Vascular and Cardiac Prognostic Determinants in Patients with Gynecological Cancers: A Six-Year Follow-up Study

Background: The aim of this study was to assess the role of cardiac and vascular parameters as all-cause mortality determinants in patients suffering from gynecological cancers. Methods: This was an observational, prospective, non-randomized, and non-controlled study. Forty-seven consecutive patients (mean age: 58 ± 13 years) were enrolled after cancer staging. All patients underwent evaluation of vascular (common carotid intima-media thickness (mean C-IMT), flow-mediated dilation of the brachial artery (FMD), and antero-posterior diameter of the infrarenal abdominal aorta (APAO)) and cardiac function and morphology before cancer-related interventions. A 6-year follow-up was carried out to assess the overall survival of the whole population. Results: Twenty patients (42%) died by the time of the 6-year follow-up. The brachial artery FMD values were higher in the survivors than the non-survivors (9.71 ± 3.53% vs. 6.13 ± 2.62%, p < 0.001), as well as the LVEF (60.8 ± 3.0% vs. 57.8 ± 4.4%, p = 0.009). There were no differences in the mean C-IMT, APAO, and other echocardiographic parameters. ROC curve analysis identified a baseline LVEF < 57% and FMD value < 5.8% as the best cut-offs. Kaplan–Meier evaluation showed that the LVEF, tricuspid annular plane systolic excursion, and FMD were the best predictors of all-cause mortality, although only the LVEF and FMD were confirmed in multivariate Cox regression analysis. Conclusions: The LVEF and brachial artery FMD are independent prognostic determinants in patients with gynecological cancers.

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P1885Cha2ds-2vasc score lacks of ability to predict mortality in patients attending the emergency department with atrial fibrillation in the presence of troponin i

European Heart Journal ◽

10.1093/eurheartj/ehz748.0633 ◽

2019 ◽

Vol 40 (Supplement_1) ◽

Author(s):

M I Gonzalez Del Hoyo ◽

G Cediel ◽

A Carrasquer ◽

G Bonet ◽

K Vasquez-Nunez ◽

...

Keyword(s):

Heart Failure ◽

Atrial Fibrillation ◽

Emergency Department ◽

Regression Analysis ◽

Troponin I ◽

Cox Regression ◽

Cox Regression Analysis ◽

All Cause Mortality

Abstract Background CHA2DS2-VASc score has been used as a surrogate marker for predicting outcomes beyond thromboembolic risk in patients with atrial fibrillation (AF). Likewise, cardiac troponin I (cTnI) is a predictor of mortality in AF. Purpose This study aimed to investigate the association of cTnI and CHA2DS2-VASc score with long-term prognosis in patients admitted to the emergency department with AF. Methods A retrospective cohort study conducted between January 2012 and December 2013, enrolling patients admitted to the emergency department with AF and having documented cTnI measurements. CHA2DS2-VASc score was estimated. Primary endpoint was 5-year all-cause mortality, readmission for heart failure (HF), readmission for myocardial infarction (MI) and the composite end point of major adverse cardiac events defined as death, readmission for HF or readmission for MI (MACE). Results A total of 578 patients with AF were studied, of whom 252 patients had elevated levels of cTnI (43.6%) and 334 patients had CHA2DS2-VASc score >3 (57.8%). Patients with elevated cTnI tended to be oldercompared with those who did not have cTnI elevation and were more frequently comorbid and of higher ischemic risk, including hypertension, prior MI, prior HF, chronic renal failure and peripheral artery disease. The overall median CHA2DS2-VASc score was higher in those with cTnI elevation compared to those patients elevated cTnI levels (4.2 vs 3.3 points, p<0.001). Main diagnoses at hospital discharge were tachyarrhythmia 30.3%, followed by heart failure 17.7%, respiratory infections 9.5% and acute coronary syndrome 7.3%. At 5-year follow-up, all-cause death was significantly higher for patients with cTnI elevation compared with those who did not have cTnI elevation (56.4% vs. 27%; logrank test p<0.001). Specifically, for readmissions for HF and readmissions for MI there were no differences in between patients with or without cTnI elevation. In addition, MACE was reached in 165 patients (65.5%) with cTnI elevation, compare to 126 patients (38.7%) without cTnI elevation (p<0.001). On multivariable Cox regression analysis, cTnI elevation was an independent predictor of all-cause death (hazard ratio, 1.67, 95% confidence interval [CI]: 1.24–2.26, p=0.001) and of MACE (hazard ratio 1.47, 95% confidence interval 1.15–1.88; P=0.002), but it did not reach statistical significance for readmissions for MI and readmissions for HF. CHA2DS2-VASc score was a predictor on univariate Cox regression analysis for each endpoint, but it did not reach significance on multivariable Cox regression analysis for any endpoint. Conclusions cTnI is independently associated with long-term all-cause mortality in patients attending the emergency department with AF. cTnI compared to CHA2DS2-VASc score is thus a biomarker with predictive capacity for mortality in late follow-up, conferring utility in the risk stratification of patients with atrial fibrillation.

