incidence of MI during the period from 2006 to 2014 in a Japanese rural population, especially in the elderly.

Identification of Jasmonic Acid and Jasmonoyl-Isoleucine, and Characterization of AOS, AOC, OPR and JAR1 in the Model Lycophyte Selaginella moellendorffii.

Jasmonic acid (JA) is involved in a variety of physiological responses in seed plants. However, the detection and role of JA in lycophytes, a group of seedless vascular plants, have remained elusive until recently. This study provides the first evidence of 12-oxo-phytodienoic acid (OPDA), JA and jasmonoyl-isoleucine (JA-Ile) in the model lycophyte Selaginella moellendorffii. Mechanical wounding stimulated the accumulation of OPDA, JA and JA-Ile. These data were corroborated by the detection of enzymatically active allene oxide synthase (AOS), allene oxide cyclase (AOC), 12-oxo-phytodienoic acid reductase 3 (OPR3) and JA-Ile synthase (JAR1) in S. moellendorffii. SmAOS2 is involved in the first committed step of JA biosynthesis. SmAOC1 is a crucial enzyme for generating the basic structure of jasmonates and is actively involved in the formation of OPDA. SmOPR5, a functionally active OPR3-like enzyme, is also vital for the reduction of (+)-cis-OPDA, the only isomer of the JA precursor. The conjugation of JA to Ile by SmJAR1 demonstrates that S. moellendorffii produces JA-Ile. Thus, the four active enzymes have characteristics similar to those in seed plants. Wounding and JA treatment induced the expression of SmAOC1 and SmOPR5. Furthermore, JA inhibited the growth of shoots in S. moellendorffii, which suggests that JA functions as a signaling molecule in S. moellendorffii. This study proposes that JA evolved as a plant hormone for stress adaptation, beginning with the emergence of vascular plants.

Identification of Plants That Inhibit Lipid Droplet Formation in Liver Cells: Rubus suavissimus Leaf Extract Protects Mice from High-Fat Diet-Induced Fatty Liver by Directly Affecting Liver Cells.

Fatty liver disease is a condition in which abnormally large numbers of lipid droplets accumulate in liver cells. Fatty liver disease induces inflammation under conditions of oxidative stress and may result in cancer. To identify plants that protect against fatty liver disease, we examined the inhibitory effects of plant extracts on lipid droplet formation in mouse hepatoma cells. A screen of 98 water extracts of plants revealed 4 extracts with inhibitory effects. One of these extracts, Rubus suavissimus S. Lee (Tien-cha or Chinese sweet tea) leaf extract, which showed strong inhibitory effects, was tested in a mouse fatty liver model. In these mouse experiments, intake of the plant extract significantly protected mice against fatty liver disease without affecting body weight gain. Our results suggest that RSE directly affects liver cells and protects them from fatty liver disease.

Functional analysis of allene oxide cyclase, MpAOC, in the liverwort Marchantia polymorpha.

12-Oxo-phytodienoic acid (OPDA) is an intermediate in jasmonic acid (JA) biosynthesis. OPDA exerts JA-dependent and JA-independent biological effects; therefore, it is considered a signaling molecule in flowering plants. OPDA is induced by bacterial infection and wounding and inhibits growth in the moss Physcomitrella patens. The functions of OPDA and allene oxide cyclase (AOC) in the liverwort Marchantia polymorpha were explored, which represents the most basal lineage of extant land plants. The analysis of OPDA showed that it is present in M. polymorpha and is increased by wounding. OPDA has been suggested to be involved in the response to environmental stresses. Moreover, OPDA showed growth inhibitory activity in M. polymorpha. Nonetheless JA in M. polymorpha was not found in this study. AOC synthesizes OPDA from an unstable allene oxide. A database search of the M. polymorpha genome identified only a putative gene encoding allene oxide cyclase (MpAOC). Recombinant MpAOC showed AOC activity similar to that in flowering plants. MpAOC was localized to chloroplasts, as in flowering plants. Expression of MpAOC was induced by wounding and OPDA treatment, and positive feedback regulation of OPDA was demonstrated in M. polymorpha. Overexpression of MpAOC increased the endogenous OPDA level and suppressed growth in M. polymorpha. These results indicate the role of OPDA as a signaling molecule regulating growth and the response to wounding in the liverwort M. polymorpha.

