BP-lowering Treatment 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.

The relationship between lung MIBG uptake and clinical response to renal denervation

Abstract Background Renal denervation (RDN) reduces the sympathetic overdrive and can optimize blood pressure control in patients with difficult-to-treat hypertension (DTH). However, a substantial proportion of patients undergoing RDN do not show a clinical response to the procedure, making it critical to identify novel and more accurate predictors. The metaiodobenzylguanidine (MIBG) scintigraphy allows non-invasive assessment of sympathetic nerve activity. Yet, studies evaluating the heart and kidney MIBG uptake as predictors of clinical response to RDN provided conflicting results, and a comprehensive evaluation of the MIBG uptake in different organs of DTH patients undergoing RDN is lacking. Purpose To explore if a more comprehensive evaluation of MBG uptake in the kidneys, heart and lungs can predict the clinical response to RDN. Methods Eighteen patients with DTH underwent evaluation of their clinical and pharmacological history, office and ambulatory BP values and levels of cardiovascular risk factors. A rest echocardiography, carotid vascular ultrasound and MIBG scintigraphy were also performed before RDN. The patient’s pharmacological history and office and ambulatory BP values were re-evaluated after 3 months from RDN. We considered responders (R) those subjects with a significant reduction of the office BP values on stable BP-lowering treatment or a reduced burden of BP-lowering medications while maintaining optimal control of the office BP. Results Ten patients could be classified as R (1 woman, mean age 49±10 years), while 7 were non-responders (NR, 2 women, mean age 53±8 years). The reduction in office systolic and diastolic BP (baseline vs 3 months) was significantly larger in R vs NR (p=0.01 for both). The burden of BP-lowering medications after the procedure was reduced by 39% in R, compared to 2% in NR (p<0.01). Responders had a higher baseline HR and prevalence of carotid atherosclerosis than NR (p<0.05 for both). In early MIBG acquisitions, the lung/mediastinum ratio on both sides showed higher MIBG uptake in R vs NR (p<0.05). There was a higher MIBG uptake in the right vs. left lung in the whole population and in R vs NR. In late acquisitions, only the left side showed a significant difference between R and NR (p<0.05). The associations between the lung/mediastinum ratio MIBG uptake and response to RDN remained significant after adjusting for the baseline clinical predictors of the RDN response. All other MIBG scintigraphy parameters were similar between groups. Conclusions Our results suggest that RDN might be less effective in patients with an advanced burden of hypertension-mediated target organ damage and confirm a higher HR as a reliable predictor of the clinical response to the procedure. We also document a novel association between the lung/mediastinum ratio MIBG uptake and response to RDN that, if confirmed in future studies, might provide a novel marker to improve the selection of patients undergoing RDN.

Process Evaluation of an Ambulance-Delivered Early Intensive Blood Pressure-Lowering Stroke Trial: Design, Rationale, and Reflection

Introduction: The fourth INTEnsive ambulance-delivered blood pressure Reduction in hyper-ACute stroke Trial (INTERACT4) is a large-scale, multicenter, prospective, randomized, open-label, blinded endpoint assessment trial, initiated in an ambulance in China, aiming at evaluating the effectiveness and safety of prehospital blood pressure (BP) lowering in patients with suspected acute stroke and elevated BP. A prespecified process evaluation is intended to explore the implementation of the trial intervention, provide support to interpret the trial outcomes and put forward suggestions to scale up the intervention in broader settings in the future. Methods: This process evaluation is a mixed-methods design, and follows the Normalization Process Theory (NPT) and the UK Medical Research Council (UK MRC) guidance. Fidelity, reach, acceptability, appropriateness, adoption, sustainability, and relevant contextual factors and mechanisms affecting the implementation of prehospital early intensive BP-lowering treatment will be analyzed. Semi-structured interviews with ambulance staff, ward and emergency department clinicians, and nurses are undertaken to explore perceptions of the intervention, contextual factors, and potential suggestions for future implementation in practice. Data from observational records, surveys, conventional monitoring data, on-site records, and case report forms will be analyzed to understand background care and context. Conclusion: The process evaluation of INTERACT4 will provide insights for the implementation of prehospital early intensive BP-lowering intervention in different health systems and help better explain the trial results for further scale up.

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 <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 <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 <140/90 mmHg in about 80% of the patients. These findings should inform clinical care, guideline recommendations and hypertension control programs.

