Arslani et al.

Critical Care (2023) 27:14

https://doi.org/10.1186/s13054-022-04299-0

RESEARCH Open Access

Temporal trends in mortality and provision

of intensive care in younger women and men
with acute myocardial infarction or stroke
Ketina Arslani1,2†, Janna Tontsch3,4†, Atanas Todorov5,6, Bianca Gysi3, Mark Kaufmann4,7, Fabian Kaufmann3,
Alexa Hollinger3,7, Karin Wildi3,8,9, Hamid Merdji3,10,11, Julie Helms10,11, Martin Siegemund3,7,
Catherine Gebhard5,6,12, Caroline E. Gebhard3,7* and on behalf of the Swiss Society of Intensive Care Medicine

Abstract
Background Timely management of acute myocardial infarction (AMI) and acute stroke has undergone impressive
progress during the last decade. However, it is currently unknown whether both sexes have profited equally from
improved strategies. We sought to analyze sex-specific temporal trends in intensive care unit (ICU) admission and
mortality in younger patients presenting with AMI or stroke in Switzerland.
Methods Retrospective analysis of temporal trends in 16,954 younger patients aged 18 to ≤ 52 years with AMI or
acute stroke admitted to Swiss ICUs between 01/2008 and 12/2019.
Results Over a period of 12 years, ICU admissions for AMI decreased more in women than in men (− 6.4% in women
versus − 4.5% in men, p < 0.001), while ICU mortality for AMI significantly increased in women (OR 1.2 [1.10–1.30],

†
Ketina Arslani and Janna Tontsch contributed equally to this work
*Correspondence:
Caroline E. Gebhard
evacaroline.gebhard@usb.ch
1
Department of Cardiology, University Hospital Basel, Basel, Switzerland
2
Department of Cardiology, Rigshospitalet, Copenhagen University
Hospital, Copenhagen, Denmark
3
Intensive Care Unit, Department of Acute Medicine, University Hospital
Basel, Petersgraben 4, 4031 Basel, Switzerland
4
Department of Anesthesiology, University Hospital Basel, Basel,
Switzerland
5
Department of Nuclear Medicine, University Hospital Zurich, Zurich,
Switzerland
6
Center for Molecular Cardiology, University of Zurich, Zurich, Switzerland
7
University of Basel, Basel, Switzerland
8
Critical Care Research Group, The University of Queensland, Brisbane,
Australia
9
Cardiovascular Research Group, Basel, Switzerland
10
Université de Strasbourg (UNISTRA), Faculté de Médecine; Hôpitaux
universitaires de Strasbourg, Service de Médecine Intensive-Réanimation,
Nouvel Hôpital Civil, Strasbourg, France
11
INSERM (French National Institute of Health and Medical Research),
UMR 1260, Regenerative Nanomedicine (RNM), FMTS, Strasbourg, France
12
Department of Cardiology, University Hospital Bern, Bern, Switzerland

© The Author(s) 2023. Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which
permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the
original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or
other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line
to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory
regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this
licence, visit http://​creat​iveco​mmons.​org/​licen​ses/​by/4.​0/. The Creative Commons Public Domain Dedication waiver (http://​creat​iveco​
mmons.​org/​publi​cdoma​in/​zero/1.​0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.
Arslani et al. Critical Care (2023) 27:14 Page 2 of 12

p = 0.032), but remained unchanged in men (OR 0.99 [0.94–1.03], p = 0.71). In stroke patients, ICU admission rates
increased between 3.6 and 4.1% per year in both sexes, while ICU mortality tended to decrease only in women (OR
0.91 [0.85–0.95, p = 0.057], but remained essentially unaltered in men (OR 0.99 [0.94–1.03], p = 0.75). Interventions
aimed at restoring tissue perfusion were more often performed in men with AMI, while no sex difference was noted
in neurovascular interventions.
Conclusion Sex and gender disparities in disease management and outcomes persist in the era of modern inter-
ventional neurology and cardiology with opposite trends observed in younger stroke and AMI patients admitted to
intensive care. Although our study has several limitations, our data suggest that management and selection criteria
for ICU admission, particularly in younger women with AMI, should be carefully reassessed.
Keywords Gender gap, Gender bias, Mortality trend, Critical care, Cardiovascular diseases, Sex disparities
Graphical Abstract

Background studies report increasing stroke incidence and case fatal-

Despite major therapeutic advances during the last dec- ity rates in younger individuals [8–10] with inconsistent
ade, cardiovascular and cerebrovascular diseases are still data being reported about gender differences in terms of
among the leading causes of death and serious long-term stroke interventions, outcome and care [7, 11, 12].
disability worldwide [1, 2]. While overall incidence and A rising incidence and case fatality for AMI have been
case fatality rates for stroke or acute myocardial infarc- observed in younger women, but not in men [13–15].
tion (AMI) have steadily declined since the 1980s owing Moreover, in younger men, the incidence rate of hospi-
to improved primary and secondary prevention and talization and excess mortality has even decreased over
technical refinement [3, 4], concerns about different time [4, 16]. Although exact mechanisms accounting
trends in diagnostics, treatment and outcome in women for these differential time trends in younger women and
and men still remain. In fact, while overall stroke inci- men are lacking, an increase in comorbidities and car-
dence has decreased over the last decade [3, 5–7], recent diovascular risk factors, in particular smoking, gender
Arslani et al. Critical Care (2023) 27:14 Page 3 of 12

