Protein Intake and Mortality in Older Adults With Chronic Kidney Disease.

Importance: Avoiding high protein intake in older adults with chronic kidney disease (CKD) may reduce the risk of kidney function decline, but whether it can be suboptimal for survival is not well known. Objective: To estimate the associations of total, animal, and plant protein intake with all-cause mortality in older adults with mild or moderate CKD and compare the results to those of older persons without CKD. Design, Setting, and Participants: Data from 3 cohorts (Study on Cardiovascular Health, Nutrition and Frailty in Older Adults in Spain 1 and 2 and the Swedish National Study on Aging and Care in Kungsholmen [in Sweden]) composed of community-dwelling adults 60 years or older were used. Participants were recruited between March 2001 and June 2017 and followed up for mortality from December 2021 to January 2024. Those with no information on diet or mortality, with CKD stages 4 or 5, or undergoing kidney replacement therapy and kidney transplant recipients were excluded. Data were originally analyzed from June 2023 to February 2024 and reanalyzed in May 2024. Exposures: Cumulative protein intake, estimated via validated dietary histories and food frequency questionnaires. Main Outcomes and Measures: The study outcome was 10-year all-cause mortality, ascertained with national death registers. Chronic kidney disease was ascertained according to estimated glomerular filtration rates, urine albumin excretion, and diagnoses from medical records. Results: The study sample consisted of 8543 participants and 14 399 observations. Of the 4789 observations with CKD stages 1 to 3, 2726 (56.9%) corresponded to female sex, and mean (SD) age was 78.0 (7.2) years. During the follow-up period, 1468 deaths were recorded. Higher total protein intake was associated with lower mortality among participants with CKD; adjusted hazard ratio (HR) for 1.00 vs 0.80 g/kg/d was 0.88 (95% CI, 0.79-0.98); for 1.20 vs 0.80 g/kg/d, 0.79 (95% CI, 0.66-0.95); and for 1.40 vs 0.80 g/kg/d, 0.73 (95% CI, 0.57-0.92). Associations with mortality were comparable for plant and animal protein (HRs, 0.80 [95% CI, 0.65-0.98] and 0.88 [95% CI, 0.81-0.95] per 0.20-g/kg/d increment, respectively) and for total protein intake in participants younger than 75 years vs 75 years or older (HRs, 0.94 [95% CI, 0.85-1.04] and 0.91 [95% CI, 0.85-0.98] per 0.20-g/kg/d increment in total protein intake, respectively). However, the hazards were lower among participants without CKD than in those with CKD (HRs, 0.85 [95% CI, 0.79-0.92] and 0.92 [95% CI, 0.86-0.98] per 0.20-g/kg/d increment, respectively; P = .02 for interaction). Conclusions and Relevance: In this multicohort study of older adults, higher intake of total, animal, and plant protein was associated with lower mortality in participants with CKD. Associations were stronger in those without CKD, suggesting that the benefits of proteins may outweigh the downsides in older adults with mild or moderate CKD.

Alcohol Consumption Patterns and Mortality Among Older Adults With Health-Related or Socioeconomic Risk Factors.

Importance: Alcohol consumption is a leading cause of morbidity and mortality that may be more important in older adults with socioeconomic or health-related risk factors. Objective: To examine the association of alcohol consumption patterns with 12-year mortality and its modification by health-related or socioeconomic risk factors. Design, Setting, and Participants: This prospective cohort study used data from the UK Biobank, a population-based cohort. Participants were current drinkers aged 60 years or older. Data were analyzed from September 2023 to May 2024. Exposure: According to their mean alcohol intake in grams per day, participants' drinking patterns were classified as occasional: ≤2.86 g/d), low risk (men: >2.86-20.00 g/d; women: >2.86-10.00 g/d), moderate risk (men: >20.00-40.00 g/d; women: >10.00-20.00 g/d) and high risk (men: >40.00 g/d; women: >20.00 g/d). Main Outcomes and Measures: Health-related risk factors were assessed with the frailty index, and socioeconomic risk factors were assessed with the Townsend deprivation index. All-cause and cause-specific mortality were obtained from death certificates held by the national registries. Analyses excluded deaths in the first 2 years of follow-up and adjusted for potential confounders, including drinking patterns and preferences. Results: A total of 135 103 participants (median [IQR] age, 64.0 [62.0-67.0] years; 67 693 [50.1%] women) were included. In the total analytical sample, compared with occasional drinking, high-risk drinking was associated with higher all-cause (hazard ratio [HR], 1.33; 95% CI, 1.24-1.42), cancer (HR, 1.39; 95% CI, 1.26-1.53), and cardiovascular (HR, 1.21; 95% CI, 1.04-1.41) mortality; moderate-risk drinking was associated with higher all-cause (HR, 1.10; 95% CI, 1.03-1.18) and cancer (HR, 1.15; 95% CI, 1.05-1.27) mortality, and low-risk drinking was associated with higher cancer mortality (HR, 1.11; 95% CI, 1.01-1.22). While no associations were found for low- or moderate-risk drinking patterns vs occasional drinking among individuals without socioeconomic or health-related risk factors, low-risk drinking was associated with higher cancer mortality (HR, 1.15; 95% CI, 1.01-1.30) and moderate-risk drinking with higher all-cause (HR, 1.10; 95% CI, 1.01-1.19) and cancer (HR, 1.19; 95% CI, 1.05-1.35) mortality among those with health-related risk factors; low-risk and moderate-risk drinking patterns were associated with higher mortality from all causes (low risk: HR, 1.14; 95% CI, 1.01-1.28; moderate risk: HR, 1.17; 95% CI, 1.03-1.32) and cancer (low risk: HR, 1.25; 95% CI, 1.04-1.50; moderate risk: HR, 1.36; 95% CI, 1.13-1.63) among those with socioeconomic risk factors. Wine preference (>80% of alcohol from wine) and drinking with meals showed small protective associations with mortality, especially from cancer, but only in drinkers with socioeconomic or health-related risk factors and was associated with attenuating the excess mortality associated with high-, moderate- and even low-risk drinking. Conclusions and Relevance: In this cohort study of older drinkers from the UK, even low-risk drinking was associated with higher mortality among older adults with health-related or socioeconomic risk factors. The attenuation of mortality observed for wine preference and drinking only during meals requires further investigation, as it may mostly reflect the effect of healthier lifestyles, slower alcohol absorption, or nonalcoholic components of beverages.

