Proton Conduction in Gly-X (X = Ser, Ser-Gly-Ser) and GS50.

In recent years, the use of biomaterials has been required from the viewpoint of biocompatibility of electronic devices. In this study, the proton conductivity of Glycyl-L-serine (Gly-Ser) was investigated to clarify the relationship between hydration and proton conduction in peptides. From the crystal and conductivity data, it was inferred that the proton conductivity in hydrated Gly-Ser crystals is caused by the cleavage and rearrangement of hydrogen bonds between hydration shells formed by hydrogen bonds between amino acids and water molecules. Moreover, a staircase-like change in proton conduction with hydration was observed at n = 0.3 and 0.5. These results indicate that proton transport in Gly-Ser is realized by hydration water. In addition, we also found that hydration of GSGS and GS50 can achieve proton conduction of Gly-Ser tetrameric GSGS and GS50 containing repeating sequences. The proton conductivity at n = 0.3 is due to percolation by the formation of proton-conducting pathways. In addition to these results, we found that proton conductivity at GS50 is realized by the diffusion constant of 3.21 × 10-8 cm2/s at GS50.

Spermiogenesis in Caenorhabditis elegans: An Excellent Model to Explore the Molecular Basis for Sperm Activation.

C. elegans spermiogenesis converts non-motile spermatids into motile, fertilization-competent spermatozoa. Two major events include the building of a pseudopod required for motility and fusion of membranous organelles (MOs)-intracellular secretory vesicles-with the spermatid plasma membrane required for the proper distribution of sperm molecules in mature spermatozoa. The mouse sperm acrosome reaction-a sperm activation event occurring during capacitation-is similar to MO fusion in terms of cytological features and biological significance. Moreover, C. elegans fer-1 and mouse Fer1l5, both encoding members of the ferlin family, are indispensable for MO fusion and acrosome reaction, respectively. Genetics-based studies have identified many C. elegans genes involved in spermiogenesis pathways; however, it is unclear whether mouse orthologs of these genes are involved in the acrosome reaction. One significant advantage of using C. elegans for studying sperm activation is the availability of in vitro spermiogenesis, which enables combining pharmacology and genetics for the assay. If certain drugs can activate both C. elegans and mouse spermatozoa, these drugs would be useful probes to explore the mechanism underlying sperm activation in these two species. By analyzing C. elegans mutants whose spermatids are insensitive to the drugs, genes functionally relevant to the drugs' effects can be identified.

CXCL12 promotes CCR7 ligand-mediated breast cancer cell invasion and migration toward lymphatic vessels.

Chemokines are a family of cytokines that mediate leukocyte trafficking and are involved in tumor cell migration, growth, and progression. Although there is emerging evidence that multiple chemokines are expressed in tumor tissues and that each chemokine induces receptor-mediated signaling, their collaboration to regulate tumor invasion and lymph node metastasis has not been fully elucidated. In this study, we examined the effect of CXCL12 on the CCR7-dependent signaling in MDA-MB-231 human breast cancer cells to determine the role of CXCL12 and CCR7 ligand chemokines in breast cancer metastasis to lymph nodes. CXCL12 enhanced the CCR7-dependent in vitro chemotaxis and cell invasion into collagen gels at suboptimal concentrations of CCL21. CXCL12 promoted CCR7 homodimer formation, ligand binding, CCR7 accumulation into membrane ruffles, and cell response at lower concentrations of CCL19. Immunohistochemistry of MDA-MB-231-derived xenograft tumors revealed that CXCL12 is primarily located in the pericellular matrix surrounding tumor cells, whereas the CCR7 ligand, CCL21, mainly associates with LYVE-1+ intratumoral and peritumoral lymphatic vessels. In the three-dimensional tumor invasion model with lymph networks, CXCL12 stimulation facilitates breast cancer cell migration to CCL21-reconstituted lymphatic networks. These results indicate that CXCL12/CXCR4 signaling promotes breast cancer cell migration and invasion toward CCR7 ligand-expressing intratumoral lymphatic vessels and supports CCR7 signaling associated with lymph node metastasis.

