Publications by authors named "Charlotte Andersson"

192 Publications

Long-Term Mortality Associated With Use of Carvedilol Versus Metoprolol in Heart Failure Patients With and Without Type 2 Diabetes: A Danish Nationwide Cohort Study.

J Am Heart Assoc 2021 Sep 17;10(18):e021310. Epub 2021 Sep 17.

Department of Cardiology Herlev and Gentofte Hospital Copenhagen University Hellerup Denmark.

Background Carvedilol may have favorable glycemic properties compared with metoprolol, but it is unknown if carvedilol has mortality benefit over metoprolol in patients with type 2 diabetes (T2D) and heart failure with reduced ejection fraction (HFrEF). Methods and Results Using Danish nationwide databases between 2010 and 2018, we followed patients with new-onset HFrEF treated with either carvedilol or metoprolol for all-cause mortality until the end of 2018. Follow-up started 120 days after initial HFrEF diagnosis to allow initiation of guideline-directed medical therapy. There were 39 260 patients on carvedilol or metoprolol at baseline (mean age 70.8 years, 35% women), of which 9355 (24%) had T2D. Carvedilol was used in 2989 (32%) patients with T2D and 10 411 (35%) of patients without T2D. Users of carvedilol had a lower prevalence of atrial fibrillation (20% versus 35%), but other characteristics appeared well-balanced between the groups. Totally 11 306 (29%) were deceased by the end of follow-up. We observed no mortality differences between carvedilol and metoprolol, multivariable-adjusted hazard ratio (HR) 0.97 (0.90-1.05) in patients with T2D versus 1.00 (0.95-1.05) for those without T2D, for difference =0.99. Rates of new-onset T2D were lower in users of carvedilol versus metoprolol; age, sex, and calendar year adjusted HR 0.83 (0.75-0.91), <0.0001. Conclusions In a contemporary clinical cohort of HFrEF patients with and without T2D, carvedilol was not associated with a reduction in long-term mortality compared with metoprolol. However, carvedilol was associated with lowered risk of new-onset T2D supporting the assertion that carvedilol has a more favorable metabolic profile than metoprolol.
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http://dx.doi.org/10.1161/JAHA.121.021310DOI Listing
September 2021

The genomics of heart failure: design and rationale of the HERMES consortium.

ESC Heart Fail 2021 Sep 3. Epub 2021 Sep 3.

Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.

Aims: The HERMES (HEart failure Molecular Epidemiology for Therapeutic targetS) consortium aims to identify the genomic and molecular basis of heart failure.

Methods And Results: The consortium currently includes 51 studies from 11 countries, including 68 157 heart failure cases and 949 888 controls, with data on heart failure events and prognosis. All studies collected biological samples and performed genome-wide genotyping of common genetic variants. The enrolment of subjects into participating studies ranged from 1948 to the present day, and the median follow-up following heart failure diagnosis ranged from 2 to 116 months. Forty-nine of 51 individual studies enrolled participants of both sexes; in these studies, participants with heart failure were predominantly male (34-90%). The mean age at diagnosis or ascertainment across all studies ranged from 54 to 84 years. Based on the aggregate sample, we estimated 80% power to genetic variant associations with risk of heart failure with an odds ratio of ≥1.10 for common variants (allele frequency ≥ 0.05) and ≥1.20 for low-frequency variants (allele frequency 0.01-0.05) at P < 5 × 10 under an additive genetic model.

Conclusions: HERMES is a global collaboration aiming to (i) identify the genetic determinants of heart failure; (ii) generate insights into the causal pathways leading to heart failure and enable genetic approaches to target prioritization; and (iii) develop genomic tools for disease stratification and risk prediction.
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http://dx.doi.org/10.1002/ehf2.13517DOI Listing
September 2021

SARS-CoV-2 infection in pregnancy in Denmark-characteristics and outcomes after confirmed infection in pregnancy: A nationwide, prospective, population-based cohort study.

Acta Obstet Gynecol Scand 2021 Aug 31. Epub 2021 Aug 31.

Department of Obstetrics and Gynecology, The North Denmark Regional Hospital Thisted, Thisted, Denmark.

Introduction: Assessing the risk factors for and consequences of infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) during pregnancy is essential to guide clinical care. Previous studies on SARS-CoV-2 infection in pregnancy have been among hospitalized patients, which may have exaggerated risk estimates of severe outcomes because all cases of SARS-CoV-2 infection in the pregnant population were not included. The objectives of this study were to identify risk factors for and outcomes after SARS-CoV-2 infection in pregnancy independent of severity of infection in a universally tested population, and to identify risk factors for and outcomes after severe infection requiring hospital admission.

Material And Methods: This was a prospective population-based cohort study in Denmark using data from the Danish National Patient Register and Danish Microbiology Database and prospectively registered data from medical records. We included all pregnancies between March 1 and October 31, 2020 and compared women with a positive SARS-CoV-2 test during pregnancy to non-infected pregnant women. Cases of SARS-CoV-2 infection in pregnancy were both identified prospectively and through register linkage to ensure that all cases were identified and that cases were pregnant during infection. Main outcome measures were pregnancy, delivery, maternal, and neonatal outcomes. Severe infection was defined as hospital admission due to coronavirus disease 2019 (COVID-19) symptoms.

Results: Among 82 682 pregnancies, 418 women had SARS-CoV-2 infection during pregnancy, corresponding to an incidence of 5.1 per 1000 pregnancies, 23 (5.5%) of which required hospital admission due to COVID-19. Risk factors for infection were asthma (odds ratio [OR] 2.19, 95% CI 1.41-3.41) and being foreign born (OR 2.12, 95% CI 1.70-2.64). Risk factors for hospital admission due to COVID-19 included obesity (OR 2.74, 95% CI 1.00-7.51), smoking (OR 4.69, 95% CI 1.58-13.90), infection after gestational age (GA) 22 weeks (GA 22-27 weeks: OR 3.77, 95% CI 1.16-12.29; GA 28-36 weeks: OR 4.76, 95% CI 1.60-14.12), and having asthma (OR 4.53, 95% CI 1.39-14.79). We found no difference in any obstetrical or neonatal outcomes.

Conclusions: Only 1 in 20 women with SARS-CoV-2 infection during pregnancy required admission to hospital due to COVID-19. Risk factors for admission comprised obesity, smoking, asthma, and infection after GA 22 weeks. Severe adverse outcomes of SARS-CoV-2 infection in pregnancy were rare.
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http://dx.doi.org/10.1111/aogs.14252DOI Listing
August 2021

Importance of smoking cessation for cardiovascular risk reduction.

Eur Heart J 2021 Aug 28. Epub 2021 Aug 28.

Section of Cardiovascular Medicine, Department of Medicine, Boston Medical Center, Boston University School of Medicine, Boston, MA, USA.

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http://dx.doi.org/10.1093/eurheartj/ehab541DOI Listing
August 2021

Insulin resistance genetic risk score and burden of coronary artery disease in patients referred for coronary angiography.

PLoS One 2021 18;16(6):e0252855. Epub 2021 Jun 18.

Department of Cardiology, Bispebjerg and Frederiksberg Hospital, Copenhagen, Denmark.

