High Cardiovascular Research Articles

Abstract 4141496: Methylation changes in monocytes of type 2 diabetes patients with cardiovascular disease are associated with apoptosis and inflammation pathways.

Background: Monocytes have been implicated in the initiation and progression of cardiovascular (CV) complications of type 2 diabetes (T2D). Aim: We investigated diabetes-induced methylation changes and enriched pathways in circulating monocytes of T2D patients. We compared T2D vs. non-T2D participants and analyzed T2D patients according to diabetes control. Further, we assessed methylation changes in a subset of patients with poor diabetes control and high CV risk following a 6-month treatment intensification. Methods: We recruited consecutively 200 participants, 160 with T2D and 40 non-diabetes controls. Circulating monocytes were sorted using the FACSAria2 ™ cell sorter. Samples were sequenced using enhanced reduced representation bisulfite sequencing. Methylation data was processed with Lumi and limma R packages to obtain batch and covariate corrected differential expression values for the indicated comparisons. Ingenuity Pathway Analysis (Qiagen) was used to identify enriched pathways for each tested condition. Differentially methylated genes used for pathway analysis were those with a p-value < 0.05 and an absolute logFC value ≥ 0.5. Results: There were 1122 differentially methylated genes when comparing T2D to non-T2D patients. Among the top five enriched canonical pathways, apoptosis signaling was predicted to be activated, while the RHO GTPase cycle and LPS-stimulated MAPK signaling pathways were predicted to be inhibited. Within patients with diabetes, there were 1670 differentially methylated genes comparing those with poor control (HbA1c ≥ 7%) vs. good control (HbA1c<7%). Among the top five enriched pathways, synthesis of DNA, DNA replication signaling, and cell cycle checkpoints were activated while inhibition of ARE-mediated mRNA degradation pathway was inhibited. In patients who responded to treatment intensification (Δ HbA1c = -1.5%, p= 0.02), 1377 differentially methylated genes and differentially inhibited pathways such as non-homologous end-joining and cellular response to heat stress were identified. In non-responders, we identified 1582 differentially methylated genes and activated pathways, including inhibition of mRNA degradation pathways and p14/p19 ARF signaling. Conclusion: Treatment intensification in T2D patients with CVD and poor control showed the presence of differentially methylated genes affecting pathways regulating cell proliferation and inflammation and are known to be associated with diabetic CVD complications.

Abstract 4137636: Cardiac radiation dose and changes in physical activity and quality of life in patients with locally advanced lung cancer

Background: Physical activity is associated with prognosis in cancer. However, in non-small cell lung cancer (NSCLC), a high cardiovascular (CV) population, the relationships between RT dose, physical activity, and CV patient-reported outcomes remain unclear. We determined the associations between cardiac radiation dose-volume metrics and changes in physical activity and quality-of-life (QoL) in patients treated with definitive chemoradiation. Methods: NSCLC participants treated with chemoradiation were enrolled in a multi-center longitudinal cohort study. Self-reported physical activity via Godin–Shephard Leisure-Time Physical Activity Questionnaire (Godin) and QoL via Functional Assessment of Chronic Illness Therapy (FACIT) Fatigue and Dyspnea Scales were collected at baseline, end of RT, 6, and 12 months post-RT. Changes in Godin and FACIT scores over time were examined using linear mixed-effects models. Multivariable linear regression via generalized estimating equations assessed the associations between: 1) mean heart dose (MHD) and longitudinal changes in physical activity and QoL, and 2) concurrent changes in physical activity and FACIT scores. Results: Across 101 participants, the mean age was 66 years, with 57% male, 66% White, and 25% Black. The median (Q1, Q3) MHD was 10.8 Gy (6.1,16.3). Very low physical activity [9 (0, 25)], high dyspnea [4 (1, 9)], and low fatigue [39 (31,46)] were reported at baseline. With chemoRT, there was a significant worsening of physical activity ( P = 0.03), fatigue ( P < 0.001), and dyspnea ( P < 0.001). Each 1-Gy increase in MHD was associated with a modest decline in physical activity (-0.28; 95% CI -0.53, -0.02, P = 0.03), and higher physical activity was associated with a concurrent decrease in fatigue ( P < 0.001) and dyspnea ( P = 0.007) (Table). Conclusions: In locally advanced NSCLC, physical activity levels prior to RT were very low, and higher cardiac radiation dose was associated with a further decline in physical activity. Increased physical activity was associated with concurrent decreases in fatigue and dyspnea. Strategies to promote physical activity may result in improved QoL in this high CV group.

Adherence to the 2019 ESC/EAS guidelines for dyslipidaemia management in a large rheumatoid arthritis cohort: Data from the CORDIS Study Group of the Italian Society of Rheumatology

Background/aimLipid-lowering therapy prescription is low in rheumatoid arthritis (RA) patients, often not achieving lipid threshold target despite treatment. However, evidence derives from small, monocentric cohorts. We assessed adherence to lipid-lowering treatment for primary cardiovascular (CV) prevention in a RA cohort according to international guidelines. MethodsA cross-sectional analysis of an Italian RA cohort was performed. Disease-related features and traditional CV risk factors were collected. The 10-year CV risk was estimated by Systematic COronary Risk Evaluation 2 (SCORE-2) algorithm. The primary preventive dyslipidaemia strategy was assessed according to 2019 European Society of Cardiology/European Atherosclerosis Society guidelines. Results1.133 RA patients (78.2% female, aged 60.6±10.2 years) free from CV events were included. According to SCORE-2, 42.9% of patients were at moderate risk (1–5-%), 33.3% at high risk (5–10%) and 23.7% at very high risk (>10%). In the whole cohort, 12.9% of patients with <5%, 23.6% with 5–10% and 32.3% with >10% risk were on statin, respectively (p<0.001). According to 2019 ESC/EAS guidelines, 51.5% of patients had LDL-c at target. Among patients with LDL-c not at target, 76% were not on lipid-lowering treatment. At multivariate analysis, patients with higher CV risk had significantly lower probability of LDL-c at target. ConclusionIn a wide Italian RA cohort, more than 50% of patients had high or very high CV risk. In these, lipid-lowering treatment prescription is suboptimal leading to not achievement of LDL-c target. Physicians should improve lipid screening and primary prevention therapy to reduce CV risk and improve CV comorbidity in RA patients.

