Sex-specific Cutoffs Research Articles

Abstract 12529: Sex-Specific Mortality Associated With High Left Ventricular Ejection Fraction After ST-segment Elevation Myocardial Infarction

Introduction: Using sex-specific cutoffs, high left ventricular ejection fraction (LVEF) is associated with increased mortality in women but not in men with chronic coronary syndromes. Purpose: To explore the association between LVEF and mortality after an acute coronary syndrome in women and men. Methods: Using population-derived sex-specific LVEF cutoffs, we compared characteristics and outcomes of 1,953 ST-segment Elevation Myocardial Infarction (STEMI) patients (1,399 men and 554 women) presenting at Minneapolis Heart Institute between 2003 and 2020. Patients who had a follow-up LVEF measurement available within 2 months of the index hospitalization were included in the analysis. Sex specific cutoffs for post STEMI LVEF were a) for men, >70% (high), 47-70% (normal), <47% (low); b) for women, >72% (high), 50-72% (normal), <50% (low). Standard cutoffs were: >65% (high), 55-65% (normal), <55% (low). Results: When comparing high vs normal vs low LVEF, 1-year mortality was 0% vs 0.8% vs 4.4% in men ( P log-rank <0.001) and 13.3% vs 2.2% vs 3.4% in women ( P log-rank =0.03) (Figure). Five-year mortality was 0% vs 5.1% vs 12% in men ( P log-rank <.001) and 13.3% vs 11.4% vs 19.9% in women ( P log-rank =0.18). The findings were not replicated when standard LVEF cutoffs were used (1-year mortality in women was 6.1% vs 2.5% vs 2.5%, P log-rank =0.33). After adjustment for baseline variables and comorbidities (age, diabetes, dyslipidemia, hypertension, history of MI, door-to-balloon time less than 90 minutes, and the presence of congestive heart failure), high LVEF was associated with 1-year mortality when compared with normal LVEF in women (HR, 10.83; 95% CI, 1.94-60.57, P =0.007). Landmark analysis showed that among women alive beyond 1 year, 5-year mortality was 0% vs 9.4% vs 16.1%, P log-rank =0.31. Conclusion: High LVEF after STEMI using sex-specific cutoffs is associated with lower 1-year survival in women but not in men.

Different prognostic impact of glucose uptake in visceral adipose tissue according to sex in patients with colorectal cancer

The purpose of this study was to investigate whether sex differences in visceral fat volume and glucose uptake measured by positron emission tomography/computed tomography (PET/CT) in abdominal visceral fat can stratify overall survival (OS) in patients with colorectal cancer (CRC). We retrospectively enrolled 293 patients diagnosed with CRC who underwent PET/CT before surgical resection. Fluorodeoxyglucose uptake of visceral adipose tissue (VAT-SUV) and subcutaneous adiposity tissue (SAT-SUV) were measured using PET/CT. The relative VAT (rVAT) was defined as the visceral fat volume normalized to the total volume of fat (VAT plus SAT). We defined sex-specific cutoff values for VAT-SUV, SAT-SUV, and rVAT. Univariate and multivariate analyses using Cox proportional hazard regression analysis were performed to identify the independent prognostic factors. The study population comprised 181 men and 112 women. The rVAT (0.40 vs. 0.29, p < 0.001) and VAT-SUV (0.55 vs. 0.48, p = 0.007) were significantly greater in men than in women. High rVAT (than low rVAT) and high VAT-SUV (than low VAT-SUV) showed a worse prognosis in male and female patients, respectively. Multivariate analysis indicated that the combination of rVAT and VAT-SUV was an independent prognostic factor for predicting OS in both male and female patients. The combination of rVAT and VAT-SUV could differentiate the patients with the best survival outcome from the other three individual groups in female patients, but not in males. Glucose uptake and relative volume of visceral fat may provide a new risk stratification for patients with CRC, especially female patients.

Sarcopenia as a Predictor of Survival in Patients with Pancreatic Adenocarcinoma After Pancreatectomy.

To determine whether sarcopenia can potentially predict worse survival after resection of pancreatic ductal adenocarcinoma. Sarcopenia is correlated with poor outcomes in hepatopancreatobiliary malignancies, but the relationship of both its qualitative and quantitative features with patient survival after pancreatectomy has not been investigated in a western population. Preoperative cross-sectional computed tomography scans of consecutive patients who underwent pancreatectomy in 2005-2017 were evaluated for skeletal muscle index (SMI), intramuscular adipose tissue content (IMAC), and visceral-to-subcutaneous adipose tissue area ratio (VSR). Sex-specific categorical cut-offs were determined. Findings were correlated with outcome. The study included 111 patients, 47% of whom were female, with a median age of 67 years (range: 35-87 years), and median body mass index of 23kg/m2 (range: 16-40kg/m2); 77% had a Whipple procedure and 66% received adjuvant chemotherapy. Low SMI correlated with poor overall survival (OS) (P = 0.007), disease-specific survival (DSS) (P = 0.006), and recurrence-free survival (RFS) (P = 0.01). High IMAC correlated with poor OS (P = 0.04). Patients with high IMAC tended to have a shorter DSS (P = 0.09), with no correlation with RFS (P = 0.6). VSR was not associated with survival. Multivariable analysis yielded an independent association of low SMI with OS (HR = 1.7, 95%CI: 1.1-2.8, P = 0.02), DSS (HR = 1.8, 95%CI:1.03-3.2, P = 0.04), and RFS (HR = 1.8, 95%CI: 1.1-2.8, P = 0.01), and of high IMAC with OS (HR = 1.9, 95%CI: 1.1-3.1, P = 0.01). Both qualitative and quantitative measures of skeletal muscle were independently associated with impaired survival in patients with resectable PDAC. Sarcopenia might serve as an early radiographic surrogate of aggressive tumor behavior, with potential implications for clinical decision-making and future study.

