Christian Torp-pedersen | Aalborg University (original) (raw)

Papers by Christian Torp-pedersen

Research paper thumbnail of β-Blocker–Associated Risks in Patients With Uncomplicated Hypertension Undergoing Noncardiac Surgery

JAMA Internal Medicine, 2015

Perioperative β-blocker strategies are important to reduce risks of adverse events. Effectiveness... more Perioperative β-blocker strategies are important to reduce risks of adverse events. Effectiveness and safety may differ according to patients' baseline risk. To determine the risk of major adverse cardiovascular events (MACEs) associated with long-term β-blocker therapy in patients with uncomplicated hypertension undergoing noncardiac surgery. Association study based on in-hospital records and out-of-hospital pharmacotherapy use using a Danish nationwide cohort of patients with uncomplicated hypertension treated with at least 2 antihypertensive drugs (β-blockers, thiazides, calcium antagonists, or renin-angiotensin system [RAS] inhibitors) undergoing noncardiac surgery between 2005 and 2011. Various antihypertensive treatment regimens, chosen as part of usual care. Thirty-day risk of MACEs (cardiovascular death, nonfatal ischemic stroke, nonfatal myocardial infarction) and all-cause mortality, assessed using multivariable logistic regression models and adjusted numbers needed to harm (NNH). The baseline characteristics of the 14 644 patients who received β-blockers (65% female, mean [SD] age, 66.1 [12.0] years) were similar to those of the 40 676 patients who received other antihypertensive drugs (57% female, mean [SD] age, 65.9 [11.8] years). Thirty-day MACEs occurred in 1.3% of patients treated with β-blockers compared with 0.8% of patients not treated with β-blockers (P < .001). β-Blocker use was associated with increased risks of MACEs in 2-drug combinations with RAS inhibitors (odds ratio [OR], 2.16 [95% CI, 1.54-3.04]), calcium antagonists (OR, 2.17 [95% CI, 1.48-3.17]), and thiazides (OR, 1.56 [95% CI, 1.10-2.22]), compared with the reference combination of RAS inhibitors and thiazides. Results were similar for all-cause mortality. Risk of MACEs associated with β-blocker use seemed especially pronounced for patients at least 70 years old (number needed to harm [NNH], 140 [95% CI, 86-364]), for men (NNH, 142 [95% CI, 93-195]), and for patients undergoing acute surgery (NNH, 97 [95% CI, 57-331]), compared with patients younger than 70 years, women, and patients undergoing elective surgery, respectively. Antihypertensive treatment with a β-blocker may be associated with increased risks of perioperative MACEs and all-cause mortality in patients with uncomplicated hypertension.

Research paper thumbnail of Association of Selected Antipsychotic Agents With Major Adverse Cardiovascular Events and Noncardiovascular Mortality in Elderly Persons

Journal of the American Heart Association, 2015

Data from observational studies have raised concerns about the safety of treatment with antipsych... more Data from observational studies have raised concerns about the safety of treatment with antipsychotic agents (APs) in elderly patients with dementia, but this area has been insufficiently investigated. We performed a head-to-head comparison of the risk of major adverse cardiovascular events and noncardiovascular mortality associated with individual APs (ziprasidone, olanzapine, risperidone, quetiapine, levomepromazine, chlorprothixen, flupentixol, and haloperidol) in Danish treatment-naïve patients aged ≥70 years. We followed all treatment-naïve Danish citizens aged ≥70 years that initiated treatment with APs for the first time between 1997 and 2011 (n=91 774, mean age 82±7 years, 35 474 [39%] were men). Incidence rate ratios associated with use of different APs were assessed by multivariable time-dependent Poisson regression models. For the first 30 days of treatment, compared with risperidone, incidence rate ratios of major adverse cardiovascular events were higher with use of lev...

Research paper thumbnail of Prognostic importance of plasma NT-pro BNP in chronic heart failure in patients treated with a β-blocker: Results from the Carvedilol Or Metoprolol European Trial (COMET) trial

Background: Plasma levels of N-terminal pro-brain natriuretic peptide (NT-pro BNP) are increased ... more Background: Plasma levels of N-terminal pro-brain natriuretic peptide (NT-pro BNP) are increased in patients with chronic heart failure (CHF). Beta-blockers (BB) may,influence these levels but it is unclear whether changes in NT-pro BNP reflect concomitant,changes in prognosis. Objectives: To assess the prognostic importance of NT-pro BNP at baseline and during follow-up, in patients in whom beta-blocker therapy is initiated.

Research paper thumbnail of T01-P-016 The insulin resistance syndrome and endothelial dysfunction — Does nateglinide make a difference?

Atherosclerosis Supplements, 2005

Research paper thumbnail of Opportunities for improvement: anticoagulation in patients undergoing total knee or hip replacement

Journal of Orthopaedic Science, 2015

According to guidelines, initiation of pharmacological thromboprophylaxis after total knee or hip... more According to guidelines, initiation of pharmacological thromboprophylaxis after total knee or hip replacement is recommended and associated with improved patient outcomes. However, data on how these recommendations are followed in clinical practice are sparse. All patients undergoing first-time total knee or hip replacement in Denmark 2008-2011 were identified. By cross-referencing Danish nationwide registries, quantitative use of anticoagulants administered orally and subcutaneously post-discharge was assessed by number of claimed prescriptions after surgery. Logistic regression analysis was used to identify factors associated with initiation of prophylaxis. A total of 50,389 patients were included in the study (median age 69, inter-quartile range 62-76). Novel oral anticoagulants were initiated in 14.7 % of the patients and heparins/fondaparinux in 2.3 % of the patients. The use of anticoagulants increased from 6.3 % in 2008 to 30.0 % of patients in 2011. Among patients initiating prophylaxis with a novel oral anticoagulant post-discharge, almost all were treated according to guidelines in terms of treatment duration. Factors significantly associated with an increased chance of prophylaxis among total hip replacement patients were: age (per 10-year increments) and female gender. Use of pharmacological thromboprophylaxis after total knee or hip replacement was low, but increasing during the study period. This is probably due to increased availability of novel oral anticoagulants. Further initiatives to increase guideline recommended use of prophylactic anticoagulation after orthopaedic surgery are warranted.

