Glycated haemoglobin levels among 3295 hospitalized COVID-19 patients, with and without diabetes, and risk of severe infection, admission to an intensive care unit and all-cause mortality.

AIM: To determine the risk of adverse outcomes across the spectrum of glycated haemoglobin (HbA1c) levels among hospitalized COVID-19 patients with and without diabetes. MATERIALS AND METHODS: Danish nationwide registries were used to study the association between HbA1c levels and 30-day risk of all-cause mortality and the composite of severe COVID-19 infection, intensive care unit (ICU) admission and all-cause mortality. The study population comprised patients hospitalized with COVID-19 (3 March 2020 to 31 December 2020) with a positive polymerase chain reaction (PCR) test and an available HbA1c ≤ 6 months before the first positive PCR test. All patients had at least 30 days of follow-up. Among patients with diabetes, HbA1c was categorized as <48 mmol/mol, 48 to 53 mmol/mol, 54 to 58 mmol/mol, 59 to 64 mmol/mol (reference) and >64 mmol/mol. Among patients without diabetes, HbA1c was stratified into <31 mmol/mol, 31 to 36 mmol/mol (reference), 37 to 41 mmol/mol and 42 to 47 mmol/mol. Thirty-day standardized absolute risks and standardized absolute risk differences are reported. RESULTS: We identified 3295 hospitalized COVID-19 patients with an available HbA1c (56.2% male, median age 73.9 years), of whom 35.8% had diabetes. The median HbA1c was 54 and 37 mmol/mol among patients with and without diabetes, respectively. Among patients with diabetes, the standardized absolute risk difference of the composite outcome was higher with HbA1c < 48 mmol/mol (12.0% [95% confidence interval {CI} 3.3% to 20.8%]) and HbA1c > 64 mmol/mol (15.1% [95% CI 6.2% to 24.0%]), compared with HbA1c 59 to 64 mmol/mol (reference). Among patients without diabetes, the standardized absolute risk difference of the composite outcome was greater with HbA1c < 31 mmol/mol (8.5% [95% CI 0.5% to 16.5%]) and HbA1c 42 to 47 mmol/mol (6.7% [95% CI 1.3% to 12.1%]), compared with HbA1c 31 to 36 mmol/mol (reference). CONCLUSIONS: Patients with COVID-19 and HbA1c < 48 mmol/mol or HbA1c > 64 mmol/mol had a higher associated risk of the composite outcome. Similarly, among patients without diabetes, varying HbA1c levels were associated with higher risk of the composite outcome.

The association between cardiovascular disease admission rates and the coronavirus disease 2019 lockdown and reopening of a nation: a Danish nationwide cohort study.

AIMS: To investigate the admission rates of cardiovascular diseases, overall and according to subgroups, and subsequent mortality rates during the coronavirus disease 2019 societal lockdown (12 March 2020) and reopening phase (15 April 2020) in Denmark. METHODS AND RESULTS: Using Danish nationwide registries, we identified patients with a first-time acute cardiovascular admission in two periods: (i) 2 January-16 October 2019 and (ii) 2 January-15 October 2020. Weekly incidence rates of a first-time cardiovascular admission, overall and according to subtypes, in the two periods were calculated. The incidence rate of first-time cardiovascular admissions overall was significantly lower during the first weeks of lockdown in 2020 compared with a similar period in 2019 but increased after the gradual reopening of the Danish society. A similar trend was observed for all subgroups of cardiovascular diseases. The mortality rate among patients admitted after March 12 was not significantly different in 2020 compared with 2019 [mortality rate ratio 0.98; 95% confidence interval (CI) 0.91-1.06)]. CONCLUSION: In Denmark, we observed a substantial decrease in the rate of acute cardiovascular admissions, overall and according to subtypes, during the first weeks of lockdown. However, after the gradual reopening of the Danish society, the admission rates for acute cardiovascular diseases increased and returned to rates similar to those observed in 2019. The mortality rate in patients admitted with cardiovascular diseases during lockdown was similar to that of patients during the same period in 2019.

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.

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.

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

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.

Association Between Prescribed Ibuprofen and Severe COVID-19 Infection: A Nationwide Register-Based Cohort Study.

Recommendations regarding ibuprofen use in relation to coronavirus disease 2019 (COVID-19) have been conflicting. We examined the risk of severe COVID-19 between ibuprofen-prescribed and non-ibuprofen patients with COVID-19 in a nationwide register-based study of patients with COVID-19 in Denmark between the end of February 2020 and May 16, 2020. Patients with heart failure (n = 208), < 30 years (n = 575), and prescribed other nonsteroidal anti-inflammatory drugs (n = 57) were excluded. Patients with ibuprofen prescription claims between January 1, 2020, and before COVID-19 diagnosis or April 30, 2020 (last available prescription) were compared with patients without ibuprofen prescription claims. Outcome was a 30-day composite of severe COVID-19 diagnosis with acute respiratory syndrome, intensive care unit admission, or death. Absolute risks and average risk ratios comparing outcome for ibuprofen vs. non-ibuprofen patients standardized to the age, sex, and comorbidity distribution of all patients were derived from multivariable Cox regression. Among 4,002 patients, 264 (6.6%) had ibuprofen prescription claims before COVID-19. Age, sex, and comorbidities were comparable between the two study groups. Standardized absolute risks of the composite outcome for ibuprofen-prescribed vs. non-ibuprofen patients were 16.3% (95% confidence interval (CI) 12.1-20.6) vs. 17.0% (95% CI 16.0-18.1), P = 0.74. The standardized average risk ratio for ibuprofen-prescribed vs. non-ibuprofen patients was 0.96 (95% CI 0.72-1.23). Standardized absolute risks of the composite outcome for patients with ibuprofen prescription claims > 14 days before COVID-19 vs. ≤ 14 days of COVID-19 were 17.1% (95% CI 12.3-22.0) vs. 14.3% (95% CI 7.1-23.1). In conclusion, in this nationwide study, there was no significant association between ibuprofen prescription claims and severe COVID-19.

Association Between Male Sex and Outcomes of Coronavirus Disease 2019 (COVID-19)-A Danish Nationwide, Register-based Study.

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 16 May 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 4842 COVID-19 patients, 2281 (47.1%) were men. Median age was 57 [25%-75% 43-73] for men versus 52 [38-71] for women (P < .001); however, octogenarians had equal sex distribution. Alcohol diagnosis, diabetes, hypertension, sleep apnea, prior MI and IHD (all P < .001) as well as AF, stroke, and HF (all P = .01) were more often seen in men, and so was CKD (P = .03). Obesity diagnosis (P < .001) were more often seen in women. Other comorbidity differences were insignificant (P > .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.

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

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.