All-cause Mortality In Men Research Articles

Plasma fibrinogen levels and all-cause and cause-specific mortality in an Italian adult population: results from the Moli-sani study

Epidemiological data on the association between fibrinogen levels and mortality are scarse and controversial. Longitudinal analyses were performed, separately by sex, on 17,689 individuals from the Moli-sani study [53% women, ≥35 years, free from cardiovascular disease (CVD) or cancer at enrolment], to evaluate the association between plasma fibrinogen and all-cause and cause-specific mortality. Over a median follow-up of 11.2 years, 1,058 deaths (34.7% CVD, 36.3% cancer) were ascertained. Both in the lowest (1.12-2.64 g/L) and highest (≥3.62 g/L) fibrinogen quintiles, women had an increased all-cause mortality hazard, when compared with third quintile (2.97-3.23 g/L). Dose-response analyses showed a U-shaped relationship in women (P overall <0.0001; P non-linear association <0.0001), but a positive linear association for all-cause mortality in men (P overall 0.0038; P non-linear association 0.76). Similar trends for a U-shaped association were observed for CVD mortality, while no association was observed with cancer deaths. A U-shaped association of fibrinogen levels with other-cause mortality was also found in both sexes. This study shows that not only higher but also lower fibrinogen levels represent hazard for mortality when compared to normal levels; U-shaped curves being prevalently observed in women.

Associations among cardiorespiratory fitness, C-reactive protein, and all-cause mortality in men and women.

We examined individual and joint associations among high-sensitivity C-reactive protein (CRP), cardiorespiratory fitness (fitness), and mortality in healthy men and women. Between January 1, 2000 and December 31, 2016, 30,077 adults (31.3% women) received a comprehensive physical examination. Fitness was determined from maximal treadmill exercise test duration. Participants were categorized as unfit (Quintile 1) and fit (Quintiles 2-5), and by normal (<2 mg/L) and elevated (≥2 mg/L) CRP categories. Adjusted hazard ratios (HRs) with 95% confidence interval (CI) for all-cause mortality were computed with Cox regression. During an average of 10.1 years of follow-up, 576 deaths occurred. Following adjustment for age, smoking status, sex, exam year, body mass index, systolic blood pressure, total cholesterol, triglyceride:high-density lipoprotein ratio, and fasting glucose, HR (95% CI) for all-cause mortality were 1.0 (referent) and 1.52 (1.14-2.02) for fit and unfit categories, respectively. Corresponding values for normal and elevated CRP categories were 1.0 and 1.50 (1.20-1.89), respectively. When grouped by fitness and CRP category, there was significantly greater mortality risk in the unfit than the fit category within the elevated CRP category (HR = 1.77 (1.14-2.75)), but not in the normal CRP category (HR = 1.38 (0.96-1.98)). Each 1 metabolic equivalent increment in fitness and 1 mg/L increment in CRP were associated with 10.0% (95% CI: 5.1-14.8%) decreased and 7.3% (95% CI: 2.0%-12.9%) increased mortality hazard, respectively. Compared to the unfit, fit individuals have an attenuated mortality risk within each CRP category. Thus, higher fitness appears to provide some protection against all-cause mortality, particularly among those with elevated levels of inflammation.

A Systematic Review of Studies Assessing Efficacy and Cardiovascular Safety of Testosterone Replacement Therapy in Men with Late-Onset Hypogonadism Due to Obesity ± Type 2 Diabetes Mellitus

Background: There is a lack of consensus regarding efficacy and cardiovascular (CV) safety of testosterone-replacement therapy (TRT) in men with late-onset hypogonadism (LOH) secondary to obesity ±type 2 diabetes mellitus (T2DM). This is because of limited number of prospective randomized clinical trials (RCTs) in this cohort. Methods: A comprehensive retrospective review of medical literature was carried out using Preferred Reporting Items for Systematic Reviews and Meta-Analyses framework to assess the CV outcomes and safety of TRT in men with LOH. The review included scientific publications from January 2000 to July 2021, which included men with obesity ± T2DM. Results: Out of the 723 publications, which were identified on preliminary screening, 154 conformed to broad inclusion criteria for this systematic review of literature. Out of these 154 publications, 34 studies with a total number of 4,365,684 patients were finally included for this systematic review (9 randomized controlled trials, 6 meta-analyses and 19 observational studies). Studies investigating whether TRT offers protection against CV disease (CVD) and stroke generally concluded that the use of Testosterone (T) in middle-aged to elderly men has no detrimental impact on their CV risk. Older men with T2DM, obesity and metabolic syndrome are likely to benefit from TRT, as several studies point to an improvement in insulin sensitivity, markers of inflammation, time to Angina, CV risk, CV mortality, and even all-cause mortality. Conclusions: This retrospective systematic review of the literature, suggests modest efficacy of TRT in reducing major adverse cardiovascular events (MACEs) and all-cause mortality in men with LOH secondary to obesity and/or T2DM. TRT was associated with an increased risk of overall CVDs and MACE only when T preparations were given at supratherapeutic dosage or when TRT was offered to frail men. The findings of the current review could not confirm TRT as a cause of adverse CV events.

