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.

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.

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.

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.