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.

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.

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.

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.

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.

Secondhand Tobacco Smoke and Functional Impairments in Older Adults Living in the Community.

BACKGROUND/AIM: There has been no comprehensive examination of the potential association of SHS with broad functional limitation assessment in older adults, where functional limitations are burdensome and challenging. METHODS: We examined 2258 community-dwelling non-smoking older adults from the Seniors-Enrica-2-cohort. At baseline (2017) and follow-up (2019) grip strength was measured with a Jamar dynamometer, lower-extremity performance with the Short Physical Performance Battery (SPPB), overall physical function using the physical component summary (PCS) of the Spanish version of the SF-12, frailty with a Deficits Accumulation Index (DAI), and mobility limitations with the Rosow-Breslau scale. Baseline exposure to SHS was assessed by serum cotinine, and past exposure was self-reported. Cross-sectional analyses were performed using linear and logistic regression models, whereas functional performance changes were examined using repeated measures models with robust SE estimates. RESULTS: Overall, the median (IQR) serum cotinine concentration was 0.079 (0.035-0.175) ng/ml, with 20 participants presenting concentrations ≥3 ng/ml. Compared to the unexposed, fully-adjusted models showed that the highest exposure group (≥0.239 ng/ml) presented lower grip strength (mean difference: -1.05 kg; 95% CI = -1.80, -0.31) and higher DAI scores (1.52; 95% CI = 0.38, 2.66) at baseline. Similarly, in models of self-reported past exposure, never-smokers who had lived with ≥2 smokers or been exposed to higher SHS cumulative doses showed lower baseline SPPB values, higher DAI scores, and higher prevalence of mobility limitations. In prospective analyses, those in the highest quartile of baseline cotinine presented harmful SPPB [-0.24 (-0.46, -0.02)] and DAI [1.28 (0.00, 2.55)] changes, and higher risk of mobility limitations [hazard ratio: 1.64; 95% CI = 1.01, 2.68] than the unexposed. CONCLUSIONS: SHS exposure over the life-course and during old age may accelerate functional decline. IMPLICATIONS: This manuscript provides a comprehensive examination of the relationship between secondhand smoke exposure and a broad range of functional limitations in older adults. Results show that: (i) non-smokers who had been exposed to higher cumulative doses of SHS in adulthood show worse physical function than non-exposed. (ii) Exposure to SHS during old age, as measured with cotinine concentrations, is associated with accelerated short-term functional declines. (iii) The effects of SHS are stronger among older adults with chronic morbidities. (iv) Results suggest that more efforts are needed to protect older adults from passive smoking, especially to those with chronic conditions because of their potential greater vulnerability to the effects of SHS.

Prospective association between dietary magnesium intake and physical performance in older women and men.

PURPOSE: Magnesium is a profuse intracellular cation with a key role in muscle function and cellular senescence. The aim was to examine the prospective association between 5 year changes in dietary intake of magnesium and changes in physical performance among older men and women. METHODS: Prospective study conducted over 863 community-dwellers aged ≥ 65 years from the Seniors-ENRICA cohort (Spain). In 2012 and 2017, a validated computerized face-to-face diet history was used to record the consumption of up to 880 foods. From these data, we estimated changes in dietary magnesium intake. The Short Physical Performance Battery (SPPB) was also conducted in both time points and we obtained changes in the score during follow-up, with positive values indicating physical performance improvement. RESULTS: Over 5 years of follow-up, an increase in magnesium intake was associated with an increment in the SPPB score among older women [multivariate ß (95% confidence interval): 1.01 (0.49; 1.52), p-trend: 0.001]. In addition, changes from non-adherence to adherence to both estimated average requirement and recommended dietary allowance during follow-up period were associated with an increment in SPPB score among older women [1.14 (0.36; 1.92) and 0.84 (0.22; 1.47), respectively]. No significant associations between changes in magnesium intake and changes in SPPB score were observed in men. CONCLUSIONS: Both increase of magnesium intake and change from non-adherence to adherence to dietary reference magnesium intake was prospectively associated with better physical performance among older women, but not among men.