Edible mushroom intake and risk of all-cause and cause-specific mortality: results from the Korean Genome and Epidemiology Study (KoGES) Cohort.

Mushroom is rich in protein, fiber, vitamins, and essential amino acids. A relationship between mushroom consumption and a lower all-cause mortality risk has been reported. This study aimed to examine the association of mushroom consumption with all-cause and cause-specific mortality. Data were extracted from the Korean Genome and Epidemiology Study cohort. Mortality outcomes were confirmed from 2001-2020 death records provided by the Korea National Statistical Office. Mushroom intake was assessed using food frequency questionnaires and categorized into four groups: none, <1 serving per week, 1-3 servings per week, and ≥3 servings per week. Cox proportional hazard regression was used to calculate the hazard ratios (HRs) and 95% confidence intervals (CIs) for mortality. The 152 828 participants ≥40 years had a mean age of 53.7 years. Over a mean 11.6-year follow-up, 7085 deaths were recorded. In men, consuming <1 and 1-3 servings per week of mushroom was associated with lower risks of all-cause (HR = 0.858, 95% CI = 0.793-0.929; HR = 0.902, 95% CI = 0.819-0.993) and cardiovascular disease (CVD) (HR = 0.767, 95% CI = 0.632-0.930; HR = 0.762, 95% CI = 0.601-0.967) mortality than non-consumption. In women, consuming <1 and 1-3 servings per week of mushrooms was associated with a lower risk of all-cause mortality (HR = 0.864, 95% CI = 0.784-0.952; HR = 0.869, 95% CI = 0.771-0.980) than non-consumption. This prospective cohort study demonstrated that low and medium mushroom consumption is associated with a lower risk of all-cause mortality in men and women. However, only men who consumed <1 and 1-3 servings per week of mushrooms exhibited a lower risk of CVD mortality.

THE RELATIONSHIP BETWEEN EMPLOYMENT AND ALL-CAUSE MORTALITY IN JAPANESE COMMUNITY-DWELLING OLDER ADULTS

Abstract It is well known that social contribution such as working maintains the functional health and prevents frailty of older adults. However, the effect of employment in old age with frailty on health outcomes is not well-established.This 3.6-year prospective study examined the influence of working on all-cause mortality in urban community-dwelling Japanese older adults. Participants were 10,591 initially non-disabled residents (5,180 men; 5,411 women) aged 65–84 years of Ota City, Tokyo, Japan. We applied the Cox proportional hazard model by gender and with/without frailty, controlling for age, years of education, equivalent income, number of chronic diseases, body mass index, instrumental activities of daily living (IADLs), smoking and drinking status, exercise habits, social activities, and social interaction for evaluating the predictive value of working status (full-time worker, part time worker, occasional worker and non-worker) at baseline for all-cause mortality.During a follow-up of 3.6 years, 328 (3.1%) individuals died. Compared with non-workers, independent multivariate-hazard ratios (95% confidence intervals) of part-time workers for all-cause mortality in men with/without frailty were 0.35 (0.13–0.97) and 0.54 (0.28–1.01), respectively. Corresponding female multivariate-adjusted HRs with/without frailty were 1.21 (0.34–4.34) and 0.23 (0.05–0.99). Also, for both genders, full-time workers and occasional workers did not have significantly lower adjusted hazard ratios of all-cause mortality, compared to non-workers, regardless of frailty. In conclusion, moderate employment resulted in lower risk of all-cause mortality, even in frail older men.

