Multiple Cardiovascular Risk Factors Research Articles

The role of sex on the prevalence of cardiovascular risk factors in children and adolescents with Type 1 diabetes: The SWEET international database

ObjectiveTo assess the prevalence of cardiovascular risk factors (CVRFs) in children and adolescents with type 1 diabetes (T1D) in the International SWEET registry and the possible role of clinical variables in modifying the risk of having single or multiple CVRFs. Study designThe study is a cross-sectional study. Cut-off points for CVRFs were fixed according to International Society for Pediatric and Adolescent Diabetes (ISPAD) guidelines and WHO parameters: LDL cholesterol (LDL-C) > 100 mg/dL; Systolic Blood Pressure (BP-SDS) > 90th percentile for sex, age, and height; BMI-SDS > 2SD for sex and age. Logistic regression models were applied to evaluate variables associated with at least 1 or 2 CVRFs among registry children and adolescents. Results29,649 individuals with T1D (6–18 years, T1D ≥ 2 years) participating in the SWEET prospective multicenter diabetes registry were included. In the cohort, 41 % had one or more CVRFs, and 10 % had two or more CVRFs. Thirty-five percent of enrolled individuals had LDL-C > 100 mg/dL, 26 % had BMI-SDS > 2SD, and 17 % had Systolic BP-SDS > 90th percentile. Females had higher frequency than males of having 1 or 2 CVRFs (45.1 % vs 37.4 %, 11.8 % vs 7.8 %; p < 0.001). Multivariable logistic regression models showed that sex (female), HbA1c category (>7.0 %), and age (>10 years) were associated with a higher chance of having at least 1 or 2 CVRFs (p < 0.001). ConclusionsIn children and adolescents with T1D, female sex, in addition to HbA1c above 7 %, and older age (>10 years) was associated with a higher risk of having at least a CVRF (LDL-C, BMI-SDS, BP) according to internationally defined cut-offs.

Multicenter evaluation of tofacitinib retention and safety in rheumatoid arthritis - why cardiovascular risk factors do not equate to overt risk.

This multicenter, real-world, retrospective cohort study aimed to assess the effectiveness and safety of tofacitinib (TOFA) in rheumatoid arthritis (RA). Two hundred nine patients with active RA treated with TOFA, unresponsive to at least 2 conventional synthetic disease-modifying drugs, were recruited. Clinical characteristics were extracted from an electronic registry and supplemented with manual chart review and data linkage with ambulatory care. Drug retention and reasons for discontinuation were evaluated. Median (interquartile range) follow-up in the whole sample was 16.9 (5.93-31.7) months. Mean (standard deviation) age was 51.44 (±11.84) years, with female predominance (n = 168, 80.4%). Only 30 patients (14.4%) had no pre-existing traditional cardiovascular (CV) risk factor at TOFA initiation. Tofacitinib retention rates were high, with median survival estimated at 89.3% at 6 months, 82.4% at 12 months, and 60.4% at 24 months. Ineffectiveness was the primary cause of discontinuation (n = 50). The rate of adverse events (AEs) was relatively low, with lipid abnormalities, blood count alterations, and infectious events among the most common. No major adverse CV event was reported. The incidence rate of AEs necessitating treatment switch was 60.34 (95% CI: 37-92) per 1,000 person-years of follow-up. Presence of multiple (> 3) CV risk factors was associated with lower odds of TOFA retention and treatment effectiveness. Tofacitinib demonstrated high retention rates and a favorable safety profile in RA patients, including those with traditional CV risk factors. Tofacitinib may be a valuable treatment option for RA patients when combined with individualized CV risk management. Further studies are warranted to explore the long-term effects of TOFA and its CV impact in larger populations.

Mediating effect of vascular calcification in galectin-3-related mortality in hemodialysis patients

Galectin-3 levels have been studied as a potential biomarker for predicting cardiovascular (CV) risk and mortality in hemodialysis (HD) patients. Recently, a close relationship between galectin-3 and vascular calcification (VC) has been reported. Here, we investigated the role of VC as a mediating factor in the association between galectin-3 and mortality. Serum galectin-3 and baseline aortic arch calcification (AoAC) score were measured in 477 incident HD patients. Mortality data were obtained at a median follow-up of 40 months. Causal mediation analysis was performed to examine the effect of vascular risk factors on galectin-3-related mortality. The prevalence of AoAC in HD patients was 57% (n = 272), and elevated galectin-3 levels were associated with a significantly increased risk of AoAC. When the galectin-3 level was divided by the median level of 37 ng/mL, a higher galectin group increased the risk of all-cause mortality by 1.71-fold (95% CI 1.02–2.92, p = 0.048), even after adjustment for multiple CV risk factors. Mediation analysis showed that both the direct effect of the galectin-3 on mortality (β = 0.0368, bootstrapped 95% CI [0.0113–0.0622]) and the indirect effects were significant. AoAC score and high-sensitivity CRP levels significantly mediated the association between galectin-3 and mortality (total indirect effects: β = 0.0188, bootstrapped 95% CI [0.0066–0.0352]). This study suggests that the association between high galectin-3 and mortality may be partially mediated by higher VC and inflammatory state in HD patients.

