Increased CV Risk Research Articles

Human Gut Microbiota in Cardiovascular Disease.

The gut ecosystem, termed microbiota, is composed of bacteria, archaea, viruses, protozoa, and fungi and is estimated to outnumber human cells. Microbiota can affect the host by multiple mechanisms, including the synthesis of metabolites and toxins, modulating inflammation and interaction with other organisms. Advances in understanding commensal organisms' effect on human conditions have also elucidated the importance of this community for cardiovascular disease (CVD). This effect is driven by both direct CV effects and conditions known to increase CV risk, such as obesity, diabetes mellitus (DM), hypertension, and renal and liver diseases. Cardioactive metabolites, such as trimethylamine N -oxide (TMAO), short-chain fatty acids (SCFA), lipopolysaccharides, bile acids, and uremic toxins, can affect atherosclerosis, platelet activation, and inflammation, resulting in increased CV incidence. Interestingly, this interaction is bidirectional with microbiota affected by multiple host conditions including diet, bile acid secretion, and multiple diseases affecting the gut barrier. This interdependence makes manipulating microbiota an attractive option to reduce CV risk. Indeed, evolving data suggest that the benefits observed from low red meat and Mediterranean diet consumption can be explained, at least partially, by the changes that these diets may have on the gut microbiota. In this article, we depict the current epidemiological and mechanistic understanding of the role of microbiota and CVD. Finally, we discuss the potential therapeutic approaches aimed at manipulating gut microbiota to improve CV outcomes. © 2024 American Physiological Society. Compr Physiol 14:5449-5490, 2024.

ECG screening and prevention of sudden cardiac death in endurance athletes over 40

Abstract Introduction CV diseases increase with age. There are many athletes aged >40 years who practise in certain endurance sports (marathon, ultramarathon and cycling), that involve very high intensity physical exertion and prolonged efforts. This population, like others athletes, undergo to annual examination with a medical history, spirometry, urine test and exercise test. CVdisease and sudden cardiac death (SCD) are the main cause of mortality in athletes during sport and this specific population group are at increased CV risk due to their multiple comorbidities, so this kind of screening remains controversial. Aims The primary aim of the study is to evaluate whether a 5-minute 'mini Holter ECG', associated with the conventional examination, can have an additional role for early screening and prevention of CV diseases in older endurance sport population. Materials The population were selected as part of the larger 'Heart And Run' project, an ECG collection of endurance athletes of the main sports clubs in Rome - Italy. A control group of healty individiuals was collected for comparison. The ECG traces were recorded at rest for 5 minutes with the Kardia Mobile device 6L™. HRV indices were analysed using the software Kubios. The study group were compared for an ECG morphological analysis and HRV parameters in the time and frequency domain. Results A total of 353 subjects (182 athletes, 171 controls) were analysed. The athlets show a significantly higher incidence of sinus arrhythmias, LAFB, 1°degree AVB, Jpoint elevation and STsegment abnormalities. We found also a significantly shorter QTc in athlets compared to controls (395.95 ± 29.51 ms vs. 411.6 ± 29.01 ms), suggestive of greater protection from malignant ventricular arrhythmias. In line with the ECG findings, the HRV PNS (-0.25 ± 1.25 vs -1.05 ± 1.45) and SNS (0.69 ± 1.44 vs 2.38 ± 1.89) indices were respectively higher and lower in the athletes group than in the controls group. Differences between the two groups were also found in the time and frequency HRV domain analysis (SDNN, RMSSD, NN50 and pNN50). Due to the absence of normality range, we considered values lower of the 5th or higher of the 95th percentile range, for the main HRV parameters, as abnormals. We identified 29/182 virtually abnormal HRV individuals. Those patients could be at increased CV risk, worthy of further investigation. In total, out-of-range HRV values or morphological abnormalities were detected in 54 athletes (29%), a population that will need further attention through follow-up and additional examinations. Conclusions Despite competitive endurance sports are associated with increased vagal tone, which is virtually protective against CV diseases, even in athletes over 40, the addition of the 5-minute cardiac 'mini Holter' could increase the sensitivity in detection of CV disease, in a specific high-risk group of athletes, suggesting additional clinical and instrumental investigations in such patients.

