Gender Disparities in Stroke Risk Profiles: A Single Centre Observational Study

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Pakistan currently ranks fifth in the global stroke burden. The absence of population-based studies has limited data on stroke etiology, risk factors, and hyperacute management practices. This study aimed to compare risk factor profiles of male and female stroke patients and assess gender differences in time-to-presentation at a private tertiary care hospital. Methods: This retrospective, cross-sectional study was conducted at Aga Khan University Hospital from January 2016 to December 2018. Patients with ischemic or hemorrhagic stroke were included. De-identified clinical and radiological data, including demographics, vascular risk factors, and treatment details, were analyzed using chi-square and t‐tests, with odds ratios (ORs) calculated where appropriate. Results: Of 1,074 patients, 674 (62.7%) were male and 400 (37.2%) female. Females were older (64.5 vs. 61.1 years, p < 0.001) and had higher admission stroke severity (NIHSS 7.9 vs. 6.3, p < 0.001). Hypertension and atrial fibrillation were more common in females (83.0% vs. 76.4%, p = 0.011; 15.0% vs. 7.3%, p < 0.001), whereas smoking was predominantly male (20.6% vs. 3.0%, p < 0.001). Time-to-presentation did not differ significantly (p = 0.788), with about one-quarter arriving within 4.5 hours. Despite this, only 27 patients (2.8%) received r-tPA, more often men than women (20 vs. 7; OR 1.82, p = 0.218). Discharge mRS scores were similar (p = 0.178). Conclusion: Sex differences were evident in age, stroke severity, hypertension, atrial fibrillation, and smoking, while time-to-presentation and outcomes were comparable. Despite similar time-to-presentation, fewer women received thrombolysis. These findings mirror global literature, where women present older and with greater severity, while men carry higher lifestyle-related risks. Improving awareness, early detection, and equitable access to hyperacute therapies are essential to addressing these disparities in Pakistan’s overburdened healthcare system, and developing sex-specific strategies may improve both prevention and treatment outcomes. Stroke Gender disparities Pakistan Introduction The ever-increasing number of stroke cases in Pakistan, especially in rural populations, are posing a significant detriment to Pakistan’s already crippling healthcare infrastructure. Currently, Pakistan ranks fifth in the global stroke burden( 1 ). The ongoing socioeconomic conditions are further contributing to the rise in stroke numbers – especially in the younger population – with data showing that strokes are occurring as much as ten years earlier in our population as compared to the western cohorts( 2 ). The average incidence of stroke is estimated to be roughly 250 per 100,000 people per year, equating to about 350,000 new cases annually( 3 ). However, misdiagnoses, underreporting and the absence of a national stroke registry raises significant concern that these figures markedly underrepresent the true burden of this deadly disease( 4 ). The lack of population-based studies in Pakistan has resulted in limited data on stroke etiology, risk factors, and hyperacute management practices. Local literature highlights the challenges faced by low and middle-income countries (LMICs), where health system constraints impede both prevention and treatment. Stroke remains a leading cause of disability and mortality worldwide, with well-established risk factors including hypertension, diabetes, dyslipidemia, smoking, and elevated body mass index( 5 , 6 ). These highlight the urgent need for robust primary prevention strategies. Acute stroke care in Pakistan faces additional hurdles. Public awareness is low, logistical barriers delay timely presentation, and access to specialized care remains scarce. Only ten tertiary centers have dedicated stroke units across the country, and fewer than six facilities offer hyperacute stroke interventions such as intravenous thrombolysis( 7 ). This challenge is further exacerbated by the severe shortage of neurologists, with only one available for approximately a million people( 1 ).These gaps underscore the critical need to expand stroke expertise and strengthen healthcare infrastructure. This study aims to compare the risk factor profiles in male and female stroke patients and evaluate gender differences in time-to-presentation at a private tertiary care hospital in Pakistan. Methodology This retrospective, cross-sectional, observational study was conducted at the Aga Khan University Hospital from January 2016 to December 2018. Patients diagnosed with ischemic or hemorrhagic stroke were included, while those with traumatic brain injuries, subarachnoid hemorrhage, those who left against medical advice, or those who declined physician-recommended treatment were excluded. Clinical and radiological data were collected and recorded in Microsoft Excel in accordance with hospital policy. The study received an exemption from the Institutional Ethical Review Committee. Data collected included demographics, clinical characteristics, vascular risk factors, and treatment details including administration of intravenous recombinant tissue Plasminogen Activator (rt-PA). Stroke severity was assessed at admission using the National Institutes of Health Stroke Scale (NIHSS), a validated and widely used clinical examination tool for quantifying neurological impairment in stroke patients( 8 ). Functional outcomes at discharge were assessed using the modified Rankin Scale (mRS), a standardized measure of disability and dependence in daily activities( 9 ). To maintain confidentiality, all participants were assigned unique study codes, and the dataset was de-identified. Access to the data was restricted to the principal investigator and subsequently shared with the statistician for analysis. Statistical Analysis STATA version 17 was used for statistical analysis. Means and standard deviations were computed for continuous variables, whereas frequencies and percentages were computed for categorical variables. Comparative analysis was conducted using t-test for continuous variables and chi-squared test for categorical variables. P-values < 0.05 were considered significant. Results A total of 1,074 patients were included in the registry, comprising 674 (62.7%) males and 400 (37.2%) females. The mean age of the cohort was 62.4 ± 13.6 years. Females were significantly older at presentation than males (64.5 ± 13.5 vs. 61.1 ± 13.5 years, p < 0.001) (Table 1 ). The majority of patients (95.6%) presented through the emergency department, with only a small proportion referred to consulting clinics (4.3%) or outside facilities (0.9%). This pattern was similar across both sexes (Table 1 ). Stroke severity at admission, assessed using the NIHSS, was significantly higher in females than in males (7.9 ± 5.8 vs. 6.3 ± 5.3, p < 0.001). Table 1 Baseline Characteristics and Risk Factors by Sex Variable Total (N = 1074) Male (N = 674) Female (N = 400) p-value Demographics Age, mean ± SD (years) 62.4 ± 13.6 61.1 ± 13.46 64.5 ± 13.5 < 0.001 NIHSS, mean ± SD 6.92 ± 5.54 6.32 ± 5.32 7.88 ± 5.76 < 0.001 Admission Source Consulting clinic 46 (4.3%) 33 (4.9%) 13 (3.3%) 0.195 Emergency room 1026 (95.5%) 640 (94.9%) 386 (96.5%) 0.195 Outside referral 1 (0.1%) 1 (0.2%) 0 (0%) 0.195 Risk Factors Hypertension 847 (78.9%) 515 (76.4%) 332 (83.0%) 0.011 Diabetes mellitus 565 (52.6%) 361 (53.6%) 204 (51.0%) 0.416 Atrial fibrillation 109 (10.2%) 49 (7.3%) 60 (15.0%) < 0.001 Current smoker 151 (14.1%) 139 (20.6%) 12 (3.0%) < 0.001 Ex-smoker 61 (5.7%) 53 (7.86%) 8 (2.0%) < 0.001 History of TIA 123 (11.5%) 63 (9.35%) 60 (15.0%) 0.005 Ischemic heart disease (MI) 79 (7.4%) 56 (8.3%) 23 (5.75%) 0.120 Valvular heart disease 41 (3.8%) 19 (2.8%) 22 (5.5%) 0.027 Dyslipidemia 110 (10.2%) 74 (10.980%) 36 (9.0%) 0.301 Chronic kidney disease 48 (4.5%) 35 (5.19%) 13 (3.25%) 0.136 Active malignancy 7 (0.7%) 5 (0.7%) 2 (0.5%) 0.634 Carotid artery disease 98 (9.1%) 67 (9.9%) 31 (7.8%) 0.228 Regarding vascular risk factors, hypertension was the most prevalent comorbidity, affecting 78.9% of the cohort, with a slightly higher proportion in females (83.0%) compared to males (76.4%). This difference was statistically significant (p = 0.011). Diabetes mellitus was present in over half the cohort (52.6%), with comparable prevalence among males (53.5%) and females (51.0%). Atrial fibrillation (AF) showed a notable gender difference, being more prevalent in females (15.0%) than in males (7.3%). This was highly significant (p < 0.001, OR = 0.45). Conversely, current smoking was significantly more common among males (20.6%) compared to females (3.0%) (p < 0.001, OR = 8.38). A similar trend was observed for ex-smokers (7.9% in males vs. 2.0% in females; p < 0.001, OR = 4.23). A history of transient ischemic attack (TIA) was reported in 11.5% of all patients, with a slightly higher frequency in females (15.0% vs. 9.4%) (p = 0.005, OR = 0.59). Ischemic heart disease (IHD) was more common in males (8.3%) than in females (5.8%). Valvular heart disease, on