Differences In Cardiovascular Outcomes Research Articles

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.

Abstract 9607: Sex Differences in Cardiovascular Outcomes in Dialysis Patients

Background: 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 to the general population. Little is known about sex differences in cardiovascular outcomes in dialysis patients which precludes sex-specific therapies. Methods: We evaluated 508,822 patients who initiated dialysis between 1/1/2005 and 12/31/2014 using the United States Renal Data System with linked Medicare claims. We determined rates of hospitalizations for cardiovascular events, defined by acute coronary syndrome, heart failure, and stroke. We examined the association of sex with the outcome of cardiovascular events, cardiovascular death, and all-cause death, using adjusted time-to-event models. Results: The mean age of patients in the study cohort was 70±12 years, and 44.7% were women. The cardiovascular event rate was 232 PTPY (95% CI, 231-233), with a higher rate in women than in men (248 PTPY; 95% CI, 247-250 vs. 219 PTPY; 95% CI, 217-220). Women had a 13% higher risk of cardiovascular events than did men (HR, 1.13; 95% CI, 1.11-1.14). Women had a 15% higher risk of heart failure (HR, 1.15; 95% CI, 1.13-1.16), a 29% higher risk of stroke (HR, 1.29; 95% CI, 1.26-1.32), and no difference in risk of acute coronary syndrome (HR, 0.99; 95% CI, 0.97-1.01). Women had a lower risk of cardiovascular death (HR, 0.84; 95% CI, 0.83-0.85), and a lower risk of all-cause death, as compared to men (OR, 0.92; 95% CI, 0.91-0.93). Conclusion: 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. Further studies are needed to better understand the factors associated with sex differences in cardiovascular outcomes in patients with kidney failure.

Abstract 9692: Sex Differences in Cardiovascular Outcomes of SGLT-2 Inhibitors in Heart Failure Randomized Controlled Trials: A Systematic Review and Meta-Analysis

Background: Randomized controlled trials (RCTs) of sodium-glucose transporter-2 inhibitors (SGLT-2is) have proven to be effective in decreasing major adverse cardiovascular events (MACE) in patients with heart failure. A recently published meta-analysis showed that the use of SGLT-2i among women with diabetes resulted in less reduction in MACE vs. men. This study aims to determine sex differences in MACE in patients with chronic heart failure. Methods: We systematically searched the medical database until April 30, 2022, and retrieved all the RCTs using SGLT-2is with specified CV outcomes. We used PRISMA, Preferred Reporting Items for a Review and Meta-analysis. We pooled the hazard ratio (HR) of MACE in both sexes, did a meta-analysis, and analyzed the odds ratio (OR) of MACE based on sex. Statistical analysis was completed with the use of Cochrane Review Manager (RevMan) version 5.4. Results of the pooled hazard ratio (HR) and the 95% confidence interval (CI) were made based on intention-to-treat analysis. Results: Figure 1 shows the results of the meta-analysis of 4 RCTs conducted with SGLT-2is (n=20725) vs. placebo. MACE was significantly lower in males and females taking SGLT-2is (men - HR 0.76; 95% CI 0.69 to 0.83; p=0.00001; women - HR 0.72; 95% CI 0.63 to 0.83; p=0.00001). Pooled data from three of the RCTs (n=7233) revealed a greater reduction in MACE in females vs. males (OR 1.32; 95% CI 1.14 to 1.53; p=0.0002). Conclusion: SGLT-2is reduce the risk of MACE in patients with heart failure, regardless of sex. However, the benefits were more pronounced in females, contrary to the meta-analysis of SGLT-2is in patients with diabetes. This finding may reflect an actual sex difference due to physiologic or behavioral factors or can be due to inadequate statistical power. More sex-based RCTs may help establish these sex differences in cardiovascular outcomes.

Age, sex, race, BMI, and duration of diabetes differences in cardiovascular outcomes with glucose lowering drugs in type 2 diabetes: A systematic review and meta-analysis.

