Paraoxonase 1 concerning dyslipidaemia, cardiovascular diseases, and mortality in haemodialysis patients.
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SUBMITTER: Grzegorzewska AE
PROVIDER: S-EPMC7990965 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Cigarette smoking effects might correspond with paraoxonase 1 gene (PON1) single nucleotide variants (SNVs). We investigated the association of PON1 rs705379, rs854560, and rs662 with cardiovascular mortality in hemodialysis (HD) patients concerning conventional cigarette smoking. Cardiovascular, cardiac, coronary heart disease (CHD)- and non-CHD-related deaths were analyzed in 206 HD cigarette smokers and 659 HD non-smokers. P-values were adjusted for sex, age, and high-density lipoprotein cholesterol. Among all smokers, the rs705379 TT genotype was associated with cardiovascular (P = 0.028), cardiac (P = 0.046), and cardiac non-CHD-related (P = 0.001) mortality. Non-diabetic smokers showed similar qualitative significance to all smokers concerning mentioned death rates (P-values 0.011, 0.044, and 0.009, respectively). In diabetic non-smokers, the rs705379 T allele correlated with CHD-related deaths (P = 0.020). The rs854560 T allele was associated with lower cardiovascular mortality in non-diabetic smokers (P = 0.008). The rs854560 TT genotype showed a negative non-significant correlation with non-CHD-related cardiac death in all non-smokers (P = 0.079). In diabetic smokers, the rs662 G allele was associated with higher cardiac mortality (P = 0.005). In all non-smokers and non-diabetic non-smokers, the rs662 G correlated with cardiovascular deaths (P = 0.020 and P = 0.018, respectively). Genotyping PON1 SNVs may help argue HD smokers harboring the rs705379 TT genotype or T allele and non-smokers possessing the rs662 G allele for prevention against cardiovascular diseases. These groups are more burdened genetically for cardiovascular mortality.
| S-EPMC8484566 | biostudies-literature
Project description:BackgroundThe energy homeostasis-associated gene (ENHO), retinoid X receptor alpha gene (RXRA), and liver X receptor alpha gene (LXRA) are involved in adipogenic/lipogenic regulation. We investigated whether single-nucleotide polymorphisms in these genes (ENHO rs2281997, rs72735260; RXRA rs749759, rs10776909, rs10881578; LXRA rs2279238, rs7120118, rs11039155) are associated with dyslipidaemia, related comorbidities and survival of haemodialysis (HD) patients also tested for T-helper (Th) cell interleukin genes (IL).MethodsThe study was carried out in 873 HD patients. Dyslipidaemia was diagnosed by the recommendations of the Kidney Disease Outcomes Quality Initiative (K/DOQI) guidelines (2003); atherogenic dyslipidaemia was referred to if the TG/HDL cholesterol ratio was equal to or higher than 3.8. Genotyping of ENHO SNPs, LXRA SNPs, and IL12A rs568408 was carried out using HRM analysis. RXRA SNPs, IL12B rs3212227, and IL18 rs360719 were genotyped using PCR-RFLP analysis. The circulating adropin concentration was determined in 126 patients by enzyme-linked immunosorbent assay. Survival probability was analysed using the Kaplan-Meier method in 440 patients followed through 7.5 years.ResultsDyslipidaemia by K/DOQI was diagnosed in 459 patients (91% revealed hyper-LDL- cholesterolaemia), atherogenic dyslipidaemia was diagnosed in 454 patients, and 231 patients were free of dyslipidaemia by both criteria. The variant allele (T) of ENHO rs2281997 was associated with the hyper-LDL cholesterolaemic pattern of dyslipidaemia by K/DOQI. The frequency of atherogenic dyslipidaemia was lower in T-allele bearers than in CC-genotype patients. The rs2281997 T allele was associated with lower cardiovascular mortality in HD patients showing atherogenic dyslipidaemia. ENHO, RXRA, and LXRA showed epistatic interactions in dyslipidaemia. Circulating adropin was lower in atherogenic dyslipidaemia than in non-atherogenic conditions. RXRA rs10776909 was associated with myocardial infarction. Bearers of LXRA rs2279238, rs7120118 or rs11039155 minor alleles showed higher mortality. ENHO SNP positions fell within the same DNase 1 hypersensitivity site expressed in the Th1 cell line. Epistatic interactions occurred between rs2281997 and Th1 IL SNPs (rs360719, rs568408).ConclusionsAtherogenic dyslipidaemia occurs in HD patients in whom ENHO encodes less adropin. ENHO, RXRA, and LXRA SNPs, separately or jointly, are associated with dyslipidaemia, myocardial infarction, and survival in HD patients. Differences in the availability of transcription binding sites may contribute to these associations.
