AGP Report: Continuous Glucose Monitoring
10. Cardiovascular Disease and Risk Management: Standards of
Medical Care in Diabetes—2022
Diabetes Care 2022;45(Suppl. 1):S144–S174 | https://doi.org/10.2337/dc22-S010
American Diabetes Association Professional Practice Committee*
The American Diabetes Association (ADA) “Standards of Medical Care in Diabetes”
includes the ADA’s current clinical practice recommendations and is intended to pro-vide the components of diabetes care, general treatment goals and guidelines, and tools to evaluate quality of care. Members of the ADA Professional Practice Commit-tee, a multidisciplinary expert committee (https://doi.org/10.2337/dc22-SPPC), are responsible for updating the Standards of Care annually, or more frequently as war-ranted. For a detailed description of ADA standards, statements, and reports, as well as the evidence-grading system for ADA’s clinical practice recommendations, please refer to the Standards of Care Introduction (https://doi.org/10.2337/dc22-SINT).
Readers who wish to comment on the Standards of Care are invited to do so at professional.diabetes.org/SOC.
For prevention and management of diabetes complications in children and adoles-cents, please refer to Section 14, “Children and Adolescents” (https://doi.org/
10.2337/dc22-S014).
Atherosclerotic cardiovascular disease (ASCVD)—defined as coronary heart disease (CHD), cerebrovascular disease, or peripheral arterial disease presumed to be of atherosclerotic origin—is the leading cause of morbidity and mortality for individu-als with diabetes and results in an estimated $37.3 billion in cardiovascular-related spending per year associated with diabetes (1). Common conditions coexisting with type 2 diabetes (e.g., hypertension and dyslipidemia) are clear risk factors for ASCVD, and diabetes itself confers independent risk. Numerous studies have shown the efficacy of controlling individual cardiovascular risk factors in preventing or slowing ASCVD in people with diabetes. Furthermore, large benefits are seen when multiple cardiovascular risk factors are addressed simultaneously. Under the cur-rent paradigm of aggressive risk factor modification in patients with diabetes, there is evidence that measures of 10-year coronary heart disease (CHD) risk among U.S.
adults with diabetes have improved significantly over the past decade (2) and that ASCVD morbidity and mortality have decreased (3,4).
Heart failure is another major cause of morbidity and mortality from cardio-vascular disease. Recent studies have found that rates of incident heart failure hospitalization (adjusted for age and sex) were twofold higher in patients with diabetes compared with those without (5,6). People with diabetes may have heart failure with preserved ejection fraction (HFpEF) or with reduced ejection fraction (HFrEF). Hypertension is often a precursor of heart failure of either type, and ASCVD can coexist with either type (7), whereas prior myocardial infarction (MI) is often a major factor in HFrEF. Rates of heart failure hospitali-zation have been improved in recent trials including patients with type 2
*A complete list of members of the American Diabetes Association Professional Practice Com-mittee can be found at https://doi.org/10.2337/
dc22-SPPC.
This section has received endorsement from the American College of Cardiology.
Suggested citation: American Diabetes Asso-ciation Professional Practice Committee. 10.
Cardiovascular disease and risk management:
Standards of Medical Care in Diabetes—2022.
Diabetes Care 2022;45(Suppl. 1):S144–S174
© 2021 by the American Diabetes Association.
Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered.
More information is available at https://
diabetesjournals.org/journals/pages/license.
10.CARDIOVASCULARDISEASEANDRISKMANAGEMENT
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diabetes, most of whom also had ASCVD, with sodium–glucose cotrans-porter 2 (SGLT2) inhibitors (8–10).
For prevention and management of both ASCVD and heart failure, cardiovas-cular risk factors should be systematically assessed at least annually in all patients with diabetes. These risk factors include duration of diabetes, obesity/overweight, hypertension, dyslipidemia, smoking, a family history of premature coronary dis-ease, chronic kidney disdis-ease, and the presence of albuminuria. Modifiable abnormal risk factors should be treated as described in these guidelines. Notably, the majority of evidence supporting inter-ventions to reduce cardiovascular risk in diabetes comes from trials of patients with type 2 diabetes. Few trials have been specifically designed to assess the impact of cardiovascular risk reduction strategies in patients with type 1 diabetes.
