RESUMO
AIM: The effects of weight loss with a partial or total meal replacement programme (MRP) on atherosclerotic cardiovascular disease (ASCVD) risk factors are not fully understood, in particular in people at higher CV risk. In the 52-week randomized controlled OPTIWIN study in men and women with obesity, meal replacement programme (total for first 26 weeks, partial for the ensuing 26 weeks) with OPTIFAST (OP) resulted in significantly greater weight loss compared with a low-calorie food-based (FB) dietary plan, both as part of a comprehensive lifestyle intervention [OP (n = 135)/FB (n = 138) week 26: -12.4%/-6.0%, p < .001; week 52: -10.5%/-5.5%, p < .001]. Here, we examined effects on ASCVD risk factors and 10-year ASCVD risk. MATERIALS AND METHODS: Participants with body mass index 30-55 kg/m2 and age 18-70 years, and not on anti-obesity medications, were recruited. The effects on systolic and diastolic blood pressure (SBP, DBP), lipid parameters and 10-year ASCVD risk were analysed as changes over time using linear mixed models. Subgroup analyses were conducted for changes in SBP, DBP and ASCVD risk by categories of age (<40, 40-59, ≥60 years), baseline SBP (≥130 mmHg) and sex. RESULTS: Baseline characteristics were well balanced (OP/FB females 86%/79%, mean age 47/47 years, body mass index 38.4/39.2 kg/m2 , 10-year ASCVD risk <5% 87%/74%, dysglycaemia 52%/50%). At week 26, SBP/DBP were significantly reduced with OP versus FB, and a greater proportion achieved BP ≤130/80 mmHg [odds ratio 2.11 (95% confidence interval 1.10, 4.03), p = .024]. All lipid parameters as well as 10-year ASCVD risk were significantly improved with OP versus FB. A similar, but slightly attenuated pattern was observed at 52 weeks. Across subgroups, greater reductions for SBP, DBP and ASCVD risk were generally seen with OP versus FB with quantitatively higher baseline SBP and age, and in men. CONCLUSIONS: In people with obesity at low ASCVD risk, OP significantly reduced cardiovascular risk factors and 10-year predicted risk for ASCVD.
Assuntos
Aterosclerose , Hipertensão , Adulto , Masculino , Humanos , Feminino , Pessoa de Meia-Idade , Adolescente , Adulto Jovem , Idoso , Obesidade/complicações , Obesidade/epidemiologia , Pressão Sanguínea , Fatores de Risco , Redução de Peso , Lipídeos , Hipertensão/tratamento farmacológicoRESUMO
AIMS: To examine the effect of pioglitazone on epicardial (EAT) and paracardial adipose tissue (PAT) and measures of diastolic function and insulin sensitivity in patients with type 2 diabetes mellitus (T2DM). METHODS: Twelve patients with T2DM without clinically manifest cardiovascular disease and 12 subjects with normal glucose tolerance (NGT) underwent cardiac magnetic resonance imaging to quantitate EAT and PAT and diastolic function before and after pioglitazone treatment for 24 weeks. Whole-body insulin sensitivity was measured with a euglycaemic insulin clamp and the Matsuda Index (oral glucose tolerance test). RESULTS: Pioglitazone reduced glycated haemoglobin by 0.9% (P < 0.05), increased HDL cholesterol by 7% (P < 0.05), reduced triacylglycerol by 42% (P < 0.01) and increased whole-body insulin-stimulated glucose uptake by 71% (P < 0.01) and Matsuda Index by 100% (P < 0.01). In patients with T2DM, EAT (P < 0.01) and PAT (P < 0.01) areas were greater compared with subjects with NGT, and decreased by 9% (P = 0.03) and 9% (P = 0.09), respectively, after pioglitazone treatment. Transmitral E/A flow rate and peak left ventricular flow rate (PLVFR) were reduced in T2DM versus NGT (P < 0.01) and increased following pioglitazone treatment (P < 0.01-0.05). At baseline normalized PLVFR inversely correlated with EAT (r = -0.45, P = 0.03) but not PAT (r = -0.29, P = 0.16). E/A was significantly and inversely correlated with EAT (r = -0.55, P = 0.006) and PAT (r = -0.40, P = 0.05). EAT and PAT were inversely correlated with whole-body insulin-stimulated glucose uptake (r = -0.68, P < 0.001) and with Matsuda Index (r = 0.99, P < 0.002). CONCLUSION: Pioglitazone reduced EAT and PAT areas and improved left ventricular (LV) diastolic function in T2DM. EAT and PAT are inversely correlated (PAT less strongly) with LV diastolic function and both EAT and PAT are inversely correlated with measures of insulin sensitivity.
