Periodontal diseases may increase risk of vascular calcification in cardiovascular diseases but the potential mechanisms are not defined. Fetuin, a naturally-occurring serum glycoprotein in humans, protects against ectopic arterial calcification. We considered that patients with periodontitis could be at increased risk of developing calcifying atheromas because periodontal-disease associated enzymes may enter the circulation and subsequently degrade fetuin, thereby disrupting its ability to inhibit calcification. By in silico investigation, MMP -3 and -7 were predicted to cleave fetuin but only MMP-7 actually degraded human fetuin in vitro. MMP-7 degradation of fetuin was time- and concentration- dependent and was inhibited by an MMP Inhibitor. By mass spectrometry the presence of novel, MMP-7-mediated cleavage sites in fetuin were found. Fetuin bound tightly to MMP-7 (kd =2.96 x 10-9 M). The degradation of fetuin by MMP-7 could explain, at least in part, the apparent association between periodontal diseases and calcifying atheromas.

Periodontal diseases may increase risk of vascular calcification in cardiovascular diseases but the potential mechanisms are not defined. Fetuin, a naturally-occurring serum glycoprotein in humans, protects against ectopic arterial calcification. We considered that patients with periodontitis could be at increased risk of developing calcifying atheromas because periodontal-disease associated enzymes may enter the circulation and subsequently degrade fetuin, thereby disrupting its ability to inhibit calcification. By in silico investigation, MMP -3 and -7 were predicted to cleave fetuin but only MMP-7 actually degraded human fetuin in vitro. MMP-7 degradation of fetuin was time- and concentration- dependent and was inhibited by an MMP Inhibitor. By mass spectrometry the presence of novel, MMP-7-mediated cleavage sites in fetuin were found. Fetuin bound tightly to MMP-7 (kd =2.96 x 10-9 M). The degradation of fetuin by MMP-7 could explain, at least in part, the apparent association between periodontal diseases and calcifying atheromas.

Introduction: Cardiovascular disease (CVD) is the leading cause of global mortality and its prevalence is increasing among black South Africans in spite of their favourable lipid profile. Apolipoprotein E (ApoE) is a well-described risk factor for CVD and certain polymorphisms within this gene alter the lipid profile. The author hypothesised that there are population-specific effects within the ApoE gene that are responsible for the favourable lipid profile observed in black South Africans whose effects are being altered by environmental factors. Objectives: The main aim of this study was to investigate the associations between specific ApoE single nucleotide polymorphisms (SNPs) and the lipid profile of a black South African population, taking into account certain environmental and phenotypic factors in order to explore the interaction effects between these variables. Methods: Genotyping within this cross-sectional study (n=1 588), nested within the Prospective Urban and Rural Epidemiology (PURE) study, was achieved using Illumina‘s® GoldenGate Genotyping Assay with VeraCode® technology on the BeadXpress® platform (proprietary multiplex fluorescent hybridisation assays on a bead array substrate) or the Bio-Rad CFX Manager© (version 2.0). The Konelab20i™ auto analyser was used for quantitative determination of serum total cholesterol; high-density lipoprotein cholesterol (HDL-C) and triglyceride (TG) concentrations. Low-density lipoprotein cholesterol concentrations were estimated by the Friedewald equation. Results: All SNPs adhered to the assumptions of the Hardy-Weinberg equilibrium, yet the frequency of the SNPs often differed from that reported in other ethnic groups. The well-reported rs429358 and rs7412 SNPs (as the constituent SNPs of the haplotype-genotypes) presented with the strongest associations with various components of the blood lipid profile in the black South African cohort under investigation. Two gene-environment (rs405509 and rs7412) interaction effects on TG remained significant after conducting post hoc tests. Two genotype-phenotype interaction effects between the rs7412 SNP and body mass index and gamma-glutamyl transferase on the HDL-C concentrations remained significant after conducting post hoc tests. Conclusions: The variety of associations between these particular SNPs and the blood lipid profile determined in the present cohort strongly indicates that it is integral to any public health investigation into CVD development that these SNPs be investigated. This study further produced greater insight into the biological mechanisms underlying serum lipid and cholesterol concentrations in a black South African population. Therefore, from these results it is evident that the lipid profile of black South Africans is most definitely influenced by not only genetic variations in the ApoE gene and certain environmental factors, but by the interaction between these factors as well. The present study is the largest study to date to investigate the effect of polymorphisms in the ApoE gene on the lipid profile of black South Africans. / MSc (Nutrition), North-West University, Potchefstroom Campus, 2014

The aim of this thesis was to investigate socio-economic status in relation to morbidity and mortality, in particular cardiovascular disease among women using data from two population based studies from Sweden. The secondary aim was to explore mechanisms potentially linking socio-economic status to health, assessing for example dental, dietary, and lifestyle factors. Samples: The Population Study of Women in Gothenburg Sweden was begun in 1968-69. A representative random sample of 1,622 women was selected according to date of birth and within the strata 38, 46, 50, 54, and 60 years of age; the participation rate was 90 percent. The Gerontological and Geriatric Population Studies in Gothenburg (H-70) are based on representative samples of 70-year olds from Göteborg, Sweden who participated in a series of cross sectional and longitudinal studies between1971 and 2000. Participation rates ranged from 86 percent for men and 83 percent for women in the 1901/2 birth cohort to 65 percent for men and 69 percent for women in the 1930 birth cohort. Main results: High socio-economic status was associated with a decreased risk for cardiovascular disease [RR 0.49; CI 0.24 – 0.99] in middle aged women independently of risk factors such as smoking and obesity;moreover opposing monotonic trends were seen for mortality from cancer and cardiovascular disease in relation to socio-economic status. Tooth loss, a proxy for cumulative lifetime oral infection was also associated with an increased risk for cardiovascular disease in women independently of socio-economic factors such as the husband’s occupational category, income, and educational level. Among 70-year old cohorts, later-born women were heavier and had higher body mass index than earlier-born women within the high education group only. However, secular increases in waist-hip ratio were seen in both educational groups. Compared to earlier-born cohorts of 70-year old men, later-born cohorts had higher body mass index and cholesterol levels across social strata, and heart disease and diabetes mellitus became more prevalent. Among the elderly, secular trends indicated greater improvements in cardiovascular risk factors among women than men, with exception to smoking and alcohol consumption. Diet quality and food selection were assessed in relation to socio-economic status in the youngest cohort of 70-year olds born in 1930. Socio-economic disparities in diet quality were detected in men but not in women. Conclusions: From a public health perspective, it is suggested that risk factor patterns should be investigated in association with socio-economic status in order to expose health inequalities, and to develop more equitable interventions for cardiovascular disease prevention.

