Age-specific mortality trends in heart failure over 25 years: a retrospective Danish nationwide cohort study.

BACKGROUND: Despite advances in heart failure care reducing mortality in clinical trials, it remains unclear whether real-life cohorts have had similar improvements in life expectancy across the age spectrum. We aimed to investigate how mortality trends changed in patients with heart failure over the past 25 years, stratified by age groups. METHODS: Using Danish nationwide registries, we identified patients with new-onset heart failure aged 18-95 years. The 5-year all-cause mortality risk and the absolute risk difference of mortality between patients with heart failure and age-matched and sex-matched heart failure-free controls were assessed using Kaplan-Meier estimates and multivariable Cox regression models. Mortality trends were analysed across five calendar periods (1996-2000, 2001-05, 2006-10, 2011-15, and 2016-20) and three age groups (<65 years, 65-79 years, and ≥80 years). FINDINGS: 194 997 patients with heart failure were included. Mortality significantly decreased from 1996-2000 (66% [95% CI 65·5-66·4]) to 2016-20 (43% [42·1-43·4]), with similar results shown in all age groups (<65 years: 35% [33·9-36·1] to 15% [14·6-16·3]; 65-79 years: 64% [63·1-64·5] to 39% [37·6-39·6]; and ≥80 years: 84% [83·1-84·3] to 73% [71·7-73·9]). Adjusted mortality rates supported these associations. The absolute risk difference declined notably in younger age groups (<65 years: 29·9% [28·8-31·0] to 12·7% [12·0-13·4] and 65-79 years: 41·1% [40·3-41·9] to 25·1% [24·4-25·8]), remaining relatively stable in those aged 80 years or older (30·6% [29·9-31·3] to 28% [27·2-28·8]). INTERPRETATION: Over 25 years, there has been a consistent decrease in mortality among patients with heart failure across age groups, albeit less prominently in patients aged 80 years or older. Further insight is needed to identify effective strategies for improving disease burden in older patients with heart failure. FUNDING: None. TRANSLATION: For the Danish translation of the abstract see Supplementary Materials section.

Risk of cardiovascular disease in patients with multiple sclerosis treated with fingolimod compared to natalizumab: A nationwide cohort study of 2095 patients in Denmark.

BACKGROUND: Fingolimod may be associated with risk of developing cardiovascular disease (CVD). Studies including reference groups and long follow-up are scarce. OBJECTIVES: We hypothesized that patients treated with fingolimod would be at higher risk of developing CVD compared to patients treated with natalizumab. METHODS: A nationwide 12-year cohort study linking individual-level data from the Danish Multiple Sclerosis Registry with health registries on 2095 adult patients with multiple sclerosis (MS) without any health records of CVD at follow-up start. Exposure to fingolimod and natalizumab was defined by the first treatment of at least 3 months. Cohort entry was from 2011 to 2018. We defined CVD as a composite measure, including hypertension, ischemic heart disease, atrial fibrillation, heart failure, and stroke. We used multivariable adjusted Cox regression. RESULTS: There were 28.8 and 17.4 CVD events per 1000 person-years in fingolimod and natalizumab groups, respectively. Compared to natalizumab-treated patients, fingolimod-treated patients had a higher risk of CVD (hazard ratio (HR) = 1.57; 95% confidence interval (CI) = 1.18-2.08). Hypertension comprised 200 of 244 CVD events. CONCLUSION: We found an increased risk of CVD in patients with MS treated with fingolimod. This increased risk was mainly due to hypertension.

Temporal Trends in Noncardiovascular Morbidity and Mortality Following Acute Myocardial Infarction.

