Overt Cardiovascular Disease Research Articles

UNATTENDED AUTOMATIC BLOOD PRESSURE MEASUREMENTS VS. CONVENTIONAL OFFICE READINGS IN PREDICTING HYPERTENSION-MEDIATED ORGAN DAMAGE

Objective: Hypertension, a major cardiovascular risk, requires accurate blood pressure measurement. Conventional office measurements (OBPM) are error-prone and systematically biased by the white coat effect. Unattended office blood pressure measurement (UOBPM) is emerging as an alternative to mitigate this bias. However, its ability to predict hypertension-mediated organ damage (HMOD), indicating disease progression, remains debated. This study compares UOBPM with OBPM in terms of their association with various HMODs, including left ventricular hypertrophy (LVH), left atrial enlargement (LAE), left ventricular systolic and diastolic dysfunction, intima-media complex (IMT) thickening, microalbuminuria and abnormal pulse wave velocity (PWV). Design and method: Hypertensive patients without overt cardiovascular disease were recruited, interviewed, and examined. Subsequently, blood pressure measurements were conducted in standard conditions in a randomized sequence in each patient: 1) UOBPM: After 5 minutes of solitary rest in the examination room, blood pressure was automatically measured three times at 1-minute intervals with OMRON HEM 907 device. 2) OBPM: After 5 minutes of rest, a physician performed three automated measurements at 1-minute intervals with the same device. Subsequent evaluations aimed to detect HMODs, including echocardiography, carotid artery ultrasound, PWV assessment, and laboratory tests. Receiver operating characteristic (ROC) analysis was performed for each HMOD in both measurement groups, and the areas under the ROC curves were compared. Results: The study enrolled 219 patients(55% females, mean age 55 ±14 years). The average systolic blood pressure in UOBPM was lower by 4,2 mmHg (p<0,001) compared to OBP while the difference in diastolic pressure was 1,9 mmHg (p<0,001). Both measurement methods were associated with the presence of the following HMODs: LAE, IMT thickening, and abnormal PWV. Neither method allowed for the prediction of LVH, systolic and diastolic dysfunction of the left ventricle, elevated ACR, or the presence of atherosclerotic plaques in the carotid arteries. Furthermore, ROC curve analyses revealed no difference between the two methods in predicting HMOD (Table 1). Conclusions: Both measurement techniques exhibited satisfactory predictive ability for the presence of certain HMOD. However, based on the study results, no significant differences could be inferred between the two methods with respect to their predictive performance.

HYPERTENSION RELATED NETOSIS IS STRONGLY DEPENDENT ON NIGHTTIME BLOOD PRESSURE IN A COHORT OF NEWLY DIAGNOSED, TREATMENT NAÏVE HYPERTENSIVE PATIENTS

Objective: Over the last years, accumulating evidence has highlighted the key role of immunity in the inflammatory environment of essential hypertension (EH). Neutrophil extracellular traps (NETs) formation represents a protective innate immune mechanism of the neutrophils. However, excessive release of NETs (NETosis) has been shown to exert a potent pro-inflammatory and pro-thrombotic effect. Even though NETosis is increasingly implicated in the thrombo-inflammatory environment of cardiovascular disease, experimental and clinical data regarding the association between NETs and EH are scarce. Design and method: We recruited newly diagnosed, untreated hypertensives (UHTs) without overt cardiovascular disease and healthy, normotensive individuals (NTs). Office BP was measured according to guidelines. Ambulatory and central BP parameters were measured with the Mobil-O-Graph device. Plasma levels of NETs including myeloperoxidase (MPO)-DNA were determined by ELISA. Results: A total of 139 individuals including 99 UHTs and 40 NTs were included in the study. Levels of MPO-DNA were increased in UHTs compared to NTs (p<0.001). In multivariate analysis after adjustment for confounding variables (body mass index, hemoglobin, uric acid, high sensitivity c-reactive protein), hypertension was the strongest independent predictor of incident NETosis (p<0.001). Among the ambulatory BP indices, peripheral nighttime systolic BP (F:5.937; p=0.016) and central nighttime diastolic BP (F:4.751; p=0.031) were the strongest prognosticators of hypertension related NETosis (Optimal Scaling ANOVA; p=0.028). Conclusions: In a cohort of newly diagnosed, treatment-naïve hypertensive patients, nighttime BP indices are the strongest factors that can predict, independently, an increased NETosis, adding to the superior significance of nocturnal BP in cardiovascular prognosis. Further research is needed to clarify the association of NETs with hypertension as well as hypertension-mediated target organ damage.

