bluuebunny/crossref_metadata_2025 huggingface dataset:
Contribution of TNF-R1 to reduced exercise capacity in hypertensive heart disease. Mediating role of left atrial mechanical function reserve
Authors: Kosowski W , Zachwyc J , Woznicka A K , Mysiak A , Przewlocka-Kosmala M , Ponikowski P , Kosmala W
Published: November 2023

Background

Tumor necrosis factor alpha (TNF-alpha) plays a relevant pathophysiological role in cardiovascular disorders, including hypertensive heart disease (HHD) – a clinical condition frequently contributing to the development of heart failure with preserved ejection fraction (HFpEF). TNF receptor 1 (TNF-R1) has been found to mediate proinflammatory and proapoptotic effects of TNF-alpha, and its soluble circulating form proved to be effective in predicting incident HF. Existing evidence indicates the association between TNF pathways activation and cardiac dysfunction, but exact mechanisms mediating this link are unclear.

Objectives

We sought to investigate the association of TNF-R1 with exercise capacity, and left ventricular (LV) and left atrial (LA) function reserve in asymptomatic patients with HHD.

Methods

We enrolled 80 (55±12 yo) patients with HHD and normal exercise tolerance (stage A and B HF). Echocardiography (including LA and LV strain assessment) was performed at rest and immediately post exercise test. Blood samples for TNF-R1 were drawn in fasting conditions. Exercise reserve of cardiac function parameters was calculated by subtracting resting value from exercise value.

Results

The study population was categorized into 2 subsets using a median value of exercise capacity (9.2 METs). Patients with higher exercise capacity were characterized by lower TNF-R1 concentrations and higher LA reservoir and LA contractile strain reserves (Table). No significant intergroup differences were found for exercise reserves in LV ejection fraction (LVEF), LV global longitudinal strain and diastolic parameters (e’ and E/e’). TNF-R1 significantly correlated with peak atrial longitudinal strain (PALS) and peak atrial contraction strain (PACS) reserves (r=-0.27; p<0.02 and r=-0.24; p<0.04, respectively), but not with LVEF, global longitudinal strain (GLS), e’ and E/e’ reserves. Regression-based mediation analysis revealed that the relationships between TNF-R1 and exercise capacity were mediated by PALS and PACS reserve, as evidenced by the reduction in variance of exercise capacity (METs) explained by TNF-R1 after the inclusion of PALS and PACS reserve to the models (decrease in beta coefficient from -0.24 to -0.19 for PALS, and to -0.20 for PACS, Figure).

Conclusions

In patients with HHD, higher TNF-R1 is associated with lower exercise capacity, and this relationship may be mediated by lower LA strain reserve. This finding may contribute to elucidating the mechanisms behind the involvement of the left atrium in HF progression.Mediation analysis
Sympathetic nerve activity reactivity is associated with cardiac fibrosis in humans
Authors: Blythe H , Adams Z H , Hope K A , Baker R P , Sheikh A A , Suleiman M S , Nightingale A K , Hart E C
Published: November 2023

Background

Hypertension causes cardiac remodelling and left ventricular hypertrophy (LVH) in some individuals but not others [1-3]. 90% of people with heart failure preserved ejection fraction (HFpEF) have hypertension. One possible mechanism is increased sympathetic drive resulting in cardiac fibrosis. Resting sympathetic nerve activity (SNA) is associated with cardiac remodelling in both animals and humans and progressively increases from hypertension to LVH to HFpEF.

However, humans are not in a constant rested state, and are frequently exposed to multiple physiological stressors throughout the day, resulting in surges in SNA. Amplified SNA reactivity to stressors may contribute to cardiac remodelling more than elevated resting SNA levels, as intermittent β-adrenergic receptor stimulation with isoprenaline in mice has been shown to cause more severe cardiac fibrosis when compared to a sustained isoprenaline administration [4].

Purpose

To determine whether resting SNA and/or SNA reactivity to a physiological stressor (cold pressor test) were associated with cardiac fibrosis in humans.

Methods

Nineteen (10M, 9F; 48 ± 13 years; BMI: 25.9 ± 3.2 kg/m²) participants with varying ambulatory blood pressures (SBP: 126±13 mmHg, DBP: 83±8 mmHg, SBP range: 111-153 mmHg, DBP range: 68-96 mmHg), provided written informed consent. Blood pressure (Finometer), heart rate (ECG) and muscle SNA (peroneal microneurography) were recorded simultaneously during a 5-minute baseline, and a 2-minute rest, 3-minute cold pressor test (3-4°C) and 5-minute recovery. Cardiac extracellular volume (ECV) was measured using magnetic resonance imaging (1.5T Avanto, Siemens) as an index of cardiac fibrosis. Simple linear regressions were conducted between baseline SNA and ECV, and change in SNA from rest to peak cold pressor test and ECV using SPSS.

Results

Resting SNA was not associated with ECV. However, the absolute change in SNA burst incidence (bursts/100 heartbeats) and burst frequency (bursts/minute, Figure 1) from rest to peak cold pressor test, were positively associated with ECV, showing that the greater the SNA response to a stressor, the higher the ECV. Specifically, for every 1 burst/100 heartbeat increase in burst incidence (from rest to peak cold pressor test), ECV increased by 0.120%, and for every 1 burst/minute increase in burst frequency (from rest to peak cold pressor test), ECV increased by 0.128%.

Conclusion

SNA reactivity but not resting SNA level was found to be a predictor of ECV, where the greater the SNA response to a stressor, the higher the ECV. This indicates that intermittent surges in SNA may be more important for promoting cardiac fibrosis than the overall level of resting SNA in humans.Figure 1.
Plasma aldosterone concentration / plasma renin activity ratio in patients with essential hypertension before treatment
Authors: Nakayama M , Miyamoto Y , Morimoto T , Arima Y , Tsujita K
Published: November 2023

Background

The renin–angiotensin–aldosterone-sodium system, an important player in maintaining blood pressure, is influenced by antihypertensive drugs. However, the analysis of the renin-aldosterone-sodium system in hypertensive patients without adrenal adenoma without antihypertensive drugs is not still enough.

