In the present study Fourier Transform Infrared (FTIR) and Attenuated Total Reflectance FTIR (ATR-FTIR) Spectroscopy were used to examine the effects of simvastatin on structure, composition and function of macromolecules of three different rat skeletal muscles EDL (Extensor Digitorium Longus), DIA (Diaphragm) and SOL (Soleus) containing different amount of slow and fast twitch fibers, at molecular level. Simvastatin, a lipophilic statin, is widely used in the treatment of hypercholesterolemia and cardiovascular diseases due to its higher efficacy. However, long term usage of statins give rise to many adverse effects on different tissues and organs. Skeletal muscle accounts for around 45 % of the total body weight and has a high metabolic rate and blood flow. As a consequence, it is highly exposed to drugs within the circulation. Therefore, it is one of the target tissues of statins. The two main types of muscle fibers are type I (slow-twitch) and type II (fast-twitch) fibers / having different structural organization and metabolic features. EDL is a fast twitch muscle while SOL is slow twitch muscle. On the other hand, DIA shows intermediate properties between slow and fast twitch muscle. The results of ATR-FTIR and FTIR spectra revealed a considerable decrease in protein and lipid content of simvastatin treated skeletal muscles, indicating protein breakdown or decreased protein synthesis and increased lipolysis. Moreover changes in protein structure and conformation were observed. In simvastatin treatment, muscle membrane lipids were more ordered and the amount of unsaturated lipids was decreased possibly due to lipid peroxidation. The drug treatment caused a decrease in the content of nucleic acids, especially RNA, and hydrogen and non-hydrogen bonded phospholipids in the membrane structures of skeletal muscles. In all of the spectral parameters investigated EDL muscle was more severely affected from statin treatments while SOL was less affected from the drug treatments. Thus, FTIR and ATR-FTIR spectroscopy appear to be useful methods to evaluate the effects of statin on skeletal muscle tissues at molecular level.

Quality of a prescription drug is uncertain to patients, physicians and even the manufacturer of the drug. Because this uncertainty can deter physicians from prescribing the drug, it is important to investigate how various marketing communication activities help reveal the true quality of its product. In particular, this study investigates publicity and advertising under quality uncertainty. Chapter 1 studies the effect of publicity on consumer demand with a reduced form approach. Chapter 2 structurally investigates the roles of detailing and publicity when the information spill-over is present. Both chapters study the market of anti-cholesterol drugs (statins). Chapter 1 investigates the effects of publicity (media coverage) on consumer demand. The main obstacle to measuring the impact of publicity is that data on media coverage are difficult to interpret. To overcome this obstacle, we propose a new way to code information presented in news articles, mapping the information to a multi-dimensional attribute space. We combine our publicity data with data on sales, detailing, medical journal advertising, direct-to-consumer advertising (DTCA) and landmark clinical trial outcomes, and estimate a demand model. Our results suggest that not all forms of publicity are equal. In chapter 2, we study consumer learning about scientific evidence and its impact on demand for pharmaceutical products by using the Bayesian learning model. Unlike previous literature, our learning model allows consumer’s prior quality perceptions to be correlated across brands. This unique feature of the model allows us to investigate information spill-over effects across brands. The information spill-over allows late entrants to free-ride on first movers’ investment in clinical trials and marketing activities and to gain late mover advantage. In addition to using product level market share data, we supplement them with switching rates and discontinuing rates. The switching rate data are particularly useful for taking the presence of switching costs into consideration, which has been ignored in the literature using product-level data. Our estimated structural model has implications for managers in allocating resources to various types of marketing activities more efficiently and helps forecast returns of clinical trials that are sponsored by pharmaceutical firms.