THE INVESTIGATION OF TRANSFERABILITY OF DEFINITIONS OF CARDIOMETABOLIC AND VASCULAR AGING PHENOTYPES ACROSS MULTIPLE COHORTS

Objective: According to the European guidelines for the prevention of cardiovascular diseases (CVD) (2021), Russia was identified as a country with a very high CV risk. We aimed to investigate the applicability of the standardized definitions of vascular aging phenotypes (VP) in Russian population and align them with the existing reference datasets. Design and method: In 2012-2013 1,600 residents of St. Petersburg (age 21-67) were randomly examined as a part of the multicenter epidemiological study. Anthropometry, blood pressure measurement, blood biochemistry analysis were taken. Subjects completed questionnaires describing their lifestyle, current health condition and medication usage. 618 patients (42% men) from initial cohort with a mean age of 48 [37;55] years were randomly subsampled for carotid-femoral pulse wave velocity assessment (Sphygmocor). The VP were defined using the ‘Reference Values for Arterial Stiffness’ Collaboration database which included 16,867 measurements from eight European countries populations15 to 97 years. According to the criteria, patients with overt CVD, diabetes mellitus and the use of antihypertensive, lipid-lowering therapy were excluded from the analysis of VP. Results: The Russian cohort had significantly higher prevalence of CVD (11,4% compared to 6,9% in the Nreference population, p=5.65x10-5), intake of antihypertensives (28,1% compared to 14,3% in the reference, p<1x10-16) and lipid-lowering therapy (6,1% compared to 4,1%, p=0.025, Figure 1A). Additionally, our cohort had significantly higher prevalence of optimal BP (40,2% vs 28%, p=4.6x10-7) and lower prevalence of first-degree (p=0.048) and second degree (p=0.00084) hypertension (Figure 1B). Comparison of the prevalence of VP between the European and Russian cohorts showed a significant decrease of the early vascular aging (EVA) phenotype with age in the Russian population (p=0.011). The prevalence of the supernormal vascular aging phenotype (SUPERNOVA) in the group of 60-69 years old was higher in the Russian population (p=0.0035) Conclusions: A higher prevalence of CVD was demonstrated in the study cohort despite lower hypertension burden and higher CV drugs intake compared to the European cohort. Multidirectional trajectories of EVA and SUPERNOVA VP with age were detected in Russian population, potentially indicating the presence of the clearing selection pressure at the older age (Agreement No 075-15-2022-301).

A Convolutional Neural Network Classifies Beat-to-Beat Arterial Pressure Spectrograms and Wavelet Transforms according to Age, Sex, and Metabolic State: Novel Frequencies for Cardiovascular Risk Appraisal

Hemodynamic homeostasis is under the control of multiple systems. Continuous blood pressure (BP) time series carry information relevant to the pathophysiological status of the cardiovascular system. Beside average BP, different measures of variability provide prognostic value for distinguishing between cardiovascular risk states. The latter are derived from time- and frequency- domain analysis of BP recordings and are limited by their capacity to provide cumulative risk appraisal among different risk groups. The prediabetic state is associated with cardiovascular risk which is often described to be age- and sex-specific. In this study, we sought to determine distinctive features of continuous arterial pressure (AP) time-series for risk appraisal in a pre-established prediabetic rat model. To overcome the shortcomings associated with conventional BP variability parameters, we trained a convolutional neural network (CNN) using spectrograms and scalograms generated from short-term Fourier- and Morlet wavelet- transforms of AP time series, respectively, from male and female prediabetic rats fed a mild hypercaloric diet for 12- or 24- weeks and their corresponding controls. The CNN consisted of 5 convolutional layers, separated by batch normalization, ReLU activation, and max pooling. The outcome of the fifth convolutional layer had 40% of the data dropped out and delivered to a fully-connected dense layer and then to a softmax function. The data was divided into 80% training, 10% validation, and 10% test sets. The model classified spectrograms and scalograms with test accuracy of 90%+ for the different binary and multi-class classification tasks. On backward propagation of model scores, different salient frequencies were identified as critical features for classification of AP time-series. The identified frequencies were much higher than those typically used in conventional power spectral density (PSD) analysis. Using 3-way ANOVA or principal component analysis for comparison and clustering of the different cardiovascular risk groups of age, sex, and metabolic disease, respectively, according to PSD at the identified peaks does not yield suffcient risk appraisal. This indicates that the CNN possibly captures non-linear relations which are undetectable using inherently linear methods.The results indicate sex- and age-specific patterns of cardiovascular deterioration in prediabetes. Use of artificial intelligence models for the identification of abnormal BP fluctuation patterns can provide suffcient risk appraisal needed for early intervention, particularly in at-risk patients lacking clinical signs of overt cardiovascular disease. None. 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.

