Greater Reductions in Blood Pressure in Hypertensive Patients Further Reduce Stroke Risk
Raised blood pressure, hypertension, is very influential on the trajectory of age-related disease. It speeds up the development of atherosclerosis, and makes stroke and heart attack due to rupture of atherosclerotic plaques more likely. It causes a raised rate of rupture in small blood vessels, producing microbleeds that harm delicate tissues in the brain, kidney, and elsewhere. The size of these effects is large enough that forcing a reduction in blood pressure without addressing any of the underlying dysfunction that causes hypertension can still produce benefits.
The better path forward, however, would be to address the causes. This approach should be easier, in sense of being more efficient, more cost-effective, and also produce more extensive benefits by reducing the impact of all of the other problems that those underlying causes produce. Damage to tissues never has just one consequence. What causes hypertension? To a first approximation, this is a problem of stiffening of blood vessels. As blood vessels fail to contract and relax appropriately, the feedback mechanisms controlling blood pressure become distorted, resulting in hypertension.
Why do blood vessels stiffen? Because of cross-linking in the extracellular matrix of blood vessel walls, changing its structural properties, particularly elasticity, and separately because of loss of elastin in the extracellular matrix. Because senescent cells and other sources of chronic inflammation lead to calcification of blood vessel tissue, as well as dysfunction in the smooth muscle cells responsible for constriction. Those smooth muscle cells are further hampered by mitochondrial dysfunction, as illustrated by the point that ways of boosting mitochondrial activity reduce blood pressure in older individuals. There is never just one cause, but all of these causes can in principle be repaired. We just need to build the rejuvenation biotechnologies to do it.
In 2010, the absolute number of people with a first stroke in the world was 16.9 million, and the number with stroke-related deaths was 5.9 million. Therefore, prevention of primary and secondary stroke is a priority. Elevated blood pressure (BP) is the most relevant and prevalent risk factor for stroke. Reduction in BP is the most effective intervention to prevent both primary and secondary strokes. In clinical trials for primary prevention of cardiovascular events, including stroke, the lower the better seems acceptable for stroke prevention in hypertensive patients, with less than 115 mm Hg suggested as the optimum target level of systolic BP.
After a stroke, lowering BP in the chronic stage reduced the rates of recurrent stroke among both hypertensive and nonhypertensive patients in the Perindopril Protection Against Recurrent Stroke Study (PROGRESS). A post hoc analysis of the PROGRESS suggested that the optimum target level of systolic BP for the prevention of recurrent stroke is less than 120 mm Hg. In the Secondary Prevention of Small Subcortical Strokes (SPS3) randomized trial, the BP target was first evaluated in patients with recent stroke. The trial randomly assigned those with lacunar stroke to a systolic BP target of 130 to 149 mm Hg or less than 130 mm Hg, and the authors showed that the use of a systolic BP target less than 130 mm Hg is likely to be beneficial, especially for the prevention of hemorrhagic stroke.
A recent meta-analysis demonstrated that strict and aggressive control of BP with achieved mean systolic and diastolic BP levels less than 130 mm Hg and less than 85 mm Hg, respectively, seemed to be beneficial for secondary prevention. In primary prevention, the Systolic Blood Pressure Intervention Trial (SPRINT) proved the benefit of aggressive BP control, demonstrating that targeting a systolic BP less than 120 mm Hg resulted in lower rates of major cardiovascular events compared with less than 140 mm Hg. Although a pooled analysis of three studies (3632 participants) comparing different systolic BP targets suggested that intensive BP lowering reduced the rate of recurrent stroke, no clinical trials to date have tested the effect of such aggressive BP lowering for secondary stroke prevention.
In the Recurrent Stroke Prevention Clinical Outcome (RESPECT) Study, we herein tested the hypothesis that targeting intensive BP lowering of systolic and diastolic blood BP less than 120 mm Hg and less than 80 mm Hg, respectively, reduces the rate of stroke recurrence compared with a standard BP-lowering regimen. In this randomized clinical trial that included 1263 patients with a history of stroke, intensive blood pressure control to less than 120/80 mm Hg tended to reduce stroke recurrence compared with standard blood pressure control (less than 140/90 mm Hg). When this finding was pooled with the results of prior trials of intensive blood pressure control for secondary stroke prevention in an updated meta-analysis, intensive blood pressure treatment significantly reduced stroke recurrence by 22%.