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Prognostic Significance of Fragmented QRS in Patients with Hypertrophic Cardiomyopathy

Cardiology ◽

10.1159/000471845 ◽

2017 ◽

Vol 138 (1) ◽

pp. 26-33 ◽

Cited By ~ 3

Author(s):

Xili Lu ◽

Wei Wang ◽

Ling Zhu ◽

Yilu Wang ◽

Kai Sun ◽

...

Keyword(s):

Hypertrophic Cardiomyopathy ◽

Clinical Outcomes ◽

Cox Regression ◽

Prognostic Significance ◽

Cox Regression Analysis ◽

Fragmented Qrs ◽

All Cause Mortality ◽

The Relationship ◽

Cvd Mortality

Objectives: The relationship between a fragmented QRS (fQRS) and clinical outcomes in patients with hypertrophic cardiomyopathy (HCM) remains unclear. This study aimed to investigate the prognostic significance of fQRS in patients with HCM. Methods: Between 2000 and 2012, 326 unrelated patients with HCM (72% male with a mean age of 52 years) were included and were divided into 2 groups: those with fQRS and those without fQRS. Results: A total of 105/326(32.2%) patients with HCM presented with fQRS at enrollment. During a follow-up of 5.3 ± 2.4 years, 33 patients died, 30 of cardiovascular disease (CVD). Cox regression analysis revealed that fQRS predicted a higher risk of all-cause mortality (adjusted hazard ratio [HR] 2.24; 95% confidence interval [CI] 1.08-4.64; p = 0.030) and CVD mortality (adjusted HR 2.68; 95% CI 1.22-5.91; p = 0.014). Our study also showed that fQRS increased the risk of heart failure-related death (adjusted HR 3.75; 95% CI 1.24-11.30; p = 0.019). Conclusions: Our results indicate that fQRS is associated with adverse clinical outcomes in patients with HCM.

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Association of Different Physical Activity Domains on All-Cause Mortality in Adults Participating in Primary Care in the Brazilian National Health System: 4-Year Follow-up

Journal of Physical Activity and Health ◽

10.1123/jpah.2016-0067 ◽

2017 ◽

Vol 14 (1) ◽

pp. 45-51 ◽

Cited By ~ 3

Author(s):

Bruna C. Turi ◽

Jamile S. Codogno ◽

Romulo A. Fernandes ◽

Xuemei Sui ◽

Carl J. Lavie ◽

...