Racial Disparity in Microvascular Function in Men with Newly Diagnosed Prostate Cancer

BACKGROUND:Cardiovascular disease (CVD) is a leading cause of death in men with prostate cancer. In addition, non-Hispanic Black (NHB) men experience worse CVD-related mortality compared to their non-Hispanic White (NHW) counterparts, although the reason for this racial disparity remains unclear. Notably, vascular endothelial dysfunction often precedes the emergence of overt CVD. Indeed, conduit-vessel dysfunction, micro-vascular dysfunction, and arterial stiffness are independent predictors of CVD risk. Thus, the purpose of this study was to comprehensively assess vascular health in recently diagnosed NHB and NHW men with prostate cancer. Methods: Twenty-eight men (10 NHW, 18 NHB) with a new clinical diagnosis of prostate cancer (within 3 months) participated in this study. Flow-mediated dilation (FMD) was performed to represent conduit-vessel vascular endothelial function. Cutaneous post occlusive reactive hyperemia (PORH) with local thermal heating (LTH) and iontophoresis of acetylcholine were performed to represent various mechanisms regulating microvascular function. Lastly, pulse wave velocity (PWV) and pulse wave analysis (PWA) were performed to assess central and aortic stiffness, respectively. Data are reported as mean ± SD. Results: A 4-year age difference ( p=0.131) was observed between NHB (65±7 years) and NHW (69±6 years) men. No differences in BMI or clinical laboratory values were observed between NHB and NHW patients (all p>0.05). NHB men exhibited significantly lower microvascular function compared to NHW men, including PORH (NHB: 117±44 PU vs NHW: 207±47 PU; p<0.001), LTH (NHB: 180±73 PU vs NHW: 281±65 PU; p=0.003), and iontophoresis (NHB: 67±28 PU vs NHW: 136±38 PU; p<0.001). No differences in FMD ( p=0.596), PWV ( p=0.695), or PWA ( p=0.883) were observed between groups. CONCLUSION: The results of the current study provide compelling evidence that microvascular dysfunction is present in NHB men who are recently diagnosed with prostate cancer compared to their NHW counterparts. Given that NHB men were 4 years younger, these data support that the microvascular dysfunction may accelerate vascular aging and contribute to the racial disparity in CVD following prostate cancer diagnosis. Supported by: AHA SFRN 863621 (RAH). 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.

Short and long-term complications of hypertensive disorders of pregnancy: lifelong cardiovascular risks we cannot ignore.

Hypertensive disorders of pregnancy (HDP) pose a significant threat to maternal cardiovascular health, with emerging research shedding light on the enduring risks beyond the gestational period. This review highlights updates regarding cardiovascular risks associated with HDP and their implications for long-term health. Patients with a history of HDP are at an elevated risk of developing chronic hypertension, ischemic heart disease, stroke, valvular heart disease, and heart failure.Not surprisingly, patients with HDP experience higher rates of maternal and fetal adverse events in the antepartum and immediate postpartum periods, with high readmission rates for cardiovascular complications. The high risk of chronic hypertension after a HDP then leads to the development of subclinical disease over 5-10 years with overt cardiovascular disease becoming most prevalent in the decades following pregnancy. Early hypertension management in the antepartum and postpartum periods has lifelong health benefits and highlights the need for seamless postpartum transitions with close blood pressure monitoring and cardiovascular risk mitigation. HDP significantly increases the risk of short and long-term adverse cardiovascular events. Integrated healthcare models that assess and address postpartum cardiovascular risk are necessary to improve the cardiovascular health and longevity of those effected by HDP.

Association between Arterial Stiffness and Higher Burden of Atrial Arrhythmia in Elderly Hypertensive Patients without Atrial Fibrillation.

Arterial stiffness is associated with higher burden of atrial arrhythmias and worsening left atrial function (conduit and reservoir), even before dilation of this cavity. PACs: premature atrial contractions; cfPWV: carotid-femoral pulse wave velocity. Increased arterial stiffness is currently an independent risk factor for atrial fibrillation, but the pathophysiological mechanisms of this arrhythmia remain an area of knowledge gap to be explored. To investigate the existence of an association between arterial stiffness and the density of premature atrial contractions (PACs) in hypertensive individuals without atrial fibrillation. Cross-sectional study with hypertensive patients without diagnosed atrial fibrillation, who were studied with speckle-tracking echocardiography to assess left atrial (LA) strain and carotid-femoral pulse wave velocity (cfPWV) to assess arterial stiffness. All patients underwent 24h-ECG Holter and laboratory tests. Significance level was set at p<0.05. Seventy participants from a single centre without overt cardiovascular disease were included. The cfPWV was correlated with higher density of PACs in 24h-Holter monitoring, independently of LV mass index (1.48 [1.08-2.03], p-value 0.005). Increased cfPWV was correlated with decreased LA strain values, with Spearman correlation coefficients of -0.27 (p-value 0.027) and -0.29 (p-value 0.018) for reservoir and conduit 2D Strain, respectively. In this study with hypertensive patients, it was possible to demonstrate an association between arterial stiffness and higher density of atrial arrhythmias. Furthermore, arterial stiffness was associated with lower left atrial strain values for reservoir and conduit functions.

