Based on the GBD 1990 and 2021 data, this study provides an in-depth analysis of the sex differences in the global and regional burden of IHD. Given the significant impact of IHD on human health, policymakers can gain valuable insights by analyzing the sex disparities in the IHD burden. These analyses will help formulate effective health policies and distribute resources efficiently. Furthermore, by analyzing data for various age groups and from several SDI regions, we can observe the varied patterns and features of the global IHD burden (Figs. 3 and 4). The findings from this study highlight significant trends and sex disparities in the burden of IHD globally and across various demographics and regions from 1990 to 2021. These results underscore the evolving nature of IHD as a public health challenge and the necessity of targeted interventions to address sex disparities and regional variations.

There are significant differences in the global and regional burden of IHD between men and women. Consistent with previous studies, our study indicated that the IHD burden in men was significantly greater than in women [32, 33]. Men may bear a higher disease burden from IHD due to greater exposure to most major risk factors, including elevated rates of high systolic blood pressure and high fasting plasma glucose, along with unhealthy habits such as cigarette smoking, excessive alcohol consumption, staying up late, and a diet high in fat. Additionally, men are more likely than women to delay seeking medical help for health issues [34].

One of the primary risk factors for CVDs with the lowest SPR of SEV is smoking, indicating that males usually make up the majority of tobacco users [35]. In 2019, there were 1.14 billion smokers worldwide. The ASPR of tobacco smoking among individuals aged 15 and older was 32.7% for males and 6.62% for females. Despite a notable decrease in smoking rates since 1990 (27.5% among males and 37.7% among females aged 15 and older), population growth has contributed to an increase in the total number of smokers, rising from 0.99 billion in 1990 to 1.14 billion in 2019. Data from the GBD indicate that from 1990 to 2019, the prevalence of male tobacco use declined significantly in 135 countries (66%), while among females, it decreased substantially in only 68 countries (33%) [36]. Men are substantially more likely to smoke in low- and middle-income nations where regions lack the resources necessary to control tobacco use effectively [37, 38].

Furthermore, global CVD mortality linked to smoking has increased from 1,781,364 in 1990 to 2,247,325 in 2021, representing a 26.16% rise. However, the ASMR decreased from 46.47 per 100,000 in 1990 to 26.29 per 100,000 in 2021. During this period, the incidence of smoking-related CVD remained consistently higher among men. Moreover, the decline in disease burden has advanced more slowly for men than for women, with an estimated annual percentage change in ASMR of -1.78 for men compared to -3.25 for women [39]. Our result demonstrated that while men have much more exposure to smoking, the exposure of women to secondhand smoke is higher compared to men. However, the SPR of exposure to smoking and being a secondhand smoker has decreased from 1990 to 2021. These trends can also explain a portion of the observed results regarding the decrease in the SPR of IHD’s burden, as well as the higher burden among males in low-SDI and low-middle SDI regions.

According to the GBD 2019 report, global trends in CVD deaths and DALYs related to poor physical activity showed a steady rise in these patterns for both sexes, with females outnumbering males. In contrast, a steady decline in ASMR and ASDR was observed in both sexes. The number of deaths and DALYs attributed to low physical activity was higher in males compared to females before the age group of 70–74. However, this trend changed, with females subsequently experiencing higher rates than males [40]. The estimated annual percentage change of -1.44 indicates that the associated ASMR has shown a downward trend, decreasing from 12.55 in 1990 to 8.6 in 2019. Similarly, the ASDR has an estimated annual percentage change of -1.3 and declined from 181.64 to 127. Before reaching the 75–79 age group, females had slightly higher rates than males, with minimal differences between the two up to the 85–89 age group. However, beyond this range, females exhibited significantly higher rates than males. Furthermore, both male and female ASDRs consistently increased with age, particularly showing a notable rise after the 75–79 age group [40].

Although our findings aligns with the previous reports regarding the decrease in ASMR and ASPR due to IHD, previous studies have only addressed the DALY and Mortality attributed to risk factors such as low physical activity in IHD, but have failed to address the change in sex differences of risk factors, regardless of their attributed burden. While previous studies have demonstrated that the ASDR and ASMR attributed to low physical activity have decreased with similar trends in both sexes, we found that women are experiencing more sex differences regarding exposure to low physical activity compared to 1990, indicating the increasing gap between women and men in terms of physical activity.

