bluuebunny/crossref_metadata_2025 huggingface dataset:
Control of arterial hypertension in the context of metabolically-associated disease: challenges and opportunities in Ukraine
Authors: Chendey T
Published: October 2024

Background/Introduction

Arterial hypertension is a prevalent, but modifiable cardiovascular (CV) risk factor. Effective control of blood pressure (BP) is associated with decreased rates of CV morbidity and mortality, as was convincingly demonstrated in randomized clinical trials. There is a substantial gap between BP control in clinical trials and real clinical practice due to multiple factors – e.g. lack of awareness, low medication compliance, side effects of medications, and insufficient availability of medical care – to name the few. The association between poor BP control and metabolically associated disease (MAD) like diabetes and obesity is widely acknowledged and considered the key challenge in effective management of arterial hypertension.

Purpose

To determine patterns of awareness and control of arterial hypertension in the context of MAD in Ukrainian outpatient patient sample.

Methods

We enrolled 309 subjects (108 with MAD and 201 without MAD). MAD was defined as the presence of type 2 diabetes and/or overweight/obesity. All subjects were consented for the structured interview and triple sitting BP measurement with an automated device.

Results

MAD-positive and MAD-negative groups were comparable by age (54.4±1.34 vs 51.8±1.2 years, p=0.29), systolic BP (141.3±2.0 vs 137.4±1.6 mm Hg, p=0.082), diastolic BP (85.2±1.2 vs 82.5±0.9 mm Hg, p=0.13). Presence of MAD was associated with increased odds of having BP>139/89 mm Hg (odds ratio [OR] 1.66, 95% confidence interval [CI] 1.04-2.67, p=0.035), better awareness on hypertension (OR 2.65, CI 1.64-4.28, p=0.0001), and less prevalent normotension (OR 0.51, CI 0.31-0.84, p=0.008). Among MAD-positive patients without history of HTN, 50% actually had elevated office BP, although it did not reach statistical significance as compared to MAD-negative subjects (OR 1.32 CI 0.68-2.56, p=0.42, see Picture 1). Less MAD-positive patients did not take any antihypertensive drugs (37.0% vs 56.7%, difference -19.7%, CI -8.03 to -30.51%, p=0.001), and more of them were taking 3 antihypertensive drugs (17.6% vs 7.5%, difference 10.1% CI 2.58-18.85. p=0.007). Only 53.7% of MAD-positive subjects and 39.8% of MAD-negative subjects claimed they were taking BP-lowering medications on a regular basis (p=0.02). There was no difference in achievement of BP control between MAD-positive and MAD-negative groups (39.2 vs 38.7% for subjects who were aware of HTN, 31.9 vs 31.3% of all hypertensive individuals, p=NS for both). More MAD-positive than MAD-negative subjects admitted they consume alcohol several times per week or daily (22.2 vs 12.4%, p=0.025).

Conclusions

MAD disease is associated with more prevalent HTN and better awareness on elevated BP. MAD requires more intensive BP-lowering therapy to achieve target BP, but the compliance to medications is suboptimal.Patterns of awareness and BP control
Comparison of intensive treatment versus standard treatment in lowering blood pressure and its association with cognitive decline and dementia: a systematic review and meta-analysis
Authors: Bresciani L , Silva A L M , Menegaz A , Sano V K T , Lobo A O M , Morbach V , De Moraes F C A , Alves F
Published: October 2024

Background

The ideal blood pressure target level for preventing cognitive decline or dementia in patients with systemic arterial hypertension (SAH) remains unclear.

Purpose

This study aims to investigate whether intensive blood pressure reduction compared to standard treatment is associated with a reduced risk of cognitive decline or dementia in adults with SAH.

Methods

PubMed, Scopus and Cochrane databases were searched for randomized clinical trials (RCTs) comparing intensive treatment versus standard treatment for blood pressure reduction in patients with SAH. A random-effects model was used for analyzing the results, which were presented as relative risk (RR) with a 95% confidence interval (CI). Heterogeneity was examined using the I² statistic. Statistical analysis was performed using R software version 4.2.3.

Results

A total of 5 RCTs and 46,658 patients were included, of whom 23,726 (50,85%) underwent intensive therapy for SAH treatment. The mean age of participants ranged from 62.8 to 80.9 years in the intensive treatment group while it ranged from 63.3 to 80.3 years in the standard treatment group. Occurrence of dementia or probable dementia was significantly lower in the intensive treatment group (3.8% vs. 4,3%; RR 0.88; 95% CI: 0.80 - 0.96; p= 0.0049; I²=0%). Dementia or Cognitive decline (16.4% vs. 18.8%; RR 0.87; 95% CI 0.83 - 0.90; p < 0.000001; I²=0%), and cognitive decline (13.2% vs. 15.2%; RR 0.88; 95% CI 0.80 - 0.98; p= 0.014; I²=53%) also tended towards the intensive treatment group. Additionally, no significant association was found in mortality (6.4% vs. 7.3%; RR 0.87; 95% CI 0.75 - 1.02; p= 0.09; I²=28%) and serious adverse effects (34.4% vs. 35.5%; RR 0.99; 95% CI 0.92 - 1.06; p=0.73; I²=63%).

Conclusion

Our study shows that intensive blood pressure treatment is associated with a fewer occurrence of dementia, probable dementia and cognitive decline in comparison to the standard blood pressure target.General Analysis
Orthostatic blood pressure changes and incident atrial fibrillation in patients with hypertension: Insights from the SPRINT trial
Authors: Wang J , Jiang C , He L , Xia S J , Li S T , Lv W H , Wang Z , Guo X Y , Li S N , Tang R B , Long D Y , Sang C H , Du X , Dong J Z , Ma C S
Published: October 2024

Background

Exaggerated orthostatic changes in systolic blood pressure (SBP) were associated with adverse cardiovascular events. However, the predictive role of SBP hyperactivity to standing on incident atrial fibrillation (AF) is unclear.