Aims: Insulin resistance associates with development of metabolic syndrome and risk of cardiovascular disease. The link between insulin resistance and cardiovascular disease is complex and multifactorial. Confirming the genetic link between insulin resistance, type 2 diabetes, and coronary artery disease, as well as the extent of coronary artery disease, is important and may provide better risk stratification for patients at risk. We investigated whether a genetic risk score of 53 single nucleotide polymorphisms known to be associated with insulin resistance phenotypes was associated with diabetes and burden of coronary artery disease.

Methods And Results: We genotyped patients with a coronary angiography performed in the capital region of Denmark from 2010-2014 and constructed a genetic risk score of the 53 single nucleotide polymorphisms. Logistic regression using quartiles of the genetic risk score was performed to determine associations with diabetes and coronary artery disease. Associations with the extent of coronary artery disease, defined as one-, two- or three-vessel coronary artery disease, was determined by multinomial logistic regression. We identified 4,963 patients, of which 17% had diabetes and 55% had significant coronary artery disease. Of the latter, 27%, 14% and 14% had one, two or three-vessel coronary artery disease, respectively. No significant increased risk of diabetes was identified comparing the highest genetic risk score quartile with the lowest. An increased risk of coronary artery disease was found for patients with the highest genetic risk score quartile in both unadjusted and adjusted analyses, OR 1.21 (95% CI: 1.03, 1.42, p = 0.02) and 1.25 (95% CI 1.06, 1.48, p<0.01), respectively. In the adjusted multinomial logistic regression, patients in the highest genetic risk score quartile were more likely to develop three-vessel coronary artery disease compared with patients in the lowest genetic risk score quartile, OR 1.41 (95% CI: 1.10, 1.82, p<0.01).

Conclusions: Among patients referred for coronary angiography, only a strong genetic predisposition to insulin resistance was associated with risk of coronary artery disease and with a greater disease burden.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0252855PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8213191PMC
June 2021

Framingham Heart Study: JACC Focus Seminar, 1/8.

J Am Coll Cardiol 2021 Jun;77(21):2680-2692

National Heart, Lung, and Blood Institute and Boston University's Framingham Heart Study, Framingham, Massachusetts, USA; Section of Preventive Medicine and Epidemiology and Cardiovascular Medicine, Departments of Medicine and Epidemiology, Boston University Schools of Medicine and Public Health, Boston, Massachusetts, USA. Electronic address:

The Framingham Heart Study is the longest-running cardiovascular epidemiological study, starting in 1948. This paper gives an overview of the various cohorts, collected data, and most important research findings to date. In brief, the Framingham Heart Study, funded by the National Institutes of Health and managed by Boston University, spans 3 generations of well phenotyped White persons and 2 cohorts comprised of racial and ethnic minority groups. These cohorts are densely phenotyped, with extensive longitudinal follow-up, and they continue to provide us with important information on human cardiovascular and noncardiovascular physiology over the lifespan, as well as to identify major risk factors for cardiovascular disease. This paper also summarizes some of the more recent progress in molecular epidemiology and discusses the future of the study.
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http://dx.doi.org/10.1016/j.jacc.2021.01.059DOI Listing
June 2021

Sex-Specific Prevalence, Incidence, and Mortality Associated With Atrial Fibrillation in Heart Failure.

JACC Clin Electrophysiol 2021 Apr 22. Epub 2021 Apr 22.

Department of Medicine, Section of Cardiovascular medicine, Boston Medical Center, Boston University School of Medicine, Boston, Massachusetts, USA; Department of Cardiology, Copenhagen University Hospital Herlev and Gentofte, Gentofte, Denmark. Electronic address:

Objectives: This study sought to investigate the mortality associated with atrial fibrillation (AF) in men and women with heart failure (HF) according to the sequence of presentation and rhythm versus rate control.

Background: The sex-specific epidemiology of AF in HF is sparse.

Methods: Using the Danish nationwide registries, all first-time cases of HF were identified and followed for all-cause mortality from 1998 to 2018.

Results: Among 252,988 patients with HF (mean age: 74 ± 13 years, 45% women), AF presented before HF in 54,064 (21%) and on the same day in 27,651 (11%) individuals, similar in women and men. Among patients without AF, the cumulative 10-year incidence of AF was 18.7% (95% confidence interval [CI]: 18.2% to 19.1%) in women and 21.3% (95% CI: 21.0% to 21.6%) in men. On follow-up (mean: 6.2 ± 5.8 years), adjusted mortality rate ratios were 3.33 (95% CI: 3.25 to 3.41) in women and 2.84 (95% CI: 2.78 to 2.90) in men if AF antedated HF, 3.45 (95% CI: 3.37 to 3.56) in women versus 2.76 (95% CI: 2.69 to 2.83) in men when AF and HF were diagnosed concomitantly, and 4.85 (95% CI: 4.73 to 4.97) in women versus 3.89 (95% CI: 3.80 to 3.98) in men when AF developed after HF. Compared with rate control for AF, a rhythm-controlling strategy was associated with lowered mortality in inverse probability-weighted models across all strata and in both sexes (hazard ratios: 0.75 to 0.83), except for women who developed AF after HF onset (hazard ratio: 1.03).

Conclusions: More than half of all men and women with HF will develop AF during their clinical course, with prognosis associated with AF being worse in women than men. Further studies are needed to understand the underlying mechanisms.
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http://dx.doi.org/10.1016/j.jacep.2021.02.021DOI Listing
April 2021

All-cause mortality and location of death in patients with established cardiovascular disease before, during, and after the COVID-19 lockdown: a Danish Nationwide Cohort Study.

Eur Heart J 2021 Apr;42(15):1516-1523

Department of Cardiology, Herlev-Gentofte University Hospital, Herlev, Denmark.

Background: On 13 March 2020, the Danish authorities imposed extensive nationwide lockdown measures to prevent the spread of the coronavirus disease 2019 (COVID-19) and reallocated limited healthcare resources. We investigated mortality rates, overall and according to location, in patients with established cardiovascular disease before, during, and after these lockdown measures.

Methods And Results: Using Danish nationwide registries, we identified a dynamic cohort comprising all Danish citizens with cardiovascular disease (i.e. a history of ischaemic heart disease, ischaemic stroke, heart failure, atrial fibrillation, or peripheral artery disease) alive on 2 January 2019 and 2020. The cohort was followed from 2 January 2019/2020 until death or 16/15 October 2019/2020. The cohort comprised 340 392 and 347 136 patients with cardiovascular disease in 2019 and 2020, respectively. The overall, in-hospital, and out-of-hospital mortality rate in 2020 before lockdown was significantly lower compared with the same period in 2019 [adjusted incidence rate ratio (IRR) 0.91, 95% confidence interval (CI) CI 0.87-0.95; IRR 0.95, 95% CI 0.89-1.02; and IRR 0.87, 95% CI 0.83-0.93, respectively]. The overall mortality rate during and after lockdown was not significantly different compared with the same period in 2019 (IRR 0.99, 95% CI 0.97-1.02). However, the in-hospital mortality rate was lower and out-of-hospital mortality rate higher during and after lockdown compared with the same period in 2019 (in-hospital, IRR 0.92, 95% CI 0.88-0.96; out-of-hospital, IRR 1.04, 95% CI1.01-1.08). These trends were consistent irrespective of sex and age.

