Impaired Peripheral Microvascular Function and Risk of Major Adverse Cardiovascular Events in Patients With Coronary Artery Disease

Young, An; García, Mariana; Sullivan, Samaah; Liu, Chang; Moazzami, Kasra; Ko, Yi‐An; Shah, Amit; Kim, Jeong Hwan; Pearce, Brad D.; Uphoff, Irina; Bremner, J. Douglas; Raggi, Paolo; Quyyumi, Arshed A.; Vaccarino, Viola

doi:10.1161/atvbaha.121.316083

Cited by 17 publications

(13 citation statements)

References 54 publications

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“…In the present study, we hypothesized that living donor-KTx (LD-KTx) has beneficial effects on endothelial function and vessel stiffness in the microcirculation, assessed using EndoPAT—a device previously reported to identify patients with early coronary atherosclerosis and CVD [ 29 , 30 ]. Therefore, we compared functional and biochemical markers of endothelial function and vascular stiffness in patients at KTx (baseline) vs. two years post living-donor KTx (postKTx).…”

Section: Introductionmentioning

confidence: 99%

Indoxyl Sulphate Retention Is Associated with Microvascular Endothelial Dysfunction after Kidney Transplantation

Hobson

Arefin

Rahman

et al. 2023

IJMS

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Kidney transplantation (KTx) is the preferred form of renal replacement therapy in chronic kidney disease (CKD) patients, owing to increased quality of life and reduced mortality when compared to chronic dialysis. Risk of cardiovascular disease is reduced after KTx; however, it is still a leading cause of death in this patient population. Thus, we aimed to investigate whether functional properties of the vasculature differed two years post-KTx (postKTx) compared to baseline (time of KTx). Using the EndoPAT device in 27 CKD patients undergoing living-donor KTx, we found that vessel stiffness significantly improved while endothelial function worsened postKTx vs. baseline. Furthermore, baseline serum indoxyl sulphate (IS), but not p-cresyl sulphate, was independently negatively associated with reactive hyperemia index, a marker of endothelial function, and independently positively associated with P-selectin postKTx. Finally, to better understand the functional effects of IS in vessels, we incubated human resistance arteries with IS overnight and performed wire myography experiments ex vivo. IS-incubated arteries showed reduced bradykinin-mediated endothelium-dependent relaxation compared to controls via reduced nitric oxide (NO) contribution. Endothelium-independent relaxation in response to NO donor sodium nitroprusside was similar between IS and control groups. Together, our data suggest that IS promotes worsened endothelial dysfunction postKTx, which may contribute to the sustained CVD risk.

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Section: Introductionmentioning

confidence: 99%

Indoxyl Sulphate Retention Is Associated with Microvascular Endothelial Dysfunction after Kidney Transplantation

Hobson

Arefin

Rahman

et al. 2023

IJMS

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“…More specifically, cardiac systolic and diastolic function and the carotid artery's elasticity are affected in CCS with a higher burden of cancer treatment, and the latter correlates with apolipoprotein abnormalities. These ultrasonographical and lipid and apolipoprotein markers are known risk-factors for future CVD in different patient populations (25)(26)(27)(28)(29), but how they predict CVD in CCS remains elusive.…”

Section: Discussionmentioning

confidence: 99%

“…In the present study, endothelial vasomotor function assessed with PAT-RHI was decreased in CCS but no correlation with carotid stiffness nor cardiac function was observed. PAT-RHI has been reported to correlate with endothelial vasomotor response in the coronary circulation ( 24 ) and to predict cardiovascular outcome in individuals with CVD risk factors ( 25 , 46 ). PAT-RHI has been widely studied in other patient cohorts but to our knowledge only two previous studies assessed PAT-RHI in CCS: one in young acute lymphoblastic leukemia survivors ( 47 ) and the other in young Hodgkin lymphoma survivors ( 48 ).…”

Section: Discussionmentioning

confidence: 99%

“…Peripheral vascular endothelial function was assessed by measuring peripheral arterial tonometry–reactive hyperaemia index (PAT-RHI) using the Endo-PAT 2000 (Itamar Medical, Caesarea, Israel). This method has previously been reported to correlate with endothelial function in the coronary circulation ( 24 ) and to be predictive for CVD ( 25 ). All measurements were done following a standardized procedure specified by the manufacturer ( www.itamar-medical.com ).…”