Cross Sex Steroid Therapy and Baseline Cardiac Function in a Rodent Model of Gender Affrming Hormone Therapy in the Male Rat

Transgender females (TGF) are individuals who are born biologically male, but identify as female. Gender-Affrming Hormone Therapy (GAHT), consisting of 17β-Estradiol (E2) supplementation with androgen suppression [i.e. castration (CTX)], is used in TGFs to match their physical characteristics with their perceived gender. Previously, we reported that E2+CTX in the normotensive male Sprague-Dawley (SD) rat is associated with a significant increase in E2 and decrease in testosterone, body weight, and lean mass. Whether GAHT enhances cardiac morbidity and mortality in the transgender population on GAHT relative to cisgender individuals is still unclear. Moreover, the sustained effect of high E2 coupled to androgen suppression in male rats on their cardiac morphology and function is unknown. Thus, this study tested the hypothesis that GAHT in the adult male SD rat is associated with impaired cardiac function under baseline conditions. Methods: Adult male SDs (13 weeks of age) were randomly assigned to either: Control or E2+CTX therapy (E2 at 5 mg/day, pellet sc, replaced every 3 weeks, with CTX performed at 15 weeks of age) (n=8/grp). Baseline cardiac function was measured via echocardiogram (VEVO 3100), body composition via EchoMRI. Results: at 28 weeks of age, total lean mass and body weight were significantly decreased in the E2+CTX group, as previously observed; total fat mass did not differ between groups. Heart rate was significantly decreased; yet, other indices of cardiac function were not altered at baseline. Although no major differences in baseline cardiac function were observed, the long-term impact of GAHT on CV health and the ability of the heart to respond to secondary challenges are unknown. This study is ongoing and further studies will determine the ability of the heart to recover from secondary insults in order to determine if GAHT in males is associated with increased CV risk. [Formula: see text] Funding sources: HL143459, P20-GM-104357, P20-GM121334, T32-HL105324. 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.

Association of gestational diabetes with long-term risk of premature mortality, and cardiovascular outcomes and risk factors: A retrospective cohort analysis in the UK Biobank.

To investigate the association of gestational diabetes mellitus (GDM) with premature mortality and cardiovascular (CVD) outcomes and risk factors. Parous women recruited to the UK Biobank cohort during 2006-2010 were followed up from their first delivery until 31 October 2021. The data were linked to Hospital Episode Statistics and mortality registries. Multivariate Cox proportional hazard models investigated associations of GDM with all-cause mortality, CVD, diabetes, hypertension and dyslipidaemia. The maximum total analysis time at risk and under observation was 9 694 090 person-years. Among 220 726 women, 1225 self-reported or had a recorded diagnosis of GDM. After adjusting for confounders and behavioural factors, GDM was associated with increased risk for premature mortality [hazard ratio (HR): 1.44, 95% confidence interval (CI): 1.12-1.86], particularly CVD-related death (HR: 2.38, 95% CI: 1.63-3.48), as well as incident total CVD (HR: 1.50, 95% CI: 1.30-1.74), non-fatal CVD (HR: 1.41, 95% CI: 1.20-1.65), diabetes (HR: 14.37, 95% CI: 13.51-15.27), hypertension (HR: 1.49, 95% CI: 1.38-1.60), and dyslipidaemia (HR: 1.30, 95% CI: 1.22-1.39). The total CVD risk was greater in women with GDM who did not later develop diabetes than in those with GDM and diabetes. Women with GDM are at increased risk of premature death and have increased CV risk, emphasizing the importance of interventions to prevent GDM. If GDM develops, the diagnosis represents an opportunity for future surveillance and intervention to reduce CVD risk factors, prevent CVD and improve long-term health.

Cardiovascular Diseases Risk Reduction And Lifestyle Modification:Cross Sectional Ansalysis Of Patient Responses.

A decrease in cardiovascular event risk with a decrease in total and LDL – cholesterol level is termed as “cholesterol paradox” or “risk factor reversal”. Cardiovascular risk does not have a linear relationship between LDL – cholesterol levels, and other substantial risk factors of cardiovascular events are being disregarded.The aim of this study is, to identify modifiable risk factors of cardiovascular events other than those well proved to cause dyslipidemia. A cross-sectional study was conducted with 652 participants in a tertiary care hospital. Patients were grouped into two, based on the history of cardiovascular events. Demographics and patient responses captured using pre-validated questionnaires were analyzed. 5mL blood samples were collected by venipuncture and lipid profile was estimated. Association between cardiovascular events and explanatory variables. was determined using Chi square test and Odds ratio at 95% confidence intervals. Higher risk of CV events was found among smokers 0.232 [0.144 – 0.373]. Consumption of white sugar, refined oil, processed cold beverages and fast food products increased CV risk respectively. Moreover, total cholesterol, LDL-C and triglycerides were found to decrease after one year of counselling the patients. The classical hypothesis of dyslipidemia induced atherosclerosis may not be the predominant cause of CV events. Herein, we report no association between high fat diet and CV risk while we observed higher risk in consumers of refined and ultra processed food products. However, significant control of cholesterol was observed in patients who shifted to Unrefined food products.

Circulating isomiRs May Be Superior Biomarkers Compared to Their Corresponding miRNAs: A Pilot Biomarker Study of Using isomiR-Ome to Detect Coronary Calcium-Based Cardiovascular Risk in Patients with NAFLD.

