High blood pressure is common in patients with diabetes. Both hypertension and diabetes are independent risk factors for poor cardiovascular outcomes. Obviously the concomitant presence of both HTN and DM in an individual magnifies the chance for CVD events. It is important to screen, diagnose and treat high blood pressure appropriately in someone with diabetes, particularly type 2.
ADA published a position statement on the subject in Diabetes Care, September 2017. The article is comprehensive in regard to proper diagnosis, clinic vs. home BP measurements, target blood pressure values, life style modifications, pharmacological agent initiation and titration, and barriers to therapy. Recommendations are listed below with slightly modified wording for easier and succinct reading:
DEFINITIONS, SCREENING, AND DIAGNOSIS
Blood pressure should be measured at every routine clinical care visit. Patients found to have an elevated blood pressure (≥140/90 mmHg) should have blood pressure confirmed using multiple readings, including measurements on a separate day, to diagnose hypertension.
ALL hypertensive patients with diabetes should have home blood pressure monitored to identify white-coat hypertension.
Orthostatic measurement of blood pressure should be performed during initial evaluation of hypertension and periodically at follow-up, or when symptoms of orthostatic hypotension are present, and regularly if orthostatic hypotension has been diagnosed.
BLOOD PRESSURE TARGETS
Most patients with diabetes and hypertension should be treated to a systolic blood pressure goal of <140 mmHg and a diastolic blood pressure goal of <90 mmHg.
Lower systolic and diastolic blood pressure targets, such as <130/80 mmHg, may be appropriate for individuals at high risk of cardiovascular disease if they can be achieved without undue treatment burden.
Pharmacologic Antihypertensive Treatment
Patients with confirmed office-based blood pressure ≥140/90 mmHg should, in addition to lifestyle therapy, have timely titration of pharmacologic therapy to achieve blood pressure goals.
Patients with confirmed office-based blood pressure ≥160/100 mmHg should, in addition to lifestyle therapy, have prompt initiation and timely titration of two drugs or a single-pill combination of drugs demonstrated to reduce cardiovascular events in patients with diabetes.
Treatment for hypertension should include drug classes demonstrated to reduce cardiovascular events in patients with diabetes: ACE inhibitors, angiotensin receptor blockers (ARBs), thiazide-like diuretics, or dihydropyridine CCBs. Multiple-drug therapy is generally required to achieve blood pressure targets (but not a combination of ACE inhibitors and ARBs).
An ACE inhibitor or ARB, at the maximum tolerated dose indicated for blood pressure treatment, is the recommended first-line treatment for hypertension in patients with diabetes and urine albumin-to-creatinine ratio ≥300 mg/g creatinine (A) or 30–299 mg/g creatinine (B). If one class is not tolerated, the other should be substituted.
For patients treated with an ACE inhibitor, ARB, or diuretic: eGFR and serum K+ levels should be monitored.
In patients receiving pharmacologic antihypertensive treatment, home blood pressure should be measured to promote patient engagement in treatment and adherence.
Patients with resistant hypertension who are not meeting blood pressure targets on conventional drug therapy with three agents, including a diuretic, should be referred to a certified hypertension specialist.
Patients with resistant hypertension who are not meeting blood pressure targets on conventional drug therapy with three agents should be considered for mineralocorticoid receptor antagonist therapy [like Spironolactone].
Pregnant women with diabetes and preexisting hypertension or mild gestational hypertension with systolic BP <160 mmHg, diastolic BP <105 mmHg, and no evidence of end-organ damage DO NOT NEED to be treated with pharmacologic antihypertensive therapy.
In pregnant patients with diabetes and preexisting hypertension who are treated with antihypertensive therapy, systolic or diastolic BP targets of 120–160/80–105 mmHg are suggested in the interest of optimizing long-term maternal health and fetal growth.
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Automated office blood pressure (AOBP) is an alternate method to measure blood pressure in which a fully automated device is used to make and average multiple readings (usually 3–5) taken over a few minutes, ideally while a patient rests quietly alone. AOBP was used in two large, important clinical trials, Action to Control Cardiovascular Risk in Diabetes (ACCORD) and Systolic Blood Pressure Intervention Trial (SPRINT). If the patient is alone when the readings are taken, the approach is also useful for diagnosing white-coat hypertension.AOBP generates values 5–10 mmHg lower than conventional office readings, on average. Thus, results of trials using this technique cannot be directly applied to practices that measure conventional office blood pressure. With the exception of ACCORD, most of the evidence of benefits of hypertension treatment in people with diabetes is based on conventional office measurements.
