Systolic Blood Pressure Categories Research Articles

Influences of cardiovascular disease on the relationship between baseline systolic blood pressure and adverse outcomes in diabetes: insights from large population-based study

Abstract 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.

Trends of Blood Pressure Control in Chronic Kidney Disease Among US Adults: Findings From NHANES 2011 to 2020.

Hypertension afflicts most patients with chronic kidney disease (CKD) and contributes to kidney disease progression, cardiovascular disease, and death in this patient population. The evidence and clinical guidelines support lowering blood pressure (BP) goals in patients with CKD. We evaluated if BP control improved among US adults with CKD. In the NHANES (National Health and Nutrition Examination Survey) for the periods 2011 to 2014, 2015 to 2016, and 2017 to 2020, we identified individuals with CKD defined as estimated glomerular filtration rate 20 to 59 mL/min per 1.73 m2 or urinary albumin/creatinine ratio≥30 mg/g. The following systolic BP categories were evaluated: <120, 120 to 129, 130 to 139, and ≥140 mm Hg. All measures were tested for differences between year groups accounting for sample strata, clusters, and weights. During the periods of 2011 to 2014, 2015 to 2016, and 2017 to 2020, the prevalence of CKD was stable at 14%, 13%, and 13%, respectively (P=0.4). Among those with CKD, the proportion of individuals with self-reported hypertension or taking BP medications increased from 66 in 2011 to 2014, to 69 and 86% in 2015 to 2016 and 2017 to 2020, respectively (P<0.0001). Although the number of BP medications prescribed increased significantly over time, less than half of the individuals with CKD had well-controlled BP based on the current guidelines. Although BP recognition has improved among those with CKD, a significant number of individuals with CKD do not meet their BP goal.

P210 ASSOCIATION BETWEEN FOLLOW-UP BLOOD PRESSURE AND BLOOD PRESSURE CONTROL: A META-REGRESSION ANALYSIS

Background: Blood pressure (BP) control is typically defined as BP values under certain thresholds, most commonly &lt;140/90 mmHg – but there is widespread uncertainty about how mean BP is related to BP control, and what mean BP is required to achieve BP control in 80% of patients. Objective: To assess the association between follow-up mean systolic BP (SBP) and BP control from randomised clinical trials (RCTs). Methods: We systematically searched multiple databases for relevant RCTs. We included double-blind individual RCTs (iRCTs) of adults with hypertension, randomised to BP-lowering drugs from five major antihypertensive classes for ≥2 to ≤ 26 weeks, and which reported data for follow-up mean SBP and BP control (clinic BP &lt;140/90 mmHg) at the last follow-up visit. We also included cluster RCTs (cRCTs), of adults with hypertension, randomised to any BP-lowering intervention, for any duration. The association between follow-up mean SBP and BP control at the last follow-up visit was assessed using a linear regression model. The coefficient was interpreted as the increase in percentage of patients with BP control for every 1 mmHg decrease in follow-up mean SBP. Results: Seventy iRCTs (45,836 participants) and 36 cRCTs (28,154 participants) were included. Each 1 mmHg decrease in follow-up mean SBP was associated with about 2% improvement in BP control in both iRCTs and cRCTs (R2= 78% and 76%, respectively). This finding was broadly consistent in the subgroups of BP-lowering drug classes, baseline SBP categories, and pre-trial BP-lowering treatment status in iRCTs, and country income and baseline SBP categories in cRCTs. Mean SBP levels of 125, 130, and 135 mmHg were associated with BP control rates of 78%, 67%, and 55%, respectively, in iRCTs and 80%, 68%, and 56% in cRCTs. Conclusion: Mean SBP levels of 125 mmHg are required for achieving BP control of &lt;140/90 mmHg in about 80% of the patients. These findings should inform clinical care, guideline recommendations and hypertension control programs.

Late-Life Blood Pressure and Cerebral Amyloid Angiopathy: Findings from the U.S. National Alzheimer's Coordinating Center Uniform Dataset.

