2153The relation between systemic inflammation and incident cancer in patients with stable cardiovascular disease; a cohort study

2019 ◽  
Vol 40 (Supplement_1) ◽  
Author(s):  
C C Van 'T Klooster ◽  
P M Ridker ◽  
J Hjortnaes ◽  
Y Van Der Graaf ◽  
F W Asselbergs ◽  
...  

Abstract Background Chronic systemic low-grade inflammation, measured by elevated plasma concentrations of high sensitive C-reactive Protein (CRP), is a risk factor for cardiovascular disease (CVD). There is evidence that systemic low-grade inflammation is also related to a higher risk of cancer. Purpose In the present prospective cohort study the relation between systemic low-grade inflammation and risk of cancer was evaluated in patients with clinically manifest vascular disease. Methods In total 7178 patients from the SMART cohort with manifest cardiovascular disease and plasma CRP levels ≤10 mg/L were included. Data of the cohort were linked to the Dutch national cancer registry. Cox regression models were fitted to study the relation between CRP and incident cardiovascular disease as well as incident cancer. Cancer types were classified according to anatomical location of origin, as well as histopathological subtype, irrespective of their anatomical location of origin. To adjust for potential confounding, age, sex, smoking status, packyears of smoking, and body mass index were added to the models, and additional cardiovascular risk factors, including diabetes mellitus, and systolic blood pressure. Results After a median follow-up time of 8.3 years (interquartile range 4.6–12.3) 1289 recurrent cardiovascular events (myocardial infarction, stroke, or vascular mortality) and 1072 incident cancer diagnoses were observed. CRP level was related to recurrent cardiovascular disease risk (HR 1.57; 95% CI 1.35–1.82) (Figure 1A), as well as risk of CVD and/or cancer (HR 1.45; 95% CI 1.29–1.62) (Figure 1B) comparing the third tertile of CRP to the first tertile. CRP concentration was related to total cancer risk (HR 1.33; 95% CI 1.13–1.55 for the third tertile of CRP compared to the first tertile) (Figure 1C). Especially incident lung cancer, independent of histopathological subtype, was related to CRP level (HR 2.64; 95% CI 1.77–3.93 for the third tertile of CRP compared to the first) (Figure 1D). No effect modification by smoking status or years of smoking cessation was observed of the relation between CRP and lung cancer (p-values for interaction >0.05). Incidence of epithelial neoplasms and especially squamous cell neoplasms were related to CRP concentration, irrespective of their anatomical location of origin (HR 1.17; 95% CI 1.08–1.27, and HR 1.11; 95% CI 1.02–1.20 for 1 mg/L higher CRP level respectively). Sensitivity analyses accounting for reverse causality by excluding patients with a cancer diagnosis within 1 and within 2 years of follow up showed similar results. Kaplan Meier curves per CRP tertile Conclusion Chronic systemic low-grade inflammation, measured by plasma CRP levels ≤10mg/L, is a risk factor for incident cancer, markedly lung cancer, independent of smoking status, in patients with stable cardiovascular disease.

2019 ◽  
Vol 40 (48) ◽  
pp. 3901-3909 ◽  
Author(s):  
Cilie C van’t Klooster ◽  
Paul M Ridker ◽  
Jesper Hjortnaes ◽  
Yolanda van der Graaf ◽  
Folkert W Asselbergs ◽  
...  

Abstract Aims Low-grade inflammation, measured by elevated plasma concentrations of high-sensitive C-reactive protein (CRP), is a risk factor for cardiovascular disease (CVD). There is evidence that low-grade inflammation is also related to a higher risk of cancer. The present prospective cohort study evaluates the relation between low-grade systemic inflammation and risk of cancer in patients with stable CVD. Methods and results In total, 7178 patients with stable CVD and plasma CRP levels ≤10 mg/L were included. Data were linked to the Dutch national cancer registry. Cox regression models were fitted to study the relation between CRP and incident CVD and cancer. After a median follow-up time of 8.3 years (interquartile range 4.6–12.3) 1072 incident cancer diagnoses were observed. C-reactive protein concentration was related to total cancer [hazard ratio (HR) 1.35; 95% confidence interval (CI) 1.10–1.65] comparing last quintile to first quintile of CRP. Especially lung cancer, independent of histopathological subtype, was related to CRP (HR 3.39; 95% CI 2.02–5.69 comparing last to first quintile of CRP). Incidence of epithelial neoplasms and especially squamous cell neoplasms were related to CRP concentration, irrespective of anatomical location. Sensitivity analyses after excluding patients with a cancer diagnosis within 1, 2, and 5 years of follow-up showed similar results. No effect modification was observed by smoking status or time since smoking cessation (P-values for interaction > 0.05). Conclusion Chronic systemic low-grade inflammation, measured by CRP levels ≤10 mg/L, is a risk factor for incident cancer, markedly lung cancer, in patients with stable CVD. The relation between inflammation and incident cancer is seen in former and current smokers and is uncertain in never smokers.