Assuntos
Diabetes Mellitus Tipo 2 , Resistência à Insulina , Tiazolidinedionas , Humanos , Pioglitazona/uso terapêutico , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/tratamento farmacológico , Diabetes Mellitus Tipo 2/patologia , Hipoglicemiantes/farmacologia , Hipoglicemiantes/uso terapêutico , Tiazolidinedionas/farmacologia , Tiazolidinedionas/uso terapêutico , Glicemia , Insulina , Pericárdio/diagnóstico por imagem , Pericárdio/patologia , Glucose , Tecido Adiposo/patologiaRESUMO
Recent cardiovascular outcome trials have highlighted the propensity of the antidiabetic agents, SGLT2 inhibitors (SGLT2is or -flozin drugs), to exert positive clinical outcomes in patients with cardiovascular disease at risk for major adverse cardiovascular events (MACEs). Of interest in cardiac diabetology is the physiological status of the patient with T2DM and heart failure with preserved ejection fraction (HFpEF), a well-examined association. Underlying this pathologic tandem are the effects that long-standing hyperglycemia has on the ability of the HFpEF heart to adequately deliver oxygen. It is believed that shortcomings in oxygen diffusion or utilization and the resulting hypoxia thereafter may play a role in underlying the clinical sequelae of patients with T2DM and HFpEF, with implications in the long-term decline of extra-cardiac tissue. Oxygen consumption is one of the most critical factors in indexing heart failure disease burden, warranting a probe into the role of SGLT2i on oxygen utility in HFpEF and T2DM. We investigated the role of oxygen flux in the patient with T2DM and HFpEF extending beyond the heart with focuses on cellular metabolism, perivascular fibrosis with endothelial dysfunction, hematologic changes, and renal effects with neurohormonal considerations in the patient with HFpEF and T2DM. Moreover, we give a commentary on potential therapeutic targets of these components with SGLT2i to gain insight into disease burden amelioration in patients with HFpEF and T2DM.
Assuntos
Diabetes Mellitus , Insuficiência Cardíaca , Inibidores do Transportador 2 de Sódio-Glicose , Insuficiência Cardíaca/tratamento farmacológico , Humanos , Miocárdio , Oxigênio , Volume SistólicoRESUMO
Bromocriptine-QR is a sympatholytic dopamine D2 agonist for the treatment of type 2 diabetes that has demonstrated rapid (within 1 year) substantial reductions in adverse cardiovascular events in this population by as yet incompletely delineated mechanisms. However, a chronic state of elevated sympathetic nervous system activity and central hypodopaminergic function has been demonstrated to potentiate an immune system pro-oxidative/pro-inflammatory condition and this immune phenotype is known to contribute significantly to the advancement of cardiovascular disease (CVD). Therefore, the possibility exists that bromocriptine-QR therapy may reduce adverse cardiovascular events in type 2 diabetes subjects via attenuation of this underlying chronic pro-oxidative/pro-inflammatory state. The present study was undertaken to assess the impact of bromocriptine-QR on a wide range of immune pro-oxidative/pro-inflammatory biochemical pathways and genes known to be operative in the genesis and progression of CVD. Inflammatory peripheral blood mononuclear cell biology is both a significant contributor to cardiovascular disease and also a marker of the body's systemic pro-inflammatory status. Therefore, this study investigated the effects of 4-month circadian-timed (within 2 h of waking in the morning) bromocriptine-QR therapy (3.2 mg/day) in type 2 diabetes subjects whose glycemia was not optimally controlled