Peripheral artery disease, chronic kidney disease, and recurrent admissions for acute decompensated heart failure: The ARIC study.

BACKGROUND AND AIMS: Peripheral artery disease (PAD) has not only been associated with recurrent hospitalization for acute decompensated heart failure (ADHF) but is also associated with chronic kidney disease (CKD), a known risk factor for worse heart failure outcomes. The interaction of CKD with PAD in post-discharge ADHF outcomes is not well known. METHODS: Since 2005, hospitalizations for ADHF were sampled from 4 US regions by the Atherosclerosis Risk in Communities (ARIC) study and classified by physician review. We examined the adjusted association of PAD with 1-year ADHF readmissions, in patients with and without CKD (defined by glomerular filtration rate [GFR] ≤60 mL/min/1.73 m2 [stage 3a or worse]). RESULTS: From 2005 to 2018, there were 1049 index hospitalizations for patients with ADHF (mean age 77 years, 66 % white) with creatinine data, who were discharged alive. Of these, 155 (15 %) had PAD and 66 % had CKD. In comparison to those without PAD, patients with PAD had more comorbid conditions and higher 1-year ADHF readmission rates, irrespective of CKD status. After adjustment, PAD was associated with a greater risk of 1-year ADHF readmissions, both for patients with concomitant CKD (HR, 1.70; 95 % CI: 1.29-2.24) and those without CKD (HR, 1.97; 95 % CI: 1.14-3.40); p-interaction = 0.8. CONCLUSION: Among patients hospitalized with ADHF, those with concurrent PAD have more prevalent cardiovascular comorbidities and higher likelihood of 1-year ADHF readmission, irrespective of CKD status. Integrating a more holistic approach in management of patients with concomitant heart failure, PAD and CKD may be an important strategy to improve the prognosis in this vulnerable population.

Eicosapentaenoic Acid Improves Endothelial Nitric Oxide Bioavailability Via Changes in Protein Expression During Inflammation.

BACKGROUND: Endothelial cell (EC) dysfunction involves reduced nitric oxide (NO) bioavailability due to NO synthase uncoupling linked to increased oxidation and reduced cofactor availability. Loss of endothelial function and NO bioavailability are associated with inflammation, including leukocyte activation. Eicosapentaenoic acid (EPA) administered as icosapent ethyl reduced cardiovascular events in REDUCE-IT (Reduction of Cardiovascular Events With Icosapent Ethyl-Intervention Trial) in relation to on-treatment EPA blood levels. The mechanisms of cardiovascular protection for EPA remain incompletely elucidated but likely involve direct effects on the endothelium. METHODS AND RESULTS: In this study, human ECs were treated with EPA and challenged with the cytokine IL-6 (interleukin-6). Proinflammatory responses in the ECs were confirmed by ELISA capture of sICAM-1 (soluble intercellular adhesion molecule-1) and TNF-α (tumor necrosis factor-α). Global protein expression was determined using liquid chromatography-mass spectrometry tandem mass tag. Release kinetics of NO and peroxynitrite were monitored using porphyrinic nanosensors. IL-6 challenge induced proinflammatory responses from the ECs as evidenced by increased release of sICAM-1 and TNF-α, which correlated with a loss of NO bioavailability. ECs pretreated with EPA modulated expression of 327 proteins by >1-fold (P<0.05), compared with IL-6 alone. EPA augmented expression of proteins involved in NO production, including heme oxygenase-1 and dimethylarginine dimethylaminohydrolase-1, and 34 proteins annotated as associated with neutrophil degranulation. EPA reversed the endothelial NO synthase uncoupling induced by IL-6 as evidenced by an increased [NO]/[peroxynitrite] release ratio (P<0.05). CONCLUSIONS: These direct actions of EPA on EC functions during inflammation may contribute to its distinct cardiovascular benefits.

Efficacy and safety of SGLT2 inhibitors with and without glucagon-like peptide 1 receptor agonists: a SMART-C collaborative meta-analysis of randomised controlled trials.