the other hand, was more frequently reported in females (5.5%) than in males (2.8%) (p = 0.027, OR = 0.50). Other comorbidities such as dyslipidemia (10.2%), chronic kidney disease (4.5%), active malignancy (0.7%), and carotid artery disease (9.1%) were distributed relatively evenly between the two sexes (Table 1 ). Among 953 patients with documented time of stroke onset and presentation, the distribution of presentation time windows was similar between males and females. A total of 26.4% of males and 27.2% of females presented within the critical 0–4.5-hour window, resulting in an odds ratio (OR) of 0.96 for males compared to females, indicating no significant gender difference in early presentation. In the 4.5–12-hour window, both sexes presented at equal proportions (16.6% each), yielding an OR of 1.00. For the 12–24-hour window, 28.5% of males and 25.6% of females presented within this range, with an OR of 1.16, suggesting a marginally higher—but not substantial—likelihood for males to present during this period. Conversely, 28.5% of males and 30.5% of females presented after 24 hours of stroke onset (OR 0.91), again showing no meaningful sex-based difference in delayed presentation. The overall comparison of time-to-presentation across categories showed no significant sex difference (p = 0.788) (Table 2 ). Table 2 Association Between Sex and Time to Presentation with Stroke Onset and Receipt of IV Thrombolysis (r-tPA) Variable / Time window Male (N = 586) Female (N = 367) p-value Time to Presentation 0–4.5 hours 155 (26.4%) 100 (27.2%) 0.788** 4.5–12 hours 97 (16.6%) 61 (16.6%) 12–24 hours 167 (28.5%) 94 (25.6%) > 24 hours 167 (28.5%) 112 (30.5%) Overall (time windows) – – Thrombolysis (r-tPA) 20 (3.41%) 7 (1.91%) 0.218 Discharge mRS* (mean ± SD) 2.27 ± 1.41 2.45 ± 1.41 0.178 *mRS = Modified Rankin Scale at discharge; mRS p -value from independent samples t -test (continuous outcome). **Time-to-presentation p -value represents the overall chi-square test comparing distribution across all time windows. Despite over a quarter of patients presenting within the intravenous thrombolysis treatment window, only 27 patients (2.8%) received rt-PA overall. Of these, 20 were males (3.4%) and 7 were females (1.9%), with an odds ratio of 1.82 for males compared to females. This difference was not statistically significant (p = 0.218) (Table 2 ). At discharge, the mRS score was 2.27 ± 1.41 for males and 2.45 ± 1.41 for females, with no significant difference between the sexes (p = 0.178) (Table 2 ). Overall, significant sex differences were observed in age, hypertension, atrial fibrillation, smoking status, history of TIA, and valvular heart disease, while other comorbidities, time-to-presentation, thrombolysis rates, and discharge mRS did not differ significantly. Discussion Our study presents several clinically relevant findings. We found that hypertension (83.0% vs 76.4% in males, p = 0.011) and atrial fibrillation (15.0% vs 7.3% in males, p < 0.001) were more prevalent in females. This metric is consistent with findings in the current literature, implicating these comorbidities as presenting a greater risk of stroke in women as compared to men. A recent meta-analysis of 30 cohort studies found that AF had almost double the relative risk of stroke (RR = 1.99; 95% CI: 1.46–2.71) in females as compared to males, while a pooled analysis of outcomes reported a 2-4.5 times higher risk of stroke in women, after adjusting for various risk factors( 10 , 11 ). A more recent study in Denmark, however, argued that over the last two decades, the risk of stroke among patients with AF, and the excess risk seen in female patients, have both declined( 12 ). Hypertension, too, has been shown to increase the risk for stroke in the female gender when compared with their male counterparts. A study conducted in 2020 reported that even slight increases in systolic blood pressure above 120mmHg in women disproportionately increase the chances of stroke, compared to a lower relative risk for comparable thresholds in men( 13 ). A review found that a 10mmHg increase in systolic blood pressure can elevate the risk of ischemic stroke in women by 38%( 14 ). The pathophysiology of these increased risks involves both structural and functional differences between the two genders’ cardiovascular systems. Smaller vessel diameters and increased arterial stiffness in women can amplify the hemodynamic effects of increased blood pressure to a greater extent in women. Furthermore, menopause brings with it a decrease in circulating estrogen, resulting in a loss of its Vaso protective effects and causing greater endothelial dysfunction and vascular inflammation( 15 ). We also found that women were significantly older at presentation (64.5 vs 61.1 years, p = 0.0001) and had higher stroke severity on admission, reflected by NIHSS scores (7.9 vs 6.3, p < 0.0001). These findings are in line with prior reports suggesting that female patients present later in life and with greater neurological deficits( 16 ). In light of these findings, prioritizing early detection, optimized AF management, and aggressive Blood Pressure control in women is essential to reducing sex-based disparities in stroke incidence and outcomes. Smoking and history of Myocardial Infarction (MI), on the other hand, were more prevalent among men in our cohort, presenting in 20.6% (vs 3.0% in women, p < 0.001) and 8.3% (vs 5.8% in women, p = 0.120) of men, respectively. While the difference in smoking was highly significant, the difference in myocardial infarction was not. These findings, too, are consistent with the current literature. Studies have demonstrated that men carry a greater atherosclerotic burden and account for a greater percentage of unstable plaque morphology. A meta-analysis of 42 studies found that men not only had a larger plaque as compared to women, they also had greater incidences of ulcerated plaques, intra-plaque hemorrhages, calcifications, and lipid-rich necrotic cores( 17 ). These anatomical and pathological differences likely explain the higher rate of ischemic stroke in male patients with these comorbidities. Smoking has also been established as a very important risk factor for the development of stroke, with smokers attributed to having a 1.92-fold greater risk of stroke when compared to non-smokers. Although a study found that the stroke risk from smoking was comparable in both genders, the baseline smoking population in men is significantly higher, thus driving increased population-level exposure to risk( 18 , 19 ). These findings further highlight the need to develop sex-specific preventative strategies focusing on high-risk male populations to tackle the elevated risk of stroke in susceptible men. Time from stroke onset to hospital presentation is also a very significant marker indicating pre-hospital delays. A Denmark registry analysis reported that women had longer pre-hospital delays as compared to men despite similar transport distances, primarily attributed to a greater percentage of women living alone( 20 ). Furthermore, 4 cohorts from Asian Pacific and American studies also reported greater pre-hospital delays in women, which were associated with minority ethnicities, older age, and underuse of Emergency Medical Services( 21 ). In contrast to the above literature, our study found no significant gender differences in the time from symptom onset to hospital presentation (p = 0.788). This finding is also mirrored in a population-based US study, which reported no significant difference in prehospital delays amongst genders, highlighting that sex gaps are not universal( 22 ). Understanding the role of gender disparity in healthcare is even more critical in a lower-middle-income country like Pakistan, where the healthcare infrastructure is severely overburdened and underequipped, and access to care is limited. Regardless of gender, local literature has shown substantial prehospital delays – only 21% of ischemic stroke patients in a multicenter study arrived within three hours( 23 ). The etiology for this is likely multifaceted, including low awareness, lack of appropriate diagnoses, socioeconomic status, and shortages of dedicated stroke units ( 1 ). Within an already crippling healthcare system, women represent an even further marginalized community that faces additional barriers to equitable healthcare. Sociocultural norms, reliance on elder family members, and lower rates of EMS use all contribute to a delay in seeking care for women( 24 ). Taking into account the disparities that women face, both in healthcare and otherwise, it is imperative that further research is done to truly understand the trends of prehospital delay for stroke care across genders. It is very much possible that the absence of a sex gap in our cohort is not indicative of a universal trend but rather masks sex differences due to differing local community norms or awareness levels. Although arrival times were similar, our study found that men had higher odds of receiving rt-PA as compared to women (2.97% vs 1.75%, OR 1.82, p = 0.218), but this finding did not reach statistical