on the glucagon-like peptide 1 receptor agonist on (i) gene expression status (via qPCR) of a wide array of mononuclear cell pro-oxidative/pro-inflammatory genes known to participate in the genesis and progression of CVD (OXR1, NRF2, NQO1, SOD1, SOD2, CAT, GSR, GPX1, GPX4, GCH1, HMOX1, BiP, EIF2α, ATF4, PERK, XBP1, ATF6, CHOP, GSK3ß, NFkB, TXNIP, PIN1, BECN1, TLR2, TLR4, TLR10, MAPK8, NLRP3, CCR2, GCR, L-selectin, VCAM1, ICAM1) and (ii) humoral measures of sympathetic tone (norepinephrine and normetanephrine), whole-body oxidative stress (nitrotyrosine, TBARS), and pro-inflammatory factors (IL-1ß, IL-6, IL-18, MCP-1, prolactin, C-reactive protein [CRP]). Relative to pre-treatment status, 4 months of bromocriptine-QR therapy resulted in significant reductions of mRNA levels in PBMC endoplasmic reticulum stress-unfolded protein response effectors [GRP78/BiP (34%), EIF2α (32%), ATF4 (29%), XBP1 (25%), PIN1 (14%), BECN1 (23%)], oxidative stress response proteins [OXR1 (31%), NRF2 (32%), NQO1 (39%), SOD1 (52%), CAT (26%), GPX1 (33%), GPX4 (31%), GCH1 (30%), HMOX1 (40%)], mRNA levels of TLR pro-inflammatory pathway proteins [TLR2 (46%), TLR4 (20%), GSK3ß (19%), NFkB (33%), TXNIP (18%), NLRP3 (32%), CCR2 (24%), GCR (28%)], mRNA levels of pro-inflammatory cellular receptor proteins CCR2 and GCR by 24% and 28%, and adhesion molecule proteins L-selectin (35%) and VCAM1 (24%). Relative to baseline, bromocriptine-QR therapy also significantly reduced plasma levels of norepinephrine and normetanephrine by 33% and 22%, respectively, plasma pro-oxidative markers nitrotyrosine and TBARS by 13% and 10%, respectively, and pro-inflammatory factors IL-18, MCP1, IL-1ß, prolactin, and CRP by 21%,13%, 12%, 42%, and 45%, respectively. These findings suggest a unique role for circadian-timed bromocriptine-QR sympatholytic dopamine agonist therapy in reducing systemic low-grade sterile inflammation to thereby reduce cardiovascular disease risk.
Assuntos
Doenças Cardiovasculares , Diabetes Mellitus Tipo 2 , Bromocriptina/farmacologia , Bromocriptina/uso terapêutico , Doenças Cardiovasculares/epidemiologia , Glicogênio Sintase Quinase 3 beta , Humanos , Interleucina-18 , Selectina L , Leucócitos Mononucleares , Fator 2 Relacionado a NF-E2 , Peptidilprolil Isomerase de Interação com NIMA , Proteína 3 que Contém Domínio de Pirina da Família NLR , Normetanefrina , Estresse Oxidativo , Fenótipo , Prolactina , RNA Mensageiro , Superóxido Dismutase-1 , Simpatolíticos , Substâncias Reativas com Ácido Tiobarbitúrico , Receptor 2 Toll-Like , Receptor 4 Toll-LikeRESUMO
Recent clinical trials involving the systemic effects of sodium-glucose cotransporter 2 inhibitors (SGLT2i) have revealed beneficial outcomes pertaining to the microvascular sequelae of type 2 diabetes mellitus (T2DM) such as nephropathy, as well as macrovascular effects such as major adverse cardiovascular effects (MACE). Such findings have spurred the elevation of these agents to level A-tiers of recommendation within clinical guidelines addressing the management of complicated T2DM. While the mechanisms of SGLTi (-flozin drugs) are still being elucidated, a paucity of data exists within the literature appraising the role of neuromodulation and associated mechanisms in the aforementioned outcome studies. Given the role of the nervous system in orchestrating the pathologic processes that hamper cardio-renal status, insight into this topic offers an expanded perspective on T2DM. In this review we investigate the mechanisms by which SGLTi improve cardio-renal function in T2DM patients with emphases on neural tone and nervous system physiology.
