Systolic Blood Pressure Control Research Articles

#5978 SUBCAPSULAR INJECTION OF EXTRACELLULAR VESICLES FROM MESENCHYMAL STEM CELLS, PROMOTED ADDITIONAL RENOPROTECTION IN AN EXPERIMENTAL MODEL OF CKD

Abstract Background and Aims Chronic kidney disease (CKD) is considered a public health concern worldwide, both due to its insidious and highly debilitating feature and to its high global prevalence. Clinical management of CKD is often achieved by the blockade of the renin-angiotensin-aldosterone system (RAAS). However, this treatment alone is not efficient to prevent CKD progression completely, motivating the scientific community to search for alternative treatments to control CKD progression and to detain its evolution to the end-stage renal failure. In this context, we have recently shown that the association of a single renal subcapsular injection of 2 × 106 adipose-derived mesenchymal stem cells (ASC) to RAAS blockade with the AT1RB Losartan (LOS) promoted greater renoprotection when compared to LOS monotherapy, leading to the normalization of urinary protein excretion (UPE) and to the regression of established glomerulosclerosis (GS), in experimental CKD. Since there are methodological limits for the number of ASC that can be injected under the renal capsule, and based on the current literature, which suggests the main beneficial effects of ASC are not due to direct in situ cell differentiation, but to paracrine factors produced and released by the ASC; in the present study we aimed to investigate if the association of a renal subcapsular injection of extracellular vesicles (EV) derived from ASC, to the oral treatment with LOS would promote additional renoprotective effects in a model of experimental CKD. Method The present experimental protocol was approved by the Ethics Committee for the Use of Experimental Animals of the University of São Paulo Medical School (CEUA-FMUSP No 1761/2022). EV were obtained from ASC isolated from gonadal adipose tissue of 5 male Wistar rats. Cells were cultured until P4, characterized by flow cytometry and in vitro differentiation, and kept under serum deprivation for 24 h. The conditioned culture media, containing the EV released by these cells, was ultracentrifuged and the resulting EV pellets were diluted in 100 μL of sterile PBS and used for the renal subcapsular injections. Experimental CKD was induced in 25 male Wistar rats through the surgical ligation of 2 from the 3 branches of the left renal artery, followed by the total nephrectomy of the right kidney, resulting in a 5/6 renal ablation. Additional 10 Sham-operated rats were used as control. After 15 days from surgery, the animals submitted to renal ablation were stratified into 3 groups, with closely similar mean values of body weight (BW), systolic blood pressure (SBP), UPE and urinary albumin excretion (UAE), before the start of the different treatments. Animals from CKD group were kept untreated, LOS and LOS+EV animals received diary 50 mg/Kg/d of Losartan, diluted in drinking water and LOS+EV rats underwent a second surgery for the renal subcapsular application of EV. All animals were followed until 30 days after CKD induction, when BW, SBP, UPE and UAE were analyzed again. Animals where then euthanized for the assessment of serum creatinine (SCr) and blood urea nitrogen (BUN) concentration, as well as for histological studies to determine the percentage of GS and the renal interstitial infiltration by macrophages (CD68). Results The association of a single subcapsular injection of EV derived from ASC, to the oral treatment with the AT1RB LOS, significantly improved the effects of this antihypertensive drug. CKD+LOS+EV animals exhibited normal SBP, in spite of having only 1/6 of functioning renal mass. Moreover, the combined treatment significantly reduced UAE and numerically diminished de percentage of glomerulosclerosis, compared to LOS alone. Detailed obtained results are presented in Table 1. Data are presented as Mean ± SE. Differences among groups were analyzed by one-way ANOVA: p<0.05 vs.*CONT, #CKD, †LOS. as Mean ± SE. Conclusion Despite the small number of animals in the association group, our preliminary results suggest EV from ASC to exert additional renoprotective effects when associated to LOS, especially regarding the control of SBP and the protection of the glomerular filtration barrier integrity.

#2567 ASSOCIATION OF IMBALANCE OF MYOCARDIAL OXYGEN SUPPLY/DEMAND WITH MYOCARDIAL INJURY IN END STAGE KIDNEY DISEASE PATIENTS

