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1.  Associations between Active Commuting to School and Health-Related Physical Fitness in Spanish School-Aged Children: A Cross-Sectional Study 
Active commuting (walking or cycling) to school has been positively associated with improved fitness among adolescents. However, current evidence lacks information on whether this association persists in children. The aim of this study was to examine the association of active commuting to school with different fitness parameters in Spanish school-aged children. A total of 494 children (229 girls) from five primary schools in Granada and Jaén (Spain), aged between eight and 11 years, participated in this cross-sectional study. Participants completed the Assessing Levels of Physical Activity (ALPHA) fitness test battery and answered a self-reported questionnaire regarding the weekly travel mode to school. Active commuting to school was significantly associated with higher levels of speed-agility in boys (p = 0.048) and muscle strength of the lower body muscular fitness in girls (p = 0.016). However, there were no significant associations between active commuting to school and cardiorespiratory fitness and upper body muscular fitness. Our findings suggest that active commuting to school was associated with higher levels of both speed-agility and lower body muscular fitness in boys and girls, respectively. Future studies should confirm whether increasing active commuting to school increases speed-agility and muscle strength of the lower body.
PMCID: PMC4586616  PMID: 26322487
physical activity; active transportation; public health; strength
2.  Objectively measured sedentary time and physical activity in women with fibromyalgia: a cross-sectional study 
BMJ Open  2013;3(6):e002722.
To characterise levels of objectively measured sedentary time and physical activity in women with fibromyalgia.
Cross-sectional study.
Local Association of Fibromyalgia (Granada, Spain).
The study comprised 94 women with diagnosed fibromyalgia who did not have other severe somatic or psychiatric disorders, or other diseases that prevent physical loading, able to ambulate and to communicate and capable and willing to provide informed consent.
Primary outcome measures
Sedentary time and physical activity were measured by accelerometry and expressed as time spent in sedentary behaviours, average physical activity intensity (counts/minute) and amount of time (minutes/day) spent in moderate intensity and in moderate-to-vigorous-intensity physical activity (MVPA).
The proportion of women meeting the physical activity recommendations of 30 min/day of MVPA on 5 or more days a week was 60.6%. Women spent, on average, 71% of their waking time (approximately 10 h/day) in sedentary behaviours. Both sedentary behaviour and physical activity levels were similar across age groups, waist circumference and percentage body fat categories, years since clinical diagnosis, marital status, educational level and occupational status, regardless of the severity of the disease (all p>0.1). Time spent on moderate-intensity physical activity and MVPA was, however, lower in those with greater body mass index (BMI) (−6.6 min and −7 min, respectively, per BMI category increase, <25, 25–30, >30 kg/m2; p values for trend were 0.056 and 0.051, respectively). Women spent, on average, 10 min less on MVPA (p<0.001) and 22 min less on sedentary behaviours during weekends compared with weekdays (p=0.051).
These data provide an objective measure of the amount of time spent on sedentary activities and on physical activity in women with fibromyalgia.
PMCID: PMC3686217  PMID: 23794573
Epidemiology; Preventive Medicine; Public Health; Rheumatology
3.  Acyl Coenzyme A Synthetase Long-Chain 1 (ACSL1) Gene Polymorphism (rs6552828) and Elite Endurance Athletic Status: A Replication Study 
PLoS ONE  2012;7(7):e41268.
The aim of this study was to determine the association between the rs6552828 polymorphism in acyl coenzyme A synthetase (ACSL1) and elite endurance athletic status. We studied 82 Caucasian (Spanish) World/Olympic-class endurance male athletes, and a group of sex and ethnically matched healthy young adults (controls, n = 197). The analyses were replicated in a cohort of a different ethnic origin (Chinese of the Han ethnic group), composed of elite endurance athletes (runners) [cases, n = 241 (128 male)] and healthy sedentary adults [controls, n = 504 (267 male)]. In the Spanish cohort, genotype (P = 0.591) and minor allele (A) frequencies were similar in cases and controls (P = 0.978). In the Chinese cohort, genotype (P = 0.973) and minor allele (G) frequencies were comparable in female endurance athletes and sedentary controls (P = 0.881), whereas in males the frequency of the G allele was higher in endurance athletes (0.40) compared with their controls (0.32, P = 0.040). The odds ratio (95%CI) for an elite endurance Chinese athlete to carry the G allele compared with ethnically matched controls was 1.381 (1.015–1.880) (P-value = 0.04). Our findings suggest that the ACSL1 gene polymorphism rs6552828 is not associated with elite endurance athletic status in Caucasians, yet a marginal association seems to exist for the Chinese (Han) male population.
PMCID: PMC3400600  PMID: 22829935
4.  Are ‘Endurance’ Alleles ‘Survival’ Alleles? Insights from the ACTN3 R577X Polymorphism 
PLoS ONE  2011;6(3):e17558.
