Effect of lifestyle interventions on carotid arterial structure - The DR's EXTRA study.

No lifestyle-based interventions with medium-term duration on carotid atherosclerotic have been performed so far. We aimed to investigate whether guideline-based dietary and physical activity interventions slow the progression of atherosclerotic changes in the general elderly population. 1410 Finnish men and women from a representative population sample were randomly assigned to one of six groups in the four-year intervention study: 1) reference, 2) aerobic training, 3) resistance training, 4) Nordic Diet, 5) aerobic training + Nordic Diet, 6) resistance training + Nordic Diet. The primary outcome was mean common carotid artery intima-media thickness (cIMT). The lumen diameter of the common carotid artery (cLD) was also analyzed. 567 men and 565 women aged 57 to 78 years were included. None of the intervention groups significantly slowed cIMT progression compared to the reference group. A subgroup analysis showed that men in the diet group had significantly smaller cIMT progression than in the reference group (-0.078 mm, 95% CI: -0.146 to -0.009, p = 0.02) and no significant increase in cIMT (p = 0.23). No other group showed a slowed cIMT progression. Among guideline-based lifestyle interventions, only diet leads to a significantly smaller progression of cIMT in older men of a representative population sample. No other lifestyle intervention contributed to a slowing of the progression of structural carotid markers. It must be questioned whether the guideline-based recommendations for a lifestyle change that were in place until recently are adequate to decelerate the atherosclerotic process.

Adherence to Life's simple 7 is associated with better carotid properties.

BACKGROUND AND AIMS: Cardiovascular health scores have emerged as a simple way to assess the risk to suffer from a cardiovascular disease. The American Heart Association's Life's Simple 7 constitutes of modifiable lifestyle factors to reduce cardiovascular risk. Its association with carotid properties is yet inconclusive. The aim of this study is to determine the association between the adherence to Life's Simple 7 and carotid properties in middle-aged to elderly Finns. METHODS: A representative sample of Finnish men and women aged 55-74 years was included in the present study. Carotid intima-media thickness (cIMT), lumen diameter (cLD), and carotid distensibility were measured by transcutaneous ultrasound using state-of-the-art wall contour detection techniques. The Life's Simple 7 cardiovascular health score was calculated using seven categories (body mass index, cholesterol, systolic blood pressure, fasting plasma glucose, smoking status, physical activity, and diet). In accordance to the American Heart Association, for each category, an ideal score was given 2 points, intermediate scores 1 point, and poor scores 0 points. RESULTS: In total, 1400 (49.4% male) subjects were included in the analyses. After adjusting for age and sex, we found that subjects with a an ideal cardiovascular health score had lower cLD than those with an intermediate score (-0.21 mm, 95% CI: 0.37 to -0.05 mm, p=0.005) and a poor score (-0.39 mm, 95% CI: 0.65 to -0.12 mm, p=0.001). Similarly, subjects with an ideal health score had higher carotid distensibility than those with an intermediate score (0.0032 1/kPa, 95% CI: 0.009-0.0055 1/kPa, p=0.002) and a poor score (0.0018 1/kPa, 95% CI: 0.0005-0.0032 1/kPa, p=0.004). We found no differences regarding cIMT. CONCLUSIONS: In middle-aged to elderly Finns, higher adherence to the Life's Simple 7 is associated with lower cLD and higher distensibility, but not with cIMT. Adherence to healthy lifestyle habits is therefore associated with better carotid structure and carotid function in middle-aged to elderly Finns.

Exercise, diet, and cognition in a 4-year randomized controlled trial: Dose-Responses to Exercise Training (DR's EXTRA).