Chinese herbal medicine Shenqi compound for early intervention in patients at high cardiovascular risk of type 2 diabetes mellitus: the protocol of a multicenter, randomized, double-blind, placebo-controlled trial.

Reducing multiple cardiovascular risk factors is a key link and a challenging clinical problem to reduce the risk of cardiovascular complications and death in patients with diabetes. Currently, there is a lack of clinical studies on patients with diabetes combined with multiple risk factors. Traditional Chinese medicine is believed to have therapeutic effects that contribute to the comprehensive control of multiple cardiovascular factors. This study aims to provide evidence for the efficacy and safety of Shenqi compound (SQC) for early intervention in diabetic patients at high cardiovascular risk. This study is a multicenter, randomized, double-blind, placebo-controlled trial. A total of 120 diabetic patients with high cardiovascular risk were enrolled in five research centers. After a 2-week run-in period, the intervention group received basic treatment and SQC granules, and the control group received basic treatment and placebo granules for a total of 24 weeks, with a 24-week follow-up. The endpoint outcomes are major adverse cardiovascular events and renal-related and peripheral vascular disease events. The primary efficacy outcome is carotid intima-media thickness, and the secondary efficacy outcomes are carotid shear stress, indicators of glucose and lipid metabolism, pancreatic islets function, hemorheology, traditional Chinese medicine syndrome score, and quality of life scale. Safety indicators and adverse events were used to assess the safety of SQC. This study comprehensively evaluated the efficacy and safety of SQC for early intervention in diabetic patients at high cardiovascular risk from the aspects of overall metabolic level, structure, and function of blood vessels, quality of life, and long-term follow-up of endpoint events, providing evidence-based evidence for the short-term efficacy and long-term benefits of early treatment to reduce the risk of diabetic cardiovascular complications.Trial Registration: This trial is registered in the Chinese Clinical Trial Registry on March 9, 2023, https://www.chictr.org.cn/showproj.html?proj=192803 (No. ChiCTR2300069219).

Canonical Correlation for the Analysis of Lifestyle Behaviors versus Cardiovascular Risk Factors and the Prediction of Cardiovascular Mortality: A Population Study

Objectives: To assess the overall association of lifestyle behaviors with multiple cardiovascular risk factors and mortality. Material and Methods: In the Italian Rural Areas of the Seven Countries Study, involving 1712 middle-aged men (40–59 years) enrolled in 1960, smoking habits, physical activity, dietary habits, marital status, and socioeconomic status (SES) were studied as possible determinants of 15 measurable risk factors (body mass index, tricipital and subscapular skinfold, arm circumference, systolic and diastolic blood pressure, heart rate, double product (systolic blood pressure × heart rate), vital capacity, forced expiratory volume, serum cholesterol, urine protein, urine glucose, corneal arcus and xanthelasma) using canonical correlation (CC). Results: The first CC had a value of 0.54 (R2 0.29, p &lt; 0.0001). The role of marital status was marginal; that of a high SES was contrary to expectations. The strongest behaviors based on standardized CC coefficients were dietary habits and physical activity. The risk factors mostly associated with overall lifestyle behaviors were some anthropometric and cardiovascular measurements. The mean levels of risk factors distributed in tertile classes of the CC variate score of lifestyle behaviors were largely associated in a coherent and graded way with the expected relationship of behaviors versus risk factors. In a large series of Cox models, the CC variate scores were significantly associated with 50-year coronary heart disease (CHD) mortality and much less with stroke and other heart diseases of uncertain etiology. Conclusions: Lifestyle behaviors correlate well with cardiovascular risk factors associated with CHD mortality, and CC is a useful method of analysis to detect long-term impacting characteristics.

Differences in Clinical Outcomes Between Hydroxyurea-Resistant and -Intolerant Polycythemia Vera Patients.

Previous studies have suggested that patients with polycythemia vera (PV) who exhibit hydroxyurea-resistance (HU-R) and -intolerance (HU-I) may have distinct characteristics and clinical outcomes. However, to date, no studies have reported a comparison between these two groups or assessed prognostic factors in these patients. The objective of this study was to evaluate clinical outcomes and identify prognostic factors among PV patients with HU-R or HU-I. We conducted a review of PV patients who received frontline treatment with HU from nine centers and identified 90 patients with HU-R or HU-I. The cumulative incidence of thrombosis after 7 years of HU-R/I was 21.4%, and the incidence of disease progression was 22.5%. Comparing the HU-R and HU-I groups, the HU-R group had a significantly higher rate of disease progression (36.7% vs. 0.56%, P = 0.009), while there was no significant difference in thrombosis incidence (19.0% vs. 22.9%, P = 0.463). Multivariate analysis revealed that HU-R was an independent prognostic factor for progression-free survival (hazard ratio, 6.27, 95% confidence interval, 1.83-21.47, P = 0.003). Additionally, higher lactate dehydrogenase levels, multiple cardiovascular risk factors, and prior thrombosis were identified as unfavorable predictors of overall survival. These findings suggest that patients with HU-R face a higher risk of hematological transformation, but have a comparable risk of thrombosis to patients with HU intolerance. These distinctions should guide decisions on second-line treatment options and clinical trials involving these patients.

