Risk Factors For Hypertension Research Articles

Appraising the Role of Circulating Concentrations of Micronutrients in Hypertension: A Two-sample, Multivariable Mendelian Randomization Study.

Hypertension poses a significant global health challenge, warranting exploration of novel preventive measures. This study aimed to investigate the role of circulating concentrations of various micronutrients in hypertension using a Mendelian randomization (MR) approach. Data on hypertension were obtained from FinnGen, comprising 55,917 cases and 162,837 controls of European ancestry. Fifteen micronutrients were evaluated and selected based on genome-wide association studies (GWAS) data. Instrumental single nucleotide polymorphisms (SNPs) were chosen according to strict criteria. Univariable Mendelian randomization (UVMR) analysis was conducted using the inverse variance weighted (IVW) method, supplemented by sensitivity analyses. Multivariate Mendelian randomization (MVMR) analysis was performed to assess interactions between micronutrients. In UVMR analysis, the IVW method revealed a potential influence of copper (OR = 1.052, 95% CI: 1.006-1.099, P = 0.025) and zinc (OR = 1.083, 95% CI: 1.007-1.165, P = 0.031) on hypertension. Sensitivity analyses supported these findings. MVMR analysis confirmed a direct positive effect of zinc on hypertension (OR = 1.087, 95% CI: 1.026-1.151, P = 0.005), while adjusting for zinc attenuated the effect of copper on hypertension (OR = 1.026, 95% CI: 0.987-1.066, P = 0.193). Circulating zinc levels may be a potential risk factor for hypertension, while the association with other micronutrients remains inconclusive. These findings suggest that reducing zinc intake within a healthy range may help lower hypertension risk. Future research should further explore the role of zinc and nonlinear associations for a more comprehensive understanding.

Cardiovascular effects of BRAF and MEK inhibitors in patients with melanoma: a prospective study incorporating risk scores, cardiac biomarkers and cardiovascular magnetic resonance imaging

Abstract Background BRAF and MEK inhibitors have revolutionised treatment for patients with BRAF-mutated melanoma. Unfortunately, they are associated with cardiovascular adverse effects including hypertension and cancer-therapy related cardiac dysfunction (CTRCD). The ‘real world’ incidence and risk factors for these adverse effects are poorly described. Purpose To characterise the incidence and risk factors for BRAF and MEK inhibitor-associated hypertension and CTRCD in a prospective ‘real world’ setting. Methods Prospective, observational, cohort study of patients with melanoma treated with BRAF and MEK inhibitors at a regional cancer hospital network (March 2021 - May 2023). Comprehensive assessment was performed at baseline, 4, 12 and 24 weeks following start of treatment, including home and clinic blood pressure assessment, serial echocardiography, stress-perfusion cardiovascular magnetic resonance imaging (CMR) and humoral biomarkers (Figure 1). CTRCD was defined as mild, moderate or severe in line with International Cardio-Oncology Society (IC-OS) definitions. Hypertension was defined as 7 day average home blood pressure of ≥135/85 mmHg or the initiation or escalation of anti-hypertensive therapy. Baseline cardiotoxicity risk stratification was performed using the ESC Cardio-Oncology guideline-recommended tool. Results 61 participants were enrolled. 48% developed BRAF/MEK inhibitor associated hypertension. 46% of participants developed CTRCD and, of these, 24 (86%) were classified as mild, 3 (11%) moderate and 1 (3%) severe. Left ventricular ejection fraction (LVEF) during follow up is shown in Figure 2. All participants with moderate and severe CTRCD also had BRAF/MEK inhibitor associated hypertension. After stratification with the baseline risk assessment tool, no patient in the ‘low risk’ group developed moderate or severe CTRCD. Baseline elevated NT-proBNP (>125pg/mL), history of left ventricular systolic dysfunction and atrial fibrillation were associated with the development of CTRCD. 20 participants underwent stress perfusion CMR at baseline, 4 and 24 weeks. 25% had a drop in LVEF to <50% but only 5% had a co-existing LVEF ≥10% from baseline to fulfil criteria for the diagnosis of moderate CTRCD. Conclusion BRAF and MEK inhibitor-associated hypertension and CTRCD is common, with a higher incidence in this ‘real world’ prospective cohort than observed in clinical trials. The majority of CTRCD was ‘mild’ and the long term sequalae of this remains unknown. No patients considered to be at low baseline risk for CTRCD using the ESC-recommended risk stratification tool developed moderate or severe CTRCD. These findings support the use of routine blood pressure surveillance in this group as well as baseline risk stratification to guide appropriate imaging surveillance of cardiac function.Figure 1.Schedule of study visitsFigure 2.LV function/CTRCD over time

Effects of BET Inhibition on lung micro-environmental changes in obesity-related pulmonary Arterial Hypertension (PAH)

