bluuebunny/crossref_metadata_2025 huggingface dataset:
Ten-year outcomes in patients with hypertension and primary hyperaldosteronism undergoing surgical adrenalectomy versus medical therapy: data from the multinational collaborative network TriNetX
Authors: Belo Nunes R , Brito T M , Oliveira R P , Pereira D C G , Costa L M A , Scudeler T L , Santana G C , Scudeler T L , Schneidewind R O , Cantarelli M J C , Castello Jr H , Avezum A
Published: October 2024

Background

Surgical adrenalectomy for resection of adenomas has been the standard approach for treating patients with secondary hypertension due to primary hyperaldosteronism. However, few studies explored long-term outcomes in patients treated with adrenalectomy when compared to patients treated with conservative management.

Purpose

To compare ten-year mortality and cardiovascular outcomes in patients with primary hyperaldosteronism treated with surgical adrenalectomy versus patients with primary hyperaldosteronism treated with medical therapy alone.

Methods

This retrospective cohort study used real-world data from healthcare organizations participating in the global health research collaborative network TriNetX. We performed propensity score matching for demographic and clinical characteristics and calculated hazard ratios, comparing 2.397 patients in each group. The outcomes were all-cause death, heart failure, and the composite endpoint ischemic stroke, hemorrhagic stroke, myocardial infarction, unstable angina, and aorta aneurysm or dissection (major adverse vascular events) during the 10-year follow-up.

Results

Patients undergoing surgical adrenalectomy had a lower incidence of all-cause death (3.0%) when compared with patients in medical therapy (5.0%) ( hazard ratio 0.60, 95% CI 0.45-0.81). Patients in the surgical group had a 4.6% incidence of heart failure and the medical therapy had an 8.6% incidence of heart failure (hazard ratio 0.54, 95% CI 0.42-0.69). The incidence of major adverse vascular events was lower in the surgical group (10.9%) compared to the medical therapy group (14. 1%) ( hazard ratio 0.76, 95% CI 0.65-0.90).

Conclusion

In patients with hypertension and primary hyperaldosteronism, surgical adrenalectomy was associated with lower 10-year mortality, heart failure, and major adverse vascular events compared to medical therapy alone.
More hypertensive crises in women than in men in a single emergency department
Authors: Strzelczyk E , Jilek C , Tiemann K , Lewalter T
Published: October 2024

Introduction

Hypertensive crises are a common presenting complaint in the emergency department. A hypertensive crisis includes hypertensive urgencies defined as a systolic and/or diastolic blood pressure greater than 180/120 mmHg and hypertensive emergencies with additional hypertension-mediated organ damage (HMOD). In the literature there is very little data regarding the distribution between men and women in hypertensive crises. Most data suggest a balanced distribution or a higher frequency in men, especially compared to premenopausal women.

Methods

We retrospectively analysed patient data in our hospital information system from 2022 using ICD-10 diagnoses at discharge. We included inpatient as well as outpatient cases that presented to our emergency department between 01/01/2022 and 31/12/2022 with one of the following ICD-diagnoses at discharge:

- I10.01, Benign essential hypertension With mention of hypertensive urgency

- I10.91, Essential hypertension, unspecified With mention of hypertensive urgency

- I11.01, Hypertensive heart disease with (congestive) heart failure With mention of hypertensive urgency

- I11.91, Hypertensive heart disease without (congestive) heart failure With mention of hypertensive urgency

- R03.0, Elevated blood-pressure reading, without diagnosis of hypertension

Then we compared the difference of the median age at presentation between men and women using the independent t-test.

Results

We identified 397 patients with a hypertensive crisis in the year of 2022. Overall the percentage of women in the collective of patients with any type of hypertensive crisis diagnosis was 73.0 % and thus a lot higher than the percentage of men. Women were on average 7.7 years older at presentation (p < 0.0001).

Discussion: On the basis of the available data the causes for the distribution between men and women in hypertensive crises can only be speculated. On the one hand women may measure their blood pressure more frequently than men and the urge to call an ambulance or seek medical attention may be higher. On the other hand it could be possible that arterial hypertension in general has differences in the course and underlying mechanism with a higher frequency in blood pressure peaks, symptoms at lower blood pressure values and antihypertensive medication could be less effective depending on the type of drug. Also arterial hypertension may be underdiagnosed in women. The difference in the age at presentation is probably due to a later hormonal adjustment after the menopause as shown in the literature. The findings of this small observational study should be further investigated in larger trials.
Regional variation of age-related blood pressure trajectories and their association with blood pressure control rates, disability-adjusted life years and death
Authors: Nolde J , Beaney T , Carnagarin R , Stergiou G S , Poulter N R , Schutte A E , Schlaich M P
Published: October 2024

Background/Introduction

While the relationship between blood pressure (BP) changes and increasing age is well described, age-related BP trajectories may vary substantially across different populations and associated with differential CV risk and outcomes.

Purpose

The dataset of the May Measurement Month (MMM) international campaigns enables a unique investigation of regional, socio-economic and sex differences in age-BP trajectories and their association with major public-health outcomes.

Method

Global BP data from more than 4,5 million adult (≥18 years) screenees obtained during the cross-sectional MMM campaigns in 2017, 2018, 2019, and 2021 were used for analysis. Average BP and slopes of BP changes across age groups were calculated within regional, socio-economic and sex strata. BP slopes of individuals between 30 and 70 years of age were derived from adjusted linear regression models, along with baseline BP estimates at young age. These BP slopes were correlated in regression models adjusted for baseline BP at young age with country-specific all-cause rates of DALYs (Disability-Adjusted Life Years), death (both from Global Burden of Disease Study 2019), life expectancy (World Bank data SP.DYN.LE00.IN 2019) and BP control rates (NCD Risk Factor Collaboration).