Moderate and high disease activity levels increase the risk of subclinical atherosclerosis progression in early rheumatoid arthritis: a 5-year prospective study

ObjectivesTo elucidate the association between different disease activity levels over time on long-term vascular outcomes in patients with early rheumatoid arthritis (ERA).MethodsThis was a 5-year prospective study. Patients with consecutive...

Cardiovascular sequelae of trastuzumab and anthracycline in long-term survivors of breast cancer

ObjectivesLong-term follow-up of patients treated with trastuzumab largely focuses on those with reduced left ventricular ejection fraction (LVEF) on treatment completion. This study sought to evaluate the prevalence of cardiovascular...

Increased prevalence of thyroid dysfunction in Tehran – HAMRAH study

BackgroundThe aim of the current study is to assess the prevalence of different categories of thyroid dysfunction and their associated risk factors among the modern urban population of Tehran, the capital of Iran.MethodsThe present investigation is a sub-study of the HAMRAH study, a population-based prospective study designed to assess the prevalence of traditional cardiovascular risk factors and their changes through a 10-year follow-up. 2228 (61% female) adults aged between 30 and 75 years old and with no overt cardiovascular diseases were selected through a multistage cluster randomized sampling. Blood levels of thyroid-stimulating hormone (TSH), thyroxin (T4), and triiodothyronine (T3) were measured with the aim of assessing the prevalence of abnormal thyroid function status among the modern urban Iranian population, and in order to report the total prevalence of participants with clinical hypo- or hyperthyroidism, the number of individuals taking thyroid-related drugs were added to the ones with overt thyroid dysfunction. A subgroup analysis was also performed to determine the associated risk factors of thyroid dysfunction.ResultsThe prevalence of thyroid dysfunction among the total population was 7% (95%CI: 5.9 − 8%) and 0.4% (95% CI: 0.1 − 0.6%) for subclinical and overt hypothyroidism, and 1.6% (95% CI: 1 − 2%) and 0.2% (95% CI: 0 − 0.3%) for subclinical and overt hyperthyroidism, respectively. Clinical thyroid dysfunction was detected in 10.3% of the study population (9.4% had clinical hypo- and 0.9% had clinical hyperthyroidism). In the subgroup analysis, thyroid dysfunction was significantly more prevalent among the female participants (P-value = 0.029).ConclusionsIn the current study, the prevalence of different categories of abnormal thyroid status, and also the rate of clinical hypo- and hyperthyroidism was assessed using the data collected from the first phase of the HAMRAH Study. In this study, we detected a higher prevalence of clinical and subclinical hypothyroidism among the Iranian population compared to the previous studies.

Increased Subclinical Coronary Artery Pathology in Type 2 Diabetes With Albuminuria.

Diabetes affects the kidneys, and presence of albuminuria reflects widespread vascular damage and is a risk factor for cardiovascular disease (CVD). Still, the pathophysiological association between albuminuria and CVD remains incompletely understood. Recent advantages in non-invasive imaging enable functional assessment of coronary artery pathology and present an opportunity to explore the association between albuminuria and CVD. In this cross-sectional study, we evaluated the presence of sub-clinical coronary artery pathology in people with type 2 diabetes, free of overt CVD. Using multimodal imaging, we assessed the coronary microcalcification activity (18F-sodium fluoride positron emission tomography/computed tomography (PET/CT), plaque inflammation (64Cu- DOTATATE PET/CT) and myocardial flow reserve (82Rubidium PET/CT). The study population consisted of 90 participants, stratified by albuminuria; 60 had historic or current albuminuria (urine albumin creatinine ratio (UACR) ≥ 30 mg/g)), and 30 had normoalbuminuria (UACR < 30 mg/g). We demonstrated that any albuminuria (historic or current) was associated with a more severe phenotype, in particularly higher levels of microcalcifications and impaired myocardial microvascular function, however, coronary inflammation activity was similar in people with and without albuminuria. Our findings establish a potential underlying mechanism connecting cardiovascular and kidney diseases and could indicate the initial stages of the cardiorenal syndrome.

