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BACKGROUND: The escalating prevalence of type 2 diabetes (T2DM) poses an unparalleled economic catastrophe to developing countries. Cardiovascular diseases remain the primary source of costs among individuals with T2DM, incurring expenses for medications, hospitalizations, and surgical interventions. Compelling evidence suggests that the risk of cardiovascular outcomes can be reduced by three classes of glucose-lowering therapies (GLT), including SGLT2i, GLP-1A, and pioglitazone. However, an evidence-based and cost-effective protocol is still unavailable for many countries. The objective of the current study is to compare the effectiveness and cost-effectiveness of GLT in individuals with T2DM in Brazil. METHODS: We employed Bayesian Networks to calculate the incremental cost-effectiveness ratios (ICER), expressed in international dollars (Int$) per disease-adjusted life years [DALYs] averted. To determine the effectiveness of GLT, we conducted a systematic review with network meta-analysis (NMA) to provide insights for our model. Additionally, we obtained cardiovascular outcome incidence data from two real-world cohorts comprising 851 and 1337 patients in primary and secondary prevention, respectively. Our cost analysis took into account the perspective of the Brazilian public health system, and all values were converted to Int$. RESULTS: In the NMA, SGLT2i [HR: 0.81 (95% CI 0.69-0.96)], GLP-1A [HR: 0.79 (95% CI 0.67-0.94)], and pioglitazone [HR: 0.73 (95% CI 0.59-0.91)] demonstrated reduced relative risks of non-fatal cardiovascular events. In the context of primary prevention, pioglitazone yielded 0.2339 DALYs averted, with an ICER of Int$7,082 (95% CI 4,521-10,770) per DALY averted when compared to standard care. SGLT2i and GLP-1A also increased effectiveness, resulting in 0.261 and 0.259 DALYs averted, respectively, but with higher ICERs of Int$12,061 (95% CI: 7,227-18,121) and Int$29,119 (95% CI: 23,811-35,367) per DALY averted. In the secondary prevention scenario, all three classes of treatments were deemed cost-effective at a maximum willingness-to-pay threshold of Int$26,700. Notably, pioglitazone consistently exhibited the highest probability of being cost-effective in both scenarios. CONCLUSIONS: In Brazil, pioglitazone presented a higher probability of being cost-effective both in primary and secondary prevention, followed by SGLT2i and GLP-1A. Our findings support the use of cost-effectiveness models to build optimized and hierarchical therapeutic strategy in the management of T2DM. TRIAL REGISTRATION: CRD42020194415.
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BACKGROUND: Sodium-glucose cotransporter 2 inhibitors (SGLT2i) improve endothelial dysfunction and reduce cardiovascular events in individuals with type 2 diabetes (T2D). Proprotein convertase subtilisin/kexin 9 (PCSK9i) inhibitors reduce cardiovascular events in high-risk patients. Whether the addition of PCSK9i to SGLT2i treatment adds benefits is not known. OBJECTIVES: To assess the PCSK9-i effect on the endothelial function of T2D individuals under treatment with SGLT2-i. METHODS: Individuals with T2D were randomized in a 1:1 ratio to a 16-week treatment with either empagliflozin (E) or empagliflozin plus evolocumab (EE). The primary endpoint was post-treatment change from baseline in flow-mediated dilation (FMD) at 1-min. Secondary outcomes included changes in plasma levels of nitric oxide metabolites and isoprostane. RESULTS: A total of 110 patients were enrolled, the mean age was 58 years, and 71% were men. The median post-treatment change in FMD at 1-min was 2.7% (interquartile range [IQR]: 0.9%) and 0.4% (IQR: 0.9%) in the EE and E groups, respectively (p < 0.001). There was a greater increase in plasma levels of nitrate [5.9 (16.5) vs. 2.6 (11.8); p = 0.001] and nitrite [0.14 (0.72) vs. 0.02 (0.74); p = 0.025] in the EE group than in the E group, respectively. Isoprostane reduction was more pronounced in the EE group when compared to the E group [-1.7 (5.9) vs. -1.1 (5.3); p < 0.001). CONCLUSIONS: In individuals with T2D, the addition of evolocumab on top of empagliflozin improves endothelial function.
Assuntos
Doenças Cardiovasculares , Diabetes Mellitus Tipo 2 , Anticorpos Monoclonais Humanizados , Compostos Benzidrílicos , Diabetes Mellitus Tipo 2/diagnóstico , Diabetes Mellitus Tipo 2/tratamento farmacológico , Feminino , Glucosídeos , Humanos , Isoprostanos , Masculino , Pessoa de Meia-Idade , Inibidores de PCSK9 , Pró-Proteína Convertase 9/metabolismo , Resultado do TratamentoRESUMO
BACKGROUND: Glycemic disorders are strong predictors of mortality in ST-elevation myocardial infarction (STEMI) patients, and disruption in nitric oxide (NO) production is associated with insulin-resistant states. We evaluated whether a defective allele of the neuronal nitric oxide synthase (nNOS) gene (NOS1) might influence insulin response and blood-glucose balance during the acute phase of STEMI and if post-infarction total plasma-NO levels and vasodilation scores varied across nNOS genotypes. METHODS: Consecutive patients with STEMI (n=354) underwent clinical evaluations and genotyping for the promoter variation rs41279104. In-hospital clinical and blood evaluations were performed at admission and five days after STEMI, with glycemic, insulinemic, and disposition indices assessed at the same times. Flow-mediated dilation (FMD) was assessed by reactive hyperemia on the 30th day. RESULTS: Homozygotes for the defective allele (A) showed lower glycemia and insulin sensitivity on day 1 while showing the highest ß-cell function and no changes in the circulating NO pool, which is compatible with hyperresponsive ß cells counteracting the inherent glucose-resistant state of AA patients. At day 5, glycemic scores had shifted to indicate greater insulin sensitivity among A homozygotes, paralleled by a significant yet poor increase in NO bioavailability compared to that among G carriers. All in all, defective homozygotes showed greater insulin resistance at admission that had reversed by 5 days after STEMI. Even so, A carriers developed lower FMD scores compared to G homozygotes after the acute phase. CONCLUSION: A defective nNOS allele (and due decline in NO production) seemed to elicit a hyperinsulinemia response to compensate for an insulin-resistant state during the acute phase of STEMI and to be associated with poor endothelial function after the acute phase.
