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Hypertensive Response to Exercise Linked to Endothelial Dysfunction

Scientific Updates Sponsored by Endothelix Inc. **************************************************** Clin Hypertens. 2016 Jul 26;22:17

Hypertensive response to exercise: mechanisms and clinical implication.

Kim D1, Ha JW1

1Cardiology Division, Severance Cardiovascular Hospital, Yonsei University College of Medicine, 50 Yonsei-ro, Seodaemun-gu, Seoul, 120-752 Republic of Korea.

A hypertensive response to exercise (HRE) is frequently observed in individuals without hypertension or other cardiovascular disease. However, mechanisms and clinical implication of HRE is not fully elucidated. Endothelial dysfunction and increased stiffness of large artery contribute to development of HRE. From neurohormonal aspects, excess stimulation of sympathetic nervous system and augmented rise of angiotensin II seems to be important mechanism in HRE. Increasing evidences indicates that a HRE is associated with functional and structural abnormalities of left ventricle, especially when accompanied by increased central blood pressure. A HRE harbors prognostic significance in future development of hypertension and increased cardiovascular events, particularly if a HRE is documented in moderate intensity of exercise. As supported by previous studies, a HRE is not a benign phenomenon, however, currently, whether to treat a HRE is controversial with uncertain treatment strategy. Considering underlying mechanisms, angiotensin receptor blockers and beta blockers can be suggested in individuals with HRE, however, evidences for efficacy and outcomes of treatment of HRE in individuals without hypertension is scarce and therefore warrants further studies.

Exercise-induced hypertension, cardiovascular events, and mortality in patients undergoing exercise stress testing: a systematic review and meta-analysis.


The prognostic relevance of a hypertensive response to exercise (HRE) is ill-defined in individuals undergoing exercise stress testing. The study described here was intended to provide a systematic review and meta-analysis of published literature to determine the value of exercise-related blood pressure (BP) (independent of office BP) for predicting cardiovascular (CV) events and mortality.

METHODS: Online databases were searched for published longitudinal studies reporting exercise-related BP and CV events and mortality rates.

RESULTS: We identified for review 12 longitudinal studies with a total of 46,314 individuals without significant coronary artery disease, with total CV event and mortality rates recorded over a mean follow-up of 15.2±4.0 years. After adjustment for age, office BP, and CV risk factors, an HRE at moderate exercise intensity carried a 36% greater rate of CV events and mortality (95% CI, 1.02-1.83, P = 0.039) than that of subjects without an HRE. Additionally, each 10mm Hg increase in systolic BP during exercise at moderate intensity was accompanied by a 4% increase in CV events and mortality, independent of office BP, age, or CV risk factors (95% CI, 1.01-1.07, P = 0.02). Systolic BP at maximal workload was not significantly associated with the outcome of an increased rate of CV, whether analyzed as a categorical (HR=1.49, 95% CI, 0.90-2.46, P = 0.12) or a continuous (HR=1.01, 95% CI, 0.98-1.04, P = 0.53) variable.

CONCLUSIONS: An HRE at moderate exercise intensity during exercise stress testing is an independent risk factor for CV events and mortality. This highlights the need to determine underlying pathophysiological mechanisms of exercise-induced hypertension

Skin Endothelial Function: A Window to Heart and Kidney

[Skin] Microvascular endothelial dysfunction is associated with albuminuria and CKD in older adults

Seliger SL, Salimi S, Pierre V, Giffuni J, Katzel L, Parsa A


BACKGROUND: Impairment in glomerular endothelial function likely plays a major role in the development of albuminuria and CKD progression. Glomerular endothelial dysfunction may reflect systemic microvascular dysfunction, accounting in part for the greater cardiovascular risk in patients with albuminuria. Prior studies of vascular function in CKD have focused on conduit artery function or those with ESRD, and have not examined microvascular endothelial function with albuminuria.

METHODS: We conducted a cross-sectional study among older hypertensive male veterans with stage 1-4 CKD, and hypertensive controls without CKD. Microvascular function was quantified by two distinct Laser-Doppler flowmetry (LDF) measures: peak responses to 1) post-occlusive reactive hyperemia (PORH) and 2) thermal hyperemia (TH), measured on forearm skin. Associations of each LDF measure with albuminuria, eGFR, and CKD status were estimated using correlation coefficients and multiple linear regression, accounting for potential confounders.

RESULTS: Among 66 participants (mean age 69.2 years), 36 had CKD (mean eGFR 46.1 cc/min/1.73 m(2); 30.6 % with overt albuminuria). LDF responses to PORH and TH were 43 and 39 % significantly lower in multivariate analyses among those with macroalbuminuria compared to normoalbuminuria, (β= – 0.42, p = 0.009 and β= -0.37, p = 0.01, respectively). Those with CKD had a 23.9 % lower response to PORH compared to controls (p = 0.02 after adjustment). In contrast, TH responses did not differ between those with and without CKD.


Microvascular endothelial function was strongly associated with greater albuminuria and CKD, independent of diabetes and blood pressure. These findings may explain in part the excess systemic cardiovascular risk associated with albuminuria and CKD.

Scientific Updates Sponsored by Endothelix Inc. ****************************************************


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