Purpose

We aim to assess the association between orthostatic SBP changes and incident AF.

Methods

We performed a post hoc analysis of SPRINT (Systolic Blood Pressure Intervention Trial), a randomized controlled trial comparing intensive (<120 mm Hg) and standard (<140 mm Hg) SBP interventions in participants with hypertension. Participants with standing SBP <110 mm Hg were not eligible for randomization according to the SPRINT protocol. Participants without AF who had seated and standing SBP measurements at baseline and available baseline or follow-up ECG were included in this analysis. Orthostatic SBP changes were defined as standing SBP minus seated SBP. Patients were grouped into tertiles of orthostatic SBP changes. AF was ascertained from the standard 12-lead ECG obtained at baseline, year 2, year 4, a close-out visit, and any visit when suspected of serious adverse events. We used Cox proportional regression models and restricted spline curves to assess the association of orthostatic SBP changes with incident AF.

Results

Among 8,455 participants included in this analysis, 327 incident AF cases occurred during follow-up. The restricted spline curve depicted a U-shaped relationship between orthostatic SBP changes and incident AF in the unadjusted model (P for nonlinearity = 0.012) (Figure 1). After adjusting for age, female, race, smoking, alcohol use, history of cardiovascular disease, history of chronic kidney disease, and body mass index, a SBP increase ≥ 6 mm Hg to standing was independently associated with a 43% higher risk of incident AF (HR: 1.43; 95% CI: 1.07-1.90; P = 0.014) compared to nonsignificant orthostatic SBP changes (>-4 mm Hg to <6 mm Hg). A SBP decrease ≥ 4 mm Hg to standing showed a nonsignificant higher risk of developing AF compared to SBP changes of >-4 mm Hg to <6 mm Hg (Figure 2). In subgroup analysis, the results presented a similar tendency to the main result. Sensitivity analyses also generated consistent results while additionally adjusting for seated and standing blood pressure or heart rate.

Conclusion

In this post hoc analysis of the SPRINT trial, exaggerated SBP increase to standing independently predicts incident AF.Figure 1Figure 2
Differences in resting sympathetic nervous activity between orthostatic hypertension, conventional hypertension, and healthy individuals
Authors: Ikeda T , Murai H , Hirai T , Sugimoto T , Tokuhisa H , Kobayashi D , Takata S , Fujimoto M , Sakata K , Usui S , Takamura M
Published: October 2024

Introduction

Standing places a significant hemodynamic burden on the cardiovascular system. In healthy individuals, neurohumoral reflex mechanisms, particularly the arterial baroreflex, maintain blood pressure during standing. However, in some cases, the counterregulatory response can be excessive, resulting in a condition known as orthostatic hypertension (OHT), which appears to be linked to an increased cardiovascular risk. In recent years, OHT has been recognized as an indicator for assessing the effectiveness of renal denervation. It is suggested that abnormalities in sympathetic nervous system regulation, particularly related to the renal sympathetic nerves, may play a role in influencing RDN outcomes, however, the relationship between OHT and sympathetic nerve activity remains poorly understood. This study aims to assess the differences in sympathetic nerve activity between OHT patients, conventional hypertensive(cHT) patients and healthy individuals using muscle sympathetic nerve activity (MSNA) measurements.

Methods

We conducted an examination of hypertensive patients undergoing drug treatment at our clinic between April 1, 2023, and June 30, 2023, to identify cases of OHT. OHT was defined as a sustained increase in systolic blood pressure ≥20 mmHg and/or diastolic blood pressure ≥10 mmHg within 3 minutes of standing. We measured MSNA in the cases for which consent was obtained.

Results

Among the 138 cases, 31 were diagnosed with OHT, and 7 of them consented to MSNA measurement. Of the 11 cases of cHT patients who consented, two groups were well age-matched. And it was also compared with 11 cases of healthy individuals who underwent MSNA measurement during the same period. Both of the MSNA burst frequency and burst incidence in OHT (38.4 +/- 12.2 bursts/min, 61.1 +/- 21.3 bursts/100 heartbeats) was significantly greater (p<0.05) than that in cHT (28.3 +/- 5.7 bursts/min, 44.6 +/- 11.1 bursts/100 heartbeats), and all these were significantly greater (p<0.05) than in healthy individuals (21.8 ± 7.3 bursts/min, 35.8 +/- 11.3 bursts/100 heartbeats) at rest.

Conclusions

OHT is associated with sympathetic hyperactivity compared to normal hypertensive patients, contributing to an increased cardiovascular risk. These results indicate that therapy for OHT in hypertensive patients would be required to prevent sympathetic augmentation.
Cardiovascular events risk in office-masked nocturnal hypertension defined by home blood pressure monitoring: the J-HOP nocturnal blood pressure study
Authors: Fujiwara T , Hoshide S , Sheppard J , Mcmanus R , Kario K
Published: October 2024

Background

Elevated nocturnal home blood pressure (BP) has been reported to be associated with increased risk for cardiovascular disease (CVD). Masked hypertension defined by home BP monitoring is also a strong risk factor for adverse CVD outcomes. However, no study has investigated the association between office-masked nocturnal hypertension defined by home BP monitoring and CVD events risk.

Purpose

This study aimed to examine the association between office-masked nocturnal hypertension defined by home BP monitoring and CVD events risk in a clinical practice-based population.