Growth Differentiation Factor 15 as a Biomarker of Cardiovascular Risk in Chronic Musculoskeletal Pain.

BACKGROUND: It is unknown whether growth differentiation factor 15 (GDF-15) is associated with chronic musculoskeletal pain (CMP) and whether or not its association with incident cardiovascular disease (CVD) changes according to CMP status. METHODS: In total, 1 957 randomly selected adults aged ≥65 years without prior CVD were followed up between 2015 and 2023. CMP was classified according to its intensity, frequency, and interference with daily activities. The association between GDF-15 levels and CMP was assessed using linear models with progressive inclusion of potential confounders, whereas the association between GDF-15 and CVD risk was evaluated with Cox proportional hazard models with similar adjustment and interaction terms between GDF-15 and CMP. The incremental predictive performance of GDF-15 over standard predictors was evaluated using discrimination and risk reclassification metrics. RESULTS: GDF-15 concentrations were 6.90% (95% confidence interval [CI]: 2.56; 11.25) higher in individuals with CMP, and up to 8.89% (4.07; 15.71) and 15.79% (8.43; 23.16) higher in those with ≥3 CMP locations and interfering pain. These increased levels were influenced by a higher prevalence of cardiometabolic risk factors, functional impairments, depressive symptoms, and greater levels of inflammation in individuals with CMP. In fully adjusted models, a twofold increase in GDF-15 was associated with a 1.49 increased risk (95% CI: 1.08; 2.05) of a CVD event in individuals with CMP, but not among those without CMP (1.02 [0.77; 1.35]); p-interaction 0.041. Adding GDF-15 to models including the Framingham Risk Score improved predictive performance among individuals with CMP. CONCLUSIONS: We provide evidence that GDF-15 could serve as a biomarker to assess CMP, as well as to predict CVD incidence in individuals with CMP.

Volume of alcohol intake, heavy episodic drinking, and all-cause mortality in Spain: A longitudinal population-based study.

INTRODUCTION: The impact of alcohol consumption on health, particularly in low quantities, remains controversial. Our objective was to assess the association between alcohol volume and heavy episodic drinking (HED) with all-cause mortality, while minimizing many of the known methodological issues. METHODOLOGY: This longitudinal study used data from the 2011-2012 National Health Survey and the 2014 European Health Survey in Spain. Data from 43,071 participants aged ≥ 15 years were linked to mortality records as of December 2021. Alcohol consumption categories were defined based on intake volume and frequency: never-drinkers, former drinkers, infrequent occasional drinkers (≤once/month), frequent occasional drinkers ( once /month). Regular drinkers (≥once/week) were further classified by volume: >0-10 g/day, >10-20 g/day, >20-40 g/day, and > 40 g/day. Heavy Episodic Drinking (HED) was defined as ≥ 6 and ≥ 5 standard drinks (10 g) within 4-6 h for men and women, respectively. Hazard ratios (HR) were calculated using Cox regression, adjusting for sociodemographic variables, lifestyle factors, health status, and alcohol volume or HED. RESULTS: Compared to infrequent occasional drinkers, HRs for never-drinkers and former drinkers were 1.30 (95 %CI:1.14-1.47) and 1.32 (95 %CI:1.15-1.50), respectively. No differences in mortality risk were observed for intakes up to 20 g/day, but it increased for consumptions > 20-40 g/day and > 40 g/day (HR = 1.29; 95 %CI:1.05-1.58 and HR = 1.57; 95 %CI:1.14-2.17, respectively). The HR of weekly HED vs. never was 1.31 (95 %CI:0.98-1.75). CONCLUSIONS: Compared to infrequent occasional drinking, consuming low amounts of alcohol had no impact on mortality risk. However, never-drinkers, former drinkers, individuals with regular consumption > 20 g/day, and those engaging in weekly HED, experienced higher mortality risk.

