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 Association of Blood Eosinophil and Blood Neutrophil Counts with Asthma Exacerbations in the Copenhagen General Population Study

2017 ◽  
Vol 63 (4) ◽  
pp. 823-832 ◽  
Author(s):  
Signe Vedel-Krogh ◽  
Sune Fallgaard Nielsen ◽  
Peter Lange ◽  
Jørgen Vestbo ◽  
Børge Grønne Nordestgaard
Keyword(s):  
General Population ◽  
Disease Severity ◽  
Population Study ◽  
Blood Eosinophil ◽  
Blood Neutrophil ◽  
General Population Study ◽  
Asthma Exacerbations ◽  
Increased Risk ◽  
Blood Neutrophils ◽  
Eosinophil Counts

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.

Triglycerides and remnant cholesterol associated with risk of aortic valve stenosis: Mendelian randomization in the Copenhagen General Population Study

2020 ◽  
Vol 41 (24) ◽  
pp. 2288-2299 ◽  
Author(s):  
Morten Kaltoft ◽  
Anne Langsted ◽  
Børge G Nordestgaard
Keyword(s):  
Aortic Valve ◽  
General Population ◽  
Aortic Valve Stenosis ◽  
Population Study ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
General Population Study ◽  
Plasma Triglycerides ◽  
Increased Risk ◽  
Remnant Cholesterol

Abstract Aims We tested the hypothesis that higher levels of plasma triglycerides and remnant cholesterol are observationally and genetically associated with increased risk of aortic valve stenosis. Methods and results We included 108 559 individuals from the Copenhagen General Population Study. Plasma triglycerides, remnant cholesterol (total cholesterol minus low-density lipoprotein and high-density lipoprotein cholesterol), and 16 genetic variants causing such increased or decreased levels were determined. Incident aortic valve stenosis occurred in 1593 individuals. Observationally compared to individuals with triglycerides <1 mmol/L (<89 mg/dL), the multifactorially adjusted hazard ratio for aortic valve stenosis was 1.02 [95% confidence interval (CI) 0.87–1.19] for individuals with triglycerides of 1.0–1.9 mmol/L (89–176 mg/dL), 1.22 (1.02–1.46) for 2.0–2.9 mmol/L (177–265 mg/dL), 1.40 (1.11–1.77) for 3.0–3.9 mmol/L (266–353 mg/dL), 1.29 (0.88–1.90) for 4.0–4.9 mmol/L (354–442 mg/dL), and 1.52 (1.02–2.27) for individuals with triglycerides ≥5 mmol/L (≥443 mg/dL). By age 85, the cumulative incidence of aortic valve stenosis was 5.1% for individuals with plasma triglycerides <2.0 mmol/L (77 mg/dL), 6.5% at 2.0–4.9 mmol/L (177–442 mg/dL), and 8.2% for individuals with plasma triglycerides ≥5.0 mmol/L (443 mg/dL). The corresponding values for remnant cholesterol categories were 4.8% for <0.5 mmol/L (19 mg/dL), 5.6% for 0.5–1.4 mmol/L (19–57 mg/dL), and 7.4% for ≥1.5 mmol/L (58 mg/dL). Genetically, compared to individuals with allele score 13–16, odds ratios for aortic valve stenosis were 1.30 (95% CI 1.20–1.42; Δtriglycerides +12%; Δremnant cholesterol +11%) for allele score 17–18, 1.41 (1.31–1.52; +25%; +22%) for allele score 19–20, and 1.51 (1.22–1.86; +51%; +44%) for individuals with allele score 21–23. Conclusion Higher triglycerides and remnant cholesterol were observationally and genetically associated with increased risk of aortic valve stenosis.

scholarly journals The Association between Circulating Inflammatory Markers and Metabolic Syndrome: A General Population Study

