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Cardiovascular disease and all-cause mortality: influence of fitness, fatness and genetic factors
Umeå University, Faculty of Medicine, Department of Community Medicine and Rehabilitation, Geriatric Medicine.
2017 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Background

Low aerobic fitness and obesity are associated with atherosclerosis, and thereforegreatly increase the risk of cardiovascular disease (CVD) and early death. It has long been known that atherosclerosis my begin early in life. Despite this fact, it remains unknown how obesity and aerobic fitness early in life influence the risks of atherosclerosis, CVD and death. Furthermore, it is unknown whether high aerobic fitness can compensate for the risks associated with obesity, and how genetic confounding affects the relationshipsof aerobic fitness with CVD and all-cause mortality. Thus, the main aims of this thesis were to investigate the associations of aerobic fitness in late adolescence with myocardial infarction (Study I), stroke (Study II) and all-cause mortality (Study III), and how genetic confounding influences the relationshipsof aerobic fitness with CVD, diabetes and death (Study IV).

Methods

The study population comprised up to1.3 million men who participated in mandatory Swedish military conscription. During conscription, all conscripts underwent highly standardized tests to assess aerobic fitness, body mass index, blood pressure and cognitive function. A physician also examined all conscripts. Data on subjects’ diagnoses, death and socioeconomic status during follow-up were retrieved using record linkage. Subjects were subsequently followed until the study endpoint, date of death or date of any outcome of interest. Associations between baseline variables and the risks of adverse outcomes were assessed using Cox’s proportional hazard models. Genetic confounding of the relationships between aerobic fitness and diabetes, CVD and death was assessed using a twin population and a paired logistic regression model.

Results

In Study I, low aerobic fitness at conscription was associated with an increased risk of myocardial infarction (MI) during follow-up (hazard ratio [HR] 0.82 per standard deviation increase). Similarly, in Study II, high aerobic fitness reduced the risk of stroke (HR 0.84 for ischemic stroke, HR 0.82 for hemorrhagic stroke; P < 0.001 for all), and obesity was associated with an increased risk of stroke (HR 1.15 for ischemic stroke, HR 1.18 for hemorrhagic stroke; P < 0.001 for all). In Study III, high aerobic fitness was also associated with reduced all-cause mortality later in life (HR 0.49, P < 0.001). High aerobic fitness exerted the strongest protection against death from substance and alcohol abuse, suicide and trauma (HRs 0.20, 0.41 and 0.52, respectively; P < 0.001 for all). Obese individuals with aerobic fitness were at higher risk of MI and all-cause mortality than were normal-weight individuals with low fitness (Studies I and III). In Study IV, fit twins had no reduced risk of CVD or death during follow-up compared with their unfit twin siblings (odds ratio 1.11, 95% confidence interval 0.88–1.40), regardless of how large the difference in fitness was. However, the fitter twins were protected against diabetes during follow-up.

Conclusions

Already early in life, aerobic fitness is a strong predictor of CVD and all-cause mortality later in life. In contrast to the “fat but fit” hypothesis, it seems that high aerobic fitness cannot fully compensate for the risks associated with obesity. The associationsof aerobic fitness with CVD and all-cause mortality appear to be mediated by genetic factors. Together, these findings have implications for the view of aerobic fitness as a causal risk factor for CVD and early death.

Place, publisher, year, edition, pages
Umeå: Umeå Universitet , 2017. , 83 p.
Series
Umeå University medical dissertations, ISSN 0346-6612 ; 1865
Keyword [en]
all-cause mortality, aerobic fitness, obesity, cardiovascular disease, stroke, myocardial infarction
National Category
Public Health, Global Health, Social Medicine and Epidemiology Cardiac and Cardiovascular Systems
Research subject
Epidemiology; Population studies; Cardiology
Identifiers
URN: urn:nbn:se:umu:diva-130312ISBN: 978-91-7601-611-4 (print)OAI: oai:DiVA.org:umu-130312DiVA: diva2:1066375
Public defence
2017-02-10, Aulan, Vårdvetarhuset, Umeå universitet, Umeå, 09:00 (Swedish)
Opponent
Supervisors
Available from: 2017-01-20 Created: 2017-01-17 Last updated: 2017-01-27Bibliographically approved
List of papers
1. High aerobic fitness in late adolescence is associated with a reduced risk of myocardial infarction later in life: a nationwide cohort study in men
Open this publication in new window or tab >>High aerobic fitness in late adolescence is associated with a reduced risk of myocardial infarction later in life: a nationwide cohort study in men
2014 (English)In: European Heart Journal, ISSN 0195-668X, E-ISSN 1522-9645, Vol. 35, no 44, 3133-3140 p.Article in journal (Refereed) Published
Abstract [en]

AIMS: Cardiovascular disease is the leading cause of morbidity and mortality worldwide, and signs of atherosclerosis are present in all large arteries already in adolescence. We investigated the association between high physical fitness in late adolescence and myocardial infarction (MI) later in life.