Conclusions: Among patients with established cardiovascular disease, the in-hospital mortality rate was lower and out-of-hospital mortality rate higher during lockdown compared with the same period in the preceding year, irrespective of age and sex.
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http://dx.doi.org/10.1093/eurheartj/ehab028DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7928991PMC
April 2021

Association of soluble urokinase plasminogen activator receptor levels with fibrotic and vascular manifestations in systemic sclerosis.

PLoS One 2021 22;16(2):e0247256. Epub 2021 Feb 22.

Copenhagen Lupus and Vasculitis Clinic, Centre for Rheumatology and Spine Disease, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark.

Objective: We assessed the association of suPAR (soluble urokinase plasminogen activator receptor) plasma levels with fibrotic and vascular manifestations in patients with systemic sclerosis (SSc).

Methods: suPAR plasma levels were measured in 121 consecutive patients with SSc and correlated to pulmonary and vascular features of SSc, including interstitial lung disease as characterized by percentage of predicted CO diffusing capacity (DLco) and forced vital capacity (FVC), pulmonary fibrosis by computed tomography, and pulmonary arterial hypertension, telangiectasias, and digital ulcers.

Results: Overall, 121 SSc patients (84% females; mean age, 57 ± 12 [range: 22-79] years) were enrolled; 35% had diffuse cutaneous SSc. suPAR plasma levels ranged from 1.3-10.2 [median: 2.9 (p25-p75: 2.3-3.9)] ng/mL. Log(suPAR) levels correlated with DLco (r = -0.41, p <0.0001) and FVC (r = -0.26, p = 0.004), also when adjusted for age, sex, and pulmonary hypertension. A suPAR cut-off level of >2.5 ng/mL showed a sensitivity of 91% for identifying patients with either DLco <50% or FVC < 60% of the predicted values. Similarly, 19 (90%) had a suPAR >2.5 ng/mL among those diagnosed with pulmonary fibrosis vs. 59 (60%) among those who did not (p = 0.008). suPAR values were not associated with vascular manifestations.

Conclusion: suPAR levels strongly correlated with pulmonary involvement in SSc. Future studies should test if suPAR estimation can be used for surveillance of severe pulmonary involvement in SSc.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0247256PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7899346PMC
August 2021

Risk of major cardiovascular events according to educational level before and after the initial COVID-19 public lockdown: a nationwide study.

J Epidemiol Community Health 2021 09 4;75(9):829-835. Epub 2021 Feb 4.

Department of Cardiology, Herlev and Gentofte University Hospital, Copenhagen, Denmark.

Background: During the COVID-19 pandemic, decreasing rates of hospitalisations for cardiovascular disease raised concerns for undertreatment, particularly for vulnerable groups. We investigated how the initial COVID-19 public lockdown, impacted the risk of being hospitalised with a major cardiovascular event (MCE: myocardial infarction/stroke/heart failure) according to educational level.

Methods: We grouped all Danish residents according to educational attainment level (low, medium, high) and age (40-59, 60-69, ≥70 years). In each group, we calculated the age-standardised and sex standardised risk of MCE hospitalisation in the initial COVID-19 lockdown-period (13 March 2020-3 May 2020) and in the corresponding calendar period in 2019. We calculated age-standardised and sex-standardised risks to investigate whether the COVID-19 lockdown had a differential effect on MCE incidence according to educational level.

Results: In the period in 2019, 2700 Danish residents were hospitalised with MCE, compared with only 2290 during the lockdown. During lockdown, the risk of hospitalisation for MCE decreased among residents aged ≥70 with low education (risk difference (RD) -46.2 (-73.2; -19.2) per 100,000) or medium education (RD -23.2 (-50.8; 4.3) per 100 000), but not among residents with high education (RD 5.1 (-32.3; 42.5), per 100 000). The risk of hospitalisation for MCE did not decrease significantly for the younger age groups.

Conclusions: The COVID-19 lockdown is associated with a reduced incidence for MCE, especially among low educated, elderly residents. This raises concern for undertreatment that without clinical awareness and action may widen the educational gap in cardiovascular morbidity and mortality.
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http://dx.doi.org/10.1136/jech-2020-215133DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7868126PMC
September 2021

Metabolomic Profiles and Heart Failure Risk in Black Adults: Insights From the Jackson Heart Study.

Circ Heart Fail 2021 01 19;14(1):e007275. Epub 2021 Jan 19.

Division of Cardiovascular Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA (U.A.T., D.H.K., T.Z., D.N., D.E.C., J.M.R., Z.-Z.C., B.P., M.D.B., X.S., C.S., J.G.W., R.E.G.).

Background: Heart failure (HF) is a heterogeneous disease characterized by significant metabolic disturbances; however, the breadth of metabolic dysfunction before the onset of overt disease is not well understood. The purpose of this study was to determine the association of circulating metabolites with incident HF to uncover novel metabolic pathways to disease.

Methods: We performed targeted plasma metabolomic profiling in a deeply phenotyped group of Black adults from the JHS (Jackson Heart Study; n=2199). We related metabolites associated with incident HF to established etiological mechanisms, including increased left ventricular mass index and incident coronary heart disease. Furthermore, we evaluated differential associations of metabolites with HF with preserved ejection fraction versus HF with reduced ejection fraction.

Results: Metabolites associated with incident HF included products of posttranscriptional modifications of RNA, as well as polyamine and nitric oxide metabolism. A subset of metabolite-HF associations was independent of well-established HF pathways such as increased left ventricular mass index and incident coronary heart disease and included homoarginine (per 1 SD increase in metabolite level, hazard ratio, 0.77; =1.2×10), diacetylspermine (hazard ratio, 1.34; =3.4×10), and uridine (hazard ratio, 0.79; , 3×10). Furthermore, metabolites involved in pyrimidine metabolism (orotic acid) and collagen turnover (-methylproline) among others were part of a distinct metabolic signature that differentiated individuals with HF with preserved ejection fraction versus HF with reduced ejection fraction.

Conclusions: The integration of clinical phenotyping with plasma metabolomic profiling uncovered novel metabolic processes in nontraditional disease pathways underlying the heterogeneity of HF development in Black adults.
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http://dx.doi.org/10.1161/CIRCHEARTFAILURE.120.007275DOI Listing
January 2021

The risk of cardiac events in patients receiving immune checkpoint inhibitors: a nationwide Danish study.

Eur Heart J 2021 04;42(16):1621-1631

Department of Cardiology, Copenhagen University Hospital Herlev-Gentofte, Forskning 1, 2900 Hellerup, Denmark.

Aims: The study aimed to estimate the risk of cardiac events in immune checkpoint inhibitor (ICI)-treated patients with lung cancer or malignant melanoma.

Methods And Results: The study included consecutive patients with lung cancer or malignant melanoma in 2011-17 nationwide in Denmark. The main composite outcome was cardiac events (arrhythmia, peri- or myocarditis, heart failure) or cardiovascular death. Absolute risks were estimated and the association of ICI and cardiac events was analysed in multivariable Cox models. We included 25 573 patients with lung cancer. Of these, 743 were treated with programmed cell death-1 inhibitor (PD1i) and their 1-year absolute risk of cardiac events was 9.7% [95% confidence interval (CI) 6.8-12.5]. Of the 13 568 patients with malignant melanoma, 145 had PD1i and 212 had cytotoxic T-lymphocyte-associated protein-4 inhibitor (CTLA-4i) treatment. Their 1-year risks were 6.6% (1.8-11.3) and 7.5% (3.7-11.3). The hazard rates of cardiac events were higher in patients with vs. without ICI treatment. Within 6 months from 1st ICI administration, the hazard ratios were 2.14 (95% CI 1.50-3.05) in patients with lung cancer and 4.30 (1.38-13.42) and 4.93 (2.45-9.94) in patients with malignant melanoma with PD1i and CTLA-4i, respectively. After 6 months, HRs were 2.26 (1.27-4.02) for patients with lung cancer and 3.48 (1.91-6.35) for patients with malignant melanoma and CTLA-4i.

