Additional Cardiovascular Risk Factors Research Articles

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.

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.

Glomerular filtration rate predicts pro-vascular progenitor cell depletion: insights from the IPE-PREVENTION and ORIGINS-RCE studies

Abstract Background People living with cardiometabolic disease and impaired renal function are at increased risk of experiencing adverse cardiovascular outcomes(1,2). Recent evidence indicates that individuals living with atherosclerotic cardiovascular disease (ASCVD) and type 2 diabetes (T2D) exhibit a reduction in circulating vascular regenerative (VR) cells that are essential for maintaining blood vessel homeostasis(3). However, there is limited data on whether VR cell content changes in response to cardiometabolic and kidney disorders. Purpose We sought to determine if there is an association between estimated glomerular filtration rate (eGFR) and VR cell content in individuals with ASCVD and/or diabetes. Data were from participants enrolled in the IPE-PREVENTION and ORIGINS-RCE studies. Methods IPE-PREVENTION participants had moderately elevated triglycerides (1.5 - 5.65 mmol/L) with established ASCVD and/or T2D. ORIGINS-RCE participants had established ASCVD or T2D and at least one additional cardiovascular risk factor. Circulating mononuclear cells were isolated from peripheral blood and characterized using side scatter properties (SSC) and high aldehyde dehydrogenase activity to quantify pro-angiogenic early myeloid progenitor cells (ALDHhi), and primitive versus lineage-specific cell surface marker co-expression. Participants were stratified according to those with an eGFR &amp;lt;60 mL/min/1.73m², or ≥60 mL/min/1.73m². Results Median [IQR] eGFR of the pooled cohort (n=169) was 75 [59, 88] mL/min/1.73m²; 45% had an eGFR that was &amp;lt;60 mL/min/1.73m². The stratum with eGFR &amp;lt;60 mL/min/1.73m² had fewer circulating ALDHhiSSClow progenitor cells (0.037 vs. 0.051%; P&amp;lt;0.01) (Figure 1A) and ALDHhiSSClow cells expressing CD34+ and CD133+ (49 vs. 54%; P=0.03) (Figure 1B) than that with an eGFR ≥60 mL/min/1.73m². The predictive value of eGFR on ALDHhiSSClowCD34+CD133+ frequency was conserved even after controlling for age, sex, LDL-C, BMI, and HbA1c (P&amp;lt;0.01) (Table 1). The frequency of ALDHhiSSCmid monocyte precursor cells did not differ based on eGFR status. Conclusions Low eGFR was predictive for the depletion of ALDHhiSSClow primitive progenitor cells that co-express the stem cell markers CD133 and CD34 in individuals with ASCVD and/or T2D suggesting that diminished kidney function is associated with a decrease in vessel reparative pro-angiogenic progenitor cell content. Strategies that improve circulating VR cell content in individuals living with kidney and cardiometabolic disease may provide clinically meaningful benefits.Figure 1Table 1

SGLT2 Inhibitors vs. GLP-1 Agonists to Treat the Heart, the Kidneys and the Brain.

Sodium glucose cotransporter 2 (SGLT2) inhibitors and glucagon-like-peptide-1 receptor (GLP-1-R) agonists are novel therapeutic agents used for the management of type 2 diabetes mellitus (T2DM). Recently, large-scale randomized clinical trials have been conducted to assess the cardiovascular safety of these medications. The findings of these trials have revealed that both SGLT2 inhibitors and GLP-1-R agonists exhibit favorable cardioprotective effects, including reduction in cardiovascular and all-cause mortality, a decreased risk of chronic kidney disease progression, a decrease in hospitalization for heart failure (HF), an effect shown by SGLT2 inhibitors, and stroke prevention, an effect shown by GLP-1-R agonists. Based on the results from above studies, the European and American Diabetes Associations have issued new recommendations strongly endorsing the use of SGLT2 inhibitors and GLP-1-R agonists in combination with metformin for patients with T2DM who have additional cardiovascular (CV) comorbidities or risk factors. The primary aim of this combined therapy is to prevent CV events. Although both medication groups offer beneficial effects, they demonstrate slightly different profiles. SGLT2 inhibitors have exhibited better effects regarding a reduced incidence of HF, whereas GLP-1-R agonists have shown a reduced risk of CV events, particularly stroke. Moreover, recent European Society of Cardiology as well as American College of Cardiology and American Heart Association guidelines of HF treatment stressed the importance of SGLT2 inhibitor administration in patients with HF regardless of T2DM. In this context, we present and discuss the outcomes of the most recent trials investigating the impact of SGLT2 inhibitors and GLP-1-R agonists on renal and cardiovascular outcomes in patients, both with and without T2DM. Additionally, we explore the synergistic effects of combining SGLT2 inhibitors and GLP-1-R agonists in patients with cardiovascular disease.