Identification and Synthesis of DDI-6, a Quinolinol Analog Capable of Activating Both Caenorhabditis elegans and Mouse Spermatozoa.

Sperm activation is an essential process by which the male gametes become capable of fertilization. Because the process in Caenorhabditis elegans is readily reproducible in vitro, this organism serves as an excellent model to investigate it. C. elegans sperm activation in vivo occurs during spermiogenesis. Membranous organelles (MOs) contained within spermatids fuse with the plasma membrane, resulting in extracellular release of their contents and relocation of some proteins indispensable for fertilization from the MO membrane onto the sperm surface. Intriguingly, these cytological alternations are exhibited similarly in mouse spermatozoa during the acrosome reaction, which also represents a form of sperm activation, prompting us to hypothesize that C. elegans and mice share a common mechanism for sperm activation. To explore this, we first screened a chemical library to identify compounds that activate C. elegans spermatozoa. Because a quinolinol analog named DDI-6 seemed to be a candidate sperm activator, we synthesized it to use for further analyses. This involved direct dechlorination and hydrogenolysis of commercially available 5-chloro-8-quinolinol, both of which are key steps to yield 1,2,3,4-tetrahydro-8-quinolinol, and we subsequently introduced the sulfonamide group to the compound. When C. elegans spermatids were stimulated with solvent alone or the newly synthesized DDI-6, approx. 3% and approx. 28% of spermatids became MO-fused spermatozoa, respectively. Moreover, DDI-6 triggered the acrosome reaction in approx. 20% of mouse spermatozoa, while approx. 12% became acrosome-reacted after mock stimulation. Thus, DDI-6 serves as a moderately effective activator for both C. elegans and mouse spermatozoa.

C. elegans spermatozoa lacking spe-45 are incapable of fusing with the oocyte plasma membrane.

C. elegans spe-9 class genes encode sperm proteins with indispensable roles during fertilization. We have previously reported that spe-45 belongs to the spe-9 class, based on the finding that self-sperm of spe-45(tm3715) hermaphrodites were not consumed by fertilization. In this study, we directly observed live fertilization in the spermatheca of fem-1(hc17) females after mating with spe-45(tm3715) males. As expected, it was clearly shown that spe-45 mutant spermatozoa failed to fuse with the oocyte plasma membrane. Thus, our live imaging system for C. elegans fertilization seems to be useful for evaluation of the functions of male and female gametes.

Proteinase K is an activator for the male-dependent spermiogenesis pathway in Caenorhabditis elegans: Its application to pharmacological dissection of spermiogenesis.

Caenorhabditis elegans spermiogenesis involves spermatid activation into spermatozoa. Activation occurs through either SPE-8 class-dependent or class-independent pathways. Pronase (Pron) activates the SPE-8 class-dependent pathway, whereas no in vitro tools are available to stimulate the SPE-8 class-independent pathway. Thus, whether there is a functional relationship between these two pathways is currently unclear. In this study, we found that proteinase K (ProK) can activate the SPE-8 class-independent pathway. In vitro spermiogenesis assays using Pron and ProK suggested that SPE-8 class proteins act in the hermaphrodite- and male-dependent spermiogenesis pathways and that some spermatid proteins presumably working downstream of spermiogenesis pathways, including MAP kinases, are preferentially involved in the SPE-8 class-dependent pathway. We screened a library of chemicals, and a compound that we named DDI-1 inhibited both Pron- and ProK-induced spermiogenesis. To our surprise, several DDI-1 analogues that are structurally similar to DDI-1 blocked Pron, but not ProK, induced spermiogenesis. Although the mechanism by which DDI-1 blocks spermiogenesis is yet unknown, we have begun to address this issue by selecting two DDI-1-resistant mutants. Collectively, our data support a model in which C. elegans male and hermaphrodite spermiogenesis each has its own distinct, parallel pathway.

Geriatric Nutritional Risk Index Predicts Cardiovascular Events in Patients at Risk for Heart Failure.

