Abstract The effect of alcohol intake on the pathophysiology of atherosclerotic cardiovascular disease is controversial, especially with respect to heavy alcohol intake. The pathobiology behind atherosclerosis is a complex and multiparametric phenomenon, therefore a self-organizing map (SOM), an unsupervised learning based artificial neural network technique, was applied in the present work. This study was carried out to investigate the effect of heavy alcohol intake on the pathophysiology of atherosclerosis, including several lipoproteins and adiponectin, an adipocyte-derived cytokine that may ameliorate atherosclerosis. Firstly, the effect of heavy alcohol intake on the capacity of HDL and its subclasses (HDL2 and HDL3) to mediate cholesterol efflux from macrophages was studied. Secondly, data of ultracentrifugally isolated lipoproteins were fed into SOM analysis to investigate whether this method can find diverse lipoprotein phenotypes from the heterogeneous lipoprotein data. Thirdly, the aforementioned method was applied to multivariate data of alcohol drinkers to study whether distinct metabolic profiles are associated to heavy alcohol consumption. The results revealed that HDL2, not HDL3, of heavy alcohol drinkers had an enhanced capacity to remove cholesterol from macrophages when compared with control persons. SOM analysis enhanced the ultracentrifugally based lipoprotein data and depicted several novel lipoprotein phenotypes. In addition, lipoprotein-based SOM analysis found two distinct metabolic profiles in heavy alcohol drinkers: an anti-atherogenic and a metabolic syndrome-like profile with opposite metabolic features, such as characteristics of lipoproteins, plasma concentration of adiponectin and prevalence of metabolic syndrome. These profiles also tended to differ in their CV risk. In conclusion, the enhanced cholesterol efflux capacity of HDL2 in heavy drinkers is an anti-atherogenic change linked to alcohol drinking. However, clinically it may be important to be aware that although heavy alcohol drinkers have a low LDL-C level, they differ in their other lipoprotein measures, forming distinct phenotypes with potentially different CV risks. Finally, SOM analysis of ultracentrifugally based lipoprotein data generates in silico classification of lipoprotein particles and thereby offers a new tool for lipoprotein research. / Tiivistelmä Alkoholinkäytön vaikutus ateroskleroottisen sydän- ja verisuonitaudin patofysiologiaan on kiistanalainen, etenkin runsaan alkoholinkäytön kohdalla. Koska patobiologia ateroskleroosin taustalla on monimutkainen ilmiö, tässä työssä sovellettiin menetelmänä itseorganisoituvaa karttaa, joka on ohjaamattomaan oppimiseen perustuva neuroverkkomalli. Tutkimuksen tavoitteena oli selvittää runsaan alkoholinkäytön vaikutusta ateroskleroosin patofysiologisiin merkkiaineisiin, mukaan lukien useita lipoproteiineja sekä adiponektiini, rasvasoluperäinen sytokiini, joka voi lievittää ateroskleroosia. Ensimmäisessä osatyössä tutkittiin runsaan alkoholinkäytön vaikutusta HDL:n ja sen alafraktioiden (HDL2 ja HDL3) kykyyn poistaa kolesterolia makrofageista. Toisessa osatyössä ultrasentrifuugaukseen perustuva lipoproteiiniaineisto syötettiin itseorganisoituvaan karttaan. Työssä selvitettiin löytäisikö menetelmä erilaisia lipoproteiinifenotyyppejä heterogeenisestä aineistosta. Kolmannessa osatyössä em. menetelmää sovellettiin monimuuttuja-aineistoon, joka koostui runsaasti alkoholia käyttävistä ja verrokeista. Tutkittiin, liittyykö runsaaseen alkoholinkäyttöön erilaisia metabolisia profiileja. Tulokset osoittivat, että suurkuluttajien HDL2-hiukkasen kolesterolinpoistokyky makrofageista oli suurempi kuin verrokeilla. Itseorganisoituvaan karttaan perustuva lipoproteiinien luokittelumenetelmä löysi useita uusia lipoproteiinifenotyyppejä. Lisäksi, em. menetelmä löysi suurkuluttajilta kaksi erilaista metabolista profiilia: anti-aterogeeninen ja metabolisen syndrooman kaltainen. Näillä oli vastakkaiset metaboliset piirteet, kuten lipoproteiinien ominaisuudet, adiponektiinin pitoisuus plasmassa ja metabolisen syndrooman esiintyvyys. Profiileihin liittyi mahdollisesti myös erilainen sydän- ja verisuonitautiriski. Tutkimus osoittaa, että alkoholin suurkuluttajilla havaittu parempi HDL2:n kyky poistaa kolesterolia soluista on anti-aterogeeninen muutos, joka liittyy alkoholin käyttöön. Kliinisesti voi olla merkittävää, että vaikka alkoholin suurkuluttajilla oli pieni LDL-C pitoisuus, he jakaantuivat muiden lipoproteiiniperäisten muuttujien perusteella kahteen eri fenotyyppiryhmään, joihin liittyi erilainen sydäntautiriski. Lisäksi itseorganisoituva kartta loi ultrasentrifugoinnilla eristetyille lipoproteiineille in silico -luokittelun, joten se tarjoaa uuden työkalun lipoproteiinitutkimukseen.