differences in clinical presentation and, thus, treatment carcinoma, or hematologic malignancies) are collected
delays have been proposed to account for this finding within the first 24 h of ICU admission. While the SAPS II
[14, 17, 18]. Besides differences in therapeutic options score reflects the situation at ICU admission (first 24 h),
and shifts in the distribution of traditional and non-tra- the NEMS parameters are recorded daily (per shift) until
ditional risk factors over time, gender inequality in the ICU discharge. Assessments include the daily amount
provision of resources and structural bias may impact of organ support measures (vasoactive medications,
cardio- and neurovascular disease outcomes in the mechanical ventilation and breathing aids, renal replace-
younger population [19]. We therefore sought to analyze ment therapy), interventions during ICU stay inside (e.g.,
gender-specific temporal trends in intensive care unit endotracheal intubation, placement of a pacemaker, car-
(ICU) admission and mortality over a period of 12 years dioversion, endoscopy) and outside the ICU (e.g., surgical
(2008–2019) in younger patients aged 18–52 years pre- intervention or diagnostic procedures).
senting with AMI or ischemic stroke to Swiss hospitals. From the FSO, mortality data and diagnoses of the
same period were obtained as for the MDSi dataset.
Methods Overall mortality was defined as in-hospital deaths of
Data were obtained from the Swiss ICU-registry (MDSi all patients admitted to Swiss hospitals. Younger age
- Minimal Dataset for ICUs) of the Swiss Society of was defined as age ≤ 52 years. This age cutoff was based
Intensive Care Medicine (SSICM), which contains data on the average menopausal age for women in Switzer-
from all 86 certified ICUs in Switzerland as previously land [24] to form a premenopausal female cohort and
described [19, 20]. ICU admissions and mortality for on previous studies with younger age ranging from ≤ 44
patients with AMI or ischemic stroke were obtained from to 55 years [9–14, 25]. ICU mortality was defined as all-
the MDSi database. Data of all patients identified with cause mortality during ICU stay.
AMI or ischemic stroke in all Swiss hospitals were pro-
vided by the Swiss Federal Statistical Office (FSO). The Statistical analysis
Ethics committee of Northwestern Switzerland approved Data from the MDSi database were filtered for primary
this procedure (EKNZ UBE-15/47). The study was car- admission diagnosis of AMI or ischemic stroke and
ried out according to the principles of the Declaration patients aged > 18 and ≤ 52 years. For the numbers of
of Helsinki of 1975. We adhered to the STROBE report- total admissions and deaths, Poisson models were built
ing guidelines for observational studies (Additional file 1: for primary trend analysis, which included sex and year
Table S1) [21]. of admission as covariates. Data from the FSO on death
numbers for the respective diagnosis per sex and age > 18
Variables and outcomes and ≤ 52 years were analyzed in parallel as surrogates
The primary outcome measure of this study was the tem- of overall mortality development. Analysis of mortal-
poral change in ICU mortality over 12 years. Second- ity (deaths per admission) was performed with a logistic
ary outcome measures included ICU admission rates model including all possible covariates from the SGI data
and disease severity over time. From the MDSi dataset, set. Variable reduction on the logistic model was per-
we extracted demographic data including sex, age, year formed both stepwise and using a penalized regression
of admission, information about residence prior to ICU (LASSO). Both reduction strategies resulted in selec-
admission, admission diagnosis, therapeutic (including tion of SAPS and NEMS scores as the most important
invasive) interventions before ICU admission, the Sim- explanatory variables. For both explanatory variables,
plified Acute Physiology Score (SAPS II) [22], the Nine the receiver operating characteristic (ROC) for death
Equivalents of Nursing Manpower Use Score (NEMS) prediction was analyzed, and the best predictive score
[23] of the first nursing shift and average NEMS per shift, as defined by Youden’s index [26] was analyzed for yearly
as well as ICU mortality for patients who were admitted trend. Baseline characteristics of the ICU population
for AMI or stroke between 2008 and 2019 to an ICU in were compared between men and women using t-test,
Switzerland. The selection of ischemic stroke patients parametric rank sum test, or Chi-square test as appro-
was made based on the overlapping pathogenesis and priate. Statistical analysis was performed using R version
risk factors of AMI and ischemic stroke and the provi- 3.6.1 with the packages glmnet, ROCit, and quantreg
sion of a large, uniform patient population. The SAPS II [27].
score estimates disease severity and, thus, mortality in
patients admitted to the ICU. For score calculation, the Results
worst physiological values as indicators of organ func- From January 2008 to December 2019, a total of 292,103
tion, age, type of admission and information on previous individuals were diagnosed with either an acute stroke
health status (chronic diseases such as cancer, metastatic (n = 215,397) or an AMI (n = 270,768) in Switzerland.
Arslani et al. Critical Care (2023) 27:14 Page 4 of 12