High blood pressure (BP) and cerebral amyloid angiopathy (CAA) are two common risk factors for intracranial hemorrhage, potentially leading to cognitive impairment. Less is known about the relationship between BP and CAA, the examination of which was the objective of this study. We analyzed data from 2510 participants in the National Alzheimer's Coordinating Center (NACC) who had information on longitudinal BP measurements before death and on CAA from autopsy. Using the average of four systolic BPs (SBPs) prior to death, SBP was categorized into three groups: <120 mmHg (n = 435), 120-139 mmHg (n = 1335), and ≥140 mmHg (n = 740). CAA was diagnosed using immunohistochemistry in 1580 participants and categorized as mild (n = 759), moderate (n = 529), or severe (n = 292). When adjusted for age at death, sex, APOE genotype, Braak, CERAD, antihypertensive medication use, and microinfarcts, the odds ratios (95% CIs) for CAA associated with SBPs of 120-139 and ≥140 mmHg were 0.91 (0.74-1.12) and 1.00 (0.80-1.26), respectively. Findings from predictor effect plots show no variation in the probability of CAA between the three SBP categories. Microbleeds had no association with CAA, but among those with SBP ≥ 130 mmHg, the proportion of those with microbleeds was numerically greater in those with more severe CAA (p for trend, 0.084). In conclusion, we found no evidence of an association between SBP and CAA. Future studies need to develop non-invasive laboratory tests to diagnose CAA and prospectively examine this association and its implication on the pathophysiology and outcome of Alzheimer's disease.

Optimal Systolic Blood Pressure for the Prevention of All-Cause and Cardiovascular Disease Mortality in Older Adults With Hypertension: Nationwide Population-Based Cohort Study.

Target systolic blood pressure (SBP) levels for older adults with hypertension vary across countries, leading to challenges in determining the appropriate SBP level. This study aims to identify the optimal SBP level for minimizing all-cause and cardiovascular disease (CVD) mortality in older Korean adults with hypertension. This retrospective cohort study used data from the National Health Insurance Service database. We included older adults aged 65 years or older who were newly diagnosed with hypertension and underwent a National Health Insurance Service health checkup in 2003-2004. We excluded patients who had a history of hypertension or CVD, were not prescribed medication for hypertension, had missing blood pressure or any other covariate values, and had fewer than 2 health checkups during the follow-up period until 2020. We categorized the average SBP levels into 6 categories in 10 mm Hg increments, from <120 mm Hg to ≥160 mm Hg; 130-139 mm Hg was the reference range. Cox proportional hazards models were used to examine the relationship between SBP and all-cause and CVD mortalities, and subgroup analysis was conducted by age group (65-74 years and 75 years or older). A total of 68,901 older adults newly diagnosed with hypertension were included in this study. During the follow-up period, 32,588 (47.3%) participants had all-cause mortality and 4273 (6.2%) had CVD mortality. Compared to older adults with SBP within the range of 130-139 mm Hg, individuals who fell into the other SBP categories, excluding those with SBP 120-129 mm Hg, showed significantly higher all-cause and CVD mortality. Subgroup analysis showed that older adults aged 65-74 years had higher all-cause and CVD mortality rates according to SBP categories than those aged 75 years or older. The SBP levels within the range of 120-139 mm Hg were associated with the lowest all-cause and CVD mortality rates among older Korean adults with hypertension. It is recommended to reduce SBP to <140 mm Hg, with 120 mm Hg as the minimum value for SBP, for older Korean adults with hypertension. Additionally, stricter SBP management is required for adults aged 65-74 years.

Blood Pressure, Readmission, and Mortality Among Patients Hospitalized With Acute Kidney Injury

Acute kidney injury (AKI) complicates 20% to 25% of hospital admissions and is associated with long-term mortality, especially from cardiovascular disease. Lower systolic blood pressure (SBP) following AKI may be associated with lower mortality, but potentially at the cost of higher short-term complications. To determine associations of SBP with mortality and hospital readmissions following AKI, and to determine whether time from discharge affects these associations. This retrospective cohort study of adults with AKI during a hospitalization in Veteran Healthcare Association (VHA) hospitals was conducted between January 2013 and December 2018. Patients with 1 year or less of data within the VA system prior to admission, severe or end-stage liver disease, stage 4 or 5 chronic kidney disease, end-stage kidney disease, metastatic cancer, and no blood pressure values within 30 days of discharge were excluded. Data analysis was conducted from May 2022 to February 2024. SBP was treated as time-dependent (categorized as <120 mm Hg, 120-129 mm Hg, 130-139 mm Hg, 140-149 mm Hg, 150-159 mm Hg, and ≥160 mm Hg [comparator]). Time spent in each SBP category was accumulated over time and represented in 30-day increments. Primary outcomes were time to mortality and time to all-cause hospital readmission. Cox proportional hazards regression was adjusted for demographics, comorbidities, and laboratory values. To evaluate associations over time, hazard ratios (HRs) were calculated at 60 days, 90 days, 120 days, 180 days, 270 days, and 365 days from discharge. Of 237 409 admissions with AKI, 80 960 (57 242 aged 65 years or older [70.7%]; 77 965 male [96.3%] and 2995 female [3.7%]) were included. The cohort had high rates of diabetes (16 060 patients [20.0%]), congestive heart failure (22 516 patients [28.1%]), and chronic lung disease (27 682 patients [34.2%]), and 1-year mortality was 15.9% (12 876 patients). Overall, patients with SBP between 130 and 139 mm Hg had the most favorable risk level for mortality and readmission. There were clear, time-dependent mediations on associations in all groups. Compared with patients with SBP of 160 mm Hg or greater, the risk of mortality for patients with SBP between 130 and 139 mm Hg decreased between 60 days (adjusted HR, 1.20; 99% CI, 1.00-1.44) and 365 days (adjusted HR, 0.58; 99% CI, 0.45-0.76). SBP less than 120 mm Hg was associated with increased risk of mortality at all time points. In this retrospective cohort study of post-AKI patients, there were important time-dependent mediations of the association of blood pressure with mortality and readmission. These findings may inform timing of post-AKI blood pressure treatment.

