Oxidized LDL and physical fitness in healthy young men: associations with body composition, smoking, metabolic syndrome and androgen status

Background: In the past, oxidized low density lipoprotein (ox-LDL) has been associated with an unbeneficial lipid profile. This atherogenic lipid profile increases the risk of atherosclerotic cardiovascular diseases. Physical fitness has substantial effect on serum lipoprotein concentration as well as body composition and humoral responses, however interrelationships between ox-LDL and physical fitness have not been widely examined in a nationally representative sample. Aims: This thesis evaluates how cardiorespiratory and muscular fitness associate with ox-LDL lipids and how the other known risk factors of atherosclerosis might alter these associations. Subjects and Methods: The study cohort consisted of 846 healthy young males (mean age 25.1, SD 4.6) who were gathered by voluntary nationwide recruitment. Each participant conducted a series of physical fitness tests (cardiorespiratory and muscular fitness) and answered a detailed questionnaire that included lifestyle habits (i.e. smoking and leisuretime physical activity). Venous blood samples including ox-LDL and serum lipids were also collected. Results: Higher levels of ox-LDL were found in overweight and obese men, however, high cardiorespiratory fitness seemed to protect the overweight from high levels of ox-LDL. Young men who smoked and had poor cardiorespiratory or muscular fitness possessed a higher concentration of ox-LDL lipids when compared to comparable levels of cardiorespiratory or muscular fitness non-smoking young men. Metabolic syndrome was associated with increased levels of ox-LDL and high levels of ox-LDL combined with poor cardiorespiratory and abdominal muscle fitness seems to predict metabolic syndrome in young men. Also, participants with poor cardiorespiratory fitness and low levels of testosterone had higher levels of ox-LDL when compared to participants with high cardiorespiratory fitness / low testosterone as well as those with poor cardiorespiratory fitness / high testosterone. Conclusions: Good cardiorespiratory and muscular fitness protects young men from increased levels of ox-LDL lipids. This association was discovered in young men who were categorized as being overweight, smokers, metabolic syndrome or with low levels of testosterone. Being fit seems to prevent higher levels of ox-LDL, even in young healthy

“IF ONLY I COULD�? ~ “THERE IS ALWAYS A LOOPHOLE"? Hope and hopelessness experienced by the severely depressive and nondepressive

The aim of this research was to structure a conceptual model of hope and hopelessness based on dictionary definitions, and to verify this model on the basis of the experiences of the severely depressive and non-depressive elderly. This research has produced a substantive theory of hope and hopelessness which is based on the experiences of the depressive and non-depressive elderly, and on the concept analysis of hope and hopelessness based on English dictionary definitions. The patients who participated in the research were 65 years old and older men and women (n=22) who had been admitted to a psychiatric hospital because of major depression, and another group: the non-depressive elderly (n=21), who were recruited from the pensioners’ clubs. The data were collected in interviews using the Clinical Assessment Tool, developed by Farran, Salloway and Clark (1990) and Farran, Wilken and Popovich (1992), and it produced 553 pages of written text, which were analysed using the ATLAS/ti programme. ATLAS/ti is a tool for analysing qualitative data and is based on Grounded Theory. The medical and nursing records of the depressive elderly completed source triangulation. The concept analysis of hope and hopelessness was made on the basis of the definitions of English dictionaries (n=103), using semantic analysis and the ATLAS/ti programme. The most important hope-promoting factors were human relations, health and managing in everyday living. Autonomy, self-determination and feeling of security were highly appreciated among the elderly. Hopelessness, on the other hand, was most often associated with the same factors: human relations, health and everyday living. Especially, losses of significant others were experienced as strongly hope-diminishing. Old age had brought freedom from duties concerning others, but now, when you finally had an opportunity to enjoy yourself, you could not accomplish anything; you were clasped in the arms of total inability, depression had come. The most obvious difference in the life course of the depressive and nondepressive elderly was the abundance of traumatic experiences in the childhood and youth of the depressive elderly. The continuous circulation of fearful thoughts was almost touchable, and suicidality was described in connection with these thoughts. You were afraid to be awake and also to go to sleep. Managing day by day was the goal. The research produced the Basic Social Process (BSP) of hope: achieving - maintaining - losing, which expresses a continuous balancing between Being without and Being with. The importance of the object of hope was combined with the amount of hope and disappointment. The process of approaching defined the realisation of hope and the process of withdrawal that of losing. Joy and security versus grief and insecurity defined the Being with and Being without. Two core categories were found. The first one “If only I could�? reflects lack of energy, lack of knowledge, lack of courage and lack of ability. The other one “There is always a loophole�? reflects deliberate tracing of possibilities and the belief in finding solutions, and managing.

