Multiple Risk Factors in the Hypertensive Patient: A Clinical Perspective

At a session held May 15, 2002, during the ASH annual meeting, four experts discussed how to manage multiple risk factors in the hypertensive patient.

This program was supported by an educational grant from Pfizer, Inc.

Global Risk Management for Cardiovascular Disease

Peter W. F. Wilson, MD, Professor of Medicine, Boston University School of Medicine, and director of laboratories for the Framingham Heart Study, described various aspects of risk assessment for cardiovascular disease, focusing on blood pressure measurement.

“In terms of blood pressure, population studies all seem to lead back to systolic pressure as the strongest risk factor,” he said, “while isolated systolic hypertension—which is common among the elderly—is a major risk factor in itself.”

In the past, population studies that looked at vascular risk prediction for coronary heart disease relied on continuous variables. This is changing, Dr. Wilson noted, with levels and categories becoming increasingly popular, as they don’t require exact knowledge of measurements. Risk factors generally include age, sex, BMI, blood pressure, total cholesterol, HDL, LDL, smoking, and diabetes.

“You no longer need a pocket calculator to make these estimates, you can do them with categories and score sheets,” said Dr. Wilson.

Risk tables can be downloaded from the American Heart Association and the National Heart, Lung and Blood Institute web sites, Dr. Wilson said. The programs can be used on Palm Pilots, making it easy to make calculations for individual patients. The programs are also helpful for explaining this information to patients, he noted.

Factors involved in diabetes, Dr. Wilson emphasized, are a crucial aspect of risk assessment for hypertensive patients, particularly those who have suffered a previous heart attack. Even the early stages of diabetes can boost risk, and it is possible to use this information to calculate risk as well.

For many patients, knowing LDL alone is not enough. It is important to determine whether they have insulin resistance syndrome. But, he noted, tests to identify the syndrome, such as resistance to insulin-stimulated glucose uptake are expensive and difficult to perform. Surrogates are available, however, including measuring hyperinsulinemia, glucose intolerance, hypertension, triglycerides, decreased HDL, and abdominal adiposity.

And with diabetic patients, the influence of other risk factors must be ratcheted up. The metabolic syndrome will be an increasingly important aspect of risk assessment.

Dr. Wilson concluded that “the categories rather than the continuous variables seem to work quite well in determining risk.” It’s best, he added, not to rely on a single measurement but to measure factors two or three times and use the averages to estimate risk for cardiovascular disease.

Limitations of guidelines, he pointed out, include the fact that they tend to rely on white middle class populations and many of the algorithms were developed before current treatments became available. The newer guidelines, he said, will attempt to correct this.

Global Risk Management Guidelines: JNC VI, NCEP, ATP III and ADA

“What are guidelines good for?” asked Henry R. Black, MD, the Charles J. and Margaret Roberts Professor and Chairman, Department of Preventive Medicine, Rush-Presbyterian-St. Luke’s Medical Center. “In today’s ever-more complex medical environment, when doctors have less and less time to keep up to date with the latest research, they are crucial,” he said. And to stay up to speed in preventive cardiology may be even more difficult than in other areas of medicine, he added.

Guidelines are needed not just to make treatment decisions but also to put lifestyle modification into perspective, to provide advice about evaluation, to emphasize public health, and to highlight the needs of special populations.

Several sets of guidelines are available for hypertension: the Joint National Committee VI report (JNC VI) completed in 1997; the World Health Organization and International Society of Hypertension guidelines, the latest version of which was completed in 1999; and guidelines from various national societies.

Dr. Black began by addressing the JNC VI guidelines. While these guidelines state that lifestyle modifications should be the first step for nearly everyone, there are only a handful of people with hypertension for whom these modifications will likely be enough. This lowest-risk group—women before menopause with no target organ damage—represents about 6% of all people with high blood pressure in the U.S., Dr. Black noted.

With people in this risk group A, it’s possible to wait for 12 months for lifestyle changes to get blood pressure to goal. For people in risk group B—those with another risk factor—if lifestyle changes alone have not reduced blood pressure to goal after 6 months, drug treatment should begin. And for those in Group C, with diabetes or end organ damage, drug treatment should begin even if their blood pressure is in the high normal range.