High glucose enhanced lipoprotein(a) [Lp(a)] oxidation in a manner inhibited by eicosapentaenoic acid (EPA) in vitro

Abstract Background Elevated lipoprotein(a) (Lp(a)) levels are causally and independently associated with increased cardiovascular (CV) risk. Targeted molecular therapies are in development. Levels of oxidized Lp(a) were more predictive of CV events and endothelial dysfunction in type 2 diabetes than non-oxidized forms. EPA administered as icosapent ethyl (IPE) reduced CV events in statin-treated patients (REDUCE-IT) with diabetes and high CV risk. As a fatty acid with multiple conjugated double bonds, EPA inhibits lipoprotein oxidation by a potent lipid-centric scavenging mechanism. We therefore tested the effects of EPA on oxidation of Lp(a) and non-modified LDL under conditions of high glucose to mimic aspects of hyperglycemia in vivo. Methods Lp(a) was enriched to 41% of total ApoB-containing particles from patients with elevated levels by isopycnic centrifugation. Samples of Lp(a) and non-modified LDL were incubated under high glucose (200 mg/dL) conditions at 37°C for 30 min with EPA (50 µM). Samples were then subjected to copper sulfate-induced oxidation (20 µM) monitored by formation of malondialdehyde (MDA) via a colorimetric assay. Results Lp(a) enriched plasma underwent increased oxidation, peaking at 4 hr by 32-fold compared to baseline (0.37 ± 0.04 vs 12.27 ± 0.61 µM, p&amp;lt;0.001) under conditions of high glucose. Non-modified LDL also underwent oxidation in the presence of high glucose with a distinct rate compared to Lp(a), peaking after 3 h (0.28 ± 0.09 vs 10.91 ± 0.93 µM, p&amp;lt;0.001). EPA significantly inhibited both Lp(a) and LDL oxidation in a time-dependent manner. After peak oxidation was achieved in Lp(a) (4 h) and LDL (3 h), EPA inhibited oxidation by 57% (5.29 ± 0.25 µM, p&amp;lt;0.001) and 81% (2.12 ± 0.09 µM, p&amp;lt;0.001), respectively. Conclusions Under hyperglycemic conditions, EPA inhibited oxidation of Lp(a)-enriched plasma and non-modified LDL in a time-dependent manner. The activity of EPA may arise from its lipophilic properties and highly conjugated structure that scavenges free radicals in lipid-concentrated environments. The potent antioxidant activity of EPA may contribute to reduced CV risk in patients with diabetes and elevated Lp(a).

Rosuvastatin effect on atherosclerotic plaque microcalcification

Abstract Background and Aims Atherosclerotic plaque fluorine-18 sodium fluoride (18F-NaF) uptake on positron emission tomography with computed tomography (PET-CT) identifies active microcalcification and has been shown to correlate with clinical instability in patients with cardiovascular (CV) disease. Statin therapy promotes coronary macrocalcification over time. Our aim was to investigate rosuvastatin effect on atheroma 18F-NaF uptake. Methods Subjects with high CV risk but without CV events underwent 18F-NaF-PET-CT in a single-centre. Those with subclinical atherosclerosis and significant 18F-NaF plaque uptake were included in a single-arm clinical trial, treated with rosuvastatin 20mg/daily for six months, and re-evaluated by 18F-NaF-PET-CT. Primary endpoint was reduction in maximum atheroma 18F-NaF uptake in the coronary, aortic or carotid arteries, assessed by the tissue-to-background ratio (TBR). The secondary endpoint was corrected uptake per lesion (CUL) variation. Results Forty individuals were enrolled and 38 included in the pharmacological trial; mean age was 64 years-old, two-thirds were male and most were diabetic. The 10-year expected CV risk was 9.5% (6.0-15.3) for SCORE2 and 31.7±18.7% for ASCVD systems. After six months of rosuvastatin treatment (n=34), low-density lipoprotein cholesterol lowered from 133.6±33.8 to 58.8±20.7 mg.dL-1 (60% relative reduction, p&amp;lt;0.01). There was a significant 19% reduction in maximum plaque 18F-NaF uptake after treatment, from 1.96 (1.78-2.22) to 1.53 (1.40-2.10), p&amp;lt;0.001 (primary endpoint analysis). The secondary endpoint CUL was reduced by 23% (p=0.003). Conclusion In a single-centre non-randomized clinical trial of high CV risk individuals with subclinical atherosclerosis, the maximum atherosclerotic plaque 18F-NaF uptake was significantly reduced after six months of high-intensity statin.Graphical abstractTrial design

Icosapent ethyl by baseline small dense low-density lipoprotein cholesterol: an analysis of REDUCE-IT

