Vascular and endothelial function in human hypertension, and the importance of the renin-angiotensin-aldosterone system

Background: Hypertension induces structural vascular and cardiac changes with increased arterial stiffness and left ventricular (LV) hypertrophy and is major risk factor for cardiovascular morbidity and mortality. The renin-angiotensin-aldosterone system (RAAS) and the sympathetic nervous system are important for blood pressure regulation and vascular function. Angiotensin II, the main effector of the RAAS, induces vasoconstriction, inflammation, structural vascular changes, and LV hypertrophy. Thus, treating hypertension with drugs blocking the RAAS might have advantages compared to other drug classes. The overall objective of this thesis was to increase our knowledge about the evaluation of arterial structure and function in human hypertension. Thus, the effects of treatment on indices of arterial stiffness and endothelial function were studied, and the effects beyond blood pressure reduction by blocking the RAAS were evaluated by comparison to drugs acting on the sympathetic nervous system. Material and methods: This work is based on two clinical studies. In the “Swedish irbesartan left ventricular hypertrophy versus atenolol project” (SILVHIA), 115 patients with hypertension and LV hypertrophy were randomized to treatment based on the AT1-receptor blocker irbesartan or the beta-adrenoceptor blocker atenolol for 48 weeks. Two matched control groups consisting of hypertensive patients with no LV hypertrophy and normotensive control subjects were also investigated. We studied arterial stiffness (by pulse pressure, total vascular compliance, and ambulatory arterial stiffness index) and circulating markers of inflammation and of endothelial activation. In the “Doxazosin-ramipril study” (DoRa), 71 hypertensive patients were randomized to treatment with the angiotensin-converting enzyme inhibitor ramipril or the alpha 1-adrenoceptor blocker doxazosin for 12 weeks. The effects of treatment on arterial stiffness (by pulse wave analysis with applanation tonometry and by an oscillometric single-arm cuff method) and on endothelial function were evaluated simultaneously in different vascular beds (by forearm flow-mediated vasodilatation, pulse wave analysis and beta 2-adrenoceptor agonist stimulation, skin microcirculation by laser Doppler fluxmetry and iontophoresis, and myocardial microcirculation by the subendocardial viability ratio). Results and conclusions: Antihypertensive treatment improved indices of arterial stiffness, and blocking the RAAS had additional effects on arterial stiffness beyond blood pressure reduction. There were no effects on endothelial function from the treatment. The oscillometric single cuff method was a simple and useful method to assess arterial function and to evaluate drug-induced treatment effects. Endothelial functions in different vascular beds were all related to future cardiovascular mortality risk (according to the “Systematic coronary risk evaluation”, SCORE), but not to hypertension-induced heart disease. However, the studied methods to evaluate endothelial function were poorly interrelated. Thus, drugs blocking the RAAS may offer an advantage in the treatment of hypertension beyond the effects on blood pressure reduction, as compared to other drug classes

The impact of the COVID-19 Pandemic on hypertension phenotypes (ESH ABPM COVID-19 study)

Objective: The COVID-19 pandemic had a major impact on medical care. This study evaluated the influence of the pandemic on blood pressure (BP) control and hypertension phenotypes as assessed by office and 24-hour ambulatory BP monitoring (ABPM). Design and methods: Data were collected from 33 centers including Excellence Centers of the European Society of Hypertension. Two groups of patients with treated hypertension were compared. Pandemic group: including participants who had ABPM twice - at visit 2 during the COVID-19 pandemic and visit 1 performed 9-15 months prior to visit 2. Pre-pandemic group: had ABPM at two visits, performed before the pandemic within 9-15 months interval. We determined the following hypertension phenotypes: masked hypertension, white coat hypertension, sustained controlled hypertension (SCH) and sustained uncontrolled hypertension (SUCH). We analyzed the prevalence of phenotypes and their changes between visits. Results: Data of 1419 patients, 616 (43 %) in the pandemic group and 803 (57 %) in the pre-pandemic group, were analyzed. At baseline (visit 1), the prevalence of hypertension phenotypes did not differ between groups. In the pandemic group, the change in hypertension phenotypes between two visits was not significant (p = 0.08). In contrast, in the pre-pandemic group, the prevalence of SCH increased during follow-up (28.8 % vs 38.4 %, p < 0.01) while the prevalence of SUCH decreased (34.2 % vs 27.8 %, p < 0.01). In multivariable adjusted analysis, the only factor influencing negative changes of hypertension phenotypes was the COVID-19 pandemic period. Conclusion: These results indicate a negative impact of the COVID-19 pandemic on BP control assessed by hypertension phenotypes

Vascular and endothelial function in human hypertension, and the importance of the renin-angiotensin-aldosterone system [Elektronisk resurs]