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 4305-4305
Author(s):  
Kasper Mønsted Pedersen ◽  
Sabrina Cordua ◽  
Hans Carl Hasselbalch ◽  
Christina Ellervik
Keyword(s):  
Metabolic Syndrome ◽  
General Population ◽  
Chronic Inflammation ◽  
Population Study ◽  
Inflammatory Diseases ◽  
Density Lipoprotein ◽  
Metabolic Disturbances ◽  
General Population Study ◽  
The Metabolic Syndrome ◽  
Increased Risk

Abstract INTRODUCTION Chronic inflammation has recently been proposed as the driving force for the development of the Philadelphia chromosome-negative myeloproliferative neoplasms (MPNs). Chronic inflammation is associated with various metabolic disturbances and may also contribute to the massive comorbidity burden in MPNs, which include e.g. inflammatory bowel diseases (Crohn's disease and ulcerative colitis) and polymyalgia rheumatica. Accordingly, MPNs have also been described as "inflammatory diseases". The metabolic syndrome has so far not been shown to be prevalent in patients with MPNs although the chronic inflammatory state might induce insulin resistance as in other chronic inflammatory diseases. If MPNs indeed are preceded by a chronic inflammatory drive eliciting persistent leukocytosis, monocytosis and thrombocytosis, and ultimately clonal myeloproliferation it is intriguing to consider if MPNs and metabolic syndrome share common pathways. If so, an MPN-phenotype might be expected to be associated with metabolic syndrome in the background population. Therefore, in this study, we tested the association between circulating inflammatory markers (CIMs), a phenotypical presentation of MPNs (e.g. erythrocytosis, leukocytosis, and thrombocytosis), and the metabolic syndrome in a general population study. METHODS Data sources In this cross-sectional study, we used data from 20,872 individuals from the Danish General Suburban Population Study (GESUS). Individuals were invited between January 2010 and October 2013 and data were collected through questionnaires, health examinations, and biochemical measurements. Analyses We analyzed eight CIMs (leukocytes, neutrophils, monocytes, thrombocytes, erythrocytes, hematocrit, hemoglobin, and high-sensitive CRP) and their linear association with indicators of the metabolic syndrome (according to a modified version of the US National Cholesterol Education Program Adult Treatment Panel III): HbA1c, non-fasting plasma glucose, body mass index, blood pressure, cholesterol, low-density lipoprotein, high-density lipoprotein, and triglycerides. With logistic regression, we calculated odds ratios (ORs) of metabolic syndrome in individuals with increased levels of CIMs compared to individuals with normal levels based on current Danish reference ranges. RESULTS In general, there was a positive correlation between most CIMs and indicators of the metabolic syndrome both in the age-sex-adjusted and multivariable linear regression analyses. In the age-sex-adjusted logistic regression analyses, increased levels of all CIMs were associated with increased prevalence of dyslipidemia (OR: 1.4-2.2), hypertension (OR: 1.3-3.1), diabetes mellitus (OR: 1.5-3.4), obesity (1.4-4.6), and the metabolic syndrome (OR: 1.4-2.8). However, neutrophils and thrombocytes were not significant when it came to hypertension and diabetes mellitus, respectively (Table 1). DISCUSSION & CONCLUSION In this study we examined the association between different CIMs and a wide variety of metabolic changes. To our knowledge it is the first comprehensive epidemiological study linking the phenotypical presentation of MPNs in a general population of more than 20.000 individuals with a broad spectrum of metabolic disturbances. With chronic inflammation being proposed as a trigger and consequence of both MPNs and metabolic syndrome and considering the results in the present study it is intriguing to postulate chronic inflammation as the common denominator in both metabolic syndrome leading to MPNs and MPNs leading to metabolic syndrome(Figure 1). It is of great clinical interest to investigate if an increased risk of metabolic syndrome exists in e.g. a cohort of MPN patients and whether people with incident metabolic syndrome have increased risk of MPNs and second cancer. An increased prevalence of a wide variety of metabolic disturbances following increased CIMs could potentially, if similar results are found in the MPN population, support a future change in the MPN-risk stratification. Amongst the tested CIMs only thrombocytes (> 1500 Mia/L) are currently used as a risk factor. In conclusion, elevated levels of CIMs were associated with an increased prevalence of metabolic disturbances. Our results substantiate the need for similar studies in MPN patients, being characterized by chronic inflammation and elevated cell counts. Disclosures Hasselbalch: Novartis: Research Funding.