Hypertension is defined as a sustained blood pressure ≥140/90 mmHg. This definition is based on unambiguous data that levels above this threshold are strongly associated with ASCVD, death, disability, and microvascular complications and that antihypertensive treatment in populations with baseline blood pressure above this range reduces the risk of ASCVD events. The “sustained” aspect of the hypertension definition is important, as blood pressure has considerable normal variation. The criteria for diagnosing hypertension should be differentiated from blood pressure treatment targets.
Hypertension diagnosis and management can be complicated by two common conditions: masked hypertension and white-coat hypertension. Masked hypertension is defined as a normal blood pressure in the clinic or office (<140/90 mmHg) but an elevated home blood pressure of ≥135/85 mmHg; the lower home blood pressure threshold is based on outcome studies demonstrating that lower home blood pressures correspond to higher office-based measurements. White-coat hypertension is elevated office blood pressure (≥140/90 mmHg) and normal (untreated) home blood pressure (<135/85 mmHg). Identifying these conditions with home blood pressure monitoring can help prevent overtreatment of people with white-coat hypertension who are not at elevated risk of ASCVD and, in the case of masked hypertension, allow proper use of medications to reduce side effects during periods of normal pressure.
Diabetic autonomic neuropathy or volume depletion can cause orthostatic hypotension, which may be further exacerbated by antihypertensive medications. The definition of orthostatic hypotension is a decrease in systolic blood pressure of 20 mmHg or a decrease in diastolic blood pressure of 10 mmHg within 3 min of standing when compared with blood pressure from the sitting or supine position. Orthostatic hypotension is common in people with type 2 diabetes and hypertension and is associated with an increased risk of mortality and heart failure.
It is important to assess for symptoms of orthostatic hypotension to individualize blood pressure goals, select the most appropriate antihypertensive agents, and minimize adverse effects of antihypertensive therapy. Additionally, antihypertensive medication type or timing (switch to nocturnal dosing) may require adjustment. In particular, α-blockers and diuretics may need to be stopped. People with orthostatic hypotension may benefit from support stockings or other approaches.
Epidemiologic analyses show that blood pressure ≥115/75 mmHg is associated with increased rates of ASCVD, heart failure, retinopathy, kidney disease, and mortality in a graded fashion, contributing to the evidence that blood pressure control is important in the clinical outcomes of diabetes. However, observational studies of blood pressure targets are subject to confounding factors and do not directly assess the effects of blood pressure lowering. Clinical trials and meta-analyses of clinical trials provide the strongest evidence addressing blood pressure and offer substantial guidance for treatment targets, particularly for patients with type 2 diabetes.
Treatment of hypertension to blood pressure <140/90 mmHg is supported by unequivocal evidence that pharmacologic treatment of blood pressure ≥140/90 mmHg reduces cardiovascular events as well as some microvascular complications. Intensification of antihypertensive therapy to target blood pressures lower than <140/90 mmHg (e.g., <130/80 or <120/80 mmHg) may be beneficial for selected patients with diabetes. Such intensive blood pressure control has been evaluated in landmark clinical trials and meta-analyses of clinical trials.
In ACCORD BP, intensive blood pressure control did not reduce total major atherosclerotic cardiovascular events but did reduce the risk of stroke, at the expense of increased adverse events. Specifically, compared with a target systolic blood pressure <140 mmHg, a target systolic blood pressure <120 mmHg resulted in no significant difference in the primary composite outcome of MI, stroke, or cardiovascular death (hazard ratio 0.88, 95% CI 0.73 to 1.06). Stroke was reduced by 41%, but serious adverse events attributed to antihypertensive therapy occurred in 3.3% vs. 1.3% of participants, with significantly increased incidence of hypotension, electrolyte abnormalities, and elevated serum creatinine. Therefore, the ACCORD BP results suggest that blood pressure targets more intensive than <140/90 mmHg may be reasonable in selected patients who have been educated about added treatment burden, side effects, and costs.