SummaryBackgroundSummarized data of cardiovascular outcomes trials (CVOTs) of sodium glucose cotransporter 2 inhibitors (SGLT2i) and glucagon-like peptide 1 receptor agonists (GLP-1 RAs) have shown a reduction in major adverse cardiovascular event (MACE), whether these benefits are extended in certain risk groups (elderly or obese patients or those with a longer duration of diabetes) or certain minorities (Black participants) are not clearly established. We aimed to provide overall hazard ratios (HRs) estimates for MACE of SGLT2i and GLP-1 RAs stratified by age (< 65 years vs. ≥ 65 years and < 75 years vs. ≥ 75 years), sex (male vs. female), race (Black vs. White, Black vs. Asian, and White vs. Asian), body mass index (BMI: < 30 kg/m2 vs. ≥ 30 kg/m2), and duration of diabetes (< 10 years vs. ≥ 10 years).MethodsWe performed a MEDLINE database search from inception up to July 31, 2022 to identify all placebo-controlled phase 3 CVOTs that evaluated the efficacy of SGLT2i and GLP-1 RAs on vascular events at least 1-year after randomisation in participants with type 2 diabetes, and we selected those reporting hazard ratios (HRs) for the specific risk groups for MACE. Differences on MACE in risk groups were examined using a random-effect meta-analysis. The study protocol was registered on PROSPERO (CRD42022347901).FindingsA total of 11 studies fulfilled the prespecified criteria, comprising 96,580 patients with T2D were included. Of these patients, 61,975 (64.2%) were male, 34,605 (35.8%) were female, and race groups included 74,982 (77.6%) White, 7760 (8.0%) Asian, and 4023 (4.2%) Black. In two SGLT2i trials, the HR (95% CI) for long-term diabetes duration more than10 years versus short duration was 0.84 (0.77–0.93) vs. 1.02 (0.89–1.16), respectively (Pinteraction = 0.03). In four SGLT2i trials, the MACE benefit was similar by sex (Pinteraction = 0.13), age (Pinteraction = 0.36), BMI (Pinteraction = 0.69), and race groups (Pinteraction = 0.86 between Black and White, Pinteraction = 0.98 between Black and Asian, and Pinteraction = 0.69 between White and Asian). For GLP-1 RAs, the MACE benefit from the seven trials tended to be greater for Asian (0.71, [0.58–0.87]) than for White (0.87, [0.81–0.94]), (Pinteraction = 0.07). In two GLP-1 RAs trials, the MACE outcome was reduced by 22% (0.78, 0.63–0.95) in elderly patients (≥ 75 years) while no difference was observed in those < 75 years (0.87; 0.75–1.01), (Pinteraction = 0.37). In the remaining risk groups, the MACE benefit was similar by sex (Pinteraction = 0.37), age < 65 years (Pinteraction = 0.80), duration of diabetes (Pinteraction = 0.70), and race (Pinteraction = 0.57 between Black and White, and Pinteraction = 0.15 between Black and Asian), BMI (Pinteraction = 0.78). Risk of bias was lower, and overall heterogeneity was high for sex with SGLT2i, and moderate to low for the remaining comparisons, with a I2 values ranging from 0% to 54%.InterpretationIn patients with type 2 diabetes at highest risk of cardiovascular disease or established cardiovascular disease, a greater benefit on MACE was found for elderly patients and for Asian individuals compared with White individuals with GLP-1 RAs, and those with a long duration of diabetes with SGLT2i. These findings could help in providing guidance for treatment prescription and facilitate selection and stratification of patients for future CVOTs. Furthermore, pooled individual patient-level data are urgently needed to support our conclusions, and to derive definitive evidence.FundingNone.