As depicted inFig. 10.1, a comprehen-sive approach to the reduction in risk of diabetes-related complications is recom-mended. Therapy that includes multiple, concurrent evidence-based approaches to care will provide complementary reduction in the risks of microvascular, kidney, neurologic, and cardiovascular complications. Management of glycemia,
blood pressure, and lipids and the incor-poration of specific therapies with car-diovascular and kidney outcomes benefit (as individually appropriate) are consid-ered fundamental elements of global risk reduction in diabetes.
THE RISK CALCULATOR
The American College of Cardiology/
American Heart Association ASCVD risk calculator (Risk Estimator Plus) is gener-ally a useful tool to estimate 10-year risk of a first ASCVD event (available online at tools.acc.org/ASCVD-Risk-Estimator-Plus). The calculator includes diabetes as a risk factor, since diabetes itself confers increased risk for ASCVD, although it should be acknowledged that these risk calculators do not account for the duration of diabetes or the presence of diabetes complications, such as albuminuria. Although some variability in calibration exists in various subgroups, including by sex, race, and diabetes, the overall risk prediction does not differ in those with or without diabetes (11–14), validating the use of risk calculators in people with diabetes.
The 10-year risk of afirst ASCVD event should be assessed to better stratify
ASCVD risk and help guide therapy, as described below.
Recently, risk scores and other cardio-vascular biomarkers have been dev-eloped for risk stratification of secondary prevention patients (i.e., those who are already high risk because they have ASCVD) but are not yet in widespread use (15,16). With newer, more expensive lipid-lowering therapies now available, use of these risk assessments may help target these new therapies to “higher risk” ASCVD patients in the future.
HYPERTENSION/BLOOD PRESSURE CONTROL
Hypertension, defined as a sustained blood pressure$140/90 mmHg, is com-mon acom-mong patients with either type 1 or type 2 diabetes. Hypertension is a major risk factor for both ASCVD and microvas-cular complications. Moreover, numerous studies have shown that antihypertensive therapy reduces ASCVD events, heart fail-ure, and microvascular complications.
Please refer to the American Diabetes Association (ADA) position statement
“Diabetes and Hypertension” for a detailed review of the epidemiology, diag-nosis, and treatment of hypertension (17).
Screening and Diagnosis
Recommendations
10.1 Blood pressure should be mea-sured at every routine clinical visit. When possible, patients found to have elevated blood pressure ($140/90 mmHg) should have blood pressure confirmed using multiple read-ings, including measurements on a separate day, to diagnose hypertension. A Patients with blood pressure$180/110 mmHg and cardiovascular disease could be diagnosed with hypertension at a single visit.E
10.2 All hypertensive patients with diabetes should monitor their blood pressure at home.A Blood pressure should be measured at every routine clinical visit by a trained individual and should follow the guide-lines established for the general popu-lation: measurement in the seated position, with feet on the floor and arm supported at heart level, after 5
Figure 10.1—Multifactorial approach to reduction in risk of diabetes complications. *Risk reduc-tion intervenreduc-tions to be applied as individually appropriate.
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min of rest. Cuff size should be appro-priate for the upper-arm circumfer-ence. Elevated values should preferably be confirmed on a separate day; how-ever, in patients with cardiovascular disease and blood pressure$180/110 mmHg, it is reasonable to diagnose hypertension at a single visit (18). Pos-tural changes in blood pressure and pulse may be evidence of autonomic neuropathy and therefore require adjustment of blood pressure targets.
Orthostatic blood pressure measure-ments should be checked on initial visit and as indicated.
Home blood pressure self-monitoring and 24-h ambulatory blood pressure monitoring may provide evidence of white coat hypertension, masked hyper-tension, or other discrepancies between office and “true” blood pressure (17,18a,18b). In addition to confirming or refuting a diagnosis of hypertension, home blood pressure assessment may be useful to monitor antihypertensive treatment. Studies of individuals without diabetes found that home measure-ments may better correlate with ASCVD risk than office measurements (19,20).
Moreover, home blood pressure moni-toring may improve patient medication adherence and thus help reduce cardio-vascular risk (21).
