Effect of Coronary Artery Disease risk SNPs on serum cytokine levels and cytokine imbalance in Premature Coronary Artery Disease.

BACKGROUND: Premature Coronary Artery Disease (PCAD) occurs almost a decade earlier in the South Asian population as compared to the West. Inclusion of genetic information can prove to be a robust measure to improve early risk prediction of PCAD. Aim was to estimate the genotypic distribution and risk allele frequencies of 13 Coronary Artery Disease (CAD) risk Single Nucleotide Polymorphisms in loci identified by the CARDIoGRAMplusC4D consortium namely MIA3 rs17465637; 9p21 rs10757274; CXCL12 rs1746048; APOA5 rs662799; APOB rs1042031; LPA rs3798220; LPA 10455872; MRAS rs9818870; LPL rs328; SORT1 rs646776; PCSK9 rs11591147; APOE rs429358; APOE rs7412 in Pakistani PCAD patients and controls. Moreover, the differential serum cytokine levels (IL-18, IL-10, IL-6, TNF-alpha, IL-18:IL-10 & TNF-alpha:IL-10 ratios) with respect to the genotypic distribution of these selected SNPs were determined. MATERIAL AND METHODS: The case-control study was carried out in National University of Sciences and Technology, Islamabad in collaboration with the Cardiovascular Genetics Institute, University College London, UK. Subjects (n=340) with >70% stenosis in at least a single major coronary artery on angiography were taken as PCAD cases along with 310 angiographically verified controls. ELISA was performed for measuring the concentrations of serum IL18, TNFA, IL6 and IL10. Genotyping was done using TAQMAN and KASPar assays. RESULTS: The risk allele frequencies (RAF) of APOE rs7412, CXCL12 rs1746048, 9p21 rs10757274, MIA3 rs17465637 and SORT1 rs646776 were significantly higher in the PCAD cases as compared to the controls. APOE rs429358 had the greatest influence among the selected GWAS/CARDIoGRAMplusC4D consortium CAD risk SNPs by significantly altering the serum levels of TNF-alpha, IL-10 and TNF-alpha:IL-10 ratio. It was followed by APOE rs7412 and CXCL12 rs1746048 which significantly altered the serum levels of IL-18; TNF-alpha and IL-18; IL-18:IL-10 ratio respectively. The cytokine imbalance denoted by IL-18:IL-10 was significantly higher in the risk allele carriers MIA3 rs17465637 and CXCL12 rs1746048 while TNF-alpha:IL-10 ratio was significantly raised in the risk allele carriers of APOE rs429358; MRAS rs9818870 and LPL rs328. CONCLUSION: The association of the selected SNPs with differential serum cytokine levels especially the cytokine imbalance points towards their potential causal role in the immune inflammatory pathogenic pathway of PCAD.

A Systematic Review of Whether the Use of N95 Respirator Masks Decreases the Incidence of Cardiovascular Disease in the General Population.

The usage of masks such as the N95 has increased exponentially worldwide. With the ever-increasing global rates of cardiovascular disease, it is vital that preventative measures are adopted to help tackle this crisis. N95 masks have been promoted as health prevention odysseys in the battle against viruses such as COVID-19. A systematic review was conducted on whether the N95 masks could help improve our cardiovascular health. Our data sources included PubMed, Medline and Scopus. Eleven studies met the eligibility criteria to be included in the review. N95 mask usage led to increased reports of dyspnoea, however, no significant effect was seen on blood pressure. N95 masks also showed improvement in aortic parameters. While encouraging results were yielded, further focussed studies on the use of N95 masks and the effect on various cardiovascular parameters would help strengthen the association.

Compression Stockings and Pressure Ulcers: Case Series of a Neglected Issue.

Pressure ulcers develop in patients who endure long periods of immobilization, often caused by conditions such as musculoskeletal and neurological diseases. Pressure ulcers adversely affect the patient and increase caregiver burden and healthcare costs. Typical sites for these ulcers include the sacrum, trochanters, and heels; they also occur on the nape of the neck, penis, nostrils, helix of the ear, and upper back. Compression stockings are commonly used to prevent and stop the progression of venous disorders, including deep vein thrombosis, but their role in the development of pressure ulcers is not well known. We describe three case reports of pressure ulcer development due to prolonged application of compression stockings. In each case, the nursing staff who were primarily responsible for the prevention of pressure ulcers applied the stockings continuously without any intermittent relief. Moreover, the stockings did not include manufacturer instructions, such as recommended exposure times and applications. We recommend that nursing staff be trained in pressure relief and prevention of pressure ulcers, including rare occurrences, and that manufacturers give detailed guidance regarding the safe use of compression stockings.

Role of Cytokine Gene Score in Risk Prediction of Premature Coronary Artery Disease.

AIMS: Pro- and anti-inflammatory cytokines play a significant role in early atherosclerosis. Linkage disequilibrium patterns differ between ethnic groups pointing toward the need to develop population-specific gene risk scores. Our objective was to investigate the role of a cytokine gene score in the risk prediction of premature coronary artery disease (PCAD). METHODS: A case-control study was performed at the National University of Sciences and Technology (NUST) in collaboration with the Cardiovascular Genetics Institute, University College London, United Kingdom. Three hundred forty subjects with >70% stenosis in at least one coronary vessel on angiography were labeled as PCAD cases and compared with 310 angio-negative controls. Genotyping of the rs187238 (interleukin [IL]-18), rs1800795 (IL-6), rs1800629 (tumor necrosis factor [TNF]-alpha), rs1800871 (IL-10), and rs1946519 (IL-18) SNPs was performed using KASPar and TaqMan assays. RESULTS: The odds ratio for cytokine gene score was significantly higher for PCAD (p = 0.025) when adjusted for age, sex, and ethnicity. There was a highly significant difference in gene risk allele frequency between Pakistanis and Caucasians (Northwick Park Heart Study II [NPHSII]) for rs187238 (IL-18), rs1800795 (IL-6), rs1800629 (TNF-alpha), and rs1800871 (IL-10) (p < 0.01). CONCLUSIONS: A cytokine gene score has significant discriminatory ability and potential in the risk prediction of PCAD. Cytokine gene risk allele frequencies differ significantly between Pakistanis and Caucasians supporting the need to develop population-specific gene scores.