Results

Age-related BP changes differed distinctly across global geographic regions, income levels, and between sexes. The steepest increase in BP with age was observed in populations from Africa and Europe, whereas a more gradual rise in BP with increasing age was seen in South-East Asian populations. Women had lower BP levels than men at younger ages (twenties and thirties), but subsequently experienced a more pronounced age-related BP increase resulting in diminishing sex differences across older age groups. Geographically divergent age-related BP trajectories were significantly associated with major national public health indicators. Globally, the steeper the age-related BP slope, the stronger the association with poor BP control (β = -0.46 [95% CI: -0.74; -0.19], p=0.001), increased DALY’s (β = 66155.68 [95% CI: 44847.0; 87464.36], p<0.001) and death rates. (β = 1017.3 [95% CI: 351.72; 1682.89], p=0.003).

Conclusion

Age-related BP trajectories vary considerably across global populations and contribute considerably to the variability in BP-related risks and adverse outcomes across regions. Effective public health strategies may require region-specific targeting of lifestyle and other factors contributing to adverse BP trajectories to improve health outcomes.Average blood pressure by ageAssiciations with public health metrics
One-year risk of all-cause death and major cardiovascular events in patients presenting with hypertensive crisis. A report from a global federated research health network
Authors: Bucci T , Argyris A , Alsomali A , Lam S H O , Gerra L , Proietti R , Beevers G D , Shantsila E , Shantsila A , Lip G Y H
Published: October 2024

Background

Few data are available about the clinical course of patients presenting with hypertensive crisis who are discharged alive from hospital.

Purpose

To assess the long-term risk of adverse events in patients with hypertensive crises.

Methods

Retrospective study utilizing a research health network. Based on the ICD-10-CM codes recorded between 2000 and 2022, from 85 health care associations mainly located in the United States, patients with hypertensive crisis were subdivided into hypertensive urgencies (I16.0) and hypertensive emergencies (I16.1). In those with hypertensive emergencies, the type of target organ damage was reported, ie. central nervous system (ischemic stroke, hypertensive encephalopathy, intracerebral hemorrhages), cardiovascular (CVS: myocardial infarction (MI), heart failure (HF), aorta dissection (AD)), or renal (acute kidney failure). Primary outcomes were the one-year risks of all-cause death, and major cardiovascular events (MACE: MI, stroke, cardiac arrest, AD, and HF). Secondary outcomes were the risks for each type of MACE. Cox regression analysis after propensity score matching (PSM) 1:1 was used to produce hazard ratios (HRs) and 95% Confidence Intervals (95%CIs).

Results

Overall, we identified 25 294 patients with hypertensive emergency (age 62.4±15.7, 46.1% females) and 21,737 patients with hypertensive urgency (age 63.5±17.2, 55.5% females). Patients with hypertensive emergency were more likely males, Black or African American origin and showed a higher prevalence of chronic hypertensive-related complications, vs. those with hypertensive urgency. After PSM, patients with hypertensive emergency showed a higher risk of all-cause death (HR, 1.34, 95%CI 1.25-1.44) and MACE (HR 4.09, 95%CI 3.87-4.33), vs. those with hypertensive urgency.

Of the secondary outcomes, patients with hypertensive emergency had increased risks of MI (HR 3.33, 95%CI 3.03-3.67), stroke (HR 4.73, 95%CI 4.33-5.17), cardiac arrest (HR 1.30, 95%CI 1.07-1.58), AD (HR 5.49, 95%CI 3.90-7.73), and HF (HR 3.01, 95%CI 2.74-3.14). All the different types of organ involvement during the hypertensive emergency were each associated with similar long-term risks of adverse events (Figure 1).

Conclusion

Patients with hypertensive emergency have a high long-term risk of MACE and all-cause death. Preventing the onset of target organ damage in patients with hypertensive crisis is crucial to mitigate their long-term risk of adverse events.
Histopathological myocardial changes in patients with severe aortic stenosis referred for surgical valve replacement: a CMR correlation study
Authors: Reis Santos R , Abecasis J , Lopes P , Maltes S , Ferreira A , Ribeiras R , Andrade M J , Sousa Uva M , Gil V , Felix A , Ramos S , Cardim N
Published: October 2024

Background

Myocardial fibrosis (MF) takes part in left ventricular (LV) remodeling in patients with aortic stenosis (AS), driving the transition from hypertrophy to heart failure. The structural events that occur in this transition are not fully enlightened.

Aim

To describe histopathology changes at endomyocardial biopsy (EMB) in patients with severe AS referred to surgical aortic valve replacement (AVR); to correlate them with LV tissue characterization from pre-operative cardiac magnetic resonance (CMR).

Methods

One-hundred-fifty-eight patients (73[68-77]years, 50%women) referred for surgical AVR because of severe symptomatic AS, with pre-operative CMR (n=143) with late gadolinium enhancement (LGE), T1, T2 mapping and extracellular volume fraction (ECV) quantification. Intra-operative septal EMB was obtained in 129 patients. MF was assessed through Masson ́s Trichrome histochemistry. Immunohistochemistry was performed for both inflammatory cells and extracellular matrix (ECM) characterization (Type I Collagen, Fibronectin, Tenascin C).

