U-Shaped Relationship Between Blood Pressure and All-Cause Mortality in Older Adults: The Shizuoka Study
In older adults, not only high blood pressure (BP) but also low BP was recommended to be correlated with all-cause mortality. But, the actual process responsible for the relationship among low BP and mortality has not been recognized. Aya A, et al. presented a study at the 33rd European meeting on hypertension and cardiovascular protection, Berlin on June 1, 2024 was aimed to analyse a possible confounding of antihypertensive drug use, potential comorbidities, and functional disability, as well as random error in BP measurement, in the correlation between low BP and all-cause mortality. A possibility of reverse causation (i.e., lower BP was caused by cardiovascular frailty at the end of life) was also evaluated.
The Kokuho Database in a local government, which is a prefecture-wide large dataset incorporating data on annual health checkup and health and care insurance claims was used. 337,988 individuals aged ≥ 65 (mean age: 73.5) years were assessed in this longitudinal observational study. The earliest day of participation in the annual health checkup in the study period from 2012 to 2020 was described as baseline. The insurance claims database was used to obtain the data on comorbidities, prescribed antihypertensive medications, functional disability levels, and occurrence of stroke and all-cause mortality.
In a mean follow-up period of 5.3 years, there were 27,497 cases of all-cause mortality and 11,090 cases of stroke were occurred. A U-shaped correlation was noticed among systolic BP and all-cause mortality in participants aged ≥ 75 years. The hazard ratio of systolic BP <110 mmHg for all-cause mortality was 1.14 (95% confidence interval: 1.07–1.21, P < 0.001). Simultaneously, the hazard ratio of BP ≥ 150 mmHg was 1.16. The U-shaped correlation remained substantial in the subanalyses of individuals without severe comorbidities, antihypertensive drug use, or functional disability. Similar findings were also observed in the evaluation excluding early-mortality cases within 3 years following the baseline, as well as in the analysis with the average systolic BP measured in at least two different instances within a 3-year period as a baseline value. In contrast, stroke risk increased directly with rising BP.
Low BP was correlated with all-cause mortality in older adults. The U-shaped association may not be assigned to the previously recommended factors.
Intensive BP Control for The Prevention of Cardiovascular Events Among Individuals with Hypertension at Low Cardiovascular Risk: A Target Trial Emulated Using Observational Data
There is no sufficient data is present on the optimal target blood pressure (BP) for patients with hypertension at low cardiovascular risk. Douros A, et al. presented a population-based study at the 33rd European meeting on hypertension and cardiovascular protection, Berlin on June 1, 2024 aimed to analyse whether following an intensive target BP control plan is correlated with a reduced risk of major adverse cardiovascular events (MACE) than following a standard BP control plan in this population.
A population-based cohort study was held imitating a target trial. The study was based on electronic medical records from general practices in the United Kingdom. Initially a base cohort of patients with incident hypertension at low cardiovascular risk (QRISK3-defined risk <10%) was produced. All treatment-naïve patients with systolic BP > 150 mmHg were included in the study cohort upon their first prescription for an antihypertensive drug (including combination therapy) from 1998 to 2018. The date of this prescription described the study cohort entry date. An active comparator, new-user cohort design with dynamic marginal structural models was used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for MACE to emulate a target trial of intensive (target BP: 130/80 mmHg), standard (140/90 mmHg), and modest (150/90 mmHg) BP control strategies. HRs and 95% CIs for serious adverse events (SAEs), a composite endpoint incorporating electrolyte abnormality, acute kidney injury, and antihypertensive drug-related SAEs were also assessed.
Between 77,934 patients incorporating in the study, adjusted incidence rates of MACE were 2.8, 3.2, and 3.3 per 1,000 persons per year in the intensive, standard, and modest strategy groups, respectively. The adjusted HRs (95% CIs) for the intensive versus standard strategy were 0.96 (0.86 to 1.08) for MACE and 0.91 (0.84 to 0.99) for SAEs. The adjusted HRs (95% CIs) for the modest versus standard strategy were 1.06 (0.97 to 1.16) for MACE and 0.99 (0.94 to 1.05) for SAEs. In the first five years of follow-up, cumulative hazards for MACE for the three treatment strategies are exhibited in Figure.