Sex-differences in prevalence and outcomes of the different endotypes of chronic coronary syndrome – analysis from the multi-center international ILIAS Registry

Abstract Introduction Guideline-directed management of chronic coronary syndrome (CCS) remains focused on obstructive causes of angina, and is based on established therapies derived from studies predominantly including men. This occurs despite documented higher mortality from cardiovascular causes in women compared to men, which is hypothesized to be related to a higher prevalence of coronary microvascular dysfunction (CMD) in women. However, data on the relationship between sex, the different endotypes of CCS, and related sex-specific clinical outcomes are limited. Purpose This study aimed to investigate the relationship between sex and the different endotypes of CCS, as well as sex-specific clinical outcomes of CCS endotypes. Method In patients with stable angina undergoing coronary angiography, the following invasive coronary hemodynamics were characterized: fractional flow reserve (FFR; &amp;lt;0.80 considered abnormal), coronary flow reserve (CFR; &amp;lt;2.0 considered abnormal) and microcirculatory resistance (MR) (hyperemic microvascular resistance; &amp;gt;2.5mmHg/cm/sec or index of microvascular resistance &amp;gt;25 considered abnormal). Patients were stratified into three groups: 1) hemodynamically significant obstructive coronary artery disease (oCAD) (FFR abnormal or a severe coronary stenosis requiring revascularization), 2) no-obstructive coronary artery disease but with CMD (FFR normal, but abnormal CFR and/or MR), or 3) no-obstructive coronary artery disease and no CMD (FFR normal, and normal CFR and MR). We assessed the prevalence of the CCS endotypes across sex, and sex-specific cardiovascular outcomes over a follow-up of 7 years defined as the composite endpoint of death or acute myocardial infarction. Results Amongst a total of 1987 included patients, 1435 (72.2%) were men and 552 (27.8%) were women. oCAD occurred in 904 (45.5%) patients, which was significantly more prevalent in men (48.9% (701/1435) of men vs. 36.8% (203/552) of women, p&amp;lt;0.001). In contrast, CMD was significantly more prevalent in women (19.6% (281/1435) of men vs. 24.1% (133/552) of women, p=0.031). Across the population, either oCAD or CMD occurred in 68.4% of men versus 60.9% of women (p=0.002). There were no sex-specific differences in cardiovascular outcomes across CCS entities (Figure 1). Conclusion In patients evaluated for CCS who underwent clinically indicated coronary angiography and physiological assessment, men were more likely to have oCAD and women were more likely to be classified as CMD. There were no sex-related differences in the prognosis associated with the individual CCS endotypes. Therefore, pathophysiological changes in the coronary circulation potentially underlying angina pectoris are similarly prevalent in men and women, but the high incidence of CMD in women makes women prone to underdiagnosis if no additional physiological measurements are assessed. Funding Acknowledgement Type of funding sources: None.

Day-to-day fasting plasma glucose variability on the short-term prognosis of ST-segment elevation myocardial infarction: A retrospective cohort study.

Glycemic variability in one fact that explain the differences in cardiovascular outcomes. The short-term fasting plasma glucose (FPG) variability may have an on major adverse cardiovascular events (MACE) in type 2 diabetes mellitus (T2DM) patients with ST-segment elevation myocardial infarction (STEMI). This study retrospectively analyzed T2DM patients who underwent emergent percutaneous coronary intervention (PCI) due to STEMI in Fuwai Hospital, Chinese Academy of Medical Sciences, Shenzhen, between January 2016 and March 2020. All patients underwent at least 5 FPG measurements during the perioperative period. FPG variability score (FPG-VS) was defined as the percentage of the number of FPG variations > 1 mmol/L between two adjacent FPG measurements. The Cox proportional-hazards model was used to estimate the relationship between FPG-VS and MACE. A validation set was utilized to further evaluate the prognostic value of FPG-VS in a standardized STEMI diabetic diet cohort following PCI intervention. A total of 612 patients were included in the retrospective cohort study. In comparison to the minimum quintile, FPG-VS > 60% was associated with an increased risk of 30-day MACE. Moreover, compared to FPG-VS ≤ 20%, the FPG-VS > 80% group had a higher risk of MACE (odd ratio [OR] = 4.87, 95% confidence interval [CI]: 2.55-5.28), recurrent angina pectoris (OR = 5.43, 95%CI: 2.27-8.27), nonfatal myocardial infarction (OR = 5.00, 95%CI: 2.47-7.69), heart failure (OR = 3.70, 95%CI: 1.92-5.54), malignant arrhythmia (OR = 4.63, 95%CI: 1.12-6.25) and cardiac death (OR = 1.41, 95%CI: 0.17-1.97). Consistent results were obtained after adjustment for HbA1c, demonstrating the robustness of FPGFPG-VS. Moreover, the standard diet intervention group had a lower FPG-VS index as well as a lower incidence of MACE. Higher FPG variability is associated with an increased risk of MACE within 30 days in diabetes patients receiving PCI for STEMI. A standardized diet may improve the prognosis of STEMI patients by reducing the FPG-VS.

