Longitudinal leisure-time physical activity profiles throughout adulthood and related characteristics: a 36-year follow-up study of the older Finnish Twin Cohort.

BACKGROUND: Personalized interventions aiming to increase physical activity in individuals are effective. However, from a public health perspective, it would be important to stimulate physical activity in larger groups of people who share the vulnerability to be physically inactive throughout adulthood. To find these high-risk groups, we identified 36-year leisure-time physical activity profiles from young adulthood to late midlife in females and males. Moreover, we uncovered which anthropometric-, demographic-, lifestyle-, and health-related characteristics were associated with these physical activity profiles. METHODS: We included 2,778 females and 1,938 males from the population-based older Finnish Twin Cohort Study, who responded to health and behavior surveys at the mean ages of 24, 30, 40 and 60. Latent profile analysis was used to identify longitudinal leisure-time physical activity profiles. RESULTS: We found five longitudinal leisure-time physical activity profiles for both females and males. Females' profiles were: 1) Low increasing moderate (29%), 2) Moderate stable (23%), 3) Very low increasing low (20%), 4) Low stable (20%) and 5) High increasing high (9%). Males' profiles were: 1) Low increasing moderate (29%), 2) Low stable very low (26%), 3) Moderate decreasing low (21%), 4) High fluctuating high (17%) and 5) Very low stable (8%). In both females and males, lower leisure-time physical activity profiles were associated with lower education, higher body mass index, smoking, poorer perceived health, higher sedentary time, high blood pressure, and a higher risk for type 2 diabetes. Furthermore, lower leisure-time physical activity was linked to a higher risk of depression in females. CONCLUSIONS: We found several longitudinal leisure-time physical activity profiles with unique changes in both sexes. Fewer profiles in females than in males remained or became low physically active during the 36-year follow-up. We observed that lower education, higher body mass index, and more smoking already in young adulthood were associated with low leisure-time physical activity profiles. However, the fact that several longitudinal profiles demonstrated a change in their physical activity behavior over time implies the potential for public health interventions to improve leisure-time physical activity levels.

Educational attainment, health outcomes and mortality: a within-sibship Mendelian randomization study.

BACKGROUND: Previous Mendelian randomization (MR) studies using population samples (population MR) have provided evidence for beneficial effects of educational attainment on health outcomes in adulthood. However, estimates from these studies may have been susceptible to bias from population stratification, assortative mating and indirect genetic effects due to unadjusted parental genotypes. MR using genetic association estimates derived from within-sibship models (within-sibship MR) can avoid these potential biases because genetic differences between siblings are due to random segregation at meiosis. METHODS: Applying both population and within-sibship MR, we estimated the effects of genetic liability to educational attainment on body mass index (BMI), cigarette smoking, systolic blood pressure (SBP) and all-cause mortality. MR analyses used individual-level data on 72 932 siblings from UK Biobank and the Norwegian HUNT study, and summary-level data from a within-sibship Genome-wide Association Study including >140 000 individuals. RESULTS: Both population and within-sibship MR estimates provided evidence that educational attainment decreased BMI, cigarette smoking and SBP. Genetic variant-outcome associations attenuated in the within-sibship model, but genetic variant-educational attainment associations also attenuated to a similar extent. Thus, within-sibship and population MR estimates were largely consistent. The within-sibship MR estimate of education on mortality was imprecise but consistent with a putative effect. CONCLUSIONS: These results provide evidence of beneficial individual-level effects of education (or liability to education) on adulthood health, independently of potential demographic and family-level confounders.

Smoking remains associated with education after controlling for social background and genetic factors in a study of 18 twin cohorts.