Treatment Goals
Recommendations
10.3 For patients with diabetes and hypertension, blood pressure tar-gets should be individualized through a shared decision-making process that addresses cardiovas-cular risk, potential adverse effects of antihypertensive medications, and patient pref-erences.B
10.4 For individuals with diabetes and hypertension at higher cardiovascular risk (existing atherosclerotic cardiovascular disease [ASCVD] or 10-year ASCVD risk $15%), a blood pressure target of <130/80 mmHg may be appropriate, if it can be safely attained.B 10.5 For individuals with diabetes
and hypertension at lower risk for cardiovascular disease (10-year atherosclerotic cardiovas-cular disease risk<15%), treat
to a blood pressure target of
<140/90 mmHg.A
10.6 In pregnant patients with dia-betes and preexisting hyper-tension, a blood pressure target of 110–135/85 mmHg is suggested in the interest of reducing the risk for acceler-ated maternal hypertension A and minimizing impaired fetal growth.E
Randomized clinical trials have demon-strated unequivocally that treatment of hypertension to blood pressure <140/
90 mmHg reduces cardiovascular events as well as microvascular complications (22–28). Therefore, patients with type 1 or type 2 diabetes who have hyperten-sion should, at a minimum, be treated to blood pressure targets of <140/90 mmHg. The benefits and risks of intensi-fying antihypertensive therapy to target blood pressures lower than <140/90 mmHg (e.g., <130/80 or <120/80 mmHg) have been evaluated in large randomized clinical trials and meta-anal-yses of clinical trials. Notably, there is an absence of high-quality data avail-able to guide blood pressure targets in type 1 diabetes.
Randomized Controlled Trials of Intensive Versus Standard Blood Pressure Control
The Action to Control Cardiovascular Risk in Diabetes Blood Pressure (ACCORD BP) trial provides the strongest direct assessment of the benefits and risks of intensive blood pressure control among people with type 2 diabetes (29). In ACCORD BP, compared with standard blood pressure control (target systolic blood pressure<140 mmHg), intensive blood pressure control (target systolic blood pressure <120 mmHg) did not reduce total major atherosclerotic cardiovascular events but did reduce the risk of stroke, at the expense of inc-reased adverse events (Table 10.1). The ACCORD BP results suggest that blood pressure targets more intensive than
<140/90 mmHg are not likely to imp-rove cardiovascular outcomes among most people with type 2 diabetes but may be reasonable for patients who may derive the most benefit and have been educated about added treatment bur-den, side effects, and costs, as discussed below.
Additional studies, such as the Sys-tolic Blood Pressure Intervention Trial (SPRINT) and the Hypertension Optimal Treatment (HOT) trial, also examined effects of intensive versus standard control (Table 10.1), though the rele-vance of their results to people with diabetes is less clear. The Action in Diabetes and Vascular Disease: Pre-terax and Diamicron MR Controlled Evaluation–Blood Pressure (ADVANCE BP) trial did not explicitly test blood pressure targets (30); the achieved blood pressure in the intervention group was higher than that achieved in the ACCORD BP intensive arm and would be consistent with a target blood pressure of <140/90 mmHg.
Notably, ACCORD BP and SPRINT mea-sured blood pressure using automated office blood pressure measurement, which yields values that are generally lower than typical office blood pres-sure readings by approximately 5–10 mmHg (31), suggesting that imple-menting the ACCORD BP or SPRINT protocols in an outpatient clinic might require a systolic blood pressure tar-get higher than <120 mmHg, such as
<130 mmHg.
A number of post hoc analyses have attempted to explain the apparently divergent results of ACCORD BP and SPRINT. Some investigators have argued that the divergent results are not due to differences between people with and without diabetes but rather are due to differences in study design or to charac-teristics other than diabetes (32–34).
Others have opined that the divergent results are most readily explained by the lack of benefit of intensive blood pressure control on cardiovascular mor-tality in ACCORD BP, which may be due to differential mechanisms underlying cardiovascular disease in type 2 diabe-tes, to chance, or both (35). Interest-ingly, a post hoc analysis has found that intensive blood pressure lowering increased the risk of incident chronic kidney disease in both ACCORD BP and SPRINT, with the absolute risk of inci-dent chronic kidney disease being higher in individuals with type 2 diabe-tes (36).
Meta-analyses of Trials
To clarify optimal blood pressure targets in patients with diabetes, meta-analyses have stratified clinical trials by mean
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baseline blood pressure or mean blood pressure attained in the intervention (or intensive treatment) arm. Based on these 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 (17,22,23,25–27). Among trials with lower baseline or attained blood pres-sure, antihypertensive treatment reduced the risk of stroke, retinopathy, and albumin-uria, but effects on other ASCVD outcomes and heart failure were not evident. Taken together, these meta-analyses consistently show that treating patients with baseline
blood pressure $140 mmHg to targets <140 mmHg is beneficial, while more intensive targets may offer additional (though probably less robust) benefits.
Individualization of Treatment Targets
Patients and clinicians should engage in a shared decision-making process to deter-mine individual blood pressure targets (17). This approach acknowledges that the benefits and risks of intensive blood pressure targets are uncertain and may vary across patients and is consistent with a patient-focused approach to care that values patient priorities and provider
judgment (37). Secondary analyses of ACCORD BP and SPRINT suggest that clin-ical factors can help determine individu-als more likely to benefit and less likely to be harmed by intensive blood pres-sure control (38,39).
Absolute benefit from blood pressure reduction correlated with absolute baseline cardiovascular risk in SPRINT and in earlier clinical trials conducted at higher baseline blood pressure levels (11,39). Extrapolation of these studies suggests that patients with diabetes may also be more likely to benefit from intensive blood pressure control when
Table 10.1—Randomized controlled trials of intensive versus standard hypertension treatment strategies
Clinical trial Population Intensive Standard Outcomes
ACCORD BP (29) 4,733 participants with T2D aged 40–79 years with prior evidence of CVD or multiple cardiovascular risk factors
SBP target:
<120 mmHg Achieved (mean)
SBP/DBP:
119.3/64.4 mmHg
SBP target:
130–140 mmHg Achieved (mean)
SBP/DBP:
135/70.5 mmHg
No benefit in primary end point:
composite of nonfatal MI, nonfatal stroke, and CVD death
Stroke risk reduced 41% with intensive control, not sustained through follow-up beyond the period of active treatment
Adverse events more common in intensive group, particularly elevated serum creatinine and electrolyte abnormalities ADVANCE BP (30) 11,140 participants with
T2D aged 55 years and older with prior evidence of CVD or multiple cardiovascular risk factors
Intervention: a single-pill, fixed-dose combination of perindopril and indapamide Achieved (mean)
SBP/DBP:
136/73 mmHg
Control: placebo Achieved (mean)
SBP/DBP:
141.6/75.2 mmHg
Intervention reduced risk of primary composite end point of major macrovascular and microvascular events (9%), death from any cause (14%), and death from CVD (18%)
6-year observational follow-up found reduction in risk of death in intervention group attenuated but still significant (198) HOT (221) 18,790 participants,
including 1,501 with diabetes
DBP target:
#80 mmHg Achieved (mean):
81.1 mmHg,#80 group; 85.2 mmHg,
#90 group
DBP target:
#90 mmHg In the overall trial, there was no cardiovascular benefit with more intensive targets
In the subpopulation with diabetes, an intensive DBP target was associated with a significantly reduced risk (51%) of CVD events
SPRINT (41) 9,361 participants without diabetes
SBP target:
<120 mmHg Achieved (mean):
121.4 mmHg
SBP target:
<140 mmHg Achieved (mean):
136.2 mmHg
Intensive SBP target lowered risk of the primary composite outcome 25% (MI, ACS, stroke, heart failure, and death due to CVD)
Intensive target reduced risk of death 27%
Intensive therapy increased risks of electrolyte abnormalities and AKI
ACCORD BP, Action to Control Cardiovascular Risk in Diabetes Blood Pressure trial; ACS, acute coronary syndrome; ADVANCE BP, Action in Diabetes and Vascular Disease: Preterax and Diamicron MR Controlled Evaluation–Blood Pressure trial; AKI, acute kidney injury; CVD, cardiovascular disease; DBP, dia-stolic blood pressure; HOT, Hypertension Optimal Treatment trial; MI, myocardial infarction; SBP, sydia-stolic blood pressure; SPRINT, Sydia-stolic Blood Pressure Intervention Trial; T2D, type 2 diabetes. Data from this table can also be found in the ADA position statement“Diabetes and Hypertension” (17).
