This article is more than 5 years old. Information may no longer be current.
For BP management in diabetes, debate continues on optimal definition, targets
In November, a revised guideline from the American Heart Association, the American College of Cardiology and nine other societies redefined hypertension as blood pressure greater than 130 mm Hg/80 mm Hg. The updated guideline, which lowered the threshold for hypertension from 140 mm Hg/90 mm Hg and also eliminated the category of prehypertension, created a new diagnosis for millions of Americans virtually overnight.
For adults with diabetes, however, a debate continues regarding the optimal BP threshold and treatment target.
In September, a guideline issued by the American Diabetes Association included the more relaxed BP goal of less than 140 mm Hg/90 mm Hg for most people with diabetes and emphasized the need to individualize specific BP targets for each patient. The dueling American Heart Association (AHA) and ADA guidelines have been a source of debate since they were published: At professional meetings, clinicians continue to offer differing opinions on whether a mantra of “the lower, the better” or a more nuanced BP goal for some patients with diabetes is the right strategy.
“This is a timely topic and there has been a great deal of discussion and controversy among physicians,” Helena W. Rodbard, MD, FACP, MACE, medical director of Endocrine and Metabolic Consultants in Rockville, Maryland, and a past president of the American Association of Clinical Endocrinologists and the American College of Endocrinology, told Endocrine Today. “People with diabetes have an increased risk for cardiovascular events. We must not be narrowly glucocentric and address exclusively glycemic control. We must also address blood pressure and lipids in conjunction with glycemic control.”
Different trials have demonstrated potential CV risk and benefit — depending on diabetes status — when treating to a systolic BP target less than 120 mm Hg, further complicating the debate, according to experts.
“I am partial to the AHA/[American College of Cardiology] goal of 130/80 mm Hg,” Rodbard said. “The guidelines do recommend individualization. That’s true for glycemic control, and it’s true for blood pressure. We must use our clinical judgment, which takes priority over anything else. Some people advocate higher numbers. Lower is better, as long as it can be achieved safely.”
In an editorial published in the April 3 issue of JAMA, George L. Bakris, MD, FAHA, professor of medicine and director of the Comprehensive Hypertension Center at University of Chicago Medicine and Endocrine Today Editorial Board Member, and colleagues defended the higher ADA recommendation, noting that available evidence suggests that BP targets lower than 140 mm Hg/90 mm Hg yield CV benefits for some populations, but also increase risk for adverse events. The ADA recommendation, the researchers argued, distinguishes BP thresholds used to diagnose hypertension from those used as treatment targets, similar to ADA recommendations for HbA1c thresholds.
“If you look at the totality of the data that exists, 100% of it defends a blood pressure of < 140/90 mm Hg for people with diabetes, and for that matter, people without diabetes,” Bakris told Endocrine Today. “That is irrefutable, defendable and there should be no question about that. The real issue is, what are we doing arguing about 10 mm Hg lower? The old edict was, ‘Let’s get people as low as you can go.’ We know that’s wrong. So, where are we?”
A looming debate
Before the updated 2017 position statement, the ADA recommended treating to a systolic BP target of less than 130 mm Hg, but that goal was relaxed after findings from the ACCORD-BP trial demonstrated an increased risk for adverse events in adults with advanced type 2 diabetes treated to a target of less than 120 mm Hg vs. those treated to a target of less than 140 mm Hg. In ACCORD-BP, researchers observed no between-group differences for the primary composite CV outcome, which included myocardial infarction, stroke and CV death (HR = 0.88; 95% CI, 0.73-1.06), as well as an increased risk for adverse events in the intensive BP group, including elevations in serum creatinine and electrolyte abnormalities.
More recently, the SPRINT trial demonstrated that intensive control to a systolic BP of less than 120 mm Hg resulted in CV benefit in high-risk patients with hypertension — but without diabetes — vs. routine BP control to less than 140 mm Hg. In a recent post hoc analysis of ACCORD patients meeting SPRINT criteria (hypertension and at least one risk factor for CVD), researchers observed a benefit for the more intensive BP group; however, patients in both SPRINT and ACCORD had a greater than 15% 10-year CV risk.