Results

Non-ischemic LGE was present in 106 patients (67.1%) (median fraction: 5.0% [2.0-9.7]). Native T1 was above normal: 1053ms[1024-1071] and T2 within normal range (39.3ms[37.3-42.0]). Median MF was 11.9%[6.54-19.97], with predominant type I collagen perivascular distribution (95.3%). Subendocardial cardiomyocyte ischemic-like changes were identified in 45% of EMB. There was no inflammation, despite ECM remodeling expression. MF quantification at EMB was correlated with LGE mass and indexed ECV (p=0.008; p=0.017, respectively).

Conclusion

Patients with severe symptomatic AS referred for surgical AVR have unspecific histological myocardial changes, including signs of cardiomyocyte ischemic insult. ECM remodeling is ongoing, with MF heterogeneity. These features may be recognized by comprehensive CMR involving LGE, T1 mapping derived indexes and their combination with LV morphofunctional characterization.
Prevalence and prediction of masked uncontrolled hypertension in patients recently hospitalised for an acute coronary syndrome
Authors: Hellqvist H , Erlinge D , Lindahl B , Jernberg T , Oldgren J , James S , Al-Khalili F , Kahan T , Spaak J
Published: October 2024

Background

Masked uncontrolled hypertension (MUCH) is defined as normal office blood pressure (BP) but elevated out-of-office BP in patients on antihypertensive treatment. MUCH is associated with similar cardiovascular risk as sustained hypertension and is clinically challenging since this often remains undetected without out-of-office BP measurements.

Purpose

To study the prevalence of MUCH following an acute coronary syndrome and to utilise machine learning methods to develop prediction models for identifying MUCH.

Methods

Ambulatory 24-h BP measurement (ABPM) was performed in 100 patients attending the cardiology outpatient clinic at a Swedish university hospital following an acute coronary syndrome, as part of a study which screened for co-morbidities. From the SWEDEHEART registry, 106 variables during the hospital care period and subsequent follow-up visit (after 6-10 weeks) were pre-processed including filtering on 5 or more missing values and zero or near-zero variance. Variable importance for the prediction of MUCH (office BP < 140/90 mm Hg at ABPM start but mean 24-h BP ≥ 130/80 mm Hg) was assessed using the Boruta and least absolute shrinkage and selection operator (LASSO) machine learning algorithms. Subsequently, logistic regression, LASSO and random forest models using different variable subsets were evaluated by receiver operating characteristic area under the curve (AUC) in repeated cross-validation.

Results

Age was 62.0±8.4 years, 74% male, 54% had NSTEMI and 46% STEMI. The follow-up visit and ABPM were performed at median 7 and 11 weeks, respectively, after hospital discharge. Among 90 patients with complete data and ABPM recordings, 31 had mean 24-h BP above target levels, of which 18 were identified with MUCH. Patients with MUCH had lower eGFR (68±11 vs 76±12 ml/min/1.73m², P=0.009), and more often a history of hypertension (89 vs 53%, P=0.005) and diabetes mellitus (44 vs 11%, P=0.003). In total, 65 variables where eligible for machine learning after filtering. Boruta and LASSO identified pulse pressure at the follow-up visit, serum creatinine, diabetes mellitus and history of hypertension as important predictors. Random forest, logistic regression and LASSO showed mean AUC 0.826, 0.822, and 822, respectively, in cross validation using these predictors.

Conclusions

In this small trial, one in five had MUCH at follow-up after an acute coronary syndrome, which highlights the importance of out-of-office BP measurements. The easily accessible measures of pulse pressure at the follow-up visit, serum creatinine, diabetes mellitus and history of hypertension were identified as important predictors of MUCH. A simple prediction model may be used as a clinical decision support tool after appropriate external validation.
Unleashing the potential: early evaluation of blood pressure control with novel measurements in patients with hypertension
Authors: Zhao Y , Moran L I , Yi Z
Published: October 2024

Objective

To assess the prognostic value of two novel blood pressure measurements——short-term cumulative systolic blood pressure (SBP) load and Time in Target Rang (TTR) in major adverse cardiovascular outcomes and all-cause mortality.

Method

This is a post-hoc analysis of the SPIRNT (Systolic Blood Pressure Intervention Trial). Participants with complete record of BP values and no adverse events occurred in the initial 90-days follow-up were enrolled. Short-term cumulative SBP load and TTR were calculated by the 3-month SBP values in the follow-up period (Fig 1). The primary outcome was major adverse cardiovascular events (MACEs), defined as the composite of myocardial infarction, stroke, heart failure and cardiovascular death. Secondary outcomes were the components of the primary outcomes and all-cause mortality.

Results

The study population included 8639 adults (median [IQR]or mean (%) baseline age, 67 [61,76] years; 2940 women (35.1%); Median follow-up time 3.8[3.3-4.4] years). 559 MACEs were occurred. Participants categorized by tertiles of cumulative SBP Load (T1: [0,0.1572]; T2: (0.1572 ,3.5946]; T3: (3.5946 ,30.2949]) showed a significant increase hierarchical trend (P for trend <0.05) in the incidence of MACEs and stroke. For Participants grouped by SBP TTR (T1: [0,21.2657]; T2: (21.2657 ,71.1462]; T3: (71.1462 ,100]), it indicated a decrease hierarchical trend (P for trend <0.05) in the incidence of MACEs and MI (Fig2 and Fig3). Both short-term cumulative SBP Load (HR: 1.117(1.033-1.208)) and TTR (HR: 0.861(0.785-0.945)) were correlated with MACEs independently(tabal1). According to C-statistics and Net Reclassification Indexes (NRI), short-term cumulative SBP Load and TTR both outperformed mean SBP and SBP standard derivation (SD) on the prognosis value of MACEs. Moreover, our results showed that the coefficient of cumulative SBP Load under penalty decreased to 0 with the largest log(lambda),which indicted a major role across 4 different measures in models. (Fig 4).