Exercise phenotypes have played a key role for ensuring survival over human evolution. We speculated that some genetic variants that influence exercise phenotypes could be associated with exceptional survival (i.e. reaching ≥100years of age). Owing to its effects on muscle structure/function, a potential candidate is the Arg(R)577Ter(X) polymorphism (rs1815739) in ACTN3, the structural gene encoding the skeletal muscle protein α-actinin-3. We compared the ACTN3 R577X genotype/allele frequencies between the following groups of ethnically-matched (Spanish) individuals: centenarians (cases, n = 64; 57 female; age range: 100–108 years), young healthy controls (n = 283, 67 females, 216 males; 21±2 years), and humans who are at the two end-points of exercise capacity phenotypes, i.e. muscle endurance (50 male professional road cyclists) and muscle power (63 male jumpers/sprinters). Although there were no differences in genotype/allele frequencies between centenarians (RR:28.8%; RX:47.5%; XX:23.7%), and controls (RR:31.8%; RX:49.8%; XX:18.4%) or endurance athletes (RR:28.0%; RX:46%; XX:26.0%), we observed a significantly higher frequency of the X allele (P = 0.019) and XX genotype (P = 0.011) in centenarians compared with power athletes (RR:47.6%; RX:36.5%;XX:15.9%). Notably, the frequency of the null XX (α-actinin-3 deficient) genotype in centenarians was the highest ever reported in non-athletic Caucasian populations. In conclusion, despite there were no significant differences with the younger, control population, overall the ACTN3 genotype of centenarians resembles that of world-class elite endurance athletes and differs from that of elite power athletes. Our preliminary data would suggest a certain ‘survival’ advantage brought about by α-actinin-3 deficiency and the ‘endurance’/oxidative muscle phenotype that is commonly associated with this condition.
PMCID: PMC3048287  PMID: 21407828
5.  Cardiorespiratory fitness, adiposity and incident asthma in adults 
Capsule summary
Our data support that excess fat increases the risk of incident asthma among adults, and this risk might be attenuated by higher fitness. Physical fitness enhancement in overfat people may reduce risk of incident asthma.
PMCID: PMC2836774  PMID: 20109755
Aerobic capacity; obesity; fatness; airways diseases; pulmonary function
6.  Parental History of Premature Cardiovascular Disease, Estimated GFR, and Rate of Estimated GFR Decline: Results From the Aerobics Center Longitudinal Study 
Despite cardiovascular disease (CVD) and chronic kidney disease (CKD) sharing similar etiologies and interplay, it remains unknown if a broader relationship between these diseases exists across generations. We investigated the association between parental CVD history and estimated glomerular filtration rate (eGFR) in the community.
Study Design
Cross-sectional and longitudinal analyses.
Setting & Participants
A total of 13,241 community-based adults with serum creatinine measurement and follow-up visits (from 1 to 8 visits, approximately 2 years apart) from the Aerobics Center Longitudinal Study.
Premature parental CVD history (before age of 50 years).
eGFR, decreased eGFR (<60 mL/min/1.73m2), and rate of eGFR decline.
Information of parental history was collected by protocol-standardized questionnaires. eGFR was assessed with serum creatinine.
A total of 3,339 (25.2%) participants reported a history of parental CVD. Individuals with parental CVD had significantly lower eGFR compared with those without parental CVD (69.4 ± 12.9 vs. 74.8 ± 14.2 mL/min/1.73m2; P<0.001). After multivariable adjustment, parental CVD was independently associated with higher odds of having decreased eGFR (adjusted OR, 1.68; 95% CI, 1.52–1.86). Random-coefficient models showed that individuals with parental CVD had a faster decline in eGFR compared with those without parental CVD (sex- and ethnicity-adjusted annual change of −0.47 vs. −0.41 mL/min/1.73 m2; P=0.06).
Approximately 70% of the participants did not attend a second examination.
Parental history of CVD was associated with lower baseline eGFR, higher odds of decreased eGFR, and a nominally faster rate of eGFR decline in the offspring. Such findings may imply previously unrecognized cross-generational links between both diseases and be of support in community screening programs.
PMCID: PMC4414720  PMID: 25600488
cardiovascular disease (CVD); chronic kidney disease (CKD); glomerular filtration rate (GFR); renal function; kidney disease progression; heart; kidney; random-coefficient model; parental history; risk factor; Aerobics Center Longitudinal Study (ACLS)
7.  Nutrition and Lifestyle in European Adolescents: The HELENA (Healthy Lifestyle in Europe by Nutrition in Adolescence) Study123 
Advances in Nutrition  2014;5(5):615S-623S.
Adolescence is a critical period, because major physical and psychologic changes occur during a very short period of time. Changes in dietary habits may induce different types of nutritional disorders and are likely to track into adulthood. The aim of this review is to describe the key findings related to nutritional status in European adolescents participating in the HELENA (Healthy Lifestyle in Europe by Nutrition in Adolescence) study. We performed a cross-sectional study in 3528 (1845 females) adolescents aged 12.5–17.5 y. Birth weight was negatively associated with abdominal fat mass in adolescents and serum leptin concentrations (in female adolescents), providing additional evidence for a programming effect of birth weight on energy homeostasis control. Breakfast consumption was associated with lower body fat content and healthier cardiovascular profile. Adolescents eat half of the recommended amount of fruit and vegetables and less than two-thirds of the recommended amount of milk and milk products but consume more meat and meat products, fats, and sweets than recommended. For beverage consumption, sugar-sweetened beverages, sweetened milk, low-fat milk, and fruit juice provided the highest amount of energy. Although the intakes of saturated fatty acids (FAs) and salt were high, the intake of polyunsaturated FAs was low. Adolescents spent, on average, 9 h/d of their waking time (66–71% and 70–73% of the registered time in boys and girls, respectively) in sedentary activities. Factors associated with adolescents’ sedentary behavior included the following: 1) age; 2) media availability in the bedroom; 3) sleeping time; 4) breakfast consumption; and 5) season. Sedentary time was also associated with cardiovascular risk factors and bone mineral content. In European adolescents, deficient concentrations were identified for plasma folate (15%), vitamin D (15%), pyridoxal 5′-phosphate (5%), β-carotene (25%), and vitamin E (5%). Scientists and public health authorities should raise awareness of the importance of a healthy and sustainable lifestyle as a foundation of the health of the European population, now and in the future.
PMCID: PMC4188245  PMID: 25469407
8.  A web- and mobile phone-based intervention to prevent obesity in 4-year-olds (MINISTOP): a population-based randomized controlled trial 
BMC Public Health  2015;15:95.
