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.

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 Risk of progression of interstitial pneumonia with autoimmune features to a systemic autoimmune rheumatic disease

Rheumatology ◽  
2019 ◽  
Vol 59 (6) ◽  
pp. 1233-1240 ◽  
Author(s):  
Michail K Alevizos ◽  
Jon T Giles ◽  
Nina M Patel ◽  
Elana J Bernstein
Keyword(s):  
Rheumatic Disease ◽  
Interstitial Pneumonia ◽  
Smoking Status ◽  
Medical Center ◽  
Columbia University ◽  
Autoimmune Rheumatic Disease ◽  
Increased Risk ◽  
Systemic Autoimmune Rheumatic Disease ◽  
Risk Of Progression

Abstract Objective The aim of this study was to determine the risk of developing a systemic autoimmune rheumatic disease (ARD) after an initial diagnosis of interstitial pneumonia with autoimmune features (IPAF). Methods We performed a retrospective cohort study of patients with interstitial lung disease (ILD) who were evaluated at Columbia University Irving Medical Center from 2009 to 2017. We divided patients with idiopathic ILD into two groups: those who met IPAF criteria and those who did not meet IPAF criteria at initial ILD diagnosis. We examined the association between IPAF and diagnosis of ARD during the follow-up period using a multivariable-adjusted logistic regression model. Results Of the 697 patients with ILD who were screened, 174 met inclusion criteria (50 met IPAF criteria and 124 did not). During a median follow-up period of 5.2 years, 16% (8/50) of subjects with IPAF were diagnosed with an ARD compared with 1.6% (2/124) of subjects without IPAF (P = 0.001). Adjusting for age, sex, smoking status and use of immunosuppressive therapy, the odds of progressing to an ARD were 14 times higher in subjects with IPAF than in those without IPAF (odds ratio 14.18, 95% CI 1.44–138.95, P = 0.02). Conclusion The presence of IPAF confers an increased risk of developing an ARD. Patients with IPAF should therefore be followed closely for the development of an ARD.

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 Complement C3 and High Risk of Venous Thromboembolism: 80517 Individuals from the Copenhagen General Population Study

2016 ◽  
Vol 62 (3) ◽  
pp. 525-534 ◽  
Author(s):  
Ina Nørgaard ◽  
Sune F Nielsen ◽  
Børge G Nordestgaard
Keyword(s):  
Pulmonary Embolism ◽  
Venous Thromboembolism ◽  
High Risk ◽  
General Population ◽  
Venous Thrombosis ◽  
Deep Venous Thrombosis ◽  
Population Study ◽  
Mean Value ◽  
Complement C3 ◽  
General Population Study

Abstract BACKGROUND Complement activation may contribute to venous thromboembolism, including deep venous thrombosis and pulmonary embolism. We tested the hypothesis that high complement C3 concentrations are associated with high risk of venous thromboembolism in the general population. METHODS We included 80 517 individuals without venous thromboembolism from the Copenhagen General Population Study recruited in 2003–2012. Plasma complement C3 concentrations were measured at baseline, and venous thromboembolism (n = 1176) was ascertained through April 2013 in nationwide registries. No individuals were lost to follow-up. RESULTS Complement C3 concentrations were approximately normally distributed, with a mean value of 1.13 g/L (interquartile range 0.98–1.26; SD 0.21). The cumulative incidence of venous thromboembolism was higher with progressively higher tertiles of complement C3 (log-rank trend: P = 3 × 10−8): at age 80, 7%, 9%, and 11% of individuals in the first, second, and third tertiles, respectively, had developed venous thromboembolism. Multivariable-adjusted hazard ratios for venous thromboembolism compared with individuals in the first tertile were 1.36 (95% CI, 1.16–1.59) for those in the second tertile and 1.58 (1.33–1.88) for those in the third tertile. Corresponding values were 1.36 (1.16–1.60) and 1.57 (1.33–1.87) after additional adjustment for C-reactive protein and 1.27 (1.09–1.49) and 1.31(1.10–1.57) after additional adjustment for body mass index. These results were similar for deep venous thrombosis and pulmonary embolism separately. The multivariable-adjusted hazard ratio for venous thromboembolism for a 1-g/L increase in complement C3 was 2.43 (1.74–3.40). CONCLUSIONS High concentrations of complement C3 were associated with high risk of venous thromboembolism in the general population.