Conclusions: Among patients with lung cancer and malignant melanoma, ICI treated had increased rates of cardiac events. The absolute risks were higher in these data compared with previous pharmacovigilance studies (e.g. 1.8% peri-/myocarditis 1-year risk).
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http://dx.doi.org/10.1093/eurheartj/ehaa884DOI Listing
April 2021

Prevalence and incidence of various cancer subtypes in patients with heart failure vs matched controls.

Int J Cardiol 2021 03 2;326:144. Epub 2020 Nov 2.

Department of Cardiology, Herlev and Gentofte Hospital, Copenhagen University, Herlev, Denmark; Department of Medicine, Section of Cardiovascular Medicine, Boston Medical Center, Boston University School of Medicine, Boston, MA, USA.

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http://dx.doi.org/10.1016/j.ijcard.2020.10.072DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8283746PMC
March 2021

Cardiovascular comorbidities as predictors for severe COVID-19 infection or death.

Eur Heart J Qual Care Clin Outcomes 2021 03;7(2):172-180

The Danish Heart Foundation, Copenhagen, Denmark.

Aims: Pre-existing cardiovascular diseases (CVDs) have been proposed to identify patients at higher risk of adverse coronavirus disease 2019 (COVID-19) outcomes, but existing evidence is conflicting. Thus, it is unclear whether pre-existing CVDs are independently important predictors for severe COVID-19.

Methods And Results: In a nationwide Danish cohort of hospital-screened COVID-19 patients aged ≥40, we investigated if pre-existing CVDs predict the 30-day risk of (i) composite outcome of severe COVID-19 and (ii) all-cause mortality. We estimated 30-day risks using a Cox regression model including age, sex, each CVD comorbidity, chronic obstructive pulmonary disease-asthma, diabetes, and chronic kidney disease. To illustrate CVD comorbidities' importance, we evaluated the predicted risks of death and severe infection, for each sex, along ages 40-85. In total, 4090 COVID-19 hospital-screened patients were observed as of 26 August 2020; 22.1% had ≥1 CVD, 23.7% had severe infection within 30 days and 12.6% died. Predicted risks of both outcomes at age 75 among men with single CVD comorbidities did not differ in clinically meaningful amounts compared with men with no comorbidities risks for the composite outcome of severe infection; women with heart failure (28.2%; 95% CI 21.1-37.0%) or atrial fibrillation (30.0%; 95% CI: 24.2-36.9%) showed modest increases compared with women with no comorbidities (24.0%; 95% CI: 21.4-26.9%).

Conclusions: The results showing only modest effects of CVDs on increased risks of poor COVID-19 outcomes are important in allowing public health authorities and clinicians to provide more tailored guidance to cardiovascular patients, who have heretofore been grouped together as high risk due to their disease status.
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http://dx.doi.org/10.1093/ehjqcco/qcaa081DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7665490PMC
March 2021

Biodistribution of I in mice is influenced by circadian variations.

Sci Rep 2020 09 23;10(1):15541. Epub 2020 Sep 23.

Department of Radiation Physics, Inst of Clinical Sciences, Sahlgrenska Cancer Center, Sahlgrenska Academy at the University of Gothenburg, Sahlgrenska University Hospital, SE 413 45, Gothenburg, Sweden.

Effects of radiation and biodistribution of radionuclides are often studied in animal models. Circadian rhythm affects many biological functions and may influence the biokinetics of radionuclides and observed responses. The aim of this study was to investigate if the time during the day of I injection affects the biodistribution and absorbed dose to tissues in mice. Biodistribution studies were conducted on male C57BL/6 N mice for three diurnal time-series: the animals were i.v. injected with 160 kBq I at 8 am, 12 pm or 4 pm. The activity concentration in organs and tissues was measured at 1 h to 7 days after administration and absorbed dose at day 7 was determined. Comparison between the three time-series showed statistically significant differences in activity concentration in all investigated tissues and organs. Administration performed at 12 pm resulted in general in higher absorbed dose to the organs than injection performed at 8 am and 4 pm. Time of day of administration affects the biodistribution of I in mice and consequently the absorbed dose to individual organs. These findings advocate that subsequent biodistribution studies and dosimetry calculations should consider time-point of administration as a variable that could influence the results.
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http://dx.doi.org/10.1038/s41598-020-72180-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7511401PMC
September 2020

Metabolomic signatures of cardiac remodelling and heart failure risk in the community.

ESC Heart Fail 2020 Sep 10. Epub 2020 Sep 10.

NHBLI and Boston University's Framingham Heart Study, Framingham, MA, USA.

Aims: Heart failure (HF) is associated with several metabolic changes, but it is unknown whether distinct components of the circulating metabolome may be related to cardiac structure and function, and with incident HF in the community.

Methods And Results: We assayed 217 circulating metabolites in 2336 Framingham Study participants (mean age 55 ± 10 years, 53% women) without HF at baseline. We used linear and Cox regression to relate concentrations of metabolites to left ventricular (LV) diastolic dimension, LV wall thickness, LV ejection fraction, left atrial dimension, LV ventricular mass, and aortic root size cross-sectionally and to incident HF prospectively. Bonferroni-adjusted P-values <0.05 denoted statistical significance. Circulating concentrations of kynurenine [β = -0.12 cm per standard deviation (SD) increment in normalized residual of metabolite, P = 7.3 × 10 ] and aminoadipate (-0.11 cm per SD increment, P = 2.61 × 10 ) were associated with left ventricular diastolic dimension, phosphatidylcholine (carbon:double bound = 38:6) with left atrial dimension (0.10 cm per SD increment, P = 9.7 × 10 ), and cholesterol ester (carbon:double bound = 20:5) with left atrial dimension (0.10 cm per SD increment, P = 1.4 × 10 ) in multivariable-adjusted models. During an average follow-up of 15.8 (range 0.02-23.2) years, 113 participants (5%) were diagnosed with HF with reduced ejection fraction and 106 individuals (5%) with HF with preserved ejection fraction. In multivariable analyses, concentrations of phosphatidylcholine (hazard ratio 0.63, P = 1.3 × 10 ) and ornithine (hazard ratio 1.44, P = 0.00014) were associated with HF with reduced ejection fraction.

Conclusions: Several metabolites, including the vasoactive metabolite kynurenine, were related to cardiac structure and function in our sample. Additional research is warranted to confirm our observations and investigate if these metabolites can risk stratify ambulatory individuals.
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http://dx.doi.org/10.1002/ehf2.12923DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7754777PMC
September 2020

Time trends in incidence, comorbidity, and mortality of ischemic stroke in Denmark (1996-2016).

Neurology 2020 10 14;95(17):e2343-e2353. Epub 2020 Aug 14.