Abstract Background and Aims It is well known that oxygen transport ability is impaired in patients with anemia, low hemoglobin (Hb) level, whereas the double product (DP, bpm*mmHg), consisting of the systolic blood pressure (SBP) multiplied by the heart rate (HR), is an index of myocardial oxygen consumption. The combination of these two markers could be a potential marker for balance of myocardial oxygen supply and demand. Therefore, we hypothesized that the balance of these two markers may lead to myocardial damage in end-stage kidney disease (ESKD) patients who is susceptible to vulnerable heart in oxygen balance. The purpose of this study is to examine the association of balance of DP and Hb with myocardial injury in ESKD patients. Method A single-center, cross-sectional study has conducted. From December 2010 to November 2021, 327 consecutive ESKD patients started maintenance hemodialysis (HD). Among them, 44 patients met the exclusion criteria as follows: (1) missing data of cardiac troponin T (cTnT); (2) complicating acute cardiac syndrome; (3) death during hospitalization for HD initiation, a total of 283 ESKD patients were enrolled into the study finally. The patients were divided four groups according to the high or low of Hb level of 9 g/dL and DP 12500, a median of our patients, and named low-DP/high-Hb; G1, low-DP/low-Hb; G2, high-DP/high-Hb; G3, and high-DP/low-Hb; G4. The patients with G1 group were defined as a well oxygen balanced group, whereas those with G4 was defined as an imbalance of oxygen supply and demand group. Based on the results of previous study, cTnT cut off for myocardial injury was serum cTnT ≧0.15 ng/mL. Odds ratio (OR) for myocardial injury was calculated in each group compared with well oxygen balanced group by logistic regression analysis. Results Median age was 72 years, 71% of them were male, 52.6% had diabetes. Mean Hb level was 9.09 ± 1.61, and median DP was 12144 (25% tile 10540, 75% tile 14688). Median cTnT was 0.083 (25% tile 0.057 and 75% tile 0.13), and 20.4% of patients were defined as suffering from myocardial injury latently. In the adjusted model, the odds for myocardial injury was significantly increasing in high-DP compared with low-DP (OR: 1.87, p = 0.049), while low-Hb did not show significant increment of odds for myocardial injury compared with high-Hb. As shown in the Table 1, compared to well-balanced group (G1), OR increased by exposing only high-DP (G3), however it was not statistically significant (OR 1.20, p = 0.68). Interestingly, by exposing with high-DP with low-Hb simultaneously (G4), synergistic increased OR was found compared with well-balanced (G1) group (OR 3.07, 95%CI 1.24-7.62, p = 0.015). Furthermore, these associations were enhanced and weakened if Hb cut-off level became to be lower (Hb 8 g/dL) and higher (Hb 10 g/dL), as shown in Tables 2, 3. Conclusion Imbalance of oxygen supply (Hb) and demand (DP) was associated with myocardial injury in incident HD patients. Appropriate control of anemia, SBP and HR may have possibility to prevent myocardial injury. Especially we need to pay attention more to the Hb level if BP and HR control is insufficient. Tables 1, 2, 3. Odds ratio for cTnT≧0.15 in four groups divided by DP and Hb (adjusted for age, male, CRP, albumin, diabetes mellitus).

Estimates of the global, regional, and national burden of atrial fibrillation in older adults from 1990 to 2019: insights from the Global Burden of Disease study 2019.

Atrial fibrill ation (AF) is a predominant public health concern in older adults. Therefore, this study aimed to explore the global, regional, and national burden of AF in older adults aged 60-89 between 1990 and 2019. The morbidity, mortality, disability-adjusted life years (DALYs), and age-standardized rates of AF were refined from the Global Burden of Diseases study 2019. The epidemiological characteristics were assessed based on numerical values, age-standardized rates per 100,000 person-years, and estimated annual percentage changes (EAPC). Globally, a total of 33.31 million AF cases, 219.4 thousand deaths, and 65.80 million DALYs were documented in 2019. There were no appreciable changes in EAPC from 1990 to 2019. The disease burden of AF differed significantly across different territories and countries. At the national level, China exhibited the highest number of incident cases [818,493 (562,871-1,128,695)], deaths [39,970 (33,722-46,387)], and DALYs [1,383,674 (1,047,540-1,802,516)]. At the global level, high body mass index (BMI) and high systolic blood pressure (SBP) were two predominant risk factors contributing to the proportion of AF-related deaths. AF in older adults remains a major public health concern worldwide. The burden of AF varies widely at both national and regional levels. From 1990 to 2019, the cases of incidences, deaths, and DALYs have shown a global increase. The ASIR, ASMR, and ASDR have declined in the high-moderate and high SDI regions; however, the burden of AF increased promptly in the lower SDI regions. Special attention should be paid to the main risk factors for high-risk individuals with AF, which can help control systolic blood pressure and body mass index within normal limits. Over all, it is necessary to illustrate the features of the global AF burden and develop more effective and targeted prevention and treatment strategies.

Team-Based Approach in Hypertension Management: A Quality Improvement Project.

Hypertension is a major risk factor for heart diseases and stroke among Americans; only 25% have this under control nationwide. This quality improvement project evaluated the outcomes of team-based care in hypertension control by registered nurses and certified nurse practitioners in a primary care setting. Pre/post-data analysis of blood pressure (BP) control, and BP knowledge, was done. The team provided education and counseling based on knowledge assessment during visits and used unattended automated blood pressure measurement (uAOBPM) techniques to measure BP. There was a significant reduction in systolic and diastolic BP control ( P < .001). There was a statistically significant increase in disease knowledge score pre- and postintervention ( P < .001). The team-based care approach improved patients' BP control and knowledge of the disease. The uAOBPM technique could be incorporated into clinical settings for accurate BP measurements.