Blood pressure variability assessed by office, home, and ambulatory measurements before and during antihypertensive drug treatment: a sub-analysis of the REVERENT randomized trial.

Blood pressure (BP) variability (BPV) can be assessed using office (OBP), home (HBP), or ambulatory BP (ABP) measurements. This analysis investigated the association and agreement between OBP, HBP, and ABP measurements for BPV assessment at baseline and 10 weeks after initiating antihypertensive drug therapy. Untreated hypertensive patients with elevated BPV were randomized to receive an angiotensin-converting enzyme inhibitor (ramipril) or a calcium channel blocker (nifedipine GITS) in a 10-week, open-label, blinded-end point study. BPV was assessed using standard deviation (SD) and coefficient of variation (CV) (reading-to-reading analyses). Data from 146 participants from three research centers (Athens/Greece; Milan/Italy; Shanghai/China) were analyzed [mean age 53 ± 10 (SD) years, male individuals 60%, baseline systolic OBP, HBP, and 24 h ABP 144 ± 9, 138 ± 10, and 143 ± 10 mmHg, respectively]. Post-treatment minus pre-treatment systolic CV difference was: OBP: 0.3%, P = 0.28; HBP: -0.2%, P = 0.20; 24 h ABP: 1.1%, P < 0.001. Home and ambulatory (not office) BPV indices presented weak-to-moderate correlation, both before and during treatment (range of coefficients 0.04-0.33). The correlation coefficient between systolic HBP and awake ABP CV was 0.21 and 0.28 before and during treatment, respectively ( P < 0.05/< 0.001, respectively). Home and ambulatory (not office) BPV indices presented slight-to-fair agreement (range 64-73%) in detecting participants with high systolic BPV (top quartile of respective distributions) both before and during treatment (kappa range 0.04-0.27). These data showed a weak-to-moderate association between out-of-office (but not office) BPV indices both before and during BP-lowering treatment, with reasonable agreement in detecting individuals with high BPV. Out-of-office BP measurements provide more similar and consistent BPV information than office measurements.

Revisiting Cardiovascular Benefits of Blood Pressure Reduction in Primary and Secondary Prevention: Focus on Targets and Residual Risk-A Systematic Review and Meta-Analysis.

Previous meta-analyses resurrected the debated statement "the lower, the better" following blood pressure (BP)-lowering treatment. We investigated the benefits of BP-lowering treatment at different BP targets by prevention category. The meta-analysis protocol was registered at the International Prospective Register of Systematic Reviews (CRD42022379249). The database included 115 BP-lowering or comparison trials from patients with (n=241 089) or without (n=198 937) previous cardiovascular events. Prevention disease groups were stratified by in-treatment achieved BP, drug class versus placebo, and drug class versus other classes. Risk ratios and 95% CIs of major adverse cardiovascular events were calculated. Following a standard (10/5 mm Hg) BP reduction, major adverse cardiovascular event relative risk reductions were not different between prevention groups (primary, 25% [95% CI, 18%-31%]; secondary, 28% [95% CI, 20%-37%]). For achieved systolic BP of at least 140 mm Hg, between 130 and 140 mm Hg, and <130 mm Hg (nadir, 125 mm Hg), (1) risk ratios of major adverse cardiovascular events and absolute risk reductions were not different between prevention groups across systolic BP strata, and (2) residual risk, though 4.1× greater in secondary than primary prevention, decreased in primary prevention from higher to lower systolic BP targets. The effect of separate drugs versus others on the primary outcome was not different between prevention groups. BP-lowering treatment benefits did not differ by prevention group to a nadir of 125 mm Hg for systolic BP. Although residual risk in secondary prevention is higher than in primary prevention, it gradually decreases at progressively lower systolic BP targets in primary prevention. URL: https://www.crd.york.ac.uk/PROSPERO/; Unique identifier: CRD42022379249.

