Endothelial dysfunction and cardiovascular outcome in asymptomatic patients with type 2 diabetes: A pilot study

Abstract

BackgroundType 2 diabetes mellitus (T2DM) is associated with an increased risk of cardiovascular events, but risk stratification of asymptomatic T2DM patients remains a challenging issue. We conducted a pilot study to assess whether endothelial dysfunction might help identify, among asymptomatic T2DM patients, those at increased risk of cardiovascular events.MethodsWe studied 61 consecutive T2DM patients with no evidence of cardiovascular disease and no insulin therapy. Endothelial function was assessed by flow‐mediated dilation (FMD) of the right brachial artery. The primary endpoint was a combination of major cardiovascular events (MACE: cardiovascular death, acute coronary events, coronary interventions, and acute cerebrovascular accidents). FMD was repeated at follow‐up in 48 patients (79%).ResultsA total of 10 MACE (16.4%) occurred during a mean follow‐up of 48 months, including three acute myocardial infarctions, five coronary revascularizations for stable angina, and two acute ischaemic strokes. FMD at enrolment was lower in patients with compared with patients without MACE (3.78 ± 0.97% vs 4.70 ± 1.33%, respectively; P = .04). No other clinical or laboratory variables (age, diabetes duration, glycated haemoglobin, cardiovascular risk factors, drug therapy, and nitrate‐mediated dilation) were associated with MACE. FMD at follow‐up was also lower in patients with (n = 10) compared with those without (n = 38) MACE (3.66 ± 1.29 vs 4.85 ± 1.92; P = .006).ConclusionsOur data suggest that assessment of FMD might be helpful to identify patients at increased risk of MACE among individuals with asymptomatic T2DM; accordingly, a large study is warranted to adequately define the clinical utility of FMD assessment in the management of T2DM patients.

Initiating guideline-concordant gout treatment improves arterial endothelial function and reduces intercritical inflammation: a prospective observational study

“…Our findings indicate that initiating guideline-concordant gout treatment with colchicine+XOI to target sU concentration results in significantly increased brachial artery flow-mediated vasodilation along with significant reductions in intercritical bloodstream hsCRP, ESR, IL-1β, and IL-6 concentrations, indicating that colchicine+XOI enhances vascular endothelial function and reduces baseline systemic inflammation in gout patients. Since endothelial dysfunction, elevated hsCRP, IL-1β, and IL-6 concentrations have all been associated with increased cardiovascular risk [ 26 – 28 , 38 , 42 – 44 ], and since lowering of hsCRP and IL-6 via anti-IL-1β strategies is associated with reduced rates of major adverse cardiovascular events [ 45 , 46 ], these data suggest that gout treatment with colchicine+XOI may lower cardiovascular risk. Concentrations of MPO, a marker of neutrophil activation that is also associated with increased cardiovascular risk [ 47 ], were unaffected by colchicine+XOI treatment, indicating that not all aspects of inflammation may be modulated with initiating treatment in gout.…”

“…The mean allopurinol and febuxostat doses at treatment target were 384 ± 131 mg and 53 ± 23 mg/day, respectively. The median [interquartile range] time from initiating ULT (visit 2) to achieving sU target (visit 3) was 21 [13][14][15][16][17][18][19][20][21][22][23][24][25][26][27][28] weeks for the overall group (for non-tophaceous subjects, 17 [12][13][14][15][16][17][18][19][20][21][22][23][24][25][26][27] weeks; for tophaceous patients, 29 [26][27][28][29][30][31][32][33][34][35][36][37][38][39][40][41][42] weeks).…”

“…Alternatively, we recently reported that, compared to non-gout healthy controls, patients with gout have impairment of both brachial artery flow-mediated dilation (FMD) and nitrate-mediated dilation (NMD), measurements of endothelium-dependent and endotheliumindependent (smooth muscle) arterial responsiveness respectively [25]. Impaired endothelial function assessed by FMD correlates with risk for future coronary events [26][27][28][29], and studies both in vitro and in animal models indicate that urate may impede the ability of endothelial cells to generate nitric oxide and thus limit arterial responsiveness [30,31]. Therefore, both endothelial function and inflammation may be targets for lowering cardiovascular risk in patients with gout.…”

Cardiac Rehabilitation and Endothelial Function

“…FMD has been reported to be impaired in several clinical conditions, including subjects with various CVRFs, patients with stable CAD or HF, as well as in acute settings of CAD [38,44]. Furthermore, FMD has been shown to predict cardiovascular events, particularly in patients with established cardiovascular diseases or at high cardiovascular risk [45][46][47].…”

Amelioration of Endothelial Dysfunction in Diabetes: Role of Takeda G Protein–Coupled Receptor 5

“…DM is considered to be a vascular disease in addition to a metabolic disease ( Flyvbjerg, 2010 ; Arildsen et al, 2019 ) because vascular complications account for a relatively large proportion of diabetic complications and include diabetic cardiomyopathy, diabetic nephropathy, and diabetic peripheral neuropathy. Endothelial dysfunction (ED) is the initial vascular defect that develops in DM ( Legeay et al, 2020 ; Lespagnol et al, 2020 ), and it is recognized to be an independent predictor of poor prognosis in patients with microvascular or macrovascular complications of DM ( Wiggenhauser and Kroll, 2019 ; Villano et al, 2020 ). In this review, we focus on the ED that develops in diabetes, because impairment in endothelial function usually develops before related complications manifest clinically; by reducing ED, we can minimize target organ damage, and by identifying ED, we may diagnose DM in asymptomatic individuals.…”