Conclusions

Both short-term cumulative SBP load and TTR had an independent prognosis value for MACEs superior to mean SBP and SBP SD in hypertension patients without diabetes. This study provided the evidence of novel BP measurements for early assessment of BP levels after antihypertensive treatment.
Prognostic value of cardiac magnetic resonance global circumferential strain assessed by feature tracking techniques in asymptomatic patients with significant aortic regurgitation
Authors: Carrion-Sanchez I , Ramos Cano P , Monteagudo Ruiz J M , Garcia Sebastian C , Hinojar Baydes R , Antonana Ugalde S , Garcia Martin A , Martinez-Vives P , Martin Pinacho J , Ayala Carbonero A , Gonzalez A , Zamorano J L , Fernandez-Golfin C
Published: October 2024

Introduction

Cardiac magnetic resonance feature tracking (CMR-FT) deformation techniques have gained significant interest in recent years. They provide a comprehensive evaluation of myocardial function and improve the reproducibility of echocardiography strain techniques.

Purpose

The aim of this study was to evaluate whether CMR-FT deformation parameters play a role predicting worse clinical evolution in patients with chronic significant aortic regurgitation (AR) not meeting guidelines intervention criteria.

Methods

We included 85 patients with significant AR (moderate, moderate/severe, and severe) referred for CMR. Only asymptomatic patients with preserved left ventricle ejection fraction (LVEF) were considered for inclusion. Other concomitant myocardiopathies were excluded. Conventional functional left chambers parameters as well as myocardial deformation were evaluated, including global longitudinal strain (GLS), global circumferential strain (GCS) and global radial strain (GRS). A composite clinical major outcome was assessed, including admission heart failure admission, need for aortic valvule replacement and all-cause mortality.

Results

The mean age of the sample was 62 years old. One third of the patients were females. Other clinical baseline characteristics were not significantly different between groups when compared with Chi-squared and T-test statistical analysis. Mean follow-up was 42 months (±31). 21 patients presented with the composited outcome previously described. End-diastolic and end-systolic volumes did not differ between groups. Mean end-diastolic volume (EDV) was 196 ± 6.1 mL and mean end-systolic volume (ESV) was 88 ± 3.4 mL. Mean values of CMR-FT GLS, GCS and GRS were -14.1%, 22.8% and -16.9% respectively. GCS was selected as the best predictor for the combined endpoint point, with and area under the ROC curve of 0.67. A GCS value <-17% was selected as the optimal cut-off point. This value predicted events as is shown in Kaplan-Meier curves (HR 3.6, CI 95% 1.42 - 9.02, p = 0.007). A multivariate analysis showed that this association was independent of left ventricle (LV) ejection fraction, LV volumes and left atrial (LA) volume.

Conclusion

CMR-FT deformation parameters are impaired in significant AR patients even if intervention criteria are not met. A value of GCS < -17% in this population could predict a worse clinical evolution and emerges as a promising new tool helping clinical decision making in this challenging population.Kaplan-Meier curve free-event survival
10 years after treatment with renal denervation of the sympathetic nerves for resistant hypertension: what happened to the patients and their office blood pressure? An observational study
Authors: Melchior T , Kelbaek H S , Olsen M H , Oestergaard O V , Kjoeller-Hansen L
Published: October 2024

Background

Catheter-based renal denervation of the sympathetic nerves (RDN) for resistant hypertension has long been controversial. A renewed clinical and scientific interest in defining the appropriate role of RDN in the treatment of resistant hypertension has become evident in recent years. The efficacy and safety of RDN treatment is mainly based on available data up to three years, whereas data concerning the long-term effect and safety are scarce.

Purpose

We therefore wanted to investigate the long time change in blood pressure (BP) in patients treated with RDN for resistant hypertension.

Methods

A review of data from the electronic patient journal concerning all RDN treated patients was initiated and completed in October 2023. Every registration of an office BP listed in the patient file, antihypertensive treatment, cardiovascular events, and renal function between 2012 and 2023 were registered. For each patient the average of all office post RDN blood were averaged for every year and for their complete follow-up. The outcome in blood pressure was the change in BP from baseline pre RDN office to follow-up

Results

Between January 2012 and October 2013, 19 consecutive patients underwent RDN treatment, 10 men and 9 women with a median age of 63 years (range 35-74 years). At baseline the median systolic office BP was 181 mmHg (range 162–230 mmHg) and the diastolic office BP 97 mmHg (range 82-123 mmHg) on a median of 5 (range 0-7 ) antihypertensive drugs. During follow-up the number of antihypertensive drugs were reduced in 7, unchanged in 10, and increased in 2 patients. Two patients left the outpatient clinic with normal BP after 2 years. Two patients developed heart failure after 7 years and were censored at that time-point. 15 (79%) patients had office BP recorded up to 9 or 10 years. In the 15 (79%) patients with available office BP 9 to 10 years after RDN the median systolic and diastolic office BPs were reduced by 39 mmHg (range -2 to - 66 mmHg) and 18 mmHg (range -11 to - 55 mmHg) respectively, relative reduction 22% (range 5-36%) and 20% (range 6-32), respectively.