BACKGROUND: The geriatric nutritional risk index (GNRI) is a simple and objective nutritional assessment tool for elderly patients. Lower GNRI values are associated with a worse prognosis in patients with heart failure (HF). However, few data are available regarding the prognostic effect of the GNRI value for risk stratification in patients at risk for HF.Methods and Results:We retrospectively investigated 1,823 consecutive patients at risk for HF (Stage A/B) enrolled in the IMPACT-ABI Study. GNRI on admission was calculated as follows: 14.89×serum albumin (g/dL)+41.7×body mass index/22. Patients were divided into 2 groups according to the median GNRI value (107.1). The study endpoint was a composite of cardiovascular (CV) events, including CV death and hospitalization for worsening HF. Over a 4.7-year median follow-up, CV events occurred in 130 patients. In the Kaplan-Meier analysis, patients with low GNRI (<107.1, n=904) showed worse prognoses than those with high GNRI (≥107.1, n=919) (20.2% vs. 12.4%, P<0.001). In the multivariable Cox proportional hazards analysis, low GNRI was significantly associated with the incidence of CV events (hazard ratio: 1.48, 95% confidence interval: 1.02-2.14; P=0.040). CONCLUSIONS: The simple and practical assessment of GNRI may be useful for predicting CV events in patients with Stage A/B HF.

Predictive Value of Underweight Status for Patients With Peripheral Artery Disease With Claudication.

We evaluated whether underweight status is associated with poor prognosis in patients with peripheral artery disease (PAD) with claudication, excluding critical limb ischemia. We identified 441 claudicants hospitalized for cardiovascular disease between 2005 and 2012. Patients were divided into 4 groups according to body mass index (BMI): an underweight group (BMI < 18.5 kg/m2; n = 48), a normal group (BMI = 18.5-25.0 kg/m2; n = 286), an overweight group (BMI = 25.0-30.0 kg/m2; n = 92), and an obese group (BMI ≥ 30.0 kg/m2; n = 15). The mean follow-up period was 3.5 ± 1.9 years. The underweight group had significantly lower levels of hemoglobin, albumin, estimated glomerular filtration rate, triglycerides, and hemoglobin A1c; higher levels of C-reactive protein and B-type natriuretic peptide; and a higher prevalence of hemodialysis. The incidence of all-cause death and cardiovascular death was significantly higher in the underweight group (underweight vs normal, 77.1% vs 33.0%; P < .001 and 43.3% vs 14.4%; P < .001, respectively). In a multivariate Cox analysis, underweight status was an independent predictor of all-cause death (hazard ratio, 2.53; 95% confidence interval, 1.58-4.18; P < .001). Therefore, promoting weight gain, as well as managing cardiovascular disease, may be important for underweight patients with PAD.

Comparison of platelet aggregation response in switching regimen from prasugrel to clopidogrel between CYP2C19 extensive versus non-extensive metabolizers.

Little is known about the response of platelet aggregation in patients with acute coronary syndrome (ACS) when prasugrel is changed to clopidogrel. In this study, we evaluated the pharmacodynamic effects of this medication switch. Twenty-one consecutive ACS patients received prasugrel 20 mg as a loading dose before emergent percutaneous coronary intervention and 3.75 mg as a maintenance dose on days 2-7 (prasugrel phase). From day 8, prasugrel was switched to clopidogrel 75 mg/day (clopidogrel phase). P2Y12 reaction units (PRU) were measured 2-4 h after prasugrel loading, and on days 7, 11, 13, 15, and 42. Eight patients had the CYP2C19 extensive metabolizer (EM) genotype variant, while 13 were non-EM. In the EM group, no changes were observed in PRU level between days 7 and 15 (136.8 ± 51.2 vs. 166.2 ± 41.9, P = 0.07). However, in the non-EM group, a significant increase in PRU levels was observed between days 7 and 15 (165.8 ± 57.2 vs. 223.6 ± 60.9, P = 0.002). However, 2 patients in the non-EM group (15%) showed high on-clopidogrel treatment platelet reactivity (HTPR) 2-4 h after prasugrel loading, and during the clopidogrel phase there were significant differences in the incidence of HTPR between the EM and non-EM groups. Ischemic and bleeding events were not observed during this period. In the acute phase of ACS, changing from prasugrel to clopidogrel therapy decreased the effects of suppressing platelet aggregation. However, this change was not associated with increased ischemic or bleeding events.

