Search

The vast majority of research about HDL (high-density lipoprotein) has for decades revolved around the possible role of HDL in atherosclerosis and its therapeutic potential within cardiovascular disease prevention; however, failures with therapies aimed at increasing HDL cholesterol has left questions as to what the role and function of HDL in human health and disease is. Recent observational studies have further shown that extreme high HDL cholesterol is associated with high mortality leading to speculations that HDL could in some instances be harmful. In addition, evidence from observational, and to a lesser extent genetic studies has emerged indicating that HDL might be associated with the development of other major noncardiovascular diseases, such as infectious disease, autoimmune disease, cancer, type 2 diabetes, kidney disease, and lung disease. In this review, we discuss (1) the association between extreme high HDL cholesterol and mortality and (2) the emerging human evidence linking HDL to several major diseases outside the realm of cardiovascular disease.

Incidences of pancreatic cancer and acute and chronic pancreatitis are rising globally, and often no curative treatment is available at the time of diagnosis. We tested the hypothesis that low and high plasma concentrations of pancreatic amylase are associated with increased risk of pancreatic cancer, acute pancreatitis, and chronic pancreatitis in the general population. We included 101,765 individuals (55% women) aged 20–100 years from the Copenhagen General Population Study with baseline measurements of plasma pancreatic amylase. After recruitment in 2004–2015 during a median 9 years of follow-up (range 0–15), we collected information about diagnoses of pancreatic cancer, acute pancreatitis, and chronic pancreatitis from the national Danish Patient Registry, the national Danish Cancer Registry, and the national Danish Causes of Death Registry. The median age was 58 years (interquartile range: 48–67) and the median plasma pancreatic amylase 32 U/L (26–40). During follow-up, 442 individuals were diagnosed with pancreatic cancer, 282 with chronic pancreatitis, and 401 with acute pancreatitis. Compared to individuals with pancreatic amylase levels in the 41st–60th percentiles, those with extreme low (1st–2.5th percentiles) and extreme high (97.5th–100th percentiles) pancreatic amylase had hazard ratios of 2.4 (95% confidence interval; 1.6–3.6) and 2.2 (1.4–3.7) for pancreatic cancer, of 1.8 (1.1–3.3) and 3.2 (1.8–5.6) for chronic pancreatitis, and of 1.1 (0.6–1.8) and 1.5 (0.8–2.7) for acute pancreatitis, respectively. In apparently healthy individuals from the general population, extreme low and extreme high plasma pancreatic amylase were associated with 2–threefold higher risk of both pancreatic cancer and chronic pancreatitis.

Background: The high-density lipoprotein (HDL) hypothesis of atherosclerosis has been challenged by clinical trials of cholesteryl ester transfer protein (CETP) inhibitors which failed to show significant reductions in cardiovascular events. Plasma levels of HDL-cholesterol (HDL-C) decline drastically during sepsis and this phenomenon is explained, in part, by the activity of CETP, a major determinant of plasma HDL-C levels. We tested the hypothesis that genetic or pharmacologic inhibition of CETP would preserve HDL levels and decrease mortality in clinical cohorts and animal models of sepsis. Methods: We examined the effect of a gain-of-function variant in CETP (rs1800777, p.Arg468Gln) and a genetic score for decreased CETP function on 28-day sepsis survival using Cox proportional hazard models adjusted for age and sex in the UK Biobank (n=5,949), Identification of SNPs Predisposing to Altered Acute Lung Injury Risk (iSPAAR; n=882), Copenhagen General Population Study (n=2,068), Copenhagen City Heart Study (n=493), Early Infection (n=200), St. Paul's Intensive Care Unit 2 (n=203), and Vasopressin versus Norepinephrine Infusion in Patients with Septic Shock studies (n=632). We then studied the effect of the CETP inhibitor anacetrapib in adult, female APOE*3-Leiden mice with or with human CETP expression using the cecal-ligation and puncture model of sepsis. Results: A fixed-effect meta-analysis of all 7 cohorts found that the CETP gain-of-function variant was significantly associated with increased risk of acute sepsis mortality (hazard ratio [95% confidence interval]: 1.44 [1.22-1.70], p<0.0001). In addition, a genetic score for decreased CETP function was associated with significantly decreased sepsis mortality in the UK Biobank (hazard ratio [95% confidence interval]: 0.77 [0.59-1.00] per 1 mmol/L increase in HDL-C) and iSPAAR cohorts (hazard ratio [95% confidence interval]: 0.60 [0.37-0.98] per 1 mmol/L increase HDL-C). APOE*3-Leiden.CETP mice treated with

