Lower Rates Of Cardiovascular Events Research Articles

Efficacy and safety of upadacitinib in patients with active ankylosing spondylitis refractory to biologic therapy: 2-year clinical and radiographic results from the open-label extension of the SELECT-AXIS 2 study

BackgroundThe efficacy and safety of upadacitinib in patients with ankylosing spondylitis (AS) and inadequate response/intolerance to biologic disease-modifying antirheumatic drugs (bDMARD-IR) were evaluated through 1 year in the SELECT-AXIS 2 study. Here, we assess 2-year efficacy, safety, and imaging outcomes in SELECT-AXIS 2.MethodsPatients who received continuous upadacitinib, and those who switched from placebo to upadacitinib at week 14, could enter the open-label extension (OLE). Efficacy endpoints included Assessment of SpondyloArthritis international Society (ASAS) and Axial Spondyloarthritis Disease Activity Score (ASDAS) responses, and changes from baseline in measures of disease activity, back pain, function, and quality of life. Radiographic progression was evaluated using the modified Stoke Ankylosing Spondylitis Spinal Score (mSASSS). As observed (AO) and AO with non-responder imputation (AO-NRI) analyses were used for binary endpoints; AO with mixed-effects model for repeated measures (AO-MMRM) for continuous endpoints; and AO-analysis of covariance for mSASSS. Treatment-emergent adverse events (TEAEs) in patients receiving ≥ 1 upadacitinib dose through week 104 are presented as events (E)/100 patient-years (PY). Subgroup analyses were performed by prior tumor necrosis factor/interleukin-17 inhibitor exposure and bDMARD lack of efficacy/intolerance.ResultsOf 420 patients who entered the bDMARD-IR AS study, 409 entered the OLE, and 331 (continuous upadacitinib, n = 163; placebo to upadacitinib, n = 168) completed week 104. Improvements in efficacy measures were sustained through the OLE, with similar response rates between the continuous upadacitinib and placebo to upadacitinib groups at week 104. At week 104, 64.9% and 61.7% of patients, respectively, had achieved ASAS 40% response (AO-NRI). Mean changes from baseline were similar between the two groups at week 104 across measures (ASDAS: -2.1 and -2.0; total back pain: -4.9 and -4.6, respectively; AO-MMRM). Over 93.0% of patients showed no radiographic progression (mSASSS mean change from baseline < 2) at week 104. The overall TEAE rate was 165.2 E/100 PY, with low rates of major adverse cardiovascular and venous thromboembolic events (0.3 E/100 PY each).ConclusionsUpadacitinib efficacy, including very low rates of radiographic progression, was demonstrated through 104 weeks in treatment-refractory patients with active AS. Treatment was well tolerated, with no newly identified safety signals.Trial registrationNCT04169373.

Differences in cardiovascular risk in the general population of low and high altitude residents in Peru. HIGH Altitude CArdiovascular REsearch Latin America Population Study (HIGHCARE-LAPS)

Abstract Introduction Living at high altitude (HA) is associated with profound changes in cardiovascular physiology, mostly caused by chronic hypoxia. Available data from high income countries (Switzerland, Austria) suggest beneficial effects of moderate altitude residence in terms of cardiovascular risk. Little is known, however, about cardiovascular risk profile in long-term residents of higher altitudes from low-income countries. Aim To compare cardiovascular risk estimated with validated score in population-based samples of permanent residents of low and high-altitude communities in Peru. Methods Study participants (adults permanently residing at either low or high altitude) were recruited by sex- and age-stratified random multistage cluster sampling from the general population of urban areas at different altitudes in Peru (lowlanders: &amp;lt;500 m above sea level, highlanders: cities at 3287 m, 3824 m and 4330 m). For all participants questionnaire-based information, conventional blood pressure (BP; 3 seated measurements with a validated oscillometric device) and laboratory variables were obtained. Based on the collected data atherosclerotic cardiovascular disease (ASCVD) risk was estimated according to Pooled Cohort Equations (PCE, previously calibrated in South American population). Participants below 40 years of age, with ASVCD history, with LDL-C≥190 mg/dL or on LDL-C lowering therapy were excluded from this analysis. Results The analysis included 146 lowlanders and 373 highlanders, most of whom had low 10-year ASVCD risk, with the median estimated risk being significantly higher among lowlanders. Comparisons between the groups in terms of principal variables of interest are reported in the Table. The highlanders were slightly younger, had lower BMI, conventional BP, HDL cholesterol, lower prevalence of antihypertensive medication and of diabetes, and higher heart rate. In a multivariable model the difference in ASCVD risk between lowlanders and highlanders was significant (p=0.0009) after adjusting for BMI and socio-economic variables but not after systolic BP was included in the model (p=0.800). Conclusions Residence at HA is associated with a lower estimated ASCVD risk in the general population of Peru, mainly because of lower BP levels. Considering that the prognostic value of cardiovascular risk estimates in highland populations is unknown, longitudinal cohort studies would be required to assess whether this finding is associated with a lower rate of cardiovascular events.