BACKGROUND: SGLT2 inhibitors and GLP-1 receptor agonists both improve cardiovascular and kidney outcomes in patients with type 2 diabetes. We sought to evaluate whether the benefits of SGLT2 inhibitors are consistent in patients receiving and not receiving GLP-1 receptor agonists. METHODS: We conducted a collaborative meta-analysis of trials included in the SGLT2 Inhibitor Meta-Analysis Cardio-Renal Trialists' Consortium, restricted to participants with diabetes. Treatment effects from individual trials were obtained from Cox regression models and pooled using inverse variance weighted meta-analysis. The two main cardiovascular outcomes assessed included major adverse cardiovascular events (nonfatal myocardial infarction, nonfatal stroke, or cardiovascular death), and hospitalisation for heart failure or cardiovascular death. The main kidney outcomes assessed were chronic kidney disease progression (≥40% decline in estimated glomerular filtration rate [eGFR], kidney failure [eGFR <15 mL/min/1·73 m2, chronic dialysis, or kidney transplantation], or death due to kidney failure), and the rate of change in eGFR over time. Safety outcomes were also assessed. FINDINGS: Across 12 randomised, double-blind, placebo-controlled trials, 3065 (4·2%) of 73 238 participants with diabetes were using GLP-1 receptor agonists at baseline. SGLT2 inhibitors reduced the risk of major adverse cardiovascular events in participants both receiving and not receiving GLP-1 receptor agonists (hazard ratio [HR] 0·81, 95% CI 0·63-1·03 vs 0·90, 0·86-0·94; p-heterogeneity=0·31). Effects on hospitalisation for heart failure or cardiovascular death (0·76, 0·57-1·01 vs 0·78, 0·74-0·82; p-heterogeneity=0·90) and chronic kidney disease progression (0·65, 0·46-0·94 vs 0·67, 0·62-0·72; p-heterogeneity=0·81) were also consistent regardless of GLP-1 receptor agonist use, as was the effect on the chronic rate of change in eGFR over time (heterogeneity=0·92). Fewer serious adverse events occurred with SGLT2 inhibitors compared with placebo, irrespective of GLP-1 receptor agonist use (relative risk 0·87, 95% CI 0·79-0·96 vs 0·91, 0·89-0·93; p-heterogeneity=0·41). INTERPRETATION: The effects of SGLT2 inhibitors on cardiovascular and kidney outcomes are consistent regardless of the background use of GLP-1 receptor agonists. These findings suggest independent effects of these evidence-based therapies and support clinical practice guidelines recommending the use of these agents in combination to improve cardiovascular and kidney metabolic outcomes. FUNDING: National Health and Medical Research Council of Australia and the Ramaciotti Foundation.

Demystifying the Contemporary Role of 12-Month Dual Antiplatelet Therapy After Acute Coronary Syndrome.

For almost two decades, 12-month dual antiplatelet therapy (DAPT) in acute coronary syndrome (ACS) has been the only class I recommendation on DAPT in American and European guidelines, which has resulted in 12-month durations of DAPT therapy being the most frequently implemented in ACS patients undergoing percutaneous coronary intervention (PCI) across the globe. Twelve-month DAPT was initially grounded in the results of the CURE (Clopidogrel in Unstable Angina to Prevent Recurrent Events) trial, which, by design, studied DAPT versus no DAPT rather than the optimal DAPT duration. The average DAPT duration in this study was 9 months, not 12 months. Subsequent ACS studies, which were not designed to assess DAPT duration, rather its composition (aspirin with prasugrel or ticagrelor compared with clopidogrel) were further interpreted as supportive evidence for 12-month DAPT duration. In these studies, the median DAPT duration was 9 or 15 months for ticagrelor and prasugrel, respectively. Several subsequent studies questioned the 12-month regimen and suggested that DAPT duration should either be fewer than 12 months in patients at high bleeding risk or more than 12 months in patients at high ischemic risk who can safely tolerate the treatment. Bleeding, rather than ischemic risk assessment, has emerged as a treatment modifier for maximizing the net clinical benefit of DAPT, due to excessive bleeding and no clear benefit of prolonged treatment regimens in high bleeding risk patients. Multiple DAPT de-escalation treatment strategies, including switching from prasugrel or ticagrelor to clopidogrel, reducing the dose of prasugrel or ticagrelor, and shortening DAPT duration while maintaining monotherapy with ticagrelor, have been consistently shown to reduce bleeding without increasing fatal or nonfatal cardiovascular or cerebral ischemic risks compared with 12-month DAPT. However, 12-month DAPT remains the only class-I DAPT recommendation for patients with ACS despite the lack of prospectively established evidence, leading to unnecessary and potentially harmful overtreatment in many patients. It is time for clinical practice and guideline recommendations to be updated to reflect the totality of the evidence regarding the optimal DAPT duration in ACS.

Coronary Artery Bypass Graft Failure in Women: Incidence and Clinical Implications.