Abstract Background Obesity is emerging as a pivotal risk factor for pulmonary arterial hypertension (PAH) but the underlying molecular mechanisms are poorly explored. The lung microenvironment, namely the cell-cell communication among fibroblasts, immune and endothelial cells, may significantly impact on vascular structure and function thus promoting microvascular disease in this setting. Obesity-induced chromatin modifications lead to maladaptive transcriptional programs altering cell function in different organs. Apabetalone (APA), a selective inhibitor of bromodomain and extra-terminal containing protein family (BET) proteins, prevents bromodomain-containing protein 4 (BRD4) interactions with chromatin thus modulating gene expression. Purpose To determine whether a new epi-drug, namely APA, affects the lung microenvironment in obesity-related PAH. Methods Mice were fed a normal diet (ND, control) or high-fat-diet (HFD) and L-NAME for 15 weeks to induce obesity-related PAH (obPAH). Echocardiography was performed. Pathways regulating obPAH were identified by single-cell nuclei RNA sequencing in lung specimens. Primary endothelial cells (ECs) and Fibroblasts (mFs) were freshly isolated from obPAH lungs and treated with APA for 48 hours. Cells and lung samples were used for molecular biology and histology. Cellular migration was investigated by in vitro gap closure. Results Obese mice displayed PAH as shown by increased pulmonary artery (PA) pressure, PA resistance, right ventricular wall thickness and reduced PA acceleration time. Of note, chronic APA treatment prevented PAH-related features in obese mice. To determine the cell types affected by APA, we performed scRNAseq. We found that fibroblast and endothelial cells had the highest enrichment of genes whose expression significantly correlated with echo-determined PAH features. ECs and mFs from obese mice displayed an altered phenotype whereas treatment with APA rescued obesity-driven ECs and mFs dysfunction. In obPAH ECs, we found increased expression of NF-kB p65-related inflammatory genes (IL-1β, IL-6, TNF-alpha) as well as enhanced p53 signaling. Moreover, obPAH-ECs expressed high levels of hypoxia-inducible factor (HIF1-α) and NADPH-oxidase-NOX4 with subsequent increase in ROS generation. Furthermore, APA treatment protected against cellular inflammation, senescence and oxidative stress. To evaluate the effect of APA and the paracrine response of fibroblasts, we performed a scratch assay on control mFs exposed to TGF-β or conditioned media collected from obPAH-ECs with and without APA. In both experimental settings, APA affected gap closure, suggesting that the treatment influences fibroblast migration through both a direct effect and paracrine mechanisms. Conclusions APA is able to reset the lung micro-envirnment in obesity thus reducing inflammation and senescence. BET inhibitors could represent potential therapeutic approaches in this setting.

Predictors of new-onset in-hospital atrial fibrillation in 122 089 patients admitted with COVID-19: an Australian statewide population study

Abstract Background New-onset atrial fibrillation (AF) when encountered in COVID-19 patients may be associated with increased mortality and thromboembolic events. Few studies have investigated predictors of new-onset AF in the context of COVID-19 and no study has assessed the utility of CHA2DS2VASc score in predicting new-onset AF in COVID-19 patients. Purpose This study aims to identify independent predictors of new-onset in-hospital AF in patients admitted with COVID-19. Methods Patients admitted with COVID-19 (1-Jan-2020 to 30-Sept-2021) were identified from the Admitted-Patient-Data-Collection database in an Australian state, stratified by AF status (no-AF vs new-AF during index COVID-19 admission) and followed-up until 31-Mar-2022. Patients with prior-AF were excluded from analysis. New-AF was defined as new-onset AF during the hospital admission for COVID-19. Independent predictors of new-AF were identified using multivariable logistic regression. Receiver Operating Characteristic (ROC) derived Area Under Curve (AUC) score was performed to determine the predictive power of independent predictors of new-AF. Results The cohort comprised 122089 COVID-19 patients (median age 62.7 yrs; 48.5% males) of whom 5140 developed new-AF (4.2%). Compared to patients with no-AF, patients with new-AF had a higher prevalence of comorbidities and cardiac risk factors (hypertension, diabetes and smoking) as well as a higher CHA2DS2VASc score (p < 0.001) (Table 1). Independent predictors of new-AF included referral from Emergency Department (adjusted odds ratio [aOR] =1.63, 95% confidence interval [CI]=1.49-1.78, intensive-care-unit admission (aOR=3.46, 95%CI=3.22-3.71), current/ex-smoker (aOR=1.20, 95%CI=1.12-1.27), prior coronary revascularization (percutaneous coronary intervention or coronary artery bypass graft surgery) (aOR=1.33, 95%CI=1.01-1.75), valvular heart disease (aOR=3.20, 95%CI=2.73-3.75), malignancy (aOR=1.15, 95%CI=1.02-1.29), chronic pulmonary disease (aOR=1.30, 95%CI=1.19-1.42) and higher CHA2DS2VASc score (per-1-score increase: aOR=1.62, 95%CI=1.59-1.65) (all P<0.05). CHA2DS2VASc score alone had an AUC score of 0.729 (95%CI=0.72-0.74) (Figure 1). Adding the above additional independent variables to CHA2DS2VASc score improved the predictive model to an overall AUC score of 0.773 (95%CI=0.77-0.78), p < 0.001. Conclusions This study identified patients at risk of developing new-AF in the setting of COVID-19 infection. Our multivariable logistic regression analysis that included CHA2DS2VASc score has a relatively good predictive value and if confirmed in other COVID-19 cohorts, may be used to identify patients in whom antiarrhythmic and more aggressive thromboprophylactic strategies can be considered.

