Differences In Cardiovascular Outcomes Research Articles

#83 Cardiovascular outcomes in home hemodialysis and peritoneal dialysis patients

Abstract Background and Aims Cardiovascular disease is the leading cause of morbidity and mortality in patients with end-stage kidney disease. Little is known about differences in cardiovascular outcomes between home hemodialysis (HHD) and peritoneal dialysis (PD). Methods We evaluated 68 645 patients who initiated home dialysis between 1/1/2005 and 12/31/2018 using the United States Renal Data System with linked Medicare claims. Rates for incident cardiovascular events of acute coronary syndrome, heart failure, and stroke hospitalizations were determined. Using adjusted time-to-event models, the associations of type of home dialysis modality with the outcomes of incident cardiovascular events, cardiovascular death, and all-cause death were examined. Results The mean age of patients in the study cohort was 64 ± 15 years, and 42.3% were women. Mean time of follow up was 1.8 ± 1.6 years. The unadjusted cardiovascular event rate was 95.1 per thousand person-years [PTPY] (95% CI, 93.6-96.8), with a higher rate in patients on HHD than on PD (127.8 PTPY; 95% CI, 118.9-137.2 vs. 93.3 PTPY; 95% CI, 91.5-95.1). However, HHD was associated with a slightly lower adjusted risk of cardiovascular events than PD (HR, 0.92; 95% CI, 0.85 to 0.997). Compared to PD patients, HHD patients had 42% lower adjusted risk of stroke (HR, 0.58; 95% CI, 0.48-0.71), 17% lower adjusted risk of acute coronary syndrome (HR, 0.83; 95% CI, 0.72-0.95), and no difference in risk of heart failure (HR, 1.05; 95% CI, 0.94-1.16). HHD was associated with 22% lower adjusted risk of cardiovascular death (HR, 0.78; 95% CI, 0.71-0.86) and 8% lower adjusted risk of all-cause death (HR, 0.92; 95% CI, 0.87-0.97) as compared to PD. Conclusion Relative to PD, HHD is associated with decreased risk of stroke, acute coronary syndrome, cardiovascular death, and all-cause death. Further studies are needed to better understand the factors associated with differences in cardiovascular outcomes by type of home dialysis modality in patients with kidney failure.

Sex Differences in Cardiovascular Outcomes in Patients With Kidney Failure.

Cardiovascular disease is the leading cause of mortality in patients with kidney failure, and their risk of cardiovascular events is 10 to 20 times higher as compared with the general population. We evaluated 508 822 patients who initiated dialysis between January 1, 2005 and December 31, 2014 using the United States Renal Data System with linked Medicare claims. We determined hospitalization rates for cardiovascular events, defined by acute coronary syndrome, heart failure, and stroke. We examined the association of sex with outcome of cardiovascular events, cardiovascular death, and all-cause death using adjusted time-to-event models. The mean age was 70±12 years and 44.7% were women. The cardiovascular event rate was 232 per thousand person-years (95% CI, 231-233), with a higher rate in women than in men (248 per thousand person-years [95% CI, 247-250] versus 219 per thousand person-years [95% CI, 217-220]). Women had a 14% higher risk of cardiovascular events than men (hazard ratio [HR], 1.14 [95% CI, 1.13-1.16]). Women had a 16% higher risk of heart failure (HR, 1.16 [95% CI, 1.15-1.18]), a 31% higher risk of stroke (HR, 1.31 [95% CI, 1.28-1.34]), and no difference in risk of acute coronary syndrome (HR, 1.01 [95% CI, 0.99-1.03]). Women had a lower risk of cardiovascular death (HR, 0.89 [95% CI, 0.88-0.90]) and a lower risk of all-cause death than men (HR, 0.96 [95% CI, 0.95-0.97]). Among patients undergoing dialysis, women have a higher risk of cardiovascular events of heart failure and stroke than men. Women have a lower adjusted risk of cardiovascular mortality and all-cause mortality.

Sex-Related Disparities in Cardiovascular Outcomes Among Older Adults With Late-Onset Hypertension.