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they have high absolute cardiovascular risk. Therefore, it may be reasonable to target blood pressure <130/80 mmHg among patients with diabetes and either clinically diagnosed cardiovascu-lar disease (particucardiovascu-larly stroke, which was significantly reduced in ACCORD BP) or 10-year ASCVD risk$15%, if it can be attained safely. This approach is consistent with guidelines from the American College of Cardiology/Ameri-can Heart Association, which advocate a blood pressure target <130/80 mmHg for all patients, with or without diabetes (40).
Potential adverse effects of antihy-pertensive therapy (e.g., hypotension, syncope, falls, acute kidney injury, and electrolyte abnormalities) should also be taken into account (29,36,41,42).
Patients with older age, chronic kidney disease, and frailty have been shown to be at higher risk of adverse effects of intensive blood pressure control (42). In addition, patients with orthostatic hypo-tension, substantial comorbidity, func-tional limitations, or polypharmacy may be at high risk of adverse effects, and some patients may prefer higher blood pressure targets to enhance quality of life. However, in ACCORD BP, it was found that intensive blood pressure lowering decreased the risk of cardiovascular events irrespective of baseline diastolic blood pressure in patients who also received standard gly-cemic control (43). Therefore, the pres-ence of low diastolic blood pressure is not necessarily a contraindication to more intensive blood pressure man-agement in the context of otherwise standard care.
Patients with low absolute cardiovas-cular risk (10-year ASCVD risk<15%) or with a history of adverse effects of intensive blood pressure control or at high risk of adverse effects should have a higher blood pressure target. In such patients, a blood pressure target of
<140/90 mmHg is recommended, if it can be safely attained.
Pregnancy and Antihypertensive Medications
There are few randomized controlled tri-als of antihypertensive therapy in preg-nant women with diabetes. A 2014 Cochrane systematic review of antihyper-tensive therapy for mild to moderate chronic hypertension that included 49 tri-als and over 4,700 women did notfind
any conclusive evidence for or against blood pressure treatment to reduce the risk of preeclampsia for the mother or effects on perinatal outcomes such as preterm birth, small-for-gestational-age infants, or fetal death (44). The more recent Control of Hypertension in Preg-nancy Study (CHIPS) (45) enrolled mostly women with chronic hypertension. In CHIPS, targeting a diastolic blood pres-sure of 85 mmHg during pregnancy was associated with reduced likelihood of developing accelerated maternal hyper-tension and no demonstrable adverse outcome for infants compared with tar-geting a higher diastolic blood pressure.
The mean systolic blood pressure achieved in the more intensively treated group was 133.1 ± 0.5 mmHg, and the mean diastolic blood pressure achieved in that group was 85.3 ± 0.3 mmHg. A similar approach is supported by the International Society for the Study of Hypertension in Pregnancy, which speci fi-cally recommends use of antihyperten-sive therapy to maintain systolic blood pressure between 110 and 140 mmHg and diastolic blood pressure between 80 and 85 mmHg (46). Current evidence supports controlling blood pressure to 110–135/85 mmHg to reduce the risk of accelerated maternal hypertension but also to minimize impairment of fetal growth. During pregnancy, treatment with ACE inhibitors, angiotensin receptor blockers, and spironolactone are contra-indicated as they may cause fetal dam-age. Antihypertensive drugs known to be effective and safe in pregnancy include methyldopa, labetalol, and long-acting nifedipine, while hydralzine may be con-sidered in the acute management of hypertension in pregnancy or severe preeclampsia (47). Diuretics are not rec-ommended for blood pressure control in pregnancy but may be used during late-stage pregnancy if needed for volume control (47,48). The American College of Obstetricians and Gynecologists also rec-ommends that postpartum patients with gestational hypertension, preeclampsia, and superimposed preeclampsia have their blood pressures observed for 72 h in the hospital and for 7–10 days post-partum. Long-term follow-up is recom-mended for these women as they have increased lifetime cardiovascular risk (49). See Section 15, “Management of Diabetes in Pregnancy” (https://
doi.org/10.2337/dc22-S015), for add-itional information.