BLOOD PRESSURE CONTROL IN TERTIARY-CARE HYPERTENSIVE PATIENTS DURING COVID-19 PANDEMIC

Objective: Cardiovascular risk factors distribution during the pandemic suggests worsening of the cardiovascular risk profile of hypertensive patients. At the same time, data on quality of hypertension control during the COVID-19 pandemic are scarce, in Poland. The aim of the study was to analyse the quality of blood pressure (BP) control in a group of patients who required regular control in tertiary care. Design and method: The study included hypertensive patients regularly monitored in tertiary-care out-patient clinic for at least 4 years with at least 2 visits a year prior the analysis. The size of the group was calculated based on the original data of first 50 consecutive records of patients (power of 90%). Records were retrospectively analysed with respect to office blood pressure (oBP) control. Additionally, within-visit BP variability was calculated (difference of maximum and minimum BP from 3 measurements); body weight, age, sex, duration of hypertension, number of visits per year, seasonal BP variability, use of telemedical services, comorbidities and BP-lowering treatment were recorded. Results: The study enrolled 220 patients. The values of systolic BP (sBP) before and after the break in the whole group were 135.8 ± 17.1 mm Hg vs. 137.9 ±19.5 mm Hg; P=0.08, and a diastolic BP (dBP) of 80.3 ±11.4 mm Hg vs. 82.6 ±12.2 mm Hg; p = 0.001. After adjusting for seasonal variation of BP, the respective differences were: sBP: 134.8 ± 16.5 vs. 138.0 ± 19.4; p = 0.03, and dBP: 79.4 ±10.9 vs. 82.2 ± 11.9; p = 0.004. Before 2020, 61.4% of patients were controlled (BP &lt; 140/90 mm Hg), whereas after the pandemic-driven break in regular visits the control rate decreased to 55.5% (p = 0.21). Conclusions: BP control worsened during the COVID-19 pandemic in a group of patients requiring tertiary care for hypertension.

Effects of blood pressure lowering according to baseline cardiovascular disease: systematic review and meta-analysis of randomized trials

Abstract Background Blood pressure (BP)-lowering is accompanied by reduced cardiovascular (CV) outcomes and death in hypertensive patients. There are no data on the effect of BP lowering in patients with a history of CV disease [i.e., coronary heart disease (CHD), stroke, or heart failure with preserved ejection fraction (HFpEF)]. Purpose To demonstrate the effect of BP-lowering treatment on CV events in patients with different types of baseline CV disease. Methods A systematic review was conducted to identify randomized trials in electronic databases (Pubmed and CENTRAL, search from 1966 to 11/2022) for the effect of BP-lowering treatment against placebo or less aggressive BP reduction on fatal or nonfatal cardiovascular outcomes and all-cause death. Trials or subgroups of trials were identified, including patients with a history of CV disease. We excluded heart failure studies with reduced ejection fraction, acute myocardial infarction, or acute stroke. Risk ratios (RR) were calculated with their 95% confidence interval (CI) under the random-effects model. Results We included 18 BP-lowering treatment trials with 52,359 CHD patients (mean follow-up, 4.2 years; achieved systolic/diastolic BP, 129.2/76.1 mmHg). Despite the fact that mortality outcomes, stroke, and recurrent CHD were not decreased as a result of BP-lowering therapy, the risk of the combined outcome of major CV events (i.e., myocardial infarction, stroke, and heart failure) was reduced by 11% (95% CI, 3-18%) and the risk of recurrent heart failure hospitalization by 28% (95% CI, 18-38%). In addition, we examined 8 trials with 37,866 patients with a history of stroke (mean follow-up, 2.7 years; achieved systolic/diastolic BP, 136.5/79.8 mmHg), in which BP-lowering treatment reduced recurrent stroke by 18% (95% CI, 7-27%) and CV death by 12% (95% CI, 3-21%). Among 5 heart failure trials with 11,597 patients (mean follow-up, 3.4 years; achieved systolic/diastolic BP, 130.8/76.7 mmHg), the combined outcome of major CV events was decreased by 10% (95% CI, 4-16%), and recurrent heart failure hospitalization by 12% (95% CI, 4-19%). Conclusions Maximum CV protection is offered when systolic BP is reduced to levels &amp;lt; 130 mmHg in patients with CHD, to 130-140 mmHg levels in patients with a history of stroke, and to levels of approximately 130 mmHg in patients with heart failure. These findings support the recommendation for more aggressive BP lowering in patients with a history of CHD or optimally treated patients with HFpEF, and for less aggressive BP reduction in post-stroke patients.