Increased Risk of Breast Cancer Associated With CHEK2*1100delC

2007 ◽  
Vol 26 (1) ◽  
pp. 57-63 ◽  
Author(s):  
Maren Weischer ◽  
Stig Egil Bojesen ◽  
Anne Tybjærg-Hansen ◽  
Christen Kirk Axelsson ◽  
Børge Grønne Nordestgaard
Keyword(s):  
Breast Cancer ◽  
Colorectal Cancer ◽  
General Population ◽  
Prospective Study ◽  
Case Control Study ◽  
Case Control ◽  
Chek2 1100Delc ◽  
Increased Risk ◽  
Risk Of Cancer ◽  
Control Study

Purpose CHEK2*1100delC heterozygosity has been associated with increased risk of breast, prostate, and colorectal cancer in case-control studies. We tested the hypothesis that CHEK2*1100delC heterozygosity in the general population increases the risk of cancer in general, and breast, prostate, and colorectal cancer in particular. Patients and Methods We performed a prospective study of 9,231 individuals from the Danish general population, who were observed for 34 years, and we performed a case-control study including 1,101 cases of breast cancer and 4,665 controls. Results Of the general population, 0.5% were heterozygotes and 99.5% were noncarriers. In the prospective study, multifactorially adjusted hazard ratios by CHEK2*1100delC heterozygosity versus noncarriers were 1.2 (95% CI, 0.7 to 2.1) for all cancers, 3.2 (95% CI, 1.0 to 9.9) for breast cancer, 2.3 (95% CI, 0.6 to 9.5) for prostate cancer, and 1.6 (95% CI, 0.4 to 6.5) for colorectal cancer. In the case-control study, age-matched odds ratio for breast cancer by CHEK2*1100delC heterozygosity versus noncarriers was 2.6 (95% CI, 1.3 to 5.4). The absolute 10-year risk of breast cancer in CHEK2*1100delC heterozygotes amounted to 24% in women older than 60 years undergoing hormone replacement therapy, with a body mass index of 25 kg/m2 or higher. Conclusion CHEK2*1100delC heterozygosity is associated with a three-fold risk of breast cancer in women in the general population.

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.

scholarly journals Increased Rheumatoid Factor and Deep Venous Thrombosis: 2 Cohort Studies of 54628 Individuals from the General Population

2015 ◽  
Vol 61 (2) ◽  
pp. 349-359 ◽  
Author(s):  
Christine L Meyer-Olesen ◽  
Sune F Nielsen ◽  
Børge G Nordestgaard
Keyword(s):  
General Population ◽  
Rheumatic Disease ◽  
Venous Thrombosis ◽  
Deep Venous Thrombosis ◽  
Rheumatoid Factor ◽  
General Population Study ◽  
Autoimmune Rheumatic Disease ◽  
Hazard Ratios ◽  
Increased Risk