Quality of plant-based diets and frailty incidence: a prospective analysis of UK biobank participants.

BACKGROUND: Substantial evidence supports the inverse association between adherence to healthy dietary patterns and frailty risk. However, the role of plant-based diets, particularly their quality, is poorly known. OBJECTIVE: To examine the association of two plant-based diets with incidence of physical frailty in middle-aged and older adults. DESIGN: Prospective cohort. SETTING: United Kingdom. SUBJECTS: 24,996 individuals aged 40-70 years, followed from 2009-12 to 2019-22. METHODS: Based on at least two 24-h diet assessments, we built two diet indices: (i) the healthful Plant-based Diet Index (hPDI) and (ii) the unhealthful Plant-based Diet Index (uPDI). Incident frailty was defined as developing ≥3 out of 5 of the Fried criteria. We used Cox models to estimate relative risks (RR), and their 95% confidence interval (CI), of incident frailty adjusted for the main potential confounders. RESULTS: After a median follow-up of 6.72 years, 428 cases of frailty were ascertained. The RR (95% CI) of frailty was 0.62 (0.48-0.80) for the highest versus lowest tertile of the hPDI and 1.61 (1.26-2.05) for the uPDI. The consumption of healthy plant foods was associated with lower frailty risk (RR per serving 0.93 (0.90-0.96)). The hPDI was directly, and the uPDI inversely, associated with higher risk of low physical activity, slow walking speed and weak hand grip, and the uPDI with higher risk of exhaustion. CONCLUSIONS: In British middle-age and older adults, greater adherence to the hPDI was associated with lower risk of frailty, whereas greater adherence to the uPDI was associated with higher risk.

Dietary Vitamin C Intake and Changes in Frequency, Severity, and Location of Pain in Older Adults.

BACKGROUND: Oral vitamin C supplementation has been associated with lower risk of chronic postsurgical pain. However, the effect of dietary vitamin C on pain in a nonsurgical setting is unknown. We aimed to investigate the association between dietary vitamin C intake and changes over time in chronic pain and its characteristics in community-dwelling adults aged 60 + years. METHODS: We pooled data from participants of the Seniors-ENRICA-1 (n = 864) and Seniors-ENRICA-2 (n = 862) cohorts who reported pain at baseline or at follow up. Habitual diet was assessed with a face-to-face diet history and dietary vitamin C intake was estimated using standard food composition tables. Pain changes over time were the difference between scores at baseline and follow up obtained from a pain scale that considered the frequency, severity, and number of pain locations. Multivariable-adjusted relative risk ratios were obtained using multinomial logistic regression. RESULTS: After a median follow-up of 2.6 years, pain worsened for 696 (40.3%) participants, improved for 734 (42.5%), and did not change for 296 (17.2%). Compared with the lowest tertile of energy-adjusted vitamin C intake, those in the highest tertile had a higher likelihood of overall pain improvement (RRR 1.61 [95% confidence interval 1.07-2.41], p-trend .02). Higher vitamin C intake was also associated with lower pain frequency (1.57 [1.00-2.47], p-trend = .05) and number of pain locations (1.75 [1.13-2.70], p-trend = .01). CONCLUSIONS: Higher dietary vitamin C intake was associated with improvement of pain and with lower pain frequency and number of pain locations in older adults. Nutritional interventions to increase dietary vitamin C intake with the aim of improving pain management require clinical testing.

Glyphosate exposure, muscular health and functional limitations in middle-aged and older adults.

BACKGROUND: Glyphosate is the most widely used herbicide worldwide, both in domestic and industrial settings. Experimental research in animal models has demonstrated changes in muscle physiology and reduced contractile strength associated with glyphosate exposure, while epidemiological studies have shown associations between glyphosate exposure and adverse health outcomes in critical biological systems affecting muscle function. METHODS: This study used data from a nationally representative survey of the non-institutionalized U.S. general population (NHANES, n = 2132). Urine glyphosate concentrations were determined by ion chromatography with tandem mass spectrometry. Hand grip strength (HGS) was measured using a Takei Dynamometer, and relative strength estimated as the ratio between HGS in the dominant hand and the appendicular lean mass (ALM) to body mass index (ALMBMI) ratio. Low HGS and low relative HGS were defined as 1 sex-, age- and race-specific SD below the mean. Physical function limitations were identified as significant difficulty or incapacity in various activities. RESULTS: In fully-adjusted models, the Mean Differences (MD) and 95% confidence intervals [95%CI] per doubling increase in glyphosate concentrations were -0.55 [-1.09, -0.01] kg for HGS in the dominant hand, and -0.90 [-1.58. -0.21] kg for HGS/ALMBMI. The Odds Ratios (OR) [95% CI] for low HGS, low relative HGS and functional limitations by glyphosate concentrations were 1.27 [1.03, 1.57] for low HGS; 1.43 [1.05; 1.94] for low relative HGS; 1.33 [1.08, 1.63] for stooping, crouching or kneeling difficulty; 1.17 [0.91, 1.50] for lifting or carrying items weighting up to 10 pounds difficulty; 1.21 [1.01, 1.40] for standing up from armless chair difficulty; and 1.47 [1.05, 2.29] for ascending ten steps without pause difficulty. CONCLUSIONS: Glyphosate exposure may be a risk factor for decreased grip strength and increased physical functional limitations. More studies investigating the influence of this and other environmental pollutants on functional aging are needed.