“So, it becomes somewhat controversial as to whether we can apply those [SPRINT] results to people with diabetes, when in the ACCORD study it didn’t work,” Vivian A. Fonseca, MD, assistant dean for clinical research at Tulane University School of Medicine,told Endocrine Today. “We need to look at it in the context of in whom these trials were done. The ACCORD study population had much more advanced cardiovascular disease, where it may have been too late to change the natural course of the disease.”
In the 2018 consensus statement issued by the AACE and the American College of Endocrinology (ACE), the authors recommend that BP control be individualized, but that a target of less than 130 mm Hg/80 mm Hg is appropriate for most patients.
“Less stringent goals may be considered for frail patients with complicated comorbidities or those who have adverse medication effects, while a more intensive goal (eg, < 120/80 mm Hg) should be considered for some patients if this target can be reached safely without adverse effects from medication,” Endocrine Today Chief Medical Editor Alan J. Garber, MD, PhD, MACE, professor in the departments of medicine, biochemistry and molecular biology, and molecular and cellular biology at Baylor College of Medicine in Houston, and colleagues wrote in the consensus statement.
The lack of a randomized controlled clinical trial in patients with diabetes that is designed to assess targets for BP control with outcomes such as CV events and mortality have contributed to the confusion concerning an optimal target, according to W. Timothy Garvey, MD, FACE, professor of medicine and chair of the department of nutrition sciences at the University of Alabama at Birmingham.
“When you get a situation like that, you’re going to have disagreement because everyone has to put the available data, the existing clinical trials, together and try to come up with the best judgment on how to interpret the totality of the data,” said Garvey, also a co-author of the AACE/ACE consensus statement. “I’m in favor of the AACE and AHA/[American College of Cardiology] recommendations, which I think are in fairly good agreement, and that is to try to control blood pressure to 130/80 mm Hg or below in patients with diabetes, and even try to achieve 120/80 mm Hg if it can be safely achieved in patients with very high degrees of risk.”
Lower targets, increased risk
In adults with type 2 diabetes and comorbid hypertension without CVD, evidence has suggested that achieving a target systolic BP less than 130 mm Hg was not associated with a reduction in CV risk vs. similar patients treated to a systolic BP between 130 mm Hg and 140 mm Hg.
In an analysis published online in April in Diabetes Care, Eric Wan Yuk Fai, a doctoral student in the department of family medicine and primary care at the University of Hong Kong, and colleagues analyzed data from 28,014 adults managed in general outpatient clinics of the Hong Kong Hospital Authority with type 2 diabetes and hypertension (systolic BP 130 mm Hg) and without a prior history of CVD, recruited between 2009 and 2011. Participants were stratified into three achieved systolic BP groups: less than 120 mm Hg (n = 2,079; mean age, 67 years), less than 130 mm Hg (n = 10,851; mean age, 66 years) and less than 140 mm Hg (n = 15,084; mean age, 67 years). Participants were followed from baseline (date when patients first had an increase in antihypertensive drugs prescribed) to the date of CVD event, all-cause mortality or November 2015. Primary outcome was a CVD event, and secondary outcomes included incident coronary heart disease, heart failure, stroke and all-cause mortality. Researchers used Cox proportional hazards regression to estimate the effect of different systolic BP groups on the incidence of CVD events.
Using patients who achieved a systolic BP target of 140 mm Hg as the reference group, those who achieved a target systolic BP less than 120 mm Hg saw a marked increase in the incidence of CVD (HR = 1.67; 95% CI, 1.46-1.9); no difference in likelihood was seen in those who achieved a target systolic BP less than 130 mm Hg. Results persisted after stratifying by CVD subtype. Achieving systolic BP targets of less than 120 mm Hg and less than 130 mm Hg was associated with an increase in all-cause mortality, with HRs of 2.28 and 1.19, respectively (P = .003), when compared with patients treated to the systolic target of less than 140 mm Hg.
Differing findings associated with patient comorbidities and risk factors illustrate the need for individualized treatment, with goal decided on by the patient and clinician together, according to George Grunberger, MD, FACP, FACE, chairman of the Grunberger Diabetes Institute in Bloomfield Hills, Michigan.