2021 ◽  
Vol 23 (Supplement_G) ◽  
Author(s):  
Edoardo Bertero ◽  
Luca Carmisciano ◽  
Christian Jonasson ◽  
Christoph Maack ◽  
Pietro Ameri

Abstract Aims Conflicting data exist regarding the risk of cancer in patients with heart failure (HF). It was first reported that incident cancer is more common among patients with than without HF, whereas more recent studies indicate that this association is primarily driven by comorbidities. HF, cancer, and comorbidities, such as chronic kidney disease (CKD) and chronic obstructive pulmonary disease (COPD), share numerous risk factors, including a state of chronic low-grade inflammation reflected by elevated circulating levels of pro-inflammatory cytokines. The objective of this analysis was to assess whether chronic low-grade inflammation, as measured by levels of high-sensitivity C-reactive protein (hsCRP), and comorbidities mediate the association of HF with incident cancer. Methods We used data from the 3rd wave of the Nord-Trøndelag Health Study (HUNT3), a population-based study that enrolled 50 803 individuals ≥18-year-old between October 2006 and June 2008 in the Nord-Trøndelag County (Norway), and from the administrative health care records of the same region. Associations between baseline characteristics and the development of cancer were assessed using Cox proportional hazards regression models, using time from HUNT3 enrolment as the time scale. Analyses were performed using R statistical software, version 4.0.2. Results In HUNT3, hsCRP was measured in 47 571 individuals at the time of enrolment. Of these, we excluded 2308 patients because of missing information, leaving a cohort of 45 263 subjects. The prevalence of cardiovascular disease, comorbidities, and obesity was progressively higher with increasing concentrations of hsCRP. During a median follow-up of 12 years, there were 66/408 cases of incident cancer in patients with HF at baseline and 5024/47 163 in subjects without HF, with a more than 2-fold (HR 2.30; 95% CI 1.80–2.93; P < 0.001) increase in risk of developing cancer. After adjusting for age and sex, the excess risk decreased to 43% (HR 1.43; 95% CI 1.12–1.82). When including hsCRP in the model, the HF-related risk of cancer was 33% (HR 1.33; 95% CI 1.04–1.70; P = 0.022). Furthermore, when body mass index, CKD, COPD, and smoking and drinking habits were included in the model, the risk of cancer in HF patients compared to individuals without HF was no longer significant (HR 1.23; 95% CI 0.94–1.60; P = 0.127). Age, male sex, hsCRP, COPD, obesity, and smoking habits were all associated with an increased risk of cancer. Conclusions The increased risk of cancer in HF patients compared with the general population is at least in part explained by concomitant inflammation and comorbidities.


2006 ◽  
Vol 130 (1) ◽  
pp. 86-89 ◽  
Author(s):  
Libo Qiu ◽  
Pamela D. Unger ◽  
Robert W. Dillon ◽  
James A. Strauchen

Abstract Low-grade B-cell lymphoma of mucosa-associated lymphoid tissue involving the kidney is rare. We report a series of 3 cases. The first case occurred in an 83-year-old woman who presented with back pain. The second case was a 53-year-old man with a history of sarcoidosis who was found, in the course of evaluation of sarcoidosis, to have a right renal mass. The third case occurred in a 72-year-old man who had a history of periorbital mucosa–associated lymphoid tissue lymphoma and had been treated with surgery and radiation 1 year prior to this presentation. Histologically, all 3 patients showed infiltrate of uniform small-to-medium–sized lymphocytes with irregular nuclear contours and abundant cytoplasm resembling centrocytes or monocytoid lymphoid cells. The first patient received chemotherapy without complications. The second patient underwent a partial nephrectomy and was asymptomatic at the subsequent follow-up. The third patient developed a pulmonary embolism following nephrectomy, and further follow-up is not available.