Proteomics in low CVD risk black women living with HIV: H-ART to Heart Study

Abstract Background 39 million people worldwide are living with HIV (human immunodeficiency virus), acquired immune deficiency syndrome (AIDS)-related deaths have reduced by 51% since the peak in 2004. BWLWH represent 42% of those infected but only 9% are represented in clinical trials. HIV/AIDS has been shown to be associated with the development of heart failure, pulmonary hypertension and myocarditis. Previous studies in asymptomatic PLWH have revealed a high burden of underlying CVD and subclinical disease. The H-ART to Heart study is designed to examine potential signals and pathways of cardiovascular disease (CVD) in asymptomatic BWLWH with no traditional CV risk factors compared to HIV negative controls (-). Methods A cross-sectional study comparing asymptomatic BWLWH aged 35-55yrs (diagnosed >10 yrs, with undetectable viral loads) to HIV negative controls. Black African/Caribbean women without known CV risk factors (hypertension, hyperlipidaemia, diabetes, smoking, inflammatory arthritis, depression, severe mental illness) or hepatitis co-infection were included. Assessment included blood pressure (BP), 10yr CVD risk calculation % (Q-Risk 3), bloods including lipids. A targeted discovery proteomics approach was used to evaluate 92 unique proteins using the O-link Target 96 Cardiovascular II panel. Results 48 participants were recruited (23 BWLWH; 25 controls), mean duration of HIV was 17.6 years, mean duration of ART was 11.5 years, demographic details - Age 47.7± 44.7±; p=0.06, BP 125/77 v 123/79 ; p=0.89; BMI (kg/m²) 30.1±5.1 v 28.51±4.27 p=0.25; cLDL 3.49±1.22 v 2.42±0.74 p<0.02; Total Chol:HDL ratio 3.01±0.98 v 2.77±0.56 p=0.353; Q-Risk 3 1.92%±1.27 v 1.49%±1.12 p=0.219; There were no significant differences in baseline data apart from higher mean cLDL in BWLWH. Of the 92 proteins tested, 9 were significant in BWLWH (Figure 1). As demonstrated by the Heat map. Conclusion Data from our study of asymptomatic low risk BWLWH with no CVD risk factors indicates several pathways (Figure 2.) for further investigation in this previously under investigated vulnerable patient sub group. Whether this finding is of importance in CV risk assessment of BWLWH remains to be seen.

Circulating levels of amyloid-beta (1-40) peptide associate with cardiometabolic traits and risk for metabolic dysfunction-associated steatotic liver disease

Abstract Background and Aims The ageing-associated amyloid-beta 1-40 peptide (Αbeta40) has recently emerged as a blood-based biomarker of cardiovascular disease (CVD). Its levels predict future cardiovascular death and MACE in patients with established CVD. The clinical value of Abeta40 in patients with metabolic syndrome who do not concomitantly have clinically overt CVD or other end-organ damage remains poorly understood. At the present study we investigated the clinical value of plasma Αbeta40 in patients with pre- or established metabolic syndrome who are at risk for metabolic dysfunction-associated steatotic liver disease (MASLD). Methods Αbeta40 was measured in plasma by enzyme-linked immunosorbent assay and cardiometabolic traits were determined in a mixed population (n=888) of patients with established (n=243) and pre- or without metabolic syndrome (n=645) who did not have clinical signs of established cardiometabolic disease (heart failure, coronary artery disease, MASLD, chronic kidney disease). The endpoint of the study was the association of Abeta40 with cardiometabolic indices and risk (BARD score) for MASLD. Odds ratio (OR) was calculated by ordinal regression analysis for the increasing incidence of metabolic syndrome components per increasing Abeta40 (1-SD) after adjustment for age, sex, smoking status and hyperlipidemia. Results Abeta40 levels are associated with the presence of metabolic syndrome and with higher odds for increasing incidence of metabolic syndrome components after adjustment for sex, age, smoking status, hypertension and dyslipidemia. Increased Abeta40 plasma levels were associated with decreased HDL-C levels (OR: 1.004, 95% CI:1.000-1.009, P=0.049) and increased triglyceride levels (OR: 1.007, 95%CI: 1.001-1.012, P=0.033) after adjustment for traditional cardiovascular risk factors (age, sex, smoking status, hypertension and hyperlipidemia). Among the total population (n=888), we identified n=473 subjects with increased MASLD risk if any of the following was present: hepatic steatosis index≥36 or fatty liver index≥60 or Fib-4 index≥2.67 or NAFLD score≥0.675. Among patients with high-risk for MASLD, patients with increased BARD score had significantly higher Abeta40 levels (median Abeta40 concentration in patients with BARD score≥2 vs. patients with BARD score<2: 54.9 pg/ml (IQR=38.25) vs. 41.9 pg/m (IQR=30.35), P=0.012). Increased Abeta40 levels were associated with increased odds for AST/ALT≥0.8 ratio and increased odds for BARD score≥2 after adjustment for age, sex, smoking status, hypertension and hyperlipidemia. Conclusion Our findings suggest that Abeta40 peptide is associated with cardiometabolic traits and risk for MASLD. Whether Abeta40 may emerge as an early cardiometabolic prognostic biomarker, future longitudinal studies are warranted to determine the prognostic value of Abeta40 for the development of cardiometabolic diseases in patients with metabolic syndrome.