Different systolic blood pressure targets and outcomes: a systematic review and meta-analysis of randomized trials

Abstract Background Blood pressure (BP)-lowering is accompanied by a reduction of fatal or nonfatal outcomes in hypertensive patients. However, the achieved systolic BP target associated with higher outcome benefits remains unsettled. Purpose The aim was to determine the effects of BP-lowering treatment on outcome incidence at different achieved systolic BP strata. Methods A systematic review was conducted to identify randomized trials in electronic databases (Pubmed and CENTRAL, search between 1966 and 11/2022) for the effect of BP-lowering treatment against placebo or less aggressive treatment on the composite outcome of major cardiovascular (CV) events (i.e., myocardial infarction, stroke, and heart failure). Selected studies reported outcomes in patients with or without a history of previous CV disease. Studies were categorized according to the achieved level of systolic BP in the active or more actively treated group. Risk ratios (RR) were calculated with their 95% confidence interval (CI) under the random-effects model. Results We included 51 primary prevention studies (i.e., 16 trials in which systolic BP was lowered to values no less than 140 mmHg, n=36,189 patients; 22 trials with achieved systolic BP between 130 and 140 mmHg, n=84,952; and 13 trials with achieved systolic BP less than 130 mmHg, n=41,660) and 44 secondary prevention studies (i.e., 11 trials in which systolic BP was lowered to values no less than 140 mmHg, n=12,518 patients; 19 trials with achieved systolic BP between 130 and 140 mmHg, n=71,449; and 14 trials with achieved systolic BP less than 130 mmHg, n=39,085). For a standard systolic/diastolic BP reduction of 10/5 mmHg, the relative risk of the composite outcome was reduced in all achieved systolic BP strata, without a significant trend from higher to lower systolic BP targets, in both prevention groups. In addition, there was no difference in the absolute risk reduction of the combined outcome, as calculated by the number of events prevented in every 1000 patients treated for 5 years, between the systolic BP targets in each prevention group. However, only in primary prevention did a significant negative incremental trend from higher to lower systolic BP targets for the residual risk of the combined outcome become apparent. Conclusions Although antihypertensive treatment provides CV protection to all hypertensive patients, the lower systolic BP target is associated not only with outcome benefits but also with a lower rate of residual risk in primary prevention only.

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.

BLOOD PRESSURE LOWERING TREATMENT AND BASELINE CARDIOVASCULAR RISK IN PRIMARY PREVENTION: SYSTEMATIC REVIEW AND META-ANALYSIS OF RANDOMIZED TRIALS

Objective: Blood pressure (BP) lowering is accompanied by reduced cardiovascular (CV) outcomes and death in hypertensive patients. No data are available for the effect of BP lowering in trials stratified according to baseline CV risk according to the SCORE-2 system. Design and method: A systematic review was conducted to identify randomized trials in electronic databases (Pubmed and CENTRAL, years: 1966 to 11/2022) for the effect of BP-lowering treatment against placebo, no treatment or less intense BP reduction on fatal or non-fatal CV outcomes. Selected studies reported outcomes in patients without a history of previous CV disease. In each study, we calculated baseline cardiovascular risk using SCORE-2. Risk ratios (RR) were calculated together with their 95% confidence interval (CI) under the random-effects model. Results: We studied 12 trials with low-to-moderate CV risk, n = 21,192 patients; 13 trials with high risk, n = 66,886; and 29 trials with very high risk, n = 79,061. For a standard SBP/DBP reduction of 10/5 mmHg, the relative risk of the combined outcome of major CV events (i.e., myocardial infarction, stroke, and heart failure) was decreased by 27% (95% CI, 22-35%) in the category of very high-risk patients, and by 10% in the category of high-risk patients (p value for interaction = 0.020). Also, the relative risk reduction of the combined outcome was progressively greater the higher the baseline CV risk (p trend = 0.006). The risk reduction of CV death showed a significant trend from lower to higher baseline CV risk (p trend = 0.036). CV death showed a significant reduction in the high-risk group compared to the low-moderate risk group (p = 0.005), and in the very high-risk group compared to the low-moderate risk group (p = 0.001). Conclusions: The greatest outcome benefit from BP lowering treatment in primary is observed in patients at higher baseline cardiovascular risk, as calculated by the SCORE-2.

Early blood pressure management in hemorrhagic stroke: a meta-analysis.