Abstract Background Small dense low-density lipoprotein cholesterol (sdLDL-C) is associated with cardiovascular (CV) risk. Purpose We assessed if baseline sdLDL-C modified the effect of icosapent ethyl among patients in REDUCE-IT. Methods REDUCE-IT randomized patients to icosapent ethyl vs placebo. In this post hoc analysis, patients ≥45 years with CV disease or ≥50 years with diabetes and CV risk factors were included. Patients were required to have triglycerides of 135-499 mg/dL and low-density lipoprotein cholesterol (LDL-C) of 41-100 mg/dL. Exclusion criteria included severe heart failure, acute severe liver disease, or hemoglobin A1c &amp;gt;10%. Patients were stratified by baseline calculated sdLDL-C. A threshold of 46 mg/dL was chosen because sdLDL-C greater than this cutoff has predicted CV risk despite well-controlled LDL-C. The primary outcome included a composite of CV death, nonfatal myocardial infarction (MI), nonfatal stroke, coronary revascularization, or unstable angina. The key secondary composite outcome included CV death, nonfatal MI, or nonfatal stroke. Outcomes were assessed with Cox proportional hazard models and interaction analyses were conducted to assess heterogeneity in treatment effect by baseline sdLDL-C. Results REDUCE-IT included 8179 patients, with 8157 (99.7%) patients having sdLDL-C data. Among these patients, 7698 (94.4%) had sdLDL-C &amp;lt;46 mg/dL and 459 (5.6%) had sdLDL-C ≥46 mg/dL. Median sdLDL-C was 34.2 mg/dL (interquartile range [IQR]: 30.3, 38.4 mg/dL) in the lower sdLDL-C group and 48.4 mg/dL (IQR: 47.1, 50.6 mg/dL) in the higher sdLDL-C group (Table). The placebo group had a greater event rate in the higher sdLDL-C group compared to the lower sdLDL-C group (72.0 vs 56.4 events per 1000 p-y), though event rates in the icosapent ethyl group were similar by sdLDL-C group (44.1 vs 43.3 events per 1000 p-y, respectively). Icosapent ethyl reduced the rate of the primary outcome compared with placebo (17.2% vs 22.0%; hazard ratio [HR]: 0.75 [95% CI: 0.68, 0.83]; P&amp;lt;0.0001). The number needed to treat [NNT] to avoid one primary endpoint event was 21. In the lower sdLDL-C group, icosapent ethyl decreased rates of the primary outcome (43.3 events per 1000 patient-years [p-y]) compared with the placebo group (56.4 events per 1000 p-y) (17.3% vs 21.7%; HR: 0.77 [95% CI: 0.69, 0.85]; NNT: 22). Similarly, in the higher sdLDL-C group, icosapent ethyl decreased the rate of the primary outcome (44.1 events per 1000 p-y) compared with the placebo group (72.0 events per 1000 p-y) (16.6% vs 26.4%; HR: 0.58 [95% CI: 0.38, 0.88]; NNT: 10). There was no significant interaction between treatment benefit and baseline sdLDL-C for the primary (Pinteraction = 0.22) and key secondary outcome (Pinteraction = 0.82). Findings were overall similar for the other secondary outcomes (Figure). Conclusion Icosapent ethyl reduced CV outcomes in patients with high CV risk and elevated triglycerides irrespective of low or high sdLDL-C.

Global burden of high-risk cardiovascular patients without prior myocardial infarction or stroke: VESALIUS-REAL - preliminary results from Germany

Abstract Background Clinical trial data has shown that low-density lipoprotein cholesterol (LDL-C) lowering with PCSK9-inhibitors reduced cardiovascular (CV) endpoints in patients with established atherosclerotic cardiovascular disease (ASCVD). Intervening early in patients with high CV risk prior to myocardial infarction (MI) or stroke, while perceived to be less urgent, may result in larger public health benefits. The effect of evolocumab in this population is investigated in a phase-3 clinical trial (NCT03872401: Effect of Evolocumab in Patients at High Cardiovascular Risk Without Prior Myocardial Infarction or Stroke [VESALIUS-CV]). This observational study examines the global burden of VESALIUS-CV-like population in the REAL-World ("VESALIUS-REAL") in eight regions (Germany, Hong Kong, Japan, South Korea, Sweden, Taiwan, UK and US) using a unified protocol across multiple databases. The multi-database study is ongoing, and the current analysis focuses on characteristics of VESALIUS-CV like patients in Germany. Methods Eligibility criteria are shown in the Figure. Data were obtained from the German Disease Analyzer (2013-2022), a representative claims database from Germany. Criteria were aligned with the clinical trial, and real-world definitions were created using diagnosis and procedure codes. Results A total of 195,621 patients were included in the present analysis (Table). At baseline, the median age was 71 years (Q1-Q3: 64-79) and 48% of patients were women. Approximately two-thirds of patients had atherosclerosis (48.5% had coronary artery disease, 13.8% had cerebrovascular disease and 13.8% had peripheral artery disease) and 33.7% had high-risk diabetes mellitus (DM), defined as DM with microvascular complications or chronic insulin use. The median baseline LDL-C was 139 (Q1-Q3: 113-166) mg/dL [3.6 (2.9 - 4.3) mmol/L] and 110,867 patients (57%) had an LDL-C ≥130 mg/dL (≥3.4 mmol/L). Overall, 69% of VESALIUS-CV like patients were receiving no background LLT. Conclusions Despite having atherosclerosis and/or high-risk DM and LDL-C exceeding target thresholds, a large proportion of VESALIUS-CV like patients were not on any LLT in Germany. Final results from VESALIUS-REAL will be able to report if this treatment gap is also observed in other countries.