Conclusion

During a follow-up of 9 to 10 years after RDN without a step-up in antihypertensive medication a relative decrease of ~20% in systolic and diastolic BP was observed.
The impact of blood pressure guidelines on the cardiovascular event risk in Japanese patients with coronary artery disease in a real-world database using a multimodal data acquisition system
Authors: Oba Y , Kabutoya T , Kohro T , Imai Y , Kario K , Ishii M , Tsujita K , Fujita H , Matoba T , Kiyosue A , Mizuno M , Nakayama M , Miyamoto Y , Sato H , Nagai R
Published: October 2024

Background

The European Society of Hypertension and the Japanese Society of Hypertension have established a blood pressure (BP) guideline for coronary artery disease (CAD): 130/80 mmHg. The impact of adhering to this BP guideline on the prognosis of Japanese patients with CAD after they have undergone percutaneous coronary intervention (PCI) is unclear.

Purpose

We investigated the impact of the current guideline-recommended BP value 130/80 mmHg on the prognosis of Japanese patients with CAD by using 'big data,' i.e., the Clinical Deep Data Accumulation System (CLIDAS) database.

Methods

We evaluated the data of 8,793 CAD patients who underwent cardiac catheterization at six university hospitals and Japan's National Cerebral and Cardiovascular Center (mean ± std. dev. 70 ± 11 years, 78% male, 43% with acute coronary syndrome [ACS]). We categorized the patients based on their BP management: those adhering to the guideline-recommended BP (<130/80 mmHg) and those under stricter BP control criteria (<120/70 mmHg and <110/60 mmHg). We compared the incidence of major adverse cardiovascular events (MACCEs) between these groups, with MACCEs being a composite endpoint (cardiovascular death, stroke, and myocardial infarction). We analyzed the relationship between BP classification and MACCE separately in two groups: the patients with ACS and those with chronic coronary syndrome (CCS).

Results

During an average follow-up period of 33 months, 710 MACCEs occurred, comprising 234 cardiovascular deaths, 305 strokes, and 270 myocardial infarctions, with some cases overlapping. No significant difference in the MACCE rate was observed between the group with BP below 130/80 mmHg and the group with BP above 130/80 mmHg (hazard ratio [HR] 0.88, 95% confidence interval [CI] 0.75–1.04, p=0.133). In the ACS group, the patients maintaining BP below 130/80 mmHg had a significantly lower MACCE incidence (HR 0.75, 95%CI: 0.59–0.95, p=0.017) and a significantly lower incidence of stroke (HR 0.47, 95%CI: 0.33–0.68, p<0.001), whereas no significant difference in the MACCE incidence was observed in the CCS group (HR 0.91, 95%CI: 0.73–1.13, p=0.393). Blood pressure values below 120/70 mmHg (HR 1.13, 95%CI: 0.97–1.31, p=0.109) and 110/60 mmHg (HR 1.23, 95%CI: 1.06–1.43, p=0.008), corresponded to an increased rate of MACCEs, becoming more pronounced at BP values <110/60 mmHg.

Conclusion

Achieving the BP guideline target of <130/80 mmHg is associated with improved outcomes in CAD patients, particularly regarding reducing the risk of stroke among patients with ACS. However, BP control at values that are too low may potentially worsen the prognosis for CAD patients.Kaplan–Meier curve
HbA1c variability and macrovascular benefits of intensive blood pressure control in patients with type 2 diabetes
Authors: Wang X , Pei J
Published: October 2024

Background

Hypertension is the most common and manageable cardiovascular risk factor in patients with type 2 diabetes. However, the optimal target for blood pressure (BP) control in patients with type 2 diabetes remains a subject of debate.

Purpose

The aim of this study was to classify levels of haemoglobin A1c (HbA1c) variability using a machine learning algorithm and to investigate the impact of HbA1c variability on the effectiveness of intensive BP control.

Methods

Data from the Action to Control Cardiovascular Risk in Diabetes Blood Pressure (ACCORD-BP) trial were utilised. K-means clustering was utilised to group patients into three categories with low, medium, and high HbA1c variability levels, based on the HbA1c variability score and baseline HbA1c values. The primary outcome was a composite of non-fatal myocardial infarction (MI), stroke, or death from cardiovascular causes. The secondary outcome was all-cause mortality.

Results

In patients with low HbA1c variability rather than medium or high HbA1c variability, intensive BP control significantly reduced the risk of the primary outcome on a relative scale (HR: 0.60, 95%CI: 0.40-0.90, P interaction was 0.03), non-fatal MI (HR: 0.61, 95%CI: 0.37-1.00, P interaction was 0.04), and stroke (HR: 0.19, 95%CI: 0.05-0.64, P interaction was 0.02) or absolute scales. Regardless of the variability group, intensive BP control did not reduce the risk of cardiovascular death or all-cause mortality (P interaction > 0.05) both on relative and absolute risk scales.

Conclusions

Patients with type 2 diabetes who have low HbA1c variability may benefit from intensive BP control, particularly in significantly reducing the risk of non-fatal MI and stroke.
Longitudinal associations between accelerometry-assessed sleep clusters and obesity in adolescence and young adulthood: the German GINIplus and LISA birth cohorts study
Authors: Wang M , Flexeder C , Harris C , Kress S , Schikowski T , Peters A , Standl M
Published: October 2024

Background

Some studies have identified diverse sleep patterns in adolescents and adults by considering multidimensional objective sleep parameters. However, whether sleep patterns are consistent from adolescence to young adulthood and their long-term associations with obesity remain unknown.