Social Solidarity and Fear of Crime - Community and Individual Approaches in Responses to Mass Violence after School Shootings

The aim of this study was to examine community and individual approaches in responses to mass violence after the school shooting incidents in Jokela (November 2007) and Kauhajoki (September 2008), Finland. In considering the community approach, responses to any shocking criminal event may have integrative, as well as disintegrative effects, within the neighborhood. The integration perspective argues that a heinous criminal event within one’s community is a matter of offence to collectively held feelings and beliefs, and increases perceived solidarity; whereas the disintegration perspective suggests that a criminal event weakens the social fabric of community life by increasing fear of crime and mistrust among locals. In considering the individual approach, socio-demographic factors, such as one’s gender, are typically significant indicators, which explain variation in fear of crime. Beyond this, people are not equally exposed to violent crime and therefore prior victimization and event related experiences may further explain why people differ in their sensitivity to risk from mass violence. Finally, factors related to subjective mental health, such as depressed mood, are also likely to moderate individual differences in responses to mass violence. This study is based on the correlational design of four independent cross-sectional postal surveys. The sampling frames (N=700) for the surveys were the Finnish speaking adult population aged 18–74-years. The first mail survey in Jokela (n=330) was conducted between May and June 2008, approximately six months from the shooting incident at the local high-school. The second Jokela survey (n=278) was conducted in May–June of 2009, 18 months removed from the incident. The first survey in Kauhajoki (n=319) was collected six months after the incident at the local University of Applied Sciences, March– April 2009, and the second (n=339) in March–April 2010, approximately 18 months after the event. Linear and ordinal regression and path analysis are used as methods of analyses. The school shootings in Jokela and Kauhajoki were extremely disturbing events, which deeply affected the communities involved. However, based on the results collected, community responses to mass violence between the two localities were different. An increase in social solidarity appears to apply in the case of the Jokela community, but not in the case of the Kauhajoki community. Thus a criminal event does not necessarily impact the wider community. Every empirical finding is most likely related to different contextual and event-specific factors. Beyond this, community responses to mass violence in Jokela also indicated that the incident was related to a more general sense of insecurity and was also associating with perceived community deterioration and further suggests that responses to mass violence may have both integrating and disintegrating effects. Moreover, community responses to mass violence should also be examined in relation to broader social anxieties and as a proxy for generalized insecurity. Community response is an emotive process and incident related feelings are perhaps projected onto other identifiable concerns. However, this may open the door for social errors and, despite integrative effects, this may also have negative consequences within the neighborhood. The individual approach suggests that women are more fearful than men when a threat refers to violent crime. Young women (aged 18–34) were the most worried age and gender group as concerns perception of threat from mass violence at schools compared to young men (aged 18–34), who were also the least worried age and gender group when compared to older men. It was also found that concerns about mass violence were stronger among respondents with the lowest level of monthly household income compared to financially better-off respondents. Perhaps more importantly, responses to mass violence were affected by the emotional proximity to the event; and worry about the recurrence of school shootings was stronger among respondents who either were a parent of a school-aged child, or knew a victim. Finally, results indicate that psychological wellbeing is an important individual level factor. Respondents who expressed depressed mood consistently expressed their concerns about mass violence and community deterioration. Systematic assessments of the impact of school shooting events on communities are therefore needed. This requires the consolidation of community and individual approaches. Comparative study designs would further benefit from international collaboration across disciplines. Extreme school violence has also become a national concern and deeper understanding of crime related anxieties in contemporary Finland also requires community-based surveys.

Cardiac Imaging in the Diagnosis of Coronary Artery Disease: The Value of Quantitative Imaging of Myocardial Perfusion and Deformation

Atherosclerosis is a chronic and progressive disease of the vasculature. Increasing coronary atherosclerosis can lead to obstructive coronary artery disease (CAD) or myocardial infarction. Computed tomography angiography (CTA) allows noninvasive assessment of coronary anatomy and quantitation of atherosclerotic burden. Myocardial blood flow (MBF) can be accurately measured in absolute terms (mL/g/min) by positron emission tomography (PET) with [15O] H O as a radiotracer. We studied the coronary microvascular dysfunction as a risk factor for future coronary calcification in healthy young men by measuring the coronary flow reserve (CFR) which is the ratio between resting and hyperemic MBF. Impaired vasodilator function was not linked with accelerated atherosclerosis 11 years later. Currently, there is a global interest in quantitative PET perfusion imaging. We established optimal thresholds of [15O] H O PET perfusion for diagnosis of CAD (hyperemic MBF of 2.3 mL/g/min and CFR of 2.5) in the first multicenter study of this type (Turku, Amsterdam and Uppsala). In myocardial bridging a segment of the coronary artery travels inside the myocardium and can be seen as intramural course (CTA) or systolic compression (invasive coronary angiography). Myocardial bridging is frequently linked with proximal atherosclerotic plaques. We used quantitative [15O] H O PET perfusion to evaluate the hemodynamic effects of myocardial bridging. Myocardial bridging was not associated with decreased absolute MBF or increased atherosclerotic burden. Speckle tracking allows quantitative echocardiographic imaging of myocardial deformation. Speckle tracking during dobutamine stress echocardiography was feasible and comparable to subjective wall motion analysis in the diagnosis of CAD. In addition, it correctly risk stratified patients with multivessel disease and extensive ischemia.

