Validity of Prescription-Defined and Hospital-Diagnosed Hypertension Compared with Self-Reported Hypertension in Denmark.

Purpose: Hypertension is an important risk factor in cardio-epidemiological research, but data quality remains a concern. We validated different registry-based definitions of hypertension. Patients and Methods: The cohort included all first-time responders of the Danish National Health Surveys (2010, 2013, or 2017). Prescription-defined hypertension was defined as ≥1 or ≥2 filled prescriptions of antihypertensive specific drugs in ≥1 or ≥2 different antihypertensive drug classes within 90, 180, or 365 days before survey response. Hospital-diagnosed hypertension was defined from hypertension diagnoses within five years before the survey response. Considering self-reported hypertension as the reference, we calculated the positive predictive value (PPV), the negative predictive value (NVP), the sensitivity, and the specificity of prescription-defined and hospital-diagnosed hypertension. Results: Among 442,490 survey responders, 127,247 (29%) had self-reported hypertension. For prescription-defined hypertension with 365-day lookback, the PPV was highest for ≥2 prescriptions in ≥2 drug classes (94%) and lowest for ≥1 prescription in ≥1 drug class (85%). The NPV was highest for ≥1 prescription in ≥2 drug classes (94%) and lowest for ≥1 prescription in ≥2 drug classes (80%). The sensitivity was highest for ≥1 prescription in ≥1 drug class (79%) and lowest for ≥2 prescriptions in ≥2 drug classes (30%). The specificity was ≥94% for all algorithms. The PPV and specificity did not change noteworthy with length of lookback period, whereas the NPV and the sensitivity generally were higher for longer lookback. The algorithm ≥1 prescription in ≥2 drug classes with 365-day lookback was among the best balanced across all measures of validity (PPV=88%, NPV=94%, sensitivity=75%, specificity=96%). For hospital-diagnosed hypertension, the PPV was 90%, the NPV was 76%, the sensitivity was 22%, and the specificity was 99%. Conclusion: Compared with self-reported hypertension, the algorithms for prescription-defined and hospital-diagnosed hypertension had high predictive values and specificity, but low sensitivity.

Cardiovascular safety of using non-steroidal anti-inflammatory drugs for gout: a Danish nationwide case-crossover study.

Gout attacks are treated with uric-lowering and anti-inflammatory drugs. In patients with gout, non-steroidal anti-inflammatory drugs (NSAIDs) could be both cardiovascular beneficial, due to their anti-inflammatory actions, and cardiovascular hazardous, due to their prothrombotic, hypertensive, and proarrhythmic side effects. We, therefore, examined the risk of cardiovascular events associated with NSAID use in patients with gout. We conducted a nationwide, population-based case-crossover study of all Danes ≥ 18 years of age with first-time gout during 1997-2020, who experienced a cardiovascular event (myocardial infarction, ischemic stroke, congestive heart failure, atrial fibrillation/flutter, or cardiovascular death) (n = 59,150). The exposure was use of NSAIDs, overall and according to type (ibuprofen, naproxen, or diclofenac). We used the dates 300, 240, 180, and 120 before the outcome date as reference dates. We used the Mantel-Haenszel method to calculate odds ratios (ORs) with 95% confidence intervals (CIs) of the association between NSAID use and cardiovascular events. NSAID use was overall associated with 12% decreased odds of a cardiovascular event (OR = 0.88, 95% CI: 0.85-0.91). This decreased odds ratio was observed for the use of ibuprofen (OR = 0.92, 95% CI: 0.88-0.97) and naproxen (OR = 0.85, 95% CI: 0.74-0.97), but not for the use of diclofenac (OR = 0.97, 95% CI: 0.90-1.05). Overall, use of NSAIDs was associated with decreased odds of all the individual components of the composite outcome. NSAIDs were not associated with an increased cardiovascular event rate when used in gout patients. Ibuprofen and naproxen appeared to have better cardiovascular risk profiles than diclofenac.

Influence of Low-Density Lipoprotein Cholesterol Levels on NSAID-Associated Cardiovascular Risks After Myocardial Infarction: A Population-Based Cohort Study.