We tested the causality between education and smoking using the natural experiment of discordant twin pairs allowing to optimally control for background genetic and childhood social factors. Data from 18 cohorts including 10,527 monozygotic (MZ) and same-sex dizygotic (DZ) twin pairs discordant for education and smoking were analyzed by linear fixed effects regression models. Within twin pairs, education levels were lower among the currently smoking than among the never smoking co-twins and this education difference was larger within DZ than MZ pairs. Similarly, education levels were higher among former smoking than among currently smoking co-twins, and this difference was larger within DZ pairs. Our results support the hypothesis of a causal effect of education on both current smoking status and smoking cessation. However, the even greater intra-pair differences within DZ pairs, who share only 50% of their segregating genes, provide evidence that shared genetic factors also contribute to these associations.

Alcohol consumption at age 18-25 and number of children at a 33-year follow-up: Individual and within-pair analyses of Finnish twins.

BACKGROUND: Do drinking patterns in late adolescence/early adulthood predict lifetime childlessness and number of children? Research on this question has been only tangentially relevant and the results inconsistent. The designs used to date have been compromised by genetic and environmental confounds that are poorly controlled; covariate effects of smoking and education that are often ignored; males being understudied; population-based sampling rare, and long-term prospective studies with genetically informative designs yet to be reported. METHOD: In a 33-year follow-up, we linked the drinking patterns of >3500 Finnish twin pairs, assessed at ages 18-25, to registry data on their eventual number of children. Analyses distinguished associations of early drinking patterns with lifetime childlessness from those predictive of family size. Within-twin pair analyses used fixed-effects regression models to account for shared familial confounds and genetic liabilities. Childlessness was analyzed with Cox proportional hazards models and family size with Poisson regression. Analyses within-pairs and of twins as individuals were run before and after adjustment for smoking and education, and for oral contraceptive (OC) use in individual-level analyses of female twins. RESULTS: Baseline abstinence and heavier drinking both significantly predicted lifetime childlessness in individual-level analyses. Few abstinent women used OCs, but they were nonetheless more often eventually childless; adjusting for smoking and education did not affect this finding. Excluding childless twins, Poisson models of family size showed heavier drinking at 18-25 to be predictive of fewer children in both men and women. Those associations were replicated in within-pair analyses of dizygotic twins, each level of heavier drinking being associated with smaller families. Among monozygotic twins, associations of drinking with completed family size yielded effects of similar magnitude, reaching significance at the highest levels of consumption, ruling out familial confounds. CONCLUSIONS: Compared to moderate levels of drinking, both abstinence and heavier drinking in late adolescence/early adulthood predicted a greater likelihood of lifetime childlessness and eventual number of children. Familial confounds do not fully explain these associations.

The temporal relationship between parental concern of overeating and childhood obesity considering genetic susceptibility: longitudinal results from the IDEFICS/I.Family study.

BACKGROUND: Many genes and molecular pathways are associated with obesity, but the mechanisms from genes to obesity are less well known. Eating behaviors represent a plausible pathway, but because the relationships of eating behaviors and obesity may be bi-directional, it remains challenging to resolve the underlying pathways. A longitudinal approach is needed to assess the contribution of genetic risk during the development of obesity in childhood. In this study we aim to examine the relationships between the polygenic risk score for body mass index (PRS-BMI), parental concern of overeating and obesity indices during childhood. METHODS: The IDEFICS/I.Family study is a school-based multicenter pan-European cohort of children observed for 6 years (mean ± SD follow-up 5.8 ± 0.4). Children examined in 2007/2008 (wave 1) (mean ± SD age: 4.4 ± 1.1, range: 2-9 years), in 2009/2010 (wave 2) and in 2013/2014 (wave 3) were included. A total of 5112 children (49% girls) participated at waves 1, 2 and 3. For 2656 children with genome-wide data we constructed a PRS based on 2.1 million single nucleotide polymorphisms. Z-score BMI and z-score waist circumference (WC) were assessed and eating behaviors and relevant confounders were reported by parents via questionnaires. Parental concern of overeating was derived from principal component analyses from an eating behavior questionnaire. RESULTS: In cross-lagged models, the prospective associations between z-score obesity indices and parental concern of overeating were bi-directional. In mediation models, the association between the PRS-BMI and parental concern of overeating at wave 3 was mediated by baseline z-BMI (ß = 0.16, 95% CI: 0.10, 0.21) and baseline z-WC (ß = 0.17, 95% CI: 0.11, 0.23). To a lesser extent, baseline parental concern of overeating also mediated the association between the PRS-BMI and z-BMI at wave 3 (ß = 0.10, 95% CI: 0.07, 0.13) and z-WC at wave 3 (ß = 0.09, 95% CI: 0.07, 0.12). CONCLUSIONS: The findings suggest that the prospective associations between obesity indices and parental concern of overeating are likely bi-directional, but obesity indices have a stronger association with future parental concern of overeating than vice versa. The findings suggest parental concern of overeating as a possible mediator in the genetic susceptibility to obesity and further highlight that other pathways are also involved. A better understanding of the genetic pathways that lead to childhood obesity can help to prevent weight gain. TRIAL REGISTRATION: Registry number: ISRCTN62310987 Retrospectively registered 17 September 2018.