Assuntos
Diabetes Mellitus Tipo 2 , Inibidores do Transportador 2 de Sódio-Glicose , Compostos Benzidrílicos , Canagliflozina , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/tratamento farmacológico , Glucosídeos , Humanos , Hipoglicemiantes/uso terapêutico , Rim/fisiologia , Sistema Nervoso , Inibidores do Transportador 2 de Sódio-Glicose/uso terapêuticoRESUMO
Sodium-glucose cotransporter-2 inhibitors (SGLT-2is) have been shown to mitigate the risks of cardiovascular (CV) and renal complications in patients with type 2 diabetes (T2D) and CV risk factors or CV disease (CVD). In CV outcomes trials (CVOTs) of patients with T2D and established CVD or multiple CV risk factors, empagliflozin and canagliflozin were associated with significant reductions in the risks of major adverse CV events (MACE), hospitalization for heart failure (HF) and kidney disease progression. In the DECLARE-TIMI 58 study, in which the majority of patients did not have established CVD, dapagliflozin was associated with significant reductions in the composite end point of CV death or hospitalization for HF and was noninferior to placebo with regard to MACE; although patients had relatively good renal function, dapagliflozin also showed renal benefits similar to those seen with empagliflozin and canagliflozin. This article reviews the increased risk of CVD and renal disease in patients with T2D and discusses the potential mechanisms of the cardioprotective and renoprotective effects of SGLT-2i therapy. The observed improvements in CV and renal outcomes with SGLT-2is in CVOTs suggest a class effect in this patient population and have influenced treatment guidelines for the way add-on therapy to metformin is initiated in patients with T2D and high CV risk. The overall cardioprotective and renoprotective effects of SGLT-2is in patients with T2D and high CV risk are most likely attributable to multiple mechanisms, including cardiac, haemodynamic, metabolic, anti-inflammatory and renal effects.
Assuntos
Doenças Cardiovasculares , Diabetes Mellitus Tipo 2 , Nefropatias , Inibidores do Transportador 2 de Sódio-Glicose , Doenças Cardiovasculares/etiologia , Doenças Cardiovasculares/prevenção & controle , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/tratamento farmacológico , Fatores de Risco de Doenças Cardíacas , Humanos , Hipoglicemiantes/uso terapêutico , Nefropatias/etiologia , Nefropatias/prevenção & controle , Inibidores do Transportador 2 de Sódio-Glicose/uso terapêuticoRESUMO
PURPOSE OF REVIEW: We aim to provide a comprehensive analysis of hypercoagulability in individuals affected by COVID-19. Our goal is to describe the hypercoagulable state related to the infection and provide guidance regarding the possible benefits of anti-coagulation with the support of evidence from current literature. RECENT FINDINGS: The incidence of thrombotic disease in individuals affected by COVID-19 is reported as high as 31%. A significant mortality benefit has been observed with the use of therapeutic anticoagulation in high-risk individuals. Literature supports the use of scoring systems, such as the sepsis-induced coagulopathy score, to risk-stratify individuals who might benefit from anticoagulation. COVID-19-induced hypercoagulability has been demonstrated to play a significant role in overall COVID-19 outcomes. Current literature shows promising evidence with the use of therapeutic anticoagulation in high-risk individuals. Further studies are needed to better analyze the risks and benefits of anticoagulation in this specific patient population.
Assuntos
Estado Terminal , Trombofilia , Anticoagulantes , Betacoronavirus , COVID-19 , Infecções por Coronavirus , Humanos , Incidência , Unidades de Terapia Intensiva , Pandemias , Pneumonia Viral , SARS-CoV-2RESUMO
Heart disease continues to affect health outcomes globally, accounting for a quarter of all deaths in the United States. Despite the improvement in the development and implementation of guideline-directed medical therapy, the risk of adverse cardiac events remains substantially high. Historically, it has been debated whether omega-3 polyunsaturated fatty acids provide clinical benefit in cardiac disease. The recently published REDUCE-IT trial demonstrated a statistically significant absolute risk reduction of 4.8% in its primary endpoint (cardiovascular death, nonfatal myocardial infarction, nonfatal stroke, coronary revascularization, or unstable angina) with the use of icosapent ethyl, which is a highly purified eicosapentaenoic acid (EPA) ethyl ester. However, the mechanism of action of omega-3 fatty acids is not commonly discussed. Moreover, the use of EPA was not without risk, as the incidence of atrial fibrillation was increased along with a trend towards increased bleeding risk. Thus, our aim is to help explain the function of purified EPA ethyl ester, especially at the molecular level, which will ultimately lead to a better understanding of their clinically observable effects.
Assuntos
Doenças Cardiovasculares/prevenção & controle , Ácido Eicosapentaenoico/análogos & derivados , Hipertrigliceridemia/tratamento farmacológico , Triglicerídeos/sangue , Fibrilação Atrial/induzido quimicamente , Fibrilação Atrial/epidemiologia , Biomarcadores/sangue , Doenças Cardiovasculares/sangue , Doenças Cardiovasculares/diagnóstico , Doenças Cardiovasculares/mortalidade , Suplementos Nutricionais , Regulação para Baixo , Ácido Eicosapentaenoico/efeitos adversos , Ácido Eicosapentaenoico/uso terapêutico , Feminino , Hemorragia/induzido quimicamente , Hemorragia/epidemiologia , Humanos , Hipertrigliceridemia/sangue , Hipertrigliceridemia/diagnóstico , Hipertrigliceridemia/mortalidade , Incidência , Masculino , Ensaios Clínicos Controlados Aleatórios como Assunto , Medição de Risco , Fatores de Risco , Resultado do TratamentoRESUMO
PURPOSE OF REVIEW: To evaluate the treatment of type 2 diabetes from a cardiologist's view. RECENT FINDINGS: A new era in the treatment of type 2 diabetes began for the cardiologist in 2015 with the publication of the EMPA-REG outcome trial finding a significant reduction in CV death with empagliflozin (oral sodium-glucose co-transporter-2 [SGLT2] inhibitor) in patients with type 2 diabetes at increased cardiovascular risk. Shortly thereafter, the injectable glucagon-like peptide agonists (GLP-1) liraglutide and semaglutide found a significant reduction in composite major cardiovascular events (CV death, non-fatal MI, or stroke). Both classes have demonstrated significant renal protection when added to usual care. Moreover, there may be some exciting new benefits of SGLT2 inhibitors for patients with heart failure. These research studies are underway. These two new classes of cardiovascular drugs for type 2 diabetes usher in a new era for the cardiologist who sees greater than 50% of patients with diabetes. The off-target effect of these agents is different as with all new cardiovascular compounds. While safety profiles in these populations are consistent with the known effects of these classes, new off-target effects have been seen with some agents in this class. Ongoing collaboration between cardiologists and other care providers remains important in the implementation of the evidence and care of patients with type 2 diabetes.
Assuntos
Cardiologistas , Diabetes Mellitus Tipo 2/tratamento farmacológico , Doenças Cardiovasculares/prevenção & controle , Ensaios Clínicos como Assunto , Humanos , Avaliação de Resultados em Cuidados de Saúde , Fatores de RiscoRESUMO
T2DM is a complex disease underlined by multiple pathogenic defects responsible for the development and progression of hyperglycaemia. Each of these factors can now be tackled in a more targeted manner thanks to glucose-lowering drugs that have been made available in the past 2 to 3 decades. Recognition of the multiplicity of the mechanisms underlying hyperglycaemia calls for treatments that address more than 1 of these mechanisms, with more emphasis placed on the earlier use of combination therapies. Although chronic hyperglycaemia contributes to and amplifies cardiovascular risk, several trials have failed to show a marked effect from intensive glycaemic control. During the past 10 years, the effect of specific glucose-lowering agents on cardiovascular risk has been explored with dedicated trials. Overall, the cardiovascular safety of the new glucose-lowering agents has been proven with some of the trials summarized in this review, showing significant reduction of cardiovascular risk. Against this background, pioglitazone, in addition to exerting a sustained glucose-lowering effect, also has ancillary metabolic actions of potential interest in addressing the cardiovascular risk of T2DM, such as preservation of beta-cell mass and function. As such, it seems a logical agent to combine with other oral anti-hyperglycaemic agents, including dipeptidyl peptidase-4 inhibitors (DPP4i). DPP4i, which may also have a potential to preserve beta-cell function, is available as a fixed-dose combination with pioglitazone, and could, potentially, attenuate some of the side effects of pioglitazone, particularly if a lower dose of the thiazolidinedione is used. This review critically discusses the potential for early combination of pioglitazone and DPP4i.