2021 ◽  
pp. 1-10 ◽  
Author(s):  
Noor Hamdan ◽  
Hugues Duffau

OBJECTIVE Maximal safe resection is the first treatment in diffuse low-grade glioma (DLGG). Due to frequent tumor recurrence, a second surgery has already been reported, with favorable results. This study assesses the feasibility and functional and oncological outcomes of a third surgery in recurrent DLGG. METHODS Patients with DLGG who underwent a third functional-based resection using awake mapping were consecutively selected. They were classified into group 1 in cases of slow tumor regrowth or group 2 if a radiological enhancement occurred during follow-up. All data regarding clinicoradiological features, histomolecular results, oncological treatment, and survival were collected. RESULTS Thirty-one patients were included, with a median age of 32 years. There were 20 astrocytomas and 11 oligodendrogliomas in these patients. Twenty-one patients had medical oncological treatment before the third surgery, consisting of chemotherapy in 19 cases and radiotherapy in 8 cases. No neurological deficit persisted after the third resection except mild missing words in 1 patient, with 84.6% of the patients returning to work. The median follow-up duration was 13.1 ± 3.4 years since diagnosis, and 3.1 ± 2.9 years since the third surgery. The survival rates at 7 and 10 years were 100% and 89.7%, respectively, with an estimated median overall survival of 17.8 years since diagnosis. A comparison between the groups showed that the Karnofsky Performance Scale score dropped below 80 earlier in group 2 (14.3 vs 17.1 years, p = 0.01). Median residual tumor volume at the third surgery was smaller (2.8 vs 14.4 cm3, p = 0.003) with a greater extent of resection (89% vs 70%, p = 0.003) in group 1. CONCLUSIONS This is the first consecutive series showing evidence that, in select patients with progressive DLGG, a third functional-based surgery can be achieved using awake mapping with low neurological risk and a high rate of total resection, especially when reoperation is performed before malignant transformation.


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.


2020 ◽  
Vol 76 (5) ◽  
pp. 304-312
Author(s):  
Tengfei Lin ◽  
Chonglei Bi ◽  
Yun Song ◽  
Huiyuan Guo ◽  
Lishun Liu ◽  
...  

<b><i>Objective:</i></b> The association between plasma magnesium and risk of incident cancer remains inconclusive in previous studies. We aimed to investigate the prospective relationship of baseline plasma magnesium concentrations with the risk of incident cancer and to examine possible effect modifiers. <b><i>Methods:</i></b> A nested case-control study with 228 incident cancer cases and 228 matched controls was conducted using data from the China Stroke Primary Prevention Trial (CSPPT), a randomized, double-blind, controlled trial, conducted from May 2008 to August 2013. Study outcomes included incident cancer and its subtypes. <b><i>Results:</i></b> When plasma magnesium concentrations were assessed as quartiles, a significantly higher incident risk of total cancer was found in participants in quartile 1 (&#x3c;0.76 mmol/L; odds ratio [OR] = 2.70; 95% CI: 1.33–5.49) and quartile 4 (≥0.89 mmol/L; OR = 2.05; 95% CI: 1.12–3.76), compared with those in quartile 3 (0.83 to &#x3c;0.89 mmol/L). In cancer site-specific analyses, similar trends were found for gastrointestinal cancer, esophageal cancer, gastric cancer, breast cancer, lung cancer, and other cancers. Furthermore, none of the variables, including age, sex, current smoking status, current alcohol intake, BMI, systolic blood pressure, and total cholesterol levels at baseline significantly modified the association between plasma magnesium and cancer risk. <b><i>Conclusions:</i></b> Both low and high plasma magnesium concentrations were significantly associated with an increased incident risk of cancer, compared with the reference concentrations of 0.83 to &#x3c;0.89 mmol/L among hypertensive adults.


2020 ◽  
Vol 21 (12) ◽  
pp. 4459 ◽  
Author(s):  
Andrea Baragetti ◽  
Alberico Luigi Catapano ◽  
Paolo Magni

Chronic low-grade inflammation, through the specific activation of the NACHT leucine-rich repeat- and PYD-containing (NLRP)3 inflammasome-interleukin (IL)-1β pathway, is an important contributor to the development of atherosclerotic cardiovascular disease (ASCVD), being triggered by intracellular cholesterol accumulation within cells. Within this pathological context, this complex pathway is activated by a number of factors, such as unhealthy nutrition, altered gut and oral microbiota, and elevated cholesterol itself. Moreover, evidence from autoinflammatory diseases, like psoriasis and others, which are also associated with higher cardiovascular disease (CVD) risk, suggests that variants of NLRP3 pathway-related genes (like NLRP3 itself, caspase recruitment domain-containing protein (CARD)8, caspase-1 and IL-1β) may carry gain-of-function mutations leading, in some individuals, to a constitutive pro-inflammatory pattern. Indeed, some reports have recently associated the presence of specific single nucleotide polymorphisms (SNPs) on such genes with greater ASCVD prevalence. Based on these observations, a potential effective strategy in this context may be the identification of carriers of these NLRP3-related SNPs, to generate a genomic score, potentially useful for a better CVD risk prediction, and, possibly, for personalized therapeutic approaches targeted to the NLRP3-IL-1β pathway.


