kelingwang/causation_strength_rating huggingface dataset:
An elevated blood pressure is defined as a systolic blood pressure 120–129 mmHg and a diastolic blood pressure <80 mmHg (17).
Hypertension is defined as a systolic blood pressure =130 mmHg or a diastolic blood pressure =80 mmHg (17).
This is in agreement with the definition of hypertension by the American College of Cardiology and American Heart Association (17).
Hypertension is common among people with either type 1 or type 2 diabetes.
Hypertension is a major risk factor for ASCVD, heart failure, and microvascular complications.
Moreover, numerous studies have shown that antihypertensive therapy reduces ASCVD events, heart failure, and microvascular complications.
Please refer to the ADA position statement �Diabetes and Hypertension� for a detailed review of the epidemiology, diagnosis, and treatment of hypertension (18) and recent updated hypertension guideline recommendations (17,19,20).
Blood pressure should be measured at every routine clinical visit by a trained individual and should follow the guidelines established for the general population: measurement in the seated position, with feet on the floor and arm supported at heart level, after 5 min of rest.
Cuff size should be appropriate for the upper-arm circumference (21).
Elevated values should preferably be confirmed on a separate day; however, in individuals with cardiovascular disease and blood pressure =180/110 mmHg, it is reasonable to diagnose hypertension at a single visit (19).
Postural changes in blood pressure and pulse may be evidence of autonomic neuropathy and therefore require adjustment of blood pressure targets.
Orthostatic blood pressure measurements should be checked on initial visit and as indicated.
Lifestyle intervention, including weight loss in people with overweight or obesity (when appropriate) (85), increased physical activity, and medical nutrition therapy, allows some individuals to reduce ASCVD risk factors.
Nutrition intervention should be tailored according to each person�s age, pharmacologic treatment, lipid levels, and medical conditions.
Recommendations should focus on application of a Mediterranean (83) or Dietary Approaches to Stop Hypertension (DASH) eating pattern, reducing saturated and trans fat intake, and increasing plant stanol/sterol, n-3 fatty acid, and viscous fiber (such as in oats, legumes, and citrus) intake (86,87).
Glycemic control may also beneficially modify plasma lipid levels, particularly in people with very high triglycerides and poor glycemic control.
See Section 5, �Facilitating Positive Health Behaviors and Well-being to Improve Health Outcomes,� for additional nutrition information.
In adults with diabetes, it is reasonable to obtain a lipid profile (total cholesterol, LDL cholesterol, HDL cholesterol, and triglycerides) at the time of diagnosis, at the initial medical evaluation, and at least every 5 years thereafter in individuals <40 years of age.
In younger people with longer duration of disease (such as those with youth-onset type 1 diabetes), more frequent lipid profiles may be reasonable.
A lipid panel should also be obtained immediately before initiating statin therapy.
Once an individual is taking a statin, LDL cholesterol levels should be assessed 4–12 weeks after initiation of statin therapy, after any change in dose, and annually (e.g., to monitor for medication taking and efficacy).
Monitoring lipid profiles after initiation of statin therapy and during therapy increases dose titration and statin adherence (88–90).
If LDL cholesterol levels are not responding in spite of medication taking, clinical judgment is recommended to determine the need for and timing of lipid panels.
In individual patients, the highly variable LDL cholesterol�lowering response seen with statins is poorly understood (91).
Clinicians should attempt to find a dose or alternative statin that is tolerable if side effects occur.
There is evidence for benefit from even extremely low, less than daily statin doses (92).
Home blood pressure self-monitoring and 24-h ambulatory blood pressure monitoring may provide evidence of white coat hypertension, masked hypertension, or other discrepancies between office and �true� blood pressure (22,23).
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 measurements may better correlate with ASCVD risk than office measurements (22,23).
Moreover, home blood pressure monitoring may improve medication-taking behavior and thus help reduce cardiovascular risk (24).
People with diabetes and clinicians should engage in a shared decision-making process to determine individual blood pressure targets (17).