Skeletal muscle mass index is independently associated with all-cause mortality in men: The Nagahama study.

We aimed to determine if skeletal muscle mass is a predictor of all-cause mortality and if muscle mass plays a role in the association between body mass index (BMI) and all-cause mortality in community residents. The study population consists of 3582 elderly (age ≥65 years) adults. The skeletal muscle mass index (SMI) was measured between 2013 and 2016. Men with SMI <7.0 kg/m2 and women with SMI <5.7kg/m2 were considered to have low SMI. All-cause mortality was determined by reviewing residential registry records (follow-up duration: 2564 ± 373 days). The mortality rate of the low SMI group was significantly higher than that of the normal SMI group in men (191.3 vs. 93.0 per 10 000 person-years, P < 0.001), but not in women (P=0.191). In Cox proportional hazard analysis adjusted for possible covariates, the group differences remained significant (hazard ratio=1.82, P=0.011). The results were similar when individuals who died within 1 year of follow-up were excluded from the analysis (P=0.015). Cubic splines revealed that SMI <6.9kg/m2 is a risk factor of all-cause mortality in men. BMI was found to be significantly associated with all-cause mortality in men (P=0.010), but not in women (P=0.288); however, the association disappeared after adjustment for SMI (P=0.163). SMI <6.9kg/m2 is a risk factor of all-cause mortality in men but not in women. SMI underlies the relationship between BMI and all-cause mortality. Geriatr Gerontol Int 2022; 22: 956-960.

Urinary sodium concentration predicts time to major adverse coronary events and all-cause mortality in men with heart failure over a 28–33-year period: a prospective cohort study

BackgroundLower urinary sodium concentrations (UNa) may be a biomarker for poor prognosis in chronic heart failure (HF). However, no data exist to determine its prognostic association over the long-term. We investigated whether UNa predicted major adverse coronary events (MACE) and all-cause mortality over 28–33 years.MethodsOne hundred and eighty men with chronic HF from the Kuopio Ischaemic Heart Disease Risk Factor Study (KIHD) were included. Baseline data was collected between 1984 and 1989. MACE and all-cause outcomes were obtained using hospital linkage data (1984–2017) with a follow-up of 28–33 years. Cox proportional hazards models were generated using 24-h UNa tertiles at baseline (1 ≤ 173 mmol/day; 2 = 173-229 mmol/day; 3 = 230-491 mmol/day) as a predictor of time-to-MACE outcomes, adjusted for relevant covariates.ResultsOverall, 63% and 83% of participants (n = 114 and n = 150) had a MACE event (median 10 years) and all-cause mortality event (median 19 years), respectively. On multivariable Cox Model, relative to the lowest UNa tertile, no significant difference was noted in MACE outcome for individuals in tertiles 2 and 3 with events rates of 28% (HR:0.72; 95% CI: 0.46–1.12) and 21% (HR 0.79; 95% CI: 0.5–1.25) respectively.. Relative to the lowest UNa tertile, those in tertile 2 and 3 were 39% (HR: 0.61; 95% CIs: 0.41, 0.91) and 10% (HR: 0.90; 95% CIs: 0.62, 1.33) less likely to experience to experience all-cause mortality. The multivariable Cox model had acceptable prediction precision (Harrell's C concordance measure 0.72).ConclusionUNa was a significant predictor of all-cause mortality but not MACE outcomes over 28–33 years with 173–229 mmol/day appearing to be the optimal level. UNa may represent an emerging long-term prognostic biomarker that warrants further investigation.

Association of TGFB1 rs1800469 and BCMO1 rs6564851 with coronary heart disease and IL1B rs16944 with all-cause mortality in men from the Northern Ireland PRIME study.