From the Department of Cardiology (A.Y., E.L.F., M.N.C., N.E.V., L.K., J.H.B.), Rigshospitalet, Copenhagen University Hospital; Departments of Cardiology (C.A., G.H.G.) and Neurology (C.K.), Herlev and Gentofte University Hospital, Hellerup, Denmark; Department of Medicine (C.A.), Section of Cardiovascular Medicine, Boston Medical Center, Boston University School of Medicine, MA; Institute of Clinical Medicine (C.K.), University of Copenhagen; Danish Center for Clinical Health Services Research (S.P.J.), Department of Clinical Medicine, Aalborg University; The Danish Heart Foundation (G.H.G.), Copenhagen; National Institute of Public Health (G.H.G.), University of Southern Denmark, Odense; Department of Cardiology (C.T.-P.), Nordsjællands Hospital, Hillerød; and Department of Cardiology (C.T.-P.), Aalborg University Hospital, Denmark.

Objective: To examine whether the incidence, comorbidity, and mortality of first-time ischemic stroke changed in Denmark between 1996 and 2016 overall and according to age and sex using a nationwide cohort design.

Methods: In this cohort study, 224,617 individuals ≥18 years of age admitted with first-time ischemic stroke between 1996 and 2016 were identified through Danish nationwide registries. We calculated annual age-standardized incidence rates and absolute 30-day and 1-year mortality risks. Furthermore, we calculated annual incidence rate ratios using Poisson regression, odds ratios for 30-day mortality using logistic regression, and hazard ratios for 1-year mortality using Cox regression.

Results: The overall age-standardized incidence rates of ischemic stroke per 1,000 person-years increased from 1996 (2.70 [95% confidence interval [CI] 2.65-2.76]) to 2002 (3.25 [95% CI 3.20-3.31]) and then gradually decreased to below the initial level until 2016 (1.99 [95% CI 1.95-2.02]). Men had higher incidence rates than women in all age groups except 18 to 34 and ≥85 years. Absolute mortality risk decreased between 1996 and 2016 (30-day mortality from 17.1% to 7.6% and 1-year mortality from 30.9% to 17.3%). Women between 55 and 64 and ≥85 years of age had higher mortality than men. Similar trends were observed for all analyses after multivariable adjustment. The prevalence of atrial fibrillation, hypertension, diabetes mellitus, and use of lipid-lowering medication increased during the study period.

Conclusions: The age-standardized incidence of first-time hospitalization for ischemic stroke increased from 1996 to 2002 and then gradually decreased to below the initial level until 2016. Absolute 30-day and 1-year mortality risks decreased between 1996 and 2016. These findings correspond to increased stroke prevention awareness and introduction of new treatments during the study period.
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http://dx.doi.org/10.1212/WNL.0000000000010647DOI Listing
October 2020

One-Year Mortality After Intensification of Outpatient Diuretic Therapy.

J Am Heart Assoc 2020 07 14;9(14):e016010. Epub 2020 Jul 14.

Department of Cardiology Herlev and Gentofte University Hospital Copenhagen Denmark.

Background Mortality is increased following a hospitalization for decompensated heart failure (HF), during which diuretics are usually intensified. It is unclear how risk is affected after outpatient intensification of diuretic therapy for HF. Methods and Results From nationwide administrative registers, we identified all Danish patients who were diagnosed with HF from 2001 to 2016 and received angiotensin-converting enzyme inhibitor/angiotensin receptor blocker and β blocker within 120 days. Subsequent follow-up tracked progressive events of diuretic intensification and HF hospitalization. Intensification events were defined as new addition or doubling of loop diuretic or addition of thiazide to loop diuretic. These events were included in multivariable Cox regression models, calculating 1-year mortality hazard after each year since inclusion. Patients with an intensification event or hospitalization were risk set matched to 2 nonworsened HF controls and absolute 1-year mortality risks were calculated using Kaplan-Meier estimates. We included 74 990 patients, their median age was 71 years, and 36% were women. Intensification events were associated with significantly increased mortality at all times during follow-up. One-year mortality was 18.0% after an intensification event, 22.6% after HF hospitalization, and 10.4% for matched controls with neither. In a multivariable Cox model adjusted for age, sex, ischemic heart disease, atrial fibrillation, chronic obstructive pulmonary disease, and diabetes mellitus, the hazard ratio for 1-year death after an intensification event was 1.75 (95% CI, 1.66-1.85), and it was 2.28 (95% CI, 2.16-2.41) after HF hospitalization. Conclusions In a nationwide cohort of patients with HF, outpatient intensification events were associated with almost 2-fold risk of mortality during the next year. Although HF hospitalization was associated with a higher risk, the need to intensify diuretics in the outpatient setting is a signal to review and intensify efforts to improve HF outcomes.
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http://dx.doi.org/10.1161/JAHA.119.016010DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7660734PMC
July 2020

Long-term risk of heart failure and mortality following mitral valve surgery in patients with and without right ventricular pacemaker.

J Card Surg 2020 Oct 11;35(10):2598-2604. Epub 2020 Jul 11.

Department of Medicine, Section of Cardiovascular Medicine, Boston Medical Center, Boston University School of Medicine, Boston, Massachusetts.

Objectives: Patients undergoing mitral valve surgery are at risk of developing postoperative conduction blocks and have a high incidence of heart failure (HF). Mitral valve surgery often results in reduced left ventricular systolic ejection fraction following surgery and the imposition of dyssynchrony with right ventricular (RV) pacing may further compromise stroke volume. Our aim was to investigate the risks of HF and mortality in patients with vs without RV pacemaker placement (PPM) after mitral valve surgery.

Methods: Using Danish nationwide databases, we identified all patients undergoing mitral valve repair or replacement surgery between 1997 and 2017, who were free from HF at baseline. The association of PPM implanted within 30 days following surgery with long-term risks of HF and mortality was investigated by multivariable Cox regression models.

Results: Of 4072 patients (33% female), 248 (6%) had a PPM implanted at 30-day postsurgery. Patients with PPM were older (68 vs 63 years), had a higher prevalence of concomitant aortic valve surgery (15% vs 11%), ischemic heart disease (13% vs 8%), and atrial fibrillation (19% vs 12%), compared with patients without PPM. Over a median follow-up of 5 years, 68 (27%) vs 825 (22%) patients with vs without PPM developed HF and 74 (30%) vs 1018 (27%) died. In multivariable-adjusted models, the hazard ratios associated with PPM were 1.00 (0.78-1.30), P = .93 for HF, and .96 (0.76-1.21), P = .72 for mortality.

Conclusions: Postoperative implantation of a permanent RV pacemaker does not alter the long-term risks of HF and mortality following mitral valve surgery.
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http://dx.doi.org/10.1111/jocs.14847DOI Listing
October 2020

Association between male sex and outcomes of Coronavirus Disease 2019 (Covid-19) - a Danish nationwide, register-based study.

Clin Infect Dis 2020 Jul 8. Epub 2020 Jul 8.

Department of Cardiology, Rigshospitalet, Copenhagen, Denmark.

Background And Objectives: Male sex has been associated with severe Coronavirus disease 2019 (Covid-19) infection. We examined the association between male sex and severe Covid-19 infection and if an increased risk remains after adjustment for age and comorbidities.