Of note, ACCORD BP and SPRINT measured blood pressure using AOBP, which yields values that are generally lower than typical office blood pressure by approximately 5–10 mmHg, suggesting that implementing the ACCORD BP or SPRINT protocols in a typical clinic might require a systolic blood pressure target higher than <120 mmHg.
Based on meta-analyses, antihypertensive treatment appears to be beneficial when mean baseline blood pressure is ≥140/90 mmHg or mean attained intensive blood pressure is ≥130/80 mmHg. Among trials with lower baseline or achieved blood pressure, antihypertensive treatment reduced the risk of stroke, retinopathy, and albuminuria, but effects on other ASCVD and heart failure were not evident.
Patients and clinicians should engage in a shared decision-making process to determine individual blood pressure targets, with the acknowledgment that the benefits and risks of intensive blood pressure targets are uncertain and may vary across patients. Following the ADA approach to the management of hyperglycemia, factors that influence treatment targets may include risks of treatment (e.g., hypotension, drug adverse effects), life expectancy, comorbidities including vascular complications, patient attitude and expected treatment efforts, and resources and support system. Specific factors to consider are the absolute risk of cardiovascular events, risk of progressive kidney disease as reflected by albuminuria, adverse effects, age, and overall treatment burden.
Patients who have higher risk of cardiovascular events (particularly stroke) or albuminuria and who can attain intensive blood pressure control relatively easily and without substantial adverse effects may be best suited to intensive blood pressure control.
In contrast, patients with conditions more common in older adults, such as functional limitations, polypharmacy, and multimorbidity, may be best suited to less intensive blood pressure control.
Notably, there is an absence of high-quality data available to guide blood pressure targets in type 1 diabetes. Associations of blood pressure with macrovascular and microvascular outcomes in type 1 diabetes are generally similar to those in type 2 diabetes and the general population. Given an absence of randomized trials with clinical outcomes in type 1 diabetes, effects of antihypertensive therapy can only be extrapolated from trials in other populations, potentially drawing from both ACCORD BP and SPRINT. Of note, diastolic blood pressure, as opposed to systolic blood pressure, is a key variable predicting cardiovascular outcomes in people under age 50 years without diabetes and may be prioritized in younger adults. Though convincing data are lacking, younger adults with type 1 diabetes might more easily achieve intensive blood pressure levels and may derive substantial long-term benefit from tight blood pressure control.
Lifestyle therapy consists of reducing excess body weight through caloric restriction, restricting sodium intake (<2,300 mg/day), increasing consumption of fruits and vegetables (8–10 servings per day) and low-fat dairy products (2–3 servings per day), avoiding excessive alcohol consumption (no more than 2 servings per day in men and no more than 1 serving per day in women), smoking cessation, reducing sedentary time, and increasing physical activity levels. These lifestyle strategies may also positively affect glycemic and lipid control and should be encouraged in those with even mildly elevated blood pressure. In addition, clinicians are encouraged to routinely review patient medication lists for agents that may raise blood pressure, including over-the-counter and herbal ones. As an example, one meta-analysis suggested that NSAIDs increase systolic blood pressure on average by 5 mmHg.
There is only one large trial including people with diabetes that randomized two single-pill combinations and assessed cardiovascular and renal outcomes. The Avoiding Cardiovascular Events Through Combination Therapy in Patients Living With Systolic Hypertension (ACCOMPLISH) trial enrolled participants at high risk of cardiovascular events (60% with diabetes) and demonstrated a decrease in morbidity and mortality with the ACE inhibitor benazepril + dihydropyridine CCB amlodipine VS. benazepril + thiazide-like diuretic hydrochlorothiazide. Other such trials are needed to confirm these outcomes and assess other antihypertensive medication combinations.
In the absence of albuminuria, the superiority of ACE inhibitors or ARBs over other antihypertensive agents for prevention of cardiovascular outcomes has not been consistently shown, although smaller trials suggest reduction in composite cardiovascular events and reduced progression to advanced stages of kidney disease. In general, ACE inhibitors and ARBs are considered to have similar benefits and risks, and if one is not tolerated, the other can often be used.
