Association of endothelial dysfunction with cardiovascular risk factors and new‐onset diabetes mellitus in patients with hypertension

Triches, Cristina Bergmann; Mayer, Saurus; Quinto, Beata Marie Redublo; Batista, Marcelo Costa; Zanella, Maria Teresa

doi:10.1111/jch.13269

Cited by 14 publications

(17 citation statements)

References 28 publications

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“…This, in turn, can reduce the bioavailability of NO and lead to endothelial dysfunction [21,22]. Plasma ADMA is elevated in diabetes, hypertension and diabetic nephropathy, and is an independent risk factor for all-cause mortality and cardiovascular disease [23][24][25]. Thus, modulation of ADMA levels and L-arginine/ ADMA ratio by praliciguat may imply an impact on endothelial function which, if sustained, could be associated with cardiovascular and renal benefit.…”

Section: Resultsmentioning

confidence: 99%

An exploratory, randomised, placebo-controlled, 14 day trial of the soluble guanylate cyclase stimulator praliciguat in participants with type 2 diabetes and hypertension

et al. 2019

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Aims/hypothesis Praliciguat (IW-1973), a soluble guanylate cyclase stimulator, amplifies nitric oxide signalling. This exploratory trial investigated the safety, tolerability, pharmacokinetic profile and pharmacodynamic effects of praliciguat in individuals with type 2 diabetes and hypertension. Methods This Phase IIA, double-blind, placebo-controlled trial investigated praliciguat in 26 participants with type 2 diabetes and hypertension on stable glucose-and BP-lowering therapies. Participants were randomly allocated in a 3:5:5 ratio to three groups: placebo (n = 6), praliciguat 40 mg once daily for days 1-14 (n = 10), or praliciguat 20 mg twice daily for days 1-7 then 40 mg once daily for days 8-14 (n = 10). Assessments were made in clinic and included treatment-emergent adverse events, pharmacokinetics, metabolic variables, 24 h BP and heart rate, platelet function, reactive hyperaemia index (RHI) and plasma biomarkers. Participants, the sponsor, the investigator and clinic study staff (except designated pharmacy personnel) were blinded to group assignment. Results Participants treated for 14 days with praliciguat had least-square mean change-from-baseline differences vs placebo (95% CI) of −0.7 (−1.8, 0.4) mmol/l for fasting plasma glucose, −0.7 (−1.1, −0.2) mmol/l for total cholesterol, −0.5 (−1.0, −0.1) mmol/l for LDL-cholesterol, −23 (−56, 9) for HOMA-IR in those not being treated with insulin, and −5 (−10, 1) mmHg and 3 (−1, 6) beats/min for average 24 h mean arterial pressure and heart rate, respectively. Apart from one serious adverse event (SAE; upper gastrointestinal haemorrhage), praliciguat was well tolerated. Praliciguat did not affect platelet function or RHI. Among exploratory biomarkers, plasma levels of asymmetric dimethylarginine decreased in praliciguat vs placebo recipients. Conclusions/interpretation In participants with type 2 diabetes and hypertension on standard therapies, over 14 days praliciguat was well tolerated, except for a single SAE, and showed positive trends in metabolic and BP variables. These results support further clinical investigation of praliciguat. Trial registration ClinicalTrials.gov NCT03091920. Funding This trial was funded by Cyclerion Therapeutics.

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Section: Resultsmentioning

confidence: 99%

An exploratory, randomised, placebo-controlled, 14 day trial of the soluble guanylate cyclase stimulator praliciguat in participants with type 2 diabetes and hypertension

et al. 2019

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“…Cubic, p = 0.016, R 2 = 0.075 Linear/S-model also significant Cubic, p = 0.004, R 2 = 0. who studied the association of endothelial dysfunction with CV risk factors in 191 patients with new-onset DM combined with hypertension [40]. They stratified the participants into subgroups with high ( > 0.55 μmmol/l) and low levels of plasma ADMA and monitored them for a period of 5.8 years [40]. High ADMA were seen in patients with multiple metabolic risk factors and an association between high plasma ADMA levels and the occurrence of CV death [40] was made.…”