Aim: To examine whether low-density lipoprotein cholesterol (LDL-C) levels influence the cardiovascular risk associated with non-aspirin non-steroidal anti-inflammatory drug (NSAID) use after myocardial infarction (MI). Methods: Using Danish health registries, we conducted a population-based cohort study of all adult patients with first-time MI during 2010-2020 with an LDL-C value before discharge. Based on the latest LDL-C value, we categorized patients into a low and a high LDL-C group (<3.0 vs ≥3.0 mmol/L). We used time varying Cox regression to compute hazard ratios (HRs) with 95% confidence intervals of the association between NSAID use and a major adverse cardiovascular event (MACE: recurrent MI, ischemic stroke, and all-cause death). Results: We followed 50,573 patients for a median of 3.1 years. While exposed, 521 patients experienced a MACE: 312 in the low LDL-C group and 209 in the high LDL-C group. The HRs for MACE comparing NSAID use with non-use were 1.21 (1.11-1.32) overall, 1.19 (1.06-1.33) in the low LDL-C group, and 1.23 (1.07-1.41) in the high LDL-group. The HRs for recurrent MI and ischemic stroke were comparable between the LDL-C subgroups. The HRs for all-cause death were 1.22 (1.07-1.39) in the low LDL-C group and 1.54 (1.30-1.83) in the high LDL-C group. Changing the cut-off value for LDL-C to 1.8 and 1.4 mmol/L showed consistent results. Conclusion: In patients with MI, LDL-C levels did not influence the increased risk of MACE associated with NSAID use, but might influence the association between NSAID use and all-cause death.

Autoimmune blistering disorders and cardiovascular risks: A population-based cohort study.

BACKGROUND: Autoimmune blistering disorders (ABDs) might elevate cardiovascular risk, but studies are lacking. OBJECTIVE: The objective of this study was to examine if ABDs elevate the risk of atherosclerotic cardiovascular disease, heart failure, arrhythmia, venous thromboembolism, and cardiovascular death. METHODS: A population-based cohort of Danish patients with ABD (≥18 years of age) diagnosed during 1996-2021 (n = 3322) was compared with an age- and sex-matched comparison cohort from the general population (n = 33,195). RESULTS: Compared with the general population, patients with ABDs had higher 1-year risks of atherosclerotic cardiovascular disease (3.4% vs 1.6%), heart failure (1.9% vs 0.7%), arrhythmia (3.8% vs 1.3%), venous thromboembolism (1.9% vs 0.3%), and cardiovascular death (3.3% vs 0.9%). The elevated risk persisted after 10 years for all outcomes but arrhythmia. The hazard ratios associating ABDs with the outcomes during the entire follow-up were 1.24 (1.09-1.40) for atherosclerotic cardiovascular disease, 1.48 (1.24-1.77) for heart failure, 1.16 (1.02-1.32) for arrhythmia, 1.87 (1.50-2.34) for venous thromboembolism, and 2.01 (1.76-2.29) for cardiovascular death. The elevated cardiovascular risk was observed for both pemphigus and pemphigoid. LIMITATIONS: Our findings might only generalize to patients with ABDs without prevalent cardiovascular diseases. CONCLUSION: Patients with ABDs had an elevated cardiovascular risk compared with age- and sex-matched controls.

Ability of the DANCAMI to predict the risk ischemic stroke and mortality in patients with atrial fibrillation/flutter.

