Search

Population ageing has resulted in an increasing number of older people living with chronic diseases (multimorbidity) requiring five or more medications daily (polypharmacy). Ageing produces important changes in the cardiovascular system and represents the most potent single cardiovascular risk factor. Cardiovascular diseases (CVDs) constitute the greatest burden for older people, their caregivers, and healthcare systems. Cardiovascular pharmacotherapy in older people is complex because age-related changes in body composition, organ function, homeostatic mechanisms, and comorbidities modify the pharmacokinetic and pharmacodynamic properties of many commonly used cardiovascular and non-cardiovascular drugs. Additionally, polypharmacy increases the risk of adverse drug reactions and drug interactions, which in turn can lead to increased morbi-mortality and healthcare costs. Unfortunately, evidence of drug efficacy and safety in older people with multimorbidity and polypharmacy is limited because these individuals are frequently underrepresented/excluded from clinical trials. Moreover, clinical guidelines are largely written with a single-disease focus and only occasionally address the issue of coordination of care, when and how to discontinue treatments, if required, or how to prioritize recommendations for patients with multimorbidity and polypharmacy. This review analyses the main challenges confronting healthcare professionals when prescribing in older people with CVD, multimorbidity, and polypharmacy. Our goal is to provide information that can contribute to improving drug prescribing, efficacy, and safety, as well as drug adherence and clinical outcomes.

Background: Myocardial infarction is a cardiac adverse event associated with 5-fluorouracil (5-FU). There are limited data on the incidence, risk, and prognosis of 5-FU-associated myocardial infarction. Objectives: The aim of this study was to examine the risk for myocardial infarction in patients with gastrointestinal (GI) cancer treated with 5-FU compared with age- and sex-matched population control subjects without cancer (1:2 ratio). Methods: Patients with GI cancer treated with 5-FU between 2004 and 2016 were identified within the Danish National Patient Registry. Prevalent ischemic heart disease in both groups was excluded. Cumulative incidences were calculated, and multivariable regression and competing risk analyses were performed. Results: A total of 30,870 patients were included in the final analysis, of whom 10,290 had GI cancer and were treated with 5-FU and 20,580 were population control subjects without cancer. Differences in comorbid conditions and select antianginal medications were nonsignificant (P > 0.05 for all). The 6-month cumulative incidence of myocardial infarction was significantly higher for 5-FU patients at 0.7% (95% CI: 0.5%-0.9%) versus 0.3% (95% CI: 0.3%-0.4%) in population control subjects, with a competing risk for death of 12.1% versus 0.6%. The 1-year cumulative incidence of myocardial infarction for 5-FU patients was 0.9% (95% CI: 0.7%-1.0%) versus 0.6% (95% CI: 0.5%-0.7%) among population control subjects, with a competing risk for death of 26.5% versus 1.4%. When accounting for competing risks, the corresponding subdistribution hazard ratios suggested an increased risk for myocardial infarction in 5-FU patients, compared with control subjects, at both 6 months (hazard ratio: 2.10; 95% CI: 1.50-2.95; P < 0.001) and 12 months (hazard ratio: 1.39; 95% CI: 1.05-1.84; P = 0.022). Conclusions: Despite a statistically significantly higher 6- and 12-month risk for myocardial infarction among 5-FU patients compared with populati

