Acute coronary syndromes (ACS), which include unstable angina and myocardial infarctions (MIs), are responsible for most cardiovascular deaths.1 Observational studies have determined that deaths due to both ischemic heart disease and stroke increase progressively and linearly with blood pressure; however this theory is frequently challenged. The American Heart Association recommends a target blood pressure (BP) of <130/80 mmHg in patients at high risk of ACS, but few hard outcomes data exist to support these recommendations.2,3
Bangalore and colleagues analyzed the data on the 4162 patients who participated in the PROVE IT-TIMI trial.2 The original PROVE IT-TIMI 22 trial study was an international, multicenter, randomized, double-blind, 2x2 factorial design trial of men and women at least 18 years old hospitalized with ACS in the preceding 10 days who were randomly assigned pravastatin 40 mg or atorvastatin 80 mg once daily and to receive gatifloxacin or placebo. The follow-up spanned from 18 to 36 months with visits at 30 days, 4 months, and every 4 months thereafter. The primary outcome consisted of the time from randomization to death from any cause, MI, unstable angina requiring hospitalization, revascularization with either percutaneous coronary intervention or coronary artery bypass graft, and stroke. The secondary outcome consisted of the composite of death due to coronary heart disease, nonfatal MI, or revascularization after 30 days. The data were analyzed collectively to identify any relationship between blood pressure and the primary outcome (i.e., all-cause mortality, death due to coronary heart disease, and nonfatal MI).2
Of the 4162 patients included in the study, 1000 (24%) reached the primary outcome. The authors identified a relationship between systolic pressure and the incidence of primary outcome and the relationship followed a J- or U- shaped curve rather than a linear curve as previously suggested. There was an increased event rate at both low and high systolic blood pressure (SBP) when compared to the reference range of >130 to 140 mmHg. The risk of primary outcome increased 4.9-fold in the group with SBP ≤100 mmHg and by 1.2-fold in the group with SBP >160 mmHg. The lowest event rate occurred at a SBP of 136 mmHg using a nonlinear Cox proportional hazards model with systolic pressure on a continuous scale (X2 = 49, P <0.0001). The curve was relatively flat for systolic pressures of 110 to 130 mmHg. The J- and U-shaped relationship was found with average follow-up blood pressure variables, but not with baseline systolic blood pressure variables.3
The investigators observed a similar relationship in diastolic blood pressure and the incidence of primary outcome. Again a J- or U-shaped curve was observed with increased event rates at low and high diastolic blood pressure when compared to the reference group blood pressure of >80 mmHg to 90 mmHg. The risk of primary outcome increased 3.7-fold in the group with a diastolic blood pressure ≤60 mmHg and a 2.1-fold increase in the group with diastolic blood pressure >100 mmHg. The curve was relatively flat for diastolic pressures of 70 to 90 mmHg. As seen with the systolic blood pressure, a nadir occurred at 85 mmHg using a nonlinear Cox proportional hazard model on a continuous scale (X2 = 52, P <0.0001).3 Again, consistent with the SBP data, the J- and U-shaped relationship was found only with average ...