7119 Klinefelter Syndrome in a Tertiary Referral Clinic: A Case Series and Clinical Audit

Abstract Disclosure: J. Luo: None. S. Sarlos: None. R. Giri: None. I. Sim: None. R.I. McLachlan: None. C.A. Allan: None. R. Upreti: None. Background: Klinefelter syndrome, the most common chromosomal disorder in men, remains underdiagnosed in many of those affected. Klinefelter syndrome is associated with hypogonadism and infertility, as well as an increased risk for venous thromboembolism (VTE), cardiometabolic disease, osteoporosis and gynaecomastia in adults. We studied the clinical features and disease associations in a tertiary referral cohort, and audited the care provided. Methods: Following ethics approval, adult patients with Klinefelter syndrome attending a Clinical Andrology Service in a tertiary Australian institution since 1 January 2011 were recruited. A database was established and demographics, aspects of initial diagnosis, ongoing treatments and comorbidities were documented. We audited our care using the European Academy of Andrology 2021 Guidelines for Klinefelter Syndrome. Results: Of 94 patients eligible, 57 patients consented to participation. The median age of diagnosis was 28 years, with the most common karyotype being 47,XXY (74%), followed by mosaic (20%) and higher degree polysomy (6%). Infertility (44%) and hypogonadism (33%) were the most common reasons for diagnosis. Most patients (88%) were treated with testosterone. Five men (11%) had genetic children with seven (18%) having previously attempted surgical sperm extraction. VTE occurred in seven patients (12%), with five on long-term anticoagulation following VTE diagnosis. Cardiovascular risk factor prevalence assessed at a median age of 42 years included increased BMI (72%), hypertension (25%), dyslipidaemia (70%), tobacco use (26%), impaired fasting glucose (11%) and type 2 diabetes (22%), though only one patient had a previous cardiovascular event. Osteopenia and osteoporosis were present in 28% and 4% of patients respectively, though only two patients had minimal trauma fractures. The audit of longitudinal care showed that gynaecomastia status was underreported (42%) in our clinic, whilst assessment and management of other health domains were mostly in keeping with the current recommendations. Conclusions: Klinefelter syndrome diagnosis continues to be delayed until adulthood in many men, with presentations most commonly involving infertility and/or hypogonadism. Our tertiary cohort demonstrates low rates of fertility treatment and success, which is likely multifactorial. There is a high burden of VTE, cardiovascular risk factors and reduced bone density despite testosterone treatment. Low rates of cardiovascular events and fracture may be reflective of a younger cohort as well as more aggressive risk factor management in a sub-specialist service. Gynaecomastia identification, documentation and management are areas for potential improvement. Increased awareness of Klinefelter syndrome and research into its associated risks are essential for standardising care and improving long-term outcomes. Presentation: 6/1/2024

7119 Klinefelter Syndrome in a Tertiary Referral Clinic: A Case Series and Clinical Audit

Abstract Disclosure: J. Luo: None. S. Sarlos: None. R. Giri: None. I. Sim: None. R.I. McLachlan: None. C.A. Allan: None. R. Upreti: None. Background: Klinefelter syndrome, the most common chromosomal disorder in men, remains underdiagnosed in many of those affected. Klinefelter syndrome is associated with hypogonadism and infertility, as well as an increased risk for venous thromboembolism (VTE), cardiometabolic disease, osteoporosis and gynaecomastia in adults. We studied the clinical features and disease associations in a tertiary referral cohort, and audited the care provided. Methods: Following ethics approval, adult patients with Klinefelter syndrome attending a Clinical Andrology Service in a tertiary Australian institution since 1 January 2011 were recruited. A database was established and demographics, aspects of initial diagnosis, ongoing treatments and comorbidities were documented. We audited our care using the European Academy of Andrology 2021 Guidelines for Klinefelter Syndrome. Results: Of 94 patients eligible, 57 patients consented to participation. The median age of diagnosis was 28 years, with the most common karyotype being 47,XXY (74%), followed by mosaic (20%) and higher degree polysomy (6%). Infertility (44%) and hypogonadism (33%) were the most common reasons for diagnosis. Most patients (88%) were treated with testosterone. Five men (11%) had genetic children with seven (18%) having previously attempted surgical sperm extraction. VTE occurred in seven patients (12%), with five on long-term anticoagulation following VTE diagnosis. Cardiovascular risk factor prevalence assessed at a median age of 42 years included increased BMI (72%), hypertension (25%), dyslipidaemia (70%), tobacco use (26%), impaired fasting glucose (11%) and type 2 diabetes (22%), though only one patient had a previous cardiovascular event. Osteopenia and osteoporosis were present in 28% and 4% of patients respectively, though only two patients had minimal trauma fractures. The audit of longitudinal care showed that gynaecomastia status was underreported (42%) in our clinic, whilst assessment and management of other health domains were mostly in keeping with the current recommendations. Conclusions: Klinefelter syndrome diagnosis continues to be delayed until adulthood in many men, with presentations most commonly involving infertility and/or hypogonadism. Our tertiary cohort demonstrates low rates of fertility treatment and success, which is likely multifactorial. There is a high burden of VTE, cardiovascular risk factors and reduced bone density despite testosterone treatment. Low rates of cardiovascular events and fracture may be reflective of a younger cohort as well as more aggressive risk factor management in a sub-specialist service. Gynaecomastia identification, documentation and management are areas for potential improvement. Increased awareness of Klinefelter syndrome and research into its associated risks are essential for standardising care and improving long-term outcomes. Presentation: 6/1/2024