Coronary heart disease rates show substantial geographic variation in England, which could be due to environmental variables (e.g. climate, air quality) or behavioural risk factors for coronary heart disease within populations. Previous work investigating this geographic variation has either used ecological analysis (i.e. areas as units of observation) or individual-level analysis. Ecological studies have been unable to account adequately for differences in behavioural risk factors within populations; individual-level studies have been under-powered at the area-level to include all potentially explanatory environmental variables. This thesis reports on ecological multi-level and spatial error regression analyses of coronary heart disease mortality and hospitalisation rates for all wards in England using environmental variables and synthetic estimates of the prevalence of behavioural risk factors as explanatory variables. Existing sets of synthetic estimates were subjected to studies of their validity. Validated synthetic estimates of the prevalence of smoking, low fruit and vegetable consumption, raised blood pressure, obesity and raised cholesterol were combined into a single index of unhealthy lifestyle to take account of collinearity between them. Final models successfully explained around 80% of large scale geographic variation (i.e. variation between wards in different areas of the country) in mortality rates for coronary heart disease and 60% in hospitalisation rates, and around 20% of the small scale geographic variation (i.e. variation between wards in close proximity) in mortality rates, and 30% in hospitalisation rates. The climate explained around 15% of large scale geographic variation in coronary heart disease rates after adjustment for the index of unhealthy lifestyle and socioeconomic deprivation. Urbanicity and air pollution explained a small amount of small scale geographic variation in coronary heart disease rates. The majority of explained geographic variation was due to the index of unhealthy lifestyle and deprivation. The results of this thesis confirm and extend findings from the British Regional Heart Study, report on the validity of synthetic estimates currently used to guide healthcare resource allocation, and introduce an index of unhealthy lifestyle that could be used in future ecological studies of chronic disease.

Cardiovascular magnetic resonance imaging (MRI) is a well established technique in clinical cardiology. Different MRI sequences are routinely used to assess cardiac anatomy, function, viability and other parameters that aid diagnosing cardiac disease. Conversely, cardiac magnetic resonance spectroscopy (MRS), the only available method for a non-invasive study of human cardiac metabolism, has not evolved into a clinical tool yet. The combination of both techniques holds great potential to gain insight into the causality of cardiomyopathy diseases or other medical conditions with high cardiovascular risk profile, like diabetes or obesity and improve the clinical management of cardiac diseases. Nowadays, high field clinical MR systems have the great potential of improving the low spatial and temporal resolution and reproducibility of MRS. The aim of this thesis was to develop and implement a cardiac 1H-MRS method at 3 T that can be applied in clinical routine for the assessment of creatine and lipid levels in the human myocardium. The methodological developments to advance cardiac MRS are presented first. A robust 1H-MRS method comprising an optimized single-voxel technique, phased-array coil combination routine, optimized water suppression, breath-hold averaging and post-processing methods were developed. First, reproducibility and feasibility of the method were validated in vivo by acquiring 1H-MRS of the liver in almost one hundred healthy subjects. Subsequently, myocardial lipids levels were obtained in healthy volunteers by single breath-hold 1H-MRS triggered to mid-diastole, showing good reproducibility in an acquisition time less than 12 s. The good spectral resolution achieved using this method was demonstrated by the ability to differentiate for the first time two pools of myocardial lipids in spectra from the septum of patients with suspected myocardial lipid excess. Finally, creatine levels for healthy volunteers were investigated using multiple breath-hold acquisitions. Thus, this study shows the practicality and feasibility to incorporate this rapid cardiac 1H-MRS method into clinical studies of the human myocardium.

Introduction: Some past breast cancer radiotherapy regimens led to an increased risk of death from heart disease. Although heart dose from breast cancer radiotherapy has generally reduced over the past few decades, there may still be some cardiac risk. Estimation of future risk for women irradiated today requires both measurement of their cardiac dose and dose-response relationships, which depend on cardiac dosimetry of past regimens, in conjunction with long-term follow-up data. Methods: Virtual simulation and computed tomography 3-dimensional treatment planning on a representative patient were used to estimate mean heart and coronary artery doses for women irradiated since 1950 in 71 randomised trials in the Early Breast Cancer Trialists’ Collaborative Group (EBCTCG) overview. Patient-to-patient variability in cardiac dose was assessed. Heart and coronary artery doses were also calculated for breast cancer radiotherapy regimens used since the 1950s in Sweden. Cardiac doses from contemporary (year 2006) radiotherapy were assessed for 55 patients who received tangential breast cancer irradiation at a large UK radiotherapy centre. The maximum heart distance (i.e. the maximum distance between the anterior cardiac contour and the posterior tangential field edges) was measured for the left-sided patients, and its value as a predictor of cardiac doses assessed. Results: Mean heart dose for women irradiated in the EBCTCG trials varied from <1 to 18 Gray, and mean coronary artery dose from <1 to 57 Gray. Patient-to-patient variability was moderate. Mean heart dose for women irradiated in Sweden since the 1950s varied from <1 to 24 Gray, and mean coronary artery dose from <1 to 46 Gray. Heart dose from tangential irradiation has reduced over the past four decades. However, mean heart dose for left-sided patients irradiated in 2006 was 2 Gray and around half of them still received >20 Gray to parts of the heart and left anterior descending coronary artery. For these patients, maximum heart distance was a reliable predictor of cardiac doses. For the other patients, mean heart dose varied little and was usually less than 2 Gray. Conclusions: Cardiac doses from breast cancer radiotherapy can be estimated reliably and are now available for use in deriving dose-response relationships in the EBCTCG data and in a Scandinavian case-control study. Cardiac dose has reduced over the past four decades. Therefore the cardiac risk is also likely to have reduced. Nevertheless, for some patients, parts of the heart still receive >20 Gray in the year 2006.