Objectively measured secondhand tobacco smoke and cognitive impairment in disability-free older adults.

Previous studies have suggested that exposure to secondhand smoke (SHS) may be associated with greater risk of cognitive impairment. However, no longitudinal study has examined the association of serum cotinine (as objective measure of SHS exposure) and cognitive function in older adults. We used data from 2087 non-smoking adults aged≥65 years participating in the ENRICA-2 cohort and free from limitations in Instrumental Activities of Daily Living. Cognitive function was assessed through the Mini-Mental State Examination (MMSE), the Digit Span Backwards subtest (DSBT), the Luria's motor series subtest from the Frontal Assessment Battery, the Trail Making Test A (TMT-A), the Free and Cued Selective Reminding Test (FCSRT), and the Categorical Verbal Fluency Test (CFT) of the 7 min test. Cross-sectional analyses were performed using multivariable logistic and ordered logistic models, while analyses on changes in cognition over time used multivariable repeated-measures mixed-effects models. Compared to the unexposed, those in the highest exposure group (≥0.161 ng/ml) were more likely to have cognitive impairment (MMSE<24) (odds ratio [OR]:1.64; 95% confidence interval [CI]:1.04-2.60) and lower DSBT scores (OR:1.25; 95%CI:1.00-1.57), as well as a non-significant higher odds of a lower score in the Luria test (OR:1.23; 95%CI:0.92-1.64) or episodic memory impairment (FCSRT<12, OR:1.38; 95%CI:0.90-2.11). In longitudinal analyses, those with baseline cotinine ≥0.161 ng/ml showed an increased risk of cognitive impairment (MMSE<24,OR:2.23; 95%CI:1.14-4.33; p-trend across cotinine categories = 0.028) and decreased DSBT (OR:1.23; 95%CI:1.01-1.51; p-trend across cotinine categories = 0.046). Findings show an increased risk of global cognitive impairment and declines in working memory performance in older adults exposed to SHS. More efforts are needed to protect older adults from SHS in areas not covered by smoke-free legislation.

Cadmium exposure and growth differentiation factor-15 (GDF-15) levels in non-smoking older adults.

BACKGROUND: Cadmium (Cd) exposure is a risk factor for cardiovascular disease (CVD); however, understanding the effects of Cd at the cellular level remains incomplete. Since growth differentiation factor-15 (GDF-15) is a cytokine produced in many cell types in response to tissue injury and inflammation that may capture several pathways between Cd and CVD, this study examined the relationship between blood Cd levels and serum GDF-15 concentrations in community-dwelling older adults. METHODS: Cd and GDF-15 were measured in 1942 non-smoking individuals aged 65+ with no previous history of CVD. The association of Cd with GDF-15 was evaluated in linear regression models that adjusted for sociodemographic, lifestyle and biological risk factors, inflammatory biomarkers (IL-6, C-reactive protein and neutrophil to lymphocyte ratio), and markers of vascular damage (NTproBNP and cTnT-hs). RESULTS: Geometric mean Cd exposure was 0.11 µg/L (0.09 in never- and 0.15 in former-smokers) and geometric mean GDF-15 was 1186.21 pg/mL (1182.67 in never- and 1191.66 in former-smokers). In multivariable analyses, we found a dose-response association between Cd levels and GDF-15: adjusted mean percentage differences in GDF-15 (95% confidence interval) per 2-fold increase in Cd concentrations in the overall non-smoking population and in never smokers were, respectively, 2.54% (1.01, 4.06) and 2.50% (0.47, 4.54). In spline regression, the dose-response relationship was progressive over the range of Cd concentrations with no significant departures from linearity. CONCLUSIONS: Cd exposure may be related to enhanced GDF-15 expression. Future studies with repeated GDF-15 measurements should confirm the present findings to better understand the biological mechanisms underlying this association.

Home and ambulatory blood pressure levels below target range and clinical effort to detect this condition: a population-based study in older treated hypertensives.

