scholarly journals Genetic effect modification of cis-acting C-reactive protein variants in cardiometabolic disease status

2021 ◽  
Author(s):  
Jie Zheng ◽  
Haotian Tang ◽  
Matthew S Lyon ◽  
Neil M Davies ◽  
Venexia M Walker ◽  
...  
Keyword(s):  
Causal Effect ◽  
Multivariable Analysis ◽  
Genetic Effect ◽  
Disease Status ◽  
Health Condition ◽  
Mr Studies ◽  
Genetic Associations ◽  
C Reactive Protein ◽  
Cis Acting ◽  
Reactive Protein

Mendelian randomization (MR) studies carried out among patients with a particular health condition should establish the genetic instrument influences the exposure in that subgroup, however this is normally investigated in the general population. Here, we investigated whether the genetic associations of four cis-acting C-reactive protein (CRP) variants differed between participants with and without three cardiometabolic conditions: obesity, type 2 diabetes, and cardiovascular disease. Associations of cis-genetic variants with CRP differed between obese and non-obese individuals. A multivariable analysis suggested strong independent associations of the gene-by-body mass index (BMI) interaction on CRP (P<1.18×10−8 for the CRP variants). Applying MR, we observed strong causal effect of BMI on CRP (P=2.14×10−65). In summary, our study indicates that genetic associations with CRP differ across disease sub-groups, with evidence to suggest that BMI is an effect modifier. MR studies of disease progression should report on the genetic instrument-exposure association in the disease subgroup under investigation.

scholarly journals Systematic evaluation of the causal relationship between DNA methylation and C-reactive protein

2018 ◽  
Author(s):  
Esther Walton ◽  
Gibran Hemani ◽  
Abbas Dehghan ◽  
Caroline Relton ◽  
George Davey Smith
Keyword(s):  
Dna Methylation ◽  
Multiple Testing ◽  
Causal Effect ◽  
Systematic Evaluation ◽  
Low Grade ◽  
Genetic Associations ◽  
C Reactive Protein ◽  
Individual Level ◽  
Reactive Protein ◽  
Cpg Sites

AbstractElevated C-reactive protein (CRP) levels are an indicator of chronic low-grade inflammation. Epigenetic modifications, including DNA methylation, have been linked to CRP, but systematic investigations into potential underlying causal relationships have not yet been performed.We systematically performed two-sample Mendelian randomization and colocalization analysis between CRP and DNA methylation levels, using GWAS and EWAS summary statistics as well as individual level data available through the ARIES subset of the Avon Longitudinal Study of Parents and Children (ALSPAC; 1,616 participants).We found no convincing examples for a causal association from CRP to DNA methylation. Testing for the reverse (a putative causal effect of DNA methylation on CRP), we found three CpG sites that had shared genetic effects with CRP levels after correcting for multiple testing (cg26470501 (offspring: beta=0.07 [0.03, 0.11]; mothers: beta=0.08 [0.04, 0.13]), cg27023597 (offspring: beta=0.18 [0.10, 0.25]; mothers: beta=0.20 [0.12, 0.28]) and cg12054453 (offspring: beta=0.09 [0.05, 0.13])) influenced CRP levels. For all three CpG sites, linked to the genes TMEM49, BCL3 and MIR21, increased methylation related to an increase in CRP levels. Two CpGs (cg27023597 and cg12054453) were influenced by SNPs in genomic regions that had not previously been implicated in CRP GWASs, implicating them as novel genetic associations.Overall, our findings suggest that CRP associations with DNA methylation are more likely to be driven by either confounding or causal influences of DNA methylation on CRP levels, rather than the reverse.

scholarly journals Predictors of Acute Kidney Injury After Hip Fracture in Older Adults

2020 ◽  
Vol 11 ◽  
pp. 215145932092008 ◽  
Author(s):  
Julie Braüner Christensen ◽  
Martin Aasbrenn ◽  
Luana Sandoval Castillo ◽  
Anette Ekmann ◽  
Thomas Giver Jensen ◽  
...  
Keyword(s):  
Risk Factors ◽  
Acute Kidney Injury ◽  
Hip Fracture ◽  
Blood Transfusion ◽  
Multivariable Analysis ◽  
Kidney Injury ◽  
C Reactive Protein ◽  
Hip Fracture Surgery ◽  
Reactive Protein ◽  
Fracture Surgery