This approach acknowledges that the benefits and risks of intensive blood pressure targets are uncertain and may vary across individuals and is consistent with a person-focused approach to care that values individual priorities and health care professional judgment (38).
Secondary analyses of ACCORD BP and SPRINT suggest that clinical factors can help determine individuals more likely to benefit and less likely to be harmed by intensive blood pressure control (39,40).
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 (40,41).
Extrapolation of these studies suggests that people with diabetes may also be more likely to benefit from intensive blood pressure control when they have high absolute cardiovascular risk.
This approach is consistent with guidelines from the American College of Cardiology and American Heart Association, which also advocate a blood pressure target of <130/80 mmHg for all people, with or without diabetes (18).
Potential adverse effects of antihypertensive therapy (e.g., hypotension, syncope, falls, AKI, and electrolyte abnormalities) should also be taken into account (32,34,42,43).
Individuals with older age, CKD, and frailty have been shown to be at higher risk of adverse effects of intensive blood pressure control (42).
In addition, individuals with orthostatic hypotension, substantial comorbidity, functional limitations, or polypharmacy may be at high risk of adverse effects, and some individuals may prefer higher blood pressure targets to enhance quality of life.
However, ACCORD BP demonstrated that intensive blood pressure lowering decreased the risk of cardiovascular events irrespective of baseline diastolic blood pressure in individuals who also received standard glycemic control (44).
Therefore, the presence of low diastolic blood pressure is not necessarily a contraindication to more intensive blood pressure management in the context of otherwise standard care.
Randomized clinical trials have demonstrated unequivocally that treatment of hypertension reduces cardiovascular events as well as microvascular complications (25–31).
There has been controversy on the recommendation of a specific blood pressure goal in people with diabetes.
The committee recognizes that there has been no randomized controlled trial to specifically demonstrate a decreased incidence of cardiovascular events in people with diabetes by targeting a blood pressure <130/80 mmHg.
The recommendation to support a blood pressure goal of <130/80 mmHg in people with diabetes is consistent with guidelines from the American College of Cardiology and American Heart Association (18), the International Society of Hypertension (19), and the European Society of Cardiology (20).
The committee�s recommendation for the blood pressure target of <130/80 mmHg derives primarily from the collective evidence of the following randomized controlled trials.
The Systolic Blood Pressure Intervention Trial (SPRINT) demonstrated that treatment to a target systolic blood pressure of <120 mmHg decreases cardiovascular event rates by 25% in high-risk individuals, although people with diabetes were excluded from this trial (32).
The recently completed Strategy of Blood Pressure Intervention in the Elderly Hypertensive Patients (STEP) trial included nearly 20% of people with diabetes and noted decreased cardiovascular events with treatment of hypertension to a blood pressure target of <130 mmHg (33).
While the ACCORD (Action to Control Cardiovascular Risk in Diabetes) blood pressure trial (ACCORD BP) did not confirm that targeting a systolic blood pressure of <120 mmHg in people with diabetes results in decreased cardiovascular event rates, the prespecified secondary outcome of stroke was reduced by 41% with intensive treatment (34).
The Action in Diabetes and Vascular Disease: Preterax and Diamicron MR Controlled Evaluation (ADVANCE) trial revealed that treatment with perindopril/indapamide to an achieved systolic blood pressure of ~135 mmHg significantly decreased cardiovascular event rates compared with a placebo treatment with an achieved blood pressure of 140 mmHg (35).
Therefore, it is recommended that people with diabetes who have hypertension should be treated to blood pressure targets of <130/80 mmHg.
Notably, there is an absence of high-quality data available to guide blood pressure targets in people with type 1 diabetes, but a similar blood pressure target of <130/80 mmHg is recommended in people with type 1 diabetes.
As discussed below, treatment should be individualized, and treatment should not be targeted to <120/80 mmHg, as a mean achieved blood pressure of <120/80 mmHg is associated with adverse events.