The term sedentary refers to a distinct class of activities which involve sitting or reclining and which do not cause an increase in energy expenditure above resting levels. Observational studies have reported positive associations between both sedentary time and the number of hours spent sitting per day, with risk for a number of health outcomes that are independent of moderate to vigorous physical activity (MVPA). The total time spent sitting can be amassed in different patterns (long and short bouts) and different types (watching TV, driving, working at a computer) that may have differential associations with health outcomes as well as different confounders that have yet to be properly explored. Further, limitations in current measures used to quantify sedentary behaviour and the possibility of residual confounding, mean that it is unclear whether the posture of sitting itself represents a risk to health or whether sitting is actually a proxy for low energy expenditure. This thesis aimed to examine; the associations between five separate sitting types with health risk, the prevalence of sitting behaviour in England, and the biological mechanisms which might underpin the observed negative health consequences of sitting. Using data from the Whitehall II cohort study the first four studies of this thesis examined prospective associations between sitting at work, TV viewing, non-TV leisure time sitting, total leisure time sitting (TV and non-TV leisure sitting combined) and total sitting from work and leisure, with four health outcomes; mortality, cardiovascular disease, type II diabetes and obesity. No association between any of the sitting indicators with risk for mortality or incident cardiovascular disease was found. TV viewing and total sitting were associated with an increase in risk for type II diabetes following adjustment for sociodemographic covariates and MVPA, but were attenuated following further adjustment for body mass index. None of the five sitting indicators were associated with incident obesity but being obese prior to the measurement of sitting was associated with the number of reported hours of daily TV viewing. The final study of this thesis examined the acute effect of sustained versus interrupted sitting on glucose and insulin metabolism. Interrupting sitting with repeated short bouts of light intensity walking significantly improved insulin sensitivity while repeated short bouts of standing did not. Sitting is a prevalent behaviour in English adults and varies by socio-demographic characteristics. Previously reported associations between sitting time and health risk may be confounded by light intensity physical activity and obesity. The absence of an effect of repeated standing bouts (a change in posture without a change in energy expenditure) suggests that promoting reductions in sitting without also promoting increases in movement are not likely to lead to improvements in metabolic health. New measures of sedentary behaviour are required that can be used in population studies, and can discriminate between the posture of sitting, standing and very low levels of physical activity of a light intensity. This would permit further studies that are needed to clarify the precise nature of the association between sitting and health.

The purpose of this dissertation was to explore the mechanism of association between social determinants of health (SDH), particularly limited health literacy, and disparate outcomes related to cardiovascular disease in vulnerable populations. Specific aims were to 1) compare quality of life (QOL), anxiety, and depressive symptoms between genders in implantable cardioverter defibrillator (ICD) recipients; 2) examine the association between multi-morbidity burden and QOL; 3) determine whether health literacy levels independently predict CVD risk in the male prison population; 4) examine the relationship between health literacy and decisiveness regarding end of life (EOL) choices, and 5) examine SDH as predictors of perceived poor health status in ICD recipients. Specific aim one was addressed by analysis of data collected from individuals in the Swedish ICD and Pacemaker Registry. Multiple linear regression was used to determine predictors of anxiety, depression, and quality of life in men and women. A higher prevalence of anxiety symptoms in women was noted with no differences in depressive symptoms noted between the genders. The majority of the variance in the predictive models for QOL was explained by the addition of the psychosocial variables for both genders. Specific aim two was addressed by analysis of data collected from individuals in the Swedish ICD and Pacemaker Registry. Logistic regression was used to determine predictors of QOL. Greater multi-morbidity burden was associated with lower QOL in ICD recipients. Specific aim three was addressed by analysis of data collected from male inmates enrolled in a bio-behavioral educational and counselling intervention program to reduce CVD risk. Nonlinear regression was used to determine whether health literacy was an independent predictor of CVD risk while controlling for social and clinical variables. Inmates with adequate levels of health literacy had lower ten year CVD risk profiles than those inmates with inadequate health literacy. Specific aim four was addressed by analysis of data collected from ICD recipients. Multinomial regression was used to determine predictors of decisiveness regarding EOL choices. Within the context of terminal illness, health literacy and race were found to be predictors of decisiveness regrading generator replacement while gender was found to be a predictor of decisiveness regarding the withdrawal of defibrillation therapy. Specific aim five was addressed by analysis of data collected from ICD recipients. Logistic regression was used to determine predictors of perceived poor health status. Residential status in the Central Appalachian region of Kentucky, not working outside the home, higher levels of health literacy, and comorbid depression were predictors of perceived poor/very poor health status.