BACKGROUND: Women have worse outcomes after coronary artery bypass surgery (CABG) than men. OBJECTIVES: This study aimed to determine the incidence of CABG graft failure in women, its association with cardiac events, and whether it contributes to sex-related differences in outcomes. METHODS: A pooled analysis of individual patient data from randomized clinical trials with systematic imaging follow-up was performed. Multivariable logistic regression models were used to assess the association of graft failure with myocardial infarction and repeat revascularization between CABG and imaging (primary outcome) and death after imaging (secondary outcome). Mediation analysis was performed to evaluate the effect of graft failure on the association between female sex and risk of death. RESULTS: Seven randomized clinical trials (N = 4,413, 777 women) were included. At a median imaging follow-up of 1.03 years, graft failure was significantly more frequent among women than men (37.3% vs 32.9% at the patient-level and 20.5% vs 15.8% at the graft level; P = 0.02 and P < 0.001, respectively). In women, graft failure was associated with an increased risk of myocardial infarction and repeat revascularization (OR: 3.94; 95% CI: 1.79-8.67) and death (OR: 3.18; 95% CI: 1.73-5.85). Female sex was independently associated with the risk of death (direct effect, HR: 1.84; 95% CI: 1.35-2.50) but the association was not mediated by graft failure (indirect effect, HR: 1.04; 95% CI: 0.86-1.26). CONCLUSIONS: Graft failure is more frequent in women and is associated with adverse cardiac events. The excess mortality risk associated with female sex among CABG patients is not mediated by graft failure.

Alirocumab and cardiovascular outcomes according to sex and lipoprotein(a) after acute coronary syndrome: a report from the ODYSSEY OUTCOMES study.

BACKGROUND: The ODYSSEY OUTCOMES trial (NCT01663402) compared the effects of the proprotein convertase subtilisin/kexin type 9 inhibitor alirocumab with placebo on major adverse cardiovascular events (MACE) in patients with recent acute coronary syndrome (ACS). OBJECTIVE: We assessed efficacy and safety of alirocumab versus placebo according to sex and lipoprotein(a) level. METHODS: This prespecified analysis compared the effects of alirocumab versus placebo on lipoproteins, MACE (coronary heart disease death, non-fatal myocardial infarction, fatal/non-fatal ischemic stroke, unstable angina requiring hospitalization), death, total cardiovascular events, and adverse events in 4762 women and 14,162 men followed for a median of 2.8 years. In post-hoc analysis, we evaluated total cardiovascular events according to sex, baseline lipoprotein(a), and treatment. RESULTS: Women were older, had higher baseline LDL-C levels (89.6 vs 85.3 mg/dL) and lipoprotein(a) (28.0 vs 19.3 mg/dL) and had more co-morbidities than men. At 4 months, alirocumab lowered LDL-C by 49.4 mg/dL in women and 54.0 mg/dL in men and lipoprotein(a) by 9.7 and 8.1 mg/dL, respectively (both p < 0.0001). Alirocumab reduced MACE, death, and total cardiovascular events similarly in both sexes. In the placebo group, lipoprotein(a) was a risk factor for total cardiovascular events in women and men. In both sexes, reduction of total cardiovascular events was greater at higher baseline lipoprotein(a), but this effect was more evident in women than men (pinteraction=0.08). Medication adherence and adverse event rates were similar in both sexes. CONCLUSIONS: Alirocumab improves cardiovascular outcomes after ACS irrespective of sex. Reduction of total cardiovascular events was greater at higher baseline lipoprotein(a).

Effects of catheter-based renal denervation in hypertension: a systematic review and meta-analysis.