Childhood obesity is an increasing health problem globally. Overweight and obesity may be established as early as 2–5 years of age, highlighting the need for evidence-based effective prevention and treatment programs early in life. In adults, mobile phone based interventions for weight management (mHealth) have demonstrated positive effects on body mass, however, their use in child populations has yet to be examined. The aim of this paper is to report the study design and methodology of the MINSTOP (Mobile-based Intervention Intended to Stop Obesity in Preschoolers) trial.
A two-arm, parallel design randomized controlled trial in 300 healthy Swedish 4-year-olds is conducted. After baseline measures, parents are allocated to either an intervention- or control group. The 6- month mHealth intervention consists of a web-based application (the MINSTOP app) to help parents promote healthy eating and physical activity in children. MINISTOP is based on the Social Cognitive Theory and involves the delivery of a comprehensive, personalized program of information and text messages based on existing guidelines for a healthy diet and active lifestyle in pre-school children. Parents also register physical activity and intakes of candy, soft drinks, vegetables as well as fruits of their child and receive feedback through the application. Primary outcomes include body fatness and energy intake, while secondary outcomes are time spent in sedentary, moderate, and vigorous physical activity, physical fitness and intakes of fruits and vegetables, snacks, soft drinks and candy. Food and energy intake (Tool for Energy balance in Children, TECH), body fatness (pediatric option for BodPod), physical activity (Actigraph wGT3x-BT) and physical fitness (the PREFIT battery of five fitness tests) are measured at baseline, after the intervention (six months after baseline) and at follow-up (12 months after baseline).
This novel study will evaluate the effectiveness of a mHealth program for mitigating gain in body fatness among 4-year-old children. If the intervention proves effective it has great potential to be implemented in child-health care to counteract childhood overweight and obesity.
Trial registration NCT02021786; 20 Dec 2013.
PMCID: PMC4330598  PMID: 25886009
Childhood obesity; Randomized controlled trial; Mobile phones; Body composition
9.  Follow-up in healthy schoolchildren and in adolescents with DOWN syndrome: psycho-environmental and genetic determinants of physical activity and its impact on fitness, cardiovascular diseases, inflammatory biomarkers and mental health; the UP&DOWN Study 
BMC Public Health  2014;14:400.
An objective diagnosis of sedentary behaviour as well as of the physical activity and fitness levels in youth and to better understand how lifestyle is associated with cardiovascular disease risk factors and other phenotypes is of clinical and public health interest, and might be informative for developing intervention studies focused on the promotion of physical activity in these population. The aim of this methodological paper is to describe the design and assessment in the UP&DOWN study.
The UP&DOWN study is a multi-center follow-up design where 2225 Spanish primary and secondary schoolchildren from Cadiz and Madrid, respectively, as well as 110 Spanish adolescents with Down syndrome from Madrid and Toledo were recruited to be assessed. Nine main measurement categories are assessed: i) socio-demographic and early determinants; ii) environmental determinants; iii) physical activity and sedentary behaviour; iv) health-related fitness; v) blood pressure and resting heart rate; vi) mental health; vii) dietary patterns; viii) blood samples; and ix) genetic analysis. During the 3-yr follow-up study, socio-demographic and early determinants, and genetic analysis are only assessed in the first year. Blood sampling is assessed in the first year and the third year (2nd follow-up), and all the other measurements are assessed every year.
The findings of the UP&DOWN study may help the Health Information Systems and policy makers to identify the target population for primary prevention and health promotion policies, and to develop and test preventive strategies. Moreover, these data will allow following the trends at population level, as well as to modify/adapt/create new evidence-based physical activity guidelines at national level. The findings will also serve as a scientific platform for interventional studies.
PMCID: PMC4012062  PMID: 24761982
10.  The intriguing metabolically healthy but obese phenotype: cardiovascular prognosis and role of fitness 
European Heart Journal  2012;34(5):389-397.
Current knowledge on the prognosis of metabolically healthy but obese phenotype is limited due to the exclusive use of the body mass index to define obesity and the lack of information on cardiorespiratory fitness. We aimed to test the following hypotheses: (i) metabolically healthy but obese individuals have a higher fitness level than their metabolically abnormal and obese peers; (ii) after accounting for fitness, metabolically healthy but obese phenotype is a benign condition, in terms of cardiovascular disease and mortality.
Methods and results
Fitness was assessed by a maximal exercise test on a treadmill and body fat per cent (BF%) by hydrostatic weighing or skinfolds (obesity = BF% ≥25 or ≥30%, men or women, respectively) in 43 265 adults (24.3% women). Metabolically healthy was considered if meeting 0 or 1 of the criteria for metabolic syndrome. Metabolically healthy but obese participants (46% of the obese subsample) had a better fitness than metabolically abnormal obese participants (P < 0.001). When adjusting for fitness and other confounders, metabolically healthy but obese individuals had lower risk (30–50%, estimated by hazard ratios) of all-cause mortality, non-fatal and fatal cardiovascular disease, and cancer mortality than their metabolically unhealthy obese peers; while no significant differences were observed between metabolically healthy but obese and metabolically healthy normal-fat participants.
(i) Higher fitness should be considered a characteristic of metabolically healthy but obese phenotype. (ii) Once fitness is accounted for, the metabolically healthy but obese phenotype is a benign condition, with a better prognosis for mortality and morbidity than metabolically abnormal obese individuals.
PMCID: PMC3561613  PMID: 22947612
Cardiovascular diseases; Heart diseases; Metabolic syndrome; Mortality; Obesity; Physical fitness
11.  Are centenarians genetically predisposed to lower disease risk? 
Age  2011;34(5):1269-1283.