OBJECTIVES: Comparison of the danish comorbidity index for acute myocardial infarction (DANCAMI), the charlson comorbidity index (CCI), the elixhauser comorbidity index (ECI), and the CHA2DS2-VASc score to predict ischemic stroke, cardiovascular mortality, and all-cause mortality after atrial fibrillation/flutter. MATERIALS AND METHODS: A population-based cohort study of all Danish patients with incident atrial fibrillation/flutter during 2000-2020 (n=361,901). C-Statistics were used to evaluate the discriminatory performance for predicting 1 and 5-year risks of the outcomes for a baseline model (including age and sex) +/- the individual indices. RESULTS: For the DANCAMI, the 5-year risk did not increase with comorbidity burden for ischemic stroke (5.9% for low vs. 5.6% for severe) but did increase for cardiovascular mortality (10% for low vs. 16% for severe) and all-cause mortality (33% for low vs. 61% for severe). C-Statistics for predicting 5-year ischemic stroke risk were similar for all models (0.64). C-Statistics for predicting 5-year cardiovascular mortality risk were also similar for the baseline (0.76), the DANCAMI (0.77), the CCI (0.76), the ECI (0.76), and the CHA2DS2-VASc (0.76) models. C-Statistics for predicting 5-year all-cause mortality risk were lower for the baseline (0.71) and the CHA2DS2-VASc (0.71) models than for the DANCAMI (0.75), the CCI (0.74), and the ECI (0.74) models. The 1-year C-Statistics were comparable. CONCLUSION: The DANCAMI predicted ischemic stroke and cardiovascular mortality risks similar to the CCI, the ECI, and the CHA2DS2-VASc. The DANCAMI predicted all-cause mortality risk similar to the CCI and the ECI, but better than the baseline and the CHA2DS2-VASc.

Long-term risk of atrial fibrillation or flutter after transcatheter patent foramen ovale closure: a nationwide Danish study.

AIMS: Transcatheter closure of patent foramen ovale (PFO) is the recommended stroke prevention treatment in patients ≤60 years with cryptogenic ischemic stroke and PFO. Atrial fibrillation or flutter (AF) is a known potential procedure-related complication, but long-term risk of developing AF remains unknown. This paper studied the long-term risk of developing AF following PFO closure. METHODS AND RESULTS: A Danish nationwide cohort study was conducted. During 2008-2020, this study identified a PFO closure cohort, a PFO diagnosis cohort without PFO closure, and a general population comparison cohort matched 10:1 to the PFO closure cohort on age and sex. The outcome was first-time AF diagnosis. Risk of AF and multivariable-adjusted hazard ratio (HR) of the association between PFO closure or PFO diagnosis and AF were calculated. A total of 817 patients with PFO closure, 1224 with PFO diagnosis, and 8170 matched individuals were identified. The 5 year risk of AF was 7.8% [95% confidence interval (CI): 5.5-10] in the PFO closure cohort, 3.1% (95% CI: 2.0-4.2) in the PFO diagnosis cohort, and 1.2% (95% CI: 0.8-1.6) in the matched cohort. The HR of AF comparing PFO closure with PFO diagnosis was 2.3 (95% CI: 1.3-4.0) within the first 3 months and 0.7 (95% CI: 0.3-1.7) thereafter. The HR of AF comparing PFO closure with the matched cohort was 51 (95% CI: 21-125) within the first 3 months and 2.5 (95% CI: 1.2-5.0) thereafter. CONCLUSION: Patent foramen ovale closure was not associated with any substantial increased long-term risk of developing AF beyond the well-known procedure-related short-term risk.

Impact of hemoglobin A1c level on the association between non-steroidal anti-inflammatory drug use and cardiovascular events in patients with type 2 diabetes: A population-based cohort study.

OBJECTIVE: Non-steroidal anti-inflammatory drugs (NSAIDs) should be used cautiously in patients with type 2 diabetes. We examined whether the cardiovascular risks associated with NSAID use depended on HbA1c level in patients with type 2 diabetes. METHODS: We conducted a population-based cohort study of all adult Danes with a first-time HbA1c measurement ≥48 mmol/mol during 2012-2020 (n = 103 308). We used information on sex, age, comorbidity burden, and drug use to calculate time-varying inverse probability of treatment weights. After applying these weights in a pooled logistic regression, we estimated hazard ratios (HRs) of the association between use of NSAIDs (ibuprofen, naproxen, or diclofenac) and cardiovascular events (a composite of myocardial infarction, ischemic stroke, congestive heart failure, atrial fibrillation or flutter, and all-cause death). We stratified all analyses by HbA1c level (<53 or ≥53 mmol/mol). RESULTS: For ibuprofen use, the HR of a cardiovascular event was 1.53 (95% confidence interval [CI]: 1.34-1.75) in patients with HbA1c <53 and 1.24 (95% CI: 1.00-1.53) in patients with HbA1c ≥53 mmol/mol. For naproxen use, the HR was 1.14 (95% CI: 0.59-2.21) in patients with HbA1c <53 and 1.30 (95% CI: 0.49-3.49) in patients with HbA1c ≥53 mmol/mol. For diclofenac use, the HR was 2.40 (95% CI: 1.62-3.56) in patients with HbA1c <53 and 2.89 (95% CI: 1.65-5.04) in patients with HbA1c ≥53 mmol/mol. CONCLUSIONS: In patients with type 2 diabetes, glycemic dysregulation did not affect the cardiovascular risk associated with NSAID use.