The aim of the present meta-analysis was to evaluate the outcomes and effects of different systolic blood pressure (SBP) lowering in patients with hemorrhagic stroke using data from randomized controlled trials. A total of 2592 records were identified for this meta-analysis. We finally included 8 studies (6119 patients; mean age 62.8 ± 13.0, 62.7% men). No evidence of heterogeneity between estimates (I2 = 0% < 50%, P = 0.26), or publication bias in the funnel plots (P = 0.065, Egger statistical test) was detected. Death or major disability rates were similar between patients with intensive BP-lowering treatment (SBP < 140mmHg) and those receiving guideline BP-lowering treatment (SBP < 180mmHg). Intensive BP-lowering treatment may have a better functional outcome, but the results were not significantly different (log RR = -0.03, 95% CI: -0.09 to 0.02; P = 0.55). Intensive BP-lowering treatment tended to be associated with lower early hematoma growth compared with guideline treatment (log RR = -0.24, 95% CI -0.38, -0.11; P < 0.001). Intensive BP-lowering helps reduce hematoma enlargement in the early stage of acute hemorrhagic stroke. However, this observation did not translate into functional outcomes. Further research is needed to clarify the specific scope and time of blood pressure reduction.

S-10-2: OPTIMAL BLOOD PRESSURE TARGET TO PREVENT SEVERE HYPERTENSION IN PREGNANCY: A SYSTEMATIC REVIEW AND META-ANALYSIS

Objective: Severe hypertension in pregnancy is a hypertensive crisis that requires urgent and intensive care due to its high maternal and fetal mortality. However, there still remain some discrepancies between guidelines in a target blood pressure to prevent severe hypertension in pregnancy. This study aimed to find the optimal blood pressure (BP) levels to prevent severe hypertension in pregnant women with nonsevere hypertension. Design and method: We searched Ovid MEDLINE and the Cochrane Library to identify all randomized controlled trials, which compared effects of antihypertensive drugs and placebo/no treatment or more intensive and less intensive BP-lowering treatments on adverse maternal and fetal pregnancy outcomes among pregnant women with nonsevere hypertension. A random effects model meta-analysis was performed to estimate the pooled risk ratio (RR) and 95% confidence interval (CI) for the outcomes. Results: Forty RCTs with 6355 patients were included in this study. BP lowering treatment significantly prevented severe hypertension (RR, 0.46; 95% CI, 0.37 to 0.56), preeclampsia (RR, 0.82; 95% CI, 0.69 to 0.98), severe preeclampsia (RR, 0.38; 95% CI, 0.17 to 0.84), placental abruption (RR, 0.52; 95% CI, 0.32 to 0.86), and preterm birth (before 37 weeks; RR, 0.81; 95% CI, 0.71 to 0.93), while the risk of small for gestational age infants was increased (RR, 1.25; 95% CI, 1.02 to 1.54). An achieved systolic blood pressure (SBP) of lower than 130 mmHg reduced the risk of severe hypertension to nearly one-third compared with an achieved SBP of 140 mmHg or higher, with a significant interaction of the BP levels achieved with BP lowering therapy. There was no significant interaction between BP lowering treatment and the subtypes of hypertensive disorders of pregnancy, including gestational hypertension, preeclampsia, and chronic hypertension. Conclusions: BP lowering treatment aimed at a SBP of lower than 130 mmHg and accompanied by careful monitoring of fetal growth might be recommended to prevent severe hypertension among pregnant women with nonsevere hypertension.

S-32-3: RECENT IDACO ANALYSIS ON THE RISK OF PROGRESSION TO SUSTAINED HYPERTENSION FROM WHITE-COAT HYPERTENSION OR MASKED HYPERTENSION

In the general population, the cardiovascular risk is increased in patients with masked hypertension (MH), whereas in individuals with white-coat hypertension (WCH) it is virtually the same as in the normotensive individuals. However, no conclusive evidence exists as to whether WCH and MH are accompanied by a greater rate of development of a sustained hypertensive state, i.e. hypertension both in and outside the clinical environment. We investigated the risk of progression to sustained hypertension in initially untreated participants of cohort studies included in the International Database on Ambulatory blood pressure in relation to Cardiovascular Outcome (IDACO) study. Within the IDACO, 5 populations comprising 1081 individuals had ambulatory (ABP) and conventional (CBP) blood pressure measured at baseline and at follow up. We excluded from the analysis subjects on BP-lowering treatment at baseline (n = 252) and individuals with untreated sustained hypertension at baseline (n = 80), leaving 749 subjects included in the current analysis. The cut-off value for elevated CBP was &gt; = 140/90 mm Hg and for daytime ABP &gt; = 135/85 mm Hg. At baseline, 110 individuals (14.7%) was defined as MH, 64 subjects as WCH (8.5%), and 575 (76.8%) as normotensives. MH patients were older (50 vs 45 years compared to normotensives, P &lt; 0.01) and more frequently male (50.9 vs 31.5% compared to normotensives, P &lt; 0.01). During median follow-up of 9.7 years, there were 264 incident cases of sustained hypertension. In the analyses adjusted for cohort, sex, age, body mass index, smoking and drinking, both MH (HR 2.23, 95%CI 1.57 to 3.17) and WCH (HR 1.84, 95%CI 1.37 to 2.47) significantly increased risk of progression to sustained hypertension. In conclusion, long-term risk of progression to sustained hypertension is 2-fold higher in individuals with masked hypertension or white coat hypertension at baseline as compared to normotensive subjects at baseline. However, this observation might be due to more frequent initiation of antihypertensive therapy in both groups.

