Background
Use of proton pump inhibitors (PPIs) has been associated with cardiovascular disease amongst patients not on antiplatelet therapy. The associations of PPI use, duration and dose, with risk ...of first‐time ischemic stroke and myocardial infarction (MI) are poorly understood.
Methods
All Danish individuals with no prior history of MI or stroke, who had an elective upper gastrointestinal endoscopy performed between 1997 and 2012, were identified from nationwide registries. We used multiple Poisson regression to test associations with current PPI use and its dose and used multiple cause‐specific Cox regression and g‐formula methods to analyze long‐term use.
Results
Amongst 214 998 individuals, during a median follow‐up of 5.8 years, there were 7916 ischemic strokes and 5608 MIs. Current PPI exposure was associated with significantly higher rates of both ischemic stroke (Hazard ratio (HR) 1.13; 95% confidence interval (CI) 1.08–1.19) and MI (HR 1.31, CI 1.23–1.39) after adjusting for age, sex, comorbidities and concomitant medication. High‐dose PPI was associated with increased rates of ischemic stroke (HR 1.31, CI 1.21–1.42) and MI (HR 1.43, CI 1.30–1.57). Histamine H2 receptor antagonists (H2RAs) use was not significantly associated with ischemic stroke (HR 1.02, CI 0.84–1.24) or MI (HR 1.15, CI 0.92–1.43). Long‐term users of PPIs, compared with nonusers, had a 29% (CI 5%‐59%) greater absolute risk of ischemic stroke and a 36% (CI 7%‐73%) greater risk of MI within a 6‐month period.
Conclusion
Use of PPIs was associated with increased risks of first‐time ischemic stroke and MI, particularly amongst long‐term users and at high doses.
Background
The significance of chronic kidney disease on susceptibility to COVID‐19 and subsequent outcomes remains unaddressed.
Objective
To investigate the association of estimated glomerular ...filtration rate (eGFR) on risk of contracting COVID‐19 and subsequent adverse outcomes.
Methods
Rates of hospital‐diagnosed COVID‐19 were compared across strata of eGFR based on conditional logistic regression using a nested case–control framework with 1:4 matching of patients diagnosed with COVID‐19 with controls from the Danish general population on age, gender, diabetes and hypertension. Risk of subsequent severe COVID‐19 or death was assessed in a cohort study with comparisons across strata of eGFR based on adjusted Cox regression models with G‐computation of results to determine 60‐day risk standardized to the distribution of risk factors in the sample.
Results
Estimated glomerular filtration rate was inversely associated with rate of hospital‐diagnosed COVID‐19: eGFR 61–90 mL/min/1.73m2 HR 1.13 (95% CI 1.03–1.25), P = 0.011; eGFR 46–60 mL/min/1.73m2 HR 1.26 (95% CI 1.06–1.50), P = 0.008; eGFR 31–45 mL/min/1.73m2 HR 1.68 (95% CI 1.34–2.11), P < 0.001; and eGFR ≤ 30 mL/min/1.73m2 3.33 (95% CI 2.50–4.42), P < 0.001 (eGFR > 90 mL/min/1.73m2 as reference), and renal impairment was associated with progressive increase in standardized 60‐day risk of death or severe COVID‐19; eGFR > 90 mL/min/1.73m2 13.9% (95% CI 9.7–15.0); eGFR 90–61 mL/min/1.73m2 16.1% (95% CI 14.5–17.7); eGFR 46–60 mL/min/1.73m2 17.8% (95% CI 14.7–21.2); eGFR 31–45 mL/min/1.73m2 22.6% (95% CI 18.2–26.2); and eGFR ≤ 30 mL/min/1.73m2 23.6% (95% CI 18.1–29.1).
Conclusions
Renal insufficiency was associated with progressive increase in both rate of hospital‐diagnosed COVID‐19 and subsequent risk of adverse outcomes. Results underscore a possible vulnerability associated with impaired renal function in relation to COVID‐19.
Background
Comparative data of non‐vitamin K antagonist oral anticoagulants (NOAC) are lacking in patients with atrial fibrillation (AF).
Objective
We compared effectiveness and safety of standard ...and reduced dose NOAC in AF patients.
Methods
Using Danish nationwide registries, we included all oral anticoagulant‐naïve AF patients who initiated NOAC treatment (2012–2016). Outcome‐specific and mortality‐specific multiple Cox regressions were combined to compute average treatment effects as 1‐year standardized differences in stroke and bleeding risks (g‐formula).