BACKGROUND: Due to improved management, diagnosis, and care of myocardial infarction (MI), patients may now survive long enough to increasingly develop serious noncardiovascular conditions. OBJECTIVES: This study aimed to test this hypothesis by investigating the temporal trends in noncardiovascular morbidity and mortality following MI. METHODS: We conducted a registry-based nationwide cohort study of all Danish patients with MI during 2000 to 2017. Outcomes were cardiovascular and noncardiovascular mortality, incident cancer, incident renal disease, and severe infectious disease. RESULTS: From 2000 to 2017, 136,293 consecutive patients were identified (63.2% men, median age 69 years). The 1-year risk of cardiovascular mortality between 2000 to 2002 and 2015 to 2017 decreased from 18.4% to 7.6%, whereas noncardiovascular mortality decreased from 5.8% to 5.0%. This corresponded to an increase in the proportion of total 1-year mortality attributed to noncardiovascular causes from 24.1% to 39.5%. Furthermore, increases in 1-year risk of incident cancer (1.9%-2.4%), incident renal disease (1.0%-1.6%), and infectious disease (5.5%-9.1%) were observed (all P trend <0.01). In analyses standardized for changes in patient characteristics, the increased risk of cancer in 2015 to 2017 compared with 2000 to 2002 was no longer significant (standardized risk ratios for cancer: 0.99 [95% CI: 0.91-1.07]; renal disease: 1.28 [95% CI: 1.15-1.41]; infectious disease: 1.28 [95% CI: 1.23-1.34]). CONCLUSIONS: Although cardiovascular mortality following MI improved substantially during 2000 to 2017, the risk of noncardiovascular morbidity increased. Moreover, noncardiovascular causes constitute an increasing proportion of post-MI mortality. These findings suggest that further attention on noncardiovascular outcomes is warranted in guidelines and clinical practice and should be considered in the design of future clinical trials.

Outcomes of out-of-hospital cardiac arrest in adult congenital heart disease: a Danish nationwide study.

AIMS: The risk, characteristics, and outcome of out-of-hospital cardiac arrest (OHCA) in patients with congenital heart disease (CHD) remain scarcely investigated. METHODS AND RESULTS: An epidemiological registry-based study was conducted. Using time-dependent Cox regression models fitted with a nested case-control design, hazard ratios (HRs) with 95% confidence intervals of OHCA of presumed cardiac cause (2001-19) associated with simple, moderate, and severe CHD were calculated. Moreover, using multiple logistic regression, we investigated the association between pre-hospital OHCA characteristics and 30-day survival and compared 30-day survival in OHCA patients with and without CHD. Overall, 43 967 cases (105 with simple, 144 with moderate, and 53 with severe CHD) and 219 772 controls (median age 72 years, 68.2% male) were identified. Any type of CHD was found to be associated with higher rates of OHCA compared with the background population [simple CHD: HR 1.37 (1.08-1.70); moderate CHD: HR 1.64 (1.36-1.99); and severe CHD: HR 4.36 (3.01-6.30)]. Pre-hospital cardiopulmonary resuscitation and defibrillation were both associated with improved 30-day survival in patients with CHD, regardless of CHD severity. Among patients with OHCA, simple, moderate, and severe CHD had a similar likelihood of 30-day survival compared with no CHD [odds ratio 0.95 (0.53-1.69), 0.70 (0.43-1.14), and 0.68 (0.33-1.57), respectively]. CONCLUSION: A higher risk of OHCA was found throughout the spectrum of CHD. Patients with and without CHD showed the same 30-day survival, which relies on the pre-hospital chain of survival, namely cardiopulmonary resuscitation and defibrillation.

Specialized heart failure clinics versus primary care: Extended registry-based follow-up of the NorthStar trial.

BACKGROUND: Whether continued follow-up in specialized heart failure (HF) clinics after optimization of guideline-directed therapy improves long-term outcomes in patients with HF with reduced ejection fraction (HFrEF) is unknown. METHODS AND RESULTS: 921 medically optimized HFrEF patients enrolled in the NorthStar study were randomly assigned to follow up in a specialized HF clinic or primary care and followed for 10 years using Danish nationwide registries. The primary outcome was a composite of HF hospitalization or cardiovascular death. We further assessed the 5-year adherence to prescribed neurohormonal blockade in 5-year survivors. At enrollment, the median age was 69 years, 24,7% were females, and the median NT-proBNP was 1139 pg/ml. During a median follow-up time of 4.1 (Q1-Q3 1.5-10.0) years, the primary outcome occurred in 321 patients (69.8%) randomized to follow-up in specialized HF clinics and 325 patients (70.5%) randomized to follow-up in primary care. The rate of the primary outcome, its individual components, and all-cause death did not differ between groups (primary outcome, hazard ratio 0.96 [95% CI, 0.82-1.12]; cardiovascular death, 1.00 [0.81-1.24]; HF hospitalization, 0.97 [0.82-1.14]; all-cause death, 1.00 [0.83-1.20]). In 5-year survivors (N = 660), the 5-year adherence did not differ between groups for angiotensin-converting enzyme inhibitors (p = 0.78), beta-blockers (p = 0.74), or mineralocorticoid receptor antagonists (p = 0.47). CONCLUSIONS: HFrEF patients on optimal medical therapy did not benefit from continued follow-up in a specialized HF clinic after initial optimization. Development and implementation of new monitoring strategies are needed.

