Cardiovascular Risk Reduction Research Articles

Feasibility of remotely supervised home-based high intensity interval training and effects on aerobic fitness and body composition in healthy older adults

Aging is associated with declines in aerobic fitness and increases in adiposity, both of which increase the risk of cardiovascular disease in older adults. High intensity interval training is an effective strategy for cardiovascular disease risk reduction; however, this promising exercise regimen may be inaccessible to older adults due to weight-bearing limitations or inability to travel to a fitness center. To address these barriers, we have developed a remotely supervised, home-based exercise intervention using high intensity interval training on an all-extremity non-weight-bearing ergometer (HIIT-ANE). The purpose of this study was to investigate the hypotheses that remotely supervised home-based HIIT-ANE would be feasible and lead to improvements in aerobic fitness and body composition in healthy older adults. Twenty sedentary older adults free of major clinical disease (66±1 yrs, mean ± SE) participated in this study. HIIT-ANE was remotely delivered at home under supervision via video conferencing (Zoom) and live heart rate monitoring (Zephyr OmniSense, Medtronic). HIIT-ANE consisted of a 10-min warm-up, 4 × 4-min intervals at 90% HRmax interspersed by 3 × 3-min bouts of active recovery at 70% HRmax, and a 5-min cool down and was performed on 4 days/week. Feasibility was assessed throughout the 8 weeks of HIIT-ANE. Aerobic fitness (maximal oxygen consumption) and body composition (dual-energy x-ray absorptiometry) were assessed at baseline and following an 8-week control period of normal lifestyle and an 8-week HIIT-ANE period. We found that exercise compliance to HIIT-ANE — the number of completed sessions relative to the number of scheduled sessions — was 96±1% and there were no adverse events related to the exercise intervention. Aerobic fitness increased in response to HIIT-ANE (baseline vs. post-HIIT-ANE: 23.7±1.2 vs. 27.0±1.1 ml/kg/min, P=0.001; pre- and post-HIIT-ANE: 22.5±1.2 vs. 27.0±1.1 ml/kg/min, P<0.001), but decreased following the control period (23.7±1.2 vs. 22.5±1.2 ml/kg/min, P=0.04). Body fat % (36±2 vs. 35±2%, P=0.001) and fat mass (28.4±2.0 vs. 27.0±2.0 kg, P=0.003) decreased following HIIT-ANE, but fat free mass did not significantly change ( P=0.05 for time effect; 48.5±1.7 vs. 49.3±1.7 kg). Body weight and body mass index did not change throughout the study duration ( P≥0.8 for time effect). In conclusion, remotely supervised home-based HIIT-ANE was feasible and safe and was associated with improved aerobic fitness and body composition in healthy older adults. This work was supported by the National Institute of Aging grant AG063143. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Abstract 1087: Cardiovascular Risk Prediction By Platelet Transcriptomics

Background: Hyperreactive platelets are central to atherothrombotic events, including myocardial infarction (MI) and stroke. Currently, no routine clinical test can identify individuals with hyperreactive platelets. The development of a diagnostic platelet hyperreactivity test could identify patients most likely to benefit from antiplatelet therapy to reduce cardiovascular (CV) events. Aim: To develop a diagnostic tool to discriminate platelet hyperreactivity and CV risk. Methods: Platelet aggregation (0.4 μM epinephrine) was assessed by light transmission aggregometry (LTA) and responses >60% were classified as “hyperreactive” and <40% “normoreactive”. Simultaneously, platelet RNA was collected and sequenced (RNA-seq; n=88). Using machine-based learning, a hyperreactive platelet transcriptomic signature was identified, and a Platelet Reactivity ExpreSsion Score (PRESS) was assigned to each participant. Model training performance was evaluated by 10-fold cross-validation. Signature validation was performed in (a) control cohort without CV disease (n=35), and the diagnostic capacity of PRESS was assessed in patients (b) undergoing coronary angiography (n=28) and (c) lower extremity revascularization (LER, n=129). Results: PRESS successfully identified a hyperreactive platelet phenotype in patients with CV disease (AUC 0.81, 95% CI 0.68 - 0.94) and in an independent cohort of healthy participants off antiplatelet therapy (AUC 0.77, 95% CI 0.75 - 0.79). In patients undergoing diagnostic cardiac catheterization, PRESS was significantly higher in patients experiencing an acute MI (β=1.8, adj p=0.02). Among patients undergoing LER, those with a PRESS above the median were more likely to develop a future CV event (adj HR 1.90, CI 1.07 - 3.36, p=0.027). Conclusions: A platelet-derived transcriptomic signature identified individuals with hyperreactive platelets and was associated with increased CV risk. A diagnostic platelet reactivity score may facilitate a personalized approach to antithrombotic therapy for CV risk reduction.

Continuous glucose monitoring for glycaemic control and cardiovascular risk reduction in patients with type 2 diabetes not on insulin therapy: A clinical trial.