Results
Amongst 31 522 AF patients, the distribution of NOAC/dose was as follows: dabigatran standard dose (22.4%), dabigatran‐reduced dose (14.0%), rivaroxaban standard dose (21.8%), rivaroxaban reduced dose (6.7%), apixaban standard dose (22.9%), and apixaban reduced dose (12.2%). The 1‐year standardized absolute risks of stroke/thromboembolism were 1.73–1.98% and 2.51–2.78% with standard and reduced NOAC dose, respectively, without statistically significant differences between NOACs for given dose level. Comparing standard doses, the 1‐year standardized absolute risk (95% CI) for major bleeding was for rivaroxaban 2.78% (2.42–3.17%); corresponding absolute risk differences (95% CI) were for dabigatran −0.93% (−1.45% to −0.38%) and apixaban, −0.54% (−0.99% to −0.05%). The results for major bleeding were similar for reduced NOAC dose. The 1‐year standardized absolute risk (95% CI) for intracranial bleeding was for standard dose dabigatran 0.19% (0.22–0.50%); corresponding absolute risk differences (95% CI) were for rivaroxaban 0.23% (0.06–0.41%) and apixaban, 0.18% (0.01–0.34%).
Conclusions
Standard and reduced dose NOACs, respectively, showed no significant risk difference for associated stroke/thromboembolism. Rivaroxaban was associated with higher bleeding risk compared with dabigatran and apixaban and dabigatran was associated with lower intracranial bleeding risk compared with rivaroxaban and apixaban.
Background
Data regarding the impact of preheart failure (HF) comorbidities on the prognosis of HF are scarce, especially in the younger HF patients.
Objectives
To investigate pre‐existing ...comorbidities in HF patients versus matched controls and to assess their impact on mortality.
Methods
We included all first‐time in‐hospital and outpatient diagnoses of HF from 1995 to 2017, and comorbidities antedating the HF‐diagnosis in the Danish nationwide registries. HF patients were matched with up to five controls. One‐year all‐cause mortality rates and population attributable risk (PAR) were estimated for three separate age groups (≤50, 51–74 and >74 years).
Results
Totally 280 002 patients with HF and 1 166 773 controls were included. Cardiovascular comorbidities, for example, cerebrovascular disease and ischaemic heart disease were more frequent in the oldest (17.9% and 29.7% in HF vs. 9.8% and 10.7% in controls) compared to the youngest age group (3.9% and 15.2% in HF vs. 0.7% and 0.9% in controls). Amongst patients with HF, 1‐year mortality rates (per 100 person‐years) were highest amongst those with >1 noncardiovascular comorbidity: ≤50 years (10.4; 9.64–11.3), 51–74 years (23.3; 22.9–23.7), >74 years (58.5; 57.9–59.0); hazard ratios 245.18 (141.45–424.76), 45.85 (42.77–49.15) and 24.5 (23.64–25.68) for those ≤50, 51–74 and >74 years, respectively. For HF patients ≤50 years, PAR was greatest for hypertension (17.8%), cancer (14.1%) and alcohol abuse (8.5%). For those aged >74 years, PAR was greatest for hypertension (23.6%), cerebrovascular disease (6.2%) and cancer (7.2%).
Conclusions
Heart failure patients had a higher burden of pre‐existing comorbidities, compared to controls, which adversely impacted prognosis, especially in the young.
Background
Psoriasis is a common disease and is associated with cardiovascular diseases. Systemic anti‐inflammatory drugs may reduce risk of cardiovascular events. We therefore examined the rate of ...cardiovascular events, i.e. cardiovascular death, myocardial infarction and stroke, in patients with severe psoriasis treated with systemic anti‐inflammatory drugs.
Methods
Individual‐level linkage of administrative registries was used to perform a longitudinal nationwide cohort study. Time‐dependent multivariable adjusted Cox regression was used to estimate hazard ratios (HRs) with 95% confidence intervals (CIs) of cardiovascular events associated with use of biological drugs, methotrexate, cyclosporine, retinoids and other antipsoriatic therapies, including topical treatments, phototherapy and climate therapy.