Sarcopenia in high acuity liver transplantation: Does it predict outcomes?

Sarcopenia has gained momentum as a potential risk-stratification tool in liver transplantation (LT). While LT recipients recently have more advanced end-stage liver disease, the impact of sarcopenia in high acuity recipients with a high model for end-stage liver disease (MELD) score remains unclear. We retrospectively assessed sarcopenia by calculating skeletal muscle index (SMI) from cross-sectional area at third lumbar vertebra (cm2 ) and height (m2 ) in 296 patients with a CT ≤ 30 days prior to LT. Sex-specific SMI cut-offs were developed, and its impact was assessed in patients with MELD ≥ 35. In patients with MELD ≥ 35 (n=217), men with a SMI<30 cm2 /m2 had significantly higher rates of bacteremia (P=.021) and a longer hospital stay (P<.001). Women with a SMI<34 cm2 /m2 had a longer hospital stay (P=.032). There were no relationships between SMI and survival in men and women with MELD ≥ 35. This series examined sarcopenia with a focus on high MELD patients. Although decreased SMI contributed to higher post-LT hospital stay, it did not impact patient survival, suggesting that while SMI alone may not aid in patient selection for LT, it certainly may guide perioperative care-planning in this challenging patient population.

Cachexia index as a potential biomarker for cancer cachexia and a prognostic indicator in diffuse large B-cell lymphoma.

BackgroundCancer cachexia is known to adversely affect the clinical course in patients with malignant lymphoma. The cachexia index (CXI) is a potential biomarker of cancer cachexia, and its implications for the prognosis and treatment outcome of lung cancer and aggressive lymphoma has been assessed in previous studies.MethodsA total of 267 patients diagnosed with diffuse large B‐cell lymphoma who were treated with rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone (R‐CHOP) immunochemotherapy were retrospectively reviewed. The CXI was calculated as the skeletal muscle index (SMI) × serum albumin/neutrophil–lymphocyte ratio (NLR). Although previous studies measured the SMI using the muscles of the L3 vertebral level, the present study used both the L3 vertebral muscles and the pectoralis muscles (PM) at the T4 vertebral level to measure the SMI. Depending on the type of muscles used, the CXI was termed the L3‐CXI or PM‐CXI. Using sex‐specific cutoff values for CXI, the patients were categorized as follows: (i) high‐CXI group (high L3‐CXI and high PM‐CXI), (ii) intermediate‐CXI group (high L3‐CXI and low PM‐CXI), and (iii) low‐CXI group (low L3‐CXI and low PM‐CXI).ResultsComplete responses to R‐CHOP were obtained in 145/173 (83.8%), 25/36 (69.4%), and 27/57 (47.4%) patients in the high‐CXI, intermediate‐CXI, and low‐CXI groups, respectively (P < 0.001). Treatment‐related anaemia (15.6%, 30.6%, and 26.3%, P = 0.038), thrombocytopenia (21.4%, 36.1%, and 43.9%, P < 0.001), febrile neutropenia (23.7%, 44.4%, and 36.8%, P = 0.022), and any nonhaematologic toxicity (31.2%, 44.4%, and 54.4%, P = 0.001) of Grade 3 or more were more common in the lower CXI groups than in the higher‐CXI groups. Early treatment discontinuation for reasons other than lymphoma progression also occurred more frequently in the low‐CXI group (24/57, 42.1%) compared with the intermediate‐CXI (5/36, 13.9%) and high‐CXI (18/173, 10.4%) groups (P < 0.001). Median overall survival in the high‐CXI, intermediate‐CXI, and low‐CXI groups was not reached, 50.6 months, and 14.5 months, respectively (p < 0.001). Multivariable analysis showed that low CXI was an independent negative prognostic factor for overall survival (hazard ratio 2.103, 95% confidence interval 1.278–3.460, P = 0.003).ConclusionsWe suggest that in patients with diffuse large B‐cell lymphoma, the CXI is a biomarker for cancer cachexia that can predict survival, treatment response, treatment‐related toxicity, and compliance with R‐CHOP. Patients were more clearly stratified by this new CXI category compared with the classifications described in previous studies.