significance. These findings are not only in line with global literature but also with the trends of gender disparity in Pakistan. A meta-analysis done in 2009 reported that women had 30% lower odds of receiving rt-PA as compared to men( 25 ). Other studies echo these findings – reporting Odds Ratios of 0.80 and 0.91 for women receiving thrombolytics as compared to men( 25 , 26 ). Clinician bias, greater underlying disability, uncommon presentations, and atypical symptom onset are all possible reasons for the above findings( 27 ). Thus, our findings suggest that in-hospital treatment decision-making may contribute more to treatment disparity than prehospital delays, but larger studies are required to confirm this. Our study poses several limitations. The single-center design could limit the generalizability of our results to the broader Pakistani demographic, as awareness, access to healthcare, and treatment guidelines can differ significantly across regions. Additionally, the low number of patients who received rt-PA limits the ability to draw strong, gender-specific conclusions despite an apparent numerical disparity. Since there is a dearth of published literature on this topic, specifically in the context of LMICS, larger multi-center cohorts should be conducted to validate our findings. Conclusion Stroke remains a leading cause of disability and mortality in Pakistan, with the lackluster healthcare infrastructure unable to cope with its devastating effects. In evaluating the gender disparities amongst patients presenting with stroke, our data aligned with global evidence regarding risk factors: smoking and atherosclerotic disease were more significant risk factors for men, whilst hypertension and atrial fibrillation proved to pose greater risk for women. We, however, found no significant gender disparity in time from symptom onset to hospital presentation. Although the odds of men receiving thrombolysis were nearly twice those of women, this difference did not reach statistical significance, likely reflecting the limited number of patients who received thrombolysis. In an LMIC like Pakistan, where women represent a marginalized community and the healthcare system is crippling, it is critical that more research is done to elucidate the role of gender disparity in stroke presentation and treatment, and targeted interventions are formulated to reduce the burden of this frightening disease. Abbreviations LMICs Low–and Middle–Income Countries rt PA–Recombinant Tissue Plasminogen Activator NIHSS National Institutes of Health Stroke Scale AF Atrial Fibrillation OR Odds Ratio TIA Transient Ischemic Attack IHD Ischemic Heart Disease mRS Modified Rankin Scale MI Myocardial Infarction Declarations Ethics approval and consent to participate This study was reviewed and approved by the Aga Khan University Hospital Institutional Ethical Review Committee. The study was granted exemption from full ethical review (ERC Reference: 5322 – Med – ERC - 18). The requirement for informed consent to participate was waived by the committee. The study was conducted in accordance with the ethical standards of the institutional research committee and with the 1964 Helsinki Declaration and its later amendments. Consent for publication Not applicable. This manuscript does not contain any individual person’s data in any form (including images, videos, or identifiable personal details). Availability of data and materials The datasets generated and/or analyzed during the current study are not publicly available due to hospital policy and patient confidentiality restrictions, but are available from the corresponding author on reasonable request. Competing interests The authors declare that they have no competing interests. Funding Sources None. Author Contributions: Conceptualization, Methodology: SF, MW Investigation (data collection): SF, SS Formal analysis, Validation: SSa, NA Visualization (tables): MI Writing – original draft: SS, MI Writing – review & editing: MI, SS, MW, SF, SSa, NAA Supervision, Project administration: MW All authors have read and approved the final manuscript. Acknowledgements None. References Farooq A, Venketasubramanian N, Wasay M. Stroke Care in Pakistan. Cerebrovasc Dis Extra. 2021;11(3):118–21. Khealani BA, Hameed B, Mapari UU. Stroke in Pakistan. J Pak Med Assoc. 2008;58(7):400–3. Farooq MU, Majid A, Reeves MJ, Birbeck GL. The epidemiology of stroke in Pakistan: past, present, and future. Int J Stroke. 2009;4(5):381–9. Javed S, Zaidi DA, Yaqoob E. Addressing the deficiencies in stroke care in Pakistan. Lancet. 2024;404(10453):651–2. Khealani BA, Khan M, Tariq M, Malik A, Siddiqi AI, Awan S, et al. Ischemic strokes in Pakistan: observations from the national acute ischemic stroke database. 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The Influence of Sex in Stroke Thrombolysis: A Systematic Review and Meta-Analysis. J Clin Neurol. 2018;14(2):141–52. Additional Declarations No competing interests reported. Supplementary Files STROBEchecklistv4combinedPlosMedicine.docx Cite Share Download PDF Status: Under Review Version 1 posted Reviewers agreed at journal 10 Oct, 2025 Reviewers agreed at journal 09 Oct, 2025 Reviewers invited by journal 09 Oct, 2025 Editor assigned by journal 07 Oct, 2025 Editor invited by journal 15 Sep, 2025 Submission checks completed at journal 11 Sep, 2025 First submitted to journal 11 Sep, 2025 You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. 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Saleem","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAABAklEQVRIiWNgGAWjYDCCAwxsDAw2IBZzAwOExdh4gLCWNBCLEaQlDcwgScthqCAewHf7+LMHPxLsZOe3H2x88DHnvN3a9sNAW2psonFpkTyXY27Yk5BsvOFMYrPhzG23k7edSQRqOZaW24BDi8EZHjYJ3h/MiRsYEtukeYFazA4AtTA2HMajhf2Z5J+E+sT5/Q/bf//ddi7Z7PxDQloYzKR5Eg4nNtxIbGNm3HbAzuwGAVskz/CYScskHDfecONhs2TvtuQEsxtAWxLw+IUP5LA3CdWy8/uTD374uc3O3ux8+sMHH2pscGqBAUaYgkQwI4GAchQt9kQoHgWjYBSMghEGAE+Ma+1tip5rAAAAAElFTkSuQmCC","orcid":"","institution":"Aga Khan University Hospital","correspondingAuthor":true,"prefix":"","firstName":"Shafaq","middleName":"","lastName":"Saleem","suffix":""},{"id":532806922,"identity":"ac9be560-b8ad-43f7-945f-eb49f702c111","order_by":2,"name":"Saadia Sattar","email":"","orcid":"","institution":"Aga Khan University 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Hospital","correspondingAuthor":false,"prefix":"","firstName":"Mohammad","middleName":"","lastName":"Wasay","suffix":""}],"badges":[],"createdAt":"2025-08-31 10:23:18","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-7499935/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-7499935/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":94115329,"identity":"010fee21-f6b8-48f8-84d6-873fa9456133","added_by":"auto","created_at":"2025-10-22 14:15:46","extension":"docx","order_by":0,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":69727,"visible":true,"origin":"","legend":"","description":"","filename":"FinalRevisedManuscriptStrokeGender.docx","url":"https://assets-eu.researchsquare.com/files/rs-7499935/v1/54b53c3c031ae05295b7273a.docx"},{"id":94116153,"identity":"090828c0-0e4a-4c1c-b2bd-222aadc2a281","added_by":"auto","created_at":"2025-10-22 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14:15:46","extension":"docx","order_by":0,"title":"","display":"","copyAsset":false,"role":"supplement","size":38015,"visible":true,"origin":"","legend":"","description":"","filename":"STROBEchecklistv4combinedPlosMedicine.docx","url":"https://assets-eu.researchsquare.com/files/rs-7499935/v1/07f584d8b3443481fa8b4c78.docx"}],"financialInterests":"No competing interests reported.","formattedTitle":"Gender Disparities in Stroke Risk Profiles: A Single Centre Observational Study","fulltext":[{"header":"Introduction","content":"\u003cp\u003eThe ever-increasing number of stroke cases in Pakistan, especially in rural populations, are posing a significant detriment to Pakistan\u0026rsquo;s already crippling healthcare infrastructure. Currently, Pakistan ranks fifth in the global stroke burden(\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e). The ongoing socioeconomic conditions are further contributing to the rise in stroke numbers \u0026ndash; especially in the younger population \u0026ndash; with data showing that strokes are occurring as much as ten years earlier in our population as compared to the western cohorts(\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e). The average incidence of stroke is estimated to be roughly 250 per 100,000 people per year, equating to about 350,000 new cases annually(\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e). However, misdiagnoses, underreporting and the absence of a national stroke registry raises significant concern that these figures markedly underrepresent the true burden of this deadly disease(\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e).