Association of Blood Eosinophil and Blood Neutrophil Counts with Asthma Exacerbations in the Copenhagen 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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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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Blood Neutrophil Counts are Associated with Exacerbation Frequency and Mortality in COPD

10.21203/rs.3.rs-16064/v1 ◽

2020 ◽

Author(s):

Mike Lonergan ◽

Alison J Dicker ◽

Megan L Crichton ◽

Holly R Keir ◽

Melissa K. Van Dyke ◽

...

Keyword(s):

Large Population ◽

Real Life ◽

Population Based ◽

Blood Eosinophil ◽

Blood Neutrophil ◽

Disease Heterogeneity ◽

Disease Information ◽

Increased Risk ◽

Eosinophil Counts

Abstract Background Identifying patients with COPD at increased risk of poor outcomes is challenging due to disease heterogeneity. Potential biomarkers need to be readily available in real-life clinical practice. Blood eosinophil counts are widely studied but few studies have examined the prognostic value of blood neutrophil counts (BNC). Methods In a large population-based COPD registry in the East of Scotland (TARDIS: Tayside Allergic and Respiratory Disease Information System), BNC were compared to measures of disease severity and mortality over up to 15 years follow-up. Potential mechanisms of disease modification by BNC were explored in a nested microbiome substudy. Results 178120 neutrophil counts were obtained from 7220 people (mean follow up 9 years) during stable disease periods. Median BNC was 5200cells/µL (IQR 4000-7000cells/µL). Mortality rates among those 34% with elevated BNCs (defined as 6000-15000cells/µL) at the study start were 80% higher (14.0/100 person years v 7.8/100py, P<0.001) than those with BNC in the normal range (2000-6000cells/µL). People with elevated BNC were more likely to be classified as GOLD D (46% v 33% P<0.001), have more exacerbations (mean 2.3 v 1.3/year, P<0.001), and were more likely to have severe exacerbations (13% vs. 5%, P<0.001) in the following year. Eosinophil counts were much less predictive of these outcomes. In a sub-cohort (N=276), patients with elevated BNC had increased relative abundance of Proteobacteria and reduced microbiome diversity. Conclusion High BNC may provide a useful indicator of risk of exacerbations and mortality in COPD patients.

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

European Heart Journal ◽

10.1093/eurheartj/ehaa172 ◽

2020 ◽

Vol 41 (24) ◽

pp. 2288-2299 ◽

Cited By ~ 4

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.

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

Blood ◽

10.1182/blood-2018-99-120356 ◽

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.

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Complement C3 and allergic asthma: A cohort study of the general population

European Respiratory Journal ◽

10.1183/13993003.00645-2020 ◽

2020 ◽

pp. 2000645

Author(s):

Signe Vedel-Krogh ◽

Katrine L. Rasmussen ◽

Børge G. Nordestgaard ◽

Sune F. Nielsen

Keyword(s):

High Risk ◽

General Population ◽

Allergic Asthma ◽

High Plasma ◽

Hazard Ratio ◽

Complement C3 ◽

Blood Eosinophil ◽

High Concentration ◽

General Population Study ◽

Asthma Exacerbations

Complement C3 plays a role in asthma development and severity. We tested the hypothesis that high plasma complement C3 concentration was associated with high risk of asthma hospitalisations and exacerbations.We prospectively assessed the risk of asthma hospitalisations in 101 029 individuals from the Copenhagen General Population Study with baseline measurements of plasma complement C3, and genotyped for rs1065489, rs429608, and rs448260 determining levels of complement C3. Risk of asthma exacerbations was further assessed in 2248 individuals with allergic asthma.The multivariable adjusted hazard ratio of asthma hospitalisations was 1.23(95% confidence interval 1.04–1.45) for individuals in the highest tertile(>1.19 g·L−1) of plasma complement C3 compared with those in the lowest tertile(<1.03 g·L−1). The C3 rs448260 genotype was associated with risk of asthma hospitalisations with an observed hazard ratio of 1.17(1.06–1.28) for the CC genotype compared with the AA genotype. High plasma complement C3 was associated with high levels of blood eosinophils and IgE(p for trends ≤6·10−9), but only the SKIV2L rs429608 genotype was positively associated with blood eosinophil count(p=3·10−4) and level of IgE(p=3·10−4). In allergic asthma, the multivariable adjusted incidence rate ratio for risk of exacerbations was 1.69(1.06–2.72) for individuals in the highest plasma complement C3 tertile(>1.24 g·L−1) versus the lowest(<1.06 g·L−1).In conclusion, high concentration of plasma complement C3 was associated with high risk of asthma hospitalisations in the general population and with high risk of asthma exacerbations in individuals with allergic asthma. Our findings support a causal role of the complement system in asthma severity.