Sex-differences and utility of treadmill testing in identification and genotype prediction in LQTS: a sub-study of the national LQTS registry and Canadian Hearts in Rhythm registry

Abstract Background/Purpose Long-QT (LQT) Syndrome is an inherited heart rhythm condition presenting with QT-prolongation and failure to shorten with exercise, leading to life-threatening cardiac events. The prevalent normal-to-borderline phenotype remains a challenge for diagnosis. A three-step algorithm was developed to predict genotype from phenotypic characteristics with exercise testing. Sex-specific cut offs for determining a prolonged corrected QT value are 470ms for males and 480ms for females, serving as step 1 in the algorithm. The purpose of this study is to validate the algorithm using a national cohort that is more representative of the general LQT population, with a milder phenotype and more frequent ambiguity in phenotype. Methods A review of cases in the Canadian National Long-QT Registry, housed in the HiRO Registry was undertaken. Eligible cases from September 2014 to May 2020 were included. Gene-positive patients included 93 probands and 122 first-degree relatives (FDR) with a likely-pathogenic or pathogenic mutation according to ACMG criteria, limited to LQT1/2 subtypes, with 164 and 51 patients, respectively. Controls were composed of 39 gene-negative FDRs. Continuous variables were compared by the Mann-Whitney U test for 2-group comparisons, and Kruskal-Wallis test for multiple group comparisons. The predictive value of exercise ECG characteristics were analysed using ROC analysis and optimal cut-off values for exercise ECG characteristics (supine, standing, peak exercise, 1 and 4-minutes into recovery) were determined for males and females, using a sensitivity of 0.80 for carrier status and 0.75 for subtype. Results The 4-minute recovery QTc had the best predictive value for males, with an AUC of 0.86, and a cut-off point of 442ms given a sensitivity of 0.81 and specificity of 0.86. The 4-minute recovery QTc yielded an AUC of 0.79 for females, with a cut-off of 452ms given a sensitivity of 0.81 and specificity of 0.71. The 1-minute recovery QTc had the best predictive value for females, with an AUC of 0.92 and a cut-off point of 424ms given a sensitivity of 0.82 and specificity of 0.94. In prediction of LQT1, the 1-minute recovery QTc yielded the highest AUC for both males and females, at 0.68 and 0.80, respectively. Males had a cut off of 428ms with a sensitivity of 0.75 and specificity of 0.47, while females had a cut off of 451ms given a sensitivity of 0.76 and specificity of 0.75. Conclusion The current study demonstrates that exercise testing is a valid approach to diagnosing LQTS, with a differential optimal best measurement in males vs. females. Test performance measured by AUC was generally better at all time points in females compared to males. The algorithm is a reliable and simple method for the identification and prediction of genotype for probands and FDR carriers. The algorithm should be sex-stratified at the second step, with the 4-minute recovery QTc used for males and the 1-minute recovery QTc for females. Funding Acknowledgement Type of funding sources: Public grant(s) – National budget only. Main funding source(s): Canadian Institute of Health Research

HBV Genotype: A Significant Risk Factor in Determining Which Patients With Chronic HBV Infection Should Undergo Surveillance for HCC: The Hepatitis B Alaska Study.

Information is limited regarding HBV genotype and the outcome of chronic HBV (CHB) infection. We examined the effect of HBV genotype on HCC occurrence in Alaska Native (AN) persons with CHB, where five HBV genotypes are found: A2, B6, C2, D, and F1. We calculated HCC incidence per 1,000 person-years of follow-up to determine which groups by age, sex, and genotype met current American Association for the Study of Liver Diseases (AASLD) HCC surveillance criteria. We used Poisson regression to compare HCC risk by genotype, age, sex, and Alaska region. Incidence of HCC was calculated using the sex-specific AASLD cutoff recommended for the Asian population of 50years for women and 40years for men. HCC screening was conducted semiannually using alpha-fetoprotein levels and abdominal ultrasound. Among 1,185 AN persons, median follow-up was 35.1years; 667 (63%) were male. The HBV genotype distribution was 49% D, 18% F, 13% A, 6% C, 3% B, 0.1% H, and 12% undetermined. Sixty-three cases of HCC occurred. HCC incidence for genotype F was 5.73 per 1,000 person-years of follow-up, followed by 4.77 for C, 1.28 for A, 0.47 for D, and 0.00 for B. The HCC risk was higher for genotypes F (relative rate [RR], 12.7; 95% CI, 6.1-26.4), C (RR, 10.6; 95% CI, 4.3-26.0), and A (RR, 2.9; 95% CI, 1.0-8.0) compared to genotypes B and D. Among men<40years of age and women<50years of age, genotype F had the highest incidence (4.79/1,000person-years). HBV genotype was strongly associated with HCC. HBV genotype should be considered in risk factor stratification.

Parental Adherence to Ideal Cardiovascular Health Status Was Associated With a Substantially Lower Prevalence of Overweight and Obesity in Their Offspring Aged 6-18 Years.