Background: Several sham-controlled trials have investigated the efficacy and safety of catheter-based renal denervation (RDN) with mixed outcomes. Aim: To perform a comprehensive meta-analysis of all randomized, sham-controlled trials investigating RDN with first- and second-generation devices in hypertension. Methods: We searched MEDLINE and Cochrane Library for eligible trials. Outcomes included both efficacy (24-hour and office systolic [SBP] and diastolic blood pressure [DBP]) and safety (all-cause death, vascular complication, renal artery stenosis >70%, hypertensive crisis) of RDN. We performed a study-level, pairwise, random-effects meta-analysis of the summary data. Results: Ten trials comprising 2,478 patients with hypertension while being either off- or on-treatment were included. Compared with sham, RDN reduced 24-hour and office systolic BP by 4.4 mmHg (95%CI -6.1, -2.7, p<0.00001) and 6.6 mmHg (95%CI -9.7, -3.6, p<0.0001), respectively. The 24-hour and office diastolic BP paralleled these findings (-2.6 mmHg, 95%CI - 3.6, -1.5, p<0.00001; -3.5 mmHg, 95%CI -5.4, -1.6, p=0.0003). There was no difference in 24-hour and office SBP reduction between trials with and without concomitant antihypertensive medication (p for interaction 0.62 and 0.73, respectively). There was no relevant difference concerning vascular complications (OR 1.69, 95%CI 0.57-5.0, p=0.34), renal artery stenosis (OR 1.50, 95%CI 0.06-36.97, p=0.80), hypertensive crisis (OR 0.65, 95%CI 0.30-1.38, p=0.26) and all-cause death (OR 1.76, 95%CI 0.34-9.20, p=0.50) between RDN and sham groups. Change of renal function based on eGFR was comparable between groups (p for interaction 0.84). There was significant heterogeneity between trials. Conclusions: RDN safely reduces ambulatory and office SBP/DBP vs. a sham procedure in the presence and absence of antihypertensive medication. Clinical Perspective: What is new?Several sham-controlled trials have investigated the efficacy and safety of catheter-based renal denervation (RDN) with mixed outcomes.This comprehensive meta-analysis comprising 2,478 patients shows that irrespective of the utilized method (radiofrequency-, ultrasound-or alcohol-mediated), renal denervation effectively reduced ambulatory and office systolic blood pressure.Renal denervation exhibited no additional risk concerning vascular injury or renal function impairment.What are the clinical implications?This meta-analysis supports current guidelines/consensus statements that renal denervation represents an additive treatment option in carefully selected patients with uncontrolled hypertension.

Incidence and predictors of major gastrointestinal bleeding in patients on aspirin, low-dose rivaroxaban, or the combination: Secondary analysis of the COMPASS randomised controlled trial.

BACKGROUND: The incidence of major gastrointestinal bleeding (GIB) in patients on low-dose direct-acting oral anticoagulants (DOACs) is relatively unknown. Estimates from randomised controlled trials (RCTs) are lacking. AIMS: To assess GIB incidence and predictors from RCT data of patients on aspirin, low-dose rivaroxaban, or both. METHODS: This was a secondary analysis of RCT data wherein patients received aspirin 100 mg daily and rivaroxaban 2.5 mg b.d., aspirin alone, or rivaroxaban 5 mg b.d. Patients were followed from 2013 to 2016 at 602 centres. Outcomes included overall, upper, and lower GIB. We employed multivariable logistic regression to yield odds ratios (ORs) and 95% confidence intervals for potential exposures. RESULTS: Among 27,395 patients, the annual incidence of GIB on rivaroxaban 2.5 mg b.d. with aspirin was 801.7 per 100,000 compared with 372.3 in 100,000 for aspirin. Age (OR 4.16, 2.53-6.82 for ≥75 vs. 55-64), peptic ulcer disease (PUD, OR 1.57, 1.01-2.44), liver disease (OR 2.09, 1.01-4.33), hypertension (OR 1.42, 1.04-1.94), and smoking (OR 1.85, 1.26-2.73) were associated with overall GIB. Kidney disease (OR 1.68, 1.12-2.51) was significantly associated with upper GIB, whereas diverticular disease (OR 3.75, 1.88-7.49) was associated with lower GIB. Addition of rivaroxaban to aspirin was associated more with lower GIB (OR 2.82, 1.64-4.84) than upper GIB (OR 1.86, 1.18-2.92). CONCLUSIONS: We established incidences and identified risk factors for GIB in users of low-dose DOACs. Novel risk factors included current or former smoking and diverticulosis. Future studies should aim to validate these risk factors.

Lipoprotein(a) as a cardiovascular risk factor among patients with and without diabetes Mellitus: the Mass General Brigham Lp(a) Registry.