Overexpression of RelA/SpoT homologs, PpRSH2a and PpRSH2b, induces the growth suppression of the moss Physcomitrella patens.

Two genes encoding RelA/SpoT homologs, PpRSH2a and PpRSH2b, which are involved in the synthesis of bacterial alarmone guanosine 5'-diphosphate 3'-diphosphate (ppGpp) for the stringent response, were isolated from the moss, Physcomitrella patens. A complementary analysis of PpRSH2a and PpRSH2b in Escherichia coli showed that these genes had ppGpp biosynthetic activity. The recombinant PpRSH2a and PpRSH2b were also shown to synthesize ppGpp in vitro. Both proteins were localized to the chloroplasts of P. patens. Expression of the PpRSH genes was induced upon treatment with abscisic acid or abiotic stresses, such as dehydration and UV irradiation. Overexpression of PpRSH2a and PpRSH2b caused suppression of the growth in response to 1% (w/v) of glucose. The present study suggests the existence of a mechanism to regulate the growth of P. patens, which is governed by plant RSH in chloroplasts.

Elevated blood pressure at the first measurement predicts cardiovascular disease independently from the subsequent second reading in men, but not in women.

BACKGROUND AND METHODS: There have been no investigations concerning the association of each blood pressure (BP) reading with future cardiovascular disease (CVD) when multiple measurements are taken on one occasion. This community-based, prospective cohort study (n = 23 344, mean age = 62.4 years) investigated the associations between the BP obtained from the first and second of two consecutive measurements on one occasion and future cardiovascular events in men and women. RESULTS: During the mean follow-up of 5.5 years, 624 CVD events were identified. On the Cox regression analysis of age- and BP-adjusted models, the increased CVD risk of a hypertensive first measurement (systolic BP ≥ 140 mmHg) was independent from the second measurement in men. Even in subjects without a hypertensive second measurement, the CVD risk of the hypertensive first measurement was increased in men. In women, despite a hypertensive first measurement, subjects with a systolic BP < 130 mmHg on the second measurement showed a significantly reduced risk for CVD compared with subjects who retained a hypertensive level during the two measurements. CONCLUSIONS: An elevated BP on the first measurement should not be disregarded for CVD risk estimation in men, even if the second BP moves to the normal range. In women, elevated BP on the first measurement may have relatively less meaning for CVD prediction if the second BP shifts to a normal range.

Possible usefulness of gadolinium-enhanced brain MRI for evaluating risk of perioperative hemorrhage: a case of infective endocarditis.

A 59-year-old woman visited a local hospital for fever and was diagnosed as having infective endocarditis (IE) on the basis of blood cultures and transthoracic echocardiography. Based on clinical episodes of subarachnoid hemorrhage after admission, it was judged that she was not a good candidate for urgent open heart surgery, and it was decided to treat her with conservative medical therapy for the acute phase. We explored the optimum timing for surgery by employing gadolinium (Gd) contrast medium-enhanced magnetic resonance imaging (MRI) T2* weighted image (black dots) due to her high risk of perioperative cerebral hemorrhage. After the disappearance of the contrast media enhancement effect around the black dots, open heart surgery was performed successfully on the 103rd hospitalization day. The patient was discharged 22 days after the surgery with no clinical complications. This case suggests that disappearance of the contrast media enhancement effect around the black dots may be a useful marker for optimal timing of surgery to minimize the risk of perioperative cerebral hemorrhage in patients with IE. Learning Objective. The MRI T2* weighted images including those with Gd contrast medium enhancement effect may be useful for evaluating the risk of perioperative intracranial hemorrhage in IE.

Cardiovascular risk stratification with plasma B-type natriuretic peptide levels in a community-based hypertensive cohort.