Methods: Nationwide register-based follow-up study of Covid-19 patients in Denmark until May 16, 2020. Average risk ratio comparing 30-day composite outcome of all-cause death, severe Covid-19 diagnosis or intensive care unit (ICU) admission for men versus women standardized to the age and comorbidity distribution of all patients were derived from multivariable Cox regression. Included covariates were age, hypertension, diagnoses including obesity, alcohol, sleep apnea, diabetes, chronic obstructive pulmonary disease, previous myocardial infarction (MI), ischemic heart disease (IHD), heart failure (HF), atrial fibrillation (AF), stroke, peripheral artery disease, cancer, liver-, rheumatic-, and chronic kidney disease (CKD).

Results: Of 4,842 Covid-19 patients, 2,281 (47.1%) were men. Median age was 57 [25%-75% 43-73] for men versus 52 [38-71] for women (P<0.001); however, octogenarians had equal sex distribution. Alcohol diagnosis, diabetes, hypertension, sleep apnea, prior MI and IHD (all P<0.001) as well as AF, stroke and HF (all P=0.01) were more often seen in men, and so was CKD (P=0.03). Obesity diagnosis (P<0.001) were more often seen in women. Other comorbidity differences were insignificant (P>0.05). The fully adjusted average risk ratio was 1.63 [95% CI 1.44-1.84].

Conclusions: Men with Covid-19 infection have >50% higher risk of all-cause death, severe Covid-19 infection, or ICU admission than women. The excess risk was not explained by age and comorbidities.
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http://dx.doi.org/10.1093/cid/ciaa924DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7454435PMC
July 2020

Identification of Patients with New-Onset Heart Failure and Reduced Ejection Fraction in Danish Administrative Registers.

Clin Epidemiol 2020 8;12:589-594. Epub 2020 Jun 8.

Department of Cardiology, Herlev and Gentofte University Hospital, Copenhagen, Denmark.

Background: In Danish administrative registers, ejection fraction (EF) is not recorded, which is a considerable limitation for correct subclassification of patients with heart failure (HF). We hypothesized that a diagnosis of HF combined with the recorded prescription of both renin-angiotensin system (RAS) inhibitors and beta- blockers () within 120 days could identify patients with HF and reduced ejection fraction (EF ≤40%) (HFrEF).

Methods: On two sites, we identified all patients with a first-time registration of HF as primary hospital discharge diagnosis (ICD-10: I50) between June 1, 2016, and May 31, 2018 in inpatient or outpatient settings. Patients were included if they survived the initial 120 days after discharge. Reviewing patient records, we identified patients with HFrEF, based on EF ≤ 40% and reported HF symptoms. We registered the use of at 120 days and calculated sensitivity, specificity and predictive values.

Results: A total of 704 consecutive patients with a primary diagnosis of HF were included, of whom 541 (77%) fulfilled the HFrEF criteria. Patients with HFrEF confirmed from patient records were younger (median age 73 compared to 79 years) and less frequently women (31% compared to 56%) compared to non-HFrEF patients. At baseline, 24 (4%) of HFrEF patients were treated with compared to 22 (14%) of non-HFrEF patients. At 120 days, 460 (85%) of HFrEF patients received as compared to 25 (15%) of non-HFrEF patients. This resulted in a positive predictive value of 95%, sensitivity of 85% and specificity of 85%.

Conclusion: In Denmark, the ICD-10 HF diagnosis combined with recorded treatment by 120 days after discharge has high positive predictive value and can accurately be used to identify patients with HFrEF.
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http://dx.doi.org/10.2147/CLEP.S251710DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7292248PMC
June 2020

Familial Clustering of Aortic Size, Aneurysms, and Dissections in the Community.

Circulation 2020 09 25;142(10):920-928. Epub 2020 Jun 25.

Department of Medicine, Section of Cardiovascular Medicine (R.S.V., C.A.), Boston University Schools of Public Health and Medicine, MA.

Background: Ruptured aortic aneurysm and aortic dissections are potentially preventable disorders associated with high mortality. Screening of individuals at risk may translate into elective surgical interventions and lowered mortality. It is uncertain if the risk of aortic dilation of varying degrees aggregates within families.

Methods: We investigated the risk of having thoracic and abdominal aortic sizes in the highest quartile (measured by computed tomography scans and indexed for body size) if at least 1 parent did so in the Framingham Heart Study cohorts, and estimated the incidence rates and hazard ratios of developing aortic aneurysm or dissection among first-degree relatives of those with aortic aneurysm or dissection, in comparison with age- and sex-matched controls (1:10 for aortic aneurysm and 1:100 for aortic dissection) using the Danish nationwide administrative registries.

Results: In the Framingham Heart Study, offspring (n=235) whose parent(s) had a sex- and age-standardized aortic size in the upper quartile had a multivariable-adjusted ≈3-fold increased odds ratio of belonging to the upper quartile themselves. In Denmark, a total of 68 939 individuals (mean age, 42 years) had a first-degree relative with aortic aneurysm and 7209 persons (mean age, 39 years) had a first-degree relative with aortic dissection. During an average follow-up of 7 years, first-degree relatives of patients with aortic aneurysm and dissection had a hazard ratio of 6.70 (95% CI, 5.96-7.52) for developing aortic aneurysm and a hazard ratio of 9.24 (95% CI, 5.53-15.44) for dissection in comparison with matched controls. These estimates remained unchanged on adjusting for several comorbidities, including prevalent hypertension, bicuspid aortic valve, and the Marfan syndrome. For both aortic aneurysm and dissections, the absolute event rates approached 1 per 1000 person-years for first-degree relatives versus 11 to 13 (aortic aneurysm) and 2 to 3 (aortic dissections) per 100 000 person-years among controls.

Conclusions: Increased aortic size, a precursor of aortic aneurysm and a risk factor for dissection, clusters in families. The incidence rates of aortic aneurysm and dissections approach the incidence rates of other common cardiovascular conditions in first-degree relatives, supporting the use of systematic screening for these conditions.
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http://dx.doi.org/10.1161/CIRCULATIONAHA.120.045990DOI Listing
September 2020

New-onset atrial fibrillation: incidence, characteristics, and related events following a national COVID-19 lockdown of 5.6 million people.

Eur Heart J 2020 06;41(32):3072-3079

Department of Cardiology, Herlev and Gentofte University Hospital, Copenhagen, Denmark.

Aim: To determine the incidence, patient characteristics, and related events associated with new-onset atrial fibrillation (AF) during a national COVID-19 lockdown.

Methods And Results: Using nationwide Danish registries, we included all patients, aged 18-90 years, receiving a new-onset AF diagnosis during the first 3 months of 2019 and 2020. The main comparison was between patients diagnosed during lockdown (12 March 12-1 April 2020) and patients diagnosed in the corresponding period 1 year previously. We found a lower incidence of new-onset AF during the 3 weeks of lockdown compared with the corresponding weeks in 2019 [incidence rate ratios with 95% confidence intervals (CIs) for the 3 weeks: 0.66 (0.56-0.78), 0.53 (0.45-0.64), and 0.41 (0.34-0.50)]. There was a 47% drop in total numbers (562 vs. 1053). Patients diagnosed during lockdown were younger and with a lower CHA2DS2-VASc score, while history of cancer, heart failure, and vascular disease were more prevalent. During lockdown, 30 (5.3%) patients with new-onset AF suffered an ischaemic stroke and 15 (2.7%) died, compared with 45 (4.3%) and 14 (1.3%) patients during the corresponding 2019 period, respectively. The adjusted odds ratio of a related event (ischaemic stroke or all-cause death) during lock-down compared with the corresponding weeks was 1.41 (95% CI 0.93-2.12).

