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 >85 years (0.683). Sensitivity of RCRI class >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 >85 years, respectively; the negative predictive values were >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.
To examine the risk of death associated with antiarrhythmic drug (AAD) therapy in a nationwide unselected cohort of patients with atrial fibrillation (AF).
All patients admitted with AF in Denmark from 1995 to 2004 and their subsequent use of AADs were identified by individual-level linkage of nationwide registries. Multivariable Cox proportional-hazard models with time-dependent covariates were used to analyse the risk of death associated with AAD therapy. A total of 141,500 patients were included in the study; of these 3356 (2.4%) patients received treatment with flecainide, 3745 (2.6%) propafenone, 23,346 (16.5%) sotalol, and 10,376 (7.3%) amiodarone. Annualized mortality rates were 2.54, 4.25, 5.29, and 7.42 per year per 100 person years for flecainide, propafenone, sotalol, and amiodarone, respectively. Multivariable Cox proportional-hazard models did not show increased risk of death associated with any of the AADs. Hazard ratio (95% confidence interval) for flecainide 0.38 (0.32-0.44), propafenone 0.65 (0.58-0.71), sotalol 0.65 (0.63-0.67), and amiodarone 0.94 (0.89-1.00).
In an unselected cohort of patients with AF, antiarrhythmic treatment with flecainide, propafenone, sotalol, or amiodarone was not associated with increased risk of death. From a safety perspective, this indicates appropriate selection of patients for AAD therapy.
The aim of this study was to investigate the impact of atrial fibrillation (AF) and antithrombotic treatment on the prognosis in patients with heart failure (HF) as well as vascular disease.
HF, vascular disease, and AF are pathophysiologically related, and understanding antithrombotic treatment for these conditions is crucial.
In hospitalized patients with HF and coexisting vascular disease (coronary artery disease or peripheral arterial disease) followed from 1997 to 2009, AF status was categorized as prevalent AF, incident AF, or no AF. Risk of thromboembolism (TE), myocardial infarction (MI), and serious bleeding was assessed by Cox regression models (hazard ratio [HR] with 95% confidence interval [CI]) with antithrombotic therapy and AF as time-dependent variables.
A total of 37,464 patients were included (age, 74.5 ± 10.7 years; 36.3% females) with a mean follow-up of 3 years during which 20.7% were categorized as prevalent AF and 17.2% as incident AF. Compared with vitamin K antagonist (VKA) in prevalent AF, VKA plus antiplatelet was not associated with a decreased risk of TE (HR: 0.91; 95% CI: 0.73 to 1.12) or MI (HR: 1.11; 95% CI: 0.96 to 1.28), whereas bleeding risk was significantly increased (HR: 1.31; 95% CI: 1.09 to 1.57). Corresponding estimates for incident AF were HRs of 0.77 (95% CI: 0.56 to 1.06), 1.07 (95% CI: 0.89 to 1.28), and 2.71 (95% CI: 1.33 to 2.21) for TE, MI, and bleeding, respectively. In no AF patients, no statistical differences were seen between antithrombotic therapies in TE or MI risk, whereas bleeding risk was significantly increased for VKA with and without single-antiplatelet therapy.
In AF patients with coexisting HF and vascular disease, adding single-antiplatelet therapy to VKA therapy is not associated with additional benefit in thromboembolic or coronary risk, but notably increased bleeding risk.
Comment In: J Am Coll Cardiol. 2014 Jun 24;63(24):2699-70124794117
Clinical guidelines have been criticized for encouraging the use of ß-blockers in noncardiac surgery despite weak evidence. Relevant clinical trials have been small and have not convincingly demonstrated an effect of ß-blockers on hard end points (ie, perioperative myocardial infarction, ischemic stroke, cardiovascular death, and all-cause death).
To assess the association of ß-blocker treatment with major cardiovascular adverse events (MACE) and all-cause mortality in patients with ischemic heart disease undergoing noncardiac surgery. DESIGN, SETTING, PARTICIPANTS, AND EXPOSURE: Individuals with ischemic heart disease with or without heart failure (HF) and with and without a history of myocardial infarction undergoing noncardiac surgery between October 24, 2004, and December 31, 2009, were identified from nationwide Danish registries. Adjusted Cox regression models were used to calculate the 30-day risks of MACE (ischemic stroke, myocardial infarction, or cardiovascular death) and all-cause mortality associated with ß-blocker therapy.