Section: No Model Availablementioning

confidence: 99%

“…They stratified the participants into subgroups with high ( > 0.55 μmmol/l) and low levels of plasma ADMA and monitored them for a period of 5.8 years [40]. High ADMA were seen in patients with multiple metabolic risk factors and an association between high plasma ADMA levels and the occurrence of CV death [40] was made. In another study carried out over 6.5-year period, the highest ADMA quartile was associated with increased risk for both microvascular (OR = 4.5) and incident macrovascular complications (OR = 8.3) [18].…”

Section: No Model Availablementioning

confidence: 99%

Cardiovascular Biomarkers and Calculated Cardiovascular Risk in Orally Treated Type 2 Diabetes Patients: Is There a Link?

et al. 2020

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AbstractThe aim of the study was to test the correlation of serum levels of asymmetric dimethylarginine (ADMA), endothelin 1 (ET-1), N-terminal brain natriuretic pro-peptide (NT-proBNP), and placental growth factor (PIGF-1) with estimated cardiovascular (CV) risk. The study group was composed of 102 women and 67 men with type 2 diabetes, having their glycemic and metabolic parameters assessed. All were on oral antidiabetic drugs. Serum levels of NT-proBNP and PIGF-1 were measured by electro-hemi-luminescence on an Elecsys 2010 analyzer. Enzymatic immunoassays were used for ADMA and ET-1. The Framingham Risk Score (FRS), the UKPDS 2.0 and the ADVANCE risk engines were used to calculate cardiovascular risks while statistical analysis was performed on SPSS. Levels of PIGF-1 showed no correlation with the calculated CV risks. The same was true for ADMA, except for a weak correlation with the UKPDS-based 10-year risk for stroke (Pearsons’s R=0.167, p=0.039). Plasma levels of ET-1 were correlated with the UKPDS-based 10-year risk for stroke (R=0.184, p=0.032) and fatal stroke (R=0.215, p=0.012) only. NT-proBNP was significantly correlated with all CV risk calculations: ADVANCE-based 4-yr risk (Spearman’s Rho=0.521, p<0.001); UKPDS-based 10-year risk for: CHD (Rho=0.209, p=0.01), fatal CHD (Rho=0.282, p<0.001), stroke (Rho=0.482, p<0.001), fatal stroke (Rho=0.505, p<0.001); and 10-year FRS risk (Rho=0.246, p=0.002). In conclusion, ADMA and PIGF-1 did not seem useful in stratifying CV risk while ET-1 is linked to the risk of stroke, and NT-proBNP to all CV risk estimations.

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“…ED is determined an abnormal vascular tone reaction predominantly vasoconstriction due to potential vasodilator stimuli. ED plays a pivotal role in the development of pre-hypertension and hypertension [5]. The pathophysiological mechanisms of ED development affect several factors contributing to various faces of loss of normal vascular function and structure.…”

Section: Endothelial Dysfunction In Hypertensionmentioning

confidence: 99%

The role of progenitor endothelial cell dysfunction in arterial hypertension

Berezin¹

2018

bmgt

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Hypertension remains leading cardiovascular (CV) risk factors in different population worldwide. The negative effect of hypertension on survival and CV complication partly associates with endothelial dysfunction. Recent studies have shown strong linear relation between endothelial dysfunction and morbidity and mortality in hypertensive patients. However, clear innate mechanisms contributing to target organ damages through abnormalities of vascular function are not completely understood. The lowered number and weak function of circulating endothelial progenitor cells (EPCs) is recognized new marker of endothelial dysfunction with high likely predictive value in patient populations with hypertension. The short communication is depicted the uncertain role of EPC dysfunction in pathogenesis of hypertension

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Association of endothelial dysfunction with cardiovascular risk factors and new‐onset diabetes mellitus in patients with hypertension

Abstract: Asymmetric dimethylarginine (ADMA), which is the main endogenous inhibitor of nitric oxide synthase, plays a critical role in the process of endothelial dysfunction.

Cited by 14 publications

References 28 publications

An exploratory, randomised, placebo-controlled, 14 day trial of the soluble guanylate cyclase stimulator praliciguat in participants with type 2 diabetes and hypertension

An exploratory, randomised, placebo-controlled, 14 day trial of the soluble guanylate cyclase stimulator praliciguat in participants with type 2 diabetes and hypertension

Cardiovascular Biomarkers and Calculated Cardiovascular Risk in Orally Treated Type 2 Diabetes Patients: Is There a Link?

The role of progenitor endothelial cell dysfunction in arterial hypertension

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