Insulin resistance, endothelial function, angiogenic factors and clinical outcome in non-diabetic patients with chest pain without myocardial perfusion defects

Westergren, Helena U.; Svedlund, Sara; Momo, Remi A.; Blomster, Juuso; Wåhlander, Karin; Rehnström, Erika; Greasley, Peter J.; Fritsche‐Danielson, Regina; Oscarsson, Jan; Gan, Li‐Ming

doi:10.1186/s12933-016-0353-1

Cited by 25 publications

(18 citation statements)

References 50 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…NEMO (NF-κ-B essential modulator), found at highest levels in phenogroups 3 and 5, has been suggested to be important in cardiac function, as disruption in mice leads to a HF phenotype 32. Levels of ESM-1, with the strongest association to phenogroups of any of the proteins, has previously been negatively associated with BMI and insulin resistance 33 34. Further evidence supports a role for this protein as a marker of endothelial dysfunction (upregulated in acute MI, CKD and hypertension35), which is also consistent with a purported model of global inflammation driving microvascular endothelial dysfunction in HFpEF 10 11.…”

Section: Discussionsupporting

confidence: 58%

Identification of novel pheno-groups in heart failure with preserved ejection fraction using machine learning

Hedman¹,

Hage²,

Sharma³

et al. 2020

Heart

Self Cite

104

View full text Add to dashboard Cite

ObjectiveHeart failure with preserved ejection fraction (HFpEF) is a heterogeneous syndrome. We aimed to derive HFpEF phenotype-based groups ('phenogroups') based on clinical and echocardiogram data using machine learning, and to compare clinical characteristics, proteomics and outcomes across the phenogroups.MethodsWe applied model-based clustering to 32 echocardiogram and 11 clinical and laboratory variables collected in stable condition from 320 HFpEF outpatients in the Karolinska-Rennes cohort study (56% female, median 78 years (IQR: 71–83)). Baseline proteomics and the composite end point of all-cause mortality or heart failure (HF) hospitalisation were used in secondary analyses.ResultsWe identified six phenogroups, for which significant differences in the prevalence of concomitant atrial fibrillation (AF), anaemia and kidney disease were observed (p<0.05). Fifteen out of 86 plasma proteins differed between phenogroups (false discovery rate, FDR<0.05), including biomarkers of HF, AF and kidney function. The composite end point was significantly different between phenogroups (log-rank p<0.001), at short-term (100 days), mid-term (18 months) and longer-term follow-up (1000 days). Phenogroup 2 was older, with poorer diastolic and right ventricular function and higher burden of risk factors as AF (85%), hypertension (83%) and chronic obstructive pulmonary disease (30%). In this group a third experienced the primary outcome to 100 days, and two-thirds to 18 months (HR (95% CI) versus phenogroups 1, 3, 4, 5, 6: 1.5 (0.8–2.9); 5.7 (2.6–12.8); 2.9 (1.5–5.6); 2.7 (1.6–4.6); 2.1 (1.2–3.9)).ConclusionsUsing machine learning we identified distinct HFpEF phenogroups with differential characteristics and outcomes, as well as differential levels of inflammatory and cardiovascular proteins.

show abstract

Section: Discussionsupporting

confidence: 58%

Identification of novel pheno-groups in heart failure with preserved ejection fraction using machine learning

Hedman¹,

Hage²,

Sharma³

et al. 2020

Heart

Self Cite

104

View full text Add to dashboard Cite

show abstract

“…Moreover, nitrotyrosine was also associated with higher coronary endothelial dysfunction. A previous study (19) has reported that insulin resistance is associated with endothelial dysfunction and confers independent prognostic information in patients without diabetes with chest pain without myocardial perfusion defects. However, this study did not provide any evidence about coronary endothelial dysfunction, such as that found in patients with prediabetes, or assess the specific pathway transducing prediabetes coronary environmental stimuli in stable CAD-NOCS poor outcomes.…”

Section: Discussionmentioning

confidence: 96%

Effects of Metformin Therapy on Coronary Endothelial Dysfunction in Patients With Prediabetes With Stable Angina and Nonobstructive Coronary Artery Stenosis: The CODYCE Multicenter Prospective Study