| S-EPMC6234788 | biostudies-literature
Project description:BACKGROUND:Patients with chronic kidney diseases (CKD) on haemodialysis (HD) have high morbidity and mortality rates, which are also due to the inherent risks associated with nephropathy. Non-adherence (NA) to the different demands of the treatment can have consequences for the outcome of patients undergoing HD; nevertheless, there are still doubts about such repercussions. This study was conducted to evaluate the association between NA to conventional HD and all-cause mortality and cardiovascular mortality. METHODS:We prospectively evaluated mortality in a 6-year period in a cohort of 255 patients on HD in northeast Brazil. The evaluated parameters of NA to HD were interdialytic weight gain (IDWG)???4% of dry weight (DW), hyperphosphatemia and regular attendance at treatment, assessed as the correlation between the periods on HD completed and those prescribed. We used the Cox multivariate regression model to analyse survival and the predictors of all-cause mortality and cardiovascular mortality. RESULTS:With a median follow-up period of 1493?days and a mortality rate of 9.1 per 100 people-years, there were 87 deaths, of which 54% were cardiovascular deaths. IDWG ?4% of DW was associated with a risk of all-cause mortality however presenting a borderline outcome for cardiovascular mortality, with hazard ratios of 2.02 (CI 95% 1.17-3.49, p?=?0.012) and 2.09 (CI 95% 1.01-4.35, p?=?0.047), respectively. No significant association was found between other parameters of NA and mortality. Subgroup analysis showed that for patients with IDWG ?4% of DW, malnutrition, age and diagnosis of cardiovascular and cerebrovascular diseases were associated with higher all-cause mortality. CONCLUSIONS:IDWG ?4% of DW was identified as an independent predictor of all-cause mortality and demonstrated a borderline outcome for cardiovascular mortality in patients on conventional HD. The occurrence of excessive IDWG in the presence of malnutrition represented a significant increase in the risk of death, indicating a subgroup of patients with a worse prognosis.
| S-EPMC6836324 | biostudies-literature
Project description:The distribution of adipose tissue is influenced by gender and by age, shifting from subcutaneous to visceral depots with longevity, increasing the development of several aging-related diseases and manifestations such as obesity, metabolic syndrome, and insulin resistance. Epigenetics might have an important role in aging processes. The aim of this research was to investigate the interactions between aging and epigenetic processes and the role of visceral adipose tissue, insulin resistance, and dyslipidaemia. Two different study samples of 366 and 269 adult participants were analyzed. Anthropometric, biochemical (including the triglycerides-glucose (TyG) index), and blood pressure measurements were assessed following standardized methods. Body composition measurements by Dual-energy X-ray absorptiometry (DXA) were also performed for the second sample. Methylation data were assessed by Infinium Human Methylation BeadChip (Illumina) in peripheral white blood cells. Epigenetic age acceleration was calculated using the methods DNAmAge (AgeAcc) and GrimAge (AgeAccGrim). Age acceleration (AgeAccGrim) showed better correlations than AgeAcc with most of the measured variables (waist circumference, glucose, HOMA-IR, HDL-cholesterol, triglycerides, and TyG index) for the first sample. In the second sample, all the previous correlations were confirmed, except for HOMA-IR. In addition, many of the anthropometrical measurements assessed by DXA and C-reactive protein (CRP) were also statistically associated with AgeAccGrim. Associations separated by sex showed statistically significant correlations between AgeAccGrim and HDL-cholesterol or CRP in women, whereas, in men, the association was with visceral adipose tissue mass DXA, triglycerides and TyG index. Linear regression models (model 1 included visceral adipose tissue mass DXA and TyG index and model 2 included HDL-cholesterol and CRP) showed a significant association for men concerning visceral adipose tissue mass DXA and TyG index, while HDL-cholesterol and CRP were associated in women. Moreover, structural equation modeling showed that the TyG index was mediating the majority of the visceral adipose tissue mass action on age acceleration. Collectively, these findings showed that there are different mechanisms affecting epigenetic age acceleration depending on sex. The identified relationships between epigenetic age acceleration and disease markers will contribute to the understanding of the development of age-related diseases.