Research paper thumbnail of Return to Work in Out-of-Hospital Cardiac Arrest Survivors: A Nationwide Register-Based Follow-Up Study

Circulation, Jan 12, 2015

Data on long-term function of out-of-hospital cardiac arrest survivors are sparse. We examined re... more Data on long-term function of out-of-hospital cardiac arrest survivors are sparse. We examined return to work as a proxy of preserved function without major neurologic deficits in survivors. In Denmark, out-of-hospital cardiac arrests have been systematically reported to the Danish Cardiac Arrest Register since 2001. During 2001-2011, we identified 4354 patients employed before arrest among 12 332 working-age patients (18-65 years), of whom 796 survived to day 30. Among 796 survivors (median age, 53 years [quartile 1-3, 46-59 years]; 81.5% men), 610 (76.6%) returned to work in a median time of 4 months [quartile 1-3, 1-19 months], with a median time of 3 years spent back at work. A total of 74.6% (N=455) remained employed without using sick leave during the first 6 months after returning to work. This latter proportion of survivors returning to work increased over time (66.1% in 2001-2005 versus 78.1% in 2006-2011; P=0.002). In multivariable Cox regression analysis, factors associat...

Research paper thumbnail of Time trend in Alzheimer diagnoses and the association between distance to an Alzheimer clinic and Alzheimer diagnosis

European journal of public health, Jan 31, 2014

Centralization of specialized health care in Denmark has caused increased geographical distance t... more Centralization of specialized health care in Denmark has caused increased geographical distance to health-care providers, which may be a barrier for Alzheimer patients to seek health care. We examined the incidence of Alzheimer diagnosis in Denmark between 2000 and 2009 and investigated the association between patients' distance to Alzheimer clinics and Alzheimer diagnoses. Data of all individuals aged 65+ years were collected from Danish national registers. Incidences of Alzheimer diagnoses were analysed with joinpoint regression and hazard ratios (HRs) for Alzheimer diagnoses were analysed with Cox regressions. The annual incidence of Alzheimer diagnoses increased with 32.5% [95% confidence interval (CI): 7.1-63.8] among individuals aged 65-74 years from 2000 to 2002 and with 29.1% (95% CI: 11.0-50.2) among individuals aged 75+ years from 2000 to 2003. For both groups, incidence during subsequent years stagnated (0.4%, 95% CI: -1.7 to 2.6; 2.3%, 95% CI: 1.5-6.). From 2008 to 2...

Research paper thumbnail of Effects of oral glucose load on endothelial function and on insulin and glucose fluctuations in healthy individuals

Experimental diabetes research, 2008

Postprandial hyperglycemia, an independent risk factor for cardiovascular disease, is accompanied... more Postprandial hyperglycemia, an independent risk factor for cardiovascular disease, is accompanied by endothelial dysfunction. We studied the effect of oral glucose load on insulin and glucose fluctuations, and on postprandial endothelial function in healthy individuals in order to better understand and cope with the postprandial state in insulin resistant individuals. We assessed post-oral glucose load endothelial function (flow mediated dilation), plasma insulin, and blood glucose in 9 healthy subjects. The largest increases in delta FMD values (fasting FMD value subtracted from postprandial FMD value) occurred at 3 hours after both glucose or placebo load, respectively: 4.80 +/- 1.41 (P = .009) and 2.34 +/- 1.47 (P = .15). Glucose and insulin concentrations achieved maximum peaks at one hour post-glucose load. Oral glucose load does not induce endothelial dysfunction in healthy individuals with mean insulin and glucose values of 5.6 mmol/L and 27.2 mmol/L, respectively, 2 hours af...

Research paper thumbnail of Tetrahydrobiopterin restores endothelial dysfunction induced by an oral glucose challenge in healthy subjects

American journal of physiology. Heart and circulatory physiology, 2003

An oral glucose challenge causes transient impairment of endothelial function, probably because o... more An oral glucose challenge causes transient impairment of endothelial function, probably because of increased oxidative stress. During oxidative stress, endothelial nitric oxide (NO) synthase (eNOS) becomes uncoupled because of decreased bioavailability of tetrahydrobiopterin (BH4), an essential cofactor of eNOS. Therefore, we examined whether an acute supplement of BH4 could restore endothelial dysfunction induced by an oral glucose challenge. Healthy subjects were examined in 53 experiments. Forearm blood flow was measured by venous occlusion plethysmography. Dose-response studies were obtained during intra-arterial infusion of serotonin to elicit endothelium-dependent, NO-specific vasodilation and during sodium nitroprusside (SNP) infusion to elicit endothelium-independent vasodilation. Subjects were examined before (fasting) and 1 and 2 h after an oral glucose challenge (75 g) with serotonin (n = 10) and SNP (n = 8). On different days (6R)-5,6,7,8-tetrahydro-l-biopterin dihydroch...

Research paper thumbnail of Non-vitamin K antagonist oral anticoagulation agents in anticoagulant naïve atrial fibrillation patients: Danish nationwide descriptive data 2011-2013

Europace : European pacing, arrhythmias, and cardiac electrophysiology : journal of the working groups on cardiac pacing, arrhythmias, and cardiac cellular electrophysiology of the European Society of Cardiology, 2015

Non-vitamin K antagonist oral anticoagulation (NOAC) agents have been approved for stroke prophyl... more Non-vitamin K antagonist oral anticoagulation (NOAC) agents have been approved for stroke prophylaxis in atrial fibrillation (AF). We investigated 'real-world' information on how these drugs are being adopted. Using Danish nationwide administrative registers, we identified all oral anticoagulation-naïve AF patients initiating oral anticoagulation from 22 August 2011 through 31 October 2013. Using logistic regression analysis, baseline characteristics and temporal utilization trends were compared between initiators of warfarin vs. one of the N OACs: dabigatran, rivaroxaban, or apixaban. We identified 18 611 oral anticoagulation-naïve AF patients of which 9902 (53%) initiated warfarin treatment, 7128 (38%) dabigatran, 1303 (7%) rivaroxaban, and 278 (1%) apixaban. Overall, 40% of newly initiated patients were started on dabigatran within the first 4 months of when the drug came on market. By October, 2013, 40% were being started on warfarin and dabigatran, respectively, and ano...

Research paper thumbnail of Temporal trends in coverage of historical cardiac arrests using a volunteer-based network of automated external defibrillators accessible to laypersons and emergency dispatch centers

Circulation, Jan 18, 2014

Although increased dissemination of automated external defibrillators (AEDs) has been associated ... more Although increased dissemination of automated external defibrillators (AEDs) has been associated with more frequent AED use, the trade-off between the number of deployed AEDs and coverage of cardiac arrests remains unclear. We investigated how volunteer-based AED dissemination affected public cardiac arrest coverage in high- and low-risk areas. All public cardiac arrests (1994-2011) and all registered AEDs (2007-2011) in Copenhagen, Denmark, were identified and geocoded. AED coverage of cardiac arrests was defined as historical arrests ≤100 m from an AED. High-risk areas were defined as those with ≥1 arrest every 2 years and accounted for 1.0% of the total city area. Of 1864 cardiac arrests, 18.0% (n=335) occurred in high-risk areas throughout the study period. From 2007 to 2011, the number of AEDs and the corresponding coverage of cardiac arrests increased from 36 to 552 and from 2.7% to 32.6%, respectively. The corresponding increase for high-risk areas was from 1 to 30 AEDs and c...

