Additional Cardiovascular Risk Research Articles

Tofacitinib Safety and Effectiveness in Canadian Patients with Rheumatoid Arthritis by Cardiovascular Risk Enrichment: Subanalysis of the CANTORAL Study.

ORAL Surveillance, a post-authorisation safety study of patients with rheumatoid arthritis (RA) enriched for cardiovascular (CV) risk, demonstrated increased risk of major adverse CV events (MACE) and malignancies (excluding non-melanoma skin cancer [NMSC]) for tofacitinib versus tumour necrosis factor inhibitors (TNFi). This analysis of a real-world Canadian observational study evaluated tofacitinib safety/effectiveness in patients meeting or not meeting CV risk criteria. CANTORAL included patients with moderate-to-severe RA initiating tofacitinib (10/2017-07/2020; N = 504). Interim data (data-cut: 07/2021) were stratified as CV risk-enriched (CV+ ; patients ≥ 50 years with ≥ 1 additional CV risk factor) or not CV risk-enriched (CV-; ≥ 50years without additional CV risk factors and 18-49 years with/without CV risk factors). Safety and persistence were evaluated to month (M) 36. Effectiveness outcomes to M18 included Clinical Disease Activity Index (CDAI)-defined low disease activity (LDA)/remission (CANTORAL co-primary endpoints) and Disease Activity Score in 28 joints, C-reactive protein (DAS28-4[CRP]) < 3.2/ < 2.6. Overall, 272/232 patients were included in CV+ /CV- cohorts (full analysis set) (435/356 patient-years [safety analysis set]). Incidence rates (events/100 patient-years) in CV+ /CV- cohorts were 138.5/112.5 for treatment-emergent adverse events (AEs); 17.0/5.6for serious AEs; 1.2/0.3for deaths; 5.5/1.7 for serious infections; 1.4/1.1 for herpes zoster; 1.6/0.0for MACE; 2.1/0.3for malignancies (excluding NMSC); 0.7/0.6 for NMSC; 0.5/0.0 for venous thromboembolic events. Persistence was generally comparable between cohorts. In CV+ /CV- cohorts, at M6, CDAI LDA and remission rates were 51.5%/54.6% and 12.0%/19.6%; DAS28-4(CRP) < 3.2/ < 2.6 rates were 44.0%/39.3% and 31.5%/28.8%, respectively; effectiveness was generally maintained to M18. In concordance with studies of background risk, AEs were more common in patients with CV risk enrichment, particularly those aged ≥ 65 years. Tofacitinib effectiveness/persistence were generally similar regardless of CV risk enrichment. These findings support individualised treatment benefit-risk assessment, including CV assessment/management, to optimise RA outcomes.

Prolonged Time-to-antihypertensive Therapy Worsens Organ Damage and Blood Pressure Control in Arterial Hypertension.

Delay in arterial hypertension (AH) diagnosis and late therapy initiation may affect progression towards hypertensive-mediated organ damage (HMOD) and blood pressure (BP) control. We aimed to assess the impact of time-to-therapy on BP control and HMOD in patients receiving AH diagnosis. We analysed data from the Campania Salute Network, a prospective registry of hypertensive patients (NCT02211365). At baseline visit, time-to-therapy was defined as the interval between the first occurrence of BP values exceeding guidelines-directed thresholds and therapy initiation; HMOD included left ventricular hypertrophy (LVH), carotid plaque, or chronic kidney disease. Optimal BP control was considered for average values < 140/90 mmHg. Low-risk profile was defined as grade I AH without additional cardiovascular risk factors. From 14,161 hypertensive patients, we selected 1,627 participants who were not on antihypertensive therapy. This population was divided into two groups based on the median time-to-therapy (≤ 2 years n = 1,009, > 2 years n = 618). Patients with a time-to-therapy > 2 years had higher risk of HMOD (adjusted odds ratio, aOR:1.51, 95%, CI:1.19-1.93, p < 0.001) due to increased risks of LVH (aOR:1.43, CI:1.12-1.82, p = 0.004), carotid plaques (aOR:1.29, CI:1.00-1.65, p = 0.047), and chronic kidney disease (aOR:1.68, CI:1.08-2.62, p = 0.022). Time-to-therapy > 2 years was significantly associated with uncontrolled BP values (aOR:1.49, CI:1.18-1.88, p < 0.001) and higher number of antihypertensive drugs (aOR:1.68, CI:1.36-2.08, p < 0.001) during follow-up. In low-risk subgroup, time-to-therapy > 2 years did not impact on BP control and number of drugs. In hypertensive patients, a time-to-therapy > 2 years is associated with HMOD and uncontrolled BP.