Campylobacter Species of the Oral Microbiota as Prognostic Factor for Cardiovascular Outcome after Coronary Artery Bypass Grafting Surgery.

Background: The oral microbiota has been implicated in a variety of systemic diseases, including cardiovascular (CV) disease. The main objective of this study (DRKS-ID: DRKS00015776) was to evaluate the prognostic importance of the oral microbiota for further CV events in patients undergoing coronary artery bypass grafting surgery (3-year follow-up). Methods: In this longitudinal cohort study, 102 CV patients were enrolled, of whom 95 completed the 3-year follow-up. The CV outcome was assessed using the major adverse cardiac and cerebrovascular events criteria. To evaluate subgingival colonization, 16S rRNA genes were amplified, targeting the V3/V4 region (Illumina MiSeq). Results: Regarding the specific number of operational taxonomic units (OTUs), no significant differences in CV outcome were determined (alpha diversity, Shannon index). In linear discriminant analyses and t-tests, the disease-specific differences in the beta diversity of the microbiota composition were evaluated. It was evident that bacteria species of the genus Campylobacter were significantly more prevalent in patients with a secondary CV event (p = 0.015). This hierarchical order also includes Campylobacter rectus, which is considered to be of comprehensive importance in both periodontal and CV diseases. Conclusions: Here, we proved that subgingival occurrence of Campylobacter species has prognostic relevance for cardiovascular outcomes in CV patients undergoing coronary artery bypass grafting.

Comparison of Echocardiographic Changes Between Surgery and Medication Treatment in Patients With Primary Aldosteronism.

BackgroundPrimary aldosteronism can cause cardiac dysfunction, including left ventricular hypertrophy, left ventricular diastolic dysfunction, and left atrial enlargement. A few studies have compared the cardioprotective effects between surgery and medication for primary aldosteronism, although most have not adjusted for baseline disease status. In this study, we investigated the difference in cardiovascular outcomes between surgery and medication treatment for primary aldosteronism after adjusting for baseline clinical characteristics, including aldosterone level and pretreatment echocardiographic information.Methods and ResultsWe retrospectively analyzed 220 patients diagnosed with primary aldosteronism who underwent adrenalectomy (n=144) or medication treatment (n=76) between 2009 and 2019. Echocardiographic changes were evaluated pretreatment and 1 year posttreatment. The surgery group had lower potassium, lower plasma renin activity, and higher plasma aldosterone concentration than the medication group, indicating a severe primary aldosteronism phenotype in the former. The decrease in left ventricular mass index after treatment was significantly greater in the surgery group than in the medication group (P=0.047). However, this relationship was not noted after multivariable regression analysis (standard β=−0.08, P=0.17). Additionally, decreased parameter values related to left ventricular diastolic dysfunction and left atrial enlargement were not different between the groups. Pretreatment echocardiographic values were most associated with changes in all echocardiographic parameters. The findings were consistent in the propensity score‐matched analysis.ConclusionsThis study's findings suggest that there is no difference in cardioprotective efficacy between surgical and medication treatment under similar disease severity; however, it should be considered that several study participants with severe hyperaldosteronism were managed surgically.

Diabetes Increases Risk of Cardiovascular Events in Patients Receiving Permanent Pacemaker: A Propensity Score-Matched Cohort Study.