Abstract The increase in the prevalence of overweight and obesity parallels the increase in physical inactivity and sedentary lifestyle, and leads to the worsening of cardiorespiratory fitness. Both overweight and physical inactivity are recognised risk factors for the development of cardiovascular disease, insulin resistance and type 2 diabetes, but the independent effects of cardiorespiratory fitness and obesity on cardiovascular risk factors remain debated. Lifestyle interventions are the key treatment for overweight and obesity. There are however, limited data from large population-based studies on the efficacy of exercise in modifying cardiovascular risk factors in young adults. Many of the mechanisms underlying the changes in body composition and metabolism achieved by exercise interventions are not well understood. The role of adipokines, and particularly unacylated ghrelin has been proposed in relation to changes in glucose metabolism. Individuals also vary in their response to exercise, which is, at least in part, explained by genetic factors. Improved understanding of the gene-exercise interaction is needed for the development of more targeted intervention strategies. In Finland, military service is compulsory for men. Military service includes large amounts of physical exercise but no dietary restriction. The current study evaluated the health benefits of exercise in young men attending military service in the Sodankylä Jaeger Brigade from 2005 to 2006 (N=1,112, mean age 19.2 years). Changes in endurance and strength performance, body composition, cardiometabolic risk factors and unacylated ghrelin levels were recorded at the beginning and end of the military service (6 to 12 months follow-up). Improvement in cardiometabolic risk factors was observed with improved exercise performance, an association which was attributable to changes in weight and waist circumference. Increase in unacylated ghrelin level was associated with beneficial changes in body composition and fat distribution, as well as in lipid and glucose metabolism. Significant gene-exercise interactions were observed for variants in PPARG, IRS1 and TCF7L2 on changes in weight and/or body composition. This study shows the efficacy of physical activity for the improvement of cardiometabolic health among young men. It shows that unacylated ghrelin plays an important role in the improvement of body composition, and glucose and lipid metabolism achieved by exercise. Finally, the harmful effects of common genetic variants on body composition can be counteracted by improvement in exercise performance. / Tiivistelmä Viimeaikaiset tutkimukset ovat osoittaneet, että väestötasolla ylipaino ja lihavuus lisääntyvät ja liikunta vähenee. Sekä ylipaino että vähäinen liikunta ovat tunnettuja sydän- ja verisuonitautien, insuliiniresistenssin ja tyypin 2 diabeteksen vaaratekijöitä. Monet interventiotutkimukset ovat osoittaneet, että elämäntapamuutokset ovat avainasemassa ylipainon ja lihavuuden hoidossa. Suurista väestöpohjaisista tutkimuksista saatu tieto liikunnan vaikutuksista nuorten aikuisten sydän- ja verisuonitautien vaaratekijöihin, kehonkoostumukseen ja aineenvaihduntaan on kuitenkin vähäistä. Greliinillä on ehdotettu olevan tärkeitä vaikutuksia glukoosiaineenvaihduntaan, mutta greliinin ja liikunnan yhteisvaikutuksista aineenvaihdunnan ja kehon muutoksiin on vain vähän tietoa. Vasteessa liikunta-interventioihin on lisäksi yksilökohtaisia eroja, jotka saattavat ainakin osittain selittyä geneettisillä tekijöillä. Näin ollen lisätieto geenien ja liikunnan välisistä interaktioista on tärkeää uusien, yksilökohtaisten hoitomuotojen kehittämiseksi. Varusmiespalvelus on maassamme pakollinen kaikille miehille, ja siihen sisältyy huomattava määrä liikuntaa ilman merkittäviä muutoksia ruokavaliossa. Tässä tutkimuksessa selvitettiin varusmiespalveluksen aikana tapahtuvan liikunnan ja kuntomuutosten terveyshyötyjä. Tutkimusaineiston muodostivat Sodankylän Jääkäriprikaatissa vuonna 2005 palvelukseen astuneet miehet (N=1112, keski-ikä 19.2 vuotta). Muutokset kestävyys- ja lihaskunnossa, kehonkoostumuksessa, sydän- ja verisuonisairauksien vaaratekijöissä, sekä asyloimattoman greliinin plasmatasoissa määritettiin palveluksen alussa ja lopussa (seuranta-aika 6-12 kk). Parantuneen fyysisen suorituskyvyn todettiin vaikuttavan edullisesti sydän- ja verisuonisairauksien vaaratekijöihin, joka liittyi samanaikaiseen painonlaskuun ja keskivartalolihavuuden vähenemiseen. Liikunnan ansiosta asyloimattoman greliinin plasmataso lisääntyi ja se oli yhteydessä edullisiin muutoksiin kehonkoostumuksessa ja rasvanjakautumisessa sekä glukoosi- ja lipidiaineenvaihdunnassa. Tärkeitä geeni-liikunta interaktioita todettiin insuliiniherkkyyttä säätelevien geenien (PPARG, IRS1 ja TCF7L2) vaikutuksissa painon ja/tai kehonkoostumuksen muutoksiin. Tutkimus osoitti liikunnan edullisen vaikutuksen nuorten miesten sydän- ja verisuonitautien vaaratekijöiden tasoihin. Tutkimus osoitti lisäksi, että liikunnan aiheuttamalla lisääntyneen asyloimattoman greliinin pitoisuudella oli edullisia vaikutuksia kehonkoostumukseen sekä glukoosi- ja lipidiaineenvaihduntaan. Myös insuliiniresistenssiä säätelevien geenien epäedullinen vaikutus kehonkoostumukseen väheni parantuneen fyysisen suorituskyvyn myötä.

