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Study shows mental stress causes coronary microvasculature dysfunction, detected at fingertips.

Ambulatory BP, endothelial dysfunction, and more.

J Am Heart Assoc. 2018 May 3;7(10). pii: e008532. doi: 10.1161/JAHA.118.008532.

Coronary and Peripheral Vasomotor Responses to Mental Stress.

Hammadah M1, Kim JH1, Al Mheid I1, Samman Tahhan A1, Wilmot K1, Ramadan R1, Alkhoder A1, Khayata M1, Mekonnen G1, Levantsevych O1, Bouchi Y1, Kaseer B1, Choudhary F1, Gafeer MM1, Corrigan FE 3rd1, Shah AJ1,2,3, Ward L2, Kutner M4, Bremner JD5,3, Sheps DS6, Raggi P2,7, Vaccarino V1,2, Samady H1, Mavromatis K1,3, Quyyumi AA8.

Author information 1Division of Cardiology, Department of Medicine, Emory University School of Medicine, Atlanta, GA.2Department of Epidemiology, Rollins School of Public Health Emory University, Atlanta, GA.3Atlanta VA Medical Center, Decatur, GA.4Department of Biostatistics and Bioinformatics, Rollins School of Public Health Emory University, Atlanta, GA.5Department of Psychiatry and Behavioral Sciences, Emory University School of Medicine, Atlanta, GA.6Department of Epidemiology, University of Florida College of Medicine, Gainesville, FL.7Mazankowski Alberta Heart Institute University of Alberta, Edmonton, Alberta, Canada.8Division of Cardiology, Department of Medicine, Emory University School of Medicine, Atlanta, GA aquyyum@emory.edu.

Abstract BACKGROUND: Coronary microvascular dysfunction may contribute to myocardial ischemia during mental stress (MS). However, the role of coronary epicardial and microvascular function in regulating coronary blood flow (CBF) responses during MS remains understudied. We hypothesized that coronary vasomotion during MS is dependent on the coronary microvascular endothelial function and will be reflected in the peripheral microvascular circulation. METHODS AND RESULTS: In 38 patients aged 59±8 years undergoing coronary angiography, endothelium-dependent and endothelium-independent coronary epicardial and microvascular responses were measured using intracoronary acetylcholine and nitroprusside, respectively, and after MS induced by mental arithmetic testing. Peripheral microvascular tone during MS was measured using peripheral arterial tonometry (Itamar Inc, Caesarea, Israel) as the ratio of digital pulse wave amplitude compared to rest (peripheral arterial tonometry ratio). MS increased the rate-pressure product by 22% (±23%) and constricted epicardial coronary arteries by -5.9% (-10.5%, -2.6%) (median [interquartile range]), P=0.001, without changing CBF. Acetylcholine increased CBF by 38.5% (8.1%, 91.3%), P=0.001, without epicardial coronary diameter change (0.1% [-10.9%, 8.2%], P=not significant). The MS-induced CBF response correlated with endothelium-dependent CBF changes with acetylcholine (r=0.38, P=0.03) but not with the response to nitroprusside. The peripheral arterial tonometry ratio also correlated with the demand-adjusted change in CBF during MS (r=-0.60, P=0.004), indicating similarity between the microcirculatory responses to MS in the coronary and peripheral microcirculation. CONCLUSIONS: The coronary microvascular response to MS is determined by endothelium-dependent, but not endothelium-independent, coronary microvascular function. Moreover, the coronary microvascular responses to MS are reflected in the peripheral microvascular circulation. © 2018 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley.

Biol Blood Marrow Transplant. 2018 Apr 25. pii: S1083-8791(18)30227-1. doi: 10.1016/j.bbmt.2018.04.024. [Epub ahead of print]

Ambulatory Blood Pressure and Endothelial Dysfunction in Hematopoietic Cell Transplant Patients.

Pao E1, Gove NE1, Flynn J1, Hingorani S2.

Author information 1University of Washington and Seattle Children’s Hospital.2University of Washington and Seattle Children’s Hospital; Fred Hutchinson Cancer Research Center, Clinical Research Division.

Abstract Hematopoietic cell transplantation (HCT) is a common treatment for many disorders. Albuminuria post-HCT, which may represent endothelialinjury or inflammation from graft vs. host disease, increases the risk of chronic kidney disease and non-relapse mortality at 1 year. HCT patients also have abnormal blood pressure (BP) and increased rates of cardiovascular complications. We sought to determine the relationships between albuminuria, endothelial dysfunction and BP in HCT patients. Patients ≥ 12 years of age who had their first allogeneic HCT between 2012-2015 and survived through day 80 were eligible. Peripheral endothelial function was assessed using the EndoPAT2000 device at day 80 along with 24-hour ambulatory BP monitoring (ABPM). Clinical and lab data were collected along with a urine sample for an albumin to creatinine ratio (ACR). Both logistic and linear regression analyses were used to identify associations between EndoPAT score and clinical variables. Sixty patients (median age 48y, range 14-69) completed the study. The median EndoPAT score was 2.05 (range, 1.02-4.45) and 28% (17/60) of patients had abnormal endothelial function. Forty-two patients (72%) had ambulatory hypertension (HTN) and 63% (38/60) had blunted nocturnal dipping. HTN on ABPM (p = 0.045) and blunted nocturnal dipping (p=0.04) were associated with a lower EndoPAT score. Albuminuria was not associated with EndoPAT score. There was a lack of agreement between our clinical definition of HTN (office BP and/or use of medications) and ABPM results (p = 0.04). We did not find an association with lower EndoPAT scores and albuminuria; we did find associations between abnormal nocturnal dip and HTN diagnosed by ABPM. This suggests that albuminuria may reflect local endothelial injury and inflammation rather than a systemic process. Office BP readings do not accurately reflect the true BP suggesting that 24 hour ABPM studies are needed to diagnose and treat HTN appropriately.

