High Normal Group Research Articles

Urinary extracellular vesicles as a monitoring tool for renal damage in patients not meeting criteria for chronic kidney disease.

Current definition of chronic kidney disease (CKD) identifies only advanced stages, but effective management demands early detection. Urinary albumin-to-creatinine ratio (ACR) 30mg/g is a cut-off point for CKD clinical diagnosis. Patients with lower values (normoalbuminuria) and eGFR>60mL/min/1.73m2 are considered at no increased cardiorenal risk. However, higher incidence of renal function decline and cardiovascular events have been shown within the normoalbuminuria range. Novel subclinical indicators may help to identify higher-risk patients. Urinary extracellular vesicles (uEVs) are sentinels of renal function non-invasively. Here we aimed to approach the early assessment of cardiorenal risk by investigating the protein cargo of uEVs. Hypertensive patients were classified in control group (C) with ACR<10mg/g, and high-normal group (HN) with ACR 10-30mg/g. Isolated uEVs were characterized by western blotting and electron microscopy and the protein cargo was analyzed by untargeted proteomics (LC-MS/MS) in a first discovery cohort. Protein confirmation was performed in a different cohort by ExoView. Immunohistochemistry of human kidney biopsies was also performed to evaluate the potential of uEVs to reflect renal damage. HN albuminuria does not affect the uEVs concentration, size, or tetraspanin profile. Among >6200 uEVs proteins identified, 43 define a panel significantly altered in HN patients without variation in urine, mostly annotated in the tubule (39 out of 43). The tubular transporter long-chain fatty acid transport protein 2 (SLC27A2) and the apical membrane protein amnionless (AMN) confirmed their alteration in HN patients evidencing impaired tubular reabsorption. SLC27A2 showed tubular expression and significantly reduced levels in patients with diagnostic criteria for CKD. Alterations in the EV-mediated molecular profile are evident before pathological ACR levels are reached. Direct quantitation of SLC27A2 and AMN in uEVs helps identifying normoalbuminuric subjects with higher cardiorenal risk in early monitoring of CKD.

Effects of high-normal fasting blood glucose on ART outcomes of frozen-thawed single blastocyst transfer in women with normal BMI.

This retrospective cohort study aims to investigate whether high-normal fasting blood glucose (FBG) affects assisted reproductive technology (ART) outcomes undergoing single blastocyst frozen-thawed embryo transfer (FET) cycles in women with normal body mass index (BMI). 944 women with normal BMI and FBG levels undergoing single blastocyst FET cycles were enrolled. Based on the median of FBG (4.97mmol/L, 1mmol/L = 18mg/dL), the subjects were categorized into the low-normal group (3.90 ≤ FBG ≤ 4.97 mmol/L, n = 472) and the high-normal group (4.97 < FBG < 6.10mmol/L, n = 472). Multivariable logistic regression and receiver operating characteristic (ROC) were used to analyze the relationship between high-normal FBG and ART outcomes. live birth rate (LBR). LBR was significantly lower in the high-normal group than in the low-normal group (36.8% vs. 45.1%, p = 0.010), and the miscarriage rate was considerably higher than that in the low-normal group (23.9% vs. 16.5%, p = 0.041). High-normal FBG of female was an independent predictor of live birth (adjusted OR:0.747, 95% CI: 0.541-0.963, p = 0.027) and miscarriage (adjusted OR:1.610, 95% CI: 1.018-2.547, p = 0.042). ROC analyses showed that the cut-off values of FBG (endpoints: live birth and miscarriage) were 5.07mmol/L, and 5.01mmol/L, respectively. In women with normal BMI, high-normal FBG is an independent risk factor for lower LBR and higher miscarriage rate in single blastocyst FET cycles. Attention to preconception FBG monitoring in this particular population may allow early intervention to improve ART outcomes.

Levothyroxine Treatment in Pregnant Women with Thyrotropin Levels Ranging Between 2.5 and 10 mIU/L: A Propensity Score Matched Analysis.