BACKGROUND: With implementation of stricter blood pressure (BP) treatment targets, potential for excessive BP lowering becomes an important issue, especially in older patients. OBJECTIVES: Assess the magnitude, indicators and detection effort of BP levels below-target-range (BTR-BP) recommended by the European hypertension guidelines in older treated hypertensive patients (130-139/70-79 mmHg). DESIGN: Cross-sectional, retrospective study (Seniors-ENRICA-2 cohort). SETTING: General population. SUBJECTS: 1,329 treated hypertensive patients aged ≥65, assessed with three home casual BP measurements and 24-hour ambulatory BP monitoring (ABPM). METHODS: Based on the European hypertension guidelines and the literature, BTR-BPs were defined as mean BP <130/70, <125/65, <130/70 and <110/55 mmHg, for casual BP, 24-hour BP, daytime BP and nighttime BP, respectively, and hypotension as <110/70, <105/65, <110/70 and <90/55 mmHg, respectively. RESULTS: Participants' mean age was 72 ± 4.4 (50.3%, women). Based on casual BP, 7.2% of patients were in target range (130-139/70-79 mmHg), 44.3% in BTR-BP (<130/70) and 20.8% hypotensive (<110/70). Some 44.9, 54.9 and 22.0% of patients were in BTR-BP for 24-hour BP, daytime BP and nighttime BP, respectively, and 11.0, 21.1 and 5.6%, respectively, were hypotensive. The number of patients needed for ABPM to detect one case of 24-hour-, daytime-, and nighttime-BTR-BP was 3, 2 and 5, respectively, and 10, 5 and 18, respectively, for detecting one hypotensive case. Cardiovascular disease and female sex were associated with both BTR-BP and hypotension, and the number of antihypertensive drugs was only associated with hypotension. CONCLUSIONS: BTR-BP levels were common in older treated patients at home and in everyday life, more frequent than many trials report, and daytime ABPM is highly size-efficient for detecting the low ambulatory BP conditions.

The Southern European Atlantic Diet and all-cause mortality in older adults.

BACKGROUND: The Southern European Atlantic Diet (SEAD) is the traditional diet of Northern Portugal and North-Western Spain. Higher adherence to the SEAD has been associated with lower levels of some cardiovascular risk factors and reduced risk for myocardial infarction, but whether this translates into lower all-cause mortality is uncertain. We hence examined the association between adherence to the SEAD and all-cause mortality in older adults. METHODS: Data were taken from the Seniors-ENRICA-1 cohort, which included 3165 individuals representative of the non-institutionalized population aged ≥ 60 years in Spain. Food consumption was assessed with a validated diet history, and adherence to the SEAD was measured with an index comprising 9 food components: fresh fish, cod, red meat and pork products, dairy products, legumes and vegetables, vegetable soup, potatoes, whole-grain bread, and wine. Vital status was ascertained with the National Death Index of Spain. Statistical analyses were performed with Cox regression models and adjusted for the main confounders. RESULTS: During a median follow-up of 10.9 years, 646 deaths occurred. Higher adherence to the SEAD was associated with lower all-cause mortality (fully adjusted hazard ratio [95% confidence interval] per 1-SD increment in the SEAD score 0.86 [0.79, 0.94]; p-trend < 0.001). Most food components of the SEAD showed some tendency to lower all-cause mortality, especially moderate wine consumption (hazard ratio [95% confidence interval] 0.71 [0.59, 0.86]). The results were robust in several sensitivity analyses. The protective association between SEAD and all-cause death was of similar magnitude to that found for the Mediterranean Diet Adherence Screener (hazard ratio [95% confidence interval] per 1-SD increment 0.89 [0.80, 0.98]) and the Alternate Healthy Eating Index (0.83 [0.76, 0.92]). CONCLUSIONS: Adherence to the SEAD is associated with a lower risk of all-cause death among older adults in Spain.

Association between the Mediterranean lifestyle, metabolic syndrome and mortality: a whole-country cohort in Spain.