ASSOCIATIONS OF INTER-ARM BLOOD PRESSURE DIFFERENCE WITH TREATMENT RESPONSE IN NEWLY TREATED HYPERTENSION

Objective: Inter-arm differences (IAD) in systolic blood pressure (SBP) predict future cardiovascular mortality and morbidity. IAD varies between measures and gets smaller with repeated measures. The relationship of IAD to response to antihypertensive treatment is unknown. We set out to examine associations of IAD with BP treatment response over 18 weeks in treatment-naïve adults with moderate to severe hypertension. Design and method: We previously reported that nurse-led accelerated stepwise management of treatment-naïve grade II/III hypertension is feasible, safe and effective, achieving control of SBP to &lt; 140 mmHg for 76% after 18 weeks. Using this cohort, univariable associations of IAD (mean of 8 simultaneous BP measurements) with vascular and clinical indices, and with BP change on treatment, were examined with mixed-effects linear regression models. Candidate univariable indices (p&lt;0.2) entered multivariable modelling. Regression modelling of change in IAD was undertaken. All analyses adjusted for age, sex and entry SBP. Results: For 52 participants (mean age 59; 42% female), mean (standard deviation: SD) entry SBP was 171 (13.9) mmHg falling, after protocol-led treatment intensification, to 131 (10.7) mmHg at 18 weeks; mean systolic IAD was 4.5 (4.2) mmHg at entry and 3.9 (4.3) mmHg at 18 weeks (p = 0.28). In final adjusted models, IAD at entry was associated with handedness, height, body mass index, smoking and absence of pedal pulses. Greater reduction of SBP from entry to 18 weeks was associated with lower entry IAD, greater SD of daytime ambulatory BP, smoking history and handedness. Adjusted change in IAD over 18 weeks was correlated with falls in SBP (Adjusted R2 = 0.56). Conclusions: These data associate greater systolic IAD with reduced response to intensive BP lowering, and correlate reduction in IAD with change in BP. Slower BP target achievement can carry prognostic implications, suggesting one possible mechanism whereby IAD might predict future mortality.

Systolic Blood Pressure Control Targets to Prevent Major Cardiovascular Events and Mortality in Patients With Type 2 Diabetes: A Systematic Review and Network Meta-Analysis.

Previous meta-analyses using traditional pairwise comparisons did not support intensive systolic blood pressure (SBP) control in patients with diabetes and included trials published before 2015. We aimed to identify the optimal SBP control targets in patients with type 2 diabetes using a systematic review and network meta-analysis of accumulating evidence. We systematically searched PubMed, Embase, and Cochrane Library from inception to August 29, 2022 for randomized controlled trials comparing different blood pressure targets, antihypertensive agents against placebo, or dual antihypertensive agents against single agent in patients with type 2 diabetes. Network meta-analysis was used to obtain pooled results of direct and indirect comparisons of each 5 mm Hg SBP category in association with clinical outcomes adjusted for baseline risk and intervention duration (PROSPERO [International Prospective Register of Systematic Reviews], CRD 42022316697). We identified 30 trials including 59 934 patients with type 2 diabetes. The mean achieved SBP levels ranged from 117 mm Hg to 144 mm Hg among treatment groups. A total of 7799 major cardiovascular diseases events and 4130 deaths were reported. The lowest risk of major cardiovascular diseases was found in patients with achieved SBP level of 120 to 124 mm Hg. The hazard ratio and 95% CI were 0.73 (0.52-1.02) compared with 130 to 134 mm Hg, 0.60 (0.41-0.85) compared with 140 to 144 mm Hg, and 0.41 (0.26-0.63) compared with ≥150 mm Hg. Similar results were found for cardiovascular diseases components including stroke, myocardial infarction, heart failure, and cardiovascular mortality. All-cause mortality was reduced at an achieved SBP <140 mm Hg but further reduction did not show additional benefits. Our findings support an intensive blood pressure-lowering strategy to prevent major cardiovascular diseases in patients with type 2 diabetes.

Assessment of Normal Systolic Blood Pressure Maintenance with the Risk of Coronary Artery Calcification Progression in Asymptomatic Metabolically Healthy Korean Adults with Normal Weight, Overweight, and Obesity.

Metabolically healthy obesity (MHO) is known to have a close association with subclinical coronary atherosclerosis. Despite recent data on the benefit of intensive systolic blood pressure (SBP) control in diverse clinical conditions, little is known regarding the association of normal SBP maintenance (SBPmaintain) with coronary artery calcification (CAC) progression in MHO. This study included 2724 asymptomatic adults (48.8 ± 7.8 years; 77.9% men) who had no metabolic abnormalities except overweight and obesity. Participants with normal weight (44.2%), overweight (31.6%), and obesity (24.2%) were divided into two groups: normal SBPmaintain (follow-up SBP < 120 mm Hg) and ≥elevated SBPmaintain (follow-up SBP ≥ 120 mm Hg). CAC progression was defined using the SQRT method, a difference of ≥2.5 between the square root (√) of the baseline and follow-up coronary artery calcium score. During a mean follow-up of 3.4 years, the proportion of normal SBPmaintain (76.2%, 65.2%, and 59.1%) and the incidence of CAC progression (15.0%, 21.3%, and 23.5%) was different in participants with normal weight, overweight, and obesity (all p < 0.05, respectively). The incidence of CAC progression was lower in the normal SBPmaintain group than in the ≥elevated SBPmaintain group in only participants with obesity (20.8% vs. 27.4%, p = 0.048). In multiple logistic models, compared to participants with normal weight, those with obesity had a higher risk of CAC progression. Normal SBPmaintain was independently associated with the decreased risk of CAC progression in participants with obesity. MHO had a significant association with CAC progression. Normal SBPmaintain reduced the risk of CAC progression in asymptomatic adults with MHO.