BACKGROUND: Evidence for the effects of exercise and dietary interventions on cognition from long-term randomized controlled trials (RCTs) in large general populations remains insufficient. OBJECTIVE: The objective of our study was to investigate the independent and combined effects of resistance and aerobic exercise and dietary interventions on cognition in a population sample of middle-aged and older individuals. METHODS: We conducted a 4-y RCT in 1401 men and women aged 57-78 y at baseline. The participants were randomly assigned to the resistance exercise, aerobic exercise, diet, combined resistance exercise and diet, combined aerobic exercise and diet, or control group. Exercise goals were at least moderate-intensity resistance exercise ≥2 times/wk and at least moderate-intensity aerobic exercise ≥5 times/wk. Dietary goals were ≥400 g/d of vegetables, fruit, and berries; ≥2 servings of fish/wk; ≥14 g fiber/1000 kcal; and ≤10% of energy of daily energy intake from SFAs. The primary outcome was the change in global cognition measured by the total score of the Consortium to Establish a Registry for Alzheimer's Disease (CERAD) neuropsychological tests [CERAD total score (CERAD-TS)]. The data were analyzed using the intention-to-treat principle and linear mixed-effects models. RESULTS: There was a trend toward improved CERAD-TS over 4 y in the combined aerobic exercise and diet group compared with the control group (net increase: 1.4 points; 95% CI: 0.1, 2.7; P = 0.06) adjusted for age, sex, years of education, symptoms of depression, and waist circumference at baseline. No other differences in CERAD-TS changes were found across the 6 study groups. Diet did not potentiate the effect of aerobic or resistance exercise on CERAD-TS. CONCLUSIONS: A combination of at least moderate-intensity aerobic exercise and a healthy diet may improve cognition in older individuals over 4 y, but there was no effect of either of these interventions alone, resistance training alone, or resistance exercise with a healthy diet on cognition.

Cardiorespiratory Fitness and Cognition: Longitudinal Associations in the FINGER Study.

BACKGROUND: Previous studies have found positive associations between cardiorespiratory fitness (CRF) and cognitive performance in older people but data are inconsistent and have methodological limitations. OBJECTIVE: Our aim was to study the longitudinal associations of CRF with executive functions, processing speed and memory as well as with the overall cognitive function in older people at risk for cognitive impairment. METHODS: Participants (n = 421), mean age 69.0, were a sub-sample of The Finnish Geriatric Intervention Study to Prevent Cognitive Impairment and Disability (FINGER). To be eligible, individuals were required to be 60-77 years old with a CAIDE (Cardiovascular Risk Factors, Aging and Dementia) Dementia Risk Score of at least 6 points and cognition at mean level or slightly lower than expected for age. CRF was assessed as peak oxygen uptake (VO2peak, L/min) measured directly in a symptom-limited maximal exercise test on cycle ergometer at baseline and at 24 months. Cognitive performance was assessed using an extensive neuropsychological test battery (NTB) at baseline and at 24 months. NTB data were standardized to Z scores, and analyzed with the linear mixed model. RESULTS: Over two years, VO2peak was associated with NTB total score (ß= 0.12, p = 0.01), executive functions (ß= 0.16, p = 0.01), and processing speed (ß= 0.25, p < 0.001), but not with memory (ß= 0.11, p = 0.12). CONCLUSION: Over two years follow-up, CRF was associated with executive functions and processing speed, and was related also to the overall cognitive function.

Multiancestry Genome-Wide Association Study of Lipid Levels Incorporating Gene-Alcohol Interactions.

A person's lipid profile is influenced by genetic variants and alcohol consumption, but the contribution of interactions between these exposures has not been studied. We therefore incorporated gene-alcohol interactions into a multiancestry genome-wide association study of levels of high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, and triglycerides. We included 45 studies in stage 1 (genome-wide discovery) and 66 studies in stage 2 (focused follow-up), for a total of 394,584 individuals from 5 ancestry groups. Analyses covered the period July 2014-November 2017. Genetic main effects and interaction effects were jointly assessed by means of a 2-degrees-of-freedom (df) test, and a 1-df test was used to assess the interaction effects alone. Variants at 495 loci were at least suggestively associated (P < 1 × 10-6) with lipid levels in stage 1 and were evaluated in stage 2, followed by combined analyses of stage 1 and stage 2. In the combined analysis of stages 1 and 2, a total of 147 independent loci were associated with lipid levels at P < 5 × 10-8 using 2-df tests, of which 18 were novel. No genome-wide-significant associations were found testing the interaction effect alone. The novel loci included several genes (proprotein convertase subtilisin/kexin type 5 (PCSK5), vascular endothelial growth factor B (VEGFB), and apolipoprotein B mRNA editing enzyme, catalytic polypeptide 1 (APOBEC1) complementation factor (A1CF)) that have a putative role in lipid metabolism on the basis of existing evidence from cellular and experimental models.

Novel genetic associations for blood pressure identified via gene-alcohol interaction in up to 570K individuals across multiple ancestries.

