Biomarkers for personalised prevention of chronic diseases: a common protocol for three rapid scoping reviews.

INTRODUCTION: Personalised prevention aims to delay or avoid disease occurrence, progression, and recurrence of disease through the adoption of targeted interventions that consider the individual biological, including genetic data, environmental and behavioural characteristics, as well as the socio-cultural context. This protocol summarises the main features of a rapid scoping review to show the research landscape on biomarkers or a combination of biomarkers that may help to better identify subgroups of individuals with different risks of developing specific diseases in which specific preventive strategies could have an impact on clinical outcomes. This review is part of the "Personalised Prevention Roadmap for the future HEalThcare" (PROPHET) project, which seeks to highlight the gaps in current personalised preventive approaches, in order to develop a Strategic Research and Innovation Agenda for the European Union. OBJECTIVE: To systematically map and review the evidence of biomarkers that are available or under development in cancer, cardiovascular and neurodegenerative diseases that are or can be used for personalised prevention in the general population, in clinical or public health settings. METHODS: Three rapid scoping reviews are being conducted in parallel (February-June 2023), based on a common framework with some adjustments to suit each specific condition (cancer, cardiovascular or neurodegenerative diseases). Medline and Embase will be searched to identify publications between 2020 and 2023. To shorten the time frames, 10% of the papers will undergo screening by two reviewers and only English-language papers will be considered. The following information will be extracted by two reviewers from all the publications selected for inclusion: source type, citation details, country, inclusion/exclusion criteria (population, concept, context, type of evidence source), study methods, and key findings relevant to the review question/s. The selection criteria and the extraction sheet will be pre-tested. Relevant biomarkers for risk prediction and stratification will be recorded. Results will be presented graphically using an evidence map. INCLUSION CRITERIA: Population: general adult populations or adults from specific pre-defined high-risk subgroups; concept: all studies focusing on molecular, cellular, physiological, or imaging biomarkers used for individualised primary or secondary prevention of the diseases of interest; context: clinical or public health settings. SYSTEMATIC REVIEW REGISTRATION: https://doi.org/10.17605/OSF.IO/7JRWD (OSF registration DOI).

Nut Consumption and Depression: Cross-Sectional and Longitudinal Analyses in Two Cohorts of Older Adults.

OBJECTIVES: To assess the cross-sectional and longitudinal associations between nut consumption and depression in two cohorts of older adults. DESIGN, SETTING, PARTICIPANTS AND MEASUREMENTS: The first cohort (Seniors-ENRICA-I or SE-I) included a representative sample of Spanish noninstitutionalized adults aged ≥65 years interviewed in 2010 and 2013. The second cohort (SE-II) included individuals from the Madrid region, Spain, aged ≥65 years interviewed in 2017 and in 2019. Nut consumption was estimated with a validated computer-based diet history. Depression was defined as self-reported physician-diagnosed depression or the use of antidepressants. Logistic regression models were adjusted for the main confounders. The DerSimonian and Laird random-effect method was used to meta-analyze the results from both studies. A participant-level pooled analysis was conducted to examine the robustness of our analyses. RESULTS: The SE-I included 2278 individuals (233 prevalent cases) in the cross-sectional analysis and 1534 (108 incident cases) in the longitudinal analysis; the corresponding figures for SE-II were 2726 (407 prevalent cases) and 1566 (74 incident cases). In the meta-analysis of cross-sectional results from the two studies, compared to consuming <1 serving (30 g) of nuts/week, the odds ratio (95% confidence interval) for depression was 0.90 (0.64, 1.16) for consuming 1 to <3 servings/week and 0.92 (0.70, 1.13) for consuming ≥3 servings/week; the corresponding figures for the longitudinal results were 0.90 (0.41, 1.38) and 0.66 (0.35, 0.97). CONCLUSION: Nut consumption was associated with a lower risk of depression in a pooled longitudinal analysis using data from two cohorts of older adults. Nuts should be recommended as part of a healthy diet in older adults.

Association of blood manganese concentrations with 24-h based brachial and central blood pressure, and pulse-wave velocity.