Systolic Blood Pressure, Diastolic Blood Pressure and Pulse Pressure and the Risk of Subclinical Myocardial Injury: The HUNT Study.

Subclinical myocardial injury expressed as higher cardiac troponin concentrations may represent an important intermediary between hypertension and the risk of cardiovascular disease. The study aimed to assess the relative strength of associations between systolic blood pressure (BP), diastolic BP, and pulse pressure, and subclinical myocardial injury, and how change in BP variables over time associates with subclinical myocardial injury. cTnl (cardiac troponin I) was measured in 32 968 participants of the fourth wave of the population-based cohort HUNT4 (Trøndelag Health Study) without a history of cardiovascular disease. An additional longitudinal analysis included participants from HUNT4 with BP measurements from HUNT3 (n=18 681). Associations between BP variables and cTnI concentrations were assessed by linear and logistic regression analyses. The median cTnI concentration was 1.6 ng/L (25th-75th percentiles, 0.6-3.1 ng/L), median age was 52 years (39.1-65.6 years), and 57% were female subjects. Cross-sectionally, only systolic BP categories ≥130 mm Hg associated with higher cTnI concentrations, compared with a reference systolic BP of <110 mm Hg. All categories of diastolic BP and pulse pressure were positively associated with higher cTnI concentrations when diastolic BP 70 to 79 mm Hg and pulse pressure <40 mm Hg were used as references, respectively. When comparing systolic BP, diastolic BP, and pulse pressure as continuous variables, cross-sectionally, pulse pressure most strongly associated with cTnI concentrations (P for all comparisons <0.001), whereas longitudinally, change in diastolic BP was most strongly associated with cTnI concentrations (P for all comparisons <0.05). Subjects with high pulse pressure and longitudinal increase in diastolic BP are at higher risk for subclinical myocardial injury.

Impact of guideline-directed medical therapy on systolic blood pressure and cardiovascular outcomes in patients with heart failure and low blood pressure: A systematic review and meta-analysis.

Existing research indicates that patients with heart failure (HF) may have restricted access to guideline-directed medical therapy (GDMT) when their blood pressure (BP) is comparatively low. However, recent clinical trials suggest that HF patients with low BP could still benefit from certain HF medications, which have a minimal impact on BP. This systematic review and meta-analysis was conducted to determine whether this applies to all GDMT. A systematic search of MEDLINE and EMBASE was conducted for studies published from inception to 10 January 2024. Randomized controlled trials were selected if they reported on the longitudinal change of systolic BP (SBP) due to GDMT, or the risks of cardiovascular events in HF patients based on SBP categories. Weighted mean difference (WMD), hazard ratio or relative risk, and corresponding 95% confidence intervals (CI) were pooled for meta-analysis where possible. Data from 20 studies, encompassing information on 84 782 individuals, were analysed. Overall, GDMT is associated with lower SBP (WMD, -2.16; 95% CI -2.86 to -1.46), with no significant difference between baseline low and non-low BP subgroups (interaction p = 0.810). However, SBP of the treatment group increased by 5.8 mmHg from baseline in the low SBP subgroup during follow-up, while it decreased by 4.0 mmHg in the baseline non-low SBP subgroup. GDMT demonstrated similar cardiovascular benefits and risk of hypotension between low and non-low SBP subgroups (interaction p = 0.318 and 0.903, respectively). Guideline-directed medical therapy is associated with a negligible decrease in SBP, but can provide similar cardiovascular benefits in both low and non-low SBP HF patients, with no significant interaction with SBP as to hypotension. Therefore, GDMT should be initiated and maintained in HF patients with low BP.

