Browsing by Author "Ahmed, Sofia"

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    An Intersectional Approach to Addressing Discrimination Among Pregnant Individuals in a Contemporary Population: A Cross-Sectional Study
    (2024-09-25) Dharamsi, Shazia; Metcalfe, Amy; Ahmed, Sofia; Ruzycki, Shannon
    Background: Pregnant individuals may be vulnerable to discrimination due to existing social stigma and cultural norms surrounding pregnancy and motherhood, which can be exacerbated due to gender, race, or other aspects of their identity; however, it is unclear how intersecting identities overlap and interact to shape peoples’ everyday experiences. The purpose of this study was to compare the prevalence and experiences of discrimination among pregnant individuals with diverse intersectional identities. Methods: This secondary analysis used baseline data from 1,605 participants enrolled in a longitudinal pregnancy cohort study, the P3 Cohort Study. Latent class analysis was applied to identify different subgroups within the population based on combinations of their social positions and identities (i.e., race, gender expression, emotional health, physical health, income, disability, chronic illness, and age). Perceived discrimination was assessed via the Everyday Discrimination Scale (EDS), and linear regression was performed to compare the frequency, chronicity, and overall number of discriminatory encounters between subgroups. Results: Utilizing latent class analysis, the following three subgroups emerged: (1) Mostly Privileged and Healthy; (2) Somewhat Privileged with Chronic Conditions; (3) Somewhat Privileged, Predominantly Racialized. Class 2 (βfrequency = 0.8, p = 0.042; βchronicity = 45.2, p < 0.001; βsituations = 0.4, p = 0.040) and Class 3 (βfrequency = 0.2, p < 0.001; βchronicity = 31.5, p < 0.001; βsituations = 0.5, p < 0.001) were both positively associated with the frequency, chronicity, and total number of discrimination situations relative to Class 1. The primary reported reasons underlying discrimination experiences varied across latent classes, reflecting the intersecting identities that defined each cluster.
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    Evaluating the Association between Estradiol and Quality of Life and Cardiovascular Risk and Mortality in Healthy Women and Women with Chronic Kidney Disease
    (2016) Ramesh, Sharanya; Ahmed, Sofia; Wilton, Stephen; James, Matthew; Holroyd-Leduc, Jayna
    Chronic kidney disease (CKD) is associated with a poor quality of life and high risk of cardiovascular (CV) mortality, specifically sudden cardiac death (SCD), and an upregulated renin angiotensin system. Women with end stage kidney disease (ESKD) experience premature menopause, and in healthy women menopause is correlated with a poor quality of life and higher CV mortality. A series of studies was conducted in healthy women and women with CKD to determine the associations between menopause status, serum estradiol and 1) cardiac autonomic tone (CAT), a surrogate marker for SCD, in a high Angiotensin II (AngII) state 2) mortality in women with ESKD and 3) quality of life(QoL) in women with CKD. We also summarized the impressions of healthcare workers and patients on the discussion of symptoms of low sex hormones in a clinical setting. In healthy men and women, sex hormones did not correlate with baseline CAT; however, men with lower testosterone levels were unable to maintain CAT in response to AngII. At baseline, postmenopausal women had a lower CAT in comparison to premenopausal women. In response to AngII postmenopausal women and premenopausal women in the luteal phase were unable to maintain their CAT. Through a survey of nephrologists we found that nephrologists recognize the impact of CKD on sex hormones in women but report infrequently discussing sex hormone related issues with patients. In a systematic review of studies examining the effect of postmenopausal hormone therapy on CV outcomes in women with ESKD, hormone therapy was associated with a favourable lipid profile. However, we found that peri- and premenopausal women with ESKD on hemodialysis had a higher risk of all-cause, cardiovascular and non-cardiovascular mortality compared to postmenopausal women. Furthermore menopause specific QoL scores did not correlate with kidney function in CKD women. We found that associations between menopause status and CV risk and QoL in the CKD population are complex. This body of work can be used for hypothesis generation for future studies and trials aimed to determine the mediators of cardiovascular risk and poor quality of life in this population.