La capacité des particules HDL à exercer des effets anti-athérogènes passe notamment par leur capacité à assurer le transport inverse du cholestérol (RCT). L'objectif principal de mon programme de recherche est l'étude de l'étape initiale du transport inverse du cholestérol que représente l'efflux de cholestérol du macrophage, dans le contexte des maladies métaboliques et du risque cardiovasculaire et de mortalité. J'ai étudié la relation entre l'efflux, et les conséquences sur le développement de l'athérosclérose dans un contexte métabolique particulier ; le syndrome métabolique (SM). J'ai démontré que les critères individuels du SM sont intimement liés à l'efflux et que ces deux notions sont associées de façon indépendante aux paramètres cliniques de l'athérosclérose. J'ai aussi évalué la pertinence de l'efflux de cholestérol comme biomarqueur de la mortalité. Cette étude identifie l'efflux comme prédicteur de la mortalité toutes causes confondues, indépendamment des taux de HDL-cholestérol et des facteurs de risques cardiovasculaires traditionnels, dans une population de patients traités par angioplastie coronaire primaire, suite à un infarctus du myocarde avec élévation du segment ST. Enfin, je me suis intéressée à à une situation métabolique particulière ; l'état postprandial. Mes travaux montrent que la réponse postprandiale hypertriglycéridémique physiologique observée chez des individus sans désordre métabolique ne s'accompagne pas d'altération majeure de l'efficacité du RCT ou de l'inflammation systémique. Mes travaux confirment le rôle déterminant de l'efflux dans la prévention du développement de l'athérosclérose et de la mortalité cardiovasculaire. / The contribution of high-density lipoprotein to cardiovascular benefit is closely linked to its anti-atherogenic role in the cellular cholesterol efflux. The main purpose of my project was to evaluate the efficiency of the first step of reverse cholesterol transport (RCT), which is the efflux capacity, on metabolic disorder context, on cardiovascular risk and on mortality. My research has focused on three independent and complementary parts. I have first evaluated the relationship between efflux and its consequences on atherosclerosis development in a metabolic syndrome (MetS) population. I have shown that individual criteria of MetS are closely related synergistically to cholesterol efflux capacity. In addition, established metabolic syndrome and cholesterol efflux capacity were independently associated with clinical features of atherosclerosis. In a second study I identified cholesterol efflux capacity as a predictor of all-cause mortality in consecutive ST-segment elevation myocardial infarction patients treated by primary angioplasty, independent of HDL-C, traditional cardiovascular risks or cardiac risk factors. Finally I have evaluated the consequences of postprandial hypertriglyceridemia on the functionality of key steps of RCT and associated anti-inflammatory components. My work has shown that the physiological postprandial hypertriglyceridemia response is not accompanied by a major alteration in the efficiency of RCT or systemic inflammation, on individual without metabolic syndrome. In conclusion, I have confirmed the crucial role of the first step of reverse cholesterol transport in preventing the development of atherosclerosis and cardiovascular mortality.