Exposure to green spaces, cardiovascular risk biomarkers and incident cardiovascular disease in older adults: The Seniors-Enrica II cohort.

INTRODUCTION: The impact of residential green spaces on cardiovascular health in older adults remains uncertain. METHODS: Cohort study involving 2114 adults aged ≥ 65 years without cardiovascular disease (CVD), residing in five dense municipalities (Prince et al., 2015) of the Madrid region and with detailed characterization of their socioeconomic background, health behaviors, CVD biological risk factors, and mental, physical, and cognitive health. Greenness exposure was measured using the Normalized Difference Vegetation Index (NDVI) at varying distances from participants' homes. Traffic exposure, neighborhood environment, neighborhood walkability, and socioeconomic deprivation at the census level were also assessed. Serum N-terminal pro-B-type natriuretic peptide (NT-ProBNP), high-sensitivity troponin T (hs-TnT), interleukin 6 (IL-6), and Growth Differentiation Factor 15 (GDF-15) were measured at baseline, and incident CVD events identified through electronic medical records (International Classification of Primary Care-2 codes K74, K75, K77, K90, and K92). RESULTS: After adjusting for sex, age, educational attainment, financial hardship and socioeconomic deprivation at the census level, an interquartile range (IQR) increase in NDVI at 250, 500, 750, and 1000 m around participants' homes was associated with mean differences in ProBNP of -5.56 % (95 %CI: -9.77; -1.35), -5.05 % (-9.58; -0.53), -4.24 % (-8.19, -0.19), and -4.16 % (-7.59; -0.74), respectively; and mean differences in hs-TnT among diabetic participants of -8.03 % (95 %CI: -13.30; -2.77), -9.52 % (-16.08; -2.96), -8.05 % (-13.94, -2.16) and -5.56 % (-10.75; -0.54), respectively. Of similar magnitude, although only statistically significant at 250 and 500 m, were the observed lower IL-6 levels with increasing greenness. GDF-15 levels were independent of NDVI. In prospective analyses (median follow-up 6.29 years), an IQR increase in residential greenness at 500, 750, and 1000 m was associated with a lower risk of incident CVD. The variables that contributed most to the apparent beneficial effects of greenness on CVD were lower exposure to traffic, improved cardiovascular risk factors, and enhanced physical performance. Additionally, neighborhood walkability and increased physical activity were notable contributors among individuals with diabetes. CONCLUSION: Increased exposure to residential green space was associated with a moderate reduction in CVD risk in older adults residing in densely populated areas.

Exposure to residential traffic and trajectories of unhealthy ageing: results from a nationally-representative cohort of older adults.

BACKGROUND: Traffic exposure has been associated with biomarkers of increased biological ageing, age-related chronic morbidities, and increased respiratory, cardiovascular, and all-cause mortality. Whether it is associated with functional impairments and unhealthy ageing trajectories is unknown. METHODS: Nationally representative population-based cohort with 3,126 community-dwelling individuals aged ≥60 years who contributed 8,291 biannual visits over a 10 year period. Unhealthy ageing was estimated with a deficit accumulation index (DAI) based on the number and severity of 52 health deficits, including 22 objectively-measured impairments in physical and cognitive functioning. Differences in DAI at each follow-up across quintiles of residential traffic density (RTD) at 50 and 100 meters, and closest distance to a petrol station, were estimated using flexible marginal structural models with inverse probability of censoring weights. Models were adjusted for sociodemographic and time-varying lifestyle factors, social deprivation index at the census tract and residential exposure to natural spaces. RESULTS: At baseline, the mean (SD) age and DAI score of the participants were 69.0 (6.6) years and 17.02 (11.0) %, and 54.0% were women. The median (IQR) RTD at 50 and 100 meters were 77 (31-467) and 509 (182-1802) vehicles/day, and the mean (SD) distance to the nearest petrol station of 962 (1317) meters. The average increase in DAI (95%CI) for participants in quintiles Q2-Q5 (vs Q1) of RTD at 50 meters was of 1.51 (0.50, 2.53), 0.98 (-0.05, 2.01), 2.20 (1.18, 3.21) and 1.98 (0.90, 3.05), respectively. Consistent findings were observed at 100 meters. By domains, most of the deficits accumulated with increased RTD were of a functional nature, although RTD at 50 meters was also associated with worse self-reported health, increased vitality problems and higher incidence of chronic morbidities. Living closer to a petrol station was associated with a higher incidence of functional impairments and chronic morbidities. CONCLUSIONS: Exposure to nearby residential traffic is associated with accelerated trajectories of unhealthy ageing. Diminishing traffic pollution should become a priority intervention for adding healthy years to life in the old age.

Alcohol consumption patterns and adherence to the Mediterranean diet in the adult population of Spain.