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 > 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.

OBJECTIVE: High Lp(a) (lipoprotein[a]) cause cardiovascular disease (CVD) in a primary prevention setting; however, it is debated whether high Lp(a) lead to recurrent CVD events. We tested the latter hypothesis and estimated the Lp(a)-lowering needed for 5 years to reduce CVD events in a secondary prevention setting. Approach and Results: From the CGPS (Copenhagen General Population Study; 2003-2015) of 58 527 individuals with measurements of Lp(a), 2527 aged 20 to 79 with a history of CVD were studied. The primary end point was major adverse cardiovascular event (MACE). We also studied 1115 individuals with CVD from the CCHS (Copenhagen City Heart Study; 1991-1994) and the CIHDS (Copenhagen Ischemic Heart Disease Study; 1991-1993). During a median follow-up of 5 years (range, 0-13), 493 individuals (20%) experienced a MACE in the CGPS. MACE incidence rates per 1000 person-years were 29 (95% CI, 25-34) for individuals with Lp(a)<10 mg/dL, 35 (30-41) for 10 to 49 mg/dL, 42 (34-51) for 50 to 99 mg/dL, and 54 (42-70) for ≥100 mg/dL. Compared with individuals with Lp(a)<10 mg/dL (18 nmol/L), the multifactorially adjusted MACE incidence rate ratios were 1.28 (95% CI, 1.03-1.58) for 10 to 49 mg/dL (18-104 nmol/L), 1.44 (1.12-1.85) for 50 to 99 mg/dL (105-213 nmol/L), and 2.14 (1.57-2.92) for ≥100 mg/dL (214 nmol/L). Independent confirmation was obtained in individuals from the CCHS and CIHDS. To achieve 20% and 40% MACE risk reduction in secondary prevention, we estimated that plasma Lp(a) should be lowered by 50 mg/dL (95% CI, 27-138; 105 nmol/L [55-297]) and 99 mg/dL (95% CI, 54-273; 212 nmol/L [114-592]) for 5 years.CONCLUSIONS: High concentrations of Lp(a) are associated with high risk of recurrent CVD in individuals from the general population. This study suggests that Lp(a)-lowering by 50 mg/dL (105 nmol/L) short-term (ie, 5 years) may reduce CVD by 20% in a secondary prevention setting.