To evaluate the impact of the Dexcom G6 continuous glucose monitoring (CGM) device on glycaemic control and cardiometabolic risk in patients with type 2 diabetes mellitus (T2DM) at high cardiovascular risk who are not on insulin therapy. Adults with T2DM with glycated haemoglobin (HbA1c) >7% and body mass index (BMI) ≥30 kg/m2 not using insulin were enrolled in a two-phase cross-over study. In phase 1, CGM data were blinded, and participants performed standard glucose self-monitoring. In phase 2, the CGM data were unblinded, and CGM, demographic and cardiovascular risk factor data were collected through 90 days of follow-up and compared using paired tests. Forty-seven participants were included (44% women; 34% Black; mean age 63 years; BMI 37 kg/m2; HbA1c 8.4%; 10-year predicted atherosclerotic cardiovascular disease risk 24.0%). CGM use was associated with a reduction in average glucose (184.0 to 147.2 mg/dl, p < .001), an increase in time in range (57.8 to 82.8%, p < .001) and a trend towards lower glucose variability (26.2 to 23.8%). There were significant reductions in HbA1c, BMI, triglycerides, blood pressure, total cholesterol, diabetes distress and 10-year predicted risk for atherosclerotic cardiovascular disease (p < .05 for all) and an increase in prescriptions for sodium-glucose cotransporter 2 inhibitors (36.2 to 83.0%) and glucagon-like peptide-1 receptor agonists (42.5 to 87.2%, p < .001 for both). Dexcom G6 CGM was associated with improved glycaemic control and cardiometabolic risk in patients with T2DM who were not on insulin. CGM can be a safe and effective tool to improve diabetes management in patients at high risk for adverse cardiovascular outcomes.

Physical fitness in adolescent patients with familial Mediterranean fever.

Familial Mediterranean fever (FMF) is the most frequent monogenic auto-inflammatory disease worldwide responsible for episodes of fever, serositis and musculoskeletal symptoms. Inflammatory attacks are responsible for sedentary behavior and FMF patients may be at increased cardiovascular risk. Cardiorespiratory Fitness (CRF) and physical capacities during adolescence are associated with cardiovascular mortality in adulthood. In this study, we aimed to describe the physical fitness of FMF adolescents. A monocentric retrospective study at the Versailles Hospital between January 2020 and June 2023. All FMF patients over 14-year-old who had completed a routine physical test were included. Clinical and physical data including results of the 6-minute walking test, timed unipedal stance test, Ruffier-Dickson index, 30-seconds chair-stand test and sit-and-reach test were extracted from medical records. Results were compared with previously published normative reference values and criterion-referenced standards for healthy subjects. Eighteen FMF patients (12 girls, 6 boys) were included. The median age was 16 years old [14-18]. Clinical history included joint symptoms (n = 11), chest pleuritis (n = 8), and leg pain (n = 11). Estimated VO2max was below the recommended thresholds in 13 patients, which predicts cardiovascular risk. Cardiovascular adaptation was poor in 11 patients. Low VO2max was associated with CRP > 5mg/l on test day and history of joint symptoms. FMF patients displayed altered physical capacities compared to normative values of healthy subjects. History of musculoskeletal pain, systemic inflammation and sedentary behavior may participate in impaired physical abilities and promote cardiovascular diseases in adulthood. Specific exercise programs could benefit patients for disease control and cardiovascular risk reduction.

Atherosclerosis Residual Lipid Risk-Overview of Existing and Future Pharmacotherapies.

Patients with atherosclerotic disease remain at increased risk of future events despite receiving optimal medical treatment. This residual risk is widely heterogeneous, but lipoprotein particles and their content play a major role in determining future cardiovascular events. Beyond low-density lipoprotein cholesterol (LDL-c), other lipoprotein particles have not demonstrated similar contribution to the progression of atherosclerosis. Statins, ezetimibe, and more recently, proprotein convertase subtilisin kexin 9 (PCSK9) inhibitors and bempedoic acid have confirmed the causal role of LDL-c in the development of atherosclerosis. Data on high-density lipoprotein cholesterol (HDL-c) suggested a possible causal role for atherosclerosis; nonetheless, HDL-c-raising treatments, including cholesteryl-ester transfer protein (CETP) inhibitors and niacin, failed to confirm this relationship. On the other hand, mendelian randomisation revealed that triglycerides are more implicated in the development of atherosclerosis. Although the use of highly purified eicosapentaenoic acid (EPA) was associated with a reduction in the risk of adverse cardiovascular events, this beneficial effect did not correlate with the reduction in triglycerides level and has not been consistent across large phase 3 trials. Moreover, other triglyceride-lowering treatments, such as fibrates, were not associated with a reduction in future cardiovascular risk. Studies assessing agents targeting angiopoietin-like 3 (lipoprotein lipase inhibitor) and apolipoprotein C3 antisense will add further insights into the role of triglycerides in atherosclerosis. Emerging lipid markers such as lipoprotein (a) and cholesterol efflux capacity may have a direct role in the progression of atherosclerosis. Targeting these biomarkers may provide incremental benefits in reducing cardiovascular risk when added to optimal medical treatment. This Review aims to assess available therapies for current lipid biomarkers and provide mechanistic insight into their potential role in reducing future cardiovascular risk.