Circulating Galectin-3 distinguishes global aortic aging among older women

Abstract Background Traditional cardiovascular risk factors may underestimate age-associated cardiovascular risk, particularly in estimating discrepant risks between sexes. As a marker of adverse cardiovascular events, aortic stiffness may improve risk assessment, but the requirement for advanced imaging equipment restrict widespread translation of this paradigm. Conversely, circulating blood biomarkers may augment mechanistic understanding and distinguish sex-based differences in aortic stiffness. Purpose Hypothesizing that Galectin-3 (Gal-3) is associated with aortic aging among older adults, we examined sex-based differences between Gal-3 and global aortic stiffness as assessed by a novel cardiac magnetic resonance (CMR)-derived measurement of aortic global longitudinal strain (AOGLS). Methods Community older adults without cardiovascular disease underwent simultaneous CMR with serum Gal-3 quantification using chemiluminescent microparticle immunoassays. Poorer AOGLS was defined as values below the 75th percentile of AOGLS measurements. Multivariable regression models were used to assess the association of Gal-3 with AOGLS. Results Of 255 participants (mean age 70.8 ±9.1 years, LVEF 66.3 ±8.3%), 44.3% were women. Poorer AOGLS was characterized by higher Gal-3 (B coefficient = -0.101, 95%CI [-0.167, -0.034], p = 0.003), mean age (B = -0.126, 95%CI [-0.154, -0.098], p <0.001), male sex (B = -0.991, 95%CI [-0.409, -1.572], p = 0.001), history of hypertension (B = -0.777, 95%CI [-1.364, -0.189], p = 0.010), diabetes mellitus (B = -0.888, 95%CI [-1.617,-0.158], p = 0.017), smoking (B = -1.346, 95%CI [-2.15, -0.542], p=0.001), pulse rate (B = -0.032, 95%CI [-0.055, -0.01], p = 0.005), systolic BP (B = -0.014, 95%CI [-0.025, -0.004], p = 0.009), and diastolic BP (B = -0.033, 95%CI [-0.06, -0.006], p = 0.018) on univariable linear regressions; no associations were observed with urine albumin-to-creatinine ratio, serum NT-ProBNP, or hs-Troponin I. After multivariable adjustments for sex, age, significant cardiovascular risk factors (hypertension, diabetes, smoking), and pulse rate, the inverse relationship between Gal-3 and AOGLS (Figure 1) persisted (B = -0.071 95%CI [-0.135, -0.008], adj. p = 0.028, R2 = 0.217). The association between Gal-3 and AOGLS was more marked among women (Figure 2), compared to men. Among women, higher Gal-3 characterized women with poorer AOGLS (17.04 ±3.73 ng/mL vs 15.48 ±3.55 ng/mL p = 0.040) (B = -0.120, OR 0.887, 95% CI [0.787, 0.999], adj. p = 0.048), independent of age. Conclusions Galectin-3 was adversely associated with novel CMR-derived AOGLS. Among these older adults with age-associated observations in AOGLS, Gal-3 highlighted sex-based differences in AOGLS and differentiated women with poorer AOGLS from women with better AOGLS. Serum Gal-3 measurements may be useful for detecting adverse patterns of aortic aging, particularly as an early approach in community older adults.

Peak oxygen pulse response during maximal cardiopulmonary exercise testing on a treadmill: applicability analysis of the FRIEND registry prediction equation in a Brazilian healthy sample

Abstract Background Peak oxygen uptake (VO2peak), measured by cardiopulmonary exercise test (CPET), is an established variable for prognostic assessment. Other VO2peak-derived variables, such as the peak oxygen pulse (peakO2pulse), also provide valuable information for risk stratification in patients with cardiac diseases. For individualized assessment, the measured peakO2pulse can be compared to reference standards using predictive equations, such as the FRIEND Registry [peakO2pulse = 23.2 – (0.09 × Age) – (6.6 × Sex (female:1; male: 0)]. However, the applicabilty of this equation in a Brazilian population sample has never been evaluated. Purpose To conduct an external validation of the FRIEND registry prediction equation for treadmill peakO2pulse in a sample of healthy Brazilian individuals. Methods Cross-sectional study involving subjects assessed by treadmill CPET in the Brazilian Midwest region from January 2011 to March 2020. Inclusion criteria: healthy individuals aged ≥ 20 years with a peak respiratory exchange ratio ≥ 1.00. Exclusion criteria: history of cardiovascular or pulmonary disease, presence of cardiovascular risk factors (hypertension, diabetes mellitus, current smoking, and obesity), and abnormalities on CPET. Variables were described as median and interquartile range (IQR). Statistical comparisons between measured and predicted values were conducted using the Wilcoxon signed rank test, including the calculation of the median differences and the 95% confidence interval (CI). Furthermore, Bland-Altman agreement analysis was utilized to assess the concordance between measured and estimated values. Results A total of 7,843 CPETs were performed. After applying inclusion and exclusion criteria, 3,544 assessments were included (1,574 females and 1,970 males) aged between 20 to 80 years. In the females, the median and IQR of measured peakO2pulse and predicted values were 10.4 (9.0; 12.1) and 13.1 (12.3; 13.7) ml/beat, respectively. This difference was statistically significant (p < 0.001), with a median difference of 2.54 mL/beat (95% CI: 2.40; 2.69). For males, the measured and predicted values were 17.3 (15.1; 19.7) and 19.7 (19.0; 20.2) ml/beat, respectively. The median difference was statistically significant at 2.26 mL/beat (95% CI: 2.11; 2.46) (p < 0.001) (Figure 1). Bland-Altman agreement analysis indicated a bias of 2.33 mL/beat (95% limits of agreement: -2.17 to 6.83) in females and 2.15 mL/beat (95% limits of agreement: -4.34 to 8.65) in males (Figure 2). Conclusions The study reveals that measured median peakO2pulse values are consistently lower than predicted across both sexes, highlighting a significant bias, which limits the applicability of the FRIEND registry prediction equation in the Brazilian population and underscores the international heterogeneity of the variable. The findings advocate for the development of region-specific reference standards to enhance accuracy in predicting peakO2pulse values.

Concomitant cardiac arrest on cardiogenic shock patients. Differences in clinical profile and outcomes with non-cardiac arrest patients. The Shock CAT Study

