Design and rationale for a randomized, open-label, parallel clinical trial evaluating major adverse cardiovascular events (pharmacological treatment versus diet control) in patients with high-normal blood pressure: the PRINT-TAHA9 trial.

BACKGROUND: The distinction between normal and high blood pressure remains a debated topic, with varying guidelines on when to start medication. Contemporary guidelines advocate for the initiation of antihypertensive therapy in individuals who present with high-normal blood pressure, particularly those exhibiting elevated 10-year atherosclerotic cardiovascular disease (ASCVD) risk scores. Despite these recommendations, there is a notable lack of direct evidence supporting the efficacy of treating high-normal blood pressure to prevent major adverse cardiovascular events (MACE). METHODS: The PRINT-TAHA9 trial, a unicentric, randomized, open-label, controlled, parallel clinical study, seeks to explore the effects of intensive blood pressure control on MACE in participants with high-normal blood pressure. We will enroll 1620 adults aged 18 years and above with a systolic blood pressure range of 130-140 mmHg, diastolic blood pressure under 90 mmHg, and atherosclerotic cardiovascular disease (ASCVD) risk score exceeding 7.5%. The study will be executed in five distinct phases, with each phase enrolling between 300 and 400 participants. Participants will be randomly assigned to either the treatment group receiving antihypertensive medication (amlodipine/valsartan) and a low-salt/low-fat diet or to the control group receiving a similar diet. Follow-up visits are scheduled every 6 months over a 3-year period to monitor blood pressure, evaluate medication adherence, document any adverse events, and adjust the intervention as necessary. Cox proportional hazards regression analysis will be employed to examine the disparities between the two arms. DISCUSSION: Despite guidelines promoting early treatment of elevated blood pressure, the debate continues due to insufficient evidence that such interventions significantly reduce the occurrence of MACE. This trial seeks to address this critical evidence gap. TRIAL REGISTRATION: The PRINT-TAHA9 trial was registered in October 2019 with the Iranian Registry of Clinical Trials (IRCT.ir) under the registration number IRCT20191002044961N1. https://irct.behdasht.gov.ir/trial/43092 .

Intensive blood pressure control in isolated systolic hypertension: a post hoc analysis of a cluster randomized trial.

Background: The isolated systolic hypertension (ISH) is of high prevalence, with a relatively poor prognosis. However, there is still no direct evidence to demonstrate the benefits of intensive blood pressure (BP) control among these patients. We aimed to evaluate intensive BP control with the target of <130/80 mmHg in ISH. Methods: This was a post hoc analysis of patients with ISH in the China Rural Hypertension Control Project (CRHCP), defined as systolic blood pressure (SBP) ≥ 140 mmHg and diastolic blood pressure (DBP) < 90 mmHg. The primary outcome was cardiovascular disease (CVD) including stroke, myocardial infarction, heart failure, and CVD death. Mixed-effect Cox proportional regression and generalized estimating equation models were used for analysis. Findings: In total, 7981 patients were randomly assigned to the intervention group and 8005 to the usual care group between May 8 and November 27, 2018. The median follow-up was 3.02 years (25-75%: 2.98-3.06). Mean systolic/diastolic BP at the end of 36 months follow-up was 126.5/71.2 mmHg in the intensive BP control group and 148.1/78.6 mmHg in the usual care group. The intervention group presented a substantially lower rate of composite CVD compared with the usual care group (1.52% versus 2.30%/year; multiple-adjusted hazard ratio (HR): 0.64; 95% confidence interval (CI): 0.57-0.72; P < 0.001), especially for stroke (multiple-adjusted HR: 0.61; 95% CI: 0.53-0.70; P < 0.001), HF (multiple-adjusted HR: 0.57; 95% CI: 0.36-0.91; P = 0.017) and CVD death (multiple-adjusted HR: 0.64; 95% CI: 0.50-0.83; P < 0.001). The primary composite outcome was substantially reduced by 36% in the intervention group compared with the usual care group. The further interaction analysis revealed that the reduction of primary outcome by intervention was consistent across subgroups of sex, age, education level, history of CVD, use of antihypertensive medication and baseline DBP (P > 0.05 for all interaction test). The incidences of symptomatic hypotension, syncope injurious falls and renal outcomes did not differ between the two groups, even though hypotension was increased in intervention group (RR:1.71; 95% CI: 1.28-2.28; P < 0.001). Interpretation: Intensive BP control (<130/80 mmHg) was effective and safe in patients with ISH for the prevention of CVD events. Funding: The Ministry of Science and Technology (China) of China and the Science and Technology Program of Liaoning Province, China.