Efficacy and safety of sacubitril/valsartan after six months in patients with heart failure with reduced ejection fraction and asymptomatic hypotension.

It is not clear whether sacubitril/valsartan is beneficial for patients with heart failure (HF) with reduced ejection fraction (HFrEF) and low systolic blood pressure (SBP). This study aimed to investigate the efficacy and tolerability of sacubitril/valsartan in HFrEF patients with SBP < 100 mmHg. An observational study was conducted on 117 patients, 40.2% of whom had SBP < 100 mmHg without symptomatic hypotension, and 59.8% of whom had SBP ≥ 100 mmHg in an optimized HF follow-up management system. At the 6-month follow-up, 52.4% of patients with SBP < 100 mmHg and 70.0% of those with SBP ≥ 100 mmHg successfully reached the target dosages of sacubitril/valsartan. A reduction in the concentration of N-terminal pro-B-type natriuretic peptide was similar between patients with SBP < 100 mmHg and SBP ≥ 100 mmHg (1627.5 pg/mL and 1340.1 pg/mL, respectively; P = 0.75). The effect of sacubitril/valsartan on left ventricular ejection fraction was observed in both SBP categories, with a 10.8% increase in patients with SBP < 100 mmHg (P < 0.001) and a 14.0% increase in patients with SBP ≥ 100 mmHg (P < 0.001). The effects of sacubitril/valsartan on SBP were statistically significant and inverse across both SBP categories (P = 0.001), with an increase of 7.5 mmHg in patients with SBP < 100 mmHg and a decrease of 11.5 mmHg in patients with SBP ≥ 100 mmHg. No statistically significant differences were observed between the two groups in terms of the occurrence of symptomatic hypotension, deteriorating renal function, hyperkalemia, angioedema, or stroke. Within an optimized HF follow-up management system, sacubitril/valsartan exhibited excellent tolerability and prompted left ventricular reverse remodeling in patients with HFrEF who presented asymptomatic hypotension.

Association between systolic blood pressure and target organ damage in naturally occurring cases of systemic hypertension in the dog

Chronic elevation in the systolic blood pressure (SBP) adversely affects the lifespan in the dog by causing injury to the eye, heart, kidney and brain. Understanding the association between SBP and target organ damage (TOD) helps in risk categorization and treatment planning. Therefore, a prospective study was undertaken to find the association between SBP and renal resistive index (RI) in naturally occurring cases of canine systemic hypertension. Based on the ACVIM guidelines 2018, dogs (n=135) were categorized into four risk groups of SBP, viz., A (minimal), B (low), C (moderate), and D (high). Ophthalmoscopy and echocardiography were used to assess ocular and cardiac changes, respectively. Nephrosonography, urinalysis, and RI were used to assess kidney damage. Odds ratio (OR) was used to quantify the risk of TOD for different categories of SBP. One-way Anova with Tukey's post-hoc test was used to test the effect of different SBP risk groups on urine protein creatinine ratio (UPC) and RI as well as the effect of number of TOD on the RI. Pearson's correlation test was done to see the relation of SBP with UPC and RI. Tortuous retinal vessels were common in group B with an OR of 11 (95% CI: 0.59-207). Retinal hemorrhage and left ventricular hypertrophy were common in group D with an OR of 13 (95% CI: 0.67-234) and 11 (95% CI: 0.61-207), respectively. A significant strong positive correlation of SBP with UPC (R2=0.65) and RI (R2=0.58) was observed. The renal RI significantly increased when the number of TOD was ≥ 2. It was concluded that SBP and RI are associated with the number and severity of TOD and might be valuable in risk classification in hypertensive dogs.

The effect of long-term application of guideline-directed medical therapy on systolic blood pressure in hospitalized patients with heart failure with reduced ejection fraction

