Nitroglycerin-mediated vasodilatation of the brachial artery may predict long-term cardiovascular events irrespective of the presence of atherosclerotic disease

Abstract

Aim: Nitroglycerin-mediated vasodilatation (NMD) provides insight into the NTG-induced bioactivity of smooth muscle. It is plausible that in dysfunctional smooth muscle cells, the response to nitroglycerin may become blunted. The relationship between impaired brachial artery NMD and subsequent cardiovascular events is not well established. Methods: We examined brachial artery flow-mediated dilatation (FMD) and NMD using ultrasound in 93 subjects (71 7 years, including 26 with peripheral artery disease (PAD), 37 with aortic aneurysms, 10 with PAD complicated with aneurysms, and 20 without evident arterial disease). Brachial artery responses to hyperemia and nitroglycerin were measured every minute after cuff deflation and nitroglycerin administration. Time courses of vasodilatation were assessed and maximal FMD and NMD were measured. Results: The time courses in response to NTG were sigmoidal and maximal diameter reached 7.2 1.6 minutes after NTG was administered sublingually. The mean FMD was 2.3±2.0% and the mean NMD was 17.6 7.1%. Subjects were prospectively followed for an average of 47 13 months. Eighteen subjects had an event during follow-up; events included myocardial infarction (five), unstable angina pectoris (four), stroke (two), aortic dissection (one), ruptured aortic aneurysm (three), symptomatic abdominal aortic aneurysm (two), and lower limb ischemia requiring revascularization (one). NMD and FMD were significantly lower in subjects with events than in those without an event. In a Cox proportional-hazards model, lower FMD as well as lower NMD independently predicted future cardiovascular events. Conclusion: Brachial artery nitroglycerin-mediated vasodilatation may add information to conventional risk stratification.

Vascular smooth muscle function in type 2 diabetes mellitus: a systematic review and meta-analysis

“…This study suggested a novel mechanism of cardiovascular disease in persons with type 2 diabetes. VSM dysfunction was previously reported in asymptomatic adults with risk factors for atherosclerosis [49], and it was clearly demonstrated to predict future cardiovascular events even better than endothelial function in such individuals [9,50]. Moreover, the association of VSM function with cardiovascular risk factors differed from that of endothelial function, and was more strongly related to vascular disease than endothelial function in individuals with type 2 diabetes [51].…”

Association of Endothelial and Vascular Smooth Muscle Dysfunction with Cardiovascular Risk Factors, Vascular Complications, and Subclinical Carotid Atherosclerosis in Type 2 Diabetic Patients

“…Furthermore, in type 1 diabetic patients, the levels of HbA1c and matrix metalloproteinase (MMP-9), which are involved in the metabolism of the extracellular matrix, were found to be independent predictors of impaired NMD 24) . Recently, NMD induced by nitroglycerin (300 μg) administration was clearly demonstrated to predict future cardiovascular events better than FMD in a high-risk group comprising patients with mainly peripheral artery disease and aortic aneurysm 31) . In view of the superiority of NMD to FMD, our findings are consistent with those of the aforementioned study, although the inclusion criteria and methods for the measurements of NMD in that study were different from this study.…”

Acute Hyperglycemia Impairs Vascular Function in Healthy and Cardiometabolic Diseased Subjects

“…75 Ultimately, VSM cell proliferation may signal the beginning of a detectable and significant VSM dysfunction, representing a critical event in vascular remodeling and the development of CVD. 76 Given that CVD is the single leading cause of death, accounting for 30% of the annual global mortality rate, 77 and that even healthy populations are subject to vascular dysfunction during acute hyperglycemia, there is a clear need to further investigate the effects of acute hyperglycemia on the underlying mechanisms of vascular function in vivo. Because of a surge in added sugar consumption in recent decades, predominantly in the form of sugar-sweetened beverages, 2 humans are more often in a state of acute hyperglycemia and therefore are more frequently inducing endothelial dysfunction.…”