The German Lipoprotein Apheresis Registry-Summary of the eleventh annual report

BackgroundIn 2012, the German Lipoprotein Apheresis Registry (GLAR) was launched. Real-world data on lipoprotein apheresis (LA) treatment are now available for a time period of 11 years. All patients received the maximally tolerated lipid-lowering therapy, which included statins, ezetimibe, bempedoic acid, and either proprotein convertase subtilisin/kexin type 9 (PCSK9) antibodies or antisense therapy. Methods and ResultsDuring the time period from 2012 to 2022, 92 German apheresis centers collected retrospective and prospective observational data of a total of 2,301 patients undergoing regular lipoprotein apheresis (LA) treatment of hypercholesterolemia or/and Lp(a)-hyperlipoproteinemia suffering from progressive atherosclerotic cardiovascular disease (ASCVD), with complete data sets of 1.125 patients, who were the subject of this analysis. More than 61,500 LA sessions are documented in the database. In 2022, all patients treated with LA demonstrated a significant immediate median reduction rate of LDL-C (68.8 %) and Lp(a) (72.9 %). Patient data were analyzed for the incidence rate of major coronary events (MACE) 1 and 2 years before the beginning of LA treatment (y-2 and y-1) and prospectively up to eleven years on LA treatment (y+1 to y+11). During the first two years of LA treatment (y+1 and y+2), a MACE reduction of 73 % was observed and continued to be low during y+3 to y+11, when all LA patients were analyzed. LA patients with only increased Lp(a) levels (Lp(a) ≥ 60 mg/dl (≥120 nmol/l) and an LDL-C < 100 mg/dl (<2.6 mmol/l)) had a higher MACE reduction (85 %; n = 443) in the first two years of LA treatment compared to LA patients with only increased LDL-C-levels (LDL-C ≥ 100 mg/dl (≥2.6 mmol/l); Lp(a) < 60 mg/dl (<120 nmol/l)) (53 %; n = 171). Adverse events of LA remained low (about 5 %) over the eleven years and mainly represented puncture problems (1.0 %). No side effects resulted in termination of LA therapy. ConclusionsThe current analysis of GLAR data indicates that regular LA leads to very low incidence rates of cardiovascular events in patients with high LDL-C and/or high Lp(a) levels, progressive ASCVD, and maximally tolerated lipid-lowering medication, including proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibition. Additionally, LA was safe with a low rate of adverse effects over an 11-year period. The number of enrolled patients and the duration of observation establish GLAR as the largest LA registry worldwide.

Cost-effectiveness analysis comparing single-pill combination of perindopril/amlodipine/indapamide to the free equivalent combination in patients with hypertension from an Italian national health system perspective

ABSTRACT Objective To evaluate the cost-effectiveness of a single-pill combination (SPC) of perindopril/amlodipine/indapamide versus its free equivalent combination (FEC) in adults with hypertension in Italy. Methods A Markov model was developed to perform a cost-utility analysis with a lifetime horizon and an Italian healthcare payer’s perspective. In the model, the additional effect of the SPC on blood pressure level compared with the FEC was translated into a decreased risk of cardiovascular events and CKD, which was modeled via Framingham risk algorithms. Difference in persistence rates of SPC and FEC were modeled via discontinuation rates. Results A perindopril/amlodipine/indapamide SPC is associated with lower cost and better health outcomes compared to its FEC. Over a lifetime horizon, it is associated with a 0.050 QALY gain and cost savings of €376, resulting from lower cardiovascular event rates. In the alternative scenario, where different approach for modeling impact of adherence was considered, incremental gain of 0.069 QALY and savings of €1,004 were observed. Results were robust to sensitivity and scenario analyses, indicating that use of this SPC is a cost-effective strategy. Conclusions The findings indicate that a perindopril/amlodipine/indapamide SPC is a cost-saving treatment option for hypertension in Italy, compared to its FEC.

SGLT2 inhibitors for patients with type 2 diabetes mellitus after myocardial infarction: a nationwide observation registry study from SWEDEHEART

Sodium-glucose co-transporter 2 (SGLT2) inhibitors have been shown to reduce rates of heart failure hospitalisations and cardiovascular death in patients with type 2 diabetes and prior cardiovascular disease. We hypothesised that SGLT2 inhibitors could provide cardiovascular benefits in the post-myocardial infarction setting. We aimed to investigate cardiovascular outcomes of SGLT2 inhibitor therapy in patients with type 2 diabetes mellitus after myocardial infarction in a Swedish nationwide registry. We included all patients with type 2 diabetes surviving a type 1 acute myocardial infarction from January 1, 2018 to December 31, 2021. Patients were included if they were discharged with an estimated glomerular filtration rate (eGFR)>30mL/min/1.73 m2 in the nationwide Swedish Web-system for Enhancement and Development of Evidence-based care in Heart disease Evaluated According to Recommended Therapies (SWEDEHEART) registry. We identified all patients discharged with or without an SGLT2 inhibitor prescription 120 days before or within three days after discharge from the cardiac care unit. The primary outcome measure was a composite of death and first hospitalisation for heart failure after one year analysed using an adjusted Cox regression. A total of 11,271 patients were included. Of these, 2498 (22.2%) received SGLT2 inhibitor treatment. Patients who were prescribed SGLT2 inhibitors were younger, more often presented with a STEMI and had worse left ventricular ejection fraction at index hospitalisation. SGLT2 inhibitor use was associated with lower rates of the composite outcome (hazard ratio (HR) of 0.70 (95% confidence interval (CI) 0.59-0.82). Treatment with SGLT2 inhibitors after myocardial infarction in patients with type 2 diabetes was associated with a lower rate of cardiovascular events. This work was supported by Hjärt-Lungfonden, Vetenskapsrådet, Knut and Alice Wallenberg Foundation, ALF, the Bundy Academy, and Skåne University Hospital funds.

