Key result
Elevated homocysteine is linked to ~53% higher CV risk without altering intensive BP benefits.
Why the study?
It was unknown whether homocysteine is associated with cardiovascular risk in controlled hypertensive patients and whether it modifies the benefit of intensive BP control.
Does baseline homocysteine level modify the effect of intensive blood pressure control (SBP <120 mm Hg) on the composite outcome of myocardial infarction, revascularisation, hospitalization for heart failure, stroke, or cardiovascular death in hypertensive patients with high cardiovascular risk?
RCT (n=11,220)
Open-label, blinded-outcome
1:1
Yes
Does baseline homocysteine level modify the effect of intensive blood pressure control (SBP <120 mm Hg) on the composite outcome of myocardial infarction, revascularisation, hospitalization for heart failure, stroke, or cardiovascular death in hypertensive patients with high cardiovascular risk?
Elevated baseline homocysteine is independently associated with higher cardiovascular risk in well-controlled hypertensive patients, but it does not modify the cardiovascular benefit or safety of intensive blood pressure lowering (<120 mm Hg).
Intensive BP control effect on CV outcomes consistent across homocysteine tertiles; confirms no interaction and uniform applicability in this RCT.
Background It is unknown whether homocysteine is associated with cardiovascular risk in controlled hypertensive patients, and whether it modifies the benefit of intensive blood pressure (BP) control. Methods ESPRIT was a multicenter, open-label, blinded-outcome, randomized controlled trial assigned participants with high cardiovascular risk 1:1 to intensive treatment (targeting systolic BP [SBP] below 120 mm Hg) or standard treatment (targeting SBP below 140 mm Hg). Participants were stratified into tertiles (T1: <11.7μmol/L; T2: 11.7-15.2μmol/L; T3: ≥15.2μmol/L) by baseline homocysteine. The primary outcome was a composite of myocardial infarction, revascularisation, hospitalization for heart failure, stroke or death from cardiovascular causes. We used Cox proportional hazards models to evaluate the association between homocysteine and cardiovascular events and effects of intensive treatment on cardiovascular outcomes, kidney outcome and safety outcomes. Results A total of 11220 patients (mean age, 64.6±7.1 years) were included in current study. Compared with participants in T1, participants in T3 had a significantly higher risk of primary outcome in the intensive and standard blood pressure control arms (adjusted hazard ratio, 1.53 [95% CI, 1.21-1.95] and 1.33 [95% CI, 1.06-1.67], respectively). The effect of intensive treatment on primary outcome was not modified by homocysteine tertiles, with adjusted hazard ratios of 0.84 (95%CI, 0.66–1.06), 0.87 (95%CI, 0.71–1.06) and 0.91 (95% CI, 0.77-1.09) respectively (P for interaction=0.71). There’s no significant difference of kidney outcome and safety outcomes by intensive intervention across homocysteine tertiles (all P for interaction>0.05). Conclusion Elevated homocysteine was associated with higher cardiovascular risk in well-controlled hypertensive patients, regardless of the targeting SBP level. Homocysteine did not modify the effect of intensive BP control.
No takes yet. Share an insight, caveat, or question.
Y Li (2026) conducted an RCT in Hypertension with high cardiovascular risk (n=11,220). Intensive blood pressure control (target SBP <120 mm Hg) across homocysteine tertiles vs. Standard blood pressure control (target SBP <140 mm Hg) and lowest homocysteine tertile (<11.7 μmol/L) was evaluated on Composite of myocardial infarction, revascularisation, hospitalization for heart failure, stroke or death from cardiovascular causes (HR 1.53, 95% CI 1.21-1.95, p=0.71 for interaction). Elevated homocysteine (≥15.2 vs <11.7 μmol/L) increased CV risk in intensive (aHR 1.53, 95% CI 1.21-1.95) and standard BP arms (aHR 1.33) without modifying intensive BP benefit (P_interaction=0.71).
Synapse has enriched 5 closely related papers on similar clinical questions. Consider them for comparative context: