Michelle Christina Johansen, MD

Okin PM, Kjeldsen SE, and Devereux RB. Systolic Blood Pressure Control and Mortality After Stroke in Hypertensive Patients. Stroke. 2015

What is the ideal blood pressure range for our patients? Even now in the age of modern medicine there remains debate regarding optimal blood pressure control. The familiar target that is taught in medical school is <140/90 but clearly this must be dependent on the patient population as well as the evaluated outcome. The American Heart Association (AHA) issued a new guideline this year regarding treatment of hypertension in patients with coronary artery disease (CAD) and there was much discussion at the International Stroke Conference regarding blood pressure control for intracerebral hemorrhage. The AHA statement “A lower target BP (<130/80 mm Hg) may be appropriate in some individuals with CAD, previous MI, stroke or transient ischemic attack, or CAD risk equivalents (carotid artery disease, PAD, abdominal aortic aneurysm)” is supported by level IIb evidence and would suggest more aggressive control.

What about when lower blood pressures are maintained over a long period of time? What is the impact of this upon mortality? Okin et. al seek to address this question through their post-hoc analysis of data from the LIFE study. The LIFE study enrolled 9,193 patients with hypertension and ECG left ventricular hypertrophy (LVH) in a prospective, double blind study that aimed to establish whether selective blocking of angiotensin II improves LVH and reduced cardiovascular (CV) morbidity and death. They demonstrated that losartan compared to atenolol resulted in significant reduction in the primary endpoint of cardiovascular morbidity and mortality as well as LVH. There was discussion after completion of the study regarding possible conflict of interest with Merck that was not declared by the author after a letter was circulated in Scandinavia regarding the results of the study.

Okin et. al found 541 patients who had an incident stroke during routine LIFE study follow-up with 403 being atherothrombotic, 84 embolic and 54 hemorrhagic. Patients were classified into three groups according to average on-treatment systolic blood pressure (SBP) after stroke: <144 (lowest), 144-157 and >157 (highest). Baseline BP measurements were those at time of LIFE enrollment. The risk of all cause and cardiovascular mortality in patients in the lowest and highest tertile were compared to those in the middle (144-157). During a mean follow up of about 2 years, 170 patients died and 135 from CV causes.

The authors found that SBP<144 was associated with significantly higher all-cause mortality and SBP>157 with significantly higher CV and all-cause mortality. Multivariate analysis only showed SBP<144 as a significant predictor of CV and all-cause mortality. The authors re performed the analysis restricting the outcome to death occurring >90 days after initial stroke and the outcome was the same.

How is this study to be interpreted? Is SBP <144mm Hg associated with a significantly increased risk of CV and all cause mortality? The study population was hypertensives on treatment with LVH thereby limiting generalizability. Are we therefore to steer our HTN patients with LVH away from aggressive control for fear of increased risk of death? The authors are to be commended for their attempt to answer this important question but there are many limitations to the study. The study design is post hoc with some critics referring to this as “data drudging” implying that the more you dig, the more dirt you bring up. The investigators acknowledge that it cannot be determined whether low SBP is causative of mortality or simply a marker of existing disease. Perhaps if the data had been divided further separating out those with BP <130 which is suggested by the guideline, there might be more light shed on the issue. There is a randomized, controlled trial (SHOT) which will examine lower SBP during long-term follow-up post stroke and perhaps help address the many remaining questions.