PURPOSE: The objective is to evaluate the association between various indicators of alcohol consumption and the degree of adherence to the Mediterranean diet among the Spanish adult population. METHODS: A cross-sectional study including 44,834 participants ≥ 15 years of age from the 2017 National Health Survey and the 2020 European Health Survey in Spain. Alcohol patterns were defined based on (1) average intake: individuals were classified as low risk (1-20 g/day in men and 1-10 g/day in women) and high risk (> 20 g/day in men or > 10 g/day in women), (2) binge drinking, and (3) alcoholic beverage preference. Non-adherence to the Mediterranean diet was defined as scoring < 7 points on an adapted Mediterranean Diet Adherence Screener index (range 0-10). Odds ratios (OR) were estimated using logistic regression models adjusted for relevant covariates. RESULTS: Compared to non-drinkers, low and high-risk drinkers were more likely to report non-adherence to the Mediterranean diet: ORs 1.35 (95% CI 1.23; 1.49) and 1.54 (95% CI 1.34; 1.76), respectively. Similarly, reports of binge drinking less than once a month was associated with higher likelihood of non-adherence (OR 1.17; 95% CI 1.04; 1.31). Individuals reporting no preference for a specific beverage and those with a preference for beer or for spirits had lower adherence: ORs 1.18 (95% CI 1.05; 1.33), 1.31 (95% CI 1.17; 1.46), and 1.72 (95% CI 1.17; 2.54), respectively, while a preference for wine showed no association (OR 1.01; 95% CI 0.90; 1.13). CONCLUSION: Alcohol consumption, even in low amounts, is associated with lower adherence to the Mediterranean diet. Therefore, alcoholic beverages should not be included in measures that define the Mediterranean diet.

Animal and vegetable protein intake and malnutrition in older adults: a multicohort study.

OBJECTIVES: Malnutrition is a global concern in older adults, as it negatively affects morbidity and mortality. While higher animal protein intake may help prevent and treat malnutrition, it might also increase the risk of chronic diseases and death. Conversely, vegetable protein intake might have a lower anabolic effect and not be as effective to improve nutritional status. We studied whether animal and vegetable protein intake are associated with changes in nutritional status in older adults. DESIGN: We used pooled data from two Spanish cohorts: the Seniors-ENRICA 1 and Seniors-ENRICA 2. SETTINGS AND PARTICIPANTS: 2,965 community-dwelling adults aged 62-92 years. MEASUREMENTS: Protein intake was estimated at baseline via an electronic, validated diet history. Nutritional status was assessed at baseline and after 2.6 years with the GLIM (Global Leadership Initiative on Malnutrition) phenotypic criteria: weight loss, low body mass index, and reduced muscle mass. The odds of improvements in nutritional status were assessed with logistic regression models, extensively adjusted for potential confounders. RESULTS: Higher animal and vegetable protein intake were associated with improvements in nutritional status [odds ratios (95% confidence intervals) per 0.25 g/kg/day were 1.15 (1.00, 1.32) and 1.77 (1.35, 2.32), respectively]. Cereal protein intake drove most of the latter association [2.07 (1.44, 2.98)]. Replacing 0.25 g/kg/day of total animal protein, meat, or fish protein (but not dairy or egg protein) with vegetable protein was associated with improvements in nutritional status [1.54 (1.13, 2.09), 1.70 (1.20, 2.41), and 1.77 (1.18, 2.64), respectively]. CONCLUSIONS: Higher animal and, especially, vegetable protein intake were associated with improvements in nutritional status in older adults. Replacing total animal protein, meat, or fish protein with vegetable protein may help improve malnutrition.

Blood DNA methylation and liver cancer in American Indians: evidence from the Strong Heart Study.

PURPOSE: Liver cancer incidence among American Indians/Alaska Natives has risen over the past 20 years. Peripheral blood DNA methylation may be associated with liver cancer and could be used as a biomarker for cancer risk. We evaluated the association of blood DNA methylation with risk of liver cancer. METHODS: We conducted a prospective cohort study in 2324 American Indians, between age 45 and 75 years, from Arizona, Oklahoma, North Dakota and South Dakota who participated in the Strong Heart Study between 1989 and 1991. Liver cancer deaths (n = 21) were ascertained using death certificates obtained through 2017. The mean follow-up duration (SD) for non-cases was 25.1 (5.6) years and for cases, 11.0 (8.8) years. DNA methylation was assessed from blood samples collected at baseline using MethylationEPIC BeadChip 850 K arrays. We used Cox regression models adjusted for age, sex, center, body mass index, low-density lipoprotein cholesterol, smoking, alcohol consumption, and immune cell proportions to examine the associations. RESULTS: We identified 9 CpG sites associated with liver cancer. cg16057201 annotated to MRFAP1) was hypermethylated among cases vs. non-cases (hazard ratio (HR) for one standard deviation increase in methylation was 1.25 (95% CI 1.14, 1.37). The other eight CpGs were hypomethylated and the corresponding HRs (95% CI) ranged from 0.58 (0.44, 0.75) for cg04967787 (annotated to PPRC1) to 0.77 (0.67, 0.88) for cg08550308. We also assessed 7 differentially methylated CpG sites associated with liver cancer in previous studies. The adjusted HR for cg15079934 (annotated to LPS1) was 1.93 (95% CI 1.10, 3.39). CONCLUSIONS: Blood DNA methylation may be associated with liver cancer mortality and may be altered during the development of liver cancer.

