By Michael Crawford, MD

Professor of Medicine, Chief of Clinical Cardiology, University of California, San Francisco

Dr. Crawford reports no financial relationships relevant to this field of study.

SYNOPSIS: A post-hoc analysis of patients suffering from mild to moderate aortic stenosis in a study of low-density lipoprotein cholesterol lowering showed that the optimal blood pressure for the best survival was 130-139/70-90 mmHg.

SOURCES: Nielsen OW, Sajadieh A, Sabbah M, et al. Assessing optimal blood pressure in patients with asymptomatic aortic valve stenosis: The Simvastatin Ezetimibe in Aortic Stenosis Study (SEAS). Circulation 2016;134:455-468.

O’Gara PT. Management of hypertension in patients with mild to moderate aortic stenosis: Navigating the SEAS. Circulation 2016;134:469-471.

Systemic hypertension is common in aortic stenosis patients and is associated with worse outcomes. However, little is known about what the optimal blood pressure is in these patients in whom relative hypotension may not be tolerated well. Investigators from the Simvastatin Ezetimibe in Aortic Stenosis (SEAS) trial sought to answer this question using the data from this otherwise negative study. The SEAS study excluded patients with heart failure, diabetes, or known atherosclerosis and enrolled patients with aortic flow velocities between 2.5 m/s and 4 m/s with normal ejection fraction and no symptoms.

This report is a post-hoc analysis of the data to correlate blood pressure (BP) with outcomes in 1,767 patients who had adequate measurements of aortic velocity and BP. The primary endpoint for this analysis was all-cause mortality. BP was defined as an average of all measurements during the first four years of follow-up (median 4.3 years). A U-shaped association between systolic BP (SBP) and all-cause mortality was identified with values from 130-139 associated with the best survival with diastolic (DBP) in the range of 60-90 mmHg. SBP > 139 increased the risk of death (hazard ratio [HR] = 1.7 for SBP > 160; P = 0.033) as did lower SBPs (HR = 1.6 for SBP 120-129, P = 0.039). Low SBP remained harmful in patients suffering from mild and moderate aortic stenosis. A high SBP was associated with myocardial infarction and cardiovascular death in patients with mild but not moderate aortic stenosis. These data were not changed by adjustment for a history of hypertension or antihypertensive treatment. The authors concluded that in patients with asymptomatic aortic stenosis without heart failure, diabetes, and overt atherosclerotic vascular disease, the optimal SBP is 130-139 and the optimal DBP is 70-90 mmHg.

COMMENTARY

Guidelines recommend treatment of hypertension in patients presenting with aortic stenosis, but target BPs are not given. This post-hoc observational analysis of the SEAS trial provides some useful information in this regard. SBPs > 160 and < 130 were associated with increased mortality, but mild systolic hypertension was not (140-159 mmHg). However, the authors suggested that it is reasonable to treat SBP > 140 based on their previous analysis of the SEAS data, which showed that hypertension was associated with worse outcomes in these patients. Interestingly, both the authors and the accompanying editorial provided no explanation for the reason elevated SBP is detrimental in aortic stenosis. Thus, it may be acceptable to tolerate SBPs in the 140-159 range if relative hypotension has been an issue with treatment.

The adverse effect of low DBP is easier to explain, since reducing myocardial perfusion pressure in diastole in patients who probably have high diastolic left ventricular pressures would clearly reduce myocardial oxygen supply, even if the patient had normal coronary arteries. Similar results have been observed in patients with acute coronary syndromes and acute heart failure. The higher mortality risk with high DBPs is harder to explain, but is observed in all studies of BP and outcome. Since BP levels did not influence the time to aortic valve replacement, the effect probably is mediated by augmenting coronary artery disease or other comorbidities.

In SEAS, antihypertension treatment was not regulated, but a previous analysis of this database showed that renin angiotensin aldosterone system blockers generally were safe in aortic stenosis patients. This prompted the editorialist to state that no drugs were off limits if used carefully in these patients. This is probably true for drugs we commonly use now, but may not be for some drugs such as powerful direct vasodilators (e.g., hydralazine). Also, most aortic stenosis patients are elderly and often present with multiple comorbidities that have to be taken into account with drug choice for hypertension. In aortic stenosis in particular, drugs with potent effects on AV conduction may be relatively contraindicated if there are signs of conduction disturbances, such as first-degree AV block.

Another implication of this study is that if patients are on antihypertensive therapy with an SBP < 120 or a DBP < 70 mmHg, one should consider reducing the therapy. In those with BPs in these ranges who are not on antihypertensive medication, seek other causes of relative hypotension and correct them.

The results of this study fit in with the general theme that BP targets for antihypertension treatment likely are different for different patient populations, and one size does not fit all.