The differing BP targets, he said, have the same underlying goal.
“It’s one thing to say, the higher the worse, and, theoretically, the lower the better, when you talk about glucose, HbA1c, LDL cholesterol and blood pressure,” Grunberger told Endocrine Today. “But if you have a sick individual with established atherosclerosis, for example, and you force that blood pressure down, will you actually be able to achieve immortality? That’s the dilemma with all these trials.”
“People sometimes view these guidelines as edicts from god,” Bakris said. “The reality is these are put together by people. It’s not just about the numbers. It’s about the patients and the process.”
But a lower BP target also reflects a reality that many patients simply will not reach it, Rodbard said.
“Different people are partial to one set of studies over another,” Rodbard said. “The reality is that most people don’t really achieve the goal of 130/80 mm Hg, just like most people don’t have an HbA1c of less than 7%.”
Rodbard said it is important to remember the motivation that comes with a lower BP target, for both clinicians and patients.
“A certain goal doesn’t mean we achieve that level,” Rodbard said. “If we start aiming for 140/90 mm Hg, people are going to be walking around at even higher [BP] levels. If you aim for 130/80 mm Hg, maybe the patient will achieve, say, 135/85 mm Hg, or somewhere in between.”
Management strategies
In position statements from AACE and ADA and the AHA/American College of Cardiology guideline, recommendations for the treatment of confirmed hypertension in people with diabetes are similar: angiotensin-converting enzyme (ACE) inhibitors, angiotensin II receptor blockers (ARBs), beta-blockers, calcium channel blockers (CCBs) and thiazide diuretics are favored choices for first-line treatment. The selection of therapies should be based on factors such as presence of albuminuria, CVD, heart failure and patient race.
For many patients with diabetes and comorbid hypertension, combination therapy with multiple agents is needed to reach a defined target. The AACE algorithm, for example, recommends that patients with BP 150 mm Hg/100 mm Hg or higher start immediately on combination therapy, including an ACE inhibitor or ARB, and one of the other agents.
“If the person comes in with BP 160/90 or above, you have to settle on at least two agents,” Garvey said. “It takes multiple agents to control substantially elevated BP in these patients. The only caveat is some of these patients might be overweight or obese, and weight-loss therapy can improve all the CV risk factors. So, weight loss is also a good option that’s been shown to lower BP while reducing the need for antihypertensives in some studies.”
Garvey said other therapy choices include one of the new vasodilatory beta-blockers, such as carvedilol, which has been shown to have fewer adverse metabolic effects vs. older beta-blockers.
Bakris noted that an ACE inhibitor or ARB does not have to be the first-line choice in the setting of diabetes without kidney disease, defined as an estimated glomerular filtration rate of less than 60 mL/min/1.73 m2 or at least 300 mg albuminuria per day.
“If you do not have kidney disease — microalbuminuria, which is not kidney disease, by the way — and an eGFR above 60, then I don’t care what you use,” Bakris said. “You can use a diuretic, a [renin-angiotensin-aldosterone system] blocker, a CCB, any of those are fine to get the blood pressure down. That’s what the ACC says, and that’s what [the ADA] says.
“The old edict of ‘You have diabetes, boom, you’re on an ACE inhibitor’ is gone,” Bakris said. “There is no evidence to support that rationale, but that doesn’t mean you shouldn’t do it.”
Increasing patient burden
For people with diabetes and hypertension, the biggest challenge in reaching an intensive BP goal is the need to take multiple antihypertensive medications, Rodbard said.
“Medication adherence and persistence are major concerns, particularly for people with chronic diseases, such as diabetes and hypertension,” Rodbard said. “As a clinician, I try to simplify the therapeutic regimen as much as possible, minimizing the number of drugs while maintaining efficacy.”
To help decrease medication burden when managing hypertension in the setting of diabetes, Rodbard said clinicians should prescribe therapies with complementary modes of action and opt for drugs that have prolonged effect.
In studies that aimed to achieve intensive BP control, the average number of agents used was 3.8, Grunberger said, adding that clinicians sometimes forget that it may take three or four agents to reach a BP target.