Background Type 2 diabetes was associated with a higher risk for permanent pacemaker (PPM) treatment. The difference in cardiovascular outcomes between patients with and without diabetes receiving PPM treatment remains unexplored. Method Between January 2003 and December 2017, 1742 patients receiving naïve PPM treatment comprised this retrospective cohort study and were categorized into two groups by the diagnosis of diabetes: group with diabetes (n = 632, 36.3%) and group without diabetes (n = 1110, 63.7%). The primary outcome was cardiovascular events including heart failure (HF) hospitalization and acute myocardial infarction (AMI). The secondary outcomes of this study included pacemaker infection, pacing-induced cardiomyopathy, cerebrovascular accident, cardiovascular mortality, and all-cause mortality. Propensity score matching (PSM) was applied to reduce selection bias between the study groups. Result During a mean follow-up period of 7.8 ± 4.8 years, 264 patients had a cardiovascular event. Before PSM, the incidence of cardiovascular events was higher in patients with diabetes compared to patients without diabetes (19.8% vs. 12.5%, P < 0.001), and the incidences of pacing-induced cardiomyopathy, cardiovascular mortality, and all-cause mortality were all higher in patients with diabetes compared to patients without diabetes. After PSM, the incidence of cardiovascular events was higher in patients with diabetes compared to patients without diabetes (18.8% vs. 12.3%, P = 0.015). The incidence of HF hospitalization was higher in patients with diabetes compared to patients without diabetes (15.3% vs. 10.2%, P = 0.037), whereas the incidence of AMI did not differ between the two groups. Moreover, after PSM, patients with diabetes had higher cumulative incidences of pacing-induced cardiomyopathy and all-cause mortality compared to patients without diabetes. Conclusions The prevalence of diabetes was over one-third of naïve PPM recipients of this cohort, and diabetes increased the risk of cardiovascular events in PPM recipients, especially for HF hospitalization.

Less revascularization in young women but impaired long-term outcomes in young men after myocardial infarction.

Female sex has previously been associated with poorer outcomes after myocardial infarction (MI), although evidence is scarce among young patients. We studied sex differences in cardiovascular outcomes after MI in young patients &lt;55 years old. Consecutive young (18-54 years) all-comer patients with out-of-hospital MI admitted to 20 Finnish hospitals (n = 8934, 17.3% women) in 2004-2014 were studied by synergizing national registries. Differences between the sexes were balanced by inverse probability weighting. The median follow-up period was 9.1 years (max 14.8 years). Young women with MI had more comorbidities at baseline, were revascularized less frequently, and received fewer evidence-based secondary prevention medications (P2Y12 inhibitors, renin-angiotensin signalling pathway inhibitors, statins, and lower statin dosages) after MI than young men. Long-term mortality or the occurrence of major adverse cardiovascular events (MACE; recurrent MI, stroke, or cardiovascular death) did not differ between the sexes in the unadjusted analysis. However, after baseline feature and treatment-difference adjustment, men had poorer outcomes after MI. Adjusted long-term mortality was 21.3% in men vs. 17.2% in women [hazard ratio (HR) 1.29; 95% confidence interval (CI) 1.10-1.53; P = 0.002]. Cumulative MACE rate was 33.9% in men vs. 27.9% in women during follow-up (HR 1.23; 95% CI 1.09-1.39; P = 0.001). Recurrent MI and cardiovascular death occurrences were more frequent among men. Stroke occurrence did not differ between the sexes. Young women were found to receive less active treatment after MI than young men. Nevertheless, male sex was associated with poorer long-term cardiovascular outcomes after MI in young patients after baseline feature adjustment.

