Abstract 14862: Gender Differences in Impact of CYP2C19 Polymorphism and Low Grade Inflammation on Coronary Microvascular Disease

Circulation ◽  
2014 ◽  
Vol 130 (suppl_2) ◽  
Author(s):  
Tomonori Akasaka ◽  
Seiji Hokimoto ◽  
Noriaki Tabata ◽  
Kenji Sakamoto ◽  
Kenichi Tsujita ◽  
...  

Background: Specific CYPs localized in vascular smooth muscle and endothelium contribute to the regulation of vascular tone and homeostasis. CYP2C19 two loss-of-function alleles (PM) were found to be an independent risk factor for diabetic retinopathy, and PM is associated with the coronary spasm especially in female. However, it is unknown whether CYP2C19 genotype is associated with the coronary microvascular disease. The aim was to evaluate the impact of CYP2C19 genotype on coronary microvascular disease. Methods: We examined CYP2C19 genotype in patients with microvascular disease (n=40) who were diagnosed by intra-coronary acetylcholine infusion test and healthy subjects (n=455) as control group. We defined the coronary microvascular disease that have no epicardial spasm and have angina, ischemic ECG changes, reduced coronary blood flow, or inversion of lactic acid level between intra-coronary and coronary sinus. CYP2C19 genotypes were divided into 3 groups; (1) CYP2C19*1/*1: EM, (2) one loss-of-function allele (*1/*2, *1/*3: IM), and (3) two loss-of-function alleles (*2/*2, *2/*3, *3/*3: PM). Results: The ratios of CYP2C19 genotype (EM, IM, and PM) were 33, 35, and 32% in microvascular disease group, and 32, 49, and 19% in control group. In short, PM frequency was significantly higher in microvascular disease group (32%vs19%,P=0.039). In microvascular disease group, the ratios of CYP2C19 genotype (EM, IM, and PM) were 44, 38, and 19% in male, and 25, 33, and 42% in female, respectively. Briefly, the PM frequency was significantly higher in female than in male (42%vs19%,P=0.011). Moreover, the level of hs-CRP was significantly higher in microvascular disease group (0.37±0.908 vs 0.10±0.240, P<0.001). Multivariate analysis for microvascular disease indicated that gender, high age, smoking, hypertension, and the high level of hs-CRP are predictive factors among all subjects. PM is a predictive factor for microvascular disease in female group only (OR3.214, 95%RI 1.286-8.034, P=0.012), but not in male (OR0.909, 95%RI 0.251-3.285, P=0.884). Conclusion: The CYP2C19 two loss-of-function alleles (PM) and low grade inflammation may be associated with pathophysiology of coronary microvascular disease, especially in female.

Circulation ◽  
2014 ◽  
Vol 130 (suppl_2) ◽  
Author(s):  
Tomonori Akasaka ◽  
Seiji Hokimoto ◽  
Noriaki Tabata ◽  
Kenji Sakamoto ◽  
Kenichi Tsujita ◽  
...  

Background: Several cytochrome P450 (CYP) enzyme families have been identified in extra hepatic tissues such as heart, vasculature, kidney, and lung. CYP2C19 localized in vascular smooth muscle and endothelium contributes to the regulation of vascular tone and homeostasis. However, it is unknown whether CYP2C19 genotype is associated with the vascular tonus in patients with VSA. The aim of this study was to examine the impact of CYP2C19 genotype on coronary artery spasm in patients with VSA. Methods: We examined the distribution of CYP2C19 genotype in patients with VSA (n=129) who were diagnosed by intra-coronary acetylcholine infusion test and healthy subjects (n=455) as control group. CYP2C19 genotypes were divided into 3 groups; (1) CYP2C19*1/*1: EM, (2) one loss-of-function allele (*1/*2, *1/*3: IM), and (3) two loss-of-function alleles (*2/*2, *2/*3, *3/*3: PM). Moreover, we measured the level of high-sensitive CRP (hs-CRP) as a degree of low glade inflammation in each group. Results: The ratios of CYP2C19 genotype (EM, IM, and PM) were 30, 42, and 28% in VSA group, and 32, 49, and 19% in control group. In short, PM frequency was significantly higher in VSA than in control (28% vs 19%, P=0.026). In VSA group, the ratios of CYP2C19 genotype were 36, 44, and 20% in male, and 20, 39, and 41% in female, respectively. Briefly, the PM frequency was significantly higher in female than in male (41% vs 20%, P<0.001). Moreover, the level of hs-CRP was significantly higher in VSA group than in control group (0.17±0.367 vs 0.10.±0.240, P=0.02). When patients were stratified by gender, the level of hs-CRP was significantly higher in VSA group in female (0.11±0.198 vs 0.06±0.105, P=0.031) and male (0.20±0.438 vs 0.12±0.277, P=0.044). Multivariate analysis for coronary spasm indicated high age, hypertension, and high level of hs-CRP as predictive factors among all subjects. PM is a predictive factor for coronary spasm in female group only (OR3.1, 95%RI 1.525-6.317, P=0.002), but not in male (OR0.829, 95%RI 0.453-1.518, P=0.543). Conclusion: The CYP2C19 two loss-of-function alleles (PM) and low grade inflammation may be associated with pathophysiology of coronary artery spasm and the regulation of coronary tonus, especially in female.