BACKGROUND: Diabetes mellitus (DM) and Lp(a) are well-established predictors of coronary artery disease (CAD) outcomes. However, their combined association remains poorly understood. OBJECTIVE: To investigate the relationship between elevated Lp(a) and DM with CAD outcomes. METHODS: Retrospective analysis of the MGB Lp(a) Registry involving patients ≥ 18 years who underwent Lp(a) measurements between 2000 and 2019. Exclusion criteria were severe kidney dysfunction, malignant neoplasms, and prior atherosclerotic cardiovascular disease (ASCVD). The primary outcome was a combination of cardiovascular death or myocardial infarction (MI). Elevated Lp(a) was defined as > 90th percentile (≥ 216 nmol/L). RESULTS: Among 6,238 patients who met the eligibility criteria, the median age was 54, 45% were women, and 12% had DM. Patients with DM were older, more frequently male, and had a higher prevalence of additional cardiovascular risk factors. Over a median follow-up of 12.9 years, patients with either DM or elevated Lp(a) experienced higher rates of the primary outcome. Notably, those with elevated Lp(a) had a higher incidence of the primary outcome regardless of their DM status. The annual event rates were as follows: No-DM and Lp(a) < 90th% - 0.6%; No-DM and Lp(a) > 90th% - 1.3%; DM and Lp(a) < 90th% - 1.9%; DM and Lp(a) > 90th% - 4.7% (p < 0.001). After adjusting for confounders, elevated Lp(a) remained independently associated with the primary outcome among both patients with DM (HR = 2.66 [95%CI: 1.55-4.58], p < 0.001) and those without DM (HR = 2.01 [95%CI: 1.48-2.74], p < 0.001). CONCLUSIONS: Elevated Lp(a) constitutes an independent and incremental risk factor for CAD outcomes in patients with and without DM.

Feasibility and Findings of Including Self-Identified Adult Congenital Heart Disease Patients in the INVESTED Trial.

Background: Adult congenital heart disease (ACHD) patients have significant morbidity and rise in cardiac admissions. Their outcome with high-dose influenza vaccination is unknown in comparison to those without ACHD. Objectives: The purpose of this study was to compare all-cause mortality or cardiopulmonary hospitalizations in self-identified ACHD versus non-ACHD patients receiving high- or low-dose influenza vaccination within the INfluenza Vaccine to Effectively Stop cardioThoracic Events and Decompensated heart failure trial. Methods: We prospectively included ACHD patients in the INVESTED (INfluenza Vaccine to Effectively Stop cardioThoracic Events and Decompensated heart failure) trial. The primary endpoint was all-cause death or hospitalization for cardiovascular or pulmonary causes. Results: Of the 272 ACHD patients, 132 were randomly assigned to receive high-dose trivalent and 140 to standard-dose quadrivalent influenza vaccine. Compared to the non-ACHD cohort (n = 4,988), ACHD patients were more likely to be younger, women, smokers, have atrial fibrillation, and have a qualifying event of heart failure. The primary outcome was 49.8 events versus 42.8 events per 100 person-years (adjusted HR: 1.17; 95% CI: 0.95-1.45; P = 0.144) in the ACHD group and non-ACHD group, respectively. The interaction between ACHD status and randomized treatment effect was not significant for the primary outcome (P = 0.858). Vaccine-related adverse events were similar in both groups. Conclusions: Patients who self-identify as being ACHD had similar primary outcome of all-cause death or hospitalization for cardiovascular or pulmonary causes compared to non-ACHD cohort. High-dose influenza vaccination was similar to standard-dose influenza vaccination on the primary outcome in patients who self-identify as ACHD.

One-year continuation of postpartum intrauterine contraceptive device: Findings from a prospective cohort study in India.

OBJECTIVE(S): To estimate continuation rates for postpartum intrauterine contraceptive device (PPIUD) at 6 weeks, 6 months and 1-year within existing programs in an under-resourced setting, and to identify determinants of discontinuation, removal and expulsion. STUDY DESIGN: We used a prospective cohort design and enrolled recent PPIUD adopter women across 100 public healthcare facilities in Odisha and Chhattisgarh, India. We collected their socio-demographic information and followed them up telephonically at 6 weeks, 6 months and 1 year for complications and continuation status. We assessed PPIUD continuation rates and factors associated with PPIUD discontinuation, removal, and expulsion using Cox proportional hazards modelling. RESULTS: We enrolled 916 participants (579 (63.2%) from Odisha and 337 (36.8%) from Chhattisgarh). The continuation rate of PPIUD was 88.7% at 6 weeks, 74.8% at 6 months 60.1% at one year. Once discontinued, chances of not opting for any family planning method was high (up to 81.2%). Participants with education of 6th to 12th class and those experiencing complications (pain abdomen, bleeding and discharge per vaginum) were more likely to remove the IUD with adjusted hazard ratio of 1.82 (95% CI: 1.18-2.79) and 4.39 (95% CI: 3.25-5.93) respectively. For expulsion, we did not find any factor that was statistically significant. CONCLUSION(S): PPIUD continuation rates declined considerably after the initial 6 weeks. Counselling and follow-up services for managing complications must be strengthened, especially in the first 6 weeks of PPIUD insertion, to enhance and sustain programmatic impact. IMPLICATIONS: Our findings emphasize on the need to strengthen client counseling and follow-up for management of complications, especially in the first 6 weeks of insertion of PPIUDs. Ongoing programs need to address comprehensive capacity building efforts in this regard.