Impact of Lifestyle and Socioeconomic Position on the Association Between Non-steroidal Anti-inflammatory Drug Use and Major Adverse Cardiovascular Events: A Case-Crossover Study.

INTRODUCTION: It is unknown whether the cardiovascular risks associated with non-steroidal anti-inflammatory drug (NSAID) use differ according to lifestyle and socioeconomic position. OBJECTIVE: We examined the association between NSAID use and major adverse cardiovascular events (MACE) within subgroups defined by lifestyle and socioeconomic position. METHODS: We conducted a case-crossover study of all adult first-time respondents to the Danish National Health Surveys of 2010, 2013, or 2017, without previous cardiovascular disease, who experienced a MACE from survey completion through 2020. We used a Mantel-Haenszel method to obtain odds ratios (ORs) of the association between NSAID use (ibuprofen, naproxen, or diclofenac) and MACE (myocardial infarction, ischemic stroke, heart failure, or all-cause death). We identified NSAID use and MACE via nationwide Danish health registries. We stratified the analyses by body mass index, smoking status, alcohol consumption, physical activity level, marital status, education, income, and employment. RESULTS: Compared with non-use, the OR of MACE was 1.34 (95% confidence interval: 1.23-1.46) for ibuprofen, 1.48 (1.04-2.43) for naproxen, and 2.18 (1.72-2.78) for diclofenac. When comparing NSAID use with non-use or the individual NSAIDs with each other, we observed no notable heterogeneity in the ORs within subgroups of lifestyle and socioeconomic position for any NSAID. Compared with ibuprofen, diclofenac was associated with increased risk of MACE in several subgroups with high cardiovascular risk, e.g., individuals with overweight (OR 1.52, 1.01-2.39) and smokers (OR 1.54, 0.96-2.46). CONCLUSIONS: The relative increase in cardiovascular risk associated with NSAID use was not modified by lifestyle or socioeconomic position.

Long-Term Prognostic Impact of Pulmonary Hypertension After Venous Thromboembolism.

Pulmonary embolism is a risk factor for chronic thromboembolic pulmonary hypertension (CTEPH), but the prognostic impact of CTEPH on venous thromboembolism (VTE) mortality remains unclear. We examined the impact of CTEPH and other pulmonary hypertension (PH) subtypes on long-term mortality after VTE. We conducted a nationwide, population-based cohort study of all adult Danish patients alive 2 years after incident VTE without previous PH from 1995 to 2020 (n = 129,040). We used inverse probability of treatment weights in a Cox model to calculate standardized mortality rate ratios (SMRs) of the association between receiving a first-time PH diagnosis ≤2 years after incident VTE and mortality (all-cause, cardiovascular, and cancer). We grouped PH as PH associated with left-sided cardiac disease (group II), PH associated with lung diseases and/or hypoxia (group III), CTEPH (group IV), and unclassified (remaining patients). Total follow-up was 858,954 years. The SMR associated with PH overall was 1.99 (95% confidence interval 1.75 to 2.27) for all-cause, 2.48 (1.90 to 3.23) for cardiovascular, and 0.84 (0.60 to 1.17) for cancer mortality. The SMR for all-cause mortality was 2.62 (1.77 to 3.88) for group II, 3.98 (2.85 to 5.56) for group III, 1.88 (1.11 to 3.20) for group IV, and 1.73 (1.47 to 2.04) for unclassified PH. The cardiovascular mortality rate was increased approximately threefold for groups II and III but was not increased for group IV. Only group III was associated with increased cancer mortality. In conclusion, PH diagnosed ≤2 years after incident VTE was associated with an overall twofold increased long-term mortality driven by cardiovascular causes.