S-26-2: ULTRASOUND RENAL DENERVATION ACROSS THE HYPERTENSION SPECTRUM

In addition to lifestyle changes and pharmacotherapy, endovascular catheter-based renal denervation (RDN) has emerged as a BP-lowering treatment, but early trials reported inconsistent results. Subsequently, sham-controlled trials with more optimized study designs, improved catheter designs, procedural performance, and endpoint ascertainment were successfully conducted in patients with hypertension. Among these trials, the RADIANCE-HTN trial compared endovascular ultrasound renal denervation (uRDN) with a sham procedure in two separate cohorts. Within the first (SOLO) cohort of subjects with mild-to-moderate hypertension who were weaned off medications, a 6.3 mmHg greater reduction in daytime ambulatory SBP was demonstrated with uRDN vs. a sham procedure at two months. The BP- lowering effect of uRDN was maintained at six- and twelve months with less medications needed to achieve similar BP in the uRDN group compared with the sham group. In addition, the TRIO cohort of RADIANCE-HTN randomized 136 patients with hypertension resistant to three or more antihypertensive medications. Eligible patients were switched to a daily, single-pill combination of a calcium channel blocker, an angiotensin receptor blocker, and a thiazide diuretic, and if BP remained uncontrolled, were then randomized to uRDN or a sham procedure. At 2 months, the uRDN had a 4.5 mmHg greater decrease in daytime ambulatory SBP compared with sham. The BP-lowering effect of uRDN was sustained at 6 months with less prescribed medications, notably aldosterone antagonists, vs. sham. Adverse events were infrequent and similar between groups in the two cohorts. The maintenance of a BP-lowering effect of uRDN at 6 months mirror the results of the RADIANCE-HTN SOLO trial at 6 months and therefore, demonstrates persistent BP lowering efficacy of uRDN across a broad spectrum of patients with mild hypertension to severe and resistant hypertesion.

S-17-5: EFFECT OF MINERALOCORTICOID RECEPTOR BLOCKER, ESAXERENONE, ON HOME BLOOD PRESSURE AND ALBUMINURIA IN JAPANESE HYPERTENSIVE PATIENTS WITH DKD (EX-DKD STUDY)

Objective: To investigate the effect of esaxerenone on home blood pressure (BP) and albuminuria in Japanese hypertensive patients with diabetic kidney disease (DKD) who had an inadequate response to BP-lowering treatment with a renin angiotensin system (RAS) inhibitor or a RAS inhibitor plus a calcium channel blocker (CCB). Design and method: The EX-DKD study (jRCTs061190027) was a multicenter, open-label study conducted in Japan. The study enrolled hypertensive patients with DKD who had previously received a RAS inhibitor or a RAS inhibitor plus CCB for &lt; 12 weeks, and had sitting office systolic BP (SBP) 130 to &lt; 180 mmHg and/or diastolic BP (DBP) 80 to &lt; 110 mmHg, UACR &lt; 1000 mg/g creatinine, and eGFRcreat 30 to &lt; 60 mL/min/1.73m2 at baseline. Based on baseline UACR, the patients were divided into 3 subcohorts: UACR &lt; 30, 30 to &lt; 300, and 300 to &lt; 1000 mg/g creatinine. Esaxerenone was incrementally dosed for 12 weeks: 1.25, 2.5, and 5 mg/day at the start of treatment, Week4, and Week8, respectively, based on each patient's condition. The primary efficacy endpoint was change in morning home SBP/DBP from baseline to end of treatment (EOT). Secondary endpoints included the proportion of patients achieving target BP at Week12, change in UACR from baseline to EOT, and safety (including serum potassium level). Results: The baseline characteristics of the overall study population (n = 109) were mean age, 72.6 years; male, 54.1%; morning home SBP/DBP, 135.6/75.9 mmHg; UACR &lt; 30, 30 to &lt; 300, and 300 to &lt; 1000 mg/g creatinine, 41.3%, 37.6%, and 21.1%, respectively; eGFRcreat, 49.4 mL/min/1.73m2; RAS inhibitor, 33.0%; RAS inhibitor plus CCB, 67.0%. Morning home SBP/DBP decreased significantly from baseline to EOT in the total population (-11.6/-5.2 mmHg, both p &lt; 0.001) and all UACR subcohorts (all p &lt; 0.001). Similar results were obtained for bedtime home and office BP. At Week12, 38.5% of the total population had achieved target morning home BP. UACR improved significantly from baseline to EOT in the total population and UACR subcohorts; the overall percentage change was -50.9% (p &lt; 0.001). Incidences of treatment-emergent adverse events (TEAEs) and drug-related TEAEs were 23.2% and 7.1%, respectively. The percentage of patients with serum potassium &lt;5.5 mEq/L during the study period was 2.7%, and no patients had serum potassium &lt; 6.0 mEq/L. Conclusions: Esaxerenone significantly reduced morning home BP as well as bedtime home and office BP and significantly halved albuminuria in Japanese hypertensive patients with DKD. The effects were consistent regardless of their UACR severity without clinically relevant serum potassium elevation.