Purpose

This study aimed to investigate the longitudinal associations of objectively measured and clustering-identified sleep patterns with body mass index (BMI) and overweight/obesity in adolescence and young adulthood, and to test whether these associations change over time or are modified by genetic risk.

Methods

A total of 1973 participants wearing 7-day accelerometers in either 15-year (n=1347, aged 14.3-16.4 years) and/or 20-year (n=1262, aged 19.5-22.4 years) follow-ups of German GINIplus and LISA birth cohorts were included. Sleep clusters were identified by K-means cluster analysis on 12 accelerometry-assessed sleep characteristics at each follow-up. BMI and overweight/obesity were measured by physical exams or self-/parent-reported questionnaires. Multivariable linear and logistic regression models with generalized estimating equations were tested. The interaction effects with time of follow-ups and polygenic risk scores (PRS, n=1087) for BMI were further examined.

Results

Although sleep characteristics changed from adolescence to young adulthood, such as shorter total sleep time (mean 7.2 to 6.6 hours), the consistent five sleep clusters were classified in both periods: good sleep, delayed sleep phase, sleep irregularity and variability, fragmented sleep, and prolonged sleep latency. Compared to the "good sleep" cluster, the "prolonged sleep latency" cluster showed significant associations with higher BMI (β=0.56, 95% confidence interval (CI) = [0.06, 1.05]) and increased odds of overweight/obesity (odds ratio (OR)=1.55, 95%CI= [1.02, 2.34]). PRS was associated with higher BMI (β=0.65, 95%CI= [0.39, 0.91]) and overweight/obesity (OR=1.52, 95%CI= [1.15, 2.00]), with no significant gene-sleep cluster interaction effect. Only among males, the interaction effects with time of follow-ups on overweight/obesity were observed in the "delayed sleep phase", "sleep irregularity and variability", and "fragmented sleep" clusters (p-interaction <0.05), showing more harmful effects with increasing age.

Conclusions

Five sleep patterns were identified consistently across adolescence and young adulthood, and the "prolonged sleep latency" pattern was associated with higher BMI and overweight/obesity, independent of genetic risk. For young adult males, "delayed sleep phase", "sleep irregularity and variability" and "fragmented sleep" patterns seemed to have more unfavorable impacts on overweight/obesity.
Association of COVID-19 and influenza vaccinations and cardiovascular drugs with hospitalisation and mortality in COVID-19 and Long COVID: 2-year follow-up of 17 million individuals in England
Authors: Dashtban A , Mizani M , Rafferty S , Pasea L , Tomlinson C , Mu Y , Islam N , Warren-Gash C , Denaxas S , Petersen S , Sudlow C , Khunti K , Banerjee A
Published: October 2024

Introduction

For COVID-19 and Long COVID, determining the highest-risk subgroups, particularly in the context of compound pressures such as influenza and cardiovascular disease (CVD), may identify effective interventions to prevent adverse health outcomes, and inform public health and policy decisions.

Methods

Using national, linked electronic health records for England (NHS England Secure Data Environment: via CVD-COVID-UK/COVID-IMPACT Consortium), we studied individuals with COVID-19 and Long COVID from January 2020 to February 2023. We compared all-cause hospitalisation and mortality in unmatched and matched cohort analyses, by prior CVD, high CVD risk (by QRISK2), COVID-19 and influenza vaccination status, and prescription of CVD preventive therapies. We investigated potential impact of targeted vaccination and CVD prevention strategies on mortality and hospitalisations by calculating population preventable fractions.

Results

We identified 17,373,850 individuals with COVID-19 [54.4% female; mean age 38.8 years; COVID-19 vaccination ≥2 doses:50.0%, influenza vaccination (≥1 dose):27.8%; mean follow-up 1.28 years] and 301,115 with Long Covid [61.8% female; mean age 46.0 years; COVID-19 vaccination ≥2 doses:66.4%, influenza vaccination:33.1%; mean follow-up 1.1 years]. Hospitalisation and mortality rates were 15.3% and 2.0% in COVID-19 (Long COVID rate 1.3%) and 16.8% and 1.4% in Long COVID, respectively. Adjusted risk of mortality and hospitalisation were reduced with COVID-19 vaccination ≥2 doses (COVID-19:HR 0.36, 95% CI 0.34-0.38 and 0.69, 0.68-0.69; Long COVID:0.44, 0.42-0.47 and 0.90, 0.89-0.91). With influenza vaccination, mortality was reduced, but not hospitalisation (COVID-19: 0.86, 0.85-0.86 and HR 1.01, 1.01-1.01, and Long COVID: 0.72, 0.67-0.76, and 1.05, 1.03-1.07), with greatest effect in those with prior CVD and high CVD risk. Mortality and hospitalisation were also reduced by CVD prevention in those with CVD, e.g. anticoagulants- COVID-19: 0.69, 0.69-0.70 and 0.92, 0.91-0.93; Long Covid: 0.59, 0.54-0.64, and 0.88, 0.84-0.92. COVID-19 vaccination, influenza vaccination and CVD drugs (Anticoagulants) averted 101117 of 193598, 2138 of 4017 and 16573 of 36847 preventable deaths among individuals after COVID-19, and 875 of 1189, 65 of 127 and 507 of 1007 preventable deaths among those with Long COVID, particularly in people with CVD.