Circulating miRNAs are increasingly being considered as biomarkers in various medical contexts, but the value of analyzing isomiRs (isoforms of canonical miRNA sequences) has not frequently been assessed. Here we hypothesize that an in-depth analysis of the full circulating miRNA landscape could identify specific isomiRs that are stronger biomarkers, compared to their corresponding miRNA, for identifying increased CV risk in patients with non-alcoholic fatty liver disease (NAFLD)-a clinical unmet need. Plasma miRNAs were sequenced with next-generation sequencing (NGS). Liver fat content was measured with magnetic-resonance spectrometry (MRS); CV risk was determined, beyond using traditional biomarkers, by a CT-based measurement of coronary artery calcium (CAC) score and the calculation of a CAC score-based CV-risk percentile (CAC-CV%). This pilot study included n = 13 patients, age > 45 years, with an MRS-measured liver fat content of ≥5% (wt/wt), and free of overt CVD. NGS identified 1103 miRNAs and 404,022 different isomiRs, of which 280 (25%) and 1418 (0.35%), respectively, passed an abundance threshold. Eighteen (sixteen/two) circulating miRNAs correlated positively/negatively, respectively, with CAC-CV%, nine of which also significantly discriminated between high/low CV risk through ROC-AUC analysis. IsomiR-ome analyses uncovered 67 isomiRs highly correlated (R ≥ 0.55) with CAC-CV%. Specific isomiRs of miRNAs 101-3p, 144-3p, 421, and 484 exhibited stronger associations with CAC-CV% compared to their corresponding miRNA. Additionally, while miRNAs 140-3p, 223-3p, 30e-5p, and 342-3p did not correlate with CAC-CV%, specific isomiRs with altered seed sequences exhibited a strong correlation with coronary atherosclerosis burden. Their predicted isomiRs-specific targets were uniquely enriched (compared to their canonical miRNA sequence) in CV Disease (CVD)-related pathways. Two of the isomiRs exhibited discriminative ROC-AUC, and another two showed a correlation with reverse cholesterol transport from cholesterol-loaded macrophages to ApoB-depleted plasma. In summary, we propose a pipeline for exploring circulating isomiR-ome as an approach to uncover novel and strong CVD biomarkers.

Dyslipidaemia and its management in patients with type 2 diabetes across the Middle East and Africa: the PACT-MEA study

Abstract Background There is a scarcity of high-quality epidemiological data on the clinical burden of type 2 diabetes (T2D) and cardiovascular risk (CV) in the Middle East and Africa due to under-representation of these regions in contemporary diabetes and cardiovascular trials. Multiple risk factors, including dyslipidaemia, increase CV risk in patients with T2D and established atherosclerotic cardiovascular disease (eASCVD) and those at risk for ASCVD. According to the European Society of Cardiology (ESC) 2021 Guidelines, target low-density lipoprotein cholesterol (LDL-C) for patients with T2D is <1.8 mmol/L (<1.4 mmol/L in patients with eASCVD or at very high risk). Purpose To establish the status of dyslipidaemia and its management in patients with T2D and eASCVD or high/very high ASCVD risk across the Middle East and Africa. Methods Adult patients with T2D participating in a cross-sectional, observational study in seven Middle East and African countries were included in the analysis. Laboratory and medication data were collected from medical charts of patients attending a routine health visit in 2022. Descriptive statistics were used to characterize the lipid profile and management of patients with T2D by age, diabetes duration, body mass index, HbA1c, microvascular complications, estimated glomerular filtration rate (eGFR), and urinary albumin to creatinine ratio (UACR). Results There were 3726 patients in the overall study sample (mean age, 58 ± 12; male, 53%), almost all of whom were at high (69%)/very high (30%, includes eASCVD) risk according to ESC 2021 guidelines. In patients for whom data was available in the medical record, median LDL-C (n=2525) was 2.2 mmol/L (IQR, 1.7 to 3.0), HDL-C (n=2453) was 1.1 mmol/L (IQR, 0.9 to 1.3), and triglycerides (n=2488) were 1.6 mmol/L (IQR, 1.2 to 2.3). Of the patients with high/very high ASCVD risk (n=2313), 30% met the ESC guideline-recommended target for LDL-C of <1.8 mmol/L and 16% met the target of <1.4mmol/L. Most patients were on statin therapy (77%, range across countries: 60%-87%, Table 1), with use increasing with age and duration of diabetes. More patients with T2D for ≥10 years were on high intensity statin therapy than those with T2D <10 years (37% vs 33%). A similar pattern was observed for patients with HbA1c levels ≥7% (37% vs 31%, Table 2). Most patients with nephropathy were on statins (87%); use increased with lower eGFR and higher UACR levels. Very few patients were on Ezetimibe (6.4%), fibrates (4.8%), fish oil (including icosapent ethyl) (1.4%), or proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors (0.5%). Conclusions Utilization of moderate intensity statin therapy (less than 50% LDL reduction) despite high and very high CV risk leads to failure to achieve cardioprotective LDL targets in most patients. Given the high burden of ASCVD in patients with T2D, prioritization of high intensity lipid lowering therapy is recommended.Table 1Table 2

Kidney subclinical lesions in hypertension phenotypes defined by Home Blood Pressure Monitoring among young adults enrolled in a Family Health Strategy unit

Abstract Introduction The association between kidney lesion, hypertension (HTN) and cardiovascular risk (CV) is well established. Asymptomatic patients with decreased glomerular filtration rate (GFR) and/or increased albuminuria seem to have increased CV risk. The refinement of HTN diagnosis using Home Blood Pressure Monitoring (HBPM) allows to identify individuals with different phenotypes: normotension, sustained HTN (SHT), masked HTN (MHT) and white-coat HTN (WHT), increasing diagnostic accuracy. Objective To assess kidney subclinical lesions among different hypertension (HTN) phenotypes identified by Home Blood Pressure Monitoring (HBPM) in an adult population enrolled in a Family Health Strategy unit. Design and Methods: Cross-sectional, populational study with adults between 20-50 years old enrolled in a Family Health Strategy unit in a metropolis. Sociodemographic, anthropometric and CV risk factors were registered. Office blood pressure (BP) was the average of two consecutive measurements, and HBPM followed a 7-day protocol. HBPM < 135x85 mmHg and office BP < 140x90mmHg were considered normal, identifying four phenotypes: normotension (controlled office BP and HBPM); white-coat hypertension (uncontrolled office BP and controlled HBPM); masked hypertension (controlled office BP and uncontrolled HBPM) and sustained hypertension (uncontrolled office BP and HBPM). Albuminuria was dosed in an isolated urine sample whereas glomerular filtration rate was calculated by CKD Epi formula using serum creatinine. Results A total of 483 individuals were evaluated (39% male; mean age: 37.6 ± 8.8 years). More often, individuals with white-coat hypertension (9.3%) are male, with greater neck circumference and higher prevalence of metabolic syndrome. Individuals with masked hypertension (10%) are more obese, with increased neck and waist circumferences whereas those who present sustained hypertension are predominantly male, more obese, with increased neck and waist circumferences and higher prevalence of diabetes and metabolic syndrome. Analyzing four phenotypes, a progressive albuminuria increase was observed among normotensive patients: white-coat hypertension 4.0 ± 2.2; masked hypertension 5.3 ± 3.4 and sustained hypertension 7.1 ± 1.4 mg/g creatinine. We also observed an increased serum creatinine and decreased GFR: white-coat hypertension 0.74 ± 0.16/132 ± 34; masked hypertension 0.79 ± 0.17/123 ± 28; sustained hypertension 0.81 ± 0.32/120 ± 59, respectively, although without statistical significance. Conclusion The performance of HBPM refined HTN diagnosis and was able to early identify a progressive worsening of kidney function parameters in the different phenotypes.

Abstract 13915: Comparison of Proteomic CV Risk to Established ASCVD 10-year Risk Decision Points

Introduction: The ASCVD pooled cohort equation (PCE) is well-established for CV risk assessment. Decision points for determining treatment plans are low, intermediate and high risk over 10 years, however this approach over and underestimates risk in certain subgroups. The validated CV Risk SomaSignal® Test (SST) provides 4-year risk probability of MACE allowing for timely assessment of risk, but the shorter timescale makes comparison to 10-year PCE risk less intuitive. Hypothesis: Using a previously described metacohort (n=5,575) of patients with increased CV risk, we hypothesized that PCE would stratify patients differently than the CV Risk SST, and that CV Risk score scaled to 10 years would yield an improved net reclassification index (NRI). Methods: CV Risk SST and PCE scores were calculated on metacohort plasma samples. CV risk score was scaled to 10 years by parameterizing the model for a 10-year score, and then calculating a quadratic equation for the conversion. CV risk score was stratified by four established risk bins, whereas the PCE was stratified similarly using <7.5%, 7.5%-15%, 15%-20%, and > 20% risks based on literature and practice-derived cutoffs. Event rates were compared between scores, and NRI was calculated. Results: We observed total NRI of 11.4% for the 10-year CV Risk SST vs. PCE, with up-classification (positive NRI=83.7%) mitigating down-classification (negative NRI=-0.723). Event rates for the high-risk group in the CV Risk test were higher than the PCE, and lower in the low-risk group (p < 0.05). Conclusions: The CV Risk SST stratifies patients by identifying low- and high-risk groups using thresholds that are more discriminatory than low-risk and high-risk thresholds in the PCE. For comparison, the CV risk SST can be scaled to 10-year risk, with CV risk SST having a positive NRI for identifying MACE. This reclassification can allow targeted therapies in patients at greater risk and use of non-pharmacological therapies in the low-risk patients.

Abstract 12593: Associations of Serum Uric Acid and Cardiovascular Events in a Clinical Trial of IL-1β Blockade

Background: Serum uric acid (SUA) associates with CV events, mortality, and gout. We assessed whether SUA predicts CV risk in a trial of IL-1β inhibition with canakinumab, a therapy known to reduce both CV events and gout. Aims: To validate associations between SUA and CV risk in a large cohort with chronic CAD and determine whether these associations were altered by IL-1β blockade or baseline renal function. Methods: The Canakinumab Antiinflammatory Thrombosis Outcome Study (CANTOS) randomized 10,061 patients with prior MI and hsCRP ≥ 2 mg/L to canakinumab 50 mg, 150 mg, 300 mg, or placebo subcutaneously every four weeks. SUA levels were obtained at baseline. Cox proportional hazards models compared the outcomes of major adverse cardiovascular events (MACE), CV death (CVD), and all-cause mortality (ACM) among those with baseline SUA ≤ 6.8 mg/dL, 6.8- 9.0 mg/dL, and ≥ 9.0 mg/dL (format: HR (95% CI); p). This analysis was repeated separately within canakinumab, placebo, eGFR ≥ 60 mL/min, and eGFR < 60 mL/min sub-groups. Results: High SUA associated with MACE (1.66 (1.38-1.99); p<0.0001), CVD (2.52 (1.98-3.21); p<0.0001), and ACM (2.43 (2.01-2.94); p<0.0001) compared to low SUA. These associations were minimally attenuated after adjustment for age, sex, BMI, smoking, hypertension, diabetes, LDL-C, and hsCRP. After further adjusting for eGFR and diuretic use, high SUA independently predicted CVD and ACM. In the IL-1β blockade arm, high SUA associated with MACE (1.82 (1.46-2.26); p<0.0001), CVD (2.80 (2.10-3.73); p<0.0001), and ACM (2.72 (2.17-3.40); p<0.0001). In participants with normal eGFR, high SUA associated with CVD and ACM, but not MACE. Conclusions: These data from a large cohort of patients with chronic CAD confirm that individuals with elevated SUA have increased CV risk despite aggressive medical therapies. IL-1β blockade did not modify these associations. Future trials may consider inclusion of patients with high SUA and CKD as a method to increase absolute risk.

Abstract 15758: Platelet Aggregation is Elevated in Psoriasis and Associated With Cardiovascular Risk

Introduction: Psoriasis is associated with increased CV risk the mechanisms and prevention of which are not fully known. We evaluated the platelet phenotype (implicated in atherothrombosis) and in vitro response to aspirin in patients with psoriasis and its association with vascular stiffness and coronary atherosclerosis. Methods: Patients with psoriasis (n = 64, age 47.9 ± 15 years, 65% male), percent body surface area (BSA) of psoriasis 3%, were compared to controls (n = 40, age 40.8 ± 16 years, 45% male). Percent platelet aggregation in response to agonists adenosine diphosphate (ADP), collagen (Col), and arachidonic acid (AA - with and without aspirin) was measured in freshly isolated platelet-rich plasma via light transmission aggregometry (LTA). Vascular stiffness (via pulse wave velocity [PWV]) and CT coronary angiography were each performed as readouts of CV risk. Results: Compared to controls, psoriasis patients were older, of Caucasian ethnicity (Figure 1A), and overweight, but otherwise similar. Platelet aggregation after treatment with Col (p=0.01), ADP (p < 0.01), and AA (p = 0.05) were all higher in psoriasis vs. control (Figure 1B-D). Platelet aggregation after activation with high dose AA was similar between groups (Figure 1E) however co-incubation with high dose AA plus aspirin displayed incomplete platelet inhibition of psoriasis platelets vs. controls (Figure 1F). Platelet aggregation to low dose AA and high dose AA plus aspirin co-incubation were each higher in those with enhanced vascular stiffness (figure 1G/1H) and the presence of coronary plaque (Figure 1I/1J). Conclusion: Platelet aggregation is consistently elevated in psoriasis across a variety of agonists, incompletely inhibited by aspirin, and associated with biomarkers of CV risk such as vascular stiffness and the presence of coronary plaque. These findings highlight the need to evaluate various anti-platelet strategies to reduce atherothrombotic risk in patients with psoriasis.

