scholarly journals Low-Grade Inflammation in the Association between Mild-to-Moderate Hypertriglyceridemia and Risk of Acute Pancreatitis: A Study of More Than 115000 Individuals from the General Population

2019 ◽  
Vol 65 (2) ◽  
pp. 321-332 ◽  
Author(s):  
Signe E J Hansen ◽  
Christian M Madsen ◽  
Anette Varbo ◽  
Børge G Nordestgaard
Keyword(s):  
Acute Pancreatitis ◽  
General Population ◽  
Low Grade ◽  
General Population Study ◽  
Reactive Protein ◽  
Hazard Ratios ◽  
Heart Study ◽  
Blood Leukocyte ◽  
Low Grade Inflammation ◽  
Multivariable Adjustment

Abstract BACKGROUND How mild-to-moderate hypertriglyceridemia (2–10 mmol/L; 177–886 mg/dL) potentially causes acute pancreatitis is unknown; however, cellular studies indicate that inflammation might be a driver of disease progression. We tested the hypotheses that (a) mild-to-moderate hypertriglyceridemia is associated with low-grade inflammation and that (b) the association between mild-to-moderate hypertriglyceridemia and risk of acute pancreatitis depends on low-grade inflammation. METHODS From the Copenhagen General Population Study and the Copenhagen City Heart Study, 117865 men and women 20–100+ years of age with measurements of nonfasting plasma triglycerides at baseline were followed prospectively for development of acute pancreatitis. RESULTS After multivariable adjustment, a 1 mmol/L (89 mg/dL) higher nonfasting triglyceride concentration was associated with 17% (95% CI, 16%–18%, P = 3 × 10−17) higher plasma C-reactive protein (CRP) and a 4.2% (4.0%–4.4%, P = 6 × 10−17) higher blood leukocyte count. Higher concentrations of nonfasting triglycerides were associated almost linearly with higher risk of acute pancreatitis (P for trend = 5 × 10−6), with hazard ratios of 1.5 (95% CI, 0.9–2.5), 2.0 (95% CI, 1.1–3.6), 2.2 (95% CI, 1.0–4.7), 4.2 (95% CI, 1.6–11.5), and 7.7 (95% CI, 3.0–19.8) in individuals with nonfasting triglycerides of 1.00–1.99 mmol/L (89–176 mg/dL; 46% of the population), 2.00–2.99 mmol/L (177–265 mg/dL; 17%), 3.00–3.99 mmol/L (266–353 mg/dL; 6%), 4.00–4.99 mmol/L (354–442 mg/dL; 2%), and ≥5mmol/L(443 mg/dL; 2%), respectively, vs individuals with <1 mmol/L (89 mg/dL; 27%). The association with risk of acute pancreatitis appeared more pronounced in individuals with CRP of ≥1.39 mg/L (P for trend = 0.001) and leukocytes of ≥7 × 109/L (P = 2 × 10−4) than in those with CRP <1.39 mg/L (P = 0.03) and leukocytes <7 × 109/L (P = 0.04); however, there was no formal evidence of statistical interaction (P = 0.38 for CRP and P = 0.41 for leukocytes). CONCLUSIONS Mild-to-moderate hypertriglyceridemia is associated with low-grade inflammation and higher risk of acute pancreatitis. The association between mild-to-moderate hypertriglyceridemia and risk of acute pancreatitis is possibly partly mediated by low-grade inflammation.

scholarly journals Serum Soluble CD163 Predicts Risk of Type 2 Diabetes in the General Population

2011 ◽  
Vol 57 (2) ◽  
pp. 291-297 ◽  
Author(s):  
Holger J Møller ◽  
Ruth Frikke-Schmidt ◽  
Søren K Moestrup ◽  
Børge G Nordestgaard ◽  
Anne Tybjærg-Hansen
Keyword(s):  
Type 2 Diabetes ◽  
General Population ◽  
Low Grade ◽  
Reactive Protein ◽  
Soluble Cd163 ◽  
Hazard Ratios ◽  
Heart Study ◽  
Increased Risk ◽  
Study Participants