Smoking history and breast cancer risk by pathological subtype: MCC-Spain study.

INTRODUCTION: The role of cigarette smoking on breast cancer risk remains controversial, due to its dual carcinogenic-antiestrogenic action. METHODS: In the population-based multi-case-control study (MCC-Spain), we collected epidemiological and clinical information for 1733 breast cancer cases and 1903 controls, including smoking exposure. The association with breast cancer, overall, by pathological subtype and menopausal status, was assessed using logistic and multinomial regression models. RESULTS: Smokers had higher risk of premenopausal breast cancer, particularly if they had smoked ≥30 years (AOR=1.75; 95% CI: 1.04-2.94), although most estimates did not achieve statistical significance. In contrast, among postmenopausal women, smoking was associated with lower risk of breast cancer, mainly in overweight and obese women. The strongest risk reductions were observed among postmenopausal women who had stopped smoking ≥10 years before cancer diagnosis, particularly for HER2+ tumors (AOR=0.28; 95% CI: 0.11-0.68); p for heterogeneity = 0.040). Also, those who had smoked <10 pack-years (AOR=0.68; 95% CI: 0.47-0.98) or 10-25 pack-years (AOR=0.62; 95% CI: 0.42-0.92) during their lifetime were at a reduced risk of all breast cancer subtypes (p for heterogeneity: 0.405 and 0.475, respectively); however, women who had smoked more than 25 pack-years showed no reduced risk. CONCLUSIONS: Menopausal status plays a key role in the relationship between tobacco and breast cancer for all cancer subtypes. While smoking seems to increase the risk in premenopausal woman, it might be associated to lower risk of breast cancer among postmenopausal women with excess weight.

Blood Selenium Concentrations Are Inversely Associated with the Risk of Undernutrition in Older Adults.

BACKGROUND: Selenium is an essential trace element with an antioxidant and anti-inflammatory capacity that has been associated in experimental studies with beneficial effects on appetite control, the regulation of the gut microbiota, and control of the anabolic-catabolic balance. The main aim of the present study was to evaluate the association between circulating selenium concentrations and the risk of developing undernutrition in older adults. METHODS: This was a cohort study with 1398 well-nourished community-dwelling individuals aged ≥ 65 years residing in Spain in 2017, who were followed for a mean of 2.3 years. Whole blood selenium was measured at baseline using inductively coupled plasma-mass spectrometry. Undernutrition was assessed at baseline and at follow-up, and defined as having at least one of the three GLIM phenotypic criteria (involuntary weight loss, a low body mass index, and a reduced muscle mass) and at least one of the two etiologic criteria (reduced food consumption or nutrient assimilation and inflammation/disease burden). RESULTS: During the follow-up, 142 participants (11%) developed moderate undernutrition and 113 (8.8%) severe undernutrition. The standardized relative risks of moderate and severe undernutrition at the 75th percentile of Se levels versus the 25th were 0.90 and 0.70, respectively. In dose-response analyses, the risk of severe undernutrition decreased linearly with increasing selenium concentrations. This association was independent of protein intake or diet quality and was stronger among participants with a diagnosis of a musculoskeletal disorder. CONCLUSIONS: The results suggest that an adequate dietary selenium status is needed to prevent undernutrition in older adults. Also, this may open the door for clinical trials with selenium supplementation, at doses considered as safe, to prevent undernutrition.

Urinary Phthalate Metabolites and Slow Walking Speed in the Korean Elderly Environmental Panel II Study.

BACKGROUND: Previous epidemiological studies have suggested that phthalate exposure may contribute to neurocognitive and neurobehavioral disorders and decreased muscle strength and bone mass, all of which may be associated with reduced physical performance. Walking speed is a reliable assessment tool for measuring physical performance in adults age 60 y and older. OBJECTIVE: We investigated associations between urinary phthalate metabolites and slowness of walking speed in community-dwelling adults ages 60-98 y. METHODS: We analyzed 1,190 older adults [range, 60-98 y of age; mean±standard deviation (SD) , 74.81±5.99] from the Korean Elderly Environmental Panel II study and measured repeatedly up to three times between 2012 and 2014. Phthalate exposure was estimated using the following phthalate metabolites in urine samples: mono-(2-ethyl-5-hydroxyhexyl) phthalate (MEHHP), mono-(2-ethyl-5-oxohexyl) phthalate (MEOHP), mono-n-butyl phthalate (MnBP), mono-(2-ethyl-5-carboxypentyl) phthalate (MECPP), and mono-benzyl phthalate (MBzP). Slowness was defined as a walking speed of <1.0meter/second. We used logistic and linear regression models to evaluate the association between each urinary phthalate metabolite and slowness or walking-speed change. We also used Bayesian kernel machine regression (BKMR) to examine overall mixture effects on walking speed. RESULTS: At enrollment, MBzP levels were associated with an increased odds of slowness [odds ratio (OR) per doubling increase: 1.15, 95% confidence interval (CI): 1.02, 1.30; OR for the highest vs. lowest quartile: 2.20 (95% CI: 1.12, 4.35) with p-trend across quartiles=0.031]. In longitudinal analyses, MEHHP levels showed an increased risk of slowness [OR per doubling increase: 1.15 (95% CI: 1.02, 1.29), OR for the highest vs. lowest quartile: 1.47 (95% CI: 1.04, 2.06), p- trend=0.035]; whereas those with higher MnBP showed a reduced risk of slowness [OR per doubling increase: 0.84 (95% CI: 0.74, 0.96), OR in the highest (vs. lowest) quartile: 0.64 (95% CI: 0.47, 0.87), p-trend=0.006]. For linear regression models, MBzP quartiles were associated with slower walking speed (p-trend=0.048) at enrollment, whereas MEHHP quartiles were associated with slower walking speed, and MnBP quartiles were associated with faster walking speed in longitudinal analysis (p-trend=0.026 and <0.001, respectively). Further, the BKMR analysis revealed negative overall trends between the phthalate metabolite mixtures and walking speed and DEHP group (MEHHP, MEOHP, and MECPP) had the main effect of the overall mixture. DISCUSSION: Urinary concentrations of prevalent phthalates exhibited significant associations with slow walking speed in adults ages 60-98 y. https://doi.org/10.1289/EHP10549.