It is unclear whether sex-based differences in cardiovascular outcomes exist in late-onset hypertension. This is a population-based cohort study in Ontario, Canada of 266 273 adults, aged ≥66 years with newly diagnosed hypertension. We determined the incidence of the primary composite cardiovascular outcome (myocardial infarction, stroke, and congestive heart failure), all-cause mortality, and cardiovascular death by sex using Cox proportional hazard models adjusted for demographic factors and comorbidities. The mean age of the total cohort was 74 years, and 135 531 (51%) were female. Over a median follow-up of 6.6 (4.7-9.0) years, females experienced a lower crude incidence rate (per 1000 person-years) than males for the primary composite cardiovascular outcome (287.3 versus 311.7), death (238.4 versus 251.4), and cardiovascular death (395.7 versus 439.6), P<0.001. The risk of primary composite cardiovascular outcome was lower among females (adjusted hazard ratio, 0.75 [95% CI, 0.73-0.76]; P<0.001) than in males. This was consistent after adjusting for the competing risk of all-cause death with a subdistributional hazard ratio, 0.88 ([95% CI, 0.86-0.91]; P<0.001). Females had a lower risk of cardiovascular outcomes compared with males within a population characterized by advanced age and new hypertension. Our results highlight that the severity of outcomes is influenced by sex in relation to the age at which hypertension is diagnosed. Further studies are required to identify sex-specific variations in the diagnosis and management of late-onset hypertension due to its high incidence in this group.

Cardiovascular Outcomes in Patients on Home Hemodialysis and Peritoneal Dialysis.

Cardiovascular disease is the leading cause of morbidity and mortality in patients with end-stage kidney disease. Little is known about differences in cardiovascular outcomes between home hemodialysis (HHD) and peritoneal dialysis (PD). We evaluated 68,645 patients who initiated home dialysis between 1/1/2005 and 12/31/2018 using the United States Renal Data System with linked Medicare claims. Rates for incident cardiovascular events of acute coronary syndrome, heart failure, and stroke hospitalizations were determined. Using adjusted time-to-event models, the associations of type of home dialysis modality with the outcomes of incident cardiovascular events, cardiovascular death, and all-cause death were examined. The mean age of patients in the study cohort was 64±15 years, and 42.3% were women. Mean time of follow up was 1.8±1.6 years. The unadjusted cardiovascular event rate was 95.1 per thousand person-years [PTPY] (95% CI, 93.6-96.8), with a higher rate in patients on HHD than on PD (127.8 PTPY; 95% CI, 118.9-137.2 vs. 93.3 PTPY; 95% CI, 91.5-95.1). However, HHD was associated with a slightly lower adjusted risk of cardiovascular events than PD (HR, 0.92; 95% CI, 0.85 to 0.997). Compared to PD patients, HHD patients had 42% lower adjusted risk of stroke (HR, 0.58; 95% CI, 0.48-0.71), 17% lower adjusted risk of acute coronary syndrome (HR, 0.83; 95% CI, 0.72-0.95), and no difference in risk of heart failure (HR, 1.05; 95% CI, 0.94-1.16). HHD was associated with 22% lower adjusted risk of cardiovascular death (HR, 0.78; 95% CI, 0.71-0.86) and 8% lower adjusted risk of all-cause death (HR, 0.92; 95% CI, 0.87-0.97) as compared to PD. Relative to PD, HHD is associated with decreased risk of stroke, acute coronary syndrome, cardiovascular death, and all-cause death. Further studies are needed to better understand the factors associated with differences in cardiovascular outcomes by type of home dialysis modality in patients with kidney failure.

Comparing Racial Disparities of Cardiovascular Manifestations in Sickle Cell Trait

Introduction Sickle cell trait (SCT) is a genetic condition that affects millions of people globally, particularly those of African and Mediterranean descent. Various mechanisms have been suggested to contribute to cardiovascular pathology in SCT patients, including chronic anemia, arteriopathy, and cardiac remodeling. However, whether SCT carriers, particularly African Americans (AA), are at an increased risk for cardiovascular disease remains controversial. This study aimed to investigate potential differences in cardiovascular outcomes between AA and non-AA SCT carriers. Methods We screened the National Inpatient Sample (NIS) database 2016-2018 for cardiovascular outcomes during hospital admission in African American SCT carriers and compared them to SCT carriers of other races. The primary outcomes were major adverse cardiovascular events, including acute myocardial infarction, cardiac arrest, stroke, acute heart failure, and in-hospital mortality. Secondary outcomes included World Health Organization (WHO) group 5 pulmonary hypertension, acute pulmonary edema, valvular disease, pericarditis, tachyarrhythmia, conduction disorders, acute deep venous thrombosis and/or pulmonary embolism, avascular necrosis, and rhabdomyolysis. Univariate analysis was conducted, with a P value &amp;lt;0.05 considered statistically significant. Results A total of 29,060 SCT admissions were analyzed, with 24,659 attributed to African Americans and the remaining to other races. The study found that majority of the patients admitted were female (86% of African American patients and 84% of patients from other races). The average age of patients was 37 years for African Americans and 40 years for other races. African American patients had higher rates of comorbidities such as hypertension, diabetes, chronic kidney disease, and oral anticoagulant use compared to patients of other races. The study also found that African American SCT patients had a significantly higher risk of acute heart failure (5.7% vs. 3.5%, p&amp;lt;0.01), tachyarrhythmia (4.9% vs. 3.6%, p&amp;lt;0.01), and conduction disorders (1.6% vs. 1.1%, p=0.02) compared to patients of other races. Acute myocardial infarction (1.1% vs. 0.9%), valvular disease (2.7% vs. 2.3%), acute deep vein thrombosis/pulmonary embolism (2.2% vs. 2.0%), and rhabdomyolysis (0.6% vs. 0.5%) occurred at a higher rate in African American patients but did not reach statistical significance. Similarly, in-hospital mortality (0.7% vs 0.9%), cardiac arrest (0.4% vs 0.5%), and pericarditis (0.1% vs 0.2%), although occurring at lower rates in the AA population, did not reach statistical significance. Acute pulmonary edema (0.2% vs 0.2%), pulmonary hypertension (group 5) (0.1% vs 0.1%), stroke (1.1% vs 1.1%) and avascular necrosis (0.1% vs 0.1%) had similar rates in both AA and other races but did not reach statistical significance. Conclusion/Discussion African American patients with sickle cell trait compared to other races had higher rates of acute heart failure, tachyarrhythmias, and other conduction disorders. Aggressive screening for cardiac conditions and management of risk factors including smoking, obesity, high blood pressure, hyperlipidemia, etc., are warranted in this population to improve cardiovascular outcomes. Although the NIS database provides this study with large patient data, this study may be limited by difference in the number of patients in AA and other race cohorts at baseline, coding error, underreporting, misclassification, retrospective nature, and lack of matching. Further studies analyzing the cardiovascular morbidity and mortality in sickle cell trait carriers, including benefit of use of medications for primary/secondary prevention of cardiovascular conditions are warranted.