The role of familial confounding in the associations of physical activity, smoking and alcohol consumption with early exit from the labour market.

We investigated the associations between health behaviors and sustainable working life outcomes including all-cause disability pension, disability pensions due to musculoskeletal and mental diagnoses and unemployment. The role of familial factors behind these associations was studied by analysing discordant twin pairs. Our data included Swedish twins born in 1925-1986 (51891 twin individuals). Baseline data based on two independent surveys in 1998-2003 and 2005-2006 for health behaviors were linked to national registers on disability pension and unemployment until 2016. Cox proportional hazards models for hazard ratios (HR) with 95% confidence intervals (CI) were estimated for the whole sample adjusting for covariates. Analyses of health behavior discordant twin pairs (n = 5903 pairs) were conducted using conditional Cox models. In the whole cohort, the combination of healthy behaviors was associated with lower risk for all-cause disability pension, disability pension due to musculoskeletal diagnoses or mental diagnoses, and for unemployment (HRs 0.56-0.86, 95% CIs 0.51-0.92) as did being physically active (HRs 0.69-0.87, 95% CI 0.65-0.92). The discordant pair analyses confirmed the lower risk among those having healthy behaviors (HR 0.70-0.86) or being physically active (HR 0.86-0.87) for all-cause disability pension, disability pension due to musculoskeletal diagnoses, and for unemployment. To conclude, controlling the effects of covariates or familial confounding (i.e. discordant twin pair analyses) shows that being physically active or having several healthy behaviors predict better working life outcomes. This points towards independent association between healthy behavior and longer working life.

Joint association between education and polygenic risk score for incident coronary heart disease events: a longitudinal population-based study of 26 203 men and women.

BACKGROUND: Genetic vulnerability to coronary heart disease (CHD) is well established, but little is known whether these effects are mediated or modified by equally well-established social determinants of CHD. We estimate the joint associations of the polygenetic risk score (PRS) for CHD and education on CHD events. METHODS: The data are from the 1992, 1997, 2002, 2007 and 2012 surveys of the population-based FINRISK Study including measures of social, behavioural and metabolic factors and genome-wide genotypes (N=26 203). Follow-up of fatal and non-fatal incident CHD events (N=2063) was based on nationwide registers. RESULTS: Allowing for age, sex, study year, region of residence, study batch and principal components, those in the highest quartile of PRS for CHD had strongly increased risk of CHD events compared with the lowest quartile (HR=2.26; 95% CI: 1.97 to 2.59); associations were also observed for low education (HR=1.58; 95% CI: 1.32 to 1.89). These effects were largely independent of each other. Adjustment for baseline smoking, alcohol use, body mass index, igh-density lipoprotein (HDL) and total cholesterol, blood pressure and diabetes attenuated the PRS associations by 10% and the education associations by 50%. We do not find strong evidence of interactions between PRS and education. CONCLUSIONS: PRS and education predict CHD events, and these associations are independent of each other. Both can improve CHD prediction beyond behavioural risks. The results imply that observational studies that do not have information on genetic risk factors for CHD do not provide confounded estimates for the association between education and CHD.