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Blood eosinophil count and risk of pneumonia hospitalisations in individuals with COPD

European Respiratory Journal ◽

10.1183/13993003.00120-2018 ◽

2018 ◽

Vol 51 (5) ◽

pp. 1800120 ◽

Cited By ~ 9

Author(s):

Signe Vedel-Krogh ◽

Børge G. Nordestgaard ◽

Peter Lange ◽

Jørgen Vestbo ◽

Sune F. Nielsen

Keyword(s):

High Risk ◽

General Population ◽

Eosinophil Count ◽

Inhaled Corticosteroids ◽

Chronic Obstructive ◽

Blood Eosinophil ◽

Exacerbation Rate ◽

General Population Study ◽

Blood Eosinophil Count ◽

Eosinophil Counts

Blood eosinophil count in chronic obstructive pulmonary disease (COPD) is associated with higher exacerbation rate and favourable response to corticosteroids; however, frequent exacerbations and use of inhaled corticosteroids could elevate pneumonia risk. We tested the hypothesis that high blood eosinophil counts are associated with high risk of pneumonia in individuals with severe COPD from the general population.We included 7180 individuals with COPD from the Copenhagen General Population Study, including 643 with forced expiratory volume in 1 s (FEV1) <50% predicted between 2003 and 2011. All primary discharge diagnoses of pneumonia during follow-up were recorded.Among individuals with COPD and FEV1<50% pred, the multivariable adjusted incidence rate ratio was 2.17 (95% CI 1.31–3.58) for pneumonia comparing individuals with blood eosinophil counts ≥0.34×109 cells·L−1versus<0.34×109 cells·L−1. In individuals with clinical COPD, defined by recent exacerbation, ≥10 pack-years of smoking and FEV1<70% pred, the corresponding risk was 4.52 (2.11–9.72). Risk of pneumonia did not differ by blood eosinophil count in individuals with COPD and FEV1≥50% pred.In individuals with COPD and FEV1<50% pred, blood eosinophil count ≥0.34×109 cells·L−1was associated with high risk of hospitalisation due to pneumonia.

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

Clinical Chemistry ◽

10.1373/clinchem.2010.156802 ◽

2011 ◽

Vol 57 (3) ◽

pp. 459-466 ◽

Cited By ~ 33

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.

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

Clinical Chemistry ◽

10.1373/clinchem.2015.249680 ◽

2016 ◽

Vol 62 (2) ◽

pp. 335-342 ◽

Cited By ~ 7

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.

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Blood Neutrophil Counts are Associated with Exacerbation Frequency and Mortality in COPD

10.21203/rs.3.rs-16064/v2 ◽

2020 ◽

Author(s):

Mike Lonergan ◽

Alison J Dicker ◽

Megan L Crichton ◽

Holly R Keir ◽

Melissa K. Van Dyke ◽

...