Influencing factors of plasma BACE1 and its relationship with plasma Aβ: A cross-sectional study of a cognitively normal population of Shunyi cohort (P10-6.009)

<h3>Objective:</h3> The aim of this study was to firstly describe the concentration and activity of plasma BACE1 in a community cohort of China, and to explore its influencing factors and its relationship with plasma Aβ. <h3>Background:</h3> BACE1, as the rate-limiting step in the Aβ production, is considered as a candidate biomarker of Alzheimer’s disease (AD) and is also involved in the disruption of cerebral vessels. <h3>Design/Methods:</h3> 887 cognitively healthy subjects form Shunyi cohort were included in this cross-sectional study. We used linear regression analysis to investigate the relationship between the concentration and activity of plasma BACE1 with common AD and vascular disease risk factors, with plasma Aβ42 and Aβ40 concentrations. <h3>Results:</h3> The concentration of BACE1 in present study was 4.46(2.89–6.93) ng/ml and the activity was 344.19(249.7–437.41) RFU/min. After adjusting for age, sex, ApoE4 allele, increasing age [β (SE) =0.05 (0.02), p=0.021] and increasing systolic blood pressure [β (SE) =0.03 (0.01), p=0.015] were positively correlated with lnBACE1 activity. lnhsCRP[β (SE) =0.07 (0.02), p=0.001] and lnTNF-α[β (SE) =0.24 (0.08), p=0.002] were positively correlated with lnBACE1 activity. The concentration of lnBACE1 was negatively correlated with the concentration of Aβ42[β (SE) =−0.86 (0.28), p=0.003] and Aβ40[β (SE) =−15.6 (2.13), p &lt; 0.001], while was positively associated with Aβ42/40 [β (SE) =0.10 (0.02), p &lt; 0.001]. There was no significant correlation between lnBACE1 activity and Aβ concentration. <h3>Conclusions:</h3> BACE1 activity but not concentration increased with age. Control of systolic blood pressure, screening and intervention of systemic inflammation may reduce BACE1 activity in cognitively normal population. Decreased plasma Aβ42 and Aβ40 concentrations and elevated Aβ42/40 may reflect the early state of cognitive decline caused by neurodegenerative and vascular diseases. <b>Disclosure:</b> Ziang Pan has nothing to disclose. Dr. Gao has nothing to disclose. Ding-Ding Zhang has nothing to disclose. Ming Yao has nothing to disclose. Jun Ni has nothing to disclose. Lixin Zhou has nothing to disclose. Dr. Shen has nothing to disclose. Yi-Cheng Zhu has nothing to disclose.

Circulating Interlukin-32 and Altered Blood Pressure Control in Individuals with Metabolic Dysfunction.

Fatty liver disease is most frequently related to metabolic dysfunction (MAFLD) and associated comorbidities, heightening the risk of cardiovascular disease, and is associated with higher hepatic production of IL32, a cytokine linked with lipotoxicity and endothelial activation. The aim of this study was to examine the relationship between circulating IL32 concentration and blood pressure control in individuals with metabolic dysfunction at high risk of MAFLD. IL32 plasma levels were measured by ELISA in 948 individuals with metabolic dysfunction enrolled in the Liver-Bible-2021 cohort. Higher circulating IL32 levels were independently associated with systolic blood pressure (estimate +0.008 log10 per 1 mmHg increase, 95% c.i. 0.002-0.015; p = 0.016), and inversely correlated with antihypertensive medications (estimate -0.189, 95% c.i. -0.291--0.088, p = 0.0002). Through multivariable analysis, IL32 levels predicted both systolic blood pressure (estimate 0.746, 95% c.i 0.173-1.318; p = 0.010) and impaired blood pressure control (OR 1.22, 95% c.i. 1.09-1.38; p = 0.0009) independently of demographic and metabolic confounders and of treatment. This study reveals that circulating IL32 levels are associated with impaired blood pressure control in individuals at risk of cardiovascular disease.

The impact of the COVID-19 pandemic on blood pressure control after a stroke or transient ischemic attack among patients at VA medical centers

ObjectiveTo study factors associated with systolic blood pressure(SBP) control for patients post-discharge from an ischemic stroke or transient ischemic attack(TIA) during the early months of the COVID-19 pandemic compared to pre-pandemic periods within the Veterans Health Administration(VHA). Materials and MethodsWe analyzed retrospective data from patients discharged from Emergency Departments or inpatient admissions after an ischemic stroke or TIA. Cohorts consisted of 2,816 patients during March–September 2020 and 11,900 during the same months in 2017-2019. Outcomes included primary care or neurology clinic visits, recorded blood pressure readings and average blood pressure control in the 90-days post-discharge. Random effect logit models were used to compare clinical characteristics of the cohorts and relationships between patient characteristics and outcomes. ResultsThe majority (73%) of patients with recorded readings during the COVID-19 period had a mean post-discharge SBP within goal (<140 mmHg); this was slightly lower than the pre-COVID-19 period (78%; p=0.001). Only 38% of the COVID-19 cohort had a recorded SBP in the 90-days post-discharge compared with 83% of patients during the pre-pandemic period (p=0.001). During the pandemic period, 29% did not have follow-up primary care or neurologist visits, and 33% had a phone or video visit without a recorded SBP reading. ConclusionsPatients with an acute cerebrovascular event during the initial COVID-19 period were less likely to have outpatient visits or blood pressure measurements than during the pre-pandemic period; patients with uncontrolled SBP should be targeted for follow-up hypertension management.