Purpose

We analyzed plasma aldosterone level, renin activity, serum potassium level, and serum sodium level in hypertensive patients without adrenal adenoma before treatment.

Methods

We measured plasma aldosterone concentration (PAC; pg/mL), plasma renin activity (PRA; ng/mL/h), serum potassium and sodium levels (mEq/L) in 456 consecutive new hypertensive patients untreated with antihypertensive drugs. We sampled all blood after 30 minutes bedrest. We excluded 28 cases with blood pressures less than 135/85 mmHg at rest, 4 patients with adrenal adenoma, and 3 patients with renovascular hypertension. We analyzed 421 patients with essential hypertension before treatment (232 males, mean age 56.5±12.8 years, and 189 females, mean age 61.0±13.5 years).

Results

There was a significant positive correlation between PRA and PAC (ρ=0.2445, p<0.001). There was a significant positive correlation between PAC/PRA ratio and serum sodium levels (ρ=0.1604, p=0.0027); however, no correlation was observed between PAC/PRA ratio and serum potassium levels. There were significant negative correlations between PRA and serum sodium levels (ρ=-0.1925, p<0.001). However, there was no correlation between PAC and serum sodium levels. On univariate analyses, a high PAC/PRA ratio (>200) was significantly associated with female (p<0.001), high serum sodium level (p=0.003), and low pulse rate (p=0.02). Multiple logistic analyses revealed that the most predictive independent factor for high PAC/PRA was female (p<0.001). On analyses of gender differences, the incidence rates of high PAC/PRA (>200) were 33.9% in females and 16.4% in males. There was a significant positive correlation between PRA and PAC in both genders (males: ρ=0.2731, p<0.001; females: ρ=0.1976, p=0.0064). In females, there was a significant positive correlation between PAC/PRA and serum sodium levels (ρ=0.2221, p=0.0043); however, there were no significant correlations between PAC/PRA and serum sodium levels in males. In females, there was a significant negative correlation between PRA and serum sodium levels (ρ=-0.2668, p<0.001); however, there were no significant correlations between PRA and serum sodium levels in males. Serum sodium levels were significantly higher in females than in males (p=0.02).

Conclusion

We revealed gender differences in the renin-aldosterone-sodium system in patients with essential hypertension before treatment.
Blood pressure and cardiovascular disease in Koreans with and without diabetes mellitus
Authors: Han S , Park S , Kim Y G , Park G M
Published: November 2023

Background

We sought to evaluate the association between blood pressure (BP) levels and development of cardiovascular diseases (CVDs) in Korean subjects with and without diabetes mellitus (DM).

Methods

Using the National Sample Cohort of Korea, we analyzed 272,736 subjects aged 20–80 years without previous CVDs who underwent regular health checks between 2009 and 2010. Subjects on anti-hypertensive medications were excluded. CVD was defined as a composite of cardiovascular death, myocardial infarction, and stroke. Participants were grouped by 10mm Hg intervals of systolic BP (SBP) (<110, 110-119, 120-129, 130-139, 140-149, 150-159, >160mmHg) and by 5mm Hg intervals of diastolic BP (DBP) (<70, 70-74, 75-80, 80-84, 85-90, 90-99, >100mmHg).

Results

The mean age of the study population was 44.5 ± 12.7 years and 144,179 (52.9%) were men. During the follow-up period (median 10.1 [interquartile range, 9.5–10.5] years), 2,715 subjects had 2,840 CVD events, namely, 952 cardiovascular deaths, 1,171 myocardial infarctions, and 717 strokes. In subjects without DM (n=250,302), compared with SBP <110 mmHg as the reference group, the risk of CVD significantly increased with increasing SBP groups (all p<0.05). On the other hand, in DBP groups analyses, only subjects with DBP >100 mmHg was associated with a significantly higher risk of CVDs compared with DBP <70 mmHg as the reference group. In subjects with DM (n=22,434), there was no increased risk of CVD among subjects with SBP 110-129 mmHg compared with SBP <110 mmHg, but SBP ≥130 mm Hg was associated with a significant increase in the incidence of CVDs. However, in DBP groups analyses, there was no significant association of incidence CVDs across DBP groups compared with DBP <70 mmHg.

Conclusions

In individuals without DM, those with SBP >110 or DBP >100mmHg have a significantly higher risk of CVD. However, in individuals with DM, those with SBP >130 mmHg was only associated with an increased risk of CVD. These results suggest that hypertension management could vary according to the presence of DM.
Association of pulse pressure with risk of major adverse cardiovascular events among cardiovascular outcome trial participants
Authors: Agarwal N , St Jean J , Van Iterson E H , Laffin L
Published: November 2023

Background

Hypertension is a well-established risk factor for the development for cardiovascular (CV) disease and accumulating evidence also implicates elevated pulse pressure (PP), a surrogate marker for arterial stiffness, as an independent risk factor for major adverse cardiovascular events (MACE).

Purpose

The study aimed to assess the association of PP with MACE among participants in multiple CV outcome clinical trials. It also aimed to determine if the presence of various CV comorbidities impacts the association between PP and MACE.

Methods

Adult patients between the ages of 19-98 years (n = 65,382, mean age 63) enrolled in five large CV outcome trials (ACCELERATE, STRENGTH, PRECISION, ALECARDIO, and LIGHT) with independently adjudicated clinical end points were identified. Baseline demographics, medical history, blood pressures, and CV medications were collected. Univariate and multivariate analyses were generated and analyzed for temporal trends, risk, and adjusted survival.