KEYWORDS: albuminuria; ambulatory blood pressure monitor; endothelial dysfunction; hematopoietic cell transplant; hypertension

Clin Exp Rheumatol. 2018 Apr 12. [Epub ahead of print]

Prediction of organ involvement in systemic sclerosis by serum biomarkers and peripheral endothelial function. Kawashiri SY1, Nishino A2, Igawa T3, Takatani A3, Shimizu T3, Umeda M3, Fukui S3, Okada A4, Suzuki T4, Koga T3, Iwamoto N3, Ichinose K3, Tamai M3, Nakashima M5, Mizokami A6, Matsuoka N7, Migita K8, Ogawa F9, Ikeda S10, Maemura K10, Nakamura H3, Origuchi T3, Maeda T11, Kawakami A3. Author information Abstract OBJECTIVES: To identify prognostic factors among serum biomarkers and endothelial vasodilator function findings in patients with systemic sclerosis (SSc). METHODS: This is a clinical observational study. We assessed 60 consecutive SSc patients (44 limited cutaneous-type, 16 diffuse cutaneous-type). Circulating growth differentiation factor-15 (GDF-15), placenta growth factor (PlGF), endostatin, vascular endothelial growth factor (VEGF), and pentraxin 3 (PTX3) were measured by ELISA. Peripheral endothelial function was measured by forearm blood dilatation response to brachial artery occlusion using noninvasive plethysmography (EndoPAT2000), which is associated with nitric-oxide-dependent vasodilatation and yields a reactive hyperemia index (RHI). We evaluated whether abnormalities in these values were associated with type of SSc – namely, diffuse cutaneous SSc (dcSSc) or limited cutaneous SSc (lcSSc) – or organ involvement including interstitial lung disease (ILD), digital ulcer (DU) and estimated right ventricular systolic pressure (RVSP) by echocardiography >30 mmHg. RESULTS: SSc patients showed significantly elevated serum GDF-15, PlGF, endostatin and VEGF but not PTX3 compared with controls. GDF-15 and PlGF were high in dcSSc patients. EndoPAT-RHI was low, and incidence of RVSP >30 mmHg was high in dcSSc. Multivariate analysis revealed that elevated GDF-15 was highly predictive of dcSSc, ILD or RVSP >30 mmHg. PlGF for DU was also found. Conversely, a low EndoPAT-RHI value was predictive of the presence of dcSSc, ILD or DU. CONCLUSIONS: This is the first study to inclusively investigate the relationships among biomarkers, EndoPAT-RHI and organ involvement in patients with SSc. Our data suggest a complex pathological progression of SSc through fibrotic impairment and microvascular damage.

Curr Hypertens Rep. 2018 May 7;20(5):44. doi: 10.1007/s11906-018-0835-5.

Modulation of Vascular Reactivity by Perivascular Adipose Tissue (PVAT).

Agabiti-Rosei C1,2, Paini A3, De Ciuceis C3, Withers S4, Greenstein A4, Heagerty AM4, Rizzoni D3.

Author information 1Department of Medicine, Manchester University, Manchester, UK. agabiticlaudia@gmail.com.2Clinica Medica, Department of Medical and Surgical Sciences, University of Brescia, c/o 2a Medicina Spedali Civili di Brescia, Piazza Spedali Civili 1, 25100, Brescia, Italy. agabiticlaudia@gmail.com.3Clinica Medica, Department of Medical and Surgical Sciences, University of Brescia, c/o 2a Medicina Spedali Civili di Brescia, Piazza Spedali Civili 1, 25100, Brescia, Italy.4Department of Medicine, Manchester University, Manchester, UK.

Abstract PURPOSE OF REVIEW: In this review, we discuss the role of perivascular adipose tissue (PVAT) in the modulation of vascular contractility and arterial pressure, focusing on the role of the renin-angiotensin-aldosterone system and oxidative stress/inflammation. RECENT FINDINGS: PVAT possesses a relevant endocrine-paracrine activity, which may be altered in several pathophysiological and clinical conditions. During the last two decades, it has been shown that PVAT may modulate vascular reactivity. It has also been previously demonstrated that inflammation in adipose tissue may be implicated in vascular dysfunction. In particular, adipocytes secrete a number of adipokines with various functions, as well as several vasoactive factors, together with components of the renin-angiotensin system which may act at local or at systemic level. It has been shown that the anti-contractile effect of PVAT is lost in obesity, probably as a consequence of the development of adipocyte hypertrophy, inflammation, and oxidative stress. Adipose tissue dysfunction is interrelated with inflammation and oxidative stress, thus contributing to endothelial dysfunction observed in several pathological and clinical conditions such as obesity and hypertension. Decreased local adiponectin level, macrophage recruitment and infiltration, and activation of renin-angiotensin-aldosterone system could play an important role in this regard.

KEYWORDS: Hypoxia; Melatonin; Oxidative stress; Perivascular adipose tissue; Small arteries

Endothelial Function Scientific Update Sponsored by Endothelix Inc.

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