Use of secondary prevention medications in metropolitan and non-metropolitan areas: an analysis of 41 925 myocardial infarctions in Australia.

People in remote areas may have more difficulty accessing healthcare following myocardial infarction (MI) than people in metropolitan areas. We determined whether remoteness was associated with initial and 12-month use of secondary prevention medications following MI in Victoria, Australia. We included all people alive at least 90 days after discharge following MI between July 2012 and June 2017 in Victoria, Australia (n = 41 925). We investigated dispensing of P2Y12 inhibitors (P2Y12i), statins, angiotensin-converting enzyme inhibitors or angiotensin receptor blockers (ACEIs/ARBs), and beta-blockers within 90 days after discharge. We estimated 12-month medication use using proportion of days covered (PDC). Remoteness was determined using the Accessibility/Remoteness Index of Australia (ARIA). Data were analysed using adjusted parametric regression models stratified by ST elevation myocardial infarction (STEMI) and non-STEMI (NSTEMI). There were 10 819 STEMI admissions and 31 106 NSTEMI admissions. Following adjustment across NSTEMI and STEMI, there were no medication classes dispensed in the 90-day post-discharge that differed in a clinically significant way from the least remote (ARIA = 0) to the most remote (ARIA = 4.8) areas. The largest difference for NSTEMI was ACEI/ARB, with 71% (95% confidence interval 70-72%) vs. 80% (76-83%). For STEMI, it was statins with 89% (88-90%) vs. 95% (91-97%). Predicted PDC for STEMI and NSTEMI was not clinically significant across remoteness, with the largest difference in NSTEMI being P2Y12i with 48% (47-50%) vs. 55% (51-59%), and in STEMI, it was ACEI/ARB with 68% (67-69%) vs. 76% (70-80%). Remoteness does not appear to be a clinically significant driver for medication use following MI. Possible differences in cardiovascular outcomes in metropolitan and non-metropolitan areas are not likely to be explained by access to secondary prevention medications.

Fish and Omega-3 Fatty Acids: Sex and Racial Differences in Cardiovascular Outcomes and Cognitive Function.

Both cardiovascular disease (CVD) and cognitive decline are common features of aging. One in 5 deaths is cardiac for both men and women in the United States, and an estimated 50 million are currently living with dementia worldwide. In this review, we summarize sex and racial differences in the role of fish and its very long chain omega-3 polyunsaturated fatty acids, eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), in preventing CVD events and cognitive decline. In prospective studies, women with higher nonfried and fatty fish intake and women and Black individuals with higher plasma levels of EPA and DHA had a lower risk of CVD. In randomized controlled trials of EPA and DHA supplementation in primary CVD prevention, Black subjects benefited in a secondary outcome. In secondary CVD prevention, both men and women benefited, and Asians benefited as a prespecified subgroup. Fish and omega-3 polyunsaturated fatty acids are associated with prevention of cognitive decline in prospective studies. In randomized controlled trials of EPA and DHA supplementation, women have cognitive benefit. DHA seems more beneficial than EPA, and supplementation is more beneficial when started before cognitive decline. Although studies in women and racial groups are limited, life-long intake of nonfried and fatty fish lowers the risk of CVD and cognitive decline, and randomized controlled trials also show the benefit of EPA and DHA supplementation. These findings should be factored into recommendations for future research and clinical recommendations as dietary modalities could be cost-effective for disease prevention.