Results

Participants had a mean baseline blood pressure of 128 /76 mm Hg and a mean PP of 52 mm Hg. Forty-five percent were women, 31% had coronary artery disease, 51% had type 2 diabetes mellitus, 84% had hypertension, 25% had history of myocardial infarction (MI), and 35% had a history of an acute coronary syndrome. The composite MACE end point included CV death, myocardial infarction, or stroke and occurred in 3712 participants (5.7%).The composite end point of all cause death, myocardial infarction, and stroke occurred in 4513 participants (6.9%).

For every 10 mm Hg increase in PP there was an increased risk of MACE (unadjusted hazard ratio (HR) 1.20, 95% CI 1.17 to 1.23). Similarly, a PP > 60 mmHg demonstrated an unadjusted HR of 1.53 (95% CI 1.43 to 1.64) compared with PP < 60 mm Hg. Although increased PP was a risk factor in both men and women, every 10 mm Hg increase in PP was associated with higher risk of MACE in women (adjusted HR 1.17, 95%CI 1.17, 1.12 to 1.22) compared with men (adjusted HR 1.09, 95% CI, 1.05 to 1.12).

Table 1 displays the adjusted HR for patients grouped by race, history of prior CV disease, or the presence of CV risk factors (diabetes and chronic kidney disease.) While most subgroups demonstrated an increased risk of MACE with increasing PP, PP was not associated with MACE among individuals with a history of stroke (HR 1.00, 95% CI 0.92 to 1.08). Kaplan-Meier survival curves comparing PP greater than or less than 60 mm Hg are seen in Figure 1.

Conclusions

Among CV outcome clinical trial participants, with independently adjudicated end points, baseline PP is associated with an increased risk for future MACE. The association stands for most participant subgroups except for participants with a prior history of stroke.Table 1Figure 1
Systolic blood pressure visit-to-visit variability and outcomes in Asian patients with established or multiple risk factors for atherosclerotic cardiovascular disease: results from the CORE-Thailand
Authors: Chichareon P , Suwanugsorn S , Wongcharoen W , Phrommintikul A
Published: November 2023

Background

It is well established that high blood pressure is associated with poor outcomes in many cardiovascular conditions. However, blood pressure (BP) is dynamic and may have variation during the follow-up. We aimed to assess the association between the systolic and diastolic blood pressure visit-to-visit variability (BP-VVV) and outcomes in Asian patients with established or multiple risk factors for atherosclerotic cardiovascular disease (ASCVD) in the Cohort Of patients with a high Risk of cardiovascular Events (CORE).

Methods

The CORE registry was a nationwide study enrolling patients with established atherosclerotic cardiovascular disease or those with multiple risk factors (at least three atherosclerotic risk factors) between April 2011 and March 2014 in 25 hospitals. Patients in the CORE registry with blood pressure measurements in at least three visits were included in the present study. BP-VVV was defined as the standard deviation (SD) of average blood pressure. Patients were grouped into quintiles of the SD of BP. The primary outcome was major adverse cardiac events (MACE), defined as all-cause mortality, all stroke, or myocardial infarction. The associations between BP-VVV (systolic and diastolic) and outcomes were assessed in the adjusted Cox regression model. The adjusted variables included age, sex, body weight, diabetes, chronic kidney disease, current smoking, established ASCVD, and treatment with ACEI or ARB. Restrict cubic spline was used to assess the association between SBP-VVV as a continuous variable and MACE in the adjusted Cox model.

Results

Of the 8,886 patients in the present study, 4041 patients (45.5%) were female, with a mean age of 65.6 years. The prevalence of hypertension was 95.9%. The mean SBP at baseline was 133 mmHg. The proportion of patients with established ASCVD was 51.1%. The mean follow-up time was 45.1 months.

The Kaplan-Meier rate of MACE at five years was 15.8%. Spline analysis showed a J-curve association between SBP-VVV and MACE. The group with the highest SBP-VVV (the fifth quintile) had a significantly higher risk of MACE than the group with the lowest SBP-VVV (the first quintile) (adjusted hazard ratio 1.26, 95% CI 1.05-1.51). Compared with the group with the lowest SBP-VVV (the first quintile), the fifth quintile had a significantly higher risk of stroke, all MI, heart failure, and renal function deterioration. The risk of PAD and bleeding were similar among the quintiles.

Conclusion

SBP-VVV significantly impacted the long-term outcomes of Asian patients with established or multiple risk factors for ASCVD. Adequate SBP control and maintaining SBP stability over time may prevent adverse events in this population.SBP-VVV and MACE
First-in-human study for evaluating the accuracy of blood pressure measurement using the ring-type device with a photoplethysmography
Authors: Kim J , Park S W
Published: November 2023

Background

Early diagnosis of hypertension and optimal blood pressure (BP) control are important for prevention of cardiovascular morbidity and mortality. The 24-hour BP is better predictive of cardiovascular outcome than the office BP. However, conventional non-invasive BP measurement by sphygmomanometer has limitations in obtaining continuous BP and its variability in daily life. Recently, a ring-type BP measuring device, CART-I Plus (Sky Lab Inc, South Korea) without a cuff has been developed.

Purpose

This study was a prospective, single arm, first-in-human pivotal trial to evaluate accuracy of blood pressure measurement by the new device.

Methods

The ring-type smart wearable blood monitoring device measures photoplethysmography signals from the proximal phalanx and transmits the data wirelessly to the connected smartphone, to monitor the BP (Figure 1). A cuff was worn on arm to check the reference BP by auscultation, while the test device was worn on the finger of the opposite arm to check the test BP simultaneously. Measurements were repeated for up to three sets each on the left and right arms. The primary outcome measure was mean error and standard deviation of BP differences between the test device and the reference readings.