Circulation ◽  
2015 ◽  
Vol 132 (suppl_3) ◽  
Author(s):  
tomonori akasaka ◽  
Seiji Hokimoto ◽  
Hisao Ogawa

Background: Specific CYPs localized in vascular smooth muscle and endothelium contribute to the regulation of vascular tone and homeostasis. CYP2C19 poor metabolizer(PM) is reported to be an independent risk factor for coronary artery disease. And, CYP2C19 PM is correlated with an increase in the circulating levels of hs-CRP in female. However, it is unknown whether CYP2C19 genotype is associated with the coronary microvascular disorder (CMVD).So, we examined gender differences in effect of CYP2C19 genotype and low grade inflammation on CMVD. Methods: We examined CYP2C19 genotypes in patients with CMVD (n=54) diagnosed by an intracoronary acetylcholine infusion test, with healthy subjects (n=76) serving as the control. CMVD was defined as the presentation of no coronary artery stenosis in angiography, no epicardial spasms, inversion of lactic acid levels between intracoronary and coronary sinuses in the intracoronary acetylcholine-provocation test, and an adenosine triphosphate-induced CFR<2.5. CYP2C19 genotypes were divided into 3 groups: (1) CYP2C19*1/*1 , extensive metabolizer (EM), (2) one loss-of-function allele (*1/*2, *1/*3; intermediate metabolizer [IM]), and (3) two loss-of-function alleles (*2/*2, *2/*3, *3/*3;[PM]). Results: The ratios of CYP2C19 genotype (EM,IM,and PM) were 31,39,and 30% in CMVD , and 32,49,and 19% in control. There is no significant difference in frequency of CYP2C19 genotype in overall (P=0.146). But, PM frequency was significantly higher in CMVD in only female (34% vs 16%, P=0.042). In level of hs-CRP, there is no significant difference between CMVD and control (0.111±0.080 vs 0.083±0.128,P=0.122), but significantly higher in CMVD in only female (0.112±0.106 vs 0.066±0.106,P=0.002). Moreover, in CMVD, mean of hs-CRP in CYP2C19 PM is significantly higher than that of EM in female (0.115±0.074 vs 0.046±0.039,P=0.034). Multivariate analysis for CMVD indicated that hypertension and chronic kidney disease are predictive factors among all subjects (OR 3.931,P=0.003, OR 3.146,P=0.026). High level of hs-CRP and CYP2C19 PM are predictive factors for CMVD in only female (OR3.864,P=0.047, OR6.079,P=0.042). Conclusion: CYP2C19 PM and low grade inflammation may be associated with CMVD, especially in female.


2016 ◽  
Vol 310 (11) ◽  
pp. H1494-H1500 ◽  
Author(s):  
Tomonori Akasaka ◽  
Seiji Hokimoto ◽  
Daisuke Sueta ◽  
Noriaki Tabata ◽  
Kenji Sakamoto ◽  
...  