Sex-specific difference in cardiac function in patients with systemic sclerosis: association with cardiovascular outcomes

BackgroundCardiovascular involvement is one of the leading causes of mortality in systemic sclerosis (SSc) and is reported to be higher in men as compared with women. However, the cause of...

Sex Differences in Cardiovascular Outcomes and Cholesterol-Lowering Efficacy of PCSK9 Inhibitors: Systematic Review and Meta-Analysis

BackgroundGuideline-recommended low-density lipoprotein cholesterol (LDL-C) thresholds are often not achieved in women. The proprotein convertase subtilisin/kexin type-9 inhibitor (PCSK9i) monoclonal antibodies can help further reduce LDL-C and major adverse cardiovascular events (MACE) although differences in efficacy by sex and type are less understood. ObjectivesThe authors sought to determine if there are differences in the efficacy of LDL-C lowering and reduction in the risk of MACE by sex and type of PCSK9i. MethodsA comprehensive literature search was done through October 17, 2022, for published trials comparing PCSK9i vs control. Outcomes assessed were LDL-C reduction and incidence of MACE following the use of PCSK9i vs placebo, stratified by sex and type of PCSK9i used. ResultsWe identified 16 trials with 54,996 adults, and 15,143 (27.5%) of them were female. PCSK9i significantly reduced MACE compared to placebo in both women (HR: 0.86, 95% CI: 0.74-0.97, P < 0.001) and men (HR: 0.85, 95% CI: 0.79-0.91, P < 0.001) with no significant sex difference (MD −0.01, 95% CI: −0.14 to −0.13, P = 0.930). PCSK9i also significantly reduced LDL-C levels in both sexes at 12 weeks (females: MD −62.57, 95% CI: −70.24 to −54.91, P < 0.001; males: MD −66.19, 95% CI: −72.03 to −60.34, P < 0.001) and 24 weeks (females: MD −47.52, 95% CI: −52.94 to −42.09, P < 0.001; males: MD −54.07, 95% CI: −59.46 to −48.68, P < 0.001). Significant sex difference was seen in the LDL reduction of PCSK9i for both 12 weeks (males vs females: MD −4.55, 95% CI: −7.34 to −1.75, P < 0.01) and 24 weeks (males vs females: MD −7.11, 95% CI: −9.99 to −4.23, P < 0.001). ConclusionsThe use of PCSK9i results in significant LDL-C and MACE reduction in both males and females. While there is no significant sex difference in MACE reduction, LDL-C reduction is greater in males than in females. Our data support the equal use of PCSK9i in all eligible patients, regardless of sex.

Angiotensin II type 2 receptor-mediated dilation is greater in the cutaneous microvasculature of premenopausal women compared with men.

Differential activation of the renin-angiotensin system (RAS) likely contributes to sex differences in cardiovascular outcomes in premenopausal women compared with age-matched men. Women demonstrate reduced activation of the vasoconstrictor angiotensin II type 1 receptors (AT1R) compared with men, and evidence suggests that women also likely have increased sensitivity of the vasodilatory angiotensin II type 2 receptors (AT2R). However, few in vivo studies have directly examined sex differences in AT2R-mediated dilation, or the balance between AT1R- and AT2R-mediated vascular responses in humans. Using the cutaneous microcirculation as a model, we hypothesized that AT2R-mediated dilation would be greater in premenopausal women compared with men, and that AT1R-blockade would augment AT2R-mediated dilation to a greater extent in men than in women. Twelve healthy women (22 ± 3 yr) and 12 men (23 ± 5 yr) had two intradermal microdialysis fibers placed in the ventral forearm for graded infusions of compound 21 (AT2R agonist; 10-12 to 10-8 M) in a control fiber site and a site treated with 43 µM losartan (AT1R antagonist). Red blood cell flux was measured continuously by laser-Doppler flowmetry, and cutaneous vascular conductance [CVC = flux/mean arterial pressure (MAP)] was normalized to maximum [%max; 28 mM sodium nitroprusside (SNP) + 43 °C]. Women had greater AT2R-mediated dilation compared with men (women: 25 ± 4 vs. men: 15 ± 2%max, P = 0.03). Local AT1R inhibition increased AT2R-mediated dilation in men (losartan: 26 ± 4 vs. control: 15 ± 2%max, P < 0.001) but had no effect in women (losartan: 27 ± 6 vs. control: 25 ± 4%max, P > 0.05). These data suggest that premenopausal women have a greater AT2R-mediated vasodilation response than men, and that AT1R activation inhibits AT2R-mediated dilation in men, but not in women.NEW & NOTEWORTHY Premenopausal women have greater protection against cardiovascular disease than age-matched men. However, the role of vasoconstrictor angiotensin II type 1 receptors (AT1R) and vasodilatory angiotensin II type 2 receptors (AT2R) in mediating these sex differences is unclear. Here, we demonstrate that women have greater AT2R-mediated vasodilation than men and that AT1R negates AT2R-mediated dilation in men, but not in women.

