RESUMEN
BACKGROUND: Atherosclerotic cardiovascular disease (ASCVD) is a leading cause of global mortality, often associated with high blood levels of LDL cholesterol (LDL-c). Medications like statins and PCSK9 inhibitors, are used to manage LDL-c levels and reduce ASCVD risk. Recent findings connect the gut microbiota and its metabolites to ASCVD development. We showed that statins modulate the gut microbiota including the production of microbial metabolites involved in the regulation of cholesterol metabolism such as short chain fatty acids (SCFAs) and bile acids (BAs). Whether this pleiotropic effect of statins is associated with their antimicrobial properties or it is secondary to the modulation of cholesterol metabolism in the host is unknown. In this observational study, we evaluated whether alirocumab, a PCSK9 inhibitor administered subcutaneously, alters the stool-associated microbiota and the profiles of SCFAs and BAs. METHODS: We used stool and plasma collected from patients enrolled in a single-sequence study using alirocumab. Microbial DNA was extracted from stool, and the bacterial component of the gut microbiota profiled following an amplicon sequencing strategy targeting the V3-V4 region of the 16S rRNA gene. Bile acids and SCFAs were profiled and quantified in stool and plasma using mass spectrometry. RESULTS: Treatment with alirocumab did not alter bacterial alpha (Shannon index, p = 0.74) or beta diversity (PERMANOVA, p = 0.89) in feces. Similarly, circulating levels of SCFAs (mean difference (95% confidence interval (CI)), 8.12 [-7.15-23.36] µM, p = 0.25) and BAs (mean difference (95% CI), 0.04 [-0.11-0.19] log10(nmol mg-1 feces), p = 0.56) were equivalent regardless of PCSK9 inhibition. Alirocumab therapy was associated with increased concentration of BAs in feces (mean difference (95% CI), 0.20 [0.05-0.34] log10(nmol mg-1 feces), p = 0.01). CONCLUSION: In statin-treated patients, the use of alirocumab to inhibit PCSK9 leads to elevated levels of fecal BAs without altering the bacterial population of the gut microbiota. The association of alirocumab with increased fecal BA concentration suggests an additional mechanism for the cholesterol-lowering effect of PCSK9 inhibition.
RESUMEN
BACKGROUND: Angiography and embolization (AE) is a lifesaving, high radiation dose procedure for treatment of abdominal arterial hemorrhage (AAH). Interventional radiologists have utilized pre-procedure CT angiography (CTA) and newer fluoroscopic systems in an attempt to reduce radiation dose and procedure time. PURPOSE: To study the factors contributing to the radiation dose of AE for AAH and to compare to the reference standard. MATERIALS AND METHODS: This retrospective single-centre observational cohort study identified 154 consecutive AE procedures in 138 patients (median age 65 years; interquartile range 54-77; 103 men) performed with a C-arm fluoroscopic system (Axiom Artis DTA or Axiom Artis Q (Siemens Healthineers)), between January 2010 and December 2017. Parameters analysed included: demographics, fluoroscopy system, bleeding location, body mass index (BMI), preprocedural CT, air kerma-area product (PKA), reference air kerma (Ka,r), fluoroscopy time (FT) and the number of digital subtraction angiography (DSA) runs. Factors affecting dose were assessed using Mann-Whitney U, Kruskal-Wallis one-way ANOVA and linear regression. RESULTS: Patients treated with the new angiographic system (NS) had a median PKA, median Ka,r, Q3 PKA and Q3 Ka,r that were 74% (p < 0.0005), 66%(p < 0.0005), 55% and 52% lower respectively than those treated with the old system (OS). This dose reduction was consistent for each bleeding location (upper GI, Lower GI and extraluminal). There was no difference in PKA (p = 0.452), Ka,r (p = 0.974) or FT (p = 0.179), between those who did (n = 137) or did not (n = 17) undergo pre-procedure CTA. Other factors significantly influencing radiation dose were: patient BMI and number of DSA runs. A multivariate model containing these variables accounts for 15.2% of the variance in Ka,r (p < 0.005) and 45.9% of the variance of PKA (p < 0.005). CONCLUSION: Radiation dose for AE in AAH is significantly reduced by new fluoroscopic technology. Higher patient body mass index is an independent key parameter affecting patient dose. Radiation dose was not influenced by haemorrhage site or performance of pre-procedure CTA.