Statins, common cholesterol control drugs, are appreciated to have promising anticancer activity through inhibition of the mevalonate pathway. Several lines of evidence suggest that certain tumours are susceptible to statins, but the underlying molecular features arbitrating this sensitivity remain unknown. We hypothesize that (i) not all statins will behave equivalently in the context of anticancer therapy, and (ii) a molecularly-defined subset of tumours are intrinsically sensitive to statins. My objectives have therefore been to further our understanding of functional differences between statins influencing their anticancer effects, and to investigate molecular features associated with statin sensitivity in breast cancer. Specifically, this thesis addresses two aims: (i) to characterize differential interactions between four statins and the xenobiotic transporter P-glycoprotein (P-gp; also known as ABCB1), and (ii) to identify molecular features associated with fluvastatin and lovastatin sensitivity in breast tumour cell lines. We first characterized the interactions of statins with P-gp in vitro and in multidrug-resistant (MDR) tumour cells. While lovastatin could directly bind to P-gp and modulate MDR, no significant interactions were observed with fluvastatin. Fluvastatin may therefore be appropriate for use in unselected patients, to avoid adverse drug interactions with coadministered P-gp substrate chemotherapeutics. Fluvastatin has also shown promise in breast cancer treatment, where molecular features predictive of statin sensitivity would be particularly valuable. A panel of 19 immortalized breast cell lines was therefore characterized for sensitivity to fluvastatin and lovastatin. Relatively statin-sensitive cells underwent apoptosis upon statin treatment, and were more likely to have an estrogen receptor alpha (ERα)-negative, basal-like phenotype. By mining available baseline gene expression data, a candidate 10-gene signature predictive of fluvastatin sensitivity was also generated. Taken together, this research provides insight into molecular markers of statin sensitivity that may facilitate fast-tracking of these drugs to clinical trials in subsets of cancer patients most likely to respond.

Quality of a prescription drug is uncertain to patients, physicians and even the manufacturer of the drug. Because this uncertainty can deter physicians from prescribing the drug, it is important to investigate how various marketing communication activities help reveal the true quality of its product. In particular, this study investigates publicity and advertising under quality uncertainty. Chapter 1 studies the effect of publicity on consumer demand with a reduced form approach. Chapter 2 structurally investigates the roles of detailing and publicity when the information spill-over is present. Both chapters study the market of anti-cholesterol drugs (statins). Chapter 1 investigates the effects of publicity (media coverage) on consumer demand. The main obstacle to measuring the impact of publicity is that data on media coverage are difficult to interpret. To overcome this obstacle, we propose a new way to code information presented in news articles, mapping the information to a multi-dimensional attribute space. We combine our publicity data with data on sales, detailing, medical journal advertising, direct-to-consumer advertising (DTCA) and landmark clinical trial outcomes, and estimate a demand model. Our results suggest that not all forms of publicity are equal. In chapter 2, we study consumer learning about scientific evidence and its impact on demand for pharmaceutical products by using the Bayesian learning model. Unlike previous literature, our learning model allows consumer’s prior quality perceptions to be correlated across brands. This unique feature of the model allows us to investigate information spill-over effects across brands. The information spill-over allows late entrants to free-ride on first movers’ investment in clinical trials and marketing activities and to gain late mover advantage. In addition to using product level market share data, we supplement them with switching rates and discontinuing rates. The switching rate data are particularly useful for taking the presence of switching costs into consideration, which has been ignored in the literature using product-level data. Our estimated structural model has implications for managers in allocating resources to various types of marketing activities more efficiently and helps forecast returns of clinical trials that are sponsored by pharmaceutical firms.

Background: Surgical stress during resection surgery for colon cancer has previously been shown to be associated with adverse postoperative outcomes. Statin and beta-blocker treatment have been shown to lower postoperative complications and mortality, and been hypothesized to reduce the surgical stress response, although this correlation has not been studied clinically. Aim: To investigate whether perioperative beta-blocker and/or statin treatment reduce the postoperative C-reactive protein (CRP) response. Material and methods: All patients who underwent right sided hemicolectomy or sigmoid resection for cancer at Örebro University Hospital during 2012-2017 were included in this study. Initially, any treatment with statins, beta-blockers or both were compared to those with no treatment. After initial analyses, four treatment groups were compared regarding postoperative CRP response, namely no treatment, statin, beta-blocker, and combination treatment. Comparisons regarding complications were also performed for the four groups. Results: A total of 260 patients were included in this study. The no treatment group had a lower peak postoperative CRP than the treatment group, when comparing any treatment versus no treatment. There were no significant differences in postoperative CRP within the four treatment groups. There was no significant difference in complication rate between any of the treatment groups when compared to no treatment. Conclusion: Treatment with statin or beta-blocker therapy does not reduce the postoperative CRP response. A combination of both treatments demonstrated a trend towards a reduction regarding postoperative CRP response compared with the two treatments individually assessed. Larger studies are needed to verify the results of this study.