SPRINT provides the strongest evidence to support lower blood pressure goals in individuals at increased cardiovascular risk, although this trial excluded people with diabetes (32).
The trial enrolled 9,361 individuals with a systolic blood pressure of =130 mmHg and increased cardiovascular risk and treated to a systolic blood pressure target of <120 mmHg (intensive treatment) versus a target of <140 mmHg (standard treatment).
The primary composite outcome of MI, coronary syndromes, stroke, heart failure, or death from cardiovascular causes was reduced by 25% in the intensive treatment group.
The achieved systolic blood pressures in the trial were 121 mmHg and 136 mmHg in the intensive versus standard treatment group, respectively.
Adverse outcomes, including hypotension, syncope, electrolyte abnormality, and acute kidney injury (AKI), were more common in the intensive treatment arm; risk of adverse outcomes needs to be weighed against the cardiovascular benefit of more intensive blood pressure lowering.
ACCORD BP provides the strongest direct assessment of the benefits and risks of intensive blood pressure control in people with type 2 diabetes (34).
In the study, a total of 4,733 individuals with type 2 diabetes were assigned to intensive therapy (targeting a systolic blood pressure <120 mmHg) or standard therapy (targeting a systolic blood pressure <140 mmHg).
The mean achieved systolic blood pressures were 119 mmHg and 133 mmHg in the intensive versus standard group, respectively.
The primary composite outcome of nonfatal MI, nonfatal stroke, or death from cardiovascular causes was not significantly reduced in the intensive treatment group.
The prespecified secondary outcome of stroke was significantly reduced by 41% in the intensive treatment group.
Adverse events attributed to blood pressure treatment, including hypotension, syncope, bradycardia, hyperkalemia, and elevations in serum creatinine, occurred more frequently in the intensive treatment arm than in the standard therapy arm (Table 10.1 ).
Of note, the ACCORD BP and SPRINT trials targeted a similar systolic blood pressure <120 mmHg, but in contrast to SPRINT, the primary composite cardiovascular end point was nonsignificantly reduced in ACCORD BP.
The results have been interpreted to be generally consistent between both trials, but ACCORD BP was viewed as underpowered due to the composite primary end point being less sensitive to blood pressure regulation (32).
The more recent STEP trial assigned 8,511 individuals aged 60–80 years with hypertension to a systolic blood pressure target of 110 to <130 mmHg (intensive treatment) or a target of 130 to <150 mmHg (33).
In this trial, the primary composite outcome of stroke, acute coronary syndrome, acute decompensated heart failure, coronary revascularization, atrial fibrillation, or death from cardiovascular causes occurred in 3.5% of individuals in the intensive treatment group versus 4.6% in the standard treatment group (hazard ratio [HR] 0.74 [95% CI 0.60–0.92]; P = 0.007).
In this trial, 18.9% of individuals in the intensive treatment arm and 19.4% in the standard treatment arm had a diagnosis of type 2 diabetes.
Hypotension occurred more frequently in the intensive treatment group (3.4%) compared with the standard treatment group (2.6%), without significant differences in other adverse events, including dizziness, syncope, or fractures.
In ADVANCE, 11,140 people with type 2 diabetes were randomized to receive either treatment with a fixed combination of perindopril/indapamide or matching placebo (35).
The primary end point, a composite of cardiovascular death, nonfatal stroke infarction, or worsening renal or diabetic eye disease, was reduced by 9% in the combination treatment.
The achieved systolic blood pressure was ~135 mmHg in the treatment group and 140 mmHg in the placebo group.
The Hypertension Optimal Treatment (HOT) trial enrolled 18,790 individuals and targeted diastolic blood pressure <90 mmHg, <85 mmHg, or <80 mmHg (36).
The cardiovascular event rates, defined as fatal or nonfatal MI, fatal and nonfatal strokes, and all other cardiovascular events, were not significantly different between diastolic blood pressure targets (=90 mmHg, =85 mmHg, and =80 mmHg), although the lowest incidence of cardiovascular events occurred with an achieved diastolic blood pressure of 82 mmHg.