Position of Beta-blockers in the Treatment of Hypertension Today: An Indian Consensus.

Management of essential hypertension (HTN) remains challenging, with contemporary control being achieved in <1/10 of the cases, especially when aligned with the recently updated guidelines of American College of Cardiology (ACC) or International Society of Hypertension (ISH). The place and positioning of beta-blockers have been evolving, with recent focused updates, such as the European Society of Hypertension (ESH) 2023 guidelines, that may hold relevance for the Indian phenotypic traits of premature cardiovascular disease (CVD), fragile coronary architecture, and/or high resting heart rate. To further develop consensus on the clinical role and relevance of beta-blockers, including nebivolol, an Indian consensus was evolved with graded recommendations on their clinical role in HTN, HTN with additional cardiovascular (CV) risk, or type 2 diabetes mellitus (T2DM). An expert review panel was constituted, comprising interventional and clinical cardiologists as experts, to synthesize the literature for the development of a validated knowledge, attitude, and practice (KAP) survey questionnaire. Research databases, including Cochrane Systematic Reviews, PubMed, and Google Scholar, were accessed for contemporary information and guidelines on beta-blockers updated until Dec 2023. Delphi rounds were conducted to develop graded recommendations based on the strength, quality of evidence, and the agreement among the panelists (n = 9). Consensus was achieved on the graded recommendations, with ≥70% of national panelists in agreement. Ninety-six percent of respondents opined that the new ESH HTN guidelines (2023) help gain confidence in using beta-blockers, which are considered first-line drugs for the treatment of HTN. Beta-blockers, including nebivolol, can be recommended in patients with HTN with high resting heart rates, including young hypertensive patients under 40 years of age. For people under 60 years old with HTN, regardless of whether they have comorbid diseases, beta-blockers are the recommended drug choice. Ninety-five percent of respondents opined that nebivolol is the preferred beta-blocker in hypertensive patients with T2DM, followed by bisoprolol and metoprolol. More than 90% of respondents opined that the three most commonly preferred beta-blockers by experts in patients with angina were nebivolol, metoprolol, and bisoprolol. Beta-blockers, including nebivolol, can be considered initial-line therapy for HTN management in real-life settings in India and nebivolol is preferred because of its two important properties: highest beta-1 selectivity and endothelial-dependent vasodilation.

The Silent Threat: A Retrospective Cohort Study on the Impact of Prediabetes on ST-Elevation Myocardial Infarction Survival-A Call to Action!

Background: Prediabetes is frequently underdiagnosed and undertreated, yet it poses significant cardiovascular risks. This study investigates the impact of prediabetes on short- and long-term survival outcomes in patients who experienced ST-elevation myocardial infarction (STEMI). Methods: In this retrospective, single-center cohort study, we evaluated 725 STEMI patients stratified into non-diabetic, prediabetic, and diabetic groups based on HbA1c levels at presentation. A Kaplan-Meier survival analysis was employed to compare long-term outcomes over a three-year follow-up period. Cardiovascular risk factors, including hypertension and dyslipidemia, were analyzed across the groups. The discriminatory power of HbA1c for predicting all-cause mortality was assessed using an Area Under the Receiver Operating Characteristic (AUROC) analysis. Results: Of the 725 patients, 407 (56.1%) were non-diabetic, 184 (25.4%) were prediabetic, and 134 (18.5%) were diabetic. Prediabetic patients exhibited significant additional cardiovascular risk factors, such as arterial hypertension (67.4%) and dyslipidemia (78.3%), with prevalence rates between those of non-diabetic and diabetic patients. The Kaplan-Meier analysis revealed that at a three-year follow-up, prediabetic patients faced a survival disadvantage, with a significant decrease in survival rates compared to non-diabetic patients (log-rank p = 0.016); their survival outcomes approached those of diabetic patients (p = 0.125). The AUROC analysis demonstrated that HbA1c was a significant predictor of short- and long-term mortality, with a cut-off value of 5.75% and an Area Under the Curve (AUC) of 0.580-0.617 (95% CI: 0.458-0.721), indicating a moderate ability to predict survival in patients with STEMI. Conclusions: Prediabetes significantly worsens survival outcomes following STEMI, nearly approaching the risk level of diabetes. Integrating rigorous cardiovascular risk management strategies for prediabetic individuals, including lifestyle interventions and potentially pharmacological treatments, could prevent the progression to diabetes and mitigate associated cardiovascular risks.

