Impact of hyperaemic stenosis resistance on long-term outcomes of stable angina in the ILIAS Registry.

BACKGROUND: The hyperaemic stenosis resistance (HSR) index was introduced to provide a more comprehensive indicator of the haemodynamic severity of a coronary lesion. HSR combines both the pressure drop across a lesion and the flow through it. As such, HSR overcomes the limitations of the more traditional fractional flow reserve (FFR) or coronary flow reserve (CFR) indices. AIMS: We aimed to identify the diagnostic and prognostic value of HSR and evaluate the clinical implications. METHODS: Patients with chronic coronary syndromes (CCS) and obstructive coronary artery disease were selected from the multicentre ILIAS Registry. For this study, only patients with combined Doppler flow and pressure measurements were included. RESULTS: A total of 853 patients with 1,107 vessels were included. HSR more accurately identified the presence of inducible ischaemia compared to FFR and CFR (area under the curve 0.71 vs 0.66 and 0.62, respectively; p<0.005 for both). An abnormal HSR measurement was an independent and important predictor of target vessel failure at 5-year follow-up (hazard ratio 3.80, 95% confidence interval: 2.12-6.73; p<0.005). In vessels deferred from revascularisation, HSR seems to identify more accurately those vessels that may benefit from revascularisation rather than FFR and/or CFR. CONCLUSIONS: The present study affirms the theoretical advantages of the HSR index for the detection of ischaemia-Âinducing coronary lesions in a large CCS population. (Inclusive Invasive Physiological Assessment in Angina Syndromes Registry [ILIAS Registry], ClinicalTrials.gov: NCT04485234).

Molecular detection and genetic characterisation of pathogenic Theileria, Anaplasma and Ehrlichia species among apparently healthy sheep in central and western Kenya.

Tick-borne diseases (TBDs) caused by Theileria, Babesia, Anaplasma and Ehrlichia species are common in tropical and subtropical regions. In this study, we investigated the presence and genetic diversity of Theileria spp., Anaplasma ovis, B. ovis, E. ruminantium and Anaplasma spp. in sheep from the Machakos and Homa Bay counties of Kenya. In order to improve the diagnosis and control of ovine TBDs, a total of 76 blood samples from apparently healthy sheep were screened using a polymerase chain reaction (PCR). The assays were conducted using primers based on Theileria spp. 18S rRNA, Anaplasma ovis Major surface protein-4 (AoMSP4), B. ovis 18S rRNA, E. ruminantium pCS20 and Anaplasma spp. 16S rRNA. The overall infection rates for Theileria spp., A. ovis, E. ruminantium and Anaplasma spp. were 39/76 (51.3%), 26/76 (34.2%), 6/76 (7.9%) and 31/76 (40.8%), respectively. The overall co-infection was 47/76 (61.8%). All Theileria spp. positive samples were confirmed to be of Theileria ovis on sequencing. A phylogenetic analysis of the 18S rRNA gene sequences of T. ovis revealed that all isolates of this study clustered with T. ovis sequences extracted from the GenBank suggesting this gene is highly conserved. E. ruminantium pCS20 sequences were in the same clade on the phylogenetic tree. However, three AoMSP4 sequences from this study appeared in the same clade, while one sequence formed a separate branch revealing genetic divergence. The 16S rRNA sequencing revealed uncharacterised Anaplasma spp. and A. ovis. The phylogenetic analyses of the uncharacterised Anaplasma spp. revealed that the two sequences from this study appear in an independent clade from other sequences extracted from the GenBank. This study provides important information regarding the occurrence of tick-borne pathogens and their degree of genetic diversity among sheep in Kenya, which is useful for the diagnosis and control of TBDs.

High circulating follistatin-like protein 1 as a biomarker of a metabolically unhealthy state.

The inflammatory biomarkers that fully characterize the metabolically unhealthy (MU) state-which is a risk factor for cardiovascular disease (CVD)-remain unclear. Recent studies suggest follistatin-like protein 1 (FSTL1) could be used as a biomarker for inflammation and CVD, however there is little information on FSTL1 levels in the MU state. We aimed to evaluate the associations between FSTL1, the presence of MU state and subclinical coronary atherosclerosis. In a cross-sectional study, we evaluated FSTL1 levels and their relationship with the presence of MU state and coronary artery plaques in 230 Korean patients. Significant increase in FSTL1 levels was observed in subjects with MU state (p = 0.020), but not those with obesity state according to body mass index criteria (p = 0.790). After adjusting for confounders, the odd ratio (OR) for the MU state among patients in the highest FSTL1 tertile (T3) was higher in comparison with the lowest tertile (T1) (OR = 3.60, 95% confidence interval [95% CI] = 1.20-10.83). In a subgroup (n = 66), FSTL1 levels were also marginally higher in patients with plaques (p = 0.098). The OR for plaque presence in patients with T3 was significantly higher in comparison with T1 after adjusting for confounders (OR = 12.51, 95% CI = 1.15-135.73). Plasma FSTL1 may be a useful biomarker for the risk of MU state and CVD.

Genome-wide association study for radiographic vertebral fractures: a potential role for the 16q24 BMD locus.

Vertebral fracture risk is a heritable complex trait. The aim of this study was to identify genetic susceptibility factors for osteoporotic vertebral fractures applying a genome-wide association study (GWAS) approach. The GWAS discovery was based on the Rotterdam Study, a population-based study of elderly Dutch individuals aged > 55 years; and comprising 329 cases and 2666 controls with radiographic scoring (McCloskey­Kanis) and genetic data. Replication of one top-associated SNP was pursued by de-novo genotyping of 15 independent studies across Europe, the United States, and Australia and one Asian study. Radiographic vertebral fracture assessment was performed using McCloskey­Kanis or Genant semi-quantitative definitions. SNPs were analyzed in relation to vertebral fracture using logistic regression models corrected for age and sex. Fixed effects inverse variance and Han­Eskin alternative random effects meta-analyses were applied. Genome-wide significance was set at p < 5 × 10− 8. In the discovery, a SNP (rs11645938) on chromosome 16q24 was associated with the risk for vertebral fractures at p = 4.6 × 10− 8. However, the association was not significant across 5720 cases and 21,791 controls from 14 studies. Fixed-effects meta-analysis summary estimate was 1.06 (95% CI: 0.98­1.14; p = 0.17), displaying high degree of heterogeneity (I2 = 57%; Qhet p = 0.0006). Under Han­Eskin alternative random effects model the summary effect was significant (p = 0.0005). The SNP maps to a region previously found associated with lumbar spine bone mineral density (LS-BMD) in two large meta-analyses from the GEFOS consortium. A false positive association in the GWAS discovery cannot be excluded, yet, the low-powered setting of the discovery and replication settings (appropriate to identify risk effect size > 1.25) may still be consistent with an effect size < 1.10, more of the type expected in complex traits. Larger effort in studies with standardized phenotype definitions is needed to confirm or reject the involvement of this locus on the risk for vertebral fractures.