Potential environmental determinants of BP and hypertension in older adults are far less known than their lifestyle risk factors. Manganese (Mn) is an essential element for life that may induce changes in blood pressure (BP), but the direction of the association is unclear. We aimed to examine the association of blood manganese (bMn) with 24-h-based brachial, central BP (cBP), and pulse-wave velocity (PWV). With this purpose, we analyzed data from 1009 community-living adults aged >65 years without BP medication. bMn was measured using inductively-coupled plasma-mass spectrometry and 24-h BP with validated devices. The association of bMn (median: 6.77 µg/L; IQR: 5.59-8.27) with daytime brachial and central systolic (SBP) and with diastolic BP (DBP) was non-linear, with BP increases up to around the median of Mn and then stabilization or slight rightward decrease. Mean BP differences (95% confidence interval) comparing Mn Q2 to Q5 (vs Q1 quintile) for brachial daytime SBP were 2.56 (0.22; 4.90), 3.59 (1.22; 5.96), 3.14 (0.77; 5.51) and 1.72 (-0.68; 4.11) mmHg, respectively; and 2.22 (0.70, 3.73), 2.55 (1.01, 4.08), 2.45 (0.91; 3.98), and 1.68 (0.13; 3.24), respectively, for DBP. Daytime central-pressures showed a similar dose-response relationship with bMn as daytime brachial-pressures. The association with nighttime BP was linearly positive for brachial BPs, and only increasing for Q5 for cBP. Regarding PWV, a tendency to significant linear increase along bMn levels was observed (p-trend = 0.042). The present findings extend the scarce evidence on the association between Mn and brachial BP to 2 other vascular parameters, suggesting Mn levels as a candidate risk factor for increasing levels of both brachial and cBPs in older adults, yet further research is needed with larger cohort studies in adults at all age ranges.

Plant-Based Diets and All-cause and Cardiovascular Mortality in a Nationwide Cohort in Spain: The ENRICA Study.

OBJECTIVE: To investigate the associations of a healthful plant-based diet index (hPDI) and an unhealthful plant-based diet index (uPDI) with all-cause and cardiovascular disease (CVD) mortality in Spanish adults. PATIENTS AND METHODS: We analyzed data from 11,825 individuals 18 years of age or older, representative of the Spanish population, recruited between 2008 and 2010 and followed-up to 2020. Food consumption was collected at baseline using a validated dietary history, which served to calculate two plant-based diet indices based on 18 major food groups (range, 18-90 points). For (1) hPDI only the consumption of healthy plant foods (whole grains, fruits, vegetables, nuts, legumes, vegetable oils, and tea/coffee) received positive scores; whereas for (2) uPDI, only the consumption of less healthy plant foods (fruit juices, sugar-sweetened beverages, refined grains, potatoes, and sweets/desserts) received positive scores. Multivariable-adjusted Cox models were used to estimate HRs and their 95% CIs. RESULTS: After a median follow-up of 10.9 and 9.8 years, 699 all-cause and 157 CVD deaths were ascertained, respectively. Each 10-point increase in hPDI was associated with 14% lower risk of all-cause death (HR, 0.86; 95% CI, 0.74 to 0.99), and 37% lower risk of CVD death (HR, 0.63; 95% CI, 0.46 to 0.85). No significant associations were found for uPDI. CONCLUSION: Higher adherence to an hPDI diet, but not to a uPDI, was associated with lower all-cause and CVD mortality. This suggests that the quality of the plant food consumed is paramount to achieve diet-related benefits in mortality. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT02804672.

The Medium-Term Changes in Health-Related Behaviours among Spanish Older People Lifestyles during Covid-19 Lockdown.

OBJECTIVES: The aim was to evaluate general changes and investigate the association between diet quality, physical activity (PA), and sedentary time (ST) during COVID-19 lockdown and the subsequent 7-month changes in health-related behaviours and lifestyles in older people. PARTICIPANTS: 1092 participants (67-97y) from two Spanish cohorts were included. DESIGN: Telephone-based questionaries were used to evaluate health-related behaviours and lifestyle. Multinomial logistic regression analyses with diet quality, PA, and ST during lockdown as predictors for health-related behaviours changes post-lockdown were applied. RESULTS: Diet quality, PA, and ST significantly improved post-lockdown, while physical component score of the SF-12 worsened. Participants with a low diet quality during lockdown had higher worsening of post-lockdown ST and anxiety; whereas those with high diet quality showed less likelihood of remaining abstainers, worsening weight, and improving PA. Lower ST was associated with a higher likelihood of remaining abstainers, and worsening weight and improving social contact; nevertheless, higher ST was linked to improvement in sleep quality. Lower PA was more likely to decrease alcohol consumption, while higher PA showed the opposite. However, PA was more likely to be associated to remain abstainers. CONCLUSIONS: Despite improvements in lifestyle after lockdown, it had health consequences for older people. Particularly, lower ST during lockdown seemed to provide the most medium-term remarkable lifestyle improvements.