Coronary artery calcium score and other risk factors in patients at moderate and high risk of cancer therapy-related cardiovascular toxicity

BackgroundThe presence and burden of coronary artery calcium (CAC) is a strong predictor of cardiovascular events. Current guidelines of the European Society of Cardiology (ESC) for cardio-oncology do not recommend the use of the CAC score to determine the status of risk in cancer patients. The aim of this study is to evaluate the presence and burden of CAC on cardiac tomography and the distribution of the cardiovascular toxicity risk factors in patients with moderate and high baseline risk of cancer therapy-related cardiovascular toxicity.MethodsThe study prospectively included cancer patients, diagnosed and qualified for systemic treatment with anthracycline chemotherapy. Clinical data and blood samples were collected from all patients. Additionally, the echocardiography and coronary computed tomography (CCTA) with the calculation of the coronary artery calcium (CAC) score were performed.ResultsA total of 80 patients (mean age 60.5 years, 75 female) were included in the study. The majority of patients (62, 77.5%) had breast cancer, 11 (13.8%) were diagnosed with sarcoma, and 7 (8.8%) with lymphoma. There were 42 (52.5%) patients classified as having moderate (MR) and 38 (47.5%) as having high risk (HR) of cancer therapy-related cardiovascular toxicity according to current ESC guidelines. In comparison with moderate risk, high risk patients were older and more likely to have hypertension, hyperlipidaemia and chronic kidney disease. The mean coronary artery calcium score was significantly higher in the HR group (150.4 vs. 24.8; p = 0.000). Furthermore, cardiac biomarkers were also higher in high-risk patients (p = 0.000). In echocardiographic parameters global longitudinal strain (GLS) was lower (p = 0.012), and diastolic dysfunction was more common in the HR group. However, the left ventricle ejection fraction (LVEF) was similar in the MR and HR groups.ConclusionsIn patients at high and moderate risk for cancer therapy-related cardiovascular toxicity, cardiovascular toxicity risk factors were common and more prevalent in the high-risk group. The coronary artery calcium score was also significantly higher in the high-risk group. Assessing the presence and burden of coronary artery calcium is an attractive option to assess additional cardiovascular risk in cancer patients.

Cannabinoids and the heart-apsychiatrist's perspective.

The partial legalization of cannabis in Germany in 2024 will affect both medical and recreational use of cannabis. Tetrahydrocannabinol (THC), the main psychoactive component of the cannabis plant, influences heart rate and blood pressure through the endocannabinoid system. Acute and chronic use can pose cardiovascular risks. There is evidence of alink between cannabis use and cardiovascular events such as stroke and myocardial infarction, although studies show conflicting results. The non-psychoactive cannabidiol (CBD) could have anti-inflammatory and antioxidant effects. Smoking cannabis poses additional cardiovascular risks similar to tobacco. Given these risks, cardiologists should routinely ask their patients about possible cannabis use and inform them about the potential cardiovascular dangers. The article also highlights the psychiatric risks of cannabis use, including dependence and psychosis, and emphasizes the need for interdisciplinary collaboration between cardiologists and psychiatrists to effectively manage cannabis-related health problems.

ApoA-I Infusions and Burden of Ischemic Events After Acute Myocardial Infarction: InsightsFrom the AEGIS-II Trial.