2010 ◽  
Vol 24 (4) ◽  
pp. 239-244 ◽  
Author(s):  
Mayur Brahmania ◽  
Eric Lam ◽  
Jennifer Telford ◽  
Robert Enns

BACKGROUND: Endoscopic mucosal resection (EMR) has been proposed as a primary method of managing patients with dysplasia- or mucosal-based cancers of the esophagus.OBJECTIVES: To evaluate the use of EMR for the treatment of Barrett’s esophagus with dysplasia or early adenocarcinoma, assessing efficacy, complication rates and long-term outcomes.METHODS: All patients who underwent EMR at St Paul’s Hospital (Vancouver, British Columbia) were reviewed. Eligible patients were assessed with aggressive biopsy protocols. Detected cancers were staged with both endoscopic ultrasound imaging and computed tomography. Appropriate patients were offered EMR using a commercially available mucosectomy device. EMR was repeated at six- to eight-week intervals until complete. Patients with less than one year of follow-up or who were undergoing other ablative methods were excluded.RESULTS: Twenty-two patients (all men) with a mean (± SD) age of 67±10.6 years were identified. The mean duration of gastroesophageal reflux disease was 17 years (range four to 40 years) and all were receiving proton pump inhibitor therapy. The mean length of Barrett’s esophagus was 5.5±3.5 cm. One patient had no dysplasia (isolated nodule), three had low-grade dysplasia, 15 had high-grade dysplasia (HGD) and three had adenocarcinoma. A mean of 1.7±0.83 endoscopic sessions were performed, with a mean of 6±5.4 sections removed. Following EMR, three patients developed strictures; two of these patients had pre-existing strictures and the third required two dilations, which resolved his symptoms. There were no other complications. Three patients underwent esophagectomy. Two had adenocarcinoma or HGD in a pre-existing stricture. The third patient had an adenocarcinoma not amenable to EMR. One patient with a long segment of Barrett’s esophagus underwent radiofrequency ablation. At a median follow-up of two years (range one to three years), the remaining 18 patients (82%) had no evidence of HGD or cancer.CONCLUSION: Most patients with esophageal dysplasia can be managed with EMR. Individuals with pre-existing strictures require other endoscopic and/or surgical methods to manage their dysplasia or adenocarcinoma.


Diabetologia ◽  
2019 ◽  
Vol 63 (2) ◽  
pp. 253-260 ◽  
Author(s):  
Martijn C. G. J. Brouwers ◽  
Nynke Simons ◽  
Coen D. A. Stehouwer ◽  
Aaron Isaacs

Abstract Non-alcoholic fatty liver disease (NAFLD) is highly prevalent among individuals with type 2 diabetes. Although epidemiological studies have shown that NAFLD is associated with cardiovascular disease (CVD), it remains unknown whether NAFLD is an active contributor or an innocent bystander. Plasma lipids, low-grade inflammation, impaired fibrinolysis and hepatokines are potential mediators of the relationship between NAFLD and CVD. The Mendelian randomisation approach can help to make causal inferences. Studies that used common variants in PNPLA3, TM6SF2 and GCKR as instruments to investigate the relationship between NAFLD and coronary artery disease (CAD) have reported contrasting results. Variants in PNPLA3 and TM6SF2 were found to protect against CAD, whereas variants in GCKR were positively associated with CAD. Since all three genes have been associated with non-alcoholic steatohepatitis, the second stage of NAFLD, the question of whether low-grade inflammation is an important mediator of the relationship between NAFLD and CAD arises. In contrast, the differential effects of these genes on plasma lipids (i.e. lipid-lowering for PNPLA3 and TM6SF2, and lipid-raising for GCKR) strongly suggest that plasma lipids account for their differential effects on CAD risk. This concept has recently been confirmed in an extended set of 12 NAFLD susceptibility genes. From these studies it appears that plasma lipids are an important mediator between NAFLD and CVD risk. These findings have important clinical implications, particularly for the design of anti-NAFLD drugs that also affect lipid metabolism.


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