Attention should be paid to futile recanalization after endovascular treatment in acute ischemic stroke

With the accumulation of research evidence and clinical experience, an increasing number of patients benefit from vascular recanalization therapies. Although successful recanalization of the occluded artery has been achieved, neurological deficits persist after endovascular treatment, which defined as"futile reperfusion". Compared with the successful recanalization, successful reperfusion predicts final infarct size and clinical outcome more accurately. At present, the known influencing factors of futile reperfusion include older age, female, high baseline National Institute of Health stroke scale (NIHSS) score, hypertension, diabetes, atrial fibrillation, reperfusion treatment strategy, large infarction core volume, and collateral circulation status. The incidence of futile reperfusion in China is significantly higher than that in western population. However, few studies focused on its mechanism and influencing factors. To date, many clinical studies have attempted to reduce the occurrence of futile recanalization regarding antiplatelet therapy, blood pressure management and treatment process improvement. However, only one effective measure has been achieved in blood pressure management: systolic blood pressure control below 120 mmHg (1 mmHg=0.133 kPa) should be avoided after successful recanalization. Therefore, future studies are warranted to promote the establishment and maintenance of collateral circulation, as well as neuroprotective therapy.

Machine-learning-based high-benefit approach versus conventional high-risk approach in blood pressure management.

In medicine, clinicians treat individuals under an implicit assumption that high-risk patients would benefit most from the treatment ('high-risk approach'). However, treating individuals with the highest estimated benefit using a novel machine-learning method ('high-benefit approach') may improve population health outcomes. This study included 10 672 participants who were randomized to systolic blood pressure (SBP) target of either <120 mmHg (intensive treatment) or <140 mmHg (standard treatment) from two randomized controlled trials (Systolic Blood Pressure Intervention Trial, and Action to Control Cardiovascular Risk in Diabetes Blood Pressure). We applied the machine-learning causal forest to develop a prediction model of individualized treatment effect (ITE) of intensive SBP control on the reduction in cardiovascular outcomes at 3 years. We then compared the performance of high-benefit approach (treating individuals with ITE >0) versus the high-risk approach (treating individuals with SBP ≥130 mmHg). Using transportability formula, we also estimated the effect of these approaches among 14 575 US adults from National Health and Nutrition Examination Surveys (NHANES) 1999-2018. We found that 78.9% of individuals with SBP ≥130 mmHg benefited from the intensive SBP control. The high-benefit approach outperformed the high-risk approach [average treatment effect (95% CI), +9.36 (8.33-10.44) vs +1.65 (0.36-2.84) percentage point; difference between these two approaches, +7.71 (6.79-8.67) percentage points, P-value <0.001]. The results were consistent when we transported the results to the NHANES data. The machine-learning-based high-benefit approach outperformed the high-risk approach with a larger treatment effect. These findings indicate that the high-benefit approach has the potential to maximize the effectiveness of treatment rather than the conventional high-risk approach, which needs to be validated in future research.

Community health volunteer for blood pressure control in rural people with stroke in India: Pilot randomised trial

ObjectiveTo test the hypothesis that an Accredited social health activist (ASHA), a community health volunteer in a task-sharing model can help in sustained control of systolic blood pressure (BP) in rural people with Stroke and hypertension at 6 months follow up. MethodsIn this randomized trial two rural areas (Pakhowal and Sidhwan bet) with 70 and 94 villages respectively were screened for people with stroke and hypertension. They were assigned to either ASHA-assisted BP control in addition to standard-of-care (Pakhowal-intervention Group) or standard-of-care alone (Sidhwan bet- Control Group). Assessors blinded to intervention conducted the baseline and 6 months follow-up visits to measure risk factors in both the rural areas. ResultsA total of 140 people with stroke with mean age of 63.7 ± 11.5 years and 44.3% females were randomised. The baseline systolic BP was higher in the intervention group (n = 65,173.5 ± 22.9 mmHg) compared to the control group (n = 75,163 ± 18.7 mmHg, p = 0.004). The follow-up systolic BP was lower in the intervention group compared to the control group 145 ± 17.2 mmHg and 166.6 ± 25.7 mmHg respectively (p < 0.0001). According to the intention-to-treat analysis a total of 69.2% of patients in the intervention group achieved systolic BP control compared to 18.9% in the control group patients (OR 9, 95% CI 3.9-20.3; p < 0.0001). ConclusionTask sharing with ASHA a community health volunteer can improve BP control in rural people with stroke and hypertension. They can also help in the adoption of healthy behaviour. Clinical trial registration numberctri.nic.in, CTRI/2018/09/015709.