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BACKGROUND: The glucose-lowering independent effect of sodium glucose cotransporter-2 inhibitors (SGLT2i) on arterial wall function has not yet been clarified. This study aims to assess whether SGLT2i treatment can attenuate endothelial dysfunction related to type 2 diabetes mellitus (T2D) compared with glucose-lowering equivalent therapy. METHODS: In a prospective, open-label, single-center, randomized clinical trial, 98 patients with T2DM and carotid intima-media thickness above the 75th percentile were randomized 1:1 to 12 weeks of therapy with dapagliflozin or glibenclamide in addition to metformin in glucose-lowering equivalent regimens. The coprimary endpoints were 1-min flow-mediated dilation (FMD) at rest and 1-min FMD after 15 min of ischemia followed by 15 min of reperfusion time (I/R). RESULTS: Ninety-seven patients (61% males, 57 ± 7 years) completed the study. The median HbA1c decreased by - 0.8 (0.7)% and -0.7 (0.95)% following dapagliflozin and glibenclamide, respectively. The first coprimary endpoint, i.e., rest FMD changed by + 3.3(8.2)% and - 1.2(7.5)% for the dapagliflozin and glibenclamide arms, respectively (p = 0.0001). Differences between study arms in the second coprimary endpoint were not significant. Plasma nitrite 1 min after rest FMD was higher for dapagliflozin [308(220) nmol/L] than for glibenclamide (258[110] nmol/L; p = 0.028). The resistive indices at 1 min [0.90 (0.11) vs. 0.93 (0.07); p = 0.03] and 5 min [0.93 (0.07) vs. 0.95 (0.05); p = 0.02] were higher for the glibenclamide group than for the dapagliflozin group. Plasma biomarkers for inflammation and oxidative stress did not differ between the treatments. CONCLUSIONS: Dapagliflozin improved micro- and macrovascular endothelial function compared to glibenclamide, regardless of glycemic control in patients with T2DM and subclinical carotid atherosclerotic disease.
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Compostos Benzidrílicos/uso terapêutico , Glicemia/efeitos dos fármacos , Doenças das Artérias Carótidas/tratamento farmacológico , Diabetes Mellitus Tipo 2/tratamento farmacológico , Endotélio Vascular/efeitos dos fármacos , Glucosídeos/uso terapêutico , Glibureto/uso terapêutico , Inibidores do Transportador 2 de Sódio-Glicose/uso terapêutico , Vasodilatação/efeitos dos fármacos , Adulto , Idoso , Compostos Benzidrílicos/efeitos adversos , Biomarcadores/sangue , Glicemia/metabolismo , Brasil , Doenças das Artérias Carótidas/sangue , Doenças das Artérias Carótidas/diagnóstico por imagem , Doenças das Artérias Carótidas/fisiopatologia , Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/diagnóstico , Diabetes Mellitus Tipo 2/fisiopatologia , Quimioterapia Combinada , Endotélio Vascular/metabolismo , Endotélio Vascular/fisiopatologia , Feminino , Glucosídeos/efeitos adversos , Glibureto/efeitos adversos , Hemoglobinas Glicadas/metabolismo , Humanos , Masculino , Metformina/uso terapêutico , Pessoa de Meia-Idade , Estudos Prospectivos , Inibidores do Transportador 2 de Sódio-Glicose/efeitos adversos , Fatores de Tempo , Resultado do TratamentoRESUMO
BACKGROUND AND AIM: Obesity-related decline in high-density lipoprotein (HDL) functions such as cholesterol efflux capacity (CEC) has supported the notion that this lipoprotein dysfunction may contribute for atherogenesis among obese patients. We investigated if potentially other HDL protective actions may be affected with weight gain and these changes may occur even before the obesity range in a cross-sectional analysis. METHODS AND RESULTS: Lipid profile, body mass index (BMI), biochemical measurements, and carotid intima-media thickness (cIMT) were obtained in this cross-sectional study with 899 asymptomatic individuals. Lipoproteins were separated by ultracentrifugation and HDL physical-chemical characterization, CEC, antioxidant activity, anti-inflammatory activity, HDL-mediated platelet aggregation inhibition were measured in a randomly-selected subgroup (n = 101). Individuals with increased HDL-C had an attenuated increase in cIMT with elevation of BMI (interaction effect ß = -0.054; CI 95% -0.0815, -0.0301). CEC, HDL-C, HDL size and HDL-antioxidant activity were negatively associated with cIMT. BMI was inversely correlated with HDL-mediated inhibition of platelet aggregation (Spearman's rho -0.157, p < 0.03) and CEC (Spearman's rho -0.32, p < 0.001), but surprisingly it was directly correlated with the antioxidant activity (Spearman's rho 0.194, p = 0.052). Thus, even in non-obese, non-diabetic individuals, increased BMI is associated with a wide change in protective functions of HDL, reducing CEC and increasing antioxidant activity. In these subjects, decreased HDL concentration, size or function are related to increased atherosclerotic burden. CONCLUSION: Our findings demonstrate that in non-obese, non-diabetic individuals, the increasing values of BMI are associated with impaired protective functions of HDL and concomitant increase in atherosclerotic burden. (AU)