\u003c/p\u003e\u003cp\u003eThe lack of population-based studies in Pakistan has resulted in limited data on stroke etiology, risk factors, and hyperacute management practices. Local literature highlights the challenges faced by low and middle-income countries (LMICs), where health system constraints impede both prevention and treatment. Stroke remains a leading cause of disability and mortality worldwide, with well-established risk factors including hypertension, diabetes, dyslipidemia, smoking, and elevated body mass index(\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e, \u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e). These highlight the urgent need for robust primary prevention strategies.\u003c/p\u003e\u003cp\u003eAcute stroke care in Pakistan faces additional hurdles. Public awareness is low, logistical barriers delay timely presentation, and access to specialized care remains scarce. Only ten tertiary centers have dedicated stroke units across the country, and fewer than six facilities offer hyperacute stroke interventions such as intravenous thrombolysis(\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e). This challenge is further exacerbated by the severe shortage of neurologists, with only one available for approximately a million people(\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e).These gaps underscore the critical need to expand stroke expertise and strengthen healthcare infrastructure.\u003c/p\u003e\u003cp\u003eThis study aims to compare the risk factor profiles in male and female stroke patients and evaluate gender differences in time-to-presentation at a private tertiary care hospital in Pakistan.\u003c/p\u003e"},{"header":"Methodology","content":"\u003cp\u003eThis retrospective, cross-sectional, observational study was conducted at the Aga Khan University Hospital from January 2016 to December 2018. Patients diagnosed with ischemic or hemorrhagic stroke were included, while those with traumatic brain injuries, subarachnoid hemorrhage, those who left against medical advice, or those who declined physician-recommended treatment were excluded.\u003c/p\u003e\u003cp\u003eClinical and radiological data were collected and recorded in Microsoft Excel in accordance with hospital policy. The study received an exemption from the Institutional Ethical Review Committee. Data collected included demographics, clinical characteristics, vascular risk factors, and treatment details including administration of intravenous recombinant tissue Plasminogen Activator (rt-PA). Stroke severity was assessed at admission using the National Institutes of Health Stroke Scale (NIHSS), a validated and widely used clinical examination tool for quantifying neurological impairment in stroke patients(\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e). Functional outcomes at discharge were assessed using the modified Rankin Scale (mRS), a standardized measure of disability and dependence in daily activities(\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e).\u003c/p\u003e\u003cp\u003eTo maintain confidentiality, all participants were assigned unique study codes, and the dataset was de-identified. Access to the data was restricted to the principal investigator and subsequently shared with the statistician for analysis.\u003c/p\u003e\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e\u003ch2\u003eStatistical Analysis\u003c/h2\u003e\u003cp\u003eSTATA version 17 was used for statistical analysis. Means and standard deviations were computed for continuous variables, whereas frequencies and percentages were computed for categorical variables. Comparative analysis was conducted using t-test for continuous variables and chi-squared test for categorical variables. P-values\u0026thinsp;\u0026lt;\u0026thinsp;0.05 were considered significant.\u003c/p\u003e\u003c/div\u003e"},{"header":"Results","content":"\u003cp\u003eA total of 1,074 patients were included in the registry, comprising 674 (62.7%) males and 400 (37.2%) females. The mean age of the cohort was 62.4\u0026thinsp;\u0026plusmn;\u0026thinsp;13.6 years. Females were significantly older at presentation than males (64.5\u0026thinsp;\u0026plusmn;\u0026thinsp;13.5 vs. 61.1\u0026thinsp;\u0026plusmn;\u0026thinsp;13.5 years, p\u0026thinsp;\u0026lt;\u0026thinsp;0.001) (Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e). The majority of patients (95.6%) presented through the emergency department, with only a small proportion referred to consulting clinics (4.3%) or outside facilities (0.9%). This pattern was similar across both sexes (Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e). Stroke severity at admission, assessed using the NIHSS, was significantly higher in females than in males (7.9\u0026thinsp;\u0026plusmn;\u0026thinsp;5.8 vs. 6.3\u0026thinsp;\u0026plusmn;\u0026thinsp;5.3, \u003cem\u003ep\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.001).\u003c/p\u003e\u003cp\u003e\u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab1\" border=\"1\"\u003e\u003ccaption language=\"En\"\u003e\u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e\u003cdiv class=\"CaptionContent\"\u003e\u003cp\u003eBaseline Characteristics and Risk Factors by Sex\u003c/p\u003e\u003c/div\u003e\u003c/caption\u003e\u003ccolgroup cols=\"5\"\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e\u003cthead\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c1\"\u003e\u003cp\u003eVariable\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c2\"\u003e\u003cp\u003eTotal (N\u0026thinsp;=\u0026thinsp;1074)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c3\"\u003e\u003cp\u003eMale (N\u0026thinsp;=\u0026thinsp;674)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c4\"\u003e\u003cp\u003eFemale (N\u0026thinsp;=\u0026thinsp;400)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c5\"\u003e\u003cp\u003ep-value\u003c/p\u003e\u003c/th\u003e\u003c/tr\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c1\"\u003e\u003cp\u003eDemographics\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/th\u003e\u003cth align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/th\u003e\u003cth align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/th\u003e\u003cth align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/th\u003e\u003c/tr\u003e\u003c/thead\u003e\u003ctbody\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eAge, mean\u0026thinsp;\u0026plusmn;\u0026thinsp;SD (years)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e62.4\u0026thinsp;\u0026plusmn;\u0026thinsp;13.6\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e61.1\u0026thinsp;\u0026plusmn;\u0026thinsp;13.46\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e64.5\u0026thinsp;\u0026plusmn;\u0026thinsp;13.5\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eNIHSS, mean\u0026thinsp;\u0026plusmn;\u0026thinsp;SD\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e6.92\u0026thinsp;\u0026plusmn;\u0026thinsp;5.54\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e6.32\u0026thinsp;\u0026plusmn;\u0026thinsp;5.32\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e7.88\u0026thinsp;\u0026plusmn;\u0026thinsp;5.76\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eAdmission Source\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eConsulting clinic\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e46 (4.3%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e33 (4.9%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e13 (3.3%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e0.195\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eEmergency room\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e1026 (95.5%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e640 (94.9%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e386 (96.5%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e0.195\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eOutside referral\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e1 (0.1%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e1 (0.2%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0 (0%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e0.195\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eRisk Factors\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eHypertension\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e847 (78.9%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e515 (76.4%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e332 (83.0%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e0.011\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eDiabetes mellitus\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e565 (52.6%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e361 (53.6%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e204 (51.0%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e0.416\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eAtrial fibrillation\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e109 (10.2%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e49 (7.3%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e60 (15.0%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eCurrent smoker\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e151 (14.1%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e139 (20.6%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e12 (3.0%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eEx-smoker\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e61 (5.7%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e53 (7.86%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e8 (2.0%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eHistory of TIA\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e123 (11.5%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e63 (9.35%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e60 (15.0%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e0.005\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eIschemic heart disease (MI)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e79 (7.4%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e56 (8.3%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e23 (5.75%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e0.120\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eValvular heart disease\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e41 (3.8%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e19 (2.8%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e22 (5.5%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e0.027\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eDyslipidemia\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e110 (10.2%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e74 (10.980%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e36 (9.0%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e0.301\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eChronic kidney disease\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e48 (4.5%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e35 (5.19%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e13 (3.25%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e0.136\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eActive malignancy\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e7 (0.7%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e5 (0.7%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e2 (0.5%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e0.634\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eCarotid artery disease\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e98 (9.1%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e67 (9.9%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e31 (7.8%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e0.228\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003c/tbody\u003e\u003c/colgroup\u003e\u003c/table\u003e\u003c/div\u003e\u003c/p\u003e\u003cp\u003eRegarding vascular risk factors, hypertension was the most prevalent comorbidity, affecting 78.9% of the cohort, with a slightly higher proportion in females (83.0%) compared to males (76.4%). This difference was statistically significant (p\u0026thinsp;=\u0026thinsp;0.011). Diabetes mellitus was present in over half the cohort (52.6%), with comparable prevalence among males (53.5%) and females (51.0%). Atrial fibrillation (AF) showed a notable gender difference, being more prevalent in females (15.0%) than in males (7.3%). This was highly significant (p\u0026thinsp;\u0026lt;\u0026thinsp;0.001, OR\u0026thinsp;=\u0026thinsp;0.45). Conversely, current smoking was significantly more common among males (20.6%) compared to females (3.0%) (p\u0026thinsp;\u0026lt;\u0026thinsp;0.001, OR\u0026thinsp;=\u0026thinsp;8.38). A similar trend was observed for ex-smokers (7.9% in males vs. 2.0% in females; p\u0026thinsp;\u0026lt;\u0026thinsp;0.001, OR\u0026thinsp;=\u0026thinsp;4.23). A history of transient ischemic attack (TIA) was reported in 11.5% of all patients, with a slightly higher frequency in females (15.0% vs. 9.4%) (p\u0026thinsp;=\u0026thinsp;0.005, OR\u0026thinsp;=\u0026thinsp;0.59). Ischemic heart disease (IHD) was more common in males (8.3%) than in females (5.8%). Valvular heart disease, on the other hand, was more frequently reported in females (5.5%) than in males (2.8%) (p\u0026thinsp;=\u0026thinsp;0.027, OR\u0026thinsp;=\u0026thinsp;0.50). Other comorbidities such as dyslipidemia (10.2%), chronic kidney disease (4.5%), active malignancy (0.7%), and carotid artery disease (9.1%) were distributed relatively evenly between the two sexes (Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e).\u003c/p\u003e\u003cp\u003eAmong 953 patients with documented time of stroke onset and presentation, the distribution of presentation time windows was similar between males and females. A total of 26.4% of males and 27.2% of females presented within the critical 0\u0026ndash;4.5-hour window, resulting in an odds ratio (OR) of 0.96 for males compared to females, indicating no significant gender difference in early presentation. In the 4.5\u0026ndash;12-hour window, both sexes presented at equal proportions (16.6% each), yielding an OR of 1.00. For the 12\u0026ndash;24-hour window, 28.5% of males and 25.6% of females presented within this range, with an OR of 1.16, suggesting a marginally higher\u0026mdash;but not substantial\u0026mdash;likelihood for males to present during this period. Conversely, 28.5% of males and 30.5% of females presented after 24 hours of stroke onset (OR 0.91), again showing no meaningful sex-based difference in delayed presentation. The overall comparison of time-to-presentation across categories showed no significant sex difference (p\u0026thinsp;=\u0026thinsp;0.788) (Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e).\u003c/p\u003e\u003cp\u003e\u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab2\" border=\"1\"\u003e\u003ccaption language=\"En\"\u003e\u003cdiv class=\"CaptionNumber\"\u003eTable 2\u003c/div\u003e\u003cdiv class=\"CaptionContent\"\u003e\u003cp\u003eAssociation Between Sex and Time to Presentation with Stroke Onset and Receipt of IV Thrombolysis (r-tPA)\u003c/p\u003e\u003c/div\u003e\u003c/caption\u003e\u003ccolgroup cols=\"4\"\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e\u003cthead\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c1\"\u003e\u003cp\u003eVariable / Time window\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c2\"\u003e\u003cp\u003eMale (N\u0026thinsp;=\u0026thinsp;586)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c3\"\u003e\u003cp\u003eFemale (N\u0026thinsp;=\u0026thinsp;367)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c4\"\u003e\u003cp\u003ep-value\u003c/p\u003e\u003c/th\u003e\u003c/tr\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c1\"\u003e\u003cp\u003eTime to Presentation\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/th\u003e\u003cth align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/th\u003e\u003cth align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/th\u003e\u003c/tr\u003e\u003c/thead\u003e\u003ctbody\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e0\u0026ndash;4.5 hours\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e155 (26.4%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e100 (27.2%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\" morerows=\"3\" rowspan=\"4\"\u003e\u003cp\u003e0.788**\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e4.5\u0026ndash;12 hours\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e97 (16.6%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e61 (16.6%)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e12\u0026ndash;24 hours\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e167 (28.5%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e94 (25.6%)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u0026gt;\u0026thinsp;24 hours\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e167 (28.5%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e112 (30.5%)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eOverall (time windows)\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e\u0026ndash;\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e\u0026ndash;\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eThrombolysis (r-tPA)\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e20 (3.41%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e7 (1.91%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0.218\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eDischarge mRS* (mean\u0026thinsp;\u0026plusmn;\u0026thinsp;SD)\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e2.27\u0026thinsp;\u0026plusmn;\u0026thinsp;1.41\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e2.45\u0026thinsp;\u0026plusmn;\u0026thinsp;1.41\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0.178\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003c/tbody\u003e\u003c/colgroup\u003e\u003ctfoot\u003e\u003ctr\u003e\u003ctd colspan=\"4\"\u003e*mRS\u0026thinsp;=\u0026thinsp;Modified Rankin Scale at discharge; mRS \u003cem\u003ep\u003c/em\u003e-value from independent samples \u003cem\u003et\u003c/em\u003e-test (continuous outcome).\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd colspan=\"4\"\u003e**Time-to-presentation \u003cem\u003ep\u003c/em\u003e-value represents the \u003cb\u003eoverall chi-square test\u003c/b\u003e comparing distribution across all time windows.