Methods

This was a prospective observational study including Japanese participants with CVD or high risk of CVD. Three office BPs were taken on two different occasions. Nocturnal home BP was measured three times per night for two weeks. The association between office-masked nocturnal hypertension and incident total CVD events (including fatal and non-fatal stroke and coronary heart disease) was examined using Cox regression.

Results

2,545 participants were followed for the mean of 7.1 years (18,116 person-years), during which 152 (6.0%) CVD events occurred. Mean age (standard deviation) was 63.3 (10.3) years; 49.0% were male; 82.6% took antihypertensive medications. The proportions of participants with normotension (office BP <140/90 mmHg and nocturnal home BP <120/70 mmHg), white-coat hypertension (office BP ≥140/90 mmHg and nocturnal home BP <120/70 mmHg), office-masked nocturnal hypertension (office BP <140/90 mmHg and nocturnal home BP ≥120/70 mmHg), and sustained hypertension (office BP ≥140/90 mmHg and nocturnal home BP ≥120/70 mmHg) were 25.3%, 14.4%, 23.2%, and 37.1%, respectively. The office-masked nocturnal hypertensive group and sustained hypertensive group had higher incidence rates of total CVD events compared with the normotensive group. Relative to normotension, those with both office-masked nocturnal hypertension (adjusted hazard ratio [aHR] 1.72, 95% confidence interval [CI] 1.01–2.92) and sustained hypertension (aHR 1.75, 95%CI 1.03–2.96) had similarly increased CVD risk, even after adjustment for daytime home BP values.

Conclusions

Screening for office-masked nocturnal hypertension with home BP monitoring identifies a potentially important group of patients with increased risk for incident CVD events for whom additional preventative measures may be appropriate.
Invasive validation of central blood pressure measurements using a suprasystolic monitor
Authors: Scalia A , Ghafari C , Scott R F , Rochd E M , Caulier F , Phillips R , Carlier S G
Published: October 2024

Interest in the assessment of Central Blood Pressure (cBP) is steadily growing since it is a better predictor of myocardial infarction, stroke, or death than Peripheral Blood Pressure (pBP). However, pBP remains the first line for the diagnosis of hypertension (HTN) due to the ease and speed of the measurement.

We sought to validate a new method to estimate cBP from brachial sphygmomanometer measurements.

We estimated cBP using a sphygmomanometer that can record, after conventional pBP measurements, the pressure in the cuff maintained at a constant suprasystolic pressure. cBP is calculated using a method based on applying a physics-based model of the left subclavian artery to the brachial arterial branch to the suprasystolic brachial artery pressure waveforms. We compared this noninvasive estimated cBP to an invasive gold-standard measurement during cardiac catheterization. After clinically indicated cardiac catheterization requiring a haemodynamic assessment of a moderate coronary artery stenosis by Fractional Flow Reserve (FFR), the wire that incorporates a high fidelity electronic pressure transducer was positioned into the guiding catheter left in the ascending aorta. Simultaneous measurements were performed with a cuff placed on the patient's left arm. The output signals were recorded in a custom-based acquisition system. The comparison was obtained on the same 10 seconds recorded by the cuff and the pressure wire. The goal will be to reach 85 patients as recommended by the ARTERY Society Task Force. It recommends as an accuracy criterion to achieve a mean difference ≤ 5 mmHg with a standard deviation (SD) ≤ 8 mmHg, which are the standards adopted for this study. Patients with aortic stenosis, atrial fibrillation, or frequent (supra)ventricular extrasystoles were excluded.

A total of 197 pairs of measured-estimated cBP were analysed in 78 patients with a mean age of 63 ± 8 yo, 75% of whom were men, 70% had hypertension, 26% fdiabetes, 93% dyslipidemia, 41% were tobacco users and 14% suffered from clinical peripheral artery diseases without history of revascularization. The median (InterQuartiles 25-75%) pBP was 123 [112 134] / 70 [64 77] mmHg. Measured cBP was 102 [92 11] / 78 [70 84] mmHg with a central augmentation index of 34 [23 44] %. The mean difference between estimated and measured systolic cBP was 4.9 ± 6.5 mmHg, while it was -3.9 ± 5.8 mmHg for diastolic cBP, meeting the prespecified accuracy criteria.

In conclusion, our approach based on an exact matching and comparison of non-invasive suprasystolic arm cuff measurements and high-fidelity aortic BP validates that an estimation of central aortic blood pressure that can be easily carried out in daily practice and might improve HTN management. It remains to be demonstrated that more cardiovascular complications will be avoided by guiding the antihypertensive therapy with cBP instead of pBP measurements.Bland-Altman of estimated - measured cBP
Arterial hypertension in the era of obesity bias: the impact of obesity status on pharmacological treatment intensification in patients with diabetes
Authors: Heiden Telo G , Matzenbacher L S , Friedrich Fontoura L , Avila G O , Gheno V , Brum M A B , Teixeira J B , Erthal I N , Schneiders J , Schaan B D , Alessi J , Telo G H
Published: October 2024

Background

Obesity is recognized as a significant risk factor for several chronic conditions, such as diabetes and hypertension. Despite the growing healthcare needs of individuals with obesity, they often encounter obesity bias, potentially impacting the quality of medical care they receive.

Purpose

The aim of this study was to explore the impact of obesity on the appropriateness of antihypertensive treatment decisions in individuals with concurrent diabetes and hypertension.