Do Hepatic Fibrosis and Steatosis Measured by Hepatic Transient Elastography (FibroScan) Predict Cardiovascular Risk in Patients with Non-alcoholic Fatty Liver Disease: An Observational Cross-sectional Study

Objectives: Non-alcoholic fatty liver disease (NAFLD) has been associated with increased cardiovascular risk (CVR) in the previous studies. In the majority, ultrasonography has been used to diagnose and stage NAFLD, which lacks sensitivity and is non-quantitative. Other more sensitive, comprehensive, and quantitative diagnostic tools such as vibration-controlled transient elastography (TE) have largely been underused in research work. TE-driven liver stiffness measurement (LSM) and controlled attenuation parameter (CAP) provide an accurate and simplified estimation of liver fibrosis and steatosis, respectively. Therefore, we aimed to analyze the association between these two objective, robust parameters and CVR. Materials and Methods: In this observational cross-sectional study, NAFLD participants were divided into two distinct categories of steatosis (CAP &lt;290 and ≥290 dB) and fibrosis (LSM &lt;10 and ≥10 kPa). Their CVR assessment was done by calculating Framingham risk score (FRS), American College of Cardiology/American Heart Association Pooled Cohort Equation Score (ACC/AHA PCES), and carotid intimal medial thickness (CIMT). Results: A greater number of participants presented with mild-moderate fibrosis (n = 41, 62.1%) as compared to severe fibrosis (n = 25, 37.8%) whereas severe steatosis participants predominated (n = 52, 78%) as compared to mild-moderate steatosis. The presence of significant fibrosis (LSM ≥10 kPa) was independently and significantly associated with FRS, ACC/AHA PCES, and CIMT. On the other hand, the presence of significant steatosis (CAP ≥290 dB/m) was not significantly associated with any CVR marker (FRS, ACC/AHA PCES, or CIMT), though a greater number of participants with CIMT &gt;0.7 belonged to severe steatosis group. Conclusion: Subjects with severe fibrosis (LSM ≥10) had a significantly higher CVR, whereas severe steatosis (CAP ≥290) alone failed to predict CVR. Therefore, CVR reduction strategies can be targeted primarily in NAFLD subjects with fibrosis, particularly in resource-limited healthcare settings.

Unexplained Residual Risk In Type 2 Diabetes: How Big Is The Problem?

What is new? Cardiovascular disease (CVD) is the leading cause of mortality in type 2 diabetes (T2D) individuals. Of the major risk factors for CVD, less than 10% of T2D people meet the American Diabetes Association/American Heart Association recommended goals of therapy. The present review examines how much of the absolute cardiovascular (CV) risk in type 2 diabetes patients can be explained by major CV intervention trials. Multiple long-term cardiovascular (CV) intervention trials have examined the effect of specific target-directed therapies on the MACE endpoint. Only one prospective study, STENO-2, has employed a multifactorial intervention comparing intensified versus conventional treatment of modifiable risk factors in T2D patients, and demonstrated a 20% absolute CV risk reduction. If the absolute CV risk reduction in these trials is added to that in the only prospective multifactorial intervention trial (STENO-2), the unexplained CV risk is 44.1%. What are the clinical implications? Potential explanations for the unaccounted-for reduction in absolute CV risk in type 2 diabetes (T2D) patients are discussed. failure to take into account synergistic interactions between major cardiovascular risk factors is responsible for the unexplained CV risk in T2D patients. Simultaneous treatment of all major CV risk factors to recommended AHA/ADA guideline goals is required to achieve the maximum reduction in CV risk.

Effect of oesophagectomy on lipid profiles in patients with oesophageal cancer combined with hyperlipidaemia: a retrospective study

BackgroundSurgery is widely regarded as a pivotal therapeutic approach for treating oesophageal cancer, and clinical observations have revealed that many oesophageal cancer patients also present with concomitant hyperlipidaemia. It is surprising that few studies have been performed to determine how blood lipid levels are affected by oesophageal cancer resection. This research was designed to assess the influence of oesophageal cancer resection on lipid profiles among individuals diagnosed with both oesophageal cancer and hyperlipidaemia.MethodsA retrospective analysis was carried out on 110 patients with hyperlipidaemia and oesophageal cancer who had undergone oesophagectomy at the 900th Hospital of the Joint Logistics Support Force of the Chinese People's Liberation Army. Preoperative and postoperative serological data were collected at seven-, thirty-, sixty-day-, and one-year-long intervals. Changes in lipid levels were compared, the remission of various types of hyperlipidaemia was statistically assessed, and Pearson correlation was used to analyse the association between lipid changes and preoperative body weight. The research sought to assess the reduction in body weight and the proportion of body weight lost one year following surgery.ResultsNoteworthy decreases were observed in total cholesterol (TC), triglyceride (TG), and low-density lipoprotein (LDL) levels, with TC decreasing from 6.20 mmol/L to 5.20 mmol/L, TG decreasing from 1.40 mmol/L to 1.20 mmol/L, and LDL decreasing from 4.50 mmol/L to 3.30 mmol/L. Conversely, there was a notable increase in high-density lipoprotein (HDL) levels, which increased from 1.20 mmol/L to 1.40 mmol/L (P < 0.05) compared to the preoperative levels. Notably, the remission rates for mixed hyperlipidaemia (60.9%) and high cholesterol (60.0%) were considerably greater than those for high triglycerides (16.2%). Alterations in TC at one year postoperatively correlated with preoperative weight and weight loss (r = 0.315, -0.216); changes in TG correlated with preoperative weight, percentage of total weight loss (TWL%), and weight reduction (r = -0.295, -0.246, 0.320); and changes in LDL correlated with preoperative weight, TWL%, and weight loss (r = 0.251, 0.186, and -0.207). Changes in non-high-density lipoprotein(non-HDL) were linked to preoperative weight (r = 0.300), and changes in TG/HDL were correlated with preoperative weight and TWL% (r = -0.424, -0.251).ConclusionsOesophagectomy significantly improved lipid profiles in oesophageal cancer patients, potentially leading to a reduction in overall cardiovascular risk.