Our study purpose was to compare a disease-related polygenic profile that combined a total of 62 genetic variants among (i) people reaching exceptional longevity, i.e., centenarians (n = 54, 100–108 years, 48 women) and (ii) ethnically matched healthy controls (n = 87, 19–43 years, 47 women). We computed a ‘global’ genotype score (GS) for 62 genetic variants (mutations/polymorphisms) related to cardiometabolic diseases, cancer or exceptional longevity, and also specific GS for main disease categories (cardiometabolic risk and cancer risk, including 36 and 24 genetic variations, respectively) and for exceptional longevity (7 genetic variants). The ‘global’ GS was similar among groups (centenarians: 31.0 ± 0.6; controls 32.0 ± 0.5, P = 0.263). We observed that the GS for hypertension, cancer (global risk), and other types of cancer was lower in the centenarians group compared with the control group (all P < 0.05), yet the difference became non significant after adjusting for sex. We observed significant between-group differences in the frequency of GSTT1 and GSTM1 (presence/absence) genotypes after adjusting for multiple comparisons. The likelihood of having the GSTT1 low-risk (functional) allele was higher in centenarians (odds ratio [OR] 5.005; 95% confidence interval [CI], 1.810–13.839), whereas the likelihood of having the GSTMI low-risk (functional) allele was similar in both groups (OR 1.295; 95% CI, 0.868 –1.931). In conclusion, we found preliminary evidence that Spanish centenarians have a lower genetic predisposition for cancer risk. The wild-type (i.e., functional) genotype of GSTT1, which is associated with lower cancer risk, might be associated with exceptional longevity, yet further studies with larger sample sizes must confirm these findings.
PMCID: PMC3448993  PMID: 21894447
Centenarians; Genetics; Exceptional longevity; Ageing
12.  Nonreplication of an Association of Apolipoprotein E2 With Sinistrality 
Laterality  2012;18(2):251-261.
A recent report found that left-handed adolescents were over three-fold more likely to have an Apolipoprotein (APOE) ε2 allele. This study was unable to replicate this association in young-adults (N=166). A meta-analysis of nine other datasets (N = 360 to 7,559, Power > 0.999) including that of National Alzheimer’s Coordinating Center also failed to find an over-representation of ε2 among left-handers indicating that this earlier outcome was most likely a statistical artifact.
PMCID: PMC3770935  PMID: 22721421
APOE; handedness; right
13.  Muscular strength and adiposity as predictors of adulthood cancer mortality in men 
We examined the associations between muscular strength, markers of overall and central adiposity and cancer mortality in men.
Prospective cohort study including 8,677 men aged 20-82 years followed from 1980 to 2003. Participants were enrolled in The Aerobics Centre Longitudinal Study, the Cooper Clinic in Dallas, Texas, U.S. Muscular strength was quantified by combining 1-repetition maximal measures for leg and bench presses. Adiposity was assessed by body mass index (BMI), percent body fat, and waist circumference.
Cancer death rates per 10,000 person-years adjusted for age and examination year were: 17.5, 11.0, and 10.3 across incremental thirds of muscular strength (P=0.001); 10.9, 13.4, and 20.1 across BMI groups of 18.5-24.9, 25.0-29.9, and ≥30kg/m2, respectively (P=0.008); 11.6 and 17.5 for normal (<25%) and high percent body fat (≥25%), respectively (P=0.006); and 12.2 and 16.7 for normal (≤102 cm) and high waist circumference (>102 cm), respectively (P=0.06). After adjusting for additional potential confounders, hazard ratios (95% confidence intervals) were 1.00 (referent), 0.65 (0.47-0.90), and 0.61 (0.44-0.85) across incremental thirds of muscular strength, respectively (P=0.003 for linear trend). Further adjustment for BMI, percent body fat, waist circumference, or cardiorespiratory fitness had little effect on the association. The associations of BMI, percent body fat, or waist circumference with cancer mortality did not persist after further adjusting for muscular strength (all P≥0.1).
Higher levels of muscular strength are associated with lower cancer mortality risk in men, independent of clinically established measures of overall and central adiposity, and other potential confounders.
PMCID: PMC3762582  PMID: 19366909
Muscular strength; obesity; cancer; cardiorespiratory fitness; resistance exercise
15.  Objectively Measured Physical Activity and Sedentary Time during Childhood, Adolescence and Young Adulthood: A Cohort Study 
PLoS ONE  2013;8(4):e60871.
To know how moderate-to-vigorous physical activity (MVPA) and sedentary time change across lifespan periods is needed for designing successful lifestyle interventions. We aimed to study changes in objectively measured (accelerometry) MVPA and sedentary time from childhood to adolescence and from adolescence to young adulthood.
Estonian and Swedish participants from the European Youth Heart Study aged 9 and 15 years at baseline (N = 2312) were asked to participate in a second examination 6 (Sweden) to 9/10 (Estonia) years later. 1800 participants with valid accelerometer data were analyzed.
MVPA decreased from childhood to adolescence (−1 to −2.5 min/d per year of follow-up, P = 0.01 and <0.001, for girls and boys respectively) and also from adolescence to young adulthood (−0.8 to −2.2 min/d per year, P = 0.02 and <0.001 for girls and boys, respectively). Sedentary time increased from childhood to adolescence (+15 and +20 min/d per year, for girls and boys respectively, P<0.001), with no substantial change from adolescence to young adulthood. Changes in both MVPA and sedentary time were greater in Swedish than in Estonian participants and in boys than in girls. The magnitude of the change observed in sedentary time was 3–6 time larger than the change observed in MVPA.