Thyroid function in the elderly and sex hormones in elderly men: reference intervals and associations with health

Aims: The aims were to create clinically feasible reference intervals for thyroidstimulating hormone (TSH) and free thyroxine (FT4) and to analyze associations between thyroid function and self-rated health, neuropsychiatric symptoms, depression and dementia in the elderly. The second aim was also to establish reference intervals for sex hormones and to analyze associations between sex hormone levels and self-rated health, symptoms, depression and dementia in elderly men. Subjects and methods: The study population comprised 1252 subjects aged 65 years or over, living in the municipality of Lieto, south-western Finland. Self-rated health, life satisfaction, symptoms, depression, and dementia were assessed with specific questions, clinical examination and tools such as the Zung Self-report Depression Scale and the Mini-Mental State Examination. Independent variables were dichotomized, and associations of these variables with TSH, FT4 or sex hormone levels were assessed. Levels of TSH and FT4 in thyroid disease–free women and women treated with thyroxine were also compared. Results: Elevated concentrations of thyroid peroxidase antibodies (TPOAb) or thyroglobulin antibodies (TgAb) were found to have a marked effect on the upper reference limit for TSH among women, who were thyroid antibody positive more higher than suggested in several recent guidelines. After age adjustment, there were no associations between TSH levels and self-rated health, life satisfaction, or most neuropsychiatric symptoms in the thyroid disease-free population. Although women with thyroxine treatment for primary hypothyroidism had far higher TSH levels than thyroid disease-free women, there were no differences between thyroid-disease free women and women with stable thyroxine treatment regarding self-rated health, life satisfaction or symptoms. Age had a significant positive association with luteinizing hormone (LH), follicle 2 practice, one range in men aged 65 years or over can be used for T, E2 and FSH measured with the AutoDelfia method, but two separate reference intervals should be used for fT, LH and SHBG. After adjustment for age, higher levels of T and fT were associated with better self-rated health (SRH) in the reference population. After adjustment for age and body mass index (BMI), there were no associations between sex hormone concentrations and self-rated health, life satisfaction or most symptoms in concentration. Conclusion: Age-specific reference intervals were derived for thyroid function and sex hormones based on comprehensive data from a community-dwelling population with a high participation rate. The results do not support the need to decrease the upper reference limit for TSH or to lower the optimal TSH target in levothyroxine treatment in older adults, as recommended in recent guidelines. Older age or being overweight symptoms among elderly men. The associations of single symptoms with T levels were inconsistent among elderly men, although the association of low T level with diagnosed depression might be clinically significant.

Surgically-treated Hip Fracture in older People. With Special Emphasis on Mortality Analysis

Hip fractures are associated with significant morbidity and mortality. Cervical and trochanteric fractures have a different morphometry, surgical treatment, and outcome. Polypharmacy, common in older people, is associated with increased mortality. The risk factors for mortality can be identified based on cause-of-death analysis. In this population-based study, 461 older, surgically in 1999-2000 treated hip fracture patients were enrolled. Incidence, morphometry, medication, mortality, and cause-of-death were analysed. Hip fractures were most commonly sustained by women, occurred mostly indoors, and often in institutions. One in four patients had sustained a previous fracture. Routine clinical radiographs revealed no differences in the hip geometry between hip fracture types. Age-adjusted mortality was higher in men than in women during the follow-up. Chronic lung disease and male sex were predictors of mortality after cervical fracture. In men, potent anticholinergics were associated with excess age-adjusted mortality. Men were more likely to die from circulatory disease and dementia after hip fracture than women. Mortality after hip fracture was 3-fold higher than that of the general population, including every cause-of-death class. Fracture prevention in institutions and homes, indoor safety measures, and treatment of chronic lung diseases should be encouraged. Hip morphometry analyses require more accurate measures than that provided by routine radiographs. Careful use of potent anticholinergics may reduce mortality. Compared to the general population, excess mortality after hip fracture was evident up to 9 years after hip fracture. Cause-of-death analysis indicates that all major comorbidities require optimal treatment after hip fracture surgery.