Cardiovascular outcomes of SGLT-2 inhibitors and GLP-1 agonist based on race, ethnicity, and gender: A systematic review and meta-analysis of randomized trials

The ethnic differences in cardiovascular outcomes with sodium-glucose cotransporter-2 inhibitors (SGLT2i) and glucagon-like peptide-1 (GLP-1) receptor agonists in patients with type 2 diabetes and heart failure are not well established. We conducted the current study to evaluate the effects of both drugs on the major adverse cardiovascular effects (MACE) stratified by race, ethnicity, and gender. We searched Medline (via PubMed), Embase, and the Cochrane Library for randomized controlled trials (RCTs) investigating the effects of SGLT2 inhibitors and GLP-1 receptor agonists on the MACE risk. The data of MACE were pooled as risk ratios (RRs), with 95% confidence intervals, using R software (meta-package 4.9-0) for windows and a subgroup analysis was conducted. Sixteen RCTs were finally included in the meta-analysis. In patients with T2DM and high cardiovascular risk, the effect showed that SGLT-2 inhibitors and GLP-1 receptor agonists significantly reduced the MACE risk among the White and Asian populations, and both males and females. Subgroup analysis showed no significant differences between SGLT2 inhibitors and GLP-1 receptor agonists on the MACE outcomes stratified by race, ethnicity, or gender. In patients with known heart failure, the effect showed that SGLT-2 inhibitors significantly reduced MACE risk in all subgroups. It remains unclear whether the lack of significant reduction in MACE risk and significant heterogenicity observed could be because of inconsistent representation of these ethnic groups across RCTs. Further multicenter RCTs with a larger sample size are recommended to evaluate the effect of these drugs to better understand the ethnic difference in cardiovascular outcomes.

Assessment of Pretreatment With Oral P2Y12 Inhibitors and Cardiovascular and Bleeding Outcomes in Patients With Non-ST Elevation Acute Coronary Syndromes

The practice of pretreatment with oral P2Y12 inhibitors in non-ST elevation acute coronary syndromes (NSTEACS) remains common; however, its association with improved cardiovascular outcomes is unclear. To assess the association between oral P2Y12 inhibitor pretreatment and cardiovascular and bleeding outcomes in patients with NSTEACS. On March 20, 2021, PubMed, MEDLINE, Embase, Scopus, Web of Science, Science Direct, clinicaltrials.gov, and the Cochrane Central Register for Controlled Trials were searched from database inception. Randomized clinical trials of patients with NSTEACS randomized to either oral P2Y12 inhibitor pretreatment (defined as prior to angiography) or no pretreatment (defined as following angiography, once coronary anatomy was known) among patients undergoing an invasive strategy. This study followed Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines. Data on publication year, sample size, clinical characteristics, revascularization strategy, P2Y12 inhibitor type and dosage, time from pretreatment to angiography, and end point data were independently extracted by 2 authors. A random-effects model was used, including stratification by (1) P2Y12 inhibitor type, (2) revascularization strategy, and (3) access site. The primary end point was 30-day major adverse cardiac events (MACEs). Secondary end points were 30-day myocardial infarction (MI) and cardiovascular death. The primary safety end point was 30-day major bleeding (defined according to individual studies). A total of 7 trials randomizing 13 226 patients to either pretreatment (6603 patients) or no pretreatment (6623 patients) were included. The mean age of patients was 64 years and 3598 (27.2%) were female individuals. Indication for P2Y12 inhibitors was non-ST elevation myocardial infarction in 7430 patients (61.7%), radial access was used in 4295 (32.6%), and 10 945 (82.8%) underwent percutaneous coronary intervention. Pretreatment was not associated with a reduction in 30-day MACE (odds ratio [OR], 0.95; 95% CI, 0.78-1.15; I2 = 28%), 30-day MI (OR, 0.90; 95% CI, 0.72-1.12; I2 = 19%), or 30-day cardiovascular death (OR, 0.79; 95% CI, 0.49-1.27; I2 = 0%). The risk of 30-day major bleeding was increased among patients who underwent pretreatment (OR, 1.51; 95% CI, 1.16-1.97; I2 = 41%). The number needed to harm to bring about 1 major bleeding event with oral P2Y12 inhibitor pretreatment was 63 patients. In this study, pretreatment with oral P2Y12 inhibitors among patients with NSTEACS prior to angiography, compared with treatment once coronary anatomy is known, was associated with increased bleeding risk and no difference in cardiovascular outcomes. Routine pretreatment with oral P2Y12 inhibitors in patients with NSTEACS receiving an early invasive strategy is not supported by this study.