Artificial intelligence for cardiovascular disease risk assessment in personalised framework: a scoping review.

Background: The field of precision medicine endeavors to transform the healthcare industry by advancing individualised strategies for diagnosis, treatment modalities, and predictive assessments. This is achieved by utilizing extensive multidimensional biological datasets encompassing diverse components, such as an individual's genetic makeup, functional attributes, and environmental influences. Artificial intelligence (AI) systems, namely machine learning (ML) and deep learning (DL), have exhibited remarkable efficacy in predicting the potential occurrence of specific cancers and cardiovascular diseases (CVD). Methods: We conducted a comprehensive scoping review guided by the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) framework. Our search strategy involved combining key terms related to CVD and AI using the Boolean operator AND. In August 2023, we conducted an extensive search across reputable scholarly databases including Google Scholar, PubMed, IEEE Xplore, ScienceDirect, Web of Science, and arXiv to gather relevant academic literature on personalised medicine for CVD. Subsequently, in January 2024, we extended our search to include internet search engines such as Google and various CVD websites. These searches were further updated in March 2024. Additionally, we reviewed the reference lists of the final selected research articles to identify any additional relevant literature. Findings: A total of 2307 records were identified during the process of conducting the study, consisting of 564 entries from external sites like arXiv and 1743 records found through database searching. After 430 duplicate articles were eliminated, 1877 items that remained were screened for relevancy. In this stage, 1241 articles remained for additional review after 158 irrelevant articles and 478 articles with insufficient data were removed. 355 articles were eliminated for being inaccessible, 726 for being written in a language other than English, and 281 for not having undergone peer review. Consequently, 121 studies were deemed suitable for inclusion in the qualitative synthesis. At the intersection of CVD, AI, and precision medicine, we found important scientific findings in our scoping review. Intricate pattern extraction from large, complicated genetic datasets is a skill that AI algorithms excel at, allowing for accurate disease diagnosis and CVD risk prediction. Furthermore, these investigations have uncovered unique genetic biomarkers linked to CVD, providing insight into the workings of the disease and possible treatment avenues. The construction of more precise predictive models and personalised treatment plans based on the genetic profiles of individual patients has been made possible by the revolutionary advancement of CVD risk assessment through the integration of AI and genomics. Interpretation: The systematic methodology employed ensured the thorough examination of available literature and the inclusion of relevant studies, contributing to the robustness and reliability of the study's findings. Our analysis stresses a crucial point in terms of the adaptability and versatility of AI solutions. AI algorithms designed in non-CVD domains such as in oncology, often include ideas and tactics that might be modified to address cardiovascular problems. Funding: No funding received.

Pathophysiology of Preeclampsia-Induced Vascular Dysfunction and Implications for Subclinical Myocardial Damage and Heart Failure.

Tragically, preeclampsia is a leading cause of pregnancy-related complications and is linked to a heightened risk for morbid and fatal cardiovascular disease (CVD) outcomes. Although the mechanism connecting preeclampsia to CVD risk has yet to be fully elucidated, evidence suggests distinct pathways of early and late preeclampsia with shared CV risk factors but with profound differences in perinatal and postpartum risk to the mother and infant. In early preeclampsia, <34 weeks of gestation, systemic vascular dysfunction contributes to near-term subclinical myocardial damage. Hypertrophy and diastolic abnormalities persist postpartum and contribute to early onset heart failure (HF). This HF risk remains elevated decades later and contributes to premature death. Black women are at the highest risk of preeclampsia and HF. These findings support closer monitoring of women postpartum, especially for those with early and severe preeclampsia to control chronic hypertension and reduce the potentially preventable sequelae of heightened CVD and HF risk.

One-Month Versus Three-Month Dual-Antiplatelet Therapy in High Bleeding Risk Patients With Chronic Kidney Disease.