In people with diabetic kidney disease, hyperkalemia risk dramatically increases when the estimated glomerular filtration rate (eGFR) is below 45 or serum potassium is >4.5 while the patient is already receiving a diuretic. Moreover, the combination of reduced eGFR and elevated potassium in a given patient can raise the risk eightfold for hyperkalemia development if spironolactone and an ACEi/ARB are added (85).
Thiazide-like diuretics are only effective in maintaining volume and reducing the risk of hyperkalemia down to an eGFR of 30. Below an eGFR of 30, a long-acting loop diuretic, such as torsemide, should be prescribed instead.
Evidence suggests an association between absence of nocturnal blood pressure dipping and ASCVD events. A meta-analysis of clinical trials found a small benefit of evening versus morning dosing of antihypertensive medications with regard to blood pressure control but no data on clinical effects. In two subgroup analyses of a single subsequent randomized clinical trial, moving at least one antihypertensive medication to bedtime significantly reduced cardiovascular events, but results were based on small numbers of events.
Self-management is a key component of diabetes care and extends to antihypertensive treatment. Home blood pressures may improve patient medication adherence and reduce cardiovascular risk factors. Furthermore, evidence suggests home blood pressure monitoring is as accurate as 24-h ambulatory blood pressure monitoring and may better correlate with ASCVD risk than office measurements.
Hyperinsulinemia and exogenous insulin may theoretically lead to hypertension through vasoconstriction and sodium and fluid retention. However, insulin can also promote vasodilation, and basal insulin compared with standard care was not associated with a change in blood pressure in the Outcome Reduction With an Initial Glargine Intervention (ORIGIN) trial of people with type 2 diabetes or prediabetes.
Sodium–glucose cotransport 2 inhibitors are associated with a mild diuretic effect and a reduction in blood pressure of 3–6 mmHg systolic blood pressure and 1–2 mmHg diastolic blood pressure. Glucagon-like peptide 1 receptor agonists are also associated with a reduction in systolic/diastolic blood pressure of 2–3/0–1 mmHg.
Resistant hypertension is defined as blood pressure ≥140/90 mmHg despite a therapeutic strategy that includes appropriate lifestyle management plus a diuretic and two other antihypertensive drugs belonging to different classes at adequate doses. Prior to diagnosing resistant hypertension, several other conditions should be excluded.
Mineralocorticoid receptor antagonists (MRAs) are effective for management of resistant hypertension in patients with type 2 diabetes when added to existing treatment with a renin-angiotensin system (RAS) inhibitor, diuretic, and CCB, in part because they reduce sympathetic nerve activity. MRAs also reduce albuminuria and have additional cardiovascular benefits. However, adding an MRA to an ACE inhibitor or ARB may increase the risk for hyperkalemic episodes. Hyperkalemia can be managed with dietary potassium restriction, potassium-wasting diuretics, or potassium binders, but long-term outcome studies are needed to evaluate the role of MRAs (with or without adjunct potassium management) in blood pressure management.
The American College of Obstetricians and Gynecologists (ACOG) does not recommend that women with mild gestational hypertension (systolic blood pressure <160 mmHg or diastolic blood pressure <110 mmHg) be treated with antihypertensive medications, as there is no benefit identified that clearly outweighs potential risks of therapy. A Cochrane systematic review did not find conclusive evidence for or against blood pressure treatment for mild to moderate preexisting hypertension to reduce the risk of preeclampsia, preterm birth, small-for-gestational-age infants, or fetal death. For pregnant women at high risk of preeclampsia, low-dose aspirin is recommended starting at 12 weeks of gestation to reduce the risk of preeclampsia.
For pregnant women requiring antihypertensive therapy, blood pressure should be maintained between 120-160 / 80-105 mmHg, as lower blood pressure levels may be associated with impaired fetal growth. Pregnant women with hypertension and evidence of end-organ damage including cardiovascular and renal diseases may be considered for lower blood pressure targets (i.e., <140/90 mmHg) to avoid the progression of these diseases during pregnancy.
During pregnancy, treatment with ACE inhibitors, ARBs, or spironolactone is contraindicated, as they may cause fetal damage. Antihypertensive drugs known to be effective and safe in pregnancy include methyldopa, labetalol, hydralazine, and long-acting nifedipine.