Coronary atherosclerotic burden in master athletes: relationship with cardiovascular risk and volume of exercise

Abstract Background Although prior studies suggesting an association between coronary artery calcification (CAC) and lifelong exercise, the clinical relevance and mechanisms for this interaction remains unknown. Recent evidence suggests that a significant amount of exercise might not be linked to a more favourable composition of coronary plaques. We aimed to analyse the prevalence of high coronary atherosclerotic (CAS) burden assessed by coronary CT scan (CCTA) in master athletes, according to cardiovascular (CV) risk and volume of exercise. Methods A total of 105 master male athletes (48±5.6 years old), asymptomatic and without known CV disease, were prospectively studied. A high CAS burden was defined as the presence of at least one of the following characteristics in CCTA: CAC score &amp;gt;100; CAC score &amp;gt;75th percentile; obstructive plaques; plaques in the left main, three vessels or two vessels including the proximal anterior descending artery; segment Involvement Score (SIS) &amp;gt;5; CT-adapted Leaman score (CT-LeSc) ≥5T. his variable was evaluated according to the CV risk, stratified by SCORE2, and volume of exercise, determined by metabolic equivalent task score (MET/hour/week). Results Most athletes (n=88) were engaged in endurance sports, during 17.1±9.8 years, with a median exercise volume of 66 [IQR 44-103] METs/hour/week. The mean SCORE2 was 2.8±1.5%, with 76.9% of athletes classified as having a low to moderate CV risk, and none having very high-risk. A high CAS burden was present in 25.7% of the athletes, without significant differences according to the SCORE2 risk categories [Low- Moderate Vs. High Risk: 25.5% Vs. 37.5%, respectively ; p=0.142] nor volume of exercise [below Vs. above median: 30.6% Vs. 21.4%, respectively; p=0.283)] (Figure 1 A). Combining these variables, athletes with high CV risk and a high volume of exercise showed significantly higher occurrence of a high CAS burden compared to those with low-moderate risk and high volume of exercise (50% Vs. 15.6%; p=0.017). Among athletes with low-moderate risk, high volume of exercise trended to be protective (15.6% Vs. 31.4%; p=0,092), while there was a similar rate of high CAS burden in athletes with low volume of exercise, independently of risk class (Figure 1B). Conclusions In our cohort of master athletes, one fourth demonstrated a high burden of CAS burden evaluated by CCTA. While a higher volume of exercise combined with high cardiovascular risk showed an association with worse coronary composition it trended to be protective in athletes with lower risk. Integrating clinical and exercise-related data is crucial for evaluating athletes amidst the complex associations between exercise, cardiovascular risk, and CAS burden, necessitating longitudinal studies for comprehensive understanding.Figure 1Figure 2

Masked hypertension is highly prevalent among patients with high-normal office blood pressure - based on the results of the Hungarian ABPM Registry

Abstract Background Current European guidelines recommend initiating antihypertensive treatment for patients with high-normal office blood pressure (HNOBP) if their cardiovascular (CV) risk is very high.1 Ambulatory blood pressure monitoring (ABPM) is a recommended tool to identify whitecoat- (WCH) and masked hypertension (MH), and both conditions can be present in patients with HNOBP. Purpose The purpose of our study was to assess the prevalence of white-coat and masked hypertension in patients with HNOBP, the proportion of very high CV risk, and to identify the predictors of WCH and MH. Methods We collected data from the Hungarian ABPM Registry, which is an ongoing, multicenter, open-label, observational study including 38720 adult patients. ABPMs were performed with validated Meditech ABPM-06 monitors. We analyzed the ABPM curves of 4389 HNOBP patients. In the diagnosis of hypertension, 24 hour-, daytime- and nighttime mean BP values were each considered separately. OBP measurements and ABPMs were performed by GPs, internists and cardiologists. 89 patients were excluded due to missing data. Results ABPM recordings confirmed MH in 67.4%(n=2899) of the cases, while WCH in 15.3%(n=659). In 17.3%(n=742) BP was in HN category both in the office and with ABPM (apparent high-normal blood pressure /appHNBP/). WCH patients (57.11±17.47) were older, than appHNBP (54.54±16.9), and MH patients (53.38±16.70)(p&amp;lt;0.001). WCH (19.4%, n=489) and appHNBP (19.4%, n=488) were more frequent among females, than in males (14.3%, n=254; 9.6%, n=170, respectively, p&amp;lt;0.001). However, MH was more prevalent in males compared to females (76.2%(n=1355) vs 61.2%(n=1544), respectively, p&amp;lt;0.001). Snoring, obesity and diabetes mellitus were more frequent in MH than in appHNBP and WHC patients (Snoring: 30.6%(n=887) vs. 25.7%(n=191) vs. 20.8%(n=137), p&amp;lt;0.001; Obesity: 22.9%(n=663) vs. 16.0%(n=119) vs. 13.4%(n=88), p&amp;lt;0.001;Diabetes mellitus: 12.1%(n=350) vs. 8.9%(n=66) vs. 9.9%(n=65), respectively, p=0.025). Independent predictors of WCH were age (OR=1.01[1.003;1.02]), female sex (OR=1.50[1.19;1.89]) and snoring (OR=0.76[0.59;0.97]). Independent predictors of MH were male sex (OR=1.69[1.43;2.00]), snoring (OR=1.27[1.06;1.53]) and obesity (OR=1.55[1.25;1.92]). 76% of all patients received antihypertensive treatment irrespective of the BP groups (WCH: 76.2%(n=502), appHNBP: 76.3%(n=566), MH: 76.5%(n=2217), p=NS). 11.7%(n=502) of all patients had very high CV risk and only 2.5%(n=25) did not receive antihypertensive treatment. Similar results were found among WCH, appHNBP and MH patients (very high CV risk: 13.8%(n=91) vs. 11.2%(n=83) vs.11.7%(n=328), p=NS; no treatment: 1.9%(n=3) vs. 1.7%(n=3) vs. 2.8%(n=19), p=NS). Conclusions In patients with HNOBP, MH is highly prevalent. MH might be suspected in young, obese, male patients with diabetes mellitus and snoring. WCH was more frequent in older females. Based on our data, the majority of patients with HNOBP and very high CV risk are treated.