New perspectives on the high-density lipoprotein system and its role in the prevention and treatment of atherosclerotic cardiovascular disease.

The causal role of high-density lipoprotein (HDL) in atherosclerotic cardiovascular disease (CVD) remains debated. Considering recent evidence, the purpose of this review is to a provide a focused update and new perspectives on HDL and CVD. A Mendelian randomization study demonstrated an increased risk of CVD when HDL-cholesterol was predominantly transported in larger HDL particles and a decreased risk of CVD when HDL-cholesterol was predominantly transported in smaller HDL particles. Moreover, another Mendelian randomization study demonstrated that concentration and content of medium HDL particles is associated with CVD. A Mendelian randomization study that utilized stratified analyses demonstrated that individuals with HDL-cholesterol 50 mg/dl or less were at increased risk of CVD. Lastly, the AEGIS-II trial demonstrated that CSL112, a human apolipoprotein A-I that increases cholesterol efflux, did not significantly reduce cardiovascular events in patients at very high risk. Exploratory analyses showed that patients treated with CSL112 had numerically lower rates of cardiovascular events. Qualitative markers of HDL may be causally related to CVD. There is a need for ongoing research into HDL therapeutics that promote the biological properties of HDL. The optimal cohort or disease state that will benefit from these therapies needs to be identified.

Cardiovascular Events During Pregnancy: Implications for Adverse Pregnancy Outcomes in Individuals With Autoimmune and Rheumatic Diseases.

This study examined maternal cardiovascular (CV) events relative to adverse pregnancy outcomes among individuals with autoimmune rheumatic diseases (ARDs), primary antiphospholipid syndrome (APS), and those with neither. Using a California population-based birth cohort (2005-2020), we identified those with CV events (CVEs), ARDs, and APS through International Classification of Diseases, 9th and 10th revisions, Clinical Modification codes in maternal discharge records. Selected adverse pregnancy outcomes identified from birth certificates were preterm birth (PTB; < 37 weeks' gestation), small-for-gestational-age infants (SGA; birth weight < 10th percentile for age and sex), and a composite of either outcome. Adjusted risk ratios (aRRs) for adverse outcomes and their 95% CIs were calculated. CVEs occurred more frequently in individuals with ARDs (265 of 19,340 [1.4%]) and primary APS (428 of 7758 [5.5%]) than those without (17,130 of 7,004,334 [0.3%]). The presence vs absence of CVEs was associated with a greater incidence of adverse outcomes in ARD (53.2% vs 26.6%), APS (30.6% vs 20.7%), and non-ARD/APS pregnancies (28.2% vs 15.2%). CVEs were associated with increased risks of SGA in all groups (aRRs 1.2-1.5) and PTB in ARD (aRR 1.6, 95% CI 1.3-2.0) and non-ARD/APS (aRR 1.7, 95% CI 1.7-1.8) pregnancies. CVEs were associated with modestly increased risks (20-70%) for PTB, SGA, or both across the groups. Notably, > 50% of ARD pregnancies with CVEs experienced adverse pregnancy outcomes. Given that ARD and APS pregnancies have higher (although still low) rates of CVEs and have higher baseline risks of adverse pregnancy outcomes than the general population, the additional burden conferred by CVEs is clinically important.

#853 Kidney-protective medication and risk of adverse clinical outcomes in patients with chronic kidney disease: preliminary findings from DISCOVER CKD