Keyword(s):

Large Population ◽

Real Life ◽

Population Based ◽

Blood Eosinophil ◽

Blood Neutrophil ◽

Disease Heterogeneity ◽

Disease Information ◽

Increased Risk ◽

Eosinophil Counts

Abstract Background: Identifying patients with COPD at increased risk of poor outcomes is challenging due to disease heterogeneity. Potential biomarkers need to be readily available in real-life clinical practice. Blood eosinophil counts are widely studied but few studies have examined the prognostic value of blood neutrophil counts (BNC).Methods: In a large population-based COPD registry in the East of Scotland (TARDIS: Tayside Allergic and Respiratory Disease Information System), BNC were compared to measures of disease severity and mortality for up to 15 years follow-up. Potential mechanisms of disease modification by BNC were explored in a nested microbiome substudy. Results: 178120 neutrophil counts were obtained from 7220 people (mean follow up 9 years) during stable disease periods. Median BNC was 5200cells/µL (IQR 4000-7000cells/µL). Mortality rates among the 34% of patients with elevated BNCs (defined as 6000-15000cells/µL) at the study start were 80% higher (14.0/100 person years v 7.8/100py, P<0.001) than those with BNC in the normal range (2000-6000cells/µL). People with elevated BNC were more likely to be classified as GOLD D (46% v 33% P<0.001), have more exacerbations (mean 2.3 v 1.3/year, P<0.001), and were more likely to have severe exacerbations (13% vs. 5%, P<0.001) in the following year. Eosinophil counts were much less predictive of these outcomes. In a sub-cohort (N=276), patients with elevated BNC had increased relative abundance of Proteobacteria and reduced microbiome diversity.Conclusion: High BNC may provide a useful indicator of risk of exacerbations and mortality in COPD patients.

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Low high-density lipoprotein and increased risk of several cancers: 2 population-based cohort studies including 116,728 individuals

Journal of Hematology & Oncology ◽

10.1186/s13045-020-00963-6 ◽

2020 ◽

Vol 13 (1) ◽

Cited By ~ 1

Author(s):

Kasper Mønsted Pedersen ◽

Yunus Çolak ◽

Stig Egil Bojesen ◽

Børge Grønne Nordestgaard

Keyword(s):

General Population ◽

Population Study ◽

Density Lipoprotein ◽

Hdl Cholesterol ◽

Apolipoprotein A1 ◽

General Population Study ◽

Heart Study ◽

Increased Risk ◽

Low Hdl ◽

Copenhagen City Heart Study

Abstract Background Increasing evidence suggests that high-density lipoprotein (HDL) may play a role in cancer development. We tested the hypothesis that low HDL levels are associated with increased risk of cancer. Methods Individuals from two population-based cohorts, the Copenhagen General Population Study (2003–2015, N = 107 341), and the Copenhagen City Heart Study (1991–1994, N = 9387) were followed prospectively until end of 2016 to assess low plasma HDL cholesterol and apolipoprotein A1 as risk factors for cancer using Cox proportional hazard regression. Results During up to 25 years follow-up, we observed 8748 cancers in the Copenhagen General Population Study and 2164 in the Copenhagen City Heart Study. In the Copenhagen General Population Study and compared to individuals with HDL cholesterol ≥ 2.0 mmol/L (≥ 77 mg/dL), multivariable adjusted hazard ratios (HRs) for any cancer were 1.13 (95% confidence interval 1.04–1.22) for individuals with HDL cholesterol of 1.5–1.99 mmol/L (58–77 mg/dL), 1.18 (1.08–1.30) for HDL cholesterol of 1.0–1.49 mmol/L (39–58 mg/dL), and 1.29 (1.12–1.48) for individuals with HDL cholesterol < 1.0 mmol/L (< 39 mg/dL). Correspondingly, compared to individuals with apolipoprotein A1 ≥ 190 mg/dL, HRs for any cancer were 1.06 (0.96–1.17) for individuals with apolipoprotein A1 of 160–189 mg/dL, 1.18 (1.07–1.30) for apolipoprotein A1 of 130–159 mg/dL, and 1.28 (1.13–1.46) for individuals with apolipoprotein A1 < 130 mg/dL. Among 27 cancer types, low HDL cholesterol and/or apolipoprotein A1 were associated with increased risk of multiple myeloma, myeloproliferative neoplasm, non-Hodgkin lymphoma, breast cancer, lung cancer, and nervous system cancer. Results were overall similar in women and men separately, and in the Copenhagen City Heart Study. Conclusions Low HDL levels were associated with increased risk of several cancers. Increased risk was most pronounced for hematological and nervous system cancer, and to a minor extent for breast and respiratory cancer.

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