Fatores de risco convencionais e emergentes para infarto agudo do miocárdio entre diabéticos e não diabéticos

Os distúrbios do metabolismo glicêmico e o infarto agudo do miocárdio (IAM) compartilham uma íntima relação. Os eventos cardiovasculares são as causas mais frequentes de óbitos entre os pacientes diabéticos e estes carregam uma carga de aterosclerose mais extensa e mais grave que a população não diabética. Entretanto, a prevalência de diabetes entre infartados e as relações entre o tempo de seu diagnóstico e a ocorrência do IAM são nebulosas, especialmente pelas dificuldades de determinação do início dos distúrbiosglicometabólicos. A prevalência de diabetes mellitus entre 200 pacientes acometidos de seu primeiro episódio de IAM, provindos da região metropolitana de Belo Horizonte, MG, foi de 29% IC95%[22,9;35,9]. O cálculo da amostra foi feito a partir de uma estimativa de 24,5%, um valor intermediário entre 21,6% e 33,28%, respectivamente as prevalências de pacientes com IAM sabidamente diabéticos e aqueles encontrados com glicemias de jejum 126mg/dL. Entre os diabéticos 22,4% foram diagnosticados na vigência do evento cardiovascular, em que uma glicemia de jejum126mg/dL, medida entre o 4º e o 11º dia pósIAM, era confirmada oito semanas depois da alta hospitalar ou após seis semanas de hospitalização. Agregando-se os pacientes diabéticos com aqueles com valores de glicemia de jejum entre 110mg/dL e 126mg/dL, portanto com intolerância à glicemia de jejum,resultou que 40% IC95%[28,5;42,1] de todos os pacientes infartados apresentaram um distúrbio glicometabólico. Entre os diabéticos, 44,8%IC95% [32,0;58,3] tiveram seu diagnóstico ou na vigência do IAM ou até no ano que precedeu o episódio, revelando uma característica metabólica da catástrofe cardíaca. Considerando a cintura abdominal como a medida clínica da resistência tissular à ação da insulina, estes pacientes apresentaram um valor mediano de 93,5cm, para os homens e mulheres. Como ainda não há estudos brasileiros em bases populacionais para definição de nossos valores étnicos, sugerimoseste valor como referência para o diagnóstico da síndrome metabólica, pelo menos para a população de origem da amostra, até se conseguir uma medida mais consistente como padrão. Também nesta amostra foi avaliada a prevalência de outros fatores de risco para IAM, tanto daqueles chamados convencionais porque se revelaram aos primeiros estudos epidemiológicos, quanto dos emergentes que surgiram dos estudos em bases globais como o INTERHEART. Considerando que estes fatores de risco convencionais, não comportamentais, podem todos pertencer a um terreno comum cuja patogenia estariarelacionada à presença de resistência tissular à ação da insulina, realizou-se um estudo de caso-controle comparando-se a prevalência destes fatores, e de outros fatores emergentes, em pacientes acometidos de seu primeiro IAM procurando-se sua associação com diabetes mellitus, como variável resposta. Constatou-se que os diabéticos têm IAM em faixas etárias semelhantes aos não diabéticos, mas as mulheres têm prevalência 2,5 vezes maior. A presençade aterosclerose, medida pelos valores da pressão arterial sistólica mesmo sob o tratamento intensivo do IAM, e pelo Índice Tornozelo Braquial (ITB) foi mais evidente e mais grave entre os diabéticos. Também o tabagismo no passado, e os valores de glicohemoglobina A1c maiores que a mediana de 6% - portanto distantes das recomendações terapêuticas para proteção das lesões microvasculares - estiveram associados ao diabetes. Os valores de LDL-C reduzidos, 173 mg/dL, estiveram associados de forma independente aos pacientes diabéticos, que por sua vezusaram o automóvel como meio mais freqüente de transporte urbano,possivelmente revelando um efeito deletério que a imobilidade pode causar neste grupo. Também considerando que diabetes pode ser conceituado como um equivalente vascular, tornando os diabéticos pacientes vulneráveis aos eventos aterotrombóticos, portadores de placas de ateroma passíveis de desestabilização, realizou-se um estudo caso-controle entre pacientes diabéticos que sofreram seu primeiro infarto e pacientes diabéticos que ainda não o sofreram, para avaliar a associação de fatores de risco cardiovascular para a variável resposta infarto agudo do miocárdio. Não houve associação ao infarto agudo para nenhuma variável que medisse o estado psicológico ou emocional, fosse como atributo de longa duração ou que tivesse surgido no ano anterior ao evento. A aterosclerose, medida pelo ITB foi significativamente mais freqüente entre os infartados diabéticos, mas não se mostrou independente na análise multivariada. Já o tabagismo, presente ou passado, revelou-se significativamente associado ao IAM entre diabéticos. O uso regular de estatinas, a atividade física regular e o uso de ônibus, ou caminhar a pé, como transporte urbano, revelaram-se fatores de proteção, depois de ajustados