Management of Patients with Diabetes and Resistant Hypertension
Diabetic patients with hypertension have an increased risk of cardiovascular disease (CVD), necropathy, and chronic kidney disease compared with non-diabetics.1 Resistant hypertension is particularly concerning among diabetics.
Dr. Vivian Fonseca, Professor of Medicine and Pharmacology, Tulane University Health Sciences Center, discusses the significance of resistant hypertension in diabetic patients and approaches for effective patient management.
Hypertension and Diabetes
The coexistence of hypertension in diabetes is of concern because of the strong linkage with CVD, stroke, progression of kidney disease, and diabetic retinopathy. It has been demonstrated that a progressive decrease in systolic blood pressure (SBP) is associated with average reductions in rates of diabetes-related mortality, myocardial infarction, and the microvascular complications of retinopathy or nephropathy. Studies including large diabetic populations have demonstrated that adequate BP control improves CVD outcomes, especially stroke, when aggressive BP targets are achieved.1
Resistant hypertension is most commonly defined as blood pressure greater than 140/90 mmHg in patients who are treated with 3 antihypertensives, including a diuretic, or controlled hypertension on 4 or more agents.1 Resistant hypertension is distinct from non-controlled hypertension, which includes those noncompliant with therapy, and does not apply to patients whose blood pressure measurement is subject to a “white-coat effect.”
There is no definitive estimate for the prevalence of resistant hypertension in the United States. According to data from the National Health and Nutrition Education Survey (NHANES) from 1988-2000, only 53.1% of people taking medication for hypertension had blood pressure that was under control, or 31% of all hypertensive participants. Of those with diabetes only one-quarter had their hypertension controlled.2
The Antihypertensive and Lipid Lowering Trial to Prevent Heart Attack (ALLHAT) attempted to distinguish resistant from uncontrolled hypertension. It found that after 5 years of follow-up, 27% of participants were on 3 or more medications and 49% of participants were controlled on 1–2 medications with 50% requiring 3 or more.3 In a study of 1,911 treated hypertensive patients followed for almost 4 years, 19% were found to be resistant at the end of the study.4 Independent variables included diabetes, history of cardiovascular disease, duration of hypertension, left ventricular hypertrophy, and estimated glomerular filtration rate (eGFR).
Resistant Hypertension and Diabetes
“Blood pressure control in diabetes is extremely important,” says Dr. Fonseca. “It has a huge impact on complications, particularly necropathy, and cardiovascular events.” It has been shown that chronic kidney disease and advanced retinopathy are significantly higher in individuals with resistant hypertension than in those with nonresistant hypertension or uncontrolled hypertension. Patients with resistant hypertension were older, more frequently women, and had significantly higher waist circumference, albuminuria and serum creatinine, and lower glomerular filtration rate.5
Managing Resistant Hypertension in Diabetics
“There’s some confusion about what the goal of treatment should be, based on the results of some recent studies,” notes Dr. Fonseca. “The Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure(JNC 7) recommended that BP in diabetics be controlled to levels of 130/80 mmHg or lower.6 Subsequent studies, in particular the ACCORD study, showed that targeting SBP of 120 mmHg did not reduce events compared to people whose SBP was in the range of 130-140 mmHg.7 Furthermore, the greatest risk reduction appears to be in people who had much higher SBP of 150 or 160 mmHg. A reduction of SBP to 140 mmHg resulted in a significant reduction in events.
“As a result of these findings, the American Diabetes Association (ADA) has moved its SBP goal from less than 130 mmHg to less than 140 mmHg, with the caveat that some people may benefit from lower levels, particularly those with kidney disease.8 The guideline published by the Eighth Joint National Committee (JNC 8) also recommends a target blood pressure of 140/90 mmHg.1
“It should be noted that the SPRINT trial was recently published and showed that in non-diabetic patients an SBP of 120 mmHg led to a reduction in cardiovascular events.9 While SPRINT did not include anyone with diabetes, you now have a discrepancy between two major trials, which the medical community is not quite sure how to interpret.