Abstract Background and Aims Renin-angiotensin-system inhibitors (RASi) have been a foundational therapy in chronic kidney disease (CKD) for several decades. Sodium-glucose co-transporter-2 inhibitors (SGLT2i) have also emerged as a critical disease-modifying therapy in CKD, with contemporary data from trials showing SGLT2i to significantly improve kidney and cardiovascular (CV) outcomes in patients with or without diabetes. Nonetheless, several studies have revealed sub-optimal prescribing of RASi and/or SGLT2i therapy (both herein referred to as kidney-protective medication) in patients with CKD. Using prospective data from the DISCOVER CKD study, we conducted an exploratory analysis to assess the association of kidney-protective medication real-world use with mortality risk, CV events (fatal and non-fatal), and hospitalisation in patients with CKD. Method DISCOVER CKD (NCT04034992) is a multi-country, non-interventional cohort study designed to characterise the epidemiology of CKD, including describing patient characteristics, disease progression, clinical outcomes, patient journey, practice patterns, and clinical management. In the prospective phase, patients with CKD were recruited from the UK, USA, Spain, Italy, Sweden and Japan between September 2019 and June 2022. Clinical data were extracted manually from patients’ health records into a standardised case report form. The current analysis includes 12 months’ follow-up data. A Cox proportional hazards model was used to compare the risk of all-cause mortality and CV events and a negative binomial regression model was used to compare the risk of all-cause hospitalisation between patients receiving and not receiving kidney-protective medication at baseline, with adjustments for age, sex, CKD stage, diabetes mellitus, hyperkalaemia, and heart failure. DISCOVER CKD received research ethics board approval, and informed consent was obtained from all patients. Results Of the 1052 patients enrolled in DISCOVER CKD, 643 (61.1%) were receiving kidney-protective medication in the form of RASi (n = 618) and SGLT2i (n = 147) at baseline. The mean age of participants receiving and not receiving kidney-protective medication was 62.4 years and 62.7 years, respectively; 34.4% and 40.8%, respectively, were female. Most patients had CKD stage 3A (n = 332, 31.6%) or 3B (n = 308, 29.3%), and 8.4% (n = 88) had ongoing dialysis. Body mass index (30.4 vs 29.4 kg/m2) and blood pressure were similar for those receiving kidney-protective medication versus those who were not. Laboratory assessments were also generally similar, although estimated glomerular filtration rate (eGFR; 40.9 vs 33.7 mL/min/1.73 m2) and haemoglobin (132.0 g/L vs 124.0 g/L) were higher in patients receiving kidney-protective medication versus those not. During the follow-up, patients receiving kidney-protective medication had a 67% lower risk of all-cause mortality (hazard ratio [HR] 0.33; 95% confidence interval [CI] 0.12–0.80, p = 0.019), and a 20% lower risk of all-cause hospitalisation (HR, 0.80; 95% CI 0.64–0.99, p = 0.042) compared with patients not receiving kidney-protective medication. In the population without pre-existing CV disease, a trend towards a lower rate of CV events was observed in patients with kidney-protective medication (CV events rates: 2.2 vs 3.2 per 100 person-years; HR, 0.38; 95% CI 0.12–1.08, p = 0.074 (Figure). Conclusion In this multinational CKD cohort, preliminary analysis indicates that using kidney-protective medication was associated with lower risks of adverse outcomes including death. Further analysis to mitigate potential confounding will be performed to confirm these preliminary findings.

#1447 Calcimimetics improve impaired cardiac function and contractility in chronic phosphate loading by activating the CaSR/cAMP signaling cascade

Abstract Background and Aims High phosphate loading stimulate the synthesis of PTH and FGF23 and is associated with increased cardiovascular (CV) mortality. In hemodialysis patients, the administration of calcimimetics led to reductions in PTH and FGF23 and the latter was associated with a lower rate of CV events. We have previously shown that mice with a high dietary phosphate load show elevated PTH and FGF23 levels and develop impaired systolic cardiac function, which could be improved by calcimimetics. Calcimimetics are allosteric activators of the calcium-sensing receptor (CaSR). Phosphate (Pi) was shown to inactivate the parathyroid CaSR at concentrations &amp;gt;1.4 mM Pi. Whether calcimimetics contribute to CV event reduction indirectly via lowering PTH and FGF23 or directly via activation of the cardiac CaSR is unknown. Method Wild-type mice were fed a high phosphate diet (HPD) ± etelcalcetide (Etl) or a normal phosphate diet (NPD), cardiac function was assessed by echocardiography and Millar catheterization, and cardiac tissue was harvested for histology and RNAseq analyses. In addition, isolated adult mouse cardiomyocytes (AMCM) were stimulated ex vivo with PTH, FGF23 or Pi, contractility and calcium handling were measured with the addition of Etl and activity analyses were performed. Results In addition to the positive effect on HPD-induced systolic cardiac dysfunction, Etl improved impaired LV contractility and reduced fibrosis. RNAseq analyses revealed reduced Ca, PKA and cAMP signaling by HPD. Ex vivo stimulation of AMCM with PTH and FGF23 had no functional effects. In contrast, Pi significantly worsened contractility and Ca handling, which was blunted by Etl co-stimulation. Downstream of cardiac CaSR, Pi reduced the formation of cAMP, which led to PKA-dependent dephosphorylation of PLN and subsequently to lower Serca2a activity, which was ultimately responsible for the reduced contractility. Etl led to improved cardiomyocyte contractility via increased cAMP synthesis and increased PLN phosphorylation and Serca2a activity. Conclusion Our data suggest that Etl ameliorates the Pi-induced pathologic cardiac phenotype associated with high phosphate load via direct activation of CaSR/cAMP signaling cascade, resulting in improvement of cardiomyocyte contractility.

Coronary Plaque in Athletes.

The relationship between vigorous physical activity (PA) and the development of coronary atherosclerosis has remained less explored for many years. Recently, literature data have focused on coronary atherosclerosis in athletes showing that prevalence is not trivial, that there are differences among various types of sport, and that there are some peculiar features. As a matter of fact, plaque composition in athletes seems to be characterized by calcium rather than soft components. Specific mechanisms through which vigorous PA influences coronary artery disease are not yet fully understood. However, the prevalent calcific nature of coronary plaques in athletes could be related with a trend in a lower cardiovascular event rate.

Dietary salt intake in chronic kidney disease: recent studies and their practical implications.