Lipid Management in Kidney Transplant Recipients Per KDIGO and American Heart Association Guidelines: A Single-Center Experience.

The 2013 Kidney Disease: Improving Global Outcomes (KDIGO) guidelines recommends statin treatment for all adult kidney transplant recipients (KTRs), except those aged <30 years of age and without prior cardiovascular risk factors (CVRF), but does not specify on-treatment low-density lipoprotein cholesterol (LDL) target levels. The 2018 American Heart Association (AHA) guidelines addressed the management of hyperlipidemia in the general population based on an individualized approach of the CVRF with a specific on-treatment LDL target. To analyze dyslipidemia management according to the recommendations of the KDIGO and AHA guidelines. This retrospective study included all KTRs who underwent transplantation between January 2017 and May 2020 at King Abdulaziz Medical Center, Riyadh, Saudi Arabia. The rate of statins prescription in general, rate of statins prescription among KTRs per their CVRF, and rate of achieving the proposed LDL goals, as defined by the AHA, were analyzed. A total of 287 KTRs were included. Of the 214 (74.6%) patients aged ≥30 years, 80% received a statin. Statins were prescribed in 93% and 96% of KTRs with diabetes or coronary artery disease, respectively. In patients aged ≥30 years, LDL targets, per AHA guidelines, were achieved in 62% with a target of 2.6 mmol/l, and in 19% with a target of 1.8 mmol/l. Statin therapy resulted in non-significant changes in the mean LDL values from baseline to 12 months after transplantation (P = 0.607), even when only patients prescribed statin after transplantation were included (P = 0.34). By applying the KDIGO guidelines, a high rate of statin prescriptions was achieved among KTRs with multiple CVRF and KTRs in general. However, a significant proportion of these KTRs did not achieve the LDL targets proposed by the AHA guidelines, suggesting that higher-intensity statins would be required to achieve these targets.

Adjusted Global Antiphospholipid Syndrome Score (aGAPSS) and PLT, APTT: Predictive Value of Thrombotic Risk Assessment in SLE Patients.

Risk assessment of vascular thrombosis in SLE patients with the presence of antiphospholipid antibodies (aPL) remains a challenge. The adjusted global antiphospholipid syndrome score (aGAPSS) has been validated and used to predict aPL-related thrombosis in SLE patients in some countries. Relevant data of aGAPSS in thrombotic evaluation in SLE population from China has not been reported. We aim to validate aGAPSS in thrombosis assessment in Chinese patients with SLE and to explore the correlations of aGAPSS with routine laboratory parameters and their clinical significance as well. A total of 166 consecutive SLE patients were retrospectively analyzed. Multivariate logistic regression analysis was performed to examine the impact of multiple cardiovascular risk factors and laboratory parameters in recurrent thrombosis risk in SLE. ROC was conducted to explore the discriminative ability of aGAPSS and platelet (PLT), activated partial thromboplastin time (APTT), alone or in combination. Significantly higher value of aGAPSS was seen in SLE patients with vascular thrombosis. ROC curve indicated that aGAPSS of 3.5 or more had the best diagnostic accuracy for the prediction of aPL-related thrombosis in SLE patients. PLT with cutoff of 187.5 x 109/L and APTT with 37.5 seconds were predictors of aPL-related thrombosis as well. The combination of aGAPSS with PLT and APTT improved AUC compared to aGAPSS alone. The aGAPSS could predict the risk of aPL-related vascular thrombosis in SLE patients from China. The combination of aGAPSS with PLT and APTT was first time proved to have better predictive performance in thrombosis risk assessment in SLE.

The role of periprocedural hemodynamic variables during carotid stenting for the mid-term general mortality in advanced age patients.

Carotid stenting may produce significant bradycardia and/or hypotension. This may have negative short- and long-term effects for the elderly high-risk patients. Their cerebral hemodynamics is with exhausted adaptive capacity because of the multiple cardiovascular risk factors, advanced age, and significant stenosis.