Research paper thumbnail of Risk stratification by ambulatory blood pressure monitoring across JNC classes of conventional blood pressure

American journal of hypertension, 2014

Guidelines propose classification of conventional blood pressure (CBP) into normotension (<120... more Guidelines propose classification of conventional blood pressure (CBP) into normotension (<120/<80 mm Hg), prehypertension (120-139/80-89 mm Hg), and hypertension (≥140/≥90 mm Hg). To assess the potential differential contribution of ambulatory blood pressure (ABP) in predicting risk across CBP strata, we analyzed outcomes in 7,826 untreated people recruited from 11 populations. During an 11.3-year period, 809 participants died (276 cardiovascular deaths) and 639, 383, and 225 experienced a cardiovascular, cardiac, or cerebrovascular event. Compared with normotension (n = 2,639), prehypertension (n = 3,076) carried higher risk (P ≤ 0.015) of cardiovascular (+41%) and cerebrovascular (+92%) endpoints; compared with hypertension (n = 2,111) prehypertension entailed lower risk (P ≤ 0.005) of total mortality (-14%) and cardiovascular mortality (-29%) and of cardiovascular (-34%), cardiac (-33%), or cerebrovascular (-47%) events. Multivariable-adjusted hazard ratios (HRs) for strok...

Research paper thumbnail of Ambulatory hypertension subtypes and 24-hour systolic and diastolic blood pressure as distinct outcome predictors in 8341 untreated people recruited from 12 populations

Circulation, Jan 5, 2014

Data on risk associated with 24-hour ambulatory diastolic (DBP24) versus systolic (SBP24) blood p... more Data on risk associated with 24-hour ambulatory diastolic (DBP24) versus systolic (SBP24) blood pressure are scarce. We recorded 24-hour blood pressure and health outcomes in 8341 untreated people (mean age, 50.8 years; 46.6% women) randomly recruited from 12 populations. We computed hazard ratios (HRs) using multivariable-adjusted Cox regression. Over 11.2 years (median), 927 (11.1%) participants died, 356 (4.3%) from cardiovascular causes, and 744 (8.9%) experienced a fatal or nonfatal cardiovascular event. Isolated diastolic hypertension (DBP24≥80 mm Hg) did not increase the risk of total mortality, cardiovascular mortality, or stroke (HRs≤1.54; P≥0.18), but was associated with a higher risk of fatal combined with nonfatal cardiovascular, cardiac, or coronary events (HRs≥1.75; P≤0.0054). Isolated systolic hypertension (SBP24≥130 mm Hg) and mixed diastolic plus systolic hypertension were associated with increased risks of all aforementioned end points (P≤0.0012). Below age 50, DBP...

Research paper thumbnail of Age-specific differences between conventional and ambulatory daytime blood pressure values

Hypertension, 2014

Mean daytime ambulatory blood pressure (BP) values are considered to be lower than conventional B... more Mean daytime ambulatory blood pressure (BP) values are considered to be lower than conventional BP values, but data on this relation among younger individuals <50 years are scarce. Conventional and 24-hour ambulatory BP were measured in 9550 individuals not taking antihypertensive treatment from 13 population-based cohorts. We compared individual differences between daytime ambulatory and conventional BP according to 10-year age categories. Age-specific prevalences of white coat and masked hypertension were calculated. Among individuals aged 18 to 30, 30 to 40, and 40 to 50 years, mean daytime BP was significantly higher than the corresponding conventional BP (6.0, 5.2, and 4.7 mm Hg for systolic; 2.5, 2.7, and 1.7 mm Hg for diastolic BP; all P<0.0001). In individuals aged 60 to 70 and ≥70 years, conventional BP was significantly higher than daytime ambulatory BP (5.0 and 13.0 mm Hg for systolic; 2.0 and 4.2 mm Hg for diastolic BP; all P<0.0001).The prevalence of white coat...

Research paper thumbnail of Use of thyroid hormones in relation to pregnancy: a Danish nationwide cohort study

Acta Obstetricia et Gynecologica Scandinavica, 2015

To determine the rate of exposure of pregnant women to levothyroxine and to assess changes in the... more To determine the rate of exposure of pregnant women to levothyroxine and to assess changes in these rates before, during and after pregnancy. Register-based cohort study. Danish nationwide registers. All women having a live birth in Denmark between 1 January 1997 and 31 December 2010 (n = 912 342). All pregnant women in the study period were identified from the Danish Medical Birth Register. Exposed women were identified from the Danish National Prescription Register, based on redemption of levothyroxine prescriptions before, during or after pregnancy. The rate of pregnant women redeeming levothyroxine prescriptions and maternal characteristics. We identified a fourfold increase in levothyroxine prescription redemption during the study period, from 0.34% in 1997 to 1.39% by 2010. A mean of 0.79% of our cohort received levothyroxine. Most of the women who were using levothyroxine before pregnancy continued the therapy during their pregnancy, but 9.4% stopped redeeming their prescriptions. Overall, 0.28% of our cohort received a levothyroxine prescription for the first time within 9 months after pregnancy. Fewer women than expected received levothyroxine treatment during pregnancy even though a fourfold increase was observed during the study period. Furthermore, one of 10 discontinued treatments during pregnancy. These findings all indicate that too few women are treated for hypothyroidism during pregnancy. Further research is needed to determine whether hypothyroid pregnant women are suboptimally treated and the possible consequences for the mother and fetus.

Research paper thumbnail of Setting thresholds to varying blood pressure monitoring intervals differentially affects risk estimates associated with white-coat and masked hypertension in the population

Hypertension, 2014

Outcome-driven recommendations about time intervals during which ambulatory blood pressure should... more Outcome-driven recommendations about time intervals during which ambulatory blood pressure should be measured to diagnose white-coat or masked hypertension are lacking. We cross-classified 8237 untreated participants (mean age, 50.7 years; 48.4% women) enrolled in 12 population studies, using ≥140/≥90, ≥130/≥80, ≥135/≥85, and ≥120/≥70 mm Hg as hypertension thresholds for conventional, 24-hour, daytime, and nighttime blood pressure. White-coat hypertension was hypertension on conventional measurement with ambulatory normotension, the opposite condition being masked hypertension. Intervals used for classification of participants were daytime, nighttime, and 24 hours, first considered separately, and next combined as 24 hours plus daytime or plus nighttime, or plus both. Depending on time intervals chosen, white-coat and masked hypertension frequencies ranged from 6.3% to 12.5% and from 9.7% to 19.6%, respectively. During 91 046 person-years, 729 participants experienced a cardiovascul...