Cardiovascular changes in the NZB/W F1 mouse model of lupus nephritis.

Patients with systemic lupus erythematosus (SLE), an autoimmune disease, have a higher risk of cardiovascular (CV) disease and death. In addition, up to 40%-50% of SLE patients develop lupus nephritis (LN) and chronic kidney disease, which is an additional CV risk factor. Thus, the individual contributions of LN and other SLE-specific factors to CV events are unclear. In this study, we investigated the effect of LN on the development of CV changes using the female NZBxNZW F1 (NZB/W) mouse model of lupus-like disease, with female NZW mice as controls. Standard serologic, morphologic, immunohistologic, and molecular analyses were performed. In a separate group of NZB/W mice, systolic blood pressure (BP) was measured during the course of the disease using tail plethysmography. Our data show marked CV changes in NZB/W mice, i.e., increased heart weight, hypertrophy of the left ventricle (LV) and septum, and increased wall thickness of the intramyocardial arteries and the aorta, which correlated with the progression of renal damage, but not with the age of the mice. In addition, systolic BP was increased in NZB/W mice only when kidney damage progressed and proteinuria was present. Pathway analysis based on gene expression data revealed a significant upregulation of the response to interferon beta in NZB/W mice with moderate kidney injury compared with NZB mice. Furthermore, IFI202b and IL-6 mRNA expression is correlated with CV changes. Multiple linear regression analysis demonstrated serum urea as a surrogate marker of kidney function and IFI202b expression as an independent predictor for LV wall thickness. In addition, deposition of complement factors CFD and C3c in hearts from NZB/W mice was seen, which correlated with the severity of kidney disease. Thus, we postulate that the pathogenesis of CV disease in SLE is affected by renal impairment, i.e., LN, but it can also be partly influenced by lupus-specific cardiac expression of pro-inflammatory factors and complement deposition.

COVID-19 severity and cardiovascular outcomes in SARS-CoV-2-infected patients with cancer and cardiovascular disease

BackgroundData regarding outcomes among patients with cancer and co-morbid cardiovascular disease (CVD)/cardiovascular risk factors (CVRF) after SARS-CoV-2 infection are limited. ObjectivesTo compare Coronavirus disease 2019 (COVID-19) related complications among cancer patients with and without co-morbid CVD/CVRF. MethodsRetrospective cohort study of patients with cancer and laboratory-confirmed SARS-CoV-2, reported to the COVID-19 and Cancer Consortium (CCC19) registry from 03/17/2020 to 12/31/2021. CVD/CVRF was defined as established CVD or no established CVD, male ≥ 55 or female ≥ 60 years, and one additional CVRF. The primary endpoint was an ordinal COVID-19 severity outcome including need for hospitalization, supplemental oxygen, intensive care unit (ICU), mechanical ventilation, ICU or mechanical ventilation plus vasopressors, and death. Secondary endpoints included incident adverse CV events. Ordinal logistic regression models estimated associations of CVD/CVRF with COVID-19 severity. Effect modification by recent cancer therapy was evaluated. ResultsAmong 10,876 SARS-CoV-2 infected patients with cancer (median age 65 [IQR 54–74] years, 53% female, 52% White), 6253 patients (57%) had co-morbid CVD/CVRF. Co-morbid CVD/CVRF was associated with higher COVID-19 severity (adjusted OR: 1.25 [95% CI 1.11–1.40]). Adverse CV events were significantly higher in patients with CVD/CVRF (all p<0.001). CVD/CVRF was associated with worse COVID-19 severity in patients who had not received recent cancer therapy, but not in those undergoing active cancer therapy (OR 1.51 [95% CI 1.31–1.74] vs. OR 1.04 [95% CI 0.90–1.20], pinteraction <0.001). ConclusionsCo-morbid CVD/CVRF is associated with higher COVID-19 severity among patients with cancer, particularly those not receiving active cancer therapy. While infrequent, COVID-19 related CV complications were higher in patients with comorbid CVD/CVRF. (COVID-19 and Cancer Consortium Registry [CCC19]; NCT04354701).

Association Between Plasma Levels of ANGPTL3, 4, 8 and the Most Common Additional Cardiovascular Risk Factors in Patients with Hypertension.