Abstract 13199: Generalizability and Prognostic Implications of Dapagliflozin and Finerenone in a Community-Based Cohort of Individuals With Diabetes and Chronic Kidney Disease

Introduction: Dapagliflozin (DAPA-CKD) and finerenone (FIDELIO-DKD) have shown to improve renal and cardiovascular (CV) outcomes in patients with type 2 diabetes (T2D) and chronic kidney disease (CKD). Hypothesis: We hypothesize individuals in a community-cohort who meet trial criteria will have higher rates of adverse outcomes. Methods: Adults with CKD from the Chronic Renal Insufficiency Cohort (CRIC) study were included. The inclusion criteria from each trial were applied to participants with T2D. Differences in characteristics and composite kidney and CV outcomes were assessed between trial eligibility groups. The estimated number of events prevented (NEP) over 3 years were calculated based on relative risk reduction estimates. Results: Among 2816 participants (mean [SD] age 62 [10], 41% female, 48% Black), 1545 (54.9%), 1458 (51.8%), and 1314 (46.7%) met DAPA-CKD, FIDELIO-DKD, and both inclusion criteria, respectively. Participants who met DAPA-CKD but not FIDELIO-DKD enrollment criteria were more likely to be Black and have higher CV, T2D, and kidney disease severity. Participants who met DAPA-CKD criteria (vs. ineligible) had higher rates of composite kidney (17.6% vs. 14.6%; p=0.006) and CV (15.5% vs. 12.6%; p=0.03) outcomes. Conversely, FIDELIO-DKD eligible participants had lower incidence of composite kidney outcomes (12.6% vs. 19.4%; p&lt;0.001) and no differences in CV outcomes (14.2 vs. 14.2%; p=0.99). The estimated NEP per 1000 patients with dapagliflozin was 60 and 43 for kidney and CV outcomes, respectively, compared with 21 and 19 for finerenone ( Fig ). Notable differences in NEP were observed between races for dapagliflozin but not finerenone treatment, with Black patients having significantly higher kidney and CV NEP ( Fig ). Conclusions: In a community-based registry of CKD patients, approximately half of patients would be eligible for dapagliflozin or finerenone. The estimated NEP was higher with dapagliflozin compared to finerenone.

Sex Differences in Cardiovascular Outcomes of Older Adults After Myocardial Infarction.

BackgroundEvidence on the impact of sex on prognoses after myocardial infarction (MI) among older adults is limited. We evaluated sex differences in long‐term cardiovascular outcomes after MI in older adults.Methods and ResultsAll patients with MI ≥70 years admitted to 20 Finnish hospitals during a 10‐year period and discharged alive were studied retrospectively using a combination of national registries (n=31 578, 51% men, mean age 79). The primary outcome was combined major adverse cardiovascular event within 10‐year follow‐up. Sex differences in baseline features were equalized using inverse probability weighting adjustment. Women were older, with different comorbidity profiles and rarer ST‐segment–elevation MI and revascularization, compared with men. Adenosine diphosphate inhibitors, anticoagulation, statins, and high‐dose statins were more frequently used by men, and renin‐angiotensin‐aldosterone inhibitors and beta blockers by women. After balancing these differences by inverse probability weighting, the cumulative 10‐year incidence of major adverse cardiovascular events was 67.7% in men, 62.0% in women (hazard ratio [HR], 1.17; CI, 1.13–1.21; P<0.0001). New MI (37.0% in men, 33.1% in women; HR, 1.16; P<0.0001), ischemic stroke (21.1% versus 19.5%; HR, 1.10; P=0.004), and cardiovascular death (56.0% versus 51.1%; HR, 1.18; P<0.0001) were more frequent in men during long‐term follow‐up after MI. Sex differences in major adverse cardiovascular events were similar in subgroups of revascularized and non‐revascularized patients, and in patients 70 to 79 and ≥80 years.ConclusionsOlder men had higher long‐term risk of major adverse cardiovascular events after MI, compared with older women with similar baseline features and evidence‐based medications. Our results highlight the importance of accounting for confounding factors when studying sex differences in cardiovascular outcomes.