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Aterosclerose , HDL-Colesterol , ObesidadeRESUMO
BACKGROUND AND AIM: Obesity-related decline in high-density lipoprotein (HDL) functions such as cholesterol efflux capacity (CEC) has supported the notion that this lipoprotein dysfunction may contribute for atherogenesis among obese patients. We investigated if potentially other HDL protective actions may be affected with weight gain and these changes may occur even before the obesity range in a cross-sectional analysis. METHODS AND RESULTS: Lipid profile, body mass index (BMI), biochemical measurements, and carotid intima-media thickness (cIMT) were obtained in this cross-sectional study with 899 asymptomatic individuals. Lipoproteins were separated by ultracentrifugation and HDL physical-chemical characterization, CEC, antioxidant activity, anti-inflammatory activity, HDL-mediated platelet aggregation inhibition were measured in a randomly-selected subgroup (n = 101). Individuals with increased HDL-C had an attenuated increase in cIMT with elevation of BMI (interaction effect ß = -0.054; CI 95% -0.0815, -0.0301). CEC, HDL-C, HDL size and HDL-antioxidant activity were negatively associated with cIMT. BMI was inversely correlated with HDL-mediated inhibition of platelet aggregation (Spearman's rho -0.157, p < 0.03) and CEC (Spearman's rho -0.32, p < 0.001), but surprisingly it was directly correlated with the antioxidant activity (Spearman's rho 0.194, p = 0.052). Thus, even in non-obese, non-diabetic individuals, increased BMI is associated with a wide change in protective functions of HDL, reducing CEC and increasing antioxidant activity. In these subjects, decreased HDL concentration, size or function are related to increased atherosclerotic burden. CONCLUSION: Our findings demonstrate that in non-obese, non-diabetic individuals, the increasing values of BMI are associated with impaired protective functions of HDL and concomitant increase in atherosclerotic burden.
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HDL-Colesterol/sangue , Dislipidemias/sangue , Sobrepeso/sangue , Aumento de Peso , Adulto , Idoso , Antioxidantes/análise , Biomarcadores/sangue , Índice de Massa Corporal , Doenças das Artérias Carótidas/sangue , Doenças das Artérias Carótidas/diagnóstico por imagem , Doenças das Artérias Carótidas/fisiopatologia , Espessura Intima-Media Carotídea , Estudos Transversais , Dislipidemias/diagnóstico , Dislipidemias/fisiopatologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Sobrepeso/diagnóstico , Sobrepeso/fisiopatologia , Agregação Plaquetária , Medição de Risco , Fatores de Risco , Adulto JovemRESUMO
Hyperglycemia during myocardial infarction (MI) has a strong and direct association with mortality. In stable patients and experimental models, statins favor the elevation of glycaemia. The present study investigated whether short-course treatment with statins during MI can influence glucose homeostasis and thus the clinical outcome. In this prospective study, euglycemic hyperinsulinemic clamp (EHC) was performed at second (D2) and sixth (D6) day after MI in patients randomized to simvastatin (S)10 or 80 mg/day during hospitalization (n = 27). In addition, patients (n = 550) were treated without (WS) or with simvastatin (S) at 20, 40 or 80 mg/day had HOMA2S on admission (D1) and fifth (D5) day after MI. According to EHC, insulin sensitivity increased by 20 ± 60% in S10 and decreased by -6 ± 28% in S80 (p = 0.025). Consistently, the changes in HOMA2S between D1 and D5 were 40 ± 145% (WS), 22 ± 117% (S20), 16 ± 61% (S40) and -2% ± 88% (S80) (p = 0.001). In conclusion, statin during the acute phase of MI reduces insulin sensitivity in a dose-dependent manner.
