Association Study of Genetic Variants in Calcium Signaling-Related Genes With Cardiovascular Diseases

Background: Calcium ions (Ca2+) play an essential role in excitation–contraction coupling in the heart. The association between cardiovascular diseases (CVDs) and genetic polymorphisms in key regulators of Ca2+ homeostasis is well established but still inadequately understood.Methods: The associations of 11,274 genetic variants located in nine calcium signaling-related genes with 118 diseases of the circulatory system were explored using a large sample from the United Kingdom Biobank (N = 308,366). The clinical outcomes in electronic health records were mapped to the phecode system. Survival analyses were employed to study the role of variants in CVDs incidence and mortality. Phenome-wide association studies (PheWAS) were performed to investigate the effect of variants on cardiovascular risk factors.Results: The reported association between rs1801253 in β1-adrenergic receptor (ADRB1) and hypertension was successfully replicated, and we additionally found the blood pressure-lowering G allele of this variant was associated with a delayed onset of hypertension and a decreased level of apolipoprotein A. The association of rs4484922 in calsequestrin 2 (CASQ2) with atrial fibrillation/flutter was identified, and this variant also displayed nominal evidence of association with QRS duration and carotid intima-medial thickness. Moreover, our results indicated suggestive associations of rs79613429 in ryanodine receptor 2 (RYR2) with precordial pain.Conclusion: Multiple novel associations established in our study highlight genetic testing as a useful method for CVDs diagnosis and prevention.

Maternal Dietary Carbohydrate Intake and Newborn Aortic Wall Thickness

Evidence from animal models indicates that maternal diet during pregnancy affects offspring cardiometabolic health. Improving carbohydrate quality during high-risk pregnancies reduces aortic intima-medial thickness; a marker for early atherosclerosis; in the infant offspring. We sought to determine whether maternal carbohydrate quantity and quality are associated with newborn aortic intima-medial thickness in healthy pregnancies. Maternal diet throughout pregnancy was evaluated in 139 mother–child dyads using a validated food frequency questionnaire. Carbohydrate intake was expressed as quantity (% total energy), quality (fibre, glycaemic index), and glycaemic burden (glycaemic load). Aortic intima-medial thickness was measured by high-frequency ultrasound of the neonatal abdominal aorta. Neither quantity nor quality of maternal carbohydrate intake during pregnancy was associated with meaningful differences in offspring maximum aortic intima-medial thickness with the exception of fibre intake in women with overweight or obesity which was inversely associated (−8 μm [95% CI −14, −1] per g fibre, p = 0.04). In healthy pregnancy, the quantity and quality of maternal carbohydrate intake is likely not a meaningful modifiable lifestyle factor for influencing offspring vascular health. The effect of carbohydrate quality may only be evident in high-risk pregnancies, consistent with previous findings. These findings may be confirmed in prospective dietary trials in pregnancy.

An impact of intima media thickness of carotids in cardio vascular profile

Low blood pressure truly includes a worse prognosis than the excessive blood strain. This mechanism,bills for the "reverse causation "seen within the haemodialysis’ patients, the company of conventional risk elements, such as high blood pressure, hyperlipidemia, and obesity, appear to be a worst diagnosis.Exogenous erythropoietic products can growth blood strain and requirement of antihypertensive tablets.30 Chronic ECFV overload secondary to activation of renin-angiotensin-aldosterone axisand disturbances inside the stability of vasoconstrictors and the vasodilators make a contribution to high blood pressure. Improvement in blood pressure can be introduced out with oral sodium restriction, diuretics, and fluid elimination with dialysis. Some patients will continue to be hypertensive notwithstanding of the careful attention to ECFV reputation. LVH is related with reduced endurance of sufferers on hemo/peritoneal dialysis .Lower five year survival charge in ESRD patients with LVH have a 30% than people missing LVH. This have a look at produces the mean carotid artery intima-medial thickness turned into higher in sufferers with superior CKD although it did now not attain statistical significance, probable due to smaller sample size.It was also observed that carotid intima medial thickness had no correlation with dyslipidemia. Even though the patients had maintained significantly normal cholesterol and high HDL levels, there was an increase in CIMT. Therefore, CKD patients, CIMT cannot be predicted based on the traditional atherosclerotic risk factors like serum cholesterol and HDL.

P6204Oral vaccination of Lactococcus lactis expressing Ling Zhi 8 protein prevents nonalcoholic fatty liver and early atherogenesis in cholesterol-fed rabbits

Background Atherosclerosis is an inflammatory disease characterized by lipid deposits in the subendothelial space leading to severe inflammation. Nonalcoholic fatty liver disease (NAFLD) shares several risk factors with atherosclerosis. Epidemiology studies have indicated that NAFLD may be an independent risk factor for atherosclerosis. Anti-inflammation therapy by inhibiting IL-1β led to a significantly lower cardiovascular event rate in recent clinical trial (CANTOS trial). Ling Zhi 8 (LZ8) is an immunomodulatory protein that possesses a broad range of pharmacological properties, including anti-inflammatory activities. Methods and findings In this study, we developed an oral vaccination of Lactococcus lactis expressing LZ8 protein in a nisin-controlled gene expression system and investigated its anti-inflammation properties. Experimental rabbits received commercial rabbit chow supplemented with 2% cholesterol for 5 weeks and recombinant LZ8 L. lactis vaccine once a day on weekdays. The expression of IL-1β in the aorta (Figure A) was significantly suppressed after LZ8 vaccination. Moreover, in hematoxylin and eosin staining of the aorta, the intima-medial thickness was decreased, and foam cells were significantly reduced in the sub-endothelial space (Figure C). LZ8 also inhibited the expression of IL-1β in the liver (Figure B), decreased fat droplet deposits and infiltration of inflammatory cells (Figure D), and improved liver function by decreasing liver enzymes. Figure 1 Conclusions Our results suggest that LZ8 could be used as a therapeutic tool to improve both atherosclerosis and NAFLD due to its anti-inflammatory effect. Acknowledgement/Funding TCVGH-1067317C, TCVGH-1063108C