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TIGHTER CONTROL OF BLOOD PRESSURE CAN PREVENT MORE STROKES
SAN ANTONIO, TEXAS—One of the major central nervous system consequences of hypertension is stroke,” said Philip A. Wolf, MD. “Clinically, as we move from a younger to an older age-group, as the blood pressure goes up, the incidence of stroke increases.” According to the 140/90 criteria set forth in the Sixth Report of the Joint National Committee on the Prevention, Detection, and Treatment of High Blood Pressure (JNC-6), roughly two thirds of Americans have hypertension. Two thirds of those in the age-group between 65 and 89 have isolated systolic hypertension on the order of 160/90. In those people who have this severe hypertension, stroke incidence is very high.
“However,” Dr. Wolf added in his address to the 27th International Stroke Conference, “most strokes occur not in people with severe hypertension but in those with mild hypertension, with systolic readings between 140 and 159. This is true of hemorrhagic as well as ischemic stroke, so in terms of public health problems, you have to pay attention to mild as well as severe hypertension when checking for stroke.” Incidence of stroke was shown to increase among high normals (130 to 139) compared to those with normal, average blood pressure (< 130). “According to JNC-6 systolic hypertension criteria, 20% of strokes occur in persons with high moderate hypertension and 30% in those with mild hypertension (140 to 159), together accounting for half of the strokes that occur. If you add to these groups persons with high normal blood pressure (130 to 139), you have almost three quarters of the total strokes occurring in categories of less than severe hypertension (180 +). Therefore, we have to focus on these less severe levels of elevated blood pressure,” Dr. Wolf recommended. He is a Professor of Neurology at Boston University School of Medicine.
AN IMPORTANT PART OF STROKE RISK
“It’s clear that blood pressure is only one ingredient for risk of stroke and that the presence of associated risk factors such as diabetes, cigarette smoking, and other cardiovascular diseases each adds something to the risk of stroke,” Dr. Wolf said. “A man age 70 with a systolic blood pressure of 120 and associated risk factors has a risk of stroke substantially higher than a man of the same age with a systolic blood pressure of 180 but without the attendant risk factors.”
Nonetheless, hypertension alone doubles your risk of having silent infarcts, and “as systolic blood pressure increases, there is an increase in white matter hyperintensities in the brain. We also looked at brain atrophy and related it to the Framingham stroke risk profile. As far as the relation [of hypertension] to the total cerebral brain volume, the brain is obviously smaller, with a strong inverse relationship between the total stroke risk score and the total cerebral brain volume,” he added.
REDUCING THE RISKS
After Dr. Wolf’s illumination of the causal relationship between hypertension and stroke, William Elliott, MD, PhD, Professor of Preventive Medicine, Internal Medicine, and Pharmacology at Rush Medical College of Rush University at Rush– Presbyterian–St. Luke’s Medical Center in Chicago, spoke on the topic of reducing blood pressure and, subsequently, the risk of stroke. In what he termed “the longest title ever for a 20-minute lecture,” Dr. Elliott addressed three questions: Are lifestyle modifications effective? Does it matter which agent is used? Does it matter to what level blood pressure is lowered? “The objectives are pretty simple,” he said. “There are already lifestyle modifications that have been shown to reduce blood pressure.” These include attaining and maintaining ideal body weight, restricting dietary sodium intake, reducing alcohol consumption “to less than 2 oz per day for men and less than 1 oz per day for women,” and increasing physical activity.
“These are all things that have been shown in repetitive studies to lower blood pressure,” Dr. Elliott elaborated. “There are other interventions that are considered adjunctive but for which we don’t have any clinical trial information. We’re all told to maintain adequate intake of potassium, calcium, and magnesium, and reduce our saturated fat and increase our dietary fiber, and of course we should not smoke. The good news is that this stuff does work. For example, when you do lose weight and keep it off for a year, your blood pressure ends up lower than it was at the start, and that’s the way it’s supposed to work.”
OTHER PREVENTIVE MEASURES
Dr. Elliott described the Trial of Hypertension Prevention as “a very large study of fairly young people with diastolics not quite in the hypertensive range. It showed that weight reduction was the most effective therapy, salt reduction was the second most effective measure, and everything else didn’t seem to work very well.”
In particular, Dr. Elliott focused on the DASH (Dietary Approaches to Stopping Hypertension) trial’s sodium-related findings. “If you eat a controlled diet and intake low sodium, your blood pressure—both systolic and diastolic—is significantly reduced compared to those taking high salt,” he observed. “The problem is that reducing sodium works particularly well in short-term studies, but when you look at long-term studies, unfortunately it seems that as time goes on people don’t restrict themselves as well in terms of diet, and certainly they don’t lower their blood pressure very well. At least in the Hypertension Prevention Trial, a few years down the road it pretty much didn’t make any difference whether participants received advice to reduce dietary sodium—probably because they didn’t continue it.
“Nonetheless,” he said, “dietary salt restriction is a good idea. Data from the MEAS-1 study show that in the overweight people at a 19-year follow-up, a 100-mmol increase in sodium intake was significantly associated with a higher risk of stroke by 32% and, furthermore, almost a doubling of stroke mortality. So, increasing sodium intake is not generally a good idea, particularly if you are overweight in the United States.”