\u003c/td\u003e\u003c/tr\u003e\u003c/tfoot\u003e\u003c/table\u003e\u003c/div\u003e\u003c/p\u003e\u003cp\u003eDespite over a quarter of patients presenting within the intravenous thrombolysis treatment window, only 27 patients (2.8%) received rt-PA overall. Of these, 20 were males (3.4%) and 7 were females (1.9%), with an odds ratio of 1.82 for males compared to females. This difference was not statistically significant (p\u0026thinsp;=\u0026thinsp;0.218) (Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e).\u003c/p\u003e\u003cp\u003eAt discharge, the mRS score was 2.27\u0026thinsp;\u0026plusmn;\u0026thinsp;1.41 for males and 2.45\u0026thinsp;\u0026plusmn;\u0026thinsp;1.41 for females, with no significant difference between the sexes (p\u0026thinsp;=\u0026thinsp;0.178) (Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e).\u003c/p\u003e\u003cp\u003eOverall, significant sex differences were observed in age, hypertension, atrial fibrillation, smoking status, history of TIA, and valvular heart disease, while other comorbidities, time-to-presentation, thrombolysis rates, and discharge mRS did not differ significantly.\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eOur study presents several clinically relevant findings. We found that hypertension (83.0% vs 76.4% in males, p\u0026thinsp;=\u0026thinsp;0.011) and atrial fibrillation (15.0% vs 7.3% in males, p\u0026thinsp;\u0026lt;\u0026thinsp;0.001) were more prevalent in females. This metric is consistent with findings in the current literature, implicating these comorbidities as presenting a greater risk of stroke in women as compared to men. A recent meta-analysis of 30 cohort studies found that AF had almost double the relative risk of stroke (RR\u0026thinsp;=\u0026thinsp;1.99; 95% CI: 1.46\u0026ndash;2.71) in females as compared to males, while a pooled analysis of outcomes reported a 2-4.5 times higher risk of stroke in women, after adjusting for various risk factors(\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e, \u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e). A more recent study in Denmark, however, argued that over the last two decades, the risk of stroke among patients with AF, and the excess risk seen in female patients, have both declined(\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e). Hypertension, too, has been shown to increase the risk for stroke in the female gender when compared with their male counterparts. A study conducted in 2020 reported that even slight increases in systolic blood pressure above 120mmHg in women disproportionately increase the chances of stroke, compared to a lower relative risk for comparable thresholds in men(\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e). A review found that a 10mmHg increase in systolic blood pressure can elevate the risk of ischemic stroke in women by 38%(\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e). The pathophysiology of these increased risks involves both structural and functional differences between the two genders\u0026rsquo; cardiovascular systems. Smaller vessel diameters and increased arterial stiffness in women can amplify the hemodynamic effects of increased blood pressure to a greater extent in women. Furthermore, menopause brings with it a decrease in circulating estrogen, resulting in a loss of its Vaso protective effects and causing greater endothelial dysfunction and vascular inflammation(\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e).\u003c/p\u003e\u003cp\u003eWe also found that women were significantly older at presentation (64.5 vs 61.1 years, p\u0026thinsp;=\u0026thinsp;0.0001) and had higher stroke severity on admission, reflected by NIHSS scores (7.9 vs 6.3, p\u0026thinsp;\u0026lt;\u0026thinsp;0.0001). These findings are in line with prior reports suggesting that female patients present later in life and with greater neurological deficits(\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e).\u003c/p\u003e\u003cp\u003eIn light of these findings, prioritizing early detection, optimized AF management, and aggressive Blood Pressure control in women is essential to reducing sex-based disparities in stroke incidence and outcomes.\u003c/p\u003e\u003cp\u003eSmoking and history of Myocardial Infarction (MI), on the other hand, were more prevalent among men in our cohort, presenting in 20.6% (vs 3.0% in women, p\u0026thinsp;\u0026lt;\u0026thinsp;0.001) and 8.3% (vs 5.8% in women, p\u0026thinsp;=\u0026thinsp;0.120) of men, respectively. While the difference in smoking was highly significant, the difference in myocardial infarction was not. These findings, too, are consistent with the current literature. Studies have demonstrated that men carry a greater atherosclerotic burden and account for a greater percentage of unstable plaque morphology. A meta-analysis of 42 studies found that men not only had a larger plaque as compared to women, they also had greater incidences of ulcerated plaques, intra-plaque hemorrhages, calcifications, and lipid-rich necrotic cores(\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e). These anatomical and pathological differences likely explain the higher rate of ischemic stroke in male patients with these comorbidities. Smoking has also been established as a very important risk factor for the development of stroke, with smokers attributed to having a 1.92-fold greater risk of stroke when compared to non-smokers. Although a study found that the stroke risk from smoking was comparable in both genders, the baseline smoking population in men is significantly higher, thus driving increased population-level exposure to risk(\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e, \u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e). These findings further highlight the need to develop sex-specific preventative strategies focusing on high-risk male populations to tackle the elevated risk of stroke in susceptible men.\u003c/p\u003e\u003cp\u003eTime from stroke onset to hospital presentation is also a very significant marker indicating pre-hospital delays. A Denmark registry analysis reported that women had longer pre-hospital delays as compared to men despite similar transport distances, primarily attributed to a greater percentage of women living alone(\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e). Furthermore, 4 cohorts from Asian Pacific and American studies also reported greater pre-hospital delays in women, which were associated with minority ethnicities, older age, and underuse of Emergency Medical Services(\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e). In contrast to the above literature, our study found no significant gender differences in the time from symptom onset to hospital presentation (p\u0026thinsp;=\u0026thinsp;0.788). This finding is also mirrored in a population-based US study, which reported no significant difference in prehospital delays amongst genders, highlighting that sex gaps are not universal(\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e).\u003c/p\u003e\u003cp\u003eUnderstanding the role of gender disparity in healthcare is even more critical in a lower-middle-income country like Pakistan, where the healthcare infrastructure is severely overburdened and underequipped, and access to care is limited. Regardless of gender, local literature has shown substantial prehospital delays \u0026ndash; only 21% of ischemic stroke patients in a multicenter study arrived within three hours(\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e). The etiology for this is likely multifaceted, including low awareness, lack of appropriate diagnoses, socioeconomic status, and shortages of dedicated stroke units (\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e). Within an already crippling healthcare system, women represent an even further marginalized community that faces additional barriers to equitable healthcare. Sociocultural norms, reliance on elder family members, and lower rates of EMS use all contribute to a delay in seeking care for women(\u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e).\u003c/p\u003e\u003cp\u003eTaking into account the disparities that women face, both in healthcare and otherwise, it is imperative that further research is done to truly understand the trends of prehospital delay for stroke care across genders. It is very much possible that the absence of a sex gap in our cohort is not indicative of a universal trend but rather masks sex differences due to differing local community norms or awareness levels.