Following an acute myocardial infarction (AMI), patients remain at risk for subsequent cardiovascular (CV) events. In the AEGIS-II trial, CSL112, a human apolipoprotein A-I derived from plasma that enhances cholesterol efflux, did not significantly reduce the first occurrence of CV death, myocardial infarction (MI), or stroke through 90days compared with placebo. However, an analysis involving only the first event may not capture the totality of the clinical impact of an intervention because patients may experience multiple events. This prespecified exploratory analysis examines the effect of CSL112 on total burden of nonfatal ischemic events (ie, recurrent MI and stroke) and CV death. A total of 18,219 patients with AMI, multivessel coronary artery disease, and additional CV risk factors were randomized to either 4weekly infusions of 6g CSL112 (n=9,112) or matching placebo (n=9,107). Anegative binomial regression model was applied to estimate the effect of CSL112 compared with placebo on the rate ratio (RR) of ischemic events. For CV death, MI, and stroke, there were numerically fewer total events at 90days (503 vs 545 events; rate ratio [RR]: 0.88; 95%CI: 0.76-1.03, P=0.11), and nominally significantly fewer total events at 180 days (745 vs 821 events, RR: 0.87; 95%CI: 0.77-0.99; P=0.04) and 365days (1,120 vs 1,211 events; RR 0.89; 95%CI: 0.80-0.99; P=0.04). Subsequent events constituted 13% of events at 90days, 17% at 180days, and 22% at 1 year. Similar findings were seen with the total occurrence of nonfatal MI and CV death. When type II MIs, unlikely to be modified by enhancing cholesterol efflux, were excluded, there were nominally significant reductions in the total occurrence of nonfatal MI (excluding type 2) and CV death at all timepoints (90days: RR: 0.81; 95%CI: 0.68-0.97; P=0.02; 180days: RR: 0.82; 95%CI: 0.71-0.95; P< 0.01; 365days: RR: 0.86; 95%CI: 0.76-0.98; P=0.02). In this prespecified exploratory analysis of the AEGIS-II trial, 4weekly infusions of CSL112 among high-risk patients after AMI significantly reduced the total burden of nonfatal ischemic events and CV death at 180 and 365days compared with placebo. (AEGIS-II [Study to Investigate CSL112 in Subjects With Acute Coronary Syndrome]; NCT03473223).

Abstract P223: Impact Of Dynamic Or Static Training On Flow-Mediated Dilatation Following Prolonged Head-Down Tilt Bedrest

Cardiovascular deconditioning, cephalad fluid shifts, and altered sympathetic activity in weightlessness may elicit changes in vascular structure and function akin to vascular ageing. Head-down tilt bedrest is an established terrestrial model for weightlessness and elicits similar cardiovascular responses. We hypothesized that 30 days head-down tilt bedrest (HDTBR) worsens flow mediated dilation (FMD), a non-invasive endothelial function marker, and that daily orthostatic stimuli or physical exercise attenuates the response. Fourty-seven healthy individuals (20 women, age 35±9 years, BMI 23.7±2.6 kg/m 2 ) were assigned to 30 days of strict HDTBR and divided into four groups: Daily 6 hours of upright sitting (positive control, n=11); 6 hours of -25 mmHg lower body negative pressure (n=12); 60 minutes of supine cycling followed by 6 hours of thigh cuff venous occlusion 6 days per week (n=12), or no countermeasure (negative control, n=12). We measured upper arm blood pressure and heart rate 5 days before and immediately after bedrest. We assessed plasma volume by carbon monoxide-rebreathing 2 days before and on day 28 of bedrest. We determined FMD of the brachial artery 5 days before, on day 28 of bedrest, and after 13-day recovery. We collected blood samples to measure pro- and anti-inflammatory cytokines. Heart rate was elevated after bedrest (p&lt;0.0001) but remained constant in seated and cycling groups (seated MD 5±2 /min, cycling MD 5±2, p=0.0051). Systolic blood pressure increased in all groups (MD 4±1 mmHg, p=0.0004). Diastolic blood pressure was higher post-bedrest in the control group (MD 8±2 mmHg, p=0.0002) but remained constant in the countermeasure groups. Plasma volume was reduced after bed rest (MD -400±37 ml, p&lt;0.0001) but maintained in the cycling group (MD 147±72 ml, p=0.0001). FMD did not differ between groups, but was higher at bedrest (MD 1.9±0.8 %, p=0.0481), whereas recovery values did not differ from baseline. Resting brachial artery diameter tended to be higher at bedrest (p=0.0876). Cytokines revealed no clinically relevant inflammatory response. Head-down tilt bedrest-induced cardiovascular deconditioning, which was not completely abolished by any countermeasure, paradoxically increased flow-mediated brachial vasodilation. Additional cardiovascular risk factors may be required to express endothelial dysfunction in the face of reduced physical activity.

Additional cardiovascular disease risk factors present in children with familial hypercholesterolemia at the first visit

Additional cardiovascular disease risk factors present in children with familial hypercholesterolemia at the first visit

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

BackgroundDiabetes mellitus (DM) and Lp(a) are well-established predictors of coronary artery disease (CAD) outcomes. However, their combined association remains poorly understood.ObjectiveTo investigate the relationship between elevated Lp(a) and DM with CAD outcomes.MethodsRetrospective 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).ResultsAmong 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).ConclusionsElevated Lp(a) constitutes an independent and incremental risk factor for CAD outcomes in patients with and without DM.