For all patients, the goal is to begin treatment with small doses of drugs—in some cases as fixed low-dose combinations—and titrate upward. Treatment can begin with diuretics, beta blockers, ACE inhibitors, calcium antagonists, or angiotensin receptor blockers (ARBs), all of which have been shown to reduce morbidity and mortality. Dr. Black believes that all five classes of drugs will likely be included as first-line therapy in the next set of JNC recommendations.

Some drugs provide added benefit for other conditions, which can help physicians determine which to choose. For example, alpha-blockers can help men with prostatism, while thiazides may be helpful for those who are at risk of osteoporosis.

JNC V recommended substituting or adding drugs, but Dr. Black questioned the wisdom of sequential monotherapy. “It makes more sense to add a second agent to the first one, and that ought to be a diuretic if you haven’t used that first,” he said. If a two- or three-drug combination doesn’t get the patient to the goal, Dr. Black recommended referring the patient to a hypertension specialist.

For high LDL, lifestyle changes are recommended, and statins are the drug therapy of choice. If goal is not reached, resins could be added to statins. For LDL with high triglycerides, lifestyle modification plus fibrates, niacin, or fish oil should be tried. For diabetic dyslipidemia, LDL cholesterol also is the primary target, he added, even though HDL-cholesterol is often low and triglycerides high.

It’s often difficult to treat patients with low HDLs, he noted. “These patients ought to achieve the LDL goal and then work on increasing HDL through weight loss and exercise,” he advised.

Dr. Black closed by discussing patients with hypertension and diabetes. The goal for such patients should be to bring blood pressure down to less than 130/85 mm Hg. Begin with ACE inhibitors or ARBs, he advised, and titrate. If this doesn’t bring the patient to the goal, add thiazides.

The American Diabetes Association recently changed its guidelines to recommend ACE inhibitors or ARBs if a patient has no proteinuria or microalbuminuria. For patients on ACE inhibitors who’ve had an MI recently, beta blockers should be added.

The stricter goals imposed by JNC VI may be too tough to achieve, he noted. “I think one of the problems with some guidelines is that they’re unachievable,” Dr. Black said. “Guidelines should be achievable or people will throw up their hands and say, why bother, I can’t do it.”

Guidelines have helped bring more effective treatment into practice, he continued, for example, the use of systolic measurement as a better predictor of risk than diastolic pressure, reasonable recommendations about the use of calcium antagonists, and the treatment of older people with hypertension.

Practical Applications of Global Risk Guidelines: Interactive Case Study Presentation and Discussion

To provide some concrete examples of how to use global risk guidelines, Steven M. Haffner, MD, and Richard H. Grimm, Jr., MD, PhD, presented three studies on patients with hypertension and multiple risk factors.

Dr. Haffner is Professor of Internal Medicine, Department of Internal Medicine, Division of Clinical Epidem-iology, University of Texas Health Science Center. Dr. Grimm is Director of the Berman Center for Clinical Outcomes and Clinical Research and Section Head of Clinical Epidemiology, Hennepin County Medical Center in Minneapolis.

Dr. Haffner began by noting that he is often asked whether the metabolic syndrome carries the same risks as diabetes. The risk with metabolic syndrome is intermediate between coronary heart disease and diabetes and normal risk, he noted, “so you shouldn’t necessarily try to think about them as equivalent to CHD.” Also, he pointed out, while people with diabetes tend to have the metabolic syndrome, not all of them do.

Case #1
Dr. Haffner presented the first case, a 50-year-old woman who has had diabetes for three years. She takes no medicines and doesn’t smoke. Her BMI is 29. Her blood pressure is 155/90, her hemoglobin A1C is 7.5%. Her HDL is 38, her triglycerides are 350, and her total cholesterol is 258. Her urine albumin is 80 mg/day, above the microalbuminuria cutpoint of 30 mg/day, and she has normal TSH.

The normal TSH is important, Dr. Haffner noted, because hypothyroidism can raise LDL cholesterol. “Everybody with a seriously elevated LDL should get their thyroid functions measured,” he said.

Under the new NCEP ATP III guidelines, he pointed out, the woman’s relatively short duration of diabetes would make it a coronary artery disease equivalent. Then her LDL goal would be less than 100.

“I think you would start with pharmacologic therapy at the same time as you’d start with behavioral therapy, and that therapy is likely to be a statin in this case,” Dr. Haffner said. The behavioral therapy would involve encouraging her to lose weight, increase physical activity, and reduce her intake of saturated fat.