Re-correction osteotomy with osteophyte graft for correction loss with non-union after high tibial osteotomy.

A 68-year-old man with right knee varus osteoarthritis was treated by lateral closed-wedge high tibial osteotomy. A correction loss with non-union occurred 6 months after surgery and a re-correction osteotomy was performed. Removing the proximal screws of the lateral plate, a medial opening-wedge re-osteotomy was performed. Arthroscopically harvested osteophytes were used to fill the gap after opening. An additional medial locking plate was installed on the medial side. Finally, the proximal lateral screws were reinserted and locked again. Mature trabecular continuity was obtained in the gap by 6 months, and there was no varus deformity 4 years after re-correction. Re-correction osteotomy could be a viable treatment when lateral compartment osteoarthritis has not progressed and good range of motion still exists. Osteophyte grafting may be an effective option not only to avoid iliac bone grafting but also to promote bone healing in re-osteotomy.

Plausible link between circa'bi'dian activity rhythms and circadian clock systems in the large black chafer Holotrichia parallela.

Two-day rhythms, referred to as circa'bi'dian rhythms, have been reported in humans and mosquitos. However, these rhythms only appear under constant conditions, and the functional mechanisms of 2-day rhythms were unknown. Here, we report clear circabidian rhythms of large black chafers (Holotrichia parallela, Coleoptera: Scarabaeidae) in both the laboratory and field. Under 12 h:12 h light:dark (L:D) conditions at 25°C, H. parallela appeared on the ground at the beginning of the dark phase every 2 days. Under constant darkness, H. parallela exhibited free-running with a period of 47.9±0.3 h, suggesting the existence of a clear circabidian rhythm entrained to two 12 h:12 h L:D cycles. Phase responses of the circabidian rhythm to light pulses occurred under constant darkness in a phase-dependent manner. Phase responses suggest that there are two circadian cycles, each consisting of a less-responsive and more-responsive period, in a circabidian oscillation, and the circabidian rhythm is driven by the circadian clock. A mark-recapture study showed that beetles repeatedly appeared on the same tree approximately every 2 days. However, the periodicity was not as rigid as that observed under laboratory conditions in that individuals often switched appearance days. For instance, a large precipitation made the 2-day rhythm shift phase by half a cycle of the rhythm at a time. We propose a novel function of the circadian clock characterized by the release of an output signal every two cycles to produce the 2-day rhythm.

Closed Wedge Distal Femoral Osteotomy with a Polyaxial Locking Plate Designed for the Proximal Tibia: Minimum 5-Year Outcomes.

Since distal femoral varus osteotomy (DFO) -specific plates had not been available in Japan before 2015, we performed DFO using a plate for tibia. The purpose of this study was to elucidate the efficacy and problems associated with the non-specific plate in DFO. We used NCB-PT plates (Zimmer Inc.) in the upside-down position and the minimum 5-year outcomes were evaluated. The mean preoperative weight bearing line ratio and Japanese Orthopaedic Association score improved from 97.6%±35.8% and 68.0±11.5, respectively, to 44.0%±16.1% and 82.0±7.6, respectively, 1 year postoperatively and to 42.8%±15.7% and 86.0±8.2, respectively, 5 years postoperatively. The flexion range decreased from 149.0°±6.5° to 138.0°±5.7° 1 year postoperatively and to 135.0°±20.9° 5 years postoperatively. Although DFO using the NCB-PT plate provided mid-term benefits, it resulted in a loss of knee flexion, possibly due to excessive coverage of the medial femoral epicondyle.

Spermatogenesis.

Most organisms consist of two cell lineages - somatic cells and germ cells. The former are required for the current generation, and the latter create offspring. Male and female germ cells are usually produced during spermatogenesis and oogenesis, which take place in the testis and the ovary, respectively. Spermatogenesis involves the differentiation of spermatogonial stem cells into spermatocytes via mitotic cell division and the production of haploid spermatids from the tetraploid primary spermatocytes via meiotic cell division. Spermatids subsequently give rise to spermatozoa in the final phase of spermatogenesis, called spermiogenesis. These fundamental steps, where mitotic proliferation precedes meiosis during spermatogenesis, are observed in a wide variety of organisms. However, developing a comprehensive understanding of the cell biology and genetics of spermatogenesis is difficult for most species because it occurs within a complex testicular environment characterized by the intimate association of developing sperm with accessory cells. In this Primer, we summarize the processes of spermatogenesis occurring in two pivotal model animals - mouse and Caenorhabditis elegans - and compare them to consider which important features might be evolutionarily conserved.