Results
A total of 6902 patients (9662 treatment exposures) with a maximum follow‐up of 5 years were included. Incidence rates per 1000 patients‐years for cardiovascular events were 4.16, 6.28, 6.08, 18.95 and 14.63 for biological drugs, methotrexate, cyclosporine, retinoid and other therapies respectively. Relative to other therapies, methotrexate (HR 0.53; CI 0.34–0.83) was associated with reduced risk of the composite endpoint and a comparable but non‐significant protective effect was observed with biological drugs (HR 0.58; CI 0.30–1.10), whereas no protective effect was apparent with cyclosporine (HR 1.06; CI 0.26–4.27) and retinoids (HR 1.80; CI 1.03–2.96). Tumour necrosis factor inhibitors (HR 0.46; CI 0.22–0.98) were linked to reduced event rates, whereas the interleukin‐12/23 inhibitor ustekinumab (HR 1.52; CI 0.47–4.94) was not.
Conclusion
Systemic anti‐inflammatory treatment with methotrexate was associated with significantly lower rates of cardiovascular events during long‐term follow‐up compared to patients treated with other antipsoriatic therapies. The treatment strategy in patients with severe psoriasis may have an impact on cardiovascular outcomes and randomized trials to evaluate the cardiovascular safety and efficacy of systemic antipsoriatic therapies are called for.
Background
Mounting evidence suggests that dermatomyositis/polymyositis (DM/PM) are associated with increased risk of atherosclerotic events and venous thromboembolism. However, data on the ...association between DM/PM and other cardiac outcomes, especially heart failure (HF), are scarce.
Objectives
To examine the long‐term risk and prognosis associated with adverse cardiac outcomes in patients with DM/PM.
Methods
Using Danish administrative registries, we included all patients ≥18 years with newly diagnosed DM/PM (1996–2018). Risks of incident outcomes were compared with non‐DM/PM controls from the background population (matched 1:4 by age, sex, and comorbidity). In a secondary analysis, we compared mortality following HF diagnosis between DM/PM patients with HF and non‐DM/PM patients with HF (matched 1:4 by age and sex).
Results
The study population included 936 DM/PM patients (median age 58.5 years, 59.0% women) and 3744 matched non‐DM/PM controls. The median follow‐up was 6.9 years. Absolute 10‐year risks of incident outcomes for DM/PM patients vs matched controls were as follows: HF, 6.98% (CI, 5.16–9.16%) vs 4.58% (3.79–5.47%) (P = 0.002); atrial fibrillation, 10.17% (7.94–12.71%) vs 7.07% (6.09–8.15%) (P = 0.005); the composite of ICD implantation/ventricular arrhythmias/cardiac arrest, 1.99% (1.12–3.27%) vs 0.64% (0.40–0.98%) (P = 0.02); and all‐cause mortality, 35.42% (31.64–39.21%) vs 16.57% (15.10–18.10%) (P < 0.0001). DM/PM with subsequent HF was associated with higher mortality compared with HF without DM/PM (adjusted hazard ratio 1.58 CI, 1.01–2.47).
Conclusion
Patients with DM/PM had a higher associated risk of HF and other adverse cardiac outcomes compared with matched controls. Among patients developing HF, a history of DM/PM was associated with higher mortality.
Background: Female sex has been suggested as a risk factor for stroke/thromboembolism in patients with non‐valvular atrial fibrillation (AF) and has therefore been included within risk scores, e.g. ...the CHA2DS2‐VASc score, and guidelines.
Objectives: To investigate the risk of stroke/thromboembolism associated with female sex in non‐valvular AF patients.
Patients/Methods: Using the national Danish registers, we identified non‐anticoagulated patients discharged with non‐valvular AF (1997–2008), and subdivided the population into three age intervals: < 65, 65–74 and ≥ 75 years. We calculated stroke rates according to sex, and assessed the stroke risk associated with female sex by using Cox regression analysis.
Results: We included 87 202 AF patients, and 44 744 (51.3%) were female. The rate of stroke/thromboembolism for females aged < 65 and 65–74 years was not increased as compared with men, whereas the rate for females aged ≥ 75 years was increased. At both 1‐year and 12‐year follow‐up, female sex did not increase the risk of stroke for patients aged < 75 years. At 1‐year follow‐up, the hazard ratios associated with female sex were 0.89 (95% confidence interval CI 0.70–1.13) and 0.91 (95 CI 0.79–1.05) for patients aged < 65 and 65–74 years, respectively, and being female and aged ≥ 75 years was associated with an increased risk of stroke of 1.20 (95 CI 1.12–1.28).