Epidemiologic studies in the general population show that the level of dietary salt intake is associated with increases in blood pressure (BP), cardiovascular events, and mortality. According to trial data, reducing salt intake lowers the incidence of these 3 outcomes. On the basis of this evidence, the World Health Organization and other bodies recommend restricting salt intake. The association of salt intake with BP and cardiovascular disease has also been seen in chronic kidney disease (CKD), and trials of salt reduction in CKD have shown benefit, reflected by reduced BP and a lower rate of cardiovascular events. However, these trials have typically used resource‑intensive approaches to dietary salt reduction that are not suitable for routine clinical care, and salt intake typically remains high in people with CKD. The OxSalt care bundle is a low‑cost intervention that was demonstrated in the OxCKD1 trial to help people with CKD lower their salt intake, and could be applied in routine clinical practice.

Ethnic Differences in Thrombotic Profiles of Acute Coronary Syndrome Patients and Relationship to Cardiovascular Outcomes: A Comparison of East Asian and White subjects.

East Asians (EAs), compared to white Caucasians (W), have a lower risk of ischemic heart disease and a higher risk of bleeding with antithrombotic medications. The underlying mechanisms are incompletely understood. We sought to compare thrombotic profiles of EA and W patients with myocardial infarction (MI) and relate these to cardiovascular outcomes. In a prospective study in the United Kingdom and Korea, blood samples from patients (n = 515) with ST- or non-ST-elevation MI (STEMI and NSTEMI) were assessed using the Global Thrombosis Test, measuring thrombotic occlusion (OT) and endogenous fibrinolysis (lysis time [LT]). Patients were followed for 1 year for major adverse cardiovascular events (MACE) and bleeding. EA patients showed reduced OT (longer OT) compared to W (646 seconds [470-818] vs. 436 seconds [320-580], p < 0.001), with similar LT. In STEMI, OT (588 seconds [440-759] vs. 361 seconds [274-462], p < 0.001) and LT (1,854 seconds [1,389-2,729] vs. 1,338 seconds [1,104-1,788], p < 0.001) were longer in EA than W. In NSTEMI, OT was longer (OT: 734 seconds [541-866] vs. 580 seconds [474-712], p < 0.001) and LT shorter (1519 seconds [1,058-2,508] vs. 1,898 seconds [1,614-2,806], p = 0.004) in EA than W patients. MACE was more frequent in W than EA (6.3 vs. 1.9%, p = 0.014) and bleeding infrequent. While OT was unrelated, LT was a strong independent predictor of MACE event after adjustment for risk factors (hazard ratio: 3.70, 95% confidence interval: 1.43-9.57, p = 0.007), predominantly in W patients, and more so in STEMI than NSTEMI patients. EA patients exhibit different global thrombotic profiles to W, associated with a lower rate of cardiovascular events.

Comparing cardiovascular outcomes and costs of perindopril-, enalapril- or losartan-based antihypertensive regimens in South Africa: real-world medical claims database analysis

Abstract Background Effective strategies for hypertension management are essential to reduce associated morbidity and mortality in sub-Saharan Africa, where blood pressure control rates are alarmingly low. Renin-angiotensin-aldosterone system (RAAS) inhibitors are recommended as first-line treatment; however, differences in class or molecule-specific effects have not been conclusively demonstrated. Purpose This real-world study analysed medical insurance claims data to assess clinical and cost outcomes of antihypertensive therapy based on the three most commonly prescribed RAAS inhibitors in South Africa: perindopril, losartan and enalapril. Methods Patients on standard doses of perindopril, enalapril or losartan (alone or in combination with other agents) for ≥12 months prior to January 2015 were identified from a large, South African private health insurance database. Anonymised patient-level claims over the next 5 years (January 2015 to December 2019) were analysed in patients with ≥80% adherence. The primary outcome was the risk-adjusted rate of the composite of myocardial infarction (MI), ischaemic heart disease (IHD), heart failure (HF) or stroke. The key secondary clinical outcome was the risk-adjusted all-cause mortality rate; risk-adjusted costs per life per month (PLPM) in South African Rands (ZAR) were also assessed. Results In total, 63,489 patients who received perindopril (n=32,857), losartan (n=16,693) or enalapril (n=13,939) were included. Within the 5-year study period, the risk-adjusted rate of ≥1 claim for MI, IHD, HF or stroke (primary outcome) was significantly lower with perindopril than losartan (205 vs 221 per 1000 patients; P&amp;lt;0.0001) or enalapril (205 vs 223 per 1000 patients; P&amp;lt;0.0001). The risk-adjusted all-cause mortality rate was also significantly lower with perindopril than enalapril (100 vs 139 deaths per 1000 patients; P=0.007), but similar to that with losartan (100 vs 94 deaths per 1000 patients; P=0.650). Perindopril was also associated with significantly lower overall risk-adjusted costs than the other agents, with mean (95% confidence interval) costs PLPM of ZAR 1342 (87–8973) for perindopril, ZAR 1466 (104–9365) for losartan (P=0.0044) and ZAR 1540 (77–10,546) for enalapril (P=0.0003). Conclusion In this real-world analysis of South African individuals with hypertension, perindopril-based regimens were associated with a lower rate of cardiovascular events (MI, IHD, HF and stroke) over 5 years than enalapril- or losartan-based regimens. Perindopril also provided considerably greater cost-saving benefits, both statistically and socioeconomically, compared with the other RAAS inhibitor agents. Although these observations need to be confirmed in a broader South African population, including those treated in the public health sector, they may have significant implications for the choice of antihypertensive therapy.Time to outcome event over 5 yearsRisk-adjusted cost in South African Rand