Abstract Background According to the current guidelines in heart failure (HF) with reduced ejection fraction (HFrEF) the implementation and titration of guideline-directed medical therapy (GDMT) is recommended. Although just symptomatic hypotension is known as a factor limiting the initiation or uptitration of GDMT, in everyday practice asymptomatic hypotension often has a negative impact on the long-term application of GDMT in HFrEF, even though patients with lower systolic blood pressure (SBP) have worse prognosis. Aim To assess the application of combined neurohormonal antagonist therapy (triple therapy [TT]: RASi[ACEi/ARB/ARNI]+βB+MRA) based on SBP during an index HF hospitalization, and to evaluate the long-term application of TT on SBP and on mortality. Patients and methods: The data of 247 consecutive HFrEF patients (male:75%, age:66[56-74]years, ischemic:46%, diabetes:40%, hypertension:63%, atrial fibrillation:46%, LVEF:25[20-30]%, eGFR:58[39-73]ml/min/1.73m2,SBP:118[102-134]mmHg) were analysed retrospectively, who had been admitted to the HF Unit of our tertiary centre due to HF in 2019-2021 and then were followed up for one year. Patients were divided into three SBP categories based on SBP measured at admission: SBP1:&amp;lt;100mmHg (n = 46), SBP2:100-120mmHg (n = 98), SBP3:&amp;gt;120mmHg (n = 103) (respectively). The applicability of TT at hospital discharge and at 1 year were assessed comparing SBP categories with Chi-square test. The changes of SBP within each category were compared with Wilcoxon test. 1-year all-cause mortality (ACM) was investigated with Kaplan-Meier method and log-rank test. Results At discharge, 77% of the patients received TT in the total cohort. Lower SBP at admission led to lower application ratio of βB (72-89-87%, p = 0.019), while RASi and MRA use was consistent across SBP categories (87-89-89%; 91-98-93%, p&amp;gt;0.05). TT application at discharge did not differ significantly among the subgroups (65-81-79%, p = 0.107). 1-year ACM was 23% in the total cohort, with significantly higher mortality rates in lower SBP groups (33-27-15%, p = 0.022). At 1 year TT application remained high; 65% in SBP1, 78% in SBP2 and 72% in SBP3 group. No differences (p&amp;gt;0.05) were seen in terms of βB (87-88-91%), RASi (81-89-84%) and MRA use (77-86-82%) in SBP groups. In the effect of GDMT, in the SBP1 and SBP2 group, SBP significantly (p&amp;lt;0.0001) rose (SBP1: from 92[85-95] to 110[95-127]mmHg, SBP2: from 111[104-117] to 124[110-133]mmHg; discharge vs. 1 year), while in the highest SBP group significant decrease was verified (from 137[129-146] to 130[118-145]mmHg, p = 0.002). Conclusions Our study results confirmed that low SBP is associated with a poor prognosis in HFrEF. Low SBP is a relevant influencing factor of GDMT initiation and long-term application, even though among these patients increase in SBP can be expected due to the use of GDMT. Our results indicate that low SBP should not make physicians be hesitant to optimize therapy in severe HFrEF.

Effectiveness of Valsartan's Single-Pill Combination Therapies on Blood Pressure Control in Hypertensive Patients: Malaysian Single-Centre Real-World Experience.

Uncontrolled hypertension can cause cardiovascular disease and is an important public health issue. Single-pill combination (SPC) therapies possess combined blood pressure (BP)-lowering effect and may improve compliance to treatment. This study assessed the effectiveness of valsartan (Val)-based SPC therapies in achieving BP control in hypertensive patients. This was a retrospective study. Data were extracted from the hybrid medical records of patients from the Institut Jantung Negara (IJN), Malaysia. Adults with established diagnosis of hypertension and on prescription of Val-based SPC therapies as part of routine medical care from 1 January 2013 to 31 December 2018, with ≥ 1 year of follow-up were included. Primary endpoint was proportion of patients achieving therapeutic BP control (BP < 140/90 mmHg). Secondary outcomes included change from baseline (CFB) in systolic BP (SBP) and diastolic BP (DBP), and subgroup analysis was based on baseline SBP categories and presence of diabetes. Study included 409 hypertensive patients. The mean (standard deviation [SD]) age of the population was 65.1 (10.6) years old, with male predominance (61.6%). Proportion of patients achieving target BP between baseline and follow-up were 57.0% (P < 0.001). Mean CFB in SBP and DBP were recorded as 19.52 mmHg and 7.47 mmHg, respectively. Over half of the patients achieved the target BP in all subgroups categorised by SBP at baseline, except the subgroup of SBP 160 mmHg-179 mmHg. SPC therapies were continued in 97.3% of patients at 1-year follow-up. Patients using Val-based SPC therapies had significant reduction in BP with good tolerability, with 57% of patients achieving target BP over a prolonged 1-year follow-up period. Uptake of SPC therapy is warranted to improve patient care and outcomes in hypertension.

Prognosis of Systolic Pressure 130 to 139 According to Risk. A Prospective Cohort Study Between 1992 and 2019.