FRI099 Advanced Lipoprotein Analysis In Patients With Cushing’s Syndrome

Abstract Disclosure: R.T. Varghese: None. R. McGlotten: None. M. Sampson: None. A. Prakash: None. R. Shamburek: None. A.T. Remaley: None. R. Muniyappa: None. L.K. Nieman: None. Introduction: Cushing syndrome (CS) patients have a higher mortality rate due to increased cardiovascular disease (CVD). Analysis of lipoprotein particles with nuclear magnetic resonance (NMR) spectroscopy provides additional insights into CVD risk beyond the standard lipid panel. The goal of the study was to better characterize the lipid abnormalities in patients with CS by using high-resolution separation of lipoprotein particles. Methods: We measured plasma lipids (Cholesterol, TC; calculated low density lipoprotein, LDL; triglycerides, TG; high density lipoprotein, HDL) by the traditional enzymatic assay and lipoprotein particles by NMR spectroscopy. Measures of inflammation and insulin resistance were also derived from NMR spectra. Values are shown as mean ± SEM or median [IQR]. Results: After initial evaluation, 42 subjects (mean age 47.4 ± 2.5 years; 28 females; weight 85.0 ± 3.1 kg) had Cushing's disease (n=23), ectopic ACTH secretion (n=17), or adrenal adenoma (n=2). Ten patients were on chronic statin therapy, and 14 subjects had type 2 diabetes mellitus (T2DM). The control group comprised 45 subjects without T2DM [mean age 45.4 ± 2.1 years and weight (83.5 ± 2.7) kg]. None in the control group were on statin therapy. Compared to controls, CS patients had significantly higher systolic (135 ±2 vs. 119 ±2 mm Hg, p<0.001) and diastolic blood pressure (79 ±2 vs. 71 ±1 mm Hg, p<0.001), HbA1c (6.1 [5.4-7.5] vs. 5.4 [5.0-5.7], p<0.001), plasma glucose (103 [90-137] vs 94 [89-100] mg/dL, p=0.003), and insulin (17[12-26] vs 11[7-15] uU/mL, p=0.01) levels. Compared to controls, patients with CS had significantly higher triglyceride concentration (116 [84 -146] vs 87 [62-120] mg/dL, p=0.02) and lower LDL concentration (90 [69 -113] vs 108 [90 -125] mg/dL, p=0.04). However, total cholesterol and HDL cholesterol concentrations were not different. LDL particle size in CS was smaller (20.5[20.0-21.0] vs 21.0 [20.7-21.2] nm, p=0.01) and VLDL particle size was larger (49.8 ± 0.9 vs 45.7 ± 1.0 nm, p=0.002) than in controls. No difference was noted between groups in HDL particle number or size or in LDL and VLDL particle number. In the group with CS, a marker of inflammation, GlycA (Glycan N-acetylglucosamine) (494.5 ± 18.2 vs. 382.5 ± 9.0 µmol/L, p<0.001) and Lipoprotein Insulin Resistance score (LPIR) (46.4 ± 3.1 vs. 36.2 ± 3.1, p=0.02) were significantly higher. There were no group differences in branch-chained amino acids (BCCA) levels. These differences remained even when patients with type 2 diabetes and those on statin therapy were excluded. Conclusions: These data suggest that the higher inflammatory and insulin resistance state, dysglycemia, hypertension, and altered lipoprotein profiles may contribute to the increased CV risk in patients with Cushing’s syndrome. Early detection and treatment for these abnormalities may attenuate CV risk. Presentation: Friday, June 16, 2023

Unmasking Heterogeneity of Sleep Apnea.

Sleep apnea is heterogeneous in multiple dimensions. There are different physiological risk factors that may have clinical relevance. However, assessing them is challenging. An approach to ascertain them using a simple model of ventilatory control has been proposed. It is based, however, on untenable assumptions. There are limited validation data and reproducibility is not stellar. There are also different symptom subtypes. They have been found in multiple population-based and clinical cohorts worldwide. Symptomatic benefit from therapy is most marked in the excessively sleepy subtype. This group may also be the group at increased CV risk from obstructive sleep apnea.

The impact of EMA recommendations on the real-life use of Janus kinases inhibitors for rheumatoid arthritis: the Expanded Risk Score in RA as a tool to quantify the risk of cardiovascular events.