Conclusions: Following a national lockdown in Denmark, a 47% drop in registered new-onset AF cases was observed. In the event of prolonged or subsequent lockdowns, the risk of undiagnosed AF patients developing complications could potentially translate into poorer outcomes in patients with AF during the COVID-19 pandemic.
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http://dx.doi.org/10.1093/eurheartj/ehaa494DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7337750PMC
June 2020

Association of Angiotensin-Converting Enzyme Inhibitor or Angiotensin Receptor Blocker Use With COVID-19 Diagnosis and Mortality.

JAMA 2020 Jul;324(2):168-177

The Heart Center, University Hospital of Copenhagen, Rigshospitalet, Copenhagen, Denmark.

Importance: It has been hypothesized that angiotensin-converting enzyme inhibitors (ACEIs)/angiotensin receptor blockers (ARBs) may make patients more susceptible to coronavirus disease 2019 (COVID-19) and to worse outcomes through upregulation of the functional receptor of the virus, angiotensin-converting enzyme 2.

Objective: To examine whether use of ACEI/ARBs was associated with COVID-19 diagnosis and worse outcomes in patients with COVID-19.

Design, Setting, And Participants: To examine outcomes among patients with COVID-19, a retrospective cohort study using data from Danish national administrative registries was conducted. Patients with COVID-19 from February 22 to May 4, 2020, were identified using ICD-10 codes and followed up from day of diagnosis to outcome or end of study period (May 4, 2020). To examine susceptibility to COVID-19, a Cox regression model with a nested case-control framework was used to examine the association between use of ACEI/ARBs vs other antihypertensive drugs and the incidence rate of a COVID-19 diagnosis in a cohort of patients with hypertension from February 1 to May 4, 2020.

Exposures: ACEI/ARB use was defined as prescription fillings 6 months prior to the index date.

Main Outcomes And Measures: In the retrospective cohort study, the primary outcome was death, and a secondary outcome was a composite outcome of death or severe COVID-19. In the nested case-control susceptibility analysis, the outcome was COVID-19 diagnosis.

Results: In the retrospective cohort study, 4480 patients with COVID-19 were included (median age, 54.7 years [interquartile range, 40.9-72.0]; 47.9% men). There were 895 users (20.0%) of ACEI/ARBs and 3585 nonusers (80.0%). In the ACEI/ARB group, 18.1% died within 30 days vs 7.3% in the nonuser group, but this association was not significant after adjustment for age, sex, and medical history (adjusted hazard ratio [HR], 0.83 [95% CI, 0.67-1.03]). Death or severe COVID-19 occurred in 31.9% of ACEI/ARB users vs 14.2% of nonusers by 30 days (adjusted HR, 1.04 [95% CI, 0.89-1.23]). In the nested case-control analysis of COVID-19 susceptibility, 571 patients with COVID-19 and prior hypertension (median age, 73.9 years; 54.3% men) were compared with 5710 age- and sex-matched controls with prior hypertension but not COVID-19. Among those with COVID-19, 86.5% used ACEI/ARBs vs 85.4% of controls; ACEI/ARB use compared with other antihypertensive drugs was not significantly associated with higher incidence of COVID-19 (adjusted HR, 1.05 [95% CI, 0.80-1.36]).

Conclusions And Relevance: Prior use of ACEI/ARBs was not significantly associated with COVID-19 diagnosis among patients with hypertension or with mortality or severe disease among patients diagnosed as having COVID-19. These findings do not support discontinuation of ACEI/ARB medications that are clinically indicated in the context of the COVID-19 pandemic.
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http://dx.doi.org/10.1001/jama.2020.11301DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7305566PMC
July 2020

Incidence of New-Onset and Worsening Heart Failure Before and After the COVID-19 Epidemic Lockdown in Denmark: A Nationwide Cohort Study.

Circ Heart Fail 2020 06 2;13(6):e007274. Epub 2020 Jun 2.

Department of Cardiology, Herlev and Gentofte Hospital, Denmark (C.A., M.L., A.H., C.M., G.G., M.S.).

Background: The Danish government ordered a public lockdown on March 12, 2020, because of the coronavirus disease 2019 (COVID-19) pandemic. We investigated the immediate consequences of such a lockdown for patients with heart failure (HF).

Methods: Using the Danish nationwide administrative databases, we investigated the incidence of new-onset HF and hospitalizations for worsening HF before and after the lockdown (January 1 to March 11 versus March 12 to March 31) in 2020 versus 2019. We also investigated the mortality for all patients with HF and in COVID-19-infected patients with HF.

Results: Rates of new-onset HF between January 1 and March 11 were comparable for 2020 and 2019 (1.83 versus 1.78 per 10 000 person-years; =0.19), while hospitalizations for worsening HF were slightly higher in 2020 versus 2019 (1.04 versus 0.93 per 1000 person-years; =0.02). In the lockdown period, rates of new-onset HF diagnoses (1.26 versus 2.25 per 1000 person-years) and of hospitalizations for worsening HF (0.63 versus 0.99 per 1000 person-years) were significantly lower in 2020 versus 2019 ( for both, <0.0001). Mortality was similar before and after the national lockdown for the population with HF. We observed 90 HF patients with diagnosed COVID-19 infection, of whom 37% (95% CI, 23%-50%) died within 15 days.

Conclusions: The number of patients hospitalized with worsening HF or diagnosed with new-onset HF was markedly reduced after lockdown but has not yet impacted mortality in HF patients at a population-based level. However, these data raise concerns for a potential undertreatment of HF currently that may impact prognosis in the longer term.
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http://dx.doi.org/10.1161/CIRCHEARTFAILURE.120.007274DOI Listing
June 2020

Prevalence and incidence of various Cancer subtypes in patients with heart failure vs matched controls.

Int J Cardiol 2020 10 22;316:209-213. Epub 2020 May 22.

Department of Cardiology, Herlev and Gentofte Hospital, Copenhagen University, Herlev, Denmark; Department of Medicine, Section of Cardiovascular Medicine, Boston Medical Center, Boston University School of Medicine, Boston, MA, USA.

Background: Patients with heart failure (HF) may be at increased risks of cancer, but the magnitude of risk for various cancer subtypes is insufficiently investigated.

Method: Using the Danish Nationwide administrative databases between 1997 and 2017, we estimated the prevalence, incidence and relative risk for all-cause cancer in new-diagnosed HF vs. age and sex-matched controls (up to 5 controls per HF case) before and after adjustment for comorbidities.

Results: Among the 167,633 people in the heart failure group and 837,126 individuals in the control group, there was a higher prevalence of several comorbidities, including cancer (17% vs. 10%) in the HF group; odds ratio 1.72 (1.70-1.75). Patients with heart failure also had higher cancer incidence (cancer incidence rate 3.02 [2.97-3.07] per 100 person-years), compared with controls (cancer incidence rate 1.89 [1.88-1.90]); hazards ratio 1.38 (1.36-1.40). However, after adjustment for comorbidities the increased risk of malignancy was greatly attenuated (hazards ratio 1.14 [1.12-1.16] for incident all-cause cancer) and dissipated altogether after additional adjustment for medications (multivariable adjusted hazards ratio 0.93 [0.91-0.96] for all-cause cancer). In a homogeneous cohort of patients with ischemic heart disease, the increased risk of all-cause cancer was only marginally increased after adjustment for baseline comorbidities (hazards ratio 1.05 [1.02-1.08]).