Methods

In this multicenter cross-sectional study, patients with type 2 diabetes and arterial hypertension who were receiving outpatient care across four centers in Southern Brazil were enrolled. Participants were categorized into two groups based on their Body Mass Index (BMI): eutrophic (BMI <25.0 kg/m²) and patients with obesity (BMI ≥30.0 kg/m²). The primary outcome evaluated was the difference in pharmacological treatment decisions for hypertension between groups, considering individualized hypertension targets from American Diabetes Association (ADA), European Society of Hypertension (ESH), and European Society of Cardiology (ESC). Analysis was conducted on whether patients failed to receive necessary treatment intensification, comparing groups through multivariable logistic regression.

Results

The study comprised 204 individuals with type 2 diabetes and arterial hypertension, including 53 eutrophic and 151 patients with obesity. It was observed that patients with obesity more frequently fail to receive appropriate treatment intensification when compared to eutrophic individuals. This finding was statistically significant across the hypertension targets set by the ESH (adjusted Odds Ratio [OR] 2.03 [95% Confidence Interval [CI] 1.08-3.83], p = 0.022), ESC (adjusted OR 1.94 [95% CI 1.03-3.65], p = 0.035), and ADA (adjusted OR 2.01 [95% CI 1.07-3.79], p = 0.021).

Conclusion

The study indicates that obesity may contribute to disparities in the management of hypertension, suggesting a link between obesity status and therapeutic inertia in treating arterial hypertension among these patients.
Injectable angiotensinogen inhibition therapy for hypertension: a systematic review and meta-analysis
Authors: Gomez V , Yadav A , Gmach Taffarel L , Bozko Collini M , Villa Martignoni F
Published: October 2024

Introduction

Hypertension is the leading risk factor worldwide for cardiovascular mortality, and the development of kidney disease. Management of hypertension involves multiple approaches that involve daily tablet ingestion, with high rates of non-adherence. There is an unmet need for innovative interventions to improve adherence to treatment.

Purpose

We aimed to perform a systematic review and meta-analysis to investigate the role of injectable angiotensinogen (AGT) inhibitors, such as Zilebesiran and IONIS-AGT-LRx, in the treatment of hypertension.

Methods

PubMed, Embase, and the Cochrane Library were systematically searched for randomized controlled clinical trials (RCTs) comparing injectable AGT inhibitors versus placebo. Efficacy was assessed through mean changes in angiotensinogen, systolic blood pressure (SBP), and diastolic blood pressure (DBP). We also examined safety endpoints. We computed pooled mean differences (MD) or risk ratios (RR) for continuous and binary outcomes, respectively, under a random-effects model with a 95% confidence interval (CI).

Results

Four studies were included for a total of 512 patients, of whom 279 (54.5%) were male, with a mean age of 57 years old; 349 (68.2%) were white. The mean baseline SBP was 142 ± 19.9 mmHg. In a pooled analysis, mean change of AGT decreased significantly with injectable AGT inhibitor compared with placebo (MD -77.86 %; 95% CI -107.49 to -48.23; p<0.01). Similarly, mean change in SBP (MD -14.15 mmHg; 95% CI -19.53 to -8.78; p=0.30) and DBP (MD -8.49 mmHg; 95% CI -9.98 to -7.00; p=0.78) were also significantly lower in the injectable AGT inhibitor group compared with placebo. AGT inhibitors were well tolerated, without associations with serious adverse events, adverse events related to discontinuation, death, hyperkalaemia, or hypotension. However, there was an increase in injection site reaction with these agents compared with placebo (RR 5.86; 95% CI 1.14 to 30.17; p=0.83).

Conclusions

In this meta-analysis of RCTs, injectable AGT inhibitors were associated with a significant decrease in mean AGT, SBP, and DBP as compared with placebo. There were no significant differences between groups in serious adverse events, although injection site reaction was more common in patients treated with injectable AGT inhibitors.Forest plot of mean change in SBP
Degree of joint risk factor control and incident all cause dementia in hypertensive patients
Authors: Chen M , Ning Y , Zhao C , An J , Tang M , Tse G , Chan S , Lei X , Qiang H , Yu H , Bai C , Yan Y , Wang D , Li G
Published: October 2024

Background

Hypertension (HT) is a known modifiable risk factor for dementia. This study evaluates the impact of effectively controlling multiple modifiable risk factors in HT patients on the incidence of dementia.

Methods

Data from the UK Biobank (2006-2010) were used in this longitudinal study, including essential HT patients and non-HT participants, excluding those with pre-existing dementia or less than two years of follow-up. The study focused on seven risk factors: physical activity, smoking status, blood pressure, body mass index, glycosylated hemoglobin levels, lipids, and urinary Albumin-to-Creatinine Ratio. The Cox model evaluated the association between the degree of risk factor control and the incidence of dementia, while linear regression models analyzed the brain abnormalities among different risk factor control groups.

Results

Of 291,720 participants, 86,675 had HT. Over a median follow-up of 14.3 years, dementia developed in 2,002 HT and 1,379 non-HT participants. Compared with non-HT individuals, a gradual decrease in dementia risk in HT patients with the number of well-controlled risk factors was observed (hazard ratio: 2.01 [95% confidence interval (CI) 1.73-2.34] to 1.25 [95% CI 1.13-1.40]). While within HT patients, with the highest level of control lowering the risk to 0.63 (95% CI [0.54-0.73]). Moreover, HT patients with better well-controlled risk factors had lower geometric mean for white matter hyperintensity volume and increased total brain parenchymal volume, gradually narrowing the gap with non-HT individuals.