Temporal trends in the incidence of malignancy in heart failure: a nationwide Danish study.

AIMS: Cancer and heart failure (HF) share risk factors, pathophysiological mechanisms, and possibly genetics. Improved HF survival may increase the risk of cancer due to a competing risk. Whether the incidence of cancer has increased over time in patients with HF as survival has improved is unclear. Therefore, temporal trends of new onset cancer in HF patients between 1997 and 2016 were investigated. METHODS AND RESULTS: Using Danish nationwide registers, 103 711 individuals alive, free of cancer, and aged 30-80 years 1 year after HF diagnosis (index date) were included between 1 January 1997 and 31 December 2016. A five-year incidence rate of cancer for each year after index date was calculated. The median age and proportion of women at the index date decreased with advancing calendar time [1997-2001: 70.3 interquartile range (Q1-Q3 62.5-75.7), 60.9% men; 2012-16: 67.6 (59.2-73.8), 67.5% men]. The five-year incidence rate of cancer was 20.9 and 20.2 per 1,000 person-years in 1997 and 2016, respectively. In a multivariable Cox regression model, the hazard rates between index years 1997 (reference) and 2016 were not significantly different [hazard ratio 1.09 (0.97-1.23)]. The five-year absolute risk of cancer did not change with advancing calendar year, going from 9.0% (1997-2001) to 9.0% (2012-16). Five-year cumulative incidence of survival for HF patients increased with advancing calendar year, going from 55.9% (1997-2001) to 74.3% (2012-2016). CONCLUSION: Although cancer rates during 1997-2016 have remained stable within 1-6 years after the HF diagnosis, long-term survival following a HF diagnosis has increased significantly.

Lifetime risk of comorbidity in patients with simple congenital heart disease: a Danish nationwide study.

AIMS: In a continuously ageing population of patients with congenital heart disease (CHD), understanding the long-term risk of morbidity is crucial. The aim of this study was to compare the lifetime risks of developing comorbidities in patients with simple CHD and matched controls. METHODS AND RESULTS: Using the Danish nationwide registers spanning from 1977 to 2018, simple CHD cases were defined as isolated atrial septal defect (ASD), ventricular septal defect (VSD), pulmonary stenosis, or patent ductus arteriosus in patients surviving until at least 5 years of age. There were 10 controls identified per case. Reported were absolute lifetime risks and lifetime risk differences (between patients with simple CHD and controls) of incident comorbidities stratified by groups and specific cardiovascular comorbidities. Of the included 17 157 individuals with simple CHD, the largest subgroups were ASD (37.7%) and VSD (33.9%), and 52% were females. The median follow-up time for patients with CHD was 21.2 years (interquartile range: 9.4-39.0) and for controls, 19.8 years (9.0-37.0). The lifetime risks for the investigated comorbidities were higher and appeared overall at younger ages for simple CHD compared with controls, except for neoplasms and chronic kidney disease. The lifetime risk difference among the comorbidity groups was highest for neurological disease (male: 15.2%, female: 11.3%), pulmonary disease (male: 9.1%, female: 11.7%), and among the specific comorbidities for stroke (male: 18.9%, female: 11.4%). The overall risk of stroke in patients with simple CHD was mainly driven by ASD (male: 28.9%, female: 17.5%), while the risks of myocardial infarction and heart failure were driven by VSD. The associated lifetime risks of stroke, myocardial infarction, and heart failure in both sexes were smaller in invasively treated patients compared with untreated patients with simple CHD. CONCLUSION: Patients with simple CHD had increased lifetime risks of all comorbidities compared with matched controls, except for neoplasms and chronic kidney disease. These findings highlight the need for increased attention towards early management of comorbidity risk factors.

Type 2 diabetes mellitus and higher rate of complete atrioventricular block: a Danish Nationwide Registry.