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Inibidores de Hidroximetilglutaril-CoA Redutases/administração & dosagem , Resistência à Insulina , Insulina/metabolismo , Infarto do Miocárdio com Supradesnível do Segmento ST/tratamento farmacológico , Sinvastatina/administração & dosagem , Adulto , Esquema de Medicação , Feminino , Hospitalização , Humanos , Inibidores de Hidroximetilglutaril-CoA Redutases/farmacologia , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Infarto do Miocárdio com Supradesnível do Segmento ST/metabolismo , Sinvastatina/farmacologia , Adulto JovemRESUMO
INTRODUÇÃO. A obesidade se associa a declínio na capacidade de efluxo de colesterol (CEC) mediada por HDL. Embora esse dado tenha apoiado a noção de que a disfunção do HDL contribui para a aterogênese em pacientes obesos, a perda funcional da HDL também pode envolver outros domínios funcionais e se estabelecer mesmo antes dos valores limiares para obesidade, ou seja, ainda em valores compatíveis com sobrepeso. MÉTODOS. Perfil lipídico, índice de massa corporal (IMC), medidas bioquímicas e espessura médio-intimal (cIMT) foram obtidos neste estudo transversal com 899 indivíduos assintomáticos. Funções de HDL e caracterização físico-química de HDL foram medidas em um subgrupo (n=101). RESULTADOS. Foi identificada interação do IMC sobre a associação entre HDL-C e cIMT (ß=-1,8; p<0,0001). Enquanto que, de forma geral, o HDL-C reduzido foi associado ao aumento da cIMT, os indivíduos com níveis elevados de HDL-C apresentaram associação atenuada entre o IMC e cIMT. Foi encontrada uma associação negativa entre CEC e cIMT (ß=-0,2; p<0,047) e entre atividade antioxidante de HDL e cIMT (ß=-0,2; p<0,038) mesmo após ajuste para idade, sexo, IMC, HDL-C e insulina no plasma. O IMC foi inversamente associado à inibição da agregação plaquetária mediada por HDL (r=-0,2, p<0,03) e CEC (r=-0,3, p<0,001), mas diretamente associada à atividade antioxidante (r=0,2, p<0,047). Uma variável composta de CEC e atividade antioxidante transformadas em z-score permaneceu aproximadamente constante à medida em que o tamanho de HDL se altera em função do excesso de peso. Valores crescentes dessa variável composta foram associados à cIMT (R2 polinomial=0,26, p<0,001), sugerindo que a alteração do tamanho da HDL pode representar uma adaptação biológica bem-sucedida ao excesso de peso. CONCLUSÃO. O aumento do IMC está associado à disfunção global da HDL, que contribui para aumentar a carga aterosclerótica. Nesse cenário, a alteração do tamanho da HDL não justifica o aumento do desenvolvimento da doença aterosclerótica. (AU)
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Aumento de Peso , HDL-ColesterolRESUMO
BACKGROUND: Myocardial infarction (MI) elicits an intense acute inflammatory response that is essential for cardiac repair. However, an excessive inflammatory response also favors myocardial apoptosis, cardiac remodeling, and cardiovascular mortality. Omega-3 polyunsaturated fatty acids (ω-3) bear anti-inflammatory effects, which may mitigate the inflammatory response during MI. This study investigated whether ω-3 intake is associated with attenuation of the MI-related inflammatory response and cardiac remodeling. METHODS: ST-elevation MI (STEMI) patients (n = 421) underwent clinical, biochemical, nutritional, 3D echocardiogram, Cardiac Magnetic Resonance imaging (CMRi) at 30 days and 3D echocardiogram imaging at six months after the MI. Blood tests were performed at day one (D1) and day five (D5) of hospitalization. Changes in inflammatory markers (ΔD5-D1) were calculated. A validated food frequency questionnaire estimated the nutritional consumption and ω-3 intake in the last 3 months before admission. RESULTS: The intake of ω-3 below the median (< 1.7 g/day) was associated with a short-term increase in hs-C-reactive protein [OR:1.96(1.24-3.10); p = 0.004], Interleukin-2 [OR:2.46(1.20-5.04); p = 0.014], brain-type natriuretic peptide [OR:2.66(1.30-5.44); p = 0.007], left-ventricle end-diastolic volume [OR:5.12(1.11-23.52)]; p = 0.036] and decreases in left-ventricle ejection fraction [OR:2.86(1.47-6.88); p = 0.017] after adjustment for covariates. No differences were observed in the extension of infarcted mass obtained by CMRi. CONCLUSION: These findings suggest that a reduced daily intake of ω-3 may intensify outcome-determining mechanisms after STEMI, such as acute inflammatory response and late left ventricular remodeling. TRIAL REGISTRATION: Clinical Trial Registry number and website: NCT02062554 .
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Ácidos Graxos Ômega-3/farmacologia , Inflamação/sangue , Inflamação/etiologia , Infarto do Miocárdio com Supradesnível do Segmento ST/complicações , Remodelação Ventricular/fisiologia , Biomarcadores/sangue , Brasil , Estudos de Coortes , Ecocardiografia Tridimensional/métodos , Ácidos Graxos Ômega-3/administração & dosagem , Feminino , Seguimentos , Ventrículos do Coração/diagnóstico por imagem , Humanos , Imageamento por Ressonância Magnética/métodos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Infarto do Miocárdio com Supradesnível do Segmento ST/sangue , Infarto do Miocárdio com Supradesnível do Segmento ST/diagnóstico por imagem , Inquéritos e QuestionáriosRESUMO
The prevalence of type 2 diabetes mellitus (T2DM) in the elderly grew sharply over the last decade. Reduced insulin sensitivity and secretory capacity, weight gain, sarcopenia, and elevated adiposity are all common metabolic and body changes in the aging population that favor an increased risk of hypoglycemia, frailty syndrome, falls, and cognitive dysfunction. First line antidiabetic therapy is frequently not safe in older individuals because of its high risk of hypoglycemia and prevalent co-morbid diseases, such as chronic kidney disease, osteoporosis, cardiovascular disease, and obesity. Sodium-glucose cotransporter 2 inhibitor (SGLT2i) is a new class of antidiabetic therapy that inhibits glucose and sodium reabsorption on renal proximal convoluted tubule. Its effect is well demonstrated in various clinical scenarios in the younger population. This review and metanalysis describe particularities of the SGLT2i on the elderly, with mechanistic insights of the potential benefit and remaining challenges about the use of these drugs in this important age group. Further, we will present a meta-analysis of the main effects of SGLT2i reported in post-hoc studies in which the median age of the subgroups analyzed was over 60 years. Despite the absence of specific clinical trials for this population, our findings suggest that SGLT2i therapy on older individuals is effective to lower glucose and maintain its effect on systolic blood pressure and body weight.
