Nationwide time trends in patients hospitalized for acute coronary syndrome: a worrying generational and social effect among women

Abstract

Aims

To estimate the time trends in the annual incidence of patients hospitalized for acute coronary syndrome (ACS) in France from 2009 to 2021 and to analyse the current sex and social differences in ACS, management, and prognosis.

Methods and results

All patients hospitalized for ACS in France were selected from the comprehensive National Health Insurance database. Age-standardized rates were computed overall and according to age group (over or under 65 years), sex, proxy of socioeconomic status, and ACS subtype [ST-segment elevation (STSE) and non-ST-segment elevation]. Patient characteristics and outcomes were described for patients hospitalized in 2019. Differences in management (coronarography, revascularization), and prognosis were analysed by sex, adjusting for cofonders. In 2019, 143,670 patients were hospitalized for ACS, including 53,227 STSE-ACS (mean age = 68.8 years; 32% women). Higher standardized incidence rates among the most socially deprived people were observed. Women were less likely to receive coronarography and revascularization but had a higher excess in-hospital mortality. In 2019, the age-standardized rate for hospitalized ACS patients reached 210 per 100 000 person-year. Between 2009 and 2019, these rates decreased by 11.4% (men: −11.2%; women: −14.0%). Differences in trends of age-standardized incidence rate have been observed according to sex, age, and social status. Middle aged women (45–64 years) showing more unfavourable trends than in other age classes or in men. In addition, among women the temporal trends were more unfavourable as social deprivation increased.

Conclusion

Despite encouraging overall trends in patients hospitalized for ACS rates, the increasing trends observed among middle-aged women, especially socially deprived women, is worrying. Targeted cardiovascular prevention and close surveillance of this population should be encouraged.

Introduction

Cardiovascular disease is the leading cause of mortality worldwide with more than 17 million deaths annually. Ischaemic heart disease and stroke account for the majority of deaths relating to cardiovascular disease, and despite declining, ischaemic heart disease remains one of the largest contributors to disease burden.¹ A decreasing trend in acute coronary syndrome (ACS) or myocardial infarction (MI) was recently observed in several countries,^2–9 with annual decreases in ACS rates of 6% in New Zealand⁸ and 4% for MI in Europe² until the early 2000s. In North America, the rates of incident acute myocardial infarction (AMI) have declined in recent decades, with a 15% decrease of hospitalizations for MI between 2000 and 2009 in Canada⁶ and a 47% decrease between 2000 and 2014 in California.¹⁰

Nevertheless, several studies highlighted sex and age-specific differences, with an increase in ACS incidence in people under 65 years, in particular for women over the last decade.^3,5,6,11 These studies showed a significant decrease in AMI incidence and recurrence in people over 65 years. In people under 65 years, no significant trends were described in men while an increase in women under the age of 55 years has been described.³ For example, between 1995 and 2014, in the USA, the proportion of AMI hospitalizations attributable to young patients increased from 1995 to 2014 and was especially pronounced among women.¹² A French study based on hospitalization data found an overall decrease in the rates of age-standardized patients hospitalized for ACS until 2014 but a worrying increase in the 35–64 age group, particularly among women (+6.3%).¹¹ These unfavourable trends were in line with the increasing prevalence of smoking and obesity, a decline in physical activity, and high rates of hypercholesterolaemia, hypertension, and diabetes among middle-aged women.^11,13–15 Furthermore, many studies highlight the influence of social inequalities in the incidence of ACS, although their impact on the temporal trends of ACS incidence has not yet been studied. Close monitoring of incidence of cardiovascular diseases, in particular in ACS, is necessary to identify at an early stage the populations with an unfavourable evolution and develop targeted actions, to provide valid tools to evaluate the results of preventive strategies, and to anticipate care needs. Nevertheless, since 2014, no estimates of these incidence of ACS have been made in France, and there are growing concerns about their dynamics in younger adults. Since the last study, many regulatory and public health measures have been adopted in France, especially campaigns to promote a healthy diet^16–18 or to advise against smoking^19,20 and to allow easier access to nicotine replacement therapy. In addition regulations requiring plain packaging and to increase the price of tobacco have been taken.²¹ Nevertheless, cardiovascular risk factors are following unfavourable trends, particularly in women of menopause age and socially deprived women, which could have serious consequences on the epidemiology of ACS. Moreover, several international studies have shown sex differences in the management of ACS, with less revascularization, longer delays to the first medical contact and door-to-balloon time and a higher case-fatality rates at 3 days in women than in men.^22–27

The study aims to evaluate recent time trends (2009–21) in patients hospitalized for ACS (both ST-segment elevation and non-ST-segment elevation) in France according to sex, age, and socioeconomic status. It especially aims to investigate whether the unfavourable trends observed among young women (under 65 years) have been reversed and whether the socioeconomic gap has been reduced. The secondary aim was to analyse the current sex and social differences in ACS management and prognosis.