Influence of multiple risk factor control level on cardiovascular outcomes in hypertensive patients.

OBJECTIVE: The relationship between the level of baseline risk factor control and cardiovascular outcomes in hypertensive patients with blood pressure intervention is not well understood. It is also unclear whether the level of baseline risk factor control is persuasively associated with cardiovascular outcomes in hypertensive patients with blood pressure lowering strategy. METHOD: We performed an analysis of the Strategy of Blood Pressure Intervention in the Elderly Hypertensive Patients (STEP) trial. Participants without complete baseline risk factor data were excluded. The primary outcome was a composite of cardiovascular events and all-cause mortality. Cox proportional hazard models were used to calculate the hazard ratio (HR) and estimate association between risk factor control levels (≥6, 5, 4, and ≤ 3) and cardiovascular outcomes. RESULTS: A total of 8337 participants were involved in the analysis and the median follow-up period was 3.19 years. Each additional risk factor uncontrolled was associated with a 24% higher cardiovascular risk (HR 1.24, 95% CI 1.11-1.37). Compared with participants with optimal risk factor control, those with ≤ 3 factors control exhibited 95% higher cardiovascular risk (HR 1.95, 95% CI 1.37-2.77). The corresponding protective effects of multiple risk factor modification were not influenced by intensive or standard antihypertensive treatment (P for interaction = 0.71). CONCLUSIONS: A stepwise association was observed between cardiovascular risk and the number of risk factor control in hypertensive patients. The more risk factor was modified, the less cardiovascular risk was observed, irrespective of different blood pressure lowering strategies. Comprehensive risk factor control strategies are warranted to reduce cardiovascular disease risk in hypertensive patients. Trial registration STEP ClinicalTrials.gov number, NCT03015311. Registered 2 January 2017.

Heterogeneous Effects of Intensive Glycemic and Blood Pressure on Cardiovascular Events Among Diabetes by Living Arrangements.

BACKGROUND: Although living alone versus with others is a key social element for cardiovascular prevention in diabetes, evidence is lacking about whether the benefit of intensive glycemic and blood pressure (BP) control differs by living arrangements. We thus aim to investigate heterogeneity in the joint effect of intensive glycemic and BP control on cardiovascular events by living arrangements among participants with diabetes. METHODS AND RESULTS: This study included 4731 participants with diabetes in the ACCORD-BP (Action to Control Cardiovascular Risk in Diabetes-Blood Pressure) trial. They were randomized into 4 study arms, each with glycated hemoglobin target (intensive, <6.0% versus standard, 7.0-7.9%) and systolic BP target (intensive, <120 mm Hg versus standard <140 mm Hg). Cox proportional hazard models were used to estimate the joint effect of intensive glycemic and BP control on the composite cardiovascular outcome according to living arrangements. At a mean follow-up of 4.7 years, the cardiovascular outcome was observed in 445 (9.4%) participants. Among participants living with others, intensive treatment for both glycemia and BP showed decreased risk of cardiovascular events compared with standard treatment (hazard ratio [HR], 0.68 [95% CI, 0.51-0.92]). However, this association was not found among participants living alone (HR, 0.96 [95% CI, 0.58-1.59]). P for interaction between intensive glycemic and BP control was 0.53 among participants living with others and 0.009 among those living alone (P value for 3-way interaction including living arrangements was 0.049). CONCLUSIONS: We found benefits of combining intensive glycemic and BP control for cardiovascular outcomes among participants living with others but not among those living alone. Our study highlights the critical role of living arrangements in intensive care among patients with diabetes.

Is Intensive Blood Pressure Control Indicated in Older Patients with Hypertension?

PURPOSE OF REVIEW: This review aims to evaluate intensive blood pressure control in older adults, assessing its necessity, effectiveness, benefits and risks including cardiovascular outcomes, adverse events, quality of life, and overall mortality. RECENT FINDINGS: Recent studies have supported that intensive antihypertensive treatment lowers the rates of cardiovascular events compared to standard treatment in older patients with hypertension, and it may also reduce the risk of cognitive decline. Intensive blood pressure lowering strategies are associated with reduced risk of cardiovascular morbidity and mortality as well as all-cause mortality, without compromising quality of life or functional status, and are relatively well tolerated in this patient population. Evidence suggests that maintaining systolic blood pressure below 130 mm Hg can yield cardiovascular and cognitive benefits in older patients with hypertension, particularly among those at risk of myocardial infarction or stroke. However, clinicians should vigilantly monitor for adverse events and engage in shared decision-making when pursuing intensive blood pressure goals tailored to individual risks and benefits.