Categorization as a cytochrome P-450 (CYP) 2C19 poor metabolizer (PM) is reported to be an independent risk factor for cardiovascular disease. It is correlated with an increase in the circulating levels of high-sense C-reactive protein (hs-CRP) in women only, although its role in coronary microcirculation is unclear. We examined sex differences in the impact of the CYP2C19 genotype and low-grade inflammation on coronary microvascular disorder (CMVD). We examined CYP2C19 genotypes in patients with CMVD ( n = 81) and in healthy subjects as control ( n = 81). CMVD was defined as the absence of coronary artery stenosis and epicardial spasms, the presence of inverted lactic acid levels between the intracoronary and coronary sinuses, or an adenosine triphosphate-induced coronary flow reserve ratio < 2.5. CYP2C19 PMs have two loss-of-function (LOF) alleles (*2, *3). Extensive metabolizers have no LOF alleles, and intermediate metabolizers have one LOF allele. The ratio of CYP2C19 PM and hs-CRP levels in CMVD was significantly higher than that of controls, especially in women (40.9 vs. 13.8%, P = 0.013; 0.11 ± 0.06 vs. 0.07 ± 0.04 mg/dl, P = 0.001). Moreover, in each CYP2C19 genotype, hs-CRP levels in CMVD in CYP2C19 PMs were significantly higher than those of the controls, especially in women (0.15 ± 0.06 vs. 0.07 ± 0.03, P = 0.004). Multivariate analysis for CMVD indicated that the female sex, current smoking, and hypertension were predictive factors, and that high levels of hs-CRP and CYP2C19 PM were predictive factors in women only (odds ratio 3.5, 95% confidence interval 1.26–9.93, P = 0.033; odds ratio 4.1, 95% confidence interval 1.15–14.1, P = 0.038). CYP2C19 PM genotype may be a new candidate risk factor for CMVD via inflammation exclusively in the female population.


2013 ◽  
Vol 2013 ◽  
pp. 1-6 ◽  
Author(s):  
Fen-qin Chen ◽  
Jiao Wang ◽  
Xiao-bo Liu ◽  
Xiao-yu Ma ◽  
Xiu-bin Zhang ◽  
...  

Although the pathogenetic mechanism of DN has not been elucidated, an inflammatory mechanism has been suggested as a potential contributor. This study was designed to explore the relationship between low-grade inflammation and renal microangiopathy in T2DM. A total of 261 diabetic subjects were divided into three groups according to UAE: a normal albuminuria group, a microalbuminuria group, and a macroalbuminuria group. A control group was also chosen. Levels of hs-CRP, TNF-α, uMCP-1, SAA, SCr, BUN, serum lipid, blood pressure, and HbA1c were measured in all subjects. Compared with the normal controls, levels of hs-CRP, TNF-α, uMCP-1, and SAA in T2DM patients were significantly higher. They were also elevated in the normal albuminuria group,P<0.05. Compared with the normal albuminuria group, levels of these inflammatory cytokines were significantly higher in the microalbuminuria and macroalbuminuria group,P<0.01. The macroalbuminuria group also showed higher levels than the microalbuminuria group,P<0.01. Also they were positively correlated with UAE, SBP, DBP, LDL-C, and TC. We noted no significance correlated with course, TG, or HDL-C. Only TNF-α; was positively correlated with HbA1c. This study revealed the importance of these inflammatory cytokines in DN pathogenesis. Further studies are needed to fully establish the potential of these cytokines as additional biomarkers for the development of DN.


Author(s):  
Pradeep Kumar ◽  
Preeti Sharma ◽  
Rachna Sharma ◽  
Gaurav Gupta ◽  
Anchal Chaudhary

Objective: Subclinical hypothyroidism (SCH) patients may present with abnormal lipid profile more specifically in patients having thyroid-stimulating hormone (TSH) >10 mIU/L. Since the contradiction still lies with patients having TSH <10 mIU/L, so the role of high-sensitive C-reactive protein (Hs- CRP) may be important with the prediction of inflammatory cardiovascular risk.Methods: Recently diagnosed 30 SCH patients both male and female were recruited and compared 30 normal healthy adults. Age and body mass index (BMI) of the study population were noted. Thyroid profile including TSH, FT4, and T3 was measured by an enzyme-linked immunosorbent assay (ELISA). Total cholesterol, triglycerides, and high-density lipoprotein (HDL) cholesterol were measured by the CHOD-POD method, GPO-PAP method, and CHOD-POD/phosphotungstic method. Low-density lipoprotein (LDL) cholesterol and very low-density cholesterol were measured by Friedewald formula. Lipoprotein ratios were also calculated. An ELISA was also used for the estimation of Hs-CRP.Results: The significant results were obtained in this study. BMI was significantly (<0.01) elevated in patients’ group compared to the control group. In the thyroid profile, TSH was significantly (<0.05) different between the groups. Total cholesterol, triglycerides, and LDL-cholesterol were significantly (<0.01) elevated in the case group. A significantly lower concentration of HDL cholesterol was observed in SCH patients when compared with control subjects. There was an elevated concentration of lipoprotein ratios in patients group. The mean concentration of Hs-CRP was highly significant between the groups. The level was higher in the case group compared to the control group. In patients’ group, there was a positive association (β- 0.36) (confidence interval 95%–0.002–0.536) between TSH and Hs-CRP. This association was highly significant.Conclusion: SCH patients having TSH <10 μIU/ml were characterized by dyslipidemia and elevated Hs-CRP. Increased lipoprotein ratios and Hs-CRP may promote low-grade inflammation in SCH patients, by which cardiovascular risk can be developed.