Aims Reports have suggested an increased risk of aortic and mitral regurgitation associated with oral fluoroquinolones (FQs) resulting in a safety warning published by the European Medicines Agency (EMA). However, these findings have not yet been replicated.Methods and results Using Danish administrative registers, we conducted a nested case-control study in a nationwide cohort of individuals between 2005 and 2018. Cases were defined as the first occurrence of aortic or mitral regurgitation. Exposure of interest was the use of oral FQs. Hazard ratios (HRs) with 95% confidence intervals (95% CI) were obtained by fitting time-dependent Cox regression models, with penicillin V as comparator, to assess the association between FQ use and incident valvular regurgitation. We identified 38 370 cases of valvular regurgitation with 1 115 100 matched controls. FQ exposure was not significantly associated with increased rates of aortic or mitral regurgitation (HR 1.02, 95% CI 0.95-1.09) compared with penicillin V users. Investigating the cumulative defined daily doses (cDDD) of FQs yielded similar results with no significant association between increasing FQ use and valvular regurgitation (e.g. HR 1.08, 95% CI 0.95-1.23 for cDDD >10 compared with cDDD 1-5). These results were consistent across several analyses including a cohort of patients with hypertension and using a case definition based on valvular surgical interventions.Conclusions In a nationwide nested case-control study, FQs were not significantly associated with increased rates of valvular regurgitation. Our findings do not support a possible causal connection between FQ exposure and incident valvular regurgitation.

BACKGROUND: Dispatching citizen responders through a smartphone application (app) holds the potential to increase bystander cardiopulmonary resuscitation (CPR) and defibrillation in out-of-hospital cardiac arrest (OHCA).OBJECTIVES: This study investigated arrival at the OHCA location of app-dispatched citizen responders before the Emergency Medical Services (EMS) and the association with bystander CPR and bystander defibrillation.METHODS: Suspected OHCAs with alerted citizen responders from September 1, 2017, to August 31, 2018, were included. Citizen responders located 1.8 km (1.1 miles) from the OHCA were dispatched to start CPR or retrieve an automated external defibrillator. OHCAs where at least 1 citizen responder arrived before EMS were compared with OHCAs where EMS arrived first. In both groups, random bystanders could be present before the arrival of citizen responders and the EMS. Primary outcomes were bystander CPR and bystander defibrillation, which included CPR and defibrillation by citizen responders and random bystanders.RESULTS: Citizen responders were alerted in 819 suspected OHCAs, of which 438 (53.5%) were confirmed cardiac arrests eligible for inclusion. At least 1 citizen responder arrived before EMS in 42.0% (n = 184) of all included OHCAs. When citizen responders arrived before EMS, the odds for bystander CPR increased (odds ratio: 1.76; 95% confidence interval: 1.07 to 2.91; p = 0.027) and the odds for bystander defibrillation more than tripled (odds ratio: 3.73; 95% confidence interval: 2.04 to 6.84; p < 0.001) compared with OHCAs in which citizen responders arrived after EMS.CONCLUSIONS: Arrival of app-dispatched citizen responders before EMS was associated with increased odds for bystander CPR and a more than 3-fold increase in odds for bystander defibrillation. (The HeartRunner Trial; NCT03835403).

Purpose: The impact of endogenous androgen levels on the risk of type 2 diabetes in women remains uncertain. The objective was to investigate associations between endogenous androgen levels and risk of type 2 diabetes in young women without established comorbidity.Methods: In this retrospective cohort study, women aged 18 to 50 years who underwent measurement of plasma testosterone, dehydroepiandrosterone-sulfate (DHEA-S), dihydrotestosterone (DHT), and sex hormone-binding globulin (SHBG) for the first time from January 2007 to December 2015 were included. Androgens were analyzed using tandem liquid chromatography mass spectrometry. Women with established comorbidity were excluded, using Danish healthcare registries. We calculated incidence rate ratios (IRRs, 95% confidence intervals) of type 2 diabetes according to quartiles of plasma androgens using multivariate Poisson regression models.Results: A total of 8876 women, with a mean ± SD age of 38.5 ± 4.6 years and a median (interquartile range [IQR]) follow-up duration of 8.1 (6.6-9.4) years, were eligible for analyses. During 69 728 person-years, 69 women were diagnosed with type 2 diabetes. Women in the highest quartile of plasma total testosterone and calculated free testosterone displayed increased risk of type 2 diabetes compared with the lowest quartile: IRR 1.97 (1.01; 3.85), P = .048 and IRR 7.32 (2.84; 18.83), P < .001. SHBG was inversely associated with type 2 diabetes, Q4 versus Q1; IRR 0.06 (0.02; 0.21), P < .001. Plasma DHEA-S and DHT were not associated with incident type 2 diabetes.Conclusions: Higher levels of plasma total and free testosterone were associated with increased risk of type 2 diabetes among women.