Keyword(s):

Physical Activity ◽

Mortality Risk ◽

Cox Regression ◽

National Health System ◽

Circulatory System ◽

Cox Regression Analysis ◽

Circulatory System Diseases ◽

All Cause Mortality ◽

Males And Females

Background:Evidence has shown that physical activity (PA) is associated with low mortality risk. However, data about reduced mortality due to PA are scarce in developing countries and the dose–response relationship between PA from different domains and all-cause mortality remains unclear. Thus, the aim of this study is to investigate the association of PA from different domains on all-cause mortality among Brazilian adults.Methods:679 males and females composed the study sample. Participants were divided into quartile groups according to PA from different domains (occupational, sports, and leisure-time). Medical records were used to identify the cause of the death. Cox regression analysis was performed to determine the independent associations of PA from different domains and all-cause mortality.Results:During the follow-up period, 59 participants died. The most prevalent cause of death was circulatory system diseases (n = 20; 33.9% [21.8%–45.9%]). Higher scores of occupational (HR= 0.45 [95% CI: 0.20–0.97]), sports (HR= 0.44 [95% CI: 0.20–0.95]) and overall PA (HR= 0.40 [95% CI: 0.17–0.90]) were associated with lower mortality, even after adjustment for confounders.Conclusions:The findings in this study showed the importance of being active in different domains to reduce mortality risk.

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Ultrafiltration rate and diabetes as useful indicators of cardiovascular-related death in hemodialysis patients below 60 years of age

Postępy Higieny i Medycyny Doświadczalnej ◽

10.5604/01.3001.0010.7010 ◽

2017 ◽

Vol 71 (0) ◽

pp. 0-0

Author(s):

Marcin Krzanowski ◽

Katarzyna Krzanowska ◽

Artur Dziewierz ◽

Małgorzata Banaszkiewicz ◽

Artur Jurczyszyn ◽

...

Keyword(s):

Regression Analysis ◽

Cox Regression ◽

Mortality Data ◽

Cox Regression Analysis ◽

Time To Death ◽

All Cause Mortality ◽

Dm Type 2 ◽

Related Mortality

Background: The survival rate of elderly hemodialyzed (HD) patients is commonly thought to be poor. In a prospective, single center, non-interventional, observational study, the cause of all-cause and cardiovascular (CV) and heart failure (HF) mortality in this patient group were examined and compared with a younger cohort (below 60 years). Material/Methods: The study included 223 patients (90 women and 133 men) with age ranging from 34.5 to 75.0 years treated with HD. Median duration of HD was 70.0 months (24.0-120.0). Mortality data was collected over a period of six years. We divided patients into groups: <60 (n=123), ≥60 years (n=100), and with (n=33) and without DM type 2 (n=190). Results: During a six-year follow-up, 100 patients (44.8%) died, including 83 (37.2%) patients who died due to CV reasons. Median follow-up was 2015.0 days (946.0-2463.0) with the median time to death of 1166.0 days (654.5-1631.0). The factors negatively affecting patients’ survival in univariate Cox regression analysis included for all-cause mortality were: inter-dialytic weight gain (IDWG) (hazard ratio [HR]=1.60; p=0.01), ultrafiltration (UF) rate (HR=3.63; p=0.012) for group <60 years; for CV death: UF rate (HR=4.20; p=0.03), DM (HR=5.11; p=0.002) for group <60 years; for HF death: mellitus type 2 (DM) (HR=2.93; p=0.027) for group ≥60 years). In a multivariate Cox regression analysis for patients <60 years, the UF rate was the only independent predictor of all-cause mortality (HR 3.63 (1.34-9.67); p=0.011). Both DM (HR 4.91 (1.71-14.10); p=0.003) and UF rate (HR 3.62 (1.04-12.61); p=0.044) were independent predictors of CV-related mortality in patients <60 years. Conclusions: The UF rate can be a simple, useful indicator of higher long-term all-cause and CV mortality in HD patients <60 years of age. Also, DM may be a predictor of CV–related mortality in younger HD patients.