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Diabetes Mellitus Tipo 2/tratamento farmacológico , Hipoglicemiantes/uso terapêutico , Inibidores do Transportador 2 de Sódio-Glicose/uso terapêutico , Idoso , Idoso de 80 Anos ou mais , Doenças Cardiovasculares/tratamento farmacológico , Doenças Cardiovasculares/metabolismo , Diabetes Mellitus Tipo 2/metabolismo , Idoso Fragilizado , Humanos , Insulina/metabolismo , Pessoa de Meia-Idade , Fatores de Risco , Resultado do TratamentoRESUMO
SUMMARY The prevalence of type 2 diabetes mellitus (T2DM) in the elderly grew sharply over the last decade. Reduced insulin sensitivity and secretory capacity, weight gain, sarcopenia, and elevated adiposity are all common metabolic and body changes in the aging population that favor an increased risk of hypoglycemia, frailty syndrome, falls, and cognitive dysfunction. First line antidiabetic therapy is frequently not safe in older individuals because of its high risk of hypoglycemia and prevalent co-morbid diseases, such as chronic kidney disease, osteoporosis, cardiovascular disease, and obesity. Sodium-glucose cotransporter 2 inhibitor (SGLT2i) is a new class of antidiabetic therapy that inhibits glucose and sodium reabsorption on renal proximal convoluted tubule. Its effect is well demonstrated in various clinical scenarios in the younger population. This review and metanalysis describe particularities of the SGLT2i on the elderly, with mechanistic insights of the potential benefit and remaining challenges about the use of these drugs in this important age group. Further, we will present a meta-analysis of the main effects of SGLT2i reported in post-hoc studies in which the median age of the subgroups analyzed was over 60 years. Despite the absence of specific clinical trials for this population, our findings suggest that SGLT2i therapy on older individuals is effective to lower glucose and maintain its effect on systolic blood pressure and body weight.
RESUMO A prevalência da diabetes mellitus tipo 2 em idosos cresceu muito na última década. A redução na sensibilidade à insulina e na capacidade secretora, ganho de peso, sarcopenia e adiposidade elevada são todas alterações metabólicas e corporais comuns entre a população idosa. Essas mudanças críticas favorecem o aumento no risco de hipoglicemia, síndrome de fragilidade, quedas e disfunções cognitivas. A primeira linha de tratamento contra a diabete muitas vezes não é segura para indivíduos mais velhos devido ao alto risco de hipoglicemia e a prevalência de comorbidades patogênicas, como doença renal crônica, osteoporose, doença cardiovascular e obesidade. Os inibidores do cotransportador sódio-glicose 2 (SGLT2) são uma nova classe de tratamento contra a diabete que inibe reabsorção de glicose e sódio na parte convoluta do túbulo proximal. Seu efeito é claramente demonstrado em diversos cenários clínicos em populações mais jovens. Esta revisão e meta-análise descreve as particularidades dos SGLT2 na população idosa, abordando os mecanismos dos potenciais benefícios e desafios ainda presentes do uso destes medicamentos nesse grupo etário tão importante. Além disso, apresentaremos uma meta-análise dos principais efeitos dos SGLT2 encontrados em estudos post-hoc nos quais a idade média dos subgrupos analisados foi acima de 60 anos. Apesar da ausência de ensaios clínicos que incluem essa população, os dados encontrados sugerem que o tratamento com SGLT2 em idosos é eficaz para diminuir os níveis de glicose e tem efeitos na pressão arterial sistólica e no peso corporal.
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Humanos , Idoso , Idoso de 80 Anos ou mais , Diabetes Mellitus Tipo 2/tratamento farmacológico , Inibidores do Transportador 2 de Sódio-Glicose/uso terapêutico , Hipoglicemiantes/uso terapêutico , Doenças Cardiovasculares/metabolismo , Doenças Cardiovasculares/tratamento farmacológico , Fatores de Risco , Idoso Fragilizado , Diabetes Mellitus Tipo 2/metabolismo , Insulina/metabolismo , Pessoa de Meia-IdadeRESUMO
BACKGROUND: Although stress hyperglycemia after myocardial infarction (MI) is consistently associated with increased mortality, recent studies suggest that the addition of upstream markers of glucose metabolism may improve risk identification. Hence, our aim was to evaluate the association between insulin sensitivity changes during MI hospitalization and outcomes. METHODS: A prospective cohort of 331 consecutive ST-Elevation MI (STEMI) patients without insulin provision therapy was used for the analyses. Blood samples were collected upon admission (D1) and after 5days (D5) of the inciting event. We measured blood glucose and insulin to estimate insulin sensitivity using the updated Homeostasis Model Assessment (HOMA2S). Patients were assessed for intra-hospital death and major adverse cardiac events (MACE) during follow-up. RESULTS: HOMA2S was 62%±52% on D1 and 86%±57% on D5 (p<0.001). Total follow-up was a median of 2 (0.9-2.8) years and found a U-shaped relation between the change in HOMA2S from D1 to D5 (ΔHOMA2S) and major adverse cardiac events (MACE) (p=0.017). Fully adjusted cox-regression models showed that patients from T1 and T3 were about 2.5 times more prone to suffer from MACE than those in T2. Net Reclassification Index adding ΔHOMA2S as a categorical variable dichotomized as T2 and T1 or T3 to a model of GRACE risk score with glucose D1 yielded a better predictive model (0.184 [95% CI 0.124-0.264]; p=0.032). CONCLUSION: A U-shaped curve describes the relation between insulin sensitivity change and MACE during acute phase STEMI and, thus indicating that acute dysglycemia must be appreciated in light of a time spectrum and insulin levels.