Methods

Data source

This study was conducted using the French National Health Data System [Système National des Données de Santé (SNDS)] which includes data for the entire French population with the universal public health insurance (around 67 000 000 inhabitants). It contains comprehensive data on health insurance claims and hospital discharges, thus providing detailed information on the real-life health management of the French population.^28,29 The SNDS is a medico-administrative tool with several linked databases. The system contains demographic data as well as exhaustive data on the medical reimbursements of all individuals with the universal social security coverage (see Supplementary material online, Supplementary Material). The SNDS includes the National Hospital Discharge Database [Programme de médicalisation des systèmes d’information (PMSI)], which collects all data on public and private hospital stays. The PMSI provides data such as diagnoses based on the International Classification of Diseases, 10th Revision (ICD-10) codes, hospital deaths, and information about certain procedures performed during the hospital stay that are coded according to the French classification of medical procedures [Classification Commune des Actes Médicaux (CCAM)].

Study population

All patients hospitalized for ACS in France between 2009 and 2021 were included. Acute coronary syndrome was defined by codes I20.0 and I21 to I24 of the ICD-10, which were recorded in the SNDS as the main diagnosis for the entire stay in the hospital or medical unit or as the associated diagnosis in the case of I21. For each patient, we selected the first hospitalization for ACS of each year (index hospitalization). The ACS subtype was specified according to the ICD-10 codes: ST-segment elevation acute coronary syndromes (STSE-ACS) (I21.0, I21.1, I21.2, I21.3) and non-ST-segment elevation acute coronary syndromes (NSTSE-ACS) (I20.0, I21.4, I21.9, I22, I23, I24)^30,31 (see Supplementary material online, Table S1).

Data collection

Patient characteristics included age, sex, ACS subtype, proxy of socioeconomic status (FDep), the Charlson index score of comorbidities,³² and medical history. The level of social deprivation was estimated from the French deprivation index (FDep) developed by Rey et al.³³ The FDep is a geographical index based on four sociodemographic variables for each French commune (smallest administrative unit), which reflects a major part of spatial socioeconomic heterogeneity in a homogeneous manner across the entire country. The FDep divides the population into five quintiles according to the socioeconomic level of their commune of residence, with Q1 corresponding to the fifth of the French population living in the least deprived areas and Q5 to the fifth living in the most deprived areas. The FDep is only applicable for people living in metropolitan France. We used the most recent estimation of this index from 2015. This index is routinely used by healthcare authorities to analyse spatial health inequalities, but it can also be used as a proxy to estimate socioeconomic disparities.

In order to describe patients hospitalized for ACS in 2019, we retrieved additional data from the SNDS for these patients. Patient medical history was identified from diagnoses during hospitalizations in the last 5 years and from LTD status. Patients with LTD status are entitled to 100% reimbursement of all healthcare expenditure related to that particular disease²⁸ (see Supplementary material online, Supplementary Material). Obesity was identified from diagnoses during hospitalizations in the 2 years preceding or following the index hospitalization, the associated diagnoses from the index hospitalization, and the procedures for obesity surgery. Tobacco was estimated from the hospitalization diagnoses and reimbursements for tobacco replacement therapy in the 2 years preceding or following the index hospitalization. Treatment prescribed before hospitalization was identified from the drug reimbursement database (SNDS). The ATCs codes of treatments included are listed in Supplementary material online, Supplementary Material. Patient were considered to be treated if they had received at least three deliveries of the treatment in the previous year (one for nitrates) or two deliveries if one of them was a large packaging. During the hospital stay for ACS, we recorded medical and management information: length of stay, procedures such as coronarography, percutaneous coronary intervention (PCI), and coronary artery bypass graft (CABG), admission to an intensive care unit (ICU), cardiovascular complications (associated diagnoses), and in-hospital deaths. Early in-hospital mortality was defined as mortality within the first 3 days of hospitalization.