BackgroundHistorically, high levels of morbidity and mortality have been associated with cardiovascular disease in the Northern Ireland population. Previously reported associations between single nucleotide polymorphisms (SNPs) and cardiovascular disease within other populations have not always been consistent.ObjectiveTo investigate associations between 33 SNPs with fatal or non-fatal incident coronary heart disease (CHD) events and all-cause mortality in the Northern Irish participants of the Prospective Epidemiological Study of Myocardial Infarction (PRIME).MethodPhase 2 of the PRIME study prospectively evaluated 2,010 men aged 58–74 years in Northern Ireland for more than 10 years for incident CHD events (myocardial infarction, percutaneous coronary intervention, coronary artery bypass, and cardiac death) and more than 15 years for all-cause mortality. SNPs previously reported in association with cardiovascular outcomes were evaluated against incident CHD events and all-cause mortality using Cox’s proportional hazards models adjusted for established cardiovascular disease risk factors.ResultsDuring the follow-up period, 177 incident CHD events were recorded, and 821 men died. Both BCMO1 rs6564851 (Hazard ratio [HR] = 0.76; 95% confidence intervals [CI]: 0.60–0.96; P = 0.02) and TGFB1 rs1800469 (HR = 1.30; CI: 1.02–1.65; P = 0.04) were significantly associated with incident CHD events in adjusted models. Only IL1B rs16944 was significantly associated with all-cause mortality (HR = 1.18; CI: 1.05–1.33; P = 0.005). No associations remained significant following Bonferonni correction for multiple testing.ConclusionWe report a novel association between BCMO1 rs6564851 and risk of incident CHD events. In addition, TGFB1 rs1800469 and IL1B rs16944 were associated with the risk of incident CHD events and all-cause mortality outcomes respectively, supporting previously reported associations.

Association between Outdoor Air Pollution Exposure and Handgrip Strength: Findings from the French CONSTANCES Study.

Association between Outdoor Air Pollution Exposure and Handgrip Strength: Findings from the French CONSTANCES Study.

FIB-4 index and liver fibrosis are risk factors for long-term outcomes in atrial fibrillation-related stroke

ObjectiveLiver fibrosis (LF) is associated with a poor prognosis in patients with ischemic stroke (IS). We aimed to assess whether LF affects long-term outcomes in patients with atrial fibrillation-related stroke or such effects vary according to sex. MethodsWe conducted a multicenter prospective cohort study of Korean patients with atrial fibrillation-related IS. We calculated the fibrosis-4 (FIB-4) index, and LF degree was categorized into two groups (non-advanced vs. advanced) based on the FIB-4 index. Recurrent IS, major adverse cardiac events (MACEs), and all-cause mortality were evaluated using Cox proportional hazard model. ResultsA total of 2897 patients were included; the median age was 75 (interquartile range 68–80) years, and 51.8% were men. The median follow-up period was 16.3 months. Of these patients, 23% had advanced LF indicated by FIB-4 index. Multivariable analysis in all populations demonstrated that the FIB-4 index and advanced LF were significantly associated with MACEs and all-cause mortality but not with recurrent IS. Furthermore, a sex disparity was observed in the outcomes of the patients. A high FIB-4 index in men was a significant predictor of recurrent IS [subdistribution hazard ratio (95% confidence interval): 1.08 (1.02–1.14)]. However, the significance of advanced LF disappeared in MACEs in women and in all-cause mortality in men. ConclusionThe FIB-4 index and advanced LF indicated by FIB-4 index are independent prognostic factors for long-term outcomes in Asian patients with atrial fibrillation-related IS. However, these predictors may contribute differently to patient outcomes depending on the sex.

Analysis of the relationship between sex and prescriptions for guideline-recommended therapy in peripheral arterial disease, in relation to 1-year all-cause mortality: a primary care cohort study

ObjectivesTo explore population patterns of sex-based incidence and prevalence of peripheral arterial disease (PAD), guideline-directed best medical therapy prescriptions and its relationship with all-cause mortality at 1 year.DesignA retrospective cohort...

Abstract 027: Cumulative Consumption Of Sulfur Amino Acids And Risks Of Cardiovascular Disease And Mortality; Analysis Of Two Prospective Cohort Studies