Abstract Background Mortality on cardiogenic shock (CS) remains undesirable, although CS patients with or without concomitant CA may have different prognoses and clinical profile. Purpose The aim is to analyse differences in clinical profile, management, in-hospital prognosis and mid-term mortality in CS patients with and without cardiac arrest on admission in a Mediterranean cohort. Method Shock CAT study was a multicentre, prospective, observational study conducted between December 2018 and December 2019 in eight public University hospitals in Catalonia (Spain), including CS patients of different aetiologies. Data on clinical presentation, biomarkers, management, including mechanical cardiac/circulatory support (MCS), in-hospital and 6 months mortality were analysed comparing patients with and without CA at admission. Results A total of 382 CS patients (p) were included: CA 34.8% (n=133 p) and non-CA 65.2% (n=249 p). CA patients were younger than non-CA (61.9 vs 67.4 years, p<0.001) with higher prevalence of men (82% vs 71.8%, p= 0.024). Acute coronary syndrome was the main CS cause (60.7%) and ST elevation myocardial infarction (STEMI) was higher in CA patients than non-CA (55.6% vs 42.6%, p<0.001). In CA group, time to recover of spontaneous circulation was 24 min (IQR: 14-40 min) and hypothermia was performed in 55% of cases. CA patients had less prevalence of cardiovascular risk factors (hypertension, diabetes and dyslipidaemia) and lower pH at admission (7.19 vs 7.31, p<0.001) and higher lactate peak (6.9 vs 5.0, p=0.001) than non-CA patients. MCS was implanted in 35.3% of all CS patients, with lower use in CA patients (23.3% vs 41.8%, p<0.001), mainly due to lower intraaortic balloon pump (19.5% vs 35.5%, p=0.001), without differences in the use of extracorporeal membrane oxygenation (ECMO) (11.4% vs 8.7%, p=0.40) or Impella (10.6% vs 12.8%. p=0.54). Cardshock score was higher in CA patients than non-CA (4.68 vs 4.2, p=0.038), without differences in IABP score (2.31 vs 2.20, p= 0.621) or SCAI D/E (42.1% vs 33.3%, p= 0.090). In-hospital mortality was higher in CA patients (42.9% vs 27.7%, p=0<0.001). Moreover, 6-months mortality remains higher in CA than non-CA patients, although without statistical significance (47.7% vs 38.3%, p=0.079). Conclusions In a Mediterranean CS cohort, concomitant CA patients were younger, with higher prevalence in men with STEMI. MCS had a lower used in CA patients, although without differences in ECMO or Impella. In-hospital mortality was 35% higher in CA patients than non-CA, although 6-months mortality only trend to be higher in CA group.

Efficacy and tolerability of triple sequential combination therapies with selexipag in patients with pulmonary arterial hypertension: insights from a single-centre study

Abstract Background and aims In this single-centre study we aimed to evaluate the efficacy and tolerability of prostacyclin receptor agonist selexipag in patients with pulmonary arterial hypertension (PAH). Methods The study included 110 out of the 1071 patients enrolled in the Evaluation of Pulmonary Hypertension Risk factors Associated with Survival study (EUPHRATES) and treated with selexipag added on background dual PAH therapies. The ESC/ERS 2022, SPAHR, French Registry, COMPERA 2.0 and REVEAL lite 2 models were used for risk predictions. Results Age (mean+SD) was 43.4+16.5 years and 84.5 % of patients were female. The PAH was idiopatic, and was associated with congenital heart disease (CHD), connective tissue disease (CTD) and drug in 47.2 %, 46.4 %, 5.5 % and 1 %, respectively. Background dual therapies, functional class (FC) was II, III and IV in 20 %, 65 %, and 15 % of patients. Six-minute walk distance (6MWD) was 314 + 134 m and serum N-terminal-pro-brain natriuretic peptide (NT-proBNP) level was 882+1732 ng/l. Tricuspid annular planary excursion (TAPSE) and tissue velocity (St), right atrial area and pulmonary arterial diameter were 2.02+0.48 cm,12.4+2.8 cm/sec,21.4+7.2 cm2 and 3.54+0.77 cm, respectively. Invasively evaluated pulmonary arterial mean pressure was 60.2±19.9 mm Hg, and pulmonary vascular resistance was 12.3±10.8 Wood units. COMPERA 2.0 1st, 2nd, 3rd and 4th risk strata were noted in 15.5 %, 31.8 %, 2.7 % and 10 %, and French Registry strata 0,1,2 and 3 were documented in 70 %, 14.5 %, 11 %, and 4.5 %, respectively. The SPAHR and REVEAL Lite 2 scores were 1.9+0.5 and 5.9+2.6, respectively. Background combinations were as follows; macitentan+tadalafil in 46.6 %, macitentan+sildenafil in13.6 %, macitentan+ riociguat in 6.8 %, bosentan +tadalafil in 8.7 %, bosentan+sildenafil in 16.5 %, bosentan+riociguat in 1 %, ambrisentan +tadalafil in 1.9 %, and ambrisentan+sildenafil in 2.9 % of patients. Maximally tolerable selexipag doses (ug)were 1600 bid in 21%, 1400 bid in 5 %, 1200 bid in 11%, 1000 bid in 17%, 800 bid in 12%, 600 bid in 9%, 400 bid in 14%, and 200 bid in 11%.Median follow-up period was 527( 278-831) days, and discontiuation rates of selexipag was 13.6 %. Headache, jaw-pain, diarrhoea, nausea, vomiting and flushing were main side effects. The changes in FC, 6MWD, Nt-pro-BNP and echocardiographic measures were not significant. French Registry score (p<0.001) and COMPERA 2.0 score (p<0.001) showed improvements, but SPAHR and REVEAL lite 2 did not. However, other PAH cohort compared with IPAH showed more pronounced improvements in REVEAL lite 2 and SPAHR scores. Clinical worsening and mortality rates were 23.6 % and 10.9 %, respectively. Survival for 1, 3 and 5 years were 95.8 %, 95.8 and 83.7 % in IPAH, and 92.6 %, 84.1 % and 78.8 % in other PAH patients. Conclusion Our results seem to be consistent with efficacy and tolerability of selexipag-included combinations in patients with PAH.