An intensive strategy was not correlated with a reduced risk of MACE as compared to a standard BP control strategy in hypertensive patients at low cardiovascular risk.
Significant Increases in Peripheral and Central Blood Pressure in Children at Much Lower Body Mass Index Than Expected
Wilmsmeier L, presented the session held at the European Society of Hypertension (ESH) on 1st June 2024, at Berlin, that discussed at which BMI-level significant increases in either central (cBP) or peripheral BP (pBP) can be detected in young children.
The cBP and pBP were measured in 1,183 schoolchildren (first/ second graders; mean age 7.9±0.6 years; 51% male). pBP measurements were performed with a validated oscillometric device (Dinamap-VC150-GE). cBP was measured noninvasively with the Mobil-O-Graph (IEM). Multivariable linear regression models (corrected for age, sex, height) were used to compare pBP/cBP values of children with a BMI<50th percentile (pct) with children separated in five groups according to BMI pct (>=50th-<65thpct; >=65th-<75thpct; >=75th-<85thpct; >=85th-<95thpct; >=95thpct).
- Peripheral systolic blood pressure (pSBP) was 104±8mmHg (M±SD), peripheral diastolic blood pressure (pDBP) 61±6mmHg (M±SD); 5% of the cohort displayed hypertensive pBP values >=95thpct.
- In the unadjusted analysis, an increase in pSBP (Fig.1A) and cSBP (Fig.1B) already at a BMI around 60thpct was noted.
- Further analysis comparing the corrected means revealed that pSBP showed already a significant increase for children with a BMI>=75thpct (ß=1.8, p=0.026) when compared to children with a BMI<50thpct.
- For the model including pDBP no significant effects were seen.
- cSBP significantly increased already in children with a BMI >=65thpct. (ß=1.7, p=0.031), while cDBP increased significantly in children with a BMI >=75thpct (ß=1.5; p=0.012) when compared to children with a BMI<50thpct.
Increases in body weight affect pBP and particularly cBP at much lower BMI pct level than expected. These results are alarming as pediatricians usually get concerned at BMI levels above the 85th pct. Given the important interaction between both risk factors and their track from childhood to adulthood, effective overweight prevention must take place in early childhood.
The Importance of Cardiac Magnetic Resonance Imaging in the Assessment of the Risk of Cardiac Arrhythmias in Patients with Arterial Hypertension
Wysocki A, presented the session held at the European Society of Hypertension (ESH) on 1st June 2024, at Berlin, assessed the relationship between the presence of late gadolinium enhancement at the right ventricular insertion point (RVIP) determined by CMRI and the occurrence of cardiac arrhythmias in patients with arterial hypertension
30 patients with essential hypertension were qualified for the study, 18 men and 12 women, the average age of the subjects was 55.5 ± 12.4 years. All subjects underwent cardiac magnetic resonance imaging and 24-hour Holter ECG monitoring. Based on the presence of LGE at the right ventricular insertion point, assessed by CMRI, the subjects were divided into two subgroups. The first subgroup consisted of subjects with LGE at the right ventricular insertion point (RVIP + subgroup), while the second subgroup consisted of subjects without LGE at the right ventricular insertion point (RVIP – subgroup).
- Subjects with LGE at the right ventricular insertion point were characterized by higher maximum and minimum heart rates in 24-hour Holter ECG recordings compared to subjects without LGE at the right ventricular insertion point (p < 0.05).
- In subjects with LGE at the right ventricular insertion point, Holter ECG evaluation revealed a statistically significantly higher number of single premature supraventricular beats, single premature ventricular beats, and supraventricular tachycardias compared to subjects without LGE at the right ventricular insertion point (p < 0.05).
- The regression analysis performed showed that a longer time from the diagnosis of hypertension and the occurrence of LGE at the right ventricular insertion point assessed using CMRI are independent risk factors for cardiac arrhythmias (p < 0.05).
Cardiac magnetic resonance imaging by identifying of late gadolinium enhancement at the right ventricular insertion point may be a useful diagnostic method in assessing the risk of cardiac arrhythmias in a group of patients with arterial hypertension.