PS-C08-8: OUTCOMES FROM BLOOD PRESSURE REDUCTION IN PATIENTS WITH DIFFERENT BASELINE CARDIOVASCULAR RISK: SYSTEMATIC REVIEW AND META-ANALYSIS OF RANDOMIZED TRIALS

Objective: Blood pressure (BP) lowering is accompanied by reducing cardiovascular (CV) outcomes and death in hypertensive patients. No data are available for the effect of BP lowering in trials stratified according to baseline CV risk that was assessed according to SCORE-2. Design and method: A systematic review was conducted to identify randomized trials in electronic databases (Pubmed and CENTRAL, years: 1966 to 9/2021) for the effect of BP-lowering treatment against placebo or less aggressive BP reduction on 6 fatal or non-fatal CV outcomes and all-cause death. Selected studies reported outcomes in patients without a history of previous CV disease. In each study, we calculated baseline cardiovascular risk using SCORE-2. Risk ratios (RR) were calculated together with their 95% confidence interval (CI) under the random-effects model. Results: We included 54 studies (i.e., 12 trials with low-to-moderate CV risk, n = 21,192 patients; 13 trials with high risk, n = 66,886; and 29 trials with very high risk, n = 79,061). For a standard SBP/DBP reduction of 10/5 mmHg, the relative risk of the combined outcome of major CV events (i.e., myocardial infarction, stroke, and heart failure) was decreased by 27% (95% CI, 22–35%) in the category of very high-risk patients, and this reduction was significantly greater (P = 0.02) compared to high-risk trials (0.90 [95% CI, 0.77–1.04]). Moreover, CV death showed a significant reduction in the high-risk group compared to the low-moderate risk group (p = 0.005), as well as in the very high-risk group compared to the low-moderate risk group (p = 0.001). The same pattern was observed for all-cause death in the very high-risk group compared to the high-risk group (p = 0.045). Conclusions: The greatest outcome benefit from BP lowering in primary prevention is observed in patients at higher baseline cardiovascular risk as calculated by the SCORE-2.

Blood pressure lowering and prevention of dementia: an individual patient data meta-analysis.

Observational studies indicate U-shaped associations of blood pressure (BP) and incident dementia in older age, but randomized controlled trials of BP-lowering treatment show mixed results on this outcome in hypertensive patients. A pooled individual participant data analysis of five seminal randomized double-blind placebo-controlled trials was undertaken to better define the effects of BP-lowering treatment for the prevention of dementia. Multilevel logistic regression was used to evaluate the treatment effect on incident dementia. Effect modification was assessed for key population characteristics including age, baseline systolic BP, sex, and presence of prior stroke. Mediation analysis was used to quantify the contribution of trial medication and changes in systolic and diastolic BP on risk of dementia. The total sample included 28 008 individuals recruited from 20 countries. After a median follow-up of 4.3 years, there were 861 cases of incident dementia. Multilevel logistic regression reported an adjusted odds ratio 0.87 (95% confidence interval: 0.75, 0.99) in favour of antihypertensive treatment reducing risk of incident dementia with a mean BP lowering of 10/4 mmHg. Further multinomial regression taking account of death as a competing risk found similar results. There was no effect modification by age or sex. Mediation analysis confirmed the greater fall in BP in the actively treated group was associated with a greater reduction in dementia risk. The first single-stage individual patient data meta-analysis from randomized double-blind placebo-controlled clinical trials provides evidence to support benefits of antihypertensive treatment in late-mid and later life to lower the risk of dementia. Questions remain as to the potential for additional BP lowering in those with already well-controlled hypertension and of antihypertensive treatment commenced earlier in the life-course to reduce the long-term risk of dementia. Class I evidence in favour of antihypertensive treatment reducing risk of incident dementia compared with placebo.