Background: Parental health status had a potential influence on offspring health. This study aimed to investigate the separate associations between paternal and maternal cardiovascular health statuses and the prevalence of childhood overweight and obesity in the offspring.Methods: Data were from a cross-sectional study conducted in seven provinces or cities of China in 2013. A total of 29,317 children aged 6–18 years old and their parents, making up 9,585 father-offspring pairs and 19,732 mother-offspring pairs, were included in the final analysis. Information on parental cardiovascular health status factors (dietary behaviors, body mass index (BMI), smoking, physical activity, hypertension, and diabetes mellitus) was obtained from the structured self-administrated questionnaires. Based on the health status factors, we then generated an ideal cardiovascular health (iCVH) score. The overweight and obesity of children were defined using age- and sex-specific cutoffs based on the International Obesity Task Force criteria. A multilevel log-binomial regression model was used to assess the association between parental cardiovascular health status and prevalence of childhood overweight and obesity in the offspring.Results: The prevalence of pediatric overweight and obesity was 22.0% in the father-offspring subset and 23.8% in the mother-offspring subset, respectively. Fathers with ideal BMI, non-smoking, and absence of hypertension and diabetes, and mothers with ideal BMI, ideal physical activity, and absence of hypertension and diabetes were found to be associated with lower prevalence of overweight and obesity in the offspring. The prevalence of offspring overweight and obesity was significantly decreased with the parental iCVH scores increased. Each additional increase in paternal and maternal iCVH factor was associated with a 30% and 27% lower prevalence of overweight and obesity in the offspring. Compared with children whose parental iCVH scores ≤ 3, offspring whose fathers or mothers met all six iCVH factors had 67% [prevalence ratio (PR): 0.33, 95%CI: 0.25–0.42] and 58% (PR: 0.42, 95%CI: 0.29–0.62) lower prevalence of overweight and obesity, respectively.Conclusions: Parental adherence to iCVH status was associated with a lower prevalence of pediatric overweight and obesity in offspring. Our findings support the intervention strategy that parents should involve in the obesity intervention program for children.

Visceral obesity enhances inflammatory response after laparoscopic colorectal resection.

AimsC‐reactive protein (CRP) is used for monitoring postoperative inflammation (POI) and detecting infectious complications. The aim of this study was to assess the effect of visceral obesity (VO) on acute POI measured through CRP after elective laparoscopic colorectal resection.MethodsPre‐operative Computed tomography images of 357 patients who underwent laparoscopic colorectal resection were analyzed. Visceral adipose tissue (VAT) area was measured for each patient. VO was defined as VAT area >163.8 cm2 in men and >80.1 cm2 in women according to accepted sex‐specific cut‐offs. Postoperative outcomes and CRP values were compared between VO and non‐VO groups. The most appropriate CRP value for identifying infectious complications in the two groups was assessed with receiver operating characteristic (ROC) curves. Univariate and multivariate analyses were conducted for factors affecting POI including VO.ResultsNo differences in postoperative outcomes and infectious complications were found in VO patients (62.2% of the overall population). Both in the overall cohort and in patients without infectious complications, VO was associated with higher CRP values on postoperative day (POD) 1, POD2, POD3, and POD5. A positive correlation was found between VAT and CRP on all PODs. VO independently predicted higher CRP on POD1‐3 in patients without infectious complications but not in those who developed complications. ROC curves analysis showed optimal accuracy for detection of infectious complications for CRP on POD3 in both groups, though the optimal cut‐off value was higher in VO group (154 vs 136 mg/L).ConclusionsVO is not associated to increased complications after laparoscopic colorectal resection. Nevertheless, it is independently associated to higher CRP in the overall population and in patients without infectious complications. Consequently, CRP values on POD3 higher than cut‐offs commonly adopted in the clinical practice should be carefully evaluated in VO patients to assess the occurrence of infectious complications.

OS05.3.A Temporal muscle thickness as surrogate parameter of sarcopenia in newly diagnosed glioblastoma patients:translational imaging analysis of the CENTRIC EORTC 26071-22072 and CORE trials