Objective: To clarify the association between levothyroxine (LT4) treatment and various adverse pregnancy outcomes in pregnant women with thyrotropin (TSH) levels ranging between 2.5 and 10.0 mIU/L in the first trimester, stratified according to thyroid peroxidase antibody (TPOAb) positivity and TSH level. Methods: This retrospective analysis of retrospectively and prospectively collected cohort data included Chinese pregnant women with TSH levels of 2.5-10 mIU/L and normal free thyroxine levels (11.8-18.4 pmol/L) in the first trimester. All participants were followed up until the completion of pregnancy, and information on LT4 treatment, pregnancy complications, and pregnancy outcomes was recorded. A 1:1 nearest-neighbor propensity score matching (PSM) between the LT4-treated and - untreated groups with a caliper distance of 0.02 was performed using a multivariable logistic regression model. Multivariable-adjusted modified Poisson regression was used to estimate the relative risk (RR) and 95% confidence interval (CI) of LT4 treatment for adverse pregnancy outcomes. Subgroup analyses were also performed in four subgroups simultaneously stratified by TPOAb status (negative or positive) and TSH levels (2.5-4.0 mIU/L as high-normal group and 4.0-10.0 mIU/L as SCH group). The study was registered in the Chinese Clinical Trial Registry (ChiCTR2100047394). Results: Among the 4,370 pregnant women in the study, 1,342 received LT4 treatment and 3,028 did not. The 1:1 PSM yielded 668 pairs of individuals and revealed that LT4 treatment was significantly associated with a decreased risk of pregnancy loss (RR = 0.528, 95% CI: 0.344-0.812) and an increased risk of small-for-gestational-age infants (RR = 1.595, 95% CI: 1.023-2.485). Subgroup analyses suggested that the above effects of LT4 treatment were mainly from TPOAb-negative participants. LT4 treatment was associated with an increased risk of preterm birth (RR = 2.214, 95% CI: 1.016-4.825) in TPOAb-positive pregnant women with high-normal TSH levels. Conclusion: LT4 treatment was significantly associated with a lower risk of pregnancy loss and a higher risk of small-for-gestational-age infants in pregnant women with TSH levels of 2.5-10 mIU/L. An increased risk of preterm birth was observed in the LT4-treated group among TPOAb-positive participants with TSH levels of 2.5-4.0 mIU/L.

Early neutrophil trajectory following clozapine may predict clozapine response – Results from an observational study using electronic health records

BackgroundClozapine has unique effectiveness in treatment-resistant schizophrenia and is known to cause immunological side-effects. A transient spike in neutrophils commonly occurs in the first weeks of clozapine therapy. There is contradictory evidence in the literature as to whether neutrophil changes with clozapine are linked to treatment response. AimsThe current study aims to further examine the neutrophil changes in response to clozapine and explore any association between neutrophil trajectory and treatment response. MethodsA retrospective cohort study of patients undergoing their first treatment with clozapine and continuing for at least 2 years identified 425 patients (69% male/31% female). Neutrophil counts at baseline, 3 weeks and 1 month were obtained predominantly by linkage with data from the clozapine monitoring service. Clinical Global Impression- Severity (CGI-S) was rated from case notes at the time of clozapine initiation and at 2 years. Latent class growth analysis (LCGA) was performed to define distinct trajectories of neutrophil changes during the first month of treatment. Logistic regression was then conducted to investigate for association between the trajectory of neutrophil count changes in month 1 and clinical response at 2 years as well as between baseline neutrophil count and response. ResultsOf the original cohort, 397 (93%) patients had useable neutrophil data during the first 6 weeks of clozapine treatment. LCGA revealed significant differences in neutrophil trajectories with a three-class model being the most parsimonious. The classes had similar trajectory profiles but differed primarily on overall neutrophil count: with low, high-normal and high neutrophil classes, comprising 52%, 40% and 8% of the sample respectively. Membership of the high-normal group was associated with significantly increased odds of a positive response to clozapine, as compared to the low neutrophil group [Odds ratio (OR) = 2.10, p-value = 0.002; 95% confidence interval (95% CI) = 1.31–3.36]. Baseline neutrophil count was a predictor of response to clozapine at 2 years, with counts of ≥5 × 109/l significantly associated with positive response (OR = 1.60, p-value = 0.03; 95% CI = 1.03–2.49). ConclusionsOur data are consistent with the hypothesis that patients with low-level inflammation, reflected in a high-normal neutrophil count, are more likely to respond to clozapine, raising the possibility that clozapine exerts its superior efficacy via immune mechanisms.

High-normal serum uric acid predicts macrovascular events in patients with type 2 diabetes mellitus without hyperuricemia based on a 10-year cohort