Are there sex differences in cardiovascular outcomes in non-dialysis CKD patients?

Sex differences for cardiovascular (CV) risk and outcomes in chronic kidney disease (CKD) patients not on dialysis have been scarcely or never investigated. We therefore studied this important aspect in a cohort of CKD stage 2-5 in the south of Italy. We tested the relationship between sex and fatal and non-fatal major CV events in a cohort of 759 stage 2-5 CKD patients followed up for a median time of 36 months. Out of 759 patients, 455 were males (60%) and the remaining 304 patients were females (40%). During the follow-up, 42 patients died, and 118 had fatal and non-fatal CV events. On univariate Cox regression analyses, the male sex failed to be associated with all-cause mortality but was strongly related to the incidence rate of fatal and non-fatal major CV events [hazard ratio (HR) 1.75, 95% confidence interval (CI) 1.18-2.60, P=.006]. Data adjustment for a series of major potential confounders did not materially affect the strength of this relationship (HR 1.78, 95% CI 1.03-3.09). Further analysis testing the effect of age on major CV outcomes by sex showed an effect modification by this risk factor on the same outcome (P=.037) because the HR of male versus female CV events increased progressively with aging. Male patients in stage G2-5 CKD had a higher risk for CV events compared with female patients. Age was shown to be a risk modifier for the association between sex and CV events and this risk increased linearly across a wide age spectrum in CKD patients.

Determining the association of rurality and cardiovascular disease among prostate cancer survivors

PurposeRural disparities in prostate cancer survivorship and cardiovascular disease remain. Prostate cancer treatment also contributes to worse cardiovascular disease outcomes. Our objective was to determine whether rural-urban differences in cardiovascular outcomes contribute to disparities in prostate cancer survivorship. Materials and MethodsData were collected from the Utah Population Database. Rural and urban prostate cancer survivors were matched by diagnosis year and age. Cox proportional hazards models were used to estimate hazard ratios for cardiovascular disease (levels 1–3) based on rural-urban classification, while controlling for demographic and socioeconomic characteristics. We identified 3,379 rural and 16,253 urban prostate cancer survivors with a median follow-up of 9.3 years. ResultsResults revealed that rural survivors had a lower risk of hypertension (HR 0.90), diseases of arteries (HR 0.92), and veins (HR 0.92) but a higher risk of congestive heart failure (HR 1.17). Interactions between level 2 cardiovascular diseases and rural/urban status, showed that diseases of the heart had a distinct between-group relationship for all-cause (P = 0.005) and cancer-specific mortality (P = 0.008). ConclusionsThis study revealed complex relationships between rural-urban status, cardiovascular disease, and prostate cancer. Rural survivors were less likely to be diagnosed with screen-detected cardiovascular disease but more likely to have heart failure. Further, the relationship between cardiovascular disease and survival was different between rural and urban survivors. It may be that our findings underscore differences in healthcare access where rural patients are less likely to be screened for preventable cardiovascular disease and have worse outcomes when they have a major cardiovascular event.

A-23 | Gender Disparities in Cardiovascular Outcomes of Percutaneous Coronary Intervention for Chronic Total Occlusions

Several studies have demonstrated the utility of percutaneous coronary intervention (PCI) in improving cardiovascular outcomes in patients with chronic total occlusions (CTOs). However, the differences in clinical outcomes based on gender have not been well elucidated. This meta-analysis aims to evaluate the differences in cardiovascular outcomes of CTO PCI based on gender. A literature search was conducted for studies reporting on clinical endpoints after CTO PCI based on gender. The primary endpoint was all-cause mortality. Secondary endpoints included procedural success, recurrent acute myocardial infarction (AMI), and composite major adverse cardiovascular events (MACE). The search included the following databases: Ovid MEDLINE, EMBASE, Web of Science, and Google Scholar. The search was not restricted to time or publication status. A total of 14 studies with 15,129 patients with CTO PCIs (2804 females, 12325 males) met inclusion criteria. Mean follow-up was 48 months. Female gender was associated with a trend toward higher risk of all-cause mortality and MACE and lower procedural success; however, this was not statistically significant (OR 1.2, 95% CI 0.98-1.48; p=0.08; OR 1.26, 95% CI 0.99-1.59; p=0.06; OR 1.12, 95% CI 0.98-1.27; p=0.08). There was no significant difference in the risk of recurrent AMI on long-term follow-up post-PCI in females compared to males (OR 1.07, 95% CI 0.82-1.40; p=0.61). Female patients who undergo CTO PCI have similar procedural success without increased risk of long-term all-cause mortality, MACE, or recurrent AMI compared to male patients.