Changing patterns in clinical, echocardiographic and haemodynamic characteristics, and management strategies that may be translated to improved survival in pulmonary hypertension

Abstract Background and aims In this retrospective analysis of a single-center series on pulmonary hypertension (PH), we aimed to evaluate clinical, echocardiographic, and hemodynamic characteristics, management strategies, morbidity, and mortality in PH subgroups across three consecutive periods. Methods The study included 1071 patients enrolled in the Evaluation of Pulmonary Hypertension Risk factors Associated with Survival study (EUPHRATES). In reference to enrollment time, patients were assessed in three periods ; before 2016, the era of primarily monotherapy or sequential combinations; between 2016 and 2019, post-approval and reimbursement of macitentan in our country, marking a shift towards more proactive sequential combinations; and after 2019, signifying the initiation of earlier sequential combinations with selexipag in pulmonary arterial hypertension (PAH). The ESC/ERS 2022 risk scoring, COMPERA 2.0 and REVEAL lite 2 models were used for risk predictions. Composite endpoint (CEP) definitions were adopted from the SERAPHIN and GRIPHON trials. Annual incidence curves for mortality and CEP were evaluated, but 2020 analysis was adjusted to account for the possible adverse effects of the COVID-19. Results During the 1st, 2nd and 3rd periods, 481, 352, and 238 patients with PH were diagnosed, respectively. Incident cases comprised 91% of them. Idiopathic PAH (IPAH), PAH-associated with congenital heart diseases (CHD-PAH), PAH-associated with connective tissue diseases (CTD-PAH), group II, III, IV and V PH were documented in 24 %, 28 %, 4.6 %, 4.3 %, 11%, 27 % and 0.7 % of patients, respectively. Age and female dominance remained unchanged. Incidences of Group 1 PH and CHD-PAH decreased while IPAH, drug-associated PAH, and Group II and IV PH increased across three periods (p-values varying from <0.001 to 0.03). Although baseline functional class became worse (p=0.013), six-minute walk distance, N-terminal pro brain natriuretic peptide and risk scores showed no change (p=NS). Baseline echo and hemodynamic measures became better, and triple combinations increased after 2019 (p<0.001 for all). For overall PH, rates of all-cause mortality and CEPs at 1st, 2nd and 3rd periods were 52 % and 59 %, 30 % and 35 %, and 11 % and 13 %, respectively (p< 0.001, for all). Mortality rates for 1st, 2nd and 3rd periods were 36 %, 38 % and 26 % in IPAH, 60 %, 28 % and 13 % in CHD-PAH, 55 %, 22% and 22% in CTD-PAH, 38 %, 38% and 24 % in group IV PH, respectively (p< 0.001, for all). Mortality curves showed sudden increases in 2020, but excluding 2020, a steady improvement in the annual mortality was evident. Conclusions Our findings suggest a trend towards better clinical, echocardiographic, and hemodynamic presentations and improved survival in the PAH subgroups, and Group IV PH across the three periods that might be attributed to more proactive management strategies favouring earlier initiation of combinations.

Risk factors of pediatric steroid-induced ocular hypertension.

Steroid-induced ocular hypertension (SIOH) is a significant ocular complication of pediatric steroid administration. In this study, we analyzed the risk factors associated with pediatric SIOH. We retrospectively collected data from 78 children under 20 years of age who received systemic steroids during hospitalization. The data included age, gender, primary disease, intraocular pressure (IOP) before and one month after administration, total monthly steroid dose adjusted for body weight (BW), and one-month changes in red blood cell, white blood cell, and platelet counts. A multivariate analysis was used to identify risk factors related to steroid responsiveness. Thirty patients (38.5%) were classified as steroid responders, and 48 as non-responders. The median IOP during the first month of steroid treatment was 24.0 mmHg (IQR; 23.0-28.3) for responders and 15.0 mmHg (IQR; 12.3-18.0) for non-responders. The Generalized Estimating Equations analysis revealed that younger age, male sex, primary disease, increase the amount of white blood cell (WBC) and total steroid dose per BW in one month were independently associated variables. The receiver operating characteristic analysis also revealed that the cutoff values for age, total monthly steroid dose, the increase amount of WBC were 11.0 years, 40.7mg/kg and 3.40 × 10²/µl respectively. High-dose steroid administration, especially in male, younger patients, necessitates careful monitoring for IOP changes during treatment. WBC count also needs to be monitored during IOP follow-ups. What is known Steroid-induced ocular hypertension (SIOH) is one of the essential complicationsduring steroid administration,but onlylimited analyses have been performed in children. What is new A comprehensive analysis of multiple factors was performed that are predicted to be associated with pediatric SIOH from previous literature. Younger age, male sex, primary disease, increase the amount of WBC, and highertotal monthly steroid dose were extracted as risk factors of SIOH. This study can contribute to the prediction of cases in which ophthalmologic examinations are particularly important during systemic steroid administration in children.

Clinical risk factors of bevacizumab-related hypertension in patients with metastatic colorectal cancer: a retrospective study.

Bevacizumab, a vascular endothelial growth factor (VEGF) inhibitor, is widely used as a first-line treatment for metastatic colorectal cancer (mCRC), with hypertension being a common adverse effect. However, there is limited data on the predisposing factors contributing to bevacizumab-induced blood pressure (BP) elevation. This study aims to identify clinical risk factors associated with bevacizumab-related hypertension in patients with mCRC. This retrospective study included 178 patients treated between January and June 2020. Demographic data and medical histories were extracted from hospital electronic medical records. Among the 178 patients, 54 (30.3%) developed bevacizumab-related hypertension, with a median onset time of 48days. Univariate and multivariate analyses identified pre-existing hypertension [odds ratio (OR), 3.30; 95% confidence interval (CI), 1.56-6.99] and age ≥60years (OR, 2.04; 95% CI, 1.00-4.17) as independent risk factors for bevacizumab-related hypertension. The area under the receiver operating characteristic (ROC) curve was 0.66 (95% CI, 0.57-0.75, P < 0.001). The median overall survival (OS) for the cohort was 30.53months (95% CI, 22.23-38.84). No significant differences in OS were observed between patients with and without bevacizumab-related hypertension (31.13 vs. 27.87months, P = 0.86). Pre-existing hypertension and age ≥60years are significant clinical risk factors for bevacizumab-related hypertension in mCRC patients. Bevacizumab-related hypertension did not affect overall survival. Clinicians should closely monitor BP within the first 2months of bevacizumab treatment in high-risk patients.

