scholarly journals Total and Cause-Specific Mortality by Moderately and Markedly Increased Ferritin Concentrations: General Population Study and Metaanalysis

2014 ◽  
Vol 60 (11) ◽  
pp. 1419-1428 ◽  
Author(s):  
Christina Ellervik ◽  
Jacob Louis Marott ◽  
Anne Tybjærg-Hansen ◽  
Peter Schnohr ◽  
Børge G Nordestgaard

Abstract BACKGROUND Previous population-based studies of plasma ferritin concentration have not revealed a relationship with total mortality. We tested the possible association of increased ferritin concentrations with increased risk of total and cause-specific mortality in the general population. METHODS We examined total and cause-specific mortality according to baseline plasma ferritin concentrations in a Danish population–based study (the Copenhagen City Heart Study) of 8988 individuals, 6364 of whom died (median follow-up 23 years). We also included a metaanalysis of total mortality comprising population-based studies according to ferritin quartiles or tertiles. RESULTS Multifactorially adjusted hazard ratios (HRs) for total mortality for individuals with ferritin ≥200 vs <200 μg/L were 1.1 (95% CI 1.1–1.2; P = 0.0008) overall, 1.1 (1.0–1.2; P = 0.02) in men, and 1.2 (1.0–1.3; P = 0.03) in women. Stepwise increasing concentrations of ferritin were associated with a stepwise increased risk of premature death overall (log rank, P = 2 × 10−22), with median survival of 55 years at ferritin concentrations ≥600 μg/L, 72 years at 400–599 μg/L, 76 years at 200–399 μg/L, and 79 years at ferritin <200 μg/L. The corresponding HR for total overall mortality for ferritin ≥600 vs <200 μg/L was 1.5 (1.2–1.8; P = 0.00008). Corresponding adjusted HRs for ferritin ≥600 vs <200 μg/L were 1.6 (1.1–2.3; P = 0.01) for cancer mortality, 2.9 (1.7–5.0; P = 0.0001) for endocrinological mortality, and 1.5 (1.1–2.0; P = 0.01) for cardiovascular mortality. The metaanalysis random effects odds ratio for total mortality for ferritin upper vs reference quartile or tertile was 1.0 (0.9–1.1; P = 0.3) (P heterogeneity = 0.5). CONCLUSIONS Moderately to markedly increased ferritin concentrations represent a biological biomarker predictive of early death in a dose-dependent linear manner in the general population.

2010 ◽  
Vol 56 (10) ◽  
pp. 1580-1591 ◽  
Author(s):  
Julia S Johansen ◽  
Stig E Bojesen ◽  
Anne Tybjærg-Hansen ◽  
Anne K Mylin ◽  
Paul A Price ◽  
...  

BACKGROUND Increased plasma YKL-40 is associated with short-term survival in patients with cardiovascular disease and cancer. We tested the hypothesis that increased plasma YKL-40 is associated with total and disease-specific mortality in the general population. METHODS We measured plasma YKL-40 in 8899 study participants, aged 20–95 years, in the Copenhagen City Heart Study from the Danish general population who were followed for 16 years: 3059 died, 2158 had ischemic cardiovascular disease, 2271 had cancer, and 2820 had other diseases associated with increased YKL-40. Hazard ratios for early death and absolute 10-year mortality rates were calculated according to plasma YKL-40 percentile groupings computed within sex and age decade: 0%–33%, 34%–66%, 67%–90%, 91%–95%, and 96%–100%. RESULTS Median survival age decreased from 83 years for participants with plasma YKL-40 in category 0%–33% to 69 years in category 96%–100% (trend, P < 0.0001). Risk of early death was increased (multifactorially adjusted hazard ratios) by 10% for YKL-40 category 34%–66%, by 30% for 67%–90%, by 70% for 91%–95%, and by 90% for 96%–100% vs YKL-40 category 0%–33% (trend, P < 0.0001). Corresponding increases in participants with ischemic cardiovascular disease were 10%, 20%, 80%, and 60% (P < 0.0001); in those with cancer were 10%, 20%, 50%, and 70% (P < 0.0001); and in those with other diseases were 10%, 20%, 40%, and 60% (P < 0.0001). Highest absolute 10-year mortality rates were 78% and 90% in women and men, respectively, who were >70 years old, smoked, and were in YKL-40 category 96%–100%. CONCLUSIONS Increased plasma YKL-40 is associated with risk of early death from cardiovascular disease, cancer, and other diseases in the general population.


2021 ◽  
Author(s):  
Yu Xie ◽  
Changzhi Huang ◽  
Xingchen Zhu ◽  
Jiayu Wang ◽  
Xikang Fan ◽  
...  