| S-EPMC6653993 | biostudies-literature
Project description:BackgroundThe impact of arteriovenous fistula (AVF) or graft (AVG) thrombosis on mortality has been sparsely studied. This study investigated the association between AVF/AVG thrombosis and all-cause and cardiovascular mortality.MethodsThe data from 2439 patients with AVF or AVG undergoing maintenance haemodialysis (HD) included in the A Study to Evaluate the Use of Rosuvastatin in Subjects on Regular Hemodialysis: An Assessment of Survival and Cardiovascular Events trial (AURORA) were analysed using a time-dependent Cox model. The incidence of vascular access (VA) thrombosis was a pre-specified secondary outcome.ResultsDuring follow-up, 278 AVF and 94 AVG thromboses were documented. VA was restored at 22 ± 64 days after thrombosis (27 patients had no restoration with subsequent permanent central catheter). In multivariable survival analysis adjusted for potential confounders, the occurrence of AVF/AVG thrombosis was associated with increased early and late all-cause mortality, with a more pronounced association with early all-cause mortality {hazard ratio [HR] < 90 days 2.70 [95% confidence interval (CI) 1.83-3.97], P < 0.001; HR > 90 days 1.47 [1.20-1.80], P < 0.001}. In addition, the occurrence of AVF thrombosis was significantly associated with higher all-cause mortality, whether VA was restored within 7 days [HR 1.34 (95% CI 1.02-1.75), P = 0.036] or later than 7 days [HR 1.81 (95% CI 1.29-2.53), P = 0.001].ConclusionsAVF/AVG thrombosis should be considered as a major clinical event since it is strongly associated with increased mortality in patients on maintenance HD, especially in the first 90 days after the event and when access restoration occurs >7 days after thrombosis. Clinicians should pay particular attention to the timing of VA restoration and the management of these patients during this high-risk period. The potential benefit of targeting overall patient risk with more aggressive treatment after AVF/AVG restoration should be further explored.
| S-EPMC7025348 | biostudies-literature
Project description:BackgroundHypertensive haemodialysis patients may be at a high risk for cardiovascular events. This study was undertaken to ascertain whether the calcium channel blocker amlodipine reduces mortality and cardiovascular events in these high-risk patients.MethodsWe evaluated the effects of amlodipine on cardiovascular events in 251 hypertensive haemodialysis patients in an investigator-designed, prospective, randomized, double-blind, placebo-controlled, multicenter trial. One hundred and twenty-three patients were randomly assigned to amlodipine (10 mg once daily) and 128 to placebo. The primary endpoint was mortality from any cause. The secondary endpoint was a composite variable consisting of mortality from any cause or cardiovascular event. Analysis was by intention-to-treat. The trial was registered with ClinicalTrials.gov (number NCT00124969).ResultsThe median age of patients was 61 years (25% percentile - 75% percentile, 47-69), and the median follow-up was 19 months (8-30). Fifteen (12%) of the 123 patients assigned to amlodipine and 22 (17%) of the 128 patients assigned to placebo had a primary endpoint [hazard ratio 0.65 (95% CI 0.34-1.23); P = 0.19]. Nineteen (15%) of the 123 haemodialysis patients assigned to amlodipine and 32 (25%) of the 128 haemodialysis patients assigned to placebo reached the secondary composite endpoint [hazard ratio 0.53 (95% CI 0.31-0.93); P = 0.03].ConclusionAmlodipine safely reduces systolic blood pressure and it may have a beneficial effect on cardiovascular outcomes in hypertensive haemodialysis patients.
| S-EPMC2568006 | biostudies-literature
Project description:The human body has biological redox systems capable of preventing or mitigating the damage caused by increased oxidative stress throughout life. One of them are the paraoxonase (PON) enzymes. The PONs genetic cluster is made up of three members (PON1, PON2, PON3) that share a structural homology, located adjacent to chromosome seven. The most studied enzyme is PON1, which is associated with high density lipoprotein (HDL), having paraoxonase, arylesterase and lactonase activities. Due to these characteristics, the enzyme PON1 has been associated with the development of neurodegenerative diseases. Here we update the knowledge about the association of PON enzymes and their polymorphisms and the development of multiple sclerosis (MS), amyotrophic lateral sclerosis (ALS), Alzheimer's disease (AD) and Parkinson's disease (PD).