Cardiovascular Risk Factors Have Different Effects on Total Brain Volume and Cerebral White Matter Lesions Over Time: The Helius Study
Cardiovascular risk factors have been associated with brain volume reduction and the development of cerebral white matter lesions (WML), both early markers of cognitive decline and cerebrovascular disease. Vriend. E. M.C., presented the session held at the European Society of Hypertension (ESH) on 1st June 2024, at Berlin, that evaluated the prognostic value of cardiovascular risk factors on brain and WML volumes in a middle-aged, multi-ethnic population.
A baseline data and 3T brain magnetic resonance imaging (MRI) scans were used in 562 participants of Moroccan, South-Asian Surinamese, and Dutch descent from the HELIUS study. Brain volume and WML volumes were determined using automated segmentation pipelines based on MP-RAGE and 3D-FLAIR scans. Linear regression analyses, adjusted for age, sex, and ethnicity, were performed to assess the association between (change in) cardiovascular risk factors and brain and WML volumes. The mean age was 58.5 (standard deviation 7.7) years, 45% was female. Median follow-up time was 8.4 [interquartile range 7.4; 9.5] years. Both elevated BMI and presence of diabetes at baseline as well as increases in BMI and HbA1C levels over time were significantly associated with reduced brain volume at follow-up. Hypertension, systolic and diastolic blood pressure levels, the use of antihypertensive medication, new-onset hypertension, and history of cerebrovascular disease were all independently and positively associated with WML volume.
Elevated body weight and diabetes mellitus significantly contribute to decreased brain volumes, whereas hypertension and cerebrovascular disease are key risk factors for the development of WML. The present findings underscore the importance of obesity and hypertension in mid-life as predictors of future risk of cerebrovascular disease.
Blood Pressure Variability and Target Organ Damage Indices in Patients with Type 2 Diabetes Mellitus
Ippokratis Z, presented the session held at the European Society of Hypertension (ESH) on 1st June 2024, at Berlin, that compared increased BPV and target organ damage indices on patients with Type 2 DM (T2DM) and control individual: implication of CV risk. Blood pressure variability (BPV) has been identified as an in-dependent predictor of cardiovascular (CV) risk and morbidity.
In cross-sectional study, identified individuals with T2DM and adequate controls. Patients were matched to controls on a 1:1 ratio used propensity score matching. Matching was based on age, gender, BMI, previous diagnosis of hypertension and office Systolic and Diastolic BP values. Office BP values were measured and Ambulatory BP Monitoring was performed, and central BP and Pulse Wave Velocity were calculated with validated devices. The BPV parameters of ARV and weighted Standard deviation (wSD) were calculated by standardized formulas based on the ABPM data.
A total of 190 individuals (95 with DM and 95 controls) were studied (mean age was 55.0±10.0) and 63% were males. Notably, the DM group had only slightly elevated HbA1c and preserved eGFR, indicates a cohort with adequate DM control. 24-hour SBP ARV correlated with age, Aortic SBP and PWV (r = 0.295, 0.287 &0.253 respectively, p for all < 0.001). DM patients had significantly increased 24-hour SBP ARV (10.00±2.40 vs 9.40±1.76, p = 0.049) and significantly elevated PWV (8.93±1.89 vs. 8.30±1.69, p =0.017) compared to the control group.
T2DM patients with adequate glycemic control, BPV indices are significantly higher compared to euglycemic controls explain the prognostic significance for CV risk, as diabetes disrupts BP homeostasis early, possibly via impaired endothelial function.
Hypertensive Nephropathy: Transcriptomics of Kidney Biopsies Predicts Long Term Outcome and Identifies Therapeutic Targets
Chen T, presented the session held at the European Society of Hypertension (ESH) on 1st June 2024, at Berlin, that evaluated the potential markers and novel therapeutic targets for hypertensive nephropathy progression. Hypertensive nephropathy (HN) represented a major cause of chronic kidney disease, but the reasons for disease progression on some patients remain unclear.