Few reports have examined the utility of plasma B-type natriuretic peptide (BNP) testing for cardiovascular (CV) risk stratification in real-world hypertensive subjects. Subjects of the study were community-based hypertensive patients (n = 5,865). The CV event rate within each BNP quartile was estimated, and a Cox regression model was used to determine the relative hazard ratio (HR) among the quartiles. Furthermore, to determine the usefulness of BNP as a biomarker in combination with the Framingham risk score (FRS), the predictive abilities in terms of area under the curve of receiver operating characteristic analysis, net reclassification improvement, and integrated discrimination improvement indices were determined. The mean follow-up duration was 5.6 years. The highest quartile showed a significantly higher rate of CV events compared with the lower quartiles (p <0.001). After adjustment for established CV risk factors, the HR for CV events increased significantly according to the quartile (p value for trend <0.03), and the HR for the highest quartile was significantly elevated compared with the lowest quartile (HR 1.59, 95% confidence interval 1.16 to 2.19). The predictive abilities of BNP in terms of sensitivity and specificity for CV events were comparable with those of FRS. When BNP was added to an FRS-only model, the predictive abilities in terms of area under receiver operating characteristic curve, net reclassification improvement, and integrated discrimination improvement were significantly increased (all; p <0.001). Elevated BNP levels are thus a useful biomarker for CV risk stratification in unselected real-world hypertensive subjects. Adding BNP to an established CV risk score improves the predictive ability in this cohort.

Comparison of the incidence of acute decompensated heart failure before and after the major tsunami in Northeast Japan.

On March 11, 2011, a huge tsunami attacked the northeastern coast of Japan after a magnitude 9 earthquake. No reports have investigated the impact of tsunamis on the incidence of cardiovascular disease, especially heart failure (HF). We investigated the number and clinical characteristics of hospitalized patients with acute decompensated HF (ADHF) in the east coast of Iwate hit by the tsunami (tsunami area) for a 12-week period around the disaster. For comparison with previous years, numbers of ADHF were surveyed in the corresponding area in 2009 and 2010. In addition, to elucidate the impact of the tsunami, a similar study was performed in a remote area where the tsunami had minimal effect (control area). After the disaster, the number of patients with ADHF in the tsunami area was significantly increased compared to the predisaster period (relative risk 1.97, 95% confidence interval 1.50 to 2.59). The peak was found 3 to 4 weeks after the disaster. In contrast, in the control area, no significant change in ADHF events was observed (relative risk 1.29, 95% confidence interval 0.94 to 1.78). There was a significant correlation between changes in the number of ADHF admissions and percent tsunami flood area (r = 0.73, p <0.001) or the number of shelter evacuees (r = 0.83, p <0.001). In conclusion, these findings suggest that large and sudden changes in daily life and the trauma associated with a devastating tsunami have a significant impact on the incidence of ADHF.

Plasma B-type natriuretic peptide is useful for cardiovascular risk assessment in community-based diabetes subjects: comparison with albuminuria.

Diabetes mellitus (DM) is a strong risk factor for cardiovascular (CV) disease. Plasma B-type natriuretic peptide (BNP) levels are elevated in various types of cardiac diseases. Increased plasma BNP levels have been reported to be associated with CV risk in apparently healthy individuals. However, no studies have yet examined the specific value of plasma BNP for predicting CV incidence in unselected DM subjects in a community-based population.In a community-based DM cohort (n = 1,059, mean = 66 years), baseline BNP levels were determined, and CV events were followed and captured prospectively. The cohort was divided by plasma BNP quintiles. The Cox proportional hazard model was used to determine the relative hazard ratios (HR) among the quintiles. In addition, the effects of adding the plasma BNP or urine albumin-to-creatinine ratio (UACR) to an established CV risk scoring model was examined by calculating the area under the receiver operating characteristic (ROC) curve (AUC).During the 5.7 year follow-up period, CV events were identified in 65 of the DM cohort. There was a significant association between plasma BNP levels and CV event rate (P < 0.001). HR was significantly increased in the highest quintile compared to the lowest (HR = 4.38; 95%CI 1.69 -11.84). The AUC generated from ROC analysis of the Framingham risk score for predicting general CV events was improved by adding BNP testing (from 0.66 to 0.74; P = 0.05), but not by adding UACR (from 0.66 to 0.67; P = 0.49).In a community sample of people with DM, plasma BNP levels above the 80 percentile are directly associated with CV risk, and measurement of plasma BNP alone or in conjunction with an established CV risk score is of value in predicting CV events in these subjects.