Research paper thumbnail of Risk of Myocardial Infarction and Death Associated With the Use of Nonsteroidal Anti-Inflammatory Drugs (NSAIDs) Among Healthy Individuals: A Nationwide Cohort Study

Clinical Pharmacology & Therapeutics, 2008

Use of some nonsteroidal anti-inflammatory drugs (NSAIDs) is associated with increased cardiovasc... more Use of some nonsteroidal anti-inflammatory drugs (NSAIDs) is associated with increased cardiovascular risk in several patient groups, but whether this excess risk exists in apparently healthy individuals has not been clarified. Using a historical cohort design, we estimated the risk of death and myocardial infarction associated with the use of NSAIDs. Participants in the study were selected from the Danish population and were defined as healthy according to a history of no hospital admissions and no concomitant selected pharmacotherapy. The source population consisted of 4,614,807 individuals, of whom 1,028,437 were included in the study after applying selection criteria. Compared to no NSAID use, hazard ratios (95% confidence limits) for death/myocardial infarction were 1.01 (0.96-1.07) for ibuprofen, 1.63 (1.52-1.76) for diclofenac, 0.97 (0.83-1.12) for naproxen, 2.13 (1.89-2.41) for rofecoxib, and 2.01 (1.78-2.27) for celecoxib. A dose-dependent increase in cardiovascular risk was seen for selective COX-2 inhibitors and diclofenac. Caution should be exercised in NSAID use in all individuals, and particularly high doses should be avoided if possible.

Research paper thumbnail of Age-Specific Performance of the Revised Cardiac Risk Index for Predicting Cardiovascular Risk in Elective Noncardiac Surgery

Circulation: Cardiovascular Quality and Outcomes, 2015

The revised cardiac risk index (RCRI) holds a central role in preoperative cardiac risk stratific... more The revised cardiac risk index (RCRI) holds a central role in preoperative cardiac risk stratification in noncardiac surgery. Its performance in unselected populations, including different age groups, has, however, not been systematically investigated. We assessed the relationship of RCRI with major adverse cardiovascular events in an unselected cohort of patients undergoing elective, noncardiac surgery overall and in different age groups. We followed up all individuals ≥ 25 years who underwent major elective noncardiac surgery in Denmark (January 1, 2005, to November 30, 2011) for the 30-day risk of major adverse cardiovascular events (ischemic stroke, myocardial infarction, or cardiovascular death). There were 742 of 357,396 (0.2%), 755 of 74.889 (1.0%), 521 of 11,921 (4%), and 257 of 3146 (8%) major adverse cardiovascular events occurring in RCRI classes I, II, III, and IV. Multivariable odds ratio estimates were as follows: ischemic heart disease 3.30 (95% confidence interval, 2.96-3.69), high-risk surgery 2.70 (2.46-2.96), congestive heart failure 2.65 (2.29-3.06), cerebrovascular disease 10.02 (9.08-11.05), insulin therapy 1.62 (1.37-1.93), and kidney disease 1.45 (1.33-1.59). Modeling RCRI classes as a continuous variable, C statistic was highest among age group 56 to 65 years (0.772) and lowest for those aged &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;gt;85 years (0.683). Sensitivity of RCRI class &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;gt;I (ie, having ≥ 1 risk factor) for capturing major adverse cardiovascular events was 59%, 71%, 64%, 66%, and 67% in patients aged ≤ 55, 56 to 65, 66 to 75, 76 to 85, and &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;gt;85 years, respectively; the negative predictive values were &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;gt;98% across all age groups. In a nationwide unselected cohort, the performance of the RCRI was similar to that of the original cohort. Having ≥ 1 risk factor was of moderate sensitivity, but high negative predictive value for all ages.

Research paper thumbnail of Survival after out-of-hospital cardiac arrest in relation to sex: a nationwide registry-based study

Resuscitation, 2014

Crude survival has increased following an out-of-hospital cardiac arrest (OHCA). We aimed to stud... more Crude survival has increased following an out-of-hospital cardiac arrest (OHCA). We aimed to study sex-related differences in patient characteristics and survival during a 10-year study period. Patients≥12 years old with OHCA of a presumed cardiac cause, and in whom resuscitation was attempted, were identified through the Danish Cardiac Arrest Registry 2001-2010. A total of 19,372 patients were included. One-third were female, with a median age of 75 years (IQR 65-83). Compared to females, males were five years younger; and less likely to have severe comorbidities, e.g., chronic obstructive pulmonary disease (12.8% vs. 16.5%); but more likely to have arrest outside of the home (29.4% vs. 18.7%), receive bystander CPR (32.9% vs. 25.9%), and have a shockable rhythm (32.6% vs. 17.2%), all p<0.001. Thirty-day crude survival increased in males (3.0% in 2001 to 12.9% in 2010); and in females (4.8% in 2001 to 6.7% in 2010), p<0.001. Multivariable logistic regression analyses adjusted...

Research paper thumbnail of Diurnal variations in incidence and outcome of out-of-hospital cardiac arrest including prior comorbidity and pharmacotherapy: a nationwide study in Denmark

Resuscitation, 2014

To investigate diurnal variations in incidence and outcomes following out-of-hospital cardiac arr... more To investigate diurnal variations in incidence and outcomes following out-of-hospital cardiac arrest (OHCA). OHCA of presumed cardiac etiology were identified through the nationwide Danish Cardiac Arrest Registry (2001-2010). Time of day was divided into three time periods: daytime 07.00-14.59; evening 15.00-22.59; and nighttime 23.00-06.59. We identified 18,929 OHCA patients, aged ≥18 years. The median age was 72 years (IQR 62-80) and the majority were male (67.5%). OHCA occurrence varied across time periods, with 43.9%, 35.7% and 20.6% occurring during daytime, evening and nighttime, respectively. Nighttime patients were more likely to have: severe comorbidity (i.e. COPD), arrest in private home (87.2% vs. 69.0% and 73.0% daytime and evening, respectively), non-witnessed arrest (51.2% vs. 48.4% and 43.7%), no bystander CPR (75.9% vs. 68.4% and 66.1%), longer time interval from recognition of OHCA to rhythm analysis (12 min vs. 11 min and 11 min), and non-shockable heart rhythm (80...