2018 ◽  
Vol 6 (8) ◽  
pp. 1349-1353 ◽  
Author(s):  
Ghada M. El Kassas ◽  
Manal A. Shehata ◽  
Maged A. El Wakeel ◽  
Ahmed F. Amer ◽  
Fatma A. Elzaree ◽  
...  

BACKGROUND: Obesity is a multifactorial disease, associated with metabolic disorders and chronic low-grade inflammation. Procalcitonin (PCT) is well known as a biomarker of infection, and systemic inflammation. Recently, it has potential as a marker for chronic low-grade inflammation.AIM: This study aims to evaluate the role of serum PCT as an inflammatory biomarker in the diagnosis of obesity-related low-grade inflammation.METHOD: In this case-control study, 50 obese and 35 normal weight children and adolescents aged 5–15 years were enrolled. Anthropometric parameters were measured in all subjects. Blood samples were collected for measurement of lipid profile, blood glucose, insulin, high sensitivity-CRP (Hs-CRP) and serum procalcitonin. Serum (PCT) levels were assessed using enzyme-linked immunosorbent assay.RESULTS: Obese participants had higher concentrations of serum PCT, total cholesterol, triglycerides, LDL-c, glucose and Hs-CRP than control group. On correlation analysis, procalcitonin had significant positive correlation with (BMI) z-score (P = 0.02), insulin (P = 0.00), insulin resistance (HOMA-IR) (P = 0.006), Hs-CRP (P = 0.02), total cholesterol (P = 0.04) and triglycerides (P = 0.00) in obese group.CONCLUSION: The increased serum procalcitonin concentrations were closely related to measures of adiposity, Hs-CRP and insulin resistance, suggesting that PCT may be an excellent biomarker for obesity-related chronic low-grade inflammation in children and adolescents.


2021 ◽  
Vol 22 (5) ◽  
pp. 2602
Author(s):  
Emilie Viennois ◽  
Benoit Chassaing

Inflammation is a well-characterized critical driver of gastrointestinal cancers. Previous findings have shown that intestinal low-grade inflammation can be promoted by the consumption of select dietary emulsifiers, ubiquitous component of processed foods which alter the composition and function of the gut microbiota. Using a model of colitis-associated cancer, we previously reported that consumption of the dietary emulsifiers carboxymethylcellulose or polysorbate-80 exacerbated colonic tumor development. Here, we investigate the impact of dietary emulsifiers consumption on cancer initiation and progression in a genetical model of intestinal adenomas. In APCmin mice, we observed that dietary emulsifiers consumption enhanced small-intestine tumor development in a way that appeared to be independent of chronic intestinal inflammation but rather associated with emulsifiers’ impact on the proliferative status of the intestinal epithelium as well as on intestinal microbiota composition in both male and female mice. Overall, our findings further support the hypothesis that emulsifier consumption may be a new modifiable risk factor for colorectal cancer (CRC) and that alterations in host–microbiota interactions can favor gastrointestinal carcinogenesis in individuals with a genetical predisposition to such disorders.


Circulation ◽  
2014 ◽  
Vol 130 (suppl_2) ◽  
Author(s):  
Satoshi Niijima ◽  
Michiaki Nagai ◽  
Satoshi Hoshide ◽  
Mami Takahashi ◽  
Masahisa Shimpo ◽  
...  