Background and aimsThe upper limits of normal serum uric acid (SUA) or the lower limits of hyperuricemia were frequently set at 420 or 360 μmol/L (7.0 or 6.0 mg/dL). We aimed to explore the association between high-normal SUA (360 ≤ SUA≤420 μmol/L) and incidence of macrovascular and renal events based on a 10-year cohort with type 2 diabetes mellitus (T2DM) to explore which cut-off was more appropriate. Methods and resultsA total of 2988 patients with T2DM without hyperuricemia (SUA≤420 μmol/L) were included and followed up. Cox proportional hazards models and restricted cubic spline regression were used to evaluate the relationship between baseline SUA (as continuous and categorical variable) and macrovascular and renal events. Patients were grouped as low-normal (SUA<360 μmol/L) and high-normal groups based on baseline SUA, and the latter group had higher incidence of macrovascular events. Multivariate Cox regression analysis indicated that baseline levels of SUA were significantly associated with cardiovascular (HR = 1.385, 95%CI:1.190–1.613, P < 0.001) and peripheral vascular events (HR = 1.266, 95%CI:1.018–1.574, P = 0.034), and the linear association existed. Moreover, fully adjusted multivariable Cox analyses indicated high-normal SUA increased the risks of cardiovascular (HR = 1.835, 95%CI:1.319–2.554, P < 0.001) and peripheral vascular events (HR = 1.661, 95%CI:1.000–2.760, P = 0.050) compared to low-normal SUA. ConclusionsBaseline SUA levels were positively associated with cardiovascular and peripheral vascular events, and high-normal SUA increased the risks of these events in patients with T2DM even without hyperuricemia. A threshold value for SUA of 360 μmol/L should be more appropriate in terms of predicting macrovascular events risks compared to the value of 420 μmol/L.

Serum vitamin E level and functional prognosis after traumatic brain injury with intracranial injury: A multicenter prospective study.

Traumatic brain injury (TBI) is a major public health problem with high mortality and disability. Vitamin E, one of the antioxidants for treatment of TBI, has not been sufficiently evaluated for predicting prognosis of TBI. This study aimed to evaluate the prognostic value of vitamin E on functional outcomes of TBI patients with intracranial injury. A multi-center prospective cohort study was conducted in five university hospitals between 2018 and 2020. Adult TBI patients who visited the emergency department (ED) with intracranial hemorrhage or diffuse axonal injury confirmed by radiological examination were eligible. Serum vitamin E levels (mg/dL) were categorized into 4 groups: low (0.0-5.4), low-normal (5.5-10.9), high-normal (11.0-16.9), and high (17.0-). Study outcomes were set as 1- and 6-month disability (Glasgow outcome scale (GOS) 1-4). Multilevel logistic regression analysis was conducted to calculate the adjusted odds ratios (AORs) of vitamin E for related outcomes. Among 550 eligible TBI patients with intracranial injury, the median (IQR) of serum vitamin E was 10.0 (8.0-12.3) mg/dL; 204/550 (37.1%) had 1-month disability and 197/544 (36.1%) had 6-month disability of GOS 1-4. Compared with the high-normal group, the odds of 1-month disability and 6-month disability increased in the low and low-normal group (AORs (95% CIs): 3.66 (1.62-8.27) and 2.60 (1.15-5.85) for the low group and 1.63 (1.08-2.48) and 1.60 (1.04-2.43) for the low-normal group, respectively). Low serum vitamin E level was associated with poor prognosis at 1 and 6 months after TBI with intracranial injury.

Comparison of reproductive outcomes in subclinical hypothyroidism women with high-normal versus low-normal thyroid-stimulating hormone levels after treatment with levothyroxine.

Reproductive outcomes in euthyroid women with high-normal thyroid-stimulating hormone (TSH) levels are comparable to those in euthyroid women with low TSH levels; however, few studies have investigated whether strictly controlled TSH levels after levothyroxine (LT4) treatment impair reproductive outcomes in infertile women with subclinical hypothyroidism (SCH). This study aimed to investigate the impact of high-normal versus low-normal TSH levels on reproductive outcomes in women undergoing their first in vitro fertilisation and embryo transfer (IVF-ET) cycle. This was a retrospective cohort study. Patients were divided into low-normal (TSH < 2.5 mIU/L, and ≥0.27 mIU/L) and high-normal (TSH ≥ 2.5 mIU/L, and <4.2 mIU/L) groups based on TSH levels after LT4 treatment. TSH levels after LT4 treatment and before ovarian stimulation were recorded. Reproductive outcomes were compared between the low-normal and high-normal TSH groups and between the euthyroid and LT4-treated groups. A total of 6002 women, 548 of whom were LT4-treated women, were finally included in this study. Among the LT4-treated women, 129 women had low-normal TSH levels, and 167 women had high-normal TSH levels. The clinical pregnancy rate, miscarriage rate, and live birth rate were comparable between the low-normal and high-normal groups (all p > .05). When adjusted by age, anti-Mullerian hormone (AMH) levels, infertility duration, transferred embryos, and dose and duration of LT4 treatment, high-normal TSH levels neither significantly decreased miscarriage (adjusted odds ratio [aOR] = 2.27, 95% confidence interval [CI] = 0.77-6.69, p = .14) nor increased clinical pregnancy (aOR = 1.15, 95% CI = 0.70-1.89, p = .57 or live birth (aOR = 0.97, 95% CI = 0.60-1.59, p = .92). Similar obstetric outcomes were observed between the low-normal and high-normal TSH groups after LT4 treatment and between the euthyroid and LT4-treated groups (all p ≥ .05). High-normal TSH levels did not have adverse effects on clinical and obstetric outcomes when compared with low-normal TSH levels after LT4 treatment. However, whether it is appropriate to set 2.5 mIU/L as the goal of treatment before IVF/ICSI remains to be determined in further well-designed studies.