Among individuals aged > 18 and ≤ 52 years, 34,024 were to men (41 ± 9 vs 44 ± 7 years old, p < 0.001). No sex dif-
diagnosed with AMI (5293 women, 15.6%) and 18,043 ferences in NEMS and SAPS II were observed in stroke
(6774 women, 37.5%) with stroke. patients directly after admission (17.8 ± 9.0 points in
men vs 17.6 ± 8.8 points in women, p = 0.542) and dur-
Baseline characteristics, ICU admission and mortality ing ICU stay. No significant differences in the LOS and
temporal trends in ICU patients with AMI the absolute number of deaths over the whole period
Over the 12-year period, 13´449 [16.6% women] indi- were observed between women and men. No sex dif-
viduals > 18 and ≤ 52 years were admitted to an ICU for ferences before ICU admission were observed regard-
AMI. No significant age difference was observed between ing neurovascular interventions in patients with stroke
women and men (45 ± 6 vs 45 ± 5 years old, p = 0.229). (312 [14.7%] in men vs 199 [14.3%] in women, p = 0.485).
There was no significant sex difference in SAPS II, while Interventions during ICU stay (endoscopy, intubation,
the initial NEMS after admission (17.8 ± 8.0 vs 17.1 ± 7.7 cardioversion, diagnostic procedures, or subsequent sur-
points, p < 0.001) and the average NEMS per shift geries) were similar in men and women as were organ
(16.8 ± 6.4 vs 16.3 ± 6.6 points, p < 0.001) were higher support measures including mechanical ventilation (425
in men than in women. Lengths of ICU stay (LOS) and [20.1%] in men vs 248 [17.9%] in women, p = 0.111) and
the absolute number of deaths over the whole period vasoactive support (595 [28.1%] in men vs 395 [28.4%]
were similar between women and men. Prior to ICU in women, p = 0.868). Noninvasive respiratory support
admission, men with AMI underwent more frequently was more frequently used in men (1078 [51.0%] vs 632
cardiovascular interventions (percutaneous coronary [45.5%] in women, p = 0.002). Table 1 depicts the baseline
intervention [PCI]: 6222 [55.5%] in men vs 1081 [48.5%] characteristics of the ICU study population.
in women, p < 0.001; CABG surgery: 987 [8.8%] in men Overall mortality rates for stroke in Switzerland did
vs 106 [4.75%] in women, p < 0.001). In general, men not show a significant time trend between 2008 and
received more subsequent interventions during ICU stay 2019 in either sex. ICU mortality rates in patients with
(intubation, cardioversion, endoscopies) (622[5.54%] in stroke showed a trend toward a yearly decline of − 4.1%
men vs 148 [6.63%] in women, p = 0.049), more organ in women (OR 0.91 [0.85–0.95], p = 0.057), but remained
support such as mechanical ventilation (1330 [11.9%] in unchanged in men (OR 0.99 [0.94–1.03] p = 0.75, Fig. 4).
men vs 185 [8.3%] in women, p < 0.001) and vasoactive ICU admission rates for stroke increased over the
support (2520 [22.5%] in men vs 437 [19.6%] in women, study period in both sexes by + 3.6 to + 4.1% per year
p = 0.003). Table 1 lists the baseline characteristics of the ([2.9–4.2%], p < 0.001 in men and [3.3–4.9%], p < 0.001
ICU study population. in women, p = 0.6 for men vs women, Fig. 2B). Disease
In Switzerland, the overall mortality rate for AMI severity as indicated by SAPS II in patients with stroke
decreased by − 3.8 to − 6.3% per year between 2008 and admitted to the ICU decreased over time in women only
2019 in both sexes. Conversely, ICU mortality rates in (women: OR 0.91 [0.89–0.94], p = 0.002; men OR 0.96
younger women with AMI, but not in age-matched men, [0.94–0.98], p = 0.08; p = 0.067 for women vs men), while
have increased over time (women: OR 1.2 [1.10–1.30], nursing workload (NEMS) decreased in both sexes (over-
p = 0.032; men: (OR 0.99 [0.94–1.03], p = 0.71, Fig. 1). all: OR 0.91, p < 0.001; women: 0.91 [0.89–0.93], p < 0.001;
Contemporaneously, ICU admission rates for younger men: 0.92 [0.91–0.93], p < 0.001, Fig. 3B). When mortality
women have declined by − 6.4% per year (−[5.8–7% trends for stroke over time were adjusted for SAPS II and
per year], p < 0.001) but significantly less so in men NEMS, mortality changes were no longer evident.
(− 4.5% [4.2–4.8%], p < 0.001; p = 0.002 for women vs
men, Fig. 2A). Disease severity as indicated by SAPS II Discussion
in patients with AMI admitted to the ICU has increased In this large, nationwide registry in Switzerland, sex- and
over time (OR 1.05 [1.02–1.08], p < 0.001) in both sexes, age-specific temporal trends in ICU admission and mor-
while NEMS, an indicator of nursing workload, has tality rates were evaluated in younger patients with AMI
declined (OR 0.96 [0.95–0.97], p = 0.007, Fig. 3A). When or stroke between 2008 and 2019. While we found that
ICU mortality trends over time were adjusted for SAPS the overall mortality rate for AMI in Switzerland has sub-
II and NEMS, mortality changes were no longer evident.
stantially declined by approximately 5% per year over the
last 12 years in both men and women, we observed an
Baseline characteristics, ICU admission and mortality increasing ICU mortality in younger women with AMI
temporal trends in ICU patients with acute stroke as compared to men. On the other hand, ICU admission
From 2008 to 2019, 3505 [39.6% women] patients rates for AMI decreased significantly more in younger
aged > 18 and ≤ 52 years were admitted to ICU for women as compared to men. In stroke patients, a trend
stroke. Women with stroke were younger as compared
Arslani et al. Critical Care (2023) 27:14 Page 5 of 12

Table 1 Baseline characteristics of the ICU study populations aged ≤ 52 years stratified by sex
Acute myocardial infarction age ≤ 52 years Stroke age ≤ 52 years
Overall Men n = 11,218 Women p-value Overall Men n = 2116 Women p-value
n = 13,449 (83.4%) n = 2231 n = 3505 (60.4%) n = 1389
(16.6%) (39.6%)