Ankle-brachial Index for the Prognosis of Cardiovascular Disease in Patients with Mild Renal Insufficiency.

Objective A low ankle-brachial index (ABI) is a known predictor for future cardiovascular events and mortality in patients with chronic kidney disease (CKD). While most prior studies have defined CKD as an estimated glomerular filtration rate (eGFR) <60 mL/min/1.73 m2, recent reports have suggested that the cardiovascular risk may be increased even in early stages of renal insufficiency. We hypothesized that a low ABI may predict future cardiovascular morbidity and mortality in patients with mild impairment of the renal function. Methods The IMPACT-ABI study was a retrospective, single-center, cohort study that enrolled and obtained ABI measurements for 3,131 patients hospitalized for cardiovascular disease between January 2005 and December 2012. From this cohort, we identified 1,500 patients with mild renal insufficiency (eGFR =60-89 mL/min/1.73 m2), and stratified them into 2 groups: ABI ≤0.9 (low ABI group; 9.2%) and ABI >0.9 (90.8%). The primary outcome measured was the cumulative incidence of major adverse cardiovascular events (MACE; cardiovascular death, myocardial infarction, and stroke). Results Over a mean follow-up of 5.0 years, 101 MACE occurred. The incidence of MACE was significantly higher in patients with low ABI than in those with ABI >0.9 (30.2% vs. 14.4%, log rank p<0.001). A low ABI was associated with MACE in a univariate Cox proportional hazard analysis. A low ABI remained an independent predictor of MACE in a multivariate analysis adjusted for cardiovascular risk factors (hazard ratio (HR): 2.27; 95% confidence interval (CI): 1.33-3.86; p=0.002). Conclusion Low ABI was an independent predictor for MACE in patients with mild renal insufficiency.

Impressive predictive value of ankle-brachial index for very long-term outcomes in patients with cardiovascular disease: IMPACT-ABI study.

BACKGROUND: The ankle-brachial index (ABI) is a marker of generalized atherosclerosis and is predictive of future cardiovascular events. However, few studies have assessed its relation to long-term future cardiovascular events, especially in patients with borderline ABI. We therefore evaluated the relationship between long-term future cardiovascular events and ABI. METHODS: In the IMPACT-ABI study, a single-center, retrospective cohort study, we enrolled 3131 consecutive patients (67 ± 13 years; 82% male) hospitalized for cardiovascular disease and measured ABI between January 2005 and December 2012. After excluding patients with an ABI > 1.4, the remaining 3056 patients were categorized as having low ABI (≤ 0.9), borderline ABI (0.91-0.99), or normal ABI (1.00-1.40). The primary endpoint was MACE (cardiovascular death, myocardial infarction [MI] and stroke). The secondary endpoints were cardiovascular death, MI, stroke, admission due to heart failure, and major bleeding. RESULTS: During a 4.8-year mean follow-up period, the incidences of MACE (low vs. borderline vs. normal: 32.9% vs. 25.0% vs. 14.6%, P<0.0001) and cardiovascular death (26.2% vs. 18.7% vs. 8.9%, P<0.0001) differed significantly across ABIs. The incidences of stroke (9.1% vs. 8.6% vs. 4.8%, P<0.0001) and heart failure (25.7% vs. 20.8% vs. 8.9%, P<0.0001) were significantly higher in the low and borderline ABI groups than in the normal ABI group. But the incidences of MI and major bleeding were similar in the borderline and normal ABI groups. The hazard ratios for MACE adjusted for traditional atherosclerosis risk factors were significantly higher in patients with low and borderline ABI than those with normal ABI (HR, 1.93; 95%CI: 1.44-2.59, P < 0.0001, HR, 1.54; 95% CI: 1.03-2.29, P = 0.035). CONCLUSIONS: The incidence of long-term adverse events was markedly higher among patients with low or borderline ABI than among those with normal ABI. This suggests that more attention should be paid to patients with borderline ABIs, especially with regard to cardiovascular death, stroke, and heart failure.

