ABSTRACT
BACKGROUND: Despite adequate glucocorticoid (GC) and mineralocorticoid (MC) replacement therapy, patients suffering from primary adrenal insufficiency (AI) have an increased mortality, mainly due to cardiovascular diseases. Only little knowledge exists on the contribution of MC substitution to the cardiovascular risk. Therefore, this study investigates the impact of plasma renin concentration on parameters of micro- and macrovascular function. METHODS: 26 patients with primary AI [female = 18, age: 51 (28; 78) years; BMI: 24 (18; 40) kg/m2; disease duration: 18 (5; 36) years] were included in this cross-sectional analysis. Intima media thickness (IMT) and pulse wave velocity (PWV) were investigated to assess macrovascular remodeling and arterial stiffness. Microvascular function was estimated by post-occlusive reactive hyperemia using laser Doppler fluxmetry. Baseline perfusion, biological zero, peak perfusion, time to peak and recovery time were recorded. Patients were grouped according to their median plasma renin concentration of previous visits (Reninhigh vs Reninlow) and were compared to a group of healthy women [age: 44 (43; 46) years; BMI: 24.2 (21.8; 27.5)]. RESULTS: PWV was significantly higher in AI patients compared to controls [9.9 (5; 18.5) vs 7.3 (6.8; 7.7) m/s; p < .01], whereas no differences in microvascular function could be found. In Reninlow time to peak perfusion was significantly longer [6.0 (3; 15) vs 3.5 (1.5; 11) s; p < .05], whereas no differences in IMT and PWV were observed between Reninhigh and Reninlow. No impact of GC dose was observed. CONCLUSIONS: Microvascular function is not impaired in patients with primary AI under adequate replacement therapy, although higher renin concentrations are associated with subclinical improvements. No relation between RAAS activity and macrovascular function is observed, while arterial stiffness might be increased in primary AI.
Subject(s)
Addison Disease/physiopathology , Cardiovascular Diseases/pathology , Carotid Intima-Media Thickness , Microcirculation , Vascular Stiffness , Adult , Aged , Austria/epidemiology , Cardiovascular Diseases/epidemiology , Case-Control Studies , Cross-Sectional Studies , Female , Follow-Up Studies , Humans , Male , Middle Aged , Prognosis , Risk FactorsABSTRACT
BACKGROUND: Proprotein convertase subtilisin kexin type 9 (PCSK9) inhibitors have emerged as important therapeutic options for patients unable to achieve the low-density lipoprotein cholesterol (LDLC) target or to tolerate alternative lipid-lowering agents. The aim of this study was to investigate the efficacy of PCSK9 inhibitor treatment in tertiary routine care, by determining the percentage of patients reaching individual LDLC target levels 1 year after treatment initiation. PATIENTS AND METHODS: Patients routinely started on PCSK9 inhibitors at our lipid clinic between 2017 and 2020 were retrospectively analyzed. Attainment of the LDLC target, utilization of follow-ups, cardiovascular events and effects on laboratory parameters were investigated. RESULTS: In this study 347 patients were included, with the majority managed in secondary prevention (94.5%). The LDLC target was achieved by 44.9% after ca. 14 months, with differences between statin users and non-users (51.0% vs. 22.7%; pâ¯< 0.001). The median LDLC decreased from 126.00â¯mg/dL at baseline to 48â¯mg/dL (-61.6%; -77.00â¯mg/dL; pâ¯< 0.001) after ~2 months and to 60â¯mg/dL (-52.9%; -59.00â¯mg/dL; pâ¯< 0.001) after ~14 months. Median lipoprotein(a) levels decreased significantly from 184.0â¯nmol/L to 165.5â¯nmol/L (-25.9%; -25.5â¯nmol/L; pâ¯= 0.001) after ~2 months, whereas no effects on creatine kinase, amylase and lipase were detectable. Of the patients 15% utilized 4 follow-ups. The PCSK9 inhibitor intolerance occurred in 3.5% of patients. CONCLUSION: With the effect of LDL-lowering remaining constant over 14 months, PCSK9 inhibitor treatment showed effective and sustainable LDLC lowering in a majority of patients in secondary prevention, bringing them closer to the recommended LDLC goal, particularly those under concomitant statin medication. Treatment with PCSK9 inhibitors appears to be well-tolerated, confirming data from clinical trials in real life.