Health behaviours and psychosocial working conditions as predictors of disability pension due to different diagnoses: a population-based study.

BACKGROUND: To investigate whether the clustering of different health behaviours (i.e. physical activity, tobacco use and alcohol consumption) influences the associations between psychosocial working conditions and disability pension due to different diagnoses. METHODS: A population-based sample of 24,987 Swedish twins born before 1958 were followed from national registers for disability pension until 2013. Baseline survey data in 1998-2003 were used to assess health behaviours and psychosocial Job Exposure Matrix for job control, job demands and social support. Cox proportional hazards models were used to calculate hazard ratios (HR) with 95% confidence intervals (CI). RESULTS: During follow-up, 1252 disability pensions due to musculoskeletal disorders (5%), 601 due to mental diagnoses (2%) and 1162 due to other diagnoses (5%) occurred. In the models controlling for covariates, each one-unit increase in job demands was associated with higher (HR 1.16, 95%CI 1.01-1.33) and in job control with lower (HR 0.87, 95%CI 0.80-0.94) risk of disability pension due to musculoskeletal disorders among those with unhealthy behaviours. Among those with healthy behaviours, one-unit increase of social support was associated with a higher risk of disability pension due to mental and due to other diagnoses (HRs 1.29-1.30, 95%CI 1.04-1.63). CONCLUSIONS: Job control and job demands were associated with the risk of disability pension due to musculoskeletal disorders only among those with unhealthy behaviours. Social support was a risk factor for disability pension due to mental or other diagnoses among those with healthy behaviours. Workplaces and occupational health care should acknowledge these simultaneous circumstances in order to prevent disability pension.

The Older Finnish Twin Cohort - 45 Years of Follow-up.

The older Finnish Twin Cohort (FTC) was established in 1974. The baseline survey was in 1975, with two follow-up health surveys in 1981 and 1990. The fourth wave of assessments was done in three parts, with a questionnaire study of twins born during 1945-1957 in 2011-2012, while older twins were interviewed and screened for dementia in two time periods, between 1999 and 2007 for twins born before 1938 and between 2013 and 2017 for twins born in 1938-1944. The content of these wave 4 assessments is described and some initial results are described. In addition, we have invited twin-pairs, based on response to the cohortwide surveys, to participate in detailed in-person studies; these are described briefly together with key results. We also review other projects based on the older FTC and provide information on the biobanking of biosamples and related phenotypes.

Associations of mortality with own blood pressure using son's blood pressure as an instrumental variable.

High systolic blood pressure (SBP) causes cardiovascular disease (CVD) and is associated with mortality from other causes, but conventional multivariably-adjusted results may be confounded. Here we used a son's SBP (>1 million Swedish men) as an instrumental variable for parental SBP and examined associations with parents' cause-specific mortality, avoiding reverse causation. The hazard ratio for CVD mortality per SD (10.80 mmHg) of SBP was 1.49 (95% CI: 1.43, 1.56); SBP was positively associated with coronary heart disease and stroke. SBP was also associated positively with all-cause, diabetes and kidney cancer mortality, and negatively with external causes. Negative associations with respiratory-related mortality were probably confounded by smoking. Hazard ratios for other causes were imprecise or null. Diastolic blood pressure gave similar results to SBP. CVD hazard ratios were intermediate between those from conventional multivariable studies and Mendelian randomization and stronger than those from clinical trials, approximately consistent with an effect of exposure duration on effect sizes. Plots of parental mortality against offspring SBP were approximately linear, supporting calls for lower SBP targets. Results suggest that conventional multivariable analyses of mortality and SBP are not substantially confounded by reverse causation and confirm positive effects of SBP on all-cause, CVD and diabetes mortality.