Prognostic Impact of Diastolic Wall Strain in Patients at Risk for Heart Failure.

Diastolic wall strain (DWS) is based on the linear elastic theory, according to which decreased wall thinning during diastole reflects reduced left ventricular compliance and thus increased diastolic stiffness. Increased diastolic stiffness as assessed by DWS is associated with a worse prognosis in patients who have heart failure (HF) with preserved ejection fraction. However, there are no data about the prognostic value of DWS derived by M-mode echocardiography in patients at risk for HF. We retrospectively enrolled 1829 consecutive patients without prior HF who were hospitalized for cardiovascular (CV) diseases in our hospital between 2005 and 2012. Patients were divided into two groups stratified by DWS (median value 0.34). The study endpoint was the composite of major adverse cardiovascular events (MACE), including all-cause death, myocardial infarction, stroke, and hospitalization for HF. Over a 4.2-year median follow-up, adverse events were observed in 322 patients (17.6%). In Kaplan-Meier analysis, patients with low DWS (≤ 0.34, n = 915) showed worse prognoses than those with high DWS (> 0.34, n = 914) (MACE incidence 39.4% versus 31.9%, P = 0.011). In multivariate Cox proportional hazards analysis after the adjustment for age, sex, and echocardiographic parameters, low DWS (≤ 0.34) was significantly associated with the incidence of MACE (hazard ratio: 1.26, 95% confidence interval: 1.01-1.59; P = 0 .045). In patients without prior HF, DWS is an independent predictor of MACE. Simple assessment of DWS might improve risk stratification for CV events in those patients.

Factors Predicting Recovery of Oral Intake in Stroke Survivors with Dysphagia in a Convalescent Rehabilitation Ward.

BACKGROUND: Percutaneous endoscopic gastrostomy may be performed in dysphagic stroke patients. However, some patients regain complete oral intake without gastrostomy. This study aimed to investigate the predictive factors of intake, thereby determining gastrostomy indications. METHOD: Stroke survivors admitted to our convalescent rehabilitation ward who underwent gastrostomy or nasogastric tube placement from 2009 to 2015 were divided into 2 groups based on intake status at discharge. Demographic data and Functional Independence Measure (FIM), Dysphagia Severity Scale (DSS), National Institutes of Health Stroke Scale, and Glasgow Coma Scale (GCS) scores on admission were compared between groups. We evaluated the factors predicting intake using a stepwise logistic regression analysis. RESULTS: Thirty-four patients recovered intake, whereas 38 achieved incomplete intake. Mean age was lower, mean body mass index (BMI) was higher, and mean time from stroke onset to admission was shorter in the complete intake group. The complete intake group had less impairment in terms of GCS, FIM, and DSS scores. In the stepwise logistic regression analysis, BMI, FIM-cognitive score, and DSS score were significant independent factors predicting intake. The formula of BMI × .26 + FIM cognitive score × .19 + DSS score × 1.60 predicted recovery of complete intake with a sensitivity of 88.2% and a specificity of 84.2%. CONCLUSIONS: Stroke survivors with dysphagia with a high BMI and FIM-cognitive and DSS scores tended to recover oral intake.

The usefulness of brachial-ankle pulse wave velocity in predicting long-term cardiovascular events in younger patients.