Effects of Physical Activity, Vascular Burden and Clinical Diagnosis on White Matter Integrity

AbstractBackgroundAlzheimer’s disease (AD) is the most common type of dementia. Both degenerative and vascular pathology tend to contribute to dementia as AD coexists with single or multiple cardiovascular risk factors (vascular burden). Modifiable lifestyle factor such as physical activity has been associated with lower vascular burden (VB) and a lower risk of dementia. To test whether physical activity characterised as being inactive or active helped preserve white matter microstructure in a sample consisting of healthy controls and patients from the clinical AD continuum (mild cognitive impairment to dementia) with either low or high VB.Method213 participants were recruited from three memory clinics and were classified as being either physically active (n = 113) or inactive (n = 100) based on the Cardiovascular Risk Factors, Aging and Dementia (CAIDE) questionnaire. Voxel‐wise tract‐based spatial statistics (TBSS) was carried out using a set of 5000 permutations and threshold‐free cluster enhancement (TFCE) to find significant clusters for fractional anisotropy (FA), axial diffusivity (AxD), mean diffusivity (MD) and radial diffusivity (RD).ResultParticipants who were physically active had higher FA and lower AxD, MD and RD values relative to the inactive participants. Changes in indices of WM integrity were widespread across the brain covering mainly association and projection tracts but a few commissural tracts. A three‐way interaction effect between Group × Physical Activity × VB was found for FA that was present in mainly projection tracts with a rightward asymmetry along with some association and commissural tracts. Post hocs revealed greater FA in physically active patients with high VB compared with inactive patients with high VB in projection and association/limbic tracts with a rightward asymmetry. Furthermore, the patients with high VB showed higher FA in bilateral projection fibers and cerebellar regions compared with inactive controls with high VB.ConclusionTBSS analysis revealed that high risk patients such as those with high VB achieved the maximum benefit by being physically active as it led to a much greater preservation of white microstructure relative to controls with high VB. This preservation of white matter microstructure was only observed in patients but not in controls.

Association of the Complement System with Subclinical Atherosclerosis in Psoriasis: Findings from an Observational Cohort Study

Psoriasis is a chronic and inflammatory disease that affects the skin and joints and is associated with multiple comorbidities and cardiovascular risk factors. Consequently, patients with psoriasis have an increased risk of cardiovascular diseases such as atherosclerosis, a chronic pathology that shares common inflammatory and immune-response mechanisms with psoriasis, including vascular inflammation and complement activation. To better understand the relationship between atherosclerosis and psoriasis, a proteomics study followed by a bioinformatics analysis was carried out, with a subsequent validation step using ELISA and western blotting. When the plasma from patients with psoriasis alone was compared with that from patients with psoriasis and atherosclerosis, 31 proteins of interest related to the complement system and oxygen transport were identified. After the validation phase, 11 proteins appeared to define the presence of subclinical atherosclerosis in patients with psoriasis, indicating the importance of complement cascades in the development of atherosclerotic plaques in individuals with psoriasis. These results are a step forward in understanding the pathological pathways implicated in the cardiovascular risk associated with this population, which may represent an interesting starting point for developing predictive tools that improve the follow-up of these patients and design more effective therapies.

Cardiological parameters predict mortality and cardiotoxicity in oncological patients.

Oncological patients suspected at risk for cardiotoxicity are recommended to undergo intensified cardiological surveillance. We investigated the value of cardiac biomarkers and patient-related risk factors [age, cardiovascular risk factors (CVRFs), and cardiac function] for the prediction of all-cause mortality (ACM) and the development of cardiotoxicity. Between January 2016 and December 2020, patients with oncological diseases admitted to the Cardio-Oncology Unit at the Heidelberg University Hospital were included. They were evaluated by medical history, physical examination, 12-lead electrocardiogram, 2D echocardiography, and cardiac biomarkers [high-sensitivity cardiac troponin T (hs-cTnT) and N-terminal pro-brain natriuretic peptide (NT-proBNP)]. The primary endpoint was defined as ACM and the secondary endpoint was defined as cardiotoxicity, as defined by the European Society of Cardiology. Of the 1971 patients enrolled, the primary endpoint was reached by 490 patients (25.7%) with a median of 363.5 [interquartile range (IQR) 121.8, 522.5] days after presentation. Hs-cTnT of ≥ 7ng/L [odds ratio (OR) 1.82, P<0.001] and NT-proBNP (OR 1.98, P<0.001) were independent predictors of ACM, while reduced left ventricular ejection fraction was not associated with increased ACM (P=0.85). The secondary endpoint was reached by 182 patients (9.2%) with a median of 793.5 [IQR 411.2, 1165.0] days. Patients with multiple CVRFs (defined as high risk, n=886) had an increased risk of cardiotoxicity (n=100/886, 11.3%; hazard ratio 1.57, P=0.004). They showed elevated baseline values of hs-cTnT (OR 1.60, P=0.006) and NT-proBNP (OR 4.00, P<0.001) and had an increased risk of ACM (OR 1.43, P=0.031). In cancer patients, CVRF accumulation predicts cardiotoxicity whereas elevated hs-cTnT or NT-proBNP levels are associated with ACM. Accordingly, less intensive surveillance protocols may be warranted in patients with low cardiac biomarker levels and absence of CVRFs.