Conclusion

In HT patients, a higher degree of well-controlled risk factors seemed to be associated with progressively lower risks of dementia and brain abnormalities.HRs of all-cause dementia in patientsGMRs of different risk factors on target
Mildly decreased egfr modifies the association between uric acid and risk of kidney function decline: a 5-year population-based cohort study
Authors: Li Z Y , Wu S S , Li D , Wang G , Zhang N , Zhao F , Hao J , Yang C L , Song J S , Gu X Z , Huang R C
Published: October 2024

Background

the role of uric acid (UA) in chronic kidney disease (CKD) remains controversial. In this study, the effects of UA levels on risk of kidney function (KF) decline in patients with normal or mildly decreased KF at baseline were investigated.

Methods

Data were extracted from the community-based Tongzhou Cohort Study. The cohort of 4246 patients was divided into the normal KF group (estimated glomerular filtration rate [eGFR] ≥ 90 mL/min/1.73 m2) or mildly decreased KF group (60 ≤ eGFR < 90 mL/min/1.73 m2). The primary endpoint was the risk of kidney function decline, which defined as a composite of a ≥ 30% decrease in eGFR from baseline or new onset of CKD diagnosed during the annual checkups.

Results

A total of 284 participants reached the primary endpoint during the 5-year follow-up period. There was a significant interaction between UA levels and baseline eGFR (p < 0.001). Restricted cubic spline analysis revealed a U-shaped association between baseline UA levels and the risk of decreased KF for participants with normal KF (cut-off value = 5.0 mg/dL; pnonlinear = 0.025) and a linear association for participants with mildly decreased KF (pnonlinear = 0.384). The odds ratio of an increase in UA levels by 1 mg/dL was 1.15 [95% confidence interval (CI) 1.02–1.31, p = 0.028] for the primary endpoint and 1.15 (95% CI = 1.01–1.31, p = 0.037) for new onset of CKD for participants with mildly decreased KF.

Conclusion

The association between uric acid and risk of KF decline was U-shaped in participants with normal KF while linear in participants with mildly decreased KF.
Blood pressure polygenic risk scores associate with resistant hypertension in individuals with type 1 diabetes
Authors: Sanez Taehtisalo H , Antikainen A , Mutter S , Lithovius R , Groop P H , Kontula K K , Hiltunen T P , Sandholm N
Published: October 2024

Background

Hypertension is a major risk factor of global disease burden, but treatment goals are often not met. A subset of individuals with hypertension is affected by treatment-resistant hypertension (RHTN), and they suffer from increased cardiovascular morbidity and mortality. Early identification of individuals at risk of RHTN could lead to more efficient antihypertensive drug treatment.

Purpose

The aim of this study was to investigate whether polygenic risk scores (PRS) for systolic (SBP) and diastolic blood pressure (DBP) predict RHTN in individuals with or without type 1 diabetes (T1D).

Methods

We performed association analyses between PRSs and RHTN in two Finnish cohorts: The Finnish Diabetic Nephropathy Study (FinnDiane) and the Finnish individuals of the LIFE Study (LIFE-Fin).

FinnDiane is an ongoing, observational nationwide study aiming to identify genetic and clinical risk factors for complications of T1D. We included data from 778 adults (476 with RHTN and 302 with controlled hypertension).

LIFE is a randomized, double-blind study evaluating long-term effects of losartan compared with atenolol in patients with signs of left ventricular hypertrophy. We used SBP and DBP data from 378 Finnish individuals (173 with RHTN and 205 with controlled hypertension) at the four-year visit of the study.

In FinnDiane, RHTN was defined as SBP ≥130 or DBP ≥85 mmHg and the use of three or more antihypertensive drugs, or SBP <130 and DBP <85 mmHg and the use of four or more antihypertensive drugs. In LIFE-Fin, RHTN was defined as SBP ≥140 or DBP ≥90 mmHg and the use of three or more antihypertensive drugs. Controlled hypertension was defined as the use of three or fewer antihypertensive drugs and SBP <130 and DBP <85 mmHg in FinnDiane, and as SBP <140 and DBP <90 mmHg in LIFE-Fin.

We calculated a PRS for each participant using genome-wide association study data for 1,098,015 genetic variants; the variant-specific data were derived from UK Biobank based PRS-CS-method computed PRSs (1).

Results

We observed significant associations of SBP and DBP PRSs with RHTN in FinnDiane (OR 1.56 [1.30; 1.87], P = 1.8e-6, and OR 1.25 [1.04; 1.50], P = 0.02, per one-SD increase of the PRS value) when adjusted for age, sex, estimated glomerular filtration rate and body mass index. The association between SBP PRS and RHTN remained significant when T1D individuals with or without albuminuria were analysed separately. Neither SBP nor DBP PRSs were significantly associated with RHTN in LIFE-Fin.

Conclusion

Higher SBP PRSs associate with higher risk of RHTN in individuals with T1D, with or without albuminuria, but not in nondiabetic individuals with hypertension. It remains to be investigated whether general blood pressure genetics contribute to RHTN in the general population.
Influences of cardiovascular disease on the relationship between baseline systolic blood pressure and adverse outcomes in diabetes: insights from large population-based study
Authors: Cai A , Feng Y Q , Nie Z Q
Published: October 2024

Objective

To evaluate the influences of cardiovascular disease (CVD) on the relationship between baseline systolic blood pressure (SBP) and adverse outcomes in diabetes.

Methods

This is an observational study of 16431 community-dwelling adults with diabetes and 7.8% had CVD. The relationship between SBP (either as a categorical or continuous variable) with major adverse cardiovascular event (MACE) and all-cause death were evaluated by baseline CVD status using multivariable-adjusted Cox proportional hazard models and restricted cubic spline.