Additionally, “when you look at older cohorts, what you see is that sodium restriction and weight loss actually keep more people off of their pills and out of the hospital as compared to people who don’t restrict their salt and don’t lose any weight. So if you want to keep people off their pills and nonhypertensive, the best thing to do is both salt reduction and weight loss,” he advised.
ARE LIFESTYLE MODIFICATIONS ENOUGH?
The closest we can come to a randomized clinical trial for the relationship between lifestyle modifications and stroke is the Treatment for Mild Hypertension Study, Dr. Elliott said. “Unfortunately the primary event here was not stroke but major coronary disease events. Even so, when you look at lifestyle modifications alone as compared to those who got lifestyle modifications in addition to drug therapy, coronary heart disease was still reduced, but the P value for the trial is not particularly impressive and not significant. The fun part about this is when you put in stroke with the other major events, all of a sudden this P value becomes very interesting. Lifestyle modifications are not as impressive in reducing cardiovascular and other events [such as stroke] as compared with drug therapy plus lifestyle modifications,” he noted.
“So, if you ask me, the answer to the first question—should we be giving lifestyle modifications to everybody?—is yes,” Dr. Elliott said. “Lifestyle modifications are effective in lowering blood pressure in the short-term but not so effective in the long-term, and they are probably inferior to medications in preventing stroke, although there’s no clinical trial information to prove that point,” he concluded.
A WIDE ARRAY OF ANTIHYPERTENSIVES
The second question Dr. Elliott addressed was whether it matters which antihypertensive agent is used to reduce blood pressure. “Very few large comparative trials have been done up to 1997 which compared a particular antihypertensive drug to another active therapy,” Dr. Elliott said. “But I’m pleased to say that [in placebo-controlled trials] placebo has never been more effective than any antihypertensive drug.”
Whether some drugs are better than others at preventing stroke is somewhat controversial, he admitted. “We’re gathering data on this even now through some meta-analyses of clinical trials. If you look at diuretics and beta blockers, if you look at low- and high-dose diuretics, if you look at beta blockers alone, etc, it shows that clearly any drug is better than a placebo in preventing stroke.”
According to a current hypothesis, Dr. Elliott continued, calcium channel blockers may be more effective than other methods at preventing stroke. “A comparison of all therapies showed there is about a 10% reduction on the calcium channel blocker side compared to the other therapies, but it is not quite statistically significant,” he said. “There was a [recent report] in the Journal of the American College of Cardiology that claims this is wrong and that it is significant, but before we get too excited, please broaden your perspective a little beyond stroke as the only important end point. Consider the fact that if a person has a heart attack or heart failure or any major cardiovascular event with a therapy that prevents stroke, you may not be doing them an big favor overall. Such complications are more common when you give calcium agonists as compared to other antihypertensive therapies, and so, some caution is suggested in recommending calcium agonists to prevent stroke because of the other things that they may not prevent as well,” Dr. Elliott advised.
“The only drug that we have right now that should not, according to some, be used as initial therapy for hypertension is an alpha blocker,” he noted. “Almost 10% more people had cardiovascular events on alpha blockers than on diuretics, and many of those turned out to be heart failure, where the risk was in fact doubled.”
HOW LOW CAN YOU GO?
“The last question I was asked to address is how much do you lower blood pressure,” Dr. Elliott said. “This goes back to the question of whether there is a blood pressure beyond which lowering the blood pressure further is harmful? The only direct evidence so far, if you look at this in randomized treatment, is from the HOT study, which randomized almost 18,000 patients to diastolic blood pressure less than 80, 85, or 90 and then followed them for 3.8 years looking for stroke, heart attack, or cardiovascular disease–related death. What they found for stroke was that you didn’t prevent or cause more strokes by having a person’s diastolic blood pressure less than or equal to 80 as compared to 85 or 90—it wasn’t significantly different. However, the diabetic population showed statistical significance for diastolic less than 80 reducing overall risk of cardiovascular events.
“Probably,” Dr. Elliott contended, “most patients with hypertension will be told to keep their blood pressure less than 140/90. People with diabetes and renal impairment are now beginning to show 130/80 as the target level, and the American Diabetes Association and the National Kidney Foundation both believe this is a solid way to improve cardiovascular disease rates in diabetics.”
END POINTS
“Lifestyle modifications, especially weight loss and sodium restriction, are effective short-term ways to lower blood pressure, but they are less effective than drug therapies at reducing strokes in the long-term,” Dr. Elliott said in review. “Any hypertensive agent that lowers blood pressure is probably going to reduce stroke risk. Probably, alpha blockers are worse than other drug classes; however, it’s not because of strokes but because of heart disease, and heart failure particularly, that this is no longer recommended as initial, naked, single-agent therapy. Blood pressure should be reduced to 140/90 in cases of uncomplicated hypertension and lower in patients with diabetes or renal impairment. How much lower, we can argue about later,” he demurred.
What is certain is that, as Dr. Wolf noted, “of the 42 million people with hypertension, 32 million are unaware, untreated, or uncontrolled. This is a large population for whom improving risk factors would be recommended … particularly because hypertension can promote vascular injury to the brain through mechanisms other than stroke, and management of the risks may improve outcomes even in clinically stroke-free subjects.”
NR
—C. Justin Romano
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