The decline in MVPA (overall change = 30 min/d) and increase sedentary time (overall change = 2∶45 h/d) observed from childhood to adolescence are of concern and might increase the risk of developing obesity and other chronic diseases later in life. These findings substantially contribute to understand how key health-related behaviors (physical activity and sedentary) change across important periods of life.
PMCID: PMC3634054  PMID: 23637772
16.  Are mitochondrial haplogroups associated with extreme longevity? A study on a Spanish cohort 
Age  2011;34(1):227-233.
Mitochondrial haplogroups could influence individual susceptibility to mitochondrial DNA (mtDNA) damage, and human longevity, as indicated by previous studies with Caucasian (European) or Asian cohorts. Here, we compared the frequency of mtDNA haplogroups in a group of Spanish (Caucasian) centenarians (n = 65, aged 100–108 years, 58 women, most from the central part of Spain) and a group of healthy young adults (n = 138, 62 women, aged 20–40 years) of the same ethnic origin. We did not find significant differences between centenarians and the control group (P > 0.2). Only two centenarians (both women) had the haplogroup J, which hampered comparison with the control group (n = 15, five women). Our data confirm that the potential effects of mitochondrial haplogroups on human longevity might be population/geographic specific, with important differences between studies (notably, with regard to the previously reported potential benefit brought about by the haplogroup J) arising from the different living environment and ethnic background of the study cohorts.
PMCID: PMC3260354  PMID: 21274636
Genetics; Mitochondria; Centenarians
17.  Physical Activity Attenuates the Effect of Low Birth Weight on Insulin Resistance in Adolescents 
Diabetes  2011;60(9):2295-2299.
To examine whether physical activity influences the association between birth weight and insulin resistance in adolescents.
The study comprised adolescents who participated in two cross-sectional studies: the Healthy Lifestyle in Europe by Nutrition in Adolescence (HELENA) study (n = 520, mean age = 14.6 years) and the Swedish part of the European Youth Heart Study (EYHS) (n = 269, mean age = 15.6 years). Participants had valid data on birth weight (parental recall), BMI, sexual maturation, maternal education, breastfeeding, physical activity (accelerometry, counts/minute), fasting glucose, and insulin. Insulin resistance was assessed by homeostasis model assessment–insulin resistance (HOMA-IR). Maternal education level and breastfeeding duration were reported by the mothers.
There was a significant interaction of physical activity in the association between birth weight and HOMA-IR (logarithmically transformed) in both the HELENA study and the EYHS (P = 0.05 and P = 0.03, respectively), after adjusting for sex, age, sexual maturation, BMI, maternal education level, and breastfeeding duration. Stratified analyses by physical activity levels (below/above median) showed a borderline inverse association between birth weight and HOMA-IR in the low-active group (standardized β = −0.094, P = 0.09, and standardized β = −0.156, P = 0.06, for HELENA and EYHS, respectively), whereas no evidence of association was found in the high-active group (standardized β = −0.031, P = 0.62, and standardized β = 0.053, P = 0.55, for HELENA and EYHS, respectively).
Higher levels of physical activity may attenuate the adverse effects of low birth weight on insulin sensitivity in adolescents. More observational data, from larger and more powerful studies, are required to test these findings.
PMCID: PMC3161315  PMID: 21752955
18.  The ACTN3 R577X Polymorphism across Three Groups of Elite Male European Athletes 
PLoS ONE  2012;7(8):e43132.
The ACTN3 R577X polymorphism (rs1815739) is a strong candidate to influence elite athletic performance. Yet, controversy exists in the literature owing to between-studies differences in the ethnic background and sample size of the cohorts, the latter being usually low, which makes comparisons difficult. In this case:control genetic study we determined the association between elite athletic status and the ACTN3 R577X polymorphism within three cohorts of European Caucasian men, i.e. Spanish, Polish and Russian [633 cases (278 elite endurance and 355 power athletes), and 808 non-athletic controls]. The odds ratio (OR) of a power athlete harbouring the XX versus the RR genotype compared with sedentary controls was 0.54 [95% confidence interval (CI): 0.34–0.48; P = 0.006]. We also observed that the OR of an endurance athlete having the XX versus the RR genotype compared with power athletes was 1.88 (95%CI: 1.07–3.31; P = 0.028). In endurance athletes, the OR of a “world-class” competitor having the XX genotype versus the RR+RX genotype was 3.74 (95%CI: 1.08–12.94; P = 0.038) compared with those of a lower (“national”) competition level. No association (P>0.1) was noted between the ACTN3 R577X polymorphism and competition level (world-class versus national-level) in power athletes. Our data provide comprehensive support for the influence of the ACTN3 R577X polymorphism on elite athletic performance.
PMCID: PMC3420864  PMID: 22916217
19.  Effectiveness of a Tai-Chi Training and Detraining on Functional Capacity, Symptomatology and Psychological Outcomes in Women with Fibromyalgia 
Background. The purpose was to analyze the effects of Tai-Chi training in women with fibromyalgia (FM). Methods. Thirty-two women with FM (mean age, 51.4 ± 6.8 years) attended to Tai-Chi intervention 3 sessions weekly for 28 weeks. The outcome measures were: tenderness, body composition, functional capacity and psychological outcomes (Fibromyalgia impact questionnaire (FIQ), Short Form Health Survey 36 (SF-36)). Results. Patients showed improvements on pain threshold, total number of tender points and algometer score (all P < 0.001). The intervention was effective on 6-min walk (P = 0.006), back scratch (P = 0.002), handgrip strength (P = 0.006), chair stand, chair sit & reach, 8 feet up & go and blind flamingo tests (all P < 0.001). Tai-Chi group improved the FIQ total score (P < 0.001) and six subscales: stiffness (P = 0.005), pain, fatigue, morning tiredness, anxiety, and depression (all P < 0.001). The intervention was also effective in six SF-36 subscales: bodily pain (P = 0.003), vitality (P = 0.018), physical functioning, physical role, general health, and mental health (all P < 0.001). Conclusions. A 28-week Tai-Chi intervention showed improvements on pain, functional capacity, symptomatology and psychological outcomes in female FM patients.