Efficacy of sotagliflozin by diabetes duration: a secondary analysis of SCORED

Abstract Background Sotagliflozin is a sodium-glucose cotransporter (SGLT) 1 and SGLT2 inhibitor. SCORED randomized patients with type 2 diabetes (DM) and high cardiovascular (CV) risk to sotagliflozin or placebo. Purpose We evaluated if diabetes duration affects HF and CV outcomes when comparing sotagliflozin with placebo in SCORED, as diabetes duration can modify CV risk. Methods SCORED enrolled patients with DM (hemoglobin A1c ≥7%), chronic kidney disease (glomerular filtration rate of 25-60 mL/minute per 1.73 m2), and CV risk factors. Patients were randomized to sotagliflozin compared with placebo. Patients in SCORED were stratified by diabetes duration, into categories of &amp;lt;10 years, 10-19 years, or ≥20 years. The primary endpoint was total CV death, hospitalization for HF, or urgent visit for HF. Secondary endpoints were total hospitalization for HF or urgent visit for HF, as well as total CV death, nonfatal myocardial infarction, and nonfatal stroke (MACE). Outcomes were assessed using marginal proportional hazard models stratified according to HF criteria and geographic region where non-CV death was a competing terminal event. Subgroup analyses were assessed with natural cubic splines of interaction between treatment and continuous diabetes duration. Results In SCORED, 10,579 (99.9%) of 10,584 patients had complete data on diabetes duration, with 2412 (22.8%), 4424 (41.8%), 3743 (25.9%) having diabetes duration of &amp;lt;10, 10-19, and ≥20 years respectively. Median (Q1, Q3) diabetes duration was 16.4 years (10.4, 22.4 years), while mean hemoglobin A1c was 8.6%, 8.7%, and 8.7% respectively by diabetes duration. The rate of the primary endpoint was lower in the sotagliflozin group (5.6 events per 100 patient-years [p-y]) compared with the placebo group (7.5 events per 100 p-y) (HR: 0.74; 95% CI: 0.63, 0.88). Event rates among diabetes duration subgroups indicated that rates in both the placebo group and relative treatment benefit increased with increasing diabetes duration, with 5.6 vs 5.8 events per 100 p-y, 6.1 vs 7.4 events per 100 p-y, and 4.6 vs 8.5 events per 100 p-y for diabetes duration &amp;lt;10, 10-19, and ≥20 years respectively. Spline analysis indicated increasing treatment benefit with increasing duration when modeled continuously (Figure Panel A; PSpline=0.02). Similar findings were observed for the secondary HF outcome of hospitalization for HF or urgent visit for HF, with increased treatment benefit with duration (Figure Panel B; PSpline=0.10). Total MACE was lower in the sotagliflozin group (4.8 events per 100 patient-years) than in the placebo group (6.3 events per 100 patient-years) (HR: 0.77; 95% CI: 0.65, 0.91), without significant difference in relative treatment benefit by duration (Figure Panel C; PSpline=0.30). Conclusions Sotagliflozin improved HF and MACE outcomes in patients with high CV risk, with increasing treatment benefit for HF outcomes among patients with longer diabetes duration.

Development and validation of a cardiovascular risk prediction model for Sri Lankans using machine learning.

Sri Lankans do not have a specific cardiovascular (CV) risk prediction model and therefore, World Health Organization(WHO) risk charts developed for the Southeast Asia Region are being used. We aimed to develop a CV risk prediction model specific for Sri Lankans using machine learning (ML) of data of a population-based, randomly selected cohort of Sri Lankans followed up for 10 years and to validate it in an external cohort. The cohort consisted of 2596 individuals between 40-65 years of age in 2007, who were followed up for 10 years. Of them, 179 developed hard CV diseases (CVD) by 2017. We developed three CV risk prediction models named model 1, 2 and 3 using ML. We compared predictive performances between models and the WHO risk charts using receiver operating characteristic curves (ROC). The most predictive and practical model for use in primary care, model 3 was named "SLCVD score" which used age, sex, smoking status, systolic blood pressure, history of diabetes, and total cholesterol level in the calculation. We developed an online platform to calculate the SLCVD score. Predictions of SLCVD score were validated in an external hospital-based cohort. Model 1, 2, SLCVD score and the WHO risk charts predicted 173, 162, 169 and 10 of 179 observed events and the area under the ROC (AUC) were 0.98, 0.98, 0.98 and 0.52 respectively. During external validation, the SLCVD score and WHO risk charts predicted 56 and 18 respectively of 119 total events and AUCs were 0.64 and 0.54 respectively. SLCVD score is the first and only CV risk prediction model specific for Sri Lankans. It predicts the 10-year risk of developing a hard CVD in Sri Lankans. SLCVD score was more effective in predicting Sri Lankans at high CV risk than WHO risk charts.