Abstract Metabolic syndrome (MetS) is a cluster of obesity-related cardiometabolic risk factors. It predicts the development of cardiovascular disease and type 2 diabetes, which are major public health concerns. Visceral obesity and insulin resistance are the predominant underlying factors of MetS, other diagnostic components being elevated blood pressure, high triglycerides, and low HDL-cholesterol. The most important treatment of MetS is through lifestyle changes. There are limited data concerning the prevalence of MetS among young populations. Furthermore, even though the effects of physical activity on MetS components are well established at an individual basis and in some subpopulations, large population-based data about associations of young men’s fitness and MetS-related cardiometabolic risk factor changes are warranted. In Finland, military service is compulsory for males. In 2005, 1,160 young men (mean age 19.2 years, range 18–28 years) were followed throughout their military service (6–12 months) in the Sodankylä Jaeger Brigade. The military service period includes high amounts of physical exercise, but no dietary restrictions. Physical fitness, anthropometrics, body composition, and cardiometabolic risk factors were assessed at the beginning and at the end of military service. Among the entire study population, the prevalence of MetS was 3.5–6.8 %, depending on the definition used, and increased in parallel with an increasing body mass index. On the average, the military training period resulted in a decrease in body weight and amount of fat tissue, especially visceral fat, and improved physical fitness. Body composition and fitness improvements were more pronounced in overweight and obese service men. Beneficial changes in body composition and related cardiovascular risk factor improvements were associated with increased physical fitness, especially aerobic fitness. This study indicates that an improvement in physical fitness is related to improvements in body fat distribution and cardiovascular health at population level in young men. This is an age when co-morbidities are usually as yet non-existing, but might be most efficiently prevented by lifestyle changes, such as becoming physically active. / Tiivistelmä Metabolinen oireyhtymä on tyypin 2 diabeteksen ja valtimosairauksien riskitekijäryväs. Sen osatekijöitä vyötärölihavuuden lisäksi ovat kohonnut verenpaine, insuliiniresistenssi, korkea veren triglyseridipitoisuus ja HDL-kolesterolin pitoisuus. Viime vuosina metabolinen oireyhtymä on yleistynyt lihavuuden lisääntymisen myötä. Lihavuuden ja sen liitännäissairauksien tärkeimpiä hoitokeinoja ovat laihtumiseen tähtäävät elintapamuutokset. Liikunnan tiedetään johtavan edullisiin kehonkoostumusmuutoksiin sekä kardiovaskulaaririskitekijöiden parantumiseen. Laajat väestötason tutkimukset nuorten aikuisten kunnon ja varhaisten valtimosairausriskitekijöitten muutosten välisistä yhteyksistä kuitenkin puuttuvat. Varusmiespalvelus tarjoaa ainutlaatuisen mahdollisuuden tarkastella nuoria miehiä laajassa, lähes valikoitumattomassa väestöotoksessa, sillä Suomessa varusmiespalvelus on pakollinen kaikille miehille. Vuonna 2005 1160 miestä (keski-ikä 19,2 vuotta, vaihteluväli 18–28 vuotta) astui palvelukseen Sodankylän jääkäriprikaatissa. Kehonkoostumus, fyysinen kunto, antropometria sekä veren rasva-arvot mitattiin varusmiespalveluksen (6–12 kk) alussa ja lopussa. Metabolisen oireyhtymän vallitsevuus oli 3,5–6,8 % käytetystä määritelmästä riippuen. Se oli yleisempi korkeimmissa painoindeksiluokissa. Keskimäärin koko aineistossa varusmiesten paino laski, kehon rasvan määrä väheni ja kunto parani palvelusaikana. Edulliset muutokset fyysisessä kunnossa ja kehon koostumuksessa korostuivat ylipainoisilla ja lihavilla varusmiehillä. Nämä muutokset, erityisesti painon ja sisälmysrasvan väheneminen, olivat yhteydessä kestävyyskunnon paranemiseen. Vastaavasti kardiovaskulaaririskitekijöiden edulliset muutokset olivat yhteydessä erityisesti kestävyyskunnon paranemiseen ja vyötärölihavuuden vähenemiseen. Tämän tutkimuksen perusteella voidaan todeta, että nuorten miesten valtimosairauksien riskitekijöiden muutos on yhteydessä fyysisen kunnon nousuun. Nuoret miehet tulee saada lisäämään vapaa-ajan liikuntaa myös siviilielämässä. Keski-iässä yleistyvät valtimosairaudet ja diabetes voisivat olla huomattavissa määrin torjuttavissa vaikuttamalla nuorten miesten liikuntatottumuksiin.