Age (years), 45 ± 5.4 45 ± 5.4 45 ± 5.7 0.229 43 ± 7.9 44 ± 7.3 41 ± 8.5 < 0.001
mean ± SD
Transfer from 3140 (23.3) 2646 (23.6) 494 (22.1) 0.176 482 (13.8) 277 (13.1) 205 (14.8) 0.353
other hospital,
n (%)
Direct admis- 9684 (72.0) 8042 (71.7) 1642 (73.6) 2591 (73.9) 157 74.3) 1018 (73.3)
sions, n (%)
Other, n (%) 625 (4.6) 530 (4.7) 95 (4.3) 432 (12.3) 266 (12.6) 166 (12.0)
SAPS II (points) - 18.37 ± 9.32 18.34 ± 9.26 18.53 ± 9.61 0.382 20.16 ± 12.25 20.47 ± 12.47 19.69 ± 11.9 0.061
mean ± SD
NEMS score
(points)
  1st shift, 17.68 ± 7.93 17.80 ± 8.00 17.05 ± 7.56 < 0.001 17.72 ± 8.92 17.8 ± 8.98 17.61 ± 8.82 0.542
mean ± SD
  Average 16.72 ± 6.44 16.81 ± 6.40 16.3 ± 6.58 < 0.001 17.91 ± 7.92 18 ± 7.43 17.78 ± 8.61 0.436
NEMS/shift,
mean ± SD
LOS (days), 0.93 (0.66–1.44) 0.94 (0.67–1.45) 0.9 (0.61–1.42) 0.273 1.16 (0.86–2.06) 1.16 (0.87–2.09) 1.18 (0.84–2.01) 0.624
median (IQR)
Deaths, n (%) 62 (0.46) 50 (0.45) 12 (0.54) 0.678 77 (2.2) 44 (2.08) 33 (2.38) 0.640
Interventions < 0.001 0.485
before ICU
admission
  PCI, n (%) 7303 (54.3) 6222 (55.46) 1081 (48.45) 31 (0.88) 20 (0.95) 11 (0.79)
  Neurovascu- 9 (0.07) 8 (0.07) 1 (0.04) 511 (14.58) 312 (14.74) 199 (14.33)
lar interven-
tions, n (%)
  CABG sur- 1093 (8.13) 987 (8.8) 106 (4.75) 1 (0.03) 1 (0.05) 0 (0)
gery, n (%)
  Heart valve 26 (0.19) 18 (0.16) 8 (0.36) 1 (0.03) 1 (0.05) 0 (0)
surgery, n
(%)
  Aortic sur- 2 (0.01) 1 (0.01) 1 (0.04) 1 (0.03) 1 (0.05) 0 (0)
gery, n (%)
  Cardiovascu- 209 (1.55) 173 (1.54) 36 (1.61) 100 (2.85) 52 (2.46) 48 (3.46)
lar unspeci-
fied, n (%)
  Other, n (%) 279 (2.07) 226 (2.01) 53 (2.38) 389 (11.1) 230 (10.87) 159 (11.45)
  None, n (%) 4485 (33.35) 3556 (31.7) 929 (41.64) 2452 (69.96) 1492 (70.51) 960 (69.11)
Interventions
during ICU stay
  Interven- 3383 (25.15) 2838 (25.3) 545 (24.43) 0.402 1454 (41.48) 899 (42.49) 555 (39.96) 0.147
tions
performed
outside the
ICU, n (%)*
  Interven- 770 (5.73) 622 (5.54) 148 (6.63) 0.049 769 (21.94) 461 (21.79) 308 (22.17) 0.818
tions
performed
inside the
ICU, n (%)**
Mechanical ven- 1515 (11.26) 1330 (11.86) 185 (8.29) < 0.001 673 (19.2) 425 (20.09) 248 (17.85) 0.111
tilatory support,
n (%)
Arslani et al. Critical Care (2023) 27:14 Page 6 of 12

Table 1 (continued)
Acute myocardial infarction age ≤ 52 years Stroke age ≤ 52 years
Overall Men n = 11,218 Women p-value Overall Men n = 2116 Women p-value
n = 13,449 (83.4%) n = 2231 n = 3505 (60.4%) n = 1389
(16.6%) (39.6%)

Supplementary 8862 (65.89) 7483 (66.71) 1379 (61.81) < 0.001 1710 (48.79) 1078 (50.95) 632 (45.5) 0.002
ventilatory
care***, n (%)
Vasoactive
agents
  One, n (%) 2957 (21.99) 2520 (22.46) 437 (19.59) 0.003 990 (28.25) 595 (28.12) 395 (28.44) 0.868
  Multiple, n 684 (5.09) 594 (5.3) 90 (4.03) 0.015 233 (6.65) 144 (6.81) 89 (6.41) 0.694
(%)
Renal replace- 119 (0.88) 94 (0.84) 25 (1.12) 0.239 13 (0.37) 8 (0.38) 5 (0.36) 1
ment therapy,
n (%)
AMI, acute myocardial infarction; CABG, coronary artery bypass graft; LOS, length of stay in ICU; PCI, percutaneous coronary intervention; SAPS II, Simplified Acute
Physiology Score II; NEMS, Nine Equivalents of Nursing Manpower Use Score; ICU, intensive care unit. p-values are reported for comparison between women and men.
Comparisons were performed using t-test, nonparametric rank-sum test, or Chi-square test as appropriate
*Specific interventions outside the ICU: surgical intervention or diagnostic procedures; the intervention/procedure is related to the severity of illness of the patient
and makes an extra demand upon manpower efforts in the ICU
**Specific interventions in the ICU: such as endotracheal intubation, introduction of pacemaker, cardioversion, endoscopy
***Spontaneous breathing via endotracheal or tracheostomy, supplementary oxygen with spontaneous breathing

toward a decrease in ICU mortality in younger women, significantly more over time compared to men despite a
but not in men was observed while ICU admission rates similar increase in disease severity in both sexes. There-
increased in both sexes. fore, our data indicate that gender inequalities in access
The overall decrease in mortality trends observed in to specialized medicine may impose an additional bur-
women and men with AMI in Switzerland is consistent den on younger women and that triage decisions for ICU
with published literature and can mainly be attributed to admission might have been applied more strictly to the
technical refinements, improved therapies, and applica- young female population. Gender differences in disease
tion of guideline-directed therapies to both sexes lead- pathophysiology as symptom perception or presentation
ing to a narrowing of the gender gap, which was present and diagnostic biases may contribute to the inequality in
in earlier studies [28, 29]. Despite increasing awareness ICU admission observed between younger women and
of sex and gender differences in cardiovascular disease men [19]. In our study, a drop in ICU admissions for
manifestation [30, 31], treatment strategies and care [32, AMI in 2015 can be noted, which was more pronounced
33], younger women still encounter poorer outcomes in women. At that time, the use of high-sensitive tro-
following an AMI as compared to men [13]. Our data ponin (hs-cTnT) was implemented in triage decisions,
confirm this observation by demonstrating an increase allowing to identify patients with smaller myocardial
in ICU AMI-related mortality in women ≤ 52 years damage at an earlier stage leading to earlier reperfusion
between 2008 and 2019. Female sex hormones have therapy and reduced use of ICU resources [37]. Despite
been discussed to have a protective effect on cardio- international recommendations for sex-specific hs-cTnT
vascular diseases [34]. Given that the age cutoff in our cutoff values with younger women having the lowest
study population was specifically selected to determine thresholds [38], the lack to implement them in clinical
a premenopausal female cohort [24], other factors must practice is still evident [39], potentially leading to under-
outweigh the potential benefit of hormonal cardiovascu- estimation or even misdiagnosis of AMI in younger
lar protection in critically ill younger women with AMI women [40, 41].
admitted to ICU. An increase in comorbidities, non- The fact that the increased ICU mortality trend in
traditional risk factors, and a growing burden of psycho- relation to severity of illness in our study was no longer
social stress in younger women, all of them associated evident indicates that this trend is explainable by the
with worse cardiovascular outcomes, might account for admission of more severely ill patients over the years—
this time alarming temporal trend [34–36]. However, which particularly affects the female population given
while ICU mortality increased in younger women, we their higher ICU mortality observed. Consistent with
also show that women’s ICU admission rates declined published literature, men with AMI in our study were
Arslani et al. Critical Care (2023) 27:14 Page 7 of 12