Prevalence, incidence, and treatment of dyslipidemia in patients with high or very high cardiovascular risk in Germany

Background2019 ESC/EAS guidelines on management of dyslipidemia outline treatment goals of LDL-C reduction in patients with high and very high cardiovascular (CV) risk. ObjectiveTo describe the proportion, clinical characteristics, and treatment practices of adult patients with dyslipidemia and high or very high CV risk in Germany. MethodsBased on German claims data from 2010-2019, a retrospective cross-sectional study on prevalence, incidence, and treatment pathways in patients with dyslipidemia and high and very high CV risk is performed. ResultsBetween 2010 and 2019, there were 213 to 233 adult patients per 1,000 with prevalent dyslipidemia based on ICD 10 codes. Annual incidence ranged from 31.7 to 40.2 per 1,000. In 2019, 1.2% and 22.8% of the prevalent patients are classified to high or very high CV risk. Out of these patients, 61.7% and 78.5% received lipid lowering treatments (LLT). Among incidence patients, prescription rates are further apart between high-risk and very-high-risk patients, at 56.6% and 79.2%. Cross-sectional analysis showed that in 2019 statin monotherapy is the most common LLT (87.2%) administered mainly at moderate dose (59.9%). In that year, 2.7% and 8.4% of the patients received ezetimibe as monotherapy or in combination with statins. The proportion of treatment pause, or discontinuation was 56.6% over time, with subsequent re-initiation for 42.0% of patients. ConclusionsAnalysis indicates that despite recommendations, intensive treatment therapies are underutilized in clinical practice even in high and very high CV risk patients with primary hypercholesterolemia/mixed dyslipidemia, who may have benefited from LLT optimization.

Coronary Artery Disease, Family History, and Screening Perspectives: An Up-to-Date Review.

Family history for CAD (coronary artery disease) is an established cardiovascular (CV) risk factor and it is progressively acquiring importance in patients' CV risk stratification. Numerous studies have demonstrated that individuals with a first-degree relative affected by CAD have a significantly higher risk of developing the condition themselves; in particular, when CAD occurs at an early age in relatives. Indeed, recently published CCS (chronic coronary syndrome) ESC (European Society of Cardiology) guidelines include family history (FH) as a risk factor to consider when calculating pre-test risk for CAD. ESC guidelines on preventive cardiology (2021) only suggested CV risk assessment in the presence of a positive FH for CV disease, not considering it in the actual risk scores. Evidence suggests that positive anamnesis for relatives affected by CAD correlates with ACS (acute coronary syndrome) and CAD, with slight differences in relative risk as far as the degree of kinship is concerned. Genetic factors contribute to this correlation by influencing key processes that affect heart health, such as cholesterol metabolism, blood pressure regulation, and inflammatory responses. New technologies in the genetics field are increasing the availability of genome sequencing, and new polymorphism panels are being tested as predictive for CAD, objectifying familiarity. Advances in imaging techniques allow the assessment of coronary atherosclerosis and its composition, and these are acquiring strength in evidence and recommendations in ESC guidelines as a way to define coronary disease in low and low-to-intermediate risk patients and to guide medical therapy and interventional procedures. Use of these emerging tools to guide screening is likely to be extended, beyond high CV risk patients, to individuals with FH for early CAD and/or specific genetic profiles, as recent evidence in the literature is suggesting.

Hemodynamic phenotypes in chronic kidney disease patients based on linear regression of blood pressure parameters.

Classic and non-classic cardiovascular (CV) risk factors accumulate in chronic kidney disease (CKD), contributing to vascular remodeling and hemodynamic abnormalities. This study aimed to determine hemodynamic phenotypes based on linear regression of blood pressure (BP) parameters in stage G3-G4 CKD patients at very high CV risk. 24-h ambulatory BP monitoring (ABPM), carotid-femoral pulse wave velocity (PWV) and central BP were obtained from 52 patients (aged 60±11years, BMI 30±6kg/m2) with stage G3-G4 CKD (eGFR 44±12mL/min./1.73m2). Linear BP regression coefficients were generated to determine hemodynamic phenotypes using ABPM data. Coexisting hypertension was present in 45 (86%) patients, out of whom 33 (73%) had BP controlled. 24-h mean systolic/diastolic BP was 128±18/75±12mm Hg. Twenty-six patients demonstrated the harmonious (H) and 26 patients diastolic dysfunctional (D) hemodynamic phenotypes. eGFR was not significantly different between both phenotypes. Compared to phenotype H, patients with phenotype D were older (57±11 vs. 63±10 years, p=.04), had higher PWV (8.2 [7.3-10.3] vs. 9.7 [8.3-10.9]m/s, p=.02), ambulatory arterial stiffness index (AASI) (0.31±0.1 vs. 0.40±0.1, p=.02), systolic BP (128 [122-130] vs. 137 [130-150] mm Hg, p=.001) and systolic BP variability (BPV) (11.7±2.3 vs. 15.7±3.4mm Hg, p<.0001). Our findings suggest that one in two patients with stage G3-G4 CKD demonstrates an unfavorable D hemodynamic phenotype based on a linear regression model, associated with higher PWV, AASI, systolic BP, and systolic BPV. Further studies are required to assess the clinical utility of hemodynamic phenotypes and whether the D phenotype may predict latent circulatory disorders and outcomes.

Characteristics of Patients With Atherosclerotic Cardiovascular Disease in Belgium and Current Treatment Patterns for the Management of Elevated LDL-C Levels.

Dyslipidemia remains the major cause of atherosclerotic cardiovascular disease (ASCVD). Lipid management in patients with increased cardiovascular (CV) risk needs improvement across Europe, and data gaps are noticeable at the country level. We described the current treatment landscape in Belgium, hypothesizing that lipid management in patients with ASCVD remains inadequate and aiming to understand the reasons. Using data from an anonymized primary care database in Belgium derived from 494 750 individuals, we identified those with any CV risk factor between November 2019 and October 2022 and described the clinical features of patients with ASCVD. The main outcomes were the proportion of patients (i) receiving lipid-lowering therapies (LLTs), (ii) per low-density lipoprotein cholesterol (LDL-C) threshold, stratified per LLT, (iii) reaching the 2021 ESC recommended LDL-C goals, and (iv) LDL-C reduction per type of LLT was also determined. Among 40 888 patients with very high CV risk, 24 859 had established ASCVD. Most patients with ASCVD were either receiving monotherapy (59.6%) or had no documented LLT (25.1%). Further, 64.2% of those with no documented LLT exhibited LDL-C levels ≥ 100 mg/dL. Among common treatment options, one of the greatest improvements in LDL-C levels was achieved with combination therapy of statin and ezetimibe, reducing LDL-C levels by 41.5% (p < 0.0001). Yet, in this group, 24.8% of patients had still LDL-C levels ≥ 100 mg/dL and only 20.7% were at goal. Our study emphasizes the importance of developing strategies to help patients achieve their LDL-C goals, with a focus on supporting the implementation of combination LLT in routine clinical practice.