Pre-existing depression predicts survival in cardiovascular disease and cancer.

BACKGROUND: Previous studies have found depression to be negatively associated with the prognosis of both cardiovascular disease (CVD) and cancer, but this may partly reflect reverse causality. We limited the possibility of reverse causality by measuring depression before the first diagnosis of CVD or cancer. METHODS: We used an 11% longitudinal random sample of the Finnish population aged 25 years or older who are residents of Finland for at least 1 year between 1987 and 2007, with an 80% oversample of those who died during this period. Those who had their first incidence of coronary heart disease (CHD) (n=107 966), stroke (n=68 685) or cancer (n=113 754) between 1998 and 2012 were followed up for cause-specific mortality from the date of diagnosis until the end of 2012. Depression was defined as having antidepressant purchases two to three calendar years before the incidence. Logistic and Cox regression models were used to examine short-term and long-term mortality by depression status. RESULTS: Long-term mortality after diagnosis was 1.34 (95% CI 1.25 to 1.44) for CHD, 1.26 (95% CI 1.15 to 1.37) for stroke and 1.10 (95% CI 1.04 to 1.16) for cancer in those who had used antidepressants in two consecutive calendar years as compared with those with no purchases. Short-term mortality from CHD was elevated among persons with depression (OR=1.30; 95% CI 1.06 to 1.61), but no association was found for stroke. CONCLUSION: Pre-existing depression is associated with a worse prognosis of CHD, stroke and cancer. More attention in the healthcare system is needed for patients with chronic diseases who have a history of depression.

Familial Resemblance in Dietary Intakes of Children, Adolescents, and Parents: Does Dietary Quality Play a Role?

Information on familial resemblance is important for the design of effective family-based interventions. We aimed to quantify familial correlations and estimate the proportion of variation attributable to genetic and shared environmental effects (i.e., familiality) for dietary intake variables and determine whether they vary by generation, sex, dietary quality, or by the age of the children. The study sample consisted of 1435 families (1007 mothers, 438 fathers, 1035 daughters, and 1080 sons) from the multi-center I.Family study. Dietary intake was assessed in parents and their 2-19 years old children using repeated 24-h dietary recalls, from which the usual energy and food intakes were estimated with the U.S. National Cancer Institute Method. Food items were categorized as healthy or unhealthy based on their sugar, fat, and fiber content. Interclass and intraclass correlations were calculated for relative pairs. Familiality was estimated using variance component methods. Parent-offspring (r = 0.11-0.33), sibling (r = 0.21-0.43), and spouse (r = 0.15-0.33) correlations were modest. Parent-offspring correlations were stronger for the intake of healthy (r = 0.33) than unhealthy (r = 0.10) foods. Familiality estimates were 61% (95% CI: 54-68%) for the intake of fruit and vegetables and the sum of healthy foods and only 30% (95% CI: 23-38%) for the sum of unhealthy foods. Familial factors explained a larger proportion of the variance in healthy food intake (71%; 95% CI: 62-81%) in younger children below the age of 11 than in older children equal or above the age of 11 (48%; 95% CI: 38-58%). Factors shared by family members such as genetics and/or the shared home environment play a stronger role in shaping children's intake of healthy foods than unhealthy foods. This suggests that family-based interventions are likely to have greater effects when targeting healthy food choices and families with younger children, and that other sorts of intervention are needed to address the intake of unhealthy foods by children.

Association between long-term smoking and leisure-time physical inactivity: a cohort study among Finnish twins with a 35-year follow-up.