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Long term clinical impact of successful recanalization of chronic total occlusion in patients with and without type 2 diabetes mellitus

10.21203/rs.3.rs-28914/v1 ◽

2020 ◽

Author(s):

Chuan-Tsai Tsai ◽

Wei-Chieh Huang ◽

Hsin-I Teng ◽

Yi-Lin Tsai ◽

Tse-Min Lu

Keyword(s):

Diabetes Mellitus ◽

Cox Regression ◽

Total Occlusion ◽

Long Term Outcome ◽

Chronic Total Occlusions ◽

Cox Regression Analysis ◽

All Cause Mortality ◽

Diabetes Patients

Abstract Background Diabetes mellitus is one of the risk factors for coronary artery disease and frequently associated with multivessels disease and poor clinical outcomes. Long term outcome of successful revascularization of chronic total occlusions (CTO) in diabetes patients remains controversial. Methods and results From January 2005 to December 2015, 739 patients who underwent revascularization for CTO in Taipei Veterans General Hospital were included in this study, of which 313 (42%) patients were diabetes patients. Overall successful rate of revascularization was 619 (84%) patients whereas that in diabetics and non-diabetics were 265 (84%) and 354 (83%) respectively. Median follow up was 1095 days (median: 5 years, interquartile range: 1–10 years). During 3 years follow-up period, 59 (10%) in successful group and 18 (15%) patients in failure group died. Although successful revascularization of CTO was non-significantly associated with better outcome in total cohort (Hazard ratio (HR):0.593, 95% confidence interval (CI): 0.349–0.008, P:0.054), it might be associated with lower risk of all-cause mortality (HR: 0.307, 95% CI: 0.156–0.604, P: 0.001) and CV mortality (HR: 0.266, 95% CI: 0.095–0.748, P: 0.012) in diabetics (P: 0.512). In contrast, successful CTO revascularization didn’t improve outcomes in non-diabetics (all p > 0.05). In multivariate cox regression analysis, successful CTO revascularization remained an independent predictor for 3-years survival in diabetic subgroup (HR: 0.289, 95% CI: 0.125–0.667, P: 0.004). The multivariate analysis result was similar after propensity score matching (all-cause mortality, HR: 0.348, 95% CI: 0.142–0.851, P: 0.021). Conclusion Successful CTO revascularization was associated with reduced long term all-cause/cardiovascular mortality in diabetics but not in non-diabetic population.

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Biomarkers representing key aging-related biological pathways are associated with subclinical atherosclerosis and all-cause mortality: The Framingham Study

PLoS ONE ◽

10.1371/journal.pone.0251308 ◽

2021 ◽

Vol 16 (5) ◽

pp. e0251308

Author(s):

Cecilia Castro-Diehl ◽

Rachel Ehrbar ◽

Vanesa Obas ◽

Albin Oh ◽

Ramachandran S. Vasan ◽

...

Keyword(s):

Regression Models ◽

Molecular Mechanisms ◽

Cox Regression ◽

Subclinical Atherosclerosis ◽

Intima Media Thickness ◽

Carotid Intima Media Thickness ◽

Community Dwelling ◽

Linear Regression Models ◽

Biomarkers Of Aging ◽

All Cause Mortality

Background Increased oxidative stress, leukocyte telomere length (LTL) shortening, endothelial dysfunction, and lower insulin-like growth factor (IGF)-1 concentrations reflect key molecular mechanisms of aging. We hypothesized that biomarkers representing these pathways are associated with measures of subclinical atherosclerosis and all-cause mortality. Methods and results We evaluated up to 2,314 Framingham Offspring Study participants (mean age 61 years, 55% women) with available biomarkers of aging: LTL, circulating concentrations of IGF-1, asymmetrical dimethylarginine (ADMA), and urinary F2-Isoprostanes indexed to urinary creatinine. We evaluated the association of each biomarker with coronary artery calcium [ln (CAC+1)] and carotid intima-media thickness (IMT). In multivariable-adjusted linear regression models, higher ADMA levels were associated with higher CAC values (βADMA per 1-SD increase 0.25; 95% confidence interval [CI] [0.11, 0.39]). Additionally, shorter LTL and lower IGF-1 values were associated with higher IMT values (βLTL −0.08, 95%CI −0.14, −0.02, and βIGF-1 −0.04, 95%CI −0.08, −0.01, respectively). During a median follow-up of 15.5 years, 593 subjects died. In multivariable-adjusted Cox regression models, LTL and IGF-1 values were inversely associated with all-cause mortality (hazard ratios [HR] per SD increase in biomarker, 0.85, 95% CI 0.74–0.99, and 0.90, 95% CI 0.82–0.98 for LTL and IGF-1, respectively). F2-Isoprostanes and ADMA values were positively associated with all-cause mortality (HR per SD increase in biomarker, 1.15, 95% CI, 1.10–1.22, and 1.10, 95% CI, 1.02–1.20, respectively). Conclusion In our prospective community-based study, aging-related biomarkers were associated with measures of subclinical atherosclerosis cross-sectionally and with all-cause mortality prospectively, supporting the concept that these biomarkers may reflect the aging process in community-dwelling adults.