The role of exercise training on cardiovascular risk factors and heart disease in patients with chronic kidney disease G3-G5 and G5D: a Clinical Consensus Statement of the European Association of Preventive Cardiology of the ESC and the European Association of Rehabilitation in Chronic Kidney Disease.

Cardiovascular (CV) morbidity and mortality is high in patients with chronic kidney disease (CKD). Most patients reveal a high prevalence of CV risk factors such as diabetes or arterial hypertension and many have manifest cardiovascular disease (CVD), such as coronary artery disease and chronic heart failure with an increased risk of clinical events including sudden cardiac death. Diabetes mellitus and hypertension contribute to the development of CKD and the prevalence of CKD is in the range of 20-65% in diabetic and 30-50% in hypertensive patients. Therefore, prevention and optimal treatment of CV risk factors and comorbidities are key strategies to reduce CV risk and improve survival in CKD. Beyond common CV risk factors, patients with CKD are often physically inactive and have low physical function leading to subsequent frailty with muscle fatigue and weakness, sarcopenia and increased risk of falling. Consequently, the economic health burden of CKD is high, requiring feasible strategies to counteract this vicious cycle. Regular physical activity and exercise training (ET) have been shown to be effective in improving risk factors, reducing CVD and reducing frailty and falls. Nonetheless, combining ET and a healthy lifestyle with pharmacological treatment is not frequently applied in clinical practice. For that reason, this Clinical Consensus Statement reviews the current literature and provides evidence-based data regarding the role of ET in reducing CV and overall burden in patients with CKD. The aim is to increase awareness among cardiologists, nephrologists, and healthcare professionals of the potential of exercise therapy in order to encourage implementation of ET in clinical practice, eventually reducing CV risk and disease, as well as reducing frailty in patients with CKD G3-G5D.

Existing and emerging GLP-1 receptor agonist therapy: Ramifications for diabetic retinopathy screening.

GLP-1 receptor agonist treatment revolutionised the management of type 2 diabetes mellitus with significant enhancement of cardiovascular risk reduction. They have been instrumental in effectively managing the glycaemic control of this at-risk patient group. This class of drugs are associated with rapid improvement in glucose levels and consequently, transient early worsening of pre-existing diabetic retinopathy (DR) which is well-recognised, but this paradox is less commonly perceived in routine clinical practice. The recent shortage of supply has resulted in an enforced hiatus to prescribing all existing GLP-1 receptor agonists, which is expected to last all through 2024. This becomes even more pertinent as their DR could have progressed due to worsening HbA1c as a result of the unforeseen interruption to GLP-1 receptor agonist treatment. Therefore, when these medications are recommenced in a few months' time, all prescribers need to be aware of these patients' most up-to-date DR status and liaise with their affiliated screening service.

There are those who would like zero LDL cholesterol.

The overwhelming evidence that the reduction of LDL cholesterol (LDLc) levels is associated with a parallel reduction in cardiovascular (CV) risk has led the scientific community to progressively and constantly reduce the optimal therapeutic targets of LDLc, both in patients with known CV disease and in patients undergoing primary prevention. The recent introduction of proprotein convertase subtilisin/kexin type 9 inhibitors has allowed clinicians to observe reductions in LDLc levels that go well beyond the limits set by the main international guidelines; following the 'the lower the better' paradigm, it is natural to ask how low LDLc can be reduced, whether this intervention is associated with a further reduction in CV risk and, above all, whether there are no issues related to safety in the use of polypharmacotherapies that determine an extreme reduction in LDLc levels. The purpose of this article is to summarize the main scientific evidence on the topic, trying to provide an answer to all clinicians who 'would like their LDLc to be-almost-zero'.