AIMS: The present study aimed to determine the association between Type 2 diabetes mellitus (T2DM) and third-degree (complete) atrioventricular block. METHODS AND RESULTS: This nationwide nested case-control study included patients older than 18 years, diagnosed with third-degree atrioventricular block between 1 July 1995 and 31 December 2018. Data on medication, comorbidity, and outcomes were collected from Danish registries. Five controls, from the risk set of each case of third-degree atrioventricular block, were matched on age and sex to fit a Cox regression model with time-dependent exposure and time-dependent covariates. Subgroup analysis was conducted with Cox regression models for each subgroup. We located 25 995 cases with third-degree atrioventricular block that were matched with 130 004 controls. The mean age was 76 years and 62% were male. Cases had more T2DM (21% vs. 11%), hypertension (69% vs. 50%), atrial fibrillation (25% vs. 10%), heart failure (20% vs. 6.3%), and myocardial infarction (19% vs. 9.2%), compared with the control group. In Cox regression analysis, adjusting for comorbidities and atrioventricular nodal blocking agents, T2DM was significantly associated with third-degree atrioventricular block (hazard ratio: 1.63, 95% confidence interval: 1.57-1.69). The association remained in several subgroup analyses of diseases also suspected to be associated with third-degree atrioventricular block. There was a significant interaction with comorbidities of interest including hypertension, atrial fibrillation, heart failure, and myocardial infarction. CONCLUSION: In this nationwide study, T2DM was associated with a higher rate of third-degree atrioventricular block compared with matched controls. The association remained independent of atrioventricular nodal blocking agents and other comorbidities known to be associated with third-degree atrioventricular block.

Temporal changes in risk of cardiovascular events in people with newly diagnosed type 2 diabetes with and without cardiovascular disease.

AIMS: Examine temporal changes in the risk of cardiovascular events in people with newly diagnosed type 2 diabetes with and without cardiovascular disease (CVD). METHODS: 283,600 individuals with newly diagnosed type 2 diabetes and age-, sex-, and CVD-matched controls without diabetes were identified through Danish nationwide registries between 1997 and 2014. Using Cox regression models, we report the standardized absolute 5-year risk of cardiovascular death, myocardial infarction, stroke, and heart failure for people with diabetes and controls. RESULTS: Individuals with newly diagnosed diabetes were at increased risk of cardiovascular events compared to controls. From 1997-2002 to 2009-2014 reductions in cardiovascular events for people with diabetes were: cardiovascular death; 26.5% to 13.8% in people with CVD and from 7.3% to 3.2% in people without CVD, myocardial infarction; 13.1% to 6.5% in people with CVD and from 4.1% to 1.9% in people without CVD, stroke; 14.2% to 8.8% in people with CVD and from 4.9% to 2.2% in people without CVD, and heart failure; 21.0% to 13.8% in people with CVD and from 5.0% to 2.6% in people without CVD. The risk of cardiovascular events declined more among people with diabetes than controls. CONCLUSIONS: Newly diagnosed type 2 diabetes was associated with an increased risk of cardiovascular events, and the risk decreased significantly 1997-2014 in both people with and without CVD. Furthermore, the excess risk associated with type 2 diabetes decreased significantly during the study period.

Temporal trends in initiation of mineralocorticoid receptor antagonists and risk of subsequent withdrawal in patients with heart failure: a nationwide study in Denmark from 2003-2017.

AIMS: Despite landmark heart failure (HF) with reduced ejection fraction (HFrEF) trials showing effect of mineralocorticoid receptor antagonists (MRA) on the risk of death and HF hospitalization, it has been suggested that MRAs are underutilized or frequently withdrawn. This study sought to identify temporal trends in the initiation of MRAs and the subsequent risk of withdrawal and adherence of MRAs in HF patients treated with a renin-angiotensin system inhibitor and a beta-blocker in Denmark from 2003-2017. METHODS AND RESULTS: From nationwide registries, we identified patients receiving a diagnosis of HF. Use of MRA was identified by at least one prescription within 6 months after the diagnosis. The absolute risk of withdrawal with treatment was assessed with cumulative incidence, accounting for the competing risk of death. To estimate adherence, we calculated the proportion of days covered. We included 51 512 patients with incident HF. During the study period, 20 779 (40.3%) patients initiated MRA therapy. The incidence of withdrawal of MRA was 49.2% throughout the study period; 48.0% of the HF patients were adherent to the treatment. Among patients withdrawing treatment with MRA, the cumulative incidence of reinitiating was 36.6%. CONCLUSIONS: In a nationwide cohort of patients with HF, approximately half of the patients received MRA as third-line therapy within the first 6 months after diagnosis and approximately half of these withdrew MRA within 5 years. These findings warrant an increasing focus on retention to MRA treatment in a real-life setting.