BACKGROUND: In patients with non-ST-segment elevation acute coronary syndrome (NSTEACS), coronary pathology may range from structurally normal vessels to severe coronary artery disease.OBJECTIVES: The purpose of this study was to test if coronary computed tomography angiography (CTA) may be used to exclude coronary artery stenosis ≥50% in patients with NSTEACS.METHODS: The VERDICT (Very Early Versus Deferred Invasive Evaluation Using Computerized Tomography in Patients With Acute Coronary Syndromes) trial (NCT02061891) evaluated the outcome of patients with confirmed NSTEACS randomized 1:1 to very early (within 12 h) or standard (48 to 72 h) invasive coronary angiography (ICA). As an observational component of the trial, a clinically blinded coronary CTA was conducted prior to ICA in both groups. The primary endpoint was the ability of coronary CTA to rule out coronary artery stenosis (≥50% stenosis) in the entire population, expressed as the negative predictive value (NPV), using ICA as the reference standard.RESULTS: Coronary CTA was conducted in 1,023 patients-very early, 2.5 h (interquartile range [IQR]: 1.8 to 4.2 h), n = 583; and standard, 59.9 h (IQR: 38.9 to 86.7 h); n = 440 after the diagnosis of NSTEACS was made. A coronary stenosis ≥50% was found by coronary CTA in 68.9% and by ICA in 67.4% of the patients. Per-patient NPV of coronary CTA was 90.9% (95% confidence interval [CI]: 86.8% to 94.1%) and the positive predictive value, sensitivity, and specificity were 87.9% (95% CI: 85.3% to 90.1%), 96.5% (95% CI: 94.9% to 97.8%) and 72.4% (95% CI: 67.2% to 77.1%), respectively. NPV was not influenced by patient characteristics or clinical risk profile and was similar in the very early and the standard strategy group.CONCLUSIONS: Coronary CTA has a high diagnostic accuracy to rule out clinically significant coronary artery disease in patients with NSTEACS.

Objective: Metabolic syndrome entails hypertension, hyperglycemia, obesity and hypercholesterolemia. This syndrome increases the risk of cardiovascular disease and diabetes. Hyperglycemia during coronary reperfusion is associated with a poor prognosis. Contrastingly, targeting correction of hyperglycemia in clinical trials has not improved clinical outcome or has even been detrimental. H2 O2 is produced under hyperglycemic conditions and under reperfusion. This study aims to provide a mechanistic approach evaluating the impact of high glucose on the endothelial nitric oxide pathway in a H2 O2 -rich environment. Methods and results: HUVECs (human umbilical vein endothelial cells) were exposed to high glucose (20 mM) for either 20 or 72 hours co-incubated with or without H2 O2 (400 µM) for 30 minutes as models of increased oxidative stress during acute and prolonged hyperglycemia, respectively. The presence of reactive oxygen species (ROS) in both mitochondria and cytoplasm was measured by fluorescence activated cell sorting (FACS). Phosphorylation of endothelial nitric oxide synthase (eNOS) on threonine 495 (Thr495) and serine 1177 (Ser1177) was assessed by western blotting. Short-term (20 hours) high concentration of glucose alone increased ROS in mitochondria to 133.5% (p<0.05), whereas prolonged (72 hours) did not increase mitochondrial ROS. The increase in mitochondrial ROS could be attenuated by the anti-oxidant N-acetyl-L-cysteine (NAC). Incubation with H2 O2 for 30 minutes resulted in an increase in Thr495 phosphorylation (to 425%, p<0.01) and a decrease in Ser1177 phosphorylation (to 50.6%, p<0.01). Preincubation for 20 hours with 10 and 20 mM glucose did not affect phosphorylation of Thr495 and Ser1177. Stimulating HUVECs that were pre-incubated with 20 mM glucose for 72 hours with H2 O2 increased Thr495 phosphorylation to 146.6% (p<0.05). PKC inhibition attenuated the H2 O2 -induced Thr495 phosphorylation in cells incubated with high glucose lev