Guidelines recommend pharmacological treatment for systolic blood pressure (SBP) of 130 to 139 mm Hg in secondary prevention. However, uncertainty persists in primary prevention in low cardiovascular risk patients (CVR). Cohort study representative of the general population of Albacete/Southeast Spain. We examined 1029 participants with untreated BP and free of cardiovascular disease, followed-up during 1992 to 2019. Cox regression modeled the association of SBP with cardiovascular morbidity and mortality (outcome-1) and cardiovascular morbidity and all-cause mortality (outcome-2). Participants' mean age was 44.8 years (53.8%, women; 77.1% at low-CVR); 20.3% had SBP 120 to 129; 13.0% 130 to 139 at low-CVR and 3.4% at high-CVR; and 27.4% ≥140 mm Hg. After a 25.7-year median follow-up, 218 outcome-1 and 302 outcome-2 cases occurred. Unadjusted hazard ratios (HR) of outcome-1 for these increasing SBP categories (versus <120) were 2.72, 2.27, 11.54, and 7.52, respectively; and 2.69, 2.32, 10.55, and 7.34 for outcome-2 (all P<0.01). After adjustment for other risk factors, hazard ratio (95% CI) of outcome-1 were 1.49 (0.91-2.44), 1.65 (0.94-2.91, P=0.08), 1.36 (0.72-2.57), and 1.82 (1.15-2.88), respectively, and 1.39 (0.91-2.11), 1.69 (1.05-2.73), 1.09 (0.63-1.88), and 1.64 (1.11-2.41) for outcome-2. Compared with 130 to 139 at low-CVR, hazard ratio for 130 to 139 at high-CVR was 4.85 for outcome-1 (P<0.001) and 4.43 for outcome-2 (P<0.001). In this primary prevention population of relatively young average age, untreated SBP of 130 to 139 mm Hg at low-CVR had long-term prognostic value and might benefit from stricter SBP targets. High-CVR patients had nonsignificant higher risk (limited sample size) but 4-fold greater risk when compared with low-CVR. Overall, results indicate the importance of risk stratification, supporting risk-based decision-making.

Sex-Specific Effects of Blood Pressure Lowering Pharmacotherapy for the Prevention of Cardiovascular Disease: An Individual Participant-Level Data Meta-Analysis.

Whether the relative effects of blood pressure (BP)-lowering treatment on cardiovascular outcomes differ by sex, particularly when BP is not substantially elevated, has been uncertain. We conducted an individual participant-level data meta-analysis of randomized controlled trials of pharmacological BP lowering. We pooled the data and categorized participants by sex, systolic BP categories in 10-mm Hg increments from <120 to ≥170 mm Hg, and age categories spanning from <55 to ≥85 years. We used fixed-effect one-stage individual participant-level data meta-analyses and applied Cox proportional hazard models, stratified by trial, to analyze the data. We included data from 51 randomized controlled trials involving 358 636 (42% women) participants. Over 4.2 years of median follow-up, a 5-mm Hg reduction in systolic BP decreased the risk of major cardiovascular events both in women and men (hazard ratio [95% CI], 0.92 [0.89-0.95] for women and 0.90 [0.88-0.93] for men; P for interaction, 1). There was no evidence for heterogeneity of relative treatment effects by sex for the major cardiovascular disease, its components, or across the different baseline BP categories (all P for interaction, ≥0.57). The effects in women and men were consistent across age categories and the types of antihypertensive medications (all P for interaction, ≥0.14). The effects of BP reduction were similar in women and men across all BP and age categories at randomization and with no evidence to suggest that drug classes had differing effects by sex. This study does not substantiate sex-based differences in BP-lowering treatment.

Intensive blood pressure control and the progression of IgA nephropathy: a cohort study using marginal structural models.

In chronic kidney disease, current guidelines recommend systolic blood pressure (SBP) below 120mmHg. However, the renoprotective effect of intensive blood-pressure (BP) lowering on immunoglobulin A nephropathy (IgAN) remains undetermined. We aimed to determine the effect of intensive BP control on the progression of IgAN. At Peking University First Hospital, 1530 patients with IgAN were enrolled. An examination of the relationship between baseline and time-updated BP and composite kidney outcomes, defined as development of end-stage kidney disease (ESKD) or a 30% decline in estimated glomerular filtration rate (eGFR), was conducted. Baseline and time-updated BPs were modeled using multivariate causal hazards models and marginal structural models (MSMs). In a median follow-up of 43.5 (interquartile range 27.2, 72.7) months, 367 (24.0%) patients experienced the composite kidney outcomes. No significant associations were found between baseline BP and the composite outcomes. Using MSMs with time-updated SBP for analysis, a U-shaped association was found. In reference to SBP 110-119mmHg, hazard ratios (95% confidence intervals) for the SBP categories <110, 120-129, 130-139 and ≥140mmHg were 1.48 (1.02-2.17), 1.13 (0.80-1.60), 2.21 (1.54-3.16) and 2.91 (1.94-4.35), respectively. The trend was more prominent in patients with proteinuria ≥1g/day and eGFR ≥60mL/min/1.73 m2. After analyzing time-updated diastolic BP, no similar trend was observed. In patients with IgAN, intensive BP control during the treatment period may retard the kidney disease progression, but the potential risk of hypotension still needs to be considered.