Highlights of Cardiovascular Disease Prevention Studies Presented at the 2024 American College of Cardiology Conference.

To summarize selected late-breaking science on cardiovascular (CV) disease prevention presented at the 2024 Scientific Session of the American College of Cardiology (ACC) conference. The LIBerate-HR trial showed the efficacy and safety of lerodalcibep, a subcutaneous injection that prevents binding of Pro-Protein Convertase Subtilisin/Kexin (PCSK) 9 to low-density lipoprotein (LDL)-receptors resulting in LDL-cholesterol (LDL-C) lowering in patients at very high risk or high risk of atherosclerotic CV disease (ASCVD). The AEGIS-II randomized patients with type 1 myocardial infarction (MI) with multivessel coronary artery disease and additional CV risk factors and found no benefit in major adverse CV events (MACE) with CSL112, an apolipoprotein A1 infusion shown to increase cholesterol efflux capacity. The Bridge-TIMI 73a trial showed a significant reduction in triglyceride (TG) levels with olezarsen, an antisense mRNA, in patients with moderate hyperTG with elevated CV risk. The BE ACTIVE trial showed significant improvement in step counts in patients given behavioral and financial incentives. The DRIVE study showed a significant increase in the prescription of either sodium-glucose co-transporter-2 inhibitors or glucagon-like peptide-1 receptor agonists in patients with type 2 diabetes mellitus (T2DM) at elevated CV or renal risk with a remote team-based, non-licensed navigator and clinical pharmacist approach. The TACTiC trial showed increased and sustained use of statin therapy by patient-driven use of a web-based portal that calculated the ASCVD risk score and gave prompts. The VICTORIAN-INITIATE trial showed efficacy and safety in early use of inclisiran in patients with ASCVD who did not reach target LDL-C < 70mg/dL despite maximally tolerated statin therapy. The ARISE-HF trial showed no difference in change of peak oxygen consumptionwith the use of an oral aldose reductase inhibitor, AT-001, in patients with well-controlled T2DM and diabetic cardiomyopathy with high-risk features compared to placebo. The PREVENT trial showed a significant reduction in target vessel failure at 2years in patients with non-flow limiting vulnerable plaques with percutaneous coronary intervention and optimal medical therapy (OMT) compared to OMT alone. The late-breaking clinical science presented at the 2024 Scientific Session of the ACC paves the way for an evidence-based alternative to statin therapy and provides data on several common clinical scenarios encountered in daily practice.

Prevalence, Clustering, and Current Management of Cardiovascular Risk Factors Upon First Referral to Hypertension Specialists: the APPROACH Study.

Several observational studies have been conducted to assess the prevalence of cardiovascular risk factors in hypertensive patients; however, none has yet investigated prevalence, clustering, and current management of cardiovascular risk factors upon first referral to hypertension specialists, which is the aim of the present study. Consecutive adult outpatients with essential/secondary hypertension were included at the time of their first referral to hypertension specialists at 13 Italian centers in the period April 2022-2023 if they had at least one additional major cardiovascular risk factor among LDL-hypercholesterolemia, type 2 diabetes, and cigarette smoking. Prevalence, degree of control, and current management strategies of cardiovascular risk factors were assessed. A total of 255 individuals were included, 40.2% women and 98.4% Caucasian. Mean age was 60.3±13.3years and mean blood pressure [BP] was 140.3±17.9/84.8±12.3mmHg). Most participants were smokers (55.3%), had a sedentary lifestyle (75.7%), suffered from overweight/obesity (51%) or high LDL-cholesterol (41.6%), had never adopted strategies to lose weight (55.7%), and were not on a low-salt diet (57.4%). Only a minority of patients reported receiving specialist counseling, and 27.9% had never received recommendations to correct unhealthy lifestyle habits. Nearly 90% of individuals with an estimated high/very high cardiovascular risk profile did not achieve recommended LDL-cholesterol targets. In patients with hypertension, both pharmacological and lifestyle therapeutic advice are yet to improve before referral to hypertension specialists. This should be considered in the primary care setting in order to optimize cardiovascular risk management strategies.