Thrombotic profile of East Asian and Western ACS patients and relationship to cardiovascular outcomes

Abstract Background East Asian patients compared to Westerners, have a lower risk of ischemic heart disease and a higher risk of bleeding with antithrombotic medications. The underlying mechanisms are incompletely understood. Genetic differences may underlie lower coagulant and inflammation levels in EA compared to W populations. Objectives We sought to compare thrombotic profiles of East Asian and Western patients with myocardial infarction (MI) and relate these to cardiovascular outcomes. Methods In a 2 centre, prospective, observational study in the U.K. and Korea, blood samples from patients (n=515) with ST- or non-ST-elevation MI (STEMI and NSTEMI) were assessed using the Global Thrombosis Test, measuring thrombotic occlusion (OT) and endogenous fibrinolysis (LT) times. In STEMI patients, blood samples were taken immediately upon arrival, whilst in NSTEMI patients, blood samples were taken after DAPT loading. Patients were followed for 1 year for major adverse cardiovascular events and major bleeding. Results Major adverse cardiovascular events occurred significantly more frequently in Western than in East Asian patients (6.27% vs. 1.92%, p=0.014), driven by a higher rate of cardiovascular death (3.53% vs. 0.38%, p=0.01), with minimal major bleeding events (0.39% vs. 0.38%, p=1.0). East Asian patients showed reduced platelet reactivity (longer OT) compared to Western patients (646s [470-818] vs. 436s [320-580], p&amp;lt;0.001), with similar LT. In STEMI, OT (588s [440-759] vs. 361s [274-462], p&amp;lt;0.001) and LT (1854s [1389-2729] vs. 1338s [1104-1788], p&amp;lt;0.001) were longer in East Asian patients than Westerners. In NSTEMI, OT was longer (OT 734s [541-866] vs. 580s [474-712], p&amp;lt;0.001) and LT shorter (1519s [1058-2508] vs. 1898s [1614-2806], p=0.004) in East Asian than Western patients. While OT was unrelated, LT was a strong independent predictor of MACE after adjustment for risk factors (HR 3.70, 95% CI 1.43-9.57, p=0.007), predominantly in Western patients, and more so in STEMI than NSTEMI. Conclusion East Asian patients exhibit different global thrombotic profiles to Westerners, associated with a lower rate of cardiovascular events. The lower platelet reactivity in East Asian STEMI patients, even before antiplatelet therapy, may explain contribute to the lower risk of subsequent adverse ischaemic events.

Cancelled STEMI patients: what happen to them?

Abstract Introduction In the STEMI care network, the number of inappropriate cases sent to cathlab remains high 1. The use of technological innovations to share the diagnostic ECG tracing with the cardiology department has been shown to be effective in improving patient discrimination. Objective Our aim was to study the characteristics and prognosis (at discharge and 1-year follow-up) of patients whose transfer to the cathlab was cancelled. Material and Method Prospective study analysing all STEMI alert activations in 2022. Information on ECG pattern and clinical history was transmitted using an APP (ODiSEA 2-3) and used for cancellation. Patient characteristics, myocardial infarction, ECG activation pattern, angiography results, final diagnosis and clinical events during admission and 1-year follow-up were recorded. Patients who underwent urgent coronary angiography were excluded from the study. Results A total of 406 infarction codes were activated through the ODISEA APP. 122 (30%) of these were cancelled. The characteristics of the patients are shown in Table 1. Reasons for cancellation based on ECG pattern are shown in Figure 1.B. The most common were ST depression (23%) and intraventricular conduction disturbances (22.9%). The final diagnosis was ACS in 32.8% (STEMI 2.5%, NSTEMI 27% and unstable angina 3.3%). In the remaining 67.2%, the final diagnosis was atypical chest pain with negative biomarkers in 22.9%, arrhythmia in 17.2%, pericarditis in 9%, gastrointestinal pathology in 4.9%, heart failure in 4.9%, aortic dissection in 3.2%, PTE in 1.6% and other pathologies in 3.5%. (Figure 1.A). Coronary angiography was performed in 41 patients (33.6%). There were 36.6% with one vessel, 9.8% with two vessels and 22% with three vessels. Percutaneous revascularisation was required in 70% of patients. Discharge from the emergency department occurred in 46% of the patients. Hospital mortality occurred in 14 patients (11.4%). Of these, 3 (2.4%) were due to cardiac causes. Regarding events at 12 months, 6 (4.9%) were deaths (5 natural deaths and 1 due to cancer). 5 patients (4%) had ACS, 3 patients (2.4%) had stroke and 1 patient (0.8%) had digestive bleeding. Conclusions STEMI alert cancelled transfer patients are older, have more comorbidities and are less likely to have a final diagnosis of ACS or to have coronary lesions. They have a high rate of non-cardiovascular in-hospital mortality and a low rate of cardiovascular events at one year of follow-up.A.Final diagnosis. B. ECG patternTable 1.Patients characteristics

Impact of Active vs Passive Statin Selection for Primary Prevention: The CorCal Vanguard Trial