Abstract Background: Insulin-like growth factor 1 (IGF-1) is an important growth factor modulating development, homeostasis, and aging. However, whether and how circulating IGF-1 concentrations influence early death risk in the general population remains largely unknown. Methods: We included 380,997 participants who had serum IGF-1 measurement and no history of cancer, cardiovascular disease (CVD) or diabetes at baseline from UK Biobank, a prospective cohort study initiated in 2006-2010. Restricted cubic splines and Cox proportional hazards regression models were used to assess the association between baseline IGF-1 concentrations and all-cause and cause-specific mortality. Results: Over a median follow-up of 8.8 years, 10,753 of the participants died, including 6110 from cancer and 1949 from CVD. Dose-response analysis showed a U-shaped relationship between IGF-1 levels and mortality. Compared to the fifth decile of IGF-1, the lowest decile was associated with 39% (95% CI: 29%-50%), 20% (95% CI: 8%-34%), and 39% (95% CI: 14%-68%) higher risk of all-cause, cancer, and CVD mortality, respectively, while the highest decile was associated with 17% (95% CI: 7%-28%) and 38% (95% CI: 11%-71%) higher risk of all-cause and CVD mortality, respectively. The results remained stable in detailed stratified and sensitivity analyses. Conclusions: Our findings indicate that both low and high concentrations of serum IGF-1 are associated with increased risk of mortality in the general population. Our study provides a basis for future interrogation of underlying mechanisms of IGF-1 in early death occurrence and possible implications for mitigating the risk.


2020 ◽  
Vol 4 (Supplement_2) ◽  
pp. 226-226
Author(s):  
Xiaoran Liu ◽  
Marta Liu Guasch-Ferré ◽  
Deirdre Liu ◽  
Yanping Li

Abstract Objectives We aim to 1) examine the association between walnut consumption and subsequent total and cause-specific mortality; 2) to estimate life expectancy that would be potentially gained by varying intake of walnuts in U.S. women and men. Methods Walnut consumption was assessed using validated food frequency questionnaires in 1998 (baseline year) and updated every 4 years. We included data from 68,308 women of the Nurses’ Health Study (1998–2016) and 26,760 men of the Health Professionals Follow-up Study (1998–2016) who were free of cancer, heart disease, and stroke at baseline. We used Cox regression models adjusting for confounders to estimate mortality risk associated with walnut consumption stratified by sex and dietary quality. We used population based multistate life tables to calculate the differences in life expectancy and years lived in relation to walnut consumption. Results During up to 18 years of follow-up, we documented 30,502 deaths from any cause. The multivariable-adjusted hazard ratios (HRs) for total mortality across categories of walnut intake (servings/week), as compared to non-consumers, were 0.91 (95% confidence interval [CI], 0.89–0.94), for <1 serving/week, 0.87 (95% CI, 0.83–0.92) for 1 serving/week, 0.79 (95% CI, 0.75–0.85), for 2–4 servings/week, and 0.77 (95% CI,: 0.71–0.81) for >= 5 servings/week (P for trend <0.0001). Per 0.5 serving/day walnut consumption was associated of a reduced risk of total mortality (HR: 0.82, 95% CI,: 0.77–0.88), CVD mortality (HR: 0.78, 95% CI,: 0.67–0.33), and cancer mortality (HR: 0.93, 95% CI:, 0.81–1.07) in participants with a suboptimal diet (AHEI score <60% of cohort distribution). A greater life expectancy of 1.78 years in women and 1.94 years in men was observed among those who consumed walnuts more than 5 servings/week, compared to non-consumers at age 60. Conclusions Higher walnut consumption was associated with lower risk for total mortality and longer estimated life expectancy among U.S. men and women of two prospective cohort studies. Our results provide evidence on the potential role of walnut in the prevention of premature death. Funding Sources UM1 CA186107, UM1 CA176726, UM1 CA167552 Y.L. was partly funded by the California Walnut Commission. The funders have no roles in the design and conduct of the study.


2018 ◽  
Vol 64 (7) ◽  
pp. 1113-1124 ◽  
Author(s):  
Katrine Laura Rasmussen ◽  
Børge Grønne Nordestgaard ◽  
Sune Fallgaard Nielsen

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.


2009 ◽  
Vol 27 (4) ◽  
pp. 572-578 ◽  
Author(s):  
Julia S. Johansen ◽  
Stig E. Bojesen ◽  
Anne K. Mylin ◽  
Ruth Frikke-Schmidt ◽  
Paul A. Price ◽  
...  

PurposeElevated plasma YKL-40 is a biomarker of poor prognosis in cancer patients. We tested the hypotheses that elevated plasma YKL-40 predicts risk of cancer as well as survival after a cancer diagnosis in the general population.Patients and MethodsA prospective cohort study of 8,899 subjects (20 to 95 years) from the Danish general population, the Copenhagen City Heart Study, observed for 11 years for cancer incidence and 14 years for death: 1,432 participants had a first incident cancer, 968 of these died. Hazard ratios (HRs) for cancer events and death after events according to plasma YKL-40 in sex and 10 years age percentile categories: 0% to 33%, 34% to 66%, 67% to 90%, 91% to 95%, and 96% to 100%.ResultsThe cumulative incidence of gastrointestinal cancer increased with increasing YKL-40 (trend P < .0001). Multifactorially adjusted HRs for gastrointestinal cancer were 1.0 (95% CI, 0.7 to 1.5) for YKL-40 in category 34% to 66%, 1.5 for 67% to 90% (95% CI, 1.0 to 2.3), 2.4 for 91% to 95%, (95% CI, 1.3 to 4.6), and 3.4 for 96% to 100% (95% CI, 1.9 to 6.1) versus YKL-40 category 0% to 33% (P < .0001). Participants with any cancer event and YKL-40 category 91% to 100% had a median survival time after the diagnosis of 1 year versus 4 years in participants with YKL-40 category 0% to 33% (P < .0001). Corresponding values for gastrointestinal cancer were 6 months versus 1 year (P = .007). Multifactorially adjusted HRs for early death were 1.8 (95% CI, 1.3 to 2.5; P < .0001) after any cancer and 2.4 (95% CI, 1.3 to 4.3; P = .005) after gastrointestinal cancer in participants with YKL-40 category 91% to 100% versus 0% to 33%.ConclusionIn the general population, elevated plasma YKL-40 predicts increased risk of gastrointestinal cancer and decreased survival after any cancer diagnosis.