BACKGROUND Activation of adipose tissue macrophages with concomitant low-grade inflammation is believed to play a central role in the development of type 2 diabetes. We tested whether a new macrophage-derived biomarker, soluble CD163 (sCD163), identifies at-risk individuals before overt disease has developed. METHODS A prospective cohort study of 8849 study participants from the general population, the Copenhagen City Heart Study, was followed for 18 years for incidence of type 2 diabetes. Risk of disease was calculated according to age- and sex-adjusted percentile categories of serum sCD163 concentrations: 0%–33%, 34%–66%, 67%–90%, 91%–95%, and 96%–100%. RESULTS A total of 568 participants developed type 2 diabetes. The cumulative incidence increased with increasing baseline sCD163 (trend P < 0.001), and sCD163 was strongly associated with known risk factors such as physical inactivity, body mass index, C-reactive protein, and triglycerides (all P < 0.001). Multifactorially adjusted hazard ratios for type 2 diabetes were 1.4 (95% CI, 1.0–1.9), 2.4 (1.8–3.2), 3.8 (2.6–5.5), and 5.2 (3.6–7.6) for categories 34%–66%, 67%–90%, 91%–95%, and 96%–100%, respectively, vs the 0%–33% category. In overweight men 50–70 and >70 years of age, serum sCD163 concentrations in the top 5% group predicted an absolute 10-year risk of type 2 diabetes of 29% and 36% vs 7% and 8% in the lowest percentile group. Equivalent values in women were 19% and 24% vs 4% and 5%. CONCLUSIONS Increased concentrations of sCD163 predict increased risk of type 2 diabetes in the general population and may be useful for identification of high-risk overweight individuals.

scholarly journals Complement C3 and Risk of Diabetic Microvascular Disease: A Cohort Study of 95202 Individuals from the General Population

2018 ◽  
Vol 64 (7) ◽  
pp. 1113-1124 ◽  
Author(s):  
Katrine Laura Rasmussen ◽  
Børge Grønne Nordestgaard ◽  
Sune Fallgaard Nielsen
Keyword(s):  
Diabetic Retinopathy ◽  
General Population ◽  
Microvascular Disease ◽  
Complement C3 ◽  
General Population Study ◽  
Hazard Ratios ◽  
Genome Wide ◽  
Heart Study ◽  
Increased Risk ◽  
High Concentrations

Abstract BACKGROUND Whether the complement system is involved in the development of diabetic microvascular disease is unknown. We tested the hypothesis that high concentrations of complement C3 are associated with increased risk of diabetic retinopathy, nephropathy, and neuropathy in individuals from the general population. METHODS We studied 95202 individuals from the general population with baseline measurements of complement C3, genotyped for rs1065489, rs429608, and rs448260 determining concentrations of complement C3, and enrolled in the Copenhagen General Population Study from 2003 through 2013, following them until April 10, 2013. Rs1065489, rs429608, and rs448260 were identified with genome-wide association scans in 3752 individuals from the Copenhagen City Heart Study. RESULTS The cumulative incidence was increased from the lowest tertile to the highest tertile of complement C3 for diabetic retinopathy (log-rank trend, P = 1 × 10−20), nephropathy (P = 7 × 10−15), and neuropathy (P = 5 × 10−10). Multifactorially adjusted hazard ratios for a 1 SD higher concentration of complement C3 were 1.87 (95% CI, 1.61–2.18) for diabetic retinopathy, 1.90 (1.62–2.23) for diabetic nephropathy, and 1.56 (1.29–1.89) for diabetic neuropathy. The multifactorially adjusted hazard ratio for individuals with the highest vs lowest tertile of complement C3 was 3.29 (1.78–6.07) for retinopathy, 2.71 (1.42–5.16) for nephropathy, and 2.40 (1.26–4.54) for neuropathy. CONCLUSIONS High baseline concentrations of complement C3 were associated with increased risk of diabetic retinopathy, nephropathy, and neuropathy in individuals from the general population. These epidemiological findings were substantiated by a Mendelian randomization approach, potentially indicating causality.

Body Mass Index, Triglycerides, and Risk of Acute Pancreatitis: A Population-Based Study of 118 000 Individuals

2019 ◽  
Vol 105 (1) ◽  
pp. 163-174 ◽  
Author(s):  
Signe E J Hansen ◽  
Christian M Madsen ◽  
Anette Varbo ◽  
Børge G Nordestgaard
Keyword(s):  
Body Mass Index ◽  
Acute Pancreatitis ◽  
General Population ◽  
Body Mass ◽  
Population Based ◽  
Population Based Study ◽  
General Population Study ◽  
Heart Study ◽  
Adjusted Model ◽  
Multivariable Adjusted Model