The effect of intensive blood pressure lowering on left ventricular hypertrophy in patients with hypertension: a systematic review and meta-analysis of randomized controlled trials.

Background: We conducted a comprehensive systematic review to examine the efficacy of intensive blood pressure lowering on the risk of left ventricular hypertrophy (LVH). Methods: We searched PubMed, Scopus, Web of Science, Cochrane Central, and EMBASE for all relevant randomized controlled trials. The primary outcome was the incidence of left ventricular hypertrophy. We used the risk ratio (RR) and hazard ratio (HR) with a 95% confidence interval as our effect sizes. Results: Four studies, comprising 20,747 patients, were included. Intensive blood pressure lowering was linked with a diminished LVH incidence (RR: 0.66, 95% CI [0.56-0.77]). We also found that intensive blood pressure lowering increased the risk of LVH regression in patients with baseline LVH (RR: 1.21, 95% CI [1.11-1.32]). Finally, intensive blood pressure lowering was linked with a reduced risk of cardiovascular disease (HR: 0.71, 95% CI [0.60-0.85]). No significant heterogeneity was seen in either outcome. Conclusion: Our study suggests that intensive blood pressure lowering effectively reduces the risk of LVH and cardiovascular disease. An interactive version of our analysis can be accessed here: https://databoard.shinyapps.io/lvh_hypertophy/.

Impact of baseline cardiovascular risk on the outcomes of intensive blood pressure intervention: a post hoc analysis of the China rural hypertension control project.

BACKGROUND: The 2018/2023 ESC/ESH Guidelines underlined a gap how baseline cardiovascular disease (CVD) risk predicted blood pressure (BP) lowering benefits. Further, 2017 ACC/AHA Guideline and 2021 WHO Guideline recommended implementation studies about intensive BP control. Now, to bridge these guideline gaps, we conducted a post hoc analysis to validate whether the baseline CVD risk influences the effectiveness of the intensive BP control strategy, which was designed by China Rural Hypertension Control Project (CRHCP). METHODS: This is a post hoc analysis of CRHCP, among which participants were enrolled except those having CVD history, over 80 years old, or missing data. Subjects were stratified into quartiles by baseline estimated CVD risk and then grouped into intervention and usual care group according to original assignment in CRHCP. Participants in the intervention group received an integrated, multi-faceted treatment strategy, executed by trained non-physician community health-care providers, aiming to achieve a BP target of < 130/80 mmHg. Cox proportional-hazards models were used to estimate the hazard ratios of outcomes for intervention in each quartile, while interaction effect between intervention and estimated CVD risk quartiles was additionally assessed. The primary outcome comprised myocardial infarction, stroke, hospitalization for heart failure, or CVD deaths. RESULTS: Significant lower rates of primary outcomes for intervention group compared with usual care for each estimated CVD risk quartile were reported. The hazard ratios (95% confidence interval) in the four quartiles (from Q1 to Q4) were 0.59 (0.40, 0.87), 0.54 (0.40, 0.72), 0.72 (0.57, 0.91) and 0.65 (0.53, 0.80), respectively (all Ps < 0.01). There's no significant difference of hazard ratios by intervention across risk quartiles (P for interaction = 0.370). Only the relative risk of hypotension, not symptomatic hypotension, was elevated in the intervention group among upper three quartiles. CONCLUSIONS: Intensive BP lowering strategy designed by CRHCP group was effective and safe in preventing cardiovascular events independent of baseline CVD risk. TRIAL REGISTRATION: The trial is registered with ClinicalTrials.gov, NCT03527719.

Electrocardiographic tracking of left ventricular hypertrophy in hypertension: incidence and prognostic outcomes from the SPRINT trial.

