New Study Supports More Appropriate Blood Pressure Levels for Post-ACS Patients
Abstract & Commentary
By Michael H. Crawford, MD
Source: Bangalore S, et al. What is the optimal blood pressure in patients after acute coronary syndromes? Relationship of blood pressure and cardiovascular events in the pravastatin or atorvastatin evaluation and infection therapy-thrombolysis in myocardial infarction (PROVE IT-TIMI) 22 trial. Circulation. 2010;122:2142-2151.
The relationship between blood pressure and cardiovascular events remains controversial, especially in patients with coronary artery disease who may need increased pressures to have adequate myocardial perfusion. Thus, Bangalore and colleagues analyzed data from the Pravastatin or Atorvastatin Evaluation and Infection Therapy (PROVE IT) trial to determine the relationship of blood pressure to cardiovascular outcomes in patients with acute coronary syndromes (ACS). Blood pressure was managed at the discretion of the patient's physician. For this analysis, average blood pressure was calculated using all post-baseline values until the end of the study or an event occurred. The main drug intervention results of the trial have previously been reported for the 4,162 patients with ACS. All patients were divided into blood pressure groups in increments of 10mm/Hg. The primary cardiovascular event outcome was reached in 24% of the patients. The relationship between blood pressure and these events exhibited a J- or U-shaped curve, with increased events at low or high systolic blood pressure. This relationship held in the raw data after adjustment for differences in baseline characteristics of the patient. Cardiovascular events were lowest, at a blood pressure of 136/85 mm Hg. The curve was flat between pressures of 110 to 130 mm Hg systolic and 70 to 90 mm Hg diastolic. These findings were similar in the drug-treatment groups vs. the entire cohort. Examination of individual cardiovascular events showed that there were too few strokes (< 1%) to derive a meaningful relationship to blood pressure. Separating the data by systolic and diastolic blood pressure did not change the results. So a low diastolic pressure was no worse than a low systolic pressure for cardiac ischemic endpoints. The authors concluded that too low a blood pressure, especially < 110/70 mm Hg may be dangerous in post-ACS patients.
This study further supports the growing data that lower is not always better in blood-pressure control. That there is a J- or U-shaped curve with blood pressure and mortality is obvious, the only argument is where the nadir is. The conventional wisdom is that in high-risk individuals for cardiovascular (CV) events such as diabetics, the level should be at the lower end of the normal range, or < 120/80 mm Hg. However, the data to support this recommendation is sparse, and the recent ACCORD trial showed that there was no difference in CV events in type-II diabetes patients treated to a target systolic blood pressure of < 140 vs. < 120 mm Hg.
Several studies have shown similar results in more general high-risk populations. The Hypertension Optimal Treatment study showed a nadir for CV events at about 145/85 mm Hg. The Framingham post-myocardial infarction study showed similar results, as did the International Verapamil Trandolapril study and ON TARGET. Also, a recent Cochrane meta-analysis showed no difference in CV events with blood pressures of < 135/85 vs. 140-160/90-100 mm Hg. Thus, it seems we can return to the old standard of < 140/90 mm Hg, and not worry too much if we cannot quite get a patient below that level without adverse drug effects.
Of course, this was an observational study that did not control medication use or set targets for blood pressure. There were major differences in the clinical characteristics of the different blood-pressure groups. They attempted to correct for the obviously important differences such as age, but it is impossible to control for every factor, and there is always the possibility of unmeasured comorbidities influencing the results. Also, a relationship between blood pressure and events does not prove causation. In addition, there were more patients with blood pressures < 110mm Hg (about 1,500) than with blood pressures > 140 (about 600), and very few with pressures > 160 (63). So, the study was biased toward finding problems with low blood pressures. Finally, the results are only applicable to ACS patients with tight lipid control, since this was the population studied.
The mechanism of this observed relationship, if it is causal, cannot be elucidated from this study. However, analyses showed that it was not explained by pulse pressure. In fact, the ratio of myocardial infarction to stroke tended to increase at low diastolic pressures. This suggests that stroke is independent of pulse pressures. The likely reason myocardial infarcts increased is the lowered coronary perfusion pressure anticipated with a low diastolic-driving pressure in the coronary arteries, rather than the widened pulse pressure. Post-ACS patients would be expected to be especially vulnerable to reduced coronary dividing pressure. The nadir for diastolic pressure and CV events was 80-90 mm Hg in this study and >130 mm Hg for systolic blood pressure. Thus, in post-ACS patients, blood pressures nearer the 140/90 normal upper limit may be the most appropriate.