Results

After a median follow-up of 3.4 years, 2145 (13.1%) MACE and 1025 (6.2%) all-cause death occurred. In the overall participants there was a linear relationship between SBP and MACE (P-nonlinear=0.55) and a U-shaped relationship between SBP and all-cause death (P-nonlinear=0.002). In participants free of CVD, in reference to SBP < 120 mmHg group, the risks for MACE increased as SBP category (120-129, 130-139, and ≥ 140 mmHg) advanced (P-trend < 0.001) and there was a linear relationship (P-nonlinear=0.75; Figure 1A); while the risks for all-cause death were lower in SBP of 120-139 mmHg and 140-159 mmHg groups while higher in SBP ≥ 160 mmHg group, and there was a U-shaped relationship (P-nonlinear<0.001; Figure 1B). Notably, in participants with existing CVD the relationship between SBP with MACE and all-cause death did not show any specific pattern.

Conclusion

The relationship between baseline SBP with MACE and all-cause death varied substantially by baseline CVD status. Future studies to investigate the threshold of initiating BP-lowering treatment and the appropriate BP target in diabetes may consider applying a CVD-based stratification strategy.
Impact of appendicular skeletal muscle mass on effect of intensive blood pressure control
Authors: Pei J , Wang X
Published: October 2024

Background

Appendicular skeletal muscle mass (ASM) is associated with cardiovascular diseases (CVDs) and chronic kidney diseases (CKDs). However, whether low ASM affects the efficacy of intensive systolic blood pressure control is currently uncertain.

Purpose

To examine the impact of low ASM on the effects of intensive SBP control on cardiovascular and kidney outcomes.

Methods

Data from the Systolic Blood Pressure Intervention Trial (SPRINT) and the Action to Control Cardiovascular Risk in Diabetes Blood Pressure (ACCORD-BP) trials was used. The primary outcome was a composite of myocardial infarction, acute coronary syndrome without myocardial infarction, stroke, heart failure, and cardiovascular death. The prespecified incident CKD was defined as a >30% decrease in estimated glomerular filtration rate to a value <60 mL/min/1.73 m2.

Results

A total of 14,017 patients were included in this study, 2203 (15.7%) of whom had low ASM. Over a median follow-up of 3.26 years, 1,032 primary outcomes and 460 incident CKD were observed. Patients with low ASM had a significantly higher risk of primary outcome and CKD. Intensive SBP control effects on cardiovascular outcomes were not significantly different on a relative scale or absolute scale. But low ASM significantly amplified the increased risk of CKD associated with intensive SBP control, on an absolute scale (P for interaction = 0.04).

Conclusions

Low ASM is one of the markers of increased risk of CVD and CKD, and it did not affect the cardiovascular benefits of intensive treatment, but significantly amplified the increased risk of CKD associated with intensive SBP control.
Interaction between subclinical carotid atherosclerosis endotype and biological sex: a study from IMPROVE cohort
Authors: Chen Q , Bergman O , Ziegler L , Baldassarre D , Tremoli E , Strawbridge R , Eriksson P , Gigante B
Published: October 2024

Background

Carotid-intima media thickness (c-IMT) is a measure of subclinical carotid atherosclerosis and a predictor of future atherosclerotic cardiovascular events (ASCVD). We have recently generated, using an artificial intelligence approach, four endotypes (E) of subclinical atherosclerosis, i.e. subgroups of individuals predisposed to both c-IMT progression and ASCVD. Each E is defined by a set of demographic, clinical, and molecular data and characterize individuals with a low (E1), intermendiate (E2), high (E3) and very high (E4) cardiovascular risk profile. We observed an unbalanced distribution of males and females across the 4 endotypes, with a higher prevalence of female in the low risk E1.

Purpose

To estimate the interaction between biological sex and the 4 endotypes on measures of c-IMT progression and ASCVD risk.

Methods

We performed our study on 3121 individuals from the IMPROVE cohort, which includes participants with at least three ASCVD risk factors. We estimated the interaction between biological sex and the endotypes generated in the IMPROVE on (1) c-IMT and carotid plaque measurements after 30 months of follow-up (c-IMTfastest-progr, Area of plaquesbulb-progr) by linear regression (β, SE) and (2) with the 3-year ASCVD risk by Cox [hazard ratio (HR), 95% confidence interval (CI)] regression model. Crude estimates were adjusted by batch effect for biomarker measurement, geographical region and/or baseline ultrasonographic measures. Adjusted models further included ASCVD common risk factors.

Results

As shown in Figure 1, we did not observe any significant interaction between endotypes and biological sex on 30-month carotid ultrasound progression measures, and 3-year-ASCVD risk. In both the crude and adjusted models on c-IMTfastest-progr, Area of plaquesbulb-progr, and 3-year ASCVD, the p-value for interaction ranged from 0.18 to 0.98. While E4 was associated with the strongest cardiovascular risk profile in both males and females.

Conclusions

Our results indicate that the association between endotypes and progression of subclinical atherosclerosis and ASCVD risk mirrors a specific risk profile not entirely explained by differences in biological sex.
Independent and joint associations of urinary potassium excretion with cardiovascular death: a national population-based cohort study
Authors: Lin C , Tian Y , Li X
Published: October 2024

Background

Elevated potassium excretion is associated with lower blood pressure, as well as reduced risks of cardiovascular disease (CVD) death. However, the impact of varied sodium levels on this association remains a topic of debate, and the mediators of this association besides blood pressure remain uncertain.

Purpose

To examine the joint association of potassium and sodium with CVD mortality risk, and to identify potential mediating factors of this association.