BACKGROUND: This study explores the impact of intensive blood pressure (BP) control on left ventricular hypertrophy (LVH) incidence and evaluates the prognostic implications of LVH status (pre-existing/new-onset/persistent/regression) using Systolic Blood Pressure Intervention Trial (SPRINT) Electrocardiogram Data. METHODS: Poisson regression was used to assess new-onset LVH and LVH regression rates. Multivariable-adjusted Cox proportional hazard models determined the risk of adverse cardiovascular events (ACE), a composite of myocardial infarction (MI), non-MI acute coronary syndrome, stroke, heart failure, or cardiovascular death, alongside safety adverse events. RESULTS: In 8,016 participants, intensive BP control significantly reduced new-onset LVH (8.27 vs. 14.79 per 1000-person years; adjusted p<0.001) and increased LVH regression (14.89 vs. 11.89 per 1000-person years; adjusted p<0.001). Elevated ACE risk was notable in participants with pre-existing LVH [adjusted HR: 1.94 (95% CI: 1.25-2.99); p = 0.003], new-onset LVH [adjusted 1.74 (95% CI: 1.16-2.60); p = 0.007], and persistent LVH[adjusted HR: 1.96 (95% CI: 1.11-3.46); p = 0.020], compared to those without LVH. Intriguingly, LVH regression attenuated this risk increment [adjusted HR: 1.57 (95% CI: 0.98-2.53); p = 0.062]. Achieving a BP target of < 120/80 mmHg nullified the increased ACE risk in those with pre-existing LVH. CONCLUSIONS: Intensive BP control is instrumental in both reducing the emergence of LVH and fostering its regression. Pre-existing, new-onset LVH and persistent LV remain a predictor of adverse cardiovascular prognosis, whereas LVH regression and achieving on-treatment BP < 120/80 mmHg in pre-existing LVH individuals may further mitigate residual cardiovascular risk. CLINICAL TRIAL REGISTRATION: URL: ClinicalTrials.gov Unique Identifier: NCT01206062.

Association of intensive blood pressure management with cardiovascular outcomes in patients using multiple classes of antihypertensive medications: a post-hoc analysis of the STEP Trial.

High medication burden is associated with poor treatment effect and high risk of cardiovascular outcomes. This study aimed to investigate the association between the antihypertensive medication burden and cardiovascular outcomes in the STEP trial. This post-hoc analysis of the STEP trial enrolled 8511 participants, including 8041 with low burden and 470 with high burden. High antihypertensive medication burden was defined as being treated with ≥3 different classes of prescribed antihypertensive medications. The primary outcome was a composite of cardiovascular outcomes. Fine-Gray model was used in this study. Among all participants, high antihypertensive medication burden was associated with a higher risk of the primary outcome compared with low medication burden (HR, 1.52; 95% CI, 1.03-2.24), which was consistent in the standard group (HR, 1.95; 95% CI, 1.20-3.18) and the intensive group (HR, 1.10; 95% CI, 0.57-2.13; Pinteraction = 0.18). The beneficial effects of intensive systolic blood pressure (SBP) control on the primary outcome remained significant in the high burden group (HR, 0.42; 95% CI, 0.19-0.95) and the low burden group (HR, 0.79; 95% CI, 0.63-0.98; Pinteraction = 0.18). At 24 months, the percentage of participants achieving the target SBP was lower in the high medication burden group (risk ratio, 0.93; 95% CI, 0.89-0.98). In both standard and intensive treatment groups, participants with a high medication burden were harder to achieve the target SBP (Pinteraction = 0.65). High antihypertensive medication burden was associated with worse SBP control and a greater risk of cardiovascular events. Intensive SBP control showed cardiovascular benefits in both medication burden groups. Trial registration: STEP ClinicalTrials.gov number, NCT03015311. Registered 2 January 2017.

Estimated Pulse Wave Velocity and Cognitive Outcomes: A Post hoc Analysis of SPRINT-MIND.

BACKGROUND: Arterial stiffness has been confirmed to be associated with cognitive impairment. Carotid-femoral pulse wave velocity (cfPWV) is widely regarded as the gold standard for assessing arterial stiffness, yet it is not readily accessible. In response, the use of estimated pulse wave velocity (ePWV) has been proposed as a more accessible and cost-effective alternative. ePWV not only offers ease of calculation but also covers a broader spectrum of vascular aging processes, some of which may be distinct from those detected by cfPWV. The aim of our study was to investigate the association between ePWV and cognitive outcomes in SPRINT-MIND (Systolic Blood Pressure Intervention Trial Memory and Cognition in Decreased Hypertension). METHODS: This study was a post hoc analysis of the SPRINT-MIND. The primary endpoint was a composite outcome including probable dementia and mild cognitive impairment (MCI). The calculation of ePWV was based on age and mean blood pressure. The association between ePWV and cognitive outcomes was assessed Using Cox regression analysis. The response of ePWV to antihypertensive treatment at 12 months was used to define treatment efficacy. RESULTS: 8,563 patients were enrolled. The ePWV was found to be independently associated with risk of probable dementia (Tertile 3 vs. Tertile 1: HR, 95% CI: 1.70, 1.08-2.68, P = 0.023, P for trend = 0.013), MCI (Tertile 3 vs. Tertile 1: HR, 95% CI: 2.35, 1.71-3.23, P < 0.001, P for trend < 0.001), and the composite outcome of probable dementia or MCI (Tertile 3 vs. Tertile 1: HR, 95% CI: 2.17, 1.65-2.86, P < 0.001, P for trend < 0.001). The combined effect of treatment allocation and the response of ePWV to treatment exhibited that intensive/ePWV responders had the lowest risk of the primary outcome (Log-rank P = 0.002). CONCLUSIONS: EPWV demonstrated independent predictive value for cognitive outcomes in SPRINT-MIND.