Results

The final analysis included 89 subjects, 47% of whom were male, with a mean age of 40.1 years. We collected 526 sets of systolic BP (SBP) and 513 sets of diastolic BP (DBP), with ranges of 80 to 175 mmHg and 43 to 122 mmHg, respectively. In sample-wise comparison (Figure 2), the mean error between the test device and the reference was 0.16 ± 5.90 mmHg (95% limit of agreements [LOA] -11.41 to 11.72) in SBP and -0.07 ± 4.68 (95% LOA -0.26 to 9.10) in DBP. The test device showed a good correlation with the reference for SBP (r=0.94, p<0.001) and DBP (r=0.95, p<0.001). In subject-wise comparison, the test device showed a good correlation with the reference for SBP (r=0.98, p<0.001) and DBP (r=0.98, p<0.001), with a mean error of 0.17 ± 3.67 mmHg (95% LOA -7.04 to 7.7) in SBP and 0.02 ± 3.21 mmHg (95% LOA -6.27 to 6.31) in DBP.

Conclusion

The new ring-type BP measuring device had a good correlation for SBP and DBP with minimal bias compared with a auscultation method. It has the potential to provide accurate BP in daily life.
Effect of arterial hypertension in cardiopulmonary status and right ventricle function after hospitalization for Sars-Cov-2
Authors: Kariori M , Fragoulis C , Chrysochoou C , Konstantinidis D , Leontsinis I , Andrikou I , Iliakis P , Mantzouranis E , Konstantinou K , Kalos T , Grigoriou K , Aggeli C , Thomopoulos C , Tsioufis K
Published: November 2023

Introduction

There is little data concerning the impact of SARS-Cov-2 infection on the cardiopulmonary status and right ventricle (RV) function of patients with arterial hypertension (HTN).

Purpose

The purpose of our study was to investigate whether hospitalization for COVID19 affects the functional status of hypertensive patients, using cardiopulmonary test and echocardiographic parameters, 3 months after the first day of infection.

Methods

All subjects underwent cardiorespiratory exercise using Bruce or modified Bruce protocol where all cardiorespiratory parameters were evaluated. Echocardiographic parameters including right ventricle longitudinal strain were analyzed using an offline program. Subjects with history of HTN were divided into two groups according to hospitalization for Covid-19 infection. Group I included 34 subjects who were hospitalized for Sars-Cov-2 infection and Group II included 28 subjects without need for hospitalization.

Results

Out of total population of 198 patients with COVID19 infection, sixty-two subjects were hypertensives (mean age: 61±10 years, 58.1 % males, history of coronary artery disease: 16.1%) who were evaluated 3 months after the symptoms onset. Of demographic characteristics in hospitalized patients, only age (63±8 vs. 52±11 years, p<0.001) was significantly higher. When analyzing cardiopulmonary test parameters, oxygen consumption (ml/kg/min) both maximum (21±4 vs. 23.5±4, p:0.01) and during the 1st minute of recovery (15.5±2 vs. 21±25, p: 0.02), VO2_AT (17±4 vs. 27.5±32) and PETCO2 (39±4 vs. 38±19 mmHg, p:0.03) were impaired comparing to non-hospitalized subjects. Out of echocardiographic parameters, diameter of left atrium (mm), differed significantly between two groups (41±6 vs.38±5 p: 0.02). The absolute mean value of right ventricle strain (RVLS, (%): 13±8 vs. 23±3, p:0.04) was impaired to hypertensives despite the fact that left ventricle ejection fraction was similar between two groups probably due to small sample size. Using linear regression analysis adjusted for age, gender, hospitalization, and LVEF, hospitalization (p: 0.001) proved to be independent predictive factor for RVLS in hypertensive patients.

Conclusion

To conclude our study highlighted negative impact of hospitalization for Sars-Cov-2 infection in the capacity for exercise and in right ventricle functionality, implying the severity of disease as a negative independent predictive factor in hypertensive patients.
Efficacy and safety of perindopril/indapamide/amlodipine single-pill combination in essential hypertension
Authors: Wang J , Bricout S , Zhu H , Li X , Zhang X , Sun Y , Zhao X , Li Z , Zhao R , Sun Y , Yao Z , Li H , Lu W , Jiang Y , Han Q
Published: November 2023

Background

In hypertensive patients uncontrolled with dual therapy, perindopril, indapamide and amlodipine triple therapy form one of the core drug treatments recommended by the latest European (ESC/ESH 2018) and International (ISH 2020) Guidelines, ideally used as single-pill combination (SPC) to improve adherence to treatment.

Purpose

To assess efficacy and safety of the SPC of Perindopril arginine 5 mg/Indapamide 1.25 mg/Amlodipine 5 mg (P5/I1.25/A5) compared to the free combination of Perindopril tert-butylamine 4 mg/Indapamide 1.25 mg (P4/I1.25) plus Amlodipine 5 mg (P4/I1.25 +A5) and of the titration to higher doses up to P10/I.2.5/A10 for SPC and P8/I.2.5+A10 for free combination, in patients with essential uncontrolled hypertension.

Methods

A randomized, double-blind, controlled, 7-month phase III study in hypertensive Asian patients uncontrolled with dual therapy (Systolic Blood Pressure (SBP) ≥140 and <180mmHg and Diastolic Blood Pressure (DBP) ≥90 and <110 mmHg). After a 1-month run-in period on P4/I1.25, patients were randomized to a 6-month parallel group period to receive the triple therapy either as SPC (P5/I1.25/A5) or as free combination (P4/I1.25+A5), potentially up-titrated to higher doses after 2 and 4 months if BP remained uncontrolled.

Results

532 patients (mean SBP/DBP 150.4/97.2 mmHg, mean age 56 years) were randomized to receive SPC or free combination.