Lifetime Risk of Heart Failure and Trends in Incidence Rates Among Individuals With Type 2 Diabetes Between 1995 and 2018.

Background There are limited data on the lifetime risk of heart failure (HF) in people with type 2 diabetes and how incidence has changed over time. We estimated the cumulative incidence and incidence rates of HF among Danish adults with type 2 diabetes between 1995 and 2018 using nationwide data. Methods and Results In total, 398 422 patients (49% women) with type 2 diabetes were identified. During follow-up, 36 400 (9%) were diagnosed with HF and 121 459 (30%) were censored due to death. Using the Aalen-Johansen estimators, accounting for the risk of death, the estimated residual lifetime risk of HF at age 50 years was calculated as 24% (95% CI 22%-27%) in women and 27% (25%-28%) in men. During the observational period, the proportion of patients treated with statins, angiotensin-converting enzyme inhibitors or angiotensin II receptor blockers, and metformin increased from <30% to >60%. Similarly, the annual incidence rates of HF decreased significantly, with declines being greater in older versus younger individuals (5% versus 2% in age >50 versus ≤50 years, respectively; P<0.0001) and in women versus men (5% versus 4%, P=0.02), but similar in patients with and without IHD (4% versus 4%, P=0.53). Conclusions The current lifetime risk of HF in type 2 diabetes approximates 1 in 4 for men and women. Paralleled by an increase in use of evidence-based pharmacotherapy over the past decades, the risk of developing HF has declined across several subgroups and regardless of underlying IHD, suggesting that optimal diabetes treatment can mitigate HF risk.

Time Trends in Simple Congenital Heart Disease Over 39 Years: A Danish Nationwide Study.

Background We describe calendar time trends of patients with simple congenital heart disease. Methods and Results Using the nationwide Danish registries, we identified individuals diagnosed with isolated ventricular septal defect, atrial septal defect, patent ductus arteriosus, or pulmonary stenosis during 1977 to 2015, who were alive at 5 years of age. We reported incidence per 1 000 000 person-years with 95% CIs, 1-year invasive cardiac procedure probability and age at time of diagnosis stratified by diagnosis age (children ≤18 years, adults >18 years), and 1-year all-cause mortality stratified by diagnosis age groups (5-30, 30-60, 60+ years). We identified 15 900 individuals with simple congenital heart disease (ventricular septal defect, 35.2%; atrial septal defect, 35.0%; patent ductus arteriosus, 25.2%; pulmonary stenosis, 4.6%), of which 75.7% were children. From 1977 to 1986 and 2007 to 2015, the incidence rates increased for atrial septal defect in adults (8.8 [95% CI, 7.1-10.5] to 31.8 [95% CI, 29.2-34.5]) and in children (26.6 [95% CI, 20.9-32.3] to 150.8 [95% CI, 126.5-175.0]). An increase was only observed in children for ventricular septal defect (72.1 [95% CI, 60.3-83.9] to 115.4 [95% CI, 109.1-121.6]), patent ductus arteriosus (49.2 [95% CI, 39.8-58.5] to 102.2 [95% CI, 86.7-117.6]) and pulmonary stenosis (5.7 [95% CI, 3.0-8.3] to 21.5 [95% CI, 17.2-25.7]) while the incidence rates remained unchanged for adults. From 1977-1986 to 2007-2015, 1-year mortality decreased for all age groups (>60 years, 30.1%-9.6%; 30-60 years, 9.5%-1.0%; 5-30 years, 1.9%-0.0%), and 1-year procedure probability decreased for children (13.8%-6.6%) but increased for adults (13.3%-29.6%) were observed. Conclusions Increasing incidence and treatment and decreasing mortality among individuals with simple congenital heart disease point toward an aging and growing population. Broader screening methods for asymptomatic congenital heart disease are needed to initiate timely treatment and follow-up.

Compliance in Primary Prevention With Statins and Associations With Cardiovascular Risk and Death in a Low-Risk Population With Type 2 Diabetes Mellitus.