Thirty-day risk of MACE and all-cause mortality.
Of 28,263 patients with ischemic heart disease undergoing surgery, 7990 (28.3%) had HF and 20,273 (71.7%) did not. ß-Blockers were used in 4262 (53.3%) with and 7419 (36.6%) without HF. Overall, use of ß-blockers was associated with a hazard ratio (HR) of 0.90 (95% CI, 0.79-1.02) for MACE and 0.95 (0.85-1.06) for all-cause mortality. Among patients with HF, use of ß-blockers was associated with a significantly lower risk of MACE (HR, 0.75; 95% CI, 0.70-0.87) and all-cause mortality (0.80; 0.70-0.92), whereas among patients without HF, there was no significant association of ß-blocker use with MACE (1.11; 0.92-1.33) or mortality (1.15; 0.98-1.35) (P
Heart failure has been suggested to increase the risk of developing diabetes. We investigated the relation between heart failure severity, defined by loop-diuretic dosage, and the risk of developing diabetes in a nationwide cohort of patients with heart failure.
We followed all Danish patients discharged from hospitalisation for first-time heart failure in 1997-2010, without prior use of hypoglycaemic agents, until a claimed prescription for hypoglycaemic agents, death or 31 December 2010. The association of loop-diuretic dosage (furosemide equivalents) 90 days after discharge (study baseline) with risk of diabetes was estimated by multivariate Cox regression models.
In total, 99,362 patients were included and divided into five loop-diuretic dose groups: 30,838 (31%) used no loop diuretics; 24,389 (25%) used >0-40 mg/day; 17,355 (17%) used >40-80 mg/day; 11,973 (12%) used >80-159 mg/day; and 14,807 (15%) used =160 mg/day. A total of 7,958 patients (8%) developed diabetes. Loop-diuretic dosages were associated with an increased risk of developing diabetes in a dose-dependent manner. Concomitant use of renin-angiotensin system inhibitors (RASis) attenuated the risk (p value for interaction
Although the relation between stroke risk factors and stroke in patients with atrial fibrillation (AF) has been extensively examined, only few studies have explored the association of AF and the risk of ischaemic stroke/systemic thromboembolism/transient ischaemic attack (stroke/TE/TIA) in the presence of concomitant stroke risk factors.
From nationwide registries, all persons who turned 50, 60, 70, or 80 from 1997 to 2011 were identified. Persons receiving warfarin were excluded. The absolute risk of stroke/TE/TIA was reported for a 5-year period, as was the absolute risk ratios for AF vs. no AF according to prior stroke and the number of additional risk factors. The study cohort comprised of 3 076 355 persons without AF and 48 189 with AF. For men aged 50 years, with no risk factors, the 5-year risk of stroke was 1.1% (95% confidence interval 1.1-1.1); with AF alone 2.5% (1.8-3.2); with one risk factor and no prior stroke or AF 2.5% (2.3-2.7); and with one factor, no prior stroke and AF 2.9% (1.4-4.3). In men aged 50 years with prior stroke as the only risk factor, 5-year risk was 10.2% (9.1-11.3). In men aged 70 years, the corresponding risks were 4.8% (4.7-4.9), 6.8% (5.7-7.9), 6.6% (6.3-6.8), 8.7 (7.4-9.9), and 19.1% (18.1-20.1), respectively. In women aged 50 years, the risk was of 0.7% (0.7-0.7), 2.1% (0.9-3.2), 1.6% (1.4-1.8), 4.1% (0.6-7.6), and 7.2% (6.3-8.2), respectively, and in women aged 70 years 3.4% (3.3-3.5), 8.2% (7.0-9.5), 4.6% (4.4-4.8), 9.1% (7.5-10.6), and 15.4% (14.5-16.4), respectively.
Stroke/TE/TIA risk was particularly increased when prior stroke/TE/TIA was present. Atrial fibrillation is associated with an increase in risk of stroke/TE/TIA in the absence of other risk factors but only a moderate increase in risk when other risk factors are present.
Perioperative ß-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 ß-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 (ß-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 ß-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 ß-blockers compared with 0.8% of patients not treated with ß-blockers (P?
Diabetes in patients with heart failure or myocardial infarction (MI) increases morbidity and mortality, but little is known about the impact of obesity on the risk of developing diabetes in these populations.
A cohort of patients consecutively hospitalized with heart failure (n?=?3472) or MI (n?=?5723) was followed in the period 1995-2006.