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.

scholarly journals Extreme Nonfasting Remnant Cholesterol vs Extreme LDL Cholesterol as Contributors to Cardiovascular Disease and All-Cause Mortality in 90000 Individuals from the General Population

2015 ◽  
Vol 61 (3) ◽  
pp. 533-543 ◽  
Author(s):  
Anette Varbo ◽  
Jacob J Freiberg ◽  
Børge G Nordestgaard
Keyword(s):  
Myocardial Infarction ◽  
General Population ◽  
Mortality Risk ◽  
Ldl Cholesterol ◽  
Hazard Ratios ◽  
Increased Risk ◽  
All Cause Mortality ◽  
Remnant Cholesterol ◽  
Shaped Pattern

Abstract BACKGROUND Increased nonfasting remnant cholesterol, like increased LDL cholesterol, is causally associated with increased risk for ischemic heart disease (IHD). We tested the hypothesis that extreme concentrations of nonfasting remnant and LDL cholesterol are equal contributors to the risk of IHD, myocardial infarction (MI), and all-cause mortality. METHODS We compared stepwise increasing concentrations of nonfasting remnant and LDL cholesterol for association with risk of IHD, MI, and all-cause mortality in approximately 90 000 individuals from the Danish general population. During up to 22 years of complete follow-up, 4435 participants developed IHD, 1722 developed MI, and 8121 died. RESULTS Compared with participants with nonfasting remnant cholesterol <0.5 mmol/L (19.3 mg/dL), hazard ratios for IHD ranged from 1.3 (95% CI 1.1–1.5) for remnant cholesterol of 0.5–0.99 mmol/L (19.3–38.2 mg/dL) to 2.4 (1.9–2.9) for remnant cholesterol of ≥1.5 mmol/L (58 mg/dL) (P for trend <0.001). Compared with participants with LDL cholesterol <3.0 mmol/L (115.8 mg/dL), hazard ratios for IHD ranged from 1.3 (1.1–1.5) for LDL cholesterol of 3–3.99 mmol/L (115.8–154 mg/dL) to 2.3 (1.9–2.8) for LDL cholesterol of ≥5 mmol/L (193 mg/dL) (P < 0.001). Corresponding hazard ratios for MI ranged from 1.8 (1.4–2.3) to 3.4 (2.5–4.8) for remnant cholesterol (P < 0.001), and from 1.7 (1.4–2.2) to 4.7 (3.5–6.3) for LDL cholesterol (P < 0.001). Nonfasting remnant cholesterol concentrations were associated stepwise with all-cause mortality ranging from hazard ratio 1.0 (0.9–1.1) to 1.6 (1.4–1.9) (P < 0.001), whereas LDL cholesterol concentrations were associated with decreased all-cause mortality risk in a U-shaped pattern, with hazard ratios from 0.8 (0.7–0.8) to 0.9 (0.8–1.0) (P = 0.002). After mutual adjustment, LDL cholesterol best predicted MI, and remnant cholesterol best predicted all-cause mortality. CONCLUSIONS Both lipoproteins were associated equally with risk of IHD and MI; however, only nonfasting remnant cholesterol concentrations were associated stepwise with increased all-cause mortality risk.

scholarly journals The physical activity paradox in cardiovascular disease and all-cause mortality: the contemporary Copenhagen General Population Study with 104 046 adults

2021 ◽  
Vol 42 (15) ◽  
pp. 1499-1511 ◽  
Author(s):  
Andreas Holtermann ◽  
Peter Schnohr ◽  
Børge Grønne Nordestgaard ◽  
Jacob Louis Marott
Keyword(s):  
Physical Activity ◽  
Cardiovascular Disease ◽  
General Population ◽  
Leisure Time ◽  
Leisure Time Physical Activity ◽  
Occupational Physical Activity ◽  
General Population Study ◽  
Hazard Ratios ◽  
All Cause Mortality

Abstract Aims  Leisure time physical activity associates with reduced risk of cardiovascular disease and all-cause mortality, while these relationships for occupational physical activity are unclear. We tested the hypothesis that leisure time physical activity associates with reduced major adverse cardiovascular events (MACE) and all-cause mortality risk, while occupational physical activity associates with increased risks. Methods and results  We studied 104 046 women and men aged 20–100 years in the Copenhagen General Population Study with baseline measurements in 2003–2014 and median 10-year follow-up. Both leisure and occupational physical activity were based on self-report with four response categories. We observed 7913 (7.6%) MACE and 9846 (9.5%) deaths from all causes. Compared to low leisure time physical activity, multivariable adjusted (for lifestyle, health, living conditions, and socioeconomic factors) hazard ratios for MACE were 0.86 (0.78–0.96) for moderate, 0.77 (0.69–0.86) for high, and 0.85 (0.73–0.98) for very high activity; corresponding values for higher occupational physical activity were 1.04 (0.95–1.14), 1.15 (1.04–1.28), and 1.35 (1.14–1.59), respectively. For all-cause mortality, corresponding hazard ratios for higher leisure time physical activity were 0.74 (0.68–0.81), 0.59 (0.54–0.64), and 0.60 (0.52–0.69), and for higher occupational physical activity 1.06 (0.96–1.16), 1.13 (1.01–1.27), and 1.27 (1.05–1.54), respectively. Similar results were found within strata on lifestyle, health, living conditions, and socioeconomic factors, and when excluding individuals dying within the first 5 years of follow-up. Levels of the two domains of physical activity did not interact on risk of MACE (P = 0.40) or all-cause mortality (P = 0.31). Conclusion  Higher leisure time physical activity associates with reduced MACE and all-cause mortality risk, while higher occupational physical activity associates with increased risks, independent of each other.