para todas as variáveis qualitativas. Quanto às variáveis metabólicas, os diabéticos que sofreram seu primeiro infarto não tiveram os maiores valores de glicemia e glicohemoglobina A1c associados ao evento, mas sim os valores intermediários, entre 150 mg/dL e 200 mg/dL para a glicemia, e menores que 6,7% para a glicohemoglobina A1c. Os pacientes infartados tiveram uma razão de chances 60 vezes maior para valores de HDLC abaixo de 32mg/dL e 18,7 vezes se estes valores estivessem entre 32,1 mg/dL e 42,0 mg/dL, e para a fração LDL-C, as concentrações abaixo de 86,8mg/dL estiveram associadas de forma independente ao infarto com razão de chances de 7,3 vezes. Como o episódio de infarto agudo interfere nas concentrações das frações lipídicas mas, aparentemente, não altera as razões entre estas frações, foi analisado um modelo de regressão para estas razões. Este mostrou que arazão Colesterol total/HDL-C >4,5 está associada de forma independente ao infarto agudo do miocárdio entre diabéticos, e ajusta-se para todas as outras variáveis metabólicas, substituindo-as, exceto para glicemia e glicohemoglobina.STUDY 1. ACUTE MYOCARDIAL INFARCTION AS A METABOLIC DISEASE: PREVALENCE AND LENGTH OF TIME OF DIABETES MELLITUS DIAGNOSIS.Acute myocardial infarction (AMI) and glucometabolic disturbances share an intimate relationship. Diabetics carry an atherosclerostic charge greater than non-diabetics and cardiovascular diseases are their outstanding cause of death. Patients with AMI have a prevalence of diabetes greater than general population and both diagnoses are frequently brought about together. Relations between duration of diabetes and occurrence of AMI are still nebulous, markedly determined by problems in establishing the onset of glucometabolic disorders.Prevalence of diabetes mellitus among 200 patients in their first acutemyocardial infarction arrived from the metropolitan area of Belo Horizonte, main city of Minas Gerais Brazil, was 29% CI95%[22,9;35,9]. Patient sample was calculated estimating a prevalence of 24,5%, a value between 21,6% and 33,28%, respectively the indices of known diabetes mellitus and fasting blood glycemia126mg/dL in first diagnoses of AMI patients. Diabetes was looked for through patients histories as well as active search, measuring fasting blood glucose and adopting WHO and ADA diagnostic criteria. Patients without known diabetes but with fasting blood glucose measurement 126mg/dL were reevaluated 8 weeks after hospital discharge by their primary physicians, and diabetes diagnosis was established only if confirmed by another dosage. Diabetes diagnosis was accomplished at the acute instance of infarction in22,4% of all diabetic patients. Summing up all diabetic patients with those with fasting blood glucose between 110mg/dL and 126mg/dL, known as fasting glucose intolerance, resulted 40% of some glucometabolic disturbance between patients with acute myocardial infarction. Within all diabetic patients 44,8%CI95%[32,0;58,3] had their diagnosis made at the instance of or in the year before the acute catastrophe. These data corroborate acute myocardial infarction as a metabolic disease. Abdominal obesity as a marker of increased risk of CVD was assessed through waist circumference. A median value of 93,5cm for both men and women was disclosed. Since there are no Brazilian population data base for waist circumference distribution we suggest these values as a reference for the metabolic syndrome diagnosis, at least in the original population where samplewas drawn. In addition, for the first time in Minas Gerais other conventional and emergent risk factors to CVD had their prevalence estimated among patients in their first AMI episode.STUDY 2. ACUTE MYOCARDIAL INFARCTION AS A METABOLIC DISEASE: RISK MARKERS TO DIABETES MELLITUS IN THE FIRST EPISODE.Diabetes mellitus as an independent risk factor to acute myocardial infarction (AMI) is partially interpreted due to its burden of cardiovascular factors. The common soil theory explains the connection of obesity, hypertension, dyslipidemia and diabetes through the insulin resistance and hyperinsulinemic status. Our aim was to evaluate the association of cardiovascular risk indicators among patients in their first AMI episode leading up to the presence of DM as a response variable, in a reverse way from classic studies. In a case-control study, conventional and emergent cardiovascular risk factors and other markers were compared between 73 diabetic patients and 142 nondiabetics in their first AMI. Two final logistic regression models were obtained. The first assessed gender, age, tobacco use, stress, cardiovascular family (CVF) history, hypertension history, ankle brachial index (ABI), regular exercise, urban locomotion and fever reported in the last 30 days. After adjustment, age,current tobacco use, stress, regular exercise, CVF and hypertension history did not show statistical