Background: Recent intervention trials have been conducted in patients at high cardiovascular risk, and their results have reopened the issue whether lowering blood pressure to normotensive values is of greater benefit than lowering blood pressure below 140/90 mmHg. These trials have made widespread use of concomitant therapies (lipid-lowering, antiplatelet and background antihypertensive agents). The question has been addressed whether in these trials a bottom level of cardiovascular risk (i.e. one that cannot be further reduced) rather than a bottom level of blood pressure (i.e. one below which risk cannot be further reduced) was achieved.
Methods: The 'residual risk', that is, the incidence of major cardiovascular events achieved in trials with antihypertensive agents, was calculated by reviewing endpoint data in all major trials after classifying them into four categories according to patients' baseline cardiovascular risk: low-risk patients; elderly patients; diabetic patients; high-risk patients.
Results: Low rates of major cardiovascular events (below 3-6% in 5 years) were only achieved in trials enrolling low-risk patients. In elderly hypertensive patients, hypertensive patients with diabetes and particularly patients with previous cardiovascular disease quite rarely could incidence of major cardiovascular events be reduced below a bottom level of 12-14% in 5 years, and remained within the high-risk range (above the conventional threshold of 10% in 5 years) despite extensive use of concomitant therapies.
Conclusion: In high-risk patients there is a 'ceiling effect' for treatment benefits. Delaying therapeutic correction of cardiovascular risk factors until a high level of risk is achieved blunts the full benefits of interventions.