The aim of this PhD thesis was to expand the current knowledge of “traditional Sami” diet and lifestyle, and to test aspects of the Sami diet and lifestyle, specifically dietary pattern, macronutrient distribution and coffee consumption, in population-based epidemiological studies of mortality and incident cardiovascular disease and cancer in a general population. In Paper I, semi-structured interviews were conducted with 20 elderly Sami concerning their parent’s lifestyle and diet 50-70 years ago. Questionnaire data from 397 Sami and 1842 matched non-Sami were also analyzed, using non-parametric tests and partial least square methodology.  In Papers II-IV, mortality data and incident cancer data for participants in the Västerbotten Intervention Program (VIP) cohort were used for calculations of hazard ratios by Cox regression. In Paper II, a Sami diet score (0-8 points) was constructed by adding one point for each intake above the median for red meat, fatty fish, total fat, berries and boiled coffee, and one point for each intake below the median for vegetables, bread and fibre. In Paper III, deciles of energy-adjusted carbohydrate (descending) and protein (ascending) intake were added to create a Low-Carbohydrate, High-Protein (LCHP) score (2-20 points). In Paper IV, filtered and boiled coffee consumption was studied in relation to incident cancer. In Paper V, a nested case-control study of filtered and boiled coffee consumption and acute myocardial infarction, risk estimates were calculated by conditional logistic regression. Surprisingly, fatty fish may have been more important than reindeer meat for the Sami of southern Lapland in the 1930’s to 1950’s, and it is still consumed more frequently by reindeer-herding Sami than other Sami and non-Sami. Other dietary characteristics of the Sami 50-70 years ago and present-day reindeer-herding Sami were high intakes of fat, blood, and boiled coffee, and low intakes of bread, fibre and cultivated vegetables (Paper I). Stronger adherence to a “traditional Sami” diet, i.e. a higher Sami diet score, was associated with a weak increase in all-cause mortality, particulary apparent in men (Paper II). A diet relatively low in carbohydrates and high in protein, i.e. a high LCHP score, did not predict all-cause mortality compared with low LCHP score, after accounting for saturated fat intake and established risk factors (Paper III).  Neither filtered nor boiled coffee consumption was associated with cancer for all cancer sites combined, or for prostate or colorectal cancer. For breast cancer, consumption of boiled coffee ≥4 versus &lt;1 occasions/day was associated with a reduced risk. An increased risk of premenopausal and a reduced risk of postmenopausal breast cancer were found for both total and filtered coffee. Boiled coffee was positively associated with the risk of respiratory tract cancer, a finding limited to men (Paper IV). A positive association was found between consumption of filtered coffee and the risk of acute myocardial infarction in men (Paper V). In conclusion, the findings of Paper I, in particular the relative importance of fatty fish compared to reindeer meat in the “traditional Sami” diet of the 1930’s-1950’s, suggest that aspects of cultural importance may not always be of most objective importance. The findings of Papers II-V generally did not support health benefits for the factors studied. The relatively good health status of the Sami population is therefore probably not attributable to the studied aspects of the “traditional Sami” lifestyle, but further investigation of cohorts with more detailed information on dietary and lifestyle items relevant for “traditional Sami” culture is warranted. / Syftet med denna avhandling var att beskriva livsstil och kostvanor hos samer. Det var också att undersöka hur en ”traditionell samisk” livsstil påverkar risken att insjukna av eller dö i cancer och hjärt-/kärlsjukdom i en norrländsk normalbefolkning. En majorietsbefolkning har alltså undersökts ur ett minoritetsperspektiv. Avhandlingen belyser framför allt kostvanor, fördelning av de näringsämnen som innehåller energi (kolhydrat, protein, fett) och konsumtion av kok- och bryggkaffe. Bakgrunden till undersökningarna var att samerna, till skillnad från de flesta andra urfolk i världen, kan förvänta sig ett lika långt liv som majoritetsbefolkningen. När det gäller hjärtkärlsjukdom finns inga stora etniska skillnader, men samiska män, särskilt renskötande, har lägre risk att drabbas av cancer än icke-samer. Det finns ingen entydig förklaring till samernas relativt goda hälsa, men det kan finnas ett samband med kostvanor och livsstil. Delstudie I var en intervjustudie med äldre samer och fungerade som bakgrund för de andra delstudierna. Tjugo äldre samer intervjuades om sina föräldrars livsstil och kostvanor för 50-70 år sedan. Dessutom analyserades kostdata från 81 renskötande och 226 icke-renskötande samer och 1842 matchade icke-samer för att se vilka skillnader som fanns mellan grupperna. Intervjuerna visade överraskande att fet fisk kan ha varit viktigare än renkött för samerna i södra Lappland under 1930-1950-talen. Fet fisk äts fortfarande i högre utsträckning av renskötande samer än av andra samer och icke-samer. Saker