BACKGROUND: Evidence is limited about the joint health effects of the Mediterranean lifestyle on cardiometabolic health and mortality. The aim of this study was to evaluate the association of the Mediterranean lifestyle with the frequency of the metabolic syndrome (MS) and the risk of all-cause and cardiovascular mortality in Spain. METHODS: Data were taken from ENRICA study, a prospective cohort of 11,090 individuals aged 18+ years, representative of the population of Spain, who were free of cardiovascular disease (CVD) and diabetes at 2008-2010 and were followed-up to 2017. The Mediterranean lifestyle was assessed at baseline with the 27-item MEDLIFE index (with higher score representing better adherence). RESULTS: Compared to participants in the lowest quartile of MEDLIFE, those in the highest quartile had a multivariable-adjusted odds ratio 0.73 (95% confidence interval (CI) 0.5, 0.93) for MS, 0.63. (0.51, 0.80) for abdominal obesity, and 0.76 (0.63, 0.90) for low HDL-cholesterol. Similarly, a higher MELDIFE score was associated with lower HOMA-IR and highly-sensitivity C-reactive protein (P-trend < 0.001). During a mean follow-up of 8.7 years, 330 total deaths (74 CVD deaths) were ascertained. When comparing those in highest vs. lowest quartile of MEDLIFE, the multivariable-adjusted hazard ratio (95% CI) was 0.58 (0.37, 0.90) for total mortality and 0.33 (0.11, 1.02) for cardiovascular mortality. CONCLUSIONS: The Mediterranean lifestyle was associated with lower frequency of MS and reduced all-cause mortality in Spain. Future studies should determine if this also applies to other Mediterranean countries, and also improve cardiovascular health outside the Mediterranean basin.

Cross-sectional and prospective associations of sleep, sedentary and active behaviors with mental health in older people: a compositional data analysis from the Seniors-ENRICA-2 study.

BACKGROUND: Most studies on the effects of sleep, sedentary behavior (SB), and physical activity (PA) on mental health did not account for the intrinsically compositional nature of the time spent in several behaviors. Thus, we examined the cross-sectional and prospective associations of device-measured compositional time in sleep, SB, light PA (LPA) and moderate-to-vigorous PA (MVPA) with depression symptoms, loneliness, happiness, and global mental health in older people (≥ 65 years). METHODS: Data were taken from the Seniors-ENRICA-2 study, with assessments in 2015-2017 (wave 0) and 2018-2019 (wave 1). Time spent in sleep, SB, LPA and MVPA was assessed by wrist-worn accelerometers. Depression symptoms, loneliness, happiness, and global mental health were self-reported using validated questionnaires. Analyses were performed using a compositional data analysis (CoDA) paradigm and adjusted for potential confounders. RESULTS: In cross-sectional analyses at wave 0 (n = 2489), time-use composition as a whole was associated with depression and happiness (all p < 0.01). The time spent in MVPA relative to other behaviors was beneficially associated with depression (γ = -0.397, p < 0.001), loneliness (γ = -0.124, p = 0.017) and happiness (γ = 0.243, p < 0.001). Hypothetically, replacing 30-min of Sleep, SB or LPA with MVPA was beneficially cross-sectionally related with depression (effect size [ES] ranged -0.326 to -0.246), loneliness (ES ranged -0.118 to -0.073), and happiness (ES ranged 0.152 to 0.172). In prospective analyses (n = 1679), MVPA relative to other behaviors at baseline, was associated with favorable changes in global mental health (γ = 0.892, p = 0.049). We observed a beneficial prospective effect on global mental health when 30-min of sleep (ES = 0.521), SB (ES = 0.479) or LPA (ES = 0.755) were theoretically replaced for MVPA. CONCLUSIONS: MVPA was cross-sectionally related with reduced depression symptoms and loneliness and elevated level of happiness, and prospectively related with enhanced global mental health. Compositional isotemporal analyses showed that hypothetically replacing sleep, SB or LPA with MVPA could result in modest but significantly improvements on mental health indicators. Our findings add evidence to the emerging body of research on 24-h time-use and health using CoDA and suggest an integrated role of daily behaviors on mental health in older people.

The salivary proteome reflects some traits of dietary habits in diabetic and non-diabetic older adults.