BACKGROUND: How mild-to-moderate hypertriglyceridemia (2–10 mmol/L; 177– 886 mg/dL) potentially causes acute pancreatitis is unknown; however, cellular studies indicate that inflammation might be a driver of disease progression. We tested the hypotheses that (a) mild-to-moderate hypertriglyceridemia is associated with low-grade inflammation and that (b) the association between mild-to-moderate hypertriglyceridemia and risk of acute pancreatitis depends on low-grade inflammation. METHODS: From the Copenhagen General Population Study and the Copenhagen City Heart Study, 117 865 men and women 20–100+ years of age with measurements of nonfasting plasma triglycerides at baseline were followed prospectively for development of acute pancreatitis. RESULTS: After multivariable adjustment, a 1 mmol/L (89 mg/dL) higher nonfasting triglyceride concentration was associated with 17% (95% CI, 16%–18%, P = 3 × 10 -17 ) higher plasma C-reactive protein (CRP) and a 4.2% (4.0%–4.4%, P = 6 × 10 -17 ) higher blood leukocyte count. Higher concentrations of nonfasting triglycerides were associated almost linearly with higher risk of acute pancreatitis (P for trend = 5 × 10 -6 ), with hazard ratios of 1.5 (95% CI, 0.9–2.5), 2.0 (95% CI, 1.1–3.6), 2.2 (95% CI, 1.0–4.7), 4.2 (95% CI, 1.6–11.5), and 7.7 (95% CI, 3.0–19.8) in individuals with nonfasting triglycerides of 1.00–1.99 mmol/L (89–176 mg/dL; 46% of the population), 2.00–2.99 mmol/L (177–265 mg/dL; 17%), 3.00–3.99 mmol/L (266–353 mg/dL; 6%), 4.00–4.99 mmol/L (354–442 mg/dL; 2%), and ≥5mmol/L(443 mg/dL; 2%), respectively, vs individuals with <1 mmol/L (89 mg/dL; 27%). The association with risk of acute pancreatitis appeared more pronounced in individuals with CRP of ≥1.39 mg/L (P for trend = 0.001) and leukocytes of ≥7 × 10 9 /L (P = 2 × 10 -4 ) than in those with CRP <1.39 mg/L (P = 0.03) and leukocytes <7 × 10 9 /L (P = 0.04); however, there was no formal

BACKGROUND: HDL is quantitatively the most important lipoprotein in most species and mechanistic evidence points toward a role for HDL in normal immune function. We tested the hypothesis that concentrations of HDL cholesterol are associated with risk of autoimmune disease. METHODS: From 2 studies of the general population-the Copenhagen General Population Study and the Copenhagen City Heart study-we included 107954 and 9387 individuals with baseline measurements of HDL cholesterol. These were followed with the national Danish Patient Registry from baseline in 2003-2015 or 1991-1994 through 2017, during which time 4078 and 1101 individuals developed autoimmune disease in the 2 studies. RESULTS: In the Copenhagen General Population Study, compared to individuals with HDL cholesterol ≥2.0 mmol/L (77 mg/dL), the multifactorially adjusted hazard ratios for any autoimmune disease were 1.06 (95% CI, 0.94-1.19) for individuals with HDL cholesterol of 1.5-1.99 mmol/L (58-77 mg/dL), 1.18 (95% CI, 1.04-1.35) for individuals with HDL cholesterol of 1.0-1.49 mmol/L (39-58 mg/dL), and 1.84 (95% CI, 1.52-2.22) for individuals with HDL cholesterol < 1.0 mmol/L (39 mg/dL) (Pfor trend <0.001). These results were similar when excluding events within 5 years of baseline, in women and men separately, for events at baseline, irrespective of low-grade inflammation or triglyceride concentrations, for the apolipoprotein A1 part of HDL, and for more restrictive end point definitions. Finally, the Copenhagen City Heart Study provided independent confirmation. CONCLUSIONS: Low HDL cholesterol level is associated with high risk of autoimmune disease in individuals from the general population. Our observational findings cannot determine causality.