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Malnutrition Affects Cholesterol Paradox in Coronary Artery Disease: a 41,229 Chinese Cohort Study

10.21203/rs.3.rs-266119/v1 ◽

2021 ◽

Author(s):

Bo Wang ◽

Jin Liu ◽

Shiqun Chen ◽

Ming Ying ◽

Guanzhong Chen ◽

...

Keyword(s):

Cox Regression ◽

Cox Model ◽

Cox Regression Analysis ◽

Coronary Syndrome ◽

Kaplan Meier ◽

All Cause Mortality ◽

Chinese Cohort ◽

Artery Disease

Abstract Background: Several studies found that baseline low LDL-C concentration was associated with poor prognosis in patients with acute coronary syndrome (ACS), which was called “cholesterol paradox”. Low LDL-C concentration may reflect underlying malnutrition, which was strongly associated with increased mortality. We objected to investigate the cholesterol paradox in patients with CAD and the effects of malnutrition.Method: A total of 41,229 CAD patients admitted to Guangdong Provincial People's Hospital in China were included in this study from January 2007 to December 2018, and divided into two groups (LDL-C < 1.8 mmol/L, n=4,863; LDL-C ≥ 1.8 mmol/L, n = 36,366). We used Kaplan-Meier method and Cox regression analyses to assess the association between LDL-C levels and long-term all-cause mortality and the effect of malnutrition. Result: In this real-world cohort (mean age 62.94 years; 74.94% male), there were 5257 incidents of all-cause death during a median follow-up of 5.20 years [Inter-quartile range (IQR): 3.05-7.78 years]. Kaplan–Meier analysis showed that low LDL-C levels were associated with worse prognosis. After adjusting for baseline confounders (e.g., age, sex and comorbidities, etc.), multivariate Cox regression analysis revealed that low LDL-C level (<1.8mmol/L) was not significantly associated with all-cause mortality (adjusted HR, 1.04; 95% CI, 0.96-1.24). After adjustment of nutritional status, risk of all-cause mortality of patients with low LDL-C level decreased (adjusted HR, 0.90; 95% CI, 0.83-0.98). In the final multivariate Cox model, low LDL-C level was related to better prognosis (adjusted HR, 0.91; 95% CI, 0.84-0.99).Conclusion: Our results demonstrate that the cholesterol paradox persisted in CAD patients, but disappeared after accounting for the effects of malnutrition.

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P1787 Pharmacologic stress test: still an important prognostic factor? a follow-up study

European Heart Journal - Cardiovascular Imaging ◽

10.1093/ehjci/jez319.1143 ◽

2020 ◽

Vol 21 (Supplement_1) ◽

Author(s):

V Ferreira ◽

L Moura Branco ◽

A Galrinho ◽

P Rio ◽

S Aguiar Rosa ◽

...