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    Obstructive sleep apnea treatment with continuous positive airway pressure therapy improves renin angiotensin system activity
    (2012-08-28) Nicholl, David; Ahmed, Sofia
    Background Obstructive sleep apnea (OSA) is strongly associated with cardiorenal disease. Limited studies suggest that renin angiotensin system (RAS) activation may mediate this relationship. We sought to determine the effect of continuous positive airway pressure (CPAP) on the hemodynamic and circulating RAS component responses to Angiotensin II (AngII) infusion. Methods Twelve moderate-severe OSA subjects with hypoxia were studied in high-salt balance before and 1 month after starting treatment with CPAP. Mean arterial pressure (MAP), plasma renin activity (PRA), and aldosterone were measured in response to AngII (3ng/kg/minx30min, 6ng/kg/minx30min, 30min recovery). Results CPAP corrected OSA; reduced MAP (95±2 vs 89±2mmHg, p=0.019), aldosterone (179±27 vs 115±14pmol/L, p=0.006), and protein excretion (69[39,341] vs 48[22,204]mg/day, p=0.002); and increased MAP sensitivity to 3ng/kg/min AngII (10±2 vs 15±2mmHg, p=0.019), but not 6ng/kg/min AngII or recovery. RAS component sensitivity was unaffected. Conclusions CPAP treatment decreased RAS activity and increased hemodynamic sensitivity to AngII, supporting a role for the RAS in mediating OSA-induced hypertension.
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    Prenatal Exposure to a Low Dose of BPS Causes Sex-Dependent Alterations to Vascular Endothelial Function in Adult Offspring
    (2022-06) Connors, Liam; Thompson, Jennifer; Cole, William; Habibi, Hamid; Ahmed, Sofia
    Background: Bisphenol A (BPA) is among the world’s most ubiquitous industrial chemicals, used as a plasticizer in the manufacture of plastics and epoxy resins. Bisphenols interfere with estrogen receptor (ER) signaling, which modulates vascular function through stimulation of nitric oxide (NO) production by endothelial nitric oxide synthase (eNOS). After regulatory agencies declared BPA to be a toxic substance in 2010, manufacturers turned to substitutes such as bisphenol S (BPS). BPS can cross into the placenta, and it accumulates in the fetal compartment to a greater extent than BPA, potentially interfering with key developmental events. Little is known regarding the developmental impact of exposure to BPA analogues, particularly with respect to vascular development and later-life vascular function. Objective: To determine if prenatal BPS exposure influences vascular health in adulthood through modulation of NO production. Methods: Mesenteric arteries were excised from 12-week-old male and female C57BL/6 mice prenatally exposed to 250 nM BPS and mounted on a pressure myograph. Contractile and dilatory function was assessed by generating concentration-response curves to phenylephrine (Phe) and the endothelium-dependent dilator, acetylcholine (ACh). Wire myography was used to assess dilatory responses of aortic rings after acute exposure to BPS in the bath in the presence or absence of pharmacological inhibitors of eNOS and ER. Results: Vessels isolated from prenatally-exposed males did not exhibit changes in their dilatory or contractile responses. Whereas increased ACh dilation and increased sensitivity to Phe were observed in microvessels from female BPS-exposed mice. The increase in dilation was blocked by inhibition of eNOS. Aortic rings isolated from female mice and acutely exposed to BPS had increased dilatory responses to ACh that were eliminated with inhibition of eNOS or ER. Conclusions: Prenatal BPS exposure leads to endothelium-dependent alterations of vascular function in a sex-specific manner that appears to be modulated by interaction with ER.