Adult patients (n=43; n=16 females, mean age 53 years) with biopsy-verified HN were categorized as ’early’ (estimated glomerular filtration rate (eGFR) >45 ml/min/1.73m2) or ’late’ disease (eGFR <45 ml/min/1.73m2) at the time of biopsy. Patients were further divided into “stable” (eGFR decline <3 ml/min/year) or “progressive” (eGFR decline >3 ml/min/year or start of renal replacement therapy) after median follow-up of 10 years (5-22). TruSeq Exome sequencing was executed after RNA extraction (miRNeasy FFPE kit, Qiagen) at Novogene, Cambridge, UK. Quality control and data analysis was performed using R Studio (v4.2.0) and QIAGEN Ingenuity Pathway Analysis.
- Analyzed the subgroups of HN patients: early stable (ES, n=11), early progressive (EP, n=11), late stable (LS, n=9) and late progressive (LP, n=12). Differentially expressed genes (DEG, fold change (FC) >1.5 and p-value < 0.05) were identified, with n=265 in ES vs. EP, and n=674 in LS vs. LP.
- Principal component analysis (PCA) showed separation of ES vs. EP and LS vs. LP (Figure 1), K-nearest neighbour (KNN) analysis of DEG identified a 6-gene classifier was in LS vs. LP (19/21 samples correctly classified), while IER5L and CNTNAP5 were the top 2-gene classifier in ES vs. EP (20/21 samples). These classifiers, as well as other DEGs such as PER1, YB1, TIMP3, ADAMTS4, IGFBP5 and EGF could represented novel targets to inhibit disease progression.
- Differentially regulated pathways were associated with regulation of TP53 activity and circadian rhythm involving melatonin metabolism was in ES vs. EP, and metabolic processes related to water-soluble vitamins, glutathione and sphingolipids was in LS vs. LP.
Transcriptomic profiling from diagnostic kidney biopsies with HN can distinguish future disease progression from non-progression and may identify novel therapeutic targets.
Increased Blood Pressure Variability and Decreased Heart Rate Variability in Older Vs. Younger Individuals: Markers of Disturbed Cardiovascular Autonomic Modulation with Ageing?
Stoenoiu MS, presented the session held at the European Society of Hypertension (ESH) on 1st June 2024, at Berlin, that compared BPV and HRV in older vs. younger individuals from 2018 to 2023 calendar year. Aging affects cardiovascular regulation through arterial baroreflex dysfunction and increased arterial stiffness, with an impact on blood pressure (BP) and heart rate (HR) variability (V), established risk factors for cardiovascular morbidity and mortality.
1080 hypertensive patients (704 younger, 40-55yrs, YH and 376 older, >=75yrs, OH) underwent 24h BP monitoring (ABPM) from 2018 to 2023. Patients with known dysautonomy, Parkinson or other neurodegenerative diseases were excluded. Short-term BPV indexes includes standard deviation (SD), weighted standard deviation (wSD), average real variability (ARV), coefficient of variation (CV), and variability independent of mean (VIM) were estimated over 24h. HRV was assessed by SD and CV of heart rate measured during ABPM. The same analysis was replicated in a sample of 343 untreated individuals from the general population (309 YH; 34 OH).
As compared to YH, (mean age: 49.5±4.5yrs), OH (mean age: 80.2±4.5yrs) had significantly higher 24h systolic BPV (SD: 15.7±4.6 vs.13.6±4.0; wSD: 15.5±4.6 vs.13.5±4.0; ARV: 12.3±2.9 vs.10.0±2.7; VIM: 15.8±4.5 vs.13.9±4.0 mm Hg; CV: 12.2±3.5 vs.10.8±3.1%; p<0.001). In contrast, 24h HRV was significantly lower in OH than in YH group (SD: 7.2±3.0 vs. 9.1±3.4 beats/min; CV: 11.5±4.5 vs. 12.8.1±4.5%; p<0.001). Higher tertiles of BPV were associated with higher mean pulse pressure and higher pulsatility (pulse pressure normalized for mean arterial pressure), in both YH and OH. Similar results were obtained when comparing OH vs. YH individuals in the general population sample, both for 24h systolic BPV (SD: 14.7±3.1 vs.12.2±2.8; wSD: 14.9±3.1 vs.12.7 ±3.0; ARV: 11.5±2.1 vs.9.2±2.0; VIM: 13.6±2.5 vs.12.3±2.4 mmHg; CV: 11.4±2.1 vs.10.1±2.0%; p<0.01) and HRV (SD: 8.8±3.2 vs. 11.3±3.4 beats/min; CV: 12.7±4.5 vs. 15.1±4.3%; p<0.01).