Background: Ischaemic heart disease is a diagnostic and therapeutic challenge to most general practitioners. We sought to identify diagnostic characteristics and prognoses of patients in primary care that received exercise electrocardiography (ECG). We compared the ECG test results with respect to probability of subsequent cardiologist referrals. We also aimed to identify determinants for pre-hospital delays and lack of statin treatment before a first-time myocardial infarction (MI). Methods: Setting: Region of Jämtland Härjedalen, Sweden (adult population, approximately 99 000); study period 2010-2014. Patients and study designs: studies I and II: 865 patients referred to exercise ECG. Primary outcome: Incidence of cardiovascular events (I) and cardiologist referrals within six months after exercise ECG (II). Observed outcomes were compared to predictions from multivariable logistic models. Study III: 265 patients with first-time MI. Characteristics were analysed for determinants of pre-hospital delay ≥ 2 hours. Study IV: Survey of 931 patients with first-time MI. Analyses of characteristics associated with rates of statin treatment in patients with previously diagnosed cardiovascular diseases (CVD). Results: Study I: Exercise test results were associated with exertional chest pain, a pathologic ST-T segment on resting ECG, angina diagnosis according to the patient's opinion, and medication for dyslipidaemia. Cardiovascular events occurred in 52.7%, 18.3%, and 2.0% of patients with positive (ST-segment depression >1mm and chest pain indicative of angina), inconclusive (ST depression or chest pain), or negative tests, respectively. Study II: Positive or inconclusive exercise tests were associated with cardiologist referrals. Among patients with positive exercise tests, referral rates decreased with age, after adjusting for co-morbidity. Self-employed women were referred to cardiologic evaluations more often than other employed women. Study III: The first medical contact was a primary care facility for 52.3% of patients. The pre-hospital delay time was ≥ 2 h for 67.0% of patients in primary care and 44.7% of patients that called emergency medical services or were self-referred to hospital. Study IV: Among patients with prior CVD, 34.5% received current statin treatment before for the first MI. Statin treatment rates decreased with age, after adjusting for CVD and diabetes; women ≥70 years old were treated half as often as men of the same age. Conclusions: Clinical characteristics can be used to identify patients at low risk of cardiac events. The prognosis in patients with a negative exercise ECG was benign for six months after the exercise ECG. Exercise tests are important for selecting patients that require cardiologic evaluations. Age, gender, and employment status interacted with rates of referrals for cardiac evaluation. The pre-hospital delay time was considerably prolonged, particularly when primary care was the first medical contact. Only one third of patients with a prior CVD received statin treatment. Pre-MI statin treatment decreased with age, particularly among women ≥70 years old. In making medical decisions, it is necessary to be aware of biases regarding age, gender, and socioeconomic status. Methodologies for case finding and follow-up need to be improved and implemented in clinical practice. Keywords: Exercise ECG, Ischaemic heart disease, Myocardial infarction, Pre-hospital delay, Primary care, Prognosis, Referral, Statins, Secondary prevention / Sammanfattning på svenska: Bakgrund och syfte: Patienter med ischemisk hjärtsjukdom (IHD) utgör en diagnostisk och terapeutisk utmaning för läkare inom primärvården. Arbets-EKG är en vanlig metod vid utredning av patienter som söker till primärvården för besvär som kan vara förorsakade av IHD. Vi undersökte primärvårdspatienter remitterade till arbets-EKG, med avseende på de kliniska karakteristika (egenskaper och symtom) som kunde associeras med resultatet av arbets-EKG och med prognosen inom sex månader efter undersökningen. Vi jämförde arbets-EKG-svaren med avseende på efterföljande remittering för utredning vid hjärtklinik. Vi kartlade även faktorer av betydelse för tidsfördröjningen före sjukhusvård och för sekundärpreventiv behandling med kolesterolsänkande läkemedel (statiner), före insjuknande i hjärtinfarkt. Metod: De studier som ingår i avhandlingsarbetet (studier