Association of plasma uric acid levels with cognitive function among non-hyperuricemia adults: A prospective study

The neuroprotective roles of uric acid are still controversial. One possible explanation is that previous studies included participants with hyperuricemia, which might interfere with clarifying the association. Therefore, this study aimed to investigate the prospective association between plasma uric acid levels and cognitive function among non-hyperuricemia adults. A total of 7828 participants from the China Health and Retirement Longitudinal Study (CHARLS) who were free from hyperuricemia, brain damage, mental retardation, or memory-related diseases at baseline were included. According to the baseline plasma uric acid levels, participants were classified into low (<3.5mg/dL for men and <2.5mg/dL for women), low-normal (3.5-4.9mg/dL for men and 2.5-3.9mg/dL for women), and high-normal groups (4.9-7.0mg/dL for men and 3.9-6.0mg/dL for women). Cognitive function tests covered the domains of executive function (time orientation, numerical ability, and drawing) and episodic memory (immediate and delayed word recall). We used generalized estimating equation models to evaluate the average difference in cognitive function within 4-years' follow-up across different uric acid groups. Compared with the high-normal group, participants with lower uric acid levels were associated with poorer cognitive performance during 4-years' follow-up. The corresponding level of difference was-0.24 (95% CI:-0.47,-0.01) for low group, and-0.13 (95% CI:-0.26,-0.01) for low-normal group. The associations were significant and similar for the specific domain of executive function (P<0.001). In addition, a stronger association was observed among participants with baseline age ≥60 years (P<0.05 for interaction). Our study supports a potential detrimental role of low levels of plasma uric acid on cognitive function among Chinese adults without hyperuricemia. More research is warranted to confirm this finding and identify the optimal plasma uric acid level for cognitive benefits.

Prevalence of target organ damage in subjects with high-normal blood pressure without known cardiovascular and kidney disease

Abstract Background Heterogeneous results have been obtained regarding the presence of Target Organe Damage (TOD) in subjects with high-normal Blood Pressure (BP) value (sistoly 130–139, diastolic 85–89 mmHg). Purpose Aim of our study was to assess the prevalence of TOD in healthy subjects with high-normal BP comparing them with subjects with BP values that are considered normal (&amp;lt;130/85 mmHg) or indicative of hypertension (≥140/90 mmHg). Methods 755 otherwise healthy subjects participated at the present analysis. TOD was evaluated as Pulse Wave Velocity (PWV), Left Ventricular Mass Index (LVMI) and carotid Intima-Media Thickness (IMT) and plaque. Results When subjects were classified according to BP levels we found that high-normal BP group showed intermediate values of PWV and LMVI with higher value of IMT. This corresponds to intermediate prevalence of arterial stiffness (PWV&amp;gt;10 m/s: 3.4% vs 2.3% for normal and 9.6% for high BP groups, p=0.0014), Left Ventricular Hypertrophy – LVH (32.4% vs 25.7% for normal and 46.6% for high BP groups, p=0.0001) while there were no differences for IMT&amp;gt;0.9 or carotid plaque. At multivariable analysis the odds of having a PWV&amp;gt;10 m/s (OR=1.75, 95% C.I. 0.59–5.16), an IMT&amp;gt;0.9 mm (OR=1.81, 95% C.I. 0.60–5.00) or a LVH (OR=1.1, 95% C.I. 0.72–1.67) in the high-normal group resulted not different to the normal group. Conclusions In our otherwise healthy population, high-normal BP values were not related to aortic, carotid or cardiac TOD. Funding Acknowledgement Type of funding sources: None.

Prevalence of hypertension mediated organ damage in subjects with high-normal blood pressure without known hypertension as well as cardiovascular and kidney disease.

Purpose of our study was to assess the prevalence of hypertension mediated organ damage (HMOD) in healthy subjects with high-normal Blood Pressure (BP) comparing them with subjects with BP values that are considered normal (<130/85 mmHg) or indicative of hypertension (≥140/90 mmHg). Seven hundred fifty-five otherwise healthy subjects were included. HMOD was evaluated as pulse wave velocity (PWV), left ventricular mass index (LVMI), and carotid intima-media thickness (IMT) and plaque. When subjects were classified according to BP levels we found that the high-normal BP group showed intermediate values of PWV and higher values of IMT. This corresponds to intermediate prevalence of arterial stiffness, while there were no differences for increased IMT or carotid plaque. No subjects showed left ventricular hypertrophy. At multivariable analysis, the odds of having arterial stiffness or carotid HMOD in the high-normal group resulted not different to the normal group. In conclusion, in our otherwise healthy population, high-normal BP values were not related to aortic, carotid or cardiac HMOD.