Background: Hypertension induces structural vascular and cardiac changes with increased arterial stiffness and left ventricular (LV) hypertrophy and is major risk factor for cardiovascular morbidity and mortality. The renin-angiotensin-aldosterone system (RAAS) and the sympathetic nervous system are important for blood pressure regulation and vascular function. Angiotensin II, the main effector of the RAAS, induces vasoconstriction, inflammation, structural vascular changes, and LV hypertrophy. Thus, treating hypertension with drugs blocking the RAAS might have advantages compared to other drug classes. The overall objective of this thesis was to increase our knowledge about the evaluation of arterial structure and function in human hypertension. Thus, the effects of treatment on indices of arterial stiffness and endothelial function were studied, and the effects beyond blood pressure reduction by blocking the RAAS were evaluated by comparison to drugs acting on the sympathetic nervous system. Material and methods: This work is based on two clinical studies. In the “Swedish irbesartan left ventricular hypertrophy versus atenolol project” (SILVHIA), 115 patients with hypertension and LV hypertrophy were randomized to treatment based on the AT1-receptor blocker irbesartan or the beta-adrenoceptor blocker atenolol for 48 weeks. Two matched control groups consisting of hypertensive patients with no LV hypertrophy and normotensive control subjects were also investigated. We studied arterial stiffness (by pulse pressure, total vascular compliance, and ambulatory arterial stiffness index) and circulating markers of inflammation and of endothelial activation. In the “Doxazosin-ramipril study” (DoRa), 71 hypertensive patients were randomized to treatment with the angiotensin-converting enzyme inhibitor ramipril or the alpha 1-adrenoceptor blocker doxazosin for 12 weeks. The effects of treatment on arterial stiffness (by pulse wave analysis with applanation tonometry and by an oscillometric single-arm cuff method) and on endothelial function were evaluated simultaneously in different vascular beds (by forearm flow-mediated vasodilatation, pulse wave analysis and beta 2-adrenoceptor agonist stimulation, skin microcirculation by laser Doppler fluxmetry and iontophoresis, and myocardial microcirculation by the subendocardial viability ratio). Results and conclusions: Antihypertensive treatment improved indices of arterial stiffness, and blocking the RAAS had additional effects on arterial stiffness beyond blood pressure reduction. There were no effects on endothelial function from the treatment. The oscillometric single cuff method was a simple and useful method to assess arterial function and to evaluate drug-induced treatment effects. Endothelial functions in different vascular beds were all related to future cardiovascular mortality risk (according to the “Systematic coronary risk evaluation”, SCORE), but not to hypertension-induced heart disease. However, the studied methods to evaluate endothelial function were poorly interrelated. Thus, drugs blocking the RAAS may offer an advantage in the treatment of hypertension beyond the effects on blood pressure reduction, as compared to other drug classes

The usefulness of a single arm cuff oscillometric method (Arteriograph) to assess changes in central aortic blood pressure and arterial stiffness by antihypertensive treatment: results from the Doxazosin-Ramipril Study

Purpose: Inhibition of the renin-angiotensin system may have effects on vascular structure and function beyond the effects on blood pressure (BP) reduction. We studied the ability of a single arm cuff oscillometric method (Arteriograph, TensioMed, Hungary) to assess effects of antihypertensive treatment on BP and arterial stiffness. Furthermore, this technique was compared to pulse wave analysis and applanation tonometry (SphygmoCor, AtCor Medical, Australia). Materials and methods: Brachial and aortic BP, augmentation index (AIx), and carotid-femoral pulse wave velocity (PWV) was simultaneously assessed by both techniques in 71 untreated hypertensive patients. Thereafter, 58 completed double-blind randomized treatment for 12 weeks with ramipril or doxazosin. Results: Treatment (assessed by the Arteriograph) reduced aortic more than brachial systolic BP (−13.2 vs. −11.2 mm Hg; p = .002) and improved all indices of arterial stiffness. This greater reduction in aortic to brachial systolic BP was more marked by ramipril than by doxazosin (−20.9 and −17.1 vs. −4.3 and −4.2 mm Hg; p = .006), with a similar trend for AIx (−6.2 vs. −2.2%; p = .058). Both devices showed correlations for aortic and brachial systolic and diastolic BP and AIx (r = 0.75–0.86, all p < .001), while agreement for PWV was weaker (r = 0.28; p = .043). The Arteriograph generally recorded higher values for aortic BP and AIx than the SphygmoCor. Conclusions: Antihypertensive treatment reduced aortic systolic BP more than brachial BP and improved arterial stiffness. Blocking the renin-angiotensin system may have additional effects beyond BP reduction. We demonstrate the feasibility of the Arteriograph to monitor changes in BP and arterial stiffness by treatment

Treatment of hypertensive left ventricular hypertrophy

Background: The development and risk potential of hypertension-induced left ventricular (LV) hypertrophy has been well described in epidemiological studies. Regression of LV hypertrophy reduces cardiovascular morbidity and mortality. However, the best treatment strategy is still debated, as well as the appropriate blood pressure target in these patients. Objective: We here review the treatment of LV hypertrophy and the potential benefit on clinical outcomes, against a background of the epidemiology and pathophysiology. Results: Both hemodynamic and non-hemodynamic mechanisms contribute to hypertensive LV hypertrophy, which is characterized by an inappropriate myocardial fibrosis. Stringent blood pressure control reduces LV hypertrophy. Blockers of the renin-angiotensin-aldosterone system may have valuable effects on cardiac and electrophysiological remodelling beyond the effects of blood pressure reduction. Thus, they represent a cornerstone in the treatment of hypertensive LV hypertrophy, but most often other antihypertensive drug classes need to be added. Current guidelines indicate a blood pressure target in most patients with hypertensive LV hypertrophy of 120–130/80 mmHg. Conclusions: LV hypertrophy and myocardial fibrosis are important characteristics of hypertensive heart disease and associated with untoward prognosis. Regression of LV hypertrophy reduces cardiovascular morbidity and mortality. New drugs under development may add additional benefit