“That gets back to the original issue: What are you, as a clinician, going to ask patients to do, knowing that they are not going to feel any better?” Grunberger said. “No one ever comes to me saying, ‘My blood pressure hurts’ or ‘My cholesterol is really bothering me.’ And then I’m going to put them on 12 drugs that will certainly cause them financial strain no matter what insurance plan they have and, probably, one or more side effects, and they won’t feel any better. Then people are surprised that 60% of people are not still taking their medications at 1 year, and this is for life.”
Grunberger emphasized the importance of presenting patients with treatment options. Not every patient, he said, will want to take on the burden of intensive BP control, and it is important to discuss that idea up front.
“These days, I can bring anyone’s blood pressure, cholesterol or glucose down to any level I want, theoretically,” Grunberger said. “You have to look at a completely different issue: Will the patient with a specific blood pressure live a longer, happier life? We don’t have the answer for that.”
It is also important to consider other changes to improve other risk factors, Garvey said.
“When we talk about blood pressure, it’s important that we engage in total risk factor improvement,” Garvey said. “If we pay attention to glycemia, lipids and blood pressure all together, we can improve outcomes over and above paying attention to any one of those factors alone. So, blood pressure, yes, but, we must look at it in the context of the overall risk burden.” – by Regina Schaffer
- References:
- de Boer IH, et al. JAMA. 2018;doi:10.1001/jama.2018.0642.
- de Boer IH, et al. Diabetes Care. 2017;doi:10.2337/dci17-0026.
- Garber AJ, et al. Endocr Pract. 2018;doi:10.4158/CS-2017-0153.
- Wan EYF, et al. Diabetes Care. 2018;doi:10.2337/dc17-2443.
- Whelton PK, et al. Hypertension. 2017;doi:10.1161/HYP.0000000000000065.
- For more information:
- George L. Bakris, MD, can be reached at University of Chicago Medicine, 5841 S. Maryland Ave., Chicago, IL 60637; email: gbakris@medicine.bsd.uchicago.edu.
- Vivian Fonseca, MD, FRCP, can be reached at Tulane University Health Sciences Center, 1430 Tulane Ave. - SL 53, New Orleans, LA 70112; email: vfonseca@tulane.edu.
- W. Timothy Garvey, MD, FACE, can be reached at the University of Alabama at Birmingham, Director, UAB Diabetes Research Center, 1720 Second Ave. South, Birmingham, AL 35294; email: garveyt@uab.edu.
- George Grunberger, MD, FACP, FACE, can be reached at the Grunberger Diabetes Institute, 43494 Woodward Ave. #208, Bloomfield Hills, MI 48302; email: grunberger@gdi-pc.com.
- Helena W. Rodbard, MD, FACP, MACE, can be reached at Endocrine and Metabolic Consultants, 3200 Tower Oaks Blvd., Suite 250, Rockville, MD 20852; email: hrodbard@comcast.net.
Disclosures: Bakris reports he is a principal investigator for studies for Bayer, a steering committee member for trials sponsored by Janssen and Vascular Dynamics and a consultant for Merck, Relypsa and Vascular Dynamics. Fonseca reports receiving contracted research payments (paid to institution) from Abbott, Asahi, Eli Lilly, Endo Barrier, Gilead Sciences and Novo Nordisk; receiving consultant fees from Abbott, Amgen, AstraZeneca, Boehringer Ingelheim, Eli Lilly, Janssen, Novo Nordisk, Pamlab, Sanofi-Aventis and Takeda; and serving on speakers bureaus for Abbott, Amgen, AstraZeneca, Boehringer Ingelheim, Eli Lilly, Janssen, Novo Nordisk, Pamlab, Sanofi-Aventis, Takeda. Garvey reports he is a consultant for the American Medical Group Association, Merck and Novo Nordisk. Rodbard reports she has received grant support and consultant fees from AstraZeneca, Boehringer Ingelheim, Janssen, Lilly, Novo Nordisk and Sanofi.
Click here to read the 
, "Should patients with diabetes, microalbuminuria and normal BP be treated with renin-angiotensin system blockade?"