Stroke is the fifth leading cause of death in the country and the top reason for adult disability (1). Each year about 795,000 people experience a stroke in the United States with nearly 25% of these strokes being recurrent events in people with a prior history of a stroke (2). Hypertension is the considered to be the most important modifiable risk factor for stroke. Therefore, treatment of hypertension is one of the most effective strategies for primary and secondary prevention of stroke (3). In a large meta-analysis from 2002, which included 1 million patients, a direct association was seen between blood pressure measurements and risk of vascular mortality including stroke and ischemic heart disease (4). There is a continuous relationship with risk throughout the normal range of blood pressure, down at least as far as 115/75 mm Hg according to this meta-analysis of 61 prospective clinical studies. However, there has been a lack of consensus among experts about the most appropriate blood pressure targets for cardiovascular disease and stroke prevention.
In the Secondary Prevention of Small Subcortical Strokes (SPS-3) trial, investigators compared systolic blood pressure targets of 130-149 mm Hg and less than 130 mm Hg (5). About 3000 patients with a recent history of an MRI confirmed lacunar stroke were randomized to one of the two treatment groups and followed for a mean of 3.7 years. Primary outcome of recurrent stroke was seen at a lower rate in the lower target group with an annualized stroke rate of 2.25% as compared to 2.77% in the higher target group. Despite a signal toward benefit of a lower BP target, these results did not reach statistical significance. The rates of intracerebral hemorrhage were noted to be significantly lower with a lower BP target.
In a clinical trial enrolling patients with diabetes and a high cardiovascular risk, blood pressure target of less than 120 mm Hg was not superior to a target of less than 140 mm Hg for reducing risk of cardiovascular events with the exception of stroke (6). In this study, the intensive blood pressure target lead to a significant risk reduction for stroke but not for myocardial infarction or all-cause mortality.
To further ascertain an ideal blood pressure target, investigators in the SPRINT trial enrolled over 9000 persons with SBP of more than 129 mm Hg without a history of diabetes (7). The participants were randomized to intensive treatment (target <120 mm Hg) or standard treatment groups (target <140 mm Hg). Primary outcome was a composite of myocardial infarction, heart failure, stroke or vascular death. After a median follow up of 3.3 years, the trial was stopped early due to a significantly lower rate of primary composite outcome in the intensive blood pressure group as compared to the standard treatment. Interestingly, even though there was a signal of benefit for stroke risk reduction, this was not statistically significant. The investigators of the study make note of this finding and hypothesize that this could be due to the fact that this trial excluded patients with a prior history of stroke and TIA. This has also raised questions about the limited applicability of these results to patients with a history of stroke.
The investigators also looked at cognitive outcomes for the two groups of patients in this trial (8). The composite outcome of mild cognitive impairment and dementia was seen in a significantly lower number of patients in the intensive BP treatment group as compared to the standard treatment group. Due to the early termination of SPRINT, the study was underpowered to show a significant difference in the risk of dementia.
The current guidelines (9) from the American Heart Association/ American College of Cardiology recommend initiating treatment at SBP>130 mm Hg for patients with a high cardiovascular risk. Using the current definition of hypertension, it is estimated that 46% of adults in the US have hypertension and about 36% should be prescribed antihypertensive medications (10). Applying these new guidelines, only about half of all US adults on medications for hypertension are currently below the target BP numbers.
With hypertension playing such an important role in the development of the two most common neurological illnesses (Stroke and cognitive disorders), authors of a recent paper in JAMA Neurology (11) urge neurologists to play a greater role in treatment of hypertension as a preventive strategy for their patients. Traditionally stroke neurologists and neurointensivists have been involved in treatment of the cardiovascular risk factors including hypertension but most of that is done after the patient has had a major event such as an ischemic stroke or intracerebral hemorrhage. The authors argue that neurologists should participate in treatment of hypertension for their patients as a primary preventive strategy as it would lead to an overall improved brain health of our ageing population.
To learn more about the latest advancements in the field of hypertension research, I encourage the readers to attend Hypertension 2019 Scientific Sessions being held in New Orleans September 5-8, 2019.
- Vital Signs: Recent trends in stroke death rates – United States, 2000-2015. MMWR 2017;66.
- Benjamin EJ, Blaha MJ, Chiuve SE, et al. on behalf of the American Heart Association Statistics Committee and Stroke Statistics Subcommittee. Heart disease and stroke statistics—2017 update: a report from the American Heart Association. Circulation. 2017;135:e229-e445.
- Katsanos AH, Filippatou A, Manios E, et al. Blood pressure reduction and secondary stroke prevention: a systematic review and metaregression analysis of randomized clinical trials. Hypertension. 2017;69(1):171-179.
- Lewington S, Clarke R, Qizilbash N, Peto R, Collins R; Prospective Studies Collaboration. Age-specific relevance of usual blood pressure to vascular mortality: a meta-analysis of individual data for one million adults in 61 prospective studies Lancet. 2002;360(9349):1903-1913.
- Benavente OR, Coffey CS, Conwit R, et al; SPS3 Study Group. Blood-pressure targets in patients with recent lacunar stroke: the SPS3 randomised trial. Lancet. 2013;382(9891):507-515.
- Cushman WC, Evans GW, Byington RP, et al. Effects of intensive blood-pressure control in type 2 diabetes mellitus. N Engl J Med 2010;362:1575-1585
- Wright JT Jr, Williamson JD, Whelton PK, et al; SPRINT Research Group. A randomized trial of intensive versus standard blood-pressure control [published correction appears in N Engl J Med. 2017;377(25):2506]. N Engl J Med. 2015;373(22):2103-2116.
- Williamson JD, Pajewski NM, Auchus AP, et al; SPRINT MIND Investigators for the SPRINT Research Group. Effect of intensive vs standard blood pressure control on probable dementia: a randomized clinical trial.JAMA. 2019;321(6):553- 561
- Whelton PK, Carey RM, Aronow WS, et al.
- 2017 ACC/AHA/AAPA/ABC/ACPM/AGS/APhA/ASH/ASPC/NMA/PCNA Guideline for the Prevention, Detection, Evaluation, and Management of High Blood Pressure in Adults: A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines. J Am Coll Cardiol 2018;71:e127-e248.
- Muntner P, Carey RM, Gidding S, et al. Potential US population impact of the 2017 ACC/AHA high blood pressure guideline. Circulation. 2018;137(2): 109-118.
- Betjemann J, Hemphill JC, Sarkar U. Time for Neurologists to Drop the Reflex Hammer on Hypertension. JAMA Neurol.Published online August 19, 2019. doi:10.1001/jamaneurol.2019.2588
Siddharth Sehgal is a Vascular Neurologist at Lahey Hospital and Medical Center in Burlington, Massachusetts. His clinical interests include stroke in the young and cryptogenic stroke. Throughout his career, he has been extensively involved in public education programs about stroke awareness. @sehgalsid17