Conclusion: Patients with heart failure had a slightly increased risk of various cancer subtypes, but the risks were mainly driven by comorbidities.
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http://dx.doi.org/10.1016/j.ijcard.2020.05.035DOI Listing
October 2020

Age-specific trends in incidence and survival of out-of-hospital cardiac arrest from presumed cardiac cause in Denmark 2002-2014.

Resuscitation 2020 07 15;152:77-85. Epub 2020 May 15.

Department of Cardiology, The Cardiovascular Research Centre, Herlev and Gentofte Hospital, University of Copenhagen, Hellerup, Denmark; Department of Medicine, Section of Cardiovascular Medicine Boston Medical Center, Boston University Boston, MA, USA.

Background: The general cardiovascular health has improved throughout the last few decades for middle-aged and older individuals, but the incidence of several cardiovascular diseases is reported to increase in younger people. We aimed to assess the age-specific incidence and mortality rates associated with out-of-hospital-cardiac-arrest (OHCA) between 2002 and 2014.

Methods: We used the Danish Cardiac Arrest Register to identify patients with OHCA of presumed cardiac etiology. We calculated the annual incidence rates (IR) and 30-day mortality rates (MR) in 7 age groups (18-34 years, 35-44 years, 45-54 years, 55-64 years, 65-74 years, 75-84 years and ≥85 years, and ≤50 vs. >50 years).

Results: Between 2002 and 2014, IR of OHCA decreased in individuals aged 65-74 and 75-84 years (158.08 to 111.2 and 237.5 to 217.09 per 100,000 person-years) and increased in the oldest from 201.01 to 325.4 pr. 100.000 person-years. In 18-34-years incidence of OHCA increased from 1.7 to 2.6 per 100.000 person-years. When stratifying into age ≤50 vs. >50 years, the IR deviated in those >50 years (from 117.8 in 2002 to 91 in 2008 to 117.4 in 2014100,000 person-years). The prevalence of acute myocardial infarction and heart failure prior to OHCA increased in the younger patient group in contrast to the older segment (AMI: ≤50 years: 10% to 16%, vs. >50 years: 25% to 23%, heart failure: ≤50 years 6% to 14%, vs. >50 years: 21% to 24%).

Conclusion: Over the last decades, incidence rates of OHCA decreased in individuals aged 65-84, but increased in individuals older than 85. An increase was also observed in younger individuals, potentially indicating a need for better cardiovascular disease prevention in younger adults.
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http://dx.doi.org/10.1016/j.resuscitation.2020.05.005DOI Listing
July 2020

Readmission and death in patients admitted with new-onset versus worsening of chronic heart failure: insights from a nationwide cohort.

Eur J Heart Fail 2020 10 30;22(10):1777-1785. Epub 2020 Mar 30.

Department of Cardiology, Herlev and Gentofte University Hospital, Herlev, Denmark.

Aims: To examine the rates of all-cause mortality and heart failure (HF) readmission in patients hospitalized with decompensated HF according to HF duration - new-onset HF and worsening of chronic HF.

Methods And Results: In this nationwide observational cohort study, 17 176 patients were included at first hospital admission for HF in the period 2013-2015 using data from Danish nationwide registries. In total, 8860 (51.6%) patients were admitted with new-onset HF and 8316 (48.4%) with worsening of chronic HF. Patients with worsening of chronic HF were characterized by a greater comorbidity burden compared with patients with new-onset HF. The rates of outcomes were examined by multivariable Cox regression models, adjusted for age, sex, and comorbidity. Worsening of chronic HF was associated with a higher rate of the composite endpoint of all-cause mortality or HF readmission [hazard ratio (HR) 1.37, 95% confidence interval (CI) 1.31-1.43], all-cause mortality (HR 1.22, 95% CI 1.16-1.28), and HF readmission (HR 1.81, 95% CI 1.69-1.93) compared with new-onset HF. There was an interaction between atrial fibrillation (AF), HF duration, and outcome: in worsening of chronic HF, the rate of the composite endpoint was higher in patients with AF compared with those without (HR 1.12, 95% CI 1.07-1.19), whereas in new-onset HF, the rate of the composite endpoint was lower in patients with AF compared with those without (HR 0.91, 95% CI 0.85-0.96) (P-value for interaction <0.001).

Conclusions: Among patients hospitalized with decompensated HF, worsening of chronic HF was associated with poorer outcomes compared with new-onset HF.
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http://dx.doi.org/10.1002/ejhf.1800DOI Listing
October 2020

Incidence of Ischemic Stroke in Individuals With and Without Aortic Valve Stenosis: A Danish Retrospective Cohort Study.

Stroke 2020 05 27;51(5):1364-1371. Epub 2020 Mar 27.

From the Department of Cardiology, Herlev and Gentofte Hospital, University of Copenhagen, Hellerup, Denmark (C. Andreasen, G.H.G., C. Andersson).

Background and Purpose- Aortic valve stenosis may lead to atrial and ventricular remodeling, predisposes to atrial fibrillation, and may also be an independent risk factor of ischemic stroke. However, information on stroke rates among persons with aortic valve stenosis are sparse. We aimed to determine the incidence rates and relative risks of ischemic stroke in individuals with diagnosed aortic valve stenosis compared with age- and sex-matched controls. Methods- All patients with incident aortic valve stenosis aged >18 years (n=79 310) and age- and sex-matched controls were identified using the Danish nationwide registries (1997-2017). Incidence rates per 1000 person-years (PY) and multivariable adjusted hazard ratios with 95% CIs were reported. Results- In total, 873 373 individuals (median age 77 years, 51.5% men, 9.1% with aortic valve stenosis) were included. Ischemic stroke occurred in 70 205 (8.0%) individuals during 4 880 862 PY of follow-up. Incidence rates of ischemic stroke were 13.3/1000 PY among the controls compared with 30.4/1000 PY in patients with aortic valve stenosis, corresponding to a hazard ratio of 1.31 (95% CI, 1.28-1.34). In all age-groups, the incidence rates and relative risks were significantly increased in patients with aortic valve stenosis compared with controls, but the relative risk was greater for younger individuals (eg, age group, 18-45 years: hazard ratio, 5.94 [95% CI, 4.10-8.36]). In patients with aortic valve stenosis above 65 years of age, the risk of ischemic stroke was markedly lower after aortic valve replacement (30.3 versus 19.6/1000 PY before and after valve replacement). Among people with atrial fibrillation the incidence rate of ischemic stroke was 1.5 times higher when aortic valve stenosis was present (33.0/1000 PY versus 49.9/1000 PY). Conclusions- People with aortic valve stenosis have a significantly increased risk of ischemic stroke compared with age- and sex-matched controls. Future studies are warranted to explore whether antithrombotic therapy may be beneficial in some individuals.
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http://dx.doi.org/10.1161/STROKEAHA.119.028389DOI Listing
May 2020
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