Background We examined whether primary prevention with statins and high adherence to statins reduce the associated risk of cardiovascular events or death in a low-risk population with type 2 diabetes mellitus (T2D). Methods and Results Using Danish nationwide registers, we included patients with new-onset T2D, aged 40 to 89 years, between 2005 and 2011, who were alive 18 months following the T2D diagnosis (index date). In patients who purchased statins within 6 months following T2D diagnosis, we calculated the proportion of days covered (PDC) within 1 year after the initial 6-month period. We studied the combined end point of myocardial infarction, stroke, or all-cause mortality, whichever came first, with Cox regression. Reported were standardized 5-year risk differences for fixed comorbidity distribution according to statin treatment history, stratified by sex and age. Among 77 170 patients, 42 975 (56%) were treated with statins, of whom 31 061 (72%) had a PDC ≥80%. In men aged 70 to 79 years who were treated with statins, the standardized 5-year risk was 22.9% (95% CI, 21.5%-24.3%), whereas the risk was 29.1% (95% CI, 27.4%-30.7%) in men not treated, resulting in a significant risk reduction of 6.2% (95% CI, 4.0%-8.4%), P<0.0001. The risk reduction associated with statins increased with advancing age group (women: age 40-49 years, 0.0% [95% CI, -1.0% to 1.0%]; age 80-89 years, 10.8% [95% CI, 7.2%-14.4%]). Standardizing to all patients treated with statins, PDC <80% was associated with increased risk difference (reference PDC ≥80%; PDC <20%, 4.2% [95% CI, 2.9%-5.6%]). Conclusions This study supports the use of statins as primary prevention against cardiovascular diseases or death in 18-month surviving low-risk patients with T2D, with the highest effect in the elderly and adherent patients.

Prediction of first cardiovascular disease event in 2.9 million individuals using Danish administrative healthcare data: a nationwide, registry-based derivation and validation study.

Aims: The aim of this study was to derive and validate a risk prediction model with nationwide coverage to predict the individual and population-level risk of cardiovascular disease (CVD). Methods and results: All 2.98 million Danish residents aged 30-85 years free of CVD were included on 1 January 2014 and followed through 31 December 2018 using nationwide administrative healthcare registries. Model predictors and outcome were pre-specified. Predictors were age, sex, education, use of antithrombotic, blood pressure-lowering, glucose-lowering, or lipid-lowering drugs, and a smoking proxy of smoking-cessation drug use or chronic obstructive pulmonary disease. Outcome was 5-year risk of first CVD event, a combination of ischaemic heart disease, heart failure, peripheral artery disease, stroke, or cardiovascular death. Predictions were computed using cause-specific Cox regression models. The final model fitted in the full data was internally-externally validated in each Danish Region. The model was well-calibrated in all regions. Area under the receiver operating characteristic curve (AUC) and Brier scores ranged from 76.3% to 79.6% and 3.3 to 4.4. The model was superior to an age-sex benchmark model with differences in AUC and Brier scores ranging from 1.2% to 1.5% and -0.02 to -0.03. Average predicted risks in each Danish municipality ranged from 2.8% to 5.9%. Predicted risks for a 66-year old ranged from 2.6% to 25.3%. Personalized predicted risks across ages 30-85 were presented in an online calculator (https://hjerteforeningen.shinyapps.io/cvd-risk-manuscript/). Conclusion: A CVD risk prediction model based solely on nationwide administrative registry data provided accurate prediction of personal and population-level 5-year first CVD event risk in the Danish population. This may inform clinical and public health primary prevention efforts.

Immune Checkpoint Inhibitor Treatment and Ophthalmologist Consultations in Patients with Malignant Melanoma or Lung Cancer-A Nationwide Cohort Study.

