Subclinical heart remodeling and dysfunction in relation to peripheral endothelial dysfunction: A general population study

Abstract BACKGROUND Blood eosinophil count is a marker of eosinophilic airway inflammation and disease severity in asthma. However, blood neutrophil count might also be associated with disease severity. We tested the hypothesis that high blood eosinophil and neutrophil counts are both associated with the risk of asthma exacerbations among individuals with asthma from the general population. METHODS From the Copenhagen General Population Study with 81351 participants, we included 4838 with self-reported asthma. We recorded baseline blood eosinophil and neutrophil counts, and asthma exacerbations during follow-up in 2003–2011, defined as moderate (short-course treatment of prednisolone) or severe (hospitalization). RESULTS The multivariable-adjusted incidence rate ratios (IRRs) were 1.28 (95% CI, 1.06–1.55) for moderate exacerbations and 1.55 (1.20–2.00) for severe exacerbations for individuals with blood eosinophil counts >0.29 × 109/L (highest tertile) vs individuals with blood eosinophil counts <0.18 × 109/L (lowest tertile). For blood neutrophils, the multivariable-adjusted IRRs were 2.14 (1.74–2.63) for moderate exacerbations and 1.18 (0.89–1.55) for severe exacerbations for individuals with blood neutrophil counts >4.85 × 109/L (highest tertile) vs individuals with blood neutrophil counts <3.77 × 109/L (lowest tertile). Blood eosinophil and neutrophil counts interacted on moderate exacerbations (P = 3 × 10−4), but not on severe exacerbations. CONCLUSIONS High blood eosinophil counts are associated with an increased risk of both moderate and severe asthma exacerbations, while high blood neutrophil counts are associated with an increased risk of moderate, but not severe exacerbations.

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From Epidemiology to Daily Life: Linking Daily Life Stress Reactivity to Persistence of Psychotic Experiences in a Longitudinal General Population Study

PLoS ONE ◽

10.1371/journal.pone.0062688 ◽

2013 ◽

Vol 8 (4) ◽

pp. e62688 ◽

Cited By ~ 41

Author(s):

Dina Collip ◽

Johanna T. W. Wigman ◽

Inez Myin-Germeys ◽

Nele Jacobs ◽

Catherine Derom ◽

...

Keyword(s):

General Population ◽

Population Study ◽

Life Stress ◽

Stress Reactivity ◽

Daily Life ◽

Psychotic Experiences ◽

General Population Study

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

Journal of Clinical Oncology ◽

10.1200/jco.2015.63.3594 ◽

2016 ◽

Vol 34 (11) ◽

pp. 1208-1216 ◽

Cited By ~ 50

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.

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