Abstract BACKGROUND Temporal muscle thickness (TMT) was described as surrogate parameter of skeletal muscle mass. This study aimed to investigate the prognostic relevance of TMT in patients with newly diagnosed glioblastoma. MATERIAL AND METHODS TMT was assessed in cranial magnetic resonance images (MRI) of 755 pts enrolled in the CENTRIC EORTC 26071-22072 study (n=508) and CORE study (n=247). Predefined sex-specific TMT cutoff values were used to categorize “patients at risk of sarcopenia” and “patients with normal muscle status” at baseline. Furthermore, patients were categorized according to the extent of TMT loss over time. Cox models adjusted for other explanatory variables were used to evaluate the associations with progression-free survival (PFS) and overall survival (OS). RESULTS Overall, 510/755 (67.6%) patients were categorized as “at risk of sarcopenia” and 245/755 (32.4%) patients had normal muscle status at baseline. In both study cohorts patient at risk of sarcopenia at baseline had significantly higher risk of progression and death than patients with normal muscle status (CENTRIC: PFS = HR 0.16, 95% CI: 0.12, 0.21, p&amp;lt;0.001; OS = HR 0.341, 95% CI: 0.27, 0.44, p &amp;lt; 0.001; CORE: PFS = HR 0.29, 95% CI: 0.21, 0.39, p&amp;lt;0.001; OS = HR 0.365, 95% CI: 0.27, 0.49, p&amp;lt;0.001). In multivariate Cox models adjusted for other important prognostic parameters similar results were obtained. In patients at risk for sarcopenia the extent of TMT loss over time showed a significant inverse correlation with median OS times (CENTRIC: p &amp;lt; 0.001, CORE: p = 0.005, log-rank test), but not in patients with normal baseline muscle mass in both study cohorts (CENTRIC: p = 0.538, CORE: p = 0.28, log-rank test). CONCLUSION TMT identifies patients with newly diagnosed glioblastoma at risk for progressive sarcopenia and adverse outcomes. Early intervention for muscle mass preservation including exercise and resistance training as well as nutritional support may prevent skeletal muscle loss and improve patient outcome in this group of patients.

P14.55 Quantitative muscle mass biomarkers are independent prognosis factors in primary central nervous system lymphoma: the role of L3-Skeletal Muscle Index and temporal muscle thickness

Abstract BACKGROUND Appropriate patient stratification is of paramount importance in patients with primary central nervous system lymphomas (PCNSL) in order to improve therapeutic choices and to reduce treatment-related neurotoxicity. Age and performance status, two widely used prognostic indicators, may not be the most appropriate parameters for an optimal patient stratification, as age seldom reveals the true biological frailty of a patient and performance status scores are subject to inter-rater variability. Quantitative muscle biomarkers such as the skeletal-muscle-index at the third lumbar vertebra (L3-SMI) and temporal muscle thickness (TMT) are associated with worse prognosis in several oncological diseases. We aim to evaluate the role of these biomarkers in predicting survival in patients with PCNSL undergoing high-dose methotrexate-based chemotherapy. MATERIAL AND METHODS L3-SMI and TMT were calculated on abdominal CT and brain high-resolution 3D-T1-weighted-MR images, respectively, using predefined validated methods. Standardized sex-specific cut-offs were used to divide patients in different risk categories. Kaplan-Meier plots were calculated, and survival analysis was performed using log-rank tests, univariate, and multivariable Cox-regression models, calculating hazard ratios (HR) and 95% confidence intervals (CI), also adjusting for potential confounders (age, sex, and performance status). RESULTS Forty-three patients were included in this study. Median follow-up was 23 months (interquartile range 12–40); at median follow-up, rates of progression-free and overall survival for the cohort were 46% and 57%, respectively. Thirteen (30%) and 11 (26%) patients showed L3-SMI or TMT values below the predefined cut-offs. Subgroup analyses showed a significant association between quantitative muscle mass biomarkers and progression-free and overall survival. One-year progression free and overall survival rates were 8% and 21% for the 13 patients with L3-SMI below the standard cut-off value, respectively, compared to 66% and 68% for the 30 patients with L3-SMI above the cut-off values. Likewise, one-year progression free and overall survival rates were 10% and 15% for the 11 patients with low TMT, respectively, compared to 61% and 70% for the 32 patients with high TMT. In Cox-regression multivariable analysis patients with low L3-SMI or TMT showed significantly worse progression-free (HR 4.40, 95%CI 1.66–11.61, p = 0.003; HR 4.40, 95%CI 1.68–11.49, p=0.003, respectively) and overall survival (HR 3.16, 95%CI 1.09–9.11, p = 0.034; HR 4.93, 95%CI 1.78–13.65, p=0.002, respectively) compared to patients with high L3-SMI or TMT. CONCLUSION Quantitative muscle mass evaluation assessed by both L3-SMI and TMT is a promising tool to identify PCNSL patients at high risk of negative outcome. Confirmatory studies on larger independent series are warranted.

Validating mid-upper arm circumference (MUAC) cut off points as an indicator of nutritional status among nine tribal populations of India

Mid-upper arm circumference (MUAC) is an alternative anthropometric measurement to assess undernutrition but a universally accepted cut-off is yet to be established. The objectives of the present study are to determine whether the proposed sex-specific global cut-offs are suitable across several tribes in India. This cross-sectional study was conducted among nine tribal populations in India (1046 males, 1087 females). Weight, height and MUAC values were obtained, and body mass index (BMI) was calculated. The BMI cut-off (&lt;18.5 kg/m2) was used to determine chronic energy deficiency (CED). The ROC Curve analyses of binomial logistic regression for MUAC versus CED revealed optimal cut-off point of MUAC as 23.8 cm (in males) and 21.8 cm (in females). MUAC cut-offs were similar in females, relative to males, in all tribes. Males with MUAC&lt;24cm and females with MUAC&lt;22 encompassed significantly higher numbers of CED than those with MUAC≥24 and ≥22 cm, respectively (χ2-value males: 254.9, p&lt;0.001; females: 493.60, p&lt;0.01). A single cut off point of MUAC may not be universally applicable for diverse populations and both sexes as well. It seemed that there is no alternative than to undertake further validation studies in various populations before using the MUAC cut off to identify undernourished or CED condition.