#2710 SEX DIFFERENCE IN CARDIOVASCULAR RISK IN PATIENTS WITH CHRONIC KIDNEY DISEASE: A POOLED ANALYSIS OF FOUR COHORT STUDIES

Abstract Background and Aims Progression of chronic kidney disease (CKD) has proven to be faster in men than in Women [1-3]. Whether the same holds true for cardiovascular risk remains ill-defined. Method We conducted a pooled analysis of 4 cohort studies from 40 nephrology clinics in Italy including patients with CKD (estimated GFR&amp;lt;60 ml/min/1.73m2 or higher if proteinuria &amp;gt;0.15 g/day). The aim was to compare multivariable-adjusted risk (Hazard Ratio, 95% Confidence Interval) of a composite cardiovascular endpoint (cardiovascular death and non-fatal myocardial infarction, congestive heart failure, stroke, revascularization, peripheral vascular disease, and nontraumatic amputation) in women (n = 1,192) versus men (n = 1,635). Results At baseline, women had slightly higher systolic blood pressure (SBP) as compared with men (139±19 vs 138±18 mmHg, P = 0.049), lower eGFR (33.4 vs 35.7 mL/min/1.73 m2 , P = 0.001) and lower urine protein excretion (0.30 g/day vs 0.45 g/day in men, P&amp;lt;0.001). Women did not differ from men in age and prevalence of diabetes while having a lower prevalence of cardiovascular disease, left ventricular hypertrophy and smoking habit. During a median follow-up of 4.0 years, 517 fatal and non-fatal cardiovascular events were registered (199 in women and 318 in men). The adjusted risk of cardiovascular events was lower in women (0.73, 0.60-0.89, P = 0.002) than in men; however, the cardiovascular risk advantage of women progressively diminished as SBP (as continuous variable) increased (P for interaction = 0.021; Figure 1). Similar results were obtained when considering SBP categories; when compared to men, women had a lower cardiovascular risk for SBP &amp;lt;130 mmHg (0.50, 0.31-0.80; P = 0.004) and between 130–140 mmHg (0.72, 0.53-0.99; P = 0.038), while no difference was observed for SBP&amp;gt;140 mmHg (0.85, 0.64-1.11; P = 0.232). Conclusion Higher BP levels abolish the cardiovascular protection seen in female vs male patients with overt CKD. This finding supports the need for higher awareness of hypertensive burden in women with CKD.

#5289 INTRARENAL RENIN-ANGIOTENSIN SYSTEM ACTIVATION ALTERS RELATIONSHIP BETWEEN SYSTOLIC BLOOD PRESSURE AND PROGRESSION OF CHRONIC KIDNEY DISEASE

Abstract Background and Aims Elevated blood pressure (BP) and intrarenal renin-angiotensin system (RAS) activity are closely related to chronic kidney disease (CKD) progression. However, interrelationship between BP and intrarenal RAS activity on the risk of CKD progression is unknown. Method We analyzed 2,076 participants from the Korean Cohort Study for Outcomes in Patients With CKD. The main exposure was systolic BP (SBP). The urinary angiotensinogen-to-creatinine (u-AGT/Cr) ratio was stratified according to the median value (3.65 μg/gCr). The primary outcome was a composite kidney outcome of a ≥50% decline in estimated glomerular filtration rate from baseline measurement or initiation of kidney replacement therapy. Results During 10,550 person-years of follow-up (median, 5.2 years), the composite outcome occurred in 800 (38.5%) participants. In the multivariable cause-specific hazard model, higher SBP was associated with an increased risk of CKD progression. There was a significant interaction between SBP and u-AGT/Cr ratio on the risk of the primary outcome (P-for-interaction = 0.019). In patients with u-AGT/Cr &amp;lt;3.65 μg/gCr, the hazard ratios (HRs) (95% confidence intervals [CIs]) for SBP 120–129, 130–139, and ≥140 mmHg were 1.47 (1.08-2.01), 1.74 (1.26-2.39), and 2.43 (1.76-3.37), respectively, compared with SBP &amp;lt;120 mmHg. In addition, each 10 mmHg increase in SBP was associated with an 18% higher risk of CKD progression. Moreover, there was a greater decline in the estimated glomerular filtration rate among the higher SBP categories. However, these associations were not observed in patients with u-AGT/Cr ≥3.65 μg/gCr. Conclusion Urinary angiotensinogen levels may modify the association between SBP and adverse kidney outcomes.