I-IV) genomfördes i Region Jämtland och Härjedalen, befolkningsunderlag cirka 99 000 personer i åldrar från 20 år och äldre, under åren 2010-2014. Undersökta patienter och studiedesign: Studier I och II: Prospektiv studie av 865 patienter undersökta med arbets-EKG, klassificerade som: positivt arbets-EKG (dynamisk ST-sänkning >1mm under arbetsprov och bröstsmärta typisk för kärlkramp), inkonklusivt (ST-sänkning eller bröstsmärta) eller negativt arbets-EKG. Utfallsvariabler: hjärt-kärlhändelser (instabil kärlkrampssjukdom, hjärtinfarkt, öppen kranskärlsoperation, ballongvidgning av kranskärl och kardiovaskulära dödsfall) (I) och remittering för utredning vid hjärtklinik inom sex månader efter arbets-EKG (II). Observerade hjärt-kärlhändelser jämfördes med förväntat utfall, enligt multivariabla statistiska modeller. Studie III: Retrospektiv studie av 265 patienter med förstagångs hjärtinfarkt, analyserade med avseende på faktorer av betydelse för tid från symtomdebut och till sjukhusvård, med brytpunkten två timmar eller längre tid för vård på sjukhus. Studie IV: Tvärsnittsstudie av 931 patienter med förstagångs hjärtinfarkt. Patienter med tidigare hjärt-kärlsjukdom analyserades med avseende på statinbehandling före hjärtinfarkten. Resultat: Studie I: Faktorer associerade med arbets-EKG-resultatet (positivt eller inkonklusivt svar mot negativt svar) var: ansträngningskorrelerad bröstsmärta före arbetsprovet, ST-T-segmentsförändringar på vilo-EKG, kärlkrampsdiagnos enligt patientens egen bedömning, samt medicinering för förhöjda kolesterolvärden i blodet. Hjärt-kärlhändelser inträffade i 52.7%, 18.3%, och 2.0% bland patienter med positivt, inkonklusivt respektive negativt arbets-EKG. Studie II: Resultatet från arbets-EKG styrde remitteringen av patienter till hjärtklinik, med högre sannolikhet för remiss efter positivt test. Bland patienter med positivt arbets-EKG remitterades färre patienter vid stigande ålder, justerat för tidigare känd hjärt-kärlsjukdom. Egenföretagande kvinnor blev oftare remitterade än andra kvinnor, justerat för ålder, bröstsmärtesymtom och arbets-EKG-svar. Studie III: I 52.3% av samtliga fall var primärvården (personligt besök eller via telefonrådgivning) den första vårdkontakten för patienter med förstagångs hjärtinfarkt. Tidsfördröjningen före sjukhusvård var 2 timmar eller mer bland 67.0% av alla patienter från primärvården och 44.7% bland de patienter som först ringde larmcentralen (112) eller sökte direkt till sjukhusets akutmottagning. Studie IV: Patienter med tidigare konstaterad hjärt-kärlsjukdom hade en pågående statinbehandling i 34.5% av fallen, före insjuknandet i förstagångs hjärtinfarkt. Andelen patienter med pågående statinbehandling avtog med stigande ålder, justerat för diabetes och tidigare hjärt-kärlsjukdom. Kvinnor från 70 år och äldre erhöll statinbehandling hälften så ofta som jämförbara män. Slutsats: Patienter med låg risk för hjärt-kärlhändelser kan identifieras före remittering till arbets-EKG, med hjälp av kliniska karakteristika. Patienter med negativt svar på arbets-EKG har en god prognos, med få hjärt-kärlhändelser inom sex månader efter arbetsprovet. Urvalet av patienter som remitteras för fortsatt hjärtutredning styrs av resultatet från arbets-EKG, men interaktioner mellan ålder, kön och anställningsförhållanden påverkar sannolikheten för remittering. Tiden från symtomdebut och till sjukhusvård var avsevärt fördröjd, särskilt för de patienter som primärt kontaktade primärvården. Endast en tredjedel av alla patienter med tidigare konstaterad hjärt-kärlsjukdom hade en pågående statinbehandling vid hjärtinfarktinsjuknandet. Andelen patienter med pågående statinbehandling avtog med högre ålder, särskilt bland kvinnor från 70 års ålder och äldre. En ökad medvetenhet om hur ålder, kön och social ställning påverkar den medicinska beslutsprocessen är angelägen. Metoder för bättre identifiering och uppföljning av riskpersoner behöver utvecklas och införas i den medicinska verksamheten. Nyckelord och förklaringar: Arbets-EKG (kliniskt arbetsprov på ergometercykel med samtidig EKG-registrering), positivt arbets-EKG (talar för kärlkrampssjukdom), negativt arbets-EKG (talar för frånvaro av sjukdom). EKG (elektrokardiografi), hjärtinfarkt, ischemisk hjärtsjukdom (sjukdomstillstånd med otillräcklig blodtillförsel till hjärtat), sekundärprevention (förhindra återinsjuknande i tidigare genomliden sjukdom).