Background: Preclinical studies suggested that high intakes of sulfur amino acids (SAA), including methionine and cysteine, may increase risk of age-related chronic diseases. Until now, no epidemiologic studies have investigated habitual dietary intake of SAA in relation to risk of cardiovascular disease (CVD) and mortality. Methods: We prospectively followed 120,699 participants in the Nurses’ Health Study (1984-2016) and Health Professionals Follow-up Study (1986-2016) cohorts who had no known history of cancer, CVD, or diabetes at baseline. Diet was assessed using a validated food frequency questionnaire that was updated every 2-4 years. Multivariable Cox regression models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for CVD and all-cause and CVD mortality across quintiles of energy adjusted SAA intake. Results: During up to 32 years of follow up, we documented 13,547 incident CVD events and 33,958 deaths, of which 7637 were due to CVD. Participants on average consumed more than 2-fold the recommended daily allowance of SAA (19 mg/kg/day), and the main food sources included beef, chicken, and milk. After adjustment for non-dietary and dietary risk factors including total energy intake, higher SAA intake was significantly associated with higher risks of CVD, CVD mortality, and all-cause mortality in men and women. In the meta-analysis combining both cohorts, comparing participants in the highest quintile with those in the lowest quintile of SAA intake, HRs (95% CI) were 1.12 (1.05, 1.20) for CVD, 1.28 (1.11, 1.47) for CVD mortality, and 1.15 (1.11, 1.19) for all-cause mortality. These associations were similar across strata of age, body mass index, physical activity, ratio of animal to plant protein, smoking, and alcohol consumption (p interaction &gt; 0.05 for all), and they remained significant after further adjustment for total protein intake. Conclusions: Our data suggest that high SAA intake is associated with greater risks of CVD and mortality in men and women.

Intake of Flavonoids and Flavonoid-Rich Foods and Mortality Risk Among Individuals With Parkinson Disease: A Prospective Cohort Study.

Although flavonoids have the potential to exert neuroprotective benefits, evidence of their role in improving survival rates among individuals with Parkinson disease (PD) remains lacking. We aimed to prospectively study the association between prediagnosis and postdiagnosis flavonoid intakes and risk of mortality among individuals with PD identified from 2 large ongoing cohorts of US men and women. Included in the current analysis were 599 women from the Nurses' Health Study and 652 men from the Health Professionals Follow-Up Study who were newly diagnosed with PD during follow-up. Dietary intakes of total flavonoid and its subclasses, together with major flavonoid-rich foods (tea, apples, berries, orange and orange juice, and red wine), were repeatedly assessed with a validated food frequency questionnaire every 4 years. Mortality was ascertained via the National Death Index and state vital statistics records. We documented 944 deaths during 32 to 34 years of follow-up. A higher total flavonoid intake before PD diagnosis was associated with a lower future risk for all-cause mortality in men (hazard ratio [HR] comparing 2 extreme quartiles 0.53, 95% confidence interval [CI] 0.39, 0.71; p for trend < 0.001) but not in women (HR 0.93, 95% CI 0.68, 1.28; p for trend = 0.69) after adjustment for age, smoking status, total energy intake, and other covariates. The pooled HR comparing the extreme quartiles was 0.70 (95% CI 0.40, 1.22; p for trend = 0.25) with significant heterogeneity (p = 0.01). For flavonoid subclasses, the highest quartile of anthocyanins, flavones, and flavan-3-ols intakes before diagnosis had a lower mortality risk compared to the lowest quartile (pooled HR 0.66, 0.78, and 0.69, respectively; p < 0.05 for all); for berries and red wine, participants consuming ≥3 servings per week had a lower risk (pooled HR 0.77, 95% CI 0.58, 1.02; and pooled HR 0.68, 95% CI 0.51, 0.91, respectively) compared to <1 serving per month. After PD diagnosis, greater consumptions of total flavonoid, subclasses including flavonols, anthocyanins, flavan-3-ols, and polymers, and berries and red wine were associated with lower mortality risk (p < 0.05 for all). Among individuals with PD, higher consumption of flavonoids, especially anthocyanins and flavan-3-ols, and flavonoid-rich food such as berries and red wine was likely to be associated with a lower risk of mortality.

Abstract PO-168: Association of urinary PGE-M with all-cause mortality in men with prostate cancer is influenced by aspirin use