A focused update to the 2019 NLA scientific statement on use of lipoprotein(a) in clinical practice

Since the 2019 National Lipid Association (NLA) Scientific Statement on Use of Lipoprotein(a) in Clinical Practice was issued, accumulating epidemiological data have clarified the relationship between lipoprotein(a) [Lp(a)] level and cardiovascular disease risk and risk reduction. Therefore, the NLA developed this focused update to guide clinicians in applying this emerging evidence in clinical practice. We now have sufficient evidence to support the recommendation to measure Lp(a) levels at least once in every adult for risk stratification. Individuals with Lp(a) levels <75 nmol/L (30 mg/dL) are considered low risk, individuals with Lp(a) levels ≥125 nmol/L (50 mg/dL) are considered high risk, and individuals with Lp(a) levels between 75 and 125 nmol/L (30-50 mg/dL) are at intermediate risk. Cascade screening of first-degree relatives of patients with elevated Lp(a) can identify additional individuals at risk who require intervention. Patients with elevated Lp(a) should receive early, more-intensive risk factor management, including lifestyle modification and lipid-lowering drug therapy in high-risk individuals, primarily to reduce low-density lipoprotein cholesterol (LDL-C) levels. The U.S. Food and Drug Administration approved an indication for lipoprotein apheresis (which reduces both Lp(a) and LDL-C) in high-risk patients with familial hypercholesterolemia and documented coronary or peripheral artery disease whose Lp(a) level remains ≥60 mg/dL [∼150 nmol/L)] and LDL-C ≥ 100 mg/dL on maximally tolerated lipid-lowering therapy. Although Lp(a) is an established independent causal risk factor for cardiovascular disease, and despite the high prevalence of Lp(a) elevation (∼1 of 5 individuals), measurement rates are low, warranting improved screening strategies for cardiovascular disease prevention.

The Association Between State Characteristics and Latinx People's Treated Hypertension in Established and New Latinx Destination States: A Multilevel Analysis.

This study sought to quantify the contributions of state-level factors including income inequality, state's legislature political control, and Medicaid expansion in new and established Latinx destination states on Latinx individuals' treated hypertension. Mixed-effects logistic regression analyses were conducted to analyze 2017 Behavioral Risk Factor Surveillance System data from 7524 Latinx adults nested within 39 states. Overall, 70% reported being pharmacologically treated for hypertension, and 66% resided in established destination states. Compared with Latinx people in established destination states, Latinx people in new destinations had lower odds of having treated hypertension (odds ratio [OR] = 0.72, 95% CI = 0.54-0.95). Within established Latinx destinations, the odds of treated hypertension were lower in states where legislatures expanded Medicaid than in states that did not expand Medicaid (OR = 0.84, 95% CI = 0.79-0.89). However, after controlling for the effects of individual-level factors, this association was no longer statistically significant. In new Latinx destination states, Medicaid expansion, legislatures' political control, and income inequality were not associated with treated hypertension. The study results highlight the importance of considering both individual- and state-level factors, as the interplay of such factors could hinder the successful implementation of cardiovascular risk reduction interventions.

The Global Shortage of Glucagon-Like Peptide-1 Receptor Agonists

The global shortage of glucagon-like peptide-1 (GLP-1) receptor agonists, which are highly sought after as treatments for type 2 diabetes and obesity, is increasing. This deficit is attributed to the unexpected increase in demand for GLP-1 receptor agonists. This has caused significant harm to patients with type 2 diabetes mellitus who are already using GLP-1 receptor agonists for blood sugar management, weight loss, or reduction of cardiovascular risk or those who are looking to start. To address this situation, doctors need to adjust medications considering the patient condition and clinical guidelines and must provide better education on lifestyle modifications such as diet and exercise. Close cooperation between regulatory agencies and manufacturers is needed to mass-produce GLP-1 receptor agonists, as are societal efforts to prevent the trend of GLP-1 receptor agonist use as diet pills.

Understanding The Role of SGLT2 Inhibitors in Cardiovascular Risk Reduction for Type 2 Diabetes Patients-A Literature Review

Introduction: Type 2 diabetes mellitus (T2DM) is associated with an increased risk of cardiovascular events and heart failure. Sodium-glucose cotransporter 2 (SGLT2) inhibitors have emerged as a novel class of antidiabetic agents with potential cardiovascular benefits. This systematic review aims to evaluate the impact of SGLT2 inhibitors on reducing cardiovascular events and heart failure hospitalizations in patients with T2DM. Aims: The review aims to comprehensively evaluate the impact of SGLT2 inhibitors on reducing cardiovascular events, including MACE, and HF hospitalizations in patients with T2DM. Methods: A comprehensive literature search was conducted in major electronic databases like PubMed, Google Scholar and Science Direct to identify relevant studies. Studies investigating the cardiovascular outcomes of SGLT2 inhibitors in T2DM patients were included. Data extraction and quality assessment were performed independently by three reviewers using predefined criteria. Results: A total of 17 studies met the inclusion criteria and were included in the review. The analysis of clinical trials, including EMPA-REG OUTCOME, CANVAS Program, and DECLARE-TIMI 58, demonstrated significant reductions in MACE and HF hospitalizations with SGLT2 inhibitors compared to placebo or standard care. Real-world evidence from studies such as the CVD-REAL and EASEL studies further supported these findings, showing consistent cardiovascular benefits of SGLT2 inhibitors in routine clinical practice. The findings suggest that SGLT2 inhibitors are associated with a reduction in cardiovascular events, including myocardial infarction, stroke, and cardiovascular mortality, as well as a decreased risk of heart failure hospitalizations in patients with T2DM. Conclusion: This systematic review provides evidence supporting the cardiovascular benefits of SGLT2 inhibitors in T2DM management. The findings underscore the importance of considering these agents as part of comprehensive cardiovascular risk reduction strategies in T2DM patients. Further research is necessary to explicate the mechanisms underlying these benefits and optimize their clinical use.

