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Abstract: We have previously shown increased vascular reactivity to angiotensin (Ang) II in familial combined hyperlipidemia. However, this has not been well studied in familial hypercholesterolemia (FH), a condition with incipient endothelial dysfunction. This study aimed to examine microvascular and macrovascular responses to Ang II in FH. Therefore, we investigated the effects of a 3-hour infusion of Ang II on blood pressure and forearm skin microvascular function in 16 otherwise healthy patients with FH and matched healthy controls. Skin microvascular hyperemia was studied by laser Doppler fluxmetry during local heating. Microvascular resistance was determined by the ratio of mean arterial pressure to microvascular hyperemia. Macrovascular reactivity was assessed by changes in brachial blood pressure. Compared with the controls, the FH group had increased baseline systolic blood pressure (127 ± 14 vs. 115 ± 12 mm Hg; P = 0.02), while systolic blood pressure responses were similar (+24 ± 9 vs. +21 ± 7 mm Hg; P = 0.26) after 3 hours of Ang II infusion. At baseline, there were no group differences in microvascular hyperemia or resistance. However, after 3 hours of Ang II infusion, heat-induced microvascular hyperemia was less pronounced in FH (126 ± 95 vs. 184 ± 102 arbitrary units; P = 0.01), while microvascular resistance during heat-induced hyperemia was increased (1.9 ± 0.9 vs. 0.9 ± 0.8, P = 0.01), as compared to controls. Both these responses were further pronounced 1 hour after stopping Ang II. In conclusion, despite similar blood pressure responses to Ang II in the FH group and controls, microvascular dilatation capacity was impaired in the FH group, indicating endothelial dysfunction. These findings and increased microvascular resistance may lead to hypertension and microvascular complications in FH., Competing Interests: The authors report no conflicts of interest., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Introduction: We examined potential prothrombotic and proinflammatory effects of angiotensin II in 16 otherwise healthy familial hypercholesterolaemia subjects and 16 matched controls., Methods: Markers of fibrinolysis, thrombin generation and inflammation were assessed in plasma before, during and 1h after a 3h intravenous infusion of angiotensin II. In addition, placebo experiments with saline infusion were carried out., Results: Baseline plasminogen activator inhibitor type-1 activity and plasmin-antiplasmin-complex concentrations were similar in FH and controls, as were interleukin-6, leukocyte counts and C-reactive protein. Fibrinogen levels were higher in FH, and we observed a greater thrombin generating potential in FH (calibrated automated thrombogram), but no signs of elevated thrombin generation in vivo (prothrombin fragment 1+2). During angiotensin infusion plasminogen activator inhibitor type-1 activity decreased and plasmin-antiplasmin-complex concentrations increased similarly in FH and controls. Total and maximal amount of thrombin generated was unchanged, as were prothrombin-fragment-1+2 levels. Interleukin-6 and leukocyte counts increased similarly in both groups during angiotensin infusion, while fibrinogen tended to increase in FH and increased in controls. During saline infusion plasminogen activator inhibitor type-1 activity and prothrombin fragment 1+2 concentrations fell, whereas other markers were unchanged., Conclusions: FH exhibits an increased thrombin generation potential, an intact fibrinolysis, and has no convincing signs of inflammation. Angiotensin has proinflammatory effects, and might have minor profibrinolytic and procoagulatory effects., (© The Author(s) 2015.)

Objectives: Patients with familial combined hyperlipidemia (FCHL) are at increased risk of hypertension and cardiovascular disease. We examined if patients with FCHL have altered microvascular and macrovascular responses to angiotensin II, a principal mediator of the renin-angiotensin-aldosterone system., Methods: Sixteen patients with FCHL and 16 healthy controls were investigated before, during and after a 3 h intravenous infusion of angiotensin II (10 ng/kg/min). Forearm skin microcirculation was studied by laser Doppler fluxmetry during rest and local heating to 44 degrees C (microvascular hyperemia)., Results: Baseline systolic blood pressures were 129 +/- 13 and 123 +/- 12 mmHg in FCHL patients and controls (P = 0.11), respectively. Angiotensin II elicited a greater systolic blood pressure response in the FCHL group (+32 +/- 13 mmHg) than in the control group (+20 +/- 11 mmHg; P < 0.001). At 3 h angiotensin II infusion, microvascular hyperemia increased in the controls (P < 0.001), whereas microvascular hyperemia was unchanged in the FCHL patients (P < 0.01, between groups)., Conclusion: In healthy individuals, a 3 h intravenous infusion of angiotensin II enhances heat-induced microvascular hyperemia. In FCHL, this microvascular hyperemia is impaired and the systolic blood pressure response is increased. A reduced microvascular dilatation capacity in FCHL may contribute to the observed blood pressure elevation and promote development of micro- and macrovascular complications.