CONTEXT: How best to identify families with premature myocardial infarction is unclear.OBJECTIVE: We compared approaches to identify familial premature myocardial infarction in the general population using different familial hypercholesterolemia (FH) criteria and low-density lipoprotein (LDL) cholesterol cut-points.DESIGN AND SETTING: Clinical and mutation criteria for FH and LDL cholesterol cut-points were applied for identification of familial premature myocardial infarction in 106,732 individuals from the Copenhagen General Population Study.RESULTS: FH criteria identified 898 (13%) cases with familial premature myocardial infarction, leaving 5856 (87%) cases undetected. The ORs for familial premature myocardial infarction, compared with the respective remainder groups, were 4.7 (95% CI, 3.7 to 6.0) for clinical FH by Dutch Lipid Clinic Network criteria, 4.4 (4.0 to 4.7) for Simon Broome criteria, 2.1 (95% CI, 1.7 to 3.6) for Make Early Diagnosis to Prevent Early Death criteria, 2.1 (95% CI, 1.4 to 3.3) for FH mutation, and 1.4 (95% CI, 1.3 to1.6) for LDL cholesterol ≥5 mmol/L (193 mg/dL). For these risk groups, the sensitivity (true positive rate) for identification of familial premature myocardial infarction were 1.3%, 13%, 1.6%, 0.9%, and 7.1%, respectively. Compared with universal screening of a similar fraction of the population, the relative increase in sensitivity for these risk groups was 3.8-fold [fraction of population examined: 0.3%, 3.3-fold (4%), 2.0-fold (0.8%), 2.0-fold (0.4%), and 1.4-fold (5.3%), respectively].CONCLUSION: Criteria for FH identify a small fraction of individuals with familial premature myocardial infarction in the general population. Actively identifying families with premature myocardial infarction would be of potential preventive importance, and this study provides data that could be used to choose the best method for such family identification.

Background and purpose - Several studies suggest a global increase of centenarians during the 21st century. We describe temporal trends of hip fracture incidence and mortality in this group and compare these patients with a group of younger hip fracture patients with regards to comorbidities and mortality. Patients and methods - The full study population included all hip fractures that occurred in Denmark (n = 154,047) between 1996 and 2012. Patients aged 100 or above were identified (n = 507) and hip fracture patients between the ages of 70 to 99 years (n = 124,007) were used for comparison. Data were accessed from national registries. Trends in incidence over time were analyzed using a log-linear regression model, mortality was analyzed using the Kaplan-Meier estimator and trends in mortality over time were analyzed using a log-binomial regression model to obtain relative risk estimates. Results and interpretation - The centenarian patients had fewer comorbidities than the younger comparison group, but mortality was higher at all timepoints. There was no statistically significant change in mortality over time but the incidence of hip fracture among centenarians decreased during the same time period. Our findings describe the characteristics of an emerging group of hip fracture patients and could be of use in the planning of healthcare in the years to come.

OBJECTIVE: to test the hypothesis that excess mortality conferred by diabetes following hip fracture decreases with advancing age.METHODS: a nationwide population-based cohort study including 154,047 patients who were admitted with a hip fracture in Denmark from 1996 to 2012. Information on hip fracture diagnosis, diabetes, other comorbidities, and the primary outcome all-cause mortality was collected using the national Danish health registries. The association between diabetes and all-cause mortality according to age was assessed using Cox proportional hazards regression in the age categories: <50, 50-59, 60-69, 70-79, 80-89 and ≥90 years.RESULTS: during a median follow-up of 3 years (interquartile range: 1-6 years, 603,091 person-years) 114,990 died from any cause. In total, 8% (n = 12,158) of the patients had diabetes at baseline and had unadjusted, and age, sex and Charlson Comorbidity Index adjusted hazard ratios for all-cause mortality of 1.19 (95% confidence interval: 1.16-1.21) and 1.14 (1.12-1.17) as compared to patients without diabetes. The sex and Charlson Comorbidity Index adjusted hazard ratios according to age were 1.64 (1.34-2.02) for patients <50 years, 1.26 (1.12-1.40) for patients 50-59 years, 1.21 (1.13-1.29) for patients 60-69 years, 1.11 (1.07-1.16) for patients 70-79 years, 1.10 (1.07-1.14) for patients 80-89 years and 1.09 (1.02-1.16) for patients ≥90 years. There was a statistically significant interaction between diabetes and age (P < 0.001).CONCLUSIONS: diabetes is associated with excess mortality following hip fracture across all ages, but the excess mortality decreases with advancing age.