Device-measured movement behaviors and cardiac biomarkers in older adults without major cardiovascular disease: the Seniors-ENRICA-2 study.

BACKGROUND: High-sensitivity cardiac troponin T (hs-cTnT) and N-terminal pro-brain natriuretic peptide (NT-proBNP) are biomarkers of myocardial infarction and heart failure, respectively, and indicate cardiovascular risk. Since low physical activity (PA) and sedentary behavior (SB) are also associated with higher cardiovascular risk, and this association could be a consequence of higher levels of cardiac biomarkers, we examined the association of device-measured movement behaviors with hs-cTnT and NT-proBNP in older men and women without major cardiovascular disease (CVD). METHODS: We used data from 1939 older adults from the Seniors-ENRICA-2 study. Accelerometers were used to assess time spent in sleep, SB, light PA (LPA), and moderate-to-vigorous PA (MVPA). Linear regression models were fitted separately in eight strata defined by sex, by median total PA time, and by the presence of subclinical cardiac damage according to cardiac biomarkers levels. RESULTS: In the less active men with subclinical cardiac damage, spending 30 min/day more of MVPA was associated with a mean percentage difference (MPD) (95% confidence interval) in hs-cTnT of - 13.1 (- 18.3, - 7.5); MPDs in NT-proBNP per 30 min/day increment were 5.8 (2.7, 8.9) for SB, - 19.3 (- 25.4, - 12.7) for LPA and - 23.1 (- 30.7, - 14.6) for MVPA. In women with subclinical cardiac damage who were less physically active, 30 min/day more of SB, LPA and MVPA were associated with MPDs in hs-cTnT of 2.1 (0.7, 3.6), - 5.1 (- 8.3, - 1.7) and - 17.5 (- 22.9, - 11.7), respectively, whereas in those more active, LPA and MVPA were associated with MPDs of 4.1 (1.2, 7.2) and - 5.4 (- 8.7, - 2.0), respectively. No associations were found with NT-proBNP in women. CONCLUSIONS: The relationship between movement behaviors and cardiac biomarkers in older adults without major CVD depends on sex, subclinical cardiac damage and PA level. More PA and less SB were generally related to lower cardiac biomarkers levels among less active individuals with subclinical cardiac damage, with greater benefits for hs-cTnT in women than men and no benefits for NT-proBNP in women.

Association between a Mediterranean lifestyle and growth differentiation factor 15: The seniors ENRICA-2 cohort.

BACKGROUND: Growth Differentiation Factor 15 (GDF-15) is a marker of inflammation and oxidative stress that has been associated with multiple age-related chronic diseases. Since lifestyle is key for preventing these adverse health outcomes, we examined the association between a Mediterranean lifestyle and GDF-15 serum concentrations in Spanish older adults. METHODS: We used cross-sectional data from 2502 older adults participating in the Seniors ENRICA-2 cohort. Adherence to the Mediterranean lifestyle was assessed with the 27-item MEDLIFE index, divided into three blocks: 1) "Mediterranean food consumption, 2) Mediterranean dietary habits, 3) Physical activity, rest, social habits, and conviviality". Analyses of the association between the MEFLIFE index and GDF-15 concentrations were performed using multivariable linear regression models adjusting for the main potential confounders. RESULTS: The MEDLIFE index was inversely associated with GDF-15. Compared with participants in the lowest quartile of the MEDLIFE score, GDF-15 mean percentage differences (95% CI) were -3.0% (-8.0, 2.3) for the second quartile, -8.7% (-13.0, -4.1) for the third quartile, and -10.1% (-15.0, -4.9) for the fourth quartile (p-trend<0.001). Block 3 of MEDLIFE, and particularly doing sufficient physical activity, adequate sleep duration, and participating in collective sports, was individually linked to lower concentrations of GDF-15. Results remained similar after excluding participants with cardiovascular disease, type 2 diabetes, or obesity. CONCLUSIONS: A Mediterranean lifestyle was associated with reduced levels of GDF-15, suggesting that a combination of multiple lifestyles may be an integral approach to reduce chronic inflammation and disease burden in older adults.

