Vascular endothelial cells produce nitric oxide (NO), which contributes to the regulation of blood pressure and regional blood flow. Endothelial nitric oxide synthase (eNOS) gene polymorphisms are associated with coronary artery disease, but their linkage with primary hypertension is controversial. A total of 103 individuals with primary hypertension and 104 normotensive control subjects were studied in Singapore. The specific genotypes for G894T missense variant in exon 7, variable number tandem repeats (VNTR) in intron 4 (eNOS 4A/B/C) and TÀ786C in the promoter were isolated using allele-specific gene amplification and restriction fragment length polymorphism to examine the association of genotype and allelic frequency in both groups. Logistic regression analysis was also used to detect the association between genotypes and hypertension. Five genotypes of intron 4 VNTR (AA, AB, BB, AC and BC) were observed. Intron 4 B/B genotype was significantly associated with the hypertension group (P ¼ 0.035), but disequilibrium of G894T and TÀ786C was absent between the two groups (P ¼ 0.419 and P ¼ 0.227), respectively. The overall distribution of allelic frequency differed significantly between the two groups, with four-repeat allele (4A) of intron 4 more frequent in the normotensive group than the hypertensive group (P ¼ 0.019). Logistic regression analysis showed that intron 4 B/B genotype was significantly associated with systolic blood pressure of individuals with body mass index greater than 25 kg/m 2 (P ¼ 0.04). In conclusion, the eNOS 4 B/B genotype is a genetic susceptibility factor for primary hypertension in a Singapore population.

BackgroundThyrotoxic periodic paralysis (TPP) is a rare complication of thyrotoxicosis characterized by acute attacks of muscle weakness and hypokalemia. Recently, variation in several genes was suggested to be associated with TPP. This study evaluated the genetic predisposition to TPP in terms of the β2-adrenergic receptor (ADRB2), androgen receptor (AR), and γ-aminobutyric acid receptor α3 subunit (GABRA3) genes.MethodsThis study enrolled 48 men with Graves disease (GD) and TPP, and 48 GD patients without TPP. We compared the frequencies of candidate polymorphisms between the two groups.ResultsThe frequency of the Gly16/Gly16 genotype in ADRB2 was not significantly associated with TPP (P=0.32). More CAG repeats (≥26) in the AR gene were not correlated with TPP (odds ratio [OR], 2.46; 95% confidence interval [CI], 0.81 to 8.09; P=0.08). The allele frequency of the TT genotype in the GABRA3 gene was not associated with TPP (OR, 1.83; 95% CI, 0.54 to 6.74; P=0.41).ConclusionThe polymorphisms in the ADRB2, AR, and GABRA3 genes could not explain the genetic susceptibility to TPP in Korean men with GD.

Funding Acknowledgements Type of funding sources: None. Introduction Selexipag is an oral selective prostacyclin IP receptor agonist indicated for treatment of pulmonary arterial hypertension (PAH). Data on its real-world safety and efficacy in Asians is lacking. Purpose We sought to evaluate the clinical characteristics, treatment regimens and outcomes of patients initiated on selexipag in a tertiary cardiac centre in Asia. Methods This was a retrospective study on all patients initiated on selexipag from January 2017 to December 2020. Baseline and follow up characteristics including demographics, functional status and clinical data were collected. Clinical outcomes evaluated included hospitalisation for PH related complications and all-cause mortality. Patients were risk stratified using the COMPERA 2.0 risk scores. Results A total of 36 PAH patients were treated with selexipag. At baseline, most patients were WHO functional class II or III (36.4% and 51.5% respectively), with a NT-proBNP of 1335 pg/ml (557 – 2918) and 6 minute walk test (6MWT) duration of 327.5 ±126.4 meters. Selexipag was initiated at 200mcg twice daily dosage for all except one patient (started at 200mcg once daily) and the maximum tolerated dose ranged from 200mcg twice daily to 1400mcg twice daily, with majority tolerating up to a dose of 600mcg twice daily (58.3%). Side effects were reported in 23 patients (63.9%), of which headache (27.8%), diarrhea (30.6%) or musculoskeletal symptoms (27.8%) were predominant. After a median follow up duration of 25.9 ± 23.1 months, selexipag was stopped in 20 patients (55.6%), of which eight patients were due to PAH progression requiring alternative therapy, and 12 patients due to side effects from selexipag. At baseline, patients were classified into low (8.3%), intermediate-low (30.6%), intermediate-high (33.3%) and high risk (27.8%) respectively. Patients who continued on selexipag at follow up showed no change (46.2%), improvement (15.4%) and deterioration (38.5%) in risk score. In the overall cohort of 36 patients, majority (75%) had at least one hospitalisation for PAH related complications and 15 patients (41.7%) demised. Conclusion In this real-world study, while selexipag was associated with a stable or improved PAH risk scores in majority of patients, there was a subset of patients with disease progression or intolerance to the medication. Further studies are warranted to identify patients who will benefit most from this therapy.

Funding Acknowledgements Type of funding sources: None. Background Stroke during Transcatheter Aortic Valve implantation (TAVI) is not an uncommon complication with potential devastating consequences. With the extension of TAVI to the low-risk patient, stroke prevention takes on increasing importance. The use of cerebral embolic protection device (EPD) reveals conflicting data. This meta-analysis aims to evaluate the clinical efficacy and safety of EPDs. Methods A comprehensive literature search for all studies till May 2022 reporting clinical safety and efficacy outcomes of the only EPD approved for use by the Food and Drug Administration (FDA) was performed. Study outcomes were divided based on time period - overall (up to 30 days and in-hospital) and short (≤7 days). Primary outcome was stroke - major and minor. Secondary outcomes included transient ischaemic attack (TIA), mortality, acute kidney injury (AKI), major vascular and bleeding complications. Results A total of 12 studies involving 288531 patients were analysed, which included 3 randomised controlled trials (RCTs), 7 propensity-matched and 2 cohort studies. Regarding overall outcomes, significant differences were noted for mortality (OR 0.59 [0.42-0.84], p=0.0036) and major stroke (OR 0.40 [0.18-0.91], p=0.028) (Fig 1). No significant differences were noted for all stroke (p=0.058), minor stroke (p=0.32), TIA (p=0.49), AKI (p=0.17), major vascular complications (p=0.40) and major bleeding complications (p=0.11). There was significant heterogeneity across the studies for mortality (p=0.032) and all stroke (p=0.009). In the subgroup analysis of studies reporting ≤7 days outcomes (n=5), EPDs showed significantly lower rates of all stroke (0.33 [95% CI 0.19-0.56], p=<0.0001), major stroke (0.19 [0.08-0.48], p=0.0004) and major bleeding complications (OR 0.29 [0.10-0.79], p=0.016), but no significant differences for mortality (p=0.67) and minor stroke (p=0.070). There was no significant heterogeneity across the studies (all p>0.05) Conclusions In this meta-analysis including non-randomised studies, the use of EPDs was associated with lower mortality and major stroke rates, although significant heterogeneity was noted for the studies reporting mortality. Further ongoing larger scale RCTs will further clarify these results.