Abstract Background: Chronic inflammation has been implicated in prostate cancer etiology and progression. The pro-inflammatory cyclooxygenase (COX) pathway, where arachidonic acid is converted to bioactive prostaglandins and eicosanoids via the COX1 and COX2 enzymes, has been linked to elevated systemic inflammation. Urinary PGE-M is a stable and measurable metabolite of prostaglandin E2 (PGE2). PGE2 is a product of the inflammatory COX signaling pathway and elevated levels have been associated with risk of cancer in many sites including colorectal and gastric cancers. PGE2 synthesis can be inhibited by aspirin. We investigated the association of PGE-M with lethal prostate cancer in a case-control study of African American and European American men. Identifying PGE-M as a novel marker of aggressive disease would have importance for high risk groups like men of African descent who experience a disproportionately high burden of prostate cancer lethality. Methods: We measured urinary PGE-M using mass-spectrometry. Samples were obtained from 977 cases and 1022 controls at time of recruitment. For analysis, we assessed PGE-M as either a continuous measure or assigned PGE-M values to quartiles and median with cutoff points determined using the distribution of PGE-M values among all controls. We applied multivariable logistic and Cox regression modeling to examine associations of PGE-M with prostate cancer and participant survival. Median survival follow-up was 8.4 years with 246 deaths among cases. Self-reported aspirin use over the past five years was assessed with a questionnaire. Race/ethnicity was self-reported. Results: Urinary PGE-M levels did not differ between men with prostate cancer and population-based controls. We report a lack of robust PGE-M inhibition in both cases and controls who reported aspirin use in our study. We observed no association between PGE-M and aggressive disease as defined by the National Comprehensive Cancer Network risk score. We also observed no association between PGE-M and prostate cancer-specific survival. However, we observed a statistically significant association between higher (&amp;gt; median) PGE-M and all-cause mortality in African American cases who did not regularly use aspirin (HR = 2.04, 95% CI 1.23-3.37). Among cases, who reported using aspirin, there was no association. Conclusions: Our study does not support a meaningful association between urinary PGE-M and prostate cancer. Moreover, PGE-M levels were not associated with aggressive prostate cancer. However, the observed association between elevated PGE-M and all-cause mortality in AA non-aspirin users reinforces the potential benefit of aspirin to reduce mortality among African American men with prostate cancer. Citation Format: Maeve Kiely, Ginger L. Milne, Tsion Z. Minas, Tiffany H. Dorsey, Wei Tang, Cheryl J. Smith, Francine Baker, Christopher A. Loffredo, Clayton Yates, Michael B. Cook, Stefan Ambs. Association of urinary PGE-M with all-cause mortality in men with prostate cancer is influenced by aspirin use [abstract]. In: Proceedings of the AACR Virtual Conference: 14th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2021 Oct 6-8. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2022;31(1 Suppl):Abstract nr PO-168.

Anti-mullerian hormone attenuates insulin resistance and systemic inflammation in old obese C57BL/6 male mice.

Epidemiological studies show that Anti-mullerian hormone (AMH) is inversely correlated with age, obesity-related diseases, and all-cause mortality in men. To further investigate the role of AMH in aging and obesity, we studied the effect of AMH treatment on the inflammatory and metabolic parameters and weight in old male C57BL/6 mice. Thirty-six old male C57BL/6 mice (18 month-old) were either on the High-Fat Diet (HFD) or Normal Diet (ND). When obesity occurred in the HFD group, each group was divided into two subgroups; AMH-treated (ND+AMH and HFD+AMH) or controls (ND and HFD). The AMH subgroup received 15 ng/gbw of recombinant AMH injection every 48h in four weeks. Then, serum AMH, CRP, fasting glucose, fasting insulin, and HOMA-IR were measured and analyzed. AMH injection decreased CRP level (HFD =622.86±25.73, HFD+AMH =543.2±24.99 ng/ml, p= 0.003), fasting insulin (HFD=1.50± 0.34, HFD+AMH =0.8±0.25 ng/ml, p=0.006) and HOMA-IR (HFD=12.76± 2.88, HFD+AMH =7.06±2.31, p=0.008) in the obese old mice comparison with control. In ND group, just CRP levels dropped following AMH injection (ND=451.24±20.61, ND+AMH= 326.8±23.76 ng/ml; p=0.001). Accelerated weight gain was observed in HFD+AMH compared with the HFD subgroup (p<0.05). In conclusion, increasing the circulating level of AMH could subside the systemic inflammation through decreasing CRP levels regardless of diet type and enhance insulin sensitivity in old obese mice. It can also lead to higher weight gain, without inflammation, in old obese male mice who are on an HFD.