Racial/ethnic differences in cardiovascular outcomes in a universal healthcare system: insights from the CARTaGENE cohort

Abstract Background While prior studies have shown racial/ethnic differences in cardiovascular (CV) outcomes within private or mixed health care systems, it remains uncertain whether inequalities in cardiovascular outcomes exist between different races and ethnicities in universal health care contexts. We aimed to determine whether there are racial/ethnicity disparities in long-term CV outcomes within a single-payer universal health care system. Methods The CARTaGENE study is a population-based prospective cohort study with enrollment of 19,996 individuals between 40–69 years in 2009, in the province of Quebec, Canada. Participants residing in four large metropolitan areas were randomly chosen from the provincial health insurance registry by strata of age, sex, and postal codes. Follow-up was available up to 2016. For this analysis, we retained only participants without prior known CV disease. The primary composite endpoint was time to the first CV event or intervention (CV death, acute coronary syndrome, heart failure, coronary revascularization, ischemic stroke, or peripheral vascular event or revascularization). We used unadjusted and adjusted Cox proportional hazard models to evaluate the association of self-defined race/ethnicity with the primary endpoint. Results There were 17,802 eligible participants with a mean age of 51 years (52.5% females) with 111,312 person-years of follow-up (median follow-up of 6.6 years). South Asian (SA) participants had the highest prevalence of diabetes mellitus (29%) and hypertension (32%). After adjustment for age and sex, SA ethnicity was associated with a 95% relative increase in risk for CV events, while East/Southeast Asian (ESA) ethnicity was associated with a 42% relative decrease in risk for CV events compared to White participants. After further adjustment for socioeconomic status and CV risk factors, ESA ethnicity remained associated with a similar decreased CV risk. In contrast, the association of SA ethnicity with increased CV risk was attenuated after full adjustment for baseline characteristics (Table 1). Conclusions Racial/ethnic disparities in long-term CV outcomes are present in a single-payer universal healthcare setting. ESA ethnicity was associated with a lower risk of long-term CV outcomes. Future studies are needed to corroborate the reduced risk of long-term major CV events associated with ESA ethnicity. Understanding the reasons related to potential CV protection with ESA ethnicity could facilitate endeavors to reduce long-term CV outcomes in other races/ethnicities. Funding Acknowledgement Type of funding sources: Public hospital(s). Main funding source(s): McGill Health University Center

Association between Add-On Dipeptidyl Peptidase-4 Inhibitor Therapy and Diabetic Retinopathy Progression

This study aimed to investigate the association of add-on dipeptidyl peptidase-4 inhibitor (DPP4i) therapy and the progression of diabetic retinopathy (DR). In this retrospective population-based cohort study, we examined Taiwanese patients with type 2 diabetes, preexisting DR, and aged ≥40 years from 2009 to 2013. Prescription of DPP4i was defined as a medication possession ratio of ≥80% during the first 6 months. The outcomes included vitreous hemorrhage (VH), tractional retinal detachment, macular edema, and interventions including retinal laser therapy, intravitreal injection (IVI), and vitrectomy. Of 1,767,640 patients, 62,824 were eligible for analysis. After matching, the DPP4i and non-DPP4i groups each contained 20,444 patients. The risks of VH (p = 0.013) and macular edema (p = 0.035) were higher in the DPP4i group. The DPP4i group also had higher risks of receiving surgical interventions (retinal laser therapy (p < 0.001), IVI (p = 0.049), vitrectomy (p < 0.001), and any surgical intervention (p < 0.001)). More patients in the DPP4i group received retinal laser therapy (p < 0.001) and IVI (p = 0.001) than in the non-DPP4i group. No between-group differences in cardiovascular outcomes were noted. In the real-world database study, add-on DPP4i therapy may be associated with the progression of DR in patients with type 2 diabetes. No additional cardiovascular risks were found. The early progression of DR in rapid glycemic control was inconclusive in our study. The possible effect of add-on DPP4i therapy in the progression of DR in patients with type 2 diabetes requires further research.