Association between HDL-C and intensive blood pressure control in patients with hypertension: A post-hoc analysis of SPRINT.

Previous studies in patients with hypertension have demonstrated that there is a U-shaped association between HDL-C (high-density lipoprotein cholesterol) and the risk of cardiovascular events in male patients with hypertension. However, to the best of our knowledge, the relationship between HDL-C and intensive blood pressure control in specific cardiovascular events has never been investigated. To fill this knowledge gap, the authors analyzed the relationship between HDL-C levels and cardiovascular events in hypertensive patients within the Systolic Blood Pressure Intervention Trial (SPRINT). The SPRINT evaluated the impact of intensive blood pressure control (systolic blood pressure < 120 mm Hg) versus standard blood pressure control (systolic blood pressure < 140 mm Hg). The Cox proportional risk regression was used to investigate the association between different HDL-C status and clinical outcomes. Additional stratified analyzes were performed to evaluate the robustness of sex difference. A total of 9323 participants (6016 [64.53%] males and 3307 [35.47%] females) with hypertension from the SPRINT research were included in the analysis. The median follow-up period was 3.26 years. Our population was divided into five groups based on the HDL-C plasma levels: HDL-C < 30 mg/dL, HDL-C between 30 and 40 mg/dL, HDL-C between 40 and 60 mg/dL, HDL-C between 60 and 80 mg/dL and HDL-C > 80 mg/dL. Sensitivity analyzes showed that in the SPRINT, women in the HDL-C high population had a higher risk of mortality from all causes than men. In this cohort study, results suggest that patients with HDL-C levels higher than 80 mg/dL had lower risk of SPRINT primary outcome, cardiovascular death, and stroke, but this study tested association, not causation. HDL-C levels were associated with composite cardiovascular outcomes in male but not female patients. Our results demonstrated that in patients with hypertension, the association between HDL-C and risk of cardiovascular events is L-shaped.

Efficacy and Safety of Intensive Blood Pressure Lowering After Reperfusion Therapy in Acute Ischemic Stroke: A Systematic Review and Meta-Analysis.

OBJECTIVE: The objective of this study is to comprehensively examine the available data on the efficacy and safety of intensive blood pressure lowering (IBPL) compared to standard blood pressure control (SBPC) in patients with acute ischemic stroke following reperfusion therapy. METHODS: A comprehensive search was conducted using 4 databases, including PubMed, Cochrane, Embase, and Web of Science to collect relevant articles from inception to December 2023. The endpoints were the condition of the patient measured by the modified Rankin scale (mRS, range value from 0 [no symptoms] to 6 [death]) at 90 days, symptomatic intracranial hemorrhage, death within 90 days, recurrent ischemic stroke, and intracranial hemorrhage (ICH). RESULTS: Seven eligible studies involving 4499 participants (2218 patients in IBPL group and 2281 patients in SBPC group) were included in the analysis. Both groups demonstrated similar baseline characteristics. Within the endovascular therapy (EVT) subgroup, the IBPL group exhibited worse mRS than in SBPC group. After EVT, different IBPL targets showed worse outcomes in the mRS for the SBP <140 mmHg and SBP <120 mmHg subgroups, with no difference between IBPL and SBPC groups in the SBP <130 mmHg subgroup. In the intravenous thrombolysis subgroup, although the IBPL group exhibited less ICH, the long-term functional outcomes were not improved significantly. CONCLUSIONS: The IBPL group exhibited a less favorable functional outcome after EVT. Moreover, no worse functional outcomes were noticed in the SBP <130 mmHg subgroup after EVT. However, the functional outcome was similar after intravenous thrombolysis.

Effects of intensive blood-pressure treatment on myocardial work in elderly hypertensive patients: A subcenter study of the STEP randomized controlled trial.