Women's heart clinics to prevent cardiovascular disease in women with pregnancy-related risk factors: a prospective study

Abstract Background A woman’s risk of cardiovascular disease (CVD) is substantially increased after a diagnosis of hypertensive disorders of pregnancy (HDP), gestational diabetes (GDM), or have had a small for gestational age (SGA) baby. However, evidence for models of care that mitigate CVD risk in women with these pregnancy-related conditions is lacking. Purpose To assess the effectiveness of a Women’s Heart Clinic (WHC) on blood pressure (BP) and lipid control in women with past pregnancy-related cardiovascular risk factors. Method A six-month prospective cohort study of women aged 30-55 years with a past pregnancy diagnosis of HDP, GDM or an SGA baby. All women attended a multidisciplinary WHC comprising a cardiologist, a cardiac nurse, and a dietician, located in three cardiovascular healthcare service centers in Australia. Women were assessed at their first attendance of the WHC and at 6 months. The co-primary endpoints were: 1) BP&amp;lt;140/90mmHg or &amp;lt;130/80mmHg if diabetes mellitus and 2) total cholesterol to high density lipoprotein-cholesterol ratio (TC:HDL-C)&amp;lt;4.5. Results 156 women were recruited with a mean age of 41.0±4.2 years, 68.6% Caucasian, 20.5% South/East Asian and 80.5% university educated. Women were a mean of 3.9±2.9 years from last delivery with 23.1% past HDP only, 60.3% GDM only, 13.5% both HDP and GDM and, 3.2% with an SGA baby. All women attended a WHC at least once, with 69.5% reviewed by a dietician. The proportion meeting BP target increased (69.2% to 80.5%, p=0.004); with no significant change in women meeting lipid targets (80.6% to 83.7%, p=0.182). Women had significant reductions in mean systolic BP (-6.9mmHg, 95% confidence interval (CI): -9.1,-4.7, p&amp;lt;0.001), body mass index (-0.6kg/m2, CI: -0.8,-0.3, p&amp;lt;0.001), LDL-cholesterol (-4.2mg/dL, CI: -8.2,-0.2, p=0.042) and total cholesterol (-4.6mg/dL, CI: -9.1,-0.2, p=0.042). Heart-healthy lifestyle significantly improved with increased fish/olive oil (36.5% to 51.0%, p=0.012) and decreased fast food consumption (33.8% to 11.0%, P&amp;lt;0.001), with more women meeting exercise recommendations (84.0% to 92.9%, p=0.025). Conclusion Women at high risk for CVD due to past pregnancy-related conditions experienced significant improvements in multiple cardiovascular risk factors, after attending a Women’s Heart Clinic. This female-specific cardiovascular healthcare model has the potential to improve long-term CVD outcomes for women.Figure 1:Visual abstract

Abstract 14020: Five-Year Trends in Risk Factors for Cardiovascular Disease Among Adolescents in the United States

Introduction: Cardiovascular disease is the leading cause of death in the United States (US) and worldwide. Past studies have demonstrated a rise in sedentary life-style among adolescents. We aim to provide an up-to-date representation of the prevalence of multiple cardiovascular risk factors amongst adolescents in the US. Methods: We queried hospitalization records of adolescents of ages 10-19 years (inclusive) via the 2016-2020 National Inpatient Sample, a set of de-identified records provided by HCUP, AHRQ and partners. The trends of several risk factors were estimated (per 100,000 hospitalization) via linear-by-linear analysis as per past studies of the database. Results: Our study found an increasing trend in prediabetes (41 per 100,000 in 2016 to gradually reach 309 per 100,000 in 2020, ptrend&lt;0.01), hypertension (2334 per 100,000 in 2016 to reach 2756 per 100,000 in 2020, ptrend&lt;0.01), diabetes (5119per 100,000 in 2016 to reach 5733 per 100,000 in 2020, ptrend&lt;0.01), obesity (6153 per 100,000 in 2016 to reach 8221 per 100,000 in 2020, ptrend&lt;0.01), smoking (8166 per 100,000 in 2016 to reach 9117 per 100,000 in 2020, ptrend&lt;0.01), and family history of ischemic heart disease or cardiovascular disease (1687 per 100,000 in 2016 to reach 1922 per 100,000 in 2020, ptrend&lt;0.01, ptrend&lt;0.01) (Figure 1). In addition, the incidence of acute myocardial infarction (AMI) rose from 34 per 100,000 in 2016 to reach 68 per 100,000 in 2020 (ptrend&lt;0.01). A similar rise in events of acute ischemic stroke (AIS) was seen with 123 cases per 100,000 reported in 2016 and this increased to 156 per 100,000 in 2020 (ptrend&lt;0.01) (Figure 1). Conclusion: There is an alarming rise in various risk factors that can lead to future cardiovascular disease among adolescents. Furthermore, the incidences of AMI and AIS among adolescents are on the rise. Stronger health-related sensitization campaigns promoting healthier life-style should be mooted.