som har hög kulturell betydelse (i detta fall renkött) behöver alltså inte alltid ha lika stor betydelse ur ett objektivt, vetenskapligt perspektiv. Andra typiska särdrag hos den samiska kosten var en hög andel av fett, blod och kokkaffe och en låg andel av bröd, fibrer och odlade grönsaker. Det dagliga livet hos samerna på 1930-1950-talen präglades också mycket mer av fysisk aktivitet än vad det gör idag. De samiska männen arbetade oftast långt hemifrån, medan kvinnorna hade ansvaret hemmavid för fiske, jordbruk och trädgårdsskötsel (som introducerades under 1930-1950-talen). Kvinnorna tog även hand om hushållsarbetet och barnen. Delstudierna II-V handlade om olika aspekter av samisk kost i relation till dödlighet och sjuklighet. Till dessa användes huvudsakligen data från Västerbottens hälsoundersökningar, men i delstudie V även från MONICA-projektet, som är en del av ett multinationell forskningsprojekt om hjärt-/kärlsjukdom.  Totalt ingick på så sätt data från mer än 80 000 unika individer från en allmän, till största delen icke-samisk, normalbefolkning. Delstudie II byggde på en modell liknande den som använts för att undersöka hälsoeffekter av så kallad Medelhavsdiet.  En poängskala från 0-8 poäng, en så kallad ”Sami diet score”, skapades för att spegla likheter med ”traditionell samisk” kost. Den hälft av deltagarna som åt mest rött kött, fet fisk, fett, bär respektive kokkaffe, fick 1 poäng var, sammanlagt maximalt 5 poäng. Den hälft av deltagarna som åt minst grönsaker, bröd respektive fibrer fick också 1 poäng var, sammanlagt maximalt 3 poäng. Stora likheter med en ”traditionell samisk” kost, det vill säga höga ”Sami diet score” poäng, var förknippade med en svagt ökad dödlighet, särskilt hos männen. Det verkar därför osannolikt att den samiska kosten i sig förklarar den relativt goda hälsan hos samer. Denna fråga är dock mycket svår att undersöka, eftersom kostvanorna kan ha skiljt sig mellan olika samegrupper och över tid. Dessutom äter dagens västerbottningar mycket mindre av vissa livsmedel, jämfört med vad samerna gjorde förr i tiden. Det gäller till exempel fet fisk och bär.  För sådana livsmedel kan det därför vara extra svårt att påvisa samband med dödlighet. Syftet med kostenkäten i Västerbottens hälsoundersökningar är inte heller att spegla en ”traditionell samisk” kost. Det finns till exempel inga frågor om renkött och vilt, utan sådant kött räknas som en del av övrigt rött kött. Det här är första gången som någon undersökt betydelsen av ett ”traditionellt samiskt” kostmönster för hälsan på detta sätt. Fler liknande undersökningar i material med mer detaljerade frågor, som bättre fångar en samisk kost, är önskvärda. Lågkolhydratdieter, som har vissa likheter med den ”traditionella samiska” kosten, är både populära och kontroversiella. Eventuella långtidseffekter för hälsan är till stor del okända. I delstudie III speglades förhållandet mellan kolhydrater och protein i kosten med hjälp av så kallade LCHP (låg-kolhydrat, hög-protein) poäng. Högsta LCHP poäng fick de deltagare som åt minst kolhydrater och mest protein. Höga LCHP poäng påverkade inte risken att dö, eller att dö i cancer eller hjärt-/kärlsjukdom, efter att statistisk hänsyn tagits till intaget av mättat fett och de vanligaste riskfaktorerna. LCHP score användes i denna studie, istället för exempelvis en LCHF (low carbohydrate, high fat) variant. På så sätt kunde betydelsen av total fettmängd och av mättat fett också vägas in i analyserna. Dessutom innehåller kolhydrater och protein samma mängd energi per gram, vilket gör det lättare att byta ut dem mot varandra i en poängskala. Fett innehåller nästan dubbelt så mycket energi per gram som proteiner och kolhydrater. Inte bara olika sorters fett, utan även olika sorters protein och kolhydrater, kan spela roll för hälsan. Det är därför mycket svårt att skilja ut effekterna av mängd och kvalitet av kolhydrater, protein och fett i kosten. I delstudierna IV och V undersöktes risken att bli sjuk i cancer eller få en akut hjärtinfarkt hos västerbottningar som dricker mer respektive mindre kok- och bryggkaffe. De som drack mycket kaffe hade varken ökad generell cancerrisk, eller ökad risk för prostata- eller tjocktarmscancer. Kvinnor som drack kokkaffe ≥ 4 ggr/dag hade minskad risk för bröstcancer jämfört med kvinnor som drack &lt;1 gång/dag.  Både totalt kaffeintag och intag av bryggkaffe var kopplade till ökad risk för bröstcancer hos yngre kvinnor och minskad risk hos äldre. Män som drack mycket kokkaffe hade ökad risk för cancer i luftvägarna. Dessa resultat visar att de som dricker olika sorters kaffe kan ha olika stor risk att drabbas av olika sorters cancer. I tidigare studier har inga starka samband hittats mellan kaffedrickande och cancer. Denna studie var den första att undersöka hur cancerriskerna ser ut hos människor som dricker olika sorters kaffe. När det gäller hjärtinfarkt, hade män som drack mycket bryggkaffe ökad risk, medan inga entydiga resultat kunde visas bland män som drack mycket kokkaffe. Tidigare studier har visat motstridiga resultat när det gäller kaffe och hjärt-/kärlsjukdom, även om kaffekonsumtion är vedertaget förknippat med en del faktorer som kan öka risken att drabbas av hjärtinfarkt, till exempel ökade halter av blodfetter. Betydelsen av kokkaffe har aldrig undersökts tidigare i en studie där uppgifter om kaffedrickande samlats in i förväg. Delstudierna II-V är alla så kallade observationsstudier. I sådana studier följer deltagarna ingen bestämd forskningsplan, utan lever sina normala liv och jämförs sedan med varandra.  