After 2 months of randomized treatment, a large decrease in office SBP/DBP was observed in both the SPC (-15.0/-8.6mmHg) and the free combination group (-14.5/-8.7mmHg). The SBP-lowering effect of the SPC was shown to be non-inferior to the free combination (study primary endpoint, p<0.001). In patients uncontrolled on SPC after 2 and 4 months, titration to P10/I2.5/A5 then to P10/I2.5/A10 (in 46.1 and 17.6% patients in SPC group, respectively) led to additional SBP/DBP decrease (-9.0/-5.9 mmHg and -6.1/-3.6 mmHg, respectively). After 6 months, 64.4% of patients reached BP control. ABPM data corroborated these findings. Similar results were observed in the free combination group.

Over the 6-month randomized period, treatments were well tolerated, even at the highest doses of the SPC. The most frequently reported treatment-related adverse events were those already described for indapamide, perindopril and amlodipine, i.e., hyperuricemia, hypokalemia and cough, and were observed with a similar frequency in both groups. Peripheral edema and hypotension or orthostatic hypotension remained low.

Conclusion

Perindopril/Indapamide/Amlodipine SPC is as effective and safe as the free combination in hypertensive patients uncontrolled with dual therapy of Perindopril/Indapamide. The uptitration to higher dosages of the triple-drug SPC provided additional benefit on BP lowering and BP control without increasing pill burden.
Treatment patterns in a population of 1.4 million individuals qualifying for initiation of dual-combination blood pressure lowering therapy representing usual clinical practice
Authors: Coca A , Borghi C , Stergiou G S , Ly N F , Lee C , Tricotel A , Castelo-Branco A , Khan I , Blacher J , Abdel-Moneim M
Published: November 2023

Background

Guidelines recommend dual-combination therapy (DCT) in most hypertensive patients requiring initiation of blood pressure (BP)-lowering treatment. This strategy is proven to be more effective as compared to monotherapy in achievement of BP goals, is associated with improved adherence, persistence and reduces risk of cardiovascular (CV) events.

Purpose

To describe the patterns of treatment with BP-lowering therapies in a large hypertensive population qualifying for initiation of DCT.

Methods

The study utilized following linked databases in England: Clinical Practice Research Datalink, Hospital Episode Statistics and Office for National Statistics. Adults qualifying for DCT as per the 2018 ESC/ESH guidelines were identified during a 15-year period (2005-2019). The index date is the first date when patient became eligible for initiation of DCT as per the guidelines-based criteria. Patients were followed for 5 years from the index date and were categorized into 4 groups: (1) no treatment, (2) monotherapy, (3) combination therapy with 2 agents, (4) combination therapy with ≥3 agents. For each year during follow-up, the percent of patient-time (Pt) on these categories was summarized for the overall population and two main subgroups i.e., atherosclerotic cardiovascular disease (ASCVD) and diabetes at baseline. In addition, we estimated the 15-year event rate for the composite endpoint of nonfatal myocardial infarction, nonfatal stroke, hospitalization for heart failure, and CV death via the Kaplan Meier method.

Results

Overall, 1,426,079 individuals met the selection criteria. Mean (SD) age was 62.9 (14.1) years and ∼50% were male. Approximately 15.9% and 13.8% had ASCVD and diabetes at baseline, respectively. In overall population during 5-year follow-up (Table 1), nearly 25% of Pt during follow-up reported non-treatment with any BP-lowering therapy. Monotherapy was most common treatment pattern accounting for nearly 50% of Pt while only 25% of Pt represented DCT. Percent of Pt on monotherapy decreased from 56.7% to 42.6% (year-1 to -5), and the percent of Pt on dual-combination therapy increased from 14.9% to 25.5% (year-1 to -5). Percent of Pt on any combination therapy (≥2 agents) increased from 17.5% to 32.4% (year-1 to -5). Similar pattern was observed in ASCVD and diabetes subgroups. The 15-year event rate for the composite endpoint was 27.1% for the overall population and was 57.5% and 40.1% in ASCVD and diabetes subgroups, respectively (Table 2).

Conclusion

Our findings indicate an opportunity for substantial improvement in BP control and CV risk reduction in this population, by ensuring appropriate guideline-based initiation, of dual combination BP-lowering therapy.Table 1Table 2
Comparative evaluation of renal denervation versus pharmacological treatment on diastolic function in patients with resistant hypertension: three years follow-up
Authors: Moiseeva A , Caraus A , Moscalu V , Ciobanu N , Abras M , Cociu M , Cotelea A
Published: November 2023

Background

Several recently published sham-controlled trials of high methodological quality confirm the safety and antihypertensive effectiveness of radiofrequency renal denervation. However, special clinical interest represents a suggestion that this type of treatment may improve hypertension-mediated organ damage.

Purpose

Comparative evaluation of renal denervation versus pharmacological treatment on diastolic function in patients with resistant hypertension.

Methods

The study enrolled 125 hypertensive patients who, following 4 weeks of standardized treatment with three antihypertensive remedies, one of which were a thiazide-like diuretic in maximum tolerated daily doses (Losartan, Amlodipine and Indapamid) and confirmation of their resistance, were randomly assigned into three groups depending on the treatment supplemented to the previously administered one: group I – Moxonidine, group II – Bisoprolol and group III – renal denervation (RDN). All patients were evaluated by transthoracic echocardiography at baseline, one, two and three years follow-up. A renal denervation was performed in the main renal arteries and their branches.

Results

At 1-year follow-up Bisoprolol and RDN treatment groups showed an authentic improvement in all diastolic function parameters, while Moxonidine group noted amelioration of only E/A ratio, LAVI and TR velocity. Two years of evaluation were marked by statistically significant changes of all diastolic parameters in all three observational groups. The improvement of diastolic function parameters continued until the end of the study, when the difference in dynamics between groups is evident thanks to the inferior effect of Moxonidine compared to Bisoprolol, RDN demonstrating superiority over both pharmacological treatment groups (Table 1).