Assuntos
Diabetes Mellitus Tipo 2/diagnóstico , Diabetes Mellitus Tipo 2/tratamento farmacológico , Inibidores da Dipeptidil Peptidase IV/uso terapêutico , Hipoglicemiantes/uso terapêutico , Pioglitazona/uso terapêutico , Glicemia/efeitos dos fármacos , Glicemia/metabolismo , Diabetes Mellitus Tipo 2/sangue , Humanos , Avaliação de Resultados da Assistência ao Paciente , Melhoria de Qualidade , Resultado do TratamentoRESUMO
BACKGROUND: Studies of dipeptidyl peptidase (DPP)-4 inhibitors report heterogeneous effects on endothelial function in patients with type 2 diabetes (T2D). This study assessed the effects of the DPP-4 inhibitor linagliptin versus the sulphonylurea glimepiride and placebo on measures of macro- and microvascular endothelial function in patients with T2D who represented a primary cardiovascular disease prevention population. METHODS: This crossover study randomised T2D patients (n = 42) with glycated haemoglobin (HbA1c) ≤7.5%, no diagnosed macro- or microvascular disease and on stable metformin background to linagliptin 5 mg qd, glimepiride 1-4 mg qd or placebo for 28 days. Fasting and postprandial macrovascular endothelial function, measured using brachial flow-mediated vasodilation, and microvascular function, measured using laser-Doppler on the dorsal thenar site of the right hand, were analysed after 28 days. RESULTS: Baseline mean (standard deviation) age, body mass index and HbA1c were 60.3 (6.0) years, 30.3 (3.0) kg/m2 and 7.41 (0.61)%, respectively. After 28 days, changes in fasting flow-mediated vasodilation were similar between the three study arms (treatment ratio, gMean [90% confidence interval]: linagliptin vs glimepiride, 0.884 [0.633-1.235]; linagliptin vs placebo, 0.884 [0.632-1.235]; glimepiride vs placebo, 1.000 [0.715-1.397]; P = not significant for all comparisons). Similarly, no differences were seen in postprandial flow-mediated vasodilation. However, under fasting conditions, linagliptin significantly improved microvascular function as shown by a 34% increase in hyperaemia area (P = 0.045 vs glimepiride), a 34% increase in resting blow flow (P = 0.011 vs glimepiride, P = 0.003 vs placebo), and a 25% increase in peak blood flow (P = 0.009 vs glimepiride, P = 0.003 vs placebo). There were no significant differences between treatments in postprandial changes. Linagliptin had no effect on heart rate or blood pressure. Rates of overall adverse events with linagliptin, glimepiride and placebo were 27.5, 61.0 and 35.0%, respectively. Fewer hypoglycaemic events were seen with linagliptin (5.0%) and placebo (2.5%) than with glimepiride (39.0%). CONCLUSIONS: Linagliptin had no effect on macrovascular function in T2D, but significantly improved microvascular function in the fasting state. Trial registration ClinicalTrials.gov identifier-NCT01703286; registered October 1, 2012.