Abnormal blood pressure among individuals evaluated for tuberculosis infection in a U.S. public health tuberculosis clinic.

Tuberculosis infection (TBI) has been associated with increased cardiovascular risks. We aimed to characterize abnormal blood pressure (BP) readings in individuals with TBI. We conducted a retrospective study of adults with TBI presenting for their initial medical visit at a large midwestern U.S. public health clinic between 2019 and 2020. Abnormal BP was defined as having a systolic BP≥130mmHg and/or a diastolic BP≥80mmHg. Of 310 individuals with TBI, median age was 36years (interquartile range 27-48), 34% were male, 64% non-US-born; 58 (18.7%) were previously diagnosed with hypertension. The prevalence of any hypertension (i.e., had a history of hypertension and/or an abnormal BP reading) was 64.2% (95% confidence interval 58.7-69.4). Any hypertension was independently associated with older age, male sex, higher body mass index, and individuals of Black race. In conclusion, any hypertension was present in over half of the adults evaluated for TBI in our clinic. Established hypertension risk factors were also common among this group, suggesting that individuals with TBI could benefit from clinical and public health interventions aiming to reduce the risk of future cardiovascular events.

Secondhand smoking increased the possibility of hypertension with a significant time and frequency dose-response relationship

In this research, we investigated whether secondhand smoking (SHS) increases the possibility of hypertension. We used data from the Shaanxi baseline survey of the Regional Ethnic Cohort Study in Northwest China (RECS). Active smoking and SHS were determined by questionnaires. Hypertension was defined as self-reported or objectively measured. Multivariable logistic regression model was performed to estimate the risk of hypertension under active smoking and SHS. Compared to never-smokers, exposure to SHS had a 9% (P = 0.005) higher possibility of hypertension. The adjusted OR for exposure time of ≤ 3 h/week, 3–12 h/week, and > 12 h/week were 1.03 (P = 0.545), 1.10 ( P = 0.040), and 1.15 (P = 0.015), respectively. The adjusted OR for frequency of SHS of 1–2 times/week, 3–5 times/week, and nearly every day were 0.94 (P = 0.421), 1.01 (P = 0.846), and 1.14 (P < 0.001), respectively. Compared to smokers, additional exposure to SHS had a more than threefold increased possibility of having hypertension. The adjusted OR for hypertension was 1.07 (P = 0.254), and 1.23 (P = 0.007) in only smokers and smokers with SHS, respectively. Our study provided evidence that SHS could be a risk factor for hypertension, and additional exposure of active smokers to SHS significantly increases the possibility of hypertension. Reducing the frequency or time of SHS may be effective in preventing hypertension.

Automated quantification of cerebral microbleeds in susceptibility-weighted MRI: association with vascular risk factors, white matter hyperintensity burden, and cognitive function.

To train and validate a deep learning (DL)-based segmentation model for cerebral microbleeds (CMB) on susceptibility-weighted MRI; and to find associations between CMB, cognitive impairment, and vascular risk factors. Participants in this single-institution retrospective study underwent brain MRI to evaluate cognitive impairment between January-September 2023. For training the DL model, the nnU-Net framework was used without modifications. The DL model's performance was evaluated on independent internal and external validation datasets. Linear regression analysis was used to find associations between log-transformed CMB numbers, cognitive function (mini-mental status examination [MMSE]), white matter hyperintensity (WMH) burden, and clinical vascular risk factors (age, sex, hypertension, diabetes, lipid profiles, and body mass index). Training of the DL model (n = 287) resulted in a robust segmentation performance with an average dice score of 0.73 (95% CI, 0.67-0.79) in an internal validation set, (n = 67) and modest performance in an external validation set (dice score = 0.46, 95% CI, 0.33-0.59, n = 68). In a temporally independent clinical dataset (n = 448), older age, hypertension, and WMH burden were significantly associated with CMB numbers in all distributions (total, lobar, deep, and cerebellar; all P <.01). MMSE was significantly associated with hyperlipidemia (β = 1.88, 95% CI, 0.96-2.81, P <.001), WMH burden (β = -0.17 per 1% WMH burden, 95% CI, -0.27-0.08, P <.001), and total CMB number (β = -0.01 per 1 CMB, 95% CI, -0.02-0.001, P = .04) after adjusting for age and sex. The DL model showed a robust segmentation performance for CMB. In all distributions, CMB had significant positive associations with WMH burden. Increased WMH burden and CMB numbers were associated with decreased cognitive function. CMB = cerebral microbleed; DL = deep learning, DSC = dice similarity coefficient; MMSE = mini-mental status examination; SVD = small vessel disease; SWI = susceptibility-weighted image; WMH = white matter hyperintensity.