Conclusions

Prior CVD and high CVD risk are associated with increased hospitalisation and mortality risk in people with COVID-19 and Long COVID. Targeted improvement in COVID-19 vaccination and CVD prevention, especially in those with CVD are priority interventions in pandemics to avoid excess hospitalisation and mortality.Baseline Characteristics and OutcomesHospitalisation/mortality by COVID vaccn
Genetic predisposition of metabolic syndrome independent of weight in premature atherosclerosis
Authors: Singh S , Crooijmans J , Baars D P , Zwinderman A H , Pinto-Sietsma S J
Published: October 2024

Background

Family history is a significant predictor of premature atherosclerotic cardiovascular events, which suggest that a genetic susceptibility underlies the development of premature atherosclerosis. Rather than the influence of single classic risk factors, such as hypertension, diabetes and dyslipidemia, these risk factors could be part of an underlying genetic insulin resistance or metabolic syndrome

Methods

Data on patients and their first degree family members visiting premature atherosclerosis clinic in a university medical centre, from 2007 until 2023 was analyzed. We divided them in controls (CACs=0 and Age >40 years), subclinical ASCVD (sASCVD) (CAC score ≥80th percentile) and premature ASCVD (PAS). We used principal component analysis (PCA) for clustering the predictor variables and generalized linear mixed model (GLMM) to analyze the mutual relationship between different clusters. The model performance was further validated in predicting the premature ASCVD.

Result

There were 1551 individuals divided across control (n=438), sASCVD (n=309) and PAS (804). We found 12 variables univariate significantly related to sASCVD. Using a principal component analysis (PCA) approach, these variables were loaded across 4 clusters which were defined as 1. Metabolic (elevated glucose or diabetes, elevated blood pressure or Hypertension, elevated Triglycerides, elevated waist circumference and elevated LDL-C); 2. Liver (elevated ALAT, elevated GGT, elevated triglycerides, decreased thrombocytes) 3. Inflammatory (decreased HDL-C, elevated Triglycerides and elevated leucocyte count) and 4. Lipid (elevated Lp(a) and elevated LDL-C). After mutual correction and model building, the metabolic (OR; 95% CI) (1.82; 1.48-2.27) and Liver clusters (1.20; 1.00-1.45) were only found to be significantly associated with risk of sASCVD. However, we did not find any association of inflammatory (1.19; 0.98-1.44) and lipid cluster (1.19; 0.99-1.41) with risk of sASCVD. Besides, association of these clusters with risk of sASCVD significantly varies among families suggested from variance of intercept when family was kept as a random effect in GLMM model and no interaction was noticed with BMI. We checked the performance of this model on premature atherosclerosis cohort and found model had a good discriminatory (AUC, 0.762; 0.735-0.790; P=0.001) ability for predicting PAS [Figure 1].

Conclusion

In conclusion, our findings are suggestive of a significant association between metabolic syndrome factors and an increased risk of sASCVD in individuals with family history of premature atherosclerosis, regardless of weight. This association suggests the potential genetic predisposition towards premature atherosclerosis driving the observed metabolic parameters clustering in these individuals. Besides, the model demonstrated robust discriminatory power to predict premature atherosclerosis.ROC curve for premature atherosclerosis
Comparison of the predicting value for incident cardiovascular events by vascular age based on brachial-ankle pulse wave velocity or carotid-femoral pulse wave velocity
Authors: Dong D T , Fan F F , Chen C H , Dong D Z , Yang Y L , Luo L Y , Qiu Q Z , Fang F R , Zheng Z Q , Zhang Z X , Zhang Z Y
Published: October 2024

Background

There is a good correlation between brachial-ankle pulse wave velocity（baPWV）and carotid-femoral pulse wave velocity (cfPWV). Whether baPWV has the same predictability for cardiovascular risk as cfPWV in calculating vascular age remains to be clarified.

Purpose

This study examines which vascular age calculated by baPWV or cfPWV has a stronger association with the risk of cardiovascular events.

Methods

This prospective cohort study included 5725 participants from a community atherosclerosis cohort in Beijing, China. Vascular age was the predicted age in a multivariable regression model, including classical cardiovascular risk factors (sex, systolic and diastolic blood pressure, glycemia, triglyceride, low density lipoprotein cholesterol, waist, body mass index, heart rate, smoking) and treatment (anti-hypertensive agents, hypoglycemic agents, lipid-lowering agents) and pulse wave velocity. Residuals between chronological age and vascular age were defined as ∆-age, and the 10th and 90th percentiles of ∆-age were used as cutoffs to define supernormal vascular aging, normal vascular aging, and early vascular aging, respectively. The major adverse cardiovascular event was a composite of myocardial infarction, stroke, and cardiovascular death. The study used Cox proportional hazards regression to examine the association between vascular age and major adverse cardiovascular events.

Results

During the median 3-year follow-up period, 172 endpoint events were observed. After adjusting for age and sex, ∆-age as a continuous variable calculated by baPWV was significantly and increasingly associated with cardiovascular events (every 1-year increase led to a rise of 1.04% [95% confidence interval [CI]: 1.00%-1.08%; p=0.03] in cardiovascular events risk). After adjusting for age, sex, smoking, body mass index, hypertension, diabetes, dyslipidemia, anti-hypertensive agents, lipid-lowering agents, hypoglycemic agents, family history of atherosclerotic cardiovascular disease, and estimated glomerular filtration rate, early vascular aging group calculated by baPWV had an increased risk of cardiovascular events (hazard ratio: 1.76; 95% CI: 1.19-2.62 p=0.005), compared with the normal vascular aging group. In contrast, no significant results were observed in vascular age calculated by cfPWV.