Conclusions

Renal denervation demonstrated efficacy in improving of all parameters of diastolic function starting with 12 months of evaluation, the beneficial effect being maintained until the end of the surveillance period. At the same time, minimally invasive treatment has been shown to be superior to pharmacological treatment with SNS- blockers in improving diastolic function.
Association of ultra-processed foods with cardiovascular disease and hypertension in australian women
Authors: Pant A , Gribbin S , Machado P , Hodge A , Moran L , Marschner S , Zaman S
Published: November 2023

Background

Ultra-processed food (UPF) intake has increased in the past few decades, yet knowledge around the long-term effects on cardiovascular disease (CVD) risk is limited. Moreover, the magnitude of the impact of UPF intake on CVD in Australia has not been established.

Objective

To investigate the association of UPF intake with incident CVD and hypertension in a population-based cohort of middle-aged women.

Methods

Women aged 46-55 years were prospectively recruited into the Australian Longitudinal Study on Women’s Health and followed for 15 years. UPFs were defined according to the NOVA classification, and the contribution of these foods to total dietary intake was estimated. Outcomes were incident CVD (self-reported heart disease/stroke) and/or hypertension. Logistic regression models assessed the association between UFP intake and endpoints with adjustment made for confounders.

Results

A total 10,006 women (mean age 52.5±1.5) with an average UPF intake of 26.6% of total food dietary intake (mean 347.8 g/d) were included. Over 15 years of follow-up, 1,038 incident CVD and 4,204 hypertension cases occurred. Higher UPF intake was associated with higher risk of CVD (ptrend=0.05) and hypertension (ptrend=0.02). The highest intake of UPF (mean 42% of total food intake) versus the lowest UPF intake (mean 14.2% of total food intake) was associated with incident CVD [odds ratio (OR) 1.35, 95% confidence interval (CI) 1.03-1.78; p=0.03)] and hypertension [OR 1.33, 95% CI 1.06-1.66; p=0.01].

Conclusion

In middle-aged women, a higher intake of ultra-processed food was associated with increased CVD risk and hypertension. These findings lend support to minimising UPF intake as a component of a heart-healthy diet.
Physical activity and sedentary behavior patterns in individuals with a bicuspid aortic valve compared to healthy controls
Authors: Schreurs B A , Hopman M T E , Van Kimmenade R R J , Eijsvogels T M H
Published: November 2023

Background

A bicuspid aortic valve (BAV) is the most common congenital heart disease and associated with a higher lifetime risk of cardiovascular morbidity and mortality. Management of cardiovascular risk factors, including habitual physical (in)activity, is therefore key. However, little is known about physical activity (PA) and sedentary behavior (SB) patterns in individuals with BAV compared to healthy controls while there is debate how PA may influence BAV related cardiovascular complications.

Purpose

To compare objectively measured PA and SB characteristics between individuals with BAV and healthy age- and sex-matched controls.

Methods

Adults with BAV from our outpatient clinic were approached to participate and matched with age and sex- matched controls from the general population. SB, moderate-to-vigorous PA (MVPA) and step count were objectively assessed for 24 h/day during 8 consecutive days using an accelerometer (activPAL3 micro®) attached to the subject’s thigh. Transthoracic echocardiograms of the BAV participants were used to determine the presence of valvular dysfunction and to measure aortic diameters. Aortic dilatation was defined as >40 mm at the sinus of Valsalva or in the ascending aorta, whereas valvular dysfunction was defined as moderate-to-severe aortic stenosis or regurgitation according to current ESC guidelines.

Results

We recruited 100 BAV individuals (45±16 years old; 59% male), of which n=12 had valve dysfunction, n=22 had aortic dilatation and n=20 had a combination of valve dysfunction and aortic dilatation. We also included 100 healthy age- and sex-matched controls.

SB was comparable between the BAV and control group (9.3 [8.5-10.2] vs 9.3 [8.2-10.2] hrs/day, p=0.84), whereas time spent in MVPA (72 [59-89] vs 98 [75-116] min/day, p <0.001) and daily step count (4,826 [4,004-5,801] vs 6,252 [4,784-7,484] steps/day, p<0.001) were markedly lower in individuals with BAV (Figure 1). Furthermore, no significant differences in SB, MVPA or step-count were found across BAV disease severity subgroups (Figure 2).

Conclusion

Individuals with BAV are less physically active compared to age- and sex-matched healthy controls. These differences were independent of disease severity, indicating that the lower activity patterns were not due to functional or disease-related limitations.Figure 1.Figure 2.
Excessive daytime sleepiness, morning tiredness, loud snoring, and prognostic biomarkers in patients with chronic coronary syndrome
Authors: Olszowka M , Hagstrom E , Hadziosmanovic N , Ljunggren M , Denchev S , Manolis A J , Wallentin L , White H D , Stewart R A H , Held C
Published: November 2023

Background

Sleep-related breathing disorders (SRBD) are related to cardiovascular outcomes in patients with chronic coronary syndrome (CCS). Whether SRBD-related symptoms are associated with prognostic biomarkers in patients with CCS is not established.

Methods

Associations between frequency (never/rarely, sometimes, often, always) of self-reported SRBD-relatedsymptoms (excessive daytime sleepiness [EDS]; morning tiredness [MT]; loud snoring [LS]; multiple awakenings/night; gasping, choking, or apnea when asleep) and levels of biomarkers related to cardiovascular prognosis (high-sensitivity C-reactive protein [hs-CRP], interleukin 6 [IL-6], high-sensitivity cardiac Troponin T [hs-cTnT], N-terminal pro B-type natriuretic peptide [NT-proBNP], cystatin C, growth differentiation factor 15 [GDF-15] and lipoprotein-associated phospholipase A2 activity) were assessed at baseline in 15,640 patients with CCS on optimal secondary preventive therapy in the STABILITY trial. Cross-sectional associations were assessed by adjusted linear regression models with never/rarely as reference.