However, in people with diabetes, there was a significant 51% reduction in the treatment group with a target diastolic blood pressure of <80 mmHg compared with a target diastolic blood pressure of <90 mmHg.
To clarify optimal blood pressure targets in people with diabetes, multiple meta-analyses have been performed.
One of the largest meta-analyses included 73,913 people with diabetes.
Compared with a less tight blood pressure control, allocation to a tighter blood pressure control significantly reduced the risk of stroke by 31% but did not reduce the risk of MI (37).
Another meta-analysis of 19 trials that included 44,989 individuals showed that a mean blood pressure of 133/76 mmHg is associated with a 14% risk reduction for major cardiovascular events compared with a mean blood pressure of 140/81 mmHg (31).
This benefit was greatest in people with diabetes.
An analysis of trials including people with type 2 diabetes and impaired glucose tolerance with achieved systolic blood pressures of <135 mmHg in the intensive blood pressure treatment group and <140 mmHg in the standard treatment group revealed a 10% reduction in all-cause mortality and a 17% reduction in stroke (29).
More intensive reduction to <130 mmHg was associated with a further reduction in stroke but not other cardiovascular events.
Several meta-analyses stratified clinical trials by mean baseline blood pressure or mean blood pressure attained in the intervention (or intensive treatment) arm.
Based on these analyses, antihypertensive treatment appears to be most beneficial when mean baseline blood pressure is =140/90 mmHg (17,25,26,28–30).
Among trials with lower baseline or attained blood pressure, antihypertensive treatment reduced the risk of stroke, retinopathy, and albuminuria, but effects on other ASCVD outcomes and heart failure were not evident.
There are few randomized controlled trials of antihypertensive therapy in pregnant individuals with diabetes.
A 2018 Cochrane systematic review of antihypertensive therapy for mild to moderate chronic hypertension included 63 trials and over 5,909 women and suggested that antihypertensive therapy probably reduces the risk of developing severe hypertension but may not affect the risk of fetal or neonatal death, small-for-gestational-age babies, or preterm birth (45).
The Control of Hypertension in Pregnancy Study (CHIPS) (46) enrolled mostly women with chronic hypertension.
In CHIPS, targeting a diastolic blood pressure of 85 mmHg during pregnancy was associated with reduced likelihood of developing accelerated maternal hypertension and no demonstrable adverse outcome for infants compared with targeting 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 specifically recommends use of antihypertensive therapy to maintain systolic blood pressure between 110 and 140 mmHg and diastolic blood pressure between 80 and 85 mmHg (47).
The more recent Chronic Hypertension and Pregnancy (CHAP) trial assigned pregnant individuals with mild chronic hypertension to antihypertensive medications to target a blood pressure goal of <140/90 mmHg (active treatment group) or to control treatment, in which antihypertensive therapy was withheld unless severe hypertension (systolic pressure =160 mmHg or diastolic pressure =105 mmHg) developed (control group) (48).
The primary outcome, a composite of preeclampsia with severe features, medically indicated preterm birth at <35 weeks of gestation, placental abruption, or fetal/neonatal death, occurred in 30.2% of female participants in the active treatment group versus 37.0% in the control group (P < 0.001).
The mean systolic blood pressure between randomization and delivery was 129.5 mmHg in the active treatment group and 132.6 mmHg in the control group.
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 (ARBs), direct renin inhibitors, and spironolactone are contraindicated, as they may cause fetal damage.
Special consideration should be taken for individuals of childbearing potential, and people intending to become pregnant should switch from an ACE inhibitor/ARB or spironolactone to an alternative antihypertensive medication approved during pregnancy.
Antihypertensive drugs known to be effective and safe in pregnancy include methyldopa, labetalol, and long-acting nifedipine, while hydralazine may be considered in the acute management of hypertension in pregnancy or severe preeclampsia (49).
Diuretics are not recommended for blood pressure control in pregnancy but may be used during late-stage pregnancy if needed for volume control (49,50).