Under the various guidelines, he continued, the goal would be to reduce this patient’s blood pressure to high normal, and the American Diabetes Association guidelines would actually suggest bringing it down below 130/80. An ACE inhib-itor, though it is not clear which one, would be recommended.

After the patient has been following the behavioral program and taking 10 mg of atorvastatin, her BMI is down to 28, blood pressure is at 145/82, and her HbA1C is 7%. Her LDL is 95, while her HDL is 41 and her triglycerides are 270. Her urine albumin has been brought down to 50 mg a day.

The next step, because her blood pressure is still too high, would be to increase her atorvastatin dose and add amlodipine and tell the patient to return 6 weeks later. Upon her return, her blood pressure is 137/77 and her hemoglobin A1C is 6.8%. The HDL stayed the same, while the LDL went down to 85, and the urine albumin dropped to 35 mg per day.

Continued focus on controlling the woman’s blood pressure would likely help bring her urine albumin down further, Dr. Haffner said.

Case #2
Next, Dr. Grimm presented two cases based on his current research. “Both of these cases come from clinical trials, so we’re not following guidelines so much as we’re doing studies trying to get evidence to set new guidelines,” he said.

Case #2 is a 59-year-old African-American woman who has had diabetes for 3 years. While she was a heavy smoker for many years, she quit about 10 years ago. She has no history of angina, but a strong family history of atherosclerotic heart disease.

When the woman came in for evaluation she was taking 500 mg of metformin a day, Dr. Grimm explained. She was obese, although the rest of her physical was fine. She had “significant albuminuria,” and a blood pressure of 147/89 (isolated systolic hypertension). Her hemoglobin A1C was 9.9%, her total cholesterol was 240, her triglycerides were 220, her HDL was 48 and her LDL was 140.

The woman was started on 20 mg of lisinopril and 10 mg atorvastatin a day. She came back after a month and her blood pressure was not much improved, so amlodipine was prescribed. After 3 months, her blood pressure was down to 134/82, and chlorthalidone was added. In a month, her systolic pressure had come down to 117.

Dr. Grimm presented the woman’s risk for cardiovascular disease before and after treatment, which was based on the Framingham-like risk predictions from the Multiple Risk Factor Intervention Trial (MRFIT). While her 15-year risk of coronary heart disease death was 24% when treatment began, about 9 months later it was down to 6%.

“This tool does not eliminate the need to assess patients’ risk using the Framingham point system,” said Dr. Grimm. “But it is useful for motivating patients to make changes and for showing them how well they’ve done for positive support and to reinforce favorable risk factor changes,” he noted.

Case #3
Case #3 is a 61-year-old white woman who is a participant in a large clinical trial. She’s had hypertension for 4 years, and diabetes for about 11 years. She had suffered an MI and a CVA a couple of years before entering the program. The woman had a history of high cholesterol, and while she had been a heavy smoker in the past she quit about 6 years before entering the program.

Upon entering the program, the woman weighed 165 pounds and her blood pressure was 154/77, meaning she also had isolated systolic hypertension. Her cholesterol was 325, LDL 192, HDL 42, and triglycerides 450. Her hemoglobin A1C was 7.1%, her creatinine was 0.8, and she tested negative for urine albumin.

Dr. Grimm and his colleagues started the woman on an ACE inhibitor and a diuretic. But within a month, the drugs had to be stopped because the woman developed a cough. The doctors switched the woman to chlorthalidone 12.5 mg and atorvastatin. A month later, an ARB and diuretic combination was added. The following month, her ARB dosage was boosted and amlodipine was added at 5 mg. The woman’s atorvastatin dose was also increased to 20 mg at this time.

The woman’s systolic pressure was still at 138 two months later, so reserpine (0.1 mg) was added. “This may seem odd because reserpine hasn’t been used for some time,” he said. But NIH studies have shown that older drugs like this one, as well as clonidine and hydralazine, have been helpful in further bringing down blood pressure in patients for whom multiple drug regimens aren’t doing the job.

This brought the woman’s systolic pressure down to 110 mmHg. Eight months after therapy was initiated her weight was down to 152. The woman’s total cholesterol was 188, her triglycerides were 200, her LDL cholesterol was 96 and her HDL was 48. Her hemoglobin A1C also improved, to 6.8%. While her estimated 15-year risk of coronary heart disease death was 39% when she began treatment, after 9 months of treatment it was 8%.

All contents Copyright © 1999 - 2002 Medical Association Communications