Angiotensin II type 2 receptor-mediated dilation is greater in the cutaneous microvasculature of premenopausal women compared to men

Sex differences in the activation of the renin-angiotensin system (RAS) likely contribute to differences in cardiovascular outcomes in premenopausal women compared to age-matched men. It is established that women have a reduced activation of the vasoconstrictor angiotensin II – angiotensin II type 1 receptor (AT 1 R) pathway. Emerging evidence suggests that this may be mediated by a shift toward the more recently described vasodilatory RAS, including increased sensitivity of the vasodilatory angiotensin II type 2 receptor (AT 2 R). However, few in vivo studies have directly examined sex differences in AT 2 R-mediated dilation, or the balance between AT 1 R- and AT 2 R-mediated vascular responses in humans. Using the cutaneous microcirculation as a model, we hypothesized that AT 2 R-mediated dilation would be greater in premenopausal women compared to men, and that AT 1 R-blockade would augment AT 2 R-mediated dilation to a greater extent in men than in women. Eight healthy women (22±3 years) and 11 healthy men (23±5 years) participated in 1 experimental visit. Two intradermal microdialysis fibers were placed in the skin of the ventral forearm for graded infusions of either compound 21 (C21, AT 2 R agonist; 10 -12 - 10 -3 mol/L) alone or C21 + 43 μmol/L losartan (AT 1 R antagonist). Red blood cell flux was measured over each microdialysis site by laser-Doppler flowmetry. Cutaneous vascular conductance was calculated (CVC=doppler flux/mean arterial pressure) and normalized to maximum (%CVCmax; 28mM SNP+43°C). Women had a greater peak vasodilation response to C21 compared to men (27.2±5.7 versus 18.2±2.7 %CVCmax; p=0.03). AT 1 R-inhibition augmented peak C21-mediated dilation in men (31.3±4.5 versus 18.2±2.7 %CVCmax; p=0.009) but had no effect in women (24.5±6.5 versus 27.2±5.7 %CVCmax; p=0.34). These data suggest that premenopausal women have a greater AT 2 R-mediated vasodilation response than men, and that AT 1 R activation inhibits AT 2 R-mediated dilation in men, but not in women. This study is supported by National Heart, Lung, and Blood Institute Grant R00HL138133. Clinicaltrials.gov identifier: NCT05576155 This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Higher risk of adverse cardiovascular outcomes in females with type 2 diabetes Mellitus: an Umbrella review of systematic reviews.

Previous studies have shown that females with type 2 diabetes mellitus (T2DM) may have excess mortality risk compared to their male counterparts. An important next step to address the high global burden of T2DM and cardiovascular disease (CVD) is an umbrella review to summarize data on sex differences in cardiovascular outcomes for patients with T2DM and assess the strength of the evidence observed. Medline and Embase were searched from inception till 7 August 2022 for systematic reviews and meta-analyses studying the effects of sex on cardiovascular outcomes in T2DM patients. Results from reviews were synthesized with a narrative synthesis, with a tabular presentation of findings and forest plots for reviews that performed a meta-analysis. 27 review articles evaluating sex differences in cardiovascular outcomes were included. Females with T2DM had a higher risk of developing coronary heart disease (CHD; RRR: 1.52, 95%CI: 1.32-1.76, P < 0.001), acute coronary syndrome (ACS; RRR: 1.38, 95%CI: 1.25-1.52, P < 0.001), heart failure (RRR: 1.09, 95%CI: 1.05-1.13, P < 0.001) than males. Females had a higher risk of all-cause mortality (RRR: 1.13, 95%CI: 1.07-1.19, P < 0.001), cardiac mortality (RRR: 1.49, 95%CI: 1.11-2.00, P = 0.009) and CHD mortality (RRR: 1.44, 95%CI: 1.20-1.73, P < 0.001) as compared to males. This umbrella review demonstrates that females with T2DM have a higher risk of cardiovascular outcomes than their male counterparts. Future research should address the basis of this heterogeneity and epidemiological factors for better quality of evidence, and identify actionable interventions that will narrow these sex disparities.

Effects of Metabolic Syndrome on Cardiovascular Outcomes of Psoriatic Patients with Coronary Artery Disease: A Single Center Retrospective Cohort Study.