Light cigarette smoking and all-cause mortality in Spain. A national population-based cohort study.

PURPOSE: Regular light cigarette consumption (light smoking) is increasing in many countries; however, few studies have assessed its impact on mortality. The main aim of this study is to estimate the association between the number of cigarettes consumed and all-cause mortality in Spain while focusing on light smoking. METHODS: Longitudinal study based on data from 42,902 individuals aged ≥15 years included in the 2011-2012 (Spanish) National Health Survey or the 2014 European Health Survey for Spain. Data were linked with the mortality registry up to December 2020. Multivariate Cox regression models were used to estimate hazard ratios (HR) adjusted for sociodemographic variables, lifestyle factors, and health status indicators. RESULTS: Compared to never smokers, the mortality HR for nondaily smokers was 1.30 (95% CI: 0.81-2.09), increasing to 2.23 (95% CI: 1.25-3.96) among those smoking 1-2 cigarettes/d, and to 1.54 (95%CI: 1.14-2.07) for consumers of 3-5 cigarettes/day. When individuals who reported trying to quit during the previous year were excluded, resulting HRs were 1.31 (95% CI: 0.81-2.10), 1.48 (95% CI: 0.69-3.19) and 1.64 (95% CI: 1.16-2.34), respectively. CONCLUSIONS: Compared to never smokers, consumers of small quantities of tobacco, that is, light smoking, had an increased mortality risk. In view of these results, we suggest the need for awareness-raising campaigns regarding how smoking even a small number of cigarettes a day causes serious harm to one´s health.

Plant-based diets and risk of frailty in community-dwelling older adults: the Seniors-ENRICA-1 cohort.

Frailty is a geriatric syndrome that leads to increased risk of hospitalization, disability, and death. The effect of plant-based diets defined by the quality of their plant foods is unclear. Our objective is to study the association between two plant-based diet indices and the occurrence of frailty among community-dwelling older adults in Spain. We analyzed data from 1880 individuals aged ≥ 60 years from the Spanish Seniors ENRICA-1 cohort. We used a validated diet history to build two indices: (a) the healthful Plant-based Diet Index (hPDI) where healthy plant foods received positive scores, whereas less-healthy plant foods and animal foods received reverse scores; and (b) the unhealthful Plant-based Diet Index (uPDI), with positive scores to less-healthy plant foods and reverse scores to animal and healthy plant foods. Incident frailty was defined with the Fried phenotype. Study associations were summarized with odds ratios (OR) and 95% confidence intervals (CI) obtained from multivariable logistic models. After 3.3 years of follow-up, 136 incident frailty cases were ascertained. Comparing the highest vs. the lowest tertile of adherence, the OR [95% CI] for frailty was 0.43 (0.25-0.74; p-trend = .003) for the hPDI, and 2.89 (1.73-4.84; p-trend < .001) for the uPDI. Higher consumption of healthy plant foods was inversely associated with frailty (0.39 [0.23-0.66; p-trend < 0.001]); higher consumption of unhealthy plant foods was associated with higher frailty risk (2.40 [1.23-4.71; p-trend = .01]). In older adults, the hPDI was associated with lower risk of frailty, while the opposite was found for the uPDI.

Performance and validation of the Healthy Heart Score model for predicting 12-year cardiovascular mortality in a nationwide Mediterranean population.

INTRODUCTION AND OBJECTIVES: The Healthy Heart Score (HHS) is a lifestyle-based equation for predicting cardiovascular disease (CVD) risk and may serve as a tool in primordial prevention. However, its performance outside North American populations is unknown. This study assessed the performance of the HHS for estimating CVD mortality in the adult population of Spain. METHODS: We analyzed data from the ENRICA cohort, comprising 10 228 participants free of chronic disease and representative of the Spanish population aged ≥ 18-years, who were recruited from 2008 to 2010 and were followed up to 2020. The HHS includes body mass index, alcohol, physical activity, smoking, and a 5-component dietary score. The HHS was calculated at baseline using the sex-specific beta coefficients from the original development cohorts. Model discrimination was assessed using the Harrell c-statistic and Gonen-Heller c-statistic for survival data, and calibration was evaluated through calibration plots. RESULTS: After a median follow-up of 11.8 years, 110 CVD deaths were ascertained. The discrimination of the HHS was similar for women (Harrell c, 0.91; 95%CI, 0.87-0.95; Gonen-Heller-c, 0.85; 95%CI, 0.83-0.88) and men (Harrell c, 0.91; 95%CI, 0.88-0.94; Gonen-Heller c: 0.85; 95%CI, 0.83-0.88). After recalibration by the sex-specific baseline survival function, the calibration became optimal for: a) all deciles of predicted CVD risk except the highest decile, where HHS underestimated the risk, and b) all age groups except 70 years and older, where there was an underestimation. CONCLUSIONS: In this Spanish cohort, the HHS showed good discrimination and calibration for predicting CVD death. The performance of HHS in other European populations and its implementation in the clinical setting warrants further investigation.