Research paper thumbnail of β-Blocker–Associated Risks in Patients With Uncomplicated Hypertension Undergoing Noncardiac Surgery

JAMA Internal Medicine, 2015

Perioperative β-blocker strategies are important to reduce risks of adverse events. Effectiveness... more Perioperative β-blocker strategies are important to reduce risks of adverse events. Effectiveness and safety may differ according to patients&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39; baseline risk. To determine the risk of major adverse cardiovascular events (MACEs) associated with long-term β-blocker therapy in patients with uncomplicated hypertension undergoing noncardiac surgery. Association study based on in-hospital records and out-of-hospital pharmacotherapy use using a Danish nationwide cohort of patients with uncomplicated hypertension treated with at least 2 antihypertensive drugs (β-blockers, thiazides, calcium antagonists, or renin-angiotensin system [RAS] inhibitors) undergoing noncardiac surgery between 2005 and 2011. Various antihypertensive treatment regimens, chosen as part of usual care. Thirty-day risk of MACEs (cardiovascular death, nonfatal ischemic stroke, nonfatal myocardial infarction) and all-cause mortality, assessed using multivariable logistic regression models and adjusted numbers needed to harm (NNH). The baseline characteristics of the 14 644 patients who received β-blockers (65% female, mean [SD] age, 66.1 [12.0] years) were similar to those of the 40 676 patients who received other antihypertensive drugs (57% female, mean [SD] age, 65.9 [11.8] years). Thirty-day MACEs occurred in 1.3% of patients treated with β-blockers compared with 0.8% of patients not treated with β-blockers (P &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; .001). β-Blocker use was associated with increased risks of MACEs in 2-drug combinations with RAS inhibitors (odds ratio [OR], 2.16 [95% CI, 1.54-3.04]), calcium antagonists (OR, 2.17 [95% CI, 1.48-3.17]), and thiazides (OR, 1.56 [95% CI, 1.10-2.22]), compared with the reference combination of RAS inhibitors and thiazides. Results were similar for all-cause mortality. Risk of MACEs associated with β-blocker use seemed especially pronounced for patients at least 70 years old (number needed to harm [NNH], 140 [95% CI, 86-364]), for men (NNH, 142 [95% CI, 93-195]), and for patients undergoing acute surgery (NNH, 97 [95% CI, 57-331]), compared with patients younger than 70 years, women, and patients undergoing elective surgery, respectively. Antihypertensive treatment with a β-blocker may be associated with increased risks of perioperative MACEs and all-cause mortality in patients with uncomplicated hypertension.

Research paper thumbnail of Association of Selected Antipsychotic Agents With Major Adverse Cardiovascular Events and Noncardiovascular Mortality in Elderly Persons

Journal of the American Heart Association, 2015

Data from observational studies have raised concerns about the safety of treatment with antipsych... more Data from observational studies have raised concerns about the safety of treatment with antipsychotic agents (APs) in elderly patients with dementia, but this area has been insufficiently investigated. We performed a head-to-head comparison of the risk of major adverse cardiovascular events and noncardiovascular mortality associated with individual APs (ziprasidone, olanzapine, risperidone, quetiapine, levomepromazine, chlorprothixen, flupentixol, and haloperidol) in Danish treatment-naïve patients aged ≥70 years. We followed all treatment-naïve Danish citizens aged ≥70 years that initiated treatment with APs for the first time between 1997 and 2011 (n=91 774, mean age 82±7 years, 35 474 [39%] were men). Incidence rate ratios associated with use of different APs were assessed by multivariable time-dependent Poisson regression models. For the first 30 days of treatment, compared with risperidone, incidence rate ratios of major adverse cardiovascular events were higher with use of lev...

Research paper thumbnail of Prognostic importance of plasma NT-pro BNP in chronic heart failure in patients treated with a β-blocker: Results from the Carvedilol Or Metoprolol European Trial (COMET) trial

Background: Plasma levels of N-terminal pro-brain natriuretic peptide (NT-pro BNP) are increased ... more Background: Plasma levels of N-terminal pro-brain natriuretic peptide (NT-pro BNP) are increased in patients with chronic heart failure (CHF). Beta-blockers (BB) may,influence these levels but it is unclear whether changes in NT-pro BNP reflect concomitant,changes in prognosis. Objectives: To assess the prognostic importance of NT-pro BNP at baseline and during follow-up, in patients in whom beta-blocker therapy is initiated.

Research paper thumbnail of T01-P-016 The insulin resistance syndrome and endothelial dysfunction — Does nateglinide make a difference?

Atherosclerosis Supplements, 2005

Research paper thumbnail of Opportunities for improvement: anticoagulation in patients undergoing total knee or hip replacement

Journal of Orthopaedic Science, 2015

According to guidelines, initiation of pharmacological thromboprophylaxis after total knee or hip... more According to guidelines, initiation of pharmacological thromboprophylaxis after total knee or hip replacement is recommended and associated with improved patient outcomes. However, data on how these recommendations are followed in clinical practice are sparse. All patients undergoing first-time total knee or hip replacement in Denmark 2008-2011 were identified. By cross-referencing Danish nationwide registries, quantitative use of anticoagulants administered orally and subcutaneously post-discharge was assessed by number of claimed prescriptions after surgery. Logistic regression analysis was used to identify factors associated with initiation of prophylaxis. A total of 50,389 patients were included in the study (median age 69, inter-quartile range 62-76). Novel oral anticoagulants were initiated in 14.7 % of the patients and heparins/fondaparinux in 2.3 % of the patients. The use of anticoagulants increased from 6.3 % in 2008 to 30.0 % of patients in 2011. Among patients initiating prophylaxis with a novel oral anticoagulant post-discharge, almost all were treated according to guidelines in terms of treatment duration. Factors significantly associated with an increased chance of prophylaxis among total hip replacement patients were: age (per 10-year increments) and female gender. Use of pharmacological thromboprophylaxis after total knee or hip replacement was low, but increasing during the study period. This is probably due to increased availability of novel oral anticoagulants. Further initiatives to increase guideline recommended use of prophylactic anticoagulation after orthopaedic surgery are warranted.