Fig. 1 Mortality trends over time in women and men with acute myocardial infarction admitted to intensive care units in Switzerland. Data are
presented as observed deaths per 1000 patients in ICU each year (points) and modeled trends (lines)

also more frequently referred to reperfusion thera- The number of stroke patients, in particular younger
pies and received more often organ support upon ICU demographic groups have multiple risk factors and
admission and during ICU stay than women, including comorbidities such as coagulopathies, smoking, and rec-
mechanical ventilation and vasoactive medication [34, reational drug use, has substantially increased during the
42]. This phenomenon is known as the ‘Yentl Syndrome’ last decade [45, 46]. The latter might account for the fact
[43] and might be particularly pronounced in younger that overall stroke-related mortality rates remained sta-
women [44]. ble over time, despite refinements in treatment strategies
In contrast to the decline in overall mortality from AMI such as advanced imaging techniques and invasive rep-
in Switzerland, stroke-related mortality has not changed erfusion strategies. While ICU admission is frequently
over time. However, an increase in ICU admission rates limited to the severely affected patient with the need
over time in both sexes, alongside a stronger decline in for more invasive monitoring, advanced organ support
ICU case severity and ICU mortality in younger women, measures and management of stroke complications,
but not in men, was observed in these patients. [47–49] the increase in ICU admissions over time might
Arslani et al. Critical Care (2023) 27:14 Page 8 of 12

Fig. 2 A Time trends of overall mortality, ICU mortality, and ICU admission in patients with acute myocardial infarction. B Time trends of overall
mortality (no statistically significant change over time), ICU mortality (no statistically significant change over time, but tendency toward decline in
women), and ICU admission in patients with ischemic stroke. Data are presented as observed numbers of patients in each year, with dotted lines
representing overall patients admitted to the ICU, dashed lines showing overall deaths reported to the FSO, and continuous lines showing deaths
reported in the ICU. FSO, Swiss Federal Statistical Office; ICU, intensive care unit

Fig. 3 A Time trends of disease severity estimated by SAPS II and nursing workload estimated by NEMS in ICU patients admitted with acute
myocardial infarction. B Time trends of disease severity estimated by SAPS II and nursing workload estimated by NEMS in ICU patients admitted
with ischemic stroke. ICU, intensive care unit; NEMS, Nine Equivalents of Nursing Manpower Use Score; SAPS II, Simplified Acute Physiology Score II.
Data are presented as fraction of ICU patients at or above the threshold for the respective score (SAPS ≥ 39 or NEMS ≥ 21)
Arslani et al. Critical Care (2023) 27:14 Page 9 of 12

Fig. 4 Mortality trend over time in patients with ischemic stroke admitted to intensive care units in Switzerland. Data are presented as observed
deaths per 1000 patients in ICU each year (points) and modeled trends (lines)

also mirror such advances in treatment strategies which the number of stroke patients being referred for neuro-
necessitates more intense observation following, for vascular interventions, whereas recent studies have even
example, endovascular treatments. In contrast to AMI described higher rates of endovascular thrombectomy
patients, the temporal alterations in ICU admissions did in women [50, 51]. Less aggressive treatment for stroke
not differ between men and women, suggesting that the prevention in women with atrial fibrillation leading to
gender gap, still observed in AMI patients, has narrowed thromboembolic stroke has been previously discussed
in stroke patients. This finding is supported by previous as a possible explanation for the higher rates of invasive
studies, reporting the disappearance of gender disparities stroke therapy in women [52]. Given the younger age of
in stroke outcomes when access to specialized therapies, our cohort and the lower rates of atrial fibrillation, this
such as thrombolysis or stroke unit admission was pro- may explain the equal rate of interventions observed in
vided equally for women and men [51–53]. Consistent our study.
with this notion, no gender difference was observed in
Arslani et al. Critical Care (2023) 27:14 Page 10 of 12