Statistical analysis

The sociodemographic and medical characteristics of patients hospitalized for ACS were described for 2019 [the most recent available year before the coronavirus disease 2019 (COVID-19) pandemic] and were classified by sex and ACS subtype. Qualitative variables were compared using χ² test (or Fisher exact test) and quantitative variables using t-test. Poisson regression models were used to assess the sex differences in terms of the rates of coronarography, PCI, CABG, ICU admission, cardiac complications, and in-hospital mortality. These models were adjusted for age, socioeconomic status (FDep³³) Charlson comorbidity index,³² history of cardiovascular hospitalization, ACS subtype, antihypertensive and antidiabetic treatment, obesity, tobacco use, as well as prognostic outcomes.

Crude and age-standardized rates (standardized to the 2010 European population) of hospitalized ACS patients were computed for the overall population and then separately by sex, socioeconomic quintile (Fdep), and ACS subtypes. National average population data for 2009–21 was obtained from the National Institute of Statistics and Economic Studies (INSEE). Absolute and relative differences in rates were computed for 2009–19 (excluding 2020–21) to identify trends prior to the COVID-19 pandemic. Poisson regression was applied to calculate the average annual percentage change between 2009 and 2019, by age group and sex, using the population log as an offset variable. Sensitivity analyses were conducted by restricting the sample to patients with ACS coded as the main diagnosis (exclusion of I21 as the associated diagnosis). Statistical analyses were performed with the SAS software (version 7.11, SAS Institute Inc., Cary, NC, USA).

Ethics approval

Specific ethics committee approval was not required for this study. The French National Public Health Agency (Santé publique France) has permanent access to the pseudonymized healthcare reimbursement data in application of the provisions of articles R. 1461-12 et seq. of the French Public Health Code with rules and criteria similar to the Helsinki declaration. The French National Public Health Agency also has permanent full access to the SNDS by decree³⁴ and authorization to perform studies based on SNDS data from the French Data Protection Authority (CNIL). All methods were carried out in accordance with the relevant guidelines and regulations.

Results

Characteristics of patients hospitalized for acute coronary syndrome in 2019

In 2019, 143,670 patients were hospitalized for ACS: 53 227 for STSE-ACS and 90 443 for NSTSE-ACS (Table 1, Supplementary material online, Table S2). Mean age of hospitalized ACS patients was 69.4 years (67.4 years for STSE-ACS and 70.6 years for NSTSE-ACS), and one-third were women (31.0% for STSE-ACS and 33.9% for NSTSE-ACS). Men were significantly younger than women (67.0 vs. 74.4 years, P < 0.0001). A higher proportion of ACS patients was in the most socially deprived quintile compared with the least deprived quintile, with the social gradient being more accentuated for women than for men: 15% of ACS women were in the least deprived quintile vs. 25% in the most deprived quintile compared with 16% and 22% for men, respectively. Women had significantly more comorbidities than men (P < 0.0001) (Table 1).

Tobacco use was identified in more than one in two STSE-ACS patients under 65 years (56.8% of women vs. 56.2% of men, P = 0.52) and in more than 40% of NSTSE-ACS patients under 65 years (42.3% of women vs. 46.1% of men, P < 0.0001). Over 65 years, the tobacco use rates were lower, especially among women (9.2% and 10.2% of women vs. 20.3% and 21.2% of men for STSE-ACS and NSTSE-ACS, respectively). Obesity rates were significantly higher in women than in men for patients under 65 years (16.8% of men vs. 21.5% of women for STSE-ACS, P < 0.0001; 20.1% of men vs. 23.3% of women for NSTSE-ACS, P < 0.0001), and with no significant difference after 65 years (14% of STSE-ACS vs. 17% of NSTSE-ACS). (see Supplementary material online, Table S2).