#2595 Evolution of hemoglobin and serum uric acid levels after SGLT2i initiation in patients with and without diabetic nephropathy

Abstract Background and Aims Sodium-glucose cotransporter 2 inhibitors (SGLT2i) are glucose-lowering drugs that inhibit glucose reabsorption in the proximal tubule, enhancing urinary glucose excretion. SGLT2i exhibit significant cardio- and renoprotective effects due to their capacity to increase diuresis and weight loss and reduce intraglomerular and blood pressure. Moreover, recent studies have described the potential of SGLT2i to improve additional cardiovascular risk factors, such as anemia or hyperuricemia. In this study, we aimed to describe the evolution of hemoglobin (Hb) and serum uric acid (SUA) levels in CKD patients with and without diabetic nephropathy before and after the initiation of SGLT2i therapy. Method CKD patients with and without diabetic nephropathy that were followed in the outpatient clinic of a tertiary referral academic hospital during January 2020 to September 2023 and that started SGLT2i therapy during that period were randomly recruited in the study. Patient characteristics, CKD staging, and levels of Hb and SUA before and after SGLT2i initiation were compared between groups. Hb and SUA levels were averaged considering all available laboratory controls during the last 12 months before treatment initiation and any available controls after treatment start. Results Demographic and clinical characteristics of enrolled patients are summarized in Fig. 1. Subjects with diabetic nephropathy were significantly older, more commonly hypertensive, presented worse kidney function, had received SGLT2i for a lengthier time and had lower hemoglobin values. We observed no change in hemoglobin levels after the initiation of SGLT2i in our sample, independently of diabetic nephropathy status or CKD stage (Fig. 2A, C). In contrast, SUA levels decreased significantly both in patients with and without diabetic nephropathy (Fig. 2B). This effect was observed across all the spectrum of CKD in our sample (Fig. 2D). Conclusion In our sample, SGLT2i initiation was associated with a significant decrease in SUA levels, both in patients with and without diabetic nephropathy and independently of CKD stage, which may help to explain its cardio- and nephroprotective effects. No change in Hb levels was observed, possibly due to a low prevalence of anaemia in our sample.

Risk of Venous Thromboembolism With Tofacitinib Versus Tumor Necrosis Factor Inhibitors in Cardiovascular Risk-Enriched Rheumatoid Arthritis Patients.

The ORAL Surveillance trial found a dose-dependent increase in venous thromboembolism (VTE) and pulmonary embolism (PE) events with tofacitinib versus tumor necrosis factor inhibitors (TNFi). We aimed to assess VTE incidence over time and explore risk factors of VTE, including disease activity, in ORAL Surveillance. Patients with rheumatoid arthritis (RA) aged 50 years or older with at least one additional cardiovascular risk factor received tofacitinib 5 or 10 mg twice daily (BID) or TNFi. Post hoc, cumulative probabilities and incidence rates (patients with first events/100 patient-years) by 6-month intervals were estimated for adjudicated VTE, deep vein thrombosis, and PE. Cox regression models identified risk factors. Clinical Disease Activity Index leading up to the event was explored in patients with VTE. Cumulative probabilities for VTE and PE were higher with tofacitinib 10 mg BID, but not 5 mg BID, versus TNFi. Incidence rates were consistent across 6-month intervals within treatments. Across treatments, risk factors for VTE included prior VTE, body mass index greater than or equal to 35 kg/m2, older age, and history of chronic lung disease. At the time of the event, most patients with VTE had active disease as defined by Clinical Disease Activity Index. Incidences of VTE and PE were higher with tofacitinib (10 > 5 mg BID) versus TNFi and were generally consistent over time. Across treatments, VTE risk factors were aligned with previous studies in the general RA population. These data highlight the importance of assessing VTE risk factors, including age, body mass index, and VTE history, when considering initiation of tofacitinib or TNFi in patients with active RA.

Apolipoprotein A1 Infusions and Cardiovascular Outcomes after Acute Myocardial Infarction