PMCID: PMC3357550  PMID: 22649476
20.  A Prospective Study of Muscular Strength and All-cause Mortality in Men with Hypertension 
To assess the impact of muscular strength on mortality in men with hypertension.
Muscular strength is inversely associated with mortality in healthy men, but this association has not been examined in men with hypertension.
We followed 1506 hypertensive men aged ≥ 40 years enrolled in the Aerobics Center Longitudinal Study from 1980 to 2003. Participants received an extensive medical examination at baseline. Muscular strength was quantified by combining one repetition maximum (1-RM) measures for leg and bench press, and cardiorespiratory fitness (CRF) assessed by maximum exercise test on a treadmill.
During an average follow-up of 18.3 years, 183 deaths occurred. Age adjusted death rates per 10 000 man-years across incremental thirds of muscular strength were 81.8, 65.5 and 52.0 (P<0.05 for linear trend). Multivariable Cox regression hazard ratios were 1.0 (reference), 0.81 (95% confidence interval, 0.57 to 1.14), and 0.59 (0.40 to 0.86) across incremental thirds of muscular strength. After further adjustment for CRF, those participants in the upper third of muscular strength still had a lower risk of death (0.66; 0.45 to 0.98). In the muscular strength and CRF combined analysis, men simultaneously in the upper third of muscular strength and high fitness group had the lowest mortality risk among all combination groups (0.49; 0.30 to 0.82), with men in the lower third of muscular strength and low fitness group as reference.
High levels of muscular strength appear to protect hypertensive men against all-cause mortality, and this is in addition to the benefit provided by CRF.
PMCID: PMC3098120  PMID: 21527158
Hypertension; muscular strength; cardiorespiratory fitness; mortality
21.  Land- and water-based exercise intervention in women with fibromyalgia: the al-andalus physical activity randomised controlled trial 
The al-Andalus physical activity intervention study is a randomised control trial to investigate the effectiveness of a land- and water-based exercise intervention for reducing the overall impact of fibromyalgia (primary outcome), and for improving tenderness and pain-related measures, body composition, functional capacity, physical activity and sedentary behaviour, fatigue, sleep quality, health-related quality of life, and cognitive function (secondary outcomes) in women with fibromyalgia.
One hundred eighty women with fibromyalgia (age range: 35-65 years) will be recruited from local associations of fibromyalgia patients in Andalucía (Southern Spain). Patients will be randomly assigned to a usual care (control) group (n = 60), a water-based exercise intervention group (n = 60) or a land-based exercise intervention group (n = 60). Participants in the usual care group will receive general physical activity guidelines and participants allocated in the intervention groups will attend three non-consecutive training sessions (60 min each) per week during 24 weeks. Both exercise interventions will consist of aerobic, muscular strength and flexibility exercises. We will also study the effect of a detraining period (i.e., 12 weeks with no exercise intervention) on the studied variables.
Our study attempts to reduce the impact of fibromyalgia and improve patients' health status by implementing two types of exercise interventions. Results from this study will help to assess the efficacy of exercise interventions for the treatment of fibromyalgia. If the interventions would be effective, this study will provide low-cost and feasible alternatives for health professionals in the management of fibromyalgia. Results from the al-Andalus physical activity intervention will help to better understand the potential of regular physical activity for improving the well-being of women with fibromyalgia.
Trial registration ID: NCT01490281
PMCID: PMC3350451  PMID: 22336292
22.  Health-related quality of life of Spanish children with cystic fibrosis 
Quality of Life Research  2012;21(10):1837-1845.
To investigate (1) the contributions of sex, age, nutritional status- and physical-fitness-related variables on health-related quality of life (HRQOL) in Spanish children with cystic fibrosis, and (2) the agreement on HRQOL between children and their parents.
In 28 children aged 6–17 years, body mass index percentile, percentage body fat, physical activity, pulmonary function, cardiorespiratory fitness, functional mobility, and dynamic muscle strength were determined using objective measures. HRQOL was measured using the revised version of the cystic fibrosis questionnaire. Simple and multiple linear regression analyses were performed to determine the variables associated with HRQOL. To assess the agreement on HRQOL between children and parents, intra-class correlation coefficients (ICCs) were calculated.
Girls reported worse emotional functioning, a higher treatment burden, and more respiratory problems than boys. Greater functional mobility appeared associated with a less favourable body image and more eating disturbances. Agreement on HRQOL between children and parents was good to excellent, except for the domain of treatment burden.
Sex and age were stronger predictors of HRQOL than nutritional status- or physical-fitness-related variables. Children reported a lower treatment burden than their parents perceived them to have.
PMCID: PMC3496548  PMID: 22219170
Cystic fibrosis; Quality of life; Children; Parents; Physical fitness; Nutritional status
23.  Psychological Well-Being, Cardiorespiratory Fitness, and Long-Term Survival 
Psychological well-being is associated with mortality/survival. Although cardiorespiratory fitness (CRF) is one of the strongest predictors of mortality, studies examining the relationship between well-being and survival seldom account for the possible effects of CRF.
This study examined the independent associations of psychological well-being components (low level of negative emotion and high level of positive emotion) and CRF, as well as their combined effects, with survival.