Shortening the duration of dual-antiplatelet therapy (DAPT) after percutaneous coronary intervention (PCI) was shown to be effective and safe in patients at high bleeding risk (HBR). We aimed to investigate the effect of 1 versus 3-month DAPT on outcomes after drug-eluting stent in HBR patients with or without chronic kidney disease (CKD). Data from 3 prospective single-arm studies (XIENCE Short DAPT Program) enrolling HBR patients after successful coronary implantation of cobalt-chromium everolimus-eluting stent (XIENCE, Abbott) were analyzed. Subjects were eligible for DAPT discontinuation at 1 or 3 months if free from ischemic events. The primary end point was all-cause death or any myocardial infarction. The key secondary end point was Bleeding Academic Research Consortium Type 2 to 5 bleeding. Outcomes were assessed from 1 to 12 months after PCI. CKD was defined as baseline creatinine clearance <60 ml/min. Of 3,286 patients, 1,432 (43.6%) had CKD. One-month versus 3-month DAPT was associated with a similar 12-month risk of the primary outcome irrespective of CKD status (CKD: 9.5% vs 10.9%, adjusted hazard ratio 0.86, 95% confidence interval 0.60 to 1.22; no-CKD: 6.6% vs 5.6%, adjusted hazard ratio 1.15, 95% confidence interval 0.77 to 1.73; p interaction 0.299). Bleeding Academic Research Consortium 2 to 5 bleeding rates were numerically but not significantly lower with 1-month versus 3-month DAPT in both CKD (9.9% vs 12%) and no-CKD (6.4% vs 9.0%) patients. In conclusion, in HBR patients, 1-month versus 3-month DAPT was associated with a similar risk of ischemic complications and a trend toward fewer bleeding events at 12 months after PCI, irrespective of CKD status.

Cost-Effectiveness of Sotagliflozin in SOLOIST-WHF.

BACKGROUND: The efficacy of sotagliflozin in patients with diabetes and recent worsening of heart failure was shown in the SOLOIST-WHF trial. However, the cost-effectiveness of sotagliflozin in these patients has not been previously investigated. OBJECTIVES: The authors sought to determine the cost-effectiveness of sotagliflozin in patients with diabetes and recent worsening of heart failure. METHODS: Based on SOLOIST-WHF trial data (N = 1,222), we constructed a Markov model to estimate the lifetime impact of sotagliflozin from a U.S. health care sector perspective. Cost data were sourced from the National Inpatient Sample. Life expectancy was modeled from census data and modified by the mortality rate in SOLOIST-WHF. Fatal and nonfatal event rates were carried forward from the trial data. Utility was assessed from the published reports. RESULTS: Lifetime quality-adjusted life-years (QALYs) were 4.43 and 4.04 in the sotagliflozin and placebo groups, respectively, and lifetime costs were $220,113 and $188,198 in the sotagliflozin and placebo groups, respectively. The point estimate incremental cost-effectiveness ratio was $81,823 per QALY gained. The probability of being cost-effective was 3.6%, 67.5%, and 89.4% at willingness-to-pay thresholds of $50,000, $100,000, and $150,000, respectively, per QALY gained. CONCLUSIONS: In patients with diabetes and recent worsening of heart failure, sotagliflozin is cost-effective in the U.S. using commonly accepted willingness-to-pay thresholds. (Effect of Sotagliflozin on Cardiovascular Events in Participants With Type 2 Diabetes Post Worsening Heart Failure [SOLOIST-WHF]; NCT03521934).

DCRM 2.0: Multispecialty practice recommendations for the management of diabetes, cardiorenal, and metabolic diseases.

The spectrum of cardiorenal and metabolic diseases comprises many disorders, including obesity, type 2 diabetes (T2D), chronic kidney disease (CKD), atherosclerotic cardiovascular disease (ASCVD), heart failure (HF), dyslipidemias, hypertension, and associated comorbidities such as pulmonary diseases and metabolism dysfunction-associated steatotic liver disease and metabolism dysfunction-associated steatohepatitis (MASLD and MASH, respectively, formerly known as nonalcoholic fatty liver disease and nonalcoholic steatohepatitis [NAFLD and NASH]). Because cardiorenal and metabolic diseases share pathophysiologic pathways, two or more are often present in the same individual. Findings from recent outcome trials have demonstrated benefits of various treatments across a range of conditions, suggesting a need for practice recommendations that will guide clinicians to better manage complex conditions involving diabetes, cardiorenal, and/or metabolic (DCRM) diseases. To meet this need, we formed an international volunteer task force comprising leading cardiologists, nephrologists, endocrinologists, and primary care physicians to develop the DCRM 2.0 Practice Recommendations, an updated and expanded revision of a previously published multispecialty consensus on the comprehensive management of persons living with DCRM. The recommendations are presented as 22 separate graphics covering the essentials of management to improve general health, control cardiorenal risk factors, and manage cardiorenal and metabolic comorbidities, leading to improved patient outcomes.

Impact of Frailty on the Benefits of Dual Pathway Inhibition for the Secondary Prevention of Cardiovascular Events in the COMPASS Randomized Trial.