Background: Recently, several studies have reported that long sleep duration was independently associated with increased aortic stiffness. On the other hand, high-sensitive C-reactive protein (hs-CRP) was associated with increased aortic stiffness. In this study, the relationships among self-reported sleep duration, hs-CRP and pulse wave velocity (PWV) were investigated in the Japanese at high-risk of cardiovascular disease. In addition, we investigated whether antihypertensive treatment moderated these relationships or not. Methods: Among 4310 patients with one or more cardiovascular risks recruited for the Japan Morning Surge-Home Blood Pressure Study, brachial-ankle PWV and hs-CRP measurement were performed in the 2304 patients (64.7 years old, male 49.6%). A self-administered questionnaire included items on daily sleep duration was used. Results: According to the sleep duration (6h or less,6h to 8h,8h or more per night), significant associations of sleep duration were observed with PWV (1594 vs 1644 vs 1763 cm/s, p<0.0001).In the multiple regression analysis adjustment for confounders including age body mass index, total cholesterol, HbA1c and clinic systolic blood pressure (SBP), long sleep duration (8h or more per night) (B: 29, 95%CI: 1.0-56, p<0.05) and log hs-CRP (B: 25, 95%CI: 3.1-48, p<0.05) were significantly positively associated with PWV. A significant interaction was found between long sleep duration and antihypertensive agent non-use for PWV (p<0.05). Especially, in the group without calcium channel blockers (CCBs), long sleep duration was significantly associated with PWV (p<0.01), while a marginal significant synergetic relationship was observed between long sleep duration and log hs-CRP for PWV (p=0.07). On the other hand, there were no significant interactions between long sleep duration and angiotensin receptor blockers non-use. Conclusions: Long sleep duration and hs-CRP were significant indicators of increased PVW in the high-risk Japanese population. In those without CCBs, long sleep duration served as a strong determinant for arterial stiffness, marginally interacted by low-grade inflammation. CCBs use might be important not to aggravate artery remodeling caused by long sleep duration.


Foods ◽  
2021 ◽  
Vol 10 (9) ◽  
pp. 2202
Author(s):  
Micaelle Oliveira de Luna Freire ◽  
Luciana Caroline Paulino do Nascimento ◽  
Kataryne Árabe Rimá de Oliveira ◽  
Alisson Macário de Oliveira ◽  
Thiago Henrique Napoleão ◽  
...  

High-fat diet (HFD) consumption has been linked to dyslipidemia, low-grade inflammation and oxidative stress. This study investigated the effects of a mixed formulation with Limosilactobacillusfermentum 139, L. fermentum 263 and L. fermentum 296 on cardiometabolic parameters, fecal short-chain fatty acid (SCFA) contents and biomarkers of inflammation and oxidative stress in colon and heart tissues of male rats fed an HFD. Male Wistar rats were grouped into control diet (CTL, n = 6), HFD (n = 6) and HFD with L. fermentum formulation (HFD-Lf, n = 6) groups. The L.fermentum formulation (1 × 109 CFU/mL of each strain) was administered twice a day for 4 weeks. After a 4-week follow-up, biochemical parameters, fecal SCFA, cytokines and oxidative stress variables were evaluated. HFD consumption caused hyperlipidemia, hyperglycemia, low-grade inflammation, reduced fecal acetate and propionate contents and increased biomarkers of oxidative stress in colon and heart tissues when compared to the CTL group. Rats receiving the L. fermentum formulation had reduced hyperlipidemia and hyperglycemia, but similar SCFA contents in comparison with the HFD group (p < 0.05). Rats receiving the L. fermentum formulation had increased antioxidant capacity throughout the colon and heart tissues when compared with the control group. Administration of a mixed L. fermentum formulation prevented hyperlipidemia, inflammation and oxidative stress in colon and heart tissues induced by HFD consumption.


2021 ◽  
pp. 31-32
Author(s):  
Parag Gupta ◽  
Lal Pranay Singh

Background: Diabetes mellitus is the most common metabolic disorder characterized by metabolic abnormalities and long term complications. It is characterized by hyperglycemia resulting from defect in insulin secretion and in its action. It has become a leading cause of morbidity and mortality world over. hs- CRP is a marker of low-grade inammation and it is raised in patients with type 2 DM. The present study was undertaken with the objective of studying the relation of High Sensitivity CRP (hs-CRP) in patients of type 2 Diabetes Mellitus and in non-diseased population. Methods: This was a comparative observational study, conducted at Diabetic clinic, Index Medical College, Indore during August 2014 to July 2015. Cases and control were selected as per the inclusion criteria. Statistical analysis was done using SPSS v20. Mean age of the group was 48years. The mean hs CRP in the diabe Results: tic group was 0.45 compared with 0.35, in the control group. hs CRP levels are directly related to insulin resistance and is Conclusion: highly associated with diabetic population.


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