Vascular Regenerative Cell Exhaustion in Diabetes: Translational Opportunities to Mitigate Cardiometabolic Risk

Terenzi, Daniella C.; Trac, Justin Z.; Teoh, Hwee; Gerstein, Hertzel C.; Bhatt, Deepak L.; Al‐Omran, Mohammed; Verma, Subodh; Hess, David A.

doi:10.1016/j.molmed.2019.03.006

Cited by 21 publications

(19 citation statements)

References 90 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The connection between microvascular diseases and CV events is further supported by emerging experimental and clinical data 1,6 . A post hoc analysis of EMPA‐REG OUTCOME investigated the risk of microvascular disease on CV outcomes using Cox proportional hazards models.…”

Section: Discussionmentioning

confidence: 96%

“…12 While we did not evaluate the relationship between microvascular risk and heart failure, there are emerging experimental and clinical data to support this link. 1,6 Indeed, in EMPA-REG OUTCOME, microvascular disease history was a stronger determinant of heart failure (1.63 [1.06-2.49], P = .0245) compared with MACE (1.16 [0.92-1.48], P = .2144).…”

Section: Discussionmentioning

confidence: 99%

“…These include diabetes‐induced changes in endothelial structure and function within the micro‐ and macrovasculature, increased production of reactive oxygen species, augmented mitochondrial superoxide release, and changes in protein kinase C metabolism 5 . In addition, microvascular complications have been linked to an increased risk of heart failure in diabetes, 5 and microvascular rarefaction (vasculopenia) has emerged as an important pathophysiological component of diabetic heart failure 6 …”

Section: Introductionmentioning

confidence: 99%

“…5 In addition, microvascular complications have been linked to an increased risk of heart failure in diabetes, 5 and microvascular rarefaction (vasculopenia) has emerged as an important pathophysiological component of diabetic heart failure. 6 The relationship between microvascular disease and macrovascular risk has not been thoroughly investigated in contemporary cardiovascular (CV) outcomes trials, with just one post hoc analysis published to date. 1 Compared with prior observational and clinical studies, these trials have been conducted in the context of guidelinerecommended background therapy including statins, blood pressure control, renin-angiotensin system inhibitors and glycaemic control.…”

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Impact of microvascular disease on cardiovascular outcomes in type 2 diabetes: Results from the LEADER and SUSTAIN 6 clinical trials

Verma

Bain

Honoré

et al. 2020

Diabetes Obesity Metabolism

Self Cite

View full text Add to dashboard Cite

The randomized, double-blind, cardiovascular outcomes trials LEADER (NCT01179048) and SUSTAIN 6 (NCT01720446) showed cardiovascular risk reduction in patients with type 2 diabetes treated with liraglutide and semaglutide, respectively, compared with placebo. This post hoc analysis examined the impact of microvascular disease at baseline on cardiovascular outcomes in these trials, and the efficacy of liraglutide (1.8 mg) and once-weekly semaglutide (0.5-1.0 mg) in patients with and without microvascular disease. In total, 9340 patients from LEADER and 3297 patients from SUSTAIN 6 were included in this analysis; of these, 5761 and 2356 had a history of microvascular disease at baseline and 3835 and 1640 had a history of both microvascular and macrovascular disease, respectively. Patients with microvascular disease were shown to have an increased risk of major adverse cardiovascular events compared with patients without microvascular disease (hazard ratio

show abstract

Section: Discussionmentioning

confidence: 96%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Impact of microvascular disease on cardiovascular outcomes in type 2 diabetes: Results from the LEADER and SUSTAIN 6 clinical trials

Verma

Bain

Honoré

et al. 2020

Diabetes Obesity Metabolism

Self Cite

View full text Add to dashboard Cite

show abstract

“…Additional studies have revealed an important cross-talk between inflammation and vascular repair and regenerationdan effect that appears to be transduced by increased levels of oxidative stress. 16,17 Markers of inflammation (notably high-sensitivity C-reactive protein [hsCRP]) have been shown to identify patients at heightened risk of atherosclerosis, and in whom additional risk-reduction strategies (eg, therapy with statins) may be valuable. 18,19 A causal role of inflammation in atherosclerosis has also been recently demonstrated in the Canakinumab Antiinflammatory Thrombosis Outcome Study (CANTOS) trial, in which the interleukin-1b antagonist canakinumab was studied in patients with a history of myocardial infarction.…”

mentioning

confidence: 99%