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    Public perceptions during the first wave of the COVID-19 pandemic in Canada: a demographic analysis of self-reported beliefs, behaviors, and information acquisition
    (2022-04-09) Leigh, Jeanna P.; Brundin-Mather, Rebecca; Soo, Andrea; FitzGerald, Emily; Mizen, Sara; Dodds, Alexandra; Ahmed, Sofia; Burns, Karen E. A.; Plotnikoff, Kara M.; Rochwerg, Bram; Perry, Jeffrey J.; Benham, Jamie L.; Honarmand, Kimia; Hu, Jia; Lang, Raynell; Stelfox, Henry T.; Fiest, Kirsten
    Abstract Introduction We explored associations between sociodemographic factors and public beliefs, behaviors, and information acquisition related to the coronavirus disease 2019 (COVID-19) to identify how the experiences of subpopulations in Canada may vary. Methods We administered a national online survey through Ipsos Incorporated to adults residing in Canada. Sampling was stratified by population age, sex, and regional distributions. We used descriptive statistics to summarize responses and test for differences based on gender, age, educational attainment, and household income using chi-squared tests, followed by weighted logistic regression. Results We collected 1996 eligible questionnaires between April 26th and May 1st, 2020. Respondents mean age was 50 years, 51% were women, 56% had a post-secondary degree, and 72% had a household income <$100,000. Our analysis found differences within the four demographic groups, with age effects most acutely evidenced. Respondents 65 years and older were more likely to perceive the pandemic as very serious, less likely to report declines in overall health, and more likely to intend to get vaccinated, compared to 18–29 year olds. Women overall were more likely to report negative outcomes than men, including stress due to the pandemic, and worsening social, mental/emotional, and spiritual health. Respondents 45 and older were more likely to seek and trust information from traditional Canadian news sources, while 18-29 year olds were more likely to seek and trust information on social media; overall, women and respondents with a post-secondary degree were more likely to access and trust online information from public health sites. Conclusion This study found important demographic differences in how adults living in Canada perceived the COVID-19 pandemic, the impacts on their health, and their preferences for information acquisition. Our results highlight the need to consider demographic characteristics in tailoring the format and information medium to improve large scale acceptance and uptake of mitigation and containment measures.
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    Reproductive Health and Contraception in Females with Chronic Kidney Disease
    (2022-06-03) Chang, Danica; Ahmed, Sofia; Dumanski, Sandra; Brennand, Erin; Ruzycki, Shannon
    Background: Chronic kidney disease (CKD) is a global epidemic that affects >13% of the population worldwide. Abnormal uterine bleeding is common in CKD, but most studies are limited to the kidney failure population. Abnormal menstruation is associated with cardiovascular risk, despite CKD already being a risk factor for cardiovascular disease. Pregnancy is known to be risky in CKD, therefore, contraception is paramount to prevent unplanned pregnancies in this reproductive-aged population; however, existing literature, though limited to the dialysis and transplant populations, has found that contraceptive use is low. Objectives: Using two separate yet complementary studies, we had multiple objectives. Project 1 aimed to describe self-assessed menstruation and contraceptive use among females across all stages of CKD using a global online survey. Project 2 aimed to (1) describe menstruation and changes in menstrual patterns with CKD progression, and (2) assess associations between reproductive hormones and menstrual patterns among females with kidney failure. Methods: In Project 1, females aged 18-50 years with a CKD diagnosis were invited to participate in an online survey. The survey was disseminated globally through 112 kidney organizations, patient groups, and social media. Whereas, in Project 2, females aged 18-50 years were recruited from dialysis