P132 CARDIOVASCULAR RISK ASSESSMENT IN HYPERTENSIVE PATIENTS WITH TYPE 2 DIABETES: A CROSS-SECTIONAL EPIDEMIOLOGICAL STUDY IN COLOMBIA (SNAPSHOT STUDY)

Background and objective: Cardiovascular (CV) risk is determined by an interplay of risk factors. The goal of the study was to assess CV risk in hypertensive patients with type 2 diabetes in Colombia. Methods: SNAPSHOT, a cross-sectional, observational, multicenter, epidemiological study, involved patients enrolled by 20 investigators (mostly cardiologists [75.0%] and internists [20.0%]) in Colombia. CV risk was assessed by investigators and compared to the calculated CV risk based on ESC 2021 (SCORE2&amp;2-OP) guidelines. Results: The analysis set included 459 patients; mean age (SD) was 68.7 (10.5) years, most patients were female (58.0%), and overweight/obese (73.4%), 21.4% were former smokers and 2.4%, active smokers. A combination of risk factors (male gender, age ≥65years, BMI≥30 kg/m2, smoking) was reported for most patients: 43.8% of patients had 1 of these risk factors, 38.1% had 2 risk factors, 6.1% had 3 risk factors, and 0.2% had all 4 risk factors. Most patients (91.7%) had at least 1 comorbidity in addition to hypertension and type 2 diabetes. Overall, 85.6% of patients had dyslipidemia, 39.7% had chronic kidney disease, and 33.8% had at least one additional CV comorbidity, mainly coronary or other arterial revascularization (18.1%) and acute coronary syndromes (13.5%). 48.4% of patients had diabetes-related target organ damage. CV risk perceived by investigators was low (0.7%), moderate (20.9%), high (35.7%) or very high (42.7%), whereas calculated CV risk according to SCORE2&amp;2-OP was either high (34.6%) or very high (65.4%) (Figure). The prevalence of high and very high CV risk was similar when calculated according to the 2016 (SCORE1) guidelines. Investigators estimated CV risk accurately versus SCORE2&amp;2-OP in only 41.6% of patients, while they underestimated it in 47.9% of patients. Conclusions: Hypertensive patients with diabetes in Colombia are at very high risk of CV disease, but this risk is frequently underestimated by physicians. Enhancing physician education on guideline recommendations and treatment intensification could improve risk factor control.

Associations Between the Superwoman Schema, Stress, and Cardiovascular Health Among African-American Women.

African-American (AA) women are less likely to achieve ideal cardiovascular (CV) health compared with women of other racial/ethnic subgroups, primarily due to structural and psychosocial barriers. A potential psychosocial construct relevant to ideal CV health is the superwoman schema (SWS). We explored whether the SWS was associated with perceived stress, CV risk factors, and overall CV health among AA women. This cross-sectional analysis of the FAITH! Heart Health+ Study was conducted among AA women with high cardiometabolic risk. Pearson correlation evaluated associations between SWS and CV risk factors (e.g., stress, hypertension, diabetes, etc.). The 35-item SWS questionnaire includes five domains. Stress was measured by the 8-item Global Perceived Stress Scale (GPSS). CV health was assessed using the American Heart Association Life's Simple 7 (LS7) rubric of health behaviors/biometrics. Data acquisition spanned from February to August 2022. The 38 women included in the analysis (mean age 54.3 [SD 11.5] years) had a high CV risk factor burden (71.1% hypertension, 76.3% overweight/obesity, 28.9% diabetes, 39.5% hyperlipidemia). Mean GPSS level was 7.7 (SD 5.2), CV health score 6.7 (SD 1.8), and SWS score 60.3 (SD 18.0). Feeling an "obligation to help others" and "obligation to present an image of strength" had strongest correlations with GPSS score among all SWS domains (r = 0.51; p = .002 and r = 0.39; p = .02, respectively). Correlation among the SWS domains and traditional CV risk factors was not statistically significant. Our findings suggest that an obligation to help others and to project an image of strength could be contributing to stress among AA women.

Rationale for Increasing Doses of Statins in Everyday Clinical Practice

HMG-CoA reductase inhibitors (statins) were discovered in the early 1970s in Japan and were originally used to treat patients with hereditary hyperlipidemia. In the late 1990s and early 2000s, clinical trials using statins for primary and secondary prevention showed the possibility of reducing cardiovascular (CV) and, in some cases, all-cause mortality. Intensive statin therapy (atorvastatin 80 mg/day and rosuvastatin 40 mg/day) compared to initial doses provides an additional 16% reduction in CV complications. Regression studies with the original rosuvastatin using intracoronary ultrasound and other modern methods have shown the possibility of stabilization and regression of atherosclerosis in the carotid and coronary arteries. High-dose statin therapy is generally well tolerated; the incidence of clinically significant adverse liver reactions does not exceed 2-3 per 100,000 people, and the incidence of myopathies with increased creatine kinase over 10 upper limits of normal is not higher than 1 per 10,000 people per year. Long-term statin treatment does not increase the risk of dementia and, in some studies, reduced the risk of Alzheimer's disease. Achieving target levels of low-density lipoprotein cholesterol (LDL-C) in routine practice does not exceed 5-11%; one of the main reasons for that is the rare (2-3%) prescription of high doses of statins. Increasing statin doses in routine clinical practice will optimize the treatment of patients with high CV risk and will contribute to further reduction of mortality in our country.