Methods

Based on the ChinaHEART (China Health Evaluation And risk Reduction through nationwide Teamwork) project, participants aged 35-75 from 239 sites across all 31 provinces in the mainland of China were recruited from November 2014 to December 2022. We collected spot urine samples from participants and estimated 24-hour sodium and potassium excretion using the Kawasaki formula. Death records were captured through data linkage with the National Mortality Surveillance System and Vital Registration. Multiple regressions were used to analyze the association between potassium excretion and CVD death, as well as to examine the addictive interaction of potassium and sodium.

Results

This study included 270,991 participants with a mean age of 55.8±9.8 years, and 60.5% of them were female. The mean potassium excretion was 54.36±12.58 mmol/d , which was higher in males and people living in the north. Findings revealed a positive correlation between low urinary potassium levels and CVD death , and the lowest adjusted hazard rate for CVD mortality was 0.65 (95% CI: 0.58-0.73) in the group with the highest potassium excretion (i.e. ≥64.27 mmol/d) compared with the reference group (<43.79 mmol/d), after adjusting for sociodemographic characteristics, medical histories, and lifestyles. Age modified the association between potassium excretion and risk of CVD death (P for interaction=0.031). In addition to systolic blood pressure (16.6%), heart rate (2.2%) also served as the significant mediator between urinary potassium excretion and CVD death. The relative excess risk of interaction (RERI) of lower potassium excretion and lower sodium was significantly positive (RERI=0.22, 95% CI: 0.02-0.42), which implied the synergy effect.

Conclusion

Potassium intake in the Chinese population is evidently lower than the guideline recommendations, and increasing potassium intake, especially in the population aged <65 years, may reduce the risk and burden of cardiovascular and other diseases. Moreover, when sodium intake is insufficient, supplementation with both sodium and potassium salt can achieve greater health benefits.Graphic abstract
The Cardiovascular Disease Burden Associated with secondhand smoke, 1990-2019: an age-period-cohort analysis of the Global Burden of Disease study
Authors: Jiang H , Liu Z , Wei P J , Ouyang W , Wang S Z , Zhang F W , Pan X B
Published: October 2024

Background

Over the past three decades, global regions have shown significant differences in the burden of cardiovascular disease (CVD), and secondhand smoke is a major risk factor contributing to this burden. Nevertheless, a comprehensive understanding of the global trends and associations between second-hand smoke and cardiovascular disease is lacking.

Methods

Using data from the Global Burden of Disease (GBD) study 1990-2019, an age-period-cohort (APC) analysis was conducted to investigate trends in cardiovascular disease-related mortality in populations affected by secondhand smoke globally over the past 30 years and its association with age, period, and birth cohort.

Results

Over the past 30 years, the number of cardiovascular deaths caused by secondhand smoke has increased significantly worldwide, from 432.6 thousand in 1990 (95% UI: 357.4-508.3) to 598.5 thousand in 2019 (95% UI: 489.7-713.5), an increase of 38.4% (95% UI: 26.8%-49.5%). In 2019, cardiovascular disease accounted for 45.9% of all deaths attributable to secondhand smoke in both men and women globally. Among cardiovascular diseases, ischemic heart disease became the main component, accounting for 66.4% compared with stroke. The gender composition of cardiovascular deaths due to secondhand smoke is slightly lower in men (46.5%) than in women (53.5%). Longitudinal analyses using age-time-cohort models show that global CVD-related mortality from secondhand smoke has improved overall over the past three decades, but there are differences between regions, genders, and CVD subtypes. It is worth noting that the higher the socio-demographic index (SDI) level, the greater the reduction in mortality, with a staggering 39.1% reduction in high SDI areas (95% UI: 35.6%-42.3%), in sharp contrast to virtually no change in mortality in low SDI areas (0.1% (95% UI: -52.4%-62.2%)). During the period 2003-2007, cardiovascular disease-related mortality decreased significantly, with an average annual percentage change of -1.48%.

Conclusion

The study highlights the importance of using secondhand smoke as a modifiable risk factor for the global burden of cardiovascular disease. Further research is vital to understand the factors that lead to differences in countries and regions at different levels of development, gender differences and differences in cardiovascular disease subtypes.
A novel electrocardiogram-based model for prediction of dementia: the Atherosclerosis Risk in Communities (ARIC) study
Authors: Chen D , Yao Y , Moser E , Wang W , Soliman E , Mosley T , Pan W E I
Published: October 2024

Background

Current dementia prediction models, such as the UK Biobank Dementia Risk Score (UKBDRS, 12 variables), are limited by having variables that are difficult to obtain, subjectively measured, and self-reported. Although individual ECG parameters are linked to higher dementia risk, no study has combined multiple ECG parameters to create an ECG model for dementia prediction.

Purpose

Using data from the ARIC study, a prospective community-based cohort of Black and White participants in the USA that started in 1987-89, we created an ECG model (based on 7 pre-defined ECG parameters linked to dementia) and compared its model discrimination with the UKBDRS.

Methods

Participants without prevalent dementia from 2 baselines were included: Visit 4 (V4, 1996-98) and V5 (2011-13). Seven ECG parameters were examined: heart rate, abnormal P-wave terminal force in lead V1 (PTFV1), prolonged P wave duration, abnormal P wave axis, advanced interatrial block, left ventricular hypertrophy (LVH, Cornell voltage criteria), and corrected QT interval (QTc). Dementia cases were identified through 2019 using in-person and phone cognitive assessments, hospitalisation codes, and death certificates. Using a backward selection method (keeping variables with P<0.10 and age, since it is an important dementia risk factor), parsimonious Cox regression models were constructed for prediction of dementia over the longest available follow-up (V4: 23 years, V5: 8 years). Model discrimination of the ECG models and UKBDRS variables was evaluated by the Harrell’s C-statistic (95% CI).