PURPOSE: Objective markers of usual diet are of interest as alternative or validating tools in nutritional epidemiology research. The main purpose of the work was to assess whether saliva protein composition can reflect dietary habits in older adults, and how type 2 diabetes impacted on the saliva-diet correlates. METHODS: 214 participants were selected from 2 European cohorts of community-dwelling older adults (3C-Bordeaux and Seniors-ENRICA-2), using a case-control design nested in each cohort. Cases were individuals with type 2 diabetes. Dietary information was obtained using the Mediterranean Diet Adherence Screener (MEDAS). Saliva was successfully obtained from 211 subjects, and its proteome analyzed by liquid chromatography-tandem mass spectrometry. RESULTS: The relative abundance of 246 saliva proteins was obtained across all participants. The salivary proteome differed depending on the intake level of some food groups (especially vegetables, fruits, sweet snacks and red meat), in a diabetic status- and cohort-specific manner. Gene Set Enrichment Analysis suggested that some biological processes were consistently affected by diet across cohorts, for example enhanced platelet degranulation in high consumers of sweet snacks. Minimal models were then fitted to predict dietary variables by sociodemographic, clinical and salivary proteome variables. For the food group «sweet snacks¼, selected salivary proteins contributed to the predictive model and improved its performance in the Seniors-ENRICA-2 cohort and when both cohorts were combined. CONCLUSION: Saliva proteome composition of elderly individuals can reflect some aspects of dietary patterns.

Toxic metals in toenails as biomarkers of exposure: A review.

Toenails have been used as biomarkers of exposure to toxic metals, but their validity for this purpose is not yet clear and might differ depending on the specific agent. To evaluate this issue, we reviewed the literature on: a) the time-window of exposure reflected by toenails; b) the reproducibility of toenail toxic-metal levels in repeated measures over time; c) their relationship with other biomarkers of exposure, and; d) their association with potential determinants (i.e. sociodemographic, anthropometric, or lifestyle characteristics) or with sources of exposure like diet or environmental pollution. Thus, we performed a systematic review, searching for articles that provided original data for levels of any of the following toxic metals in toenails: aluminum, beryllium, cadmium, chromium, mercury, nickel, lead, thallium and uranium. We identified 88 articles, reporting data from 67 different research projects, which were quite heterogeneous with regard to population profile, sample size and analytical technique. The most commonly studied metal was mercury. Concerning the time-window of exposure explored by toenails, some reports indicate that toenail cadmium, nickel and lead may reflect exposures that occurred 7-12 months before sampling. For repeated samples obtained 1-6 years apart, the range of intraindividual correlation coefficients of aluminum, chromium and mercury was 0.33-0.56. The correlation of toxic metal concentrations between toenails and other matrices was higher for hair and fingernails than for urine or blood. Mercury levels were consistently associated with fish intake, while other toxic metals were occasionally associated with specific sources (e.g. drinking water, place of residence, environmental pollution, and occupation). The most frequently evaluated health endpoints were cardiovascular diseases, cancer, and central nervous system diseases. Available data suggest that toenail mercury levels reflected long-term exposures and showed positive associations with fish intake. The lack of standardization in sample collection, quality control, analytical techniques and procedures - along with the heterogeneity and conflicting results among studies - mean it is still difficult to conclude that toenails are a good biomarker of exposure to toxic metals. Further studies are needed to draw solid conclusions about the suitability of toenails as biomarkers of exposure to toxic metals.

Health Decline Is Associated with Reports of No Coffee Consumption Years After Reporting Coffee Consumption Among Older Adults in Spain.