BackgroundStatins can improve outcomes in high-risk primary prevention populations. However, application in clinical practice has lagged. ObjectivesThe objective of this study was to compare an active vs a passive strategy (ie, usual care) to statin prescription for primary prevention of atherosclerotic cardiovascular disease (ASCVD). MethodsA total of 3,770 patients ≥50 years of age without a history of ASCVD or statin use were invited to enroll in CorCal, with 601 consenting to participate. These patients were randomized 1:1 to statin initiation guided by the pooled cohort equation or by coronary artery calcium scoring (CACS). Outcomes (2.8-year follow-up) compared patients managed actively vs passively (randomly invited but declined or did not respond). ResultsPatient demographics were well matched. Statin recommendation was common among enrolled patients (41.7%). During follow-up, 25.3% of active patients were taking a statin vs 9.8% managed passively (P < 0.0001). Active patients had more lipid panels (median 2.0 vs 1.0), lower low-density lipoprotein cholesterol (109 vs 117 mg/dL) (both P < 0.0001), and a low rate of major adverse cardiovascular events during follow-up (0.6% vs 1.0%, P = 0.47). Statistical comparisons included t-tests, chi-squared tests, nonparametric tests, and time-to-event tests as appropriate. ConclusionsAn active approach to statin selection for primary ASCVD prevention identified a large treatment opportunity and led to over twice as many patients on statins compared to passive (usual care) management. A large CorCal Outcomes Trial is underway to more definitively assess the impact on outcomes of active management of statins for primary prevention.

From Snoring to Soaring: Unveiling the Positive Effects of Continuous Positive Airway Pressure Ventilation on Cardiovascular Health in Patients With Obstructive Sleep Apnoea Through a Systematic Review.

Increased cardiovascular (CV) morbidity and death are linked to obstructive sleep apnoea (OSA). The primary method of treating OSA is continuous positive airway pressure (CPAP). CPAP has some debatable outcomes on CV events in people suffering from OSA. The current study investigates how CPAP affects CV outcomes. The goalis to evaluate CPAP's effectiveness in lowering CV outcomes in OSA patients.We used a computer to search the PubMed, PubMed Central Library, Science Direct, and Google Scholar databases for studies comparing the effects of CPAP and a control group on CV outcomes in OSA patients. These included randomised control trials (RCT), narrative reviews, systematic reviews, case-control studies, observational studies and meta-analyses. A total of 52,937 patients were included in the final analysis of six RCTs, four observational studies, 10 meta-analyses, one case-control study, two systematic reviews and one narrative review. The weighted mean follow-up lasted for a period of between three months and nine years. The risk of major cardiovascular adverse events (MACE) was the same for both the CPAP and control groups.According to subgroup analysis, patients with lower MACE adherence rates (four hours per night) were more likely to use CPAP. The risk of all-cause mortality, CV-related complications causing mortality, acute myocardial infarction acute stroke, or hospitalisations for angina was the same in the CPAP and control groups.The primary outcome was that in patients with therapy with CPAP in addition to usual care and usual care alone did not prevent CV events in patients with moderate-to-severe OSA and existing CV illness. Patients with OSA who utilise CPAP may not experience fewer CV events. Patients who use CPAP consistently (four hours per night) could benefit from improved CV results. Future research must assess how well-adherent patients with severe OSA and low CV event rates respond to CPAP therapy. In patients who use CPAP for more than four hours each night, CPAP therapy may minimise the risk of MACE and stroke. Additional randomised trials requiring adequate CPAP time adherence are needed to support this perception. Despite the fact that there is no evidence to support the claim that CPAP therapy improves CVoutcomes, bias difficulties, CPAP adherence problems, and the patient groups included in each RCT may have made it more difficult to generalise the findings to all patients. Future research is therefore needed to look at these relevant results.

Accelerated Diagnostic Protocols Based on High-Sensitivity Troponin in the Diagnosis of Thoracic Pain: A Systematic Review

Background: The progress of high-sensitivity troponin for accelerated diagnostic protocols to assess chest pain, allows the identification of patients admitted to the emergency room with low-risk chest pain for a major adverse cardiovascular event, that could be early and safely discharged, saving time and resources. Objective: The aim of this study was to assess clinical trials using accelerated diagnostic protocols based on high-sensitivity troponin. Methods: A search of randomized clinical trials evaluating accelerated diagnostic protocols based on high-sensitivity troponin in emergency services was carried out in MEDLINE/Ovid, Cochrane and EMBASE database, using the assessment criteria of the Cochrane manual and the PRISMA strategy. Results: After screening 3509 studies, 5 clinical trials, including 1513 patients, were analyzed. Early discharges were identified in 409 (27%) of patients, in 91% of cases for ESC 0/3-h protocols, 72% for 0/1-h, 48% for EDACS, 40% for HEART, 19% and 32% for ADPT and 8% and 18% for standard care protocols. The negative predictive value was high, in the 99.1-100% range. Mean length of hospital stay was lower for the 0/1-h and ESC 0/3-h protocols, with 4.6 and 5.6 hours, respectively. Conclusions: Accelerated diagnostic protocols in chest pain using high-sensitivity troponin allow a higher proportion of early discharges with a low rate of major cardiovascular events, with reduction in length of hospital stay and resources used.