Keyword(s):

Regression Analysis ◽

Cox Regression ◽

Stress Test ◽

Bypass Graft ◽

Dobutamine Stress ◽

Left Ventricular ◽

Cox Regression Analysis ◽

Kaplan Meier ◽

All Cause Mortality

Abstract Introduction Dobutamine stress echocardiography (DSE) is an established exam for evaluation of extent and severity of coronary artery disease. Purpose To analyse the results and complications of DSE and identify prognostic predictors in patients (P) who underwent DSE for myocardial ischemia detection. Methods 220P who underwent consecutive DSE from 2013 to 2017. P with significant valvular disease were excluded. Clinical data, echocardiographic parameters and data from follow up (FU) regarding all-cause mortality and MACEs were analysed. Mean age 64.8 ± 12.0 years(Y), 143 men (65%). Results 88P (40%) had positive, 102 had negative and 30 had inconclusive DSE; complications rate of 15%. Prevalence of hypertension, diabetes mellitus (DM), dyslipidemia, prior MI, percutaneous coronary interventionc (PCI), coronary arterial bypass graft (CABG) and HF was 82.7%, 42.3%, 67.7%, 35.9%, 31.8%, 10.9% and 9.5%, respectively. Mean left ventricular endsystolic (LVSD) and enddiastolic dimensions were 33.7 ± 8.9 and 52.8 ± 7.1 mm. Mean resting wall motion score index (rWMSI) and peak (pWMSI) were 1.16 ± 0.28 and 1.24 ± 0.34. Mean resting GLS (rGLS) and peak GLS (pGLS) were -16.3 ± 4.3 and -16.6 ± 4.3. Mean no. of ischemic segments was 1.7 ± 2.4 and 16.8% had ischemia >3 segments. There was ischemia in left anterior descending (LAD) coronary in 53P and in circumflex and right coronary territories in 18 and 68P. 22.6% had more than one ischemic territory. 43P (49.4%) underwent intervention, 38 with PCI and 5 with CABG. During a mean FU of 38.8 ± 16.8 months, 47 MACEs were observed, including 32 deaths (14.5%). Positive DSE (p = 0.012), no. of ischemic segments (p = 0.019), ischemia in the LAD (p = 0.003), rGLS (p = 0.038) and pGLS (p = 0.038) were related to the occurrence of MACEs. In Cox regression analysis, age (p = 0.005), DM (p = 0.005), HF (p = 0.006), prior CABG (p = 0.015), LVSD (p = 0.026), rWMSI (p = 0.029), pWMSI (p = 0.013) and pGLS (p = 0.038) were associated with increased all-cause mortality. Kaplan–Meier survival analysis showed that survival was significantly worse for ischemia > 3 segments (log rank 0.005), ischemia of more than one territory (log rank 0.025) and pWMSI >1.5 (log rank < 0.0005). With multivariate Cox regression analysis, age >65Y (HR 4.22, p = 0.004), DM (HR 2.49,p = 0.038) and pWMSI > 1.5 (HR 9.73,p = 0.007) were independently associated with all-cause mortality. Conclusion In patients who underwent DSE there were some baseline and DSE-related independent predictors of long-term prognosis: age, DM and peak WMSI. Abstract P1787 Figure. Kaplan–Meier curves

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Association of Soluble Klotho Level with Adverse Outcomes in Patients on Maintenance Hemodialysis

Disease Markers ◽

10.1155/2020/4923970 ◽

2020 ◽

Vol 2020 ◽

pp. 1-7

Author(s):

Li-xia Yu ◽

Qi-feng Liu ◽

Jian-hua Feng ◽

Sha-sha Li ◽

Xiao-xia Gu ◽

...

Keyword(s):