Abstract Objective The incidence of acute pancreatitis is rising worldwide and currently no curative treatment exists. Clarification of preventable risk factors is important for the reduction of morbidity and mortality from acute pancreatitis. In this study, we tested the hypothesis that the risk of acute pancreatitis associated with body mass index (BMI) is partly mediated through elevated triglycerides. Design We included 118 085 individuals from 2 prospective cohort studies, the Copenhagen City Heart Study and the Copenhagen General Population Study, with BMI measured at baseline. Diagnosis of acute pancreatitis was assessed from the national Danish registries, as hospitalization or death due to acute pancreatitis. Results Higher BMI was associated with higher risk of acute pancreatitis with a multivariable-adjusted hazard ratio of 1.4 (95% CI, 1.1–1.8) for BMI of 25–29.9, 2.1 (1.6–2.9) for BMI of 30–34.9, and 2.8 (1.8–4.3) for BMI > 35, compared with individuals with BMI of 18.5–24.9. Triglycerides mediated 29% (95% CI, 12%–46%; P = 0.001) of the association between BMI and risk of acute pancreatitis in the age- and sex-adjusted model and 22% (6%–39%; P = 0.008) in the multivariable-adjusted model. Conclusion Higher BMI is associated with higher risk of acute pancreatitis in individuals from the general population, partly mediated through higher triglycerides. This indicates a potential for preventing acute pancreatitis by reducing BMI and triglycerides in individuals with high values.

Increased Risk for Other Cancers in Addition to Breast Cancer for CHEK2*1100delC Heterozygotes Estimated From the Copenhagen General Population Study

2016 ◽  
Vol 34 (11) ◽  
pp. 1208-1216 ◽  
Author(s):  
Charlotte Näslund-Koch ◽  
Børge G. Nordestgaard ◽  
Stig E. Bojesen
Keyword(s):  
Breast Cancer ◽  
General Population ◽  
Population Study ◽  
Cell Cycle Checkpoint ◽  
Loss Of Function ◽  
General Population Study ◽  
Chek2 1100Delc ◽  
Hazard Ratios ◽  
Increased Risk ◽  
Age And Sex

Purpose CHEK2 is a cell cycle checkpoint regulator, and the CHEK2*1100delC germline mutation leads to loss of function and increased breast cancer risk. It seems plausible that this mutation could also predispose to other cancers. Therefore, we tested the hypothesis that CHEK2*1100delC heterozygosity is associated with increased risk for other cancers in addition to breast cancer in the general population. Patients and Methods We examined 86,975 individuals from the Copenhagen General Population Study, recruited from 2003 through 2010. The participants completed a questionnaire on health and lifestyle, were examined physically, had blood drawn for DNA extraction, were tested for presence of CHEK2*1100delC using Taqman assays and sequencing, and were linked over 1943 through 2011 to the Danish Cancer Registry. Incidences and risks of individual cancer types, including breast cancer, were calculated using Kaplan-Meier estimates, Fine and Gray competing-risks regressions, and stratified analyses with interaction tests. Results Among 86,975 individuals, 670 (0.8%) were CHEK2*1100delC heterozygous, 2,442 developed breast cancer, and 6,635 developed other cancers. The age- and sex-adjusted hazard ratio for CHEK2*1100delC heterozygotes compared with noncarriers was 2.08 (95% CI, 1.51 to 2.85) for breast cancer and 1.45 (95% CI, 1.15 to 1.82) for other cancers. When stratifying for sex, the age-adjusted hazard ratios for other cancers were 1.54 (95% CI, 1.08 to 2.18) for women and 1.37 (95% CI, 1.01 to 1.85) for men (sex difference: P = .63). For CHEK2*1100delC heterozygotes compared with noncarriers, the age- and sex-adjusted hazard ratios were 5.76 (95% CI, 2.12 to 15.6) for stomach cancer, 3.61 (95% CI, 1.33 to 9.79) for kidney cancer, 3.45 (95% CI, 1.09 to 10.9) for sarcoma, and 1.60 (95% CI, 1.00 to 2.56) for prostate cancer. Conclusion CHEK2*1100delC heterozygosity is associated with 15% to 82% increased risk for at least some cancers in addition to breast cancer. This information may be useful in clinical counseling of patients with this loss-of-function mutation.

scholarly journals Dietary Fiber's Effect on High Sensitivity C-reactive Protein Serum in Sedentary Workers

2021 ◽  
Vol 5 (1) ◽  
pp. 40
Author(s):  
Livia Kurniati Saputra ◽  
Dian Novita Chandra ◽  
Ninik Mudjihartini
Keyword(s):  
Body Weight ◽  
High Sensitivity ◽  
The Body ◽  
Low Grade ◽  
C Reactive Protein ◽  
Reactive Protein ◽  
Dietary Fiber Intake ◽  
Anti Inflammatory ◽  
Low Grade Inflammation ◽  
Inflammatory Effect