Association between meal-specific daily protein intake and lean mass in older adults: results of the cross-sectional BASE-II study

Adequate total and meal-specific protein intake is considered an important prerequisite to preserve appendicular lean mass (ALM) in older adults and to prevent sarcopenia. We analyzed the meal-specific protein intake across the main meals between participants with normal vs. low ALM to BMI ratio (ALMBMI). 782 participants [59.6% men; median 69 (IQR: 65, 71) y] of the Berlin Aging Study II have been included in this analysis. ALM was assessed by dual X-ray absorptiometry. Low lean mass was defined as ALMBMI using recommended sex-specific cut-offs. A 5-day nutritional protocol was used to assess total and meal-specific protein intake. Median total protein intake was 0.89 (IQR: 0.74, 1.05) g/kg/d body weight (BW) in participants with low ALMBMI and 1.02 (IQR: 0.86, 1.21) g/kg BW in participants with normal ALMBMI (P<0.001). Daily protein intake at breakfast was similar in both groups [0.23 (95% CI: 0.20, 0.26) vs. 0.24 (95% CI: 0.23, 0.26) g/kg BW; P=0.245]. Subjects with low ALMBMI reported a lower protein intake at lunch and dinner compared with those with normal ALMBMI [0.29 (95% CI: 0.27, 0.32) vs. 0.35 (95% CI: 0.34, 0.36) g/kg BW; P=0.001 and 0.32 (95% CI: 0.30, 0.35) vs. 0.36 (95% CI: 0.35, 0.37) g/kg BW; P=0.027, respectively]. In a stepwise regression model, a higher total protein intake was positively associated with ALMBMI [ß = 0.10 (95% CI: 0.07, 0.13) P<0.001]. The protein intake at dinner was positively associated with ALMBMI [ß = 0.14 (95% CI: 0.08, 0.19) P<0.001] irrespective of protein intake at breakfast and lunch. This association disappeared after additional adjustment for total protein intake. Our data highlight an association of total protein intake and ALMBMI in older adults. Although current data support an association of high ALMBMI with protein intake at dinner in particular, this was not independent from total protein intake and the findings do not allow a conclusion on causality.

Longitudinal Association of Handgrip Strength with Medical Use and the Risk of Hospitalization in Korean Adults

OBJECTIVES Age-related loss of muscular strength may contribute to medical health condition. Decreased handgrip strength is associated with an increased risk of chronic diseases, disability, and mortality. However, it is not known whether handgrip strength is also linked with hospitalization and medical use from the long-term cohort study in middle-aged adults. Thus, we aimed to investigate the association of handgrip strength levels, medical use, and hospitalization in Korean adults.METHODS This large prospective study was based on data from Korean Longitudinal Study of Ageing 2006 to 2018. In total, 9,228 participants aged ≥45 years were included for this study. Handgrip strength was measured using dynamometer, and classified into quartiles by sex-specific cutoff point.RESULTS Significantly higher hazard ratio (HR) for hospitalization was observed in lower handgrip strength (HR: 1.22, 95% CI:1.11-1.34) compared to higher handgrip strength (reference) in the fully adjusted model. We also found longitudinal association of handgrip strength levels and the use of hospitalization and outpatient medical care during 12 years following period using mixed effect modes with time-dependent interaction.CONCLUSIONS Our results suggests that lower handgrip strength was associated with increased the risk of hospitalization and use of medical care in Korean population. This study highlights the maintaining of muscular strength may play an important role in the reduction of risk for hospitalization and medical use by preventing chronic diseases.

Sex-specific cut-off values for soluble suppression of tumorigenicity 2 (ST2) biomarker increase its cardiovascular prognostic value in the community