Durante a transição menopausal e a pós-menopausa cerca de 75% das mulheres apresentam sintomas de hipoestrogenismo, tais como fogachos. O emprego de terapia hormonal (TH) para alívio dos sintomas da menopausa está bem estabelecido, mas seus efeitos cardiovasculares (CV) permanecem controversos. Dados de estudos recentes indicam a presença de duas populações distintas quanto aos efeitos CV da TH. Essa diferenciação estaria relacionada principalmente com a idade e o tempo de pós-menopausa. Evidências sugerem também que a presença de fatores de risco cardiovascular antes do início do TH, ou de uma associação de fatores de risco, podem ser determinantes dos efeitos CV do TH. Dose de medicação, via de administração e o tipo de progestogênio utilizado em associação com estrogênio para TH também vem sendo estudados como possíveis fatores relacionados ao impacto CV do TH. O presente trabalho é composto por: 1) Ensaio clínico randomizado, comparando os efeitos da via oral baixa dose e via não oral sobre variáveis relacionadas com risco CV em uma população de mulheres saudáveis na pósmenopausa recente; 2) Ensaio clínico randomizado, onde foram avaliados os efeitos da adição de progesterona natural micronizada ao estrogênio não oral durante TH em mulheres na pós-menopausa recente; e 3) Revisão sistemática e meta-análise, onde foram sistematicamente buscados todos os artigos com TH baixa dose que avaliassem os efeitos desta terapia sobre variáveis relacionadas com risco cardiovascular: peso, índice de massa corporal, pressão arterial, proteína C reativa e lipídios. Desenvolvemos ensaio clínico randomizado, cross-over, com objetivo de avaliar os efeitos de dois tipos de tratamento hormonal na menopausa: oral baixa dose, estradiol 1 mg e drospirenona 2 mg diário e não oral, estradiol 17 β gel 1.5 mg (ou nasal 300 mcg) diário e progesterona micronizada vaginal, 200 mg, 14 dias por mês, sobre peptídeo natriurético atrial, variáveis relacionadas com inflamação e função endotelial, perfil antropométrico e metabólico em mulheres na pós-menopausa recente e sem doença clínica evidente. 101 mulheres na pós-menopausa foram alocadas aleatoriamente para iniciar o TH por um dos dois grupos de tratamento: via oral baixa dose (n=50) ou via não oral (n=51). Todas as pacientes utilizaram ambos os TH de forma seqüencial. Após o primeiro período de 2 a 3 meses de TH a paciente passava para o segundo tratamento, sem período de washout. A avaliação laboratorial foi realizada antes e após cada um dos tratamentos. A amostra do estudo foi composta por mulheres com média etária de 51 ± 3 anos e tempo de amenorréia de 22 ± 10 meses. Oitenta e seis pacientes concluíram o estudo. Peso e índice de massa corporal não se modificaram, enquanto que a circunferência da cintura reduziu de forma similar em ambos os grupos de tratamento. Colesterol total e LDL-C reduziram após ambos os TH, e triglicerídeos reduziram somente após a TH não oral. Insulina e glicemia de jejum não se modificaram. Não foram observadas modificações nos níveis de fibrinogênio, fator von Willebrand (FvW) e proteína C reativa (PCR) após TH oral. Após TH não oral, observou-se redução significativa de fibrinogênio e FvW. Níveis de PCR não se modificaram. Houve redução do número de pacientes no maior tertil de PCR (alto risco CV) após TH não oral. Essas pacientes passaram a integrar os grupos de risco intermediário e baixo. Níveis de peptídeo natriurético atrial (PNA) mantiveram-se inalterados após os ambos os TH. Não houve modificações significativas na pressão arterial e esta não se correlacionou com valores de PNA. Realizamos análise adicional do TH não oral, quanto às diferenças entre a via nasal e a percutânea e quanto aos efeitos da adição de progesterona natural micronizada ao estrogênio. Não houve diferenças significativas para todas as variáveis estudadas entre a via nasal e a via percutânea. A adição de progesterona natural micronizada não modificou os efeitos metabólicos e CV do estrogênio não oral. Foi realizada busca sistemática de todos os artigos que incluíssem como TH estrogênio baixa dose e avaliassem os efeitos deste tratamento sobre as variáveis de interesse: peso, índice de massa corporal, pressão arterial, proteína C reativa e lipídeos. Foram consultadas as bases MEDLINE, Cochrane CENTRAL, EMBASE. Foram revisadas todas as referências dos artigos de interesse e revisões e metaanálises no assunto, em busca de artigos relevantes. Após exclusão dos artigos em duplicata, 8610 artigos foram revisados. Destes, 28 artigos foram selecionados para meta-análise. Desta análise foi possível concluir que pacientes em uso de TH baixa dose apresentaram em média menor peso corporal, colesterol total e LDL-C do que não usuárias. A TH baixa dose não apresentou efeitos deletérios sobre demais variáveis estudadas. Em conclusão, ambos os TH apresentaram efeitos neutros ou benéficos sobre variáveis relacionadas com risco CV em uma população de mulheres na pósmenopausa recente e sem evidência de doença CV. A adição de progesterona natural micronizada não modificou os efeitos do estrogênio não oral. Os resultados da metaanálise sobre TH baixa dose e variáveis relacionadas com risco CV também permitem concluir que a TH baixa dose não exerceu efeitos deletérios sobre lipídeos e pressão arterial, e foi observado um possível efeito benéfico deste tratamento sobre o peso corporal. / During the menopausal transition and postmenopause about 75% of women have symptoms of hypoestrogenism symptoms such as hot flushes. The use of hormone therapy (HT) for relief of menopausal symptoms is well established, but its cardiovascular effects (CV) remain controversial. Data from more recent studies suggest the presence of two distinct populations regarding the cardiovascular effects of HT. This differentiation is related mainly to age and time after menopause. Evidence also suggests that the presence of cardiovascular risk factors before the onset of HT, or a combination of risk factors may be determinants of CV effects of HT. Medication dose, route of administration and type of progestin used in combination with estrogen for HT has also been studied as possible factors related to the CV impact of HT. This work consists of: 1) Randomized clinical trial, comparing the effects of low dose oral and non-oral route of variables related to CV risk in a population of healthy women in early postmenopausal; 2) A randomized clinical trial, which we assessed the effects of the addition of natural micronized progesterone to non-oral estrogen for HT in women in early postmenopausal; and 3) systematic review and meta-analysis, which were systematically searched all items with low-dose HT to assess the effects of this therapy on variables related to cardiovascular risk: weight, body mass index, blood pressure, C-reactive protein and lipids. A cross-over, randomized clinical trial was designed in order to evaluate the effects of