The fact that ICU mortality in our study declined triage and selection criteria for ICU admission and inva-
more substantially in female stroke patients than in male sive treatments, particularly in younger individuals with
patients during the last decade suggests that younger AMI, should be carefully reassessed. Further research is
women with stroke have greatly benefited from a closing needed to identify sex- and gender-specific disease modi-
gender gap in the provision of neurological interventions fiers during ICU stay in this population.
and intensive care.
There are several limitations to this study that should be
Abbreviations
pointed out. First, our study is observational and does not AMI Acute myocardial infarction
provide information on underlying mechanisms. Second, EKNZ Ethics Committee of Northwestern Switzerland
the datasets used contain a limited set of variables. Infor- FSO Swiss Federal Statistical Office
hs-cTnT High-sensitive troponin
mation on patient demographics, symptoms at presenta- ICU Intensive care unit
tion, preexisting conditions, cardiovascular risk factors as MDSi Minimal Dataset for ICUs
well as admission criteria or biomarkers (e.g., high-sen- SAPS II Simplified Acute Physiology Score II
SSICM Swiss Society of Intensive Care Medicine
sitivity troponin) was limited or unavailable in our study NEMS Nine Equivalents of Nursing Manpower Use Score
sample. Thus, we cannot completely rule out the potential NIHSS National Institutes of Health Stroke Scale
impact of these variables on our study endpoints. Third,
the SAPS II score was only available as a whole and not Supplementary Information
as its separate components. Since it was obtained within The online version contains supplementary material available at https://​doi.​
the first 24 h after ICU admission, it may not always reflect org/​10.​1186/​s13054-​022-​04299-0.
the severity of illness before ICU admission. In addition,
Additional file 1: Table S1. STROBE Statement—Checklist of items
SAPS II as an estimate of case severity and ICU mortal-
ity is not a specific marker for neurological impairment
Acknowledgements
as the National Institutes of Health Stroke Scale (NIHSS)
The authors thank Christian Schindler (senior statistician of the Swiss Tropical
and does not thoroughly reflect the neurologic deficits and Public Health Institute, Basel, Switzerland) for providing expert advice on
upon ICU admission [53]. Fourth, the NEMS score was the statistical analysis and for critically reviewing the manuscript. We thank
Gian-Paolo Klinke and Erwin Wüest (Federal Statistical Office, Department of
originally designed to measure the burden of nursing
Health) for providing us with the nationwide data of patients with stroke or
care. Thus, interventions like mechanical ventilation, renal AMI in Switzerland.
replacement therapy, use of vasoactive agents are only sur-
Author contributions
rogates for patients’ acuity. Fifth, our dataset does not pro-
KA, JT, CEG and AT contributed to design and conduct of the study, analyzed
vide information regarding the burden of cardiovascular and interpreted the data, wrote the manuscript, and had final responsibility
risk factors and their change over time. However, it seems in the decision to submit for publication. KA, JT, CEG and AT had full access
to the data. All authors provided critical feedback at various stages of the
questionable to what extent these factors play a key role
manuscript, approved the final version of the manuscript, and agreed to be
in our investigation since stroke and AMI show different accountable for all aspects of the work in ensuring that questions related to
temporal trends. Indeed, as both conditions are associated the accuracy or integrity of any part of the work are appropriately investigated
and resolved. All authors read and approved the final manuscript.
with the same risk factors, one would expect that their
modification results in similar outcomes. Finally, our study Funding
was conducted in stroke patients admitted to the ICU and CEG was supported by grants from the Research Foundation in Intensive Care
Medicine, University Hospital Basel, the Research Fund of the University of
did not include stroke unit admissions, thereby assuming
Basel, and the Swiss National Science Foundation (SNSF). CG was supported
more severe illness in our cohort as compared to inter- by grants from the SNSF, the Olga Mayenfisch Foundation, Switzerland, the
mediate care or stroke unit populations. Consequently, OPO Foundation, Switzerland, the Novartis Foundation, Switzerland, the Swis-
sheart Foundation, the Helmut Horten Foundation, Switzerland, the EMDO
our data may not be extrapolated to patients admitted to
Foundation, Switzerland, the Iten-Kohaut Foundation/University Hospital
stroke units and are limited to the most critically ill. Zurich Foundation, Switzerland, and the University of Zurich Foundation. KA
has received a research grant from the Swiss Academy of Medical Sciences
and the Gottfried and Julia Bangerter-Rhyner-Foundation and the Swiss
Conclusion National Science Foundation (P500PM_202963), Switzerland, outside the
Our data showing time trends over 12 years in younger submitted work. KW has received research funding from the Gottfried und
individuals with AMI or stroke suggest that gender dif- Julia Bangerter-Rhyner Foundation, the Prince Charles Hospital Foundation,
the Wesley Medical Research Foundation, the CRE ACTION (Centre of Research
ferences in ICU admission, case severity and mortal- Excellence for Advanced Cardio-Respiratory Therapies improving Organ
ity still exist in patients with AMI, while the gender gap Support) a PhD scholarship from the University of Queensland (Brisbane,
in the provision of care is closing in stroke patients, Australia), all outside the submitted work.
resulting in improved outcomes of critically ill women. Availability of data and materials
Although our data are limited by potential confounders Data are available from the University Hospital Basel Institutional Data Access
not available from the registry, our study emphasizes that for researchers who meet the criteria for access to confidential data.
Arslani et al. Critical Care (2023) 27:14 Page 11 of 12

Declarations adults hospitalized with acute myocardial infarction. Circulation.