Differences in Clinical Outcomes between Hydroxyurea-Resistant and -Intolerant Polycythemia Vera Patients

Previous retrospective studies have revealed that a substantial portion of PV patients experience resistance to hydroxyurea (HU-R) and intolerance to HU (HU-I). Currently, the therapeutic options for both groups of patients do not differ, and most clinical trials investigating second-line therapies have enrolled patients with HU-R or HU-I without considering potential clinical distinctions between the two groups. Direct comparisons between patients with HU resistance and HU intolerance have not been conducted, and prognostic factors related to clinical outcomes, such as thrombosis, bleeding, disease progression, and survival, remain unclear for patients experiencing HU resistance or intolerance. A total of 90 patients with HU-R/I were retrospectively anlyzed in this study. Among them, 44 and 46 patients fulfilled the ELN criteria defining resistance or intolerance to HU, respectively. Patients with HU-R were older at the time of diagnosis of PV (66.7 ± 13.2 years, vs. 59.8 ±11.2 years in the HU-I group, P = 0.016), had longer times to developing HU-R/I, and thus, were older at the time of HU-R/I development compared with those with HU-I. The majority of the study patients continued HU treatment with dose modification or intermittent discontinuation with anagrelide added to control platelet counts until disease progression or death because of limited second-line treatment options during the observed period. The cumulative incidence of thrombosis after 7 years of HU-R/I was 21.4%, and the incidence of disease progression was 22.5%. Comparing the HU-R and HU-I groups, the HU-R group had a significantly higher rate of disease progression (36.7% vs. 0.56%, P = 0.009), while there was no significant difference in thrombosis incidence (19.0% vs. 22.9%, P = 0.463). The type of thrombosis did not differ between the two groups (P = 0.628). Multivariate analysis revealed that HU-R was an independent prognostic factor for progression-free survival (hazard ratio = 5.57, 95% CI: 1.22 - 25.54, P = 0.027). The patients in the HU-R group had significantly lower PFS (40.2% vs. 66.1% in the HU- I group, P &amp;lt; 0.01). They also showed a trend toward lower TFS (51.0% vs. 62.1% in the HU-I group; P = 0.055) and lower OS (57.5% vs. 67.7% in the HU-I group; P = 0.060) compared to patients with HU-I. The mortality at seven years was 42.5% in the HU-R group and 32.3% in the HU-I group (P = 0.06). Higher LDH levels, multiple cardiovascular risk factors, and prior thrombosis were identified as unfavorable predictors of overall survival. These findings suggest that HU-resistant patients have a higher risk of hematological transformation but a comparable risk of thrombosis to HU-intolerant patients. These distinctions should guide decisions on second-line treatment options and clinical trials involving these patients.

Abstract 152: Exploring Age‐related Changes in Brain Metabolism among Individuals with Cardiovascular Risk Factors: An FDG‐PET Analysis

Introduction Patients with cognitive impairment often have a history of cardiovascular disease (CVD) or multiple cardiovascular risk factors (CRFs) such as hypertension, obesity, and hypercholesterolemia. The literature reports that CVD with CRFs may increase the risk of developing vascular dementia and Alzheimer’s Disease. 18F‐fluorodeoxyglucose positron emission tomography (FDG‐PET) allows for the in vivo study of cerebral glucose metabolism, and can detect metabolic alterations in several neurological diseases. As we age, the brain undergoes both structural and functional changes; the regional distribution of these alterations mirrors cognitive decline. This study aims to assess the effect of aging on regional glucose uptake in subjects with known cardiovascular risk factors. Methods In total, 40 subjects (mean age 55.9 ± 11.89 years, 50% males) with known cardiovascular risk factors underwent FDG‐PET scanning, and 70 whole brain structures were analyzed in each subject. Participants were recruited from a group of patients with chest pain syndromes who were referred for coronary CT angiography. All subjects underwent whole‐body FDG‐PET/CT imaging 180 minutes after the administration of 4.0 MBq/kg dose of FDG. The quantitative regional analysis of PET images was performed using MIMneuro version 7.1.5 (MIM Software, Inc., Cleveland, Ohio). MIMneuro provides region‐based analysis, with z‐scores generated by comparing the patient to the selected age‐matched set of normal controls. Pearson’s R was calculated and evaluated for significance in all variables. The threshold for significance was set at P &lt; 0.05. Results Various significant associations between age and FDG uptake across all 70 brain regions of interest were observed. In particular, age was found to have an inverse correlation with regional metabolism in the middle temporal gyrus (r= ‐0.364, p=0.021), superior frontal gyrus (r= ‐0.433, p=0.005), superior parietal lobule (r= ‐0.354, p=0.025), supplementary motor area (r= ‐0.436, p=0.005), and temporal operculum (r= ‐0.370, p=0.019). Conclusion The results demonstrate a significant inverse correlation between age and FDG uptake in five regions among individuals with cardiovascular risk factors. This information may be useful in the determination of whether such scans might be useful in the evaluation of patients with a history of CVD/CRF or with mild cognitive impairment (MCI). Previous literature has reported that increased medial temporal gyrus atrophy is a predictor of dementia in subjects with MCI, and alterations within this lobe mark the beginning of the disease process. Our strongest inverse correlation, the superior frontal gyrus, has been shown to be related to working memory; hypometabolism in this region has previously correlated with severity of cognitive impairments in attention, executive function, and language. Further research is needed to determine the potential for using FDG‐PET imaging as a tool for early detection and intervention for cognitive decline. If patients with CVD or CRFs can be properly diagnosed, if there exists a metabolic signature of regional functional change, intervention may prove highly beneficial for cognitive function, quality of life, and overall well‐being.