Heavy alcohol consumption is an established risk factor for hypertension; the mechanism by which alcohol consumption impact blood pressure (BP) regulation remains unknown. We hypothesized that a genome-wide association study accounting for gene-alcohol consumption interaction for BP might identify additional BP loci and contribute to the understanding of alcohol-related BP regulation. We conducted a large two-stage investigation incorporating joint testing of main genetic effects and single nucleotide variant (SNV)-alcohol consumption interactions. In Stage 1, genome-wide discovery meta-analyses in ≈131K individuals across several ancestry groups yielded 3,514 SNVs (245 loci) with suggestive evidence of association (P < 1.0 x 10-5). In Stage 2, these SNVs were tested for independent external replication in ≈440K individuals across multiple ancestries. We identified and replicated (at Bonferroni correction threshold) five novel BP loci (380 SNVs in 21 genes) and 49 previously reported BP loci (2,159 SNVs in 109 genes) in European ancestry, and in multi-ancestry meta-analyses (P < 5.0 x 10-8). For African ancestry samples, we detected 18 potentially novel BP loci (P < 5.0 x 10-8) in Stage 1 that warrant further replication. Additionally, correlated meta-analysis identified eight novel BP loci (11 genes). Several genes in these loci (e.g., PINX1, GATA4, BLK, FTO and GABBR2) have been previously reported to be associated with alcohol consumption. These findings provide insights into the role of alcohol consumption in the genetic architecture of hypertension.

Genome-wide meta-analysis of 241,258 adults accounting for smoking behaviour identifies novel loci for obesity traits.

Few genome-wide association studies (GWAS) account for environmental exposures, like smoking, potentially impacting the overall trait variance when investigating the genetic contribution to obesity-related traits. Here, we use GWAS data from 51,080 current smokers and 190,178 nonsmokers (87% European descent) to identify loci influencing BMI and central adiposity, measured as waist circumference and waist-to-hip ratio both adjusted for BMI. We identify 23 novel genetic loci, and 9 loci with convincing evidence of gene-smoking interaction (GxSMK) on obesity-related traits. We show consistent direction of effect for all identified loci and significance for 18 novel and for 5 interaction loci in an independent study sample. These loci highlight novel biological functions, including response to oxidative stress, addictive behaviour, and regulatory functions emphasizing the importance of accounting for environment in genetic analyses. Our results suggest that tobacco smoking may alter the genetic susceptibility to overall adiposity and body fat distribution.

Cardiorespiratory fitness and brain volumes in men and women in the FINGER study.

Background: high cardiorespiratory fitness (CRF) is associated with larger brain volumes but data on sex differences in the association of CRF with brain volumes are scarce. We investigated whether the association of CRF with total grey matter (GM) and white matter volumes as well as medial temporal lobe and striatum volumes is different between men and women at increased risk for Alzheimer's disease (AD). Methods: we used baseline data from The Finnish Geriatric Intervention Study to Prevent Cognitive Impairment and Disability (FINGER) in which the inclusion criteria were set to select individuals with cognitive performance at the mean level or slightly lower than expected for age according to Finnish population norms. Our sub-study included 39 randomly selected men and 29 women aged 61-75 years. CRF was assessed as peak oxygen consumption (VO2peak) measured in a maximal exercise test on cycle ergometer. Brain structural imaging was performed using a 1.5-T scanner. Results: in men, VO2peak was associated with cortical GM volume (ß = 0.56, P = 0.001) and total GM volume (ß = 0.54, P = 0.001). In women, no associations were found between VO2peak and brain volumes. VO2peak accounted for 23% and 1% of total variance of cortical GM volume as well as 25% and 4% of total variance of total GM volume in men and women, respectively. Conclusion: CRF is associated with cortical GM and total GM volumes in elderly men at increased risk for AD, but not in women.

[Update on Current Care Guideline: Physical activity and exercise training for adults in sickness and in health]. / KÄYPÄ HOITO -SUOSITUS (Päivitystiivistelmä). Liikunta.

The purpose of the guideline is to promote physical activity in the prevention, treatment and rehabilitation of diseases. Physical activity plays a key role in the management of several chronic noncommunicable diseases. In this guideline, the following diseases are discussed: endocrinological, cardiovascular, musculoskeletal and respiratory diseases, as well as depression and cancer. In addition, physical activity during pregnancy and in senior citizens is reviewed. Exercise counseling should be included as part of disease management and lifestyle guidance.