Regarding hospital management, women had a longer hospital stay than men (6.6 vs. 5.8 days for NSTSE and 8.5 vs. 7.6 days for STSE). Women underwent coronarography, PCI, and CABG and were admitted to ICU less frequently than men. These differences in management were significant for both ACS subtypes and remained significant after controlling for cofonding factors (−16.4% ICU admissions, −8.4% coronarography, −18.3% PCI, and −42.8% CABG for women compared with men) (Figure 1). After controlling for these factors and patient management, significantly higher rates of cardiogenic shock (+14.8%), ventricular or auricular septal defects (+47%), and heart failure (+7.0%) were observed, during the hospital stay for ACS, in women compared with men, although they experienced fewer rhythm and conduction disorders (−11.6%) and cardiac thrombosis (−31.2%). Early in-hospital mortality was still higher in women than in men after controlling for confounding factors (+11%). In-hospital mortality was higher in women after controlling for sociodemographic factors and cardiac comorbidities (data not shown) but not significantly higher after controlling for these sociodemographic and medical factors and management (Figure 1). The analysis by ACS subtypes showed similar results for management, although in-hospital mortality, after adjustment, was significantly higher in women for STSE-ACS (see Supplementary material online, Figure S1). Rates of coronarography, PCI, ICU admission, and hospital mortality were higher among people in the most socially deprived quintile after adjusting for confounders (data not shown).

Temporal trends

Overall acute coronary syndrome

In 2019, the age-standardized rate for patients hospitalized for ACS reached 210 per 100 000 PY and was higher in men than in women (Figure 2). Between 2009 and 2019, this rate decreased by 11.4% (men: −11.2%; women −14.0%). During the COVID-19 pandemic, the rate dropped to 197 per 100 000 PY in 2020 and 192 per 100 000 PY in 2021 (Figure 2A). The age-standardized rate for patients hospitalized for ACS decreased regardless of socioeconomic status. The difference between the least and the most socially deprived quintiles decreased between 2009 and 2019, although the rate of patients hospitalized for ACS remained higher in 2019 among the most deprived people (234 vs. 161 per 100 000 PY in the least socially deprived people). The drop in rates during the COVID-19 pandemic was more significant in the most socially deprived quintile (Figure 2D).

ST-segment elevation-acute coronary syndrome

ST-segment elevation-acute coronary syndrome decreased by 9.0% between 2009 and 2019 (15.1% for women and 7.6% for men) (Figure 3A). The trend differed according to age, with a 14.2 and 22.9% decrease in men and women over 65 years, respectively, but a 3.3 and 13.1% increase in men and women under 65 years (Figure 3B).

Temporal trends of patients hospitalized for STSE-ACS depended on socioeconomic status (Figure 3C). Among women under 65 years, increases were the greatest for the most socially deprived women (+23% vs. +12% in the least socially deprived women). Conversely, the greatest decreases for women over 65 years occurred in the most socially deprived women (−21% vs. −14% in the least socially deprived women, Supplementary material online, Figure S2). In men under and over 65 years, trends did not depend on socioeconomic status.

The analysis of the mean annual trends by age group from 2009 to 2019 showed a significant decrease in the rates of ACS patients over 75 years (−1.8% in 75- to 84-year-old men, −3.2% in women) and a significant increase in the 45–64 age group, particularly among women (+1.1% in 45- to 54-year-old women and +2.9% in 54- to 64-year-old women vs. +0.4% and +1.1% in men, respectively). A significant decrease was observed in men (−0.9%) and women (−1.6%) aged between 35 and 44 years (Figure 3D).

The mean age of men hospitalized for STSE-ACS remained stable over the study period but decreased in women from 75.3 years in 2009 to 74.0 years in 2019 and 73.4 in 2021 (data not shown).

Non-ST-segment elevation acute coronary syndrome

The rate of patients hospitalized for NSTSE-ACS decreased by 12.8% between 2009 and 2019 (Figure 4A). Among those over 65 years, the decrease was 12.6% in men and 16.6% in women. Conversely, among those under 65 years, the decrease was 14.6% in men but only 3.5% in women (Figure 4B). The analysis by level of social deprivation showed a decrease in the NSTSE-ACS hospitalization rates among the least socially deprived women under 65 but an increase among the most deprived women under 65 (−10.9% vs. +6.5%, respectively) (Figure 4D).

The analysis of the mean annual trends by age group from 2009 to 2019 showed a significant decrease in the rate of patients hospitalized for ACS in both sexes and all age groups, except for women aged 55–64 years (−0.3%, P = 0.22), and for patients under 35 years (−1.2%, P = 0.19) (Figure 4C).

The mean age of men hospitalized for NSTSE-ACS increased by nearly 2 years between 2009 (67.0 years) and 2019 (68.6 years) and remained stable in women (74 years) (data not shown).