I observationsstudier är det mycket svårt att ta hänsyn till alla möjliga störande faktorer som kan finnas i omgivningen. Därför är det i princip omöjligt att bevisa direkta samband mellan orsak och verkan i en observationsstudie. Delstudierna II-V hade emellertid den starkaste design som en observationsstudie kan ha. De byggde på en representativ normalbefolkning (= en befolkningsbaserad kohort), där data samlats in från ett stort antal personer (&gt; 80 000 unika individer) medan de ännu var friska (= en prospektiv kohort).  Resultaten av enstaka observationsstudier har störst betydelse som underlag för att planera nya liknande, eller andra typer av mer riktade undersökningar. De är med andra ord hypotesgrundande. Om däremot flera observationsstudier visar på liknande resultat brukar man utgå från att resultaten är sanna, eller åtminstone sannolika. / (Nordsamiska) Guorahallama ulbmil lea muitalit sámi biepmu ja eallinvuogi birra ja iskat got árbevirolaš sámi borranvierut, makrobiebmama juogustus ja gáffegolaheapmi  váikkuhit jámolašvuođa  ja riskka oažžut borasdávdda dehe váibmo-/ suotnadávdda dábálaš davvi-ruoŧŧelaš ássiid luhtte. Guoktelogi sámi vuorrasa ledje jearahallon daid vánhemiid eallinvuogi  ja borramuša birra 50-70 jagi áigi (Oassedutkan 1). Dasa lassin  397 sámi ja 1842 ruoŧŧelačča biebmandata guorahallojuvvo eahpe-paramehtarlaš iskamiid ja partialalaš unnimus kvadráhta metoda (PLS) mielde. Dát golbma čuovvovaš oassedutkama, gait kohortdutkamat, isket jápminsiva dehe borasdávdabuohccivuođa oaseváldiid luhtte  Västerbottenis dearvas-vuohŧaiskkademiid hárrái (64 603-77 319 iskama) ja riskkaluoitimat leat rehkenaston Cox regrešuvnna  mielde. Oassedutkamis  2  árbevirolaš sámi biebman  lea speadjalaston čuokkesskála vuostá   0 rájes gitta 8 čuoggá.  Dát bealli oaseváldiin geat leat eanemus rukses bierggu, buoiddes guoli, buoiddi, murjiid ja vuoššangáfe borran, lea ožžon 1 čuoggá juohke áidna biebmanelemeanta ovddas, oktiibuot eanemus 5 čuoggá. Vel 3 čuoggá dát bealli oaseváldiin lea ožžon geat lea unnimus šattuid, láibbi ja fiberiid borran, eanemus oktiibuot 3 čuoggá. Oassedutkamis 3 speadjalastá oktavuođa kolhydráhtaid ja proteiinnaid gaskkas  biebmamis  LCHP (vuolit-kolhydráhta, alit-proteiidna) čuoggáid bokte. Alimus LHCP čuoggát (=20) dát oasseváldit leat ožžon geat leat borran unnimus kolhydráhtaid ja eanemus proteiinnaid  ja vuolimus čuoggát (=2)  dát oasseváldit leat ožžon geat leat borran eanemus kolhydráhtaid ja unnimus proteiinnaid. Oassedutkamis 4 riska borasdávdabuohccivuođa ektui guorahallojuvvo brygg- ja vuoššangáffejuhkkiid  luhtte. Oassedutkan 5 lei goallostuvvon dárkkástus-dutkan, gos riska fáhkkatlaš healladávdda oažžut gáffejuhkkiid luhtte rehkenasto logistihkalaš eaktuduvvon regrešuvnna bokte. Sáhttá leahkit nu ahte buoiddes guolli lea rievtti mielde leamašan deaŧaleabbo sámiide go boazobiergu lulli Lapplánddas  1930-1950-logus ja badjeolbmot ain dávjábut borret dan go iežá sámiid ja ruoŧŧelaččat. Iežá sierra erenomášvuohta sámi biebmamis lei alit oassi buoiddis, mális ja vuoššangáfes ja vuolit oassi láibbis, fiberiin ja šaddaduvvon  šattuin (Oassedutkan 1). Stuora seammaláganvuođat árbevirolaš sámi biebmamiin, rievtti mielde alit Sami diet score čuoggát, ledje čatnon veahá aliduvvon jámolašvuhtii  dievdduid luhtte muhto ii fal nissoniid luhtte (Oassedutkan 2). Biebman mas vuolit oassi kolhydráhtaid ja alit oassi proteiinnat, rievtti mielde alit LHCP čuoggát, ii váikkuhan riskka jápmit, maŋŋel go lea statistihkalaččat jurddašan ahte buoiddi borrat ja mat dát leat dát sajáiduvvon riskafáktorat (Oassedutkan 3). Gáffejuhkan ii lean čatnon eaneduvvon borasdávdariskii, iige eaneduvvon riskii oažžut prostata- gassačoalleborasdávdda. Nissoniin mat juhke vuoššangáfe ≥ 4 geardde/beaivái lei geahpeduvvon riska oažžut čižžeborasdávdda go nissonat mat juhke &lt;1 geardde/beaivái.  Ollesgáffe ja brygg-gáffe ledje čatnon eaneduvvon riskii oažžut čižžeborasdávddá nuorat nissoniid luhtte ja geahpeduvvon riskii vuorrasiin luhtte. Dievdduin mat juhke ollu vuoššangáfe lei eaneduvvon riska oažžut borasdávdda (Oassedutkan 4). Dievdduin mat juhke olu brygg-gáfe lei eaneduvvon riska oažžut healladávdda (Oassedutkan 5). Vuorrasit sámiid muitalusat man olu guoli sin vánhemat leat borran boazobierggu ektui 1930-1950-logus, čujuhit ahte bealit main alit kultuvrralaš mearkkašupmi eai dárbbaš seamma nanu objektivalš mearkkašumi atnit. Oassedutkamiid 2-5 bohtosat čujuhit ahte guorahallon bealit árbevirolaš sámi biebmamis ja eallinvuogis eai váikkut gárrasit dearvvašvuođa ja buohccivuođa dábálaš davviruoŧŧelaš ássiid luhtte. / (Lulesamiska) Dán guoradallama ájggom lij sáme biebmov ja viessomvuogev tsuojgodit, ja åtsådit gåk árbbedábak sáme bårråmdábe, stuoräládusebna juohkem ja káffajuhkam nuorttalándak álmmugin, bájnná jábmemav ja bårredávddabalov ja tsåhke-/ varravárredávddabalov. Guoktalågev sáme gatjádaláduvvin sijá äjgádij viessomvuoge ja biebmo birra 50-70 jage dán åvddåla (Oasseåtsålvis 1). Biebbmodáhtá 397 sámes ja 1842 láttes guoradaláduvvin parametragahtes gähttjalimij ja muhtem miere unnemus kvadráhta vuoge (PLS) viehkijn. Gålmmå tjuovvo oasseåtsådime, gájkka kohorttaåtsådime, vuolggin Västerbottena varresvuohtaåtsådimj oassálasstij jábmemårijs jali bårredávddaskihpudagájs (64 603-77 319). Ballamoarremerustallamav dahkin Cox regressionijn.  