BackgroundCardiovascular events frequently recur after acute myocardial infarction, and low cholesterol efflux — a process mediated by apolipoprotein A1, which is the main protein in high-density lipoprotein — has been associated with an increased risk of cardiovascular events. CSL112 is human apolipoprotein A1 derived from plasma that increases cholesterol efflux capacity. Whether infusions of CSL112 can reduce the risk of recurrent cardiovascular events after acute myocardial infarction is unclear.MethodsWe conducted an international, double-blind, placebo-controlled trial involving patients with acute myocardial infarction, multivessel coronary artery disease, and additional cardiovascular risk factors. Patients were randomly assigned to receive either four weekly infusions of 6 g of CSL112 or matching placebo, with the first infusion administered within 5 days after the first medical contact for the acute myocardial infarction. The primary end point was a composite of myocardial infarction, stroke, or death from cardiovascular causes from randomization through 90 days of follow-up.ResultsA total of 18,219 patients were included in the trial (9112 in the CSL112 group and 9107 in the placebo group). There was no significant difference between the groups in the risk of a primary end-point event at 90 days of follow-up (439 patients [4.8%] in the CSL112 group vs. 472 patients [5.2%] in the placebo group; hazard ratio, 0.93; 95% confidence interval [CI], 0.81 to 1.05; P=0.24), at 180 days of follow-up (622 patients [6.9%] vs. 683 patients [7.6%]; hazard ratio, 0.91; 95% CI, 0.81 to 1.01), or at 365 days of follow-up (885 patients [9.8%] vs. 944 patients [10.5%]; hazard ratio, 0.93; 95% CI, 0.85 to 1.02). The percentage of patients with adverse events was similar in the two groups; a higher number of hypersensitivity events was reported in the CSL112 group.ConclusionsAmong patients with acute myocardial infarction, multivessel coronary artery disease, and additional cardiovascular risk factors, four weekly infusions of CSL112 did not result in a lower risk of myocardial infarction, stroke, or death from cardiovascular causes than placebo through 90 days. (Funded by CSL Behring; AEGIS-II ClinicalTrials.gov number, NCT03473223.)

Risk of extended major adverse cardiovascular event endpoints with tofacitinib versus TNF inhibitors in patients with rheumatoid arthritis: a post hoc analysis of a phase 3b/4 randomised safety study

ObjectivesCompare the risk of extended major adverse cardiovascular (CV) event (MACE) composite outcomes and component events in patients with rheumatoid arthritis (RA) treated with tofacitinib versus tumour necrosis factor inhibitors...

Icosapent ethyl modulates circulating vascular regenerative cell content: The IPE-PREVENTION CardioLink-14 trial

REDUCE-IT (Reduction of Cardiovascular Events with Icosapent Ethyl-Intervention Trial) showed that icosapent ethyl (IPE) reduced major adverse cardiovascular events by 25%. Since the underlying mechanisms for these benefits are not fully understood, the IPE-PREVENTION CardioLink-14 trial (ClinicalTrials.gov: NCT04562467) sought to determine if IPE regulates vascular regenerative (VR) cell content in people with mild to moderate hypertriglyceridemia. Seventy statin-treated individuals with triglycerides ≥1.50 and <5.6mmol/L and either atherosclerotic cardiovascular disease or type 2 diabetes with additional cardiovascular risk factors were randomized to IPE (4 g/day) or usual care. VR cells with high aldehyde dehydrogenase activity (ALDHhi) were isolated from blood collected at the baseline and 3-month visits and characterized with lineage-specific cell surface markers. The primary endpoint was the change in frequency of pro-vascular ALDHhiside scatter (SSC)lowCD133+ progenitor cells. Change in frequencies of ALDHhiSSCmid monocyte and ALDHhiSSChi granulocyte precursor subsets, reactive oxygen species production, serum biomarkers, and omega-3 levels were also evaluated. Baseline characteristics, cardiovascular risk factors, and medicationswere balanced between the groups. Compared to usual care, IPE increased the mean frequency of ALDHhiSSClowCD133+ cells (-1.00%± 2.45% vs.+7.79%± 1.70%; p= 0.02), despite decreasing overall ALDHhiSSClow cell frequency. IPE assignment also reduced oxidative stress in ALDHhiSSClow progenitors and increased ALDHhiSSChi granulocyte precursor cell content. IPE-PREVENTION CardioLink-14 provides the first translational evidence that IPE can modulate VR cell content and suggests a novel mechanism that may underlie the cardioprotective effects observed with IPE in REDUCE-IT. HLS Therapeutics provided the IPE in kind and had no role in the study design, conduct, analyses, or interpretation.

Diagnosis of hepatic steatosis and steatohepatitis in people with new-onset type 2 diabetes: a multidisciplinary approach.