Low grade inflammation has been recognized of being involved in the pathogenesis of chronic disease pandemic. Individual lifestyle plays a major role in the development of low grade inflammation. Sedentary workers are at risk of low grade inflammation due to the nature of their work. Dietary habit also contributes to inflammatory status in the body. Dietary fiber intake indirectly affects the immune system. It has been hypothesized that fiber has anti-inflammatory effects, both body weight-related and body weight-unrelated This review will focus more on body weight-unrelated anti-inflammatory effect of fiber, especially through fiber’s fermentation metabolites, the short chain fatty acid (SCFA). Its anti-inflammatory effect can be seen by monitoring a biomarker of inflammation in the body, the high sensitivity C-reactive protein (hsCRP). This review’s objective is to cover the mechanisms and role of dietary fiber intake on serum hsCRP level as a marker of low grade inflammation on sedentary workers. 

scholarly journals Metabolic biomarker profiling for identification of susceptibility to severe pneumonia and COVID-19 in the general population

eLife ◽  
2021 ◽  
Vol 10 ◽  
Author(s):  
◽  
Heli Julkunen ◽  
Anna Cichońska ◽  
P Eline Slagboom ◽  
Peter Würtz
Keyword(s):  
General Population ◽  
Disease Onset ◽  
Severe Pneumonia ◽  
Blood Sampling ◽  
Low Grade ◽  
Healthy Individuals ◽  
Metabolic Biomarkers ◽  
Low Grade Inflammation ◽  
Increased Susceptibility

Biomarkers of low-grade inflammation have been associated with susceptibility to a severe infectious disease course, even when measured prior to disease onset. We investigated whether metabolic biomarkers measured by nuclear magnetic resonance (NMR) spectroscopy could be associated with susceptibility to severe pneumonia (2507 hospitalised or fatal cases) and severe COVID-19 (652 hospitalised cases) in 105,146 generally healthy individuals from UK Biobank, with blood samples collected 2007–2010. The overall signature of metabolic biomarker associations was similar for the risk of severe pneumonia and severe COVID-19. A multi-biomarker score, comprised of 25 proteins, fatty acids, amino acids and lipids, was associated equally strongly with enhanced susceptibility to severe COVID-19 (odds ratio 2.9 [95%CI 2.1–3.8] for highest vs lowest quintile) and severe pneumonia events occurring 7–11 years after blood sampling (2.6 [1.7–3.9]). However, the risk for severe pneumonia occurring during the first 2 years after blood sampling for people with elevated levels of the multi-biomarker score was over four times higher than for long-term risk (8.0 [4.1–15.6]). If these hypothesis generating findings on increased susceptibility to severe pneumonia during the first few years after blood sampling extend to severe COVID-19, metabolic biomarker profiling could potentially complement existing tools for identifying individuals at high risk. These results provide novel molecular understanding on how metabolic biomarkers reflect the susceptibility to severe COVID-19 and other infections in the general population.

scholarly journals A Role of Inflammation and Immunity in Essential Hypertension—Modeled and Analyzed Using Petri Nets

2020 ◽  
Vol 21 (9) ◽  
pp. 3348
Author(s):  
Dorota Formanowicz ◽  
Agnieszka Rybarczyk ◽  
Marcin Radom ◽  
Piotr Formanowicz
Keyword(s):  
Essential Hypertension ◽  
Adaptive Immune System ◽  
Low Grade ◽  
Kinin System ◽  
Reactive Protein ◽  
Adaptive Immune ◽  
Key Enzyme ◽  
Kallikrein Kinin System ◽  
Low Grade Inflammation

Recent studies have shown that the innate and adaptive immune system, together with low-grade inflammation, may play an important role in essential hypertension. In this work, to verify the importance of selected factors for the development of essential hypertension, we created a Petri net-based model and analyzed it. The analysis was based mainly on t-invariants, knockouts of selected fragments of the net and its simulations. The blockade of the renin-angiotensin (RAA) system revealed that the most significant effect on the emergence of essential hypertension has RAA activation. This blockade affects: (1) the formation of angiotensin II, (2) inflammatory process (by influencing C-reactive protein (CRP)), (3) the initiation of blood coagulation, (4) bradykinin generation via the kallikrein-kinin system, (5) activation of lymphocytes in hypertension, (6) the participation of TNF alpha in the activation of the acute phase response, and (7) activation of NADPH oxidase—a key enzyme of oxidative stress. On the other hand, we found that the blockade of the activation of the RAA system may not eliminate hypertension that can occur due to disturbances associated with the osmotically independent binding of Na in the interstitium. Moreover, we revealed that inflammation alone is not enough to trigger primary hypertension, but it can coexist with it. We believe that our research may contribute to a better understanding of the pathology of hypertension. It can help identify potential subprocesses, which blocking will allow better control of essential hypertension.