Body Composition and Risk of All-Cause Mortality in Men Treated With Radiation Therapy for Prostate Cancer: A Pooled Analysis of NRG/RTOG 9406 and NRG/RTOG 0126

To validate the association between body composition and all-cause mortality in men treated with radiation therapy for localized prostate cancer (PCa). Secondarily, to integrate body composition as a factor to help classify patients by risk of all-cause mortality.All participants of NRG/RTOG 9406 and NRG/RTOG 0126 with archived computed tomography that extended cranially to include the L4-L5 interface were included. Muscle mass and muscle density were estimated by measuring the cross-sectional area and average attenuation of the paired psoas muscles on a single slice at the level of L4-L5. Bone density was estimated by measuring the average attenuation of the vertebral body cancellous bone on a single slice at mid-L5. Adipose tissue density was estimated by measuring the average attenuation of the subcutaneous adipose tissue on a single slice at L4-L5. Survival analyses, including Cox proportional hazards models, were performed to assess the relationship between body composition variables and all-cause mortality. Recursive partitioning (RPA) was utilized to create a classification tree to classify NRG/RTOG 0126 participants by risk of death, and the discriminant ability of the classification model was validated using the NRG/RTOG 9406 data set.Data from 2,066 men was included in this study (864 from NRG/RTOG 9406 and 1,202 from NRG/RTOG 0126). A total of 648 men died in the follow-up period and 51 (7.9%) were due to PCa. Psoas area, psoas density, and vertebral body density were individually associated with overall survival. In the final multivariable model, psoas area, comorbidity score, and age were associated with overall survival (Table). The RPA yielded a classification tree with 4 prognostic groups determined by age, comorbidity, and psoas cross-sectional area. When the RPA classification was applied to the NRG/RTOG 9406 validation set the discriminant ability was preserved (P < 0.001 groupwise log-rank).The results of this study strongly support that body composition is related to all-cause mortality in men with localized PCa, with most deaths due to causes other than PCa. The inclusion of psoas cross-sectional area in the RPA classification tree suggests that body composition provides additive information to age and comorbidity status for mortality prediction. This study also confirms the feasibility of performing body composition analysis using archived CT scans using NRG Oncology clinical trial data sets. These methods can be applied to other NRG Oncology data sets to further explore how body composition is related to patient outcomes.

Association of the fat-free mass index with mortality in patients with cancer: A multicenter observational study

Objectives: Low fat-free mass index (FFMI) has been related to a higher mortality in community populations. However, information on the relationship between FFMI and mortality is lacking for patients with cancer. The objective of this study was to examine the association between FFMI and all-cause mortality in Chinese cancer patients.Methods: This retrospective analysis included data on 1744 patients with cancer from a multicenter cohort study. The restricted cubic splines were used to flexibly model the association of FFMI with all-cause mortality. The association between low FFMI and overall survival was analyzed with the Kaplan–Meier method and a Cox model.Results: Among all patients, there were 702 men (40.3%) and 1042 women (59.7%). The optimal cutoff point of low FFMI was 16.31 for men and 14.14 for women. The FFMI showed an inverse association with all-cause mortality for men (per standard deviation [SD] increment; hazard ratio [HR]: 0.72; 95% confidence interval [CI], 0.60–0.87; P < 0.001) and a nonlinear relation for women (per SD increment; HR: 0.88; 95% CI, 0.78–0.99; P = 0.048). After adjustment, a low FFMI score was independently associated with an increased risk of mortality for both men and women. In addition, FFMI showed a strong L-shape (per SD increment; HR: 0.59; 95% CI, 0.46–0.76; P < 0.001) relation with all-cause mortality in elderly patients with cancer. For specific tumor type, a low FFMI score was independently associated with worse prognosis in patients with lung and upper gastrointestinal cancer.Conclusions: A low FFMI score was associated with all-cause mortality in patients with cancer, especially for elder adults with cancer. These results highlight the usefulness of the FFMI for routine clinical assessment and prognostic estimation in patients with cancer.