ANGPTL3, 4 and 8 have been reported to be involved in the regulation of lipid and glucose metabolism. The aim of this study was to investigate the expression of ANGPTL3, 4, 8 in hypertensive patients with or without overweight/obesity, T2D, and hyperlipidemia, and the possible association between their expression and the status of the aforementioned comorbidities. Plasma levels of ANGPTL3, 4, and 8 in 87 hospitalized patients with hypertension were measured using ELISA kits. Associations between circulating ANGPTLs levels and the most common additional cardiovascular risk factors were assessed using multivariate linear regression analyses. Pearson's correlation analysis was used to examine the association between ANGPTLs and clinical parameters. In the context of hypertension, (1) although not statistically significant, circulating ANGPTL3 levels were higher in the overweight/obese group than in the normal weight group; (2) circulating levels of ANGPTL3 and ANGPTL8 were significantly lower in patients with T2D than in non-diabetic patients; (3) circulating ANGPTL3 levels were significantly higher in the hyperlipidemic group than in the non-hyperlipidemic group. ANGPTL3 was associated with T2D and hyperlipidemia status, whereas ANGPTL8 was independently associated with T2D status. In addition, circulating ANGPTL3 levels were positively correlated with TC, TG, LDL-C, HCY, and ANGPTL8, and circulating ANGPTL4 levels were positively correlated with UACR and BNP. Changes in circulating ANGPTL3 and ANGPTL8 levels have been observed in hypertensive patients with the most common additional cardiovascular risk factors, suggesting a role in the common comorbidities of hypertension and cardiovascular disease. Hypertensive patients with overweight/obesity or hyperlipidemia may benefit from therapies targeting ANGPTL3.

Neurologic Implications of Spaceflight (P11-4.001)

<h3>Objective:</h3> Neurology in spaceflight has a rich history going back to the original days of the Gemini missions in the 1950s. With increased interest from governmental, commercial, and non-governmental entities the need to further address the integration of neurology and aerospace medicine as a burgeoning discipline. In preparation for the new Artemis generation, researchers and clinicians are attempting to understand better how changes to the nervous system are potentially hazardous and may compromise mission success. Long-duration spaceflight is associated with orthopedic, cardiovascular, urinary, immunologic, hematologic and neurologic changes. We aim to discuss several neurologic conditions that have been observed in astronauts, as well as discuss symptoms/syndromes which are limited to the spaceflight environment. According to NASA risk stratification, understanding particular neurologic conditions is critical as humanity sets its sights on the Moon and beyond. These conditions include cognitive changes, space motion sickness, space headache, and a progressively worsening visual acuity called Spaceflight-Associated Neuro-Ocular Syndrome (SANS). As more individuals representative of the average health of the population undergoes the rigors of spaceflight, more anticipated and unanticipated neurologic complications will occur. Patients with additional cardiovascular and neurologic risk factors will face different physiologic challenges than previous career astronauts and pilots. Primarily, neurologists will serve a vital role by applying knowledge of the central nervous system learned in the terrestrial equivalent patient to understand neuro-physiologic responses to spaceflight. This presentation aims to bring attention to and introduce this new area of neurology to help shape the future of humanity in space. <h3>Background:</h3> N/A <h3>Design/Methods:</h3> N/A <h3>Results:</h3> N/A <h3>Conclusions:</h3> N/A <b>Disclosure:</b> Dr. Rosenberg has nothing to disclose. Donna Roberts has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Guerbet. Donna Roberts has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Guerbet. The institution of Donna Roberts has received research support from Guerbet. The institution of Donna Roberts has received research support from NASA. Dr. Grimberg has nothing to disclose. Dr. Edwards has received intellectual property interests from a discovery or technology relating to health care. Dr. Saway has nothing to disclose. Sami Al Kasab has nothing to disclose.

OA08 JAK inhibitors and the risk of malignancy: a meta-analysis across licenced disease indications

Abstract Background/Aims Concerns have been raised about the risk of malignancy with Janus kinase inhibitors (JAKi) following the ORAL Surveillance study, which reported an increased incidence of malignancy with tofacitinib compared with Tumor Necrosis Factor-α inhibitors (TNFi) in people with rheumatoid arthritis (RA) aged over 50 years who had additional cardiovascular risk factors. Our objective was to estimate the risk of malignancy for all licenced JAKi across disease indications, compared with TNFi, methotrexate (MTX), and placebo. Methods A systematic search of electronic databases (Medline, EMBASE, Cochrane) was performed to identify Phase 2/3/4 RCTs and long-term extension (LTE) studies of JAKi (tofacitinib, baricitinib, upadacitinib, filgotinib, peficitinib) in adults with RA, psoriatic arthritis, psoriasis, axial spondyloarthritis, inflammatory bowel disease, or atopic dermatitis. Comparators were placebo, MTX, and TNFi. Random-effects meta-analysis was performed to compare malignancy incidence rates between JAKi and comparators. Our primary outcome measure was the incidence of all malignancies including non-melanomatous skin cancers (NMSC). Secondary outcomes were malignancies excluding NMSC, and NMSC only. Results In 62 eligible RCTs and 14 LTE studies, there were 71,767 person-years of exposure to JAKi; 2,680 to placebo; 7,827 to TNFi; and 1,074 to MTX. Comparing JAKi with placebo arms of RCTs, the incidence rate ratio (RR) for all malignancies including NMSC was not significantly different (RR 0.81; 95% CI 0.52 to 1.26; p = 0.36). Similarly, when comparing JAKi with MTX, no significant differences were observed in the incidence of malignancy (RR 0.73; 95% CI 0.33 to 1.61; p = 0.43). Compared with TNFi, however, administration of JAKi was associated with an increased incidence of malignancy (RR 1.54; 95% CI 1.19 to 2.01; p = 0.001). For all analyses, findings were consistent when excluding NMSC, when analysing NMSC only, and when including LTE data. Conclusion In trial settings, JAKi do not associate with an increased risk of malignancy compared with placebo or MTX, but are associated with an increased risk of malignancy relative to TNFi. Disclosure C. Stovin: None. M.D. Russell: Honoraria; Lilly, Galapagos, Biogen, Menarini. Other; Lilly, Pfizer, Janssen, UCB. E. Alveyn: None. O. Adeyemi: None. V. Patel: None. M.A. Adas: None. F. Atzeni: None. K.K.H. Ng: None. A.I. Rutherford: None. S. Norton: None. A.P. Cope: Consultancies; BMS, Abbvie, GSK/Galvini. Grants/research support; BMS. J.B. Galloway: Honoraria; Abbvie, Biovitrum, BMS, Celgene, Chugai, Gilead, Janssen, Lilly, Novartis, Pfizer, Roche, Sanofi, Sobi, UCB.