To evaluate in patients with rheumatoid arthritis (RA) the impact of EMA recommendations on the real-life prescription of JAK inhibitors (JAKis) and the use of the Expanded Risk Score in RA (ERS-RA) to quantify the risk of major adverse cardiac events (MACE). We conducted a retrospective analysis of real-life RA patients treated with JAKis. Patients were classified as ineligible for JAKis if they fulfilled EMA criteria (>65 years-old, history of malignancy, or increased risk of venous thromboembolic events [VTE] or MACE including smoking). Risk of MACE was defined according to ORAL Surveillance trial inclusion criteria (ORALSURV) or by using the ERS-RA. Of 194 patients enrolled, 57.9% were classified as ineligible according to EMA definition (ORALSURV criteria). The most frequent reason for ineligibility was increased MACE risk (70.2%), followed by age>65 (34.2%), smoking (30.7%), and increased risk of VTE (20.2%) or malignancy (7%). The use of the ERS-RA reduced the rate of patients carrying an increased CV risk to 18.6% (p<0.001 versus ORALSURV), leading to 46.4% overall ineligible patients. Over a drug-exposure of 337 patient/years, we observed 2 VTE, one MACE (non-fatal stroke), and one solid malignancy (all in the group of patients classified as ineligible according to both the definitions). Rigorous application of EMA indications in clinical practice could result in the exclusion of a large proportion of RA patients from treatment with JAKis. A proper quantification of the risk for MACE by dedicated tools as ERS-RA is advocated to better tailor the management of RA.

COVID-19 AND ARTERIAL STIFFNESS IN VACCINATED YOUNG ADULTS WITHOUT PRIOR CO-MORBIDITIES. A CROSS-SECTIONAL ANALYSIS OF THE FIT@4COVID COHORT STUDY

Objective: The long-term consequences of COVID-19 amongst survivors of acute infection are unknown, particularly on the cardiovascular system. Given the ability of the virus to affect the arterial wall, the question emerges to whether COVID-19 has a negative modulating effect of the vascular aging trajectory, conveying accelerated arterial stiffening and endothelial dysfunction, and thus, contributing to an increased CV risk over the life course. Objective: The main aim of this study was to ascertain the consequences of COVID-19 on arterial stiffness, by measuring PWV and thereby evaluating the presence of EVA. Secondary objectives of the study include investigating the effect of the SARS-CoV-2 infection on haemodynamic parameters measured by PWA. Design and method: A cross-sectional analysis of the initial data from the Fit@4COVID cohort was made. Carotid-femoral pulse wave velocity (PWV) and carotid pulse wave analysis (PWA) were evaluated in participants with (Covid19 group) and without (Control group) prior infection with SARS-CoV-2. Groups were matched for age and gender. Blood samples were taken for confirmation of prior exposition to the virus and to study the immune and inflammatory profile. Results: A total of 60 participants, equally divided in two groups, were enrolled, with a mean age of 20 ± 1.0 years. No significant differences were observed between groups concerning anthropometric, sociodemographic and clinical characteristics. Significant differences between-groups were observed for PWV (control: 5.84 ± 0.33 m/s, Covid19: 6.19 ± 0,47 m/s; p &lt; 0.01), even after adjusting for mean arterial pressure (p = 0.019). Significant differences were also depicted for central systolic blood pressure, with 106.40 ± 9.27 mmHg in the control group and 115.00 ± 11.23 mmHg in the Covid19 group (p = .012). Similar results were found when observing brachial systolic blood pressure, central pulse pressure and brachial pulse pressure, all of which showed higher values in the Covid19 group. Conclusions: The cross-sectional analysis of the initial Fit@4COVID data buttresses a relevant impact of the SARS-CoV-2 virus over the arterial wall, even in healthy young adults with mild forms of COVID-19. The long-term effects of COVID-19 over the cardiovascular system remains to be demonstrated.

Prevalence of Hyperuricemia and Its Association with Cardiovascular Risk Factors and Subclinical Target Organ Damage

The role of uric acid levels in the cardiovascular continuum is not clear. Our objective is to analyze the prevalence of hyperuricemia (HU) and its association with cardiovascular risk factors (CVRF), subclinical target organ damage (sTOD), and cardiovascular diseases (CVD). We evaluated the prevalence of HU in 6.927 patients included in the baseline visit of the IBERICAN study. HU was defined as uric acid levels above 6 mg/dL in women, and 7 mg/dL in men. Using adjusted logistic regression models, the odds ratios were estimated according to CVRF, sTOD, and CVD. The prevalence of HU was 16.3%. The risk of HU was higher in patients with pathological glomerular filtration rate (aOR: 2.92), heart failure (HF) (aOR: 1.91), abdominal obesity (aOR: 1.80), hypertension (HTN) (aOR: 1.65), use of thiazides (aOR: 1.54), left ventricular hypertrophy (LVH) (aOR: 1.36), atrial fibrillation (AFIB) (aOR: 1.29), and albuminuria (aOR: 1.27). On the other hand, being female (aOR: 0.82) showed a reduced risk. The prevalence of HU was higher in men, in patients presenting CVRF such as HTN and abdominal obesity, and with co-existence of LVH, atrial fibrillation (AFIB), HF, and any form of kidney injury. These associations raise the possibility that HU forms part of the early stages of the cardiovascular continuum. This may influence its management in Primary Healthcare because the presence of HU could mean an increased CV risk in the patients.