Section: Methods and Study Populationmentioning

confidence: 99%

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Characterization of Cardiac, Vascular, and Metabolic Changes in Young Childhood Cancer Survivors

et al. 2021

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Background: Childhood cancer survivors (CCS) are at an increased risk for cardiovascular diseases (CVD). It was the primary aim of this study to determine different measures of cardiac, carotid, lipid, and apolipoprotein status in young adult CCS and in healthy controls.Methods: Cardiac and common carotid artery (CCA) structure and function were measured by ultrasonography. Lipids and apolipoproteins were measured in the blood. Peripheral arterial endothelial vasomotor function was assessed by measuring digital reactive hyperemia index (PAT-RHI) using the Endo-PAT 2000.Results: Fifty-three CCS (20–30 years, 35 men) and 53 sex-matched controls were studied. The CCS cohort was divided by the median dose of anthracyclines into a low anthracycline dose (LAD) group (50–197 mg/m2, n = 26) and a high anthracycline dose (HAD) group (200–486 mg/m2, n = 27). Carotid distensibility index (DI) and endothelial function determined by PAT-RHI were both lower in the CCS groups compared with controls (p < 0.05 and p = 0.02). There was no difference in carotid intima media thickness. Atherogenic apolipoprotein-B (Apo-B) and the ratio between Apo-B and Apoliprotein-A1 (Apo-A1) were higher in the HAD group compared with controls (p < 0.01). Apo-B/Apo-A1-ratio was over reference limit in 29.6% of the HAD group, in 15.4% of LAD group, and in 7.5% of controls (p = 0.03). Measured lipid markers (low density lipoprotein and total cholesterol and triglycerides) were higher in both CCS groups compared with controls (p < 0.05). Systolic and diastolic function were measurably decreased in the HAD group, as evidenced by lower EF (p < 0.001) and lower é-wave (p < 0.005) compared with controls. CCA DI correlated with Apo-B/Apo-A1-ratio and Apo-A1. Follow-up time after treatment correlated with decreased left ventricular ejection fraction (p = 0.001).Conclusion: Young asymptomatic CCS exhibit cardiac, vascular, lipid, and apolipoprotein changes that could account for increased risk for CVD later in life. These findings emphasize the importance of cardiometabolic monitoring even in young CCS.

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“…We and others have shown that the RHI is highly predictive of adverse cardiovascular events and in patients with coronary heart disease. [31][32][33] A categorical measure of endothelial dysfunction was also defined as any decrease in RHI with mental stress (ie, a poststress RHI minus prestress RHI value <0).…”

Section: Myocardial Perfusion Imaging and Definition Of Stress-induce...mentioning

confidence: 99%

Sex Differences in Vascular Response to Mental Stress and Adverse Cardiovascular Events Among Patients With Ischemic Heart Disease

Sullivan

Young

García

et al. 2023

ATVB

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BACKGROUND: Microvascular measures of vascular dysfunction during acute mental stress may be important determinants of major adverse cardiovascular events (MACE), especially among younger and middle-aged women survivors of an acute myocardial infarction. METHODS: In the MIMS2 study (Myocardial Infarction and Mental Stress 2), individuals who had been hospitalized for a myocardial infarction in the past 8 months were prospectively followed for 5 years. MACE was defined as a composite index of cardiovascular death and first/recurring events for nonfatal myocardial infarction and hospitalizations for heart failure. Reactive hyperemia index and flow-mediated dilation were used to measure microvascular and endothelial function, respectively, before and 30 minutes after a public-speaking mental stress task. Survival models for recurrent events were used to examine the association between vascular response to stress (difference between poststress and resting values) and MACE. Reactive hyperemia index and flow-mediated dilation were standardized in analyses. RESULTS: Of 263 patients (the mean age was 51 years; range, 25–61), 48% were women, and 65% were Black. During a median follow-up of 4.3 years, 64 patients had 141 adverse cardiovascular events (first and repeated). Worse microvascular response to stress (for each SD decrease in the reactive hyperemia index) was associated with 50% greater risk of MACE (hazard ratio, 1.50 [95% CI, 1.05–2.13]; P =0.03) among women only (sex interaction: P =0.03). Worse transient endothelial dysfunction in response to stress (for each SD decrease in flow-mediated dilation) was associated with a 35% greater risk of MACE (hazard ratio, 1.35 [95% CI, 1.07–1.71]; P =0.01), and the association was similar in women and men. CONCLUSIONS: Peripheral microvascular dysfunction with mental stress was associated with adverse events among women but not men. In contrast, endothelial dysfunction was similarly related to MACE among both men and women. These results suggest a female-specific mechanism linking psychological stress to adverse outcomes.

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Impaired Peripheral Microvascular Function and Risk of Major Adverse Cardiovascular Events in Patients With Coronary Artery Disease

Cited by 17 publications

References 54 publications

Indoxyl Sulphate Retention Is Associated with Microvascular Endothelial Dysfunction after Kidney Transplantation

Indoxyl Sulphate Retention Is Associated with Microvascular Endothelial Dysfunction after Kidney Transplantation

Characterization of Cardiac, Vascular, and Metabolic Changes in Young Childhood Cancer Survivors

Sex Differences in Vascular Response to Mental Stress and Adverse Cardiovascular Events Among Patients With Ischemic Heart Disease

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