OBJECTIVES: To investigate longitudinal associations of smoking and a change in smoking status with leisure-time physical inactivity. In addition, to control whether familial confounding (genetics and shared environment) influences the associations. METHODS: Data were based on the population-based Finnish Adult Twin Cohort of 5254 twin individuals born in 1945-1957 (41% men) and who participated in all four surveys over a 35-year follow-up (1975-2011). Logistic and conditional logistic regression models with multiple covariates were used for analyses. RESULTS: Compared to never-smokers, long-term daily smokers (1975-1990) had the highest likelihood for both long-term inactivity and to change into inactive by 2011. Recurrent smoking was associated with long-term inactivity. Instead, in comparison to persistent daily smokers, quitting smoking decreased the likelihood of becoming physically inactive at leisure time. The associations remained in the analyses which accounted for multiple covariates and/or familial confounding. CONCLUSIONS: Daily smoking increases the likelihood of remaining or becoming physically inactive over the decades. Our results emphasize not only the importance of preventing smoking initiation, but also to support early smoking cessation in promotion of lifelong physical activity.

Cigarette smoking and alcohol use as predictors of disability retirement: A population-based cohort study.

BACKGROUND: This study investigated how cigarette smoking and alcohol use predict disability retirement. METHODS: Data from the longitudinal nationwide Finnish Twin Cohort study were analyzed, with clustered study design applied when computing 95% confidence intervals (CI). The sample included 21,719 individuals. Smoking and alcohol use were assessed with a questionnaire in 1975. Registry data on retirement events up till end of 2004 were obtained from the Social Insurance Institution and the Finnish Centre for Pensions. RESULTS: Disability pension was granted to 4251 participants. Among men, adjusted for age and alcohol use, former (HR=1.45, 95%CI 1.28, 1.65, p<.001) and daily smokers (HR=1.93, 95%CI 1.71, 2.17, p<.001) showed elevated disability pension risk compared to never smokers. Among women, daily smokers (HR=1.25, 95%CI 1.11, 1.40, <.001) had elevated risk. The age and smoking adjusted risk estimates for alcohol were elevated among abstainers (men HR=1.41, 95%CI 1.21, 1.65, p<.001; women HR=1.36, 95%CI 1.23, 1.52, p<.001) and heavy drinkers (men HR=1.30, 95%CI 1.18, 1.43, p<.001; women HR=1.34, 95%CI 1.04, 1.72, p=.026). Those being persistent smokers and binge drinkers had over three-fold disability risk compared to those who were binge drinkers but had only a few smoking years (men: HR=3.32, 95%CI 2.43, 4.54, p<.001; women: HR=4.05, 95%CI 2.05, 8.00, p<.001). Among men and women who were not binge drinkers, longer smoking duration was needed for elevated disability risk. CONCLUSIONS: Both smoking and excess alcohol use significantly predict disability retirement. In order to extend working careers, more attention should be paid to health behaviors, in addition to working conditions.

The CODATwins Project: The Cohort Description of Collaborative Project of Development of Anthropometrical Measures in Twins to Study Macro-Environmental Variation in Genetic and Environmental Effects on Anthropometric Traits.

For over 100 years, the genetics of human anthropometric traits has attracted scientific interest. In particular, height and body mass index (BMI, calculated as kg/m2) have been under intensive genetic research. However, it is still largely unknown whether and how heritability estimates vary between human populations. Opportunities to address this question have increased recently because of the establishment of many new twin cohorts and the increasing accumulation of data in established twin cohorts. We started a new research project to analyze systematically (1) the variation of heritability estimates of height, BMI and their trajectories over the life course between birth cohorts, ethnicities and countries, and (2) to study the effects of birth-related factors, education and smoking on these anthropometric traits and whether these effects vary between twin cohorts. We identified 67 twin projects, including both monozygotic (MZ) and dizygotic (DZ) twins, using various sources. We asked for individual level data on height and weight including repeated measurements, birth related traits, background variables, education and smoking. By the end of 2014, 48 projects participated. Together, we have 893,458 height and weight measures (52% females) from 434,723 twin individuals, including 201,192 complete twin pairs (40% monozygotic, 40% same-sex dizygotic and 20% opposite-sex dizygotic) representing 22 countries. This project demonstrates that large-scale international twin studies are feasible and can promote the use of existing data for novel research purposes.