Hypothetical intervention of targeted systolic blood pressure control of &lt; 120 mmHg on renal prognosis for persons with stage 3–4 chronic kidney disease: an application of parametric g-formula using health checkup data in Japan

The revised KDIGO guidelines recommend maintaining systolic blood pressure (sBP) < 120mmHg in patients with chronic kidney disease (CKD), based on cardiovascular and survival benefits. However, the renal benefit of this strategy remains less clear. We used data of routine health checkups in Japan. Persons whose estimated glomerular filtration rate (eGFR) was < 60mL/min/1.73 m2 in 2015 without end-stage disease were followed until 2020. We estimated the 5-year benefit of hypothetical targeted sBP control using parametric g-formula modeling, accounting for both time-fixed and time-varying confounding variables. Four sensitivity analyses, including analysis using a marginal structural model (MSM) and positive control outcome analysis, were also done. We enrolled 28,972 persons with CKD (median age: 54years, male: 69%, baseline eGFR [median]: 56mL/min/1.73m2). As compared with the natural course without a targeted intervention, there was no renoprotective effect of targeted sBP control, with a 5-year difference in eGFR of 0.65mL/min/1.73 m2 (95% confidence interval - 0.42 to 1.65mL/min/1.73 m2). MSM analysis found a similar result. In contrast, the positive control analysis using the cardiovascular outcome showed that targeted sBP control would reduce the cardiovascular disease incidence by 6.0% over 5years. A targeted sBP control strategy maintaining < 120mmHg may not yield a renoprotective effect for patients with stage 3-4 CKD, although it was expected to offer a cardiovascular benefit. Future research may be warranted in higher-risk populations, such as elderly people or those with more advanced kidney disease.

Asociación del nivel de ácido úrico en suero con los beneficios del control intensivo de la presión arterial

Introduction and objectivesIntensive systolic blood pressure (SBP) control improved outcomes in the Strategy of Blood Pressure Intervention in the Elderly Hypertensive Patients (STEP) trial. Whether the serum uric acid concentration at baseline alters the benefits of intensive SBP control is unknown. MethodsThe STEP trial was a randomized controlled trial that compared the effects of intensive (SBP target of 110 to<130mmHg) and standard (SBP target of 130 to <150mmHg) SBP control in Chinese patients aged 60 to 80 years with hypertension. The primary outcome was a composite of cardiovascular disease events. This post hoc analysis was performed to examine whether the effects of intensive SBP intervention differed by the baseline uric acid concentration using 2 models: restricted cubic spline curves and subgroup analyses, both based on the Fine-Gray subdistribution hazard model in the analysis of the primary outcome and secondary outcomes (excluding all-cause death). In the analysis of all-cause death, the Cox regression model was used. We also examined the change in the follow-up uric acid concentrations. ResultsOverall, the risk of the primary outcome rose as the cumulative uric acid concentration increased in both the intensive and standard treatment groups. Patients with intensive treatment had a lower multivariable-adjusted subdistribution hazard ratio for the primary outcome, but with a wide overlap of 95%CI. Next, we stratified patients according to their baseline uric acid concentration (tertile 1 [T1], <303.0μmol/L; tertile 2 [T2], 303.0 to <375.8μmol/L; and tertile 3 [T3], ≥375.8μmol/L). Subgroup analyses using tertiles provided HRs and 95%CI in T1 (HR, 0.55; 95%CI, 0.36–0.86; P=.008), T2 (HR, 0.80; 95%CI, 0.56–1.14; P=.22) and T3 (HR, 0.86; 95%CI, 0.60–1.21; P=.39), with an interaction P value of .29. The results for most of the secondary outcomes followed the same trends. ConclusionsThere was no evidence that the benefit of the intensive SBP control differed by baseline uric acid concentrations. This trial was registered at ClinicalTrial.gov (Identifier: NCT03015311).

Clinical significance of atherosclerotic risk factors differs in early and advanced stages of plaque formation: A longitudinal study in the general population

BackgroundCarotid plaque is a well-known prognostic factor for cardiovascular diseases. It is unclear which risk factors are associated with the transformation of carotid plaque over time. In this longitudinal study, we examined the risk factors related to carotid plaque progression. MethodsWe enrolled 738 men without medication (mean age: 55 ± 10 years) who underwent the first and second health examinations. We measured carotid plaque thickness (PT) at three points of the right and left carotid artery. Plaque score (PS) was calculated by summing all the PTs. We divided the PS into three groups: None-group (PS <1.1), Early-group (1.1 ≤ PS <5.1), and Advanced-group (PS ≥5.1). We analyzed the relationship between PS progression and parameters such as age, body mass index, systolic blood pressure (SBP), fasting blood sugar, low-density lipoprotein cholesterol (LDL-C), and smoking and exercise habits. ResultsIn multivariable logistic regression analysis, age and SBP were independent factors for PS progression from none to early stages (age, OR 1.07, p = 0.002; SBP, 10 mmHg, OR 1.27, p = 0.041). Age, follow-up period and LDL-C were independently associated factors for PS progression from early to advanced stages (age, OR 1.08,p < 0.001; follow-up period OR1.19, p = 0.041; LDL-C, 10 mg/dL, OR 1.10, p = 0.049). ConclusionsSBP was independently associated with the progress of early atherosclerosis, while LDL-C was independently associated with the progression of advanced atherosclerosis in the general population. Further studies are needed to assess whether early control of SBP and LDL-C levels can reduce the occurrence of future cardiovascular events.

