Neuropatia autonômica cardiovascular em pacientes com diabetes mellitus: perspectivas atuais / Cardiovascular autonomic neuropathy in patients with diabetes mellitus: current outlook

A neuropatia autonômica cardíaca (NAC) é uma complicação comum do diabetes mellitus (DM) e frequentemente, subdiagnosticada. A NAC está associada ao aumento da mortalidade, cardiovascular e renal, doença renal crônica e maior morbidade em pacientes com DM. Apesar dessas consequências, muitas vezes, a NAC permanece sem diagnóstico por um período prolongado. Isso geralmente porque a doença é assintomática até a fase avançada, bem como pela falta de informações e de estratégias de triagem. Clinicamente NAC se manifesta por distúrbios funcionais ou condições clínicas que envolvem desajuste das atividades reflexas cardiovasculares, tais como taquicardia em repouso, intolerância ao exercício, hipotensão ortostática, instabilidade cardiovascular intraoperatória, disfunção elétrica do coração traduzida por arritmias e isquemia miocárdica silenciosa. Essas alterações comprometem a qualidade de vida e a sobrevida dos pacientes. A NAC, segundo sua evolução, pode ser subdividida em subclínica (fase em que predominam alterações funcionais reversíveis) e clínica (quando as alterações neuronais estruturais estão plenamente estabelecidas). A avaliação da integridade do sistema nervoso autonômico é realizada por meio de exploração da atividade parassimpática, analisando o comportamento da frequência cardíaca (FC) em resposta à respiração profunda, ortostatismo ou manobra de Valsalva. A atividade simpática é explorada por meio de aferição da pressão arterial em resposta a mudança de postura (ortostatismo) e esforço isométrico. A análise da variabilidade da frequência cardíaca (VFC), no domínio do tempo, no domínio da frequência e por métodos gráficos complementam essa avaliação. Neste artigo de revisão, analisamos recentes informações sobre a epidemiologia, manifestações clínicas, diagnóstico, e tratamentos da NAC

Cardiac autonomic neuropathy (CAN) is a common and often-underdiagnosed complication of diabetes mellitus (DM). CAN is associated with increased mortality, cardiovascular disease, chronic kidney disease, and morbidity in patients with DM, but despite these significant consequences CAN often remains undiagnosed for a prolonged period. This is commonly due to the disease being asymptomatic until the later stages, as well as a lack of easily available screening strategies. Clinically, CAN is manifested by functional disorders or clinical conditions that involve maladjustment of cardiovascular reflex activities, such as tachycardia at rest, exercise intolerance, orthostatic hypotension, intraoperative cardiovascular instability, electrical dysfunction of the heart translated by arrhythmias and silent myocardial ischemia. These changes compromise patients' quality of life and survival. CAN, according to its evolution, can be subdivided into subclinical (phase in which reversible functional changes predominate) and clinical (when structural neuronal changes are fully established). The assessment of the integrity of the autonomic nervous system is performed by exploring parasympathetic activity, analyzing the heart rate in response to deep breathing, orthostatism or Valsalva maneuver. Sympathetic activity is explored by measuring blood pressure in response to a change in posture (orthostatism) and isometric effort. The analysis of heart rate variability (HRV), in the time domain, in the frequency domain and by graphic methods, complement this assessment. In this article, we review the latest developments in the epidemiology, pathogenesis, diagnosis, consequences, and treatments of CAN in patients with DM.

Uncontrolled hypertension, uncompensated type II diabetes, and smoking have different patterns of vascular dysfunction.

STUDY OBJECTIVES: We evaluated the vascular reactivity in healthy subjects, heavy smokers, uncompensated type II diabetics, and patients with uncontrolled essential hypertension. Plasma nitrite/nitrate, cyclic 3',5'-guanosine monophosphate (cGMP), and thromboxane (TX)-B(2) levels were measured. PARTICIPANTS: One hundred participants were classified into four groups: normal control subjects (n = 25), heavy smokers (n = 25), uncompensated type II diabetics (n = 25), and patients with uncontrolled essential hypertension (n = 25). INTERVENTIONS: The brachial artery diameter was measured by a high-resolution ultrasound technique before and after reactive hyperemia and glyceryl trinitrate (GTN), 0.4 mg, administration. Plasma nitrite/nitrate, cGMP, and TX-B(2) levels were also measured. RESULTS: Heavy smokers, uncompensated type II diabetics, and uncontrolled hypertensive patients showed impaired endothelium-dependent, nitric oxide (NO) flow-mediated vasodilatation (8.0 +/- 2.5%, 5.8 +/- 2.7%, and 7.2 +/- 3.3%, respectively [mean +/- SD]) when compared to the control subjects (12.6 +/- 3.6%; p < 0.01). Smokers had a normal endothelium-independent function induced by NO donor (GTN) [25.0 +/- 7.3% vs 25.3 +/- 8.5% for control subjects]. Uncompensated type II diabetics and patients with uncontrolled hypertension had impaired endothelium-independent responses (17.7 +/- 7.1% and 16.8 +/- 6.9%, respectively, vs 25.3 +/- 8.5 for normal control subjects; p < 0.05). Plasma levels of cGMP and TX-B(2) were not significantly different in the four groups, but nitrite/nitrate concentrations were increased in diabetics compared to the control subjects (266 +/- 47 micro mol/L vs 98 +/- 18 micro mol/L, p < 0.05). CONCLUSION: Both uncontrolled hypertension and type II diabetes mellitus, but not smoking, are associated with impaired vascular smooth-muscle reactivity induced by NO donors. However, only uncompensated type II diabetics showed an increase in plasma nitrite/nitrate levels, suggesting an association with excessive production and/or inactivation of NO.