Research paper thumbnail of Return to Work in Out-of-Hospital Cardiac Arrest Survivors: A Nationwide Register-Based Follow-Up Study

Circulation, Jan 12, 2015

Data on long-term function of out-of-hospital cardiac arrest survivors are sparse. We examined re... more Data on long-term function of out-of-hospital cardiac arrest survivors are sparse. We examined return to work as a proxy of preserved function without major neurologic deficits in survivors. In Denmark, out-of-hospital cardiac arrests have been systematically reported to the Danish Cardiac Arrest Register since 2001. During 2001-2011, we identified 4354 patients employed before arrest among 12 332 working-age patients (18-65 years), of whom 796 survived to day 30. Among 796 survivors (median age, 53 years [quartile 1-3, 46-59 years]; 81.5% men), 610 (76.6%) returned to work in a median time of 4 months [quartile 1-3, 1-19 months], with a median time of 3 years spent back at work. A total of 74.6% (N=455) remained employed without using sick leave during the first 6 months after returning to work. This latter proportion of survivors returning to work increased over time (66.1% in 2001-2005 versus 78.1% in 2006-2011; P=0.002). In multivariable Cox regression analysis, factors associat...

Research paper thumbnail of Time trend in Alzheimer diagnoses and the association between distance to an Alzheimer clinic and Alzheimer diagnosis

European journal of public health, Jan 31, 2014

Centralization of specialized health care in Denmark has caused increased geographical distance t... more Centralization of specialized health care in Denmark has caused increased geographical distance to health-care providers, which may be a barrier for Alzheimer patients to seek health care. We examined the incidence of Alzheimer diagnosis in Denmark between 2000 and 2009 and investigated the association between patients' distance to Alzheimer clinics and Alzheimer diagnoses. Data of all individuals aged 65+ years were collected from Danish national registers. Incidences of Alzheimer diagnoses were analysed with joinpoint regression and hazard ratios (HRs) for Alzheimer diagnoses were analysed with Cox regressions. The annual incidence of Alzheimer diagnoses increased with 32.5% [95% confidence interval (CI): 7.1-63.8] among individuals aged 65-74 years from 2000 to 2002 and with 29.1% (95% CI: 11.0-50.2) among individuals aged 75+ years from 2000 to 2003. For both groups, incidence during subsequent years stagnated (0.4%, 95% CI: -1.7 to 2.6; 2.3%, 95% CI: 1.5-6.). From 2008 to 2...

Research paper thumbnail of Effects of oral glucose load on endothelial function and on insulin and glucose fluctuations in healthy individuals

Experimental diabetes research, 2008

Postprandial hyperglycemia, an independent risk factor for cardiovascular disease, is accompanied... more Postprandial hyperglycemia, an independent risk factor for cardiovascular disease, is accompanied by endothelial dysfunction. We studied the effect of oral glucose load on insulin and glucose fluctuations, and on postprandial endothelial function in healthy individuals in order to better understand and cope with the postprandial state in insulin resistant individuals. We assessed post-oral glucose load endothelial function (flow mediated dilation), plasma insulin, and blood glucose in 9 healthy subjects. The largest increases in delta FMD values (fasting FMD value subtracted from postprandial FMD value) occurred at 3 hours after both glucose or placebo load, respectively: 4.80 +/- 1.41 (P = .009) and 2.34 +/- 1.47 (P = .15). Glucose and insulin concentrations achieved maximum peaks at one hour post-glucose load. Oral glucose load does not induce endothelial dysfunction in healthy individuals with mean insulin and glucose values of 5.6 mmol/L and 27.2 mmol/L, respectively, 2 hours af...

Research paper thumbnail of Tetrahydrobiopterin restores endothelial dysfunction induced by an oral glucose challenge in healthy subjects

American journal of physiology. Heart and circulatory physiology, 2003

An oral glucose challenge causes transient impairment of endothelial function, probably because o... more An oral glucose challenge causes transient impairment of endothelial function, probably because of increased oxidative stress. During oxidative stress, endothelial nitric oxide (NO) synthase (eNOS) becomes uncoupled because of decreased bioavailability of tetrahydrobiopterin (BH4), an essential cofactor of eNOS. Therefore, we examined whether an acute supplement of BH4 could restore endothelial dysfunction induced by an oral glucose challenge. Healthy subjects were examined in 53 experiments. Forearm blood flow was measured by venous occlusion plethysmography. Dose-response studies were obtained during intra-arterial infusion of serotonin to elicit endothelium-dependent, NO-specific vasodilation and during sodium nitroprusside (SNP) infusion to elicit endothelium-independent vasodilation. Subjects were examined before (fasting) and 1 and 2 h after an oral glucose challenge (75 g) with serotonin (n = 10) and SNP (n = 8). On different days (6R)-5,6,7,8-tetrahydro-l-biopterin dihydroch...

Research paper thumbnail of Non-vitamin K antagonist oral anticoagulation agents in anticoagulant naïve atrial fibrillation patients: Danish nationwide descriptive data 2011-2013

Europace : European pacing, arrhythmias, and cardiac electrophysiology : journal of the working groups on cardiac pacing, arrhythmias, and cardiac cellular electrophysiology of the European Society of Cardiology, 2015

Non-vitamin K antagonist oral anticoagulation (NOAC) agents have been approved for stroke prophyl... more Non-vitamin K antagonist oral anticoagulation (NOAC) agents have been approved for stroke prophylaxis in atrial fibrillation (AF). We investigated 'real-world' information on how these drugs are being adopted. Using Danish nationwide administrative registers, we identified all oral anticoagulation-naïve AF patients initiating oral anticoagulation from 22 August 2011 through 31 October 2013. Using logistic regression analysis, baseline characteristics and temporal utilization trends were compared between initiators of warfarin vs. one of the N OACs: dabigatran, rivaroxaban, or apixaban. We identified 18 611 oral anticoagulation-naïve AF patients of which 9902 (53%) initiated warfarin treatment, 7128 (38%) dabigatran, 1303 (7%) rivaroxaban, and 278 (1%) apixaban. Overall, 40% of newly initiated patients were started on dabigatran within the first 4 months of when the drug came on market. By October, 2013, 40% were being started on warfarin and dabigatran, respectively, and ano...

Research paper thumbnail of Temporal trends in coverage of historical cardiac arrests using a volunteer-based network of automated external defibrillators accessible to laypersons and emergency dispatch centers

Circulation, Jan 18, 2014

Although increased dissemination of automated external defibrillators (AEDs) has been associated ... more Although increased dissemination of automated external defibrillators (AEDs) has been associated with more frequent AED use, the trade-off between the number of deployed AEDs and coverage of cardiac arrests remains unclear. We investigated how volunteer-based AED dissemination affected public cardiac arrest coverage in high- and low-risk areas. All public cardiac arrests (1994-2011) and all registered AEDs (2007-2011) in Copenhagen, Denmark, were identified and geocoded. AED coverage of cardiac arrests was defined as historical arrests ≤100 m from an AED. High-risk areas were defined as those with ≥1 arrest every 2 years and accounted for 1.0% of the total city area. Of 1864 cardiac arrests, 18.0% (n=335) occurred in high-risk areas throughout the study period. From 2007 to 2011, the number of AEDs and the corresponding coverage of cardiac arrests increased from 36 to 552 and from 2.7% to 32.6%, respectively. The corresponding increase for high-risk areas was from 1 to 30 AEDs and c...