Age- and sex-specific causal effects of adiposity on cardiovascular risk factors.

Observational studies have reported different effects of adiposity on cardiovascular risk factors across age and sex. Since cardiovascular risk factors are enriched in obese individuals, it has not been easy to dissect the effects of adiposity from those of other risk factors. We used a Mendelian randomization approach, applying a set of 32 genetic markers to estimate the causal effect of adiposity on blood pressure, glycemic indices, circulating lipid levels, and markers of inflammation and liver disease in up to 67,553 individuals. All analyses were stratified by age (cutoff 55 years of age) and sex. The genetic score was associated with BMI in both nonstratified analysis (P = 2.8 × 10(-107)) and stratified analyses (all P < 3.3 × 10(-30)). We found evidence of a causal effect of adiposity on blood pressure, fasting levels of insulin, C-reactive protein, interleukin-6, HDL cholesterol, and triglycerides in a nonstratified analysis and in the <55-year stratum. Further, we found evidence of a smaller causal effect on total cholesterol (P for difference = 0.015) in the ≥55-year stratum than in the <55-year stratum, a finding that could be explained by biology, survival bias, or differential medication. In conclusion, this study extends previous knowledge of the effects of adiposity by providing sex- and age-specific causal estimates on cardiovascular risk factors.

Weight status in young adulthood and survival after cardiovascular diseases and cancer.

BACKGROUND: Some studies have suggested that overweight is associated with lower mortality, but these results may be affected by reverse causality. We analysed how body mass index (BMI) in young adulthood is associated with mortality in the general population and after the diagnoses of coronary heart disease (CHD), stroke and cancer. METHODS: BMI was measured at an average age of 18 years in 734 438 Swedish men born in 1950-65. Diagnoses of CHD, stroke and cancer as well as all-cause mortality were derived from registers covering the whole population, up to 31 December 2010. The follow-up of 24.56 million person-years included 33 067 cases of mortality and 19 843 CHD, 13 578 stroke and 27 365 cancer diagnoses. Hazard ratios (HR) [with 95% confidence intervals (CI)] were estimated by the Cox proportional hazards model. RESULTS: Higher mortality in the whole cohort (HR = 1.26, 1.21-1.32) as well as after the diagnosis of CHD (HR = 1.33, 1.09-1.63) or cancer (HR = 1.13, 1.01-1.25) was found in moderately overweight men (BMI 25.0-27.4 kg/m(2)) as compared with normal weight men (BMI 20.1-22.4 kg/m(2)); for stroke patients the result for the same BMI categories was not statistically significant (HR = 1.17, 0.94-1.45). Mortality increased with increasing weight status and was highest in obese men (BMI >30 kg/m(2)): HR = 2.17 (2.02-2.34) for the whole cohort, 2.35 (1.81-3.05) after the diagnosis of CHD, 2.08 (1.56-2.77) after stroke and 1.68 (1.40-2.01) after cancer. CONCLUSIONS: Even moderate overweight in young adulthood increases all-cause mortality and mortality after the diagnosis of CHD, stroke and cancer in men. Preventing overweight in young adulthood remains as an important public health issue.

Persistent smoking as a predictor of disability pension due to musculoskeletal diagnoses: a 23 year prospective study of Finnish twins.