The Ability of Comorbidity Indices to Predict Mortality After Heart Transplantation: A Validation of the Danish Comorbidity Index for Acute Myocardial Infarction, Charlson Comorbidity Index, and Elixhauser Comorbidity Index.

Advanced heart failure patients often have comorbidities of prognostic importance. However, whether total pretransplantation comorbidity burden predicts mortality in patients treated with heart transplantation (HTx) is unknown. We used population-based hospital and prescription data to examine the ability of the Danish Comorbidity Index for Acute Myocardial Infarction (DANCAMI), DANCAMI restricted to noncardiovascular diseases, Charlson Comorbidity Index, and Elixhauser Comorbidity Index to predict 30-d, 1-y, 5-y, and 10-y all-cause and cardiovascular mortality after HTx. Methods: We identified all adult Danish patients with incident HTx from the Scandiatransplant Database between March 1, 1995, and December 31, 2018 (n = 563). We calculated Harrell's C-Statistics to examine discriminatory performance. Results: The C-Statistic for predicting 1-y all-cause mortality after HTx was 0.58 (95% confidence interval [CI], 0.50-0.65) for a baseline model including age and sex. Adding comorbidity score to the baseline model did not increase the C-Statistics for DANCAMI (0.58; 95% CI, 0.50-0.65), DANCAMI restricted to noncardiovascular diseases (0.57; 95% CI, 0.50-0.64), Charlson Comorbidity Index (0.59; 95% CI, 0.51-0.66), or Elixhauser Comorbidity Index (0.58; 95% CI, 0.51-0.65). The results for 30-d, 5-y, and 10-y all-cause and cardiovascular mortality were consistent. Conclusions: After accounting for patient age and sex, none of the commonly used comorbidity indices added predictive value to short- or long-term all-cause or cardiovascular mortality after HTx.

Impact of lifestyle and socioeconomic position on use of non-steroidal anti-inflammatory drugs: A population-based cohort study.

PURPOSE: Lifestyle and socioeconomic position may confound the link between non-steroidal anti-inflammatory drugs (NSAIDs) and cardiovascular events, if associated with NSAID use. We examined this association. METHODS: We conducted a cohort study of all adult first-time responders to the Danish National Health Surveys of 2010, 2013, or 2017 without an NSAID prescription within 3 months before survey completion (n = 407 395). Study exposures were weight, smoking status, alcohol consumption, binge drinking frequency, physical activity level, marital status, highest achieved level of education, income, and employment status. We used a Cox model to compute hazard ratios of time to first redemption of an NSAID prescription and a cumulative odds model to compute odds ratios (ORs) of redeeming one additional NSAID prescription in the year after survey completion. RESULTS: Total follow-up time was 1 931 902 years. The odds of redeeming one additional NSAID prescription in the year after survey completion varied within all categories of lifestyle and socioeconomic position. The largest ORs were observed within categories of weight (1.70, 95% CI: 1.65-1.74 for obesity vs. normal weight), smoking status (1.24, 95% CI: 1.21-1.27 for current vs. never use), and education (1.44, 95% CI: 1.39-1.49 for primary or other vs. university or higher education). The Cox model showed consistent results. CONCLUSIONS: Markers of unhealthy lifestyle and low socioeconomic position were associated with initiation and prolonged NSAID use. Consideration of lifestyle and socioeconomic markers as potential confounders in NSAID studies is therefore recommended.

The West Jutland Tele-Electrocardiogram Registry (WEJU-tECG): content, data quality, and research potential.