BACKGROUND: Part of the health benefits of coffee reported in observational studies might be due to health status influencing coffee intake rather than the opposite. OBJECTIVE: We examined whether changes in health influenced subsequent reports of no coffee consumption in older adults. METHODS: Data came from 718 coffee drinkers aged ≥60 y recruited in the Seniors-Estudio de Nutrición y Salud Cardiovascular en España (ENRICA) cohort in 2008-2010 (wave 0) and followed-up in 2012 (wave 1), 2015 (wave 2), and 2017 (wave 3). Health status was measured with a 52-item deficit accumulation index (DAI) with 4 domains: functionality, self-rated health/vitality, mental health, and morbidity/health services use. Coffee intake was estimated with a validated diet history. We examined how changes in health status over a 3-y period (wave 0 to wave 1) influenced reports of no coffee consumption during the subsequent 5 y (wave 1 to wave 3) by using logistic regression models. RESULTS: Health deterioration over 3 y was associated with a higher frequency of reports of no regular coffee consumption during the subsequent 5 y (fully adjusted OR: 1.48 per 1-SD increment in DAI; 95% CI: 1.17-1.87). Deteriorating function (OR: 1.38 per 1-SD increment; 95% CI: 1.06-1.81) and mental health (OR: 1.34 per 1-SD increment; 95% CI: 1.04-1.73) were the DAI domains associated with increased reports of no regular coffee consumption. Also, individuals with worsened perceived health or hypertension onset were more likely to report no regular coffee consumption. No associations were found for decaffeinated coffee. CONCLUSIONS: Health deterioration was associated with reports of no regular coffee consumption years after reporting regular coffee consumption among older adults in Spain. A potential implication of this finding is that part of the beneficial effect of coffee consumption on health in observational studies might be due to reverse causation, which should be confirmed in future research.

Are legume-based recipes an appropriate source of nutrients for healthy ageing? A prospective cohort study.

Although legumes are rich in protein and fibre, and low in saturated fat and Na, traditional legume-based recipes include substantial amounts of processed meat, salt and potatoes, which could counteract the potential benefits of legumes. This prospective study aimed to assess the longitudinal association of consumption of different types of legumes, and traditional legume-based recipes, with unhealthy ageing in older adults. Data were taken from 2505 individuals aged ≥60 years from the Seniors-ENRICA cohort. Habitual legume consumption was assessed in 2008-2010 with a validated diet history. Unhealthy ageing was measured in the 2013, 2015 and 2017 follow-up waves, with a fifty-two-item multidimensional health deficit accumulation index (DAI) which ranges from 0 (best) to 100 (worst health). The mean age was 68·7 years, with 53·1 % of women. Among study participants, 78·4 % reported consumption of legumes, with a mean intake of 57·9 g/d. Multivariable-adjusted linear regression models did not show an association between total legume consumption and the DAI over a 7-year follow-up (non-standardised coefficient for the second and highest v. the lowest tertile of consumption: 0·94 (95 % CI -0·30, 2·17) and 0·18 (95 % CI -1·07, 1·43), respectively; Ptrend = 0·35). Similar results were observed for the 3-year and 5-year follow-ups and, separately, for lentils, beans, chickpeas and traditional legume-based recipes. According to the results obtained, consumption of legumes and traditional legume-based recipes is not associated with unhealthy ageing and can be part of a healthy diet in old age.

Physical activity less than the recommended amount may prevent the onset of major biological risk factors for cardiovascular disease: a cohort study of 198 919 adults.

OBJECTIVES: We examined the dose-response relationship between physical activity (PA) and incidence of cardiovascular disease (CVD) risk factors in adults in Taiwan. METHODS: This study included 1 98 919 participants, aged 18-97 years, free of CVD, cancer and diabetes at baseline (1997-2013), who were followed until 2016. At baseline, participants were classified into five PA levels: inactive' (0 metabolic equivalent of task (MET)-h/week), 'lower insufficiently active' (0.1-3.75 MET-h/week), 'upper insufficiently active' (3.75-7.49 MET-h/week), 'active' (7.5-14.99 MET-h/week) and 'highly active' (≥15 MET-h/week]. CVD risk factors were assessed at baseline and at follow-up by physical examination and laboratory tests. Analyses were performed with Cox regression and adjusted for the main confounders. RESULTS: During a mean follow-up of 6.0±4.5 years (range 0.5-19 years), 20 447 individuals developed obesity, 19 619 hypertension, 21 592 hypercholesterolaemia, 14 164 atherogenic dyslipidaemia, 24 275 metabolic syndrome and 8548 type 2 diabetes. Compared with inactive participants, those in the upper insufficiently active (but not active) category had a lower risk of obesity (HR 0.92; 95% CI 0.88 to 0.95), atherogenic dyslipidaemia (0.96; 0.90 to 0.99), metabolic syndrome (0.95; 0.92 to 0.99) and type 2 diabetes (0.91; 0.86 to 0.97). Only highly active individuals showed a lower incidence of CVD risk factors than their upper insufficiently active counterparts. CONCLUSION: Compared with being inactive, doing half the recommended amount of PA is associated with a lower incidence of several common biological CVD risk factors. Given these benefits, half the recommended amount of PA is an evidence based target for inactive adults.