[Physical activity of the elderly - what kind of and what for?]. / Ikääntyneiden liikunta - minkölaista ja mihin tarkoitukseen?

Starting to exercise is beneficial even at an older age. Versatile exercise improving the condition of the respiratory and circulatory system, muscle strength and mobility is effective for maintaining functional capacity, especially among those having an already impaired mobility and functional capacity. Physical exercise can slow down the progress of bone loss, and intense exercise may even serve to increase the bone density in an elderly person. The main focus of physical activity aiming at the prevention of failings and fractures is in training that improves balance and muscular strength in the lower extremities. Endurance exercise and strength training seem to diminish the impairment of cognitive functions.

The Nordic diet and cognition--The DR's EXTRA Study.

The rapid increase in the prevalence of dementia associated with ageing populations has stimulated interest in identifying modifiable lifestyle factors that could prevent cognitive impairment. One such potential preventive lifestyle factor is the Nordic diet that has been shown to reduce the risk of CVD; however, its effect on cognition has not been studied. The aim of the present study was to estimate the cross-sectional and longitudinal associations of the baseline Nordic diet with cognitive function at baseline and after a 4-year follow-up in a population-based random sample (n 1140 women and men, age 57-78 years) as secondary analyses of the Finnish Dose-Responses to Exercise Training study. The Nordic diet score was created based on reported dietary components in 4-d food records. Cognition was assessed by the Consortium to Establish a Registry for Alzheimer's Disease (CERAD) neuropsychological battery and the Mini-mental State Examination (MMSE). The baseline Nordic diet score had been positively associated with Verbal Fluency (ß 0.08 (95% CI 0.00, 0.16), P = 0.039) and Word List Learning (ß 0.06 (95% CI 0.01, 0.10), P = 0.022) at 4 years but not with the Consortium to Establish a Registry for Alzheimer's Disease total score (CERAD-TS) or MMSE at 4 years, after adjustment for baseline cognitive scores, demographic factors and health-related factors. After excluding individuals with impaired cognition at baseline, the baseline Nordic diet score had also been positively associated with the CERAD-TS (ß 0.10 (95% CI 0.00, 0.20), P = 0.042) and MMSE (ß 0.03 (95% CI 0.00, 0.06), P = 0.039) at 4 years. These associations disappeared after further adjustment for energy intake. In conclusion, the Nordic diet might have a positive association with cognition in individuals with normal cognition.

Moderators of Maintained Increase in Aerobic Exercise Among Aging Men and Women in a 4-Year Randomized Controlled Trial: The DR's EXTRA Study.

BACKGROUND: Little is known about factors that modify the effectiveness of exercise interventions in increasing exercise. We aimed to identify moderators of the effectiveness of aerobic exercise intervention in maintaining increased aerobic exercise among older individuals. METHODS: The participants of a 4-year randomized controlled trial were a population sample of 1410 men and women aged 57 to 78 years. The aerobic exercise group included 185 individuals and the control group included 169 individuals who reported low aerobic exercise at baseline. Maintained increase in aerobic exercise was defined as at least 60-minute increase in moderate-to-heavy aerobic exercise per week from baseline to 2- and 4-year assessments. RESULTS: Individuals in the aerobic exercise group were 2.5 (95% CI 1.5 to 3.9) times more likely to maintain increased aerobic exercise than those in the control group. Individuals aged < 68.5 years but not older individuals succeeded in maintaining increased aerobic exercise in the intervention group (P = .02 for interaction). Individuals who were past smokers (P = .02 for interaction), were working (P = .05 for interaction), or had symptoms of depression (P = .05 for interaction) succeeded better in maintaining increased aerobic exercise in the intervention group than other individuals. CONCLUSIONS: These findings help in more precise targeting of future exercise interventions among older individuals.

Cardiopulmonary fitness is a function of lean mass, not total body weight: The DR's EXTRA study.