TCA Cycle and Fatty Acids Oxidation Reflect Early Cardiorenal Damage in Normoalbuminuric Subjects with Controlled Hypertension.

Moderately increased albuminuria, defined by an albumin to creatinine ratio (ACR) > 30 mg/g, is an indicator of subclinical organ damage associated with a higher risk of cardiovascular and renal disease. Normoalbuminuric subjects are considered at no cardiorenal risk in clinical practice, and molecular changes underlying early development are unclear. To decipher subjacent mechanisms, we stratified the normoalbuminuria condition. A total of 37 hypertensive patients under chronic renin–angiotensin system (RAS) suppression with ACR values in the normoalbuminuria range were included and classified as control (C) (ACR < 10 mg/g) and high-normal (HN) (ACR = 10–30 mg/g). Target metabolomic analysis was carried out by liquid chromatography and mass spectrometry to investigate the role of the cardiorenal risk urinary metabolites previously identified. Besides this, urinary free fatty acids (FFAs), fatty acid binding protein 1 (FABP1) and nephrin were analyzed by colorimetric and ELISA assays. A Mann–Whitney test was applied, ROC curves were calculated and Spearman correlation analysis was carried out. Nine metabolites showed significantly altered abundance in HN versus C, and urinary FFAs and FABP1 increased in HN group, pointing to dysregulation in the tricarboxylic acid cycle (TCA) cycle and fatty acids β-oxidation. We showed here how cardiorenal metabolites associate with albuminuria, already in the normoalbuminuric range, evidencing early renal damage at a tubular level and suggesting increased β-oxidation to potentially counteract fatty acids overload in the HN range.

The Value of Ketone Bodies in the Evaluation of Kidney Function in Patients with Type 2 Diabetes Mellitus

Objectives Recent studies have shown that the slightly elevated circulating levels of ketone bodies (KBs) played a significant role in the treatment of various diseases. This study is aimed at investigating the association between different levels of KBs and kidney function in patients with type 2 diabetes mellitus (T2DM). Methods A retrospective study of 955 patients with T2DM (426 women and 529 men) admitted to our hospital from December 2017 to September 2019 was conducted. Patients were divided into different groups in line with the levels of KBs (low-normal group: 0.02-0.04 mmol/L, middle-normal group: 0.05-0.08 mmol/L, high-normal group: 0.09-0.27 mmol/L, and slightly elevated group: >0.27 and <3.0 mmol/L). Results In the present study, individuals with high-normal levels of KBs had the lowest risk of diabetic kidney disease (DKD) and increased peak systolic velocity (PSV); those with middle-normal levels of KBs had the lowest risk of increased renal arterial resistive index (RI), with a positive correlation between increased α1-microglobulin and KB concentration. In addition, the indicators of glomerulus, renal tubules, and renal arteries were all poor with slightly elevated circulating levels of KBs, and KB concentration lower than 0.09 mmol/L can be applied as the threshold for low risk of renal function damage. Conclusions In summary, slightly elevated circulating levels of ketone bodies are not of benefit for renal function in patients with type 2 diabetes mellitus.

Low-Normal Platelets and Decreasing Platelets Are Risk Factors for Hearing Impairment Development.

Identification of undefined risk factors will be crucial for the development of therapeutic strategies in hearing impairment. Platelets are likely to affect the development of sudden sensorineural hearing loss, which is a primary risk factor for permanent hearing impairment. This implies that abnormal platelets might contribute to long-term hearing loss. This study investigated the role of platelets in the development of hearing impairment over a 5-year period. This study was a retrospective cohort study and consisted of a population-based survey, which was performed for 1,897 participants in 2014 to 2019. To evaluate the effect of platelet level on hearing ability, the subjects were divided into two groups: a high-normal platelet group (25 ∼ 40 × 104 cells/μL) and a low-normal platelet group (15 ∼ 25 × 104 cells/μL). Subjects were defined as having hearing impairment when pure tone audiometry was over 25 dB HL in either ear (tested in 2017 and 2019). Incidence of hearing impairment was analyzed. Incidence of hearing impairment at low frequencies was significantly higher in the low-normal platelet group than in the high-normal group year over year. Low-normal platelet count associated with low-frequency hearing impairment (LFHI) incidence (odds ratio [OR], 2.34; 95% confidence interval [CI], 1.15-4.76). In the low-normal platelet group, subjects whose counts declined from baseline developed more LFHI than those whose counts increased over time. Further, decreasing platelets appeared to be an independent risk factor contributing to the incidence of LFHI (OR, 2.10; 95%CI, 1.09-4.06) in the low-normal platelet group. Both a low-normal platelet and a declining platelet count were independently associated with the incidence of LFHI. 3 Laryngoscope, 131:E1287-E1295, 2021.

