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What does Resistant Hypertension Mean for Diabetes Patients?

Nov 26, 2019
Editor: David L. Joffe, BSPharm, CDE, FACA

Author: Jordan Boyd, PharmD. Candidate Florida Agricultural & Mechanical University School of Pharmacy

Can a diagnosis of resistant hypertension give clinicians a clue on what patients can expect for their future?

The RIO-T2D was a prospective study that evaluated how well a diagnosis of apparent resistant hypertension, white-coat hypertension, or true resistant hypertension could predict whether or not a patient with diabetes would go on to develop specific micro and macrovascular outcomes. Microvascular outcomes assessed included retinopathy, neuropathy, and nephropathy. The macrovascular outcomes assessed were coronary, cerebrovascular, or peripheral artery diseases and events., The link between these diagnoses to all-cause mortality was also investigated. Aside from the link to macro and microvascular complications, the RIO-T2D also evaluated which BP level within the patient’s diagnosis of resistant hypertension serves as a more effective indicator of cardiovascular risk for individuals with type 2 diabetes. Past recommendations went as high as >140/90mmHg  while the new ACC/AHA guidelines recommend 130/80mmHg and place a large emphasis on ambulatory blood pressures. Patients’ measuring and recording blood pressure at home is termed 24-hour ambulatory blood pressure measurement.


A patient is diagnosed with apparent treatment-resistant hypertension when there is a failure to achieve established blood pressure goals in office despite therapy with three antihypertensive agents in differing classes on optimized doses or achieving set blood pressure goals with four or more agents. True resistant hypertension is diagnosed when the white-coat syndrome is ruled out with home blood pressure readings, and the above criteria are also met. The RIO-T2D study used these definitions to classify patients included in the study.

The study proved that apparent resistant hypertension diagnosed by two methods (using office and ambulatory blood pressures) was linked to an increased risk of the patients suffering from all of the macrovascular outcomes as well as all-cause mortality. However, the diagnosis of apparent resistant hypertension did not serve as a predictor for any of the microvascular complications.  Patients with diabetes who were diagnosed with true resistant hypertension were shown to be an accurate predictor of all of the identified macrovascular outcomes as well as all-cause mortality. True resistant hypertension also was shown to be linked to adverse renal outcomes, but there was no link found in the study to the development of neuropathy or retinopathy. Diabetes patients diagnosed with white-coat hypertension were found to have an increased risk of cardiovascular outcomes and mortality. The link of these patients to increased risk of renal outcomes was not supported.

The RIO- T2D study identified that the lower BP goals that were presented by the 2017 AHA/ACC guidelines are equivalent as prognostic tools for the occurrence of macrovascular complications and mortality. It is, however, preferred to encourage patients to test their blood pressure at home to completely rule out white coat phenomena. Ambulatory blood pressure levels also give clinicians a better chance to refine their resistant hypertension diagnoses and further be able to identify when patients are truly at risk.  Lower blood pressure goals were linked to improved risk stratification for identifying the renal disease as more cases of true resistant hypertension were identified. It was noted that using the lower thresholds increased the number of patients diagnosed with both apparent and true resistant hypertension which was, of course, expected.

The RIO-T2D did have several identifiable weaknesses. The study was conducted as an observational cohort study; therefore, a direct cause and effect relationship cannot be established. The population in the study consisted of mainly middle-aged to elderly individuals who had been diabetes patients for some time. Therefore, the results may be difficult to extrapolate to an entire population. 

To sum up all of the findings contained in RIO-T2D, it  is important to note that in patients diagnosed with type 2 diabetes, a diagnosis of apparent resistant hypertension, as well as white-coat resistant hypertension, implied that there was an increased risk of both cardiovascular and mortality outcomes. Therefore, a diagnosis of resistant hypertension could be used as a prognostic tool for patients with diabetes.  The only diagnosis that was able to predict a patient would experience negative renal outcomes was a diagnosis of true resistant hypertension, which is defined above. The biggest takeaway of this study is encouraging patients with diagnosed diabetes who are on three or more antihypertensives to test their blood pressure at home. Blood pressure cut-off goals proposed in the past, as well as newer lower goals, are both effective in cardiovascular and mortality risk prognosis. The real benefit, however, comes when patients are consistently taking blood pressure at home, and they can be classified into the correct resistant hypertension group.

Practice Pearls:

  • In patients with diabetes, the correct diagnosis of a specific type of resistant hypertension can give clinicians predictors on if a patient is at risk for macro and microvascular outcomes.
  • Older blood pressure thresholds as well as newer threshold proposed by the AHA/ACC are equivalent when being used as prognostic tools.
  • Patient monitored blood pressure at home is the most important tool in determining how to stratify patients when measuring macro and microvascular risks.

Carey RM, Calhoun DA, Bakris GL, et al.; American Heart Association Professional/ Public Education and Publications Committee of the Council on Hypertension; Council on Cardiovascular and Stroke Nursing; Council on Clinical Cardiology; Council on Genomic and Precision Medicine; Council on Peripheral Vascular Disease; Council on Quality of Care and Outcomes Research; and Stroke Council. Resistant hypertension: detection, evaluation, and management: a scientific statement from the American Heart Association. Hypertension 2018; 72:e53–e9

Whelton PK, Carey RM, Aronow WS, et al. 2017 ACC/AHA/AAPA/ABC/ACPM/AGS/APhA/ ASH/ASPC/NMA/PCNA Guideline for the prevention, detection, evaluation, and management of high blood pressure in adults: Executive Summary: a report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines. J Am Coll Cardiol 2018;71:2199–2269

Cardoso CR, Leite NC, Bacan G, Ataíde DS, Gorgonio LK, Salles GF. Prognostic Importance of Resistant Hypertension in Patients With Type 2 Diabetes: The Rio de Janeiro Type 2 Diabetes Cohort Study. Diabetes Care. 2019:dc191534. doi:10.2337/dc19-1534.

Jordan Boyd, PharmD. Candidate Florida Agricultural & Mechanical University School of Pharmacy