Selenium and impaired physical function in US and Spanish older adults.

BACKGROUND: Selenium (Se) is a trace element with a narrow safety margin. OBJECTIVES: To evaluate the cross-sectional and longitudinal dose-response association between Se exposure and measures of impaired physical function and disability in older adults. DESIGN: NHANES 2011-2014 cross-sectional (US, n = 1733, age ≥60 years) and Seniors-ENRICA-2 2017-2019 cross-sectional and longitudinal (Spain, n = 2548 and 1741, respectively, age ≥65 years) data were analyzed. Whole blood and serum Se levels were measured using inductively coupled plasma-mass spectrometry. Lower-extremity performance was assessed with the Short Physical Performance Battery, and muscle weakness with a dynamometer. Incident mobility and agility limitations, and disability in instrumental activities of daily living (IADL) were ascertained with standardized questionnaires. Analyses were adjusted for relevant confounders, including physical activity. Results across studies were pooled using random-effects meta-analysis. RESULTS: Meta-analyzed odds ratios (95% confidence interval) per log2 increase in whole blood Se were 0.54 (0.32; 0.76) for weakness, 0.59 (0.34; 0.83) for impaired lower-extremity performance, 0.48 (0.31; 0.68) for mobility limitations, 0.71 (0.45; 0.97) for agility limitations, and 0.34 (0.12; 0.56) for disability in at least one IADL. Analyses for serum Se in NHANES showed similar results. Findings suggest the inverse association with grip strength is progressive below 140 µg/L (p-value for non-linear trend in the Seniors-ENRICA-2 study = 0.13), and above 140 µg/L (p-value for non-linear trend in NHANES = 0.11). In the Seniors-ENRICA-2 cohort, with a 2.2 year follow-up period, a doubling in baseline Se levels were associated with a lower incidence of weakness [odds ratio (95% confidence interval): 0.45 (0.22; 0.91)], impaired lower-extremity performance [0.63 (0.32; 1.23)], mobility [0.43 (0.21; 0.91)] and agility [0.38 (0.18; 0.78)] limitations. DISCUSSION: In US and Spanish older adults, Se concentrations were inversely associated with physical function limitations. Further studies are needed to elucidate underlying mechanisms.

Cadmium exposure is associated with reduced grip strength in US adults.

BACKGROUND: Muscle strength is a strong predictor of all-cause mortality in the general population. Recent studies have shown an association between environmental pollution and declined grip strength. No previous research has evaluated the specific association between cadmium exposure, a well-known risk factor of several chronic diseases, and muscle strength. METHODS: Cross-sectional study among 4,197 individuals aged ≥40 years, who participated in the National Health and Nutrition Examination Survey (NHANES) 2011-2014, provided data on grip strength, and had either blood or urine cadmium determinations. Grip strength was measured using a Takei digital handgrip dynamometer, and combined grip strength was calculated as the sum of the largest reading from each hand. RESULTS: Median (interquartile range) concentrations of blood (BCd) and creatinine-corrected urine cadmium (Cr-UCd) were 0.32 µg/L (0.20-4.56) and 0.27 µg/g (0.15-0.46), respectively. After adjusting for sociodemographic, anthropometric, health-related behavioral, and clinical risk factors, and serum creatine phosphokinase concentrations, the highest (vs lowest) quartile of BCd was associated with a reduction in combined grip strength of 1.93 kg (95% confidence interval [CI]: -3.51, -0.34), p-trend <0.001. The corresponding values comparing Cr-UCd quartiles 4 vs 1 were -3.24 kg (95% CI: -5.68, -0.79), p-trend <0.001. These results were consistent across socio-demographic and clinical subgroups. CONCLUSIONS: In the US adult population, higher cadmium exposure was associated with decreased grip strength. These results may have important public health implications given the widespread cadmium exposure.

Patterns of alcohol consumption and risk of falls in older adults: a prospective cohort study.