Long-term cardiovascular risk reduction after gastric cancer surgery: a nationwide cohort study.

Gastrectomy for gastric cancer is associated with postoperative changes in cardiovascular risk factors, however, the impact of gastrectomy on cardiovascular events remains unclear. We assessed the incidence of cardiovascular events between patients undergoing gastrectomy or endoscopic resection for gastric cancer, and the general population. This retrospective nationwide cohort study included patients with gastric cancer undergoing gastrectomy(n=37,698), endoscopic resection(n=2,773), and matched control population(n=161,887) between 2004 and 2013. We included patients without a history of cancer other than gastric cancer, myocardial infarction, or ischemic stroke. The primary outcome was the incidence of major adverse cardiovascular events (MACE) such as acute myocardial infarction, revascularization, or acute ischemic stroke, in patients with gastric cancer. Among patients who underwent gastrectomy for gastric cancer, 2.9% (4.69 per 1000 person-years) developed novel MACE within the seven-year follow-up period. The gastrectomy group demonstrated a significantly decreased risk for MACE than the control population (hazard ratio[HR], 0.65; 95% confidence interval[CI], 0.61-0.69; P <0.001). Among the patients undergoing endoscopic resection for gastric cancer, 5.4% (8.21 per 1000 person-years) developed novel MACE within the seven-year follow-up period. The risk for MACE in the endoscopic resection group was not significantly different from the control population. Patients with gastric cancer who have undergone gastrectomy exhibit a reduced risk of cardiovascular diseases in comparison to the general population. In contrast, the risk for cardiovascular diseases in patients with gastric cancer who underwent endoscopic resection did not demonstrate a significant difference in cardiovascular risk in comparison to the general population.

Effects of statin therapy on diagnoses of new-onset diabetes and worsening glycaemia in large-scale randomised blinded statin trials: an individual participant data meta-analysis

Previous meta-analyses of summary data from randomised controlled trials have shown that statin therapy increases the risk of diabetes, but less is known about the size or timing of this effect, or who is at greatest risk. We aimed to address these gaps in knowledge through analysis of individual participant data from large, long-term, randomised, double-blind trials of statin therapy. We conducted a meta-analysis of individual participant data from randomised controlled trials of statin therapy that participated in the CTT Collaboration. All double-blind randomised controlled trials of statin therapy of at least 2 years' scheduled duration and with at least 1000 participants were eligible for inclusion in this meta-analysis. All recorded diabetes-related adverse events, treatments, and measures of glycaemia were sought from eligible trials. Meta-analyses assessed the effects of allocation to statin therapy on new-onset diabetes (defined by diabetes-related adverse events, use of new glucose-lowering medications, glucose concentrations, or HbA1c values) and on worsening glycaemia in people with diabetes (defined by complications of glucose control, increased use of glucose-lowering medication, or HbA1c increase of ≥0·5%). Standard inverse-variance-weighted meta-analyses of the effects on these outcomes were conducted according to a prespecified protocol. Of the trials participating in the CTT Collaboration, 19 trials compared statin versus placebo (123 940 participants, 25 701 [21%] with diabetes; median follow-up of 4·3 years), and four trials compared more versus less intensive statin therapy (30 724 participants, 5340 [17%] with diabetes, median follow-up of 4·9 years). Compared with placebo, allocation to low-intensity or moderate-intensity statin therapy resulted in a 10% proportional increase in new-onset diabetes (2420 of 39 179 participants assigned to receive a statin [1·3% per year] vs 2214 of 39 266 participants assigned to receive placebo [1·2% per year]; rate ratio [RR] 1·10, 95% CI 1·04-1·16), and allocation to high-intensity statin therapy resulted in a 36% proportional increase (1221 of 9935 participants assigned to receive a statin [4·8% per year] vs 905 of 9859 participants assigned to receive placebo [3·5% per year]; 1·36, 1·25-1·48). For each trial, the rate of new-onset diabetes among participants allocated to receive placebo depended mostly on the proportion of participants who had at least one follow-up HbA1c measurement; this proportion was much higher in the high-intensity than the low-intensity or moderate-intensity trials. Consequently, the main determinant of the magnitude of the absolute excesses in the two types of trial was the extent of HbA1c measurement rather than the proportional increase in risk associated with statin therapy. In participants without baseline diabetes, mean glucose increased by 0·04 mmol/L with both low-intensity or moderate-intensity (95% CI 0·03-0·05) and high-intensity statins (0·02-0·06), and mean HbA1c increased by 0·06% (0·00-0·12) with low-intensity or moderate-intensity statins and 0·08% (0·07-0·09) with high-intensity statins. Among those with a baseline measure of glycaemia, approximately 62% of new-onset diabetes cases were among participants who were already in the top quarter of the baseline distribution. The relative effects of statin therapy on new-onset diabetes were similar among different types of participants and over time. Among participants with baseline diabetes, the RRs for worsening glycaemia were 1·10 (1·06-1·14) for low-intensity or moderate-intensity statin therapy and 1·24 (1·06-1·44) for high-intensity statin therapy compared with placebo. Statins cause a moderate dose-dependent increase in new diagnoses of diabetes that is consistent with a small upwards shift in glycaemia, with the majority of new diagnoses of diabetes occurring in people with baseline glycaemic markers that are close to the diagnostic threshold for diabetes. Importantly, however, any theoretical adverse effects of statins on cardiovascular risk that might arise from these small increases in glycaemia (or, indeed, from any other mechanism) are already accounted for in the overall reduction in cardiovascular risk that is seen with statin therapy in these trials. These findings should further inform clinical guidelines regarding clinical management of people taking statin therapy. British Heart Foundation, UK Medical Research Council, and Australian National Health and Medical Research Council.