Non-Alcoholic-Fatty-Liver-Disease (NAFLD) is the most common cause of chronic liver disease in Western countries; closely linked to obesity and type 2 diabetes (T2DM), it is an additional cardiovascular risk factor. The aim of this study is to investigate the prevalence of NAFLD at T2DM onset. 122 newly diagnosed T2DM patients were enroled; NAFLD was diagnosed using ultrasound and fibrosis risk calculated with an FIB4-score. Intermediate and high-risk patients were referred to a hepatologist and underwent transient elastography (TE). At T2DM diagnosis, 25% of patients were overweight, 47% were obese; ultrasound steatosis was present in 79% of patients; the average FIB-4 score was 1.4 (0.7). The NAFLD population was characterised by higher presence of obesity (60%, p 0.06); hypertension (56%, p 0.00); AST (26.3 (23.6) UI/L; p 0.00); ALT (49.3(41.0) UI/L p 0.00); FIB-4 score (1.6 (0.8); p 0.00). Among patients referred to a hepatologist, at TE, 65% had severe steatosis, 22% significant fibrosis and 25% advanced fibrosis. This is the first proposal of a NAFLD screening model at T2DM diagnosis. The high prevalence of fibrosis found at the early stage T2DM confirms the compelling need for early management of NAFLD through cost-effective screening and long-term monitoring algorithms.

Prevalence of prediabesity and diabesity. Analysis of data from the 2016-17 Chilean National Health Survey

Diabesity is defined as the coexistence of obesity and type 2 diabetes (T2D), either with or without additional cardiovascular risk factors. Despite its significance, its prevalence has not yet been investigated in Chile. The objective of this study was to determine the prevalence of prediabesity and diabesity in Chilean adults. 4,985 participants older than 18 from the Chilean National Health Survey 2016-2017 were included in this cross-sectional analysis. Nutritional status was determined through the body-mass index while T2D was determined through fasting glycemia ≥126 mg / dL or self-reported medical status. Using these two variables, six phenotypes were defined: normal without diabetes, normo-diabetes, overweight without diabetes, prediabesity, obesity without diabetes, and diabesity. The prevalence of these was studied according to sociodemographic and lifestyle characteristics. The prevalence of diabesity was 5.7%, 3.6% had prediabesity, and 2.5% were classified as normo-diabetes. Additionally, the prevalence of diabetes was mainly in women, in people with less than 8 years of schooling, and in those with an age of diagnosis of 45-46 years. 9.3% of the population presented pre or diabesity, with a higher proportion of diabesity cases in women and people with lower education. Considering the projections of obesity and T2DM in Chile, it is urgent to generate actions and strategies since a large proportion of the cases of these diseases can be preventable.

Modification of Cardiovascular Risk Factors and the Evolution of The Cardiovascular Phenotype of Liver Transplant Recipients in the Long -Term Postoperative Period.

To evaluate the contribution of traditional and additional cardiovascular risk factors (CVRFs) to the development of chronic ischemic heart disease (CIHD) in liver transplant recipients during the long-term postoperative period. A single-center prospective cohort study was conducted. The study included 740 patients with chronic end-stage liver disease (CESLD) and cirrhotic cardiomyopathy (CCMP). During the observation period (5.4±2.29 years), patients were divided into two groups: liver transplant recipients (n=420) and patients with CESLD on the waiting list who did not receive a donor organ (n=320). In patients enrolled to the study upon inclusion in the waiting list, CVRFs, history, clinical and laboratory and instrumental data were studied at all stages of the hepato-cardiac continuum. During the long-term postoperative period, liver transplant recipients belonged to the group of high cardiovascular risk: over a 5-year observation period, 35.7% (n=150) of them developed metabolic syndrome (MS), 9.8% developed verified CIHD associated with MS. The incidence of traditional CVRFs was high (arterial hypertension, 88.6%; obesity, 36.6%; hypercholesterolemia, 77.8%; hypertriglyceridemia, 43.6%; reduced concentration of high-density lipoprotein cholesterol, 35.4%; increased concentrations of low-density lipoprotein cholesterol, 66.8% and very low-density lipoprotein cholesterol, 51.2%; increased atherogenic index, 61.5%). During the long-term postoperative period as compared to the period when patients were on the waiting list, additional CVRFs appeared: increases in body mass index, calcium index, nitric oxide metabolites, endothelin-1, homocysteine, intercellular adhesion molecules VCAM-1 and ICAM-1, and decreases in endothelium-dependent vasodilation and glomerular filtration rate to less than 60 ml/min/1.73 m2. A model for the development of CIHD was created. The model uses a complex of independent risk factors and demonstrates a predictive accuracy of 84.6%. The study results indicate a modification of CVRFs and a dynamic change in the cardiovascular phenotype of liver transplant recipients: progression of CCMP during their stay on the waiting list, regression of CCMP manifestations during the first 12 months after orthotopic liver transplantation, and increases in the total cardiovascular risk and likelihood of CIHD in the long-term postoperative period.