Conclusion(s)

Vascular age calculated by baPWV has a stronger predictive ability for cardiovascular events than that calculated by cfPWV in the Chinese population. Considering baPWV is a simple and convenient method, it is recommended for vascular age calculation.
Refined selection of individuals for preventive cardiovascular disease treatment with a transformer-based risk model
Authors: Rao S , Li Y , Mamouei M , Salimi-Khorshidi G , Wamil M , Nazarzadeh M , Yau C , Collins G , Vickers A , Danaei G , Rahimi K
Published: October 2024

Background

Although statistical models have been commonly used to identify patients at risk of cardiovascular disease (CVD) for preventive therapy, these models tend to over-recommend therapy [1]. Moreover, in populations with pre-existing diseases, the current approach is to indiscriminately treat all individuals, as modelling in this context is currently inadequate.

Aims

To develop and validate a novel deep learning model, the Transformer-based Risk assessment survival model (TRisk) model, for prediction of 10-year risk of CVD in both the general population and individuals with diabetes.

Methods

An open cohort of 3 million adults aged 25 to 84 years free of CVD and statin use was identified using linked primary and secondary electronic health records from 291 and 98 general practices in England, which were used for TRisk model development and external validation, respectively. Comparison against two commonly recommended statistical models (QRISK3 [2] and SCORE2 [3]) and a deep learning derivation of QRISK3 was conducted. Additional analyses compared discriminatory performance in other age groups, by sex, and across categories of socioeconomic status. Similar analyses were conducted in a subgroup of 59 thousand patients with diabetes.

Results

TRisk demonstrated superior discrimination (C index in the general population: 0.910; 95% confidence interval [CI]: 0.906 to 0.913). TRisk’s performance was found to be less sensitive to population age range than the benchmark models and outperformed other models also in all stratified analyses. All models were overall well-calibrated. In decision curve analyses, TRisk demonstrated greater net benefit than benchmark models across the range of relevant thresholds. In impact analyses, at the widely recommended 10% risk threshold and the higher 15% threshold for the general population, TRisk reduced both the total number of patients classified at high risk (by 27% and 39% respectively) and the number of false negatives as compared with currently recommended strategies. TRisk similarly outperformed other models in patients with diabetes. Compared with the widely recommended treat-all policy approach for patients with diabetes, TRisk at a 10% risk threshold would lead to deselection of 24% of individuals with a small fraction of false negatives (0.2% of cohort).

Conclusion

TRisk enabled a more targeted selection of individuals at risk of CVD compared to benchmark statistical and deep learning models, in both the general population and patients with diabetes. Incorporation of TRisk into routine clinical care would allow a reduction in the number of treatment-eligible patients in general population and subgroup with diabetes by approximately one-third and one-quarter respectively while preventing at least as many events as with currently adopted approaches.Models' discrimination on both cohortsImpact analyses for both cohorts
Cardiovascular disease risk in people with diabetes in the era of universal diabetes screening
Authors: Liang J , Jackson R , Wells S , Poppe K
Published: October 2024

Background/Introduction

Traditionally, most people with diabetes have been considered at high cardiovascular disease (CVD) risk and CVD preventive treatment has been recommended for almost all patients after diagnosis. However, guidelines are increasingly recommending a more stratified approach to preventive treatment informed by predicted CVD risk. In the early 2000’s, New Zealand initiated the world-first national diabetes screening programme, as a component of a national CVD risk assessment programme, and by 2016, approximately 90% of eligible New Zealand adults had been screened. We hypothesised that in the era of universal diabetes screening, many recently diagnosed patients will be at low CVD risk and that contemporary CVD risk prediction equations would be required to accurately assess their risk.

Purpose

We aimed to develop sex-specific 5-year CVD risk prediction models in people with diabetes in New Zealand using a contemporary natural-population based cohort, and to characterise the distribution of CVD risk.

Methods

De-identified individual-level linkage of multiple health administrative datasets was undertaken to establish a cohort of almost all adults with diabetes in the northern region of New Zealand (one-third of the national population), without CVD or heart failure, and aged 30–74 years on January 1, 2014, with follow-up linkage to hospitalisations and mortality until December 31, 2018. Sex-specific models were developed to estimate the 5-year risk of CVD hospitalisation or death, with 15 pre-defined predictors, including sociodemographic variables, diabetes-related and renal function measures.

Results

64,645 participants (median age: 57 years [IQR: 49–65]) were included in the final cohort, of whom 4,992 had first CVD events during 301,272 person-years follow-up. Models calibrated well in both women and men (Figure 1). Overall, increasing age; high deprivation level; smoking-related hospitalisations or use of smoking cessation medications; history of atrial fibrillation; high levels of haemoglobin A1c, total cholesterol to HDL cholesterol ratio, and albumin-to-creatinine ratio; use of blood pressure-lowering medications and insulin were associated with elevated CVD risk. Median 5-year CVD risks were 4.9% (IQR: 2.9%–8.1%) in women and 7.7% (4.8%–12.0%) in men. There was a wide range of predicted 5-year CVD risk, with 51% of women and 27% of men having a predicted risk below 5%, and 6% of women and 16% of men having a risk of 15% or above (Figure 2).

Conclusions

This study demonstrated marked heterogeneity in predicted CVD risk in people with diabetes in an era of universal diabetes screening. As diabetes screening is increasingly undertaken as part of a routine CVD risk assessment, these findings will have important clinical implications for accurately targeting new but expensive CVD preventive medications to the highest risk patients.