Treatment Strategies Lifestyle Intervention
Recommendation
10.7 For patients with blood pres-sure >120/80 mmHg, life-style intervention consists of weight loss when indicated, a Dietary Approaches to Stop Hypertension (DASH)-style eating pattern including reducing sodium and increasing potassium intake, moderation of alcohol intake, and increased physical activity.A
Lifestyle management is an important component of hypertension treatment because it lowers blood pressure, enhan-ces the effectiveness of some antihyper-tensive medications, promotes other aspects of metabolic and vascular health, and generally leads to few adverse effects. Lifestyle therapy consists of reducing excess body weight through caloric restriction (see Section 8,“Obesity and Weight Management for the Preven-tion and Treatment of Type 2 Diabetes,” https://doi.org/10.2337/dc22-S008), 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) (50), and increasing activity levels (51).
These lifestyle interventions are rea-sonable for individuals with diabetes and mildly elevated blood pressure (systolic
>120 mmHg or diastolic >80 mmHg) and should be initiated along with phar-macologic therapy when hypertension is diagnosed (Fig. 10.2) (51). A lifestyle ther-apy plan should be developed in collabo-ration with the patient and discussed as part of diabetes management. Use of internet or mobile-based digital platforms to reinforce healthy behaviors may be considered as a component of care, as these interventions have been found to enhance the efficacy of medical therapy for hypertension (52,53).
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Pharmacologic Interventions Recommendations
10.8 Patients with confirmed office-based blood pressure $140/
90 mmHg should, in addition to lifestyle therapy, have prompt initiation and timely titration of pharmacologic therapy
to achieve blood pressure goals.A
10.9 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 sin-gle-pill combination of drugs
demonstrated to reduce car-diovascular events in patients with diabetes.A
10.10 Treatment for hypertension should include drug classes demonstrated to reduce car-diovascular events in patients with diabetes.AACE inhibitors or angiotensin receptor
Figure 10.2—Recommendations for the treatment of confirmed hypertension in people with diabetes. *An ACE inhibitor (ACEi) or angiotensin receptor blocker (ARB) is suggested to treat hypertension for patients with coronary artery disease (CAD) or urine albumin-to-creatinine ratio 30–299 mg/g creatinine and strongly recommended for patients with urine albumin-to-creatinine ratio $300 mg/g creatinine. **Thiazide-like diuretic; long-acting agents shown to reduce cardiovascular events, such as chlorthalidone and indapamide, are preferred. ***Dihydropyridine cal-cium channel blocker (CCB). BP, blood pressure. Adapted from de Boer et al. (17).
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blockers are recommended first-line therapy for hyperten-sion in people with diabetes and coronary artery disease.A 10.11 Multiple-drug therapy is
gener-ally required to achieve blood pressure targets. However, com-binations of ACE inhibitors and angiotensin receptor blockers and combinations of ACE inhibi-tors or angiotensin receptor blockers with direct renin inhibi-tors should not be used.A 10.12 An ACE inhibitor or angiotensin
receptor blocker, at the maxi-mum tolerated dose indicated for blood pressure treatment, is the recommended first-line treatment for hypertension in patients with diabetes and uri-nary 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.B 10.13 For patients treated with an
ACE inhibitor, angiotensin recep-tor blocker, or diuretic, serum creatinine/estimated glomerular filtration rate and serum potas-sium levels should be moni-tored at least annually.B
Initial Number of Antihypertensive Medi-cations.Initial treatment for people with diabetes depends on the severity of hypertension (Fig. 10.2). Those with blood pressure between 140/90 mmHg and 159/99 mmHg may begin with a sin-gle drug. For patients with blood pressure
$160/100 mmHg, initial pharmacologic treatment with two antihypertensive medications is recommended in order to more effectively achieve adequate blood pressure control (54–56). Single-pill anti-hypertensive combinations may improve medication adherence in some patients (57).