Effects of combined histamine H1 and H2 receptor blockade on hemodynamic responses to dynamic exercise in males with high-normal blood pressure.

While postexercise hypotension is associated with histamine H1 and H2 receptor-mediated postexercise vasodilation, effects of histaminergic vasodilation on blood pressure (BP) in response to dynamic exercise are not known. Thus, in 20 recreationally active male participants (10 normotensive and 10 with high-normal BP) we examined the effects of histamine H1 and H2 receptor blockade on cardiac output (CO), mean atrial pressure (MAP), aortic stiffness (AoStiff), and total vascular conductance (TVC) at rest and during progressive cycling exercise. Compared with the normotensive group, MAP, CO, and AoStiff were higher in the high-normal group before and after the blockade at rest, while TVC was similar. At the 40% workload, the blockade significantly increased MAP in both groups, while no difference was found in the TVC. CO was higher in the high-normal group than the normotensive group in both conditions. At the 60% workload, the blockade substantially increased MAP and decreased TVC in the normotensive group, while there were no changes in the high-normal group. A similar CO response pattern was observed at the 60% workload. These findings suggest that the mechanism eliciting an exaggerated BP response to exercise in the high-normal group may be partially due to the inability of histamine receptors. Novelty Males with high-normal BP had an exaggerated BP response to exercise. The overactive BP response is known due to an increase in peripheral vasoconstriction. Increase in peripheral vasoconstriction is partially due to inability of histamine receptors.

Abstract 466: Carotid Atherosclerosis on the Association Between Hypothyroidism and Renal Dysfunction in a Healthy Japanese Population

Aim: This large-scale Japanese population study was done to evaluate the relation between the serum thyroid stimulating hormone (TSH) level and renal function. Methods: Among 1,374 residents who attended a free public physical examination between 2010 and 2011, we evaluated the data of 888 for whom the serum TSH level and estimated glomerular filtration rate (eGFR) were successfully measured. The participants were divided into three groups by TSH level (normal TSH, ≤2.4; high-normal TSH, 2.5-4.4; subclinical hypothyroid, ≥4.5 μIU/L). Multiple linear regression analysis adjusted for cardiovascular risk factors was done to determine the relation between serum TSH level and renal function. Results: The mean ± SD TSH level was 2.0±1.4 μIU/mL. Of the participants, 75.9% (n=674) had a normal TSH level, 17.9% (n=159) were high-normal TSH, and 6.2% (n=55) were subclinical hypothyroid. The mean eGFR significantly decreased with increased TSH level (normal TSH group, 79.3±14.1; high-normal TSH group, 77.4±13.0; subclinical hypothyroid group; 72.3±12.2 mL/min/1.73m2: P for trend &lt;0.01). Multiple linear regression analysis extracted log-transformed TSH level as an independent factor correlated with eGFR in the high-normal TSH group (beta=-0.18, P=0.02). Conclusions: The eGFR level significantly decreased with increased TSH level. Significant correlation between TSH and eGFR levels was found only in high-normal TSH individuals. Even in healthy individuals, increase risk of chronic kidney disease could be started from high-normal TSH level.

High-Normal Glucose Levels in a Routine Oral 1-Hour 50 g Glucose Challenge Test Are Associated with a Poorer Glycemic Status Later in Life.

Objective A 1-hour 50 g glucose challenge test (GCT) is generally used as a screening test for a 3-hour 100 g test. The future glycemic status of a pregnant woman with abnormal (high) GCT is widely discussed in the literature. On the other hand, future glycemic status of women with various glucose levels within the normal range on GCT has not yet been studied. To examine the hypothesis that lower glucose levels in GCT may result in a better glycemic status later in life, we compared the glucose levels in GCT with the glycemic status 9 years later in a large cohort in Israel. Study Design The study was performed at the Central District of Clalit Health Services, the largest health maintenance organization in Israel. From the computerized database, we gathered data on women who underwent GCT between August 2005 and August 2006.We evaluated the association between GCT results at entry and fasting glucose levels 9 years later. The study was approved by the institutional review board (IRB). We used analysis of variance (ANOVA) followed by pairwise comparisons using Tukey's method (p = 0.05) and ordinal logistic regression tests for statistical analysis. Results A total of 6,929 women performed GCT at entry. Fasting glucose levels were available 9 years later for 4,247 women. GCT results at entry level were grouped and divided into the following groups: very low GCT (&lt;100 mg%), low-normal (100–125 mg%), high-normal (126–140 mg%), and abnormal GCT (&gt;140 mg%). Fasting glucose results, as well as impaired fasting glucose 9 years following normal GCT had a direct correlation with GCT results. Ten percent of women who performed GCT had a high-normal result of 126 to 140 mg%. This high-normal group had a significantly higher fasting glucose and impaired fasting glucose (&gt;100 mg%) 9 years after performing the GCT as compared with the very low or normal GCT groups. Moreover, diabetes risk of this group was significantly higher than the lower groups. Conclusion Although GCT is only a screening test, it may serve as a practical predictor for further fasting glucose levels, impaired fasting glucose, and diabetes in a relatively short time (9 years). In this study, women with GCT levels up to 125 mg%, when tested 9 years later, had significantly lower fasting glucose and lower percentage of impaired fasting glucose and diabetes than those with GCT above 126 mg%. Women with “normal” GCT levels between 126 and 140 mg% should be closely monitored for their further glycemic status.