METHODS AND RESULTS: The study cohort comprised 743 498 Swedish men examined at the age of 18 years during conscription 1969-84. Aerobic fitness (Wmax) and muscle strength at conscription were measured using standardized methods. Myocardial infarctions occurring in the cohort were tracked through national registers. During a median follow-up period of 34 years, 11 526 MIs were registered in the cohort. After adjusting for age, body mass index (BMI), diseases, education, blood pressure, and socio-economic factors, one standard deviation increase in the level of physical fitness (Wmax) was associated with an 18% decreased risk of later MI [hazard ratio (HR) 0.82, 95% confidence interval (CI) 0.80-0.85]. The beneficial effects of Wmax were significant across all recognized BMI groups, ranging from lean (BMI < 18.5) to obese (BMI > 30) (P < 0.05 for all). However, obese men (BMI > 30) in the highest fourth of Wmax had a higher risk of MI than did lean men (BMI < 18.5) in the highest (HR 4.6, 95% CI 1.9-11.2), and lowest (HR 1.7, 95% CI 1.2-2.6) fourth of Wmax.

CONCLUSIONS: We report a significant graded association between aerobic fitness in late adolescence and MI later in life in men. However, obese men with a high aerobic fitness had a higher risk of MI than lean men with a low aerobic fitness.

Place, publisher, year, edition, pages
Oxford University Press, 2014
Keyword
Treatment, Interdisciplinary Health Team, Chronic Pain, Program Evaluation, Myocardial infarction, Physical fitness, Adolescent men
National Category
Cardiac and Cardiovascular Systems Sport and Fitness Sciences
Identifiers
urn:nbn:se:umu:diva-86981 (URN)10.1093/eurheartj/eht527 (DOI)000345378300015 ()24398666 (PubMedID)
Available from: 2014-03-17 Created: 2014-03-17 Last updated: 2017-01-18Bibliographically approved
2. Risk factors assessed in adolescence and the later risk of stroke in men: a 33-year follow-up study
Open this publication in new window or tab >>Risk factors assessed in adolescence and the later risk of stroke in men: a 33-year follow-up study
2015 (English)In: Cerebrovascular Diseases, ISSN 1015-9770, E-ISSN 1421-9786, Vol. 39, no 1, 63-71 p.Article in journal (Refereed) Published
Abstract [en]

BACKGROUND: Stroke is a common cause of death, and a leading contributor to long-term disability. The cost associated with the disease is great. Several modifiable risk factors for stroke have been found in older cohorts; however, no study to date has investigated the effects of these risk factors from late adolescence.

METHODS: The study cohort comprised 811,579 Swedish men (mean age, 18 years) that participated in the mandatory military conscription service in Sweden between 1969 and 1986. Some risk factors for stroke, such as body mass index, systolic and diastolic blood pressure, and cognitive function, were assessed at conscription. Aerobic fitness was also assessed at conscription, using a braked ergometer cycle test. Other risk factors for stroke, including stroke in subjects' parents, and socioeconomic factors including highest achieved level of education and annual income 15 years after conscription, were collected through national register linkage using the personal identification number. Stroke diagnosis among the study participants was tracked in the National Hospital Discharge Patient Register.

RESULTS: During a median follow-up period of 33 years 6,180 ischemic strokes and 2,104 hemorrhagic strokes were diagnosed in the cohort at a mean age of 47.9 years. Strong independent risk factors (all p <1.0 × 10-(6)) for ischemic stroke included low aerobic fitness (hazard ratio [HR], 0.84 per standard deviation [SD] increase), high BMI (HR, 1.15 per SD increase), diabetes (HR, 2.85), alcohol intoxication (HR, 1.93), low annual income (HR, 0.85 per SD decrease), and stroke in the mother (HR, 1.31). Similar risk factors were found for hemorrhagic stroke including low aerobic fitness (HR, 0.82 per SD increase), high BMI (HR, 1.18 per SD increase) alcohol intoxication (HR, 2.92), diabetes (HR, 2.06), and low annual income (HR, 0.75). The population attributable risks associated with all evaluated risk factors were 69% for ischemic stroke and 88% for hemorrhagic stroke (p < 0.001 for both).

CONCLUSIONS: In the present study we have shown that several known risk factors for stroke are present already in late adolescence, and that they are independent of each other. The strongest risk factors were low physical fitness, high BMI, diabetes, low annual income and a maternal history of stroke. Several of the aforementioned risk factors are potentially modifiable.

