Effect of homocysteine on the outcomes of intensive blood pressure control: a post hoc analysis of the ESPRIT trial
Y LiAbstract
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.Effect of homocysteine on primary outcome