Introduction: This study aimed to investigate the prevalence of acute kidney injury (AKI) following hip fracture surgery in geriatric patients and to identify predictors for development of AKI with a focus on possible preventable risk factors. Methods: In this retrospective cohort study, we reviewed electronic medical records of all patients above 65 years of age who underwent hip fracture surgery at Copenhagen University Hospital, Bispebjerg, Denmark, in 2018. Acute kidney injury was assessed according to the Kidney Disease Improving Global Outcomes guidelines. Multivariate logistic regression analyses were used to identify independent risk factors for AKI. Results: Postoperative AKI developed in 28.4% of the included patients (85/299). Acute kidney injury was associated with increased length of admission (11.3 vs 8.7 days, P < .001) and 30-day mortality (18/85 vs 16/214, P = .001). In multivariable analysis, higher age (odds ratio [OR]: 1.05, 95% confidence interval [CI]: 1.01-1.08, P = .004), heart disease (OR: 1.78, 95% CI: 1.01-3.11, P = .045), and postoperative blood transfusion (OR: 1.84, 95% CI: 1.01-3.36, P = .048) were associated with AKI. Moreover, a higher postoperative C-reactive protein (199.0 ± 99.9 in patients with AKI, 161.3 ± 75.2 in patients without AKI) and lower postoperative diastolic blood pressure were observed in patients developing AKI. Discussion and Conclusion: Acute kidney injury was common following hip fracture surgery and associated with longer admissions and increased mortality. Patients developing AKI were older and showed several postoperative similarities, including higher C-reactive protein, lower postoperative diastolic pressure, and the need for blood transfusion.

Predictive value of C-reactive protein for the outcome after primary intracerebral hemorrhage

2014 ◽  
Vol 121 (6) ◽  
pp. 1374-1379 ◽  
Author(s):  
Pekka Löppönen ◽  
Cheng Qian ◽  
Sami Tetri ◽  
Seppo Juvela ◽  
Juha Huhtakangas ◽  
...  
Keyword(s):  
Intracerebral Hemorrhage ◽  
Independent Predictor ◽  
Multivariable Analysis ◽  
Population Based ◽  
Unfavorable Outcome ◽  
High Morbidity ◽  
Confounding Factors ◽  
C Reactive Protein ◽  
Unconditional Logistic Regression ◽  
Reactive Protein

Object Primary intracerebral hemorrhage (ICH) carries high morbidity and mortality rates. Several factors have been suggested as predicting the outcome. The value of C-reactive protein (CRP) levels in predicting a poor outcome is unclear, and findings have been contradictory. In their population-based cohort, the authors tested whether, independent of confounding factors, elevated CRP levels on admission (< 24 hours after ictus) are associated with an unfavorable outcome. Methods The authors identified all patients who suffered primary ICH between 1993 and 2008 among the population of Northern Ostrobothnia, Finland, and from the laboratory records they extracted the CRP values at admission. Independent predictors of an unfavorable outcome (moderate disability or worse according to the Glasgow Outcome Scale at 3 months) were tested by unconditional logistic regression in a model including all the well-established confounding factors and CRP on admission. Results Of 961 patients, 807 (84%) had CRP values available within 24 hours of admission, and multivariable analysis showed elevated CRP at that point to be associated with an unfavorable outcome (OR 1.41 per 10 mg/L [95% CI 1.09–1.81], p < 0.01), together with diabetes mellitus (OR 1.99 [95% CI 1.09–3.64], p < 0.05), age (1.06 per year [95% CI 1.04–1.08], p < 0.001), low Glasgow Coma Scale score (0.75 per unit [95% CI 0.67–0.84], p < 0.001), hematoma size (1.05 per ml [95% CI 1.03–1.07], p < 0.001), and the presence of an intraventricular hemorrhage (2.70 [95% CI 1.66–4.38], p < 0.001). Subcortical location predicted a favorable outcome (0.33 [95% CI 0.20–0.54], p < 0.001). Conclusions Elevated CRP on admission is an independent predictor of an unfavorable outcome and is only slightly associated with the clinical and radiological severity of the bleeding.

scholarly journals High Specific C-Reactive Protein in Prediction of the Early Outcome of Primary Intra Cerebral Hemorrhage

2021 ◽  
pp. 54-61
Author(s):  
Khaled Eltoukhy ◽  
Mohamed Gomaa ◽  
Yasmin Ibrahim ◽  
Mohamed Saad
Keyword(s):  
Cerebral Hemorrhage ◽  
Hemorrhagic Stroke ◽  
Multivariable Analysis ◽  
University Hospital ◽  
Control Group ◽  
C Reactive Protein ◽  
Reactive Protein ◽  
Test Kit ◽  
Hs Crp ◽  
Ct Brain

Background: Primary intra cerebral hemorrhage (ICH) has high rate of disability and death. Many factors was supposed to be predictors of the outcome. The significance of measuring C-reactive protein (CRP) levels to predict the outcome is uncertain, and data have been controversial. The objective of our clinical study was to determine the relationship of hs-CRP levels with bad outcome. The authors tested if (independent of confounding factors) hs-CRP levels was elevated on admission (< 24 hours after ictus). Fifty patients with acute spontaneous hemorrhagic stroke, within 24 hours of onset confirmed by CT brain were admitted at neurology department, Mansoura University Hospital from June 2017 to September 2018. Age and sex cross-matched 50 healthy persons were studied as control group. Patient and control groups were subjected to full history, general and neurological examination, GCS on admission, National Institute of Health Stroke Scale (NIHSS) on admission, ICH score and Canadian scale on admission and after 30 days, Venous Blood samples were taken within 24 hours of onset and tested for routine laboratory investigations (liver function, serum creatinine, CBC and blood glucose) and High Sensitive C-Reactive Protein level using Enzyme Immunoassay Test Kit. Computed tomography (CT) brain was repeated 72 hours later. Multivariable regression analyses were used to evaluate associations of hs-CRP concentration and ICH outcome. Kaplan–Meier analysis was used for survival. Results: This study revealed that Hs-CRP is significantly higher in patient group (9.3 mg/l) when compared to control group (0.68 mg/dl) with p value < 0,001. There was statistically significant correlation between NIHSS and hs-CRP levels but there was no statistically significant correlation between hs-CRP levels and stroke outcome. Conclusion: Taking these covariates into multivariable analysis revealed that there is correlation between hs-CRP and hemorrhagic stroke but it cannot be used as a predictor of its outcome.

scholarly journals Association Between Inflammatory Biomarker C-Reactive Protein and Radiotherapy-Induced Early Adverse Skin Reactions in a Multiracial/Ethnic Breast Cancer Population

2018 ◽  
Vol 36 (24) ◽  
pp. 2473-2482 ◽  
Author(s):  
Jennifer J. Hu ◽  
James J. Urbanic ◽  
L. Doug Case ◽  
Cristiane Takita ◽  
Jean L. Wright ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Multivariable Analysis ◽  
High Sensitivity ◽  
Skin Toxicity ◽  
C Reactive Protein ◽  
Skin Reactions ◽  
Inflammatory Biomarker ◽  
Reactive Protein ◽  
Increased Risk ◽  
Nonobese Patients

Purpose This study examined an inflammatory biomarker, high-sensitivity C-reactive protein (hsCRP), in radiotherapy (RT)-induced early adverse skin reactions or toxicities in breast cancer. Patients and Methods Between 2011 and 2013, 1,000 patients with breast cancer who underwent RT were evaluated prospectively for skin toxicities through the National Cancer Institute–funded Wake Forest University Community Clinical Oncology Program Research Base. Pre- and post-RT plasma hsCRP levels and Oncology Nursing Society skin toxicity criteria (0 to 6) were used to assess RT-induced skin toxicities. Multivariable logistic regression analyses were applied to ascertain the associations between hsCRP and RT-induced skin toxicities after adjusting for potential confounders. Results The study comprised 623 white, 280 African American, 64 Asian/Pacific Islander, and 33 other race patients; 24% of the patients were Hispanic, and 47% were obese. Approximately 42% and 15% of patients developed RT-induced grade 3+ and 4+ skin toxicities, respectively. The hsCRP levels differed significantly by race and body mass index but not by ethnicity. In multivariable analysis, grade 4+ skin toxicity was significantly associated with obesity (odds ratio [OR], 2.17; 95% CI, 1.41 to 3.34], post-RT hsCRP ≥ 4.11 mg/L (OR, 1.61; 95% CI, 1.07 to 2.44), and both factors combined (OR, 3.65; 95% CI, 2.18 to 6.14). Above-median post-RT hsCRP (OR, 1.93; 95% CI, 1.03 to 3.63), and change in hsCRP (OR, 2.80; 95% CI, 1.42 to 5.54) were significantly associated with grade 4+ skin toxicity in nonobese patients. Conclusion This large prospective study is the first to our knowledge of hsCRP as an inflammatory biomarker in RT-induced skin toxicities in breast cancer. We demonstrate that nonobese patients with elevated RT-related change in hsCRP levels have a significantly increased risk of grade 4+ skin toxicity. The outcomes may help to predict RT responses and guide decision making.

