京都大学 / 0048 / 新制・論文博士 / 博士(医学) / 乙第13207号 / 論医博第2161号 / 新制||医||1031(附属図書館) / (主査)教授 福原 俊一, 教授 湊谷 謙司, 教授 小池 薫 / 学位規則第4条第2項該当 / Doctor of Medical Science / Kyoto University / DFAM

京都大学 / 0048 / 新制・課程博士 / 博士(社会健康医学) / 甲第21456号 / 社医博第90号 / 新制||社医||10(附属図書館) / 京都大学大学院医学研究科社会健康医学系専攻 / (主査)教授 滝田 順子, 教授 小杉 眞司, 教授 三森 経世 / 学位規則第4条第1項該当 / Doctor of Public Health / Kyoto University / DFAM

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Paraoxonase-1 (PON1) is a high density lipoprotein (HDL)-associated enzyme displaying esterase and lactonase activity. PON1 hydrolyzes the oxons of several organophosphorous insecticides (e.g. paraoxon, diazoxon and chlorpyrifos-oxon) and metabolizes lipid peroxides of low density lipoproteins (LDL) and HDL. As such, PON1 plays a relevant role in determining susceptibility of organophosphate toxicity and cardiovascular disease. The objective of this study was to determine associations of PON1 status (i.e. genotype and activity levels) with atherosclerosis (ATH) in individuals from the Southeastern United States. An additional objective was to determine whether PON1 genotype and/or PON1 activity levels influence the capacity of PON1 to metabolize chlorpyrifos-oxon (CPO) at a relatively low concentration. Data indicated increasing PON1 activity assessed by hydrolysis of phenyl acetate is associated with decreased odds of ATH. Furthermore, neither PON1 genotype nor PON1 activity levels influence capacity of PON1 to metabolize CPO at a relatively low concentration.

Mississippi has a very high prevalence of coronary artery disease (CAD) and type 2 diabetes (T2D), especially among African Americans compared to Caucasians. This project determined the L55M genotypes of paraoxonase 1 (PON1) in 187 people and evaluated associations of PON1 single nucleotide polymorphisms (SNPs), Q192R and L55M, with CAD and T2D in a Mississippian (southern) population. Significant associations were found with PON1 SNPs and race: genotypes LL, LM, QR, and RR showed significant associations with race (p values 0.0000955, 0.0024, 0.00001244, and 0.00001676, respectively), and combined genotypes LMQQ and LMRR were significantly associated with race (p values = 0.0001013 and 0.000473, respectively). While no significant associations were found between PON1 SNPs and CAD (p values > 0.2374), combined genotype LMQQ and genotype LM trended towards the likelihood of having T2D with p values = 0.0723 and 0.0931, respectively, and are suggestive of a potential biomarker for T2D risk.

Bakgrund: Trots stark evidens för att fysisk aktivitet och träning vid kranskärlssjukdom är viktiga ur ett livslångt perspektiv för individer med kranskärlssjukdom finns begränsat med forskning kring vilka metoder som kan ha effekt på vidmakthållandet av fysisk aktivitet efter att individen genomgått den centerbaserade träningen. Syfte: Syftet med den här litteraturstudien var att granska effekten av vidmakthållande hjärtrehabilitering på fysisk aktivitet och fysisk kapacitet i sex månader eller mer hos individer med kranskärlssjukdom som genomgått centerbaserad hjärtrehabilitering. Vidare var syftet att undersöka kvalitet och tillförlitlighet i ingående artiklar.  Metod: Systematiska sökningar i databaserna AMED, PubMed och PsycINFO. Tio randomiserade kontrollerade studier inkluderades. Kvalitet bedömdes med PEDro-skalan och resultatens samlade tillförlitlighet bedömdes enligt SBU GRADE.  Resultat: Kvalitén på ingående artiklar var måttlig till medelgod. Tillförlitligheten bedömdes som mycket låg enligt SBU GRADE. Resultatet indikerade, trots stor variation av interventioner, att vidmakthållande hjärtrehabilitering kan ha effekt på fysisk aktivitet och till viss del på fysisk kapacitet (kondition). För muskelstyrka ses ingen effekt.  Konklusion: Kvalitén på de ingående artiklarna var måttlig till medelgod. Enskilda artiklar visar på signifikanta resultat som indikerar att vidmakthållande hjärtrehabilitering kan ha effekt på fysisk aktivitet och kapacitet hos individer med kranskärlssjukdom. Det sammanvägda resultatet för vidmakthållande hjärtrehabiliterings effekt på fysisk aktivitet hos individer med kranskärlssjukdom har låg tillförlitlighet bedömt med SBU GRADE. För vidmakthållande hjärtrehabiliterings effekt på fysisk kapacitet (kondition och styrka) bedöms tillförlitligheten som mycket låg. / Background: Despite evidence that physical activity and training in coronary artery disease are important from a lifelong perspective for individuals with coronary artery disease, there is limited research on which methods that can support physical activity maintenance after center-based training.  Aim: The aim of this literature study was to examine the effect of maintenance cardiac rehabilitation (M-CR) on physical activity and physical capacity for six months or more in individuals with coronary artery disease after center-based cardiac rehabilitation. The aim was also to examine the quality and reliability of included articles. Method: Systematic searches in the AMED, PubMed and PsycINFO databases. Ten randomized controlled trials were included. Quality was assessed using the PEDro scale.The overall reliability of the results was assessed according to SBU GRADE guidelines. Result: The quality of included articles was moderate to average. Reliability was assessed as low to very low according to SBU GRADE. The result indicated, despite variation of interventions, that M-CR can have an effect on physical activity and to some extent on physical capacity (fitness). For muscle strength, no significant effect is seen. Conclusion: Individual articles show significant results indicating that M-CR can have an effect on physical activity and capacity in individuals with coronary artery disease. The quality of the included articles was moderate to average. The overall reliability on physical activity was assessed as low according to SBU GRADE. And the overall reliability on physical capacity (fitness and muscle strength) was assessed as very low according to SBU GRADE.

