Hypertension, known as the silent killer because the majority affected are asymptomatic, is a major risk factor for cardiovascular disease (CVD) and stroke.¹ In 2017, the American College of Cardiology (ACC) and the American Heart Association (AHA) guideline for the Prevention, Detection, Evaluation and Management of High Blood Pressure in Adults defined hypertension as a systolic blood pressure (SBP) ≥130 mmHg and a diastolic blood pressure (DBP) ≥80 mmHg.² This change from prior guidelines results in nearly half (46%) of the US adult population being defined as having hypertension. It has also led to a modest increase in initiation of antihypertensive treatment for people at higher risk for cardiovascular events.³ As diabetes also increases CVD risk, the 2017 ACC/AHA guidelines recommend pharmacologic anti-hypertensive therapy for blood pressure ≥130/80 mmHg in adults with diabetes with a treatment goal of SBP <130 mmHg and DBP <80 mmHg.² The goal of this lower target is to promote earlier and more intensive interventions in this patient population at high lifetime risk of CVD events.

The American Diabetes Association's (ADA) 2017 position statement on diabetes and hypertension recommends a higher blood pressure threshold for defining hypertension and a higher treatment threshold of SBP ≥140 mmHg and DBP ≥90 mmHg. The ADA also emphasizes the importance of a more individualized approach to blood pressure management rather than recommending all diabetic patients be treated to the same standard blood pressure of <130/80 mmHg. However, the ADA does recommend that patients with diabetes who are at a high risk for cardiovascular events, defined as an atherosclerotic CVD (ASCVD) risk score ≥10%, be initiated on anti-hypertensive treatment if SBP ≥130 mmHg or DBP ≥80 mmHg and medical therapy does not cause substantial treatment burden.⁴

Given the discrepancies between the two recent guidelines, a recent study by Muntner et al. set out to determine the concordance between hypertension prevalence and anti-hypertensive treatment recommendations for US adults with diabetes using the two different recommendations.⁵ This study sought to evaluate the impact of these discrepant definitions on the initiation and intensification of anti-hypertensive medications for patients with diabetes using data from the US National Health and Nutrition Examination Survey (NHANES) from 2011-2016. The results of the 2,266 participants highlight that for most patients with diabetes, a high level of agreement exists between the two positions. The ACC/AHA guideline and ADA position statement had concordant anti-hypertensive medication recommendations for 86.7% (95% CI: 84.4%, 88.8%) of US adults with diabetes. As expected, the prevalence of hypertension among US adults with diabetes was higher at 77.1% (73.9%, 80.0%) when using the ACC/AHA definition compared to 66.3% (63.4%, 69.1%) when using the ADA definition. The ACC/AHA's lower threshold for defining hypertension leads to a 10.8% increase in US adults with diabetes characterized as having high blood pressure, which translates into an estimated 2.9 million more adults with the diagnosis of hypertension. More similar than different, the two guidelines agree to initiate anti-hypertensive treatment in 75.2% (70.4%, 79.4%) of patients with diabetes. Also, with the ADA's more stringent goal for patients with a high CVD risk, many patients would be treated similarly regardless of which recommendation is followed. There was almost complete agreement between ACC/AHA guidelines and ADA recommendations when considering goal blood pressure levels for patients with diabetes already on anti-hypertensive medications.⁵

This study highlights a subset of patients with diabetes that will have disparities in care depending on which recommendation is followed. The authors found that 24.8% (20.6%, 29.6%) of patients would be initiated on blood pressure medications according to ACC/AHA guideline but not by the ADA position statement. This same group of patients had a mean 10-year ASCVD risk of 14.6%, and over 50% had a 10-year ASCVD risk ≥10%. This subset of patients, including 13% with personal history of CVD, would be initiated on anti-hypertensive medications based only on ACC/AHA guidelines.⁵ While the ACC/AHA guidelines consider any adult with hypertension and diabetes at high risk for CVD, the ADA suggests there is a group of diabetic patients at lower risk for CVD who would be unlikely to benefit significantly from a lower blood pressure goal.⁴ Since patients with high CVD risk benefit the most from blood pressure-lowering treatment, CVD risk is important when making a decision to initiate or intensify blood pressure medication.⁶ While the ACC/AHA recommendations clearly lead to more patients with diabetes at high risk for CVD events being initiated on blood pressure regimens, it remains unclear the degree of benefit with the lower threshold.⁵

The ADA's recommendation of a higher blood pressure threshold for initiation and target is largely driven by the results of the Action to Control Cardiovascular Risk in Diabetes-Blood Pressure (ACCORD-BP) trial. ACCORD demonstrated no significant difference in major adverse CVD events (myocardial infarction, stroke and death from CVD causes) in diabetic patients by targeting a SBP <120 mmHg versus SBP <140 mmHg. There was benefit in the secondary outcome of stroke reduction that was offset by an increase in adverse events including acute kidney injury and electrolyte abnormalities in the lower blood pressure target group.⁷

The 2015 Systolic Blood Pressure Intervention Trial (SPRINT), which excluded diabetic patients, demonstrated that a lower SBP <120 mmHg can reduce CVD events in people at high risk for CVD. The participants with a goal blood pressure of <120 mmHg did have increased risk of adverse events including hypotension, syncope, electrolyte abnormalities and acute kidney injury.⁸ While SPRINT did not include diabetic patients, a post hoc analysis examined intensive versus standard systolic blood pressure treatment in patients with pre-diabetes (fasting serum glucose ≥100 mg/dL) compared to patients with normoglycemia (fasting glucose <100mg/dL) with a composite outcome of myocardial infarction, acute coronary syndrome not resulting in myocardial infarction, stroke, acute decompensated heart failure or death from cardiovascular causes. This analysis suggests that the benefits of intensive blood pressure treatment are similar in pre-diabetic patients and normoglycemic patients.⁹