Sardu

Paolisso

Sacra³

et al. 2019

Diabetes Care

129

View full text Add to dashboard Cite

To evaluate the effect of metformin therapy on coronary endothelial function and major adverse cardiac events (MACE) in patients with prediabetes with stable angina and nonobstructive coronary stenosis (NOCS). RESEARCH DESIGN AND METHODS Metformin therapy may be needed to reduce coronary heart disease risk in patients with prediabetes. A total of 258 propensity score-matched (PSM) patients with stable angina undergoing coronary angiography were enrolled in the study. Data from 86 PSM subjects with normoglycemia (NG), 86 PSM subjects with prediabetes (pre-DM), and 86 PSM subjects with prediabetes treated with metformin (pre-DM metformin) were analyzed. During coronary angiography, NOCS was categorized by luminal stenosis <40% and fractional flow reserve >0.80. In addition, we assessed the endothelial function, measuring coronary artery diameter of left anterior descending coronary (LAD) at baseline and after the infusion of acetylcholine, by means of an intracoronary Doppler guide wire. MACE, as cardiac death, myocardial infarction, and heart failure, was evaluated at 24 months of follow-up. RESULTS At baseline, NG patients had a lower percentage of LAD endothelial dysfunction compared with pre-DM patients (P < 0.05). The pre-DM patients had a higher percentage of endothelial LAD dysfunction as compared with the pre-DM metformin patients (P < 0.05). At the 24th month of follow-up, MACE was higher in pre-DM versus NG (P < 0.05). In pre-DM metformin patients, MACE was lower compared with pre-DM patients (P < 0.05). CONCLUSIONS Metformin therapy may reduce the high risk of cardiovascular events in pre-DM patients by reducing coronary endothelial dysfunction.

show abstract

“…However, Shimizu et al demonstrated four weeks blood flow restriction resistance training to improve RHI in healthy elderly subjects with relatively low initial RHI [ 32 ]. Also, increased RHI has been associated with decreased Homeostatic model assessment of insulin resistance (HOMA-IR) after 16 weeks of exercise and diet restriction in obese women [ 33 ] and high HOMA-IR is related to decreased RHI in patients with suspected myocardial ischemia [ 34 ]. Decreased digital vasodilator function derived by EndoPAT has been associated with metabolic risk factors, including obesity, diabetes mellitus, and ratio of total to HDL cholesterol [ 35 ].…”

Section: Discussionmentioning

confidence: 99%

Randomized clinical trial studying effects of a personalized supervised lifestyle intervention program on cardiovascular status in physically inactive healthy volunteers

et al. 2018

Self Cite

View full text Add to dashboard Cite

BackgroundThe impact of personalized exercise training and a healthy dietary lifestyle in healthy volunteers on coronary flow reserve and cardiovascular function remains to be investigated in a controlled study setting.PurposeTo examine the effects of a Mediterranean-inspired diet combined with regular physical exercise (standard) and a personalized supervised exercise program (DAPS) on coronary flow reserve and cardiovascular function.ResultsThe number of males were 10 (59%) and 9 (47%) and mean age was 54 ± 12 and 55 ± 5 years in standard versus DAPS group, respectively. Primary outcomes were in addition to improved body composition and aerobic capacity, increased TDE-CFR (5.0%, CI:1.62,8.64, p = 0.005) and left ventricle ejection fraction (LVEF) during hyperemia (10.2%, CI:1.62,19.4, p = 0.022) in DAPS adjusted for the control period. Also, plasma fibrinogen decreased (−12.1%, CI:-22.0,–0.92, p = 0.035) in the DAPS group. Secondary outcomes, after adjusting DAPS intervention effects for the standard-training period, TDE-CFR and hyperemic LVEF remained significantly improved.Materials and MethodsThis randomized, controlled clinical trial (URL: http://www.clinicaltrials.gov NCT02713724) included 36 healthy volunteers who underwent exercise ECG before randomization to standard or DAPS groups. Standard-group was given gym-membership with limited instructions and general dietary advice. DAPS-group received personalized supervised exercise programs and more detailed dietary advice with regular contact with a personal trainer. Effects were evaluated after 3 months. All participants underwent coronary flow reserve by transthoracic ultrasound (TDE-CFR), blood marker analysis and examinations of vascular function. Standard-group was evaluated pre-control, post-control (=pre-intervention) and post-intervention. DAPS-group was examined at pre-intervention and post-intervention.ConclusionsA personalized supervised training- and diet program improves cardiovascular status in healthy subjects with a physically inactive lifestyle and may be a promising approach for cardiovascular prevention in the general population.

show abstract

Insulin resistance, endothelial function, angiogenic factors and clinical outcome in non-diabetic patients with chest pain without myocardial perfusion defects

Cited by 25 publications

References 50 publications

Identification of novel pheno-groups in heart failure with preserved ejection fraction using machine learning

Identification of novel pheno-groups in heart failure with preserved ejection fraction using machine learning

Effects of Metformin Therapy on Coronary Endothelial Dysfunction in Patients With Prediabetes With Stable Angina and Nonobstructive Coronary Artery Stenosis: The CODYCE Multicenter Prospective Study

Randomized clinical trial studying effects of a personalized supervised lifestyle intervention program on cardiovascular status in physically inactive healthy volunteers

Contact Info

Product

Resources

About