scholarly journals Sex-Specific Associations between Blood Pressure and Risk of Atrial Fibrillation Subtypes in the Tromsø Study

2021 ◽  
Vol 10 (7) ◽  
pp. 1514
Author(s):  
Hilde Espnes ◽  
Jocasta Ball ◽  
Maja-Lisa Løchen ◽  
Tom Wilsgaard ◽  
Inger Njølstad ◽  
...  
Keyword(s):  
Atrial Fibrillation ◽  
Blood Pressure ◽  
Proportional Hazards ◽  
Cox Proportional Hazards ◽  
Pressure Management ◽  
Reference Models ◽  
Proportional Hazards Regression ◽  
Hazard Ratios ◽  
Increased Risk

The aim of this study was to explore sex-specific associations between systolic blood pressure (SBP), hypertension, and the risk of incident atrial fibrillation (AF) subtypes, including paroxysmal, persistent, and permanent AF, in a general population. A total of 13,137 women and 11,667 men who participated in the fourth survey of the Tromsø Study (1994–1995) were followed up for incident AF until the end of 2016. Cox proportional hazards regression analysis was conducted using fractional polynomials for SBP to provide sex- and AF-subtype-specific hazard ratios (HRs) for SBP. An SBP of 120 mmHg was used as the reference. Models were adjusted for other cardiovascular risk factors. Over a mean follow-up of 17.6 ± 6.6 years, incident AF occurred in 914 (7.0%) women (501 with paroxysmal/persistent AF and 413 with permanent AF) and 1104 (9.5%) men (606 with paroxysmal/persistent AF and 498 with permanent AF). In women, an SBP of 180 mmHg was associated with an HR of 2.10 (95% confidence interval [CI] 1.60–2.76) for paroxysmal/persistent AF and an HR of 1.80 (95% CI 1.33–2.44) for permanent AF. In men, an SBP of 180 mmHg was associated with an HR of 1.90 (95% CI 1.46–2.46) for paroxysmal/persistent AF, while there was no association with the risk of permanent AF. In conclusion, increasing SBP was associated with an increased risk of both paroxysmal/persistent AF and permanent AF in women, but only paroxysmal/persistent AF in men. Our findings highlight the importance of sex-specific risk stratification and optimizing blood pressure management for the prevention of AF subtypes in clinical practice.

scholarly journals Incremental changes in QRS duration as predictor for cardiovascular disease: a 21-year follow-up of a randomly selected general population

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Xiaojing Chen ◽  
Per-Olof Hansson ◽  
Erik Thunström ◽  
Zacharias Mandalenakis ◽  
Kenneth Caidahl ◽  
...  
Keyword(s):  
Cardiovascular Disease ◽  
General Population ◽  
Cardiovascular Events ◽  
Population Sample ◽  
Cox Regression Analysis ◽  
Major Cardiovascular Events ◽  
Increased Risk ◽  
Qrs Duration ◽  
Group 1

AbstractThe QRS complex has been shown to be a prognostic marker in coronary artery disease. However, the changes in QRS duration over time, and its predictive value for cardiovascular disease in the general population is poorly studied. So we aimed to explore if increased QRS duration from the age of 50–60 is associated with increased risk of major cardiovascular events during a further follow-up to age 71. A random population sample of 798 men born in 1943 were examined in 1993 at 50 years of age, and re-examined in 2003 at age 60 and 2014 at age 71. Participants who developed cardiovascular disease before the re-examination in 2003 (n = 86) or missing value of QRS duration in 2003 (n = 127) were excluded. ΔQRS was defined as increase in QRS duration from age 50 to 60. Participants were divided into three groups: group 1: ΔQRS < 4 ms, group 2: 4 ms ≤ ΔQRS < 8 ms, group 3: ΔQRS ≥ 8 ms. Endpoints were major cardiovascular events. And we found compared with men in group 1 (ΔQRS < 4 ms), men with ΔQRS ≥ 8 ms had a 56% increased risk of MACE during follow-up to 71 years of age after adjusted for BMI, systolic blood pressure, smoking, hyperlipidemia, diabetes and heart rate in a multivariable Cox regression analysis (HR 1.56, 95% CI:1.07–2.27, P = 0.022). In conclusion, in this longitudinal follow-up over a decade QRS duration increased in almost two out of three men between age 50 and 60 and the increased QRS duration in middle age is an independent predictor of major cardiovascular events.

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