clinics around Calgary, Alberta and completed a self-administered survey to capture demographic, kidney health, and menstrual health histories. Blood samples were also collected to measure the following reproductive hormone levels: follicle-stimulating hormone, luteinizing hormone, estradiol, progesterone, testosterone, prolactin, sex hormone binding globulin, and anti-Müllerian hormone. Results: Project 1 included 98 participants [n=20 dialysis (age 35±1 years), n=59 non-dialysis (age 32±1 years), n=19 transplant (age 35±2 years)]. One participant each in the dialysis and non-dialysis groups experienced primary amenorrhea, though more reported secondary amenorrhea (n=5 dialysis, n=9 non-dialysis, n=5 transplant). Of those experiencing current menses (n=14 dialysis, n=49 non-dialysis, n=14 transplant), 86%, 94%, and 100% of the dialysis, non-dialysis, and transplant groups reported heavy menstrual bleeding. Regarding, contraception, 50%, 63%, and 37% of dialysis, non-dialysis, and transplant participants reported no use, though among users, male condoms were notably popular in the dialysis (33%) and non-dialysis (48%) groups. Project 2 comprised of 27 females [n=23 hemodialysis (age 36 (IQR: 31,44) years), n=4 peritoneal dialysis (age 38 (IQR: 30,45) years)]. In the hemodialysis group, 52% reported absent menstrual bleeding during dialysis, though only 17% reported this during CKD and 9% before CKD diagnosis (p=0.01); however, there was no difference in proportions across timepoints in the peritoneal dialysis group. Further, in both groups, the prevalence of heavy menstrual bleeding was high, but did not differ throughout the progression of CKD. All the relevant hormone levels did not differ between those with absent and present menstrual bleeding, nor in those with heavy and normal menstrual bleeding. Conclusions: Together, these projects suggest that among the female CKD population, the prevalence of abnormal menstruation is high and contraception use is low, underscoring an important gap in the sex-specific care of this population. Given the lack of associations between hormone levels and menstrual status, we highlight the uncertainty around how kidney disease affects female reproductive health.
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    Sustained Hypoxia and the Renin Angiotensin System
    (2014) Zalucky, Ann; Ahmed, Sofia; Hanly, Patrick; Poulin, Marc
    Rationale: Chronic tissue hypoxia is considered to be the unifying pathway in chronic kidney disease (CKD) progression, yet the effect of systemic hypoxia as manifested in obstructive sleep apnea (OSA) is not well understood. Limited studies suggest OSA is associated with upregulation of the renin angiotensins system (RAS) a well described pathogenic factor renal dysfuction. We sought to determine the effect of nocturnal hypoxia on the hemodynamic and circulating response to angiotensin II (AngII) infusion. Methods: Thirty-one OSA patients (14 newly diagnosed; 17 from a historic cohort) and twelve obese controls were studied. Effective renal plasma flow (ERPF), determined by para-aminohippurate clearance technique, blood pressure (BP) and circulating components of the RAS (plasma renin activity (PRA) and aldosterone) were measured at baseline and in response to angiotensin-II (AngII) infusion. Patients were stratified according to hypoxia severity, into those with IH (mean nocturnal SaO2≥90%) and sustained hypoxia (SH, mean nocturnal SaO2<90%). Results: Patients with SH (P=0.015) and IH (P=0.01) had higher baseline filtration fractions (FF) than obese controls but circulating RAS components and BP were similar. The fall in ERPF in response to AngII, was less in patients with SH than IH and obese controls after both 3ng/kg/min (P=0.004) and 6ng/kg/min (P=0.001) reflecting greater renal RAS activity. There were no differences in the BP or PRA responses, but SH patients had a more robust aldosterone response to 6ng/kg/min AngII (p=0.023) than patients with IH. Conclusion: In patients with OSA, SH is associated with greater renal RAS activity than IH. OSA patients with this hypoxia profile may be more likely to experience the vascular consequences of elevated RAS activity such as hypertension and CKD.