Abstract 015: Pioneering NaF‐PET/CT Imaging for Early Detection of Atherosclerosis: Potential Implications for Neurointerventional Surgery

Introduction Cerebrovascular disease (CVD), particularly carotid artery atherosclerosis, contributes substantially to global morbidity and mortality. The ability to precisely detect atherosclerosis is crucial, as it directly influences patient management, including decisions regarding surgical interventions. Given the high prevalence and severe outcomes of CVD, there is an urgent need for improved early detection methods. Utilizing a novel approach, this study pioneers the use of 18F‐sodium fluoride (NaF) PET/CT imaging for the early identification of microcalcification, a key marker of atherosclerosis. A nuanced understanding of vascular calcification's temporal progression may aid in optimally timing surgical interventions, such as carotid endarterectomy or carotid artery stenting, thereby reducing stroke risk. Methods Our study participant is a 31‐year‐old male with atrial fibrillation, multiple cardiovascular risk factors, and class 2 obesity, enrolled in the Cardiovascular Molecular Calcification Assessed by 18F‐NaF PET/CT (CAMONA) study. The patient underwent both FDG‐PET/CT and NaF‐PET/CT imaging. We utilized OsiriX MD software v.13.0.1 (Pixmeo SARL, Bernex, Switzerland), to compute the standardized uptake value (SUVmean), serving as a measure of disease progression in both the global brain and the bilateral carotid arteries. Subsequently, we employed MIMneuro version 7.1.5 (MIM Software, Inc., Cleveland, OH, USA) to conduct a comprehensive regional brain metabolism analysis, harnessing the power of an integrated anatomical atlas. Results NaF‐PET/CT imaging revealed elevated NaF uptake in the bilateral carotid arteries (z‐score = 0.012), suggesting notable microcalcification. Conversely, FDG‐PET/CT imaging revealed low FDG uptake in the carotid arteries, with an average SUVmean of 0.66 for both right and left carotids and a z‐score of −2.32. Analysis of global brain metabolism demonstrated decreased FDG uptake detected by FDG‐PET/CT (z‐score = ‐2.32). Concurrently, we identified a decline in regional brain metabolism, with prominent decreases observed in regions including the brainstem (z score = −1.95), medial temporal lobe (z‐score = −1.81), cerebellum (z–score = −2.13), hippocampus (z‐score = −2.13), inferior frontal gyrus (z‐score = −3.53), lateral orbital gyrus (z‐score = −3.24), and putamen (z‐score = −2.47) (Figure 1). Conclusion Our findings highlight the potential of NaF‐PET/CT imaging to enhance early detection of carotid artery atherosclerosis and cerebral hypometabolism. These results highlight the subtle, yet potent, potential of NaF‐PET/CT scans to detect active, asymptomatic cases where FDG‐PET/CT scans may not indicate high activity. The findings suggest that NaF‐PET could play a pivotal role in diagnosing and managing CVD where traditional tracers encounter limitations. Early recognition of these alterations facilitates clinical decision‐making, including determining the necessity and timing of surgical intervention. This advanced diagnostic tool presents an opportunity to improve pre‐operative assessments by providing insights into disease progression prior to macrocalcification development, a clear advantage over existing imaging modalities. The correlation between vascular calcification and decreased cerebral metabolism enhances our understanding of CVD pathophysiology, thereby paving the way for transformative therapeutic interventions. While these findings provide preliminary insight, further research is crucial to corroborate our results and delineate their potentially transformative implications on patient care, particularly in the context of surgical interventions.

A Pilot Study on the Association between Cardiovascular Risk Factors and Coronary Artery Calcification in a Group of Patients Investigated via Cardiac Computed Tomography in a European Country with High Cardiovascular Risk.