Results

EDS was associated (geometric mean ratio, 95% confidence interval) with increased levels of IL-6 (often 1.07 [1.03-1.10], always 1.15 [1.10-1.21]), GDF-15 (often 1.03 [1.01-1.06], always 1.07 [1.03-1.11]), NT-proBNP (always 1.22 [1.12-1.33]), and hs-cTnT (always 1.07 [1.01-1.12]). MT was associated with increased levels of IL-6 (often 1.05 [1.01-1.09], always 1.09 [1.04-1.15]), and GDF-15 (always 1.06 [1.03-1.10]). LS was associated with decreased levels of NT-proBNP (sometimes 0.94 [0.90-0.98], often 0.92 [0.87-0.97], always 0.87 [0.81-0.92]), and hs-cTnT (always 0.94 [0.91-0.98]).

Conclusions

In patients with CCS, gradually increased frequency of SRBD-related symptoms, such as EDS, MT, and LS, were independently and consistently associated with varying levels of IL-6, GDF-15, and NT-proBNP, each reflecting distinct pathophysiological pathways or underlying pathology of cardiovascular disease.

Figure 1. Adjusted analysis of associations between sleep-related breathing disorder-related questions and geometric mean ratios of prognostic biomarkersFigure 1A.Excessive Daytime SleepinessFigure 1B.Loud Snoring
Inferior vena cava wall thickness is associated with the presence and severity of cardiovascular disease
Authors: Fujiyoshi K , Tojo T , Ishida K , Ishida M , Yamaoka-Tojo M , Ako J
Published: November 2023

Background

Venous hypertrophy is a pathological condition that is commonly observed as individuals age. However, the clinical index and significance of venous hypertrophy are not yet fully understood.

Purpose

The purpose of this study was to clarify the relationship between clinical venous hypertrophy and cardiovascular disease (CVD).

Methods

A total of 407 patients who underwent echocardiography and evaluation of their endothelial function during a medical checkup were included in the study. Clinical venous hypertrophy was evaluated by measuring the thickness of the inferior vena cava wall (IVCWT) using echocardiography. Endothelial function was evaluated using flow-mediated dilation (FMD). CVD included ischemic heart disease, heart failure, and atrial fibrillation. The patients were divided into two groups based on the median value of IVCWT and their clinical characteristics were compared.

Results

The IVCWT was found to be normally distributed with a median value of 1.25 mm (p < 0.001). The high-IVCWT group was found to be older (62.1 ± 13.1 years versus 58.1 ± 12.0 years, p = 0.001), had a higher ratio of males (72.4% versus 60.3%, p = 0.010), a higher ratio of CVD (7.4% versus 2.7%, p = 0.002), a lower left ventricular ejection fraction (62.1 ± 10.9% versus 64.6 ± 7.6%, p = 0.009), higher levels of B-type natriuretic peptide (21.0 [12.1-48.4] pg/mL versus 14.0 [8.9-33.5] pg/mL, p = 0.039), and lower FMD values (5.36 ± 2.33% versus 5.99 ± 2.73%, p = 0.012) compared to the low-IVCWT group. Multivariate analysis revealed that IVCWT and age were independent factors for the prevalence of CVD (IVCWT: Odds ratio 2.563, 95% confidence interval 1.258-5.563, p = 0.009; age: Odds ratio 1.049, 95% confidence interval 1.021-1.078, p < 0.001). The receiver-operating characteristic analysis found that the best cut-off values for IVCWT and FMD to identify CVD were 1.60 mm and 0.49, respectively (IVCWT: area under the curve 0.731, p < 0.001, sensitivity 51%, specificity 90%; FMD: area under the curve 0.739, p < 0.001, sensitivity 80%, specificity 61%).

Conclusion

The results of this study suggest that IVCWT is associated not only with age, but also with the presence and severity of CVD.Figure 1Figure 2
Low cardiac index and high total peripheral resistance are independent predictors of mortality for acutely admitted medical patients
Authors: Hadad R , Haugaard S B , Sajadieh A
Published: November 2023

Introduction

Identification of critically ill and high-risk patients upon hospital admission represents a significant triage task in the emergency department. Rapid identification and treatment of these patients improves survival, reduces complications during admission, decrease hospitalization duration, and lower treatment cost. Hemodynamic variables such as cardiac index (CI) and total peripheral resistance (TPR) hold the potential to improve the diagnosis of critically ill patients by providing better prognostic value.

Using arterial waveform and the model flow method, CI and TPR can be measured non-invasively. These methods are validated against thermodilution, which is the golden standard.

Purpose

The purpose of the study was to examine the association between CI, TPR, and all-cause mortality within 30 and 90-day among patients admitted to acutely the emergency department or cardiac care unit.

Methods

In this observational prospective cohort study, all patients were included from the emergency department and cardiac care unit. Patients of age 18 years or older admitted to the emergency department or cardiac care unit due to acute medical disease, were included. Patients with a life expectance of 3months or less and patients unable to give informed consent were excluded. Within the first 24 hours of admission, patients underwent a 10-minute non-invasive hemodynamic measurement using arterial waveform analysis and the model-flow method. Patients were followed up to 90 days after discharge. The endpoints 30- and 90-day mortality were obtained through electronic patient journals. Cox proportional-hazard models examined the association between CI, TPR, and outcomes. All hazard models were adjusted for age, sex, BMI, heart failure, early warning score, and Charlson comorbidity score.