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Resistência à Insulina/fisiologia , Insulina/sangue , Infarto do Miocárdio com Supradesnível do Segmento ST/sangue , Infarto do Miocárdio com Supradesnível do Segmento ST/diagnóstico por imagem , Idoso , Estudos de Coortes , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Resultado do TratamentoRESUMO
BACKGROUND AND AIMS: Excess weight is a widespread condition related to increased risk of coronary heart disease (CHD). Sarcopenia is a catabolic pathway common of the aging process and also associated with CHD. In the elderly, both changes occur concurrently and it remains unclear the relative contribution on CHD risk. We aimed to investigate whether sarcopenia, excess weight, or both are associated with subclinical atherosclerosis and/or endothelial dysfunction in very elderly individuals. METHODS: We performed a cross-sectional study of cohort enrolled individuals, aged 80 years or older (n = 208), who had never manifested cardiovascular diseases. Blood tests, medical and nutritional evaluations, cardiac computed tomography, flow-mediated dilation (FMD) and physical performance tests were obtained at the study admission. Odds ratio (OR) was calculated by multivariate regression models using coronary calcium score (CCS) categories and FMD as dependent variables. Adjustment for potential confounders was done. RESULTS: Muscle mass, but not fatty mass, was inversely associated with CCS categories [OR:2.54(1.06-6.06); p = 0.018]. The lowering of gait speed was negatively related to CCS>100 [OR:2.36 (1.10-5.06); p = 0.028] and skeletal muscle index was directly associated with FMD [OR:5.44 (1.22-24.24); p = 0.026]. Total caloric intake was positively related to fatty mass [OR:2.71 (1.09-6.72); p = 0.031], but was not related to CCS. CONCLUSIONS: This study reveals that sarcopenia - comprised by reduction of muscle mass and its strength - is associated with subclinical atherosclerosis and endothelial dysfunction. Surprisingly, the excess of fatty mass seems not to be related to atherosclerotic burden in very elderly individuals.
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Composição Corporal , Doença da Artéria Coronariana/fisiopatologia , Endotélio Vascular/fisiopatologia , Ingestão de Energia , Músculo Esquelético/fisiopatologia , Sobrepeso/fisiopatologia , Sarcopenia/fisiopatologia , Aumento de Peso , Absorciometria de Fóton , Adiposidade , Fatores Etários , Idoso de 80 Anos ou mais , Doenças Assintomáticas , Angiografia Coronária/métodos , Doença da Artéria Coronariana/complicações , Doença da Artéria Coronariana/diagnóstico por imagem , Estudos Transversais , Teste de Esforço , Tolerância ao Exercício , Feminino , Avaliação Geriátrica/métodos , Humanos , Modelos Logísticos , Masculino , Tomografia Computadorizada Multidetectores , Análise Multivariada , Força Muscular , Músculo Esquelético/diagnóstico por imagem , Avaliação Nutricional , Estado Nutricional , Razão de Chances , Sobrepeso/complicações , Sobrepeso/diagnóstico , Estudos Prospectivos , Fatores de Risco , Sarcopenia/complicações , Sarcopenia/diagnóstico por imagem , VasodilataçãoRESUMO
BACKGROUND: Despite the high incidence and mortality of ST-segment elevation myocardial infarction (STEMI) among the very elderly, risk markers for this condition remain poorly defined. This study was designed to identify independent markers of STEMI among individuals carefully selected for being healthy or manifesting STEMI in < 24 h. METHODS: We enrolled participants aged 80 years or older of whom 50 were STEMI patients and 207 had never manifested cardiovascular diseases. Blood tests, medical and psychological evaluations were obtained at study admission. Odds Ratio (OR) and attributed risk (AR) were obtained by multivariate regression models using STEMI as dependent variable. RESULTS: Low glomerular filtration rate (GFR) [OR:4.41 (1.78-10.95); p = 0.001], reduced levels of HDL-C [OR:10.70 (3.88-29.46); p = 0.001], male gender [OR:12.08 (5.82-25.08); p = 0.001], moderate to severe depressive symptoms [OR:10.00 (2.82-35.50); p = 0.001], prior smoking [OR:2.00 (1.05-3.80); p = 0.034] and current smoking [OR:6.58 (1.99-21.70); p = 0.002] were significantly associated with STEMI. No association was found between STEMI and age, diabetes, hypertension, mild depressive symptoms, triglyceride or LDL-C. CONCLUSIONS: This is the first case-control study carried out with very elderlies to assess STEMI risk. Our findings indicate that reduced HDL-C, GFR, male gender, smoking habits and moderate to severe depressive symptoms are markers of STEMI in this age group. GENERAL SIGNIFICANCE: In Individuals aged 80 or more years, a greater attention must be paid to low HDL-C and GFR at the expense of conventional STEMI risk factors for younger adults such as diabetes mellitus, hypertension and high LDL-C or triglyceride.