BACKGROUND: Division by total body weight is the usual way to standardise peak oxygen uptake (peak VO2) for body size. However, this method systematically underestimates cardiopulmonary fitness in obese individuals. Our aim was to analyse whether lean-mass is a better base for a body mass-independent standard of cardiopulmonary fitness. METHODS: A population based sample of 578 men (body mass index (BMI) 19-47 kg/m(2)) and 592 women (BMI 16-49 kg/m(2)) 57-78 years of age. Peak VO2 was assessed by respiratory gas analysis during a maximal exercise test on a cycle ergometer. We studied the validity of the weight-ratio and the lean mass-ratio standards in a linear regression model. RESULTS: The weight-ratio standard implies an increase of peak VO2 per additional kg body weight with 20.7 ml/min (95% confidence interval (CI): 20.3-21.1) in women and 26.9 ml/min (95% CI: 26.4-27.5) in men. The observed increase per kg is only 8.5 ml/min (95% CI: 6.5-10.5) in men and 10.4 ml/min (95% CI: 7.5-13.4) in women. For the lean mass-ratio standard expected and observed increases in peak VO2 per kg lean mass were 32.3 (95% CI: 31.8-32.9) and 34.6 (95% CI: 30.0-39.1) ml/min for women and 36.2 (95% CI: 35.6-36.8) and 37.3 (95% CI: 32.1-42.4) ml/min in men. The lean mass-ratio standard is a body mass-independent measure of cardiopulmonary fitness in 100% of women and 58% of men; corresponding values for the weight-ratio standard were 11% and 16%. CONCLUSIONS: For comparisons of cardiopulmonary fitness across different categories of body mass, the lean mass-ratio standard should be used.

Validation of metabolic syndrome score by confirmatory factor analysis in children and adults and prediction of cardiometabolic outcomes in adults.

AIMS/HYPOTHESIS: We validated the metabolic syndrome (MetS) score by confirmatory factor analysis (CFA) in children, middle-aged men, and older women and men and by investigating the relationships of the MetS score to incident type 2 diabetes, myocardial infarction, and cardiovascular and overall death in middle-aged men. METHODS: We assessed the core features of MetS, calculated the MetS score using z scores for waist circumference, insulin, glucose, triacylglycerols, HDL-cholesterol and blood pressure, and carried out CFA to investigate whether MetS represents a single entity in population samples of 491 children, 1,900 middle-aged men, 614 older women and 555 older men from Finland. We also followed-up incident type 2 diabetes for 11 years and other outcomes for 17-18 years in middle-aged men. RESULTS: We carried out second-order CFAs in which the MetS was represented by a second-order latent variable underlying four latent variables characterised by abdominal obesity, insulin resistance, dyslipidaemia and raised blood pressure in different age groups. These second-order factors and factors derived from first-order CFA using previously proposed models were strongly associated with a composite MetS score in all age groups (r = 0.84-0.94) and similarly predicted type 2 diabetes, cardiovascular outcomes and mortality in middle-aged men. The risk of type 2 diabetes, myocardial infarction, cardiovascular death and overall death increased 3.67-, 1.38-, 1.56- and 1.44-fold, respectively, for a 1 SD increase in the MetS score. CONCLUSIONS: The MetS can be described as a single entity in all age groups. The MetS score is a valid tool for research evaluating cardiometabolic risk in different age groups. Further research is needed to define cut-off points for risk estimation in clinical practice.

Trans-ethnic fine-mapping of lipid loci identifies population-specific signals and allelic heterogeneity that increases the trait variance explained.

Genome-wide association studies (GWAS) have identified ~100 loci associated with blood lipid levels, but much of the trait heritability remains unexplained, and at most loci the identities of the trait-influencing variants remain unknown. We conducted a trans-ethnic fine-mapping study at 18, 22, and 18 GWAS loci on the Metabochip for their association with triglycerides (TG), high-density lipoprotein cholesterol (HDL-C), and low-density lipoprotein cholesterol (LDL-C), respectively, in individuals of African American (n = 6,832), East Asian (n = 9,449), and European (n = 10,829) ancestry. We aimed to identify the variants with strongest association at each locus, identify additional and population-specific signals, refine association signals, and assess the relative significance of previously described functional variants. Among the 58 loci, 33 exhibited evidence of association at P<1 × 10(-4) in at least one ancestry group. Sequential conditional analyses revealed that ten, nine, and four loci in African Americans, Europeans, and East Asians, respectively, exhibited two or more signals. At these loci, accounting for all signals led to a 1.3- to 1.8-fold increase in the explained phenotypic variance compared to the strongest signals. Distinct signals across ancestry groups were identified at PCSK9 and APOA5. Trans-ethnic analyses narrowed the signals to smaller sets of variants at GCKR, PPP1R3B, ABO, LCAT, and ABCA1. Of 27 variants reported previously to have functional effects, 74% exhibited the strongest association at the respective signal. In conclusion, trans-ethnic high-density genotyping and analysis confirm the presence of allelic heterogeneity, allow the identification of population-specific variants, and limit the number of candidate SNPs for functional studies.