Chondroplasia, the development of cartilage-like characteristics in tendinous tissue, is a form of degeneration found in tendons including those of the rotator cuff. The molecular mechanism of its development is currently unknown. An examination of the features of the torn rotator cuff and the cartilage literature led to the identification of several potential drivers of chondroplasia including cell shape change/actin cytoskeleton and hypoxia. Lovastatin caused actin cytoskeleton disruption and promoted cartilage matrix deposition in the ATDC5 model. It was the most effective member of a panel of cytoskeletal inhibitors, increasing expression of the chondrocytic markers Sox5 and Sox9 and decreasing expression of COL1A1 and COL3A1 in primary human tenocytes. Its effects were dose dependent, reversible by mevalonate addition and long term treatment induced de novo expression of collagen II. Short term hypoxia upregulated VEGF-A and chondrocytic marker gene DEC1 expression but not other chondrocyte markers. Combination treatment with hypoxia did not enhance the effects of lovastatin. These data suggest that modulation of pathways that regulate the actin cytoskeleton and cell shape may alter tenocyte phenotype.

Effet de l’atorvastatine sur la dysfonction endothéliale des artères coronaires épicardiques associée à l’hypertrophie ventriculaire gauche dans un modèle porcin Forcillo J, Aubin MC, Horn A, Shi YF, Carrier M, Tardif JC, Perrault LP Introduction: L’atorvastatine par ses effets pléiotropiques pourrait limiter la dysfonction endothéliale associée au développement de l’HVG. Méthodologie : Un cerclage de l’aorte ascendante pendant 2 mois entraîne le développement d’HVG et les groupes ont été traités avec atorvastatine 40 ou 80 mg de 60 à 90 jours. L’HVG est confirmée par échographie. La réactivité vasculaire est évaluée en chambres d’organe, la fonction endothéliale par la quantification de la GMPc et des nitrites/nitrates plasmatiques. Le stress oxydant est mesuré par les niveaux d’ANG II et de la carbonylation des protéines. Résultats : Après 60 et 90 j de cerclage, l’HVG est observée chez tous ces groupes. Les courbes concentrations-réponse des anneaux des artères coronaires épicardiques des groupes traités avec l’atorvastatine 40 et 80 mg pour 30 et 60 jours n’ont démontré aucune amélioration des relaxations dépendantes de l’endothélium. Une exacerbation significative de la dysfonction endothéliale a été observée. Les niveaux vasculaires de GMPc sont significativement diminués dans le groupe sans cerclage traité 60 d et ceux d’ANG II sont fortement augmentés chez ce dernier groupe ainsi que le groupe traité avec 80 mg pour 30 jours par rapport aux contrôles. L’expression de la carbonylation des protéines est augmentée dans le groupe témoin traité avec atorvastatine 80 mg, reflétant une augmentation du stress oxydant. Conclusion : L’administration d’atorvastatine ne prévient pas le développement de l’HVG ni la dysfonction endothéliale dans notre modèle. Au contraire l’atorvastatine à haute dose a un effet toxique sur les artères coronaires épicardiques en augmentant la dysfonction endothéliale. / Effect of atorvastatin on endothelial dysfunction of epicardial coronary arteries associated with left ventricular hypertrophy in a porcine model. Forcillo J, Aubin MC, Horn A, Shi YF, Carrier M, Tardif JC, Perrault LP Background: Atorvastatin, through pleiotropic effects, may prevent or reverse the endothelial dysfunction associated with LVH. Methods: After performing a banding of the ascending aorta for 2 months leading to the development of LVH, groups have been treated with atorvastatin 40 or 80 mg for 60 and 90 day periods. LVH was evaluated by echocardiographic studies. Vascular reactivity studies were performed in organ chambers. In vitro endothelial function was evaluated by plasmatic nitrites/nitrates, the degradations products of nitric oxide, and cGMP quantification. To quantify and qualify oxidative stress, protein carbonyl and angiotensin II levels were assessed. Results: Following 60 and 90 days of aortic banding, the development of LVH was observed in these groups. Concentration-response curves from rings of epicardial coronary arteries of groups treated with atorvastatin 40 and 80 mg for 30 and 60 days showed a significant decrease of endothelium-dependent relaxations with worsening of the endothelial dysfunction. Levels of cGMP were significantly decreased in the 60 days treated sham group and levels of ANG II were increased in the latter and also in the 90 days banded groups treated with 80 mg for 30 days compared to controls. The expression of protein carbonyl increased in the sham group treated with atorvastatin 80 mg compatible with an increase in oxidative stress. Conclusion: The administration of atorvastatin does not limit the development of LVH nor the endothelial dysfunction in our model. On the opposite, atorvastatin at a high dose has a toxic effect on epicardial coronary arteries by exacerbating the endothelial dysfunction.