Prevalence and associated factors of chronic venous disease among a modern non-western population

Abstract Background Chronic venous disease (CVD) of the lower extremities is a commonly occurring vascular disease with varied clinical manifestations and an uncertain prevalence due to differences in population characteristics and measurement techniques. Purpose The aim of this study was to assess chronic venous disease prevalence and identify associated risk factors in a modern non-western urban population. Methods 2227 adults aged 30–75 years with no overt cardiovascular diseases were randomly selected from different city districts to participate in a cardiovascular cohort. After they were informed about the examination methods, including total lower extremities exposure, 1176 (52%) of them agreed to participate. Two trained interventional cardiologists evaluated CVD using the Clinical-Etiology-Anatomy-Pathophysiology (CEAP) classification ensuring that all participants were evaluated by the same criteria in order to obtain reliable results. CVD was classified as C1–C6, and chronic venous insufficiency (CVI) as C3–C6. In this study, CVD associations were investigated using a multivariable regression model that accounted for pre-specified variables such as age, sex, body mass index (≥30 kg/m2), smoking, hypertension, diabetes mellitus, physical activity, dyslipidemia, and delivery. Results The prevalence of CVD and CVI among the participants was 36.5% (95% CI, 33.8 to 39.3) and 0.7% (95% CI, 0.3 to 1.3), respectively, and CVD prevalence was more frequent in women (44.2% vs. 23.5%). Based on multivariable analysis advanced age (OR, 1.06; 95% CI, 1.04 to 1.08), female sex (OR, 2.98; 95% CI, 2.14 to 4.14), and a body mass index of ≥30 (OR, 1.36; 95% CI, 1.03 to 1.81) were independently associated CVD. Physical activity (OR, 0.77; 95% CI, 0.58 to 1.02) was nearly protective, whereas other factors, including traditional cardiovascular risk factors, did not appear to have any meaningful association with CVD. Conclusions Our results showed that CVD was prevalent in a modern non-western urban population. Due to the low prevalence of advanced stages of the disease, mass screening is debatable, and better risk discriminators are needed.Figure 1Table 1

Cigarette smoking abolishes the mediterranean diet benefit on exercise capacity, coronary physiology and target organ damage in hypertensive males with erectile dysfunction

Abstract Background Erectile dysfunction (ED) often coexists impairing quality of life in the hypertensive aging male population. The Mediterranean diet (Med-diet) benefits cardiovascular health. Coronary flow reserve (CFR) displays the ability of the coronary circulation to increase flow. Central vascular stiffness and microalbuminuria (UMALb) represent hypertension-related target organ damage (TOD). Purpose To investigate cigarette smoking adverse effects on the Med-diet benefit in exercise capacity, coronary physiology and TOD in hypertensive males with ED. Methods We enrolled 290 hypertensive ED males (mean age: 57 yo) with no history of diabetes mellitus or overt cardiovascular disease. 121 (42%) were current cigarette smokers. Intensity of smoking referred in packs/year. All underwent a treadmill stress test (Bruce protocol), exercise capacity was validated as metabolic equivalents (METs). We measured the CFR of the LAD artery (2D echo) by performing an adenosine protocol (max dose 140μg/Kg/min over 6 min). PW Doppler measurements were achieved at the middle/distal LAD (color Doppler flow mapping). CFR was validated as ratio between peak diastolic flow velocity following drug infusion and rest. Ratios ≥ 2 indicate macro and microvascular coronary integrity. Participants were screened for the presence of UMALb (urinary albumin loss 30 – 300 mg /24 h urine volume collection). Finally a non-invasive evaluation of the carotid – femoral pulse wave velocity (PWV), estimation of central pressures and augmentation index (AIx) a parameter of wave reflection amplification were performed (Sphygmocor device). ED severity and the Med-diet adherence were assessed by the SHIM-5 (range:0-25) and the Med-diet (range:0-55) scores. Higher values indicate a better erectile ability and Med-diet compliance respectively. Results In bivariate analysis the Med-diet score was positively associated with METs, CFR and the SHIM-5 score and negatively with PWV, AIx and UMALb (p&amp;lt; 0,05). CFR, METs and the SHIM-5 score were also positively related (p&amp;lt; 0,03). In linear regression analysis the Med-diet relation remained significant after correction for age, BMI, LDL, total cholesterol and systolic blood pressure. However introducing cigarette smoking as a cofounder abolished the above relations. Packs/year were positively related to AIx, UMALb and negatively to the SHIM-5 score (p&amp;lt; 0,05). We also divided our population according to the mean Med-diet score (27) in high and low Med-diet groups .The high score group had higher METs and SHIM-5 score and lower PWV. Smokers had higher AIx and lower SHIM-5 score (pictures). Conclusion Cigarette smoking influences microvascular physiology and peripheral wave reflection and so abolishes Med-diet benefit on exercise capacity, coronary physiology, target organ damage and erectile ability in hypertensive males with ED. It is of vital importance consult this population avoiding smoking to restore cardiovascular health and quality of life.