In-hospital mortality

Between 2009 and 2019, the in-hospital mortality of patients hospitalized for ACS decreased slightly from 7.0% in 2009 to 6.1% in 2019. In 2020 and 2021, in-hospital mortality remained steady compared with 2019 (6.2 and 6.4%, respectively). Early in-hospital mortality also decreased overall between 2009 and 2019 (3.2% in 2009 vs. 2.8% in 2019) (Figure 5).

Sensitivity analysis

Sensitivity analysis, which only included patients with a primary diagnosis of ACS, identified the same results.

Discussion

This nationwide study highlighted the important sex and socioeconomic inequalities in the dynamics and management of ACS in France. Although the rates of ACS remain globally higher in men, the dynamics are more unfavourable in women between 45 and 64 years of age with significant annual increases in the number of women hospitalized but also a less frequent use of coronarography, PCI, and CABG procedures, admission in ICU as well as a higher in-hospital mortality. Moreover, the burden of ACS is highest among the most socially deprived people. Although the overall incidence gap in terms of socioeconomic status tended to decrease, we observed unfavourable dynamics among socially deprived women under 65 years, thus widening the gap between socially advantaged and deprived middle-age women.

It is a challenging task to compare our incidence rates with previous studies, since recent guidelines from the European Society of Cardiology suggested modifying the terminology used for MI and ACS. In particular, they proposed changing the terminology from unstable angina and MI to NSTSE-ACS and STSE-ACS.^30,31 The overall ACS rate included the main hospital diagnosis of ‘Other acute ischaemic heart disease’ (I24) as well as the associated diagnosis of ‘Acute myocardial infarction’ (I21), although this represents a tiny fraction of ACS.

In France as in other European and North American countries, the rates of patients hospitalized for ACS have decreased over the past few years.^2–7 These encouraging trend hid inequalities since the evolution of ACS incidence differed by sex, age, and ACS subtype. The decrease in ACS incidence among both women and men aged >65 years suggests improvements in controlling cardiovascular risk factors, once they are recognized, and a better medical attention to this population.

In 2019, we found that social disparities existed. A recent German study observed that MI decreases were greatest among men and women in the highest income group,³⁵ which could widen the gap between populations. In our study, temporal trends in the incidence among women under 65 years according to their socioeconomic status is worrying. The rate of hospitalized women increased strongly among the most socially deprived for STSE-ACS. For NSTSE-ACS, rates increased among socially deprived women but decreased among socially advantaged women of the same age.

The importance of a social gradient in cardiovascular morbidity as a function of social deprivation has been widely documented in the literature.³⁶ This can be explained by the high prevalence of traditional cardiovascular risk factors in deprived populations such as smoking, hypertension, physical inactivity, and diabetes.³⁷ However, as reported in our study and the literature, even after taking into account these behavioural and medical risk factors, social deprivation remains a significant risk factor for ACS, which can be explained by psychosocial (depression, stress), educational (low health literacy associated with drug non-compliance), employment, and environmental factors (availability and cost of healthy foods, physical features of neighbourhoods, recreational areas), which are more difficult to measure.^38–45 When developing local and targeted health strategies, these different socioeconomic settings should be taken into consideration along with the traditional cardiovascular risk factors.

In recent years, European studies observed an increase in hospitalizations for ACS in women under 60 years.^3,5,6 In France, from 2004 to 2014, the previous study based on the same data source had shown that the rates of patients hospitalized for ACS increased among people under 65 years, particularly among women.¹¹ Over the same period, (until 2014), another French study based on population registries also identified a decrease in ACS incidence but only among women over 65 years and women under 45 years.⁷ Our updated temporal trends until 2019 showed that this dynamic was maintained for STSE-ACS with an increase in the 45–65 age group, which was more significant for women. On the other hand, the ACS incidence seemed to have stabilized among 35–44 year olds in 2019. These results were a continuation of the observations of the previous decade and showed a generational effect, with a worsening of the cardiovascular health of women born between 1955 and 1975.