On the other hand, women face sex-specific risk factors. Traditional risk factors for CVD include hypertension, obesity, diabetes mellitus, and metabolic syndrome, all of which are recognized as inflammatory conditions [41]. Women are disproportionately affected by these conditions, with noticeable sex differences emerging from adolescence. Hormonal fluctuations associated with reproductive events such as menarche, pregnancy, and menopause are believed to contribute to a pro-inflammatory state in females. Furthermore, women experiencing inflammatory conditions like polycystic ovarian syndrome (PCOS), gestational diabetes, or pre-eclampsia demonstrate a cardiometabolic phenotype that heightens their risk of myocardial infarction, stroke, and coronary heart disease [42]. Generally, women who do not have significant CVD risk factors experience a certain degree of cardiovascular protection before menopause. However, after the decline of estrogen’s protective effects, women face a greater risk of major cardiovascular events compared to men [43].

Across all age groups, the SPR for IHD prevalence increased from 1990 to 2021, with adults aged 70 + years consistently showing the highest disparities. Sex differences in CVD tend to diminish with advancing age due to hormonal fluctuations and the progression of cardiovascular aging mechanisms. Premenopausal women benefit from estrogen, which exhibits vasodilatory properties and influences the excretion of nitric oxide, thereby promoting cardiovascular health. Following menopause, the reduction in estrogen levels is linked to increased arterial stiffness and a heightened risk of CVD in women, subsequently narrowing the risk disparity between genders [44,45,46]. Aging induces significant changes in cardiac structure and function, as evidenced by increased myocardial stiffness and left ventricular remodeling. These changes are observed in both genders; however, they tend to be more pronounced in women after menopause. This discrepancy may be due to differences in β-adrenergic receptor signaling and mineralocorticoid receptor expression, suggesting that these biological pathways provide greater protective benefits in premenopausal women [15, 47]. The lowest SPR was observed in the 50–54 age group, remaining relatively stable over the period. These findings highlight the importance of age-specific strategies in addressing IHD, particularly in older populations.

Globally, the estimated prevalence of IHD has shown subtle changes over the decades. In 2021, the ASPR of IHD was higher for males than for females. However, while the ASPR for males has decreased slightly since 1990, the ASPR for females increased by 4.8%. This divergence resulted in an increased SPR from 0.610 in 1990 to 0.653 in 2021, indicating a relative rise in IHD prevalence among women compared to men. Additionally, the SPR for the ASPR of IHD showed substantial regional differences. East Asia and Southern sub-Saharan Africa had the highest SPRs in 1990 and retained this position in 2021, indicating persistent sex disparities. Conversely, regions such as Southern Latin America and Western Europe had the lowest SPRs, which continued to decrease over time. The most significant increases in SPR were observed in Eastern Europe and Western sub-Saharan Africa, indicating a rise in sex-specific vulnerabilities in these regions. In contrast, regions such as Southern sub-Saharan Africa and High-income Asia Pacific experienced notable declines in SPR, pointing towards more equitable healthcare improvements or effective public health interventions targeting women.

The SPR for the ASPR of IHD increased in all SDI super-regions, except in low-middle SDI countries, which may be attributed to the underdiagnosis of women due to disparities in access to healthcare and undeveloped screening programs for IHD. The middle SDI super-region, which had the highest SPR in 1990, was surpassed by the high-middle SDI super-region in 2021. This shift highlights the importance of focusing on middle-income countries, where economic transitions may be affecting health outcomes differently across sexes. The high SDI group maintained the lowest SPR, reflecting better healthcare access and preventive measures for women in high-income countries.

The incidence of IHD showed a decreasing trend globally, with ASIR falling for both males and females. The ASIR for males and females decreased by 13.7% and 8.5%, respectively, since 1990. Despite these reductions, the SPR for ASIR increased from 0.631 to 0.670, indicating a slower decline in new IHD cases among women. The mortality rate for IHD also decreased significantly for both sexes, but while the incidence of IHD decreased more significantly in men than in women, the SPR for mortality decreased from 0.717 in 1990 to 0.624 in 2021. The total DALYs due to IHD decreased for both sexes from 1990 to 2021, with a more pronounced reduction in women (33.7%) compared to men (25.4%), leading to a decrease in the SPR for DALYs.