Research paper thumbnail of Risk stratification by ambulatory blood pressure monitoring across JNC classes of conventional blood pressure

American journal of hypertension, 2014

Guidelines propose classification of conventional blood pressure (CBP) into normotension (<120... more Guidelines propose classification of conventional blood pressure (CBP) into normotension (<120/<80 mm Hg), prehypertension (120-139/80-89 mm Hg), and hypertension (≥140/≥90 mm Hg). To assess the potential differential contribution of ambulatory blood pressure (ABP) in predicting risk across CBP strata, we analyzed outcomes in 7,826 untreated people recruited from 11 populations. During an 11.3-year period, 809 participants died (276 cardiovascular deaths) and 639, 383, and 225 experienced a cardiovascular, cardiac, or cerebrovascular event. Compared with normotension (n = 2,639), prehypertension (n = 3,076) carried higher risk (P ≤ 0.015) of cardiovascular (+41%) and cerebrovascular (+92%) endpoints; compared with hypertension (n = 2,111) prehypertension entailed lower risk (P ≤ 0.005) of total mortality (-14%) and cardiovascular mortality (-29%) and of cardiovascular (-34%), cardiac (-33%), or cerebrovascular (-47%) events. Multivariable-adjusted hazard ratios (HRs) for strok...

Research paper thumbnail of Ambulatory hypertension subtypes and 24-hour systolic and diastolic blood pressure as distinct outcome predictors in 8341 untreated people recruited from 12 populations

Circulation, Jan 5, 2014

Data on risk associated with 24-hour ambulatory diastolic (DBP24) versus systolic (SBP24) blood p... more Data on risk associated with 24-hour ambulatory diastolic (DBP24) versus systolic (SBP24) blood pressure are scarce. We recorded 24-hour blood pressure and health outcomes in 8341 untreated people (mean age, 50.8 years; 46.6% women) randomly recruited from 12 populations. We computed hazard ratios (HRs) using multivariable-adjusted Cox regression. Over 11.2 years (median), 927 (11.1%) participants died, 356 (4.3%) from cardiovascular causes, and 744 (8.9%) experienced a fatal or nonfatal cardiovascular event. Isolated diastolic hypertension (DBP24≥80 mm Hg) did not increase the risk of total mortality, cardiovascular mortality, or stroke (HRs≤1.54; P≥0.18), but was associated with a higher risk of fatal combined with nonfatal cardiovascular, cardiac, or coronary events (HRs≥1.75; P≤0.0054). Isolated systolic hypertension (SBP24≥130 mm Hg) and mixed diastolic plus systolic hypertension were associated with increased risks of all aforementioned end points (P≤0.0012). Below age 50, DBP...

Research paper thumbnail of Age-specific differences between conventional and ambulatory daytime blood pressure values

Hypertension, 2014

Mean daytime ambulatory blood pressure (BP) values are considered to be lower than conventional B... more Mean daytime ambulatory blood pressure (BP) values are considered to be lower than conventional BP values, but data on this relation among younger individuals <50 years are scarce. Conventional and 24-hour ambulatory BP were measured in 9550 individuals not taking antihypertensive treatment from 13 population-based cohorts. We compared individual differences between daytime ambulatory and conventional BP according to 10-year age categories. Age-specific prevalences of white coat and masked hypertension were calculated. Among individuals aged 18 to 30, 30 to 40, and 40 to 50 years, mean daytime BP was significantly higher than the corresponding conventional BP (6.0, 5.2, and 4.7 mm Hg for systolic; 2.5, 2.7, and 1.7 mm Hg for diastolic BP; all P<0.0001). In individuals aged 60 to 70 and ≥70 years, conventional BP was significantly higher than daytime ambulatory BP (5.0 and 13.0 mm Hg for systolic; 2.0 and 4.2 mm Hg for diastolic BP; all P<0.0001).The prevalence of white coat...

Research paper thumbnail of Use of thyroid hormones in relation to pregnancy: a Danish nationwide cohort study

Acta Obstetricia et Gynecologica Scandinavica, 2015

To determine the rate of exposure of pregnant women to levothyroxine and to assess changes in the... more To determine the rate of exposure of pregnant women to levothyroxine and to assess changes in these rates before, during and after pregnancy. Register-based cohort study. Danish nationwide registers. All women having a live birth in Denmark between 1 January 1997 and 31 December 2010 (n = 912 342). All pregnant women in the study period were identified from the Danish Medical Birth Register. Exposed women were identified from the Danish National Prescription Register, based on redemption of levothyroxine prescriptions before, during or after pregnancy. The rate of pregnant women redeeming levothyroxine prescriptions and maternal characteristics. We identified a fourfold increase in levothyroxine prescription redemption during the study period, from 0.34% in 1997 to 1.39% by 2010. A mean of 0.79% of our cohort received levothyroxine. Most of the women who were using levothyroxine before pregnancy continued the therapy during their pregnancy, but 9.4% stopped redeeming their prescriptions. Overall, 0.28% of our cohort received a levothyroxine prescription for the first time within 9 months after pregnancy. Fewer women than expected received levothyroxine treatment during pregnancy even though a fourfold increase was observed during the study period. Furthermore, one of 10 discontinued treatments during pregnancy. These findings all indicate that too few women are treated for hypothyroidism during pregnancy. Further research is needed to determine whether hypothyroid pregnant women are suboptimally treated and the possible consequences for the mother and fetus.

Research paper thumbnail of Setting thresholds to varying blood pressure monitoring intervals differentially affects risk estimates associated with white-coat and masked hypertension in the population

Hypertension, 2014

Outcome-driven recommendations about time intervals during which ambulatory blood pressure should... more Outcome-driven recommendations about time intervals during which ambulatory blood pressure should be measured to diagnose white-coat or masked hypertension are lacking. We cross-classified 8237 untreated participants (mean age, 50.7 years; 48.4% women) enrolled in 12 population studies, using ≥140/≥90, ≥130/≥80, ≥135/≥85, and ≥120/≥70 mm Hg as hypertension thresholds for conventional, 24-hour, daytime, and nighttime blood pressure. White-coat hypertension was hypertension on conventional measurement with ambulatory normotension, the opposite condition being masked hypertension. Intervals used for classification of participants were daytime, nighttime, and 24 hours, first considered separately, and next combined as 24 hours plus daytime or plus nighttime, or plus both. Depending on time intervals chosen, white-coat and masked hypertension frequencies ranged from 6.3% to 12.5% and from 9.7% to 19.6%, respectively. During 91 046 person-years, 729 participants experienced a cardiovascul...