significance. Female gender OR=2,3CI95% [1,14;4,5]; serious OR=3,4 CI95% [0,8;14,0] and moderate OR=2,1CI95% [1,1;5,8] peripheral arterial disease; previous tobacco use OR= 2,6 CI95%[1,2;5,8] and automobile preferred locomotion OR= 2,45 CI95%[1,3;4,6] were positively associated to diabetes, while a report of fever during the anterior month was inversely associated to this disease OR=0,3 CI95%[0,1;0,9]. The second model assessed measurements of blood pressure, glycohemoglobinA1c; total cholesterol; HDL-cholesterol, LDL-cholesterol; triglycerides; waist circumference and waist/hip index, and body mass index(BMI). The presence of glycohemoglobinA1c adjusted the model to a binary form with the exclusive companion of treated systolic blood pressure (SBP) (OR for glycohemoglobinA1c=12,0 CI95%[3,0;47,2].As glycohemoglobin is directly associated to blood glucose, the selection variable, a model without glycohemoglobin showed that triglycerides above 173mg/dL OR= 3,3 CI95%[1,32;8,24]; and SBP>125mm/Hg OR= 2,9 CI95% [1,2;7,0] were positivelyassociated to diabetes. Concentrations of LDL-C above 100mg/dL showed an inverse correlation to diabetes OR= 0,36 CI95%[0,15;0,84].In conclusion, among AMI patients, the following factors were significantlyassociated to the concomitant diagnosis of diabetes: female gender; systolic hypertension, even if treated; serious and moderate peripheral arterial disease; previous smoking history; automobile use; glycohemoglobin > 5.9%; LDL 176 mg/dL.STUDY 3. ACUTE MYOCARDIAL INFARCTION AS A METABOLIC DISEASE: RISK FACTORS BETWEEN DIABETIC PATIENTS.Diabetes mellitus is considered a vascular equivalent facilitating acutecardiovascular events among diabetic patients in the same way as nondiabetics with previous myocardial infarction have increased likelihood to another AMI. It is well established that diabetics carry on severe and extensive atherosclerosis, and type 1 diabetics over the third decade have an exceedingly high risk incidence of AMI and type 2 diabetics are subject to acute myocardial syndromes at any time of their diagnosis. In addition, these acute coronary syndromes are induced by plaque instability development in an undetermined period before the event. In a case-control study, psycho-emotional indicators recent and chronically presented, conventional risk factors and emergent cardiovascular markers were compared between 73 diabetics in their first episode of AMI and 110 diabetics controls with no history of AMI or any other acute atherosclerostic events, no previous thoracic pain and no EKG evidence of earlier myocardial necrosis or left bundle-branch blockade. All diabetics controls were over 35 years, 4,5% with type1 diabetes mellitus for 25,5±6,0 diagnosis years and 85,5% with type 2diabetes for 14,5±6,0 diagnosis years. In univariate analysis there was no significant association to AMI for the psychoemotional markers between the groups, even when standing for a long time or occurring in the preceding year. For all other factors two final logistic regressionmodels were obtained. The first model assessed gender, age, alcohol and tobacco use, cardiovascular family (CVF) history, hypertension story, ankle brachial index (ABI), regular exercise, urban locomotion, fever reported in the last 30 days and regular use of statins. After adjustment the following markers showed significant association to AMI: current OR=4,4 CI95%[1,57;12,4] and past OR=2,9CI95%[1,3;6,3] tobacco use; sedentary behavior OR=4,1CI95% [1,9;8,8] and urban preferred locomotion by automobile OR= 4,9CI95%[2,3;10,6]. Regular use of statins revealed protective OR=0,17 CI95% [0,04;0,66]. Values of ankle-brachial index indicating severe peripheral arterial disease remained at the limit of significance, probably by the limited number of the sample. The second model assessed measurements of fasting blood glucose, glycohemoglobinA1c; total cholesterol, LDL-C, HDL-C, triglycerides, and cholesterol ratios as Total cholesterol/HDL-C and LDL-C/HDL-C. Blood glucose values between 150mg/dL and 200mg/dL showed direct association OR=3,9 CI95%[1,4;10,7] as glycohemoglobinA1c below 6,7%OR=3,6 CI95%[1,22;10,6],and HDL-C below 32mg/dLOR=59,7 CI95% [11,08;315]. As AMI interferes with cholesterol and triglycerides analyses but presumptively not with the cholesterol ratios, a final model was performed with these ratios instead of absolute values and triglycerides, blood glucose and glycohemoglobinA1c.In this way, Total cholesterol/HDL-C ratio>4,5 became an independent marker to AMI replacing other lipid fractions, accompanied by blood glucose and glycohemoglobinA1c. In conclusion, among diabetic patients the following factors were positively associated to AMI: Current and past smoking, sedentary behavior, automobile use, blood glucose between 150mg/dL and 200mg/dL, glycohemoglobinA1cbelow 6,7% and Total cholesterol/HDL-C ratio >4,5. Regular use of statins was protective