The increase in the SPR of ASIR, coupled with a decrease in the SPR of ASMR and ASDR, can be attributed to several factors. The smaller decrease in ASIR for women may be partly due to improved diagnosis of IHD in this group. Recent advancements in diagnostic technologies, such as coronary imaging and the use of biomarkers, have facilitated the earlier and more precise identification of IHD in women [10]. Consequently, there has been a notable increase in the number of women diagnosed with IHD, which accounts for the observed rise in incidence rates—despite concurrent improvements in actual health outcomes. Moreover, the higher mortality rate among men, despite a larger reduction in incidence, suggests potential differences in disease severity and treatment adherence.

On the other hand, women with a history of diabetes, smoking, or hypertension exhibit a significantly elevated relative risk for CVD when compared to their male counterparts with identical risk factors. Notably, in the context of diabetes, although the prevalence of the condition is higher among men, studies indicate that diabetes increases cardiovascular risk by approximately three to seven times in women, compared to a two to three times increase observed in men [48, 49]. It is also evident that with the exception of women aged 30 to 44 years, female smokers face a 25% heightened risk of CVD in comparison to their male counterparts [50]. Additionally, the use of oral contraceptives further exacerbates the risk of CVD in women who engage in smoking behaviors [51]. Therefore, it can be assumed that modifying risk factors in women may have a more pronounced effect than in men. Additionally, medications like angiotensin-converting enzyme inhibitors and statins show slightly more significant improvements in cardiovascular outcomes for women than for men [52, 53]. The high proportion of YLL in the DALY rates highlights the fatal nature of IHD, while the relatively constant SPR for years lived with disability (YLD) indicates ongoing challenges in reducing the non-fatal impact of IHD on women.

Significant national variations in the SPR of ASMR for IHD were observed. Afghanistan had the highest SPR in 2021 (3.630), suggesting severe sex disparities in the IHD burden. Conversely, Yemen had the lowest SPR (0.291), indicating more equitable health outcomes. Countries like Afghanistan and the United Kingdom saw the most substantial changes in SPR, with Afghanistan experiencing the greatest increase (+ 2.813) and the United Kingdom the largest decrease (-0.525). These differences reflect the varied success of national health policies and interventions in addressing sex disparities in IHD.

Despite recent advances in managing IHD, significant sex-related challenges remain to be addressed. Multiple studies indicate that women are less frequently prescribed medications that provide cardiovascular protection compared to men. This trend is evident in both primary and secondary prevention contexts [54, 55]. Various factors may clarify this gap: women, typically smaller, tend to exhibit higher blood concentrations of medications, which can result in more pronounced side effects. Furthermore, numerous studies on drug effectiveness have historically focused on males, and factors like lower socioeconomic status among women could affect prescription practice patterns. The infrequent prescription of cardiovascular preventive medications for women leads to reduced success in controlling risk factors, ultimately hindering optimal cardiovascular outcomes for this population [56,57,58].

These results highlight the evolving nature of IHD as a public health challenge and the need for targeted interventions to address sex disparities and regional variations. Therefore, it is important to develop distinct IHD prevention programs tailored to specific SDI regions for each sex. Consequently, based on our findings, we recommend initiatives such as implementing smoking cessation programs targeted at male populations in low-SDI regions, enhancing cardiovascular screening and diagnostic accuracy for women in high-SDI areas, and addressing the changing risk factor profiles that emerge from economic transitions in middle-SDI countries. Furthermore, Public health initiatives should promote active lifestyles among women.

This study holds significance as it can help countries design customized policies and initiatives that prioritize primary preventive efforts for IHD. Nonetheless, it is important to recognize that our study has several limitations. We were unable to pinpoint the precise contributions of some key IHD subtypes, such as heart failure, chronic stable angina, acute MI, and chronic IHD, to the total death burden. The GBD data itself may have biases and limitations regarding countries and data accessibility. On the other hand, although the SPR offers a clear numerical value that represents the disparity between sexes across various health metrics, allowing for standardized comparisons between different populations or regions, it also has limitations. The SPR alone does not reflect the absolute magnitude of the disease burden, which can lead to misrepresentation in cases where sex-specific absolute numbers may still be significantly high or low, despite similar ratios. Factors affecting both genders equally, such as improvements in healthcare infrastructure, may not be captured by the SPR, potentially resulting in misinterpretation or underestimation of the progress made. Additionally, SPR may not be the ideal variable to assess sex differences, as it can be influenced by both worsening numbers for women and improving numbers for men. Thus, applying this variable in practice might be challenging. Notwithstanding this drawback, our study remains useful for guiding the development of a more targeted health policy and the allocation of resources.