\u003c/p\u003e\u003cp\u003eAlthough arrival times were similar, our study found that men had higher odds of receiving rt-PA as compared to women (2.97% vs 1.75%, OR 1.82, p\u0026thinsp;=\u0026thinsp;0.218), but this finding did not reach statistical significance. These findings are not only in line with global literature but also with the trends of gender disparity in Pakistan. A meta-analysis done in 2009 reported that women had 30% lower odds of receiving rt-PA as compared to men(\u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e). Other studies echo these findings \u0026ndash; reporting Odds Ratios of 0.80 and 0.91 for women receiving thrombolytics as compared to men(\u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e, \u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e). Clinician bias, greater underlying disability, uncommon presentations, and atypical symptom onset are all possible reasons for the above findings(\u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e). Thus, our findings suggest that in-hospital treatment decision-making may contribute more to treatment disparity than prehospital delays, but larger studies are required to confirm this.\u003c/p\u003e\u003cp\u003eOur study poses several limitations. The single-center design could limit the generalizability of our results to the broader Pakistani demographic, as awareness, access to healthcare, and treatment guidelines can differ significantly across regions. Additionally, the low number of patients who received rt-PA limits the ability to draw strong, gender-specific conclusions despite an apparent numerical disparity. Since there is a dearth of published literature on this topic, specifically in the context of LMICS, larger multi-center cohorts should be conducted to validate our findings.\u003c/p\u003e"},{"header":"Conclusion","content":"\u003cp\u003eStroke remains a leading cause of disability and mortality in Pakistan, with the lackluster healthcare infrastructure unable to cope with its devastating effects. In evaluating the gender disparities amongst patients presenting with stroke, our data aligned with global evidence regarding risk factors: smoking and atherosclerotic disease were more significant risk factors for men, whilst hypertension and atrial fibrillation proved to pose greater risk for women. We, however, found no significant gender disparity in time from symptom onset to hospital presentation. Although the odds of men receiving thrombolysis were nearly twice those of women, this difference did not reach statistical significance, likely reflecting the limited number of patients who received thrombolysis. In an LMIC like Pakistan, where women represent a marginalized community and the healthcare system is crippling, it is critical that more research is done to elucidate the role of gender disparity in stroke presentation and treatment, and targeted interventions are formulated to reduce the burden of this frightening disease.\u003c/p\u003e"},{"header":"Abbreviations","content":"\u003cdiv class=\"DefinitionList\"\u003e\u003cdiv class=\"DefinitionListEntry\"\u003e\u003cdiv class=\"Term\"\u003eLMICs\u003c/div\u003e\u003cdiv class=\"Description\"\u003e\u003cp\u003eLow\u0026ndash;and Middle\u0026ndash;Income Countries\u003c/p\u003e\u003c/div\u003e\u003c/div\u003e\u003cdiv class=\"DefinitionListEntry\"\u003e\u003cdiv class=\"Term\"\u003ert\u003c/div\u003e\u003cdiv class=\"Description\"\u003e\u003cp\u003ePA\u0026ndash;Recombinant Tissue Plasminogen Activator\u003c/p\u003e\u003c/div\u003e\u003c/div\u003e\u003cdiv class=\"DefinitionListEntry\"\u003e\u003cdiv class=\"Term\"\u003eNIHSS\u003c/div\u003e\u003cdiv class=\"Description\"\u003e\u003cp\u003eNational Institutes of Health Stroke Scale\u003c/p\u003e\u003c/div\u003e\u003c/div\u003e\u003cdiv class=\"DefinitionListEntry\"\u003e\u003cdiv class=\"Term\"\u003eAF\u003c/div\u003e\u003cdiv class=\"Description\"\u003e\u003cp\u003eAtrial Fibrillation\u003c/p\u003e\u003c/div\u003e\u003c/div\u003e\u003cdiv class=\"DefinitionListEntry\"\u003e\u003cdiv class=\"Term\"\u003eOR\u003c/div\u003e\u003cdiv class=\"Description\"\u003e\u003cp\u003eOdds Ratio\u003c/p\u003e\u003c/div\u003e\u003c/div\u003e\u003cdiv class=\"DefinitionListEntry\"\u003e\u003cdiv class=\"Term\"\u003eTIA\u003c/div\u003e\u003cdiv class=\"Description\"\u003e\u003cp\u003eTransient Ischemic Attack\u003c/p\u003e\u003c/div\u003e\u003c/div\u003e\u003cdiv class=\"DefinitionListEntry\"\u003e\u003cdiv class=\"Term\"\u003eIHD\u003c/div\u003e\u003cdiv class=\"Description\"\u003e\u003cp\u003eIschemic Heart Disease\u003c/p\u003e\u003c/div\u003e\u003c/div\u003e\u003cdiv class=\"DefinitionListEntry\"\u003e\u003cdiv class=\"Term\"\u003emRS\u003c/div\u003e\u003cdiv class=\"Description\"\u003e\u003cp\u003eModified Rankin Scale\u003c/p\u003e\u003c/div\u003e\u003c/div\u003e\u003cdiv class=\"DefinitionListEntry\"\u003e\u003cdiv class=\"Term\"\u003eMI\u003c/div\u003e\u003cdiv class=\"Description\"\u003e\u003cp\u003eMyocardial Infarction\u003c/p\u003e\u003c/div\u003e\u003c/div\u003e\u003c/div\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eEthics approval and consent to participate\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis study was reviewed and approved by the Aga Khan University Hospital Institutional Ethical Review Committee. The study was granted exemption from full ethical review (ERC Reference: 5322 – Med – ERC - 18). The requirement for informed consent to participate was waived by the committee.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eThe study was conducted in accordance with the ethical standards of the institutional research committee and with the 1964 Helsinki Declaration and its later amendments.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent for publication\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNot applicable. This manuscript does not contain any individual person’s data in any form (including images, videos, or identifiable personal details).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAvailability of data and materials\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe datasets generated and/or analyzed during the current study are not publicly available due to hospital policy and patient confidentiality restrictions, but are available from the corresponding author on reasonable request.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCompeting interests\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors declare that they have no competing interests.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding Sources\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNone.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthor Contributions:\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eConceptualization, Methodology: SF, MW\u003c/p\u003e\n\u003cp\u003eInvestigation (data collection): SF, SS\u003c/p\u003e\n\u003cp\u003eFormal analysis, Validation: SSa, NA\u003c/p\u003e\n\u003cp\u003eVisualization (tables): MI\u003c/p\u003e\n\u003cp\u003eWriting – original draft: SS, MI\u003c/p\u003e\n\u003cp\u003eWriting – review \u0026amp; editing: MI, SS, MW, SF, SSa, NAA\u003c/p\u003e\n\u003cp\u003eSupervision, Project administration: MW\u003c/p\u003e\n\u003cp\u003eAll authors have read and approved the final manuscript.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAcknowledgements\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNone.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eFarooq A, Venketasubramanian N, Wasay M. Stroke Care in Pakistan. Cerebrovasc Dis Extra. 2021;11(3):118\u0026ndash;21.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eKhealani BA, Hameed B, Mapari UU. Stroke in Pakistan. J Pak Med Assoc. 2008;58(7):400\u0026ndash;3.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eFarooq MU, Majid A, Reeves MJ, Birbeck GL. The epidemiology of stroke in Pakistan: past, present, and future. Int J Stroke. 2009;4(5):381\u0026ndash;9.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eJaved S, Zaidi DA, Yaqoob E. Addressing the deficiencies in stroke care in Pakistan. Lancet. 2024;404(10453):651\u0026ndash;2.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eKhealani BA, Khan M, Tariq M, Malik A, Siddiqi AI, Awan S, et al. Ischemic strokes in Pakistan: observations from the national acute ischemic stroke database. J Stroke Cerebrovasc Dis. 2014;23(6):1640\u0026ndash;7.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eO'Donnell MJ, Chin SL, Rangarajan S, Xavier D, Liu L, Zhang H, et al. Global and regional effects of potentially modifiable risk factors associated with acute stroke in 32 countries (INTERSTROKE): a case-control study. Lancet. 2016;388(10046):761\u0026ndash;75.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eFarooq A, Ahmed S, Wasay M. Acute Stroke Care in Pakistan. J Coll Physicians Surg Pak. 2022;32(6):695\u0026ndash;6.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eBrott T, Adams HP Jr., Olinger CP, Marler JR, Barsan WG, Biller J, et al. Measurements of acute cerebral infarction: a clinical examination scale. Stroke. 1989;20(7):864\u0026ndash;70.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003evan Swieten JC, Koudstaal PJ, Visser MC, Schouten HJ, van Gijn J. Interobserver agreement for the assessment of handicap in stroke patients. Stroke. 1988;19(5):604\u0026ndash;7.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eCamm AJ, Savelieva I. Female gender as a risk factor for stroke associated with atrial fibrillation. Eur Heart J. 2017;38(19):1480\u0026ndash;4.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eEmdin CA, Wong CX, Hsiao AJ, Altman DG, Peters SA, Woodward M, et al. Atrial fibrillation as risk factor for cardiovascular disease and death in women compared with men: systematic review and meta-analysis of cohort studies. BMJ. 2016;532:h7013.