AIM: To present the content, data quality, and research potential of the West Jutland Tele-Electrocardiogram Registry (WEJU-tECG). METHODS: Danish patients reporting symptoms indicating heart disease in the prehospital setting are subjected to a 12-lead tele-electrocardiogram (ECG) in the ambulance, which is digitally sent to a local tele-centre. WEJU-tECG is a newly established Danish registry containing information from the individual tele-ECGs received at the Regional Hospital West Jutland tele-centre. RESULTS: WEJU-tECG holds extracted information from all tele-ECGs with a valid Civil Personal Register number between 2011 and 2020. WEJU-tECG contains information on patient characteristics, tele-ECG data (including a computerised tele-ECG interpretation), vital signs, and time information. A unique Civil Personal Register number allows individual-level linkage between WEJU-tECG and other Danish registries and enables complete follow-up. WEJU-tECG contains 43,696 tele-ECGs from 29,489 different patient contacts among 20,280 different patients. WEJU-tECG contains 5566 patients with ST-segment deviations. The median age is 67 years and 45% are women. Completeness is highest for time information (100% for all variables), tele-ECG data (99% for heart rate, the specific intervals and axes, and QRS duration, and 86% for J-point deviation), and patient characteristics (100% for all variables). Completeness is lowest for vital signs (13% for systolic, diastolic, and mean arterial blood pressure, and 12% for blood oxygen saturation). The computerised tele-ECG interpretation had a negative predictive value of 80% for ST-segment elevation myocardial infarction and 94% for non-ST-segment elevation myocardial infarction and a positive predictive value of 45% for ST-segment elevation myocardial infarction and 32% for non-ST-segment elevation myocardial infarction. CONCLUSIONS: WEJU-tECG is a novel population-based tele-ECG registry with high research potential.

Type 2 diabetes and risk of diverticular disease: a Danish cohort study.

OBJECTIVES: To investigate the association between type 2 diabetes and risk of diverticular disease. Unlike previous studies, which have found conflicting results, we aimed to distinguish between diabetes types and adjust for modifiable risk factors. DESIGN: Observational cohort study. SETTING: Population-based Danish medical databases, covering the period 2005-2018. PARTICIPANTS: Respondents of the 2010 or the 2013 Danish National Health Survey, of which there were 15 047 patients with type 2 diabetes and 210 606 patients without diabetes. PRIMARY AND SECONDARY OUTCOME MEASURES: Hazard ratios (HRs) for incident hospital diagnosis of diverticular disease adjusted for survey year, sex, age, body mass index (BMI), physical activity intensity, smoking behaviour, diet and education based on Cox regression analysis. As latency may affect the association between type 2 diabetes and diverticular disease, patients with type 2 diabetes were stratified into those with <2.5, 2.5-4.9 and ≥5 years duration of diabetes prior to cohort entry. RESULTS: For patients with and without diabetes the incidence rates of diverticular disease were 0.76 and 0.54 events per 1000 person years, corresponding to a crude HR of 1.08 (95% CI 1.00 to 1.16) and an adjusted HR of 0.88 (95% CI 0.80 to 0.96). The HR was lower among patients with ≥5 years duration of diabetes (adjusted HR: 0.76, 95% CI 0.67 to 0.87) than among those with 2.5-4.9 years or <2.5 years duration. CONCLUSION: We found that patients with type 2 diabetes had a higher incidence rate of diverticular disease compared with patients without diabetes. However, after adjustment for modifiable risk factors, driven by BMI, type 2 diabetes appeared to be associated with a slightly lower risk of diverticular disease. Lack of adjustment for BMI may partially explain the conflicting findings of previous studies.

Validation of the Danish Comorbidity Index for Acute Myocardial Infarction for predicting one-year mortality in patients with venous thromboembolism.

INTRODUCTION: The Danish Comorbidity Index for Acute Myocardial Infarction (DANCAMI) was developed to predict one-year mortality after myocardial infarction. We validated DANCAMI in predicting one-year mortality after venous thromboembolism (VTE). MATERIALS AND METHODS: We identified all first-time VTE patients in Denmark during 2000-2015. Using Cox regression, we assessed the performance of DANCAMI to predict one-year all-cause mortality using Nagelkerke's R2, Harrell's C-Statistic, the net reclassification index (NRI), and the integrated discrimination improvement (IDI). We compared the performance of DANCAMI with the Charlson Comorbidity Index (CCI) and the Elixhauser Comorbidity Index (ECI) and evaluated whether DANCAMI comorbidities not included in the CCI predicted one-year mortality. We stratified the analyses by type (deep vein thrombosis [DVT] and pulmonary embolism [PE]) and presence of provoking risk factors. RESULTS: We identified 108,824 VTE patients of whom 20,649 (19%) died within one year. The R2, C-Statistic, NRI, and IDI for DANCAMI were 0.35, 0.76, 0.63, and 0.098 for VTE overall; 0.43, 0.80, 0.70, and 0.105 for DVT; and 0.24, 0.71, 0.54, and 0.083 for PE. The R2 and C-Statistic for VTE overall were 0.35 and 0.76 for CCI and 0.33 and 0.75 for ECI. After adjusting for age, sex, and all CCI comorbidities, seven DANCAMI comorbidities, not included in the CCI, predicted increased mortality. DANCAMI performed better than the CCI and ECI in predicting mortality after provoked VTE, including provoked DVT and PE. CONCLUSION: DANCAMI performed comparable to existing comorbidity indices in predicting one-year mortality after first-time VTE overall, but better after provoked VTE.