scholarly journals Glucocorticoid Receptor Gene, Low-Grade Inflammation, and Heart Failure: The Heart and Soul Study

2010 ◽  
Vol 95 (6) ◽  
pp. 2885-2891 ◽  
Author(s):  
Christian Otte ◽  
Stefan Wüst ◽  
Shoujun Zhao ◽  
Ludmila Pawlikowska ◽  
Pui-Yan Kwok ◽  
...  
Keyword(s):  
Heart Failure ◽  
Glucocorticoid Receptor ◽  
Systolic Dysfunction ◽  
Left Ventricular ◽  
Left Ventricular Ejection ◽  
Low Grade ◽  
C Reactive Protein ◽  
Reactive Protein ◽  
Glucocorticoid Receptor Gene ◽  
Low Grade Inflammation

Abstract Context: A common haplotype of the glucocorticoid receptor (GR) gene has been associated with increased susceptibility to coronary heart disease (CHD). Whether this haplotype predisposes to heart failure (HF) is unknown. Objective: The objective of the study was to determine whether GR haplotype 3 is associated with HF and whether this association is explained by low-grade inflammation (C-reactive protein). Design: In a prospective cohort study, participants were genotyped for common GR gene polymorphisms (ER22/23EK, BclI C/G, N363S, 9β A/G). Haplotype analyses were conducted. Setting: The study was conducted at one university medical center, two Veterans Affairs medical centers, and nine public health clinics. Patients: Patients included 526 white outpatients with stable CHD. Main Outcome Measures: Echocardiographic evidence of ventricular dysfunction, self-reported heart failure, and subsequent hospitalization for heart failure were measured. Results: After adjusting for age, sex, smoking, and body mass index, participants with two copies of haplotype 3 were more likely than those with 0 or 1 copy to report heart failure [hazard ratio (HR) 4.15, 95% confidence interval (CI) 1.5–11.3, P < 0.01], have systolic dysfunction (left ventricular ejection fraction <50%) (HR 3.0, 95% CI 0.9–9.9, P = 0.07), and be hospitalized for HF during a mean follow-up of 6 yr (HR 3.0, 95% CI 1.3–7.0, P = 0.01). These associations were attenuated after adjustment for higher C-reactive protein levels in patients with two copies of haplotype 3. Conclusions: We found that the GR gene haplotype 3 was associated with prevalent HF, systolic dysfunction, and subsequent HF hospitalization in patients with CHD. This association was partly mediated by low-grade inflammation.

scholarly journals Relationship between Gout and Diabetes Mellitus after Acute Pancreatitis: A Nationwide Cohort Study

2019 ◽  
Vol 47 (6) ◽  
pp. 917-923 ◽  
Author(s):  
Jaelim Cho ◽  
Nicola Dalbeth ◽  
Maxim S. Petrov
Keyword(s):  
Diabetes Mellitus ◽  
Acute Pancreatitis ◽  
Cox Regression ◽  
Social Deprivation ◽  
First Episode ◽  
Low Grade ◽  
Discharge Data ◽  
History Of ◽  
Low Grade Inflammation ◽  
The Relationship

Objective.After acute pancreatitis, individuals often have low-grade inflammation, and subsequently develop metabolic sequelae such as post-pancreatitis diabetes mellitus (PPDM). Although numerous studies have investigated the relationship between gout and type 2 diabetes, little is known about the relationship between gout and PPDM. The aim was to investigate the associations between gout and PPDM.Methods.Using nationwide pharmaceutical dispensing data linked to hospital discharge data in New Zealand, gout and PPDM were identified among individuals after first episode of acute pancreatitis between January 1, 2007, and December 31, 2015. Multivariable Cox regression analyses were conducted, adjusting for age, sex, ethnicity, social deprivation index, alcohol consumption, tobacco smoking, comorbidities, medications (glucocorticoids, statins, and estrogens), and characteristics of acute pancreatitis.Results.A total of 10,117 individuals were included in the analysis of risk for gout and 9471 in the analysis of risk for PPDM. PPDM was significantly associated with a higher risk of gout in the overall cohort (adjusted HR 1.88, 95% CI 1.15–3.06) and women (2.72, 95% CI 1.31–5.65), but not in men (1.42, 95% CI 0.73–2.78). Preexisting gout was significantly associated with a higher risk of PPDM in the overall cohort (adjusted HR 1.58, 95% CI 1.04–2.41) and women (2.66, 95% CI 1.29–5.49), but not in men (1.31, 95% CI 0.78–2.20).Conclusion.The relationship between gout and PPDM is bidirectional in the post-pancreatitis setting. A history of gout is a risk factor of PPDM, particularly in women.

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