(1) Background: Cardiovascular disease is the leading cause of mortality worldwide; the prevention and early detection of coronary artery disease are of critical importance; and the coronary artery calcium score is a powerful method in the assessment of coronary artery disease. Among European countries, Romania ranks as a country with a very high risk of cardiovascular diseases, but the data are limited in regard to the prevalence of the calcium score. (2) Methods: A retrospective study was conducted to establish the coronary calcium score in a group of patients investigated via cardiac CT and to determine the correlation with the presence of cardiovascular risk factors. (3) Results: According to the Agatston calcium score, 50% of the patients had a positive calcium score. High calcium scores above 400 UA were present in 12.6% of patients. Regarding the association between the presence of cardiovascular risk factors and the levels of coronary artery calcification, a mild level of calcification was associated with age over 50 years (X2 = 3.88, p = 0.04, OR = 3.25; 95% CI 0.94-11.14); a moderate level of calcification with the age of patients over 50 years (X2 = 6.54, p = 0.01, OR = 5.58; 95% CI 1.29-24.16), dyslipidemia (X2 = 7.28, p = 0.007, OR = 3.37; 95% CI 1.34-8.51), and arterial hypertension (X2 = 5.37, p = 0.02, OR = 2.88; 95% CI 1.14-7.27); a severe level of calcification with hypertension (X2 = 4.61, p = 0.03, OR = 7.03; 95% CI 0.90-54.81); and a very severe level of calcification with hypertension (X2 = 4.61, p = 0.03, OR = 7.03; 95% CI 0.90-54.81), smoking (X2 = 8.07, p = 0.004, OR = 4.44; 95% CI 1.47-13.44), and diabetes (X2 = 13.65, p = 0.001, OR = 6.59; 95% CI 2.5-20.18). (4) Conclusion: Half of the patients investigated by using cardiac CT had a calcium score of zero. Predictors for coronary calcium scores in relation to risk factors varied. For the very severe coronary calcification level, the strongest predictor was the presence of smoking and diabetes, which increased the odds for very severe calcification by 13.46 times. Patients who had multiple cardiovascular risk factors, hypertension, diabetes, and smoking were 9.18 times more likely to have very severe calcification.

Cardiovascular Risk in Childhood is Associated With Carotid Intima-Media Thickness and Stiffness in Adolescents and Young Adults: The KiGGS Cohort

PurposeCardiovascular risk factors are widespread among children and adolescents and may lead to accelerated vascular aging in middle adulthood. However, data are scarce on shorter-term consequences, for example, on associated distinctive vascular properties before age 30 years. This study analyzes the association of childhood exposure to cardiovascular risk factors with carotid properties in adolescents and young adults. MethodsFour thousand thirty one participants from the population-based German Health Interview and Examination Survey for Children and Adolescents cohort (aged 3–17 years) had carotid intima-media thickness (CIMT) and distensibility coefficient (DC) measurements at the second follow-up (aged 14–28 years). The assessment of cardiovascular risk factors at baseline included information about arterial hypertension, obesity, dyslipidemia, and passive smoking. ResultsSingle risk factors and the exposure to multiple cardiovascular risk factors were associated with elevated CIMT and decreased DC. Relative risks for CIMT ≥ 90th centile and/or DC ≤ 10th centile were increased in participants exposed to two (RRCIMT = 1.45 [95% confidence interval 1.11–1.91], p < .05; RRDC = 1.37 [1.02–1.84], p < .05) and ≥ three risk factors (RRCIMT = 1.66 [1.05–2.62], p < .05; RRDC = 1.25 [0.71–2.21], p > .05). DiscussionExposure to multiple cardiovascular risk factors starting in childhood is associated with measurably increased CIMT and carotid stiffness in late adolescence and early adulthood. These findings underline the importance of population-wide preventive measures to promote optimal cardiovascular health.

Aspirin for primary prevention in patients with high cardiovascular risk: insights from CORE-Thailand registry

Aspirin may be considered for primary prevention in non-elderly patients with high cardiovascular risk. However, contemporary management aimed at aggressive cardiovascular risk factor control may alter benefit-risk ratio of aspirin. Therefore, we aimed to examine the effect of aspirin for primary prevention on the long-term MACEs in a large cohort registry. Cohort Of patients with high Risk for cardiovascular Events (CORE-Thailand) registry is a prospective, multicenter, observational, longitudinal study of Thai patients with high atherosclerotic risk. Patients with established atherosclerotic cardiovascular diseases were excluded. Among 4259 patients with multiple cardiovascular risk factors, 1945 (45.7%) patients used aspirin. After propensity score matching, there were 3228 patients remained in post-matching analysis. During the median follow-up period of 58.2 months, we demonstrated that aspirin use increased risk of long-term MACEs in pre-matching cohort (unadjusted HR 1.76, 95% CI 1.43–2.17, P < 0.001) and post-matching cohort (HR 1.66 (1.31–2.10), P < 0.001). In addition, patients taking aspirin had a higher risk of bleeding than non-aspirin users in pre-matching cohort (unadjusted HR 2.28, 95% CI 1.09–4.75, P = 0.028). We demonstrated that aspirin was associated with increased risk of long-term MACEs in patients with multiple cardiovascular risk factors. Due to the non-randomized design, our results should be interpreted with caution.