The Interaction Effect between Comorbidity Burden and Venous Thromboembolism on Mortality: A Nationwide Cohort Study.

BACKGROUND: Comorbidity influences venous thromboembolism (VTE) mortality, but it is unknown whether this is due to comorbidity alone or whether biological interaction exists. OBJECTIVES: We examined whether comorbidity and VTE interact to increase VTE mortality beyond their individual effects. METHODS: This nationwide population-based cohort study included all VTE patients ≥18 years during 2000 to 2016, and an age-, sex-, and comorbidity-matched comparison cohort of individuals without VTE. We computed age-standardized mortality rates and examined interaction on the additive scale using interaction contrasts (difference in rate differences). RESULTS: After 30-day follow-up, the mortality rate per 1,000 person-years among individuals with no comorbidity was 419 (95% confidence interval [CI]: 391-447) in the VTE and 16 (95% CI: 13-18) in the comparison cohort (rate difference: 403). The corresponding mortality rate increased to 591 (95% CI: 539-643) in the VTE cohort and 38 (95% CI: 33-44) in the comparison cohort among individuals with low comorbidity (rate difference: 553). The interaction contrast (150) showed that 25% (150/591) of mortality was explained by the interaction in individuals with low comorbidity. This percentage increased to 56% for moderate and 63% for severe comorbidity. Interaction effects were largest within 30-day follow-up, for provoked VTE, in young individuals, and in individuals noncompliant to anticoagulant therapy. Dose-response patterns for interaction effects were also observed after 31-365-day and >1-5-year follow-up (p < 0.0001). Interaction effects varied between individual comorbidities. CONCLUSION: Biological interaction between comorbidity and VTE explained a substantial proportion of VTE mortality. The interaction effect increased with comorbidity burden.

Recategorization of Non-Aspirin Nonsteroidal Anti-inflammatory Drugs According to Clinical Relevance: Abandoning the Traditional NSAID Terminology.

Non-aspirin nonsteroidal anti-inflammatory drugs (NSAIDs) are frequently used to treat pain, fever, and inflammation. Historically, NSAIDs have been categorized as traditional NSAIDs and newer cyclooxygenase (COX)-2 inhibitors (coxibs). However, traditional NSAIDs also inhibit the COX-1 and COX-2 enzyme isoforms to a varying degree. This diversity of COX-1 and COX-2 selectivity within the class of traditional NSAIDs has proven clinically important, with evidence accumulating on the cardiovascular risks associated with selective COX-2 inhibition. Thus, the relative COX-2 selectivity of traditional NSAIDs correlates with their cardiovascular risk profile, being more favourable for non-selective NSAIDs, such as naproxen and low-dose ibuprofen, and less favourable for more COX-2 selective agents, such as diclofenac. To enhance clinically relevant terminology, we advocate categorizing all non-aspirin NSAIDs-including traditional NSAIDs-according to their relative COX-1 and COX-2 selectivity as either COX-1 inhibitors, non-selective NSAIDs, or COX-2 inhibitors. We further recommend subcategorizing COX-2 inhibitors as newer COX-2 inhibitors (coxibs) or older COX-2 inhibitors. Finally, we recommend examining the effects of the individual NSAIDs included in each of the proposed categories. Adhering to these recommendations will align future studies, advance interpretation of COX-specific adverse cardiovascular effects, and provide better guidance to clinicians prescribing NSAIDs.