“The bottom line, however, is that the ADA and others now have a SBP goal of less than 140mmHg. If we could achieve that in all of our patients, that would be wonderful. There are, however, are a lot of patients whose blood pressure remains above 140.”
Diagnostic and Therapeutic Approaches
“A patient who is on appropriate hypertensive therapy, including a suitable diuretic, but remains hypertensive, would typically be considered as having resistant hypertension,” says Dr. Fonseca. “At this point I think about those factors which are correctable and those which are not.
“The correctable factors include some of the endocrine disorders that are more common in people with diabetes, such as hyperaldosteronism (hyperaldo), and occasionally pheochromocytoma. Part of the reason for hyperaldo may be that in diabetics there is increased sympathetic over-activity and chronic sympathetic stimulation, which may stimulate the autonomy of the endocrine system, leading to hyperaldo. The test that should be performed is the aldosterone/plasma renin activity ratio. I may also order a 24-hour urine hyperaldo test, and may check the potassium level.
“I think there’s a lot of hyperaldo that’s missed. We’ve come to recognize this in the last few years and started to consider whether we should be screening more frequently for hyperaldo. We need to teach clinicians how to work people up for hyperaldo and how to approach it from a diagnostic perspective so that they can then treat the patient appropriately.
“Pheochromocytoma is a much rarer condition. Diagnosis includes plasma metanephrine testing and 24-hour urinary collection for catecholamines and metanephrines.
“Finally, there is the rare patient in whom no cause for resistant hypertension can be found. In these patients, we need to find the most suitable medications to control their condition.
“Resistant hypertension in diabetic patients is a concern. Given the importance of blood pressure control in this population, physicians must pay them adequate attention to find out why they’re not responding to treatment and to make sure they’re receiving appropriate therapy.”
1. James PA, Oparil S, Carter BL, et al. 2014 Evidence-Based Guideline for the Management of High Blood Pressure in Adults: Report From the Panel Members Appointed to the Eighth Joint National Committee (JNC 8). JAMA. 2014;311:507-520.
2. Hajjar I, Kotchen TA. Trends in prevalence, awareness, treatment, and control of hypertension in the United States, 1988 –2000. JAMA. 2003; 290:199 –206.
3. The ALLHAT Officers and Coordinators for the ALLHAT Collaborative Research Group. Major outcomes in high-risk hypertensive patients randomized to angiotensin-converting enzyme inhibitor or calcium channel blocker vs diuretic: the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial. JAMA. 2002;288:2981–97.
4. Tsioufis C, Kasiokogias A, Kordalis A, et al. Dynamic resistant hypertension patterns as predictors of cardiovascular morbidity: a 4-year prospective study. J Hypertens. 2014;32:415–22.
5. Solini A, Zoppini G,, Orsi E, Fondelli C, Trevisan R, et al. Resistant hypertension in patients with type 2 diabetes: clinical correlates and association with complications. J Hypertens 2014 Dec;32:2401-10.
6. Chobanian AV, Bakris GL, Black HR, et al. The Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment: the JNC7 report. JAMA. 2003;289:2560–72.
7. The ACCORD Study Group. Effects of Intensive Blood-Pressure Control in Type 2 Diabetes Mellitus. N Engl J Med2010; 362:1575-1585.
8. Fox CS, Golden SH, Anderson C, et al. Update on prevention of cardiovascular disease in adults with type 2 diabetes mellitus in light of recent evidence: A scientific statement from the American Heart Association and the American Diabetes Association. Diabetes Care. 2015; doi:10.2337/dc15-0258.
9. The SPRINT Research Group. A Randomized Trial of Intensive versus Standard Blood-Pressure Control. N Engl J Med.2015; 373:2103-2116.
Vivian A. Fonseca, MD, FRCP
Professor of Medicine and Pharmacology
Tullis Tulane Alumni Chair in Diabetes
Chief, Section of Endocrinology
Tulane University Health Sciences Center
New Orleans, LA