BACKGROUND: Individuals with frailty are at higher risk of adverse cardiovascular outcomes and bleeding. The objective of this study was to determine whether the effects of rivaroxaban 2.5mg twice daily in addition to low-dose aspirin are similar among frail compared with non-frail patients with chronic atherosclerotic vascular disease. METHODS: In the COMPASS trial (ClinicalTrials.gov number NCT01776424), patients with chronic atherosclerotic vascular disease were randomized to receive aspirin 100mg daily, aspirin 100mg daily and rivaroxaban 2.5mg twice daily or rivaroxaban 5mg twice daily. In this post hoc analysis, frailty was evaluated by constructing a cumulative deficit index from 37 diseases, signs, and symptoms. The frailty index for each participant was calculated as the proportion of the 37 deficits exhibited, with values >0.2 considered frail. The primary outcome was the composite of cardiovascular death, myocardial infarction, or stroke. Hazard ratios (HR) and 95% confidence intervals (CI) are reported. RESULTS: Frailty was present in 13% of the trial population. In non-frail individuals, adding rivaroxaban 2.5mg twice daily to aspirin reduced the primary outcome (HR, 95% CI: 0.69, 0.59-0.80) and mortality (0.75, 0.63-0.90) but increased major bleeding (1.87, 1.51-2.31); however, its effects on the primary outcome (1.06, 0.79-1.42), mortality (1.08, 0.80-1.46) and major bleeding (1.10, 0.71-1.70) were not evident among participants with frailty (respective interaction p-values 0.011, 0.049 and 0.032). CONCLUSIONS: In adults with chronic atherosclerotic vascular disease, the benefit of adding rivaroxaban 2.5mg twice daily to aspirin was not evident in patients with frailty.

Which Test Should I Order for an Inpatient Evaluation of Cardiac Ischemia?

AbstractTesting for cardiac ischemia, or for the obstructive coronary artery disease (CAD) that causes cardiac ischemia, is common among hospitalized patients. Many testing options exist. Choosing an appropriate test can be challenging and requires accurate risk stratification. Two major categories of testing are available: stress testing (also known as functional testing) and anatomical testing. Stress testing evaluates specifically for ischemia and can be conducted with or without imaging. Anatomical testing visualizes the obstructive CAD that causes ischemia. This article reviews how to choose an appropriate test for the evaluation of cardiac ischemia in the inpatient setting, using case examples to illustrate the considerations involved.

Association of Lipoprotein (a) and Standard Modifiable Cardiovascular Risk Factors With Incident Myocardial Infarction: The Mass General Brigham Lp(a) Registry.

BACKGROUND: Lipoprotein (a) [Lp(a)] is a robust predictor of coronary heart disease outcomes, with targeted therapies currently under investigation. We aimed to evaluate the association of high Lp(a) with standard modifiable risk factors (SMuRFs) for incident first acute myocardial infarction (AMI). METHODS AND RESULTS: This retrospective study used the Mass General Brigham Lp(a) Registry, which included patients aged ≥18 years with an Lp(a) measurement between 2000 and 2019. Exclusion criteria were severe kidney dysfunction, malignant neoplasm, and prior known atherosclerotic cardiovascular disease. Diabetes, dyslipidemia, hypertension, and smoking were considered SMuRFs. High Lp(a) was defined as >90th percentile, and low Lp(a) was defined as <50th percentile. The primary outcome was fatal or nonfatal AMI. A combination of natural language processing algorithms, International Classification of Diseases (ICD) codes, and laboratory data was used to identify the outcome and covariates. A total of 6238 patients met the eligibility criteria. The median age was 54 (interquartile range, 43-65) years, and 45% were women. Overall, 23.7% had no SMuRFs, and 17.8% had ≥3 SMuRFs. Over a median follow-up of 8.8 (interquartile range, 4.2-12.8) years, the incidence of AMI increased gradually, with higher number of SMuRFs among patients with high (log-rank P=0.031) and low Lp(a) (log-rank P<0.001). Across all SMuRF subgroups, the incidence of AMI was significantly higher for patients with high Lp(a) versus low Lp(a). The risk of high Lp(a) was similar to having 2 SMuRFs. Following adjustment for confounders and number of SMuRFs, high Lp(a) remained significantly associated with the primary outcome (hazard ratio, 2.9 [95% CI, 2.0-4.3]; P<0.001). CONCLUSIONS: Among patients with no prior atherosclerotic cardiovascular disease, high Lp(a) is associated with significantly higher risk for first AMI regardless of the number of SMuRFs.