Hypertension prevalence among the male population aged 35-74 years in Novosibirsk

Aim. To study the prevalence and risk factors of hypertension (HTN), structure and effectiveness of treatment coverage, as well as disease control indicators among the male population aged 35-74 years in Novosibirsk.Material and methods. This cross-sectional study of the Novosibirsk population was conducted in 2021-2023 at the Research Institute for Internal and Preventive Medicine — branch of the Federal Research Center Institute of Cytology and Genetics according to the ESSE-RF3 study protocol. A total of 1200 people aged 35-74 years living in Novosibirsk were examined. The analysis included 600 men. The response rate exceeded 70%. HTN was considered detected in systolic blood pressure (BP) ≥140 mm Hg and/or diastolic BP ≥90 mm Hg and/or in patients taking antihypertensive agents. Awareness was estimated as the proportion of individuals who had previously been informed by a physician about HTN. Treatment effectiveness was considered the proportion of individuals who achieved target BP values while taking antihypertensive therapy. Hypertension control was considered the proportion of individuals who achieved target values among all those examined with HTN. Statistical processing was performed using the SPSS software package (version 13.0). Associations were assessed using multiple logistic regression analysis. The critical significance level of the null hypothesis (p) was 0,05.Results. The medians of systolic and diastolic BP among men in No­vo­sibirsk were 136,0 [126,5; 149,5] and 89,0 [82,0; 95,5] mm Hg, respectively. The prevalence of HTN among men aged 35-74 in Novo­sibirsk was 68,9%, while 81,1% of men in Novosibirsk were aware of HTN. Among men with HTN, 54,7% take antihypertensive agents. The effectiveness of treatment among men in Novosibirsk is 32,3%, while 19,6% of men control the disease. The odds of hypertension occurrence in men with hypertriglyceridemia increased by 3,5 times, with abdominal obesity — by 2 times, with an positive family history for cardiovascular diseases — by 1,6 times, and with each year of life increased by 1,1 times.Conclusion. The prevalence of HTN among men in Novosibirsk is higher in comparison with the average Russian level. Significant risk factors for HTN include abdominal obesity, hypertriglyceridemia, and decreased physical activity. While awareness, treatment coverage, and HTN control among men aged 35-74 in Novosibirsk correspond to Russian trends, treatment effectiveness turned out to be slightly lower than in the Russian population.

The effect of cpap therapy on blood pressure in the mild obstructive sleep apnea population

This retrospective study uniquely focused on the effects of continuous positive airway pressure (CPAP) on blood pressure in patients with mild obstructive sleep apnea (OSA), a condition characterized by intermittent upper airway collapse. OSA is a well-established risk factor for hypertension, with positive airway pressure (PAP) therapy being the most common treatment. While substantial evidence supports PAP therapy in moderate and severe OSA, the impact of CPAP on mild OSA, which accounts for 50%-70% of all cases, remains underexplored. The primary objective of this study was to investigate whether CPAP therapy, particularly the degree of adherence to treatment, has a measurable impact on blood pressure regulation in patients with mild OSA. Specifically, this research aimed to evaluate whether consistent CPAP use could lower systolic and diastolic blood pressure and assess how varying levels of adherence influence these outcomes. Participants were stratified into two groups based on CPAP adherence: Group A (n = 45) included those who used CPAP for four or more hours per night on at least 70% of nights, while Group B (n = 15) consisted of those with less than four hours of CPAP use per night on 70% of nights. Interestingly, greater systolic and diastolic blood pressure reductions were observed in Group B, suggesting that lower CPAP adherence may still contribute to significant cardiovascular improvements. These findings offer new insights into the management of blood pressure in patients with mild OSA and the role of CPAP adherence.

Sex-specific associations between body mass index trajectories and risk of hypertension

BackgroundAlthough it is well established that obesity is a risk factor for hypertension, the effect of distinct long-term patterns of body mass index (BMI) on blood pressure (BP) in later life is poorly understood.MethodsBased on the China Health and Nutrition Survey, we analyzed 2920 participants aged 3–17 years with initial normal BP at baseline (1991–2011), who were followed up for the development of hypertension (1993–2015). The group-based trajectory model was applied to identify BMI trajectories, and Cox regression was used to assess their associations with hypertension risk. Stratified analyses were conducted to explore differences across subgroups.ResultsDuring an average follow-up time of 11.20 (7.69) years for males and 7.20 (5.21) years for females, 339 males and 212 females were identified with hypertension, respectively. Three BMI trajectories were identified: low-increasing (60.58% of males and 73.03% of females), moderate-increasing (33.08% of males and 24.22% of females), and high-increasing (6.34% of males and 2.76% of females). Our study found a significant positive association between a higher BMI trajectory and hypertension risk in males (all P for trend < 0.05). Specifically, males in the high-increasing BMI group had a higher risk of hypertension compared with those in the low-increasing group (HR = 1.76, 95% CI: 1.04–2.97). Stratified analyses revealed stronger associations among smokers, drinkers, and inactive individuals.ConclusionOur findings suggest that maintaining a normal BMI and healthy lifestyle from childhood may lower subsequent risk of hypertension.

The effect of results-based motivating system on metabolic risk factors of non-communicable diseases: A field trial study.

Non-communicable diseases can be controlled and managed by reducing their associated metabolic risk factors. In this study, a set of intervention packages were designed to reduce the prevalence of three common metabolic risk factors (hypertension, hyperlipidemia, and obesity and overweight) in the community by motivating non-physician health workers. A field trial study was conducted in 4 districts of Iran. Thirty-two community health centers were randomly selected. A survey of 30 to 70-year-old was conducted to measure baseline metabolic risk factors. The intervention packages focused on improving hypertension, hyperlipidemia, obesity and overweight. The interventions included goal-setting, evidence-based education, operational planning, and incentive payments for non-physician health workers. A second survey to measure the final metabolic risk factors was performed after one year. The difference-in-difference method was used to evaluate the effectiveness of the intervention packages. The average age of participants in both surveys was 49 years. The interventions had statistically significant effects only on decreasing the prevalence of overweight and obesity. The package with all the interventions except pay-for-performance decreased the odds of overweight and obesity to 0.57 (95% CI: 0.34, 0.95). Involving non-physician health workers and having action plans based on the health needs of the covered population can decrease obesity and overweight in the community. However, longer trials are needed to observe the effects on hypertension and hyperlipidemia.