Vitamin D supplementation and adverse skeletal and non-skeletal outcomes in individuals at increased cardiovascular risk: Results from the International Polycap Study (TIPS)-3 randomized controlled trial

Background and aimsVitamin D has mostly been tested in Western populations. We examined the effect of high dose vitamin D in a population drawn predominantly from outside of Western countries. Methods and resultsThis randomized trial tested vitamin D 60,000 IU monthly in 5670 participants without vascular disease but at increased CV risk. The primary outcome was fracture. The secondary outcome was the composite of CV death, myocardial infarction stroke, cancer, fracture or fall. Death was a pre-specified outcome. Mean age was 63.9 years, and 3005 (53.0%) were female. 3034 (53.5%) participants resided in South Asia, 1904 (33.6%) in South East Asia, 480 (8.5%) in South America, and 252 (4.4%) in other regions. Mean follow-up was 4.6 years. A fracture occurred in 20 participants (0.2 per 100 person years) assigned to vitamin D, and 19 (0.1 per 100 person years) assigned to placebo (HR 1.06, 95% CI 0.57–1.99, p-value = 0.86). The secondary outcome occurred in 222 participants (1.8 per 100 person years) assigned to vitamin D, and 198 (1.6 per 100 person years) assigned to placebo (HR 1.13, 95% CI 0.93–1.37, p = 0.22). 172 (1.3 per 100 person years) participants assigned to vitamin D died, compared with 135 (1.0 per 100 person years) assigned to placebo (HR 1.29, 95% CI 1.03–1.61, p = 0.03). ConclusionIn a population predominantly from South Asia, South East Asia and South America, high-dose vitamin D did not reduce adverse skeletal or non-skeletal outcomes. Higher mortality was observed in the vitamin D group. Registration numberNCT01646437.

Paradoxical Association Between Dietary Lifestyle and Cardiovascular Risk: Cross-Sectional Analysis of Patient Responses from A Tertiary Care Hospital

A decrease in cardiovascular event risk with a decrease in total and LDL – cholesterol level is termed as “cholesterol paradox” or “risk factor reversal”. Cardiovascular risk does not have a linear relationship between LDL – cholesterol levels, and other substantial risk factors of cardiovascular events are being disregarded. The aim of this study is, to identify modifiable risk factors of cardiovascular events other than those well proved to cause dyslipidemia. A cross-sectional study was conducted with 652 participants in a tertiary care hospital. Patients were grouped into two, based on the history of cardiovascular events. Demographics and patient responses captured using pre-validated questionnaires were analyzed. 5mL blood samples were collected by venipuncture and lipid profile was estimated. Association between cardiovascular events and explanatory variables. was determined using Chi square test and Odds ratio at 95% confidence intervals. Higher risk of CV events was found among smokers 0.232 [0.144 – 0.373]. Consumption of white sugar, refined oil, processed cold beverages and fast food products increased CV risk respectively. Moreover, total cholesterol, LDL-C and triglycerides were found to decrease after one year of counselling the patients. The classical hypothesis of dyslipidemia induced atherosclerosis may not be the predominant cause of CV events. Herein, we report no association between high fat diet and CV risk while we observed higher risk in consumers of refined and ultra processed food products. However, significant control of cholesterol was observed in patients who shifted to Unrefined food products.

Prognostic implications of structural heart disease and premature ventricular contractions in recovery of exercise

Premature ventricular contractions (PVCs) during recovery of exercise stress testing are associated with increased cardiovascular mortality, but the cause remains unknown. We aimed to evaluate the association of PVCs during recovery with echocardiographic abnormalities, and their combined prognostic performance. Echocardiographic abnormalities [reduced left ventricular (LV) ejection fraction, valvular heart disease, LV dilatation, LV hypertrophy, or increased filling pressures] and PVCs during recovery were identified among patients having undergone both echocardiography and exercise stress test. Among included patients (n = 3106, age 59 ± 16 years, 55% males), PVCs during recovery were found in 1327 (43%) patients, among which the prevalence of echocardiographic abnormalities was increased (58% vs. 43%, p < 0.001). Overall, PVCs during recovery were associated with increased cardiovascular mortality (219 total events, 7.9 [5.4–11.1] years follow-up; adjusted hazard ratio (HR [95% confidence interval]) 1.6 [1.2–2.1], p < 0.001). When analyzed in combination with either presence or absence of echocardiographic abnormalities, PVCs during recovery were associated with increased risk when such were present (HR 3.3 [1.9–5.5], p < 0.001) but not when absent (HR 1.5 [0.8–2.8], p = 0.22), in reference to those with neither. Our findings provide mechanistic insights to the increased CV risk reported in patients with PVCs during recovery.

Serious Mental Illness Associated with Increased CV Risk.

According to this study: Adults with serious mental illness are at increased risk for cardiovascular disease compared with their peers.