As doenças cardiovasculares (DCV) são responsáveis pelas principais causas (dislipidemias e hipertensão arterial) de morte, sendo que o tratamento convencional é feito com estatina. Hoje alguns componentes presentes em alimentos tem sido apontados como alternativas ou coadjuvantes no tratamento. O objetivo deste trabalho foi avaliar as concentrações séricas de colesterol e suas frações, triglicérides e pressão arterial em humanos. O estudo foi conduzido em três tratamentos (placebo, estatina e ω-3) com dieta de 1200 calorias por dia. Os grupos com oito pacientes cada tratamento, foram avaliados no tempo zero e 30 dias. Nos três tratamentos houveram reduções no peso, porém não houve mudanças significativas no IMC. A circunferência de cintura (CC) diminuiu aproximadamente 3 cm em todos os tratamentos. Para a circunferência do quadril (CQ) maior diminuição foi no tratamento estatina (redução de 2,44 cm). Não houve diferença em nenhum dos tratamentos para relação circunferência cintura-quadril (CCQ). As concentrações de colesterol total diminuiu 41%; 11,38% e 5% para os tratamentos estatina, dieta e ω-3, respectivamente. Para o HDL-C o tratamento estatina aumentou 10,09%, dieta diminuiu 9,65% e ω-3 não promoveu mudança nos valores. Para LDL-C os tratamentos estatina e ω-3 reduziram 49% e 3,03%, respectivamente, porém o tratamento dieta aumentou 3,46%. Para os triglicérides os tratamentos com dieta, estatina e ω-3 diminuíram 28,05%, 18,95% e 13,45% , respectivamente. A pressão arterial sistólica (PAS) e pressão arterial diastólica (PAD) no tratamento estatina diminuíram 3,52% e 4,60%, respectivamente. No tratamento dieta a redução foi de 1,82% e 5,14% na PAS e PAD, respectivamente. Já no tratamento ω-3 houve discreto aumento tanto na PAS (11,30%) quanto na PAD (9,87%). Com isso conclui-se que houve diminuição significativa na medida da circunferência do quadril. Nos três tratamentos o peso, IMC, circunferência de cintura, coeficiente cintura-quadril, concentrações de colesterol, HDL-c, LDL-c, triglicérides, PAS e PAD não influenciaram significativamente nos resultados obtidos durante o experimento. / The cardiovascular diseases are responsible for the main causes (dislipidemias and arterial hypertension) of death, being that the conventional treatment is make with statin. Today some compoments presents in food it was been pointed as alternatives or coadjutants in treatment. The objective of this research was to evaluate the concentration control of cholesterol, HDL-cholesterol, LDL-cholesterol, triglycerides and arterial pressure in humans. The study was divided in three treatments (placebo, statin and ω-3) with diet of 1,200 calories by day to every groups with eight patients each treatment, appraised in time zero and thirty days. This study showed that all the treatments had reductions of weight, but it wasn't verified changes significative in BMI. The circumference waist decreased approximately three centimeters in all the treatments, to the circumference hip there was a larger decrease in statin treatment (reduction of 2.44 centimeter). For the waist-hip circumference there wasn't difference in all the treatments. The total cholesterol had decrease of 41%; 11.38% and 5% to statin, diet and ω-3 treatments, respectively. For the HDL-cholesterol the statin treatments increased 10.09%, diet decrease 9.65% and ω-3 not promoted change in values. In LDL-cholesterol the statin and ω-3 treatments decrease 49% and 3.03%, respectively, but the diet treatment increased 3.46%. For the triglycerides the diet, statin and ω-3 treatments decrease 28.05%; 18.95% and 13.45%, respectively. The systolic arterial pressure (SAP) and diastolic arterial pressure (DAP) in statin treatment decrease 3.52% and 4.60%, respectively. In the diet treatment the decrease was of 1.82% and 5.14% in SAP and DAP, respectively. In ω-3 treatment there was a discreet increase as much SAP (11.30%) as DAP (9.87%). With this concluded that the hip circumference showed difference statistical. In three treatments the weight, BMI, waist circumferences, waisthip circumference, cholesterol, HDL-cholesterol, LDL-cholesterol, triglycerides, SAP and DAP wasn't difference in experiment.