BACKGROUND: The benefits and safety of intensive blood pressure treatment in elderly hypertensive patients have been proved in the STEP trial. However, relevant mechanisms for intensive treatment are lacking. HYPOTHESIS: We aimed to explore whether intensive blood pressure treatment is associated with left ventricular systolic function changes as evaluated by myocardial work (MW) parameters in elderly hypertensive patients compared to the standard. METHODS: Patients were randomized to the intensive group (n = 66, median age 66 years, 42.4% male) with a systolic blood pressure (SBP) goal of 110 to <130 mmHg or the standard treatment group (n = 50, median age 63.5 years, 30% male) with an SBP goal of 130-<150 mmHg in this subcenter study of the STEP trial. There was no pre-randomization echocardiographic collected. Echocardiographic exam was produced at 1-year (phase 1) and 3-year (phase 2) post-randomization. RESULTS: In phase 1, SBP was already significantly lower in the intensive treatment group than in the standard treatment group (126.5 vs. 132.1 mmHg, p < .05). During a median follow-up of 40 months, in phase 2, the intensive group still had a lower SBP than the standard treatment group (125.0 vs. 135.3 mmHg, p < .05). Both global work index (GWI) and global constructive work (GCW) decreased significantly in phase in the intensive treatment group but not in the standard group (p < .05). Global wasted work (GWW) increased and global work efficiency (GWE) declined in both groups from phase 1 to phase 2 while no significant difference between the treatment effects. Similarly, left ventricular ejection function (LVEF) and global longitudinal strain (GLS) decreased in the two groups. The multivariate linear regression analysis showed the intensive treatment appeared to be an independent predictor of the ΔGWI (ß = -110.92; 95% CI, -197.78 to -30.07, p = .008) and ΔGCW (ß = -135.11; 95% CI, -220.33 to -49.88, p = .002). CONCLUSIONS: In elderly hypertensive patients, lower SBP was associated with decreased GWI and GCW and intensive BP treatment did not improve global MW efficiency.

Influence of Baseline Diastolic Blood Pressure on the Effects of Intensive Blood Pressure Lowering: Results From the STEP Randomized Trial.

BACKGROUND: The STEP (Strategy of Blood Pressure Intervention in the Elderly Hypertensive Patients) trial demonstrated that intensive systolic blood pressure (SBP) lowering has cardiovascular benefits. However, the influence of baseline diastolic blood pressure (DBP) on the effects of intensive blood pressure lowering on cardiovascular outcomes has not been fully elucidated. METHODS: We performed a post hoc analysis of the STEP trial. Participants were randomly allocated to intensive (110 to <130 mm Hg) or standard (130 to <150 mm Hg) treatment groups. The effects of intensive SBP lowering on the primary composite outcome (stroke, acute coronary syndrome, acute decompensated heart failure, coronary revascularization, atrial fibrillation, and cardiovascular death), major adverse cardiac event (a composite of the individual components of the primary outcome except for stroke), and all-cause mortality were analyzed according to baseline DBP as both a categorical and a continuous variable. RESULTS: The 8259 participants had a mean age of 66.2±4.8 years, and 46.5% were men. Participants with lower DBP were slightly older and had greater histories of cardiovascular disease, diabetes, and hyperlipidemia. Within each baseline DBP quartile, the mean achieved DBP was lower in the intensive versus standard group. The effects of intensive SBP lowering were not modified by baseline DBP as a continuous variable or as a categorical variable (quartiles, or <70, 70 to <80, and ≥80 mm Hg; all P value for interaction >0.05). CONCLUSIONS: The beneficial effects of intensive SBP lowering on cardiovascular outcomes were unaffected by baseline DBP. Lower DBP should not be an obstacle to intensive SBP control. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT03015311.

Effect of intensive blood pressure lowering on left ventricular hypertrophy in patients with hypertension: a meta-analysis of randomized trials.

BACKGROUND: Successful antihypertensive management can limit left ventricular hypertrophy (LVH) and improve the clinical prognosis. However, it remains unclear whether intensive blood pressure (BP) lowering has a greater effect on the occurrence and regression of LVH compared to standard BP lowering. METHODS: We searched the electronic databases of PubMed, EMBASE and Web of Science from inception to 2 June 2023. Relevant and eligible studies were included. A random-effects model was used to estimate the pooled odds ratio (OR) and 95% confidence intervals (CI). RESULT: Four RCTs including 20,747 patients met our inclusion criteria. The results demonstrated that intensive BP lowering was associated with a significantly lower rate of LVH (OR 0.85; 95%CI: 0.78-0.93; I2 48.6%) in patients with hypertension compared to standard BP lowering. Subgroup analysis revealed that the effect of intensive BP lowering on LVH was more pronounced in patients with high cardiovascular disease (CVD) risk factors (OR 0.82; 95%CI: 0.72-0.93; I2 57.9%). In addition, intensive BP lowering led to significant regression of LVH (OR 0.68; 95%CI: 0.52-0.88; I2 45.5%). CONCLUSIONS: Our study suggests that intensive BP lowering should be instigated as soon as possible for optimal control of BP and to prevent regression of LVH, especially in patients with high risk of CVD. However, caution is warranted when treating hypertensive patients with LVH to systolic blood pressure (SBP) targets below 130 mm Hg.