two types of HT: low dose oral treatment, estradiol oral 1 mg and drospirenone 2 mg, by day and non-oral treatment, estradiol 1.5 mg 17 β gel by percutaneous route (or nasal route 300 mcg) by day and vaginal micronized progesterone, 200 mg/d, 14 days by month on atrial natriuretic peptide, variables associated with inflammation and endothelial function, anthropometric and metabolic variables on early and healthy postmenopausal women. One hundred one women were randomly allocated to start with one of the treatments: low dose oral treatment (n=50) or non-oral treatment (n=51). At the end the first three months period, the patients were crossed over without washout for an additional three months. Laboratory evaluated were carried before and after oral and non-oral HT. The sample of the study included postmenopausal women with a mean age of 51 years and duration of amenorrhea of 22±10 months. Eighty-six patients completed the study. Weight and body mass index remained unchanged, while the waist circumference decreased similarly in both treatment groups. Total cholesterol and LDL-cholesterol reduced after both the HT and triglycerides reduced only after nonoral HT. Insulin and fasting glucose did not change. No changes were observed in the levels of fibrinogen, von Willebrand factor (vWF) and C-reactive protein (CRP) after oral HT. After non-oral HT, there was a significant reduction of fibrinogen and vWF. CRP levels did not change. There was a reduction in the number of patients in the highest tertile of CRP (high CV risk) after non-oral HT. These patients have joined the groups of intermediate and low risk. Levels of atrial natriuretic peptide, ANP, were unchanged after both HT. There were no significant changes on blood pressure and did not correlate with values of ANP. We performed additional analysis of nonoral HT, for the differences between nasal and percutaneous and about the effects of addition of natural micronized progesterone to estrogen. There were no significant differences for all the variables studied between the nasal and percutaneously. The addition of micronized natural progesterone did not modify the metabolic and CV effects of non-oral estrogen. Systematic search of all articles that include as TH low dose estrogen and evaluate the effects of this treatment on the variables of interest was taken: weight, body mass index, blood pressure, C-reactive protein and lipids. The MEDLINE, Cochrane CENTRAL, EMBASE databases were consulted. All references of interest and reviews and meta-analyzes on the subject, in search of relevant articles were reviewed. After removing duplicate articles, 8610 articles were reviewed. Of these, 28 articles were selected for meta-analysis. From this analysis it was concluded that patients using low-dose TH had on average lower body weight, total cholesterol and LDL-C than non-users. The TH low dose showed no deleterious effects on other variables. In conclusion, low-dose oral and non-oral treatments had neutral or beneficial effects on variables related to CV risk in a population of women in early post menopausal and without evidence of CV disease. The addition of micronized natural progesterone did not modify the effects of non-oral estrogen. The results of the metaanalysis of low dose and TH variables related CV risk also showed that the TH low dose did not exert deleterious effects on lipids and blood pressure, and a possible beneficial effect of this treatment on body weight was observed.

Face aux limites de la littérature internationale sur les disparités environnementales de prévalence d’obésité (focus sur le lieu de résidence, etc.) et considérant le manque d’études empiriques réalisées en France, nous nous sommes intéressés tout d’abord aux relations entre, d’une part, les caractéristiques des environnements résidentiels et professionnels et le secteur d’activité économique et, d’autre part, deux indicateurs d’excès de graisse corporelle : l’indice de masse grasse (IMG) et le pourcentage de masse grasse (%MG). Ensuite, nous avons comparé les effets des secteurs d’activité économique sur plusieurs facteurs de risque cardiovasculaire. Finalement, à l’aide d’une étude longitudinale, nous avons évalué les liens entre les variables socio-économiques et l’évolution des paramètres anthropométriques chez les participants de l’Étude RECORD. Parallèlement à l’étude de ces relations, notre objectif méthodologique était d’explorer les biais d’attrition liés aux données manquantes dans les études longitudinales.Pour conclure, nous avons pu par ces travaux empiriques mettre en évidence des effets des caractéristiques individuelles, de l’environnement résidentiel, et des secteurs d’activité économique sur l’accumulation de la masse grasse corporelle ainsi que sur les facteurs de risque cardiovasculaire. En ce qui concerne le volet méthodologique de ce travail, d’une part nous avons été en mesure de tenir compte dans les analyses de l’environnement géographique de résidence communément pris en compte. D’autre part, nous démarquant d’une littérature sur les déterminants sociaux de l’obésité essentiellement transversale, nous montrons que selon le mécanisme des données manquantes, les méthodes statistiques communément utilisées ne permettent pas de contourner les biais potentiels induits par l’attrition dans les analyses longitudinales. / Given the limits of the international literature on the environmental disparities in obesity prevalence (focused on the residential neighborhood) and considering the lack of empirical studies conducted in France, we were interested in the relations between, on the one hand, the characteristics of residential and professional neighborhood characteritics and the work economic sector, and on the other hand, two body fat indicators: the Fat Mass Index (FMI) and the percentage of Fat Mass (%FM). Then we compared the effects of the work economic sectors on several cardiovascular risk factors. Finally using a longitudinal study, we evaluated the links between socioeconomic variables and the evolution of the anthropometric parameters among participants of the RECORD Study. Simultaneously, our methodological objective was to explore the attrition biases due to missing data in longitudinal studies.To conclude, we could by those empirical works highlight the effect of the individual and the residential characteristics, and the work economic sectors on the accumulation of body fat as well as on cardiovascular risk factors. Regarding the methodological part of this work, firstly we were able to take into account in the analysis the residential geographical environment commonly considered. Secondly, differentiating us from the transversal literature on the social determinants of obesity, we show that depending on the missing data mechanism, the statistical methods commonly used can not circumvent the potential bias introduced by attrition in longitudinal analyses.