The American College of Obstetricians and Gynecologists also recommends that postpartum individuals with gestational hypertension, preeclampsia, and superimposed preeclampsia have their blood pressures observed for 72 h in the hospital and 7–10 days postpartum.
Long-term follow-up is recommended for these individuals, as they have increased lifetime cardiovascular risk (51).
See Section 15, �Management of Diabetes in Pregnancy,� for additional information.
Lifestyle management is an important component of hypertension treatment because it lowers blood pressure, enhances the effectiveness of some antihypertensive 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 Prevention and Treatment of Type 2 Diabetes�), at least 150 min of moderate-intensity aerobic activity per week (see Section 3, �Prevention or Delay of Diabetes and Associated Comorbidities�), 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) (52), and increasing activity levels (53) (see Section 5, �Facilitating Positive Health Behaviors and Well-being to Improve Health Outcomes�).
These lifestyle interventions are reasonable for individuals with diabetes and mildly elevated blood pressure (systolic >120 mmHg or diastolic >80 mmHg) and should be initiated along with pharmacologic therapy when hypertension is diagnosed (Fig. 10.2 ) (53).
A lifestyle therapy plan should be developed in collaboration with the person with diabetes 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 (54,55).
Although minimizing hyperglycemia may be important in older individuals with diabetes, greater reductions in morbidity and mortality are likely to result from a clinical focus on comprehensive cardiovascular risk factor modification.
There is strong evidence from clinical trials of the value of treating hypertension in older adults (70,71), with treatment of hypertension to individualized target levels indicated in most.
There is less evidence for lipid-lowering therapy and aspirin therapy, although the benefits of these interventions for primary and secondary prevention are likely to apply to older adults whose life expectancies equal or exceed the time frames of the clinical trials (72).
In the case of statins, the follow-up time of clinical trials ranged from 2 to 6 years.
While the time frame of trials can be used to inform treatment decisions, a more specific concept is the time to benefit for a therapy.
For statins, a meta-analysis of the previously mentioned trials showed that the time to benefit is 2.5 years (73).
Lifestyle management in older adults should be tailored to frailty status.
Diabetes in the aging population is associated with reduced muscle strength, poor muscle quality, and accelerated loss of muscle mass, which may result in sarcopenia and/or osteopenia (74,75).
Diabetes is also recognized as an independent risk factor for frailty.
Frailty is characterized by decline in physical performance and an increased risk of poor health outcomes due to physiologic vulnerability and functional or psychosocial stressors.
Inadequate nutritional intake, particularly inadequate protein intake, can increase the risk of sarcopenia and frailty in older adults.
Management of frailty in diabetes includes optimal nutrition with adequate protein intake combined with an exercise program that includes aerobic, weightbearing, and resistance training.
The benefits of a structured exercise program (as in the Lifestyle Interventions and Independence for Elders [LIFE] study) in frail older adults include reducing sedentary time, preventing mobility disability, and reducing frailty (76,77).
The goal of these programs is not weight loss but enhanced functional status.
For nonfrail older adults with type 2 diabetes and overweight or obesity, an intensive lifestyle intervention designed to reduce weight is beneficial across multiple outcomes.
The Look AHEAD (Action for Health in Diabetes) trial is described in Section 8, �Obesity and Weight Management for the Prevention and Treatment of Type 2 Diabetes.�
Look AHEAD specifically excluded individuals with a low functional status.
It enrolled people between 45 and 74 years of age and required that they be able to perform a maximal exercise test (78,79).
While the Look AHEAD trial did not achieve its primary outcome of reducing cardiovascular events, the intensive lifestyle intervention had multiple clinical benefits that are important to the quality of life of older adults.
Benefits included weight loss, improved physical fitness, increased HDL cholesterol, lowered systolic blood pressure, reduced A1C levels, reduced waist circumference, and reduced need for medications (80).
Additionally, several subgroups, including participants who lost at least 10% of baseline body weight at year 1, had improved cardiovascular outcomes (81).