Assuntos
Artéria Braquial/efeitos dos fármacos , Diabetes Mellitus Tipo 2/tratamento farmacológico , Angiopatias Diabéticas/tratamento farmacológico , Dipeptidil Peptidase 4/metabolismo , Inibidores da Dipeptidil Peptidase IV/uso terapêutico , Endotélio Vascular/efeitos dos fármacos , Hipoglicemiantes/uso terapêutico , Linagliptina/uso terapêutico , Microvasos/efeitos dos fármacos , Compostos de Sulfonilureia/uso terapêutico , Idoso , Biomarcadores/sangue , Artéria Braquial/diagnóstico por imagem , Artéria Braquial/fisiopatologia , Estudos Cross-Over , Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/diagnóstico , Diabetes Mellitus Tipo 2/enzimologia , Angiopatias Diabéticas/diagnóstico , Angiopatias Diabéticas/enzimologia , Inibidores da Dipeptidil Peptidase IV/efeitos adversos , Quimioterapia Combinada , Endotélio Vascular/fisiopatologia , Feminino , Hemoglobinas Glicadas/metabolismo , Humanos , Hipoglicemiantes/efeitos adversos , Linagliptina/efeitos adversos , Masculino , Metformina/uso terapêutico , Microcirculação/efeitos dos fármacos , Microvasos/fisiopatologia , Pessoa de Meia-Idade , Compostos de Sulfonilureia/efeitos adversos , Fatores de Tempo , Resultado do Tratamento , Vasodilatação/efeitos dos fármacosRESUMO
In the EMPA-REG BP trial, empagliflozin significantly reduced systolic and diastolic blood pressure (SBP and DBP) compared with placebo at week 12 in patients with type 2 diabetes mellitus (T2DM) and hypertension. In a post-hoc analysis, we assessed the effect of empagliflozin on SBP and DBP using 24-hour ambulatory BP monitoring in patients categorized as dippers (sleep-time mean SBP ≤ 90% of awake-time mean; n = 417) or non-dippers (sleep-time mean SBP > 90% of awake-time mean; n = 350). In dippers, adjusted mean (SE) changes from baseline in mean 24-hour SBP (mm Hg) at week 12 were -0.2 (0.7) with placebo vs -3.8 (0.6) and -3.9 (0.7) with empagliflozin 10 and 25 mg, respectively (both P < .001 vs placebo). In non-dippers, these changes were 1.0 (0.7) with placebo vs -1.6 (0.7) with empagliflozin 10 mg ( P = .013 vs placebo) and -3.8 (0.7) with empagliflozin 25 mg ( P < .001 vs placebo). In both dippers and non-dippers, SBP and DBP patterns over 24 hours were maintained. There were no clinically relevant changes in heart rate with empagliflozin. In conclusion, empagliflozin significantly reduced mean 24-hour SBP compared with placebo in dippers and non-dippers.
Assuntos
Compostos Benzidrílicos/uso terapêutico , Pressão Sanguínea/efeitos dos fármacos , Diabetes Mellitus Tipo 2/tratamento farmacológico , Glucosídeos/uso terapêutico , Hipertensão/tratamento farmacológico , Adulto , Idoso , Monitorização Ambulatorial da Pressão Arterial , Ritmo Circadiano/efeitos dos fármacos , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/fisiopatologia , Angiopatias Diabéticas/tratamento farmacológico , Angiopatias Diabéticas/fisiopatologia , Feminino , Frequência Cardíaca/efeitos dos fármacos , Humanos , Hipertensão/complicações , Hipertensão/diagnóstico , Hipertensão/fisiopatologia , Masculino , Pessoa de Meia-Idade , Resultado do TratamentoRESUMO
PURPOSE OF REVIEW: The majority of patients with type 2 diabetes mellitus (T2DM) have hypertension requiring combination therapy. Sodium glucose cotransporter 2 (SGLT2) inhibitors are novel glucose-lowering drugs with shared and potentially unique beneficial effects on cardiovascular risk beyond glycemic control. This review focuses on the potential role of SGLT2 inhibitors in the treatment of hypertension associated with T2DM. RECENT FINDINGS: SGLT2 inhibitors reduce office SBP by 3-5âmmHg and DBP by 2-3âmmHg across all class members. Corresponding clinically meaningful, significant blood pressure (BP) lowering effects have been confirmed using 24âh ambulatory BP monitoring. SGLT2 inhibitors reduce BP irrespective of the type of background antihypertensive medication. The antihypertensive actions of SGLT2 inhibitors involve several mechanisms including modest diuretic effects, weight loss, and direct vascular effects leading to decreased arterial stiffness and vascular resistance. The first-in class cardiovascular outcome trial with empagliflozin showed a significant reduction in a composite endpoint of cardiovascular death, nonfatal stroke, and nonfatal myocardial infarction in T2DM patients at high risk for cardiovascular events. SUMMARY: SGLT2 inhibitors have clinically significant antihypertensive effects. SGLT2 inhibition could be a potentially useful supplement to the BP-lowering treatment armamentarium in patients with T2DM.