Several studies in Western populations have suggested that the control of cardiovascular risk factors is lower in women than in men.^46–48 In France, the prevalence of all cardiovascular risk factors is high in women aged 45–65 years. First, the prevalence of tobacco use increased between the 1970s and early 2000s in women, reaching in 2018 20–25% of women aged 45–65 years. This rise occurred when the women born between 1950 and 1960 reached adulthood, these being the first generations to widely adopt smoking habits in the 1970s. Conversely, in men, daily smoking decreased from 60% in the 1970s to less than 40% in the early 2000s.⁴⁹ In 2018, the prevalence of tobacco was 26% among men aged 45–65 years.¹⁹ This specific increase in the prevalence of smoking among young women is found in high-income countries.⁴⁷ Moreover, a review by Huxley et al. reported a 25% increased risk for cardiovascular diseases due to cigarette smoking in women compared to men^46,50 which makes trends in observed smoking prevalence all the more worrying. For several years, public health interventions and regulations have been implemented in France, as in other countries, to reduce the burden of smoking, prevent smoking initiation, particularly among young people, and help smokers quit.^20,21,51,52 The latest data on smoking prevalence show promising results, decreasing among the youngest age groups, even though the number of smokers still remains high.

Similarly, although the overall prevalence of overweight and obesity has remained stable in France for the past decade, it has increased by more than 20% among women aged 40–54 years, reaching 50% in 2015; while this rate decreased by 12% among men of the same age.¹³ Concerning physical activity, only 53% of French women met the physical activity recommendations compared with 70% of men in 2014–2016.⁵³ Between 2006 and 2016, the proportion of physically active men increased by 29% in men aged 40–54 years, while it decreased by 22% in women aged 40–54 years.⁵³ Even if physiological differences related to physical exercise exist between men and women,⁵⁴ regular physical activity is beneficial for both sexes in terms of reducing cardiovascular risk. Other cardiovascular risk factors also had a high prevalence in the French population, with 23% of the population affected by hypercholesterolaemia,^55,56 31% by hypertension,⁵⁷ and 7% by diabetes,¹⁵ with a significant proportion of patients being undiagnosed or untreated and sex-differences in control of these cardiovascular risk factors.^46,48 Finally, some risk factors are specific to women. In addition to the widely documented hormonal factors (premature menopause), some diseases are on the rise in women and are associated with an increased cardiovascular risk such as hypertensive disorders of pregnancy, preterm delivery, polycystic ovary syndrome, and endometriosis.^{46,47,58–61} Generally, all cardiovascular risk factors prevalence increased in French women aged 45–65 years, which seemed to translate into more cardiovascular events. These evolutions of risk factors prevalence are reflected in sex differences in temporal trends and tends to reduce the gap in ACS incidence that still exists between men and women. The decrease in NSTSE-ACS compared to the increase of STSE-ACS in middle-aged women could be explained by a tobacco-related risk of NSTSE-ACS lower than the tobacco-related risk of STSE-ACS.⁶² One consequence of the unfavourable trends in STSE-ACS in women is the decrease in the average age of disease onset, thus narrowing the gap in the age of onset between men and women. Without intervention, the projections of MI incidence show that the age difference by sex will decrease over the years, being only 5.5 years in 2035 compared with 7.8 years in 2021.⁶³ This emphasizes the importance of targeted prevention, risk factor management, and surveillance of middle-aged women for all risk factors beyond tobacco use. This is particularly important, since our description of ACS patients in 2019 showed a very high prevalence of modifiable risk factors (smoking, obesity) in those under 65 years, particularly in women, and greater social disparities in women than in men. Similarly, the French FAST-MI registry has observed an increase in the prevalence of diabetes mellitus, obesity, hypertension, and current smoking among patients with ST elevation MI.⁶⁴

We cannot completely exclude that an increase in ACS hospitalizations of middle-aged women was due to an improvement of awareness of ACS symptoms and to a decrease in out-of-hospital mortality. In fact, in the French MONICA register, a decrease in out-of-hospital mortality of women aged 35–54 years of around 3% was observed between 2000 and 2016, while this decrease was 1.6% in men of the same age.⁶⁵ The improvement in awareness among women may have contributed to the reduction in time from onset to first call.²² Nevertheless, the improvement in awareness of ACS symptoms and the reduction in the times probably lead to a decrease in complications and mortality but cannot on its own explain a specific increase in hospitalization rates in middle-aged women since few ACS remain completely silent and are not hospitalized.