2019;139(8):1047–56.
Ethics approval and consent to participate 15. DeFilippis EM, Collins BL, Singh A, Biery DW, Fatima A, Qamar A, et al.
In the annual assembly in autumn 2015, the members of the SSICM agreed Women who experience a myocardial infarction at a young age have
that all pseudonymized data from the MDSi can be used for research, once a worse outcomes compared with men: the Mass General Brigham
specific request has been approved by the appropriate scientific committee. YOUNG-MI registry. Eur Heart J. 2020;41(42):4127–37.
The Ethics committee of Northwestern Switzerland approved this procedure 16. Izadnegahdar M, Singer J, Lee MK, Gao M, Thompson CR, Kopec J, et al.
(EKNZ UBE-15/47). The scientific committee of the SSICM approved the study Do younger women fare worse? Sex differences in acute myocardial
with the above-mentioned title. infarction hospitalization and early mortality rates over ten years. J Wom-
ens Health (Larchmt). 2014;23(1):10–7.
Consent for publication 17. Leifheit-Limson EC, D’Onofrio G, Daneshvar M, Geda M, Bueno H, Spertus
Not applicable. JA, et al. Sex differences in cardiac risk factors, perceived risk, and health
care provider discussion of risk and risk modification among young
Competing interests patients with acute myocardial infarction: the VIRGO study. J Am Coll
CG has received speakers’ fees from Sanofi Genzyme, travel support from Sie- Cardiol. 2015;66(18):1949–57.
mens Health engineers, and research support from the Novartis Foundation, 18. Ladabaum U, Mannalithara A, Myer PA, Singh G. Obesity, abdominal
Switzerland, Bayer Pharmaceuticals, and Gerresheimer AG, Switzerland. The obesity, physical activity, and caloric intake in US adults: 1988 to 2010. Am
Department of Nuclear Medicine, University Hospital Zurich, holds a research J Med. 2014;127(8):717–27.
contract with GE Healthcare. 19. Todorov A, Kaufmann F, Arslani K, Haider A, Bengs S, Goliasch G, et al.
Gender differences in the provision of intensive care: a Bayesian
approach. Intensive Care Med. 2021;47:577.
Received: 23 September 2022 Accepted: 29 December 2022 20. Perren A, Cerutti B, Kaufmann M, Rothen HU, Swiss Society of Intensive
Care M. A novel method to assess data quality in large medical registries
and databases. Int J Qual Health Care. 2019;31(7):1–7. https://​doi.​org/​10.​
1093/​intqhc/​mzy249.
21. von Elm E, Altman DG, Egger M, Pocock SJ, Gøtzsche PC, Vandenbroucke
References JP. The strengthening the reporting of observational studies in epidemi-
1. Townsend N, Wilson L, Bhatnagar P, Wickramasinghe K, Rayner M, Nichols ology (STROBE) statement: guidelines for reporting observational studies.
M. Cardiovascular disease in Europe: epidemiological update 2016. Eur Int J Surg. 2014;12(12):1495–9.
Heart J. 2016;37(42):3232–45. 22. Le Gall J-R, Lemeshow S, Saulnier F. A new simplified acute physiology
2. Collaborators GBDCoD. Global, regional, and national age-sex-specific score (SAPS II) based on a European/North American multicenter study.
mortality for 282 causes of death in 195 countries and territories, JAMA. 1993;270(24):2957–63.
1980–2017: a systematic analysis for the Global Burden of Disease Study 23. Reis Miranda D, Moreno R, Iapichino G. Nine equivalents of nursing man-
2017. Lancet. 2018;392(10159):1736–88. power use score (NEMS). Intensive Care Med. 1997;23(7):760–5.
3. Koton S, Schneider AL, Rosamond WD, Shahar E, Sang Y, Gottesman RF, 24. Dratva J, Zemp E, Staedele P, Schindler C, Constanza MC, Gerbase M, et al.
et al. Stroke incidence and mortality trends in US communities, 1987 to Variability of reproductive history across the Swiss SAPALDIA cohort–pat-
2011. JAMA. 2014;312(3):259–68. terns and main determinants. Ann Hum Biol. 2007;34(4):437–53.
4. Gupta A, Wang Y, Spertus JA, Geda M, Lorenze N, Nkonde-Price C, et al. 25. Ekker MS, Verhoeven JI, Vaartjes I, Jolink WMT, Klijn CJM, de Leeuw FE.
Trends in acute myocardial infarction in young patients and differences Association of stroke among adults aged 18 to 49 years with long-term
by sex and race, 2001 to 2010. J Am Coll Cardiol. 2014;64(4):337–45. mortality. JAMA. 2019;321(21):2113–23.
5. Wang Y, Zhou L, Guo J, Wang Y, Yang Y, Peng Q, et al. Secular trends of 26. Hughes G. Youden’s index and the weight of evidence. Methods Inf Med.
stroke incidence and mortality in China, 1990 to 2016: the global burden 2015;54(2):198–9.
of disease study 2016. J Stroke Cerebrovasc Dis. 2020;29(8): 104959. 27. Team RC. R: A language and environment for statistical computing. R
6. Ioacara S, Tiu C, Panea C, Nicolae H, Sava E, Martin S, et al. Stroke mortal- Foundation for Statistical Computing, Vienna, Austria 2019 [Available
ity rates and trends in Romania, 1994–2017. J Stroke Cerebrovasc Dis. from: https://​www.R-​proje​ct.​org/.
2019;28(12): 104431. 28. Radovanovic D, Seifert B, Roffi M, Urban P, Rickli H, Pedrazzini G, et al.
7. Madsen TE, Khoury JC, Leppert M, Alwell K, Moomaw CJ, Sucharew H, Gender differences in the decrease of in-hospital mortality in patients
et al. Temporal trends in stroke incidence over time by sex and age in the with acute myocardial infarction during the last 20 years in Switzerland.
GCNKSS. Stroke. 2020;51(4):1070–6. Open Heart. 2017;4(2): e000689.
8. Krishnamurthi RV, Moran AE, Feigin VL, Barker-Collo S, Norrving B, Mensah 29. Sabbag A, Matetzky S, Gottlieb S, Fefer P, Kohanov O, Atar S, et al. Recent
GA, et al. Stroke prevalence, mortality and disability-adjusted life years in temporal trends in the presentation, management, and outcome
adults aged 20–64 years in 1990–2013: data from the global burden of of women hospitalized with acute coronary syndromes. Am J Med.
disease 2013 study. Neuroepidemiology. 2015;45(3):190–202. 2015;128(4):380–8.
9. Ekker MS, Boot EM, Singhal AB, Tan KS, Debette S, Tuladhar AM, et al. 30. Winham SJ, de Andrade M, Miller VM. Genetics of cardiovascular disease:
Epidemiology, aetiology, and management of ischaemic stroke in young importance of sex and ethnicity. Atherosclerosis. 2015;241(1):219–28.
adults. Lancet Neurol. 2018;17(9):790–801. 31. Mauvais-Jarvis F, Bairey Merz N, Barnes PJ, Brinton RD, Carrero JJ, DeMeo
10. Yahya T, Jilani MH, Khan SU, Mszar R, Hassan SZ, Blaha MJ, et al. Stroke in DL, et al. Sex and gender: modifiers of health, disease, and medicine.
young adults: current trends, opportunities for prevention and pathways Lancet. 2020;396(10250):565–82.
forward. Am J Prev Cardiol. 2020;3: 100085. 32. Vervloet M, Korevaar JC, Leemrijse CJ, Paget J, Zullig LL, van Dijk L.
11. Ekker MS, Verhoeven JI, Vaartjes I, van Nieuwenhuizen KM, Klijn CJM, de Interventions to improve adherence to cardiovascular medication: what
Leeuw FE. Stroke incidence in young adults according to age, subtype, about gender differences? A systematic literature review. Patient Prefer
sex, and time trends. Neurology. 2019;92(21):e2444–54. Adherence. 2020;14:2055–70.
12. Giroud M, Delpont B, Daubail B, Blanc C, Durier J, Giroud M, et al. Tem- 33. Punnoose LR, Lindenfeld J. Sex-specific differences in access and
poral trends in sex differences with regard to stroke incidence: the dijon response to medical and device therapies in heart failure: state of the art.
stroke registry (1987–2012). Stroke. 2017;48(4):846–9. Prog Cardiovasc Dis. 2020;63(5):640–8.
13. Gabet A, Danchin N, Juilliere Y, Olie V. Acute coronary syndrome in 34. Vallabhajosyula S, Verghese D, Desai VK, Sundaragiri PR, Miller VM. Sex
women: rising hospitalizations in middle-aged French women, 2004–14. differences in acute cardiovascular care: a review and needs assessment.
Eur Heart J. 2017;38(14):1060–5. Cardiovasc Res. 2022;118(3):667–85.
14. Arora S, Stouffer GA, Kucharska-Newton AM, Qamar A, Vaduganathan
M, Pandey A, et al. Twenty Year trends and sex differences in young
Arslani et al. Critical Care (2023) 27:14 Page 12 of 12