Abstract P278: 1-year Outcomes of A1c Reduction, Weight Loss, and Lowered QRISK3 Scores in Type 2 Diabetes Remission: Insights From an RCCT Leveraging Whole-Body Digital Twin Technology

Background and Aims: The effects of digital twin (DT) technology for remission of T2D on cardiovascular risk reduction is unknown. We evaluated the effectiveness of the DT to improve A1c and body weight and QRISK3 (QResearch Cardiovascular Disease Risk Algorithm 3), which is a prediction algorithm to estimate the 10-year risk for developing cardiovascular disease (CVD), in patients enrolled to achieve remission of T2DM. DT platform uses AI and Internet of Things, to integrate multi-dimensional data to give precision nutrition and health recommendations via the mobile app and by coaches. Materials and Methods: We evaluated the data from prospective cohort of 204 participants who had been on DT for 1 year. Remission was defined as A1C levels less than 6.5% without medication for over 3 months. Outcomes included the change in HbA1c, body weight and change in QRISK3 scores. The DT uses a machine learning algorithm to integrate clinical and sensor data to predict personal glucose response. Patients were connected to continuous glucose monitoring (CGM) throughout the study and self-recorded dietary intake using the mobile app. Results: The study participants had a mean diabetes duration of 3.7±2.6 years and a mean age of 44±8.2 years. Based on the ADA criteria, at 1 year, 73% (n=149/204) continued to be under remission. The mean QRISK3 at baseline was 12.6 (±10.7, 95% CI 11.2 to 14) which significantly reduced to 9.5 (±7.9, 95% CI 8.5 to 10.6) at 360 days, p=0.0009. A1c (%) at baseline was 8.9 (±1.8, 95% CI 8.6 to 9.1, minimum 5.5, maximum 16.2) which reduced to 6 (±0.6, 95% CI 5.9 to 6, minimum 4.7, maximum 9.2), p&lt;0.0001. Body weight (kg) at baseline was 78.3 (±14.2, 95% CI 76.4 to 80.2) which reduced to 70.7 (±12.8, 95% CI 69 to 72.4), &lt;0.0001. There was a significant correlation between the reduction in body weight and QRISK3 (Pearson r 0.24 95% CI 0.1 to 0.3, p=0.0004). However, the correlation between the reduction in A1c and QRISK3 (Pearson r 0.04, 95% CI -0.09 to 0.18, p=0.53 ns) was comparable. At baseline, there were 53% of participants who had low risk score (&lt;10), 28% as intermediate risk (10-20), 19% as high risk (&gt;20%) that at 1 year shifted to 67% as low risk, 23% as intermediate risk and 10% as high-risk scores. Conclusion: Incorporating the Digital Twin (DT) technology, which blends AI and IoT for tailored health guidance, our RCCT indicated significant 1-year advancements in A1c, weight, and QRISK3 scores among T2DM patients aiming for remission. The transformative potential of DT is evident, particularly in shifting a majority of participants towards lower cardiovascular risk categories.