Pharmacogenetic association of the NR1H3 promoter variant with antihypertensive response among patients with hypertension: A longitudinal study.

Background: The genetic factors in assessing therapeutic efficacy and predicting antihypertensive drug response are unclear. Therefore, this study aims to identify the associations between variants and antihypertensive drug response. Methods: A longitudinal study including 1837 hypertensive patients was conducted in Northern China and followed up for a median 2.24years. The associations of 11 candidate variants with blood pressure changes in response to antihypertensive drugs and with the risk of cardiovascular events during the follow-up were examined. The dual-luciferase assay was carried out to assess the effect of genetic variants on gene transcriptional activity. Results: The variant rs11039149A>G in the promoter of nuclear receptor subfamily 1 group H member 3 (NR1H3) was associated with the change in systolic blood pressure (ΔSBP) in response to calcium channel blockers (CCBs) monotherapy. Patients carrying rs11039149AG genotype showed a significant increase of systolic blood pressure (SBP) at follow-up compared with AA carriers, and the difference of ΔSBP between AG and AA carriers was 5.94mm Hg (95%CI: 2.09-9.78, p = 0.002). In 1,184 patients with CCBs therapy, SBP levels decreased in AA carriers, but increased in AG carriers, the difference of ΔSBP between AG and AA carriers was 8.04mm Hg (95%CI: 3.28-12.81, p = 0.001). Further analysis in 359 patients with CCBs monotherapy, the difference of ΔSBP between AG and AA carriers was 15.25mm Hg (95%CI: 6.48-24.02, p = 0.001). However, there was no significant difference in ΔSBP between AG and AA carriers with CCBs multitherapy. The rs11039149A>G was not associated with the cardiovascular events incidence during the follow-up. Additionally, transcriptional factor forkhead box C1 (FOXC1) bound to the NR1H3 promoter containing rs11039149A and significantly increased the transcriptional activity, while rs11039149 A to G change led to a loss-of-function and disabled FOXC1 binding. For the other 10 variants, associations with blood pressure changes or risk of cardiovascular events were not observed. Conclusion: Hypertensive patients with rs11039149AG genotype in the NR1H3 gene have a significant worse SBP control in response to CCBs monotherapy compared with AA carriers. Our findings suggest that the NR1H3 gene might act as a promising genetic factor to affect individual sensitivity to antihypertensive drugs.

The Cost of Uncontrolled Blood Pressure in Australian General Practice: A Modelling Study Using Electronic Health Records (MedicineInsight).

Hypertension is the most common condition seen in Australian general practice. Despite hypertension being amenable to lifestyle modifications and pharmacological treatment, only around half of these patients have controlled blood pressure levels (< 140/90 mmHg), placing them at an increased risk of cardiovascular disease. We aimed to estimate the health and acute hospitalisation costs of uncontrolled hypertension among patients attending general practice. We used population data and electronic health records from 634,000 patients aged 45-74 years who regularly attended an Australian general practice between 2016 and 2018 (MedicineInsight database). An existing worksheet-based costing model was adapted to calculate the potential cost savings for acute hospitalisation of primary cardiovascular disease events by reducing the risk of a cardiovascular event over the next 5 years through improved systolic blood pressure control. The model estimated the number of expected cardiovascular disease events and associated acute hospital costs under current levels of systolic blood pressure and compared this estimate with the expected number of cardiovascular disease events and costs under different levels of systolic blood pressure control. The model estimated that across all Australians aged 45-74 years who visit their general practitioner (n = 8.67 million), 261,858 cardiovascular disease events can be expected over the next 5 years at current systolic blood pressure levels (mean 137.8 mmHg, standard deviation = 12.3 mmHg), with a cost of AUD$1813 million (in 2019-20). By reducing the systolic blood pressure of all patients with a systolic blood pressure greater than 139 mmHg to 139 mmHg, 25,845 cardiovascular disease events could be avoided with an associated reduction in acute hospital costs of AUD$179 million. If systolic blood pressure is lowered further to 129 mmHg for all those with systolic blood pressure greater than 129 mmHg, 56,169 cardiovascular disease events could be avoided with potential cost savings of AUD$389 million. Sensitivity analyses indicate that potential cost savings range from AUD$46 million to AUD$1406 million and AUD$117 million to AUD$2009 million for the two scenarios, respectively. Cost savings by practice range from AUD$16,479 for small practices to AUD$82,493 for large practices. The aggregate cost effects of poor blood pressure control in primary care are high, but cost implications at the individual practice level are modest. The potential cost savings improve the potential to design cost-effective interventions, but such interventions may be best targeted at a population level rather than at individual practices.