Predictive value of serum carcinoembryonic antigen level in efficacy and prognosis for patients with rectal cancer following preoperative radiochemotherapy

To examine the association of preoperative carcinoembryonic antigen (CEA) level with the efficacy of neoadjuvant radiochemotherapy and postoperative metastasis and relapse in patients with rectal cancer. Between January 2011 and January 2014, 325 patients with local advanced rectal cancer underwent preoperative radiochemotherapy and radical operation in Department of Colorectal Cancer Surgery, Beijing University Cancer Hospital, including 194 males and 131 females. According to preoperative MRI, all the patients suffered from clinical T3-4 tumors or positive lymph nodes. Their Zubrod-ECOG-WHO score was 0-1. These patients received preoperative intensity modulated radiotherapy which consisted of 50.6 Gy in 22 fractions (IMRT GTV 50.6 Gy/CTV 41.8 Gy/22 f) with capecitabine(825 mg/m2, twice per day) as radiosensitizer. According to the preoperative serum CEA level, patients were divided into high group (125 cases) and normal group (200 cases). In high group, serum CEA level decreased into normal range in 60 patients (high-normal group) after radiochemotherapy, while it was still in high level in other 65 patients (high-high group). The differences in sensitivity to radiochemotherapy and 3-year disease free survival (DFS) of these patients were both evaluated. In high group and normal group, the complete response rates were 18.4% (23/125) and 17.5% (35/200) (χ2=0.319, P=0.660); the percentages of tumor regression grade(TRG) 0-1 patients were 68.0%(85/125) and 67.5%(135/200)(χ2=0.009, P=0.925); the T downstage rates were 63.2%(79/125) and 70.0%(140/200)(χ2=1.266, P=0.274), respectively, whose differences were all not significant. The 3-year DFS rate in high group was 62.4%, which was significantly lower than 93.5% in normal group (χ2=53.147, P=0.000). There were 65 patients in high-high group, accounting for 52% (65/125) of high group. Among these 65 patients, 44(67.7%) presented recurrence and metastasis within 3 years and the 3-year DFS was 32.3%, which was much lower than 95.0% of 60 patients in high-normal group(χ2=182.085, P=0.000). Preoperative serum CEA level may not be used to predict tumor response of rectal cancer patients who receive preoperative radiochemotherapy. However, the prognosis of patients with high CEA level is worse. Recurrence and metastasis are more likely to occur in patients with high CEA level after radiochemotherapy.

Low-Normal Systolic Blood Pressure and Secondary Stroke Risk

A recent observational study of >20,000 patients with recent ischemic stroke suggested that systolic blood pressure (SBP) maintained in a low-normal range may be associated with increased risk of recurrent stroke, especially within the first 6 months after the first stroke. Using a distinct cohort, the current study aimed to independently evaluate the relationship between low-normal SBP levels and risk of recurrent stroke through analysis of a trial dataset involving 3680 patients with recent noncardioembolic ischemic stroke aged ≥ 35 years recruited from 56 centers between September 1996 and May 2003 and followed for 2 years. Subjects were categorized based on their mean in-trial SBP value as low-normal (<120 mm Hg), high-normal (120 to <140 mm Hg), or high (>140 mm Hg). The primary outcome was stroke. Multivariate analyses used competing-risks Cox regression models. The rate of recurrent stroke was 9.1% in the low-normal group, 6.7% in the high-normal group, and 10% in the high group. The difference in recurrent stroke rate between the low-normal and high-normal groups was more prominent within the first 6 months (low-normal, 4.5%; high-normal, 2.5%; high, 3.4%) than after 6 months (low-normal, 4.6%; high-normal, 4.2%; high, 6.6%). Over the study period, compared with the high-normal group, the risk of the primary outcome trended higher in the low-normal group (adjusted hazard ratio, 1.47; 95% confidence interval, 0.94-2.29; P = .09) and was higher in the high group (adjusted hazard ratio, 1.39; 95% confidence interval, 1.08-1.79; P = .01). These results support the recently described pattern of increased risk of recurrent stroke in patients with low-normal SBP levels, especially within the first 6 months after first stroke. However, this study likely was not sufficiently powered to detect more than a strong statistical trend underlying this relationship.