BACKGROUND: Familial hypercholesterolemia (FH) is a condition with very high concentrations of low-density lipoprotein (LDL) cholesterol and high risk of ischemic heart disease including myocardial infarction. However, there is limited and contradictory information on whether FH and high LDL cholesterol per se confer high risk of ischemic stroke. We tested the hypotheses that individuals in the general population with FH and/or high LDL cholesterol have higher risk of ischemic stroke. METHODS: The associations of FH and high LDL cholesterol with ischemic stroke risk were tested in both causal, genetic, and observational analyses using 106 412 individuals from the CGPS (Copenhagen General Population Study; 2823 ischemic strokes and 3792 myocardial infarctions) and/or 10 372 individuals from the CCHS (Copenhagen City Heart Study; 945 ischemic strokes and 1142 myocardial infarctions). FH causative mutations were LDLR W23X(rs267607213), W66G(rs121908025) and W556S, and APOB R3500Q(rs5742904). A Mendelian randomization design tested whether high LDL cholesterol per se has a causal effect on ischemic stroke risk, using a combination of the FH causative mutations and common genetic variants associated with high LDL cholesterol. RESULTS: The cumulative incidences in individuals in the CGPS with and without FH causative mutations were similar for ischemic stroke (P=0.50) but not for myocardial infarction (P<0.001): at age 80 years, 4% and 7% of these individuals developed ischemic stroke and 20% and 8% myocardial infarction, with similar results in the CCHS. There was no association between clinical FH and ischemic stroke, except if personal premature ischemic heart disease was included in the clinical FH criteria. Ischemic heart disease at baseline was associated with higher ischemic stroke risk, explaining the higher ischemic stroke risk in those with high LDL cholesterol. For a 1 mmol/L higher LDL cholesterol, the genetic causal risk ratio was 1.11 (0.62-2.02) for i

Aims: Preclinical evidence has indicated that HDL may play an important role in the immune system; however, very little is known about the role of HDL in the immune system in humans. We tested the hypothesis that low and high concentrations of HDL cholesterol are associated with risk of infectious disease in the general population.Methods and results: We included 97 166 individuals from the Copenhagen General Population Study and 9387 from the Copenhagen City Heart Study with measurements of HDL cholesterol at baseline. The primary endpoint was any infectious disease requiring hospital admission, ascertained in the Danish health registries from baseline in 2003-13 or 1991-94 through 2014; 9% and 31% of individuals in the two studies experienced one or more infectious disease events. Using restricted cubic splines, there was a U-shaped association between concentrations of HDL cholesterol and risk of any infection. Following multifactorial adjustment, individuals with HDL cholesterol below 0.8 mmol/L (31 mg/dL) and above 2.6 mmol/L (100 mg/dL) had hazard ratios for any infection of 1.75 (95% confidence interval 1.31-2.34) and 1.43 (1.16-1.76), compared to those with HDL cholesterol of 2.2-2.3 mmol/L (85-95 mg/dL). In the Copenhagen City Heart Study, corresponding hazard ratios for any infection were 2.00 (1.16-3.43) and 1.13 (0.80-1.60).Conclusion: Low and high HDL cholesterol concentrations found in 21% and 8% of individuals were associated with higher risk of infectious disease in the general population. These findings do not necessarily indicate causality.

Background and purpose - While development in hip fracture incidence and mortality is well examined, none has yet looked at the temporal trends regarding prevalence of co-morbidities. Therefore we investigated changes in incidence of first hip fracture, co-morbidity prevalence, 30 day- and 1-year mortality in hip fracture patients in the Danish population during the period 1999 to 2012. Patients and methods - Patients >18 years admitted with a fractured hip in Denmark between 1996 and 2012 were identified with data for the period 1999-2012 being analyzed regarding prevalence of co-morbidities, incidence, and mortality. Results - 122,923 patients were identified. Incidence in the whole population declined but sex-specific analysis showed no changes for men. For the whole study population, 30-day and 1-year mortality remained unchanged. Age at time of first hip fracture also remained unchanged. Of the included co-morbidities a decrease in prevalence of malignancy and dementia in women was found while there was an increase in the prevalence of all remaining co-morbidities, except hemi- or paraplegia for both sexes, rheumatic diseases for women, and for men diabetes with complications, myocardial infarction, AIDS/HIV, and malignancy. Interpretation - While hip fracture incidence declined for women it was unchanged for men; likewise, 30-day and 1-year mortality rates together with age at first fracture remained unchanged. When these results are compared with the relatively large increase in the prevalence of co-morbidities, it does not seem likely that the increased disease burden is affecting either the incidence or the mortality.