Participants (N=4888) were examined in 1988–1997 and followed up for a median period of ~15 years (212 deaths, 4.3%). CRF was assessed by a maximal exercise test on a treadmill. Low-level negative emotion was defined as the minimum score of the negative emotion subscale of the CES-D scale, and high-level positive emotion as the maximum score of positive emotion subscale. Results are presented as hazard ratios (95% CIs). Data were analyzed in 2009.
After adjustment for a set of established risk factors, men and women with low levels of negative emotion had lower risk of death than those with higher levels of negative emotion, 0.66 (0.50, 0.87). The association persisted after additional adjustment for CRF and positive emotion. High level of positive emotion was not associated with survival. A high level of CRF independently predicted lower risk of death, 0.54 (0.37, 0.79), compared to a low level of CRF. The risk of death in participants with both a low level of negative emotion and a high level of CRF was 0.37 (0.22, 0.63), compared to their peers with higher levels of negative emotion/low levels of CRF.
Low levels of negative emotion and high levels of CRF are independent predictors of long-term survival in men and women. A strong combined effect was observed, as individuals with both a low level of negative emotion and a high level of CRF had a 63% lower risk of death than those with higher levels of negative emotion and a low level of CRF.
PMCID: PMC2962920  PMID: 20965381
24.  Physical Activity Attenuates the Influence of FTO Variants on Obesity Risk: A Meta-Analysis of 218,166 Adults and 19,268 Children 
Kilpeläinen, Tuomas O. | Qi, Lu | Brage, Soren | Sharp, Stephen J. | Sonestedt, Emily | Demerath, Ellen | Ahmad, Tariq | Mora, Samia | Kaakinen, Marika | Sandholt, Camilla Helene | Holzapfel, Christina | Autenrieth, Christine S. | Hyppönen, Elina | Cauchi, Stéphane | He, Meian | Kutalik, Zoltan | Kumari, Meena | Stančáková, Alena | Meidtner, Karina | Balkau, Beverley | Tan, Jonathan T. | Mangino, Massimo | Timpson, Nicholas J. | Song, Yiqing | Zillikens, M. Carola | Jablonski, Kathleen A. | Garcia, Melissa E. | Johansson, Stefan | Bragg-Gresham, Jennifer L. | Wu, Ying | van Vliet-Ostaptchouk, Jana V. | Onland-Moret, N. Charlotte | Zimmermann, Esther | Rivera, Natalia V. | Tanaka, Toshiko | Stringham, Heather M. | Silbernagel, Günther | Kanoni, Stavroula | Feitosa, Mary F. | Snitker, Soren | Ruiz, Jonatan R. | Metter, Jeffery | Larrad, Maria Teresa Martinez | Atalay, Mustafa | Hakanen, Maarit | Amin, Najaf | Cavalcanti-Proença, Christine | Grøntved, Anders | Hallmans, Göran | Jansson, John-Olov | Kuusisto, Johanna | Kähönen, Mika | Lutsey, Pamela L. | Nolan, John J. | Palla, Luigi | Pedersen, Oluf | Pérusse, Louis | Renström, Frida | Scott, Robert A. | Shungin, Dmitry | Sovio, Ulla | Tammelin, Tuija H. | Rönnemaa, Tapani | Lakka, Timo A. | Uusitupa, Matti | Rios, Manuel Serrano | Ferrucci, Luigi | Bouchard, Claude | Meirhaeghe, Aline | Fu, Mao | Walker, Mark | Borecki, Ingrid B. | Dedoussis, George V. | Fritsche, Andreas | Ohlsson, Claes | Boehnke, Michael | Bandinelli, Stefania | van Duijn, Cornelia M. | Ebrahim, Shah | Lawlor, Debbie A. | Gudnason, Vilmundur | Harris, Tamara B. | Sørensen, Thorkild I. A. | Mohlke, Karen L. | Hofman, Albert | Uitterlinden, André G. | Tuomilehto, Jaakko | Lehtimäki, Terho | Raitakari, Olli | Isomaa, Bo | Njølstad, Pål R. | Florez, Jose C. | Liu, Simin | Ness, Andy | Spector, Timothy D. | Tai, E. Shyong | Froguel, Philippe | Boeing, Heiner | Laakso, Markku | Marmot, Michael | Bergmann, Sven | Power, Chris | Khaw, Kay-Tee | Chasman, Daniel | Ridker, Paul | Hansen, Torben | Monda, Keri L. | Illig, Thomas | Järvelin, Marjo-Riitta | Wareham, Nicholas J. | Hu, Frank B. | Groop, Leif C. | Orho-Melander, Marju | Ekelund, Ulf | Franks, Paul W. | Loos, Ruth J. F.
PLoS Medicine  2011;8(11):e1001116.
Ruth Loos and colleagues report findings from a meta-analysis of multiple studies examining the extent to which physical activity attenuates effects of a specific gene variant, FTO, on obesity in adults and children. They report a fairly substantial attenuation by physical activity on the effects of this genetic variant on the risk of obesity in adults.
The FTO gene harbors the strongest known susceptibility locus for obesity. While many individual studies have suggested that physical activity (PA) may attenuate the effect of FTO on obesity risk, other studies have not been able to confirm this interaction. To confirm or refute unambiguously whether PA attenuates the association of FTO with obesity risk, we meta-analyzed data from 45 studies of adults (n = 218,166) and nine studies of children and adolescents (n = 19,268).