Evidence-based perspective on heart failure and osteoporosis: a systematic review

Aim. To study the prognostic relationship between heart failure (HF) and osteoporosis, as well to search for modern principles and approaches to the management of patients.Material and methods. A search was conducted in the PubMed, RSCI databases from 2012 to 2022 using keywords. The studies were selected according to the PRISMA algorithm.Results. Based on the results, 124 papers were received, and 9 articles were eventually selected. The age of the patients was at least 49 years (mainly elderly patients). The median follow-up ranged from 12 months to 10,5 years. The larger percentage were females.Conclusion. Osteoporosis was associated with the HF risk, and patients with heart failure had a higher risk of accidental fracture due to accelerated bone turnover. The foregoing makes it possible to consider patients with HF as a group of increased risk of osteoporosis and associated fractures, and impaired mineral metabolism as a possible additional cardiovascular risk factor.

Controversies in the Management of Antiphospholipid Syndrome.

Strategies to prevent thrombosis in antiphospholipid antibody (aPL)-positive patients are of the utmost importance. The risk of thrombosis in patients with aPLs varies, depending on additional venous thrombosis and cardiovascular risk factors, as well as associated comorbidities. Recurrent thrombosis despite treatment with vitamin K antagonists is relatively common in daily practice. In this context, the effectiveness of the new direct oral anticoagulants in antiphospholipid syndrome is debated, as well as that of low-dose aspirin for primary thromboprophylaxis. There is an urgent unmet need to recognize the subgroup of patients that may benefit from low-dose aspirin use. Here we also discuss different points of view on primary and secondary thrombosis preventions in aPL-positive patients, which were presented as a debate during the 2021 PANLAR Congress (Pan-American League of the Association of Rheumatology) and that was organized by GESAF (Argentine Society of Rheumatology APS Study Group). It is the intention of this article to provide a useful discussion to aid treatment decision-making in daily clinical practice.

Unmasking a silent killer: Prevalence of diagnosed and undiagnosed Diabetes Mellitus among people living with HIV in rural South Africa.

To document the prevalence of Impaired Glucose Tolerance (IGT) and undiagnosed Diabetes Mellitus (DM) and to identify factors associated with undiagnosed DM in People Living With HIV (PLWH). Cross-sectional study performed at Ndlovu Medical Center, Limpopo, South Africa including PLWH aged ≥18 years. Between August and November 2017, 356 HIV-positive participants were included. Information was collected on socio-demographics, DM symptoms and risk factors for DM. IGT and DM were diagnosed using random plasma glucose and/or HbA1c. Factors associated with undiagnosed DM were assessed by comparing participants with newly diagnosed DM to participants without DM. IGT was diagnosed in 172 (48.3%) participants. Twenty-nine (8.1%) participants met the definition of DM, of whom 17 (58.6%) were newly diagnosed. Compared to participants without DM, participants with DM were on average five years older, were more likely to have a positive family history for DM, were less physically active and had higher systolic blood pressure, body mass index and waist circumference. Factors associated with undiagnosed DM included age ≥45 years (OR=3.59) and physical inactivity (OR=3.17). The prevalence of IGT and DM among PLWH is high and more than half of DM cases were undiagnosed. Regular screening for DM in PLWH is recommended, especially in an aging population with additional cardiovascular disease risk factors. This article is protected by copyright. All rights reserved.