Abstract P010: Serum Vitamin D and Risk of Heart Failure: Prospective Results From the Moli-sani Study

Circulation ◽  
2016 ◽  
Vol 133 (suppl_1) ◽  
Author(s):  
Simona Costanzo ◽  
Amalia De Curtis ◽  
Augusto Di Castelnuovo ◽  
Mariarosaria Persichillo ◽  
Maria B Donati ◽  
...  
Keyword(s):  
Heart Failure ◽  
Vitamin D ◽  
Multivariable Analysis ◽  
Serum Vitamin ◽  
C Reactive Protein ◽  
Baseline Serum ◽  
Serum Vitamin D ◽  
Reactive Protein ◽  
Vitamin D Levels ◽  
Incident Cases

Introduction: Vitamin D deficiency has been associated with the progression of heart failure (HF) and Vitamin D supplementation may have protective effects in patients with HF. However, little is known on the predictive value of circulating Vitamin D levels on HF risk. Hypothesis: Low serum Vitamin D levels are associated with incident HF in a large prospective cohort of Italian adults. Methods: We analyzed 18,689 (48.4% men, age ≥35 years) HF-free individuals randomly recruited from the general population of the Moli-sani study, for whom complete data on HF and serum Vitamin D were available. Vitamin D was measured on serum by an immunoassay in the central laboratory of European BiomarCaRE project (Abbott Architect 25-OH Vitamin D, Wiesbaden, Germany). The cohort was followed up for a median of 4.2 years (80,849 person-years). Baseline serum Vitamin D was categorized in deficient/insufficient, hypovitaminosis, and normal (Table). Incident cases of HF were identified by linkage with the regional archive of hospital discharges. Hazard ratios (HRs) were calculated using Cox-proportional hazard models. Results: Subjects with normal, hypo or insufficient levels of Vitamin D were 12.2%, 79.6% and 8.2%, respectively. We identified 412 incident cases of HF. The incidence of HF was 1.1%, 2.2% and 3.9%, respectively in subjects with normal, hypo and insufficient levels of Vitamin D. After a multivariable analysis, considering a large panel of potential covariates, individuals with deficient/insufficient levels of serum Vitamin D showed a higher risk of developing HF (HR: 1.78, 95% CI: 1.07-2.97) than those with normal levels. Further adjustment for C-Reactive Protein did not modify the association (Table). Conclusions: Deficiency of Vitamin D is associated with a significantly higher risk of HF in a general adult population. This association was not explained by an inflammatory marker such as C-Reactive Protein.

On-admission Serum High-Sensitivity C-Reactive Protein Level Independently Predicts In-Hospital Mortality and Adverse Cardiovascular Events in ST-elevation Acute Myocardial Infarction

2021 ◽  
pp. 263246362110553
Author(s):  
Anggoro Budi Hartopo ◽  
Indah Sukmasari ◽  
Maria Patricia Inggriani ◽  
Thomas Rikl ◽  
Stefi Geovani Valentin Hayon ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Cardiovascular Events ◽  
Multivariable Analysis ◽  
High Sensitivity ◽  
Inflammatory Biomarkers ◽  
C Reactive Protein ◽  
Reactive Protein ◽  
St Elevation ◽  
Hs Crp ◽  
Elevation Acute Myocardial Infarction

Background: Inflammatory biomarkers are associated with adverse cardiovascular events during ST-elevation acute myocardial infarction (STEMI). We aimed to investigate the role of inflammatory biomarkers, high-sensitivity C-reactive protein (hs-CRP), and soluble ST-2 (sST2), for prediction of adverse cardiovascular events in STEMI. Methods: This was a prospective cohort study that consecutively enrolled patients with STEMI. Subjects were observed during hospitalization until discharge or fatal events happened. Adverse cardiovascular event was a compilation of cardiac mortality, acute heart failure, cardiogenic shock, reinfarction, and malignant ventricular arrhythmia. Blood samples were withdrawn on admission and inflammatory biomarkers (hs-CRP and sST2) were measured. The receiver operator characteristics curve and multivariable analysis were performed to determine which inflammatory biomarkers predict in-hospital adverse cardiovascular events and mortality. Result: Of 166 subjects, the in-hospital adverse cardiovascular events occurred in 41 subjects (24.6%) and mortality occurred in 16 subjects (9.6%). Subjects with in-hospital adverse cardiovascular events and mortality had a significantly higher hs-CRP level, but comparable sST2 level than subjects without events. The hs-CRP level was the most precise biomarkers to predict in-hospital adverse cardiovascular events (hs-CRP cut-off ≥2.75 mg/L) and mortality (hs-CRP cut-off ≥7 mg/L). Multivariable analysis indicated hs-CRP ≥2.75 mg/L as an independent predictor for in-hospital adverse cardiovascular events (adjusted odds ratio [OR]: 2.79, 95% confidence interval [CI]: 1.05-7.39, P = .039) and hs-CRP ≥7 mg/L for mortality (adjusted OR: 5.45, 95% CI: 1.13-26.18, P = .034) in STEMI. Conclusion: On admission, hs-CRP level independently predicted in-hospital adverse cardiovascular events, at cut-off level ≥2.75 mg/L, and mortality, at cut-off level ≥7 mg/L, in STEMI patients.

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