Oasseåtsådibme 2 spiedjildij avtaárvojt árbbedábak sáme biebmon tjuokkesmåhtajn nållå rájes gávtse tjuoggáj. Dat lahkke oassálasstijs gudi bårrin ienemus ruoppsis biergov, buojdes guolev, buojdev, muorjijt ja máleskáfav, oattjoj avtav tjuoggáv juohkka avta bårråmoases, aktan 5 tjuoggá ienemusát.  Ájn 3 tjuoggá oattjoj dat lahkke oassálasstijs mij båråj binnemus ruonudisájt, lájbijt ja fiberijt, aktan ienemusát 3 tjuoggá. Oasseåtsådibme 3 spiedjilt vidjurijt kolhydráhtaj ja proteijnaj gaskan biebmon nåv gåhtjodum LCHP (vuolle-kolhydráhta, alla-proteijna) tjuoggáj viehkijn.  Alemus LCHP tjuoggájt (=20) oadtjun oassálasste gudi binnemus kolhydráhtajt ja ienemus proteinajt bårrin ja vuolemus LCHP tjuoggájt (=2) oassálasste gudi ienemus kolhydráhtajt ja binnemus proteijnajt bårrin.  Oasseåtsådimen 4 åtsådaláduváj bårredávddaballo brygga- ja máleskáffajuhkkijn. Oasseåtsådibme 5 lij aktijdum guoradim-åtsådibme, gånnå káffajuhkkij tsåhkedávddaballo merustaláduváj aktijdam vihkemáhtsadime baktu. Vuordedahtek lij buojdes guolle ájnnasabbo gå boatsojbierggo sámijda oarjje Lapplándan 1930-1950-lågojn ja ájn vilá ällosáme guolev ienebut bårri gå ietjá sáme ja látte. Ietjá sierra merka sáme biebmon lij alep oasse buojdes, máles ja máleskáfas ja unnep oasse lájbes, fiberis ja sáddjidum ruonudisájs (Oasseåtsådibme 1). Árbbedábak sáme biebmo muoduk biebbmo, alep Sami diet score tjuoggáj, aktijaneduváj lasse jábmemijn sierraláhkáj ålmmåj hárráj (Oasseåtsådibme 2). Biebbmo vuolep kolhydráhttaåsijn ja alep proteijnnaåsijn, alla LCHP tjuoggáj, ittjij jábmembalov bájne, maŋŋel gå statistijkalattjat gehtjadam buojddebårråmijt ja ieme ballovidjurijt (Oasseåtsådibme 3).  Káffajuhkam lij tjanádum juogu de lasse gájkkásasj bårredávddaballuj, jali lasse prostáhta- bahtatjoallebårredávddaj. Kujnajn gudi máleskáfav juhkin ≥ niellji bäjvváj lij binnep njidtjebårredávddaballo gå buohtastahttá kujnaj gudi &lt; akti bäjvváj juhkin. Ålleskáffa ja bryggakáffa tjanáduváj lasse njidtjebårredávddaballuj nuorap kujnaj hárráj ja binnep vuorrasappoj. Ålmmåjn gudi juhkin edna máleskáfav lij lasse bårredávddaballo vuojŋŋamorgánajn (Oasseåtsådibme 4). Ålmmåjn gudi juhkin edna bryggakáfav lij lasse tsåhkedávddaballo (Oasseåtsådibme 5). Vuorrasap sámij tsuojggoma äjgádij guollebårråmis gå buohtastahttá boatsojbierggobårråmijn 1930-1950-lågo, vuosedi biele alla kultuvrak sisanos e agev dárbaha sämmi nanos objektijvak sisanov adnet. Oasseåtsådimij 2-5 båhtusa vuosedi åtsådum biele árbbedábak sámebiebmos ja viessomvuoges e varresvuodav ja skihpudagáv nuorttalándak álmmuga hárráj heva bájne. / (Sydsamiska) Dan goerehtimmien ulmie lea saemien beapmoem jïh jielemevuekiem buerkiestidh jïh dotkedh guktie aerpievuekien saemien beapmoevuekieh, makrobïepmehtimmiej juekeme jïh prïhtjhjovhkeme jaemedem jïh riskem dijpieh vaajmoe-/ jïh soeneskïemtjelassen muhteste noerhtesvöörjen sïejhmi årroji luvnie. Lea göökteluhkie saemien voeresh goerehtamme daej eejtegi jielemevuekien jïh beapmoen dïehre  50-70 jaepiej juassah (Stuhtjedotkeme 1). Dïsse lissine lea beapmoedaatam goerehtamme 397 saemijste jïh 1842 laedtijste ov-parametrihken gïehtjedimmiej jïh partiellen unnemes kvadraaten vuekien mietie (PLS).  Dah golme båetien stuhtjedotkemh, gaajhkh kohortdotkemh, leah dotkeme man gaavhtan jaameme jallh mïetskeåedtjieskïemtjelassh daej luvnie gïeh meatan Västerbottenen healsoedotkemi muhteste (64 603-77 319 dotkemh) jïh riskeryøknemh  dorjeme Cox  regresjovnen viehkine. Stuhtjedotkemisnie 2 lea mohtedamme guktie aerpievuekien saemien beapmoe vaestede låhkoeraajterasse 0 raejeste 8 raajan. Daate bielie daejstie gïeh meatan gïeh jeenemes rööpses bearkoem, buajtehks gueliem, buejtiem, muerjieh jïh voessjemeprïhtjegem byöpmedamme, leah aktem låhkoem åådtjeme fïere guhte beapmoeelementen åvteste, jeenemes 5 låhkoeh. Dïsse lissine 3 låhkoeh åådtje daate bielie daejstie gïeh meatan gïeh unnemes kruanesaath, laejpiem jïh fiberh byöpmedamme, jeenemes 3 låhkoeh. Stuhtjedotkemisnie 3 daelie mohtede kolhydraath jïh proteinh beapmosne LHCP (vuelehks-kolhydraath, jïlle-proteine) låhkoej viehkine. Jillemes LHCP låhkoem åådtjeme (=20) dah gïeh meatan gïeh vaenemes kolhydraath jïh jeenemes proteinh byöpmedamme jïh vueliehkommes LHCP låhkoem (=2) åådtjeme dah gïeh meatan gïeh jeenemes kolhydraath jïh vaenemes proteinh byöpmedamme. Stuhtjedotkemisnie 4 riskem goerehtamme mietskeåedtjieskïemtjelassem åadtjodh brygg- jïh voessjemeprïhtjegejovhkiji luvnie. Stuhjtedotkeme 5 lïj tjetskeme-dotkeme gusnie riskem ryöknoe logistihken regresjovnen baaktoe jis maahta  faahketji vaajmoedåeriesmoerh åadtjodh prïhtjhjovhkiji luvnie. Buajtehks guelie meehti vihkielåbpoe årrodh båatsoesaemide goh bovtsebearkoe åarjel Lapplaantesne 1930-1950-låhkosne jïh daamhtah båatsoesaemieh daam byöpmedieh jeenebe goh jeatjah saemieh jïh laedtieh. Jeatjah sïejhmi sjïere vuekieh saemien beapmosne lea jïlle stuhtje