| S-EPMC7824310 | biostudies-literature
Project description:ObjectiveParaoxonase 1 (PON1) is an enzyme that has antioxidant potential, which confers a protective effect against the atherosclerotic process. However, studies associating genetics, dietary patterns and PON1 activity in individuals with cardiovascular disease (CVD) are scarce. Thus, the aim of the current study was to evaluate the influence of dietary factors on serum PON1 in CVD patients.MethodsCross-sectional, sub-study of the BALANCE Program Trial. All patients aged 45 years or older and had evidence of established atherosclerotic disease in the preceding 10 years. Body weight, height, waist circumference, blood pressure, lipid profile and fasting glucose were collected. Food intake was assessed with 24-h dietary recall. Data was analyzed using SAS University Edition and a P value ≤ 0.05 was considered statistically significant. Sample was divided into three groups, according to the PON1 T(-107)C genotype (CC, CT and TT) and serum PON1 activity (Low, Medium, High).ResultsThere were no genotype differences for major factors. However, the systolic blood pressure was lower for CT individuals (p<0.05). Intake of cholesterol, saturated fatty acids (SFA) and monounsaturated fatty acids (MUFAS) was higher in patients with lower PON1 activity. Lipid ingestion tended to be higher in patients with lower PON1 activity (p=0.08). In the multivariate logistic regression model, SFA intake (P=0.03), genotype (P=0.09), gender (P=0.04), age (P=0.07) and carbohydrate intake (P=0.16) contributed the most to the serum PON1 activity.ConclusionBased on these findings, nutritional guidance for these patients becomes essential, since dietary components interact with serum PON1 activity more than genotype.
| S-EPMC10065381 | biostudies-literature
Project description:BACKGROUND AND OBJECTIVES: An understanding of cardiovascular diseases (CVD) mortality is important for the development of strategies aimed at reducing the burden of CVD. Thus, we examined the changing pattern of CVD mortality in Korea over 30 years (1983-2012) by analyzing the Cause of Death Statistics. MATERIALS AND METHODS: Deaths from diseases of the circulatory system and those of five CVD categories were analyzed: total heart diseases, acute rheumatic fever/chronic rheumatic heart disease, hypertensive heart disease, ischemic heart disease (IHD) and atherosclerosis. To assess the effects of population ageing on CVD mortality, crude and age-adjusted mortality rates were calculated. Age-adjusted mortality rates were calculated by using the direct standardization method. RESULTS: Over the 30-year period analyzed in this study, circulatory system disease mortality markedly declined. The age-adjusted mortality rate decreased by 78.5% in men and by 76.3% in women. Consistent decreasing trends were observed for mortalities from rheumatic heart disease, hypertensive heart disease, and atherosclerosis. However, IHD mortality rapidly increased during the 30 years. Crude IHD mortality showed a steady increase until 2007, after which there were fluctuations. But the penalized regression splines showed that crude IHD mortality continued to increase. Age-adjusted IHD mortality peaked in the early 2000s, and started to decrease during the last few years. CONCLUSION: In summary, total CVD mortality rate has significantly decreased over the 30-year period analyzed in this study but the IHD mortality rate has continuously increased until recently. The prevention and management of cardiovascular diseases amongst the Korean population, especially IHD, still represents a great challenge.
| S-EPMC4446814 | biostudies-other
Project description:BACKGROUND:In the general population, metabolic syndrome (MetS) is predictive of major adverse cardiovascular events (MACE). Waist circumference (WC), a component of the MetS criteria, is linked to visceral obesity, which in turn is associated with MACE. However, in haemodialysis (HD) patients, the association between MetS, WC and MACE is unclear. METHODS:In a cross-sectional study of 1000 HD patients, we evaluated the prevalence and characterised the clinical predictors of MetS. The relationship between MetS and its components, alone or in combination, and MACE (coronary diseases, peripheral arteriopathy, stroke or cardiac failure), was studied using receiver operating characteristics (ROC) curves and logistic regression. RESULTS:A total of 753 patients were included between October 2011 and April 2013. The prevalence of MetS was 68.5%. Waist circumference (>?88?cm in women, 102?cm in men) was the best predictor of MetS (sensitivity 80.2; specificity 82.3; AUC 0.80; p?<? 0.05). In multivariate analysis, MetS was associated with MACE (OR: 1.85; 95CI 1.24-2.75; p?<? 0.01), but not WC alone. There was a stronger association between the combination of abdominal obesity, hypertriglyceridaemia and low high-density lipoprotein cholesterol with MACE after exclusion of impaired fasting glucose and hypertension. CONCLUSIONS:MetS is frequent and significantly associated with MACE in our haemodialysis cohort and probably in other European dialysis populations as well. In HD patients, a new simplified definition could be proposed in keeping with the concept of the "hypertriglyceridaemic waist".
| S-EPMC7427285 | biostudies-literature