Chronic post-operative opioid use after open cardiac surgery: A Danish population-based cohort study.

BACKGROUND: Knowledge of chronic opioid use after cardiac surgery is sparse. We therefore aimed to describe the proportion of new chronic post-operative opioid use after open cardiac surgery. METHODS: We used prospectively registered data from a national prescription registry and a clinical registry of 29 815 first-time cardiac surgeries from three Danish university hospitals. Data collection spanned from 2003 to 2016. The main outcome was chronic post-operative opioid use, defined as at least one opioid dispensing in the fourth post-operative quarter. Data were assessed for patient-level predictors of chronic post-operative opioid use, including pre-operative opioid use, opioid use at discharge, comorbidities, and procedural related variables. RESULTS: The overall proportion of post-operative opioid use was 10.6% (95% CI: 10.2-10.9). The proportion of new chronic post-operative opioid use was 5.7% (95% CI: 5.5-6.0) among pre-operative opioid naïve patients. The corresponding proportions among patients, who pre-operatively used low or high dose opioid (1-500 mg or > 500 mg cumulative morphine equivalent opioid), were 68.3% (95% CI: 66.1-70.4) and 76.3% (95% CI: 74.0-78.5) respectively. Risk factors associated with new chronic post-operative opioid use included: female gender, underweight and obesity, pre-operative comorbidities, acute surgery, ICU-time > 1 day, and post-operative complications. Strongest predictor of chronic post-operative opioid use was post-discharge use of opioid within one month after surgery (odds ratio 3.3, 95% CI: 2.8-4.0). CONCLUSION: New chronic post-operative opioid use after open cardiac surgery is common. Focus on post-discharge opioid use may help clinicians to reduce rates of new chronic opioid users.

Prehospital triage of patients diagnosed with perforated peptic ulcer or peptic ulcer bleeding: an observational study of patients calling 1-1-2.

BACKGROUND: Triage systems are used in emergency medical services to systematically prioritize prehospital resources according to individual patient conditions. Previous studies have shown cases of preventable deaths in emergency medical services even when triage systems are used, indicating a potential undertriage among some conditions. The aim of this study was to investigate the triage level among patients diagnosed with perforated peptic ulcer (PPU) or peptic ulcer bleeding (PUB). METHODS: In a three-year period in Central Denmark Region, all patients hospitalized within 24 h after a 1-1-2 emergency call and who subsequently received either a PPU or a PUB (hereinafter combined and referred to as PPU/PUB) or a First Hour Quintet (FHQ: respiratory failure, stroke, trauma, cardiac chest pain, and cardiac arrest) diagnosis were investigated. A modified Poisson regression was used to estimate the relative risk of receiving the highest and lowest prehospital response level. Also, a linear regression analysis was used to estimate the relative risk of 30-day mortality. RESULTS: Of 8658 evaluated patients, 263 were diagnosed with PPU/PUB. After adjusting for relevant confounding variables, patients diagnosed with PPU/PUB were less likely to receive ambulance transportation compared to patients diagnosed with stroke, RR = 1.41 (CI: 1.28-1.56); trauma, RR = 1.28 (CI: 1.15-1.42); cardiac chest pain, RR = 1.47 (CI: 1.33-1.62); and cardiac arrest, RR = 1.44 (CI: 1.31-1.42). Among patients diagnosed with PPU/PUB, 6.5% (CI: 3.3-9.7) did not receive ambulance transportation. The proportion of patients not receiving ambulance transportation was higher among patients diagnosed with PPU/PUB compared to patients diagnosed with an FHQ diagnosis. The 30-day mortality rate among patients diagnosed with PPU/PUB was 7.8% (CI: 4.2-11.1). This was lower than the 30-day mortality rate among patients diagnosed with respiratory failure (P = 0.010), stroke (P = 0.001), and cardiac arrest (P < 0.001), but comparable to the 30-day mortality among patients diagnosed with cardiac chest pain (P = 0.080) and trauma (P = 0.281). CONCLUSION: Among patients calling 1-1-2, fewer patients diagnosed with PPU/PUB received ambulance transportation than patients diagnosed with FHQ diagnoses, despite a high mortality among patients diagnosed with PPU/PUB.