Artificial intelligence-based classification of cardiac autonomic neuropathy from retinal fundus images in patients with diabetes: The Silesia Diabetes Heart Study

BackgroundCardiac autonomic neuropathy (CAN) in diabetes mellitus (DM) is independently associated with cardiovascular (CV) events and CV death. Diagnosis of this complication of DM is time-consuming and not routinely performed in the clinical practice, in contrast to fundus retinal imaging which is accessible and routinely performed. Whether artificial intelligence (AI) utilizing retinal images collected through diabetic eye screening can provide an efficient diagnostic method for CAN is unknown.MethodsThis was a single center, observational study in a cohort of patients with DM as a part of the Cardiovascular Disease in Patients with Diabetes: The Silesia Diabetes-Heart Project (NCT05626413). To diagnose CAN, we used standard CV autonomic reflex tests. In this analysis we implemented AI-based deep learning techniques with non-mydriatic 5-field color fundus imaging to identify patients with CAN. Two experiments have been developed utilizing Multiple Instance Learning and primarily ResNet 18 as the backbone network. Models underwent training and validation prior to testing on an unseen image set.ResultsIn an analysis of 2275 retinal images from 229 patients, the ResNet 18 backbone model demonstrated robust diagnostic capabilities in the binary classification of CAN, correctly identifying 93% of CAN cases and 89% of non-CAN cases within the test set. The model achieved an area under the receiver operating characteristic curve (AUCROC) of 0.87 (95% CI 0.74–0.97). For distinguishing between definite or severe stages of CAN (dsCAN), the ResNet 18 model accurately classified 78% of dsCAN cases and 93% of cases without dsCAN, with an AUCROC of 0.94 (95% CI 0.86–1.00). An alternate backbone model, ResWide 50, showed enhanced sensitivity at 89% for dsCAN, but with a marginally lower AUCROC of 0.91 (95% CI 0.73–1.00).ConclusionsAI-based algorithms utilising retinal images can differentiate with high accuracy patients with CAN. AI analysis of fundus images to detect CAN may be implemented in routine clinical practice to identify patients at the highest CV risk.Trial registrationThis is a part of the Silesia Diabetes-Heart Project (Clinical-Trials.gov Identifier: NCT05626413).Graphical

Management of Hypertension in Patients with Type 2 Diabetes Mellitus: Indian Guideline 2024 by Association of Physicians of India and Indian College of Physicians.

In India and the Southeast Asian population, hypertension and type 2 diabetes mellitus (T2DM) are the leading lifestyle-related diseases, responsible for a majority burden of morbidity and mortality. Multiple population-spanning studies have revealed the staggering prevalence of both diseases in India, and the prevalence of both will only increase further due to factors such as an aging population, rapid urbanization, increased obesity, and sedentary lifestyles. More than 50 percent of hypertensive patients in India are also diagnosed with T2DM, and a detailed management protocol for the same is required, especially when a major portion of the disease is managed at the primary care level. The Association of Physicians of India (API) guidelines for the management of hypertension in patients with T2DM have been formulated based on consultation with leading physicians, cardiologists, diabetologists, and endocrinologists of India and Southeast Asia, keeping in mind the challenges faced by the patients in these countries and the appropriate management protocols that will be beneficial. While standard office-based blood pressure (BP) measurement forms the cornerstone of hypertension diagnosis and demands a uniform methodology to be followed, home blood pressure monitoring (HBPM) is recommended for long-term follow-up with validated devices. Ambulatory blood pressure monitoring (ABPM) offers comprehensive insights crucial for cardiovascular (CV) risk stratification. The complications of diabetic hypertension can span from increased CV risk, heart failure (HF), and renal dysfunction, and nonpharmacological and pharmacological management should be aimed toward not only control of the BP values but also protecting the end organs. While nonpharmacological measures include a focus on nutrition and diet, they also focus on approaches to weight loss, including a novel section covering the benefits of yoga. The guideline also focuses on a novel section of factors influencing CV risk, especially in the Indian population. For the pharmacological management, the guidelines address each of the categories of antihypertensive drugs, emphasizing the significance of combination therapies in the management of diabetic hypertension. In line with leading global guidelines for the management of hypertension in T2DM, for diabetic patients who often struggle with BP management and carry a high CV risk, the recommended dual combination antihypertensive therapy is particularly crucial and should be considered as first-line management therapy. While angiotensin-converting enzyme inhibitors (ACEi) or angiotensin receptor blockers (ARBs) play a highly beneficial role in the management of diabetic hypertension, a combination of ACEi or ARB with dihydropyridine calcium channel blockers (DHP-CCBs) is recommended to reduce the risk of complications and enhance patient adherence. To achieve the target of effective BP control and end-organ protection, it is beneficial and recommended to include newer CCBs (e.g., cilnidipine) in the management protocol in combination with ACEi/ARBs. Combination therapy including ARBs and DHP-CCBs should be preferred over β-blockers and thiazides. Among the CCBs, cilnidipine, a novel molecule, is a more effective and safer option for diabetic hypertensive patients in India. β-blockers should be used if there is a history of myocardial infarction (MI), HF, coronary artery disease (CAD), or stable angina along with the initial hypertensive regimen. The guideline also focuses on the novel reno- and cardioprotective molecules such as finerenone and sodium-glucose cotransporter 2 inhibitors (SGLT2i) and their benefits in the management of diabetic hypertension.