2011 ◽  
Vol 57 (3) ◽  
pp. 459-466 ◽  
Author(s):  
Christina Ellervik ◽  
Anne Tybjærg-Hansen ◽  
Børge G Nordestgaard

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 &lt;50% (log-rank P &lt; 0.0001). Multifactorially adjusted hazard ratios for total mortality for TS ≥50% vs &lt;50% were 1.4 (95% CI 1.2–1.6; P &lt; 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 &lt; 0.0001), with the highest risk conferred by TS ≥80% vs TS &lt;20% with a hazard ratio of 2.2 (1.4–3.3; P &lt; 0.001). The population-attributable risk for total mortality in the combined studies in individuals with TS ≥50% vs &lt;50% was 0.8%. In metaanalysis, the odds ratio for total mortality for TS ≥50% vs &lt;50% was 1.3 (1.2–1.5; P &lt; 0.001) under the fixed-effects model. CONCLUSIONS Individuals in the general population with TS ≥50% vs &lt;50% have an increased risk of premature death.


2020 ◽  
Vol 13 (1) ◽  
Author(s):  
Kasper Mønsted Pedersen ◽  
Yunus Çolak ◽  
Stig Egil Bojesen ◽  
Børge Grønne Nordestgaard

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.


2019 ◽  
Vol 105 (1) ◽  
pp. 163-174 ◽  
Author(s):  
Signe E J Hansen ◽  
Christian M Madsen ◽  
Anette Varbo ◽  
Børge G Nordestgaard

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 &gt; 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.


2019 ◽  
Vol 65 (1) ◽  
pp. 180-188
Author(s):  
Lise Fischer Mikkelsen ◽  
Børge G Nordestgaard ◽  
Peter Schnohr ◽  
Christina Ellervik

Abstract BACKGROUND Moderately increased plasma ferritin, as a biomarker of iron overload, has been associated with higher rates of cardiovascular death and heart failure. However, the association of moderately increased plasma ferritin with risk of atrial fibrillation in the general population is unknown. METHODS We examined the association of plasma ferritin concentrations with risk of atrial fibrillation and heart failure in metaanalyses of 35799 men and women from 3 studies of the Danish general population: the Copenhagen City Heart Study, the Danish General Suburban Population Study, and the Copenhagen General Population Study. RESULTS Multivariable adjusted fixed effects odds ratios for atrial fibrillation were 1.23 (95% CI, 1.05–1.44; P = 0.005) in men for ferritin concentration ≥300 μg/L vs &lt;300 μg/L, 1.13 (95% CI, 0.93–1.38; P = 0.22) in women for ≥200 μg/L vs &lt;200 μg/L, and 1.19 (95% CI, 1.06–1.35; P = 0.005) in both sexes combined (Psex interaction = 0.52). Corresponding fixed effects odds ratios for heart failure were 1.16 (95% CI, 0.98–1.37; P = 0.08) in men, 0.86 (95% CI, 0.67–1.10; P = 0.23) in women, and 1.05 (95% CI, 0.91–1.21; P = 0.45) in both sexes combined (Psex interaction = 0.05). Multivariable adjusted fixed effects odds ratio for atrial fibrillation per step increase in ferritin concentrations was 1.13 (95% CI, 1.06–1.21; Ptrend = 0.0005) in both sexes combined (Psex interaction = 0.59); the corresponding value for heart failure was 1.03 (95% CI, 0.95–1.11; Ptrend = 0.47) (Psex interaction = 0.08). In sensitivity analyses, there was no evidence of U-shaped relationships between plasma ferritin concentrations and risk of atrial fibrillation or heart failure in men or women. CONCLUSIONS Increased ferritin concentration is associated with increased risk of atrial fibrillation in the general population.


2006 ◽  
Vol 3 (2) ◽  
pp. 27-28 ◽  
Author(s):  
Hamid Ghodse

The association between mental illness and poor physical health has been known for decades (Philips, 1934). This is not a trivial relationship between mental ill health and minor physical problems but an association with such poor physical health that it results in premature death. For example, a study in the USA showed that the life expectancy of those with schizophrenia or other serious mental illness was 9 years shorter than for the general population (Dembling et al, 1999). Similarly, those with learning disabilities have an increased risk of early death, and this increase is greater in those with severe disability.


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