Abstract BACKGROUND The risk of deep venous thrombosis is increased in patients with rheumatoid arthritis. We tested the hypothesis that increased concentrations of rheumatoid factor are associated with increased risk of deep venous thrombosis in individuals without autoimmune rheumatic disease in the general population. METHODS We included 54628 participants from the Copenhagen City Heart Study (1981–83) and the Copenhagen General Population Study (2004–12), all with a measured concentration of IgM rheumatoid factor and without autoimmune rheumatic disease or venous thromboembolism. The main outcome was incident deep venous thrombosis. There were no losses to follow-up. RESULTS During 368381 person-years, 670 individuals developed deep venous thrombosis. A rheumatoid factor concentration ≥ vs <110 IU/mL showed the strongest association with deep venous thrombosis, with multivariable adjusted hazard ratios of 9.0 (95% CI 3.1–26) for 1-year follow-up, 4.3 (2.2–8.5) for 5-year follow-up, and 3.1 (1.7–5.6) for up to 32 years of follow-up. Compared with rheumatoid factor concentrations <15 IU/mL, the multivariable adjusted hazard ratios for deep venous thrombosis during maximum follow-up were 1.3 (1.0–1.5) for 15–29 IU/mL, 1.7 (1.0–2.8) for 30–59 IU/mL, 2.4 (1.3–4.3) for 60–119 IU/mL, and 3.0 (1.6–5.6) for ≥120 IU/mL (trend P = 6 × 10−7). Results were similar in the 2 studies separately. Obese men and women age >60 years with rheumatoid factor concentrations ≥120 IU/mL had 10% and 8% 5-year risk of deep venous thrombosis. CONCLUSIONS Increased rheumatoid factor in the general population was associated with up to 3-fold increased long-term risk and up to 9-fold increased 1-year risk of deep venous thrombosis.

scholarly journals Total Mortality by Transferrin Saturation Levels: Two General Population Studies and a Metaanalysis

2011 ◽  
Vol 57 (3) ◽  
pp. 459-466 ◽  
Author(s):  
Christina Ellervik ◽  
Anne Tybjærg-Hansen ◽  
Børge G Nordestgaard
Keyword(s):  
General Population ◽  
Population Study ◽  
Fixed Effects ◽  
Hereditary Hemochromatosis ◽  
Population Attributable Risk ◽  
Transferrin Saturation ◽  
Total Mortality ◽  
General Population Study ◽  
Increased Risk

BACKGROUND There is evidence for increased mortality in patients with clinically overt hereditary hemochromatosis. Whether increased transferrin saturation (TS), as a proxy for iron overload is associated with increased mortality in the general population is largely unknown. METHODS We examined mortality according to baseline TS in 2 Danish population–based follow-up studies (the Copenhagen General Population Study and the Copenhagen City Heart Study) comprising a total of 45 159 individuals, of whom 4568 died during up to 18 years of follow-up, and in a metaanalysis comprising the present studies and an additional general population study. RESULTS In combined studies, the cumulative survival was reduced in individuals with TS ≥50% vs <50% (log-rank P < 0.0001). Multifactorially adjusted hazard ratios for total mortality for TS ≥50% vs <50% were 1.4 (95% CI 1.2–1.6; P < 0.001) overall, 1.3 (1.1–1.6; P = 0.003) in men, and 1.5 (1.1–2.0; P = 0.005) in women. Results were similar if the 2 studies were considered separately. A stepwise increased risk of total mortality was observed for stepwise increasing levels of TS (log-rank P < 0.0001), with the highest risk conferred by TS ≥80% vs TS <20% with a hazard ratio of 2.2 (1.4–3.3; P < 0.001). The population-attributable risk for total mortality in the combined studies in individuals with TS ≥50% vs <50% was 0.8%. In metaanalysis, the odds ratio for total mortality for TS ≥50% vs <50% was 1.3 (1.2–1.5; P < 0.001) under the fixed-effects model. CONCLUSIONS Individuals in the general population with TS ≥50% vs <50% have an increased risk of premature death.