Phenotyping coronary plaque by computed tomography in premature coronary artery disease

Abstract Background Premature coronary artery disease (CAD) is an aggressive chronic disease with multiple recurrences mostly related to the progression or complication of new coronary lesions. Purpose To compare coronary plaque characteristics of individuals with premature CAD with those of incidental plaques found in matched individuals free of overt cardiovascular disease, using coronary computed tomography angiography (CCTA). Methods 106 individuals with premature CAD were matched by age, sex, smoking status, family history of CAD, and dyslipidemia with 106 controls free of overt cardiovascular disease. CCTA were standardly analyzed for CAD-RADS score, plaque composition (calcified, partially or non-calcified), and the following four high-risk plaque (HRP) features : spotty calcification, positive remodeling, napkin-ring sign, and low-attenuation plaque. Results At least one coronary plaque was found in 85% of individuals with premature CAD vs. 62% of matched controls. The prevalence of non-calcified plaques was higher among individuals with premature CAD (65.1% vs. 30.2%, p&amp;lt;0,001), as well as spotty calcification (42.5% vs. 17.9%, p&amp;lt;0.001), positive remodeling (41.5% vs. 9.4%, p&amp;lt;0.001), low-attenuation plaques (24.5% vs. 3.8%, p&amp;lt;0.001) and napkin-ring sign (1.9% vs. 0.0%) (Figure 1). Individuals with premature CAD exhibited an average of 2.2 (±2.7) HRP features per person, while the control group displayed 0.4 (±0.8) HRP per person (p&amp;lt;0.001). Within a median follow-up of 24 [16,34] months, 24 ischemic recurrent events occurred in 24 individuals, all in the in premature CAD group. Individuals with premature CAD and recurrent ischemic event had more high-risk plaque features (4.3±3.9) than those without ischemic recurrence (1.5±1.9). They displayed more frequently non-calcified plaques (91.7% vs. 57.3%) with positive remodeling (75.0% vs. 31.7%) and low-attenuation plaques (45.8% vs. 18.3%) as compared to those without ischemic recurrence (Figure 2). Conclusions Coronary atherosclerosis in individuals with premature CAD is characterized by a high and predominant burden of non-calcified plaque and unusual high prevalence of high-risk plaque features, contributing to disease progression with multiple recurrences in this setting.HRP features in study populationHRP according to ischemic recurrence

Abstract 15726: Large-Scale Plasma Proteomics and Mendelian Randomization of Cardiovascular Performance and Peak Arterio-Venous Oxygen Difference Identify Novel Biology Related to VO 2 max

Introduction: VO 2 max is the product of maximal cardiac output (Q) (maximal stroke volume (SVmax) x heart rate) and peak arterio-venous oxygen content difference (a-vO 2 diff). SVmax and peak a-vO 2 diff have important implications across the spectrum of human health and performance. However, the molecular mechanisms underlying SVmax and peak a-vO 2 diff remain largely unknown. We characterize SVmax and peak a-vO 2 diff using large-scale plasma proteomics and genotyping to identify circulating proteins and putative mediators of these traits. Methods: 763 physically inactive adults without overt cardiovascular disease underwent cardiopulmonary exercise testing with rigorous measurements of Q. High-throughput plasma proteomic profiling was performed to identify proteins associated with SVmax, a-vO 2 diff, and VO 2 max. cis-Mendelian Randomization (MR) analysis was conducted to assess causal relationships between protein markers and cardiovascular performance traits. Results: Proteomic profiling revealed associations between SVmax and several adiposity-related proteins, as well as secretory muscle factors (cathepsin B, α-actinin 2, and troponin I) (Figure). Proteins associated with peak a-vO2diff reflected oxygen-carrying capacity, muscle biology, and glucose metabolism (erythropoietin, myoglobin, fructose-1,6-bisphosphatase). Significant overlap was observed between proteins associated with SVmax, a-vO 2 diff, and VO 2 max. Cis-MR identified myocilin (MYOC) and caspase recruitment domain family member 9 (CARD9) as potential mediators of cardiovascular performance and VO 2 max. Conclusions: This study provides novel insights into the molecular influences of cardiovascular performance and VO 2 max. The identified protein markers associated with SVmax and a-vO 2 diff, along with the possible mediators MYOC and CARD9, merit further investigation into their role in endurance exercise capacity and cardiometabolic health.