Abstract 17129: Altered Subendocardial Perfusion Reserve in Patients with Normal-High Blood Pressure Assessed by Quantitative Analysis of Myocardial Perfusion MRI

Background Myocardial perfusion reserve (MPR) reflects endothelial function of the coronary artery and can be altered by various atherosclerotic risk factors. We previously reported that hypertension is associated with impairment of MPR, especially subendocardial MPR. However, information is limited regarding the impact of normal-high blood pressure (systolic blood pressure (SBP) of 130-139mmHg, diastolic blood pressure (DBP) of 85-89mmHg, or both) on MPR. Purpose To determine if MPR was already altered in patients with normal-high blood pressure by using a quantitative analysis of stress-rest myocardial perfusion MRI. Method We studied 73 subjects without hypertension (SBP&lt;140mmHg and DBP&lt;90mmHg) who did not exhibit regional myocardial ischemia and myocardial scar on stress CMR study. Subjects were divided into two groups (Normal-high group: n=19, 68±9 year-old, 17 men; Normal-optimal group (SBP&lt;130mmHg and DBP&lt;85mmHg): n=54, 68±10 year-old, 33 men) according to blood pressure. Stress-rest myocardial perfusion MRI was acquired with blood signal saturation correction, and absolute subendocardial and epicardial myocardial blood flow (MBF) and MPR were quantified. MPR were calculated as stress MBF divided by rest MBF. Result The averaged transmural MPR in subjects with normal-high blood pressure was significantly lower than that in normal-optimal group.(2.74±1.61 vs. 3.80±2.03, p=0.043). When subepicardial MBF and subendocardial MBF were analyzed separately, MPR in subepicardial myocardium did not demonstrate significant difference between two groups (3.09±1.66 vs. 4.29±2.49, p=ns). In contrast, MPR in subendocardial myocardium was significantly reduced in the high-normal group than in the normal-optimal group. (2.57±1.51 vs. 3.65±1.66, p=0.015) Conclusion In the current study evaluating subjects without regional myocardial ischemia or significant coronary artery disease, subendocardial MPR was significantly decreased in the group with normal-high blood pressure. The result of this study suggests that endothelial function of the coronary artery is already altered in patients with normal-high blood pressure.

Does a high-normal TSH level >2.5 mIU/L pose an increased risk of pregnancy loss in patients undergoing art?

To evaluate if a TSH level > 2.5 mIU/L poses an increased risk of pregnancy loss (MC) in patients who achieved a pregnancy from ART Retrospective. Women undergoing a first, fresh-embryo IVF or ICSI cycle between January 2002-2010 were analyzed.Continuous data were compared using t-test or Mann-Whitney U while categorical data were analyzed using chi-square.While adjusting for age, prior spontaneous loss (SAB) and maximum FSH levels, multivariate logistical regression was performed to determine whether TSH was predictor of MC or live birth (LB) Of the 1517 cycles reviewed, 642(42%) resulted in a positive pregnancy test.Complete data was available for 426 cycles.Of these, 358 cycles had TSH levels within normal range (0.4-4.5 mIU/L) and these cycles were grouped according to low-normal (0.4-2.5mIU/L) or high-normal (2.51-4.5mIU/L) TSH levels.Patient characteristics, including age, BMI, prior SAB, maximum FSH and etiology of infertility were statistically similar amongst groups. 241 LB (67.3%), 60 biochemical pregnancies (BC)(16.8%) and 32 MC (8.9%) were reported,with no statistical difference amongst the rates of BC, MC or LB between the two groups,however women in the low-normal group had a 7.3% higher LB rate compared to women in the high-normal group(68.4% vs. 61.1%, respectively, P=0.29).Logistical regression revealed that age and having a prior SAB were positive predictors of MC,while age,a prior SAB and high maximum FSH,were negative predictors of LB.After controlling for these predictors,logistical regression revealed that a TSH level of 0.4-2.5 mIU/L or 2.51-4.5 mIU/L prior to an IVF or ICSI cycle was not a predictor of MC(OR: 1.34, 95% CI: 0.52-3.42 P=0.55) or LB(OR: 0.73, 95% CI: 0.40-1.32 P=0.30). Having a high-normal TSH level was not a risk factor for MC, however, although there seems to be no advantage to having a TSH level ≤2.5 mIU/L in achieving a LB,this study is currently underpowered to detect a difference of 7.3% that may be clinically important.