PURPOSE: To estimate the frequency of first-time ocular events in patients treated with immune checkpoint inhibitors (ICI). METHODS: Patients with cancer in 2011-2018 in Denmark were included and followed. The outcomes were first-time ophthalmologist consultation and ocular inflammation. One-year absolute risks of outcomes and hazard ratios were estimated. RESULTS: 112,289 patients with cancer were included, and 2195 were treated with ICI. One year after the first ICI treatment, 6% of the patients with cancer, 5% and 8% of the lung cancer (LC) and malignant cutaneous melanoma (MM) patients, respectively, had a first-time ophthalmologist consultation. The risk of ocular inflammation was 1% (95% confidence interval (CI) 0.4-1.2). Among patients with MM, ICI was associated with ocular inflammation in women (HR 12.6 (95% CI 5.83-27.31) and men (4.87 (95% CI 1.79-13.29)). Comparing patients with and without ICI treatment, the risk of first-time ophthalmologist consultation was increased in patients with LC (HR 1.74 (95% CI 1.29-2.34) and MM (HR 3.21 (95% CI 2.31-4.44). CONCLUSIONS: The one-year risks of first-time ophthalmologist consultation and ocular inflammation were 6% and 1%, respectively, in patients treated with ICI. In patients with LC and MM, the risk was increased in patients with ICI compared with patients without ICI.

Does type 2 diabetes confer higher relative rates of cardiovascular events in women compared with men?

AIMS: To investigate whether diabetes confers higher relative rates of cardiovascular events in women compared with men using contemporary data, and whether these sex-differences depend on age. METHODS AND RESULTS: All Danish residents aged 40-89 years without a history major adverse cardiovascular events, including heart failure, as of 1 January 2012 until 31 December 2016 were categorized by diabetes-status and characterized by individual-level linkage of Danish nationwide administrative registers. We used Poisson regression to calculate overall and age-dependent incidence rates, incidence rate ratios, and women-to-men ratios for myocardial infarction, heart failure, ischaemic stroke, or cardiovascular death (MACE-HF). Among 218 549 (46% women) individuals with diabetes, the absolute rate of MACE-HF was higher in men than in women (24.9 vs. 19.9 per 1000 person-years). Corresponding absolute rates in men and women without diabetes were 10.1 vs. 7.0 per 1000 person-years. Comparing individuals with and without diabetes, women had higher relative rates of MACE-HF than men [2.8 (confidence interval, CI 2.9-2.9) in women vs. 2.5 (CI 2.4-2.5) in men] with a women-to-men ratio of 1.15 (CI 1.11-1.19, P < 0.001). The relative rates of MACE-HF were highest in the youngest and decreased with advancing age for both men and women, but the relative rates were higher in women across all ages, with the highest women-to-men ratio between age 50 and 60 years. CONCLUSION: Although men have higher absolute rates of cardiovascular complications, the relative rates of cardiovascular complications associated with diabetes are higher in women than in men across all ages in the modern era.

Incidence of new onset cancer in patients with a myocardial infarction - a nationwide cohort study.

BACKGROUND: Few studies have suggested that patients with myocardial infarction (MI) may be at increased risk of cancer, but further large register-based studies are needed to evaluate this subject. The aim of this study was to assess the incident rates of cancer and death by history of MI, and whether an MI is independently associated with cancer in a large cohort study. METHOD: All Danish residents aged 30-99 in 1996 without prior cancer or MI were included and were followed until 2012. Patients were grouped according to incident MI during follow-up. Incidence rates (IR) of cancer and death in individuals with and without MI and incidence rate ratios (IRR, using multivariable Poisson regression analyses) of cancer associated with an MI were calculated. RESULTS: Of 2,871,168 individuals, 122,275 developed an MI during follow-up, 11,375 subsequently developed cancer (9.3%, IR 19.1/1000 person-years) and 65,225 died (53.3%, IR 106.0/1000 person-years). In the reference population, 372,397 developed cancer (13.0%, IR 9.3/1000 person-years) and 753,767 died (26.3%, IR 18.2/1000 person-years). Compared to the reference population, higher IRs of cancer and death were observed in all age groups (30-54, 55-69 and 70-99 years) and time since an MI (0-1, 1-5 and 5-17 years) in the MI population. MI was associated with an increased risk of overall cancer (IRR 1.14, 95% CI 1.10-1.19) after adjusting for age, sex and calendar year, also when additionally adjusting for chronic obstructive pulmonary disease, hypertension, dyslipidemia, diabetes and socioeconomic status (IRR 1.08, 95% CI 1.03-1.13), but not after further adjustment for the first 6 months post-MI (IRR 1.00, 95% CI 0.96-1.05). CONCLUSION: Patients after an MI have increased incidence of cancer, which may be explained by mutual risk, occult cancers and increased surveillance. Focus on risk factor management to reduce cancer and MI is warranted.