Research paper thumbnail of Risk of Myocardial Infarction and Death Associated With the Use of Nonsteroidal Anti-Inflammatory Drugs (NSAIDs) Among Healthy Individuals: A Nationwide Cohort Study

Clinical Pharmacology & Therapeutics, 2008

Use of some nonsteroidal anti-inflammatory drugs (NSAIDs) is associated with increased cardiovasc... more Use of some nonsteroidal anti-inflammatory drugs (NSAIDs) is associated with increased cardiovascular risk in several patient groups, but whether this excess risk exists in apparently healthy individuals has not been clarified. Using a historical cohort design, we estimated the risk of death and myocardial infarction associated with the use of NSAIDs. Participants in the study were selected from the Danish population and were defined as healthy according to a history of no hospital admissions and no concomitant selected pharmacotherapy. The source population consisted of 4,614,807 individuals, of whom 1,028,437 were included in the study after applying selection criteria. Compared to no NSAID use, hazard ratios (95% confidence limits) for death/myocardial infarction were 1.01 (0.96-1.07) for ibuprofen, 1.63 (1.52-1.76) for diclofenac, 0.97 (0.83-1.12) for naproxen, 2.13 (1.89-2.41) for rofecoxib, and 2.01 (1.78-2.27) for celecoxib. A dose-dependent increase in cardiovascular risk was seen for selective COX-2 inhibitors and diclofenac. Caution should be exercised in NSAID use in all individuals, and particularly high doses should be avoided if possible.

Research paper thumbnail of Age-Specific Performance of the Revised Cardiac Risk Index for Predicting Cardiovascular Risk in Elective Noncardiac Surgery

Circulation: Cardiovascular Quality and Outcomes, 2015

The revised cardiac risk index (RCRI) holds a central role in preoperative cardiac risk stratific... more The revised cardiac risk index (RCRI) holds a central role in preoperative cardiac risk stratification in noncardiac surgery. Its performance in unselected populations, including different age groups, has, however, not been systematically investigated. We assessed the relationship of RCRI with major adverse cardiovascular events in an unselected cohort of patients undergoing elective, noncardiac surgery overall and in different age groups. We followed up all individuals ≥ 25 years who underwent major elective noncardiac surgery in Denmark (January 1, 2005, to November 30, 2011) for the 30-day risk of major adverse cardiovascular events (ischemic stroke, myocardial infarction, or cardiovascular death). There were 742 of 357,396 (0.2%), 755 of 74.889 (1.0%), 521 of 11,921 (4%), and 257 of 3146 (8%) major adverse cardiovascular events occurring in RCRI classes I, II, III, and IV. Multivariable odds ratio estimates were as follows: ischemic heart disease 3.30 (95% confidence interval, 2.96-3.69), high-risk surgery 2.70 (2.46-2.96), congestive heart failure 2.65 (2.29-3.06), cerebrovascular disease 10.02 (9.08-11.05), insulin therapy 1.62 (1.37-1.93), and kidney disease 1.45 (1.33-1.59). Modeling RCRI classes as a continuous variable, C statistic was highest among age group 56 to 65 years (0.772) and lowest for those aged &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;gt;85 years (0.683). Sensitivity of RCRI class &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;gt;I (ie, having ≥ 1 risk factor) for capturing major adverse cardiovascular events was 59%, 71%, 64%, 66%, and 67% in patients aged ≤ 55, 56 to 65, 66 to 75, 76 to 85, and &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;gt;85 years, respectively; the negative predictive values were &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;gt;98% across all age groups. In a nationwide unselected cohort, the performance of the RCRI was similar to that of the original cohort. Having ≥ 1 risk factor was of moderate sensitivity, but high negative predictive value for all ages.

Research paper thumbnail of Survival after out-of-hospital cardiac arrest in relation to sex: a nationwide registry-based study

Resuscitation, 2014

Crude survival has increased following an out-of-hospital cardiac arrest (OHCA). We aimed to stud... more Crude survival has increased following an out-of-hospital cardiac arrest (OHCA). We aimed to study sex-related differences in patient characteristics and survival during a 10-year study period. Patients≥12 years old with OHCA of a presumed cardiac cause, and in whom resuscitation was attempted, were identified through the Danish Cardiac Arrest Registry 2001-2010. A total of 19,372 patients were included. One-third were female, with a median age of 75 years (IQR 65-83). Compared to females, males were five years younger; and less likely to have severe comorbidities, e.g., chronic obstructive pulmonary disease (12.8% vs. 16.5%); but more likely to have arrest outside of the home (29.4% vs. 18.7%), receive bystander CPR (32.9% vs. 25.9%), and have a shockable rhythm (32.6% vs. 17.2%), all p<0.001. Thirty-day crude survival increased in males (3.0% in 2001 to 12.9% in 2010); and in females (4.8% in 2001 to 6.7% in 2010), p<0.001. Multivariable logistic regression analyses adjusted...

Research paper thumbnail of Diurnal variations in incidence and outcome of out-of-hospital cardiac arrest including prior comorbidity and pharmacotherapy: a nationwide study in Denmark

Resuscitation, 2014

To investigate diurnal variations in incidence and outcomes following out-of-hospital cardiac arr... more To investigate diurnal variations in incidence and outcomes following out-of-hospital cardiac arrest (OHCA). OHCA of presumed cardiac etiology were identified through the nationwide Danish Cardiac Arrest Registry (2001-2010). Time of day was divided into three time periods: daytime 07.00-14.59; evening 15.00-22.59; and nighttime 23.00-06.59. We identified 18,929 OHCA patients, aged ≥18 years. The median age was 72 years (IQR 62-80) and the majority were male (67.5%). OHCA occurrence varied across time periods, with 43.9%, 35.7% and 20.6% occurring during daytime, evening and nighttime, respectively. Nighttime patients were more likely to have: severe comorbidity (i.e. COPD), arrest in private home (87.2% vs. 69.0% and 73.0% daytime and evening, respectively), non-witnessed arrest (51.2% vs. 48.4% and 43.7%), no bystander CPR (75.9% vs. 68.4% and 66.1%), longer time interval from recognition of OHCA to rhythm analysis (12 min vs. 11 min and 11 min), and non-shockable heart rhythm (80...