Diuretics may be used during late-stage pregnancy if needed for volume control. Postpartum patients with gestational hypertension, preeclampsia, and superimposed preeclampsia should have their blood pressures observed for 72 h in the hospital and for 7–10 days' postpartum. Long-term follow-up is recommended for these women, as they have increased lifetime cardiovascular risk.
Arterial stiffness may develop during the aging process and contribute to an increase in systolic and decrease in diastolic blood pressure in older adults. Diabetes is itself associated with an increase in arterial stiffness, leading to a greater age-related increase in systolic blood pressure compared with people without diabetes. Older adults with diabetes and hypertension (mainly systolic) typically present with high risk for cardiovascular events and other age-related diseases, difficulties achieving blood pressure targets due to arterial stiffness, and high risk of iatrogenic complications, including hypoglycemia, orthostatic hypotension, and volume depletion.
In older adults with diabetes and hypertension, functional status, comorbidities, and polypharmacy are important considerations when establishing therapeutic strategies and blood pressure goals. Systolic blood pressure should be the main target of treatment. In fitter patients, a therapeutic strategy similar to that used in younger individuals may be used. In the subgroup with loss of autonomy and major functional limitations (e.g., those needing daily assistance for their basic activities), higher systolic blood pressure goals should be considered (e.g., 145–160 mmHg) and treatment should be reduced in the presence of low supine systolic blood pressure (<130 mmHg) or presence of orthostatic hypotension.
In older people with impaired vascular compliance, as indicated by a difference of >60 mmHg between systolic and diastolic pressures (i.e., pulse pressure), attempts to reach a target systolic pressure must be balanced against the risk of lowering diastolic pressure below 65–70 mmHg. Lowering diastolic pressures below this range in older adults may increase the risk for coronary heart disease, mortality, and other adverse cardiovascular outcomes.
When considering pharmacologic antihypertensive treatment in older adults with diabetes, note that β-blockers may mask signs of hypoglycemia, antihypertensive drugs can worsen orthostatic hypotension, and diuretics can exacerbate volume depletion. Cognitive dysfunction may affect medication-taking behaviors, particularly in the context of poor overall health status, multiple comorbidities, acute illness, polypharmacy, and poor nutrition. Tolerance of the antihypertensive treatment should be regularly assessed, especially orthostatic hypotension.
For people with diabetes and untreated blood pressure <140/90 mmHg, there is little evidence that antihypertensive treatment improves health outcomes. Some have suggested treatment with an ACE inhibitor or ARB to prevent or delay diabetic kidney disease, but the data do not support such an approach. In a trial of people with type 2 diabetes and normal urine albumin excretion with and without hypertension, an ARB reduced or suppressed the development of albuminuria but increased the rate of cardiovascular events. In two trials of patients without albuminuria or hypertension, one including people with type 1 diabetes and the other type 2 diabetes, RAS inhibitors did not prevent the development of diabetic glomerulopathy assessed by kidney biopsy. Therefore, RAS inhibitors are not recommended for patients without hypertension to prevent the development of diabetic kidney disease.
Hypertension is a strong, modifiable risk factor for the macrovascular and microvascular complications of diabetes. Robust literature demonstrates the clinical efficacy of lowering blood pressure, with cardiovascular and microvascular benefits demonstrated for multiple classes of antihypertensive medications.
Strong evidence from clinical trials and meta-analyses supports targeting blood pressure reduction to at least <140/90 mmHg in most adults with diabetes. Lower blood pressure targets may be beneficial for selected patients with high cardiovascular disease risk if they can be achieved without undue burden, and such lower targets may be considered on an individual basis.
In addition to lifestyle modifications, multiple medication classes are often needed to attain blood pressure goals. ACE inhibitors, ARBs, dihydropyridine CCBs, and thiazide-like diuretics have been demonstrated to improve clinical outcomes and are preferred for blood pressure control. For patients with albuminuria, an ACE inhibitor or ARB should be part of the antihypertensive regimen. Treatment should be individualized to the specific patient based on their comorbidities; their anticipated benefit for reduction in ASCVD, heart failure, progressive diabetic kidney disease, and retinopathy events; and their risk of adverse events. This conversation should be part of a shared decision-making process between the clinician and the individual patient.