Per- and polyfluoroalkyl substances and cardiometabolic diseases: A review.

Per- and polyfluoroalkyl substances (PFAS) are a group of persistent and widespread environmental pollutants that represent a high concern for human health. They have been shown to be associated with several important physiological processes such as lipid metabolism and the immune system. Consequently, PFAS are suspected to play a role in cardiometabolic disease development. However, the evidence regarding associations between PFAS and overt cardiovascular disease and type 2 diabetes remains limited and inconsistent. To address this, we conducted a review of the epidemiological evidence. A deeper understanding of potential underlying molecular mechanisms may help to explain inconsistencies in epidemiological findings. Thus, to gain more mechanistic insight, we also summarized evidence from omics and laboratory studies into an adverse outcome pathway framework. Our observations indicate the potential for associations of PFAS with multiple molecular pathways that could have opposite associations with disease risk, which could be further modified by mixture composition, lifestyle factors or genetic polymorphisms. This identifies the need for exposome studies considering mixture effects, the use of multi-omics data to gain insight in relevant pathways and the integration of epidemiological and laboratory studies to enhance mechanistic understanding and causal inference. Improved comprehension is essential for environmental health risk assessments.

Blood pressure and hypertension in type 1 diabetes mellitus patients with long duration

Type 1 diabetes mellitus (T1DM) has significantly better prognosis which has led to increased cardio-vascular diseases (CVD) prevalence. The detection of CVD risk factors and their treatment become tasks of paramount importance. Among them, high blood pressure (BP) is a target of primary purpose. Aim: to explore the blood pressure values, the prevalence of hypertension (HTN) and its management in patients with T1DM with long duration and without overt CVD, in comparison to matched controls. Participants and methods: totally, 124 patients with T1DM were matched to 59 controls by sex, age and approximate body mass index (BMI). All participants filled in questionnaires with information on demographics, physical activity, life style, concomitant diseases, treatments, presence of complications, etc. Blood samples were taken for laboratory and biomarkers investigation. Blood pressure was measured by investigators twice and the mean of the two measurements was used. HTN was accepted using standard definitions. BP values were compared using t-test. Multiple linear regression models with dependent variable BP measures and age, sex, BMI, presence of T1DM, glycated hemoglobin levels, creatinine levels as independent variables were created. ANOVA method was used to test the interaction of sex and presence of T1DM. Results: The mean age of the participants was 43.47 &amp;plusmn; 10.1 years, 54% were males. The mean duration of T1DM was 25.31 &amp;plusmn; 8.2 years and the mean HbA1c was 8.42 &amp;plusmn; 1.8% for diabetic patients. The mean blood pressure measures in T1DM groups were higher than in controls, both in males and females. The difference reached significance for SBP and pulse pressure (PP). The presence of T1DM independently affected the BP values, after adjusting for major confounders. The mean adjusted differences between T1DM and controls were 8.37 mm Hg for SBP, 4.92 mm Hg for DBP, and 5.19 mm Hg for PP (p &lt; 0.001). HTN was significantly more frequent in T1DM patients than in controls &amp;ndash; 54% vs. 27%, p = 0.0001, mainly due to already known hypertension. BP control was insufficient &amp;ndash; in only 36% and 13% of the treated hypertensive participants, respectively, for BP &lt; 140/90 and &lt; 130/80 mm Hg. The majority of the patients with HTN were treated with combination therapy, mostly single-pill fixed dosage but 30% of the hypertensive patients with diabetes did not take antihypertensive medications. Inhibitors of the renin-angiotensin system were the preferred class of medications. Conclusions: SBP and PP were significantly higher in middle-aged patients with T1DM with long duration than their control counterparts. The presence of HTN was significantly more common in T1DM. Although treated according to the current recommendations, the control of BP was far from effective. These results show the need for constant screening of patients with T1DM for HTN and other risk factors and for more aggressive antihypertensive treatment to prevent future CVD events.