Introdução: As estatinas são drogas amplamente utilizadas na prevenção primária e secundária de doenças cardiovasculares, por reduzirem o nível de colesterol. Porém alguns pacientes podem apresentar elevação da creatinofosfoquinase (CPK) e sintomas musculares relacionados ao seu uso. Além da CPK, outros marcadores de dano muscular podem apresentar alterações. Este estudo analisou a concentração dos marcadores bioquímicos, CKMB e anidrase carbônica III (CAIII) e sua relação com a presença de miosite. Métodos: Foram selecionados pacientes em tratamento com estatinas e com elevação da CPK. Foram realizadas as determinações de CKMB e CAIII e analisadas as variáveis clínicas e laboratoriais destes pacientes. Resultados: Cerca de 10% dos pacientes em tratamento com estatina apresentaram elevações de CPK acima 1x o limite superior de normalidade (LSN). Desses, 50,4% apresentaram sintomas musculares, definido como miosite. O uso de sinvastatina [OR=2,24 (IC95%:1,47-3,42)], o índice de massa corpórea > 28 Kg/m2 [OR=1,06 (IC95%: 1,01-1,10)] e a CKMB > 1xLSN [OR=1,59 (IC95%: 1,02-2,49)] apresentaram-se como preditores independentes para a ocorrência de miosite. A CKMB aumentada foi observada em 36,2% dos pacientes (7,17±4,4 ng/mL). Os pacientes com e sem miosite apresentaram valores semelhantes de CAIII (211,3±93,4pg/mL vs 204,0±84,6pg/mL; p=0,549). Pacientes diabéticos apresentaram elevações significantes de CKMB em relação aos não diabéticos (4,8±4,6ng/mL vs 3,5±2,4ng/mL; p=0,0006) e não apresentaram diferenças quanto à presença de miosite. Conclusão: A CKMB apresentou alteração em parte dos pacientes tratados com estatinas e foi um preditor independente para a presença de miosite. A CAIII não foi considerada um bom marcador de dano muscular na população deste estudo / Introduction: Statins are drugs widely used in primary and secondary prevention of cardiovascular diseases, due to the decreasing effect on cholesterol level. However, some patients may present elevated levels of creatine phosphokinase (CK) and muscle symptoms related to statin use. In addition to CK, other markers of muscle damage may present changes. This study analyzed the concentration of biochemical markers, CKMB and carbonic anhydrase III (CAIII) and related them to the presence of myositis. Methods: Patients on statin therapy and CK elevation were selected. CKMB and (CAIII) assays were performed and the clinical and laboratory variables of these patients were analyzed. Results: About 10% of the patients receiving statin therapy (6692) presented CK elevations above 1x upper reference limit (URL). Muscular symptoms, defined as myositis, were presented in 50.4% of these patients. Use of simvastatin [OR=2,24 (IC95%:1,47-3,42)], a body mass index > 28 kg / m2 [OR = 1.06 (95% CI: 1.01-1, 10)] and a concentration of CKMB > 1x URL [OR = 1.59 (95% CI: 1.02-2.49)] presented as independent predictors for the occurrence of myositis. Increased CKMB was observed in 36.2% of patients (7.17 ± 4.4 ng / mL). Patients with and without myositis had similar CAIII values (211.3 ± 93.4pg / mL vs 204.0 ± 84.6pg / mL, p = 0.549). Diabetic patients showed significant elevations of CKMB compared to non-diabetic patients (4.8 ± 4.6 ng / mL vs. 3.5 ± 2.4 ng / mL, p = 0.0006) and did not present differences regarding the presence of myositis. Conclusion: CKMB level changed in part of the patients treated with statins and this enzyme was an independent predictor for the presence of myositis. CAIII was not considered a good marker of muscle damage in the studied population