National Category
Cardiac and Cardiovascular Systems Public Health, Global Health, Social Medicine and Epidemiology
Identifiers
urn:nbn:se:umu:diva-99250 (URN)10.1159/000369960 (DOI)000348213700008 ()25547343 (PubMedID)2-s2.0-84920838888 (Scopus ID)
Available from: 2015-02-05 Created: 2015-02-05 Last updated: 2017-01-18Bibliographically approved
3. Aerobic fitness in late adolescence and the risk of early death: a prospective cohort study of 1.3 million Swedish men
Open this publication in new window or tab >>Aerobic fitness in late adolescence and the risk of early death: a prospective cohort study of 1.3 million Swedish men
2016 (English)In: International Journal of Epidemiology, ISSN 0300-5771, E-ISSN 1464-3685, Vol. 45, no 4, 1159-1168 p.Article in journal (Refereed) Published
Abstract [en]

BACKGROUND: Fitness level and obesity have been associated with death in older populations. We investigated the relationship between aerobic fitness in late adolescence and early death, and whether a high fitness level can compensate the risk of being obese.

METHODS: The cohort comprised 1 317 713 Swedish men (mean age, 18 years) that conscripted between 1969 and 1996. Aerobic fitness was assessed by an electrically braked cycle test. All-cause and specific causes of death were tracked using national registers. Multivariable adjusted associations were tested using Cox regression models.

RESULTS: During a mean follow-up period of 29 years, 44 301 subjects died. Individuals in the highest fifth of aerobic fitness were at lower risk of death from any cause [hazard ratio (HR), 0.49; 95% confidence interval (CI), 0.47-0.51] in comparison with individuals in the lowest fifth, with the strongest association seen for death related to alcohol and narcotics abuse (HR, 0.20; 95% CI, 0.15-0.26). Similar risks were found for weight-adjusted aerobic fitness. Aerobic fitness was associated with a reduced risk of death from any cause in normal-weight and overweight individuals, whereas the benefits were reduced in obese individuals (P < 0.001 for interaction). Furthermore, unfit normal-weight individuals had 30% lower risk of death from any cause (HR, 0.70; 95% CI, 0.53-0.92) than did fit obese individuals.

CONCLUSIONS: Low aerobic fitness in late adolescence is associated with an increased risk of early death. Furthermore, the risk of early death was higher in fit obese individuals than in unfit normal-weight individuals.

Place, publisher, year, edition, pages
Oxford University Press, 2016
Keyword
Fitness, obesity, death
National Category
Geriatrics Environmental Health and Occupational Health
Identifiers
urn:nbn:se:umu:diva-121364 (URN)10.1093/ije/dyv321 (DOI)000393182000030 ()26686843 (PubMedID)
Available from: 2016-06-01 Created: 2016-06-01 Last updated: 2017-03-06Bibliographically approved
4. The Risks of Cardiovascular Disease, Death and Diabetes in Twin Pairs with Discrepant Aerobic Fitness: A Nationwide Cohort Study
Open this publication in new window or tab >>The Risks of Cardiovascular Disease, Death and Diabetes in Twin Pairs with Discrepant Aerobic Fitness: A Nationwide Cohort Study
(English)Manuscript (preprint) (Other academic)
Abstract [en]

Background: In observational studies, low physical fitness has been a strong risk factor for cardiovascular disease (CVD), diabetes and mortality. As physical fitness is under strong genetic control, genetic confounding may have influenced these associations.

Methods: The study population comprised 5,710 male twin pairs that took part in mandatory Swedish conscription during the years 1972–1996. All pairs (mean age, 18.2 years) were discordant for physical fitness. The primary endpoint of CVD (stroke or myocardial infarction), or mortality and the secondary endpoint of diabetes during follow up was compared between more-fit and less-fit twin pairs using a co-twin stratified conditional logistic regression models.

Results: During a mean follow-up period of 30 years, 74 cases of CVD and 150 deaths occurred among less-fit twins, and 76 cases of CVD and 152 deaths occurred among more-fit twins. Accordingly, the more-fit twins did not have a lower risk CVD or death (multi-adjusted odds ratio [OR] 1.11, 95% confidence interval [CI] 0.88–1.40). These results remained similar when the risks of CVD and death were compared in twin pairs with at least 50 Watt difference in physical fitness (OR, 1.09; 95% CI, 0.56–2.12). In contrast, during follow up the risk of diabetes was significantly lower in more-fit twins compared to in less-fit twins (OR 0.74, 95% CI 0.55–0.98). The effect with respect to diabetes was significantly different than the risk associated with the main outcome (P = 0.032 by testing heterogeneity). Conclusions: In twin pairs discordant for physical fitness, higher fitness was not associated with a decreased risk of CVD or death, but it was associated with the onset of diabetes. These results suggest that lifestyle-obtained fitness may not be effective in reducing the risk CVD and death. 

National Category
Public Health, Global Health, Social Medicine and Epidemiology
Identifiers
urn:nbn:se:umu:diva-130342 (URN)
Available from: 2017-01-17 Created: 2017-01-17 Last updated: 2017-01-18

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