Highlights
- Isolated diastolic hypertension (IDH), defined as systolic blood pressure (SBP) < 130 mmHg and diastolic blood pressure (DBP) ≥ 80 mmHg, is associated with a cardiovascular risk reduction from pharmacological treatment similar to that seen in patients with elevated SBP.
- A 5 mmHg reduction in SBP yielded a hazard ratio (HR) of 0.91 for major cardiovascular events in patients with IDH, compared to 0.90 in those without.
- Treatment benefits remained consistent across various baseline DBP levels, including those starting below 60 mmHg, challenging concerns regarding the lower limit of the J-curve in diastolic management.
- The efficacy of BP-lowering therapy was not modified by age, prior cardiovascular disease history, or the specific methods used to measure blood pressure.
The Clinical Dilemma of Isolated Diastolic Hypertension
For decades, hypertension management has been predominantly driven by systolic blood pressure (SBP) targets, as SBP is traditionally viewed as a more potent predictor of cardiovascular outcomes, particularly in older populations. However, the clinical significance and management of isolated diastolic hypertension (IDH)—characterized by an elevated diastolic blood pressure (DBP) in the presence of a normal SBP—have remained subjects of intense debate within the cardiology community.
The 2017 ACC/AHA guidelines lowered the threshold for diagnosing hypertension to 130/80 mmHg, which significantly increased the prevalence of IDH. Conversely, other international guidelines have remained more conservative, often questioning whether treating elevated DBP in the absence of systolic hypertension provides meaningful benefit or if it potentially risks over-treatment. This uncertainty is compounded by the “J-curve” hypothesis, which suggests that lowering DBP too far (specifically below 60 or 70 mmHg) might impair coronary perfusion and increase cardiovascular risk. To address these gaps, the Blood Pressure Lowering Treatment Trialists’ Collaboration (BPLTTC) conducted an individual patient data meta-analysis to provide definitive clarity on the efficacy of treatment in this specific phenotype.
Study Design and Methodology
This study represents a robust one-stage individual participant data meta-analysis, pooling data from 51 randomized controlled trials. The total cohort included 358,325 participants. The primary objective was to compare the effects of pharmacological BP-lowering treatment on major cardiovascular events (MACE) between individuals with IDH and those without.
IDH was strictly defined as an SBP < 130 mmHg and a DBP ≥ 80 mmHg at baseline. The researchers employed Cox proportional hazard models, stratified by trial, to estimate the treatment effects. A key strength of this analysis was the stratification by baseline DBP categories, ranging from < 60 mmHg to ≥ 90 mmHg, specifically among those with baseline SBP < 130 mmHg. This allowed the team to investigate whether the relative benefit of treatment diminished at lower baseline diastolic levels.
Key Findings: Comparable Benefits Across Phenotypes
Among the 358,325 participants analyzed, 15,845 (4.4%) met the criteria for IDH. Over a median follow-up period of 4.2 years, the study yielded several critical insights:
1. Uniform Risk Reduction
The primary finding was that a 5 mmHg reduction in SBP resulted in a nearly identical reduction in the risk of major cardiovascular events regardless of IDH status. In the IDH group, the hazard ratio (HR) was 0.91 (95% CI 0.82–1.01). In the non-IDH group, the HR was 0.90 (95% CI 0.89–0.92). The P-value for interaction was 1.00, indicating that the relative effectiveness of BP-lowering therapy does not differ between these two groups.
2. No Threshold Effect for Diastolic Pressure
One of the most significant aspects of the study was the analysis of baseline DBP. The researchers found no evidence of heterogeneity in treatment effects among individuals with baseline SBP < 130 mmHg across the entire range of DBP (P for interaction = 0.26). Crucially, even in participants with a baseline DBP of less than 60 mmHg, the relative risk reduction did not diminish. This finding provides strong evidence against the concern that pharmacological BP lowering is less effective or harmful in patients who already have low diastolic readings, at least within the context of the randomized trials analyzed.
3. Subgroup Consistency
The relative treatment effects were consistent across various clinical phenotypes. There were no statistically significant differences in outcomes based on age, sex, prior history of cardiovascular disease, or the use of specific baseline medications. Furthermore, the method of BP measurement (office vs. other methods) did not alter the fundamental finding that lowering pressure in IDH is beneficial.
Expert Commentary: Shifting the Focus to Total Risk
The results from the BPLTTC collaboration challenge the traditional hesitation to treat isolated diastolic elevations. From a physiological standpoint, while DBP is a determinant of coronary artery perfusion, these data suggest that the systemic benefits of blood pressure reduction—likely mediated through reduced arterial wall stress and improved endothelial function—outweigh the theoretical risks of low DBP in most patients.
However, clinicians must interpret these findings with a nuanced view of “absolute” versus “relative” risk. While the relative risk reduction is consistent, the absolute benefit of treating a young, low-risk individual with IDH may be modest compared to treating an older patient with multiple comorbidities. Current guidelines often emphasize calculating 10-year cardiovascular risk scores to guide treatment initiation in Stage 1 hypertension (130-139/80-89 mmHg). This study reinforces that if a patient is deemed high-risk, the presence of IDH should be treated as a valid indication for therapy, just as systolic-diastolic hypertension would be.
Regarding the J-curve, this meta-analysis provides a degree of reassurance. The lack of heterogeneity down to a DBP of < 60 mmHg suggests that the “sweet spot” for blood pressure management may be broader than previously thought. Nevertheless, in clinical practice, particularly in very elderly patients or those with known severe coronary artery disease, clinicians should still exercise vigilance and monitor for symptoms of hypotension or organ hypoperfusion.
Conclusion
This individual patient data meta-analysis provides high-level evidence that pharmacological blood pressure lowering is as effective in reducing cardiovascular risk for patients with isolated diastolic hypertension as it is for those with other forms of hypertension. The findings debunk the notion that IDH is a benign condition or that it responds poorly to standard antihypertensive regimens. Furthermore, the benefit of treatment persists even at low baseline diastolic levels, suggesting that the primary focus of clinicians should remain on overall cardiovascular risk reduction rather than being deterred by isolated diastolic parameters.
References
Bidel Z, Nazarzadeh M, Canoy D, et al. Blood pressure lowering in isolated diastolic hypertension and cardiovascular risk: an individual patient data meta-analysis. Eur Heart J. 2025;ehaf962. doi:10.1093/eurheartj/ehaf962.
Whelton PK, Carey RM, Aronow WS, et al. 2017 ACC/AHA/AAPA/ABC/ACPM/AGS/APhA/ASPC/NMA/PCNA Guideline for the Prevention, Detection, Evaluation, and Management of High Blood Pressure in Adults. J Am Coll Cardiol. 2018;71(19):e127-e248.