Systolic blood pressure time in target range and long-term outcomes in patients with ischemic cardiomyopathy

The relationship between the degree of systolic blood pressure (SBP) control and outcomes remains unclear in patients with ischemic cardiomyopathy (ICM). Current control metrics may not take into account the potential effects of SBP fluctuations over time on patients. This study was a post-hoc analysis of the surgical treatment of ischemic heart failure trial which enrolled 2,136 participants with ICM. Our SBP target range was defined as 110 to 130 mm Hg and the time in target range (TTR) was calculated by linear interpolation. A total of 1,194 patients were included. Compared with the quartile 4 group (TTR 77.87%-100%), the adjusted hazard ratios and 95% confidence intervals of all-cause mortality were 1.32 (0.98-1.78) for quartile 3 group (TTR 54.81%-77.63%), 1.40 (1.03-1.90) for quartile 2 group (TTR 32.59%-54.67%), and 1.53 (1.14-2.04) for quartile 1 group (TTR 0%-32.56%). Per 29.28% (1-SD) decrement in TTR significantly increased the risk of all-cause mortality (1.15 [1.04-1.26]). Similar results were observed in the cardiovascular (CV) mortality and the composite outcome of all-cause mortality plus CV rehospitalization, and in the subgroup analyses of either coronary artery bypass grafting or medical therapy, and different baseline SBP. In patients with ICM, the higher TTR was significantly associated with decreased risk of all-cause mortality, CV mortality and the composite outcome of all-cause mortality plus CV rehospitalization, regardless of whether the patient received coronary artery bypass grafting or medical therapy, and the level of baseline SBP. TTR may be a surrogate metric of long-term SBP control in patients with ICM.

Association of Intensive vs Standard Blood Pressure Control With Regional Changes in Cerebral Small Vessel Disease Biomarkers

Little is known about the associations of strict blood pressure (BP) control with microstructural changes in small vessel disease markers. To investigate the regional associations of intensive vs standard BP control with small vessel disease biomarkers, such as white matter lesions (WMLs), fractional anisotropy (FA), mean diffusivity (MD), and cerebral blood flow (CBF). The Systolic Blood Pressure Intervention Trial (SPRINT) is a multicenter randomized clinical trial that compared intensive systolic BP (SBP) control (SBP target <120 mm Hg) vs standard control (SBP target <140 mm Hg) among participants aged 50 years or older with hypertension and without diabetes or a history of stroke. The study began randomization on November 8, 2010, and stopped July 1, 2016, with a follow-up duration of approximately 4 years. A total of 670 and 458 participants completed brain magnetic resonance imaging at baseline and follow-up, respectively, and comprise the cohort for this post hoc analysis. Statistical analyses for this post hoc analysis were performed between August 2020 and October 2022. At baseline, 355 participants received intensive SBP treatment and 315 participants received standard SBP treatment. The main outcomes were regional changes in WMLs, FA, MD (in white matter regions of interest), and CBF (in gray matter regions of interest). At baseline, 355 participants (mean [SD] age, 67.7 [8.0] years; 200 men [56.3%]) received intensive BP treatment and 315 participants (mean [SD] age, 67.0 [8.4] years; 199 men [63.2%]) received standard BP treatment. Intensive treatment was associated with smaller mean increases in WML volume compared with standard treatment (644.5 mm3 vs 1258.1 mm3). The smaller mean increases were observed specifically in the deep white matter regions of the left anterior corona radiata (intensive treatment, 30.3 mm3 [95% CI, 16.0-44.5 mm3]; standard treatment, 80.5 mm3 [95% CI, 53.8-107.2 mm3]), left tapetum (intensive treatment, 11.8 mm3 [95% CI, 4.4-19.2 mm3]; standard treatment, 27.2 mm3 [95% CI, 19.4-35.0 mm3]), left superior fronto-occipital fasciculus (intensive treatment, 3.2 mm3 [95% CI, 0.7-5.8 mm3]; standard treatment, 9.4 mm3 [95% CI, 5.5-13.4 mm3]), left posterior corona radiata (intensive treatment, 26.0 mm3 [95% CI, 12.9-39.1 mm3]; standard treatment, 52.3 mm3 [95% CI, 34.8-69.8 mm3]), left splenium of the corpus callosum (intensive treatment, 45.4 mm3 [95% CI, 25.1-65.7 mm3]; standard treatment, 83.0 mm3 [95% CI, 58.7-107.2 mm3]), left posterior thalamic radiation (intensive treatment, 53.0 mm3 [95% CI, 29.8-76.2 mm3]; standard treatment, 106.9 mm3 [95% CI, 73.4-140.3 mm3]), and right posterior thalamic radiation (intensive treatment, 49.5 mm3 [95% CI, 24.3-74.7 mm3]; standard treatment, 102.6 mm3 [95% CI, 71.0-134.2 mm3]). This study suggests that intensive BP treatment, compared with standard treatment, was associated with a slower increase of WMLs, improved diffusion tensor imaging, and FA and CBF changes in several brain regions that represent vulnerable areas that may benefit from more strict BP control. ClinicalTrials.gov Identifier: NCT01206062.