BP Lowering Reduces Vascular Risk Regardless of Baseline BP and Disease History

A 10-mmHg reduction in systolic blood pressure significantly reduces the risk of major cardiovascular events and mortality in a wide range of patients, including those with established cardiovascular disease and those with already low systolic blood pressures, according to the results of a large meta-analysis and review.

Overall, the 10-mmHg reduction in systolic blood pressure translated into a 20% reduction in major cardiovascular events, a 17% reduction in coronary heart disease, a 27% reduction in stroke, a 28% reduction in heart failure, and a 13% reduction in all-cause mortality.

“The effect of blood-pressure lowering was proportional to the degree of blood-pressure lowering, meaning the more aggressively blood pressure was lowered, the greater the benefit observed in terms of the risk of cardiovascular disease,” senior investigator Kazem Rahimi, MD, George Institute for Global Health (Oxford, UK), told TCTMD.

The results of the meta-analysis, which the researchers say are consistent with and extend the findings of the SPRINT trial, are published December 23, 2015 in the Lancet. In total, 123 studies with 613,815 patients were included in the analysis. SPRINT, a National Institutes of Health (NIH)-funded study that showed treating to a systolic target below 120 mmHg reduced the risk of MI, acute coronary syndrome, stroke, heart failure, or cardiovascular death when compared with the standard target of 140 mmHg, was included in the meta-analysis.

To TCTMD, Rahimi said elevated blood pressure is one the biggest killers worldwide and while it is well known that lowering blood pressure in patients with hypertension reduces cardiovascular events, less well known are the benefits of lowering blood pressure among individuals with blood pressure considered to be normal.

In their analysis, among individuals with systolic blood pressures less than 130 mmHg at baseline, major cardiovascular events were reduced 37% with a 10-mmHg reduction in blood pressure, while coronary heart disease was reduced 45%, stroke by 35%, heart failure by 17%, and all-cause mortality by 47%.

In addition to observing significant reductions in major cardiovascular events across a wide range of patients, including patients with systolic blood pressures >160 mmHg and those with systolic blood pressures <130 mmHg, as well as those in between, they also observed a significant benefit in patients with and without cardiovascular disease, coronary artery disease, or cerebrovascular disease.

With a 10-mmHg reduction in systolic blood pressure, major cardiovascular events were reduced 23% in those with cardiovascular disease and 26% in those without disease. In terms of all-cause mortality, individuals with cardiovascular disease had a 10% reduction in risk with each 10-mmHg reduction in blood pressure compared with the 16% reduction in risk among those without cardiovascular disease.   

“There was no evidence of a harmful effect of blood-pressure lowering, even at the lower thresholds, on kidney function,” said Rahimi. “There was no excess risk of renal failure, which SPRINT, to some extent left open.” In that trial, intensive treatment was associated with an increased risk of adverse events, such as hypotension, syncope, electrolyte abnormalities, and acute kidney injury or failure, but Rahimi said the totality of evidence does not suggest harm to the kidney with aggressive blood pressure lowering.

Call for a Revision to Current Treatment

Based on their evidence, the researchers are calling for a rethink of recently revised hypertension guidelines that—amid controversy—relaxed the treatment thresholds, with different groups making different recommendations. In the US, the Eighth Joint National Committee (JNC8) guidelines recommended treating patients 60 years of age and older to a relaxed target of 150/90 mm Hg, with a target of 140/90 mm Hg for younger individuals.

“What we’re saying is a departure, not only from targets, but also a departure from making the blood-pressure change the goal of the intervention,” said Rahimi. “What we’re saying is similar to what we’ve seen with the cholesterol guidelines with statins. The approach should be based on the individual’s total cardiovascular disease risk. If somebody has substantially elevated cardiovascular risk, irrespective of what their blood pressure is, then a discussion should take place between the physician and the patient about whether blood-pressure lowering is something they would benefit from.”

The key, he added, is not the patient’s absolute blood pressure but their absolute risk of cardiovascular events.

In an editorial, Stéphane Laurent, MD, and Pierre Boutouyrie, MD, of the University of Paris Descartes (Paris, France), point out there was no significant trend toward increased risk for any of the reported outcomes. “Thus, a J-shaped relationship could not be substantiated and the treatment effects were unlikely to be attenuated in trials that included participants with low systolic blood pressures at baseline, particularly those with less than 130 mmHg,” they write.

As for the revision to the guidelines—treating based on risk rather than a rigid blood-pressure target—Laurent and Boutouyrie argue that “since data are accumulating against the J-shaped relationship, and because energetic lowering of blood pressure seems safe and beneficial to patients, there is no reason not to apply it to high-risk patients.”

The editorialists also note the analysis examined the effects of various antihypertensive medications in clinical outcomes, and while each drug class had similar overall effectiveness in preventing cardiovascular outcomes, beta-blockers fared worse for the prevention of major cardiovascular disease, stroke, and renal failure. Calcium-channel blockers appeared a stronger choice for preventing stroke and diuretics were better than the other classes for preventing heart failure.

“These findings support the results of previous studies and thus extend the evidence available for drugs to be used preferentially in specific conditions,” write Laurent and Boutouyrie. “However, as acknowledged by the authors, the present meta-analysiscannot determine the resulting effect of combinations of drug treatments that are increasingly prescribed in routine clinical practice.”

Sources: 
1. Ettehad D, Emdin CA, Kiran A, et al. Blood pressure lowering for prevention of cardiovascular disease and death: a systematic review and meta-analysis. Lancet 2015; epub ahead of print.
2. Laurent S, Boutouyrie P. Blood pressure lowering trials: wrapping up the topic? Lancet 2015; epub ahead of print.

Disclosures:

• Rahimi reports no conflicts of interest.
• Boutouyrie has received research grants from Servier. Dr. Laurent reports no conflicts of interest.