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eNielsen PB, Br\u0026oslash;ndum RF, N\u0026oslash;hr AK, Overvad TF, Lip GYH. Risk of stroke in male and female patients with atrial fibrillation in a nationwide cohort. Nat Commun. 2024;15(1):6728.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eJi H, Kim A, Ebinger JE, Niiranen TJ, Claggett BL, Bairey Merz CN, et al. Sex Differences in Blood Pressure Trajectories Over the Life Course. JAMA Cardiol. 2020;5(3):255\u0026ndash;62.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eGorgui J, Gorshkov M, Khan N, Daskalopoulou SS. Hypertension as a risk factor for ischemic stroke in women. Can J Cardiol. 2014;30(7):774\u0026ndash;82.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eJi H, Niiranen TJ, Rader F, Henglin M, Kim A, Ebinger JE, et al. Sex Differences in Blood Pressure Associations With Cardiovascular Outcomes. Circulation. 2021;143(7):761\u0026ndash;3.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eDi Carlo A, Lamassa M, Baldereschi M, Pracucci G, Basile AM, Wolfe CD, et al. Sex differences in the clinical presentation, resource use, and 3-month outcome of acute stroke in Europe: data from a multicenter multinational hospital-based registry. Stroke. 2003;34(5):1114\u0026ndash;9.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003evan Dam-Nolen DHK, van Egmond NCM, Koudstaal PJ, van der Lugt A, Bos D. Sex Differences in Carotid Atherosclerosis: A Systematic Review and Meta-Analysis. Stroke. 2023;54(2):315\u0026ndash;26.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003ePan B, Jin X, Jun L, Qiu S, Zheng Q, Pan M. The relationship between smoking and stroke: A meta-analysis. Med (Baltim). 2019;98(12):e14872.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eRitchie H. Who smokes more, men or women?2019 8/14/2025; \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003eOurWorldinData.org\u003c/span\u003e\u003cspan address=\"http://OurWorldinData.org\" targettype=\"URL\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eMainz J, Andersen G, Valentin JB, Gude MF, Johnsen SP. Disentangling Sex Differences in Use of Reperfusion Therapy in Patients With Acute Ischemic Stroke. Stroke. 2020;51(8):2332\u0026ndash;8.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003ePotisopha W, Vuckovic KM, DeVon HA, Park CG, Hershberger PE. Sex Differences in Prehospital Delay in Patients With Acute Stroke: A Systematic Review. J Cardiovasc Nurs. 2020;35(6):E77\u0026ndash;88.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eMadsen TE, Sucharew H, Katz B, Alwell KA, Moomaw CJ, Kissela BM, et al. Gender and Time to Arrival among Ischemic Stroke Patients in the Greater Cincinnati/Northern Kentucky Stroke Study. J Stroke Cerebrovasc Dis. 2016;25(3):504\u0026ndash;10.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eKamal AK, Khealani BA, Ansari SA, Afridi M, Syed NA. Early Ischemic Stroke Presentation in Pakistan. Can J Neurol Sci / J Canadien des Sci Neurologiques. 2009;36(2):181\u0026ndash;6.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eShaikh BT, Hatcher J. Health seeking behaviour and health service utilization in Pakistan: challenging the policy makers. J Public Health (Oxf). 2005;27(1):49\u0026ndash;54.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eBushnell CD, Chaturvedi S, Gage KR, Herson PS, Hurn PD, Jim\u0026eacute;nez MC, et al. Sex differences in stroke: Challenges and opportunities. J Cereb Blood Flow Metab. 2018;38(12):2179\u0026ndash;91.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003ede Ridder I, Dirks M, Niessen L, Dippel D. Unequal access to treatment with intravenous alteplase for women with acute ischemic stroke. Stroke. 2013;44(9):2610\u0026ndash;2.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eLiu M, Li G, Tang J, Liao Y, Li L, Zheng Y, et al. The Influence of Sex in Stroke Thrombolysis: A Systematic Review and Meta-Analysis. J Clin Neurol. 2018;14(2):141\u0026ndash;52.\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"bmc-neurology","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"nurl","sideBox":"Learn more about [BMC Neurology](http://bmcneurol.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/nurl","title":"BMC Neurology","twitterHandle":"BMC_series","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"em","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"Stroke, Gender disparities, Pakistan","lastPublishedDoi":"10.21203/rs.3.rs-7499935/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-7499935/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003eBackground:\u003c/h2\u003e\u003cp\u003eThe growing stroke burden in Pakistan, particularly in rural populations, poses a serious challenge to the already strained healthcare system. Pakistan currently ranks fifth in the global stroke burden. The absence of population-based studies has limited data on stroke etiology, risk factors, and hyperacute management practices. This study aimed to compare risk factor profiles of male and female stroke patients and assess gender differences in time-to-presentation at a private tertiary care hospital.\u003c/p\u003e\u003ch2\u003eMethods:\u003c/h2\u003e\u003cp\u003eThis retrospective, cross-sectional study was conducted at Aga Khan University Hospital from January 2016 to December 2018. Patients with ischemic or hemorrhagic stroke were included. De-identified clinical and radiological data, including demographics, vascular risk factors, and treatment details, were analyzed using chi-square and t‐tests, with odds ratios (ORs) calculated where appropriate.\u003c/p\u003e\u003ch2\u003eResults:\u003c/h2\u003e\u003cp\u003eOf 1,074 patients, 674 (62.7%) were male and 400 (37.2%) female. Females were older (64.5 vs. 61.1 years, p\u0026thinsp;\u0026lt;\u0026thinsp;0.001) and had higher admission stroke severity (NIHSS 7.9 vs. 6.3, p\u0026thinsp;\u0026lt;\u0026thinsp;0.001). Hypertension and atrial fibrillation were more common in females (83.0% vs. 76.4%, p\u0026thinsp;=\u0026thinsp;0.011; 15.0% vs. 7.3%, p\u0026thinsp;\u0026lt;\u0026thinsp;0.001), whereas smoking was predominantly male (20.6% vs. 3.0%, p\u0026thinsp;\u0026lt;\u0026thinsp;0.001). Time-to-presentation did not differ significantly (p\u0026thinsp;=\u0026thinsp;0.788), with about one-quarter arriving within 4.5 hours. Despite this, only 27 patients (2.8%) received r-tPA, more often men than women (20 vs. 7; OR 1.82, p\u0026thinsp;=\u0026thinsp;0.218). Discharge mRS scores were similar (p\u0026thinsp;=\u0026thinsp;0.178).\u003c/p\u003e\u003ch2\u003eConclusion:\u003c/h2\u003e\u003cp\u003eSex differences were evident in age, stroke severity, hypertension, atrial fibrillation, and smoking, while time-to-presentation and outcomes were comparable. Despite similar time-to-presentation, fewer women received thrombolysis. These findings mirror global literature, where women present older and with greater severity, while men carry higher lifestyle-related risks. Improving awareness, early detection, and equitable access to hyperacute therapies are essential to addressing these disparities in Pakistan\u0026rsquo;s overburdened healthcare system, and developing sex-specific strategies may improve both prevention and treatment outcomes.\u003c/p\u003e","manuscriptTitle":"Gender Disparities in Stroke Risk Profiles: A Single Centre Observational Study","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-10-22 14:15:41","doi":"10.21203/rs.3.rs-7499935/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"reviewerAgreed","content":"64876255853315127468241790726755228192","date":"2025-10-10T08:47:39+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"297295472758922774670564191902838541888","date":"2025-10-09T09:15:01+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2025-10-09T08:47:59+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2025-10-07T17:02:46+00:00","index":"","fulltext":""},{"type":"editorInvited","content":"","date":"2025-09-15T19:07:20+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2025-09-11T16:15:01+00:00","index":"","fulltext":""},{"type":"submitted","content":"BMC Neurology","date":"2025-09-11T16:11:59+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"bmc-neurology","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"nurl","sideBox":"Learn more about [BMC Neurology](http://bmcneurol.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/nurl","title":"BMC Neurology","twitterHandle":"BMC_series","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"em","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"b465066d-9264-4a9e-ab32-f4b412981f51","owner":[],"postedDate":"October 22nd, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"under-review","subjectAreas":[],"tags":[],"updatedAt":"2025-10-22T14:15:41+00:00","versionOfRecord":[],"versionCreatedAt":"2025-10-22 14:15:41","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-7499935","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-7499935","identity":"rs-7499935","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}