Conclusion: Female sex was only associated with an increased risk of stroke for AF patients aged ≥ 75 years. Our study suggests that female sex should not be automatically included as an independent stroke/thromboembolic risk factor in guidelines or in the CHA2DS2‐VASc score, without careful prior consideration of the ‘age < 65 and lone AF’ criterion.
. Ahlehoff O, Gislason GH, Charlot M, Jørgensen CH, Lindhardsen J, Olesen JB, Abildstrøm SZ, Skov L, Torp‐Pedersen C, Hansen PR. (Copenhagen University Hospital Gentofte, Hellerup; Copenhagen ...University Hospital Bispebjerg, Copenhagen; National Institute of Public Health, University of Southern Denmark, Copenhagen; Copenhagen University Hospital Gentofte, Hellerup; University of Copenhagen, Copenhagen, Denmark) Psoriasis is associated with clinically significant cardiovascular risk: a Danish nationwide cohort study. J Intern Med2011; 270: 147–157.
Objective. The magnitude of the cardiovascular risk from psoriasis and psoriatic arthritis is debated. We therefore investigated the psoriasis‐related risk of adverse cardiovascular events and mortality.
Design, setting and subjects. We conducted a cohort study of the entire Danish population aged ≥18 years followed from 1997 to 2006 by individual‐level linkage of nationwide registers. Psoriasis was defined by prescription claims and classified as severe if patients received hospital‐based treatment. Time‐dependent Poisson regression models were applied to assess cardiovascular risk in patients with psoriasis and psoriatic arthritis.
Main outcome measures. All‐cause mortality, cardiovascular mortality and hospitalizations for myocardial infarction (MI), stroke and coronary revascularization were recorded.
Results. A total of 34 371 patients with mild psoriasis and 2621 with severe psoriasis, including 607 with psoriatic arthritis, were identified and compared with 4 003 265 controls. The event rates and rate ratios (RRs) of all‐cause mortality, cardiovascular death, MI, coronary revascularization, stroke and a composite of MI, stroke and cardiovascular death were increased in patients with psoriasis. The rate ratio increased with disease severity and decreased with age of onset. The overall RRs for the composite endpoint were 1.20 (95% confidence interval CI 1.14–1.25) and 1.58 (95% CI 1.36–1.82) for mild and severe psoriasis, respectively. The corresponding RRs for cardiovascular death were 1.14 (95% CI 1.06–1.22) and 1.57 (95% CI1.27–1.94). The risk was similar in patients with severe skin affection alone and those with psoriatic arthritis.
Conclusions. Psoriasis is associated with increased risk of adverse cardiovascular events and all‐cause mortality. Young age, severe skin affection and/or psoriatic arthritis carry the most risk. Patients with psoriasis may be candidates for early cardiovascular risk factor modification.
Objectives
Psoriasis is a chronic inflammatory disorder associated with cardiovascular morbidity and mortality. Systemic anti‐inflammatory drugs, including biological agents, are widely used in the ...treatment of patients with moderate to severe psoriasis and may attenuate the risk of cardiovascular disease events. We therefore examined the rate of cardiovascular disease events in patients with severe psoriasis treated with systemic anti‐inflammatory drugs.
Design, setting and participants
Individual‐level linkage of nationwide administrative databases was used to assess the event rates associated with use of biological agents, methotrexate or other therapies, including retinoids, cyclosporine and phototherapy, in Denmark from 2007 to 2009.
Main outcome measure
Death, myocardial infarction and stroke.
Results
A total of 2400 patients with severe psoriasis, including 693 patients treated with biological agents and 799 treated with methotrexate, were identified. Incidence rates per 1000 patient‐years and 95% confidence intervals (CIs) for the composite endpoint were 6.0 (95% CI 2.7–13.4), 17.3 (95% CI 12.3–24.3) and 44.5 (95% CI 34.6–57.0) for patients treated with biological agents, methotrexate and other therapies, respectively. Age‐ and sex‐adjusted hazard ratios (HRs) were 0.28 (95% CI 0.12–0.64) and 0.65 (95% CI 0.42–1.00) for patients treated with biological agents and methotrexate, respectively, using other therapies as the reference cohort. Corresponding HRs for a secondary composite endpoint of cardiovascular death, myocardial infarction and stroke were 0.48 (95% CI 0.17–1.38) and 0.50 (95% CI 0.26–0.97).
Conclusion
In this nationwide study of patients with severe psoriasis, systemic anti‐inflammatory treatment with biological agents or methotrexate was associated with lower cardiovascular disease event rates compared to patients treated with other anti‐psoriatic therapies.
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