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.

Systolic blood pressure reduction with tirzepatide in patients with type 2 diabetes: insights from SURPASS clinical program

BackgroundTirzepatide, a once-weekly glucose-dependent insulinotropic polypeptide/ glucagon-like peptide-1 receptor agonist, is approved in the United States, Europe and Japan for the treatment of type 2 diabetes. Across the SURPASS-1 to -5 clinical studies, tirzepatide 5, 10 and 15 mg demonstrated significant improvements in glycated haemoglobin A1c (HbA1c) (− 1.9 to − 2.6%), body weight (− 6.6 to − 13.9%) and systolic blood pressure (SBP) (− 2.8 to − 12.6 mmHg) at the end of study treatment.MethodsPost-hoc mediation analyses were conducted to evaluate weight-loss dependent and weight-loss independent effects of tirzepatide on SBP reductions across the 5 SURPASS studies. The safety population (all randomized patients who took at least 1 dose of study drug) of each study was analyzed. Additional analyses were conducted at individual study level or pooled across 5 SURPASS trials.ResultsThe difference in mean SBP change from baseline at 40 weeks (total effect) between the tirzepatide and comparator groups was − 1.3 to − 5.1 mmHg (tirzepatide 5 mg), − 1.7 to − 6.5 mmHg (tirzepatide 10 mg) and − 3.1 to − 11.5 mmHg (tirzepatide 15 mg). These SBP reductions were primarily mediated through weight loss, with different degrees of contributions from weight-loss independent effects across the different trials. In the SURPASS-4 study, which enrolled patients with established cardiovascular disease, weight-loss independent effects explained 33% to 57% of difference in SBP change between tirzepatide and insulin glargine groups. In a pooled analysis of the SURPASS-1 to -5 studies, there was a significant (p < 0.001) but weak correlation (r = 0.18 to 0.22) between change in body weight and SBP. Reductions in SBP with tirzepatide were not dependent on concomitant antihypertensive medications at baseline as similar reductions were observed whether participants were receiving them or not (interaction p = 0.77). The largest SBP reductions were observed in the highest baseline category (> 140 mmHg), while those in the first quartile of baseline SBP category (< 122 mmHg) observed no further decrease in SBP.ConclusionsTirzepatide-induced SBP reduction was primarily mediated through weight loss, with different degrees of contributions from weight-loss independent effects across the different trials. SBP reduction was not dependent on antihypertensive medication use but dependent on baseline SBP value, alleviating theoretical concerns of hypotension.

Associations of systolic blood pressure and in-hospital mortality in critically ill patients with acute kidney injury.

Although systolic blood pressure (SBP) is associated with acute renal injury (AKI), the relationship between baseline SBP and prognosis in critically ill patients with AKI is unclear. We aimed to assess the linearity and profile of the relationship between SBP at intensive care unit (ICU) admission and in-hospital mortality in these patients. Data of AKI patients in the ICU settings were extracted from the Medical Information Mart for Intensive Care III database. The association between seven SBP categories (< 100, 100-109, 110-119, 120-129, 130-139, 140-149, and ≥ 150mmHg) and all-cause in-hospital mortality was assessed by Cox proportional hazard models. Restricted cubic spline analysis for the multivariate Cox model was performed to explore the shape of the relationship between SBP and mortality. A total of 24,202 patients with AKI were included in this study. A typically U-shaped relationship was found between SBP at admission and in-hospital mortality. Among all SBP categories, the lowest risk of death was observed in patients with SBP around 110-119mmHg, whereas the highest was noted in patients with extremely low SBP (< 100mmHg), followed by those with extremely high SBP (≥ 150mmHg). SBP showed a significant interaction with vasopressor use and AKI stage in relation to the risk of in-hospital mortality. SBP upon admission showed a non-linear association with all-cause in-hospital mortality in critically ill patients with AKI. Patients with low or high SBP show an increased risk of mortality compared to patients with normal SBP.