Highlight
– Intensive blood pressure control lowers cardiovascular events across all cardiovascular risk tertiles.
– Higher baseline cardiovascular risk patients experience greater absolute benefit but also increased adverse events.
– Benefit-to-harm ratios favor intensive treatment regardless of baseline risk, supporting individualized therapy.
Study Background and Disease Burden
Hypertension remains a major modifiable risk factor for cardiovascular disease (CVD), contributing substantially to morbidity and mortality worldwide. Current hypertension guidelines recommend treatment targets stratified by a patient’s baseline CVD risk, aiming to maximize cardiovascular event reduction while minimizing treatment-related harms. Although intensive blood pressure control reduces cardiovascular events, its risk-benefit profile across differing baseline CVD risk levels has not been fully elucidated. This knowledge gap limits clinicians’ ability to tailor blood pressure targets optimally for individual patients.
Study Design
The present analysis used data from the STEP trial (Strategy of Blood Pressure Intervention in Older Hypertensive Patients), a large randomized controlled trial assessing intensive versus standard blood pressure treatment targets. The study included 8,262 hypertensive patients aged 60 years or older, stratified into tertiles based on baseline 10-year CVD risk.
Participants were randomized to intensive blood pressure control (target systolic blood pressure <130 mmHg) versus standard treatment targets. The primary outcome was a composite of cardiovascular events including stroke, myocardial infarction, acute heart failure, coronary revascularization, atrial fibrillation, or death from cardiovascular causes. Adverse events related to treatment, such as hypotension, syncope, or renal dysfunction, were closely monitored.
The analysis employed Cox proportional hazards models to evaluate the association between baseline CVD risk and clinical outcomes in each risk tertile. Additionally, Poisson regression models predicted absolute benefits and harms to determine the net benefit of intensive treatment.
Key Findings
Over a median follow-up of 3.32 years, 333 primary outcome events and 611 adverse events were recorded. Intensive blood pressure control significantly reduced the incidence of the primary cardiovascular outcome compared to standard treatment, with an overall hazard ratio (HR) of 0.76 (95% CI, 0.61–0.94).
Importantly, this benefit was consistent within each cardiovascular risk tertile. However, patients in the highest risk tertile experienced greater absolute risk reductions due to their elevated baseline event rates. Conversely, the hazard ratio for adverse events associated with intensive treatment was 1.1 (95% CI, 0.94–1.28), indicating a modest increase in treatment-related harms that was not statistically significant overall.
The absolute risk increase of adverse events was more pronounced in higher-risk patients. Despite this, the predicted benefit-to-harm ratio was favorable for intensive blood pressure control across all risk strata. Notably, the ratio differed significantly between tertiles, reflecting the varying balance of benefits and harms according to baseline cardiovascular risk. Nonetheless, overall, intensive blood pressure lowering demonstrated a net benefit.
Expert Commentary
This comprehensive analysis adds significant evidence supporting the principle that more intensive blood pressure lowering yields clinical benefits even among older hypertensive patients with variable cardiovascular risk profiles. It corroborates recent guideline trends endorsing personalized blood pressure targets based on overall CVD risk assessment.
While the increased absolute risk of adverse events with intensive therapy warrants caution, the benefit in cardiovascular event reduction appears to outweigh these risks across risk groups. These findings underscore the importance of nuanced clinical decision-making, integrating patient-specific factors including comorbidities, frailty, and treatment tolerability.
Limitations of the study include the relatively short median follow-up of just over three years, which may underestimate long-term harms or benefits. Additionally, the older age group studied may limit generalizability to younger populations. Further studies are also needed to identify strategies to mitigate adverse events while preserving cardiovascular benefits.
Conclusions
Intensive blood pressure control reduces major cardiovascular events across the spectrum of baseline cardiovascular risk in older hypertensive patients. Although higher-risk patients derive greater absolute cardiovascular benefit, they also face a higher absolute risk of treatment-related adverse events. Importantly, the overall balance favors intensive treatment in all risk groups, supporting the clinical implementation of risk-stratified blood pressure targets.
These results emphasize the relevance of individualized hypertension management informed by comprehensive cardiovascular risk assessment to optimize patient outcomes and minimize harm. Clinicians should consider both the enhanced benefits and potential harms when deciding on blood pressure targets, especially in higher-risk patients.
References
Dong X, Ling Q, Zhao X, Song Q, Cai J. Benefit and Harm of Intensive Blood Pressure Control by Cardiovascular Risk. Hypertension. 2025 Aug;82(8):1392-1400. doi: 10.1161/HYPERTENSIONAHA.125.25162. Epub 2025 Jun 26. PMID: 40567237.