OBJECTIVE: To investigate whether stability or changes in smoking predict disability pension (DP) due to low back diagnoses (LBD) and musculoskeletal diagnoses (MSD) after taking familial confounding into account using a co-twin design. METHOD: Longitudinal smoking patterns and multiple covariates in a population-based cohort of 17,451 Finnish twins (6959 complete pairs) born before 1958 were surveyed through questionnaires in 1975 and 1981. The outcome data were collected from the national pension registers until the end of 2004. Cox proportional hazards regression models were used for statistical analyses. RESULTS: Disability pension due to low back diagnoses was granted to 408 individuals and disability pension due to musculoskeletal diagnoses to 1177 individuals during the follow-up of 23 years. Being a persistent smoker (current smoker both 1975 and 1981) predicted a significantly increased risk for disability pension (hazard ratio 1.69, 95% confidence interval 1.46, 1.97) compared to those individuals who had never smoked. The association remained when several confounding factors, including familial factors, were taken into account. CONCLUSION: Persistent smoking predicts early disability pension due to musculoskeletal diagnoses and low back diagnoses independently from numerous confounding factors, including familial effects shared by the co-twins.

Risk factors and their combined effects on the incidence rate of subarachnoid hemorrhage--a population-based cohort study.

BACKGROUND: Prospective studies on the risk factors for subarachnoid hemorrhage (SAH) are limited. Moreover, the effect of risk factors on the incidence rates of SAH is not well known about. AIMS: In this study, we aimed to identify risk factors for SAH and characterize subgroups in a population with a high incidence of SAH. METHODS: After recording multiple potential risk factors for SAH at the time of enrollment, first ever SAH events between 1972 and 2009 were recorded through the nationwide Causes of Death Register and Hospital Discharge Register for the population-based cohort of 64 349 participants, who participated in the National FINRISK Study between 1972 and 2007 in Finland. RESULTS: During the follow-up time of 1.26 million person-years (median 17.9 years, range 0 to 37.9 years), 437 persons experienced fatal or non-fatal SAH. Crude SAH incidence was 34.8 (95% confidence interval: 31.7-38.2) per 100 000 person-years among ≥ 25-year-old persons. Female sex, high blood pressure values and current smoking were confirmed as risk factors for SAH. Previous myocardial infarction, history of premature stroke (any kind) in mother and elevated cholesterol levels in men were identified as new risk factors for SAH. Depending on the combination of risk factors, SAH incidence varied between 8 and 171 per 100 000 person-years. CONCLUSIONS: New and previously reported risk factors appear to have a much stronger association with the incidence of SAH than is ordinarily seen in cardiovascular diseases. Risk factor assessments may facilitate the identification of high-risk persons who should be the focus of preventive interventions.

Cause-specific mortality of 1-year survivors of subarachnoid hemorrhage.

OBJECTIVE: To assess long-term, cause-specific mortality rates and rate ratios of the patients alive at 1 year after subarachnoid hemorrhage (SAH). METHODS: The population-based, prospective, cohort study with a nested case-control design consisted of 64,349 persons (aged 25-74 years at enrollment) who participated in the National FINRISK Study between 1972 and 2007. Four hundred thirty-seven SAH cases, 233 one-year SAH survivors, and their matched intrinsic controls were identified and followed up until the end of 2009 through the nationwide Finnish Causes of Death Register. All-cause mortality rates and rate ratios of the 1-year SAH survivors and controls were the main outcome measures. RESULTS: Eighty-eight (37.8%) of 233 one-year SAH survivors died during the total follow-up time of 2,487 person-years (median 8.6 years, range 0.1-35.8 years). The 1-year SAH survivors had a hazard ratio of 1.96 (95% confidence interval 1.57-2.47) for death compared with the matched general population with 10 controls for each SAH survivor. One-year SAH survivors had up to 31 additional deaths per 1,000 person-years compared with controls with minimal cerebrovascular risk factors. The higher long-term risk of death among SAH survivors was attributed solely to cerebrovascular diseases, and most important modifiable risk factors for death were smoking, high systolic blood pressure (≥ 159 mm Hg), and high cholesterol levels (≥ 7.07 mmol/L). CONCLUSION: One-year SAH survivors have excess mortality, which is attributed to an exceptional risk of deadly cerebrovascular events. Aggressive post-SAH cerebrovascular risk factor intervention strategies are highly warranted.