Results

Between May 2019 and January 2023, we included 920 unselected patients from the department of emergency medicine (n=433) and cardiac care unit (n=487) from a metropolitan hospital. We observed a 3% 30-days mortality while 90-days mortality was 4.9%. The median value of CI was 3.3L, the lowest decile was 2L, and the highest decile was 4.7L. Patients with the lowest CI were older, had higher incidents of heart failure, and had more comorbidities according to Charlson’s comorbidity score (table 1). In Cox proportional hazard models, lowest decile of CI at admission was associated with a significantly higher risk of 30- and 90-days mortality. Total peripheral resistance was significantly associated with 90-day mortality (table 2).

Conclusion

Low CI ≤2.0 liter/min/m2, and high peripheral resistance measured non-invasively were associated with an increased risk of mortality among patients admitted to the emergency department or cardiac care unit. Non-invasive estimation of CI and TPR may assist in identifying high-risk patients.Table 1Table 2
Integrative interpretation of cardiopulmonary exercise tests for cardiovascular risk stratification: a machine learning approach
Authors: Cauwenberghs N , Sente J , Sabovcik F , Ntalianis E , Claes J , Claessen G , Budts W , Goetschalckx K , Cornelissen V , Kuznetsova T
Published: November 2023

Background and objectives

Cardiopulmonary exercise testing (CPET) remains underutilized for cardiovascular (CV) risk assessment. Integrative interpretation of CPET results may improve characterization of cardiorespiratory fitness and assessment of CV risk. Therefore, we explored the clinical value of CPET-based phenomapping for CV risk stratification.

Methods

We retrospectively retrieved clinical data from 2280 patients with diverse CV risk (47.9% female) who underwent maximal CPET by cycle ergometry. We derived 18 key CPET indices as well as data on fatal and non-fatal CV events (median follow-up time: 5.3 years). Next, an unsupervised clustering algorithm (Gaussian Mixture modelling) subdivided the cohort in sex-specific phenogroups solely based on differences in CPET metrics. Clinical characteristics were compared across CPET phenogroups and their multivariable-adjusted association with future CV events was determined.

Results

8 of the 18 CPET metrics were excluded from clustering due to high collinearity (i.e. an absolute Pearson correlation coefficient >0.8). Based on the remaining 10 CPET variables, the clustering algorithm subdivided the cohort in four male and four female CPET phenogroups. In both males and females, the phenogroups differed significantly in age, BMI, spirometric and CPET measurements and prevalence of hypertension, intake of antihypertensive and lipid-lowering drugs, CV disease and CV surgery (P<0.05 for trends). During follow-up, 278 males and 109 females experienced a CV event (43.9 and 16.2 events per 1000 years of follow-up, respectively). Compared to male phenogroup 1, male phenogroups 3 and 4 presented higher risk for incident CV events (multivariable-adjusted hazard ratio: 1.97 and 1.62; P≤0.027). Significant differences in risk for future CV events between the female phenogroups disappeared after adjustment for confounders.

Conclusion

Integrative CPET-based phenogrouping adequately stratified patients according to their risk for future CV events. Such phenomapping may facilitate comprehensive evaluation of CPET results and steer future CV risk management.Study flow and findings
The association of oral hypofunction/adiposity and increased arterial stiffness
Authors: Matsumoto C , Tomiyama H , Nakai T , Matsuura M , Nakano H , Shiina K , Yamashina A , Chikazu D
Published: November 2023

Background

Sarcopenia and adiposity are risk factors for cardiovascular diseases (CVD). Recently, oral hypofunction, a disease in which oral function is complexly reduced not only by aging but also by a variety of factors, has been regarded as a major risk factor for sarcopenia. However, no studies have evaluated the association between oral hypofunction/adiposity and arterial stiffness, which is a CVD marker.

Purpose

This study aimed to evaluate the association between oral hypofunction/adiposity and arterial stiffness.

Methods

Japanese Subjects aged > 50 years who underwent annual health check-ups were enrolled in this cross-sectional study. Subjects with a history of CVD or dementia were excluded from the study. Arterial stiffness was evaluated using the brachial-ankle pulse wave velocity (baPWV). Adiposity was defined as visceral fat > 100 cm2, as evaluated using abdominal computed tomography. Oral hypofunction was evaluated according to the guidelines of the Japanese Association for Dental Science. Seven oral factors were assessed: oral hygiene, oral moisture, occlusal force, tongue-lip motor function, tongue pressure, masticatory function, and swallowing function. Oral hypofunction was　diagnosed if more than 3 factors deteriorated. We categorized the participants into four groups according to the existence of oral hypofunction and adiposity. The associations between oral hypofunction/adiposity and baPWV were assessed by multivariable linear regression analysis adjusted for conventional CVD risk factors.

Results

We categorized 146 subjects (mean age:59±7 years) into four groups: subjects with both oral hypofunction and adiposity (N=16), only adiposity (N=46), only oral hypofunction (N=17), and none of them (N=67). The baPWV values of the groups were 1673±354, 1481±262, 1412±206, and 1372±254 cm/s, respectively. BaPWV in subjects with both oral hypofunction and adiposity was the highest compared to that in the other three groups (P<0.01). Multivariable linear regression analysis revealed that the combination or oral hypofunction and adiposity was significantly associated with increased arterial stiffness independent of CVD risk factors including lipid and glucose metabolism. (β=232±77, P<0.01). Also, the combination or oral hypofunction and adiposity, only adiposity, only oral hypofunction, were gradually associated with increased arterial stiffness (β=54±22, P=0.01).

Conclusion

The combination of oral hypofunction and adiposity was associated with increased arterial stiffness independent of conventional CVD risk factors. Further research on oral hypofunction/adiposity and CVD is warranted.