AIMS: Psoriasis is a common inflammatory disease that is associated with increased risk of cardiovascular disease, including myocardial infarction. Heart failure (HF) is independently associated with several cardiovascular risk factors and is a major cause of cardiovascular morbidity and mortality. The association between psoriasis and HF is unclear and we therefore investigated the risk of new-onset HF in a nationwide cohort of psoriasis patients compared with the background population.METHODS: The study included the entire Danish population aged ≥18 years followed from 1 January 1997 until HF, death or 31 December 2011. Information on comorbidity and concomitant medication was identified by individual-level linkage of administrative registers. New-onset HF was defined as first hospital admission for HF. Incidence rates of new-onset HF were calculated and adjusted hazard ratios were estimated by multivariable Cox regression models adjusted for age, gender, comorbidity and cardiovascular medications.RESULTS: A total of 5 485 856 subjects were eligible for analysis. In the study period 66 389 patients with new-onset psoriasis, including 11 242 patients with severe psoriasis, were identified. The overall incidence rates of new-onset HF were 2.82, 4.22 and 4.70 per 1000 person-years for the reference population, mild psoriasis and severe psoriasis, respectively. Compared with the reference population, the fully adjusted hazard ratios for new-onset HF were increased in patients with psoriasis with a hazard ratio 1.22 (95% confidence interval 1.16-1.29) and hazard ratio of 1.53 (95% confidence interval 1.34-1.74) for those with mild and severe disease, respectively.CONCLUSION: In this nationwide cohort, psoriasis was associated with a disease severity-dependent increased risk of new-onset HF.

Compromised autoregulation of ocular blood flow is a plausible consequence of hypertension, and studies indicate that hypertension can lead to progression of glaucoma. Initiating antihypertensive therapy in subjects with long-standing hypertension could deteriorate ocular blood flow leading ultimately to glaucomatous damage. Evidence on this topic is still equivocal but until adequate knowledge on the field has been established we recommend referral of patients disposed for glaucoma to ophthalmologic examination when initiating antihypertensive medication.

AIMS/OBJECTIVE: Conflicting data regarding cardiovascular effects of thiazolidinediones (TZDs) and extra-skeletal effects of vitamin D supported the need for a definitive trial. The Thiazolidinedione Intervention with vitamin D Evaluation (TIDE) trial aimed to assess the effects of TZDs (rosiglitazone and pioglitazone) on cardiovascular outcomes and the effects of vitamin D (cholecalciferol) on cancers and mortality.

Prior studies in heart failure (HF) have used the Modification of Diet in Renal Disease (MDRD) equation to calculate estimated glomerular filtration rate (eGFR). The Chronic Kidney Disease-Epidemiology Collaboration Group (CKD-EPI) equation provides a more-accurate eGFR than the MDRD when compared against the radionuclide gold standard. The prevalence and prognostic import of renal dysfunction in HF if the CKD-EPI equation is used rather than the MDRD is uncertain.

In ROCKET AF, rivaroxaban was non-inferior to adjusted-dose warfarin in preventing stroke or systemic embolism among patients with atrial fibrillation (AF). We aimed to investigate whether the efficacy and safety of rivaroxaban compared with warfarin is consistent among the subgroups of patients with and without previous stroke or transient ischaemic attack (TIA).

The use of n-3 fatty acids may prevent cardiovascular events in patients with recent myocardial infarction or heart failure. Their effects in patients with (or at risk for) type 2 diabetes mellitus are unknown.