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BACKGOUND: The favorable effects of insulin during myocardial infarction (MI) remain unclear due to the divergence between mechanistic studies and clinical trials of exogenous insulin administration. The rs7903146 polymorphism of the transcription factor 7-like 2 (TCF7L2) gene is associated with attenuated insulin secretion. METHODS: In non-diabetic patients with ST-elevation MI (STEMI), using such a model of genetically determined down-regulation of endogenous insulin secretion we investigated the change in plasma insulin, C-peptide, interleukin-2 (IL-2), C-reactive protein (CRP), and nitric oxide (NOx) levels between admission (D1) and the fifth day after MI (D5). Coronary angiography and flow-mediated dilation (FMD) were performed at admission and 30 days after MI, respectively. Homeostasis Model Assessment estimated insulin secretion (HOMA2%ß) and insulin sensitivity (HOMA2%S). RESULTS: Although glycemia did not differ between genotypes, carriers of the T-allele had lower HOMA2%ß and higher HOMA2%S at both D1 and D5. As compared with non-carriers, T-allele carriers had higher plasma IL-2 and CRP at D5, higher intracoronary thrombus grade, lower FMD and NOx change between D1 and D5 and higher 30-day mortality. CONCLUSION: In non-diabetic STEMI patients, the rs7903146 TCF7L2 gene polymorphism is associated with lower insulin secretion, worse endothelial function, higher coronary thrombotic burden, and higher short-term mortality. GENERAL SIGNIFICANCE: During the acute phase of MI, a lower capacity of insulin secretion may influence clinical outcome.
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OBJECTIVE: Chronic dysglycemia was recently identified as a predictor for adverse outcomes in patients with ST-elevation myocardial infarction (STEMI) treated by percutaneous coronary intervention. Data for non-diabetic patients who underwent thrombolysis is scarce. In this context, we aimed to study the effect of HbA1c on cardiovascular outcome after STEMI. METHODS: A prospective cohort of 326 non-diabetic STEMI individuals was used for the analyses. We measured plasma glucose, hemoglobin A1c [HbA1c], lipid profile, C-reactive protein (CRP), and nitrate/nitrite (NOx) upon admission and five days after STEMI (D5). Flow-mediated dilation (FMD) was performed 30 days after STEMI. During clinical follow-up, we assessed patients for incident diabetes (progression to HbA1c ≥ 6.5%) and major adverse cardiac events (MACE), defined as a composite of fatal and non-fatal MI, sudden cardiac death, and angina requiring hospitalization. RESULTS: Using ROC-curve analysis, a 5.8% HbA1c best predicted MACE with a sensitivity of 75% and specificity of 53% (AUC 0.673, p = 0.001). Patients were categorized as high HbA1c if ≥ 5.8% and low HbA1c if <5.8%. Compared with patients with low HbA1c, those with high HbA1c presented with 20% higher CRP-D5 (p = 0.009) and 19% higher ΔCRP (p = 0.01), a 32% decrease in ΔNOx (p < 0.001), and 33% lower FMD (p < 0.001). After a median follow-up of 1.9 (1.1-2.8) years, patients with high HbA1c had more incident diabetes (HR 2.3 95% CI 1.01-5.2; p = 0.048) and MACE (HR 3.32 95% CI 1.09-10.03; p = 0.03). CONCLUSION: Non-diabetic STEMI patients with high HbA1c present with decreased endothelial function and increased inflammatory response and long-term risk of MACE.
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Endotélio Vascular/fisiopatologia , Hemoglobinas Glicadas/análise , Infarto do Miocárdio/sangue , Idoso , Glicemia/análise , Artéria Braquial/patologia , Proteína C-Reativa/análise , Angiografia Coronária , Diabetes Mellitus , Dieta , Feminino , Seguimentos , Humanos , Inflamação , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Infarto do Miocárdio/complicações , Óxido Nítrico/química , Admissão do Paciente , Intervenção Coronária Percutânea , Estudos Prospectivos , Curva ROC , Fatores de Risco , Sensibilidade e Especificidade , Resultado do TratamentoRESUMO
AIM/BACKGROUND: Abundant evidence shows that coronary artery calcification (CAC) is a strong marker of structural and functional changes within the artery wall. Thus far, the implications of CAC in patients with acute coronary syndromes remain unclear. We aimed to investigate whether the CAC score is associated with impaired reperfusion during the acute phase of ST-elevation myocardial infarction (STEMI). METHODS: We enrolled 60 consecutive STEMI patients to undergo cardiac computed tomography for assessment of the CAC score within 1 week after STEMI. Coronary thrombus burden, coronary blood flow (TIMI flow), and myocardial blush grade (MBG) were evaluated systematically. Patients with maximal TIMI flow and MBG were grouped as optimal reperfusion (n=27) and their counterparts as no-reflow (NR, n=33). RESULTS: There were no differences in the clinical characteristics between groups. Patients in the NR group had higher heart rate, coronary angiographic severity, and CAC score. CAC score greater than 100 was associated independently with the presence of NR (odds ratio 4.4, 95% confidence interval 1.17-16.3). The CAC score of nonculprit coronary arteries was higher in NR individuals than in their counterparts (P=0.04). In addition, the CAC score of the isnfarct-related artery correlated negatively with the TIMI-flow rate (r=-0.54, P<0.001) and with the MBG (r=-0.32, P=0.04). CONCLUSION: The CAC score is associated with the presence of the NR phenomenon in STEMI patients.