Brachial-ankle pulse wave velocity (baPWV) is known as a significant predictor of cardiovascular events. However, the previous studies have not considered age, which can affect the baPWV value. We evaluated the predictive value of baPWV for cardiovascular events in various age groups. From January 2005 to December 2012, all patients admitted to our department with any cardiovascular disease and underwent ankle-brachial index (ABI) measurement were enrolled in the IMPACT-ABI registry. The primary endpoints included major adverse cardiovascular events (MACE; cardiovascular death, myocardial infarction, and stroke). Of the 3131 patients enrolled, 2554 were included in the analysis, whereas 577 were excluded due to missing baPWV data, ABI ≤0.9 and/or >1.4, and the previous endovascular therapy and/or surgical treatment for peripheral artery disease. Patients were divided according to age 30-59 years (n = 580), 60-69 years (n = 730), 70-79 years (n = 862), and ≥80 years (n = 330). The cumulative incidence of MACE through 5 year was significantly higher in the high baPWV group (>1644 cm/s) than in the low baPWV group (≤1644 cm/s; 8.7 vs. 4.6%; log-rank: p < 0.001). However, among the age groups, only the 30-59-year group showed a significant difference in MACE incidence between those with high and low baPWV (7.0 vs. 0.9%; log-rank: p = 0.001). In conclusion, the baPWV could serve as a useful marker to predict cardiovascular events, particularly among younger patients.

Prognostic value of ankle brachial index for future incident heart failure in patients without previous heart failure: data from the impressive predictive value of ankle brachial index for clinical long term outcome in patients with cardiovascular disease examined by ABI study.

The ankle brachial index (ABI) is regarded as a predictor of future cardiovascular events. However, the relationship between ABI and incident heart failure (HF) in patients without previous HF is poorly understood. This study aimed to assess the prognostic value of ABI for incident HF in patients without previous HF. The IMPACT-ABI study was a retrospective, single-center, cohort study that enrolled and measured ABI in 3131 patients hospitalized for cardiovascular disease between January 2005 and December 2012. From this cohort, 307 patients were excluded because of previous HF and high (>1.4) ABI. The remaining 2824 patients were stratified into three groups: low ABI (≤0.9), borderline ABI (0.91-0.99), and normal ABI (1.0-1.4). The primary endpoint was hospitalization for HF. Over a mean 4.8-year follow-up, 105 cases of HF occurred. The cumulative incidence of HF was significantly higher in patients with low and borderline ABIs than in those with normal ABI (19.3 vs. 21.0 vs. 10.4 %, log rank P <0.001). In multivariate Cox proportional hazard analysis, low ABI and borderline ABI were independent predictors of incident HF [hazard ratio (HR) 3.00; 95 % confidence interval (CI) 1.70-5.28; P < 0.001 and HR 2.68; 95 % CI 1.35-5.34; P = 0.005, respectively]. In conclusion, low and borderline ABI were strong predictors for future incident HF in patients without previous HF.

Clinical Characteristics and Outcomes of Patients with High Ankle-Brachial Index from the IMPACT-ABI Study.

BACKGROUND: Reduced ankle-brachial index (ABI) is a predictor of cardiovascular events. However, the significance of high ABI remains poorly understood. This study aimed to assess the characteristics and outcomes of patients with high ABI. METHODS: The IMPACT-ABI study was a retrospective cohort study that enrolled and examined ABI in 3,131 patients hospitalized for cardiovascular disease between January 2005 and December 2012. From this cohort, 2,419 patients were identified and stratified into two groups: high ABI (> 1.4; 2.6%) and normal ABI (1.0-1.4; 97.3%). The primary endpoint was the cumulative incidence of major adverse cardiovascular events (MACE), including cardiovascular-associated death, myocardial infarction, and stroke. RESULTS: Compared with the normal ABI group, patients in the high ABI group showed significantly lower body mass index (BMI) and hemoglobin level, but had higher incidence of chronic kidney disease and hemodialysis. Multivariate logistic regression analysis revealed that hemodialysis was the strongest predictor of high ABI (odds ratio, 6.18; 95% confidence interval (CI), 3.05-12.52; P < 0.001). During the follow-up (median, 4.7 years), 172 cases of MACE occurred. Cumulative MACE incidence in patients with high ABI was significantly increased compared to that in those with normal ABI (32.5% vs. 14.5%; P = 0.005). In traditional cardiovascular risk factors-adjusted multivariate Cox proportional hazard analysis, high ABI was an independent predictor of MACE (hazard ratio, 2.07; 95% CI, 1.02-4.20; P = 0.044). CONCLUSION: Lower BMI, chronic kidney disease, and hemodialysis are more frequent in patients with high ABI. Hemodialysis is the strongest predictor of high ABI. High ABI is a parameter that independently predicts MACE.