Prevalence and associated factors of chronic venous disease among the modern Iranian urban population

ObjectivesChronic venous disease (CVD) of the lower extremities is one of the common venous diseases in different populations, with a wide range of clinical manifestations and undetermined exact prevalence owing to different population characteristics and measurement methods. This study aimed to estimate the prevalence of CVD among the modern Iranian urban population and determine its associated risk factors. MethodsThe Heart Assessment and Monitoring in Rajaie Hospital study, a longitudinal population-based cohort, aims to investigate the baseline prevalence and the 10-year incidence of cardiovascular diseases and associated risk factors in the adult population aged 30 to 75 years with no overt cardiovascular diseases in Tehran. Two instructed interventional cardiologists performed CVD evaluation using the Clinical-Etiology-Anatomy-Pathophysiology classification. CVD was graded as C1 to C6, and chronic venous insufficiency (CVI) as C3 to C6. A multivariable regression model was used to analyze the association between CVD and prespecified covariates of age, sex, body mass index (≥30 kg/m2), smoking, hypertension, diabetes mellitus, physical activity, dyslipidemia, and delivery method. ResultsCVD prevalence among 1176 participants was 36.5% (95% confidence interval [CI], 33.8-39.3) and was higher in women than men (44.2% vs 23.5%). CVI prevalence was only 0.7% (95% CI, 0.3-1.3). Multivariable analysis showed that advanced age (odds ratio [OR], 1.06; 95% CI, 1.04-1.08), female sex (OR, 2.98; 95% CI, 2.14-4.14), and body mass index of ≥30 (OR, 1.36; 95% CI, 1.03-1.81) were independently associated with CVD. Physical activity (OR, 0.77; 95% CI, 0.58-1.02) was nearly protective, whereas other factors, including traditional cardiovascular risk factors, had no meaningful association with CVD. ConclusionsOur findings showed that CVD was prevalent in the modern Iranian urban population. However, considering the very low prevalence of the higher stages of the disease, the benefit of mass screening is debatable, and better risk discriminators should be investigated.

Association between subclinical atherosclerosis and cardiac structure and function-results from the UK Biobank Study.

Heart failure (HF) is a major health problem and early diagnosis is important. Atherosclerosis is the main cause of HF and carotid intima-media thickness (IMT) is a recognized early measure of atherosclerosis. This study aimed to investigate whether increased carotid IMT is associated with changes in cardiac structure and function in middle-aged participants of the UK Biobank Study without overt cardiovascular disease. Participants of the UK Biobank who underwent CMR and carotid ultrasound examinations were included in this study. Patients with heart failure, angina, atrial fibrillation, and history of myocardial infarction or stroke were excluded. We used multivariable linear regression models adjusted for age, sex, physical activity, body mass index, body surface area, hypertension, diabetes, smoking, ethnicity, socioeconomic status, alcohol intake, and laboratory parameters. In total, 4301 individuals (61.6 ± 7.5 years, 45.9% male) were included. Multivariable linear regression analyses showed that increasing quartiles of IMT was associated with increased left and right ventricular (LV and RV) and left atrial volumes and greater LV mass. Moreover, increased IMT was related to lower LV end-systolic circumferential strain, torsion, and both left and right atrial ejection fractions (all P < 0.05). Increased IMT showed an independent association over traditional risk factors with enlargement of all four cardiac chambers, decreased function in both atria, greater LV mass, and subclinical LV dysfunction. There may be additional risk stratification that can be derived from the IMT to identify those most likely to have early cardiac structural/functional changes.

Machine learning profiles of cardiovascular risk in patients with diabetes mellitus: the Silesia Diabetes-Heart Project

AimsAs cardiovascular disease (CVD) is a leading cause of death for patients with diabetes mellitus (DM), we aimed to find important factors that predict cardiovascular (CV) risk using a machine learning (ML) approach.Methods and resultsWe performed a single center, observational study in a cohort of 238 DM patients (mean age ± SD 52.15 ± 17.27 years, 54% female) as a part of the Silesia Diabetes-Heart Project. Having gathered patients’ medical history, demographic data, laboratory test results, results from the Michigan Neuropathy Screening Instrument (assessing diabetic peripheral neuropathy) and Ewing’s battery examination (determining the presence of cardiovascular autonomic neuropathy), we managed use a ML approach to predict the occurrence of overt CVD on the basis of five most discriminative predictors with the area under the receiver operating characteristic curve of 0.86 (95% CI 0.80–0.91). Those features included the presence of past or current foot ulceration, age, the treatment with beta-blocker (BB) and angiotensin converting enzyme inhibitor (ACEi). On the basis of the aforementioned parameters, unsupervised clustering identified different CV risk groups. The highest CV risk was determined for the eldest patients treated in large extent with ACEi but not BB and having current foot ulceration, and for slightly younger individuals treated extensively with both above-mentioned drugs, with relatively small percentage of diabetic ulceration.ConclusionsUsing a ML approach in a prospective cohort of patients with DM, we identified important factors that predicted CV risk. If a patient was treated with ACEi or BB, is older and has/had a foot ulcer, this strongly predicts that he/she is at high risk of having overt CVD.