Falls are a major health problem in older adults, but their relationship with alcohol consumption in this population remains unclear. In a cohort with 2170 older adults followed up for 3.3 years, both moderate drinking and the Mediterranean drinking pattern were associated with a lower risk of falls and injurious falls. INTRODUCTION: This study aims to examine the association between certain patterns of alcohol consumption, including the Mediterranean drinking pattern (MDP), and the risk of falls in older adults. METHODS: A prospective cohort with 2170 community-dwelling individuals aged ≥60 years was recruited in Spain in 2008-2010 and followed up through 2012. At baseline, participants reported alcohol consumption and, at the end of follow-up, their falls during the previous year. The MDP was defined as moderate alcohol consumption (threshold between moderate and heavy intake was 40 g/day for men and 24 g/day for women) with preference for wine and drinking only with meals. Analyses were conducted with negative binomial or logistic regression, as appropriate, and adjusted for the main confounders. RESULTS: Compared with never drinkers, the number of falls was lower in moderate drinkers (incidence rate ratio (95% confidence interval), 0.79 (0.63-0.99)) and drinkers with MDP (0.73 (0.56-0.96)). Also, moderate drinkers and those with MDP showed a lower risk of ≥2 falls (odds ratio (95% confidence interval), 0.58 (0.38-0.88) and 0.56 (0.34-0.93), respectively) and of falls requiring medical care (0.67 (0.46-0.96) and 0.61 (0.39-0.96), respectively). CONCLUSION: Both moderate drinking and the MDP were associated with a lower risk of falls and injurious falls in older adults. However, sound advice on alcohol consumption should balance risks and benefits.

Extracolonic Cancer in Inflammatory Bowel Disease: Data from the GETECCU Eneida Registry.

OBJECTIVES: The objective of this study was (a) To know the prevalence and distribution of extracolonic cancer (EC) in patients with inflammatory bowel disease (IBD); (b) To estimate the incidence rate of EC; (c) To evaluate the association between EC and treatment with immunosuppressants and anti-tumor necrosis factor (TNF) agents. METHODS: This was an observational cohort study. INCLUSION CRITERIA: IBD and inclusion in the ENEIDA Project (a prospectively maintained registry) from GETECCU. EXCLUSION CRITERIA: Patients with EC before the diagnosis of IBD, lack of relevant data for this study, and previous treatment with immunosuppressants other than corticosteroids, thiopurines, methotrexate, or anti-TNF agents. The Kaplan-Meier method was used to evaluate the impact of several variables on the risk of EC, and any differences between survival curves were evaluated using the log-rank test. Stepwise multivariate Cox regression analysis was used to investigate factors potentially associated with the development of EC, including drugs for the treatment of IBD, during follow-up. RESULTS: A total of 11,011 patients met the inclusion criteria and were followed for a median of 98 months. Forty-eight percent of patients (5,303) had been exposed to immunosuppressants or anti-TNF drugs, 45.8% had been exposed to thiopurines, 4.7% to methotrexate, and 21.6% to anti-TNF drugs. The prevalence of EC was 3.6%. In the multivariate analysis, age (HR=1.05, 95% CI=1.04-1.06) and having smoked (hazards ratio (HR)=1.47, 95% confidence interval (CI)=1.10-1.80) were the only variables associated with a higher risk of EC. CONCLUSIONS: Neither immunosuppressants nor anti-TNF drugs seem to increase the risk of EC. Older age and smoking were associated with a higher prevalence of EC.

Metabolically healthy obesity and health-related quality of life: A prospective cohort study.

BACKGROUND: Metabolically healthy obesity (MHO) has been associated with lower risk of diabetes than obesity with cardiometabolic abnormalities (CA). However, the effect of MHO on other health outcomes is unknown. OBJECTIVE: To examine the association of metabolic status across categories of body mass index (BMI) with health-related quality of life (HRQL). METHODS: Prospective cohort with 4397 individuals aged ≥18 years, recruited in 2008-2010 and followed-up to 2012 in Spain. Normal weight was defined as BMI <25, overweight as BMI 25-29.9, and obesity as BMI ≥30 kg/m2. Two metabolic statuses were defined: healthy (0-1 CA) and unhealthy (≥2 CA). HRQL was measured with the physical component summary (PCS) and the mental component summary (MCS) of the SF-12 questionnaire. The association of joint categories of BMI and metabolic status at baseline with HRQL at 2012 was examined using linear regression, and adjusted for the main confounders. RESULTS: Compared to healthy normal-weight subjects, the unhealthy normal-weight and the healthy overweight individuals had a similar PCS score; however, the PCS was lower (worse) among those with unhealthy overweight (-1.79; 95% confidence interval [CI]: -2.66 to -0.94), with MHO (-1.45; 95% CI: -2.67 to -0.24) and unhealthy obesity (-1.97; 95% CI: -2.88 to -1.05). Being overweight or obese was not associated with the MCS score regardless of metabolic status. CONCLUSION: Metabolically unhealthy overweight, as well as obesity regardless of metabolic status, showed a worse physical HRQL. These results suggest that both obesity and CA should be addressed to improve HRQL.