Fractures in older people - incidence, predictors and consequences

In older populations, fractures are common and the consequences of fractures may be serious both for an individual and for society. However, information is scarce about the incidence, predictors and consequences of fractures in population-based unselected cohorts including both men and women and a long follow-up. The objective of this study was to analyse the incidence and predictors of fractures as well as functional decline and excess mortality due to fractures, among 482 men and 695 women aged 65 or older in the municipality of Lieto, Finland from 1991 until 2002. In analyses, Poisson’s, Cox proportional Hazards and Cumulative Logistic regression models were used for the control of several confounding variables. During the 12-year follow-up with a total of 10 040 person-years (PY), 307 (26%) persons sustained altogether 425 fractures of which 77% were sustained by women. The total incidence of fractures was 53.4 per 1000 PY (95% confidence intervals [95% CI]: 47.9 - 59.5) in women and 24.9 per 1000 PY (95% CI: 20.4 - 30.4) in men. The incidence rates of fractures at any sites and hip fractures were associated with increasing age. No significant changes in the ageadjusted incidence rates of fractures were found in either gender during the 12-year follow-up. The predictors of fractures varied by gender. In multivariate analyses, reduced handgrip strength and body mass index (BMI) lower than 30 in women and a large number of depressive symptoms in men were independent predictors of fractures. A compression fracture in one or more thoracic or upper lumbar vertebras on chest radiography at baseline was associated with subsequent fractures in both genders. Lower body fractures independently predicted both short- (0-2 years) and long-term (up to 8 years) functional decline in mobility and activities of daily living (ADL) performance during the 8-year follow-up. Upper body fractures predicted decline in ADL performance during longterm follow-up. In the 12-year follow-up, hip fractures in men (Hazard Ratio [HR] 8.1, 95% CI: 4.4-14.9) and in women (HR 3.0, 95% CI: 1.9-4.9), and fractures at the proximal humerus in men (HR 5.4, 95% CI: 1.6-17.7) were independently associated with excess mortality. In addition, leisure time inactivity in physical exercise predicted independently both functional decline and excess mortality. Fractures are common among older people posing serious individual consequences. Further studies about the effectiveness of preventing falls and fractures as well as improving care and rehabilitation after fractures are needed.

Pharmacokinetics of Oxycodone and Paracetamol in the Elderly. Clinical Pharmacokinetic Study on Orthopaedic Surgical Patients and Healthy Volunteers

The proportion of elderly people over 65 years of age in Finland is expected to grow to over 25% by the 2025. It has been estimated that elderly people today consume nearly 40% of all drugs. Age brings about number of physiological changes that may affect the disposition, metabolism and excretion of drugs. The function of heart, lungs, liver and kidneys decreases even in healthy people, as they get older. The proportion of total body water decreases and the relative fat percentage increases. Also several other factors such as concurrent diseases, concomitant medication and nutritional factors have an effect on drug therapy in elderly. Age increases the risk of adverse drug reactions, which most often are dose-dependent. Despite all this there are not enough studies involving the elderly people and the elderly are most often excluded from clinical trials. Oxycodone is a strong opioid analgesic, which is used to treat moderate or severe pain. Paracetamol is a widely used nonopioid analgesic, which has become popular in the treatment of pain in many patient groups. In this series of studies the pharmacokinetics of oral and intravenous oxicodone as well as intravenous paracetamol in the elderly and young adult patients were investigated. Also a study investigating the interaction of oral antibiotic clarityhromycin, a known cytochrome P450 (CYP) 3A4 inhibitor, with oxycodone pharmacokinetics and pharmacodynamics in elderly and young healthy volunteers was carried out. The pharmacokinetics of oxycodone showed a clear age depency. Patients over 70 years had 50-80% higher mean exposure to oral oxycodone and a twofold greater plasma concentration than young adults 12 h after ingestion of the drug. Elderly patients had 40-80% greater exposure to intravenous oxycodone and patients over 80 years had over twofold greater plasma concentrations 8 h post dose than the young adults. The elderly patients had also greater exposure to intra venous paracetamol compared to young adults. Clarithromycin increased the exposure to oral oxycodone in both young and elderly volunteers. The elderly had marked interindividual variation in the pharmacokinetics and pharmacodynamics when clarithromycin was given concomitantly with oxycodone. Because the pharmacokinetics of oxycodone and intravenous paracetamol depend on the age of the subject, it is important to titrate the analgesic dose individually in the elderly.