Association between serum uric acid level and mortality in China

Background:Whether there is an association between serum uric acid (SUA) level and risk of mortality in the general population remains unclear. Based on the China National Survey of Chronic Kidney Disease linked to mortality data, a population-based cohort study was performed to investigate the association between SUA level and all-cause mortality, cardiovascular disease (CVD) mortality, and cancer mortality in China.Methods:The survival status of participants in the cross-sectional survey was identified from January 1, 2006 to December 31, 2017. Only 33,268 individuals with complete SUA data among the 47,204 participants were included in the analysis. We determined the rates of all-cause mortality, CVD mortality, and cancer mortality. We used Cox proportional hazards regression models to evaluate the effect of the SUA level on mortality.Results:During a total of 297,538.4 person-years of follow-up, 1282 deaths occurred. In the Cox proportional hazards regression model, the rate of all-cause mortality, CVD mortality, and cancer mortality had a U-shaped association with SUA levels only in men, whereas no significant associations were detected in women. For all-cause mortality in men, the multivariable-adjusted hazard ratios (HRs) in the first, second, and fourth quartiles compared with the third quartile were 1.31 (95% confidence interval [CI] 1.04–1.67), 1.17 (95% CI 0.92–1.47), and 1.55 (95% CI 1.24–1.93), respectively. For CVD mortality, the corresponding HRs were 1.47 (95% CI 1.00–2.18), 1.17 (95% CI 0.79–1.75), and 1.67 (95% CI 1.16–2.43), respectively. For the cancer mortality rate, only a marginally significant association was detected in the fourth quartile compared with the third quartile with an HR of 1.43 (95% CI 0.99–2.08).Conclusions:The association between SUA and mortality differed by sex. We demonstrated a U-shaped association with SUA levels for all-cause and CVD mortalities among men in China.

Peak oxygen pulse and mortality risk in healthy women and men: The Ball State Adult Fitness Longitudinal Lifestyle Study (BALL ST)

Peak oxygen pulse (O2 pulsepeak) may have predictive utility for health outcomes yet, presently, has only been examined in men and only using a single baseline measure. PurposeThe primary aim of this investigation was to evaluate the relationship between O2 pulsepeak and all-cause mortality in apparently healthy women and men. A secondary aim was to explore the relationship between longitudinal changes to O2 pulsepeak and mortality. MethodsThe sample included 3877 participants (43% women) for the primary aim and 759 participants (32% women) who performed two cardiopulmonary exercise tests ≥1 year apart for the secondary aim. Cox proportional hazard models were performed to determine the relationship between O2 pulsepeak and mortality. Prognostic peak oxygen consumption (VO2peak) and O2 pulsepeak models were compared using the concordance index and Akaike information criterion (AIC). ResultsIn the assessment from baseline, there were 730 deaths over a 24.7 ± 11.8 year follow-up period. For men, a single measure of O2 pulsepeak was inversely associated with risk for mortality (P < 0.05). However, the concordance index and AIC indicated lower discrimination compared to VO2peak models and O2 pulsepeak did not provide complementary benefit to VO2peak models. For women, O2 pulsepeak was not associated with mortality risk. In the longitudinal analysis, there were 168 deaths over a follow-up of 20.1 ± 11.4 years. Changes to O2 pulsepeak were not significantly related to mortality in either sex. ConclusionsWithin an apparently healthy cohort, a single assessment of O2 pulsepeak is related to all-cause mortality in men but not women. Further, longitudinal changes to O2 pulsepeak are not predictive of mortality in either sex. These findings suggest O2 pulsepeak may have limited prognostic utility in healthy individuals, particularly within healthy women.

Associations of total nut and peanut intakes with all-cause and cause-specific mortality in a Japanese community: the Takayama study.

Numerous epidemiological studies have suggested that nut intake is associated with a reduced risk of mortality. Although diets and lifestyles differ by regions or races/ethnicities, few studies have investigated the associations among non-white, non-Western populations. We evaluated the associations of total nut and peanut intakes with all-cause and cause-specific mortality in a population-based prospective cohort in Japan. Participants (age: ≥35 years at baseline in 1992; n 31552) were followed up until death or the end of follow-up in 2008. Those with cancer, CHD or stroke at baseline were excluded. Dietary intake was assessed only at baseline by using a validated FFQ. In total, 2901 men died during 183299 person-years and 2438 women died during 227054 person-years. The mean intakes of total nuts were 1·8 and 1·4 g/d in men and women, respectively. Although peanut intake accounted for approximately 80 % of the total nut intake, total nut and peanut intakes were inversely associated with all-cause mortality in men after adjusting for all potential confounders. For example, compared with the lowest quartile category, the adjusted hazard ratio (95 % CI) of total nut intake for all-cause mortality in men of the highest quartile category was 0·85 (95 % CI 0·75, 0·96) (Pfor trend = 0·034). Peanut intake was inversely associated with digestive disease mortality in men and CVD mortality in women. Total nut and peanut intakes, even in low amounts, were associated with a reduced risk of mortality particularly in men.