Multivariable Cox proportional-hazard models were used to estimate the risk of developing diabetes according to the World Health Organization body mass index (BMI) classification. Normal weight patients (BMI 18.5-24.9?kg/m(2)) were used as the reference.
In both populations, more than half of the patients with a BMI above 34.9?kg/m(2) developed diabetes. In heart failure patients, a BMI above 24.9?kg/m(2) was associated with an increased risk of diabetes for the three BMI groups, i.e. 25.0-29.9?kg/m(2), 30.9-34.9?kg/m(2), and >34.9?kg/m(2), with adjusted hazard ratios (HRs) of 2.16 (95% confidence interval 1.50-3.12), 3.89 (2.61-5.78), and 6.06 (3.79-9.69), respectively. In MI patients, the adjusted HRs in the three corresponding BMI groups were 1.84 (1.44-2.37), 4.31 (3.26-5.69), and 9.50 (6.70-13.46), respectively. Incident diabetes was associated with increased cardiovascular and all-cause mortality risks with adjusted HRs of greater magnitude than in prevalent diabetes.
BMI was an independent predictor of incident diabetes in patients with either heart failure or MI. More than half of the patients with a BMI above 34.9?kg/m(2) developed diabetes during follow-up. Incident diabetes carries an increased mortality risk.
Affiliations of authors: Danish Cancer Society Research Center, Copenhagen, Denmark (KR, LM, JHO); Vanderbilt University Medical Center, Vanderbilt-Ingram Cancer Center, Nashville, TN (JDB); National Council on Radiation Protection and Measurements, Bethesda, MD (JDB); Department of Cardiology, Copenhagen University Hospital, Copenhagen, Denmark (LK); Department of Oncology, Odense University Hospital, Institute of Clinical Research, University of Southern Denmark, Odense, Denmark (ME). email@example.com.
Cardiovascular disease has emerged as a serious late effect in survivors of adolescent and young adult cancer, but risk has not been quantified comprehensively in a population-based setting.
In the Danish Cancer Registry, we identified 43153 1-year survivors of cancer diagnosed at ages 15 to 39 years (1943-2009) and alive in 1977; from the Danish Civil Registration System, we randomly selected a comparison cohort of the same age and sex. Subjects were linked to the Danish Patient Register, and observed numbers of first hospitalizations for cardiovascular disease (International Classification of Diseases, Tenth Revision codes I10-I79) were compared with the expected numbers derived from the comparison cohort. We calculated the absolute excess risks attributable to status as a survivor of cancer and standardized hospitalization rate ratios (RRs). All statistical tests were two-sided.
During follow-up, 10591 survivors (24.5%) were discharged from the hospital with cardiovascular disease, whereas 8124 were expected (RR = 1.30; 95% confidence interval [CI)] = 1.28 to 1.33; P
Non steroidal anti-inflammatory drugs (NSAIDs) increase mortality and morbidity after myocardial infarction (MI). We examined cause-specific mortality and morbidity associated with NSAIDs in a nationwide cohort of MI patients.
By individual-level linkage of nationwide registries of hospitalization and drug dispensing from pharmacies in Denmark, patients aged >30 years admitted with first-time MI during 1997-2009 and their subsequent NSAID use were identified. The risk of three cardiovascular specific endpoints: cardiovascular death, the composite of coronary death and nonfatal MI, and the composite of fatal and nonfatal stroke, associated with NSAID use was analyzed by Cox proportional hazard analyses. Of 97,698 patients included 44.0% received NSAIDs during follow-up. Overall use of NSAIDs was associated with an increased risk of cardiovascular death (hazard ratio [HR] 1.42, 95% confidence interval [CI] 1.36-1.49). In particular use of the nonselective NSAID diclofenac and the selective cyclooxygenase-2 inhibitor rofecoxib was associated with increased risk of cardiovascular death (HR 1.96 [1.79-2.15] and HR1.66 [1.44-1.91], respectively) with a dose dependent increase in risk. Use of ibuprofen was associated with increased risk of cardiovascular death (HR 1.34[1.26-1.44]), whereas naproxen was associated with the lowest risk of (e.g., HR 1.27[1.01-1.59].
Use of individual NSAIDs is associated with different cause-specific cardiovascular risk and in particular rofecoxib and diclofenac were associated with increased cardiovascular morbidity and mortality. These results support caution with use of all NSAIDs in patients with prior MI.
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