Background Suppression of tumorigenicity 2 (ST2) has important cardiovascular prognostic value in community patients; however, previous analyses have utilized non-sex specific cut-off values. We assessed whether sex-specific ST2 cut-off values would improve the prognostic utility of ST2 in the asymptomatic community. Methods A total of 2042 participants underwent clinical assessment and echocardiographic evaluation. Baseline measurements of high sensitivity troponin, natriuretic peptides and ST2 were obtained in 1681 individuals. ST2, cardiac biomarkers and associated co-morbidities were evaluated by sex-specific ST2 quartile analysis. ST2 concentrations were also analysed as dichotomous variables defined as being above the sex-specific cut-off for each the outcomes of heart failure (HF), major adverse cardiac event (MACE) and mortality. Results Median ST2 concentration was 29.4 ng/mL in male subjects and 24.1 ng/mL in female subjects. Higher ST2 concentrations were associated with incident HF (p<0.001; preserved ejection fraction (EF) p<0.001, reduced EF p=0.23), MACE (p=0.003) and mortality (p<0.001) across sex-specific quartiles. Event-based, hazard ratio (HR) analysis revealed sex-specific ST2 cut-offs were significantly more predictive of incident HF, MACE and mortality compared to non-sex-specific analysis even following adjustment for cardiac co-morbidities and traditional biomarkers. Conclusions These data suggest that sex-specific cut-offs, greater than non-sex specific cut-offs, significantly impact the prognostic value of the biomarker ST2 in the asymptomatic community cohort. Clinical Significance Suppression of tumorigenicity 2 (ST2) is a biomarker which has known associations with heart failure (HF), major adverse cardiac events (MACEs) and mortality in the general population. Recent data support the concept of sex-specific cut off values and individualized approaches based on sex to predict cardiovascular disease. Given the difference in pathobiology between the sexes, the fact that such approaches improve risk stratification is understandable. Thus, when sex-specific treatments are developed, this may similarly lead to improved outcomes. The use of sex-specific ST2 cut-off values significantly improved the prognostic value in predicting HF, MACE, and mortality in an asymptomatic community. This prognostication was particularly strong for HF with preserved ejection fraction and remained clinically significant following adjustment for cardiac co-morbidities and other traditional cardiac biomarkers (NTproBNP and hscTnI).

Corrected QT Interval Is Associated With Stroke but Not Coronary Heart Disease: Insights From a General Chinese Population

Background: Prolonged heart rate-corrected QT (QTc) interval has been associated with incident cardiovascular diseases (CVD) in general Western populations. However, this association is unclear in Asian population. We aim to estimate the association between QTc interval and incident CVD in a general Chinese population.Methods: We analyzed 8,867 participants age ≥35 years and free of CVD at baseline in the Northeast China Rural Cardiovascular Health Study. A resting 12-lead electrocardiogram was performed on all participants, and QTc interval computed using the Framingham formula. Cox proportional hazards models were used to calculate hazard ratios (HRs) with 95% confidence intervals (CIs) for associations between QTc interval and incident stroke, coronary heart disease, and combined CVD events.Results: Over a median follow-up of 4.66 years, a total of 439 CVD events occurred (298 stroke cases and 152 CHD cases). After full adjustment, prolonged QTc defined by a sex-specific cutoff was associated with increased risk of developing stroke (HR: 1.82, 95% CI 1.20–2.75, P = 0.004) and combined CVD (HR: 1.52, 95% CI 1.05–2.19, P = 0.026). Spline analyses demonstrated no clear thresholds; when modeled as a linear relationship, each 10 ms increase of QTc interval was associated with an HR of 1.12 (95% CI 1.06–1.19, P < 0.001) for stroke and an HR of 1.10 (95% CI 1.05–1.15, P < 0.001) for combined CVD. Baseline QTc interval was not associated with incident CHD with either modeling strategy.Conclusions: Baseline QTc interval is associated with incident stroke and CVD in adults without prior CVD from a general Chinese population.

Inconsistent Findings of Cardiac Troponin T and I in Clinical Routine Diagnostics: Factors of Influence.

Cardiac troponins are crucial for the diagnosis of acute myocardial infarction. Despite known differences in their diagnostic implication, there are no recommendations for only one of the two troponins, cardiac troponin I (cTnI) and troponin T (cTnT) so far. In an everyday routine diagnostic, cTnT (Roche) as well as cTnI (Abbott) were measured in 5667 samples from 3264 patient cases. We investigated the number of identical or discrepant troponin findings. Regarding cTnI, we considered both, sex-dependent and unisex cutoffs. In particular, the number of cTnT positive and cTnI negative results was strikingly high in 14.0% of cTnT positive samples and increases to 23.8% by using sex-specific cTnI cutoffs. This group was considerably greater than the group of cTnI positive and cTnT negative results, also after elimination of patients with an eGFR < 60 mL/min/1.73 m2. Comparing the troponin cases with a dynamic increase or decrease between two measurements, we saw a balanced number of discrepant cases (between cTnT+/cTnI− and cTnT−/cTnI+), which was, however, still present. Using ROC analysis, sex-dependent cutoffs improved sensitivity and specificity of cTnI. This study shows in a large cohort that comparing the two cardiac troponins does not amount to identical analytical results. Consideration of sex-dependent cutoffs may improve sensitivity and specificity.

Consistent Major Differences in Sex- and Age-Specific Diagnostic Performance among Nine Faecal Immunochemical Tests Used for Colorectal Cancer Screening.