Assuntos
Pressão Sanguínea/efeitos dos fármacos , Diabetes Mellitus Tipo 2/tratamento farmacológico , Angiopatias Diabéticas/tratamento farmacológico , Hipertensão/tratamento farmacológico , Hipoglicemiantes/uso terapêutico , Inibidores do Transportador 2 de Sódio-Glicose , Compostos Benzidrílicos/uso terapêutico , Diabetes Mellitus Tipo 2/complicações , Diuréticos , Glucosídeos/uso terapêutico , Humanos , Hipertensão/complicações , Hipertensão/metabolismo , Hipoglicemiantes/farmacologia , Transportador 2 de Glucose-Sódio/metabolismo , Resistência Vascular/efeitos dos fármacos , Redução de Peso/efeitos dos fármacosAssuntos
Diabetes Mellitus Tipo 2 , Insuficiência Cardíaca , Inibidores do Transportador 2 de Sódio-Glicose , Simportadores , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/tratamento farmacológico , Glucose , Insuficiência Cardíaca/tratamento farmacológico , Humanos , Miocárdio , SódioRESUMO
IN BRIEF Congenital lipodystrophy is a rare genetic disorder characterized by a near-complete absence of fat cells, hypoleptinemia leading to a voracious appetite, and marked insulin resistance. This article focuses on the known cardiovascular manifestations of patients with congenital lipodystrophy, including cardiomyopathy, cardiac arrhythmias, and accelerated atherosclerosis arising from a markedly deranged metabolic milieu. Future research that targets leptin deficiency (metreleptin) and apoC3 mRNA (antisense oligonucleotide) could open a window for potential pharmacological treatment of this challenging disorder.
RESUMO
Vast research efforts have been devoted to providing clinical diagnostic markers of myocardial infarction (MI), leading to over one million abstracts associated with "MI" and "Cardiovascular Diseases" in PubMed. Accumulation of the research results imposed a challenge to integrate and interpret these results. To address this problem and better understand how the left ventricle (LV) remodels post-MI at both the molecular and cellular levels, we propose here an integrative framework that couples computational methods and experimental data. We selected an initial set of MI-related proteins from published human studies and constructed an MI-specific protein-protein-interaction network (MIPIN). Structural and functional analysis of the MIPIN showed that the post-MI LV exhibited increased representation of proteins involved in transcriptional activity, inflammatory response, and extracellular matrix (ECM) remodeling. Known plasma or serum expression changes of the MIPIN proteins in patients with MI were acquired by data mining of the PubMed and UniProt knowledgebase, and served as a training set to predict unlabeled MIPIN protein changes post-MI. The predictions were validated with published results in PubMed, suggesting prognosticative capability of the MIPIN. Further, we established the first knowledge map related to the post-MI response, providing a major step towards enhancing our understanding of molecular interactions specific to MI and linking the molecular interaction, cellular responses, and biological processes to quantify LV remodeling.
Assuntos
Infarto do Miocárdio/diagnóstico , Infarto do Miocárdio/fisiopatologia , Remodelação Ventricular , Algoritmos , Biomarcadores/metabolismo , Análise por Conglomerados , Simulação por Computador , Mineração de Dados , Bases de Dados de Proteínas , Matriz Extracelular/fisiologia , Ventrículos do Coração/patologia , Humanos , Informática Médica , Modelos Biológicos , Mapeamento de Interação de ProteínasRESUMO
MicroRNAs (miRNAs) are a class of post-transcriptional regulators that provide a mechanism of gene silencing by translational repression or degradation of the targeted gene. Gene expression regulation by miRNAs is involved in most if not all physiological and pathophysiological processes. Atherosclerosis is a major cardiovascular disease pathology regulated by miRNAs. Recent miRNA profiling studies have implicated the potential use of miRNAs as biomarkers in patients with atherosclerosis, as both diagnostic and prognostic indicators. This review will discuss the clinical and basic science research information that has been gleaned regarding miRNA roles in dyslipidemia, diabetes, obesity, and insulin resistance which are the major stimulators for the development of atherosclerosis.