Results

At V4, 11,520 participants (mean age, 62.8 ± 5.7 years; 56% women; 22% Black) were included; 2,427 developed dementia. At V5, 5,667 participants (mean age, 75.4 ± 5.1 years; 59% women; 22% Black) were included; 830 developed dementia. Figures 1 and 2 show the C-statistic (95%) and area under the ROC curve for the ECG model and UKBDRS variables at V4 and V5, respectively. The C-statistic (95% CI) for both ECG models were >0.70 and comparable with the corresponding UKBDRS models.

Conclusion

For middle-aged and older adults, a dementia prediction model comprising age and 4 ECG variables has good discrimination for dementia that is comparable with the 12-variable UKBDRS model. Since ECG variables are easily obtainable and objectively measured, these ECG models will be easier to adopt than the UKBDRS model. Further work to validate this model in an external cohort and develop a risk score will facilitate clinical translation.
Heterogeneous associations of traditional atherosclerotic risk factors and long-term events in different arterial territories: the EPIC Norfolk prospective population cohort
Authors: Van Den Bogaart M , Snaterse M , Van Trier T J , Martens F M A C , Peters R J G , Boekholdt S M , Jorstad H T
Published: October 2024

Background

Atherosclerotic risk factors have been associated with cardiovascular disease (CVD) events in specific arterial territories. However, these observations are limited by relatively short-term follow-up (i.e. ten years) and a focus on a limited number of outcome events. We therefore investigated associations between atherosclerotic risk factors and territory-specific cardiovascular events in a large cohort with ≥20 years follow-up.

Methods

We included participants without baseline CVD from the European Prospective Investigation of Cancer (EPIC) Norfolk prospective population cohort. The strengths of associations between CVD risk factors (smoking, low-density lipoprotein cholesterol (LDL-c), and systolic blood pressure (SBP)) and the first occurrence of a CVD event were evaluated using a competing risk-adjusted regression model. CVD events were defined as hospitalisations or death due to ischemic heart disease (IHD), ischemic stroke, haemorrhagic stroke, peripheral arterial disease (PAD) or aortic aneurysm (AA). Patients were followed-up until the first event, non-CVD death (competing risk) or end of study (15-03-2018). The model was adjusted for sex, age, diabetes, HDL-c, kidney function and body mass index. LDL-c and SBP were analysed by comparing highest versus lowest quartiles. Smoking (at baseline) was compared to never smoking.

Results

We included 23,581 participants (56% women) with a median baseline age of 58 years [interquartile range (IQR) 51-66]. During median follow up of 21.3 years (IQR 19.0-22.8), 26.4% of individuals experienced ≥1 CVD event. The first event of occurrence was IHD in 17.3%, ischemic stroke in 3.6%, haemorrhagic stroke in 1.4%, PAD in 3.1% and AA in 1.4%. LDL-c was strongest associated with IHD [adjusted hazard rate (aHR) 1.7, 95% confidence interval (CI) 1.5-1.9], SBP with ischemic stroke (aHR 1.9, 95%CI 1.5-2.5) and smoking with AA (aHR 4.8, 95%CI 3.5-6.5) (Figure 1).

Conclusions

There is considerable heterogeneity in the associations between atherosclerotic risk factors and long-term, first, territory-specific cardiovascular events. Knowledge of these differences may assist in personalised treatment decisions and risk communication.
Burden and sociodemographic disparities in cardiovascular mortality rates associated with hypercholesterolemia in united states: a nationwide county-level analysis from 2010 to 2019
Authors: Abohashem S , Civieri G , Dar T , Goudot G , Aldosoky W
Published: October 2024

Background

Hypercholesterolemia (HC), a major public health concern, has seen a rising prevalence in US adults and globally, leading to increased morbidity and mortality. Despite well-established links between HC and cardiovascular mortality (CVM), the specific impacts and disparities at the population level remain poorly understood.

Purpose

This study aims to assess the independent effects of HC on VM across the overall US population, examining variations across sociodemographic groups and geographic locations.

Methods

Age-adjusted county-level CV rates (ACVM per 100,000 individuals) between 2010 to 2019 were obtained using the Center for Disease Control and Prevention (CDC) database. Using the CDC surveillance system, HC rates per county were assessed as the proportion of adults (+18) with high total blood cholesterol. County health ranking project databases were utilized to acquire county characteristics and demographics. Poison generalized estimating equation models were employed to assess incidence rate ratios (IRR).

Results

Of 307,045,656 residents who lived in 3142 US counties in 2010, a total of 8,157,580 (2.7%) CV deaths occurred between 2010-2019. In a fully adjusted model*, high HC rates associated with high ACVM (Standardized IRR: 1.049; Figure 1). In subgroup analyses, HC rates associated with a greater ACVM among counties with high minority (IRR: 1.070) versus low (IRR: 1.043), and in rural areas (IRR: 1.052) versus urban (IRR: 1.041). Notably, this association was prominent in areas with high poverty (Q4 vs. Q1) (IRR: 1.062 vs. 1.035; p interaction <0.001; Figure 1). Further, higher ACVM rates related to HC were observed in the South and Northeast U.S. regions.

Conclusions

HC rates are independently associated with high ACVM across most sociodemographic groups and locations, with the most pronounced effect in areas with high poverty levels and minority populations. These findings call on targeted interventions and policymaking aimed at mitigating the prevalence of HC and cardiovascular burden, particularly in vulnerable populations.