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Doença da Artéria Coronariana/diagnóstico por imagem , Infarto do Miocárdio/terapia , Fenômeno de não Refluxo/epidemiologia , Intervenção Coronária Percutânea , Calcificação Vascular/diagnóstico por imagem , Idoso , Brasil/epidemiologia , Angiografia Coronária , Doença da Artéria Coronariana/epidemiologia , Feminino , Humanos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Razão de Chances , Estudos Retrospectivos , Fatores de Risco , Tomografia Computadorizada por Raios X , Calcificação Vascular/epidemiologiaRESUMO
BACKGROUND: Reduced zinc intake has been related to atherogenesis and arteriosclerosis. We verified this assumption in very old individuals, which are particularly prone to both zinc deficiency and structural and functional changes in the arterial wall. METHODS: Subjects (n = 201, 80-102 years) with uneventful cardiovascular history and who were not in use of anti-inflammatory treatments in the last 30-days were enrolled. Daily intake of zinc, lipid profile, plasma C-reactive protein (CRP), plasma zinc, flow-mediated dilation (FMD), carotid ultrasonography and cardiac computed tomography were obtained. Young's Elastic Modulus, Stiffness Index and Artery Compliance were calculated. RESULTS: There was no significant difference in clinical or laboratorial data between subjects grouped according to plasma zinc tertile, except for CRP (p = 0.01) and blood leukocytes (p = 0.002), of which levels were higher in the upper tertiles. The average daily intake of zinc was not significantly correlated with zinc or CRP plasma levels. The plasma zinc/zinc intake ratio was inversely correlated with plasma CRP levels (- 0.18; p = 0.01). There was no significant difference between the plasma zinc tertiles and FMD, carotid intima-media thickness, coronary calcium score, carotid plaque presence, remodeled noncalcified coronary plaques, or low-attenuation noncalcified coronary plaques. CONCLUSION: Although plasma zinc level is inversely related to systemic inflammatory activity, its plasma levels of daily intake are not associated to alterations in structure or function of the arterial wall. GENERAL SIGNIFICANCE: In the very elderly plasma concentrations or daily intake of zinc is not related to endothelial dysfunction, arteriosclerosis or atherosclerotic burden at coronary or carotid arteries.
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Assessment of lipid profile parameters has been considered a cornerstone in classifying individuals and populations at risk for cardiovascular disease. Recently, however, preliminary data have raised the possibility of seasonal variations in these parameters, which may cause under- or overestimation. Biological rhythms and seasonal variation of lipid profile was investigated in 227 359 consecutive individuals who underwent health checkups in primary care centers between 2008 and 2010. Plasma low-density lipoprotein cholesterol (LDL-C) >130 mg/dL was 8% more prevalent during winter than summer, with a larger difference among women and middle-aged adults (p < 0.001). High-density lipoprotein cholesterol (HDL-C) <40 mg/dL and triglycerides (TG) >150 mg/dL were respectively 9% and 5% more prevalent during the summer (p < 0.001). Variation amplitude was 3.4 ± 0.3 mg/dL for HDL-C (p = 0.005), 7 ± 2 mg/dL for LDL-C (p = 0.047), and 12 ± 9 mg/dL for TG (p = 0.058). Based on a large population sample, this study confirms the existence of biological rhythms and seasonal variation in lipid profile. This finding must be particularly accounted for in cross-sectional analyses of relative risk, prevalence, or the rate of goal achievement for lipid parameters.
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Dislipidemias/epidemiologia , Periodicidade , Estações do Ano , Adolescente , Adulto , Distribuição por Idade , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Biomarcadores/sangue , Brasil/epidemiologia , Criança , Pré-Escolar , HDL-Colesterol/sangue , LDL-Colesterol/sangue , Estudos Transversais , Dislipidemias/sangue , Dislipidemias/diagnóstico , Feminino , Humanos , Lactente , Recém-Nascido , Masculino , Pessoa de Meia-Idade , Dinâmica não Linear , Prevalência , Fatores de Risco , Distribuição por Sexo , Fatores Sexuais , Fatores de Tempo , Triglicerídeos/sangue , Adulto JovemRESUMO
BACKGROUND: The decrease of insulin sensitivity (IS) during myocardial infarction (MI) is strongly associated with increased morbidity and mortality. Recent data suggest that in individuals under stable conditions, high-density lipoprotein (HDL) may improve IS. To date, the role of HDL in the modulation of IS in acute metabolic stress conditions such as MI remains unknown. OBJECTIVE: To explore the association between plasma HDL-C and the change in IS during the acute phase of MI. METHODS: Consecutive nondiabetic patients with ST-segment elevation MI (n = 22) underwent direct measurement of IS through the euglycemic hyperinsulinemic clamp on the first morning and on the fifth day after onset of MI. Patients were grouped according to HDL-C levels at admission above and below the median value (35 mg/dL). RESULTS: At admission, there was no significant difference in baseline IS index, clinical, anthropometric, or treatment characteristics between low and high HDL groups. Between admission and fifth day, there was a decrease of 8% in IS index in the low HDL group and an 11% increase in the high HDL group (P = .001 for intragroup and P = .012 for intergroup difference). This difference remained significant after we controlled for the sex, age, waist circumference, triglycerides, baseline IS index, and statin dose during hospitalization. CONCLUSION: This is the first study to provide evidence that plasma levels of HDL-C are strongly associated with the recovery rate of IS during the acute phase of MI.