Simple SummaryWe evaluated the performance of nine faecal immunochemical tests among participants of screening colonoscopy. A total of 216 cases of advanced neoplasia (AN, colorectal cancer or advanced adenoma) and 300 randomly selected participants without AN were included. Diagnostic performance for detection of AN was assessed by sex and age (50–64 vs. 65–79 years), for each of the nine faecal immunochemical tests (FITs) individually and for all FITs combined. Major differences in diagnostic performance by sex and age were consistently seen across nine different FIT brands. Sensitivities were consistently lower, and specificities were consistently higher, for females as compared with males. Positive predictive values were similar between both sexes, but negative predictive values were higher for females. A negative FIT is less reliable in ruling out AN among men than among women and among older than among younger participants.Evidence on diagnostic performance of faecal immunochemical tests (FITs) by sex and age is scarce. We aimed to evaluate FIT performance for detection of advanced colorectal neoplasia (AN) by sex and age across nine different FIT brands in a colonoscopy-controlled setting. The faecal samples were obtained from 2042 participants of colonoscopy screening. All eligible cases with AN (n = 216) and 300 randomly selected participants without AN were included. Diagnostic performance for detection of AN was assessed by sex and age (50–64 vs. 65–79 years for each of the nine FITs individually and for all FITs combined. Sensitivity was consistently lower, and specificity was consistently higher for females as compared with males (pooled values at original FIT cutoffs, 25.7% vs. 34.6%, p = 0.12 and 96.2% vs. 90.8%, p < 0.01, respectively). Positive predictive values (PPVs) were similar between both sexes, but negative predictive values (NPVs) were consistently higher for females (pooled values, 91.8% vs. 86.6%, p < 0.01). Sex-specific cutoffs attenuated differences in sensitivities but increased differences in predictive values. According to age, sensitivities and specificities were similar, whereas PPVs were consistently lower and NPVs were consistently higher for the younger participants. A negative FIT is less reliable in ruling out AN among men than among women and among older than among younger participants. Comparisons of measures of diagnostic performance among studies with different sex or age distributions should be interpreted with caution.

Prevalence and temporal trends of anemia in patients with heart failure.

Anemia is an important comorbidity in heart failure (HF), and it is associated with increased adverse disease experience and mortality. Previous reports have focused mainly on HF presenting in healthcare settings. We, therefore, set out to establish the nationwide prevalence and temporal trends of anemia in community-based patients with HF in the US. To establish the nationwide prevalence and temporal trends of anemia in community-based patients with HF in the US. The NHANES dataset, conducted by the CDC National Center for Health Statistics was used to collect nationally representative data on the health and nutritional status of the non-institutionalized US population. We utilized the National Health and Nutrition Examination data collected over five survey cycles (2007-16). Included were participants aged 20-80 years with self-reported diagnosis of HF. Anemia was defined using 2 sex specific cut offs of 13 and 12 g/dl (cutoff 1), and 12 and 11 g/dl (cutoff 2), for men and women, respectively. The Chi square test was used to compare prevalence across different categories and survey cycles. Data analysis was done using STATA 16 with P-values < 0.05 considered statistically significant. The median hemoglobin in all HF patients was 13.5 g/dl (IQR 12.4-14.5). The prevalence of anemia among community-based patients with HF in the US was 21.34% (cutoff 1) and 9.03% (cutoff 2) and has been stable from 2007 to 2016. The burden of anemia was disproportionately higher in NH Blacks (34.48%, 95% CI 27.12-42.67) and those with BMI < 25 Kg/m2 (17.4%, 95% CI 10.9-26.64). The prevalence of anemia in patients with HF in the US is at least 9% and has remained stable over the past decade. This high persistent burden with limited proven interventions should spur further efforts aimed at identifying impactful ways of addressing anemia in patients with HF.

Computed tomography-based sarcopenia in patients receiving peritoneal dialysis: Correlation with lean soft tissue and survival

We evaluated whether the results of the computed tomography (CT)-based sarcopenia assessment were correlated with edema-free lean soft tissue (LST) and were associated with the prognosis of patients receiving peritoneal dialysis (PD). We conducted a prospective cohort study and enrolled patients aged >20 years who started to undergo PD between February 2009 and February 2012. All patients underwent LST evaluation and non-contrast abdominal CT for assessing the total skeletal muscle (TSM) and psoas muscle (PM) indices at the level of the third lumbar vertebra. We analyzed the correlation between LST and CT assessment of muscle mass. Then we determined optimal sex-specific cutoff values for TSM-defined and PM-defined sarcopenia to predict mortality, aided by the maximally selected rank statistics. A total of 158 patients were enrolled, of whom 41 (25.9%) and 65 (41.1%) had sarcopenia based on the TSM and PM indices, respectively. LST was significantly strong correlated with TSM and PM indices (r=0.517, p<0.001 and r=0.688, p<0.001, respectively). In univariate and multivariate analyses after adjusting clinical and PD-related parameters, only patients with PM-defined sarcopenia had poorer survival than did those without (hazard ratio [HR]: 2.386, 95% confidence interval [CI]: 1.315-4.330), but patients with TSM-defined sarcopenia did not show a poorer survival (HR: 1.608, 95% CI: 0.860-3.006). Sarcopenia assessment based on CT was strongly correlated with LST and PM-defined sarcopenia indicated poor prognosis in patients receiving long-term PD.