In the ARISTOTLE trial, the rate of stroke or systemic embolism was reduced by apixaban compared with warfarin in patients with atrial fibrillation (AF). Patients with AF and previous stroke or transient ischaemic attack (TIA) have a high risk of stroke. We therefore aimed to assess the efficacy and safety of apixaban compared with warfarin in prespecified subgroups of patients with and without previous stroke or TIA.

The aim of this study was to investigate the relationship between gender and survival of patients with heart failure, using data from both randomized trials and observational studies, and the relative contribution of age, left ventricular systolic function, aetiology, and diabetes to differences in prognosis between men and women.

Objectives:To analyse the relation between selective serotonin reuptake inhibitor (SSRI) use and major congenital malformations, with focus on malformations of the heart. DESIGN: Register-based retrospective nationwide cohort study, using the Danish Medical Birth Registry. SETTING: Denmark. PARTICIPANTS: Pregnant women in Denmark between 1997 and 2009 and their offspring. PRIMARY OUTCOME MEASURES: For each SSRI, ORs for major congenital malformations were estimated using multivariable logistic regression models for women exposed to an SSRI during the first trimester and for women with paused exposure during pregnancy. RESULTS: The authors identified 848¿786 pregnancies; 4183 were exposed to an SSRI throughout the first trimester and 806 pregnancies paused exposure during pregnancy. Risks of congenital malformations of the heart were similar for pregnancies exposed to an SSRI throughout the first trimester, adjusted OR 2.01 (95% CI 1.60 to 2.53), and for pregnancies with paused SSRI treatment during pregnancy, adjusted OR 1.85 (95% CI 1.07 to 3.20), p value for difference: 0.94. The authors found similar increased risks of specific congenital malformations of the heart for the individual SSRIs. Furthermore, the authors found no association with dosage. CONCLUSIONS: The apparent association between SSRI use and congenital malformations of the heart may be confounded by indications. The moderate absolute risk increase combined with uncertainty for causality still requires the risk versus benefit to be evaluated in each individual case.

The provision of sufficient basal insulin to normalize fasting plasma glucose levels may reduce cardiovascular events, but such a possibility has not been formally tested.

The efficacy and safety of prolonging prophylaxis for venous thromboembolism in medically ill patients beyond hospital discharge remain uncertain. We hypothesized that extended prophylaxis with apixaban would be safe and more effective than short-term prophylaxis with enoxaparin.

To establish the safety, tolerability and most promising regimen of darexaban (YM150), a novel, oral, direct factor Xa inhibitor, for prevention of ischaemic events in acute coronary syndrome (ACS).

BACKGROUND: To investigate the effects of statin use over the last 10 years among diabetic patients who initiated glucose-lowering medications (GLMs) in Denmark.METHODS: we identified all Danish citizens 30 years and older who claimed their first GLM between 1997 and 2006, with follow-up until 2007. Use of medications, national background, income, and hospitalizations were obtained by cross-linkage of national registries in Denmark. We analyzed factors related to initiation and interruption of statin treatment. The analyses included country of birth, citizenship and, as proxy for ethnic origin, we constructed variables based on both the subjects and on their parent's country of birth. Countries were grouped as Denmark, Western countries, Eastern countries, and Africa.RESULTS: the cohort included 143,625 subjects. Compared with persons of Danish origin, the initiation of a statin medication during follow-up was significantly lower among patients of non-Danish origin: Odds ratio for subjects of Eastern origin 0.61 [CI 0.49-0.76] and 0.37 for subjects of African origin, [CI 0.24-0.59], both p < 0.001. The risk of interrupting statin treatment once it had been initiated was also higher in these groups (hazard ratio 2.03, [CI 1.91-2.17] for Eastern subjects and 1.94, [CI 1.63-2.32] for African subjects, both p < 0.0001). Combination of ethnic parameters to refine identification of the cohort led to the same conclusions as the analysis based only on country of birth or citizenship respectively.CONCLUSION: diabetes patients of African and Eastern origin in Denmark have less chance of being treated with a statin than those of western and Danish origin despite similar access to the Danish health care system.