Cox Regression ◽

Adverse Outcomes ◽

Maintenance Hemodialysis ◽

Strongly Correlated ◽

Independent Predictive Factor ◽

Cox Regression Analysis ◽

Kaplan Meier ◽

Potential Association ◽

All Cause Mortality

Background. The predictive value of soluble Klotho (sKlotho) for adverse outcomes in patients on maintenance hemodialysis (MHD) is controversial. In this study, we aimed to clarify the potential association of sKlotho levels with adverse outcomes in this patient population. Materials. A total of 211 patients on MHD were identified and stratified according to the median sKlotho level. Patients were followed up for adverse outcomes including cardiovascular (CV) morbidity and all-cause mortality. Results. During the 36-month follow-up, 75 patients [51 CV events (including 16 CV deaths) and 40 deaths] experienced adverse outcomes. After stratification according to median sKlotho level, patients with a lower sKlotho level had a greater risk of CV events (38.2% vs. 19.5%, p = 0.006 ), all-cause mortality (28.4% vs. 11.6%, p = 0.003 ), and combined adverse outcomes (51.0% vs. 24.2%, p < 0.001 ). Similar observations were made from analyses using Kaplan-Meier survival curves. Cox regression analysis showed that a low sKlotho level was strongly correlated with CV morbidity [1.942 (1.030–3.661), p = 0.040 )], all-cause mortality [2.073 (1.023–4.203), p = 0.043 ], and combined adverse outcomes [1.818 (1.092–3.026), p = 0.021 ] in fully adjusted models. Conclusions. The sKlotho level was an independent predictive factor of adverse outcomes including CV morbidity and mortality in patients on MHD.

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Association of rs11780592 Polymorphism in the Human Soluble Epoxide Hydrolase Gene (EPHX2) with Oxidized LDL and Mortality in Patients with Diabetic Chronic Kidney Disease

Oxidative Medicine and Cellular Longevity ◽

10.1155/2021/8817502 ◽

2021 ◽

Vol 2021 ◽

pp. 1-8

Author(s):

Stefanos Roumeliotis ◽

Athanasios Roumeliotis ◽

Aikaterini Stamou ◽

Stylianos Panagoutsos ◽

Vangelis G. Manolopoulos ◽

...

Keyword(s):

Chronic Kidney Disease ◽

Kidney Disease ◽

Epoxide Hydrolase ◽

Cox Regression ◽

Oxidized Ldl ◽

Intima Media Thickness ◽

Soluble Epoxide Hydrolase ◽

Cox Regression Analysis ◽

Functional Polymorphisms ◽

All Cause Mortality

Soluble epoxide hydrolase 2 (EPHX2) is an enzyme promoting increased cellular apoptosis through induction of oxidative stress (OS) and inflammation. The EPHX2 gene which encodes soluble EPHX2 might be implicated in the pathogenesis and development of OS and atherosclerosis. We aimed to assess the possible association between two functional polymorphisms of the EPHX2 gene (rs2741335 and rs11780592) with oxidized LDL (ox-LDL), carotid atherosclerosis, mortality, and cardiovascular (CV) disease in 118 patients with diabetic chronic kidney disease (CKD). At baseline, ox-LDL and carotid intima-media thickness (cIMT) were evaluated and all patients were followed for seven years with outcomes all-cause mortality and CV events. rs11780592 EPHX2 polymorphism was associated with ox-LDL, cIMT, albuminuria, and hypertension. Compared to AG and GG, AA homozygotes had higher values of albuminuria, ox-LDL, and cIMT ( p = 0.046 , p = 0.003 , and p = 0.038 , respectively). These associations remained significant, even after grouping for the G allele. After the follow-up period, 42/118 patients died (30/60 with AA genotype, 11/42 with AG genotype, and 1/12 with GG genotype) and 49/118 experienced a new CV event (fatal or nonfatal). The Kaplan-Meier analysis revealed that patients with the AA genotype exhibited a significantly higher mortality risk, compared to patients with AG and GG genotypes ( p = 0.006 ). This association became even stronger, when AG and GG genotypes were grouped (AA vs. AG/GG, p = 0.002 ). AA homozygotes were strongly associated with all-cause mortality in both univariate (hazard ratio HR = 2.74 , confidence interval CI = 1.40 – 5.35 , p = 0.003 ) and multivariate Cox regression analysis ( HR = 2.61 , CI = 1.32 – 5.17 , p = 0.006 ). In conclusion, our study demonstrated that genetic variations of EPHX2 gene were associated with increased circulating ox-LDL, increased cIMT, and all-cause mortality in diabetic CKD. Since EPHX2 regulates the cholesterol efflux and the oxidation of LDL in foam cells and macrophages, our study suggests that a genetic basis to endothelial dysfunction and OS might be present in diabetic CKD.

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