No description available.

GH and IGF-1 play an important role in the regulation of metabolism and body composition. In patients with uncontrolled acromegaly, cardiovascular morbidity and mortality are increased but are supposed to be normalised after biochemical control is achieved. We aimed at comparing body composition and the cardiovascular risk profile in patients with controlled acromegaly and controls. A cross-sectional study. We evaluated anthropometric parameters (height, weight, body mass index (BMI), waist and hip circumference, waist to height ratio) and, additionally, cardiovascular risk biomarkers (fasting plasma glucose, HbA1c, triglycerides, total cholesterol, HDL, LDL, and lipoprotein (a), in 81 acromegalic patients (58% cured) compared to 320 age- and gender-matched controls (ratio 1:4), sampled from the primary care patient cohort DETECT. The whole group of 81 acromegalic patients presented with significantly higher anthropometric parameters, such as weight, BMI, waist and hip circumference, but with more favourable cardiovascular risk biomarkers, such as fasting plasma glucose, total cholesterol, triglycerides and HDL levels, in comparison to their respective controls. Biochemically controlled acromegalic patients again showed significantly higher measurements of obesity, mainly visceral adiposity, than age- and gender-matched control patients (BMI 29.5 ± 5.9 vs. 27.3 ± 5.8 kg/m2; P = 0.020; waist circumference 100.9 ± 16.8 vs. 94.8 ± 15.5 cm; P = 0.031; hip circumference 110.7 ± 9.9 vs. 105.0 ± 11.7 cm; P = 0.001). No differences in the classical cardiovascular biomarkers were detected except for fasting plasma glucose and triglycerides. This effect could not be attributed to a higher prevalence of type 2 diabetes mellitus in the acromegalic patient group, since stratified analyses between the subgroup of patients with acromegaly and controls, both with type 2 diabetes mellitus, revealed that there were no significant differences in the anthropometric measurements. Biochemically cured acromegalic patients pertain an adverse anthropometric risk profile, mainly because of elevated adiposity measurements, such as BMI, waist and hip circumference, compared to an age- and gender-matched primary care population.

Hintergrund und Ziel: Der hausärztliche Bereich ist von zentraler Bedeutung für die Betreuung von Patienten mit Diabetes mellitus. Die Autoren untersuchten a) die Prävalenz von Diabetes mellitus Typ 1 und Typ 2, b) die Art und Häufigkeit von nichtmedikamentösen und medikamentösen Behandlungen und deren Zusammenhang mit dem Vorliegen von diabetestypischen Komplikationen sowie c) die Qualität der Stoffwechseleinstellung anhand des HbA1c. Methodik: Auf der Grundlage einer bundesweiten Zufallsstichprobe von 3 188 Arztpraxen („response rate“ [RR] 50,6%) wurden 55 518 Patienten (RR 93,5%) im September 2003 in einer prospektiven Querschnittsstudie standardisiert mit Fragebögen, Arztgespräch und Labormessungen untersucht. Neben Diabetes mellitus wurden 28 weitere Erkrankungen explizit erfasst, darunter auch die typischen makrovaskulären (koronare Herzkrankheit, zerebrovaskuläre Erkrankungen, periphere arterielle Verschlusskrankheit) und mikrovaskulären Komplikationen (Neuropathie, Nephropathie, Retinopathie, diabetischer Fuß). Ergebnisse: Es wurde eine Prävalenz des Diabetes mellitus von 0,5% (Typ 1) bzw. 14,7% (Typ 2) dokumentiert. 49,5% (Typ 1) bzw. 50,2% (Typ 2) der Patienten hatten bereits mikro- oder makrovaskuläre Folge- bzw. Begleiterkrankungen. 