Increased BPV was associated with decreased HRV in older compared to younger individuals, both in a hypertensive cohort and in a general population sample. Age-related autonomic dysfunction and arterial stiffness, along with their prognostic implications, need further investigation.
A Novel Electro-Hydraulic Acoustic Therapy Reduces Blood Pressure in Hypertensive Patients with Chronic Kidney Disease: 12-Month Follow-Up
Wolak T, presented the session held at the European Society of Hypertension (ESH) on 1st June 2024, at Berlin, that hypothesized eHAT would reduce blood pressure (BP) and preserve renal function in patients with hypertension and CKD. Arterial hypertension (HTN) with chronic kidney disease (CKD) poses a global healthcare challenge with limited effective treatments. Electro-Hydraulic Acoustic Therapy (eHAT), a lower-energy modality vs. lithotripsy, emerges as a promising technique for relieving ischemia and promoting tissue regeneration.
20 medically treated patients with HTN and Stage IIIa/b CKD enrolled in this prospective, single-arm study were treated over 3-weeks with six eHAT sessions (2400 shockwaves/kidney; 0.09 mJ/mm2 at 2.66Hz; NephrospecTM, Curespec, Yehud, Israel). Follow-up (FU) visits at 1, 3, 6, and 12 months involved measurements of attended and unattended office BP, ambulatory BP and estimated glomerular filtration rate (eGFR).
The treatment was well tolerated. All BP measurements strongly tended to decline over 12 months and showed a similar pattern (Table 1, Figs. 1-3), whereas eGFR was well preserved (Table 1, Fig. 4). eHAT is a tolerable and safe procedure and, moreover, a 3-week regimen tends to reduce BP and preserve eGFR in patients with HTN and CKD.
eHAT may constitute a novel, safe, and non-invasive alternative therapeutic approach in the management of HTN in the context of CKD.
Day-To-Day Reproducibility of Nocturnal Blood Pressure Fall (Dipping) Evaluated with Wearable and Home Devices in Hypertensive Patients
Pengo M, presented the session held at the European Society of Hypertension (ESH) on 1st June 2024, at Berlin, that determined the reproducibility of nocturnal BP dipping estimated through a combined use of WD and HBPMN devices for daytime and night-time BP estimation within one week. Non-dipping status has been associated with increased risk of heart failure and cardiovascular events, but its detection via ambulatory blood pressure monitoring (BPM) is often suboptimal. Wearable devices (WD) and home BPM devices equipped with nocturnal measurement function (HBPMN) offer the opportunity of estimating dipping status over different days, benefiting from statistical averaging.
We recruited treated and untreated adult patients with hypertension. Patients underwent one week of home BP monitoring through a HBPMN device (NightView, OMRON Healthcare, HEM9601T-E3) and with an oscillometric WD (HeartGuide, OMRON Healthcare, HEM-6411T-MAE). Patients were asked to measure BP over one week with WD according to ESH-HBPM guidelines for daytime measurements and with HBPMN according to standard device settings for night-time measurements. Interclass correlation coefficient (ICC) was calculated to evaluate reproducibility.
76 patients were included in the study. The main characteristics are summarised as follows: age (61±11.84 years), 32 (42%) females, BMI (28.12±4.90 Kg/m2). Most of them (98%) were treated hypertensives. Office systolic and diastolic BP were 134±4.43 mmHg and 80±4.84 mmHg, respectively. The average one-week systolic BP dipping was 16.14±9.44%. When we considered patients who had dipping assessment over at least the first 5 days (37 patients), intra-individual variability in the categorical definition of dipping status was observed (Figure 1) with a suboptimal reproducibility of average nocturnal BP fall (ICC 0.60).
Nocturnal BP dipping, estimated using WD and HBPMN, shows suboptimal reproducibility, leading to inconsistent patient classification by dipping status. Future studies are needed to determine if this variability is due to technical issues or physiological changes in BP and sleep patterns.