The impact of time cost of physical exercise on health outcomes by older adults: the DR's EXTRA Study.

When the motivation for exercise is high and people are retired, the cost of time used for physical exercise may be lower and individuals may exercise more compared to individuals with a low motivational level and in working life. The aim was to study the effect of time cost of physical exercise on the amount of physical exercise and on health-related quality of life. We used 2-year data (n = 1,292) from a 4-year randomised controlled trial in a population-based sample of Eastern Finnish men and women, 57-78 years of age at baseline, in 2005-2006. In the statistical analysis, physical exercise and health outcomes were assumed to be endogenous variables explained with a set of exogenous variables. The statistical modelling was done by panel data instrumental variable regressions. Health-related quality of life was evaluated by the RAND 36-item survey and motives for exercise with a questionnaire. Joy as the motivation for physical exercise and retirement increased the amount of physical exercise per week (p < 0.001). A higher amount of exercise was associated with physical (p < 0.001) and mental (p < 0.001) components of quality of life. Moreover, a higher amount of physical exercise decreased the metabolic risk factor score (p < 0.001). The motivation and extra time, i.e. retirement, have a significant impact on the time spent on physical exercise (p < 0.001). Our data agree with the theory that high motivation and retirement lower the time cost of physical exercise. The results emphasise that motivation and the labour market position are important in determining the cost of physical exercise.

Age, marital status and changes in dietary habits in later life: a 21-year follow-up among Finnish women.

OBJECTIVE: To examine 21-year longitudinal changes in dietary habits and their associations with age and marital status among women aged 50-60 years at baseline. DESIGN: Prospective, longitudinal study of a cohort in the FINMONICA population-based risk factor survey with clinical assessments in 1982, 1992 and 2003. Dietary habits were assessed via self-reported consumption of foods typically contributing to SFA, cholesterol and sugar intakes in the Finnish diet. A dietary risk score based upon five items was used. SETTING: Kuopio region, Finland. SUBJECTS: Complete data from all three assessments for 103 women of the original cohort of 299 were included for two age groups: 50-54 and 55-60 years at baseline. RESULTS: Dietary habits improved between 1982 and 1992 and showed continued but less pronounced improvement between 1992 and 2003: within the younger age group, 78 % of the women reduced the number of dietary risk points from the 1982 to 2003 scores, whereas 3 % increased them and 19 % reported no change. In the older age group these percentages were 61 %, 23 % and 16 %, respectively. Women who remained married showed a steadier decline in dietary risk points than single women or women who were widows at the beginning of the follow-up. CONCLUSIONS: Older women make positive changes to their dietary habits but the consistency of these changes may be affected by the ageing process, marital status and changes in the latter.

Cardiorespiratory fitness and metabolic syndrome in older men and women: the dose responses to Exercise Training (DR's EXTRA) study.

OBJECTIVE: We studied the association of maximum oxygen uptake (Vo(2max)) with the development and resolution of metabolic syndrome (MetS) for 2 years in older individuals. RESEARCH DESIGN AND METHODS: Subjects were a population sample of 1,226 men and women aged 57-78 years. We assessed Vo(2max) directly by respiratory gas analysis during maximum exercise testing and used dichotomous and continuous variables for MetS. RESULTS: One SD increase in baseline Vo(2max) associated with 44% (95% CI 24-58) decreased risk of developing MetS. Individuals in the highest third of baseline Vo(2max) were 68% (37-84) less likely to develop MetS than those in the lowest third. One SD increase in Vo(2max) increased the likelihood to resolve MetS 1.8 (1.2-2.8) times. Individuals in the highest Vo(2max) third were 3.9 (1.5-9.9) times more likely to resolve MetS than those in the lowest third. CONCLUSIONS: Higher levels of cardiorespiratory fitness protect against MetS and may resolve it in older individuals.