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    The Effect of Controlled Ovarian Stimulation on Kidney Function
    (2024-07-14) Kharbanda, Sakshi; Dumanski, Sandra; Ahmed, Sofia; Foong, Shu
    Background: The global prevalence of chronic kidney disease (CKD) is >12% and prevention of CKD is a patient-identified research priority. Exogenous hormones are an important sex-specific risk factor for kidney health in females, however, it is yet unknown how the use of exogenous hormones in controlled ovarian stimulation (COS), commonly utilized in fertility treatment, effects kidney function. This study examined the effect of COS on kidney function outcomes, including measured glomerular filtration rate (mGFR) and albuminuria. Methods: Healthy females planning treatment with COS were recruited from the Regional Fertility Program in Calgary, Canada. Participants were studied immediately prior to initiation of COS treatment, as well as at the peak of COS. On each study day, iohexol was administered to the study participant and subsequent bloods draws were collected at time 60, 120, 150, 180, 210 and 240 minutes. Serum analysis for measurement of iohexol levels for each blood sample was used to calculate the mGFR. Albuminuria was measured via an albumin-creatinine ratio (ACR) in a spot urine sample. Changes in each outcome were assessed with Wilcoxon signed-rank tests. Results: Ten females initiating COS were recruited, with a median(IQR) age of 35(3) years. Most participants were nulliparous (70%), and no participants had a history of diabetes, hypertension, or CKD. Participants reported a wide variety of causes of infertility and 30% had been previously treated with COS treatment. No statistically significant changes in mGFR (p=0.13) and ACR (p=0.37) were identified during COS, though a trend towards an increase in mGFR and a decrease in ACR was demonstrated. Conclusion: Overall, treatment with COS did not result in any changes to kidney function, however this study is likely underpowered. Future studies with larger sample sizes are necessary to elucidate the effect of COS on kidney function, in order to optimize precision care in fertility treatment.
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    Vitamin D and cardiac autonomic tone: Cardiovascular implications in humans with and without chronic kidney disease
    (2015-05-20) Mann, Michelle Catherine; Ahmed, Sofia
    Vitamin D deficiency (<50nmol/L 25-hydroxy vitamin D) affects more than 1 billion people worldwide. Furthermore, cardiovascular disease (CVD) is a common cause of mortality globally. Observational studies have shown that vitamin D deficiency and CVD are associated, specifically in the chronic kidney disease (CKD) population whom are burdened with both increased risk of CVD-related death and vitamin D deficiency, though whether this relationship is causal in nature is not clear. Electrocardiogram recordings are used to quantify sympathetic and parasympathetic (vagal) control over the heart (cardiac autonomic tone, CAT), which has been shown to predict CVD-related outcomes. A series of studies was conducted across a range of populations with varying kidney function to assess the impact of vitamin D deficiency and supplementation on CAT. In healthy humans undergoing an angiotensin II (AngII) vascular stress test prior to vitamin D supplementation, subjects with low 1,25(OH)2 vitamin D experienced withdrawal of cardioprotective vagal tone and an upwards shift in overall cardiosympathovagal activity [(∆HF from baseline = -6.98±3, p=0.05; ∆LF:HF from baseline = 0.34±0.1, p=0.043 vs. above 25th percentile]. Following 4 weeks of oral vitamin D3 supplementation, vagal activity during the same AngII stressor was restored (∆HF from baseline 9.5±5 vs. -2.8±3, p=0.07 vs. pre-supplementation). The same study with vitamin D deficient IgA nephropathy (IgAN) subjects yielded similar results. The VITAH Trial then aimed to assess whether a causal relationship existed between activated vitamin D supplementation and CAT in end-stage kidney disease (ESKD) patients requiring hemodialysis. In contrast to healthy and IgAN subjects, six weeks of oral 1,25(OH)2 D supplementation (0.25mcg alfacalcidol 3x per week) or combined activated and nutritional supplementation (additional 50,000IU ergocalciferol 1x per week) enhanced cardiosympathovagal balance during hemodialysis in vitamin D deficient subjects (activated: n=13, ∆LF:HF: 0.20 ± 0.06, p<0.001 vs. ∆LF:HF in non-deficient; combined: n=8, deficient: ∆LF:HF: 0.15 ± 0.06, p<0.001 vs. ∆LF:HF in non-deficient). These novel findings indicate that vitamin D deficiency impairs the regulatory capabilities of the autonomic nervous system during vascular stress, and that vitamin D supplementation may mitigate the risk of CVD-related mortality in humans specifically in the setting of advanced CKD.