6,8% der Patienten erhielten keine Therapie, 13,5% wurden nur mit Diät/Bewegung behandelt, und 75,3% erhielten orale Antidiabetika und/oder Insulin, davon 26,6% eine Kombinationstherapie mit verschiedenen Antidiabetika. Die Behandlungsintensität war im Vergleich zu Diabetikern ohne Komplikationen bei Patienten mit mikrovaskulären Kom- plikationen deutlich höher (Odds-Ratio [OR] 3,02) als bei denen mit makrovaskulären Komplikationen (OR 0,98). Ein HbA1c-Wert ≥ 7,0% fand sich bei 39,6% der Patienten. Schlussfolgerung: Im Vergleich zu früheren Untersuchungen im hausärztlichen Bereich hat die Rate der medikamentös behandelten Diabetiker zugenommen. Eine Kombinationstherapie wird häufiger eingesetzt. Die Qualität der Einstellung scheint sich ebenfalls verbessert zu haben. / Background and Purpose: The primary care sector is of key importance for the management of patients with diabetes mellitus. The authors investigated (a) the prevalence of diabetes mellitus type 1 and type 2, (b) the type and frequency of non-drug and drug treatment and its association with the presence of diabetic complications, and (c) the quality of metabolic control by HbA1c. Method: Using a nationwide probability sample of 3,188 general practices (response rate [RR] 50.6%), a total of 55,518 (RR 93.5%) patients were assessed in a prospective cross-sectional study by their physicians in September 2003 in a standardized manner using questionnaires, physician interview, and laboratory assessments. In addition to diabetes mellitus, 28 diseases were explicitly screened for, among them typical macrovascular (coronary heart disease, cerebrovascular disease, peripheral arterial disease) and microvascular disease (neuropathy, nephropathy, retinopathy, diabetic foot) complications. Results: The prevalence of diabetes mellitus was 0.5% (type 1) and 14.7% (type 2), respectively. 49.5% (type 1) and 50.2% (type 2) of patients had micro- or macrovascular complications. 6.8% did not receive any treatment, 13.5% received non-drug treatment, and 75.3% received oral antidiabetic drugs and/or insulin (26.6% a combination of two or more). Compared to diabetics without any complications, treatment intensity was significantly higher in patients with microvascular complications (odds ratio [OR] 3.02), but not in those with macrovascular complications only (OR 0.98). An HbA1c value ≥ 7.0% was recorded in 39.6% of patients. Conclusion: Compared to previous studies in this setting, the proportion of diabetics with drug treatment has increased. More patients receive antidiabetic drug combinations. Quality of blood sugar control appears to have improved as well.

Hintergrund: Es ist bislang unklar, inwieweit etablierte Scores zur Abschätzung des kardiovaskulären Risikos (PROCAM-Score, Framingham-Score, ESC-Score Deutschland) untereinander sowie mit der subjektiven Arzteinschätzung übereinstimmen. Methodik: An einer bundesrepräsentativen Stichprobe von 8 957 Hausarztpatienten im Alter von 40–65 Jahren ohne bekannte vorangegangene kardiovaskuläre Ereignisse wurde mittels unterschiedlicher Methoden das Risiko bestimmt, innerhalb der nächsten 10 Jahre einen Herzinfarkt oder Herztod zu erleiden. Ergebnisse: Das mittlere koronare 10-Jahres-Morbiditätsrisiko wurde mit dem PROCAM-Score auf 4,9% und mit dem Framingham-Score auf 10,1% geschätzt, das mittlere kardiovaskuläre 10-Jahres-Mortalitätsrisiko mit dem ESC-Score auf 2,9%. Die behandelnden Ärzte klassifizierten nur 2,7% der Patienten als kardiovaskuläre Hochrisikofälle. Nach Framingham wurden die meisten Patienten in die Hochrisikokategorie eingeordnet (22,6%). Bezüglich der Risikokategorisierung ergab sich eine nur moderate Übereinstimmung zwischen den drei Scores (bei 34% aller Risikofälle). Bei 5,9% der Patienten kamen die drei Scores zu einer komplett unterschiedlichen Risikobewertung. Den nach den verschiedenen Risikoscores in die Hochrisikogruppe kategorisierten Patienten wurde von den behandelnden Ärzten nur in ca. 8% der Fälle ebenfalls ein hohes kardiovaskuläres Risiko zugeordnet, in ca. 48% ein mittleres Risiko und in 41–46% (je nach Score) ein geringes Risiko. Schlussfolgerung: Die Methoden ergeben nur eine relativ geringe Übereinstimmung in der Beurteilung von Risikopatienten. Besonders niedrig fällt die Übereinstimmung bei der Hochrisikogruppe mit der Einschätzung der klinischen Risikoprädiktion durch den behandelnden Hausarzt aus. Die erhebliche Abweichung zur Arztbeurteilung scheint anzudeuten, dass die etablierten Risikoscores in der Praxis derzeit einen nur eingeschränkten praktischen Stellenwert besitzen. Welche der Vorhersagen mit dem tatsächlichen Risiko am besten übereinstimmen, wird derzeit mit den prospektiven DETECT-Studiendaten geprüft.