Risk of Cancer by ATM Missense Mutations in the General Population

2008 ◽  
Vol 26 (18) ◽  
pp. 3057-3062 ◽  
Author(s):  
Sarah Louise Dombernowsky ◽  
Maren Weischer ◽  
Kristine Højgaard Allin ◽  
Stig Egil Bojesen ◽  
Anne Tybjjrg-Hansen ◽  
...  
Keyword(s):  
Breast Cancer ◽  
General Population ◽  
Cancer Susceptibility ◽  
Endocrine Tumors ◽  
Missense Mutations ◽  
Cancer Subtypes ◽  
Corpus Uteri ◽  
Hazard Ratios ◽  
Increased Risk ◽  
Risk Of Cancer

Purpose Truncating and missense mutations in the ATM gene, which cause insufficient DNA damage surveillance, allow damaged cells to proceed into mitosis, which eventually results in increased cancer susceptibility. We tested the hypotheses that ATM Ser49Cys and ATM Ser707Pro heterozygosity increase the risk of cancer overall, of breast cancer, and of 26 other cancer subtypes in the general population. Patients and Methods We genotyped 10,324 individuals from the Danish general population who were observed prospectively for 36 years, during which 2,056 developed cancer. Results Multifactorially adjusted hazard ratios for ATM Ser49Cys heterozygotes versus noncarriers were 1.2 (95% CI, 0.9 to 1.5) for cancer overall, 0.8 (95% CI, 0.3 to 2.0) for breast cancer, 4.8 (95% CI, 2.2 to 11) for melanoma, 2.3 (95% CI, 1.1 to 5.0) for prostate cancer, and 3.4 (95% CI, 1.1 to 11) for cancer of the oral cavity/pharynx. Multifactorially adjusted hazard ratios for ATM Ser707Pro heterozygotes versus noncarriers were 0.8 (95% CI, 0.6 to 1.2) for cancer overall, 0.6 (95% CI, 0.2 to 1.6) for breast cancer, 10 (95% CI, 1.1 to 93) for thyroid/other endocrine tumors, and 2.7 (95% CI, 1.0 to 7.6) for cancer of corpus uteri. Conclusion ATM missense mutations do not increase the risk of cancer overall or of breast cancer in the general population; however, we observed in exploratory analyses that ATM missense mutations may be associated with an increased risk of other cancer subtypes. As we did multiple comparisons, some of these findings could represent chance findings rather than real phenomena.

scholarly journals Increased Baseline C-Reactive Protein Concentrations Are Associated with Increased Risk of Infections: Results from 2 Large Danish Population Cohorts

2016 ◽  
Vol 62 (2) ◽  
pp. 335-342 ◽  
Author(s):  
Jeppe Zacho ◽  
Thomas Benfield ◽  
Anne Tybjærg-Hansen ◽  
Børge G Nordestgaard
Keyword(s):  
Infectious Disease ◽  
General Population ◽  
Population Study ◽  
C Reactive Protein ◽  
Cross Sectional ◽  
General Population Study ◽  
Gram Negative ◽  
Reactive Protein ◽  
Increased Risk ◽  
General Population Cohort

AbstractBACKGROUNDThe acute-phase reactant C-reactive protein (CRP) increases rapidly during an infection. We tested the hypothesis that chronic low-level increases in CRP are associated with an increased risk of infectious disease.METHODSWe studied 9660 individuals from a prospective general population cohort, including 3592 in whom infectious disease developed, and another 60 896 individuals from a cross-sectional general population study, of whom 13 332 developed infectious disease; 55% were women, and the mean age was 57 years. Hospital diagnoses of infections in 1977–2010 were based on International Classification of Diseases–coded discharge records from the national Danish Patient Registry. We measured CRP concentrations and conducted genotyping for 4 CRP polymorphisms that increase CRP. Individuals with CRP >10 mg/L were excluded because of possible ongoing infection at the time of testing.RESULTSIndividuals with CRP >3 mg/L had 1.2 and 1.7 times increased risk of infectious disease, in the prospective general population cohort and the cross-sectional general population study, respectively, compared with individuals with CRP <1 mg/L. In the combined populations, individuals in the highest CRP tertile (compared with the lowest) had an increased risk of bacterial diseases (hazard ratio 1.7, 95% CI 1.6–1.8), but not viral, mycosis, and parasitic diseases. The increased risk was mainly carried by pneumonia, sepsis, and particularly gram-negative infections. None of the genotype combinations examined conferred an increased risk of infectious disease.CONCLUSIONSChronic low-level CRP increases were associated with increased risk of bacterial infections, gram-negative infections in particular. Genotypes associated with increases in CRP were not associated with increased risk of infection.