35. Haider A, Bengs S, Luu J, Osto E, Siller-Matula JM, Muka T, et al. Sex and
gender in cardiovascular medicine: presentation and outcomes of acute
coronary syndrome. Eur Heart J. 2020;41(13):1328–36.
36. Dreyer RP, Smolderen KG, Strait KM, Beltrame JF, Lichtman JH, Lorenze
NP, et al. Gender differences in pre-event health status of young patients
with acute myocardial infarction: a VIRGO study analysis. Eur Heart J
Acute Cardiovasc Care. 2016;5(1):43–54.
37. Reichlin T, Twerenbold R, Reiter M, Steuer S, Bassetti S, Balmelli C, et al.
Introduction of high-sensitivity troponin assays: impact on myocardial
infarction incidence and prognosis. Am J Med. 2012;125(12):1205–13.
38. Thygesen K, Alpert JS, Jaffe AS, Chaitman BR, Bax JJ, Morrow DA, et al.
Fourth universal definition of myocardial infarction (2018). Circulation.
2018;138(20):e618–51.
39. Rubini Gimenez M, Twerenbold R, Boeddinghaus J, Nestelberger T,
Puelacher C, Hillinger P, et al. Clinical effect of sex-specific cutoff values
of high-sensitivity cardiac troponin T in suspected myocardial infarction.
JAMA cardiology. 2016;1(8):912–20.
40. Gartner C, Langhammer R, Schmidt M, Federbusch M, Wirkner K,
Loffler M, et al. Revisited upper reference limits for highly sensitive
cardiac troponin T in relation to age, sex, and renal function. J Clin Med.
2021;10(23):5508.
41. Lee KK, Ferry AV, Anand A, Strachan FE, Chapman AR, Kimenai DM, et al.
Sex-specific thresholds of high-sensitivity troponin in patients with sus-
pected acute coronary syndrome. J Am Coll Cardiol. 2019;74(16):2032–43.
42. Modra LJ, Higgins AM, Abeygunawardana VS, Vithanage RN, Bailey MJ,
Bellomo R. Sex differences in treatment of adult intensive care patients: a
systematic review and meta-analysis. Crit Care Med. 2022;50(6):913–23.
43. Healy B. The Yentl syndrome. N Engl J Med. 1991;325(4):274–6.
44. D’Onofrio G, Safdar B, Lichtman JH, Strait KM, Dreyer RP, Geda M, et al.
Sex differences in reperfusion in young patients with ST-segment-
elevation myocardial infarction: results from the VIRGO study. Circulation.
2015;131(15):1324–32.
45. George MG, Tong X, Bowman BA. Prevalence of cardiovascular risk factors
and strokes in younger adults. JAMA Neurol. 2017;74(6):695–703.
46. Khan SU, Khan MZ, Khan MU, Khan MS, Mamas MA, Rashid M, et al.
Clinical and economic burden of stroke among young, midlife, and
older adults in the United States, 2002–2017. Mayo Clin Proc Innov Qual
Outcomes. 2021;5(2):431–41.
47. Kirkman MA, Citerio G, Smith M. The intensive care management of acute
ischemic stroke: an overview. Intensive Care Med. 2014;40(5):640–53.
48. Carval T, Garret C, Guillon B, Lascarrou JB, Martin M, Lemarie J, et al. Out-
comes of patients admitted to the ICU for acute stroke: a retrospective
cohort. BMC Anesthesiol. 2022;22(1):235.
49. van Valburg MK, Arbous MS, Georgieva M, Brealey DA, Singer M, Geerts
BF. Clinical predictors of survival and functional outcome of stroke
patients admitted to critical care. Crit Care Med. 2018;46(7):1085–92.
50. Weber R, Krogias C, Eyding J, Bartig D, Meves SH, Katsanos AH, et al. Age
and sex differences in ischemic stroke treatment in a nationwide analysis
of 1.11 million hospitalized cases. Stroke. 2019;50(12):3494–502.
51. Otite FO, Saini V, Sur NB, Patel S, Sharma R, Akano EO, et al. Ten-year trend
in age, sex, and racial disparity in tPA (Alteplase) and thrombectomy use
following stroke in the United States. Stroke. 2021;52(8):2562–70.
52. Rexrode KM, Madsen TE, Yu AYX, Carcel C, Lichtman JH, Miller EC. The
impact of sex and gender on stroke. Circ Res. 2022;130(4):512–28.
53. Lyden PD, Lu M, Levine SR, Brott TG, Broderick J, Group NrSS. A modified
National Institutes of Health Stroke Scale for use in stroke clinical trials:
preliminary reliability and validity. Stroke. 2001;32(6):1310–7.
Ready to submit your research ? Choose BMC and benefit from:

Publisher’s Note • fast, convenient online submission

Springer Nature remains neutral with regard to jurisdictional claims in pub- • thorough peer review by experienced researchers in your field
lished maps and institutional affiliations.
• rapid publication on acceptance
• support for research data, including large and complex data types
• gold Open Access which fosters wider collaboration and increased citations
• maximum visibility for your research: over 100M website views per year

At BMC, research is always in progress.

Learn more biomedcentral.com/submissions