[Therapeutic positioning reports: Experience in Spain during the period 2013-2019]. / Informes de posicionamiento terapéutico: experiencia en España en el periodo 2013-2019.

OBJECTIVE: Describe the characteristics of the therapeutic positioning reports (TPRs) published in Spain in the period 2013-2019. DESIGN AND DATA SOURCE: Systematic review of all TPRs published in the website of the Spanish Agency of Medicines and Health Products (AEMPS). SELECTION OF STUDIES: All TPRs published since May 2013, until March 2019 DATA EXTRACTION: The main variables collected were the therapeutic groups assessed, the number of TPRs, the time of elaboration, the existence of restrictions versus the authorized indications and the information on the efficiency of medicines. RESULTS: During the period under review, 214 TPRs were carried out, with an average production time of 8.8 months, almost three times the objective of 3-month initially set. 57% of the TPRs established restrictions of use with respect to the approved indications. 26% of TPRs referred to the existence of economic data, although none included details on the efficiency. 10% of TPRs were updated. CONCLUSIONS: For TPRs to meet their objective of improving the efficiency of the assessment process and the consistency in the decisions on price, reimbursement and financing of medicines by the SNS, the deadlines established for publication must be met, incorporating systematically information on the efficiency of the drugs and including periodic updates with the new information generated.

Toenails as biomarker of exposure to essential trace metals: A review.

Health problems associated with essential trace metals can result from both inadequate (i.e., low intake) and excessive exposures (i.e., from environmental and/or occupational source). Thus, measuring the exposure level is a real challenge for epidemiologists. Among non-invasive biomarkers that intend to measure long-term exposure to essential trace metals, the toenail is probably the biological matrix with the greatest potential. This systematic review collects the current evidence regarding the validity of toenail clippings as exposure biomarker for trace metals such as boron, cobalt, copper, iron, manganese, molybdenum, selenium, silicon, vanadium and zinc. Special attention was paid to the time-window of exposure reflected by the toenail, the intraindividual variability in exposure levels over time in this matrix, and the relationship of toenail with other biomarkers, personal characteristics and environmental sources. Our search identified 139 papers, with selenium and zinc being the most studied elements. The variability among studies suggests that toenail levels may reflect different degrees of exposure and probably correspond to exposures occurred 3-12 months before sampling (i.e., for manganese/selenium). Few studies assessed the reproducibility of results over time and, for samples obtained 1-6 years apart, the correlation coefficient were between 0.26 and 0.66. Trace metal levels in toenails did not correlate well with those in the blood and urine and showed low-moderate correlation with those in the hair and fingernails. Available data suggests that for some elements (Se, Mn, Zn) toenail concentrations reflect long-term external exposures in fairly reproducible levels, while for other metals, this association has not yet been assessed. Among dietary factors, only toenail selenium showed clear associations with the intake of supplements or specific foods. The toenail levels could also represent occupational exposure, for instance, Mn exposure in welders. The scarcity of information on other essential trace elements, together with the great heterogeneity among studies makes the validation of the usage of toenails as biomarkers of exposure to these elements difficult. Standardization of sample collection, quality control, analytical techniques and reporting procedures might facilitate further research focused on the clear understanding of the significance of essential levels in this promising matrix and would enhance its utility in epidemiological research.