scholarly journals Remnant Cholesterol and Myocardial Infarction in Normal Weight, Overweight, and Obese Individuals from the Copenhagen General Population Study

2018 ◽  
Vol 64 (1) ◽  
pp. 219-230 ◽  
Author(s):  
Anette Varbo ◽  
Jacob J Freiberg ◽  
Børge G Nordestgaard
Keyword(s):  
Myocardial Infarction ◽  
Body Mass Index ◽  
Risk Factor ◽  
General Population ◽  
Population Study ◽  
Normal Weight ◽  
Overweight And Obesity ◽  
General Population Study ◽  
Hazard Ratios ◽  
Remnant Cholesterol

Abstract BACKGROUND We tested whether high remnant cholesterol is associated with high myocardial infarction risk, independent of whether an individual is normal weight, overweight, or obese. METHODS A total of 106216 individuals from the Copenhagen General Population Study were followed for up to 11 years, during which 1565 experienced a myocardial infarction. Individuals were grouped by clinically meaningful remnant cholesterol concentrations of <0.5 mmol/L (19 mg/dL), 0.5 to 0.99 mmol/L (19–38 mg/dL), 1.0 to 1.49 mmol/L (39–58 mg/dL), and ≥1.5 mmol/L (58 mg/dL), and by body mass index (BMI) of <18.5 kg/m2 (underweight), 18.5 to 24.9 kg/m2 (normal weight), 25 to 29.9 kg/m2 (overweight), and ≥30 kg/m2 (obese). RESULTS Median calculated remnant cholesterol was 0.40 mmol/L [interquartile range (IQR), 0.30–0.55 mmol/L] [15 mg/dL (12–21 mg/dL)] for underweight, 0.50 mmol/L (IQR, 0.37–0.71 mmol/L) [19 mg/dL (14–27 mg/dL)] for normal weight, 0.70 mmol/L (IQR, 0.49–1.00 mmol/L) [27 mg/dL (19–39 mg/dL)] for overweight, and 0.85 mmol/L (IQR, 0.61–1.20 mmol/L) [(33 mg/dL (24–46 mg/dL)] for obese individuals. On continuous scales, remnant cholesterol was positively correlated with BMI until reaching a plateau of approximately 1 mmol/L (39 mg/dL) at BMI >35 kg/m2. R2 from an unadjusted linear regression for the correlation between calculated remnant cholesterol and BMI was 12%. Stepwise higher remnant cholesterol was associated with stepwise higher myocardial infarction risk in a similar pattern for normal weight, overweight, and obese individuals. When compared with individuals with remnant cholesterol <0.5 mmol/L (19 mg/dL), individuals with remnant cholesterol ≥1.5 mmol/L (58 mg/dL) had hazard ratios for myocardial infarction of 2.0 (95% CI, 1.3–3.2) for normal weight, 1.9 (95% CI, 1.4–2.6) for overweight, and 2.3 (95% CI, 1.4–3.5) for obese individuals. Directly measured remnant cholesterol increased 0.91 mmol/L (95% CI, 0.89–0.94 mmol/L) [35 mg/dL (34–36 mg/dL)] per 1 mmol/L (39 mg/dL) increase in calculated remnant cholesterol. CONCLUSIONS Remnant cholesterol and BMI were positively correlated; however, high remnant cholesterol was associated with higher myocardial infarction risk across the examined BMI subcategories, indicating that remnant cholesterol is a risk factor for myocardial infarction independent of overweight and obesity.

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