Aims: To identify individuals at high risk of atherosclerotic cardiovascular disease (ASCVD), who are not definite statin eligible according to the 2016 European Society of Cardiology/European Atherosclerosis Society (ESC/EAS) guidelines, based on high concentrations of plasma triglycerides.Methods and results: From the Copenhagen General Population Study (2003-2015) 58 547 individuals aged 40-65 and free of ASCVD, diabetes, and statin use at baseline were included. Of these, 14% were definite statin eligible, 7% were not eligible and had triglycerides ≥3.0 mmol/L (264 mg/dL), and 79% were not statin eligible and had triglycerides <3.0 mmol/L (264 mg/dL). During 456 057 person-years of follow-up, 1770 individuals experienced a major adverse cardiovascular event (MACE) and 734 experienced a myocardial infarction (MI). The cumulative incidences of MACE at age 70 were 8.1% (95% confidence interval 7.3-8.9%) and 14.6% (12.6-16.8%) in statin non-eligible individuals with triglycerides <3.0 mmol/L (264 mg/dL) and ≥3.0 mmol/L (264 mg/dL), and 16.5% (14.0-19.3%) in statin eligible individuals. Corresponding cumulative incidences of MI were 3.0% (2.7-3.3%), 7.8% (6.4-9.5%), and 7.1% (5.9-8.4%), respectively. The estimated 10-year risks of MACE were 2.8% (2.6-3.0%) and 5.7% (4.9-6.6%) in statin non-eligible individuals with triglycerides <3.0 mmol/L (264 mg/dL) and ≥3.0 mmol/L (264 mg/dL), and 7.6% (6.9-8.3%) in statin eligible individuals; the median age in these three groups were 51, 51, and 60 years, respectively. Corresponding risks of MI were 1.0% (0.9-1.1%), 3.0% (2.4-3.7%), and 3.3% (2.8-3.7%), respectively.Conclusion: Statin non-eligible individuals with triglycerides ≥3.0 mmol/L (264 mg/dL) had risk of ASCVD similar to statin eligible individuals, defined according to the 2016 ESC/EAS guidelines. This illustrates an unmet need for primary prevention, calling for expansion of guidelines on statin eligibility, and the potential for placebo-con

Aims High-density lipoprotein (HDL) cholesterol concentrations are inversely associated with cardiovascular disease and mortality across a range of concentrations, but genetic evidence suggest that extreme high concentrations may paradoxically lead to more cardiovascular disease. We tested the hypothesis that extreme high concentrations of HDL cholesterol are associated with high all-cause mortality in men and women. Methods and results A total of 52 268 men and 64 240 women were included from the two prospective population-based studies, the Copenhagen City Heart Study and the Copenhagen General Population Study. During 745 452 person-years of followup, number of deaths from any cause were 5619 (mortality rate, 17.1/1000 person-years (95% confidence interval (CI): 16.7-17.6)) in men and 5059 (mortality rate, 12.1/1000 person-years (11.8-12.4)) in women. The association between HDL cholesterol concentrations and all-cause mortality was U-shaped for both men and women, with both extreme high and low concentrations being associated with high all-cause mortality risk. The concentration of HDL cholesterol associated with the lowest all-cause mortality was 1.9mmol/L (95% CI: 1.4-2.0) (73 mg/dL (54-77)) in men and 2.4mmol/L (1.8-2.5) (93mg/dL (69-97)) in women. When compared with the groups with the lowest risk, the multifactorially adjusted hazard ratios for all-cause mortality were 1.36 (95% CI: 1.09-1.70) for men with HDL cholesterol of 2.5-2.99mmol/L (97-115 mg/dL) and 2.06 (1.44-2.95) for men with HDL cholesterol ≥3.0 mmol/L (116 mg/dL). For women, corresponding hazard ratios were 1.10 (0.83-1.46) for HDL cholesterol of 3.0-3.49mmol/L (116-134mg/dL) and 1.68 (1.09-2.58) for HDL cholesterol ≥3.5 mmol/L (135 mg/dL). Conclusion Men and women in the general population with extreme high HDL cholesterol paradoxically have high all-cause mortality. These findings need confirmation in other studies.