We conducted a meta-analysis of four randomised controlled trials involving 20,747 patients with hypertension. The result suggested that intensive BP lowering should be instigated as soon as possible for optimal control of BP and to prevent regression of LVH, especially in patients with high risk of CVD. However, caution is warranted when treating hypertensive patients with LVH to SBP targets below 130 mm Hg.

Effects of intensive blood pressure control on cognitive function in patients with cerebral small vessel disease.

OBJECTIVE: This study aimed to investigate the effects of intensive blood pressure control on cognitive function in elderly patients with cerebral small vessel disease (CSVD). METHODS: From May 2020 to June 2022, 140 outpatients and inpatients with CSVD and hypertension in the Department of Neurology of Beijing Shijingshan Hospital were selected. They were randomly divided into the standard and intensive blood pressure control groups, and the dosage of antihypertensive drugs was adjusted to reduce the blood pressure to the target level. The patients were followed up for 2 years. The medical records or data at "enrollment" and "2-year follow-up" were analyzed and evaluated. The Mini-Mental State Examination (MMSE) and Montreal Cognitive Assessment (MoCA) were used to evaluate cognitive function. Cranial magnetic resonance imaging was performed to evaluate lacunar infarctions (LIs) and white matter hyperintensity (WMH). Multiple linear regression was used to analyze the correlation between MMSE scores and blood pressure, WMH, and LIs. RESULTS: (1) The MMSE and MoCA scores in the standard group were significantly lower than those at enrollment. The WMH score in the standard group was significantly higher than that at enrollment. (2) After the 2-year follow-up, the 24-h systolic blood pressure (SBP), 24-h diastolic blood pressure (DBP), daytime mean SBP, daytime mean DBP, and nighttime mean SBP in the two groups significantly decreased, which had significant statistical significance (P < 0.05). (3) The correlation between blood pressure and MMSE score was analyzed using multiple linear regression analysis. The WMH score, LIs, 24-h SBP, and 24-h DBP were independently correlated with MMSE scores. CONCLUSION: In elderly patients with hypertension, a decrease in SBP to 126 mmHg, compared with 134 mmHg, can delay cognitive impairment as well as reduce LIs and cerebral WMH lesions in patients with CSVD.

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

BACKGROUND: In chronic kidney disease, current guidelines recommend systolic blood pressure (SBP) below 120 mmHg. 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. METHODS: 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). RESULTS: 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 110-119 mmHg, hazard ratios (95% confidence intervals) for the SBP categories <110, 120-129, 130-139 and ≥140 mmHg 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 ≥1 g/day and eGFR ≥60 mL/min/1.73 m2. After analyzing time-updated diastolic BP, no similar trend was observed. CONCLUSIONS: 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.

Intensive blood pressure control for patients aged over 60: A meta-analysis of the SPRINT, STEP, and ACCORD BP randomized controlled trials.