Participants with diabetes enrolled in the ACCORD trial were enrolled late in the disease process with a mean age of 62 and 32% had a CVD event prior to study enrollment.⁷ In comparison, SPRINT participants were older, but only 17% had prior CVD.⁸ The 2017 ACC/AHA guideline will lead to initiation of therapy and more intensive treatment in diabetic patients earlier on in the disease process, prior to the average ACCORD patient population, and thus may aid in prevention of CVD events.

An individualized approach is likely the best strategy when managing blood pressure medications in patients with diabetes. While the SPRINT trial revealed that many patients including older individuals can tolerate lower blood pressure goals, lower blood pressure targets are associated with increased adverse effects including hypotension, acute kidney injury, electrolyte abnormalities, chronic kidney disease and syncope.⁸ The ACC/AHA's recommendations of a uniform blood pressure treatment target of less than <130/80 mmHg for all patients with diabetes can increase the risk of medically complex patients suffering adverse treatment effects. Adverse events and patient intolerance should be a factor when considering the appropriate blood pressure target for a patient with diabetes. The ADA's suggestion to individualize care and aim for less stringent blood pressure targets in diabetic patients with lower ASCVD risk or older diabetic patients with significant co-morbidities and pill burden will likely lead to fewer adverse outcomes.

In summary, the change in blood pressure threshold to <130/80 mmHg for the diagnosis of hypertension will lead to a 10.8% increase in prevalence of hypertension in the US diabetic population.⁸ This study by Muntner et al. has revealed that the ACC/AHA 2017 guidelines and the ADA position statement have more similarities than differences and the change in blood pressure targets will not affect clinical decisions in a majority of patients. Given the different blood pressure goals between the ACC/AHA and ADA, a subset of patients with diabetes will receive different management depending on which recommendation is followed.⁵ It is still unclear at this time if the ACC/AHA 2017 guideline changes will lead to a significant reduction in CVD events or increase in adverse treatment effects for patients with diabetes, given the lack of randomized-controlled trial data targeting the recommended thresholds in this population. Ongoing research to determine the optimal timing for initiation of anti-hypertensive therapy and target blood pressure in diabetic patients is needed. The current blood pressure recommendations are based on studies with heterogeneous patient populations and different treatment goals and endpoints. Given the current evidence, a one-size-fits-all model for initiation and intensification for blood pressure management in patient with diabetes may lead to more patients at high risk for CVD events being treated appropriately but this could also increase adverse treatment effects and pill burden. Research focused on optimal blood pressure in various subsets of patients while taking into account co-morbidities, ASCVD risk score and other clinical factors will aid in determining appropriate blood pressure targets for more individualized and in turn more effective care.

References

1. Benjamin EJ, Virani SS, Callaway CW, et al. Heart disease and stroke statistics-2018 update: a report from the American Heart Association. Circulation 2018;137:e67-492.
2. 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: a report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines. J Am Coll Cardiol 2018;71:e127-248.
3. Muntner P, Carey RM, Gidding S, et al. Potential U.S. population impact of the 2017 ACC/AHA high blood pressure guideline. J Am Coll Cardiol 2018;71:109-18.
4. de Boer IH, Bangalore S, Benetos A, et al. Diabetes and hypertension: a position statement by the American Diabetes Association. Diabetes Care 2017;40:1273-84.
5. Muntner P, Whelton PK, Woodward M, Carey RM. A comparison of the 2017 American College of Cardiology/American Heart Associaiton blood pressure guideline and the 2017 American Diabetes Association diabetes and hypertension position statement for US adults with diabetes. Diabetes Care 2018;41:2322-9.
6. Blood Pressure Lowering Treatment Trialists' Collaboration. Blood pressure-lowering treatment based on cardiovascular risk: a meta-analysis of individual patient data. Lancet 2014;384:591-8.
7. ACCORD Study Group, Cushman WC, Evans GW, et al. Effects of intensive blood-pressure control in type 2 diabetes mellitus. N Engl J Med 2010;362:1575-85.
8. SPRINT Research Gropu, Wright JT Jr, Williamson JD, et al. A randomized trial of intensive versus standard blood-pressure control. N Engl J Med 2015;373:2103-16.
9. Bress AP, King JB, Kreider KE, et al. Effect of intensive versus standard blood pressure treatment according to baseline prediabetes status: a post hoc analysis of a randomized trial. Diabetes Care 2017. [Epub ahead of print]

Clinical Topics: Acute Coronary Syndromes, Diabetes and Cardiometabolic Disease, Heart Failure and Cardiomyopathies, Prevention, Acute Heart Failure, Hypertension

Keywords: Antihypertensive Agents, Blood Pressure, Risk Factors, Cardiovascular Diseases, Acute Coronary Syndrome, Hypertension, Glucose, Blood Pressure Determination, Systole, Myocardial Infarction, Diabetes Mellitus, Hypotension, Renal Insufficiency, Chronic, Stroke, Syncope, Acute Kidney Injury, Heart Failure, Electrolytes, Metabolic Syndrome

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