Abstract P468: Correlation Among A1c Improvement, Weight Reduction, and Decreased ASCVD Risk in Participants Enrolled for Type 2 Diabetes Remission: Outcomes at 1 Year From an RCCT Using Whole-Body Digital Twin Technology

Background and Aims: The effects of digital twin (DT) technology for remission of T2D on cardiovascular risk reduction is unknown. We evaluated the effectiveness of the DT to improve A1c and body weight and ASCVD risk, in patients enrolled to achieve remission of T2DM. DT platform uses AI and Internet of Things, to integrate multi-dimensional data to give precision nutrition and health recommendations via the mobile app and by coaches. Materials and Methods: Data from 208 participants who had been on DT for 1 year were analyzed. Remission was defined as A1C levels less than 6.5% without medication for over 3 months. Outcomes included the change in HbA1c, body weight and change in ASCVD risk scores. The DT uses a machine learning algorithm to integrate clinical and sensor data to predict personal glucose response. Patients were connected to continuous glucose monitoring (CGM) throughout the study and self-recorded dietary intake using the mobile app. Results: The study participants had a mean diabetes duration of 3.7±2.7 years and a mean age of 44±8.5 years. Based on the ADA criteria, at 1 year, 72.6% (n=151/208) continued to be under remission. The mean 10-year ASCVD risk (%) at baseline was 7.9 (±7.8, 95% CI 6.8 to 8.9) which reduced to 3.6 (±4, 95% CI 3.1 to 4.2) at 360 days, p&lt;0.0001. A1c (%) at baseline was 8.9 (±1.8, 95% CI 8.7 to 9.2, minimum 5.5, maximum 16.2) which reduced to 6 (±0.6, 95% CI 5.9 to 6.1, minimum 4.7, maximum 9.2), p&lt;0.0001. Body weight (kg) at baseline was 78 (±14.3, 95% CI 76.1 to 79.9) which reduced to 70.4 (±12.9, 95% CI 68.7 to 72.1), p&lt;0.0001. There was a significant correlation between the reduction in A1c and ASCVD (Pearson r 0.41, 95% CI 0.31 to 0.5, p&lt;0.0001). Similarly, there was a significant correlation between the reduction in body weight and ASCVD (Pearson r 0.25, 95% CI 0.12 to 0.3, &lt;0.0001). At baseline, there were 49% of participants who had low risk score (&lt;5%), 16% as borderline risk (5-7.5%), 27% as intermediate risk (7.5-19.9), 8% as high risk (&gt;20%) that at 1 year shifted to 77% as low risk, 11% as borderline, 11% as intermediate risk and 1% as high-risk scores. Conclusion: The implementation of digital twin (DT) technology, utilizing AI and Internet of Things, demonstrated significant potential in T2DM management in participants enrolled to achieve remission. In our study with 208 participants, DT effectively reduced A1c levels, body weight, and ASCVD risk scores over 360 days. The correlations between reductions in A1c, body weight, and ASCVD underscore the potential of DT as a transformative tool in diabetes and cardiovascular risk management.

Abstract P299: Alteration of Cardiac Autonomic Function Through Inhalation of Biogenic Volatile Organic Compounds

Background: There is an inverse relationship between exposure to greenspaces and prevalence of cardiovascular disease and cardiovascular disease risk factors. More specifically, green exposure is associated with electrocardiogram (ECG) changes, suggesting a potential alteration of cardiac autonomic balance. One proposed mechanism by which cardiac autonomic balance may be altered is a direct physiologic effect of inhalable plant derived compounds, or biogenic volatile organic compounds (bVOCs), including limonene, α- and β-pinene which are commonly released from vegetation. Therefore, we examined the relationship between acute exposure of isolated bVOCs and cardiac autonomic tone. Hypothesis: We hypothesize that controlled exposure to isolated individual bVOCs will decrease cardiac sympathetic tone. Methods: Under controlled conditions after a bVOC washout period, healthy adults ages 18-70 were exposed to limonene (n=32), α-pinene (n=24), β-pinene (n=17), and a control (room air, n=9). Exposure consisted of one inhalation every 30 seconds for a total of 5 minutes (10 inhalations total). Pre- and post-exposure measurements of supine heart rate variability (HRV) were conducted following a 10-minute rest period. HRV was analyzed using a clean, 5-minute epoch with &gt;95% effective data length. Statistical analysis was performed using paired t-tests to determine changes in HR and HRV. Significance level was set at p&lt;0.05, a priori . Results: Our population was primarily female (56%, 18 of 32), white (53%, 17 of 32), high income (47%, 15 of 32), and had an education higher than a 4-year degree (62.5%, 20 of 32). There were significant decreases in HR when exposed to limonene (pre: 64.87±9.86bpm vs. post: 63.26±9.10bpm, p&lt;.001) and α-pinene (pre: 63.98±9.32bpm vs. post: 61.64±9.72bpm, p=.008), along with trends seen in β-pinene (pre: 65.78±10.60bpm vs. post: 63.74±9.65bpm, p=.066). Control exposure showed no difference (pre: 65.40±8.38bpm vs. post: 64.14±9.35bpm, p=.301). Normalized low- (LF) and high-frequency (HF) HRV parameters showed no change across isolated bVOCs, however the LF/HF ratio scores decreased significantly following β-pinene exposure (pre: 1.62±1.69 vs. post: 0.96±0.96, p=.039). HRV time-domain parameters RMSSD and SDNN did not change following isolate exposure. Conclusions: Post-exposure decreases in HR and LFHF ratios indicate the potential for cardiovascular disease risk reduction from bVOC exposure leading to decreased sympathetic tone. Additional work is required to determine the mechanism of exposure-related changes.