Methods and Findings
All studies identified to have data on the FTO rs9939609 variant (or any proxy [r2>0.8]) and PA were invited to participate, regardless of ethnicity or age of the participants. PA was standardized by categorizing it into a dichotomous variable (physically inactive versus active) in each study. Overall, 25% of adults and 13% of children were categorized as inactive. Interaction analyses were performed within each study by including the FTO×PA interaction term in an additive model, adjusting for age and sex. Subsequently, random effects meta-analysis was used to pool the interaction terms. In adults, the minor (A−) allele of rs9939609 increased the odds of obesity by 1.23-fold/allele (95% CI 1.20–1.26), but PA attenuated this effect (pinteraction  = 0.001). More specifically, the minor allele of rs9939609 increased the odds of obesity less in the physically active group (odds ratio  = 1.22/allele, 95% CI 1.19–1.25) than in the inactive group (odds ratio  = 1.30/allele, 95% CI 1.24–1.36). No such interaction was found in children and adolescents.
The association of the FTO risk allele with the odds of obesity is attenuated by 27% in physically active adults, highlighting the importance of PA in particular in those genetically predisposed to obesity.
Please see later in the article for the Editors' Summary
Editors’ Summary
Two in three Americans are overweight, of whom half are obese, and the trend towards increasing obesity is now seen across developed and developing countries. There has long been interest in understanding the impact of genes and environment when it comes to apportioning responsibility for obesity. Carrying a change in the FTO gene is common (found in three-quarters of Europeans and North Americans) and is associated with a 20%–30% increased risk of obesity. Some overweight or obese individuals may feel that the dice are loaded and there is little point in fighting the fat; it has been reported that those made aware of their genetic susceptibility to obesity may still choose a poor diet. A similar fatalism may occur when overweight and obese people consider physical activity. But disentangling the influence of physical activity on those genetically susceptible to obesity from other factors that might impact weight is not straightforward, as it requires large sample sizes, could be subject to publication bias, and may rely on less than ideal self-reporting methods.
Why Was This Study Done?
The public health ramifications of understanding the interaction between genetic susceptibility to obesity and physical activity are considerable. Tackling the rising prevalence of obesity will inevitably include interventions principally aimed at changing dietary intake and/or increasing physical activity, but the evidence for these with regards to those genetically susceptible has been lacking to date. The authors of this paper set out to explore the interaction between the commonest genetic susceptibility trait and physical activity using a rigorous meta-analysis of a large number of studies.
What Did the Researchers Do and Find?
The authors were concerned that a meta-analysis of published studies would be limited both by the data available to them and by possible bias. Instead of this more widely used approach, they took the literature search as their starting point, identified other studies through their collaborators’ network, and then undertook a meta-analysis of all available studies using a new and standardized analysis plan. This entailed an extremely large number of authors mining their data afresh to extract the relevant data points to enable such a meta-analysis. Physical activity was identified in the original studies in many different ways, including by self-report or by using an external measure of activity or heart rate. In order to perform the meta-analysis, participants were labeled as physically active or inactive in each study. For studies that had used a continuous scale, the authors decided that the bottom 20% of the participants were inactive (10% for children and adolescents). Using data from over 218,000 adults, the authors found that carrying a copy of the susceptibility gene increased the odds of obesity by 1.23-fold. But the size of this influence was 27% less in the genetically susceptible adults who were physically active (1.22-fold) compared to those who were physically inactive (1.30-fold). In a smaller study of about 19,000 children, no such effect of physical activity was seen.
What Do these Findings Mean?
This study demonstrates that people who carry the susceptibility gene for obesity can benefit from physical activity. This should inform health care professionals and the wider public that the view of genetically determined obesity not being amenable to exercise is incorrect and should be challenged. Dissemination, implementation, and ensuring uptake of effective physical activity programs remains a challenge and deserves further consideration. That the researchers treated “physically active” as a yes/no category, and how they categorized individuals, could be criticized, but this was done for pragmatic reasons, as a variety of means of assessing physical activity were used across the studies. It is unlikely that the findings would have changed if the authors had used a different method of defining physically active. Most of the studies included in the meta-analysis looked at one time point only; information about the influence of physical activity on weight changes over time in genetically susceptible individuals is only beginning to emerge.
Additional Information
Please access these websites via the online version of this summary at
This study is further discussed in a PLoS Medicine Perspective by Lennert Veerman
The US Centers for Disease Control and Prevention provides obesity-related statistics, details of prevention programs, and an overview on public health strategy in the United States
A more worldwide view is given by the World Health Organization
The UK National Health Service website gives information on physical activity guidelines for different age groups, while similar information can also be found from US sources
PMCID: PMC3206047  PMID: 22069379
25.  Stability of the factorial structure of metabolic syndrome from childhood to adolescence: a 6-year follow-up study 
Metabolic syndrome (MS) is a clustering of cardiometabolic risk factors that is considered a predictor of cardiovascular disease, type 2 diabetes and mortality. There is no consistent evidence on whether the MS construct works in the same way in different populations and at different stages in life.
We used confirmatory factor analysis to examine if a single-factor-model including waist circumference, triglycerides/HDL-c, insulin and mean arterial pressure underlies metabolic syndrome from the childhood to adolescence in a 6-years follow-up study in 174 Swedish and 460 Estonian children aged 9 years at baseline. Indeed, we analyze the tracking of a previously validated MS index over this 6-years period.
The estimates of goodness-of-fit for the single-factor-model underlying MS were acceptable both in children and adolescents. The construct stability of a new model including the differences from baseline to the end of the follow-up in the components of the proposed model displayed good fit indexes for the change, supporting the hypothesis of a single factor underlying MS component trends.
A single-factor-model underlying MS is stable across the puberty in both Estonian and Swedish young people. The MS index tracks acceptably from childhood to adolescence.
PMCID: PMC3193025  PMID: 21933439
Tracking; Metabolic syndrome; Confirmatory factor analysis

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