Introduction: Previous smaller studies suggest that anemia is a risk factor for mortality in patients with hip fracture. The purpose of this investigation was to assess the correlation between hemoglobin at admission with 30-day mortality following a hip fracture in a large-scale study. Patients and Methods: From January 1996 to December 2012, all patients with hip fracture (>60 years of age) admitted to Bispebjerg Hospital, Copenhagen, were identified from a local hip fracture database. We excluded conservatively treated patients and patients who died preoperatively. Results: Seven thousand four hundred twenty-one consecutive patients with hip fracture were identified. Of those 7319 had a hemoglobin measurement on admission and were thus eligible for further analysis. Mean hemoglobin for patients alive at 30 days was 7.6 (standard deviation [SD]: 1.0) and for deceased patients 7.4 (SD: 1.1), P < .0001. Mean age was 82.6 years (SD: 8.5), and 76.5% of the population were female (Nfemales = 5600). The 30-day mortality decreases for every increase in hemoglobin of 1.0 mmol/L in a univariate analysis (P < .0001). The hazard ratio (HR) with 95% confidence interval (CI) for 30-day mortality in patients with anemia (<7.3 mmol/L for females and <8.3 mmol/L for males; Nanemic = 3235) was 1.66 (CI: 1.43-1.91, P < .0001). Adjusting for age, type of fracture, gender, and comorbidities (Charlson score) slightly attenuated the risk estimate (HR: 1.21, CI: 1.03-1.41, P = .02). Conclusion: This study demonstrates increased 30-day mortality in patients with low hemoglobin at admission, even after adjusting for comorbidities., INTRODUCTION: Previous smaller studies suggest that anemia is a risk factor for mortality in patients with hip fracture. The purpose of this investigation was to assess the correlation between hemoglobin at admission with 30-day mortality following a hip fracture in a large-scale study.PATIENTS AND METHODS: From January 1996 to December 2012, all patients with hip fracture (>60 years of age) admitted to Bispebjerg Hospital, Copenhagen, were identified from a local hip fracture database. We excluded conservatively treated patients and patients who died preoperatively.RESULTS: Seven thousand four hundred twenty-one consecutive patients with hip fracture were identified. Of those 7319 had a hemoglobin measurement on admission and were thus eligible for further analysis. Mean hemoglobin for patients alive at 30 days was 7.6 (standard deviation [SD]: 1.0) and for deceased patients 7.4 (SD: 1.1), P < .0001. Mean age was 82.6 years (SD: 8.5), and 76.5% of the population were female (Nfemales = 5600). The 30-day mortality decreases for every increase in hemoglobin of 1.0 mmol/L in a univariate analysis (P < .0001). The hazard ratio (HR) with 95% confidence interval (CI) for 30-day mortality in patients with anemia (<7.3 mmol/L for females and <8.3 mmol/L for males; Nanemic = 3235) was 1.66 (CI: 1.43-1.91, P < .0001). Adjusting for age, type of fracture, gender, and comorbidities (Charlson score) slightly attenuated the risk estimate (HR: 1.21, CI: 1.03-1.41, P = .02).CONCLUSION: This study demonstrates increased 30-day mortality in patients with low hemoglobin at admission, even after adjusting for comorbidities.