Effect of blood pressure reduction on cardiovascular outcomes in patients with different baseline cardiovascular risk: systematic review and meta-analysis of randomized trials

Abstract Background/Introduction Blood pressure (BP) lowering is accompanied by a reduction on cardiovascular (CV) outcomes and death in hypertensive patients. There is no data on the effect of lowering BP in patients stratified according to their baseline CV risk as indicated by SCORE 2. Purpose The aim of this meta-analysis was to demonstrate the impact of BP-lowering treatment on the occurrence of CV events in these previously reported patients. Methods A systematic review in electronic databases (Pubmed and CENTRAL, years: 1966 to 9/2021) was conducted to identify randomized trials that study the effect of BP-lowering treatment against placebo or less aggressive BP reduction on 6 fatal or non-fatal CV outcomes and all-cause death. Selected studies reported outcomes in patients without a history of previous CV disease. In each study, baseline cardiovascular risk was estimated using SCORE-2. Risk ratios (RR) were calculated together with their 95% confidence interval (CI) under the random-effects model. Results The analysis was composed of 54 studies, of which 12 trials included patients with low-to-moderate CV risk, (n=21,192 patients), 13 trials with high CV risk patients (n=66,886) and 29 trials with very high CV risk patients (n=79,061). For a standard SBP/DBP reduction of 10/5 mmHg, the relative risk of the combined outcome of major CV events (i.e., myocardial infarction, stroke, and heart failure) was decreased by 27% (95% CI, 22–35%) in the category of very high-risk patients. This reduction was significantly greater (p=0.02) compared to high-risk trials (0.90 [95% CI, 0.77–1.04]). CV death showed a significant reduction in the high-risk group of patients compared to the low-moderate risk group (p=0.005), as well as in the very high-risk group compared to the low-moderate risk group (p=0.001). The same pattern was observed for all-cause death in the very high-risk group compared to the high-risk group (p=0.045). Conclusions With the present meta-analysis, we observed that the greatest benefit from BP lowering in primary prevention in the occurrence of CV events and mortality is observed in patients at higher baseline cardiovascular risk, as calculated by the SCORE-2. Funding Acknowledgement Type of funding sources: None.

Disentangling the varying associations between systolic blood pressure and health outcomes in the very old: an individual patient data meta-analysis.

Objectives:While randomized controlled trials have proven the benefits of blood pressure (BP) lowering in participating octogenarians, population-based observational studies suggest an association between low systolic blood pressure (SBP) and faster overall decline. This study investigates the effects of BP-lowering treatment, a history of cardiovascular diseases (CVD), and cognitive and physical fitness on the associations between SBP and health outcomes in the very old.Methods:Five cohorts from the Towards Understanding Longitudinal International older People Studies (TULIPS) consortium were included in a two-step individual participant data meta-analysis (IPDMA). We pooled hazard ratios (HR) from Cox proportional-hazards models for 5-year mortality and estimates of linear mixed models for change in cognitive and functional decline. Models were stratified by BP-lowering treatment, history of CVD, Mini-Mental State Examination scores, grip strength (GS) and body mass index (BMI).Results:Of all 2480 participants (59.9% females, median 85 years), median baseline SBP was 149 mmHg, 64.3% used BP-lowering drugs and 47.3% had a history of CVD. Overall, higher SBP was associated with lower all-cause mortality (pooled HR 0.91 [95% confidence interval 0.88–0.95] per 10 mmHg). Associations remained irrespective of BP-lowering treatment, history of CVD and BMI, but were absent in octogenarians with above-median MMSE and GS. In pooled cohorts, SBP was not associated with cognitive and functional decline.Conclusion:While in the very old with low cognitive or physical fitness a higher SBP was associated with a lower all-cause mortality, this association was not evident in fit octogenarians. SBP was not consistently associated with cognitive and functional decline.