Psoriasis is associated with an increased prevalence of cardiovascular risk factors, including metabolic syndrome (MetS). To date, it is unclear whether MetS causes differences in cardiovascular outcomes in psoriatic patients with coronary artery disease. We conducted a retrospective cohort study to determine the effects of MetS in psoriatic patients with coronary artery disease. Comparisons were made between patients with and without MetS. Cox regression analysis and Kaplan-Meier survival analysis were used to evaluate the association between variables. Of the 307 psoriatic patients with coronary artery disease, 94 met criteria (30.6%) for MetS. Individuals with MetS were more likely to be female (p <0.001). Levels of platelet counts and high-sensitivity C-reactive protein were higher in the MetS group (p = 0.038 and 0.005, respectively). After a mean follow-up of 35.32 months, major adverse cardiovascular events (MACEs) and non-fatal myocardial infarction were more likely in the MetS than the non-MetS group (33.3% vs 20.6%, p = 0.02; 26.4% vs 15.7%, p = 0.032, respectively). Kaplan-Meier estimates showed the same trend. Cox regression analysis showed that MetS (hazard ratio 1.738; 95% confidence interval 1.045-2.891; p = 0.033) and left ventricular ejection fraction (hazard ratio 0.968; 95% confidence interval 0.945-0.991; p = 0.006) were associated with an increased risk of MACEs. In psoriatic patients with coronary artery disease, MetS independently predicted MACEs. In addition, left ventricular ejection fraction was negatively associated with an increased risk of MACEs. To reduce the cardiovascular disease risk, it is necessary to increase awareness of MetS in psoriatic patients with coronary artery disease.

Real-World Evaluation of GLP-1 Receptor Agonist Therapy Persistence, Adherence and Therapeutic Inertia Among Obese Adults with Type 2 Diabetes.

In type 2 diabetes (T2D), key barriers to optimal glycaemic control include lack of persistence with treatment, reduced medication adherence and therapeutic inertia. This study aimed to assess the impact of these barriers in obese adults with type 2 diabetes treated with a GLP-1 receptor agonist (GLP-1RA) and compare them against other glucose-lowering agents in a real-world setting. A retrospective study was conducted using electronic medical records from 2014 to 2019 for adults with T2D at the ValenciaClínico-Malvarrosa Department of Health (Valencia,Spain). Four study groups were established: all GLP-1RA users, SGLT2i users, insulin users and other glucose-lowering agent users (miscellany group). To account for imbalance between groups, propensity score matching (PSM) including age, gender and pre-existing cardiovascular disease was performed. Chi-square tests were used for comparisons between groups. Time to first intensification was calculated using competing risk analysis. Among the 26,944 adults with T2D, 7392 individuals were selected following PSM, with 1848 patients in each group. At 2 years, GLP-1RA users were less persistent than non-users (48.4% versus 72.7%, p < 0.0001) but more adherent (73.8% versus 68.9%, respectively, p < 0.0001). A greater proportion of persistent GLP-1RA users than non-persistent users exhibited reduced HbA1c (40.5% versus 18.6%, respectively, p < 0.0001), but no differences in cardiovascular outcomes and death were found. Overall, therapeutic inertia was observed in 38.0% of the study population. The large majority of GLP-1RA users received treatment intensification, whereas only 50.0% of GLP-1RA non-users were intensified. Under real-life conditions, obese adults with T2D persistently treated with GLP-1RA showed improved glycaemic control. Despite benefits, persistence with GLP-1RA was limited after 2 years. Additionally, therapeutic inertia occurred in two out of three study participants. Strategies to facilitate medication adherence, persistence and treatment intensification in people with T2D should be made a priority in order to achieve and maintain glycaemic targets and improve outcomes in this population. Study registered in clinicaltrials.org with the identifier NCT05535322.

Sex differences in cardiovascular outcomes of SGLT-2 inhibitors in heart failure randomized controlled trials: A systematic review and meta-analysis

BackgroundIn patients with heart failure (HF), randomized controlled trials (RCTs) of sodium-glucose transporter-2 inhibitors (SGLT-2is) have proven to be effective in decreasing the primary composite outcome of cardiovascular death and hospitalizations for HF. A recently published meta-analysis showed that the use of SGLT-2is among women with diabetes resulted in less reduction in primary composite outcomes compared with men. This study aims to explore potential sex differences in primary composite outcomes among patients with HF treated with SGLT-2is. MethodsWe systematically searched the medical database from 2017 to 2022 and retrieved all the RCTs using SGLT-2is with specified cardiovascular outcomes. We used the PRISMA (Preferred Reporting Items for a Review and Meta-analysis) method to screen for eligibility. We evaluated the quality of studies using the Cochrane Risk of Bias tool. We pooled the hazard ratio (HR) of the primary composite outcomes in both sexes, performed a meta-analysis, and calculated the odds ratio (OR) of the primary composite outcomes based on sex. ResultsWe included 5 RCTs with a total number of 21,947 patients. Of these, 7837 (35.7 %) were females. Primary composite outcomes were significantly lower in males and females taking SGLT-2is compared to placebo (males - HR 0.77; 95 % CI 0.72 to 0.84; p = 0.00001; females - HR 0.75; 95 % CI 0.67 to 0.84; p = 0.00001). Pooled data from four of the RCTs (n = 20,725) revealed a greater occurrence of the primary composite outcomes in females compared with males (OR 1.32; 95 % CI 1.17 to 1.48; p = 0.0002). ConclusionSGLT-2is reduce the risk of primary composite outcomes in patients with HF, regardless of sex; however, the benefits were less pronounced in women. Further research needs to be done to better explain these observed differences in outcomes.