Evaluation of: Bangalore S, Steg PG, Deedwania P et al. β-Blocker use and clinical outcomes in stable outpatients with and without coronary artery disease. JAMA 308(13), 1340–1349 (2012). The number of myocardial infarctions (MIs) in population remains high and this event is a significant predictor of mortality. Information in the literature points to a reduction in mortality, reinfarction and sudden death in first year, especially in patients with high risk, if β-blockers (BBs) are used after MI. In a perspective study, Zuckerman et al. have determined outcome following pharmacotherapy after acute MI in older adults. It is apparent that a number of matters require consideration in evaluation of the effectiveness of BBs. It seems that not all patients benefit equally from treatment with BBs but such an intervention reduces mortality. It is also important to recognize that the beneficial effects of BBs should not be considered in isolation since the biological system is too complex to manipulate with the use of a single class of drugs.

Background: In most countries of the Western world there have been positive reductions in incidence of cardiovascular diseases in the past decades, among both men and women, but still mortality due to these disease groups are very high. Many studies about myocardial infarction have shown that depression after an event is related to poor medical outcomes from the disease. This means prolonged disability events of angina, arrhythmias, re-hospitalization and increased rate of mortality. In post myocardial infarction patients, depression is a major cause of both short and long term mortality. Aim: The aim of this study was to examine the scientific literature by a systematic review in order to find evidence based knowledge about the benefit of physical activity as a tool to reduce depression in patients with coronary artery event.Method: Three databases were searched (Pubmed, CINHAL, Cochrane) systematically and all articles that met inclusion criteria were examined and graded according to the criteria “Grading quality of evidence and strength of recommendations” by Atkins. A special protocol was designed further from AMSTAR by Beverley, for systematic review with and without the meta-analysis study. Results: It was evident that scientific reports fitting to the area was scarce showing that the area of interest was fairly new. Finally ten studies were included in this study, one meta-analysis, five randomized controlled trail and four clinical trials. The results showed low to moderate evidence for the use of high, moderate and low level of exercise as a tool to reduce depression in post coronary artery event patients.Conclusion: The following study concluded that, exercise shows positive effects to reduce the level of depression among coronary artery event patients.

The P2Y inhibitor, ticagrelor, has been shown to prevent thrombotic events and hence, improve morbidity and mortality in patients with acute coronary syndrome following coronary artery stent placement. Despite many clinical benefits, ticagrelor has been associated with several adverse effects, including dyspnea, easy bruising, and gastrointestinal bleeding. We report the case of a 67-year-old patient with an acute coronary artery syndrome requiring percutaneous coronary artery intervention with stenting who developed ticagrelor-induced diarrhea. The patient's ticagrelor medication was replaced with clopidogrel, and his diarrhea completely resolved within one week with no complications observed at his one-month follow-up visit. Clinicians should be aware of this adverse effect of ticagrelor so as to guide them toward possible underlying etiologies and appropriate workup of chronic diarrhea.