Finally, the epidemiology of ACS was disrupted by the COVID-19 pandemic. In 2020, the pandemic considerably affected the French healthcare system and the use of healthcare. As observed for several cardiovascular diseases including MI,^66–68 our study found a decrease in hospital admissions for ACS in 2020, which continued in 2021. Changes in habits such as increased smoking⁶⁹ and decreased initiation of cardiovascular risk treatments⁷⁰ during the pandemic may have an ongoing impact on the ACS epidemiology and should be closely monitored.

Our results showed that there were still sex-related inequalities regarding ACS management. We observed that women underwent coronarography, PCI, and CABG less often than men, regardless of cofonders. This is consistent with other studies, which showed that women underwent less revascularization and were, in general, less often treated with guideline-recommended therapies despite grassroots campaigns to raise awareness about the impact of cardiovascular disease in women.^61,71 Part of these differences can be explained by sex- and age-related physiopathological differences.^71,72 Studies have shown that women with ACS less often have plaque ruptures and present more frequently with plaque erosions than men with ACS.⁷³ Specifically, younger women with ACS present more often with type II ACS characterized by coronary artery spasms and vascular dysfunction whereas younger men present more often with type I ACS, caused by coronary artery obstruction.^73,74 However, there may also be sex-differences in care. When adjusting for cardiac comorbidities, age, and social factors, we observed a higher mortality rate in women than in men, whereas when adjusting for these factors along with management, we did not observe a disadvantage for women, except for early in-hospital mortality in STSE-ACS women. These results highlight once again the loss of chance for women due to the less intensive revascularization strategies used with them. Studies have shown that women derive similar benefits to men from early reperfusion in ACS,^75,76 as do late-presenting patients.⁷⁷ Nevertheless, several studies indicated that women are more likely to expect a delay in PCI as well as delays with the first medical contact and door-to-balloon time.^78,79 In France, higher pre-hospital delays were found in women with ST-elevation MI^80,81 although the recent FAST-MI study seems to show that these times are now close between men and women.²² These delays combined with fewer PCI contribute to the higher rates of cardiogenic shock and heart failure, not to mention the poorer prognosis in women.

Our study has several strengths. The use of nationwide administrative databases allowed the analysis of exhaustive hospital data records for the entire French population. We were able to reliably and accurately estimate the annual rate of patients hospitalized for ACS and provide real-life observations about cardiac procedures and all-cause mortality. Regarding the assessment of sex differences, our study has very good statistical power due to its exhaustive use of medico-administrative databases.

Our study also has limitations. First, unlike population-based ACS registries, this database overlooked ACS patients who were not hospitalized and who suddenly died. Second, social deprivation data were not available individually but instead approximated using a geographic proxy, notably the Fdep. Third, we may have underestimated the prevalence of obesity and tobacco use, although this bias is the same in men and women. This lack of accuracy on the risk factors has limited analyses with longitudinal models that would take into account the temporal trends of the cardiovascular risk factors, and which would detail the hypotheses explaining the temporal trends of ACS. Finally, due to the medico-administrative nature of the database, we lacked certain clinical information such as the types of coronary lesions or delays. The different pathophysiology may partly explain differences in management but it does not explain all the sex differences. We used cardiac complications as a proxy for severity for the adjustments.

Conclusion

The burden of ACS remains important in France with significant social and sex inequalities, thus widening these gaps, especially among younger adults. Middle-aged women, particularly the most socially deprived, are increasingly contributing to the burden of this disease with persistent inequalities in terms of management and prognosis. Targeted cardiovascular prevention and close surveillance of this population should be encouraged beyond what is already done for tobacco.

Supplementary material

Supplementary material is available at European Journal of Preventive Cardiology.

Author’s contributions

C.G. and V.O. initiated the conception and design of the work. All authors contributed significantly to the study design. C.G. performed the data acquisition and analysis and drafted the manuscript. All authors made substantial contributions to the interpretation of data and revised the manuscript critically for its intellectual content. All authors have read and approved submission of this manuscript and are accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved.

Acknowledgements

We thank Victoria Grace for her editing of the manuscript.

Funding

None declared.

Data availability

All SNDS data are anonymous and individually linkable. Access to data is subject to prior training and requires the authorization of CNIL. It is forbidden by law to share the data publicly (sensitive personal data). Researchers who meet the criteria for access to confidential data can gain access to the Health Data Hub (www.health-data-hub.fr, contact via [email protected]).

References

Author notes