Study of effect modifiers of genetically predicted CETP reduction.

Genetic variants in drug targets can be used to predict the long-term, on-target effect of drugs. Here, we extend this principle to assess how sex and body mass index may modify the effect of genetically predicted lower CETP levelson biomarkers and cardiovascular outcomes. We found sex and body mass index(BMI) to be modifiers of the association between genetically predicted lower CETP and lipid biomarkers in UK Biobank participants. Female sex and lower BMI were associated with higher high-density lipoprotein cholesterol and lower low-density lipoprotein cholesterol for the same genetically predicted reduction in CETP concentration. We found that sex also modulated the effect of genetically lower CETP on cholesterol efflux capacity in samples from the Montreal Heart Institute Biobank. However, these modifying effects did not extend to sex differences in cardiovascular outcomes in our data. Our results provide insight into the clinical effects of CETP inhibitors in the presence of effect modification based on genetic data. The approach can support precision medicine applications and help assess the external validity of clinical trials.

Higher risk of adverse cardiovascular outcomes in women with type 2 diabetes mellitus: an umbrella review of systematic reviews

Abstract Funding Acknowledgements Type of funding sources: None. Background Previous studies have shown that females with type 2 diabetes mellitus (T2DM) may have an excess mortality risk compared to males. Furthermore, other studies have reported sex differences in managing cardiovascular risk factors, such as controlling hypertension and hypercholesterolemia. Purpose With the growing evidence from systematic reviews examining the sex differences in cardiovascular outcomes for patients with T2DM, an umbrella review is an essential next step to synthesising and assessing the strength of the available evidence. Methods Medline and Embase were searched from inception till 7th August 2022 for systematic reviews and meta-analyses studying the effects of sex on cardiovascular outcomes in T2DM patients. Results from reviews were synthesised with a narrative synthesis, with a tabular presentation of findings and forest plots for reviews that performed a meta-analysis. AMSTAR 2 tool was used to assess the methodological quality of included reviews, while the GRADE assessment was used to assess the quality of evidence for outcomes. Results A total of 28 studies evaluating sex differences in cardiovascular outcomes were included. Females with T2DM had a higher risk of developing coronary heart disease (CHD; RRR 1.52, 95%CI 1.32–1.76, p&amp;lt;0.001), acute coronary syndrome (ACS; RRR 1.38, 95%CI 1.25–1.52, p&amp;lt;0.001), and heart failure (RRR 1.09, 95%CI 1.05–1.13, p&amp;lt;0.001) than males. In terms of mortality outcomes, females had a higher risk of all-cause mortality (RRR 1.13, 95%CI 1.07–1.19, p&amp;lt;0.001), cardiac mortality (RRR 1.49, 95%CI 1.11–2.00, p=0.009) and CHD mortality (RRR 1.44, 95%CI 1.20–1.73, p&amp;lt;0.001) as compared to males. In patients undergoing percutaneous coronary intervention, females reported higher odds of MACE (OR 1.49, 95%CI 1.07–2.07, p=0.020) and all-cause mortality (OR 1.71, 95%CI 1.46–2.00, p&amp;lt;0.001) compared to males. Females in Asia (RRR 1.12, 95%CI 1.03–1.21, p=0.006) and North America (RRR 1.10, 95%CI 1.08–1.12, p&amp;lt;0.001) were at increased risk of all-cause mortality while females in Western countries had an increased risk for cardiac death (RRR 1.84, 95%CI 1.45–2.32, p&amp;lt;0.001) compared to males. Six reviews were rated as high in quality; eight reviews were rated as moderate, and fourteen reviews were rated as low in quality. Regarding the quality of outcomes, all outcomes in non-interventional studies had a moderate quality of evidence, while all outcomes in interventional studies achieved a high quality of evidence. Conclusions This umbrella review evaluated the quality of meta-analyses and demonstrated that females with T2DM have a higher risk of cardiovascular outcomes than their male counterparts. Future studies examining the sex differences in outcomes should attempt to address the heterogeneity and epidemiological factors for a better quality of evidence. Policymakers should consider sex-specific differences in implementing effective tailored strategies to tackle T2DM.