Classes of Antihypertensive Medications.
Initial treatment for hypertension should include any of the drug classes demonstrated to reduce cardiovascular events in patients with diabetes: ACE inhibitors (58,59), angiotensin receptor blockers (ARBs) (58,59), thiazide-like diuretics (60), or dihydropyridine cal-cium channel blockers (61). In patients with diabetes and established coronary
artery disease, ACE inhibitors or ARBs are recommended first-line therapy for hypertension (62–64). For patients with albuminuria (urine albumin-to-creati-nine ratio [UACR] $30 mg/g), initial treatment should include an ACE inhibi-tor or ARB in order to reduce the risk of progressive kidney disease (17) (Fig.
10.2). In patients receiving ACE inhibitor or ARB therapy, continuation of those medications as kidney function declines to estimated glomerular filtration rate (eGFR)<30 mL/min/1.73 m2may provide cardiovascular benefit without signifi-cantly increasing the risk of end-stage kid-ney disease (65). In the absence of albuminuria, risk of progressive kidney disease is low, and ACE inhibitors and ARBs have not been found to afford superior cardioprotection when compared with thiazide-like diuretics or dihydropyri-dine calcium channel blockers (66).
b-Blockers are indicated in the setting of prior MI, active angina, or HfrEF but have not been shown to reduce mortality as blood pressure–lowering agents in the absence of these conditions (24,67,68).
Multiple-Drug Therapy. Multiple-drug therapy is often required to achieve blood pressure targets (Fig. 10.2), par-ticularly in the setting of diabetic kidney disease. However, the use of both ACE inhibitors and ARBs in combination, or the combination of an ACE inhibitor or ARB and a direct renin inhibitor, is con-traindicated given the lack of added ASCVD benefit and increased rate of adverse events—namely, hyperkalemia, syncope, and acute kidney injury (AKI) (69–71). Titration of and/or addition of further blood pressure medications should be made in a timely fashion to overcome therapeutic inertia in achiev-ing blood pressure targets.
Bedtime Dosing. Although prior analyses of randomized clinical trials found a ben-efit to evening versus morning dosing of antihypertensive medications (72,73), these results have not been reproduced in subsequent trials. Therefore, preferen-tial use of antihypertensives at bedtime is not recommended (73a).
Hyperkalemia and Acute Kidney Injury.
Treatment with ACE inhibitors or ARBs can cause AKI and hyperkalemia, while diuretics can cause AKI and either hypo-kalemia or hyperhypo-kalemia (depending on
mechanism of action) (74,75). Detection and management of these abnormali-ties is important because AKI and hyper-kalemia each increase the risks of cardiovascular events and death (76).
Therefore, serum creatinine and potas-sium should be monitored during treat-ment with an ACE inhibitor, ARB, or diuretic, particularly among patients with reduced glomerular filtration who are at increased risk of hyperkalemia and AKI (74,75,77).
Resistant Hypertension Recommendation
10.14 Patients with hypertension who are not meeting blood pressure targets on three clas-ses of antihypertensive medi-cations (including a diuretic) should be considered for min-eralocorticoid receptor antago-nist therapy.B
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 with complimentary mechanisms of action at adequate doses. Prior to diagnosing resistant hypertension, a number of other conditions should be excluded, including medication nonad-herence, white coat hypertension, and secondary hypertension. In general, bar-riers to medication adherence (such as cost and side effects) should be identi-fied and addressed (Fig. 10.2). Mineralo-corticoid receptor antagonists are effective for management of resistant hypertension in patients with type 2 dia-betes when added to existing treatment with an ACE inhibitor or ARB, thiazide-like diuretic, and dihydropyridine cal-cium channel blocker (78). Mineralocor-ticoid receptor antagonists also reduce albuminuria and have additional cardio-vascular benefits (79–82). However, adding a mineralocorticoid receptor antagonist to a regimen including an ACE inhibitor or ARB may increase the risk for hyperkalemia, emphasizing the importance of regular monitoring for serum creatinine and potassium in these patients, and long-term outcome studies are needed to better evaluate the role
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