OBJECTIVES: To evaluate the effects of intensive treatment to lower blood pressure (BP) on the risk of cardiovascular disease (CVD) among patients aged over 60 years. STUDY DESIGN: We extracted individual-level data of participants aged over 60 years from the SPRINT study and ACCORD study first, and then conducted a meta-analysis of major adverse cardiovascular events (MACEs) and other adverse events (hypotension and syncope) and renal outcomes across the SPRINT, STEP, ACCORD BP trials, which included 18,806 participants over 60 years of age. Participants were randomized to receive standard BP treatment or intensive BP treatment. MAIN OUTCOME MEASURES: Hazard ratios (HRs) were used to calculate summary statistics. RESULTS: In this meta-analysis, intensive treatment did not decrease either the all-cause mortality rate (HR: 0.98; 95 % confidence interval [CI]: 0.76-1.26; p = 0.87) or the cardiovascular mortality rate (HR: 0.77; 95 % CI: 0.54-1.08; p = 0.13). The incidence of MACEs (HR: 0.83; 95 % CI: 0.74-0.94; p = 0.003) and stroke (HR: 0.70; 95 % CI: 0.56-0.88; p = 0.002) was reduced, however. Intensive treatment had no effect on acute coronary syndrome (HR: 0.87; 95 % CI: 0.69-1.10; p = 0.24) or heart failure (HR: 0.70; 95 % CI: 0.40-1.22; p = 0.21). Intensive treatment increased the risk of hypotension (HR: 1.46; 95 % CI: 1.12-1.91; p = 0.006) and syncope (HR: 1.43; 95 % CI: 1.06-1.93; p = 0.02). Intensive treatment did not increase the risk of impaired kidney function among patients with chronic kidney disease (HR: 0.98; 95 % CI: 0.41-2.34; p = 0.96) or without chronic kidney disease (HR: 1.77; 95 % CI: 0.48-6.56; p = 0.40) at baseline. CONCLUSIONS: Intensive BP goals reduced the incidence of MACEs and increased the risk of other adverse events without significant changes in mortality or renal outcome.

Association of low diastolic blood pressure with all-cause death among US adults with normal systolic blood pressure.

Although the effect of intensive systolic blood pressure lowering is widely recognized, treatment-related low diastolic blood pressure still worrisome. This was a prospective cohort study based on the National Health and Nutrition Examination Survey. Adults (≥20 years old) with guideline-recommended blood pressure were included and pregnant women were excluded. Survey-weighted logistic regression and cox models were used for analysis. A total of 25 858 participants were included in this study. After weighted, the overall mean age of the participants was 43.17 (16.03) years, including 53.7% women and 68.1% non-Hispanic white. Numerous factors were associated with low DBP (<60 mmHg), including advanced age, heart failure, myocardial infarction, and diabetes. The use of antihypertensive drugs was also associated with lower DBP (OR, 1.52; 95% CI, 1.26-1.83). DBP of less than 60 mmHg were associated with a higher risk of all-cause death (HR, 1.30; 95% CI, 1.12-1.51) and cardiovascular death (HR, 1.34; 95% CI, 1.00-1.79) compared to those with DBP between 70 and 80 mmHg. After regrouping, DBP <60 mmHg (no antihypertensive drugs) was associated with a higher risk of all-cause death (HR, 1.46; 95% CI, 1.21-1.75). DBP <60 mmHg after taking antihypertensive drugs was not associated with a higher risk of all-cause death (HR, 0.99; 95% CI, 0.73-1.36). Antihypertensive drug is an important factor contributing to DBP below 60 mmHg. But the pre-existing risk does not increase further with an additional reduction of DBP after antihypertensive drugs treatment.

Association Between the Frailty and Cognitive Impairment Among Patients With Hypertension-A Post Hoc Analysis of the SPRINT Trial.

Background Frailty and cognitive impairment are common in the elderly, with various shared risk factors like hypertension. Frailty is a marker for future cognitive function. Moreover, whether intensive blood pressure interacted with frailty and cognitive impairment is unknown. Methods and Results We performed a post hoc analysis of data from SPRINT (Systolic Blood Pressure Intervention Trial). The relationship between frailty and a composite of probable dementia (PD) and mild cognitive impairment (MCI) was analyzed. Also, we evaluated the interaction of intensive blood pressure lowering in the relationship between frailty and cognitive impairment. A total of 8537 patients were included in our study, and 35.1% were women. The mean age of these participants was 67.9±9.3 years. According to the baseline frailty index, 1670, 4637, and 2230 patients were in fit, less fit, and frail statuses, respectively. During a mean follow-up of 4.61 years, 871 cases of PD or MCI occurred. Compared with those in fit status, those with less fit (hazard ratio [HR], 2.14 [95% CI, 1.65-2.77]) and frailty (HR, 4.28 [95% CI, 3.26-5.61]) status had a higher incidence of a composite of PD and MCI. Blood pressure control strategy interacted with the correlation between frailty and cognitive impairment. Intensive blood pressure control (HR, 2.4 [95% CI, 2.0-2.8]) accelerated the relationship between frailty and incidence of PD and MCI compared with the standard treatment group (HR, 1.8 [95% CI, 1.5-2.1]; P for interaction=0.009). Conclusions This study found that the baseline frailty status was a possible marker for the incidence of a composite of PD and MCI. Intensive blood pressure control may strengthen this correlation. Registration URL: https://clinicaltrials.gov/; Unique identifier: NCT01206062.