buejteste,  maeleste jïh voessjemeprïhtjegistie jïh vuelie stuhtje laejpeste, fiberistie jïh kruanesaatijste (Stuhtjedotkeme 1). Jeenh saemien aerpievuekien beapmoe, jïlle Sami diet score låhkoeh, provhki vuesiehtidh vaenie jeananamme jaemede ålmaj gaskemsh bene ij nyjsenæjjaj gaskemsh (Stuhtjedotkeme 2). Beapmoe man vuelehks stuhtje kolhydraath jïh stoerre stuhtje proteijnh, jeenh LCHP låhkoeh, ij leah dïjpeme riskem jaemedh, dan mænggan goh lea ussjedamme statistihken muhteste man jeene buejtiem byöpmedidh jïh sijjiedahteme riskefaktovrh ussjedamme. (Stuhtjedotkeme 3). Prïhtjhjovhkeme ij leah tjoelmesovveme jeananamme mïetskeåedtjieriskese, jallh jeananamme riskese prostaate-voeresbuejtiemïetskeåedtjiem åadtjodh. Nyjsenæjjah gïeh voessjemeprïhtjegem jovhkeme ≥ 4 aejkien/biejjesne unnemes riskem utnin njammamïetskeåedtjiem åadtjodh nyjsenæjjaj muhteste gïeh jovhkeme &lt;1 aejkien/biejjesne. Ellies prïhtjege jïh bryggeprïhtjege lea tjoelmesovveme jeananamme riskese njammamïestkeåedtjiem åadtjodh noere nyjsenæjjah luvnie jïh unniedamme riskem voeresi luvnie. Ålmah gïeh jeenh voessjemeprïhtjegem juvhkieh jeananamme riskem utnieh mïetskeåedtjiem åadtjodh girsesne (Stuhtjedotkeme 4). Ålmah gïeh jeenh bryggeprïhtjegem jovhkeme jeananamme riskem utnieh vaajmoedåeriesmoerem åadjtodh (Stuhtjedotkeme 5). Dah saemien voeresi soptsestimmieh man jeeneh gueliem daej eejtegh leah byöpmedamme bovtsebearkoem muhteste 1930-1950-låhkosne, vuesehte ahte daate bielie man vihkeles kultuvren sisvege ij eejnegen seamma objektiven sisvegem utnieh. Illeldahkh stuhtjedotkemijstie 2-5 vuesiehtieh ahte  dah bielieh mejtie lea goerehtamme saemien aerpienvuekien beapmoen jïh jielemevuekien muhteste eah healsoem jïh skïemtjelassem dïjph jeenebe goh sïejme noerhtesvöörjen årrojh. / (Umesamiska) Dahte guoreteme suptseste saamien beäpmoen jah jielemevuökien  biire jah giehtjedie guktie aarpievuökien saamien beäpmoeh, oajviebeäpmoeh jah kaavoeh mietete jaameke vahkake jah  cancerenne jah vajmoen/ virreveättennea nuorthen  allmetjeih luunie. Guökteluhke saamieih boariesh gihtjedihke lie elltie eihtegeh jielemevuökien jah beäpmoen biire dann baelie 50-70 jaapieh (Oasie 1). Jieneh beäpmoe-dataede dahkedihke lie 397 saamieiheste jah 1842 ruotseiheste dennake viehketihenne ieh parmetriske giehtjedemeh jah  partiellen unnemes kvadraten vuökien miete (PLS). Dah gullme oasieh boatien kohort- luhkemeh, allkemme lie jaamemeste jall canceremeste mieteih Västerbottenen varaasgiehtjemeih luunie (64603-77319 ollu) vahkake-tsiehkesjeme dahkedihke Cox-enne regressione. Oasienne 2 vuöjnedihke leh akte laakatjenne aarpievuökien saamien beäpmoeh vuösstede akte tsiehkesjerairoe 0 – 8. Dahte bielie deistie gieh jienemes ruöpses beärrkoede, buöjteks guöliede, buöjtiede borrein jah vuossjeme kaavoede juukein, akte tsiehkie fierte beäpmoih outeste otjoin, jienemes 5 tsiehkieh.Vielie 3 tsiehkieh dahte bielie otjoin gieh unnemes jaamoede jah urhtsede, laipiede jah fiberede borrein, jienemes 3 tsiehkeh. Oasienne 3 vuöjnedihke aktevuotta gasske kolhydrateh jah proteieneh beäpmoenne LCHP-esne (vuöleke kolhydrateh, jylloeke-proteineh) tsiehkie. Jyllemes LCHP tsiehkieh (=20) dainie mietenne unnemes kolhydrateh jah ollomes proteineh borrein jah unnemes LCHP tsiehkieh (2) dainie mietenne ollomes kolhydrateh jah unnemes proteineh borrein. Oasienne 4 giehtjedihke vahkake cancerede brygg- jah vuossjeme kaavoe juukejenne. Oasie 5 tjohkenne lin kontrolle- giehtjedeme vahkake hiehke vaajmoe-narrenne kaavoe-juukejenne tsiehkiesjdihke logistiske regressionenne. Buöjteke guölieh borretdihke mahtein vieliebe buutsebeärrkoeste saamieihesne oarrjel  saamien eätname 1930-1950 jaapienne jah vieliebe borretdihke buutsesaamieiheste guh jeätja saamieh jah ruotse-allmetjeh. Jeätja siejhme sierreme saamien beäpmoesne lin akte jylloeke oasie buöjtie-, viire-, jah vuossjeme kaavoeste jah akte vuöleke oasie laipie-, fibere-, joamoe jah urhtseste (Oasie 1). Ollu aktelaaka aarpievuökien saamien beäpmoeh, ollu Sami diet score tsiehkieh tjohkan lin vieliebe jaameme ollmaihenne sierrelaaka (oasie 2). Beäpmoihenne unne kolhydrateh jah ollu proteineh, ollu LCHP tsiehkie, ieh vahkake lasste jaamet, dann mingjelen guh statistiske ussjede valltedihke leh borremmiean gallane buöjtieste jah vihties vahkake faktoreiheste (oasie 3). Kaavoejuukeminne lin ieh vielebe aarpievuökien cancer-vahkake tjohkenne, jall vielebe vahkake prostate-kolorektale-cancere. Nyesenejah guh vuossjeme kaavoe juukein ≥4  aikieh/biejvie  unnebe vahkake nitje-cancereb lin muhteste nyesenejanneh gieh  &lt;1 aikie/biejvie juukein. Gaihkekaavoe jah brygg-kaavoe lie tjoahkan vielebe nitje cancereb nyesenejanne jah unnebe vahkake boariesh nyesenejaihenne. Ollma guh ollu vuossjeme kaavoeb juukein cancereste gonkelmesenne vieliebe vahkake otjoin (oasie 4). Ollma guh ollu brygg-kaavoe vajmoe-narreme vieleb vahkake otjoin (oasie 5). Dah boariesh saamieh suptsestemeh man jingje guöliede elltie eihtegeh buutsebeärrkoeh borrein 1930-1950-aikie, vuösiete dahte bielie veäksekes kulture miele ieh gaihke aikie darpesjedennake veäksekes objektive miele leh. Oasie 2-5 vuösiete dah giehtjedemes dahte bielie aarpievuökien saamien beäpmoen jah jielemen vuökien ieh varaas jah skieptjeme mietete ieh nuorthen almetejeh ollu.